greenmedinfo--2020-12-05--Melatonin alleviates pyroptosis of retinal neurons following acute intraocular hypertension.

BACKGROUND : Glaucoma is a multifactorial optic neuropathy progressive characterized by structural loss of retinal ganglion cells ( RGCs ) and irreversible loss of vision .
High intraocular pressure ( HIOP ) is a high risk factor for glaucoma .
It has been reported that the manners of RGCs ' loss are in-depth explored after acute HIOP injury , such as , apoptosis , autophagy and necrosis .
However , pyroptosis , a novel type of pro-inflammatory cell programmed necrosis , rarely reported after acute HIOP injury .
Researches also showed that melatonin ( MT ) possesses substantial anti-inflammatory properties @ @ @ @ @ @ @ retinal neurons death , especially pyroptosis , by acute HIOP injury is unclear .
OBJECTIVE : This study explored pyroptosis of retinal neurons and the effects of MT preventing retinal neurons form pyroptosis after acute HIOP injury .
METHOD : Establish acute HIOP model in rat by increasing the IOP and then reperfusion .
Western Blot ( WB ) was adopted to detect molecules related to pyroptosis at the protein level , such as GasderminD ( GSDMD ) , GasderminDp32 ( GSDMDp32 ) , Caspase-1 ( Casp-1 ) and Caspase-1p20 ( Casp-1p20 ) @ @ @ @ @ @ @ , as interleukin-18 ( IL-18 ) and interleukin-1β ( IL-1β ) as well .
At the same time , Immunofluorescence ( IF ) was used to co-localize Casp-1with retinal neurons to determine the position of Casp-1 expression .
Morphologically , Ethidium homodimer-III staining , a method commonly used for judging cell death , was carried out to stain dead cells .
Subsequently , Lactate Dehydrogenase ( LDH ) cytotoxicity assay kit was used to quantitative analysis the LDH released after cell disruption .
RESULTS : The results suggested that pyroptosis played a vital @ @ @ @ @ @ @ in the ganglion cell layer , by acute HIOP injury and peaked at 6h after acute HIOP injury .
Furthermore , it was found that MT might prevent retinal neurons from pyroptosis via NF-κB/NLRP3 axis after acute HIOP injury in rats .
CONCLUSION : MT treatment might be considered a new strategy for protecting retinal neurons against pyroptosis following acute HIOP injury .

BACKGROUND: Glaucoma is a multifactorial optic neuropathy progressive characterized by structural loss of retinal ganglion cells (RGCs) and irreversible loss of vision. High intraocular pressure (HIOP) is a high risk factor for glaucoma. It has been reported that the manners of RGCs' loss are in-depth explored after acute HIOP injury, such as, apoptosis, autophagy and necrosis. However, pyroptosis, a novel type of pro-inflammatory cell programmed necrosis, rarely reported after acute HIOP injury. Researches also showed that melatonin (MT) possesses substantial anti-inflammatory properties. However, whether melatonin could alleviate retinal neurons death, especially pyroptosis, by acute HIOP injury is unclear.
OBJECTIVE: This study explored pyroptosis of retinal neurons and the effects of MT preventing retinal neurons form pyroptosis after acute HIOP injury.
METHOD: Establish acute HIOP model in rat by increasing the IOP and then reperfusion. Western Blot (WB) was adopted to detect molecules related to pyroptosis at the protein level, such as GasderminD (GSDMD), GasderminDp32 (GSDMDp32), Caspase-1 (Casp-1) and Caspase-1p20 (Casp-1p20), and the products of inflammatory reactions, as interleukin-18 (IL-18) and interleukin-1β (IL-1β) as well. At the same time, Immunofluorescence (IF) was used to co-localize Casp-1with retinal neurons to determine the position of Casp-1 expression. Morphologically, Ethidium homodimer-III staining, a method commonly used for judging cell death, was carried out to stain dead cells. Subsequently, Lactate Dehydrogenase (LDH) cytotoxicity assay kit was used to quantitative analysis the LDH released after cell disruption.
RESULTS: The results suggested that pyroptosis played a vital role in retinal neurons death, especially in the ganglion cell layer, by acute HIOP injury and peaked at 6h after acute HIOP injury. Furthermore, it was found that MT might prevent retinal neurons from pyroptosis via NF-κB/NLRP3 axis after acute HIOP injury in rats.
CONCLUSION: MT treatment might be considered a new strategy for protecting retinal neurons against pyroptosis following acute HIOP injury.


greenmedinfo--2020-12-05--Melatonin ameliorates microvessel abnormalities in the cerebral cortex and hippocampus in a model of

Melatonin ameliorates microvessel abnormalities in the cerebral cortex and hippocampus in a model of Alzheimer's disease.

Melatonin can attenuate cardiac microvascular ischemia/reperfusion injury , but it remains unclear whether melatonin can also ameliorate cerebral microvascular abnormalities @ @ @ @ @ 's disease were established by six intracerebroventricular injections of amyloid-beta 1-42 , administered once every @ @ @ @ @ 30 mg/kg ) was intraperitoneally administered for 13 successive days , with the first dose @ @ @ @ @ the first administration of amyloid-beta 1-42 .
Melatonin ameliorated learning and memory impairments in the @ @ @ @ @ improved the morphology of microvessels in the cerebral cortex and hippocampus , increased microvessel density @ @ @ @ @ cerebral neurons , and decreased the expression of vascular endothelial growth factor and vascular endothelial @ @ @ @ @ 2 .
These findings suggest that melatonin can improve microvessel abnormalities in the cerebral cortex @ @ @ @ @ expression of vascular endothelial growth factor and its receptors , thereby improving the cognitive function @ @ @ @ @ disease .
This study was approved by the Animal Care and Use Committee of Jinzhou @ @ @ @ @ approval No .
2019015 ) on December 6 , 2018 .

Melatonin can attenuate cardiac microvascular ischemia/reperfusion injury, but it remains unclear whether melatonin can also ameliorate cerebral microvascular abnormalities. Rat models of Alzheimer's disease were established by six intracerebroventricular injections of amyloid-beta 1-42, administered once every other day. Melatonin (30 mg/kg) was intraperitoneally administered for 13 successive days, with the first dose given 24 hours prior to the first administration of amyloid-beta 1-42. Melatonin ameliorated learning and memory impairments in the Morris water maze test, improved the morphology of microvessels in the cerebral cortex and hippocampus, increased microvessel density, alleviated pathological injuries of cerebral neurons, and decreased the expression of vascular endothelial growth factor and vascular endothelial growth factor receptors 1 and 2. These findings suggest that melatonin can improve microvessel abnormalities in the cerebral cortex and hippocampus by lowering the expression of vascular endothelial growth factor and its receptors, thereby improving the cognitive function of patients with Alzheimer's disease. This study was approved by the Animal Care and Use Committee of Jinzhou Medical University, China (approval No. 2019015) on December 6, 2018.


greenmedinfo--2020-12-05--The present study is the first to demonstrate that melatonin can protect human alveolar epithelial c

The present study is the first to demonstrate that melatonin can protect human alveolar epithelial cells against oxidative stress.

BACKGROUND : Oxidative stress plays a critical role in pulmonary fibrosis after acute lung injury ( ALI ) , and epithelial-mesenchymal transition ( EMT ) events are involved in this process .
The purpose of this study was to investigate the protective effects of melatonin , a natural antioxidant , on lipopolysaccharide ( LPS ) -induced EMT in human alveolar epithelial cells .
METHODS : Human type II alveolar epithelial cell-derived A549 cells were incubated with LPS and melatonin alone or in combination for up to 24 h. The morphological changes of the treated cells were evaluated as well as @ @ @ @ @ @ @ and the Nrf2 signaling pathway were detected by western blot analysis and immunofluorescence staining , respectively .
To further investigate the underlying mechanisms , the effects of melatonin on cells transfected Nrf2 short hairpin RNA ( shRNA ) and the PI3K / GSK-3β signaling pathway were evaluated .
RESULTS : Treatment with melatonin upregulated Nrf2 expression , inhibited LPS-induced cell morphological change , reversed the expressions of EMT-related proteins , and reduced reactive oxygen species ( ROS ) production in A549 cells , as well as the levels of malondialdehyde ( MDA ) @ @ @ @ @ @ @ effects of melatonin were almost completely abolished in cells transfected Nrf2 shRNA .
Furthermore , the data demonstrated that melatonin could activate the PI3K/AKT signaling pathway , resulting in phosphorylation of GSK-3β ( Ser9 ) and upregulation of the Nrf2 protein in A549 cells , which ultimately attenuated LPS-induced EMT .
CONCLUSION : The present study is the first to demonstrate that melatonin can protect human alveolar epithelial cells against oxidative stress by effectively inhibiting LPS-induced EMT , which was mostly dependent on upregulation of the Nrf2 pathway via the PI3K/GSK-3β axis .
@ @ @ @ @ @ @ role of melatonin for the treatment of oxidative stress-associated diseases , as well as pulmonary fibrosis after ALI .

BACKGROUND: Oxidative stress plays a critical role in pulmonary fibrosis after acute lung injury (ALI), and epithelial-mesenchymal transition (EMT) events are involved in this process. The purpose of this study was to investigate the protective effects of melatonin, a natural antioxidant, on lipopolysaccharide (LPS)-induced EMT in human alveolar epithelial cells.
METHODS: Human type II alveolar epithelial cell-derived A549 cells were incubated with LPS and melatonin alone or in combination for up to 24 h. The morphological changes of the treated cells were evaluated as well as indexes of oxidative stress. EMT-related proteins and the Nrf2 signaling pathway were detected by western blot analysis and immunofluorescence staining, respectively. To further investigate the underlying mechanisms, the effects of melatonin on cells transfected Nrf2 short hairpin RNA (shRNA) and the PI3K / GSK-3β signaling pathway were evaluated.
RESULTS: Treatment with melatonin upregulated Nrf2 expression, inhibited LPS-induced cell morphological change, reversed the expressions of EMT-related proteins, and reduced reactive oxygen species (ROS) production in A549 cells, as well as the levels of malondialdehyde (MDA) and anti-oxidative enzymes. Yet, the effects of melatonin were almost completely abolished in cells transfected Nrf2 shRNA. Furthermore, the data demonstrated that melatonin could activate the PI3K/AKT signaling pathway, resulting in phosphorylation of GSK-3β (Ser9) and upregulation of the Nrf2 protein in A549 cells, which ultimately attenuated LPS-induced EMT.
CONCLUSION: The present study is the first to demonstrate that melatonin can protect human alveolar epithelial cells against oxidative stress by effectively inhibiting LPS-induced EMT, which was mostly dependent on upregulation of the Nrf2 pathway via the PI3K/GSK-3β axis. Further studies are warranted to investigate the role of melatonin for the treatment of oxidative stress-associated diseases, as well as pulmonary fibrosis after ALI.


greenmedinfo--2020-12-05--Melatonin is an effective and safe alternative for the treatment of chronic tension-type headache.

INTRODUCTION : Tension-type headache ( TTH ) is the most prevalent primary headache .
Every year , about 2-3 % of patients with TTH progress to chronic TTH with daily or near-daily headache , warranting preventive treatment .
The treatment of chronic TTH is complex and very often associated with significant tolerability issues .
To date , melatonin has been studied in only a few small uncontrolled trials .
The aim of this surveillance program was to evaluate the efficacy of melatonin ( Melaxen ) in patients with TTH and disruption of circadian rhythms in real-world practice .
METHODS : @ @ @ @ @ @ @ .
After the 30-day baseline period , patients took 3 mg of melatonin at bedtime for 30 days with a follow-up period of another 30 days .
VAS pain intensity assessments , Hamilton Anxiety Rating Scale ( HAM-A ) , Hamilton Depression Rating Scale ( HAM-D ) , HIT-6 and Levin sleep quality scores were obtained at the baseline visit , at month 1 , and month 2 .
RESULTS : A significant decrease in the number of headache days per month , VAS pain intensity , HAM-A , HAM-D and HIT-6 scores @ @ @ @ @ @ @ were observed throughout the study .
No treatment-emergent adverse events were reported .
CONCLUSIONS : Melatonin is an effective and safe alternative for the treatment of chronic TTH .

INTRODUCTION: Tension-type headache (TTH) is the most prevalent primary headache. Every year, about 2-3% of patients with TTH progress to chronic TTH with daily or near-daily headache, warranting preventive treatment. The treatment of chronic TTH is complex and very often associated with significant tolerability issues. To date, melatonin has been studied in only a few small uncontrolled trials. The aim of this surveillance program was to evaluate the efficacy of melatonin (Melaxen) in patients with TTH and disruption of circadian rhythms in real-world practice.
METHODS: Sixty-one patients with chronic TTH were enrolled. After the 30-day baseline period, patients took 3 mg of melatonin at bedtime for 30 days with a follow-up period of another 30 days. VAS pain intensity assessments, Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), HIT-6 and Levin sleep quality scores were obtained at the baseline visit, at month 1, and month 2.
RESULTS: A significant decrease in the number of headache days per month, VAS pain intensity, HAM-A, HAM-D and HIT-6 scores, and an improvement in sleep quality were observed throughout the study. No treatment-emergent adverse events were reported.
CONCLUSIONS: Melatonin is an effective and safe alternative for the treatment of chronic TTH.


greenmedinfo--2020-12-05--Melatonin supplementation in the management of obesity and obesity-associated disorders.

Despite the evolving advances in clinical approaches to obesity and its inherent comorbidities , the therapeutic challenge persists .
Among several pharmacological tools already investigated , recent studies suggest that melatonin supplementation could be an efficient therapeutic approach in the context of obesity .
In the present review , we have amalgamated the evidence so far available on physiological effects of melatonin supplementation in obesity therapies , addressing its effects upon neuroendocrine systems , cardiometabolic biomarkers and body composition .
Most studies herein appraised employed melatonin supplementation at dosages ranging from 1 to 20 mg/day , and most studies followed @ @ @ @ @ @ @ to 12 months .
Overall , it was observed that melatonin plays an important role in glycaemic homeostasis , in addition to modulation of white adipose tissue activity and lipid metabolism , and mitochondrial activity .
Additionally , melatonin increases brown adipose tissue volume and activity , and its antioxidant and anti-inflammatory properties have also been demonstrated .
There appears to be a role for melatonin in adiposity reduction ; however , several questions remain unanswered , for example melatonin baseline levels in obesity , and whether any seeming hypomelatonaemia or melatonin irresponsiveness @ @ @ @ @ @ @ studies and more thorough clinical trials are needed to ascertain not only the relevance of such findings but also the efficacy of melatonin supplementation .

Despite the evolving advances in clinical approaches to obesity and its inherent comorbidities, the therapeutic challenge persists. Among several pharmacological tools already investigated, recent studies suggest that melatonin supplementation could be an efficient therapeutic approach in the context of obesity. In the present review, we have amalgamated the evidence so far available on physiological effects of melatonin supplementation in obesity therapies, addressing its effects upon neuroendocrine systems, cardiometabolic biomarkers and body composition. Most studies herein appraised employed melatonin supplementation at dosages ranging from 1 to 20 mg/day, and most studies followed up participants for periods from 3 weeks to 12 months. Overall, it was observed that melatonin plays an important role in glycaemic homeostasis, in addition to modulation of white adipose tissue activity and lipid metabolism, and mitochondrial activity. Additionally, melatonin increases brown adipose tissue volume and activity, and its antioxidant and anti-inflammatory properties have also been demonstrated. There appears to be a role for melatonin in adiposity reduction; however, several questions remain unanswered, for example melatonin baseline levels in obesity, and whether any seeming hypomelatonaemia or melatonin irresponsiveness could be clarifying factors. Supplementation dosage studies and more thorough clinical trials are needed to ascertain not only the relevance of such findings but also the efficacy of melatonin supplementation.


greenmedinfo--2020-12-05--The results of this study showed that pre-operative melatonin administration could modify inflammato

The results of this study showed that pre-operative melatonin administration could modify inflammatory cytokines secretion such as IL-6.

OBJECTIVE : Cardiopulmonary bypass has been recognized as one of the main causes of systemic inflammatory response syndrome , leading to post-operative complications .
The aim of this study was to investigate the effect of melatonin on the serum levels of interleukin 6 ( IL-6 ) and IL-9 in patients undergoing coronary artery bypass grafting surgery .
METHODS : Forty-four patients undergoing elective coronary artery bypass surgery were randomly allocated into two study groups of melatonin ( n = 23 ) and placebo ( n = 21 ) .
Patients in the melatonin group received two melatonin tablet , 5 @ @ @ @ @ @ @ , 10 mg tablet ( two doses of 5 mg ) 1 h before induction of anesthesia and finally , 10 mg melatonin tablet in the intensive care unit , placebo group patients received placebo at the same time periods .
Serum levels of IL-9 and IL-6 were measured as baseline ( T1 ) , before induction of anesthesia ( T2 ) , 6 and 24 h after off pump ( T3 , T4 ) .
Data were analyzed using SPSS 23 software ( IBM Corp. , Armonk , NY , USA ) @ @ @ @ @ @ @ of IL-6 was significantly lower in the melatonin group at T3 and T4 ( p＜ 0.05 ) .
Also , in both groups , serum levels of IL-6 in T3 showed a significant increase compared to T1 .
Serum levels of IL-9 had no significant difference between the two groups at T1 , T2 , T3 , and T4 .
CONCLUSION : The results of this study showed that pre-operative melatonin administration could modify inflammatory cytokines secretion such as IL-6 while it has no significant effect on the serum levels of IL- 9 @ @ @ @ @ @ @ significant .

OBJECTIVE: Cardiopulmonary bypass has been recognized as one of the main causes of systemic inflammatory response syndrome, leading to post-operative complications. The aim of this study was to investigate the effect of melatonin on the serum levels of interleukin 6 (IL-6) and IL-9 in patients undergoing coronary artery bypass grafting surgery.
METHODS: Forty-four patients undergoing elective coronary artery bypass surgery were randomly allocated into two study groups of melatonin (n = 23) and placebo (n = 21). Patients in the melatonin group received two melatonin tablet, 5 mg daily for 3 days before surgery, 10 mg tablet (two doses of 5 mg) 1 h before induction of anesthesia and finally, 10 mg melatonin tablet in the intensive care unit, placebo group patients received placebo at the same time periods. Serum levels of IL-9 and IL-6 were measured as baseline (T1), before induction of anesthesia (T2), 6 and 24 h after off pump (T3, T4). Data were analyzed using SPSS 23 software (IBM Corp., Armonk, NY, USA).
RESULTS: The mean serum level of IL-6 was significantly lower in the melatonin group at T3 and T4 (p＜ 0.05). Also, in both groups, serum levels of IL-6 in T3 showed a significant increase compared to T1. Serum levels of IL-9 had no significant difference between the two groups at T1, T2, T3, and T4.
CONCLUSION: The results of this study showed that pre-operative melatonin administration could modify inflammatory cytokines secretion such as IL-6 while it has no significant effect on the serum levels of IL- 9. Neither of the changes was clinically significant.


greenmedinfo--2020-12-05--Melatonin attenuates AFB1-induced cardiotoxicity via the NLRP3 signalling pathway.

OBJECTIVE : This study was conducted to investigate the protective effect of melatonin against aflatoxin B1 ( AFB1 ) cardiotoxicity @ @ @ @ @ pyrin domain containing protein 3 ( NLRP3 ) signalling .
METHODS : Four groups of @ @ @ @ @ : control group ( vehicle only ) , two AFB1 ( 0.15 and 0.3 mg/kg @ @ @ @ @ a combined AFB1 ( 0.3 mg/kg ) plus melatonin ( 5 mg/kg ) -treated group @ @ @ @ @ once-daily intragastric treatment , cardiac pathologic changes were observed under optical microscopy , and oxidative/antioxidative @ @ @ @ @ homogenate .
Cardiac tissue expression ofand other important inflammasome components was also analysed .
RESULTS @ @ @ @ @ increasing concentrations of AFB1 were associated with increased oxidative stress and caused myocardial structure damage @ @ @ @ @ dose-dependently activated the NLRP3 signalling pathway .
All these indices were significantly ameliorated by combined @ @ @ @ @ high-dose AFB1 alone .
CONCLUSION : Melatonin may reduce NLRP3 inflammasome activation by inhibiting oxidative @ @ @ @ @ injury from AFB1-induced myocardial toxicity .

OBJECTIVE: This study was conducted to investigate the protective effect of melatonin against aflatoxin B1 (AFB1) cardiotoxicity by evaluating NOD-like receptor family pyrin domain containing protein 3 (NLRP3) signalling.
METHODS: Four groups of five rats each were assessed: control group (vehicle only), two AFB1 (0.15 and 0.3 mg/kg)-treated groups, and a combined AFB1 (0.3 mg/kg) plus melatonin (5 mg/kg)-treated group. After 6 weeks of once-daily intragastric treatment, cardiac pathologic changes were observed under optical microscopy, and oxidative/antioxidative parameters were measured in myocardial homogenate. Cardiac tissue expression ofand other important inflammasome components was also analysed.
RESULTS: Compared with controls, increasing concentrations of AFB1 were associated with increased oxidative stress and caused myocardial structure damage. In addition, AFB1 dose-dependently activated the NLRP3 signalling pathway. All these indices were significantly ameliorated by combined AFB1 plus melatonin treatment versus high-dose AFB1 alone.
CONCLUSION: Melatonin may reduce NLRP3 inflammasome activation by inhibiting oxidative stress and thus protect against injury from AFB1-induced myocardial toxicity.


greenmedinfo--2020-12-05--Melatonin provides protection against mitochondrial dysfunction in isoproterenol induced myocardial

Melatonin provides protection against mitochondrial dysfunction in isoproterenol induced myocardial injury.

Aims : Preventing mitochondrial dysfunction and enhancing mitochondrial health and biogenesis is a crucial therapeutic approach to ameliorate injury following acute myocardial infarction .
Although the antioxidant role of melatonin against ischemia/reperfusion injury has been reported , the exact mechanism of protection , , remains poorly understood .
This study aims to identify and elaborate upon mechanism of melatonin protection of rat cardiac mitochondria against acute myocardial infarction .
Main methods : Rats were pre-treated with melatonin ( 10 mg/kg body weight ( b.w . )
; intraperitoneally , i.p . )
before isoproterenol bitartrate ( ISO ) administration ( @ @ @ @ @ @ @ ) subcutaneously , s.c . )
and their effect on rat heart mitochondrial structure and function was studied .
Biochemical changes in activity of biomarkers of oxidative stress , antioxidant enzymes as well as Krebs ' cycle enzymes were analyzed .
Gene expression studies and Isothermal titration calorimetric studies with pure catalase and ISO were also carried out .
Key findings : Melatonin was shown to reduce ISO induced oxidative stress , by stimulating superoxide dismutase activity and removing the inhibition of Krebs ' cycle enzymes .
Herein we report for the first @ @ @ @ @ @ @ the SIRT1-PGC-1α-SIRT3 signaling pathways after ISO administration , which ultimately induces mitochondrial biogenesis .
Melatonin exhibited significant protection of mitochondrial architecture and topology along with increased calcium ion permeability and reactive oxygen species ( ROS ) generation induced by ISO .
Isothermal calorimetric studies revealed that melatonin binds to ISO molecules and sequesters them from the reaction thereby limiting their interaction with catalase along with occupying the binding sites of catalase themselves .
Significance : Activation of SIRT1-PGC-1α-SIRT3 pathway by melatonin along with its biophysical properties prevents ISO induced mitochondrial injury in rat @ @

Aims: Preventing mitochondrial dysfunction and enhancing mitochondrial health and biogenesis is a crucial therapeutic approach to ameliorate injury following acute myocardial infarction. Although the antioxidant role of melatonin against ischemia/reperfusion injury has been reported, the exact mechanism of protection,, remains poorly understood. This study aims to identify and elaborate upon mechanism of melatonin protection of rat cardiac mitochondria against acute myocardial infarction.
Main methods: Rats were pre-treated with melatonin (10 mg/kg body weight (b.w.); intraperitoneally, i.p.) before isoproterenol bitartrate (ISO) administration (25 mg/kg body weight (b.w.) subcutaneously,s.c.) and their effect on rat heart mitochondrial structure and function was studied. Biochemical changes in activity of biomarkers of oxidative stress, antioxidant enzymes as well as Krebs' cycle enzymes were analyzed. Gene expression studies and Isothermal titration calorimetric studies with pure catalase and ISO were also carried out.
Key findings: Melatonin was shown to reduce ISO induced oxidative stress, by stimulating superoxide dismutase activity and removing the inhibition of Krebs' cycle enzymes. Herein we report for the first time in rat model that melatonin activates the SIRT1-PGC-1α-SIRT3 signaling pathways after ISO administration, which ultimately induces mitochondrial biogenesis. Melatonin exhibited significant protection of mitochondrial architecture and topology along with increased calcium ion permeability and reactive oxygen species (ROS) generation induced by ISO. Isothermal calorimetric studies revealed that melatonin binds to ISO molecules and sequesters them from the reaction thereby limiting their interaction with catalase along with occupying the binding sites of catalase themselves.
Significance: Activation of SIRT1-PGC-1α-SIRT3 pathway by melatonin along with its biophysical properties prevents ISO induced mitochondrial injury in rat heart.


greenmedinfo--2020-12-05--Melatonin protects against tenofovir-induced nephrotoxicity.

Nephrotoxicity is a dose-limiting side effect of long-term use of tenofovir , a reverse transcriptase inhibitor that is used for the treatment of HIV infection and chronic hepatitis B infection .
Identifying an agent that prevents tenofovir disoproxil fumarate ( TDF ) -induced renal injury can lead to its better tolerance , and a more effective treatment can be achieved .
The present study is aimed at investigating whether melatonin , a potent antioxidant and anti-inflammatory agent , protects against TDF nephrotoxicity in rats and to determine its cellular targets .
Rats were divided into groups and treated as follows @ @ @ @ @ @ @ Rats in this group ( n = 6 ) received sterile water only by gavage for 35 days .
Group II : Rats ( n = 6 ) in this group received 600 mg/kg body weight TDF in sterile water by gavage for 35 days .
Group III : Rats ( n = 6 ) in this group received once daily 20 mg/kg bodyweight melatonin i.p .
2 h before the administration of 600 mg/kg body weight TDF in sterile water by gavage for 35 days .
Group IV : Rats were pretreated @ @ @ @ @ @ @ i.p .
2 h before the administration of sterile water by gavage .
All the rats were sacrificed on the 36th day , after overnight fast .
Melatonin pretreatment protected the rats against TDF nephrotoxicity both histologically and biochemically .
Biochemically , melatonin pretreatment attenuated TDF-induced , oxidative stress , nitrosative stress , mitochondrial pathway of apoptosis , PARP overactivation and preserved proximal tubular function ( p < 0.01 ) .
This suggests that melatonin may be useful in ameliorating TDF nephrotoxicity .

Nephrotoxicity is a dose-limiting side effect of long-term use of tenofovir, a reverse transcriptase inhibitor that is used for the treatment of HIV infection and chronic hepatitis B infection. Identifying an agent that prevents tenofovir disoproxil fumarate (TDF)-induced renal injury can lead to its better tolerance, and a more effective treatment can be achieved. The present study is aimed at investigating whether melatonin, a potent antioxidant and anti-inflammatory agent, protects against TDF nephrotoxicity in rats and to determine its cellular targets. Rats were divided into groups and treated as follows. Group I (control): Rats in this group (n = 6) received sterile water only by gavage for 35 days. Group II: Rats (n = 6) in this group received 600 mg/kg body weight TDF in sterile water by gavage for 35 days. Group III: Rats (n = 6) in this group received once daily 20 mg/kg bodyweight melatonin i.p. 2 h before the administration of 600 mg/kg body weight TDF in sterile water by gavage for 35 days. Group IV: Rats were pretreated daily with 20 mg/kg body weight melatonin i.p. 2 h before the administration of sterile water by gavage. All the rats were sacrificed on the 36th day, after overnight fast. Melatonin pretreatment protected the rats against TDF nephrotoxicity both histologically and biochemically. Biochemically, melatonin pretreatment attenuated TDF-induced, oxidative stress, nitrosative stress, mitochondrial pathway of apoptosis, PARP overactivation and preserved proximal tubular function (p<0.01). This suggests that melatonin may be useful in ameliorating TDF nephrotoxicity.


greenmedinfo--2020-12-05--Melatonin ameliorates Bisphenol S induced testicular damages.

BPS has detrimental effects on human reproductive health and emerged as an environmental contaminant for global health concern .
This study deals with the adverse impact of BPS exposure on testicular oxidative stress , inflammation and apoptosis in adult male golden hamster , Mesocricetus auratus and its amelioration by melatonin .
BPS ( 75 mg/kg BW/day ) exposure caused testicular impairment as evident by histological degenerative changes , declined sperm quality ( viability and motility ) , serum levels of testosterone and melatonin with a concomitant decrease in testicular androgen receptor ( AR ) and melatonin receptor ( MT1 ) @ @ @ @ @ @ @ increase in testicular oxidative load , inflammation ( NF-kB/COX-2 ) and apoptosis ( caspase-3 ) .
Melatonin ( 10 mg/kg BW/alternate day ) pretreatment to BPS exposed hamsters resumed normal testicular histoarchitecture , sperm quality and decreased testicular oxidative loadas evident by enhanced antioxidant enzymes ( SOD and catalase ) activities and decreased lipid peroxidation ( LPO ) level .
Further , melatonin also stimulated the testicular antioxidant proteins Nrf-2/HO-1 , SIRT-1/FOXO-1 and reduced inflammatory proteins NF-kB/COX-2 expression to counteract BPS induced testicular damages .
Melatonin administration to the BPS treated hamsters resulted @ @ @ @ @ @ @ ) , survival ( Bcl-2 ) , gap junction ( connexin-43 ) and decreased apoptosis ( caspase-3 ) .
In conclusion , our study documented the detrimental effects of BPS on testes that compromises male fertility .
Further , melatonin was found as a potent molecule that rescued the BPS induced testicular damages in male golden hamster Mesocricetus auratus .

BPS has detrimental effects on human reproductive health and emerged as an environmental contaminant for global health concern. This study deals with the adverse impact of BPS exposure on testicular oxidative stress, inflammation and apoptosis in adult male golden hamster, Mesocricetus auratus and its amelioration by melatonin. BPS (75 mg/kg BW/day) exposure caused testicular impairment as evident by histological degenerative changes, declined sperm quality (viability and motility), serum levels of testosterone and melatonin with a concomitant decrease in testicular androgen receptor (AR) and melatonin receptor (MT1) expression. The BPS exposure caused marked increase in testicular oxidative load, inflammation (NF-kB/COX-2) and apoptosis (caspase-3). Melatonin (10 mg/kg BW/alternate day) pretreatment to BPS exposed hamsters resumed normal testicular histoarchitecture, sperm quality and decreased testicular oxidative loadas evident by enhanced antioxidant enzymes (SOD and catalase) activities and decreased lipid peroxidation (LPO) level. Further, melatonin also stimulated the testicular antioxidant proteins Nrf-2/HO-1, SIRT-1/FOXO-1 and reduced inflammatory proteins NF-kB/COX-2 expression to counteract BPS induced testicular damages. Melatonin administration to the BPS treated hamsters resulted in increased testicular cell proliferation (PCNA), survival (Bcl-2), gap junction (connexin-43) and decreased apoptosis (caspase-3). In conclusion, our study documented the detrimental effects of BPS on testes that compromises male fertility. Further, melatonin was found as a potent molecule that rescued the BPS induced testicular damages in male golden hamster Mesocricetus auratus.


greenmedinfo--2020-12-05--Melatonin prevents brain damage and neurocognitive impairment induced by Plasmodium Berghei ANKA inf

Melatonin prevents brain damage and neurocognitive impairment induced by Plasmodium Berghei ANKA infection.

Cerebral malaria is characterized by permanent cognitive impairments in-infected children .
Antimalarial therapies show little effectiveness to avoid neurological deficits @ @ @ @ @ by severe malaria .
Melatonin is a well-recognized endogenous hormone involved in the control of @ @ @ @ @ blood-brain barrier integrity .
The current study has evaluated the effect of melatonin on the @ @ @ @ @ leakage , and neurocognitive impairments in mice developing cerebral malaria .
Swiss mice infected withANKA @ @ @ @ @ malaria model .
Melatonin treatment ( 5 and 10 mg/kg ) was performed for four @ @ @ @ @ , and data have shown an increased survival rate in infected mice treated with melatonin @ @ @ @ @ that melatonin treatment blocked brain edema and prevented the breakdown of blood-brain barrier induced by @ @ @ @ @ and eosin staining revealed that melatonin mitigates the histological alterations in-infected animals .
Melatonin was @ @ @ @ @ and cognitive impairments in infected mice .
Taken together , these results show for the @ @ @ @ @ prevents histological brain damages and neurocognitive alterations induced by cerebral malaria .

Cerebral malaria is characterized by permanent cognitive impairments in-infected children. Antimalarial therapies show little effectiveness to avoid neurological deficits and brain tissue alterations elicited by severe malaria. Melatonin is a well-recognized endogenous hormone involved in the control of brain functions and maintenance of blood-brain barrier integrity. The current study has evaluated the effect of melatonin on the histological alterations, blood-brain barrier leakage, and neurocognitive impairments in mice developing cerebral malaria. Swiss mice infected withANKA strain was used as cerebral malaria model. Melatonin treatment (5 and 10 mg/kg) was performed for four consecutive days after the infection, and data have shown an increased survival rate in infected mice treated with melatonin. It was also observed that melatonin treatment blocked brain edema and prevented the breakdown of blood-brain barrier induced by theinfection. Furthermore, hematoxylin and eosin staining revealed that melatonin mitigates the histological alterations in-infected animals. Melatonin was also able to prevent motor and cognitive impairments in infected mice. Taken together, these results show for the first time that melatonin treatment prevents histological brain damages and neurocognitive alterations induced by cerebral malaria.


greenmedinfo--2020-12-05--Melatonin prevents lysosomal destruction of liver tissue.

The study establishes a link between alcoholism , inflammation state , and melatonin synthesis .
The aim of our study was to evaluate the effects of melatonin on changes in the relationships between oxygen consumption ( using NADH- or FAD-generated substrates of mitochondrial respiration ) , activities of lysosomal enzymes , such as alanyl aminopeptidase ( AAP ) , leucyl aminopeptidase ( LAP ) , β-N-acetylglucosaminidase ( NAG ) , and acid phosphatase ( AcP ) , biomarkers of oxidative stress estimated by the 2-thiobarbituric acid reactive substance ( TBARS ) level as a biomarker of lipid peroxidation , carbonyl @ @ @ @ @ @ @ , and biomarkers of energy metabolism during acute ethanol-induced stress ( AES ) , and a low-dose lipopolysaccharide ( LPS ) -induced inflammatory responses in mice .
Biochemical assays of lysosomal enzymes , biomarkers of oxidative stress , and parameters of energy metabolism ( activities of alanine- and aspartate aminotransferases , succinate dehydrogenase , levels of lactate and pyruvate ) were carried out in eight groups : 1 ) untreated control , 2 ) melatonin treatment ( Mel , 10 mg/kg b.w.
, 10 days ) , 3 ) acute ethanol-induced stress ( @ @ @ @ @ @ @ days ) , 4 ) AES model with previous Mel treatment ( 10 mg/kg b.w.
, 10 days ) , 5 ) LPS-induced inflammation ( injected once intraperitoneally , 150 μg/mouse ) , 6 ) LPS-induced inflammation with previous Mel treatment ( 10 mg/kg b.w.
, 10 days ) , 7 ) LPS-induced inflammation with AES model , 8 ) LPS-induced inflammation with AES model and Mel treatment ( 10 mg/kg b.w.
, 10 days ) .
Oxidativestress caused by acute ethanol-induced intoxication and low-dose LPS-induced inflammation lead to structural and functional impairments @ @ @ @ @ @ @ prominent in kidneys than liver .
Melatonin treatment had significant effects on mitochondrial oxidation of the NADH-generated substrate , and it also decreased mitochondrial ability to oxidize FAD-generated substrate and mitochondrial coupling in both LPS- and AES-induced oxidative stress .
Melatonin exerts significant effect on the oxidation of the NAD-generated substrates .
The increased lipid peroxidation and De Ritis ratio suggest damage to intracellular membrane integrity with combined effects of ethanol and LPS-induced toxicity , which can potentially result in irreversible tissue damage .
Melatonin prevents lysosomal destruction of liver tissue and , @ @ @ @ @ @ @ AES with simultaneous LPS exposure by limiting increased activity of lysosomal enzymes and resulting oxidative stress .

The study establishes a link between alcoholism, inflammation state, and melatonin synthesis. The aim of our study was to evaluate the effects of melatonin on changes in the relationships between oxygen consumption (using NADH- or FAD-generated substrates of mitochondrial respiration), activities of lysosomal enzymes, such as alanyl aminopeptidase (AAP), leucyl aminopeptidase (LAP),β-N-acetylglucosaminidase (NAG), and acid phosphatase (AcP), biomarkers of oxidative stress estimated by the 2-thiobarbituric acid reactive substance (TBARS) level as a biomarker of lipid peroxidation, carbonyl derivatives as biomarkers of oxidatively protein damage, and biomarkers of energy metabolism during acute ethanol-induced stress (AES), and a low-dose lipopolysaccharide (LPS)-induced inflammatory responses in mice. Biochemical assays of lysosomal enzymes, biomarkers of oxidative stress, and parameters of energy metabolism (activities of alanine- and aspartate aminotransferases, succinate dehydrogenase, levels of lactate and pyruvate) were carried out in eight groups: 1) untreated control, 2) melatonin treatment (Mel, 10 mg/kg b.w., 10 days), 3) acute ethanol-induced stress (AES, 0.75 g/kg b.w., 10 days), 4) AES model with previous Mel treatment (10 mg/kg b.w., 10 days), 5) LPS-induced inflammation (injected once intraperitoneally, 150 μg/mouse), 6) LPS-induced inflammation with previous Mel treatment (10 mg/kg b.w., 10 days), 7) LPS-induced inflammation with AES model, 8) LPS-induced inflammation with AES model and Mel treatment (10 mg/kg b.w., 10 days). Oxidativestress caused by acute ethanol-induced intoxication and low-dose LPS-induced inflammation lead to structural and functional impairments, with alterations in oxygen consumption more prominent in kidneys than liver. Melatonin treatment had significant effects on mitochondrial oxidation of the NADH-generated substrate, and it also decreased mitochondrial ability to oxidize FAD-generated substrate and mitochondrial coupling in both LPS- and AES-induced oxidative stress. Melatonin exerts significant effect on the oxidation of the NAD-generated substrates. The increased lipid peroxidation and De Ritis ratio suggest damage to intracellular membrane integrity with combined effects of ethanol and LPS-induced toxicity, which can potentially result in irreversible tissue damage. Melatonin prevents lysosomal destruction of liver tissue and, to greater extent, kidney tissue during AES with simultaneous LPS exposure by limiting increased activity of lysosomal enzymes and resulting oxidative stress.


greenmedinfo--2020-12-05--Role of melatonin in periodontal disease.

Background and Aims : Melatonin is an indolamine that is primarily secreted by the pineal gland .
It has immunomodulatory as well as antioxidant properties .
It is a potent anti-oxidant that protects against inflammation and cellular damage caused by reactive oxygen species , also has potent angiogenic function that adds on to the benefits of melatonin .
As a result of these actions , melatonin may be useful as an adjuvant in the treatment of various conditions in the oral cavity .
The aim of this study is to systematically evaluate the role of melatonin in periodontal disease .
@ @ @ @ @ @ @ scientific literature was carried out using PubMed , Science Direct , Google Scholar and the Cochrane base .
Research articles were collected upto December 2017 .
Results : Melatonin may have beneficial effects in certain inflammatory oral pathologies , mainly periodontal diseases where they inhibit bone resorption destroy reactive oxygen species , stimulates osteoblastic differentiation .
Salivary melatonin could also act as a risk indicator for periodontal diseases .
Conclusion : Many studies showed that the melatonin levels in GCF , Saliva , Serum of patients suffering from chronic periodontitis is lowered suggesting @ @ @ @ @ @ @ protecting the tissue from damage caused by oxidative stress .
However , there exists no data on the concentration needed , method of application for potential benefits .
Randomized clinical trials in this field are needed to fill the lacunae and better improve our understanding .

Background and Aims: Melatonin is an indolamine that is primarily secreted by the pineal gland. It has immunomodulatory as well as antioxidant properties. It is a potent anti-oxidant that protects against inflammation and cellular damage caused by reactive oxygen species, also has potent angiogenic function that adds on to the benefits of melatonin. As a result of these actions, melatonin may be useful as an adjuvant in the treatment of various conditions in the oral cavity. The aim of this study is to systematically evaluate the role of melatonin in periodontal disease.
Methods: An extensive review of the scientific literature was carried out using PubMed, Science Direct, Google Scholar and the Cochrane base. Research articles were collected upto December 2017.
Results: Melatonin may have beneficial effects in certain inflammatory oral pathologies, mainly periodontal diseases where they inhibit bone resorption destroy reactive oxygen species, stimulates osteoblastic differentiation. Salivary melatonin could also act as a risk indicator for periodontal diseases.
Conclusion: Many studies showed that the melatonin levels in GCF, Saliva, Serum of patients suffering from chronic periodontitis is lowered suggesting that may play a pivotal role in protecting the tissue from damage caused by oxidative stress. However, there exists no data on the concentration needed, method of application for potential benefits. Randomized clinical trials in this field are needed to fill the lacunae and better improve our understanding.


greenmedinfo--2020-12-05--Protection of melatonin against long-term radon exposure-caused lung injury.

Radon is one of the major pathogenic factors worldwide .
Recently , epidemiological studies have suggested that radon exposure plays @ @ @ @ @ injury , which could further cause cancer .
However , the toxic effects and underlying @ @ @ @ @ still not clear .
Here , we identified the detailed toxic effects of long-term radon @ @ @ @ @ manifestations were inflammatory response and cell apoptosis in dose- and time-dependent manners .
In detail @ @ @ @ @ dysfunction and oxidative stress as determined by the abnormal levels of mitochondrial DNA copy number @ @ @ @ @ membrane potential , superoxide dismutase , and cycloxygenase-2 .
Furthermore , we found that melatonin @ @ @ @ @ attenuated the levels of oxidative stress caused by long-term radon exposure , which could further @ @ @ @ @ as determined by the decreased levels of cleaved caspase 3 .
Our study would provide @ @ @ @ @ on lung tissue injury caused by long-term radon exposure .

Radon is one of the major pathogenic factors worldwide. Recently, epidemiological studies have suggested that radon exposure plays an important role in lung injury, which could further cause cancer. However, the toxic effects and underlying mechanism on lung injury are still not clear. Here, we identified the detailed toxic effects of long-term radon exposure. Specifically, the manifestations were inflammatory response and cell apoptosis in dose- and time-dependent manners. In detail, it caused the mitochondrial dysfunction and oxidative stress as determined by the abnormal levels of mitochondrial DNA copy number, adenosine triphosphate, mitochondrial membrane potential, superoxide dismutase, and cycloxygenase-2. Furthermore, we found that melatonin treatment ameliorated mitochondrial dysfunction and attenuated the levels of oxidative stress caused by long-term radon exposure, which could further inhibit the lung tissue apoptosis as determined by the decreased levels of cleaved caspase 3. Our study would provide potential therapeutic application of melatonin on lung tissue injury caused by long-term radon exposure.


greenmedinfo--2020-12-05--Melatonin is a promising molecule for the treatment of perinatal asphyxia.

Hypoxic-ischemic encephalopathy ( HIE ) is the main cause of long-term neurodevelopmental morbidity in term born infants worldwide .
Melatonin @ @ @ @ @ and anti-inflammatory effects that make it a promising molecule for the treatment of perinatal asphyxia @ @ @ @ @ use of hypothermia associated with melatonin treatment may improve the neurological outcome in infants with @ @ @ @ @ 20 years , the efficacy of melatonin in reducing oxidative stress has been demonstrated in @ @ @ @ @ trials with sufficient sample size of newborns are lacking to date.Since in 2000 we were @ @ @ @ @ the neuroprotective properties of melatonin on infants , in this review , we want to @ @ @ @ @ of the investigations conducted to date .
KEY POINTS : · HIE is the main @ @ @ @ @ born infants worldwide.. · Melatonin is a promising molecule for the treatment of perinatal asphyxia.. @ @ @ @ @ and limitations of the investigations conducted on melatonin..

Hypoxic-ischemic encephalopathy (HIE) is the main cause of long-term neurodevelopmental morbidity in term born infants worldwide. Melatonin is a hormone with antioxidant and anti-inflammatory effects that make it a promising molecule for the treatment of perinatal asphyxia. Probably, the synergistic use of hypothermia associated with melatonin treatment may improve the neurological outcome in infants with HIE. In the past 20 years, the efficacy of melatonin in reducing oxidative stress has been demonstrated in animals; however, clinical trials with sufficient sample size of newborns are lacking to date.Since in 2000 we were among the first to study the neuroprotective properties of melatonin on infants, in this review, we want to summarize the advantages and limitations of the investigations conducted to date. KEY POINTS:· HIE is the main cause of morbidity in term born infants worldwide.. · Melatonin is a promising molecule for the treatment of perinatal asphyxia.. · This review summarizes advantages and limitations of the investigations conducted on melatonin..


greenmedinfo--2020-12-05--Melatonin may be a promising anticancer agent for the treatment of human tongue squamous cell carcin

BACKGROUND/AIM : The global prevalence of head and neck squamous cell carcinoma ( HNSCC ) remains high , and its @ @ @ @ @ the anticancer effects of melatonin in human tongue squamous cell carcinoma cells ( SCC-25 ) @ @ @ @ @ .
MATERIALS AND METHODS : MTT assay was used to determine cell viability .
To @ @ @ @ @ on SCC-25 cell metastasis , we conducted cell formation , wound healing , transwell migration @ @ @ @ @ blot analysis was performed to measure the levels of autophage marker proteins .
RESULTS : @ @ @ @ @ significantly reduced the viability and colony formation ability of SCC-25 cells , impairing cell migration @ @ @ @ @ assay revealed that melatonin increased the levels of autophagy markers , such as LC-3B and @ @ @ @ @ induces autophage in SCC-25 cells .
CONCLUSION : Melatonin may be a promising anticancer agent @ @ @ @ @ tongue squamous cell carcinoma .

BACKGROUND/AIM: The global prevalence of head and neck squamous cell carcinoma (HNSCC) remains high, and its prognosis poor. We investigated the anticancer effects of melatonin in human tongue squamous cell carcinoma cells (SCC-25) and its mechanisms of action.
MATERIALS AND METHODS: MTT assay was used to determine cell viability. To assess the effects of melatonin on SCC-25 cell metastasis, we conducted cell formation, wound healing, transwell migration and invasion assay. Western blot analysis was performed to measure the levels of autophage marker proteins.
RESULTS: We found that melatonin treatment significantly reduced the viability and colony formation ability of SCC-25 cells, impairing cell migration and invasion. Western blotting assay revealed that melatonin increased the levels of autophagy markers, such as LC-3B and Beclin-1. Consequently, melatonin induces autophage in SCC-25 cells.
CONCLUSION: Melatonin may be a promising anticancer agent for the treatment of human tongue squamous cell carcinoma.


greenmedinfo--2020-12-05--Melatonin increases overall survival of prostate cancer patients with poor prognosis after combined

Melatonin increases overall survival of prostate cancer patients with poor prognosis after combined hormone radiation treatment.

BACKGROUND : The antitumor and immunomodulating activities of melatonin are widely known .
These activities are based upon the multifactorial mechanism of action on various links of carcinogenesis .
In the present paper , the long-term results of the clinical use of melatonin in the combined treatment of patients with prostate cancer of various risk groups were evaluated .
MATERIALS AND METHODS : A retrospective study included 955 patients of various stages of prostate cancer ( PCa ) who received combined hormone radiation treatment from 2000 to 2019 .
Comprehensive statistical methods were used to analyze the overall survival rate @ @ @ @ @ @ @ various prognosis groups .
RESULTS : The overall survival rate of PCa patients with favorable and intermediate prognoses treated or not treated with melatonin was not statistically significantly different .
In the poor prognosis group , the median overall survival in patients taking the drug was 153.5 months versus 64.0 months in patients not using it ( < 0.0001 ) .
The 5-year overall survival rates in the research and control groups were 66.8± 1.9 and 53.7 ± 2.6 ( < 0.0001 ) respectively .
In a multivariate analysis , melatonin administration proved @ @ @ @ @ @ @ reduced the risk of death of PCa patients by more than twice ( < 0.0001 ) .
CONCLUSIONS : The multicomponent antitumor effect of melatonin is fully realized and clearly demonstrated in treatment of PCa patients with poor prognosis with a set of unfavorable factors of the tumor progression .

BACKGROUND: The antitumor and immunomodulating activities of melatonin are widely known. These activities are based upon the multifactorial mechanism of action on various links of carcinogenesis. In the present paper, the long-term results of the clinical use of melatonin in the combined treatment of patients with prostate cancer of various risk groups were evaluated.
MATERIALS AND METHODS: A retrospective study included 955 patients of various stages of prostate cancer (PCa) who received combined hormone radiation treatment from 2000 to 2019. Comprehensive statistical methods were used to analyze the overall survival rate of PCa patients treated with melatonin in various prognosis groups.
RESULTS: The overall survival rate of PCa patients with favorable and intermediate prognoses treated or not treated with melatonin was not statistically significantly different. In the poor prognosis group, the median overall survival in patients taking the drug was 153.5 months versus 64.0 months in patients not using it (<0.0001). The 5-year overall survival rates in the research and control groups were 66.8± 1.9 and 53.7 ± 2.6 (<0.0001) respectively. In a multivariate analysis, melatonin administration proved to be an independent prognostic factor and reduced the risk of death of PCa patients by more than twice (<0.0001).
CONCLUSIONS: The multicomponent antitumor effect of melatonin is fully realized and clearly demonstrated in treatment of PCa patients with poor prognosis with a set of unfavorable factors of the tumor progression.


greenmedinfo--2020-12-05--Aluminum chloride-induced amyloid β accumulation and endoplasmic reticulum stress in rat brain are a

Aluminum chloride-induced amyloid β accumulation and endoplasmic reticulum stress in rat brain are averted by melatonin.

Accumulation of aluminium ( Al ) in the brain is known to be a toxic insult that result in neurodegenerative diseases and melatonin is known to have neuroprotective role .
The present study was designed to investigate the neuroprotective effects of melatonin for aluminium chloride ( AlCl ) -induced neurotoxicity in rats .
Twelve-week old male Wistar rats were orally received 175 mg/kg AlClwith or without 5 mg/kg melatonin intraperitoneal pretreatment .
Group 3 intraperitoneally recieved 5 mg/kg melatonin and group 4 rats were orally treated with saline solution for 8 weeks .
A series of behavioral tests , biochemical @ @ @ @ @ @ @ the brain were determined after7 weeks of all treatments .
Our results indicated that AlCltreatment tends to induce memory and cognitive impairment .
However , melatonin treatment attenuated amyloid beta ( Aβ ) ( 1-42 ) level by decreasing β-secretase , augmented low-density lipoprotein receptor-related protein 1 , and neprilysin protein expression .
Moreover , AlCl-induced endoplasmic reticulum ( ER ) stress and oxidative stress was attenuated by melatonin supplementation .
In conclusion , these findings demonstrate a protective role of melatonin against Aβ peptide accumulation , ER stress and oxidative stress in @ @ @ @ @ @ @ the melatonin supplement might be an alternative way to alleviate the development of AD .

Accumulation of aluminium (Al) in the brain is known to be a toxic insult that result in neurodegenerative diseases and melatonin is known to have neuroprotective role. The present study was designed to investigate the neuroprotective effects of melatonin for aluminium chloride (AlCl)-induced neurotoxicity in rats. Twelve-week old male Wistar rats were orally received 175 mg/kg AlClwith or without 5 mg/kg melatonin intraperitoneal pretreatment. Group 3 intraperitoneally recieved 5 mg/kg melatonin and group 4 rats were orally treated with saline solution for 8 weeks. A series of behavioral tests, biochemical analysis and expression of AD-associated proteins in the brain were determined after7 weeks of all treatments. Our results indicated that AlCltreatment tends to induce memory and cognitive impairment. However, melatonin treatment attenuated amyloid beta (Aβ) (1-42) level by decreasing β-secretase, augmented low-density lipoprotein receptor-related protein 1, and neprilysin protein expression. Moreover, AlCl-induced endoplasmic reticulum (ER) stress and oxidative stress was attenuated by melatonin supplementation. In conclusion, these findings demonstrate a protective role of melatonin against Aβ peptide accumulation, ER stress and oxidative stress in the AlCl-treated AD model. Hence, the melatonin supplement might be an alternative way to alleviate the development of AD.


greenmedinfo--2020-12-05--Light at night exposure was consistently associated with higher breast cancer risk.

BACKGROUND : With the unprecedented urbanization light pollution has emerged as a ubiquitous problem , and there has been accumulating evidence on the links between exposure to light at night ( LAN ) and breast cancer risk .
We conducted a systematic review and meta-analysis of published studies on the associations between LAN exposure and breast cancer risk .
METHODS : We included all observational human studies wherein the exposure variable was LAN measured in indoor and outdoor environments , and the outcome was breast cancer .
We employed summary relative risks ( SRR ) for breast cancer by comparing @ @ @ @ @ @ @ within a random-effects model .
The National Toxicology Program 's ( NTP ) Office of Health Assessment and Translation ( OHAT ) risk of bias rating tool was adopted to assess the risk of bias in individual studies and the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) guideline was employed to assess confidence in the body of evidence .
RESULTS : A total 14 studies comprising four cohorts ( 13,155 cases among 372,802 exposed subjects ) , nine case-control and one case-referent studies of female subjects ( 39,462 cases @ @ @ @ @ @ @ and published between 2001 and 20 were included for review .
Participants in the highest LAN exposure category were associated with higher risk of breast cancer in reference to those in the lowest ( SRR : 1.12 ; 95 % CI : 1.06-1.18 ; I = 39 % for outdoor LAN , and SRR : 1.13 ; 95 % CI : 1.05-1.21 ; I = 19 % for indoor LAN ) .
Pooled evidence identified relatively pronounced association of outdoor LAN exposure and breast cancer among women with estrogen receptor positive ( ER+ @ @ @ @ @ @ @ 95 % CI : 1.04-1.40 ) and premenopausal status ( SRR : 1.21 ; 95 % CI : 1.06-1.37 ) .
The final rate of confidence in the body of evidence generated was graded as 'moderate ' based on GRADE guideline .
DISCUSSION : LAN exposure was consistently associated with higher breast cancer risk corroborating NTP 's recommendations which anticipates excessive LAN as human carcinogen .

BACKGROUND: With the unprecedented urbanization light pollution has emerged as a ubiquitous problem, and there has been accumulating evidence on the links between exposure to light at night (LAN) and breast cancer risk. We conducted a systematic review and meta-analysis of published studies on the associations between LAN exposure and breast cancer risk.
METHODS: We included all observational human studies wherein the exposure variable was LAN measured in indoor and outdoor environments, and the outcome was breast cancer. We employed summary relative risks (SRR) for breast cancer by comparing highest versus lowest categories of LAN exposure within a random-effects model. The National Toxicology Program's (NTP) Office of Health Assessment and Translation (OHAT) risk of bias rating tool was adopted to assess the risk of bias in individual studies and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guideline was employed to assess confidence in the body of evidence.
RESULTS: A total 14 studies comprising four cohorts (13,155 cases among 372,802 exposed subjects), nine case-control and one case-referent studies of female subjects (39,462 cases and 20,739 controls) across seven countries and published between 2001 and 20 were included for review. Participants in the highest LAN exposure category were associated with higher risk of breast cancer in reference to those in the lowest (SRR: 1.12; 95% CI: 1.06-1.18; I = 39% for outdoor LAN, and SRR: 1.13; 95%CI: 1.05-1.21; I = 19% for indoor LAN). Pooled evidence identified relatively pronounced association of outdoor LAN exposure and breast cancer among women with estrogen receptor positive (ER+) tumor (SRR: 1.21; 95% CI: 1.04-1.40) and premenopausal status (SRR: 1.21; 95% CI: 1.06-1.37). The final rate of confidence in the body of evidence generated was graded as 'moderate' based on GRADE guideline.
DISCUSSION: LAN exposure was consistently associated with higher breast cancer risk corroborating NTP's recommendations which anticipates excessive LAN as human carcinogen.


greenmedinfo--2020-12-05--Melatonin had a significant biochemical antioxidant effect and histological renoprotective effect.

Objectives : Diabetes mellitus is associated with oxidative stress that leads to inflammation and diabetic nephropathy .
This study aimed to determine the possible renoprotective effects of the antioxidants melatonin , vitamin D and vitamin E in diabetic rats .
Methods : We divided 108 albino rats into 12 groups.group was fed a normal diet and did not receive any medication.toconsisted of non-diabetic rats that were treated as follows : with melatonin ; with vitamin E ; with vitamin D. Groupstoconsisted of diabetic rats that were treated as follows : received no medication ; treated with insulin ; treated with @ @ @ @ @ @ @ ; treated with vitamin E ; treated with vitamin E and insulin ; treated with vitamin D andtreated with vitamin D and insulin .
Two months after treatment commenced , histological and biochemical examinations of glucose profile , oxidative stress status , renal function , homocysteine and TNF-α were performed .
Results : Total antioxidant capacity ( TAC ) increased significantly in groups G2 , 7 , 8 , 10 and 11 .
TNF-α significantly increased in G2 , but decreased in all other groups .
Creatinine increased significantly in groups G5 , @ @ @ @ @ @ @ , 11 and 12 .
In the kidneys of the diabetic rats , thickened capillary basement membrane , diffuse mesangial sclerosis and nodular glomerulosclerosis was observed .
Rats treated with melatonin showed marked improvement in these symptoms .
However , in those treated with vitamin D and E , thickened capillary basement membrane and mesangial sclerosis was still present .
Conclusions : Melatonin , administered either with or without insulin had a significant biochemical antioxidant effect and histological renoprotective effect .
Conversely , vitamin D and E did not appear to have any @ @ @ @ @ @

Objectives: Diabetes mellitus is associated with oxidative stress that leads to inflammation and diabetic nephropathy. This study aimed to determine the possible renoprotective effects of the antioxidants melatonin, vitamin D and vitamin E in diabetic rats.
Methods: We divided 108 albino rats into 12 groups.group was fed a normal diet and did not receive any medication.toconsisted of non-diabetic rats that were treated as follows:with melatonin;with vitamin E;with vitamin D. Groupstoconsisted of diabetic rats that were treated as follows:received no medication;treated with insulin;treated with melatonin;treated with melatonin and insulin;treated with vitamin E;treated with vitamin E and insulin;treated with vitamin D andtreated with vitamin D and insulin. Two months after treatment commenced, histological and biochemical examinations of glucose profile, oxidative stress status, renal function, homocysteine and TNF-α were performed.
Results: Total antioxidant capacity (TAC) increased significantly in groups G2, 7, 8, 10 and 11. TNF-α significantly increased in G2, but decreased in all other groups. Creatinine increased significantly in groups G5, 6, 7, 8, 9, 11 and 12. In the kidneys of the diabetic rats, thickened capillary basement membrane, diffuse mesangial sclerosis and nodular glomerulosclerosis was observed. Rats treated with melatonin showed marked improvement in these symptoms. However, in those treated with vitamin D and E, thickened capillary basement membrane and mesangial sclerosis was still present.
Conclusions: Melatonin, administered either with or without insulin had a significant biochemical antioxidant effect and histological renoprotective effect. Conversely, vitamin D and E did not appear to have any effects on the parameters measured.


greenmedinfo--2020-12-05--The protective effects of melatonin on aluminum-induced hepatotoxicity and nephrotoxicity in rats.

Aluminum ( Al ) is a ubiquitous element with known toxicity for both humans and animals .
Herein , we aimed to investigate the potential role of melatonin ( MEL ) in hepatotoxicity and nephrotoxicity following aluminum chloride ( AlCl ) treatment in rats .
Adult male rats were treated with AlCl ( 34 mg/kg bwt ) for eight weeks .
Exposure to AlClenhanced the serum activities of the liver transaminases ( alanine aminotransferase and aspartate aminotransferase ) and increased the level of bilirubin , in addition to the serum kidney function markers urea and creatinine .
AlClintoxication boosted oxidative @ @ @ @ @ @ @ the levels of lipid peroxidation ( LPO ) and nitric oxide ( NO ) along with simultaneous decreases in the levels of glutathione ( GSH ) , various antioxidant enzymes , andmRNA expression .
MEL ( 5 mg/kg bwt ) treatment repressed LPO and NO levels , whereas it augmented GSH content .
The activities of the antioxidant enzymes GPx , SOD , CAT , and GR were also restored concomitantly when MEL was administered before AlCl .
MEL also suppressed the apoptotic effect of AlClby enhancing Bcl-2 protein expression in the liver @ @ @ @ @ @ @ of proinflammatory cytokines .
Histopathological findings in the liver and kidney tissues confirmed the beneficial effect of MEL against AlCltoxicity .
These findings indicate that MEL prevents AlCltoxicity by enhancing the antioxidant defense system .

Aluminum (Al) is a ubiquitous element with known toxicity for both humans and animals. Herein, we aimed to investigate the potential role of melatonin (MEL) in hepatotoxicity and nephrotoxicity following aluminum chloride (AlCl) treatment in rats. Adult male rats were treated with AlCl(34 mg/kg bwt) for eight weeks. Exposure to AlClenhanced the serum activities of the liver transaminases (alanine aminotransferase and aspartate aminotransferase) and increased the level of bilirubin, in addition to the serum kidney function markers urea and creatinine. AlClintoxication boosted oxidative stress, as evidenced by increases in the levels of lipid peroxidation (LPO) and nitric oxide (NO) along with simultaneous decreases in the levels of glutathione (GSH), various antioxidant enzymes, andmRNA expression. MEL (5 mg/kg bwt) treatment repressed LPO and NO levels, whereas it augmented GSH content. The activities of the antioxidant enzymes GPx, SOD, CAT, and GR were also restored concomitantly when MEL was administered before AlCl. MEL also suppressed the apoptotic effect of AlClby enhancing Bcl-2 protein expression in the liver and kidney and decreasing the expression levels of proinflammatory cytokines. Histopathological findings in the liver and kidney tissues confirmed the beneficial effect of MEL against AlCltoxicity. These findings indicate that MEL prevents AlCltoxicity by enhancing the antioxidant defense system.


greenmedinfo--2020-12-05--Ischemic stroke, obesity, and the anti-inflammatory role of melatonin.

Obesity is a predominant risk factor in ischemic stroke and is commonly comorbid with it .
Pathologies following these conditions @ @ @ @ @ local inflammation .
Moreover , there is increasing evidence that the susceptibility for ischemic brain @ @ @ @ @ models of ischemic stroke with concomitant obesity .
Herein , we explore the proinflammatory events @ @ @ @ @ and obesity , and we discuss the influence of obesity on the inflammatory response and @ @ @ @ @ models of brain ischemia .
In addition , because melatonin is a neurohormone widely reported @ @ @ @ @ various diseases , this study also demonstrates the anti-inflammatory role and possible mechanistic actions of @ @ @ @ @ .
A summary of research findings suggests that melatonin administration has great potential to exert @ @ @ @ @ protection against obesity and ischemic stroke conditions .
However , the efficacy of this hormonal @ @ @ @ @ concomitant obesity , when more serious inflammation is generated , is still lacking .

Obesity is a predominant risk factor in ischemic stroke and is commonly comorbid with it. Pathologies following these conditions are associated with systemic and local inflammation. Moreover, there is increasing evidence that the susceptibility for ischemic brain damage increases substantially in experimental models of ischemic stroke with concomitant obesity. Herein, we explore the proinflammatory events that occur during ischemic stroke and obesity, and we discuss the influence of obesity on the inflammatory response and cerebral damage outcomes in experimental models of brain ischemia. In addition, because melatonin is a neurohormone widely reported to exhibit protective effects in various diseases, this study also demonstrates the anti-inflammatory role and possible mechanistic actions of melatonin in both epidemic diseases. A summary of research findings suggests that melatonin administration has great potential to exert an anti-inflammatory role and provide protection against obesity and ischemic stroke conditions. However, the efficacy of this hormonal treatment on ischemic stroke with concomitant obesity, when more serious inflammation is generated, is still lacking.


greenmedinfo--2020-12-05--Melatonin exerts immunoregulatory effects by balancing peripheral effector and regulatory T helper c

Melatonin exerts immunoregulatory effects by balancing peripheral effector and regulatory T helper cells in myasthenia gravis.

Myasthenia gravis ( MG ) is a prototypic organ-specific autoimmune disorder that , in most cases , is mainly mediated by antibodies against the acetylcholine receptor .
Evidence implicates CD4T helper ( Th ) cells in the development of MG , whereas regulatory T cells ( Tregs ) are associated with disease resolution .
Melatonin has important immunoregulatory effects in many T cell-mediated autoimmune diseases .
However , there are few studies on the role of melatonin in MG .
In the present study , we investigated serum melatonin levels and melatonin receptor expression in MG patients and healthy controls @ @ @ @ @ @ @ the impact of melatonin administration on peripheral CD4Th cells and related cytokine production .
Serum melatonin levels were lower in MG patients than in HCs , and MT1 expression was lower in PBMCs from MG patients than in those from HCs .
Administration of melatonin significantly decreased Th1 and Th17 cell responses and proinflammatory cytokine production .
Further investigationrevealed that melatonin administration increased FoxP3 and IL-10 expression in CD4T cells from MG patients and enhanced the suppressive function of Tregs .
These findings indicate that melatonin exerts immunoregulatory activity in MG by balancing @ @ @ @ @ @ @ well as by suppressing proinflammatory cytokine production .

Myasthenia gravis (MG) is a prototypic organ-specific autoimmune disorder that, in most cases, is mainly mediated by antibodies against the acetylcholine receptor. Evidence implicates CD4T helper (Th) cells in the development of MG, whereas regulatory T cells (Tregs) are associated with disease resolution. Melatonin has important immunoregulatory effects in many T cell-mediated autoimmune diseases. However, there are few studies on the role of melatonin in MG. In the present study, we investigated serum melatonin levels and melatonin receptor expression in MG patients and healthy controls (HCs). We also evaluated the impact of melatonin administration on peripheral CD4Th cells and related cytokine production. Serum melatonin levels were lower in MG patients than in HCs, and MT1 expression was lower in PBMCs from MG patients than in those from HCs. Administration of melatonin significantly decreased Th1 and Th17 cell responses and proinflammatory cytokine production. Further investigationrevealed that melatonin administration increased FoxP3 and IL-10 expression in CD4T cells from MG patients and enhanced the suppressive function of Tregs. These findings indicate that melatonin exerts immunoregulatory activity in MG by balancing effector and regulatory Th cell populations as well as by suppressing proinflammatory cytokine production.


greenmedinfo--2020-12-07--Melatonin intake was shown to have a significant impact on improving oxidative stress parameters.

BACKGROUND : Oxidative stress , defined as an imbalance between pro-oxidants and neutralizing antioxidants within the body , is a growing public health concern .
Oxidative stress is involved in the progression of nearly all chronic diseases .
Melatonin has been suggested to reduce oxidative stress by its potential radical scavenging properties .
OBJECTIVE : To determine the efficacy and safety of melatonin as a therapy for the improvement of oxidative stress parameters in randomized controlled trials .
METHODS : A systematic database search using Scopus , PubMed/Medline , EMBASE , Web of Science , the Cochrane Controlled Register of @ @ @ @ @ @ @ ) for studies published up to July 2020 was conducted .
We included studies which investigated the effect of supplemental melatonin compared to placebo on oxidative stress parameters in unhealthy patients .
Quantitative data synthesis was conducted using a random-effects model with standard mean difference ( SMD ) and 95 % confidence intervals ( CI ) .
Cochrane 's Q and Ivalues were used to evaluate heterogeneity .
RESULTS : A total of 12 randomized controlled trials ( RCTs ) were eligible .
The meta-analysis indicated an association between melatonin intake and a @ @ @ @ @ @ @ TAC ) ( SMD : 0.76 ; 95 % CI : 0.30 , 1.21 ; I= 80.1 % ) , glutathione ( GSH ) levels ( SMD : 0.57 ; 95 % CI : 0.32 , 0.83 ; I= 15.1 % ) , superoxide dismutase ( SOD ) ( SMD : 1.38 ; 95 % CI : 0.13 , 2.62 ; I= 86.9 % ) , glutathione peroxidase ( GPx ) ( SMD : 1.36 ; 95 % CI : 0.46 , 2.30 ; I= 89.3 % ) , glutathione reductase ( GR @ @ @ @ @ @ @ % CI : 0.65 , 1.77 ; I= 00.0 % ) activities , and a significant reduction in malondialdehyde ( MDA ) levels ( SMD : -0.79 ; 95 % CI : -1.19 , -0.39 ; I= 73.1 % ) .
Melatonin intake was not shown to significantly affect nitric oxide ( NO ) levels ( SMD : -0.24 ; 95 % CI : -0.61 , 0.14 ; I= 00.0 % ) or catalase ( CAT ) activity ( SMD : -1.38 ; 95 % CI : -1.42 , 4.18 ; I= 96.6 @ @ @ @ @ @ @ was shown to have a significant impact on improving Oxidative stress parameters .
However , future research through large , well-designed randomized controlled trials are required to determine the effect of melatonin on oxidative stress parameters in different age groups and different disease types .

BACKGROUND: Oxidative stress, defined as an imbalance between pro-oxidants and neutralizing antioxidants within the body, is a growing public health concern. Oxidative stress is involved in the progression of nearly all chronic diseases. Melatonin has been suggested to reduce oxidative stress by its potential radical scavenging properties.
OBJECTIVE: To determine the efficacy and safety of melatonin as a therapy for the improvement of oxidative stress parameters in randomized controlled trials.
METHODS: A systematic database search using Scopus, PubMed/Medline, EMBASE, Web of Science, the Cochrane Controlled Register of Trials and clinicaltrials.gov (https://clinicaltrials.gov) for studies published up to July 2020 was conducted. We included studies which investigated the effect of supplemental melatonin compared to placebo on oxidative stress parameters in unhealthy patients. Quantitative data synthesis was conducted using a random-effects model with standard mean difference (SMD) and 95 % confidence intervals (CI). Cochrane's Q and Ivalues were used to evaluate heterogeneity.
RESULTS: A total of 12 randomized controlled trials (RCTs) were eligible. The meta-analysis indicated an association between melatonin intake and a significant increase in total antioxidant capacity (TAC) (SMD: 0.76; 95 % CI: 0.30, 1.21; I= 80.1 %), glutathione (GSH) levels (SMD: 0.57; 95 % CI: 0.32, 0.83; I= 15.1 %), superoxide dismutase (SOD) (SMD: 1.38; 95 % CI: 0.13, 2.62; I= 86.9 %), glutathione peroxidase (GPx) (SMD: 1.36; 95 % CI: 0.46, 2.30; I= 89.3 %), glutathione reductase (GR) (SMD: 1.21; 95 % CI: 0.65, 1.77; I= 00.0 %) activities, and a significant reduction in malondialdehyde (MDA) levels (SMD: -0.79; 95 % CI: -1.19, -0.39; I= 73.1 %). Melatonin intake was not shown to significantly affect nitric oxide (NO) levels (SMD: -0.24; 95 % CI: -0.61, 0.14; I= 00.0 %) or catalase (CAT) activity (SMD: -1.38; 95 % CI: -1.42, 4.18; I= 96.6 %).
CONCLUSION: Melatonin intake was shown to have a significant impact on improving Oxidative stress parameters. However, future research through large, well-designed randomized controlled trials are required to determine the effect of melatonin on oxidative stress parameters in different age groups and different disease types.


greenmedinfo--2020-12-07--COVID-19 Vaccine Bombshell: FDA Documents Reveal DEATH + 21 Serious Health Conditions As Possible Ad

COVID-19 Vaccine Bombshell: FDA Documents Reveal DEATH + 21 Serious Health Conditions As Possible Adverse Outcomes

Public discussion and documents reveal that the FDA knows that rushed-to-market COVID-19 vaccines may cause a wide range of life-threatening side effects , including death .
Unless the public is made aware of their real effects , and is given a choice , their widespread coercive promotion as `` safe and effective '' and `` necessary '' violates the medical ethical principle of informed consent .
Act now via Stand for Health Freedom to stand up for your rights !
A US Food & Drug Administration advisory committee meeting titled , “ Vaccines and Related Biological Products , ” presented @ @ @ @ @ @ @ included a 27 slide powerpoint presentation by Steve Anderson , PhD , MPP Director , Office of Biostatistics & Epidemiology , Center for Biologics Evaluation and Research ( CBER ) .
Slide 16 of his presentation included a “ DRAFT Working list of possible adverse event outcomes ” associated with the imminent rollout of COVID-19 vaccines subject to FDA safety surveillance , showing that death , as well as 21 other conditions ( most which are life-threatening ) , are listed as possible adverse outcomes of the COVID-19 vaccines .
In the video @ @ @ @ @ @ @ , which we have fast-forwarded to slide 16 : The implications of this presentation are highly concerning .
FDA staff are clearly aware of the possibly lethal side effects of the COVID-19 vaccines and are preparing in advance to be on the look out for such adverse outcomes through `` post-marketing survellience . ''
This approach violates the precautionary principle , which requires that a medical intervention be proven safe before being released onto the market .
If it is known that the product may cause harm , and especially death , in @ @ @ @ @ @ @ public being fully informed of these risks , this constitutes an egregious violation of the medical ethical principles established through the Nuremberg code in order to prevent human rights violations .
The time is NOW to stand up for your fundamnetal human health rights and demand from your lawmakers and elected officials that COVID-19 ( and all vaccines ) be voluntary and not mandatory .
Please join us by taking action on the Stand For Health Freedom digital advocacy platform .
ACT NOW : Tell your governor and local legislators that COVID-19 vaccines @ @ @ @

Visit our Re-post guidelines This article is copyrighted by GreenMedInfo LLC, 2020
Public discussion and documents reveal that the FDA knows that rushed-to-market COVID-19 vaccines may cause a wide range of life-threatening side effects, including death.
Unless the public is made aware of their real effects, and is given a choice, their widespread coercive promotion as "safe and effective" and "necessary" violates the medical ethical principle of informed consent.
Act now via Stand for Health Freedom to stand up for your rights!
A US Food & Drug Administration advisory committee meeting titled, “Vaccines and Related Biological Products,” presented online on October 22, 2020, included a 27 slide powerpoint presentation by Steve Anderson, PhD, MPP Director, Office of Biostatistics & Epidemiology, Center for Biologics Evaluation and Research (CBER). Slide 16 of his presentation included a “DRAFT Working list of possible adverse event outcomes” associated with the imminent rollout of COVID-19 vaccines subject to FDA safety surveillance, showing that death, as well as 21 other conditions (most of which are possibly life-threatening), are listed as possible adverse outcomes of the COVID-19 vaccines.
In the video below, Steve Anderson discusses the presentation, which we have fast-forwarded to slide 16:
View the full powerpoint presentation from the FDA website here.
The implications of this presentation are highly concerning. FDA staff are clearly aware of the possibly lethal side effects of the COVID-19 vaccines and are preparing in advance to be on the look out for such adverse outcomes through "post-marketing survellience." This approach violates the precautionary principle, which requires that a medical intervention be proven safe before being released onto the market. If it is known that the product may cause harm, and especially death, in advance, and still released without the public being fully informed of these risks, this constitutes an egregious violation of the medical ethical principles established through the Nuremberg code in order to prevent human rights violations.
TWO IMMEDIATE CALLS TO ACTION
1) The time is NOW to stand up for your fundamnetal human health rights and demand from your lawmakers and elected officials that COVID-19 (and all vaccines) be voluntary and not mandatory. Please join us by taking action on the Stand For Health Freedom digital advocacy platform.
ACT NOW: Tell your governor and local legislators that COVID-19 vaccines must be voluntary!
2) There are two upcoming FDA advisory committee deadlines coming up for public comments ton the COVID-19 vaccines on Dec 10th and Dec. 17th. These will be livestreamed. Attend and make a comment!
Vaccines and Related Biological Products Advisory Committee December 10, 2020 Meeting Announcement


greenmedinfo--2020-12-08--Nettle tea inhibits growth of acute myeloid leukemia cells in vitro by promoting apoptosis.

( UD ) , commonly known as '' stinging nettle '' , is a herbaceous flowering plant that is a widely used agent in traditional medicine worldwide .
Several formulations of UD leaf extract have been reported to exhibit anti-inflammatory and antioxidant properties , with anticancer potential .
The current study investigated the possible anticancer properties of nettle tea , prepared fromleaves , on acute myeloid leukemia ( AML ) cell lines , and deciphered the underlying molecular mechanisms .
Treatment of AML cell lines ( U-937 and KG-1 ) with UD aqueous leaf extract resulted in a dose- and @ @ @ @ @ @ @ in apoptotic hallmarks such as phosphatidylserine flipping to the outer membrane leaflet , and DNA fragmentation as revealed by cell-death ELISA and cell-cycle analysis assays .
Apoptosis induction in U937 cells involves alterations in the expression of Bax and Bcl-2 upon exposure to nettle tea .
Furthermore , the chemical composition of UD aqueous extract indicated the presence of multiple chemical agents , such as flavonoids and phenolics , mainly patuletin , m/p-hydroxybenzoic acid , and caffeic acid , among others , to which the pro-apoptotic and anti-tumor effects may be attributed .

(UD), commonly known as"stinging nettle", is a herbaceous flowering plant that is a widely used agent in traditional medicine worldwide. Several formulations of UD leaf extract have been reported to exhibit anti-inflammatory and antioxidant properties, with anticancer potential. The current study investigated the possible anticancer properties of nettle tea, prepared fromleaves, on acute myeloid leukemia (AML) cell lines, and deciphered the underlying molecular mechanisms. Treatment of AML cell lines (U-937 and KG-1) with UD aqueous leaf extract resulted in a dose- and time-dependent inhibition of proliferation, an increase in apoptotic hallmarks such as phosphatidylserine flipping to the outer membrane leaflet, and DNA fragmentation as revealed by cell-death ELISA and cell-cycle analysis assays. Apoptosis induction in U937 cells involves alterations in the expression of Bax and Bcl-2 upon exposure to nettle tea. Furthermore, the chemical composition of UD aqueous extract indicated the presence of multiple chemical agents, such as flavonoids and phenolics, mainly patuletin, m/p-hydroxybenzoic acid, and caffeic acid, among others, to which the pro-apoptotic and anti-tumor effects may be attributed.


greenmedinfo--2020-12-07--The positive impact on depression symptoms justifies further studies employing exercise intervention

The positive impact on depression symptoms justifies further studies employing exercise interventions.

The goals of this study were to determine the feasibility of engaging youth with major depressive disorder ( MDD ) in a multimodal exercise intervention ( Healthy Body Healthy Mind ) plus usual care and to evaluate the magnitude of its effects on psychological , physical fitness , and biomarker outcomes to inform a future randomized controlled trial .
Youth ( 15 to 25 y of age ) with MDD diagnosed using the Structured Clinical Interview for DSM-IV Axis I Disorders ( SCID-I ) were eligible to participate .
Feasibility measures included recruitment , retention , and program adherence rates @ @ @ @ @ @ @ single session of motivational interviewing to enhance exercise adherence , then 1-hour , small-group supervised exercise sessions 3 times per week for 12 weeks .
Assessments were administered at baseline and at 12 weeks .
Depression symptoms were assessed using the Beck Depression Inventory ( BDI-II ) .
Physical fitness and blood biomarkers werealso measured .
Three males and 10 females with MDD , who were 18 to 24 years of age , participated .
Retention at 12 weeks was 86 % , and attendance at exercise sessions averaged 62 % ±28 % @ @ @ @ @ @ @ of participants experienced a remission of MDD based on the SCID .
Mean BDI-II scores decreased from 31.9±9.1 to 13.1±10.1 [ Cohen d effect size ( ES ) =1.96 ] .
Improvements were observed in upper ( ES=0.64 ) and lower ( ES=0.32 ) body muscular endurance .
Exercise session attendance was moderately correlated with changes in BDI-II scores ( Pearson r=0.49 ) .
It appears feasible to attract and engage someyouth with MDD in an exercise intervention .
The positive impact on depression symptoms justifies further studies employing exercise interventions as an @ @ @ @ @ @ @ with MDD .

The goals of this study were to determine the feasibility of engaging youth with major depressive disorder (MDD) in a multimodal exercise intervention (Healthy Body Healthy Mind) plus usual care and to evaluate the magnitude of its effects on psychological, physical fitness, and biomarker outcomes to inform a future randomized controlled trial. Youth (15 to 25 y of age) with MDD diagnosed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) were eligible to participate. Feasibility measures included recruitment, retention, and program adherence rates. The exercise program consisted of a single session of motivational interviewing to enhance exercise adherence, then 1-hour, small-group supervised exercise sessions 3 times per week for 12 weeks. Assessments were administered at baseline and at 12 weeks. Depression symptoms were assessed using the Beck Depression Inventory (BDI-II). Physical fitness and blood biomarkers werealso measured. Three males and 10 females with MDD, who were 18 to 24 years of age, participated. Retention at 12 weeks was 86%, and attendance at exercise sessions averaged 62%±28%. After 12 weeks, 69% of participants experienced a remission of MDD based on the SCID. Mean BDI-II scores decreased from 31.9±9.1 to 13.1±10.1 [Cohen d effect size (ES)=1.96]. Improvements were observed in upper (ES=0.64) and lower (ES=0.32) body muscular endurance. Exercise session attendance was moderately correlated with changes in BDI-II scores (Pearson r=0.49). It appears feasible to attract and engage someyouth with MDD in an exercise intervention. The positive impact on depression symptoms justifies further studies employing exercise interventions as an adjunct to routine care for young people with MDD.


greenmedinfo--2020-12-07--Urtica dioica root extract consumption for 12 weeks among BPH patients had clinically significant ef

Urtica dioica root extract consumption for 12 weeks among BPH patients had clinically significant effects on IPSS, serum hs-CRP, MDA and SOD activity.

BACKGROUND AND OBJECTIVES : Benign Prostatic Hyperplasia ( BPH ) is a common urological disorder as men get older .
BPH can cause uncomfortable urinary tract symptoms .
Given the high incidence of the disease , further research is an undeniable necessity for its better management .
In this research , the efficacy of Urtica Dioica root extract ( UDE ) on clinical and biochemical parameters were evaluated in this type of patients .
MATERIALS AND METHODS : Participants were 60 men with BPH that randomly allocated to two equal groups ( Intervention = 30 and Comparison = 30 ) @ @ @ @ @ @ @ using a computer by a trained nurse .
Intervention and comparison groups received 450 mg day-1 UDE and placebo as tablets for 12 weeks , respectively .
The main outcome was changes in International Prostate Symptoms Score ( IPSS ) from baseline to end of treatment .
Data were collected by completing a standard questionnaire and performing relevant tests based on common laboratory methods .
RESULTS : UDE had an intermediate effect on IPSS , a small effect on serum high-sensitivity C-reactive protein ( hs-CRP ) , intermediate to large effect on malondialdehyde @ @ @ @ @ @ @ on superoxide dismutase ( SOD ) activity .
The magnitude of the effects of UDE on other parameters was overall negligible compared to the comparison and not significant .
No side effects were seen in these patients following tablet usage .
CONCLUSION : UDE consumption for 12 weeks among BPH patients had clinically significant effects on IPSS , serum hs-CRP , MDA and SOD activity .

BACKGROUND AND OBJECTIVES: Benign Prostatic Hyperplasia (BPH) is a common urological disorder as men get older. BPH can cause uncomfortable urinary tract symptoms. Given the high incidence of the disease, further research is an undeniable necessity for its better management. In this research, the efficacy of Urtica Dioica root extract (UDE) on clinical and biochemical parameters were evaluated in this type of patients.
MATERIALS AND METHODS: Participants were 60 men with BPH that randomly allocated to two equal groups (Intervention = 30 and Comparison = 30). Block balanced Randomization method was performed using a computer by a trained nurse. Intervention and comparison groups received 450 mg day-1 UDE and placebo as tablets for 12 weeks, respectively. The main outcome was changes in International Prostate Symptoms Score (IPSS) from baseline to end of treatment. Data were collected by completing a standard questionnaire and performing relevant tests based on common laboratory methods.
RESULTS: UDE had an intermediate effect on IPSS, a small effect on serum high-sensitivity C-reactive protein (hs-CRP), intermediate to large effect on malondialdehyde (MDA) levels and intermediate effect on superoxide dismutase (SOD) activity. The magnitude of the effects of UDE on other parameters was overall negligible compared to the comparison and not significant. No side effects were seen in these patients following tablet usage.
CONCLUSION: UDE consumption for 12 weeks among BPH patients had clinically significant effects on IPSS, serum hs-CRP, MDA and SOD activity.


greenmedinfo--2020-12-07--Biochanin A alleviates gingival inflammation and alveolar bone loss in rats with experimental period

Biochanin A alleviates gingival inflammation and alveolar bone loss in rats with experimental periodontitis.

Biochanin A ( BA ) is an organic compound produced byandwith anti-inflammatory and antioxidative effects .
The aim of the current study was to evaluate the effects of BA on gingival inflammation and alveolar bone destruction in rats with experimental periodontitis .
Experimental rats ( n=25 ) were distributed equally into five groups : i ) Healthy control ( control ) group ; ii ) experimental periodontitis ( ligation ) group ; and iii ) and ligation plus low , medium and high dose of BA ( 12.5 , 25 and 50 mg/kg/day , respectively ) groups .
A nylon @ @ @ @ @ @ @ molars for 14 days to trigger the experimental periodontitis .
BA was intravenous injected once daily for 4 weeks .
After that , interleukin-1β ( IL-1β ) , tumor necrosis factor-α ( TNF-α ) , reactive oxygen species ( ROS ) and osteocalcin ( OCN ) levels were determined in gingival and/or serum samples using ELISA or reverse transcription-quantitative PCR .
Alveolar bone volume was assessed via hematoxylin and eosin staining and micro-computed tomography .
Osteoclasts were identified by tartrate-resistant acid phosphatase staining , and the level of the nuclear factor erythroid-2 related @ @ @ @ @ @ @ detected by immunohistochemical staining .
BA treatment groups showed alleviated alveolar bone resorption compared with the ligationgroup .
Moreover , BA treatment significantly inhibited IL-1β , TNF-α , ROS levels , and reduced leukocyte acid phosphatase-positive cells , as well as increased OCN and Nrf2 levels compared with the ligation group .
BA had beneficial effects on experimental periodontitis of rats .
BA treatment inhibitedinflammation , regulated unbalanced oxidative stress response and ameliorated the alveolar bone loss .

Biochanin A (BA) is an organic compound produced byandwith anti-inflammatory and antioxidative effects. The aim of the current study was to evaluate the effects of BA on gingival inflammation and alveolar bone destruction in rats with experimental periodontitis. Experimental rats (n=25) were distributed equally into five groups: i) Healthy control (control) group; ii) experimental periodontitis (ligation) group; and iii) and ligation plus low, medium and high dose of BA (12.5, 25 and 50 mg/kg/day, respectively) groups. A nylon ligature was inserted around rats' maxillary molars for 14 days to trigger the experimental periodontitis. BA was intravenous injected once daily for 4 weeks. After that, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS) and osteocalcin (OCN) levels were determined in gingival and/or serum samples using ELISA or reverse transcription-quantitative PCR. Alveolar bone volume was assessed via hematoxylin and eosin staining and micro-computed tomography. Osteoclasts were identified by tartrate-resistant acid phosphatase staining, and the level of the nuclear factor erythroid-2 related factor 2 (Nrf2) was also detected by immunohistochemical staining. BA treatment groups showed alleviated alveolar bone resorption compared with the ligationgroup. Moreover, BA treatment significantly inhibited IL-1β, TNF-α, ROS levels, and reduced leukocyte acid phosphatase-positive cells, as well as increased OCN and Nrf2 levels compared with the ligation group. BA had beneficial effects on experimental periodontitis of rats. BA treatment inhibitedinflammation, regulated unbalanced oxidative stress response and ameliorated the alveolar bone loss.


greenmedinfo--2020-12-07--Top Five Healthiest Holiday Foods

Top Five Healthiest Holiday Foods

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 @

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.
© Copyright 2008-2023 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.


greenmedinfo--2020-12-07--The Plan Is Unfolding for How Vaccines Will Be Monitored