greenmedinfo--2020-03-20--Curcumin inhibits the proliferation, migration, invasion, and apoptosis of diffuse large B-cell lymp

Curcumin inhibits the proliferation, migration, invasion, and apoptosis of diffuse large B-cell lymphoma cell line.

PURPOSE : Curcumin exerts its anti-cancer effects , partly by targeting special microRNAs , in human cancers .
MiR-21 is a key oncomir in carcinogenesis of multiple human cancers .
Here , we aimed to further explore the mechanistic insight into the link between curcumin and miR-21 on diffuse large B-cell lymphoma ( DLBCL ) .
MATERIALS AND METHODS : Quantitative real-time PCR assays were performed to assess the levels of miR-21 and Von Hippel-Lindau ( VHL ) mRNA .
In situ hybridization assay was used for miR-21 expression visualization in lymphoma tissues .
Western blot was used for determination @ @ @ @ @ @ @ , and cleaved caspase-3 levels .
Dual-luciferase reporter assay and RNA immunoprecipitation assay were employed to confirm the direct target of miR-21 .
MTT assay , flow cytometric analysis , and transwell assay were used to evaluate cell proliferation , apoptosis , and migration and invasion capacities , respectively .
RESULTS : Curcumin repressed the proliferation , migration , and invasion abilities and promoted apoptosis in SU-DHL-8 cells .
Curcumin inhibited miR-21 expression and curcumin exerted its anti-proliferation , anti-migration , anti-invasion , and pro-apoptosis effects by miR-21 in SU-DHL-8 cells .
VHL @ @ @ @ @ @ @ Moreover , curcumin exerted its regulatory effects on SU-DHL-8 cells by VHL .
CONCLUSION : Curcumin exerted its anti-proliferation , anti-migration , anti-invasion , and pro-apoptosis functions , at least partly , by repressing miR-21 and regulating VHL expression in DLBCL cell line .
Our findings provided a possible molecular mechanism of curcumin-mediated anti-cancer effect .

PURPOSE: Curcumin exerts its anti-cancer effects, partly by targeting special microRNAs, in human cancers. MiR-21 is a key oncomir in carcinogenesis of multiple human cancers. Here, we aimed to further explore the mechanistic insight into the link between curcumin and miR-21 on diffuse large B-cell lymphoma (DLBCL).
MATERIALS AND METHODS: Quantitative real-time PCR assays were performed to assess the levels of miR-21 and Von Hippel-Lindau (VHL) mRNA. In situ hybridization assay was used for miR-21 expression visualization in lymphoma tissues. Western blot was used for determination of VHL protein, Ki-67, caspase-3, and cleaved caspase-3 levels. Dual-luciferase reporter assay and RNA immunoprecipitation assay were employed to confirm the direct target of miR-21. MTT assay, flow cytometric analysis, and transwell assay were used to evaluate cell proliferation, apoptosis, and migration and invasion capacities, respectively.
RESULTS: Curcumin repressed the proliferation, migration, and invasion abilities and promoted apoptosis in SU-DHL-8 cells. Curcumin inhibited miR-21 expression and curcumin exerted its anti-proliferation, anti-migration, anti-invasion, and pro-apoptosis effects by miR-21 in SU-DHL-8 cells. VHL was a direct target of miR-21. Moreover, curcumin exerted its regulatory effects on SU-DHL-8 cells by VHL.
CONCLUSION: Curcumin exerted its anti-proliferation, anti-migration, anti-invasion, and pro-apoptosis functions, at least partly, by repressing miR-21 and regulating VHL expression in DLBCL cell line. Our findings provided a possible molecular mechanism of curcumin-mediated anti-cancer effect.


greenmedinfo--2020-03-20--Encapsulated curcumin enhances intestinal absorption and improves hepatic damage in alcoholic liver

Encapsulated curcumin enhances intestinal absorption and improves hepatic damage in alcoholic liver disease-induced rats.

Encapsulated curcumin ( ENCC ) was prepared from a commercial curcuminoids complex and was evaluated for its intestinal permeability and @ @ @ @ @ was evaluated using a Caco-2 intestinal cell monolayer system and the non-everted gut sac method @ @ @ @ @ evaluated in experimental rats administered alcohol for 4 weeks .
The intestinal permeability results suggested @ @ @ @ @ method for enhancing adsorption of curcumin via the intestinal epithelium .
ENCC administration resulted in @ @ @ @ @ serum indicators .
Notably , most of the indicators elevated by ethanol decreased below normal @ @ @ @ @ a high dose of ENCC .
Oral administration of ENCC also augmented the activity of @ @ @ @ @ , and both normal curcumin and ENCC significantly alleviated high levels of malondialdehyde .
Our @ @ @ @ @ effect of ENCCowing to its ability to improve bioavailability of curcumin .

Encapsulated curcumin (ENCC) was prepared from a commercial curcuminoids complex and was evaluated for its intestinal permeability and hepatoprotective effects. Intestinal permeability was evaluated using a Caco-2 intestinal cell monolayer system and the non-everted gut sac method. The hepatoprotective effect was evaluated in experimental rats administered alcohol for 4 weeks. The intestinal permeability results suggested that encapsulation is a useful method for enhancing adsorption of curcumin via the intestinal epithelium. ENCC administration resulted in the significant reduction of various serum indicators. Notably, most of the indicators elevated by ethanol decreased below normal levels when rats were administered a high dose of ENCC. Oral administration of ENCC also augmented the activity of glutathione peroxidase in the liver, and both normal curcumin and ENCC significantly alleviated high levels of malondialdehyde. Our results demonstrate a significant hepatoprotective effect of ENCCowing to its ability to improve bioavailability of curcumin.


greenmedinfo--2020-03-19--curcumin supplementation can improve serum levels of inflammatory cytokines in subjects with NAFLD.

BACKGROUND : Nonalcoholic fatty liver diseases ( NAFLD ) is a highly prevalent disease that is closely associated with several cardiometabolic complications .
The potential anti-inflammatory role of curcuminoids that have already been reported to reduce hepatic steatosis , in patients with NAFLD was explored in this study .
METHODS : This double-blind , randomized placebo-controlled trial was conducted for a period of 8 weeks in patients with NAFLD .
Subjects ( n = 55 ) were randomly allocated to receive either curcuminoids or placebo .
The curcuminoids group received one capsule containing 500 mg curcuminoids ( plus 5 mg @ @ @ @ @ @ @ day for 8 weeks and the control group received matched placebo capsules for the sameperiod .
Liver ultrasonography was performed to assess the severity of hepatic steatosis at baseline and the study end .
Serum levels of cytokines including interleukin-1α , interleukin-1β , interleukin-2 , interleukin-4 , interleukin-6 , interleukin-8 , interleukin-10 , tumor necrosis factor-α , monocytechemoattractant protein-1 , interferon γ , vascular endothelial growth factor and epidermal growth factor were measured before and after the intervention .
RESULTS : The two groups were comparable in demographic features at baseline .
The @ @ @ @ @ @ @ decrease weight compared to the placebo group ( p = 0.016 ) in patients with NAFLD .
Curcuminoids supplementation improved the severity of NAFLD according to the ultrasound results ( p = 0.002 ) .
Moreover , serum concentrations of TNF-α ( p = 0.024 ) , MCP-1 ( p = 0.008 ) and EGF ( p = 0.0001 ) were improved by curcuminoids in NAFLD patients .
CONCLUSIONS : The results of our study showed that curcumin supplementation can improve serum levels of inflammatory cytokines in subjects with NAFLD and this might @ @ @ @ @ @ @ anti-steatotic effects of curcuminoids .

BACKGROUND: Nonalcoholic fatty liver diseases (NAFLD) is a highly prevalent disease that is closely associated with several cardiometabolic complications. The potential anti-inflammatory role of curcuminoids that have already been reported to reduce hepatic steatosis, in patients with NAFLD was explored in this study.
METHODS: This double-blind, randomized placebo-controlled trial was conducted for a period of 8 weeks in patients with NAFLD. Subjects (n = 55) were randomly allocated to receive either curcuminoids or placebo. The curcuminoids group received one capsule containing 500 mg curcuminoids (plus 5 mg piperine to increase intestinal absorption) per day for 8 weeks and the control group received matched placebo capsules for the sameperiod. Liver ultrasonography was performed to assess the severity of hepatic steatosis at baseline and the study end. Serum levels of cytokines including interleukin-1α, interleukin-1β, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-α, monocytechemoattractant protein-1, interferon γ, vascular endothelial growth factor and epidermal growth factor were measured before and after the intervention.
RESULTS: The two groups were comparable in demographic features at baseline. The results showed that supplementation with curcuminoids could decrease weight compared to the placebo group (p = 0.016) in patients with NAFLD. Curcuminoids supplementation improved the severity of NAFLD according to the ultrasound results (p = 0.002). Moreover, serum concentrations of TNF-α (p = 0.024), MCP-1 (p = 0.008) and EGF (p = 0.0001) were improved by curcuminoids in NAFLD patients.
CONCLUSIONS: The results of our study showed that curcumin supplementation can improve serum levels of inflammatory cytokines in subjects with NAFLD and this might be at least partly responsible for the anti-steatotic effects of curcuminoids.


greenmedinfo--2020-03-19--Bisdemethoxycurcumin attenuates cisplatin-induced renal injury through anti-apoptosis, anti-oxidant

Bisdemethoxycurcumin attenuates cisplatin-induced renal injury through anti-apoptosis, anti-oxidant and anti-inflammatory.

Cisplatin is a widely used chemotherapy drug that is first-line therapy for a variety of tumors .
Unfortunately , its adverse effects on various normal tissues and organs , especially nephrotoxicity , threaten the life of patients .
Although the mechanism of cisplatin nephrotoxicity has been confirmed to be related to oxidative stress , apoptosis of renal tubular epithelial cells and inflammatory response , there is no effective prevention strategy in the clinic .
Here , we found that bisdemethoxycurcumin ( BDMC ) , a natural compound , can significantly attenuates cisplatin-induced apoptosis of renal tubular epithelial cells in vitro @ @ @ @ @ @ @ has a significant protective effect on cisplatin-induced kidney injury in mice at the dose of 50 mg/kg .
Mechanistically , BDMC attenuates cisplatin-induced apoptosis of renal tubular epithelial cells by inhibiting cisplatin-induced up-regulation of p53 .
Meanwhile , BDMC counteracts oxidative stress by inhibiting cisplatin-induced down-regulation of nuclear factor erythroid-2-related factor 2 ( Nrf2 ) .
BDMC also significantly reduced the expression of intercellular adhesion molecule-1 ( ICAM-1 ) and monocyte chemoattractant protein-1 ( MCP-1 ) proteins , as well as the expression and translocation of the p65 subunit of nuclear factor-κB ( @ @ @ @ @ @ @ all of which were increased in the kidney by cisplatin treatment .
Collectively , BDMC might be an effective prevention strategy which could against cisplatin-induced nephrotoxicity , and our research may shed a new light ontreatment of drug toxicity .

Cisplatin is a widely used chemotherapy drug that is first-line therapy for a variety of tumors. Unfortunately, its adverse effects on various normal tissues and organs, especially nephrotoxicity, threaten the life of patients. Although the mechanism of cisplatin nephrotoxicity has been confirmed to be related to oxidative stress, apoptosis of renal tubular epithelial cells and inflammatory response, there is no effective prevention strategy in the clinic. Here, we found that bisdemethoxycurcumin (BDMC), a natural compound, can significantly attenuates cisplatin-induced apoptosis of renal tubular epithelial cells in vitro at the concentration of 5-20 μM and has a significant protective effect on cisplatin-induced kidney injury in mice at the dose of 50 mg/kg. Mechanistically, BDMC attenuates cisplatin-induced apoptosis of renal tubular epithelial cells by inhibiting cisplatin-induced up-regulation of p53. Meanwhile, BDMC counteracts oxidative stress by inhibiting cisplatin-induced down-regulation of nuclear factor erythroid-2-related factor 2 (Nrf2). BDMC also significantly reduced the expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) proteins, as well as the expression and translocation of the p65 subunit of nuclear factor-κB (NF-κB p65) into the nucleus, all of which were increased in the kidney by cisplatin treatment. Collectively, BDMC might be an effective prevention strategy which could against cisplatin-induced nephrotoxicity, and our research may shed a new light ontreatment of drug toxicity.


greenmedinfo--2020-03-19--The combination of curcuminoids could be used as a novel target for the treatment of osteosarcoma.

BACKGROUND : Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and has also been associated with a high degree of malignancy and enhanced metastatic capacity .
Curcumin ( CUR ) is well known for its anti-osteosarcoma activity .
However , both demethoxycurcumin ( DMC ) , and bisdemethoxycurcumin ( BDMC ) are natural curcumin analogues/congeners from turmeric whose role in osteosarcoma development remains unknown .
METHODS : To evaluate the growth inhibitory effects of CUR , DMC and BDMC on osteosarcoma ( HOS and U2OS ) , breast ( MDA-MB-231 ) , and melanoma ( @ @ @ @ @ @ @ the MTT assay , annexin V-FITC /7-AAD staining , and clonogenic assay .
RESULTS : CUR , DMC , and BDMC all decreased the viability of HOS , U2OS , MDA-MB-231 , and A2058 cancer cells .
Additionally , CUR , DMC , and BDMC induced the apoptosis of HOS cells through activation of Smad 2/3 or repression of Akt signaling pathway .
Furthermore , the combination of CUR , DMC , and BDMC synergistically reduced cell viability , colony formation and increased apoptosis than either two or a single agent in HOS @ @ @ @ @ @ @ these three compounds could be used as a novel target for the treatment of osteosarcoma .

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and has also been associated with a high degree of malignancy and enhanced metastatic capacity. Curcumin (CUR) is well known for its anti-osteosarcoma activity. However, both demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are natural curcumin analogues/congeners from turmeric whose role in osteosarcoma development remains unknown.
METHODS: To evaluate the growth inhibitory effects of CUR, DMC and BDMC on osteosarcoma (HOS and U2OS), breast (MDA-MB-231), and melanoma (A2058) cancer cells, we employed the MTT assay, annexin V-FITC /7-AAD staining, and clonogenic assay.
RESULTS: CUR,DMC, and BDMC all decreased the viability of HOS, U2OS, MDA-MB-231, and A2058 cancer cells. Additionally, CUR,DMC, and BDMC induced the apoptosis of HOS cells through activation of Smad 2/3 or repression of Akt signaling pathway. Furthermore, the combination of CUR,DMC, and BDMC synergistically reduced cell viability, colony formation and increased apoptosis than either two or a single agent in HOS cells.
CONCLUSIONS: The combination of these three compounds could be used as a novel target for the treatment of osteosarcoma.


greenmedinfo--2020-03-19--Bisdemethoxycurcumin inhibits hepatocellular carcinoma proliferation.

Background : Bisdemethoxycurcumin ( BDMC ) , a stable bioactive ingredient in curcuminoids , is associated with various antitumor functions , such as proliferation inhibition , metastasis suppression and apoptosis induction , in many cancer types .
However , the mechanism of BDMC in hepatocellular carcinoma ( HCC ) remains unclear .
Methods : We assessed the toxicity and the inhibitory effect of BDMC in the HepG2 cell line by using CCK-8 and colony formation assays .
The regulatory effects of BDMC on Akt and MAPK signaling were investigated by Western blotting and immunoprecipitation .
Results : We found that @ @ @ @ @ @ @ of BDMC after 48 hrs of treatment was 59.13 μM , and BDMC inhibited proliferation in a time- and dose-dependent manner in HepG2 cells .
The inhibitory effect was caused by the inactivation of Akt signaling , but not Erk , Jnk or p38 signaling .
In addition , the inactivation of Akt signaling was attributed to the inhibition of ubiquitination mediated by K63-Ub but not K48-Ub .
Furthermore , we found that BDMC upregulated the expression of CYLD , leading to Akt deubiquitination and inactivation .
Conclusion : BDMC inhibited HCC cell @ @ @ @ @ @ @ induced by Akt inactivation via CYLD-mediated deubiquitination .

Background: Bisdemethoxycurcumin (BDMC), a stable bioactive ingredient in curcuminoids, is associated with various antitumor functions, such as proliferation inhibition, metastasis suppression and apoptosis induction, in many cancer types. However, the mechanism of BDMC in hepatocellular carcinoma (HCC) remains unclear.
Methods: We assessed the toxicity and the inhibitory effect of BDMC in the HepG2 cell line by using CCK-8 and colony formation assays. The regulatory effects of BDMC on Akt and MAPK signaling were investigated by Western blotting and immunoprecipitation.
Results: We found that the half-maximum inhibitory concentration (IC50) of BDMC after 48 hrs of treatment was 59.13 μM, and BDMC inhibited proliferation in a time- and dose-dependent manner in HepG2 cells. The inhibitory effect was caused by the inactivation of Akt signaling, but not Erk, Jnk or p38 signaling. In addition, the inactivation of Akt signaling was attributed to the inhibition of ubiquitination mediated by K63-Ub but not K48-Ub. Furthermore, we found that BDMC upregulated the expression of CYLD, leading to Akt deubiquitination and inactivation.
Conclusion: BDMC inhibited HCC cell proliferation, and that this effect was induced by Akt inactivation via CYLD-mediated deubiquitination.


greenmedinfo--2020-03-19--Curcumin as an anticancer agent in malignant mesothelioma.

Malignant mesothelioma is an infrequent tumor that initiates from the mesothelial cells lining of body cavities .
The great majority @ @ @ @ @ pleural cavity , while the remaining cases initiate in the peritoneal cavity , in the @ @ @ @ @ tunica vaginalis .
Usually , mesotheliomas grow in a diffuse pattern and tend to enclose @ @ @ @ @ the various body cavities .
Mesothelioma incidence is increasing worldwide and still today , the @ @ @ @ @ with a reported median survival of approximately one year from presentation .
Thus , the @ @ @ @ @ effective therapies is currently an urgent requirement .
The aim of this review article was @ @ @ @ @ the anti-cancer activity of curcumin and some of its derivatives on mesotheliomas .
The potential @ @ @ @ @ are discussed .

Malignant mesothelioma is an infrequent tumor that initiates from the mesothelial cells lining of body cavities. The great majority of mesotheliomas originate in the pleural cavity, while the remaining cases initiate in the peritoneal cavity, in the pericardial cavity or on the tunica vaginalis. Usually, mesotheliomas grow in a diffuse pattern and tend to enclose and compress the organs in the various body cavities. Mesothelioma incidence is increasing worldwide and still today, the prognosis is very poor, with a reported median survival of approximately one year from presentation. Thus, the development of alternative and more effective therapies is currently an urgent requirement. The aim of this review article was to describe recent findings about the anti-cancer activity of curcumin and some of its derivatives on mesotheliomas. The potential clinical implications of these findings are discussed.


greenmedinfo--2020-03-19--Thymoquinone suppresses invasion and metastasis in bladder cancer cells.

Epithelial mesenchymal transformation plays a crucial role in the metastasis of bladder cancer , which makes bladder cancer difficult to cure .
Bladder cancer is the most common malignancy of the urinary system , and distant metastasis is the leading cause of death .
Therefore , finding a bioactive drug that can specifically inhibit epithelial mesenchymal transformation may be a new direction for bladder cancer treatment in the future .
Thymoquinone ( TQ ) , the major active compound isolated from black seed oil ( Nigella sativa ) , has been reported to exhibit anti-inflammatory and anticancer abilities .
TQ @ @ @ @ @ @ @ the proliferation and metastasis of cancer cells .
However , the underlying mechanism of TQ as a tumor inhibitor in bladder cancer remains poorly understood .
First , in this research , we demonstrate that TQ can reverse EMT by upregulating epithelial markers , such as E-cadherin , and downregulating mesenchymal markers , such as N-cadherin and vimentin .
Furthermore , we demonstrate that TQ can suppress the activation of the Wnt/β-catenin signaling pathway and inhibit the expression of β-catenin target genes , such as MYC , Axin-2 , MMP7 , CyclinD1 and @ @ @ @ @ @ @ EMT and cancer progression .
Additionally , we demonstrate that TQ can inhibit the growth of xenografts and restrict the formation of tumor metastatic foci in the lung .
Taken together , our findings confirm the antimetastatic effect of TQ in bladder cancer cells for the first time and also provide new evidence for the development of TQ as a novel treatment for metastatic bladder cancer .

Epithelial mesenchymal transformation plays a crucial role in the metastasis of bladder cancer, which makes bladder cancer difficult to cure. Bladder cancer is the most common malignancy of the urinary system, and distant metastasis is the leading cause of death. Therefore, finding a bioactive drug that can specifically inhibit epithelial mesenchymal transformation may be a new direction for bladder cancer treatment in the future. Thymoquinone (TQ), the major active compound isolated from black seed oil (Nigella sativa), has been reported to exhibit anti-inflammatory and anticancer abilities. TQ can exhibit its antitumor effect by inhibiting the proliferation and metastasis of cancer cells. However, the underlying mechanism of TQ as a tumor inhibitor in bladder cancer remains poorly understood. First, in this research, we demonstrate that TQ can reverse EMT by upregulating epithelial markers, such as E-cadherin, and downregulating mesenchymal markers, such as N-cadherin and vimentin. Furthermore, we demonstrate that TQ can suppress the activation of the Wnt/β-catenin signaling pathway and inhibit the expression of β-catenin target genes, such as MYC, Axin-2, MMP7, CyclinD1 and MET, which play crucial roles in EMT and cancer progression. Additionally, we demonstrate that TQ can inhibit the growth of xenografts and restrict the formation of tumor metastatic foci in the lung. Taken together, our findings confirm the antimetastatic effect of TQ in bladder cancer cells for the first time and also provide new evidence for the development of TQ as a novel treatment for metastatic bladder cancer.


greenmedinfo--2020-03-19--Effects of thymoquinone in prevention of experimental contrast-induced nephropathy.

Objectives : This study aimed to show the effects of thymoquinone , which is known for its antioxidant , anti-inflammatory , and renal protective effects in contrast-induced nephropathy .
Materials and Methods : This is an experimental study in rats .
7 groups were included within the scope of our study : sham-vehicle ( n=3 ) , premedication-control ( n=6 ) , model ( n=6 ) , isolated thymoquinone ( n=3+3 ) , low-dose thymoquinone ( n=6 ) , and high-dose thymoquinone ( n=7 ) .
In addition to 48 hr of water deprivation , we pre-medicated the rats with @ @ @ @ @ @ @ premedication , 12.5 ml/kg dose of a high osmolar contrast agent-diatrizoat ( Urografin % 76 ) was administrated .
Thymoquinone was administrated in two different doses of 1 mg/kg and 1.75 mg/kg for four days intraperitoneally .
Renal functions , histopathological differences , oxidative stress parameters , and inflammatory indicators of rats were evaluated at the end of the study .
Results : Significant decreases were observed in levels of serum creatinine and serum BUN with low-dose thymoquinone ( 1 mg/kg ) administration .
In light microscopy , significantly less histopathological damage was @ @ @ @ @ @ @ to the contrast agent group .
While high-dose thymoquinone is accepted as ineffective biochemically , toxic evidence was identified histopathologically .
There were no significant differences between M and TA groups for serum MDA and SOD levels , which were compared to evaluate oxidative stress ( 0.99,0.98 ; respectively ) .
TNF-α , iNOS , and NF-кB gene expressions were not significantly different between all groups ( 0.748,0.531,0.910 ; respectively ) .
Conclusion : This experimental study has demonstrated for the first time the protective effect of the TQ substance for CIN in @ @ @ @ @ @ @ of biochemical and histopathological data in rats .

Objectives: This study aimed to show the effects of thymoquinone, which is known for its antioxidant, anti-inflammatory, and renal protective effects in contrast-induced nephropathy.
Materials and Methods: This is an experimental study in rats. 7 groups were included within the scope of our study: sham-vehicle (n=3), premedication-control (n=6), model (n=6), isolated thymoquinone (n=3+3), low-dose thymoquinone (n=6), and high-dose thymoquinone (n=7). In addition to 48 hr of water deprivation, we pre-medicated the rats with intra-peritoneal indomethacin and L-NAME administration. After premedication, 12.5 ml/kg dose of a high osmolar contrast agent-diatrizoat (Urografin %76) was administrated. Thymoquinone was administrated in two different doses of 1 mg/kg and 1.75 mg/kg for four days intraperitoneally. Renal functions, histopathological differences, oxidative stress parameters, and inflammatory indicators of rats were evaluated at the end of the study.
Results: Significant decreases were observed in levels of serum creatinine and serum BUN with low-dose thymoquinone (1 mg/kg) administration. In light microscopy, significantly less histopathological damage was observed in the low-dose thymoquinone group compared to the contrast agent group. While high-dose thymoquinone is accepted as ineffective biochemically, toxic evidence was identified histopathologically. There were no significant differences between M and TA groups for serum MDA and SOD levels, which were compared to evaluate oxidative stress (0.99,0.98; respectively). TNF-α, iNOS, and NF-кB gene expressions were not significantly different between all groups (0.748,0.531,0.910; respectively).
Conclusion: This experimental study has demonstrated for the first time the protective effect of the TQ substance for CIN in 1 mg/kg dose, in the accompaniment of biochemical and histopathological data in rats.


greenmedinfo--2020-03-20--Lactoferricin B reverses cisplatin resistance in head and neck squamous cell carcinoma cells.

Head and neck squamous cell carcinoma ( HNSCC ) ranks among the top most common cancers with a poor prognosis @ @ @ @ @ is still not well known .
This study is to investigate the programmed death-ligand 1 @ @ @ @ @ HNSCC , and test the effect of lactoferricin B ( LfcinB ) on chemoresistance and @ @ @ @ @ 510 HNSCC patients in TCGA database and investigated how CD274 expression was related to patient @ @ @ @ @ from HNSCC samples at local hospital with immunohistochemistry .
PD-L1 expression in the acquired cisplatin-resistant @ @ @ @ @ PCR and WB in order to test PD-L1-induced chemoresistance .
LfcinB inoculation in cisplatin-resistant HNSCC @ @ @ @ @ mice was introduced to test the effect of LfcinB on targeting cisplatin resistance and its @ @ @ @ @ ( > 125 FPKM ) from TCGA database had a significantly reduced 5-year survival rate @ @ @ @ @ survival rate in the chemotherapy and radiotherapy-treated patients ( P

Head and neck squamous cell carcinoma (HNSCC) ranks among the top most common cancers with a poor prognosis. The mechanism of chemoresistance is still not well known. This study is to investigate the programmed death-ligand 1 (PD-L1) expression in HNSCC, and test the effect of lactoferricin B (LfcinB) on chemoresistance and its mechanism. We analyzed 510 HNSCC patients in TCGA database and investigated how CD274 expression was related to patient prognosis. PD-L1 was verified from HNSCC samples at local hospital with immunohistochemistry. PD-L1 expression in the acquired cisplatin-resistant HNSCC cells was examined by PCR and WB in order to test PD-L1-induced chemoresistance. LfcinB inoculation in cisplatin-resistant HNSCC cells and in the nude mice was introduced to test the effect of LfcinB on targeting cisplatin resistance and its mechanism. High CD274 mRNA (>125 FPKM) from TCGA database had a significantly reduced 5-year survival rate, and a lower 5-year survival rate in the chemotherapy and radiotherapy-treated patients (P < .05). PD-L1 overexpression was further supported from analysis of 40 HNSCC specimens. PD-L1 and IL-6 in the established cisplatin-resistant HNSCC cells were shown significantly higher (P < .05). IL-6 and PD-L1 expression were partially inhibited by the anti-IL-6/STAT3 antibody. LfcinB displayed a direct cytotoxic effect on cisplatin-resistant HNSCC cells and HNSCC xenografts of cisplatin-resistant cells in the nude mice displayed significant reduction in tumor volume after LfcinB injection (P < .05). Besides, the increase of IL-6 and PD-L1 in cisplatin-resistant HNSCC cells was abolished in vitro by LfcinB (P < .05). PD-L1 expression in HNSCC cells correlates with poor prognosis and chemoresistance, and LfcinB might provide therapeutic potential in HNSCC patients through modulating IL-6 and PD-L1.


greenmedinfo--2020-03-20--Antimicrobial activity of immobilized lactoferrin and lactoferricin.

This website is for information purposes only .
By providing the information contained herein we are not diagnosing , treating @ @ @ @ @ or preventing any type of disease or medical condition .
Before beginning any type of @ @ @ @ @ treatment regimen , it is advisable to seek the advice of a licensed healthcare professional @

Lactoferrin and lactoferricin were immobilized on glass surfaces via two linkers, 4-azidobenzoic acid (ABA) or 4-fluoro-3-nitrophenyl azide (FNA). The resulting surfaces were characterized by X-ray photoelectron spectroscopy (XPS) and contact angle measurements. The antimicrobial activity of the surfaces was determined using Pseudomonas aeruginosa and Staphylococcus aureus strains by fluorescence microscopy. Lactoferrin and lactoferricin immobilization was confirmed by XPS showing significant increases (p < 0.05) in nitrogen on the glass surface. The immobilization of both proteins slightly increased the overall hydrophobicity of the glass. Both lactoferrin and lactoferricin immobilized on glass significantly (p < 0.05) reduced the numbers of viable bacterial cells adherent to the glass. For P. aeruginosa, the immobilized proteins consistently increased the percentage of dead cells compared to the total cells adherent to the glass surfaces (p < 0.03). Lactoferrin and lactoferricin were successfully immobilized on glass surfaces and showed promising antimicrobial activity against pathogenic bacteria. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2612-2617, 2017.


greenmedinfo--2020-03-20--A systematic review of lactoferrin use in dermatology.

Lactoferrin is a glycoprotein widely present in mammalian secretions and possesses documented protective effects , including antimicrobial and anti-inflammatory properties @ @ @ @ @ is being investigated for a myriad of diseases , there is increasing interest in its @ @ @ @ @ Our objective was to systematically review the clinical evidence for the use and efficacy of @ @ @ @ @ dermatological conditions .
Pubmed and Embase databases were searched for clinical studies evaluating lactoferrin for @ @ @ @ @ of six studies were reviewed .
Of the current clinical trials , there is encouraging @ @ @ @ @ may be beneficial in acne , psoriasis , and diabetic ulcerations .
Although the current @ @ @ @ @ research is necessary to establish lactoferrin as complementary therapy in the clinical setting .

Lactoferrin is a glycoprotein widely present in mammalian secretions and possesses documented protective effects, including antimicrobial and anti-inflammatory properties. While its therapeutic use is being investigated for a myriad of diseases, there is increasing interest in its application for skin disease. Our objective was to systematically review the clinical evidence for the use and efficacy of lactoferrin for the treatment of dermatological conditions. Pubmed and Embase databases were searched for clinical studies evaluating lactoferrin for dermatological conditions. A total of six studies were reviewed. Of the current clinical trials, there is encouraging evidence to suggest that lactoferrin may be beneficial in acne, psoriasis, and diabetic ulcerations. Although the current evidence is promising, further research is necessary to establish lactoferrin as complementary therapy in the clinical setting.


greenmedinfo--2020-03-20--Acupressure can reduce soldiers' anxiety at the acupressure points, especially at the LI4 point.

INTRODUCTION : Military service is a stressful environment .
Methods to reduce stress may result in the mental health promotion of military forces .
There are various methods for relieving anxiety .
Acupressure is one of them .
Hence , this study was carried out to explore effects of acupressure at the P6 and LI4 acupressure points on the anxiety level of army soldiers .
METHODS : A randomised double-blind design was undertaken .
A total of 120 Iranian army soldiers were randomly assigned to three groups , namely P6 , LI4 and control .
The P6 and LI4 acupressure @ @ @ @ @ @ @ level .
In the intervention groups , acupressure was applied at the P6 and LI4 points three times for 10 min at 30 min intervals .
In the control group , the thumb pad , which is not an acupressure point , was pressed .
The anxiety level of the subjects was measured before the intervention and 30 min after the last intervention .
The instruments included a demographics questionnaire and the State-Trait Anxiety Inventory .
RESULTS : There was no significant difference between the three groups with respect to the anxiety level @ @ @ @ @ @ @ the mean anxiety score in the P6 group decreased significantly from 53.35±9.7 to 49.02±9.3 ( p=0.005 ) .
The mean anxiety score in the LI4 group also decreased significantly from 53.37±8.39 to 45.47±8.16 ( p < 0.001 ) .
In the control group , there was no significant difference between the preintervention and postintervention phases ( p=0.16 ) .
In the postintervention phase , the analysis of variance test showed a significant difference between the three groups in terms of the anxiety level ( p=0.04 ) .
CONCLUSIONS : Acupressure can reduce soldiers @ @ @ @ @ @ @ especially at the LI4 point .
It is recommended that this simple and cost-effective intervention be used to relieve soldiers ' anxiety in stressful situations .

INTRODUCTION: Military service is a stressful environment. Methods to reduce stress may result in the mental health promotion of military forces. There are various methods for relieving anxiety. Acupressure is one of them. Hence, this study was carried out to explore effects of acupressure at the P6 and LI4 acupressure points on the anxiety level of army soldiers.
METHODS: A randomised double-blind design was undertaken. A total of 120 Iranian army soldiers were randomly assigned to three groups, namely P6, LI4 and control. The P6 and LI4 acupressure points are effective in lowering the anxiety level. In the intervention groups, acupressure was applied at the P6 and LI4 points three times for 10 min at 30 min intervals. In the control group, the thumb pad, which is not an acupressure point, was pressed. The anxiety level of the subjects was measured before the intervention and 30 min after the last intervention. The instruments included a demographics questionnaire and the State-Trait Anxiety Inventory.
RESULTS: There was no significant difference between the three groups with respect to the anxiety level in the preintervention phase. However, the mean anxiety score in the P6 group decreased significantly from 53.35±9.7 to 49.02±9.3 (p=0.005). The mean anxiety score in the LI4 group also decreased significantly from 53.37±8.39 to 45.47±8.16 (p<0.001). In the control group, there was no significant difference between the preintervention and postintervention phases (p=0.16). In the postintervention phase, the analysis of variance test showed a significant difference between the three groups in terms of the anxiety level (p=0.04).
CONCLUSIONS: Acupressure can reduce soldiers' anxiety at the acupressure points, especially at the LI4 point. It is recommended that this simple and cost-effective intervention be used to relieve soldiers' anxiety in stressful situations.
TRIAL REGISTRATION NUMBER: 20150715023216N4.


greenmedinfo--2020-03-20--The beneficial effect of acupressure on the severity of nausea, vomiting, and retching in pregnant w

The beneficial effect of acupressure on the severity of nausea, vomiting, and retching in pregnant women.

INTRODUCTION : Nausea and vomiting are common problems during pregnancy .
Previous studies have shown that stimulation at Neiguan ( PC6 ) acupoint can be effective in controlling pregnancy-induced nausea and vomiting .
However , more evidence is required for approving this method on controlling pregnancy-induced nausea and vomiting .
The aim of this study was to determine the efficacy of PC6 acupoint pressure stimulation on the severity of nausea , vomiting , and retching in pregnant women .
METHOD : This randomized , multi-center clinical trial was conducted on pregnant women referring to Health Centers and Ommolbanin Hospital in @ @ @ @ @ @ @ to September 2017 .
Women with first singleton pregnancy and below 12 weeks were included .
Patients were randomly allocated into three groups of ( 1 ) PC6 pressure ( 4 times a day , for 10 min ) , ( 2 ) sham acupressure , and ( 3 ) medication with vitamin B6 and metoclopramide .
Assessment of severity of nausea , vomiting , and retching was done based on the Rhodes Index on the first and fifth day ( before and after the intervention ) .
Pearson chi-square test , one-way @ @ @ @ @ @ @ were used for statistical analysis using SPSS version 18 .
This clinical trial was registered at the Iranian Registry of Clinical Trials ( IRCT ) with the code IRCT201512187265N6 .
RESULTS : Ninety patients with a mean age of 26.40± 4.73 years were studied in 3 groups of 30 .
There was no significant difference between the 3 groups in terms of the severity outcomes before the intervention , while , after the intervention , the three groups were significantly different on the fifth day in terms of vomiting frequency , distress from @ @ @ @ @ @ @ of nausea , distress from nausea , amount of vomiting , frequency of nausea , and frequency of retching ( p < 0.001 for each outcome ) .
According to the linear regression analysis , the correlation between occupation with vomiting frequency ( beta coefficient = 0.252 ) and nausea severity ( beta coefficient = -0.213 ) was statistically significant .
CONCLUSION : It seems that PC6 acupoint pressure can reduce the severity of nausea , vomiting , and retching in pregnant women .

INTRODUCTION: Nausea and vomiting are common problems during pregnancy. Previous studies have shown that stimulation at Neiguan (PC6) acupoint can be effective in controlling pregnancy-induced nausea and vomiting. However, more evidence is required for approving this method on controlling pregnancy-induced nausea and vomiting. The aim of this study was to determine the efficacy of PC6 acupoint pressure stimulation on the severity of nausea, vomiting, and retching in pregnant women.
METHOD: This randomized, multi-center clinical trial was conducted on pregnant women referring to Health Centers and Ommolbanin Hospital in Mashhad, Iran, during December 2016 to September 2017. Women with first singleton pregnancy and below 12 weeks were included. Patients were randomly allocated into three groups of (1) PC6 pressure (4 times a day, for 10 min), (2) sham acupressure, and (3) medication with vitamin B6 and metoclopramide. Assessment of severity of nausea, vomiting, and retching was done based on the Rhodes Index on the first and fifth day (before and after the intervention). Pearson chi-square test, one-way ANOVA, Kruskal-Wallis, and Wilcoxon tests were used for statistical analysis using SPSS version 18. This clinical trial was registered at the Iranian Registry of Clinical Trials (IRCT) with the code IRCT201512187265N6.
RESULTS: Ninety patients with a mean age of 26.40± 4.73 years were studied in 3 groups of 30. There was no significant difference between the 3 groups in terms of the severity outcomes before the intervention, while, after the intervention, the three groups were significantly different on the fifth day in terms of vomiting frequency, distress from retching, distress from vomiting, duration of nausea, distress from nausea, amount of vomiting, frequency of nausea, and frequency of retching (p<0.001 for each outcome). According to the linear regression analysis, the correlation between occupation with vomiting frequency (beta coefficient = 0.252) and nausea severity (beta coefficient = -0.213) was statistically significant.
CONCLUSION: It seems that PC6 acupoint pressure can reduce the severity of nausea, vomiting, and retching in pregnant women.


greenmedinfo--2020-03-20--Scalp acupuncture therapy may exhibit effects in the recovery of motor and nervous functions in pati

Scalp acupuncture therapy may exhibit effects in the recovery of motor and nervous functions in patients with acute to chronic stroke.

OBJECTIVE : To conduct a systematic review to assess the clinical effectiveness of scalp acupuncture ( SA ) for stroke .
METHODS : Literature searches were performed in 7 databases up to 16 August 2014 , and all the randomized controlled trials ( RCTs ) in which SA therapy was administered to stroke patients were selected .
Methodological quality was assessed using the Jadad score , the Cochrane risk of bias assessment , and the Standards for Reporting Interventions in Clinical Trials of Acupuncture .
RESULTS : Of a total of 2086 papers , 21 RCTs were selected .
Meta-analysis @ @ @ @ @ @ @ rates of the SA group and the body acupuncture ( BA ) group vs the medication group ( P < 0.002 , P < 0.000 001 , respectively ) , the SA plus BA group vs the BA group ( P < 0.001 ) ; in the motor function of the SA plus BA group vs the BA group ( P = 0.077 ) ; and in the nerve function of the SA group vs the SA plus BA group ( P < 0.0001 ) .
CONCLUSION : The results of our systematic @ @ @ @ @ @ @ effects in treatment efficacy and in the recovery of motor and nervous functions in patients with acute to chronic stroke .
However , because of the lack of methodological quality , the thoroughly planned clinical studies are still required .

OBJECTIVE: To conduct a systematic review to assess the clinical effectiveness of scalp acupuncture (SA) for stroke.
METHODS: Literature searches were performed in 7 databases up to 16 August 2014, and all the randomized controlled trials (RCTs) in which SA therapy was administered to stroke patients were selected. Methodological quality was assessed using the Jadad score, the Cochrane risk of bias assessment, and the Standards for Reporting Interventions in Clinical Trials of Acupuncture.
RESULTS: Of a total of 2086 papers, 21 RCTs were selected. Meta-analysis revealed significant differences in the total efficacy rates of the SA group and the body acupuncture (BA) group vs the medication group (P<0.002, P<0.000 001, respectively), the SA plus BA group vs the BA group (P<0.001); in the motor function of the SA plus BA group vs the BA group (P = 0.077); and in the nerve function of the SA group vs the SA plus BA group (P<0.0001).
CONCLUSION: The results of our systematic review showed that SA therapy may exhibit effects in treatment efficacy and in the recovery of motor and nervous functions in patients with acute to chronic stroke. However, because of the lack of methodological quality, the thoroughly planned clinical studies are still required.


greenmedinfo--2020-03-20--Acupoint combinations used for treatment of Alzheimer's disease: A data mining analysis.

OBJECTIVE : To identify the acupoint combinations used in the treatment of Alzheimer 's disease ( AD ) .
METHODS : The clinical literature regarding acupuncture and moxibustion for AD was searched and collected from databases including Chinese Biomedical Medicine , China National Knowledge Infrastructure , Wanfang Database and PubMed .
The database of acupuncture and moxibustion prescriptions for AD was established by using Excel software so as to conduct the descriptive analysis , association analysis on the data .
RESULTS : Baihui ( GV 20 ) , Sishencong ( EX-HN 1 ) , Shenmen ( HT 7 ) , @ @ @ @ @ @ @ ( PC 6 ) , Fengchi ( GB 20 ) , Taixi ( KI 3 ) , Dazhui ( GV 14 ) , Shenshu ( BL 23 ) , Sanyinjiao ( SP 6 ) , Shenting ( GV 24 ) , Fenglong ( ST 40 ) , Xuanzhong ( GB 39 ) , Shuigou ( GV 26 ) and Taichong ( LR 3 ) were of higher frequency in the treatment of AD with acupnucture and moxibustion .
Most acupoints were selected from the Governor Vessel .
The commonly used acupoints were located @ @ @ @ @ @ @ and lower limbs .
The combination of the local acupoints with the distal ones was predominated .
The crossing points among the specific points presented the advantage in the treatment .
The association analysis indicated that the correlation among Fengchi ( GB 20 ) -Baihui ( GV 20 ) was the strongest , followed by combinations of Dazhui ( GV 14 ) -Baihui ( GV 20 ) , Shenshu ( BL 23 ) - Baihui ( GV 20 ) and Neiguan ( PC 6 ) - Baihui ( GV 20 ) and indicated @ @ @ @ @ @ @ selection and combination for AD .
CONCLUSION : Our findings provide a reference for acupoints selection and combination for AD in clinical acupuncture practice .

OBJECTIVE: To identify the acupoint combinations used in the treatment of Alzheimer's disease (AD).
METHODS: The clinical literature regarding acupuncture and moxibustion for AD was searched and collected from databases including Chinese Biomedical Medicine, China National Knowledge Infrastructure, Wanfang Database and PubMed. The database of acupuncture and moxibustion prescriptions for AD was established by using Excel software so as to conduct the descriptive analysis, association analysis on the data.
RESULTS: Baihui (GV 20), Sishencong (EX-HN 1), Shenmen (HT 7), Zusanli (ST 36), Neiguan (PC 6), Fengchi (GB 20), Taixi (KI 3), Dazhui (GV 14), Shenshu (BL 23), Sanyinjiao (SP 6), Shenting (GV 24), Fenglong (ST 40), Xuanzhong (GB 39), Shuigou (GV 26) and Taichong (LR 3) were of higher frequency in the treatment of AD with acupnucture and moxibustion. Most acupoints were selected from the Governor Vessel. The commonly used acupoints were located on the head, face, neck and lower limbs. The combination of the local acupoints with the distal ones was predominated. The crossing points among the specific points presented the advantage in the treatment. The association analysis indicated that the correlation among Fengchi (GB 20)-Baihui (GV 20) was the strongest, followed by combinations of Dazhui (GV 14)-Baihui (GV 20), Shenshu (BL 23)- Baihui (GV 20) and Neiguan (PC 6)- Baihui (GV 20) and indicated the common rules of the clinical acupoint selection and combination for AD.
CONCLUSION: Our findings provide a reference for acupoints selection and combination for AD in clinical acupuncture practice.


greenmedinfo--2020-03-20--Dynamic brain activity following auricular point acupressure in chemotherapy-induced neuropathy.

Background : The objective of this study was to investigate the dynamic brain activity following auricular point acupressure ( APA ) in chemotherapy-induced neuropathy ( CIN ) .
Methods : Participants received 4 weeks of APA in an open-pilot trial with repeated observation .
Along with the clinical self-reported CIN outcomes , objective outcomes were measured over the course of the treatment by physiological changes in pain sensory thresholds from quantitative sensory testing ( QST ) and repeated functional magnetic resonance imaging scans .
Results : After 4 weeks of APA , participants had reported clinically significant improvements ( ie @ @ @ @ @ @ @ of CIN symptoms ( including pain , numbness , tingling , and stiffness ) in lower extremity stiffness ( 32 % ) , reduced foot sensitivity ( 13 % ) , and higher pain threshold ( 13 % ) .
Across the 11 intrinsic brain networks examined , there was a trend toward significance of the connectivity of the basal ganglia network ( BGN ) to the salience network ( SAL ) , which was decreased pre-APA versus immediate-APA ( effect size [ ES ] = 1.04 , = .07 ) .
The @ @ @ @ @ @ @ language network pre-APA versus delayed imaging post-APA ( ES = -0.92 , = .07 ) .
Furthermore , there was increased executive control network ( ECN ) and SAL within-network connectivity comparing pre-APA to delayed imaging post-APA , trending toward significance ( ES = 0.41 , = .09 and ES = 0.17 , = .09 , respectively ) .
Conclusion : The changes in connectivity and activity within or between the ECN , SAL , and BGN from pre- to post-APA suggest ongoing alterations in brain functional connectivity following APA , particularly in @ @ @ @ @ @ @ dorsolateral prefrontal cortices , which play significant roles in pain , memory , and cognitive function .

Background: The objective of this study was to investigate the dynamic brain activity following auricular point acupressure (APA) in chemotherapy-induced neuropathy (CIN).
Methods: Participants received 4 weeks of APA in an open-pilot trial with repeated observation. Along with the clinical self-reported CIN outcomes, objective outcomes were measured over the course of the treatment by physiological changes in pain sensory thresholds from quantitative sensory testing (QST) and repeated functional magnetic resonance imaging scans.
Results: After 4 weeks of APA, participants had reported clinically significant improvements (ie,≥30%) in a reduction of CIN symptoms (including pain, numbness, tingling, and stiffness) in lower extremity stiffness (32%), reduced foot sensitivity (13%), and higher pain threshold (13%). Across the 11 intrinsic brain networks examined, there was a trend toward significance of the connectivity of the basal ganglia network (BGN) to the salience network (SAL), which was decreased pre-APA versus immediate-APA (effect size [ES] = 1.04, = .07). The BGN also demonstrated decreased connectivity with the language network pre-APA versus delayed imaging post-APA (ES = -0.92, = .07). Furthermore, there was increased executive control network (ECN) and SAL within-network connectivity comparing pre-APA to delayed imaging post-APA, trending toward significance (ES = 0.41, = .09 and ES = 0.17, = .09, respectively).
Conclusion: The changes in connectivity and activity within or between the ECN, SAL, and BGN from pre- to post-APA suggest ongoing alterations in brain functional connectivity following APA, particularly in the insula, anterior cingulate, and dorsolateral prefrontal cortices, which play significant roles in pain, memory, and cognitive function.


greenmedinfo--2020-03-20--Active acupuncture can significantly improve insomnia.

The purpose of this study was to observe and compare the clinical efficacy of active acupuncture and placebo acupuncture in @ @ @ @ @ mood disorders .
96 patients with insomnia in Chengdu were randomly divided into two groups @ @ @ @ @ active acupuncture group ( AA group n = 48 ) received the tube of Park @ @ @ @ @ insertion .
The placebo acupuncture group ( PA group n = 48 ) received the @ @ @ @ @ with a retractable needle shaft and a blunt tip .
The same acupuncture points and @ @ @ @ @ both groups .
The overall scorefor the Pittsburgh Sleep Quality Index ( PSQI ) is @ @ @ @ @ outcomes recorded sleep rate , self-reported depression scale ( SDS ) , self-assessment anxiety scale @ @ @ @ @ 'six component ' scores of PSQI , andscale scores .
Eventually , 90 patients completed @ @ @ @ @ weeks of treatment , the total score of PSQI in the AA group was 4.6 @ @ @ @ @ PA group was 12.9 ± 1.8 ( = 3.91 ,

The purpose of this study was to observe and compare the clinical efficacy of active acupuncture and placebo acupuncture in the treatment of insomnia and mood disorders. 96 patients with insomnia in Chengdu were randomly divided into two groups (1:1). The active acupuncture group (AA group n = 48) received the tube of Park sham device with deep needle insertion. The placebo acupuncture group (PA group n = 48) received the tube of Park sham device with a retractable needle shaft and a blunt tip. The same acupuncture points and treatment cycles were used in both groups. The overall scorefor the Pittsburgh Sleep Quality Index (PSQI) is the primary outcome. Secondary outcomes recorded sleep rate, self-reported depression scale (SDS), self-assessment anxiety scale (SAS), the 'six component' scores of PSQI, andscale scores. Eventually, 90 patients completed the study. After 2 weeks of treatment, the total score of PSQI in the AA group was 4.6 ± 2.4 and in the PA group was 12.9 ± 1.8 ( = 3.91,<.1). The SAS, SDS score in the AA group were 39.9 ± 5.6/39.9 ± 5.9 and in the PA group were 59.7 ± 6.1/61.2 ± 4.4 ( = 3.38/4.9,<.1). The sleep rate were 93.8% and 25.0% (<.1). During the 1 month follow-up period, the PSQI total score in the AA group (5.2 ± 1.9) was superior to the PA group (13.1 ± 1.8) ( = 4.27,<.1). The SAS, SDS score in the AA group were 40.4 ± 5.1/42.7 ± 6.6 and in the PA group were 63.7 ± 6.6/63.5 ± 4.8 ( = 3.95/3.60,<.1). Throughout the study period, the 'six component' scores of PSQI in the AA group was superior to the PA group (each<.1). Except for tingling and cooling, other acupuncture sensations were significant differences (each<.1). Compared to the placebo acupuncture, active acupuncture can significantly improve insomnia, and clinical efficacy is maintained for at least 6 weeks.


greenmedinfo--2020-03-21--Melatonin mitigates chilling-induced oxidative stress and photosynthesis inhibition in tomato plants

Melatonin mitigates chilling-induced oxidative stress and photosynthesis inhibition in tomato plants.

Melatonin has been demonstrated to play a variety of roles in plants .
Of particular importance is its role as a potent antioxidative agent .
In the present study , we generated melatonin-deficient tomato plants using virus-induced gene silencing ( VIGS ) approach and melatonin-rich tomato plants by foliar application of melatonin .
These tomato plants were used to assess the effect of melatonin on chilling-induced oxidative stress and chilling-induced photosynthesis inhibition .
We found that melatonin deficiency increased accumulation of reactive oxygen species ( ROS ) and aggravated lipid peroxidation in chilling-stressed tomato leaves , while exogenous application of @ @ @ @ @ @ @ chilling stress , melatonin-deficient tomato plants showed impaired antioxidant capacity as evidenced by lower activities of antioxidant enzymes and decreased rations of reduced glutathione ( GSH ) /oxidized glutathione ( GSSG ) and reduced ascorbate ( AsA ) /oxidized ascorbate ( DHA ) , compared with melatonin-rich tomato plants .
Furthermore , suppression of melatonin biosynthesis led to more photosynthesis inhibition under the chilling condition and compromised the capability of subsequent photosynthesis recovery in tomato plants .
In addition , melatonin-deficient tomato plants displayed less activity of an important Calvin-Benson cycle enzyme sedoheptulose-1,7-bisphosphatase @ @ @ @ @ @ @ under chilling stress .
Collectively , our data indicate that melatonin is critical for antioxidant capacity and redox balance and is in favor of photosynthesis in tomato plants under chilling stress .

Melatonin has been demonstrated to play a variety of roles in plants. Of particular importance is its role as a potent antioxidative agent. In the present study, we generated melatonin-deficient tomato plants using virus-induced gene silencing (VIGS) approach and melatonin-rich tomato plants by foliar application of melatonin. These tomato plants were used to assess the effect of melatonin on chilling-induced oxidative stress and chilling-induced photosynthesis inhibition. We found that melatonin deficiency increased accumulation of reactive oxygen species (ROS) and aggravated lipid peroxidation in chilling-stressed tomato leaves, while exogenous application of melatonin had the opposite effect. Under chilling stress, melatonin-deficient tomato plants showed impaired antioxidant capacity as evidenced by lower activities of antioxidant enzymes and decreased rations of reduced glutathione (GSH)/oxidized glutathione (GSSG) and reduced ascorbate (AsA)/oxidized ascorbate (DHA), compared with melatonin-rich tomato plants. Furthermore, suppression of melatonin biosynthesis led to more photosynthesis inhibition under the chilling condition and compromised the capability of subsequent photosynthesis recovery in tomato plants. In addition, melatonin-deficient tomato plants displayed less activity of an important Calvin-Benson cycle enzyme sedoheptulose-1,7-bisphosphatase (SBPase) than melatonin-rich tomato plants under chilling stress. Collectively, our data indicate that melatonin is critical for antioxidant capacity and redox balance and is in favor of photosynthesis in tomato plants under chilling stress.


greenmedinfo--2020-03-21--Melatonin triggers metabolic and gene expression changes leading to improved quality traits of two s

Melatonin triggers metabolic and gene expression changes leading to improved quality traits of two sweet cherry cultivars during cold storage.

Sweet cherry is a valuable non-climacteric fruit with elevated phytonutrients , whose fruit quality attributes are prone to rapid deterioration @ @ @ @ @ damage and water loss of stem .
Here the metabolic and transcriptional response of exogenous @ @ @ @ @ commercial cultivars of sweet cherry ( Santina and Royal Rainier ) during cold storage .
@ @ @ @ @ cuticle composition and water movement may underlie the effect of melatonin in delaying weight loss @ @ @ @ @ on total soluble solids and lower respiration rate was observed in both cultivars .
Melatonin @ @ @ @ @ to anthocyanin biosynthesis , which correlates with increased anthocyanin levels and changes in skin color @ @ @ @ @ results indicate that along with modulating antioxidant metabolism , melatonin improves fruit quality traits by @ @ @ @ @ and gene expression changes , which ultimately contribute to extend sweet cherry postharvest storability .

Sweet cherry is a valuable non-climacteric fruit with elevated phytonutrients, whose fruit quality attributes are prone to rapid deterioration after harvest, especially peel damage and water loss of stem. Here the metabolic and transcriptional response of exogenous melatonin was assessed in two commercial cultivars of sweet cherry (Santina and Royal Rainier) during cold storage. Gene expression profiling revealed that cuticle composition and water movement may underlie the effect of melatonin in delaying weight loss. An effect of melatonin on total soluble solids and lower respiration rate was observed in both cultivars. Melatonin induces overexpression of genes related to anthocyanin biosynthesis, which correlates with increased anthocyanin levels and changes in skin color (Chroma). Our results indicate that along with modulating antioxidant metabolism, melatonin improves fruit quality traits by triggering a range of metabolic and gene expression changes, which ultimately contribute to extend sweet cherry postharvest storability.


greenmedinfo--2020-03-21--The results indicate that cannabinoids reduce the tumour growth in animal models of glioblastoma mul

The results indicate that cannabinoids reduce the tumour growth in animal models of glioblastoma multiforme.

Glioblastoma multiforme ( GBM ) is the most frequent and aggressive malignant brain tumour , with a poor prognosis despite available surgical and radio-chemotherapy , rising the necessity for searching alternative therapies .
Several preclinical studies evaluating the efficacy of cannabinoids in animal models of GBM have been described , but the diversity of experimental conditions and of outcomes hindered definitive conclusions about cannabinoids efficacy .
A search in different databases ( Pubmed , Web of Science , Scopus and SciELO ) was conducted during June 2019 to systematically identify publications evaluating the effects of cannabinoids in murine xenografts models @ @ @ @ @ @ @ number of animals were extracted , and a random effects meta-analysis of these results was performed to estimate the efficacy of cannabinoids .
The impact of different experimental factors and publication bias on the efficacy of cannabinoids was also assessed .
Nine publications , which satisfied the inclusion criteria , were identified and subdivided in 22 studies involving 301 animals .
Overall , cannabinoid therapy reduced the fold of increase in tumour volume in animal models of GBM , when compared with untreated controls .
The overall weighted standardized difference in means ( @ @ @ @ @ @ @ was -1.399 ( 95 % CI : -1.900 to -0.898 ; P-value < 0.0001 ) .
Furthermore , treatment efficacy was observed for different types of cannabinoids , alone or in combination , and for different treatment durations .
Cannabinoid therapy was still effective after correcting for publication bias .
The results indicate that cannabinoids reduce the tumour growth in animal models of GBM , even after accounting for publication bias .

Glioblastoma multiforme (GBM) is the most frequent and aggressive malignant brain tumour, with a poor prognosis despite available surgical and radio-chemotherapy, rising the necessity for searching alternative therapies. Several preclinical studies evaluating the efficacy of cannabinoids in animal models of GBM have been described, but the diversity of experimental conditions and of outcomes hindered definitive conclusions about cannabinoids efficacy. A search in different databases (Pubmed, Web of Science, Scopus and SciELO) was conducted during June 2019 to systematically identify publications evaluating the effects of cannabinoids in murine xenografts models of GBM. The tumour volume and number of animals were extracted, and a random effects meta-analysis of these results was performed to estimate the efficacy of cannabinoids. The impact of different experimental factors and publication bias on the efficacy of cannabinoids was also assessed. Nine publications, which satisfied the inclusion criteria, were identified and subdivided in 22 studies involving 301 animals. Overall, cannabinoid therapy reduced the fold of increase in tumour volume in animal models of GBM, when compared with untreated controls. The overall weighted standardized difference in means (WSDM) for the effect of cannabinoids was -1.399 (95% CI: -1.900 to -0.898; P-value<0.0001). Furthermore, treatment efficacy was observed for different types of cannabinoids, alone or in combination, and for different treatment durations. Cannabinoid therapy was still effective after correcting for publication bias. The results indicate that cannabinoids reduce the tumour growth in animal models of GBM, even after accounting for publication bias.


greenmedinfo--2020-03-21--Melatonin and cannabinoids: mitochondrial-targeted molecules that may reduce inflammaging in neurode

Melatonin and cannabinoids: mitochondrial-targeted molecules that may reduce inflammaging in neurodegenerative diseases.

Generally , the development and progression of neurodegenerative diseases are associated with advancing age , so they are usually diagnosed in late adulthood .
A primary mechanism underlying the onset of neurodegenerative diseases is neuroinflammation .
Based on this background , the concept of '' neuroinflammaging '' has emerged .
In this deregulated neuroinflammatory process , a variety of immune cells participate , especially glial cells , proinflammatory cytokines , receptors , and subcellular organelles including mitochondria , which are mainly responsible for maintaining redox balance at the cellular level .
Senescence and autophagic processes also play a crucial role @ @ @ @ @ @ @ .
Of particular interest , melatonin , cannabinoids , and the receptors of both molecules which are closely related , exert beneficial effects on the neuroinflammatory processes that precede the onset of neurodegenerative pathologies such as Parkinson 's and Alzheimer 's diseases .
Some of these neuroprotective effects are fundamentally related to its anti-inflammatory and antioxidative actions at the mitochondrial level due to the strategic functions of this organelle .
The aim of this review is to summarize the most recent advances in the study of neuroinflammation and neurodegeneration associated with age and @ @ @ @ @ @ @ therapeutic targets related to the endocannabinoid system and the pineal gland .

Generally, the development and progression of neurodegenerative diseases are associated with advancing age, so they are usually diagnosed in late adulthood. A primary mechanism underlying the onset of neurodegenerative diseases is neuroinflammation. Based on this background, the concept of"neuroinflammaging"has emerged. In this deregulated neuroinflammatory process, a variety of immune cells participate, especially glial cells, proinflammatory cytokines, receptors, and subcellular organelles including mitochondria, which are mainly responsible for maintaining redox balance at the cellular level. Senescence and autophagic processes also play a crucial role in the neuroinflammatory disease associated with aging. Of particular interest, melatonin, cannabinoids, and the receptors of both molecules which are closely related, exert beneficial effects on the neuroinflammatory processes that precede the onset of neurodegenerative pathologies such as Parkinson's and Alzheimer's diseases. Some of these neuroprotective effects are fundamentally related to its anti-inflammatory and antioxidative actions at the mitochondrial level due to the strategic functions of this organelle. The aim of this review is to summarize the most recent advances in the study of neuroinflammation and neurodegeneration associated with age and to consider the use of new mitochondrial therapeutic targets related to the endocannabinoid system and the pineal gland.


greenmedinfo--2020-03-21--Melatonin may be a new effective treatment of esophageal cancer.

Melatonin is an amine hormone produced by mammals and the human pineal gland .
Modern biomedical research has shown that @ @ @ @ @ However , the underlying mechanisms of these effects remain unclear .
In this study , @ @ @ @ @ melatonin on TE-1 esophageal cancer cells metastasis and study the roles of the NF-κB signaling @ @ @ @ @ process .
We found that melatonin significantly suppressed the migration and invasion of TE-1 esophageal @ @ @ @ @ activation NF-κB signaling pathway , and decreased the expression of MMP9 .
When adding NF-κB @ @ @ @ @ that the expression of MMP9 decreased while E-cadherin increased .
Taken together , the results @ @ @ @ @ cancer cell metastasis by down-regulating the NF-κB signaling pathway and MMP9 .
Therefore , melatonin @ @ @ @ @ for the effective treatment of esophageal cancer .

Melatonin is an amine hormone produced by mammals and the human pineal gland. Modern biomedical research has shown that melatonin has antitumor effects. However, the underlying mechanisms of these effects remain unclear. In this study, we explore the effect of melatonin on TE-1 esophageal cancer cells metastasis and study the roles of the NF-κB signaling pathway and MMP9 in this process. We found that melatonin significantly suppressed the migration and invasion of TE-1 esophageal cancer cells, inhibited the activation NF-κB signaling pathway, and decreased the expression of MMP9. When adding NF-κB inhibitor, the results show that the expression of MMP9 decreased while E-cadherin increased. Taken together, the results indicate that melatonin inhibits esophageal cancer cell metastasis by down-regulating the NF-κB signaling pathway and MMP9. Therefore, melatonin may be a new drug for the effective treatment of esophageal cancer.


greenmedinfo--2020-03-21--Targeting cancer stem cells by melatonin: Effective therapy for cancer treatment.

Melatonin is a physiological hormone produced by the pineal gland .
In recent decades , enormous investigations showed that melatonin @ @ @ @ @ cells and inhibit tumor metastasis and angiogenesis in variety of malignancies such as ovarian , @ @ @ @ @ breast cancer ; therefore , its possible therapeutic usage in cancer treatment was confirmed .
@ @ @ @ @ much attention from researchers in past decades , are major challenges in the treatment of @ @ @ @ @ resistant to chemotherapeutic drugs and cause recurrence of cancer and also have the ability to @ @ @ @ @ cause serious problems in the treatment of various cancers .
For these reasons , the @ @ @ @ @ a solution to destroy these cells within the tumor mass .
In recent years , @ @ @ @ @ CSCs has been investigated in some cancers .
Given the importance of CSCs in the @ @ @ @ @ this article reviewed the studies conducted on the effect of melatonin on CSCs as a @ @ @ @ @ by CSCs in the treatment of various cancers .

Melatonin is a physiological hormone produced by the pineal gland. In recent decades, enormous investigations showed that melatonin can prompt apoptosis in cancer cells and inhibit tumor metastasis and angiogenesis in variety of malignancies such as ovarian, melanoma, colon, and breast cancer; therefore, its possible therapeutic usage in cancer treatment was confirmed. CSCs, which has received much attention from researchers in past decades, are major challenges in the treatment of cancer. Because CSCs are resistant to chemotherapeutic drugs and cause recurrence of cancer and also have the ability to be regenerated; they can cause serious problems in the treatment of various cancers. For these reasons, the researchers are trying to find a solution to destroy these cells within the tumor mass. In recent years, the effect of melatonin on CSCs has been investigated in some cancers. Given the importance of CSCs in the process of cancer treatment, this article reviewed the studies conducted on the effect of melatonin on CSCs as a solution to the problems caused by CSCs in the treatment of various cancers.


greenmedinfo--2020-03-21--Bromelain has inhibitory effects on colony formation in cancer cells.

Bromelain is dotted with anticancer properties on various cancer cell lines .
Anticancer pathways of bromelain , as well related intervening signalization are under investigation .
Investigating the inhibitory potential of bromelain on AGS , PC3 , and MCF7 cells proliferation and colony formation .
The bromelain inhibitory potential on AGS , PC3 , and MCF7 cells proliferation at various bromelain concentrations was assessed by MTT ; thereby , bromelain potency on colony formation impediment was evaluated using clonogenic assays at determined 50 % inhibitory concentrations ( IC ) on four different cell densities ( 10 , 50 , 100 @ @ @ @ @ @ @ .
Bromelain inhibits AGS , PC3 , and MCF7 cells proliferation in such a dose-dependent manner .
Determined ICto AGS , PC3 , and MCF7 cells were 65 , 60 and 65μg/ml respectively .
At IC , bromelain significantly suppressed the AGS , PC3 , and MCF7 cells colony formation at four treated densities ( 10 , 50 , 100 and 200 cells per well ) .
Plating efficiency percentage and cell surviving fraction were decreased after bromelain treatment to AGS , PC3 , and MCF7 human cancer cells as a function of @ @ @ @ @ @ @ 50 or 100 , and 10 or 50 cells per well were considered to be optimum number of initial cell density for AGS , PC3 , and MCF7 cells .
Cell proliferative and colony formation inhibition are two pathways tobromelain anticancer effects .
The current study displayed a dose-dependent inhibitory effect of bromelain , as well impeding colony formation AGS , PC3 , and MCF7 human cancer cells .

Bromelain is dotted with anticancer properties on various cancer cell lines. Anticancer pathways of bromelain, as well related intervening signalization are under investigation. Investigating the inhibitory potential of bromelain on AGS, PC3, and MCF7 cells proliferation and colony formation. The bromelain inhibitory potential on AGS, PC3, and MCF7 cells proliferation at various bromelain concentrations was assessed by MTT; thereby, bromelain potency on colony formation impediment was evaluated using clonogenic assays at determined 50% inhibitory concentrations (IC) on four different cell densities (10, 50, 100, and 200 cells per well). Bromelain inhibits AGS, PC3, and MCF7 cells proliferation in such a dose-dependent manner. Determined ICto AGS, PC3, and MCF7 cells were 65, 60 and 65μg/ml respectively. At IC, bromelain significantly suppressed the AGS, PC3, and MCF7 cells colony formation at four treated densities (10, 50, 100 and 200 cells per well). Plating efficiency percentage and cell surviving fraction were decreased after bromelain treatment to AGS, PC3, and MCF7 human cancer cells as a function of initial cell density. The 50, 50 or 100, and 10 or 50 cells per well were considered to be optimum number of initial cell density for AGS, PC3, and MCF7 cells. Cell proliferative and colony formation inhibition are two pathways tobromelain anticancer effects. The current study displayed a dose-dependent inhibitory effect of bromelain, as well impeding colony formation AGS, PC3, and MCF7 human cancer cells.


greenmedinfo--2020-03-21--Bromelain treatment could potentiate the antitumor effect of cisplatin on triple-negative breast can

Bromelain treatment could potentiate the antitumor effect of cisplatin on triple-negative breast cancer 4T1 cells.

This study aimed to evaluate the antitumor enhancing effect of bromelain consumption on 4T1-challenged mice treated with cisplatin.Mice challenged with 4T1 triple-negative breast cancer cells received water , bromelain , cisplatin , or bromelain + cisplatin treatment for 28 days .
Tumor size was measured , and lung metastasis was evaluated by clonogenic assay .
Expression of tumor inflammatory genes of the harvested tumor was quantified by polymerase chain reaction array and ELISA ( enzyme-linked immunosorbent assay ) .
: All treatments significantly reduced the size of tumor and lung metastasis , with combination treatment showing the best effect .
@ @ @ @ @ @ @ showed downregulation of the expression of tumor inflammatory genes ( Gremlin [ GREM1 ] , interleukin 1β [ IL-1β ] , interleukin-4 [ IL-4 ] , nuclear factor κB subunit 1 [ NFκB1 ] , and prostaglandin-endoperoxide synthase 2 [ PTGS2 ] ) , tumor nitric oxide level , and serum IL-1β , and IL-4 levels .
On the other hand , cisplatin treatment increased the expression of selected inflammatory markers.This study suggests that bromelain treatment could potentiate the antitumor effect of cisplatin on triple-negative breast cancer 4T1 cells through modulating the tumor @ @ @

This study aimed to evaluate the antitumor enhancing effect of bromelain consumption on 4T1-challenged mice treated with cisplatin.Mice challenged with 4T1 triple-negative breast cancer cells received water, bromelain, cisplatin, or bromelain + cisplatin treatment for 28 days. Tumor size was measured, and lung metastasis was evaluated by clonogenic assay. Expression of tumor inflammatory genes of the harvested tumor was quantified by polymerase chain reaction array and ELISA (enzyme-linked immunosorbent assay).: All treatments significantly reduced the size of tumor and lung metastasis, with combination treatment showing the best effect. Also, bromelain alone and combination treatment showed downregulation of the expression of tumor inflammatory genes (Gremlin [GREM1], interleukin 1β [IL-1β], interleukin-4 [IL-4], nuclear factor κB subunit 1 [NFκB1], and prostaglandin-endoperoxide synthase 2 [PTGS2]), tumor nitric oxide level, and serum IL-1β, and IL-4 levels. On the other hand, cisplatin treatment increased the expression of selected inflammatory markers.This study suggests that bromelain treatment could potentiate the antitumor effect of cisplatin on triple-negative breast cancer 4T1 cells through modulating the tumor environmental inflammation.


greenmedinfo--2020-03-21--Antinociceptive and neuroprotective effects of bromelain in chronic constriction injury-induced neur

Antinociceptive and neuroprotective effects of bromelain in chronic constriction injury-induced neuropathic pain.

Background : The continuous search for a novel neuropathic pain drug with few or no side effects has been a main focus of researchers for decades .
This study investigated the antinociceptive and neuroprotective effects of bromelain in sciatic nerve ligation-induced neuropathic pain in Wistar rats .
Methods : Forty-eight Wistar rats randomly divided into eight groups comprised of six animals each were used for this study .
Peripheral neuropathy was inducedchronic constriction of the common sciatic nerve .
Thermal hyperalgesic and mechanical allodynia were assessed using a hotplate and von Frey filaments , respectively .
The functional recovery and @ @ @ @ @ @ @ were evaluated using the sciatic functional index test and a histological examination of the transverse section of the sciatic nerve .
The neuroprotective effects of bromelain were investigated in the proximal sciatic nerve tissue after 21 days of treatment .
Results : Bromelain significantly ( < 0.05 ) attenuated both the thermal hyperalgesia and mechanical allodynic indices of neuropathic pain .
There were improvements in sciatic function and structural integrity in rats treated with bromelain .
These rats showed significant ( < 0.05 ) increases in sciatic nerve nuclear transcription factors ( nuclear @ @ @ @ @ @ @ NrF-2 ) , antioxidant enzymes ( superoxide dismutase and glutathione ) , and reduced membrane-lipid peroxidation compared with the ligated control group .
Conclusions : This study suggest that bromelain mitigated neuropathic pain by enhancing the activities of nuclear transcription factors ( NrF-1 and NrF-2 ) which increases the antioxidant defense system that abolish neuronal stress and structural disorganization .

Background: The continuous search for a novel neuropathic pain drug with few or no side effects has been a main focus of researchers for decades. This study investigated the antinociceptive and neuroprotective effects of bromelain in sciatic nerve ligation-induced neuropathic pain in Wistar rats.
Methods: Forty-eight Wistar rats randomly divided into eight groups comprised of six animals each were used for this study. Peripheral neuropathy was inducedchronic constriction of the common sciatic nerve. Thermal hyperalgesic and mechanical allodynia were assessed using a hotplate and von Frey filaments, respectively. The functional recovery and structural architecture of the ligated sciatic nerve were evaluated using the sciatic functional index test and a histological examination of the transverse section of the sciatic nerve. The neuroprotective effects of bromelain were investigated in the proximal sciatic nerve tissue after 21 days of treatment.
Results: Bromelain significantly (<0.05) attenuated both the thermal hyperalgesia and mechanical allodynic indices of neuropathic pain. There were improvements in sciatic function and structural integrity in rats treated with bromelain. These rats showed significant (<0.05) increases in sciatic nerve nuclear transcription factors (nuclear factor erythroid-derived-2-related factors-1 [NrF-1] and NrF-2), antioxidant enzymes (superoxide dismutase and glutathione), and reduced membrane-lipid peroxidation compared with the ligated control group.
Conclusions: This study suggest that bromelain mitigated neuropathic pain by enhancing the activities of nuclear transcription factors (NrF-1 and NrF-2) which increases the antioxidant defense system that abolish neuronal stress and structural disorganization.


greenmedinfo--2020-03-21--Melatonin prevents endothelial dysfunction in SLE by activating the nuclear receptor retinoic acid-r

Melatonin prevents endothelial dysfunction in SLE by activating the nuclear receptor retinoic acid-related orphan receptor-α.

Atherosclerotic cardiovascular disease confers significant morbidity and mortality in patients with systemic lupus erythematosus ( SLE ) .
A substantial proportion of patients with SLE display accelerated endothelial dysfunction , which precedes cardiovascular disease .
Melatonin and its nuclear receptor retinoid-related orphan receptor alpha ( RORα ) have been reported to have some protective effects on the development of atherosclerosis .
However , the function of melatonin in SLE-induced endothelial dysfunction and the role that RORα plays are still unknown .
In this study , we found that RORα protein expression was decreased in aortas of lupus-prone mice and in @ @ @ @ @ @ @ ) cultured with medium containing sera of patients with SLE .
Melatonin-treated HUVECs showed a decrease of pro-inflammatory mRNAs [ interleukin-1beta ( IL-1β ) , interferon-gamma ( IFN-γ ) , and tumor necrosis factor-alpha ( TNF-α ) ] under the stimulation of SLE medium .
Melatonin increased nitric oxide and antioxidant mRNAs ( SOD1 , GPX1 , and CAT ) and downregulated reactive oxygen species ( ROS ) level in HUVECs , which may subsequently delay endothelial senescence and promote HUVEC proliferation and repair after injury .
Melatonin inhibited SLE medium-induced RAW264.7 macrophage @ @ @ @ @ @ @ less adhesion-related proteins ( ICAM-1 and VCAM-1 ) ; as a result , these cells adhered to fewer peripheral blood monocytes .
In addition , we also showed that the protective effects of melatonin on endothelial cells were largely diminished when RORα was knockdown in HUVECs .
In conclusion , by targeting the nuclear receptor RORα , melatonin preserves normal functions of endothelium in SLE by its anti-inflammatory , antioxidant , and anti-senescence effects .
RORα may have the potential to become a prophylactic or therapeutic target in preventing endothelial dysfunction and atherosclerotic @ @ @ @ @ @ @

Atherosclerotic cardiovascular disease confers significant morbidity and mortality in patients with systemic lupus erythematosus (SLE). A substantial proportion of patients with SLE display accelerated endothelial dysfunction, which precedes cardiovascular disease. Melatonin and its nuclear receptor retinoid-related orphan receptor alpha (RORα) have been reported to have some protective effects on the development of atherosclerosis. However, the function of melatonin in SLE-induced endothelial dysfunction and the role that RORα plays are still unknown. In this study, we found that RORα protein expression was decreased in aortas of lupus-prone mice and in human umbilical vein endothelial cells (HUVECs) cultured with medium containing sera of patients with SLE. Melatonin-treated HUVECs showed a decrease of pro-inflammatory mRNAs [interleukin-1beta (IL-1β), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α)] under the stimulation of SLE medium. Melatonin increased nitric oxide and antioxidant mRNAs (SOD1, GPX1, and CAT) and downregulated reactive oxygen species (ROS) level in HUVECs, which may subsequently delay endothelial senescence and promote HUVEC proliferation and repair after injury. Melatonin inhibited SLE medium-induced RAW264.7 macrophage migration. HUVECs pretreated with melatonin expressed less adhesion-related proteins (ICAM-1 and VCAM-1); as a result, these cells adhered to fewer peripheral blood monocytes. In addition, we also showed that the protective effects of melatonin on endothelial cells were largely diminished when RORα was knockdown in HUVECs. In conclusion, by targeting the nuclear receptor RORα, melatonin preserves normal functions of endothelium in SLE by its anti-inflammatory, antioxidant, and anti-senescence effects. RORα may have the potential to become a prophylactic or therapeutic target in preventing endothelial dysfunction and atherosclerotic cardiovascular disease in patients with SLE.


greenmedinfo--2020-03-21--Usefulness of melatonin as complementary to chemotherapeutic agents at different stages of the angio

Usefulness of melatonin as complementary to chemotherapeutic agents at different stages of the angiogenic process.

Chemotherapeutics are sometimes administered with drugs , like antiangiogenic compounds , to increase their effectiveness .
Melatonin exerts antitumoral actions through antiangiogenic actions .
We studied if melatonin regulates the response of HUVECs to chemotherapeutics ( docetaxel and vinorelbine ) .
The inhibition that these agents exert on some of the processes involved in angiogenesis , such as , cell proliferation , migratory capacity or vessel formation , was enhanced by melatonin .
Regarding to estrogen biosynthesis , melatonin impeded the negative effect of vinorelbine , by decreasing the activity and expression of aromatase and sulfatase .
Docetaxel and vinorelbine @ @ @ @ @ @ @ , VEGF-C , VEGFR-1 , VEGFR-3 , ANG1 and/or ANG-2 and melatonin inhibited these actions .
Besides , melatonin prevented the positive actions that docetaxel exerts on the expression of other factors related to angiogenesis like JAG1 , ANPEP , IGF-1 , CXCL6 , AKT1 , ERK1 , ERK2 , MMP14 and NOS3 and neutralized the stimulating actions of vinorelbine on the expression of FIGF , FGFR3 , CXCL6 , CCL2 , ERK1 , ERK2 , AKT1 , NOS3 and MMP14 .
In CAM assay melatonin inhibited new vascularization in combination with chemotherapeutics @ @ @ @ @ @ @ of p-AKT and p-ERK and neutralized the chemotherapeutics-caused stimulatory effect on HUVECs permeability by modifying the distribution of VE cadherin .
Our results confirm that melatonin blocks proangiogenic and potentiates antiangiogenic effects induced by docetaxel and vinorelbine enhancing their antitumor effectiveness .

Chemotherapeutics are sometimes administered with drugs, like antiangiogenic compounds, to increase their effectiveness. Melatonin exerts antitumoral actions through antiangiogenic actions. We studied if melatonin regulates the response of HUVECs to chemotherapeutics (docetaxel and vinorelbine). The inhibition that these agents exert on some of the processes involved in angiogenesis, such as, cell proliferation, migratory capacity or vessel formation, was enhanced by melatonin. Regarding to estrogen biosynthesis, melatonin impeded the negative effect of vinorelbine, by decreasing the activity and expression of aromatase and sulfatase. Docetaxel and vinorelbine increased the expression of VEGF-A, VEGF-B, VEGF-C, VEGFR-1, VEGFR-3, ANG1 and/or ANG-2 and melatonin inhibited these actions. Besides, melatonin prevented the positive actions that docetaxel exerts on the expression of other factors related to angiogenesis like JAG1, ANPEP, IGF-1, CXCL6, AKT1, ERK1, ERK2, MMP14 and NOS3 and neutralized the stimulating actions of vinorelbine on the expression of FIGF, FGFR3, CXCL6, CCL2, ERK1, ERK2, AKT1, NOS3 and MMP14. In CAM assay melatonin inhibited new vascularization in combination with chemotherapeutics. Melatonin further enhanced the chemotherapeutics-induced inhibition of p-AKT and p-ERK and neutralized the chemotherapeutics-caused stimulatory effect on HUVECs permeability by modifying the distribution of VE cadherin. Our results confirm that melatonin blocks proangiogenic and potentiates antiangiogenic effects induced by docetaxel and vinorelbine enhancing their antitumor effectiveness.


greenmedinfo--2020-03-21--Melatonin inhibits cytosolic mitochondrial-DNA induced neuroinflammatory signaling in accelerated ag

Melatonin inhibits cytosolic mitochondrial-DNA induced neuroinflammatory signaling in accelerated aging and neurodegeneration.

Chronic inflammation is a pathologic feature of neurodegeneration and aging ; however , the mechanism regulating this process is not @ @ @ @ @ endogenous free radical scavenger synthesized by neuronal mitochondria , decreases with aging and neurodegeneration .
@ @ @ @ @ levels impair mitochondrial homeostasis resulting in mitochondrial DNA ( mtDNA ) release , activation of @ @ @ @ @ in neurons .
We found increased mitochondrial oxidative stress and decreased mitochondrial membrane potential with @ @ @ @ @ ) release in brain and primary cerebro-cortical neurons of melatonin deficient aralkylamine N-acetyltransferase ( AANAT @ @ @ @ @ mtDNA activated the cGAS/STING/IRF3 pathway , stimulating inflammatory cytokine generation .
We found that Huntington @ @ @ @ @ release , cGAS activation , and inflammation , all inhibited by exogenous melatonin .
Thus @ @ @ @ @ mtDNA activated the inflammatory response in aging and neurodegeneration , a process modulated by melatonin @ @ @ @ @ suggest that AANAT knockout mice are a model of accelerated aging .

Chronic inflammation is a pathologic feature of neurodegeneration and aging; however, the mechanism regulating this process is not understood. Melatonin, an endogenous free radical scavenger synthesized by neuronal mitochondria, decreases with aging and neurodegeneration. We proposed that insufficient melatonin levels impair mitochondrial homeostasis resulting in mitochondrial DNA (mtDNA) release, activation of cytosolic DNA mediated inflammatory response in neurons. We found increased mitochondrial oxidative stress and decreased mitochondrial membrane potential with higher mitochondrial DNA (mtDNA) release in brain and primary cerebro-cortical neurons of melatonin deficient aralkylamine N-acetyltransferase (AANAT) knockout mice. Cytosolic mtDNA activated the cGAS/STING/IRF3 pathway, stimulating inflammatory cytokine generation. We found that Huntington's disease mice increased mtDNA release, cGAS activation, and inflammation, all inhibited by exogenous melatonin. Thus, we demonstrated that cytosolic mtDNA activated the inflammatory response in aging and neurodegeneration, a process modulated by melatonin. Furthermore, our data suggest that AANAT knockout mice are a model of accelerated aging.


greenmedinfo--2020-03-21--BPA induced systemic oxidative stress and could change ROS-induced signaling pathways in the brain.

We investigated the effect of bisphenol A ( BPA ) on oxidative stress and tau-related proteins in adult rat brains .
BPA ( 10 mg/L ) was administered to rats for eight weeks through their drinking water .
The reactive oxygen species ( ROS ) scavenging capacity for hydroxyl radicals in the plasma was reduced after two weeks .
In the hippocampus , four and eight weeks of BPA increased the ratio of oxidized DJ-1/DJ-1 ( PARK7 ) .
The ratio of phosphorylated-GSK3β/GSK3β and phosphorylated-AKT/AKT increased after one week of BPA treatment .
The ratio of phosphorylated JNK/JNK and phosphorylated-ERK/ERK @ @ @ @ @ @ @ the elevation could be related to tau phosphorylation .
Protein phosphatase 2A ( PP2A ) in the hippocampus decreased after eight weeks of BPA treatment .
At that time , SOD1 was significantly induced , but no changes in SOD2 expression were apparent in the hippocampus .
Furthermore , the ratio of phosphorylated-tau ( PHF-1 , Ser396/ Ser404 ) to total tau level did not change .
However , PHF-1 or other sites of tau could be phosphorylated after eight weeks in the hippocampi of rats .
BPA induced systemic oxidative stress and @ @ @ @ @ @ @ brain .
These results suggest that mitochondrial dysfunction possibly is not responsible for oxidative stress and neurodegeneration due to low doses of BPA .

We investigated the effect of bisphenol A (BPA) on oxidative stress and tau-related proteins in adult rat brains. BPA (10 mg/L) was administered to rats for eight weeks through their drinking water. The reactive oxygen species (ROS) scavenging capacity for hydroxyl radicals in the plasma was reduced after two weeks. In the hippocampus, four and eight weeks of BPA increased the ratio of oxidized DJ-1/DJ-1 (PARK7). The ratio of phosphorylated-GSK3β/GSK3β and phosphorylated-AKT/AKT increased after one week of BPA treatment. The ratio of phosphorylated JNK/JNK and phosphorylated-ERK/ERK increased after eight weeks of BPA; the elevation could be related to tau phosphorylation. Protein phosphatase 2A (PP2A) in the hippocampus decreased after eight weeks of BPA treatment. At that time, SOD1 was significantly induced, but no changes in SOD2 expression were apparent in the hippocampus. Furthermore, the ratio of phosphorylated-tau (PHF-1, Ser396/ Ser404) to total tau level did not change. However, PHF-1 or other sites of tau could be phosphorylated after eight weeks in the hippocampi of rats. BPA induced systemic oxidative stress and could change ROS-induced signaling pathways in the brain. These results suggest that mitochondrial dysfunction possibly is not responsible for oxidative stress and neurodegeneration due to low doses of BPA.


greenmedinfo--2020-03-21--Neonatal exposure to bisphenol A advances pubertal development in female rats.

Neonatal exposure to bisphenol A ( BPA ) is hypothesized to advance pubertal development .
However , the effects of @ @ @ @ @ development has not been described .
In this study , female Sprague-Dawley rats were exposed @ @ @ @ @ 5 , or 10 mg·kg·dayBPA , or corn oil vehicle alone from postnatal day 1 @ @ @ @ @ via subcutaneous injection .
We evaluated day of vaginal opening ( DVO ) , ovarian @ @ @ @ @ , and hypothalamic expression of Gnrh1 and Kiss1 in female rats at PND35 .
DVO @ @ @ @ @ exposed to 5 and 10 mg·kg·dayBPA .
Serum hormone concentrations increased as BPA dose increased @ @ @ @ @ and Kiss1 expression were increased with BPA exposure ; rats exposed to 10 mg·kg·dayBPA had @ @ @ @ @ Kiss1 expressions in terms of both messenger RNA and protein levels .
Our results suggest @ @ @ @ @ mg·kg·daydose of BPA might advance pubertal development significantly .
In addition , within the range @ @ @ @ @ , neonatal exposure to BPA may affect pubertal development in a dose-dependent manner .

Neonatal exposure to bisphenol A (BPA) is hypothesized to advance pubertal development. However, the effects of neonatal BPA exposure on pubertal development has not been described. In this study, female Sprague-Dawley rats were exposed to 0.05, 0.5, 5, or 10 mg·kg·dayBPA, or corn oil vehicle alone from postnatal day 1 (PND1) to PND10 via subcutaneous injection. We evaluated day of vaginal opening (DVO), ovarian morphology, serum hormone concentrations, and hypothalamic expression of Gnrh1 and Kiss1 in female rats at PND35. DVO was significantly advanced in rats exposed to 5 and 10 mg·kg·dayBPA. Serum hormone concentrations increased as BPA dose increased. Additionally, hypothalamic Gnrh1 and Kiss1 expression were increased with BPA exposure; rats exposed to 10 mg·kg·dayBPA had significantly upregulated hypothalamic Gnrh1 and Kiss1 expressions in terms of both messenger RNA and protein levels. Our results suggest that exposure to a 10 mg·kg·daydose of BPA might advance pubertal development significantly. In addition, within the range of 0 to 10 mg·kg·day, neonatal exposure to BPA may affect pubertal development in a dose-dependent manner.


greenmedinfo--2020-03-21--Estrogen and bisphenol A in hypertension.

PURPOSE OF REVIEW : Cardiovascular disease ( CVD ) is a non-subsiding disease that remains a leading cause of morbidity and mortality .
CVD has been associated with endocrine disruptors , such as bisphenol A ( BPA ) .
This review critically summarizes existing findings on BPA and hypertension , with particular attention to genomic , non-genomic , molecular , and cellular mechanisms of action that render BPA as a cardiovascular estrogenic disruptor .
RECENT FINDINGS : Owing to its similar estrogenic structure , BPA has been shown to affect various phenotypes that are regulated by the natural hormone , @ @ @ @ @ @ @ shown to interact with estrogen receptors , located both in the cell membrane and in the cytoplasm/nucleus .
Given that estrogen plays an important role in cardiovascular physiology , a contributing role for BPA in CVD would not be unexpected .
Existing literature , though limited , established BPA as a source of disruption in cardiovascular health , particularly hypertension .
However , effects of BPA are largely dependent on the dose , patient gender , tissue , and developmental stage of the exposed tissue/organ .
Accumulating evidence argues for an adverse effect @ @ @ @ @ @ @ this effect being gender , dose , and time specific .
Thus , comprehensive studies which take these factors and other parameters , like epigenetic factors , into account are warranted before a thorough understanding is at hand .

PURPOSE OF REVIEW: Cardiovascular disease (CVD) is a non-subsiding disease that remains a leading cause of morbidity and mortality. CVD has been associated with endocrine disruptors, such as bisphenol A (BPA). This review critically summarizes existing findings on BPA and hypertension, with particular attention to genomic, non-genomic, molecular, and cellular mechanisms of action that render BPA as a cardiovascular estrogenic disruptor.
RECENT FINDINGS: Owing to its similar estrogenic structure, BPA has been shown to affect various phenotypes that are regulated by the natural hormone, estrogen. Indeed, BPA has been shown to interact with estrogen receptors, located both in the cell membrane and in the cytoplasm/nucleus. Given that estrogen plays an important role in cardiovascular physiology, a contributing role for BPA in CVD would not be unexpected. Existing literature, though limited, established BPA as a source of disruption in cardiovascular health, particularly hypertension. However, effects of BPA are largely dependent on the dose, patient gender, tissue, and developmental stage of the exposed tissue/organ. Accumulating evidence argues for an adverse effect of BPA on blood pressure, with this effect being gender, dose, and time specific. Thus, comprehensive studies which take these factors and other parameters, like epigenetic factors, into account are warranted before a thorough understanding is at hand.