greenmedinfo--2020-03-21--Bisphenol A induces coronary endothelial cell necroptosis by activating RIP3/CamKII dependent pathwa

Bisphenol A induces coronary endothelial cell necroptosis by activating RIP3/CamKII dependent pathway.

Epidemiological studies link long term exposure to xenoestrogen Bisphenol-A to adverse cardiovascular effects .
Our previous results show that BPA induces hypertension by a mechanism involving CamKII activation and increased redox stress caused by eNOS uncoupling .
Recently , CamKII sustained activation has been recognized as a central mediator of programmed cell death in cardiovascular diseases , including necroptosis .
However , the role of necroptosis in cardiac response to BPA had not yet been explored .
Mice exposed to BPA for 16 weeks showed altered heart function , electrical conduction , and increased blood pressure .
Besides , a @ @ @ @ @ @ @ of cardiac ischemia .
The hearts exhibited cardiac hypertrophy and reduced vascularization , interstitial edema , and large hemorrhagic foci accompanied by fibrinogen deposits .
BPA initiated a cardiac inflammatory response , up-regulation of M1 macrophage polarization , and increased oxidative stress , coinciding with the increased expression of CamKII and the necroptotic effector RIP3 .
In addition , cell death was especially evident in coronary endothelial cells within hemorrhagic areas , and Evans blue extravasation indicated a vascular leak in response to Bisphenol-A .
Consistent with the in vivo findings , BPA @ @ @ @ @ @ @ of RIP3 , and CamKII activation in endothelial cells .
Necrostatin-1 , an inhibitor of necroptosis , alleviated BPA induced cardiac dysfunction and prevented the inflammatory and hemorrhagic response in mice .
Mechanistically , silencing of RIP3 reversed BPA-induced necroptosis and CamKII activation in endothelial cells , while inhibition of CamKII activation by KN-93 had no effect on RIP3 expression but decreased necroptotic cell death suggesting that BPA induced necroptosis is mediated by a RIP 3/CamKII dependent pathway .
Our results reveal a novel pathogenic role of BPA on the coronary circulation .
@ @ @ @ @ @ @ the weakening of coronary vascular wall , which caused internal ventricular hemorrhages , delaying the reparative process and ultimately leading to cardiac dysfunction .

Epidemiological studies link long term exposure to xenoestrogen Bisphenol-A to adverse cardiovascular effects. Our previous results show that BPA induces hypertension by a mechanism involving CamKII activation and increased redox stress caused by eNOS uncoupling. Recently, CamKII sustained activation has been recognized as a central mediator of programmed cell death in cardiovascular diseases, including necroptosis. However, the role of necroptosis in cardiac response to BPA had not yet been explored. Mice exposed to BPA for 16 weeks showed altered heart function, electrical conduction, and increased blood pressure. Besides, a stress test showed ST-segment depression, indicative of cardiac ischemia. The hearts exhibited cardiac hypertrophy and reduced vascularization, interstitial edema, and large hemorrhagic foci accompanied by fibrinogen deposits. BPA initiated a cardiac inflammatory response, up-regulation of M1 macrophage polarization, and increased oxidative stress, coinciding with the increased expression of CamKII and the necroptotic effector RIP3. In addition, cell death was especially evident in coronary endothelial cells within hemorrhagic areas, and Evans blue extravasation indicated a vascular leak in response to Bisphenol-A. Consistent with the in vivo findings, BPA increased the necroptosis/apoptosis ratio, the expression of RIP3, and CamKII activation in endothelial cells. Necrostatin-1, an inhibitor of necroptosis, alleviated BPA induced cardiac dysfunction and prevented the inflammatory and hemorrhagic response in mice. Mechanistically, silencing of RIP3 reversed BPA-induced necroptosis and CamKII activation in endothelial cells, while inhibition of CamKII activation by KN-93 had no effect on RIP3 expression but decreased necroptotic cell death suggesting that BPA induced necroptosis is mediated by a RIP 3/CamKII dependent pathway. Our results reveal a novel pathogenic role of BPA on the coronary circulation. BPA induces endothelial cell necroptosis, promotes the weakening of coronary vascular wall, which caused internal ventricular hemorrhages, delaying the reparative process and ultimately leading to cardiac dysfunction.


greenmedinfo--2020-03-21--Notch pathway up-regulation via curcumin mitigates bisphenol-A (BPA) induced alterations in hippocam

Notch pathway up-regulation via curcumin mitigates bisphenol-A (BPA) induced alterations in hippocampal oligodendrogenesis.

CNS myelination process involves proliferation and differentiation of oligodendrocyte progenitor cells ( OPCs ) .
Defective myelination causes onset of neurological disorders .
Bisphenol-A ( BPA ) , a component of plastic items , exerts adverse effects on human health .
Our previous studies indicated that BPA impairs neurogenesis and myelination process stimulating cognitive dysfunctions .
But , the underlying mechanism ( s ) of BPA induced de-myelination and probable neuroprotection by curcumin remains elusive .
We found that curcumin protected BPA mediated adverse effects on oligosphere growth kinetics .
Curcumin significantly improved proliferation and differentiation of OPCs upon BPA @ @ @ @ @ @ @ enhanced the mRNA expression and protein levels of myelination markers in BPA treated rat hippocampus .
Curcumin improved myelination potential via increasingβ-III tubulin-/MBPcells ( neuron-oligodendrocyte co-culture ) and augmented fluoromyelin intensity and neurofilament/MBPneurons in vivo .
In silico docking studies suggested Notch pathway genes ( Notch-1 , Hes-1 and Mib-1 ) as potential targets of BPA and curcumin .
Curcumin reversed BPA mediated myelination inhibition via increasing the Notch pathway gene expression .
Genetic and pharmacological Notch pathway inhibition by DAPT and Notch-1 siRNA exhibited decreased curcumin mediated neuroprotection .
Curcumin improved BPA @ @ @ @ @ @ @ .
Altogether , results suggest that curcumin protected BPA induced de-myelination and behavioural deficits through Notch pathway activation .

CNS myelination process involves proliferation and differentiation of oligodendrocyte progenitor cells (OPCs). Defective myelination causes onset of neurological disorders. Bisphenol-A (BPA), a component of plastic items, exerts adverse effects on human health. Our previous studies indicated that BPA impairs neurogenesis and myelination process stimulating cognitive dysfunctions. But, the underlying mechanism(s) of BPA induced de-myelination and probable neuroprotection by curcumin remains elusive. We found that curcumin protected BPA mediated adverse effects on oligosphere growth kinetics. Curcumin significantly improved proliferation and differentiation of OPCs upon BPA exposure both in-vitro and in-vivo. Curcumin enhanced the mRNA expression and protein levels of myelination markers in BPA treated rat hippocampus. Curcumin improved myelination potential via increasingβ-III tubulin-/MBPcells (neuron-oligodendrocyte co-culture) and augmented fluoromyelin intensity and neurofilament/MBPneurons in vivo. In silico docking studies suggested Notch pathway genes (Notch-1, Hes-1 and Mib-1) as potential targets of BPA and curcumin. Curcumin reversed BPA mediated myelination inhibition via increasing the Notch pathway gene expression. Genetic and pharmacological Notch pathway inhibition by DAPT and Notch-1 siRNA exhibited decreased curcumin mediated neuroprotection. Curcumin improved BPA mediated myelin sheath degeneration and neurobehavioral impairments. Altogether, results suggest that curcumin protected BPA induced de-myelination and behavioural deficits through Notch pathway activation.


greenmedinfo--2020-03-21--Lycopene alleviates disc degeneration under oxidative stress through the Nrf2 signaling pathway.

Intervertebral disc degeneration ( IDD ) is a main cause of diseases such as discogenic low back pain , cervical @ @ @ @ @ degenerative spinal stenosis , and lumbar spondylolisthesis .
Nuclear factor erythroid 2-related factor 2 ( @ @ @ @ @ transcription factor , regulates antioxidant genes and induces cellular defense mechanisms against oxidative stress .
@ @ @ @ @ protective effect of plant antioxidant lycopene on nucleus pulposus cells ( NPCs ) under oxidative @ @ @ @ @ results indicated that Nrf2 expression decreased in degenerated NPCs .
We further found that lycopene @ @ @ @ @ under oxidative stress and alleviated oxidative stress-induced apoptosis of degenerative human NPCs via Nrf2 .
@ @ @ @ @ lycopene reduced HO-induced decomposition of cartilage extracellular matrix in NPCs .
In conclusion , our @ @ @ @ @ alleviate disc degeneration under oxidative stress through the Nrf2 signaling pathway .

Intervertebral disc degeneration (IDD) is a main cause of diseases such as discogenic low back pain, cervical and lumbar disc herniation, degenerative spinal stenosis, and lumbar spondylolisthesis. Nuclear factor erythroid 2-related factor 2 (Nrf2), an important transcription factor, regulates antioxidant genes and induces cellular defense mechanisms against oxidative stress. In this study, the protective effect of plant antioxidant lycopene on nucleus pulposus cells (NPCs) under oxidative stress was investigated. The results indicated that Nrf2 expression decreased in degenerated NPCs. We further found that lycopene was protective in NP tissue under oxidative stress and alleviated oxidative stress-induced apoptosis of degenerative human NPCs via Nrf2. The results also showed that lycopene reduced HO-induced decomposition of cartilage extracellular matrix in NPCs. In conclusion, our findings suggested that lycopene may alleviate disc degeneration under oxidative stress through the Nrf2 signaling pathway.


greenmedinfo--2020-03-21--Lycopene alleviates DSS-induced colitis and behavioral disorders via mediating microbes-gut-brain ax

Lycopene alleviates DSS-induced colitis and behavioral disorders via mediating microbes-gut-brain axis balance.

Gut microbes play significant roles in colitis development .
The current study was aimed to uncover the preventive effects of @ @ @ @ @ a functional carotenoid component , on colitis and the accompanied behavior disorders .
The current @ @ @ @ @ ( 50 mg/kg bodyweight/day ) for 40 days prevented the dextran sulphate sodium ( DSS @ @ @ @ @ and inflammatory responses in male mice .
LYC improved DSS-induced depression and anxiety-like behavioral disorders @ @ @ @ @ synaptic ultra-structure damages by upregulating the expressions of neurotrophic factor and postsynaptic-density protein .
Moreover @ @ @ @ @ microbiome in colitis mice by decreasing the relative abundance of Proteobacteria and increasing the relative @ @ @ @ @ .
LYC also elevated the generation of short-chain fatty acids and inhibited the permeability of @ @ @ @ @ In conclusion , LYC ameliorate DSS-induced colitis and behavioral disorders via mediating microbes-gut-brain axis balance @

Gut microbes play significant roles in colitis development. The current study was aimed to uncover the preventive effects of lycopene (LYC), a functional carotenoid component, on colitis and the accompanied behavior disorders. The current study demonstrated that LYC treatment (50 mg/kg bodyweight/day) for 40 days prevented the dextran sulphate sodium (DSS)-induced gut barrier damages and inflammatory responses in male mice. LYC improved DSS-induced depression and anxiety-like behavioral disorders by suppressing neuroinflammation and prevented synaptic ultra-structure damages by upregulating the expressions of neurotrophic factor and postsynaptic-density protein. Moreover, LYC reshaped the gut microbiome in colitis mice by decreasing the relative abundance of Proteobacteria and increasing the relative abundance of Bifidobacterium and Lactobacillus. LYC also elevated the generation of short-chain fatty acids and inhibited the permeability of lipopolysaccharide in colitis mice. In conclusion, LYC ameliorate DSS-induced colitis and behavioral disorders via mediating microbes-gut-brain axis balance.


greenmedinfo--2020-03-21--Protective effects of lycopene on hippocampal neurotoxicity and memory impairment induced by bisphen

Protective effects of lycopene on hippocampal neurotoxicity and memory impairment induced by bisphenol A.

Bisphenol A ( BPA ) is used to produce polycarbonate plastic and epoxy resins which are used in many consumer products .
Most people encounter BPA in their daily routines .
However , it has been heavily reported that BPA has a neurotoxic effect .
The present study aimed to investigate the effect of lycopene on cognitive deficits induced by a high dose of BPA focusing on mitogen-activated protein kinase ( MAPK ) /extracellular signal-regulated kinase ( ERK ) pathway , oxidative stress , apoptosis , and memory retrieval in adult male rats .
Therefore , 72 rats were divided @ @ @ @ @ @ @ BPA group ( 50 mg/kg body weight ( bw ) ) 3 days a week for 42 days , lycopene group ( 10 mg/kg bw ) daily for 42 days , and lycopene + BPA group .
Concurrent treatment of lycopene with BPA improved the learning and cognition memory in Morris water maze and novel object recognition tests along with an increase in acetylcholine esterase activity as well as inhibition of oxidative stress by restoring reduced glutathione and suppressing malondialdehyde hippocampal level to their normal levels .
Mechanistically , lycopene upregulated the protein @ @ @ @ @ @ @ which resulted in an upsurge in its downstream cascades MAPK/ERK1/2/cAMP response element-binding protein ( CREB ) /brain-derived neurotrophic factor ( BDNF ) signaling pathway in the hippocampus of BPA-intoxicated rats .
Furthermore , concurrent treatment of lycopene with BPA prevented apoptosis by marked decrease in Bcl-2 associated X protein ( Bax ) gene expression and caspase 3 activity while restoring B-cell leukemia/lymphoma-2 ( Bcl-2 ) gene expression .
In conclusion , the present study provided evidence that lycopene exerted a neuroprotective effect against BPA intoxication in hippocampi of rats via its antioxidant properties @ @ @ @ @ @ @ inhibiting a neuronal apoptosis which reflected on improving the learning and cognition memory .

Bisphenol A (BPA) is used to produce polycarbonate plastic and epoxy resins which are used in many consumer products. Most people encounter BPA in their daily routines. However, it has been heavily reported that BPA has a neurotoxic effect. The present study aimed to investigate the effect of lycopene on cognitive deficits induced by a high dose of BPA focusing on mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, oxidative stress, apoptosis, and memory retrieval in adult male rats. Therefore, 72 rats were divided into four groups: control group, BPA group (50 mg/kg body weight (bw)) 3 days a week for 42 days, lycopene group (10 mg/kg bw) daily for 42 days, and lycopene + BPA group. Concurrent treatment of lycopene with BPA improved the learning and cognition memory in Morris water maze and novel object recognition tests along with an increase in acetylcholine esterase activity as well as inhibition of oxidative stress by restoring reduced glutathione and suppressing malondialdehyde hippocampal level to their normal levels. Mechanistically, lycopene upregulated the protein expression of tyrosine receptor kinase B, which resulted in an upsurge in its downstream cascades MAPK/ERK1/2/cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway in the hippocampus of BPA-intoxicated rats. Furthermore, concurrent treatment of lycopene with BPA prevented apoptosis by marked decrease in Bcl-2 associated X protein (Bax) gene expression and caspase 3 activity while restoring B-cell leukemia/lymphoma-2 (Bcl-2) gene expression. In conclusion, the present study provided evidence that lycopene exerted a neuroprotective effect against BPA intoxication in hippocampi of rats via its antioxidant properties, activation of MAPK/ERK pathway, and inhibiting a neuronal apoptosis which reflected on improving the learning and cognition memory.


greenmedinfo--2020-03-21--Exercise training can attenuate the inflammatory milieu in women with systemic lupus erythematosus.

Systemic lupus erythematosus ( SLE ) is an autoimmune disease characterized by chronic inflammation .
This study sought to assess the effects of an exercise training program on cytokines and soluble TNF receptors ( sTNFRs ) in response to acute exercise in SLE women .
Eight SLE women and 10 sex- , age- , and body mass index-comparable healthy controls ( HC ) participated in this study .
Before and after a 12-wk aerobic exercise training program , cytokines and sTNFRs were assessed at rest and in response to single bouts of acute moderate/intense exercise .
HC performed the acute @ @ @ @ @ @ @ the exercise training program , there was a decrease in resting TNFR2 levels ( P = 0.025 ) and a tend to reduction interleukin ( IL ) -10 levels ( P = 0.093 ) in SLE .
The resting levels of IL-6 , IL-10 , and TNF-α after the exercise training in SLE reached HC levels ( P > 0.05 ) .
In response to a single bout of acute moderate exercise , the area under the curve ( AUC ) of IL-10 was significantly reduced after the exercise training program in SLE @ @ @ @ @ @ @ the AUC of IL-10 , IL-6 , TNF-α , and sTNFR1 of SLE approached control values ( P > 0.05 ) .
In response to a single bout of acute intense exercise , the AUC of IL-10 was significantly reduced in SLE ( P = 0.015 ) .
Furthermore , the AUC of sTNFR2 tended to decrease after exercise training program in SLE ( P = 0.084 ) , but it did not reach control values ( P = 0.001 ) .
An aerobic exercise training program attenuated the inflammatory milieu in SLE @ @ @ @ @ @ @ role of exercise in an autoimmunity condition .

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation. This study sought to assess the effects of an exercise training program on cytokines and soluble TNF receptors (sTNFRs) in response to acute exercise in SLE women. Eight SLE women and 10 sex-, age-, and body mass index-comparable healthy controls (HC) participated in this study. Before and after a 12-wk aerobic exercise training program, cytokines and sTNFRs were assessed at rest and in response to single bouts of acute moderate/intense exercise. HC performed the acute exercise bouts only at baseline. After the exercise training program, there was a decrease in resting TNFR2 levels (P = 0.025) and a tend to reduction interleukin (IL)-10 levels (P = 0.093) in SLE. The resting levels of IL-6, IL-10, and TNF-α after the exercise training in SLE reached HC levels (P>0.05). In response to a single bout of acute moderate exercise, the area under the curve (AUC) of IL-10 was significantly reduced after the exercise training program in SLE (P = 0.043), and the AUC of IL-10, IL-6, TNF-α, and sTNFR1 of SLE approached control values (P>0.05). In response to a single bout of acute intense exercise, the AUC of IL-10 was significantly reduced in SLE (P = 0.015). Furthermore, the AUC of sTNFR2 tended to decrease after exercise training program in SLE (P = 0.084), but it did not reach control values (P = 0.001). An aerobic exercise training program attenuated the inflammatory milieu in SLE women, revealing a novel homeostatic immunomodulatory role of exercise in an autoimmunity condition.


greenmedinfo--2020-03-21--Physical exercise attenuates experimental autoimmune encephalomyelitis.

Multiple sclerosis ( MS ) is a chronic inflammatory disease of the central nervous system ( CNS ) caused by demyelination , immune cell infiltration , and axonal damage .
Herein , we sought to investigate the influence of physical exercise on mice experimental autoimmune encephalomyelitis ( EAE ) , a reported MS model .
Data show that both strength and endurance training protocols consistently prevented clinical signs of EAE and decreased oxidative stress , an effect which was likely due to improving genomic antioxidant defense-nuclear factor erythroid 2-related factor ( Nrf2 ) /antioxidant response elements ( ARE ) pathway-in @ @ @ @ @ @ @ exercise inhibited the production of pro-inflammatory cytokines interferon ( IFN ) -γ , interleukin ( IL ) -17 , and IL-1β in the spinal cord of mice with EAE .
Of note , spleen cells obtained from strength training group incubated with MOGshowed a significant upregulation of CD25 and IL-10 levels , with a decrease of IL-6 , MCP-1 , and tumor necrosis factor ( TNF ) -α production , mainly , during acute and chronic phase of EAE .
Moreover , these immunomodulatory effects of exercise were associated with reduced expression of @ @ @ @ @ @ @ endothelial cell adhesion molecule 1 ( PECAM-1 ) .
Finally , physical exercise also restored the expression of tight junctions in spinal cord .
Together , these results demonstrate that mild/moderate physical exercise , when performed regularly in mice , consistently attenuates the progression and pathological hallmarks of EAE , thereby representing an important non-pharmacological intervention for the improvement of immune-mediated diseases such as MS. Graphical Abstract Schematic diagram illustrating the beneficial effects of physical exercise during experimental model of MS .
Physical exercise , especially strength ( ST ) and endurance ( @ @ @ @ @ @ @ development and progression of disease , measured by the mean maximal clinical score ( 1.5 and 1.0 , respectively ) , with inhibition of 30 % and 50 % , respectively , based on the AUC , compared with EAEuntreated group .
In addition , ST and ET decreased oxidative stress , possibly , through genomic antioxidant defense , Nrf2-Keap1 signaling pathway , in the CNS .
Physical exercise inhibited the production of inflammatory cytokines , such as IFN-γ , IL-17 and IL-1β in the spinal cord after EAE induction , as well @ @ @ @ @ @ @ showed a significant upregulation of regulatory T cell markers , such as CD25 andIL-10 levels , and blocked IL-6 , MCP-1 and TNF-α production , mainly , during acute and chronic phase of EAE .
Finally , these immunomodulatory effects of exercise were associated with inhibition of adhesion molecules and reestablishment of tight junctions expression in spinal cord tissue , thereby limiting BBB permeability and transmigration of autoreactive T cells to the CNS .
NO , nitric oxide ; GPx , glutathione peroxidase , GSH , glutathione ; Nrf2 , nuclear factor ( @ @ @ @ @ @ @ , central nervous system ; BBB , blood-brain barrier ; IFN-g , interferon-gamma ; IL-17 , interleukin 17 ; IL-1b , interleukin-1beta .

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) caused by demyelination, immune cell infiltration, and axonal damage. Herein, we sought to investigate the influence of physical exercise on mice experimental autoimmune encephalomyelitis (EAE), a reported MS model. Data show that both strength and endurance training protocols consistently prevented clinical signs of EAE and decreased oxidative stress, an effect which was likely due to improving genomic antioxidant defense-nuclear factor erythroid 2-related factor (Nrf2)/antioxidant response elements (ARE) pathway-in the CNS. In addition, physical exercise inhibited the production of pro-inflammatory cytokines interferon (IFN)-γ, interleukin (IL)-17, and IL-1β in the spinal cord of mice with EAE. Of note, spleen cells obtained from strength training group incubated with MOGshowed a significant upregulation of CD25 and IL-10 levels, with a decrease of IL-6, MCP-1, and tumor necrosis factor (TNF)-α production, mainly, during acute and chronic phase of EAE. Moreover, these immunomodulatory effects of exercise were associated with reduced expression of adhesion molecules, especially of platelet and endothelial cell adhesion molecule 1 (PECAM-1). Finally, physical exercise also restored the expression of tight junctions in spinal cord. Together, these results demonstrate that mild/moderate physical exercise, when performed regularly in mice, consistently attenuates the progression and pathological hallmarks of EAE, thereby representing an important non-pharmacological intervention for the improvement of immune-mediated diseases such as MS. Graphical Abstract Schematic diagram illustrating the beneficial effects of physical exercise during experimental model of MS. Physical exercise, especially strength (ST) and endurance (ET) training protocols, inhibits the development and progression of disease, measured by the mean maximal clinical score (1.5 and 1.0, respectively), with inhibition of 30 % and 50 %, respectively, based on the AUC, compared with EAEuntreated group. In addition, ST and ET decreased oxidative stress, possibly, through genomic antioxidant defense, Nrf2-Keap1 signaling pathway, in the CNS. Physical exercise inhibited the production of inflammatory cytokines, such as IFN-γ, IL-17 and IL-1β in the spinal cord after EAE induction, as well as spleen cells obtained from ST group showed a significant upregulation of regulatory T cell markers, such as CD25 andIL-10 levels, and blocked IL-6, MCP-1 and TNF-α production, mainly, during acute and chronic phase of EAE. Finally, these immunomodulatory effects of exercise were associated with inhibition of adhesion molecules and reestablishment of tight junctions expression in spinal cord tissue, thereby limiting BBB permeability and transmigration of autoreactive T cells to the CNS. NO, nitric oxide; GPx, glutathione peroxidase, GSH, glutathione; Nrf2, nuclear factor (erythroid-derived 2)-like 2; CNS, central nervous system; BBB, blood-brain barrier; IFN-g, interferon-gamma; IL-17, interleukin 17; IL-1b, interleukin-1beta.


greenmedinfo--2020-03-21--Aerobic training modulates T cell activation in elderly women with knee osteoarthritis.

Osteoarthritis of the knee ( kOA ) is a disease that mainly affects the elderly and can lead to major physical and functional limitations .
However , the specific effects of walking , particularly on the immune system , are unknown .
Therefore , this study aimed to analyze the effect of 12 weeks of walking ( 3×/week ) on the leukocyte profile and quality of life ( QL ) of elderly women with kOA .
Sixteen women ( age : 67±4 years , body mass index : 28.07±4.16 kg/m2 ) participated in a walking program .
The variables were @ @ @ @ @ @ @ training with a progressively longer duration ( 30-55min ) and higher intensity ( 72-82 % of HRmax determined using a graded incremental treadmill test ) .
The QL was assessed using the Medical Outcomes Study 36-Item Short Form Health Survey ( SF-36 ) , and blood samples were collected for analysis with a cell counter and the San Fac flow cytometer .
Walking training resulted in a 47 % enhancement of the self-reported QL ( P < 0.05 ) and a 21 % increase in the VO2max ( P < 0.0001 ) in @ @ @ @ @ @ @ there was a reduction in CD4+ cells ( pre=46.59±7 % , post=44.58±9 % , P=0.0189 ) and a higher fluorescence intensity for CD18+CD4+ ( pre=45.30±10 , post=64.27±33 , P=0.0256 ) and CD18+CD8+ ( pre=64.2±27 , post=85.02±35 , P=0.0130 ) .
In conclusion , the walking program stimulated leukocyte production , which may be related to the immunomodulatory effectof exercise .
Walking also led to improvements in the QL and physical performance in elderly women with kOA .

Osteoarthritis of the knee (kOA) is a disease that mainly affects the elderly and can lead to major physical and functional limitations. However, the specific effects of walking, particularly on the immune system, are unknown. Therefore, this study aimed to analyze the effect of 12 weeks of walking (3×/week) on the leukocyte profile and quality of life (QL) of elderly women with kOA. Sixteen women (age: 67±4 years, body mass index: 28.07±4.16 kg/m2) participated in a walking program. The variables were assessed before and after 12 weeks of training with a progressively longer duration (30-55min) and higher intensity (72-82% of HRmax determined using a graded incremental treadmill test). The QL was assessed using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), and blood samples were collected for analysis with a cell counter and the San Fac flow cytometer. Walking training resulted in a 47% enhancement of the self-reported QL (P<0.05) and a 21% increase in the VO2max (P<0.0001) in elderly women with kOA. Furthermore, there was a reduction in CD4+ cells (pre=46.59±7%, post=44.58±9%, P=0.0189) and a higher fluorescence intensity for CD18+CD4+ (pre=45.30±10, post=64.27±33, P=0.0256) and CD18+CD8+ (pre=64.2±27, post=85.02±35, P=0.0130). In conclusion, the walking program stimulated leukocyte production, which may be related to the immunomodulatory effectof exercise. Walking also led to improvements in the QL and physical performance in elderly women with kOA.


greenmedinfo--2020-03-21--Active subjects with autoimmune type 1 diabetes have better metabolic profiles than sedentary contro

Active subjects with autoimmune type 1 diabetes have better metabolic profiles than sedentary controls.

Previous studies in humans with type 1 diabetes mellitus ( T1D ) and in nonobese diabetic mice have investigated the beneficial immunomodulatory potential of aerobic physical activity .
Performing high volume of aerobic exercise may favorably regulate autoimmunity in diabetes .
We tested whether increased physical activity is a self-sufficient positive factor in T1D subjects .
During a 3-month observational period , active ( six males ; 40.5 ± 6.1 years ; BMI : 24.5 ± 2.1 ) and sedentary ( four males , three females ; 35.9 ± 8.9 years ; BMI : 25.7 ± 3.8 ) T1D individuals @ @ @ @ @ @ @ metabolic , inflammatory , and autoimmune parameters .
At baseline and at the end of a 3-month period , glycosylated hemoglobin ( HbA1c ) , autoantibodies ( anti-GAD , anti-ZnT8 , anti-IA2 , and ICA ) and proinflammatory cytokines ( IL-6 and TNF-α ) were evaluated .
During the third month of the period , physically active T1D patients showed a significant reduction in the average glucose levels ( -9 % , p = 0.025 , by CGM ) compared to the first month values , and even their hyperglycemic episodes ( > @ @ @ @ @ @ @ % , p = 0.032 vs. first month ) .
Moreover , active T1D subjects exhibited an improved body composition with respect to sedentary controls .
No significant changes were detected as to the autoimmune and inflammatory profiles .
This study confirms the beneficial role of physical exercise associated with insulin pump therapy in order to improve metabolic control in individuals with T1D .
These preliminary positive observations need to be challenged in a prolonged interventional follow-up .

Previous studies in humans with type 1 diabetes mellitus (T1D) and in nonobese diabetic mice have investigated the beneficial immunomodulatory potential of aerobic physical activity. Performing high volume of aerobic exercise may favorably regulate autoimmunity in diabetes. We tested whether increased physical activity is a self-sufficient positive factor in T1D subjects. During a 3-month observational period, active (six males; 40.5 ± 6.1 years; BMI: 24.5 ± 2.1) and sedentary (four males, three females; 35.9 ± 8.9 years; BMI: 25.7 ± 3.8) T1D individuals on insulin pump therapy were studied for metabolic, inflammatory, and autoimmune parameters. At baseline and at the end of a 3-month period, glycosylated hemoglobin (HbA1c), autoantibodies (anti-GAD, anti-ZnT8, anti-IA2, and ICA) and proinflammatory cytokines (IL-6 and TNF-α) were evaluated. During the third month of the period, physically active T1D patients showed a significant reduction in the average glucose levels (-9%, p = 0.025, by CGM) compared to the first month values, and even their hyperglycemic episodes (>180 mg/dl) diminished significantly (-24.2%, p = 0.032 vs. first month). Moreover, active T1D subjects exhibited an improved body composition with respect to sedentary controls. No significant changes were detected as to the autoimmune and inflammatory profiles. This study confirms the beneficial role of physical exercise associated with insulin pump therapy in order to improve metabolic control in individuals with T1D. These preliminary positive observations need to be challenged in a prolonged interventional follow-up.


greenmedinfo--2020-03-21--The effects of voluntary wheel running on neuroinflammatory status.

The health benefits of exercise and physical activity ( PA ) have been well researched and it is widely accepted that PA is crucial for maintaining health .
One of the mechanisms by which exercise and PA exert their beneficial effects is through peripheral immune system adaptations .
To date , very few studies have looked at the regulation of neuroimmune reactions in response to PA. We studied the effect of voluntary wheel running ( VWR ) on pro- and anti-inflammatory cytokine levels , patterns of glial cell activation and expression of immune receptors in the brains of female C57BL/6 @ @ @ @ @ @ @ protein ( MCP ) -1 null mice , we investigated the role of this key immunoregulatory cytokine in mediating VWR-induced neuroinflammatory responses .
We demonstrated that , compared to their sedentary counterparts , C57BL/6 mice exposed for seven weeks to VWR had increased levels of pro- and anti-inflammatory cytokines , markers of glial cell activation and a trend towards increased expression of toll-like receptor ( TLR ) 4 in the brain .
Measurements of serum cytokines revealed that the alterations in brain cytokine levels could not be explained by the effects of PA @ @ @ @ @ @ @ that the modified neuroimmune status observed in the VWR group represents an activated immune system , as opposed to a less activated immune system in the sedentary group .
Since MCP-1 knockout mice displayed differing patterns of pro- and anti-inflammatory brain cytokine expression and glial activation when compared to their wild-type counterparts , we concluded that the effects of VWR on neuroimmune reactions may be modulated by MCP-1 .
These identified immunomodulatory effects of PA in the brain could contribute to the observed positive relationship between physically active lifestyles and a reduced risk @ @ @ @ @ @ @ possess a significant neuroinflammatory component .

The health benefits of exercise and physical activity (PA) have been well researched and it is widely accepted that PA is crucial for maintaining health. One of the mechanisms by which exercise and PA exert their beneficial effects is through peripheral immune system adaptations. To date, very few studies have looked at the regulation of neuroimmune reactions in response to PA. We studied the effect of voluntary wheel running (VWR) on pro- and anti-inflammatory cytokine levels, patterns of glial cell activation and expression of immune receptors in the brains of female C57BL/6 mice. By using homozygous monocyte chemoattractant protein (MCP)-1 null mice, we investigated the role of this key immunoregulatory cytokine in mediating VWR-induced neuroinflammatory responses. We demonstrated that, compared to their sedentary counterparts, C57BL/6 mice exposed for seven weeks to VWR had increased levels of pro- and anti-inflammatory cytokines, markers of glial cell activation and a trend towards increased expression of toll-like receptor (TLR) 4 in the brain. Measurements of serum cytokines revealed that the alterations in brain cytokine levels could not be explained by the effects of PA on peripheral cytokine levels. We propose that the modified neuroimmune status observed in the VWR group represents an activated immune system, as opposed to a less activated immune system in the sedentary group. Since MCP-1 knockout mice displayed differing patterns of pro- and anti-inflammatory brain cytokine expression and glial activation when compared to their wild-type counterparts, we concluded that the effects of VWR on neuroimmune reactions may be modulated by MCP-1. These identified immunomodulatory effects of PA in the brain could contribute to the observed positive relationship between physically active lifestyles and a reduced risk for a number of neurodegenerative diseases that possess a significant neuroinflammatory component.


greenmedinfo--2020-03-21--Aerobic exercise decreases lung inflammation by IgE decrement in an OVA mice model.

Aerobic exercise ( AE ) reduces lung function decline and risk of exacerbations in asthmatic patients .
However , the inflammatory lung response involved in exercise during the sensitization remains unclear .
Therefore , we evaluated the effects of exercise for 2 weeks in an experimental model of sensitization and single ovalbumin-challenge .
Mice were divided into 4 groups : mice non-sensitized and not submitted to exercise ( Sedentary , n=10 ) ; mice non-sensitized and submitted to exercise ( Exercise , n=10 ) ; mice sensitized and exposed to ovalbumin ( OVA , n=10 ) ; and mice sensitized @ @ @ @ @ @ @ OVA ( OVA+Exercise , n=10 ) .
24 h after the OVA/saline exposure , we counted inflammatory cells from bronchoalveolar fluid ( BALF ) , lung levels of total IgE , IL-4 , IL-5 , IL-10 and IL-1ra , measurements of OVA-specific IgG1 and IgE , and VEGF and NOS-2 expression via western blotting .
AE reduced cell counts from BALF in the OVA group ( p < 0.05 ) , total IgE , IL-4 and IL-5 lung levels and OVA-specific IgE and IgG1 titers ( p < 0.05 ) .
There was @ @ @ @ @ @ @ and IL-1ra lung levels in the OVA groups ( p < 0.05 ) .
Our results showed that AE attenuated the acute lung inflammation , suggesting immunomodulatory properties on the sensitization process in the early phases of antigen presentation in asthma .

Aerobic exercise (AE) reduces lung function decline and risk of exacerbations in asthmatic patients. However, the inflammatory lung response involved in exercise during the sensitization remains unclear. Therefore, we evaluated the effects of exercise for 2 weeks in an experimental model of sensitization and single ovalbumin-challenge. Mice were divided into 4 groups: mice non-sensitized and not submitted to exercise (Sedentary, n=10); mice non-sensitized and submitted to exercise (Exercise, n=10); mice sensitized and exposed to ovalbumin (OVA, n=10); and mice sensitized, submitted to exercise and exposed to OVA (OVA+Exercise, n=10). 24 h after the OVA/saline exposure, we counted inflammatory cells from bronchoalveolar fluid (BALF), lung levels of total IgE, IL-4, IL-5, IL-10 and IL-1ra, measurements of OVA-specific IgG1 and IgE, and VEGF and NOS-2 expression via western blotting. AE reduced cell counts from BALF in the OVA group (p<0.05), total IgE, IL-4 and IL-5 lung levels and OVA-specific IgE and IgG1 titers (p<0.05). There was an increase of NOS-2 expression, IL-10 and IL-1ra lung levels in the OVA groups (p<0.05). Our results showed that AE attenuated the acute lung inflammation, suggesting immunomodulatory properties on the sensitization process in the early phases of antigen presentation in asthma.


greenmedinfo--2020-03-21--High-intensity interval training reduces monocyte activation in obese adults.

Alterations in the distribution and activation of monocyte subsets are frequently observed in individuals with obesity and their participation in the pathological complications of obesity is proposed .
High-intensity interval training ( HIIT ) can be a time-efficient alternative to counteract the inflammatory outcomes of obesity , but so far , its effects on monocytes in obesity has not been fully explored .
In this study , we investigated whether 8 weeks of HIIT can modify the distribution and activation of the three monocyte subsets ( classical , intermediate and non-classical monocytes ) in individuals with obesity .
Our data @ @ @ @ @ @ @ higher percentage of non-classical monocytes compared to control , lean individuals , and consequently an imbalance among the CD16monocyte subsets .
Also , the expression of HLA-DR by intermediate monocytes is higher in insulin-resistant obese individuals , which indicates monocyte activation in obesity .
After 8 weeks of HIIT , the percentage of non-classical monocytes was reduced in individuals with obesity , restoring the balance among the CD16monocytes .
Also , the expression of HLA-DR by intermediate monocytes in insulin-resistant obese subjects was lower after HIIT .
Both findings indicate that monocyte activation @ @ @ @ @ @ @ HIIT .
These modifications were observed in the absence of changes in weight and body composition , although they were accompanied by the improvement in the metabolic status ( reduced insulin levels ) .
Our findings indicate that HIIT can be considered a time-efficient strategy to manage obesity-related monocyte alterations and strengthen the immunomodulatory potential of HIIT .

Alterations in the distribution and activation of monocyte subsets are frequently observed in individuals with obesity and their participation in the pathological complications of obesity is proposed. High-intensity interval training (HIIT) can be a time-efficient alternative to counteract the inflammatory outcomes of obesity, but so far, its effects on monocytes in obesity has not been fully explored. In this study, we investigated whether 8 weeks of HIIT can modify the distribution and activation of the three monocyte subsets (classical, intermediate and non-classical monocytes) in individuals with obesity. Our data show that individuals with obesity have a higher percentage of non-classical monocytes compared to control, lean individuals, and consequently an imbalance among the CD16monocyte subsets. Also, the expression of HLA-DR by intermediate monocytes is higher in insulin-resistant obese individuals, which indicates monocyte activation in obesity. After 8 weeks of HIIT, the percentage of non-classical monocytes was reduced in individuals with obesity, restoring the balance among the CD16monocytes. Also, the expression of HLA-DR by intermediate monocytes in insulin-resistant obese subjects was lower after HIIT. Both findings indicate that monocyte activation in individuals with obesity was reduced by HIIT. These modifications were observed in the absence of changes in weight and body composition, although they were accompanied by the improvement in the metabolic status (reduced insulin levels). Our findings indicate that HIIT can be considered a time-efficient strategy to manage obesity-related monocyte alterations and strengthen the immunomodulatory potential of HIIT.


greenmedinfo--2020-03-21--High-intensity training induces superior effects in preventing autoimmunity in experimental autoimmu

High-intensity training induces superior effects in preventing autoimmunity in experimental autoimmune encephalomyelitis.

BACKGROUND : Exercise training ( ET ) has beneficial effects on multiple sclerosis and its animal model experimental autoimmune encephalomyelitis ( EAE ) .
However , the intensity-dependent effects of ET on the systemic immune system in EAE remain undefined .
OBJECTIVE : ( 1 ) To compare the systemic immune modulatory effects of moderate versus high-intensity ET protocols in protecting against development of EAE ; ( 2 ) To investigate whether ET affects autoimmunity selectively , or causes general immunosuppression .
METHODS : Healthy mice performed moderate or high-intensity treadmill running programs .
Proteolipid protein ( PLP ) -induced @ @ @ @ @ @ @ effects specifically on the systemic immune system .
Lymph node ( LN ) -T cells from trained versus sedentary donor mice were transferred to naïve recipients and EAE severity was assessed , by clinical assessment and histopathological analysis .
LN-T cells derived from donor trained versus sedentary PLP-immunized mice were analyzed in vitro for proliferation assays by flow cytometry analysis and cytokine and chemokine receptor gene expression using real-time PCR .
T cell-dependent immune responses of trained versus sedentary mice to the nonautoantigen ovalbumin and susceptibility to Escherichia coli-induced acute peritonitis were examined @ @ @ @ @ @ @ donor mice induced significantly greater inhibition than moderate-intensity training on proliferation and generation of encephalitogenic T cells in response to PLP-immunization , and on EAE severity upon their transfer into recipient mice .
High-intensity training also inhibited LN-T cell proliferation in response to ovalbumin immunization .
E. coli bacterial counts and dissemination were not affected by training .
INTERPRETATION : High-intensity training induces superior effects in preventing autoimmunity in EAE , but does not alter immune responses to E. coli infection .

BACKGROUND: Exercise training (ET) has beneficial effects on multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the intensity-dependent effects of ET on the systemic immune system in EAE remain undefined.
OBJECTIVE: (1) To compare the systemic immune modulatory effects of moderate versus high-intensity ET protocols in protecting against development of EAE; (2) To investigate whether ET affects autoimmunity selectively, or causes general immunosuppression.
METHODS: Healthy mice performed moderate or high-intensity treadmill running programs. Proteolipid protein (PLP)-induced transfer EAE was utilized to examine ET effects specifically on the systemic immune system. Lymph node (LN)-T cells from trained versus sedentary donor mice were transferred to naïve recipients and EAE severity was assessed, by clinical assessment and histopathological analysis. LN-T cells derived from donor trained versus sedentary PLP-immunized mice were analyzed in vitro for proliferation assays by flow cytometry analysis and cytokine and chemokine receptor gene expression using real-time PCR. T cell-dependent immune responses of trained versus sedentary mice to the nonautoantigen ovalbumin and susceptibility to Escherichia coli-induced acute peritonitis were examined.
RESULTS: High-intensity training in healthy donor mice induced significantly greater inhibition than moderate-intensity training on proliferation and generation of encephalitogenic T cells in response to PLP-immunization, and on EAE severity upon their transfer into recipient mice. High-intensity training also inhibited LN-T cell proliferation in response to ovalbumin immunization. E. coli bacterial counts and dissemination were not affected by training.
INTERPRETATION: High-intensity training induces superior effects in preventing autoimmunity in EAE, but does not alter immune responses to E. coli infection.


greenmedinfo--2020-03-21--Exercise promotes resolution of acute inflammation by catecholamine-mediated stimulation of resolvin

Exercise promotes resolution of acute inflammation by catecholamine-mediated stimulation of resolvin D1 biosynthesis.

The mechanisms by which regular exercise prevents the development and progression of chronic inflammatory diseases are largely unknown .
We find that exercise enhances resolution of acute inflammation by augmenting resolvin D1 ( RvD1 ) levels and by promoting macrophage phagocytosis .
When compared with sedentary controls , mice that performed a four-week treadmill exercise regimen displayed higher macrophage phagocytic activity , enhanced RvD1 levels , and earlier neutrophil clearance following an acute inflammatory challenge .
In acute inflammatory cell extracts from exercised mice , we found elevated expression ofandand higher RvD1 levels .
Because exercise stimulates release of epinephrine @ @ @ @ @ @ @ questioned whether epinephrine exerts proresolving actions on macrophages .
Epinephrine-treated macrophages displayed higher RvD1 levels and 15-lipoxygenase-1 protein abundance , which were prevented by incubation with theα1 adrenergic receptor ( α1-AR ) antagonist prazosin .
Likewise , stimulation of the α1-AR with phenylephrine enhanced macrophage phagocytosis and RvD1 production .
During acute inflammation , prazosin abrogated exercise-enhanced neutrophil clearance , macrophage phagocytosis , and RvD1 biosynthesis .
These results suggest that exercise-stimulated epinephrine enhances resolution of acute inflammation in an α1-AR-dependent manner .
To our knowledge , our findings provide new mechanistic insights @ @ @ @ @ @ @ could lead to the identification of novel pathways to stimulate resolution .

The mechanisms by which regular exercise prevents the development and progression of chronic inflammatory diseases are largely unknown. We find that exercise enhances resolution of acute inflammation by augmenting resolvin D1 (RvD1) levels and by promoting macrophage phagocytosis. When compared with sedentary controls, mice that performed a four-week treadmill exercise regimen displayed higher macrophage phagocytic activity, enhanced RvD1 levels, and earlier neutrophil clearance following an acute inflammatory challenge. In acute inflammatory cell extracts from exercised mice, we found elevated expression ofandand higher RvD1 levels. Because exercise stimulates release of epinephrine, which has immunomodulatory effects, we questioned whether epinephrine exerts proresolving actions on macrophages. Epinephrine-treated macrophages displayed higher RvD1 levels and 15-lipoxygenase-1 protein abundance, which were prevented by incubation with theα1 adrenergic receptor (α1-AR) antagonist prazosin. Likewise, stimulation of the α1-AR with phenylephrine enhanced macrophage phagocytosis and RvD1 production. During acute inflammation, prazosin abrogated exercise-enhanced neutrophil clearance, macrophage phagocytosis, and RvD1 biosynthesis. These results suggest that exercise-stimulated epinephrine enhances resolution of acute inflammation in an α1-AR-dependent manner. To our knowledge, our findings provide new mechanistic insights into the proresolving effects of exercise that could lead to the identification of novel pathways to stimulate resolution.


greenmedinfo--2020-03-21--Immunomodulatory effects of exercise in experimental multiple sclerosis.

Multiple Sclerosis ( MS ) is a demyelinating and neurodegenerative disease .
Though a specific antigen has not been identified , it is widely accepted that MS is an autoimmune disorder characterized by myelin-directed immune attack .
Pharmacological treatments for MS are based on immunomodulatory or immunosuppressant drugs , designed to attenuate or dampen the immune reaction , to improve neurological functions .
Recently , rehabilitation has gained increasing attention in the scientific community dealing with MS .
Engagement of people with MS in exercise programs has been associated with a number of functional improvements in mobility , balance , @ @ @ @ @ @ @ studies indicate the effectiveness of exercise against fatigue and mood disorders that are frequently associated with the disease .
However , whether exercise acts like an immunomodulatory therapy is still an unresolved question .
A good tool to address this issue is provided by the study of the immunomodulatory effects of exercise in an animal model of MS , including the experimental autoimmune encephalomyelitis ( EAE ) , the Theiler 's virus induced-demyelinating disease ( TMEV-IDD ) and toxic-demyelinating models , cuprizone ( CPZ ) , and lysolecithin ( LPC ) .
So @ @ @ @ @ @ @ animal models , most of the pre-clinical data have been gained in EAE and to a lesser extent in CPZ and LPC .
These studies have highlighted beneficial effects of exercise , suggesting the modulation of both the innate and the adaptive immune response in the peripheral blood as well as in the brain .
In the present paper , starting from the biological differences among MS animal models in terms of immune system involvement , we revise the literature regarding the effects of exercise in EAE , CPZ , and LPC , @ @ @ @ @ @ @ model , including the so-far unexplored TMEV-IDD , to address the immune effects of exercise in MS .

Multiple Sclerosis (MS) is a demyelinating and neurodegenerative disease. Though a specific antigen has not been identified, it is widely accepted that MS is an autoimmune disorder characterized by myelin-directed immune attack. Pharmacological treatments for MS are based on immunomodulatory or immunosuppressant drugs, designed to attenuate or dampen the immune reaction, to improve neurological functions. Recently, rehabilitation has gained increasing attention in the scientific community dealing with MS. Engagement of people with MS in exercise programs has been associated with a number of functional improvements in mobility, balance, and motor coordination. Moreover, several studies indicate the effectiveness of exercise against fatigue and mood disorders that are frequently associated with the disease. However, whether exercise acts like an immunomodulatory therapy is still an unresolved question. A good tool to address this issue is provided by the study of the immunomodulatory effects of exercise in an animal model of MS, including the experimental autoimmune encephalomyelitis (EAE), the Theiler's virus induced-demyelinating disease (TMEV-IDD) and toxic-demyelinating models, cuprizone (CPZ), and lysolecithin (LPC). So far, despite the availability of different animal models, most of the pre-clinical data have been gained in EAE and to a lesser extent in CPZ and LPC. These studies have highlighted beneficial effects of exercise, suggesting the modulation of both the innate and the adaptive immune response in the peripheral blood as well as in the brain. In the present paper, starting from the biological differences among MS animal models in terms of immune system involvement, we revise the literature regarding the effects of exercise in EAE, CPZ, and LPC, and critically highlight the advantages of either model, including the so-far unexplored TMEV-IDD, to address the immune effects of exercise in MS.


greenmedinfo--2020-03-21--Millions of Unnecessary Pelvic Exams Performed in Teens

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greenmedinfo--2020-03-21--Increased Access to Cannabis May Reduce Opioid Prescriptions


greenmedinfo--2020-03-21--Vitamin D deficiency aggravates hepatic oxidative stress and inflammation during chronic alcohol-ind

Vitamin D deficiency aggravates hepatic oxidative stress and inflammation during chronic alcohol-induced liver injury.

Vitamin D deficiency has been reported in alcoholics .
This study is aimed at evaluating the effects of vitamin D deficiency on chronic alcohol-induced liver injury in mice .
Mice were fed with modified Lieber-DeCarli liquid diets for 6 weeks to establish an animal model of chronic alcohol-induced liver injury .
In the VDD+EtOH group , mice were fed with modified diets , in which vitamin D was depleted .
Vitamin D deficiency aggravated alcohol-induced liver injury .
Furthermore , vitamin D deficiency aggravated hepatocyte apoptosis during alcohol-induced liver injury .
Although it has a little effect on hepatic TG @ @ @ @ @ @ @ hepatic GSH depletion and lipid peroxidation .
Further analysis showed that vitamin D deficiency further increased alcohol-induced upregulation of hepatic inducible nitric oxide synthase ( ) , two NADPH oxidase subunitsand , and heme oxygenase- ( HO- ) 1 .
By contrast , vitamin D deficiency attenuated alcohol-induced upregulation of hepatic antioxidant enzyme genes , such as superoxide dismutase ( ) 1 and .
In addition , vitamin D deficiency significantly elevated alcohol-induced upregulation of hepatic proinflammatory cytokines and chemokines .
Taken together , these results suggest that vitamin D deficiency aggravates hepatic @ @ @ @ @ @ @ liver injury .

Vitamin D deficiency has been reported in alcoholics. This study is aimed at evaluating the effects of vitamin D deficiency on chronic alcohol-induced liver injury in mice. Mice were fed with modified Lieber-DeCarli liquid diets for 6 weeks to establish an animal model of chronic alcohol-induced liver injury. In the VDD+EtOH group, mice were fed with modified diets, in which vitamin D was depleted. Vitamin D deficiency aggravated alcohol-induced liver injury. Furthermore, vitamin D deficiency aggravated hepatocyte apoptosis during alcohol-induced liver injury. Although it has a little effect on hepatic TG content, vitamin D deficiency promoted alcohol-induced hepatic GSH depletion and lipid peroxidation. Further analysis showed that vitamin D deficiency further increased alcohol-induced upregulation of hepatic inducible nitric oxide synthase (), two NADPH oxidase subunitsand, and heme oxygenase- (HO-) 1. By contrast, vitamin D deficiency attenuated alcohol-induced upregulation of hepatic antioxidant enzyme genes, such as superoxide dismutase () 1 and. In addition, vitamin D deficiency significantly elevated alcohol-induced upregulation of hepatic proinflammatory cytokines and chemokines. Taken together, these results suggest that vitamin D deficiency aggravates hepatic oxidative stress and inflammation during chronic alcohol-induced liver injury.


greenmedinfo--2020-03-21--Weekly vitamin D3 supplementation improves aerobic performance in combat sport athletes.

Vitamin Dsupplementation can affect the strength and power of an athlete , however the effect on endurance performance remains unclear .
Twenty-seven recreational male combat athletes with at least 12 months experience within combat sports were recruited ( age : 24 ± 4 years , stature : 176 ± 6 cm , weight : 77 ± 14 kg ) .
Participants completed baseline testing for blood haemoglobin and haematocrit , upper and lower body VOand upper and lower body Wingate .
Following testing participants were stratified to 50000IU ( D1 ) , 80000IU ( D2 ) or 110000IU ( D3 @ @ @ @ @ @ @ then completed a 6-week placebo period followed by a 6-week supplementation period .
Retesting was carried out after the placebo and supplementation period .
There was a significant effect for time for haemoglobin and haematocrit , upper and lower body VOand upper body Wingate power ( p < 0.01 ) but no effect for dose of vitamin D given .
Performance data was normalised to vitamin D intake and there was a moderate effect size between D1 and D2 for lower body VO ( d=0.6 ) , upper body VO ( d=0.13 ) @ @ @ @ @ @ @ ) , with a large effect size between D1 and D2 for haemoglobin ( d=1.19 ) , haematocrit ( d=0.93 ) and upper body peak power ( d=0.95 ) .
There was a large effect size for D1 compared to D3 for all variables ( d > 0.8 ) .
Therefore , there is no additional benefit to increasing dose above 500000IU vitamin D per week .
Given the endurance adaptations from vitamin D supplementation and the importance of endurance for combat performance , recreational combat athletes should supplement at 50000IU per week @ @ @ @

Vitamin Dsupplementation can affect the strength and power of an athlete, however the effect on endurance performance remains unclear. Twenty-seven recreational male combat athletes with at least 12 months experience within combat sports were recruited (age: 24 ± 4 years, stature: 176 ± 6 cm, weight: 77 ± 14 kg). Participants completed baseline testing for blood haemoglobin and haematocrit, upper and lower body VOand upper and lower body Wingate. Following testing participants were stratified to 50000IU (D1), 80000IU (D2) or 110000IU (D3) of vitamin Dper week. They then completed a 6-week placebo period followed by a 6-week supplementation period. Retesting was carried out after the placebo and supplementation period. There was a significant effect for time for haemoglobin and haematocrit, upper and lower body VOand upper body Wingate power (p<0.01) but no effect for dose of vitamin D given. Performance data was normalised to vitamin D intake and there was a moderate effect size between D1 and D2 for lower body VO(d=0.6), upper body VO(d=0.13) and upper body average power (d=0.75), with a large effect size between D1 and D2 for haemoglobin (d=1.19), haematocrit (d=0.93) and upper body peak power (d=0.95). There was a large effect size for D1 compared to D3 for all variables (d>0.8). Therefore, there is no additional benefit to increasing dose above 500000IU vitamin D per week. Given the endurance adaptations from vitamin D supplementation and the importance of endurance for combat performance, recreational combat athletes should supplement at 50000IU per week for six weeks.


greenmedinfo--2020-03-21--Cannabidiol is an effective helper compound in combination with bacitracin to kill Gram-positive bac

Cannabidiol is an effective helper compound in combination with bacitracin to kill Gram-positive bacteria.

The cannabinoid cannabidiol ( CBD ) is characterised in this study as a helper compound against resistant bacteria .
CBD potentiates the effect of bacitracin ( BAC ) against Gram-positive bacteria ( Staphylococcus species , Listeria monocytogenes , and Enterococcus faecalis ) but appears ineffective against Gram-negative bacteria .
CBD reduced the MIC value of BAC by at least 64-fold and the combination yielded an FIC index of 0.5 or below in most Gram-positive bacteria tested .
Morphological changes in S. aureus as a result of the combination of CBD and BAC included several septa formations during cell division along @ @ @ @ @ @ @ muropeptide composition of treated S. aureus indicated no changes in the cell wall composition .
However , CBD and BAC treated bacteria did show a decreased rate of autolysis .
The bacteria further showed a decreased membrane potential upon treatment with CBD ; yet , they did not show any further decrease upon combination treatment .
Noticeably , expression of a major cell division regulator gene , ezrA , was reduced two-fold upon combination treatment emphasising the impact of the combination on cell division .
Based on these observations , the combination of @ @ @ @ @ @ @ a putative novel treatment in clinical settings for treatment of infections with antibiotic resistant Gram-positive bacteria .

The cannabinoid cannabidiol (CBD) is characterised in this study as a helper compound against resistant bacteria. CBD potentiates the effect of bacitracin (BAC) against Gram-positive bacteria (Staphylococcus species, Listeria monocytogenes, and Enterococcus faecalis) but appears ineffective against Gram-negative bacteria. CBD reduced the MIC value of BAC by at least 64-fold and the combination yielded an FIC index of 0.5 or below in most Gram-positive bacteria tested. Morphological changes in S. aureus as a result of the combination of CBD and BAC included several septa formations during cell division along with membrane irregularities. Analysis of the muropeptide composition of treated S. aureus indicated no changes in the cell wall composition. However, CBD and BAC treated bacteria did show a decreased rate of autolysis. The bacteria further showed a decreased membrane potential upon treatment with CBD; yet, they did not show any further decrease upon combination treatment. Noticeably, expression of a major cell division regulator gene, ezrA, was reduced two-fold upon combination treatment emphasising the impact of the combination on cell division. Based on these observations, the combination of CBD and BAC is suggested to be a putative novel treatment in clinical settings for treatment of infections with antibiotic resistant Gram-positive bacteria.


greenmedinfo--2020-03-21--Purified pharmaceutical CBD may be an effective and safe adjunctive therapy in refractory epileptic

Purified pharmaceutical CBD may be an effective and safe adjunctive therapy in refractory epileptic spasms.

OBJECTIVE : This study aimed to evaluate clinical efficacy and safety of purified pharmaceutical cannabidiol ( CBD ) as an adjunctive therapy in refractory childhood-onset epileptic spasms ( ES ) .
METHODS : Nine patients with ES were enrolled in an Institutional Review Board ( IRB ) - and Food and Drug Administration ( FDA ) -approved expanded access investigational new drug trial .
Patients received plant-derived highly purified CBD in oral solution in addition to their baseline medications at an initial dosage of 5 mg/kg/day , which was increased by 5 mg/kg/day every week to an initial target dosage @ @ @ @ @ @ @ adverse event , and parents ' subjective reports of cognitive and behavioral changes were recorded after 2 weeks and 1 , 2 , 3 , 6 , 9 , and 12 months of CBD treatment .
Responder rates ( percent of patients with > 50 % reduction in ES frequency from baseline ) were calculated .
Electrographic changes were studied in relation to CBD initiation and clinical response .
RESULTS : Overall , the responder rates in 9 patients were 67 % , 78 % , 67 % , 56 % , 78 @ @ @ @ @ @ @ % after 2 weeks and 1 , 2 , 3 , 6 , 9 , and 12 months of CBD treatment , respectively .
Three out of nine patients ( 33 % ) were ES free after two months of treatment .
Parents reported subjective improvements in cognitive and behavioral domains .
Side effects , primarily drowsiness , were seen in 89 % of patients ( n = 8 ) .
Eight of the nine ( 89 % ) patients had electroencephalographic ( EEG ) studies prior to and after initiation of CBD @ @ @ @ @ @ @ 60 % ) had resolution in their hypsarrhythmia pattern .
SIGNIFICANCE : Purified pharmaceutical CBD may be an effective and safe adjunctive therapy in refractory ES and may also be associated with improvements in electrographic findings .

OBJECTIVE: This study aimed to evaluate clinical efficacy and safety of purified pharmaceutical cannabidiol (CBD) as an adjunctive therapy in refractory childhood-onset epileptic spasms (ES).
METHODS: Nine patients with ES were enrolled in an Institutional Review Board (IRB)- and Food and Drug Administration (FDA)-approved expanded access investigational new drug trial. Patients received plant-derived highly purified CBD in oral solution in addition to their baseline medications at an initial dosage of 5 mg/kg/day, which was increased by 5 mg/kg/day every week to an initial target dosage of 25 mg/kg/day. Seizure frequency, adverse event, and parents' subjective reports of cognitive and behavioral changes were recorded after 2 weeks and 1, 2, 3, 6, 9, and 12 months of CBD treatment. Responder rates (percent of patients with>50% reduction in ES frequency from baseline) were calculated. Electrographic changes were studied in relation to CBD initiation and clinical response.
RESULTS: Overall, the responder rates in 9 patients were 67%, 78%, 67%, 56%, 78%, 78%, and 78% after 2 weeks and 1, 2, 3, 6, 9, and 12 months of CBD treatment, respectively. Three out of nine patients (33%) were ES free after two months of treatment. Parents reported subjective improvements in cognitive and behavioral domains. Side effects, primarily drowsiness, were seen in 89% of patients (n = 8). Eight of the nine (89%) patients had electroencephalographic (EEG) studies prior to and after initiation of CBD. Three out of five patients (60%) had resolution in their hypsarrhythmia pattern.
SIGNIFICANCE: Purified pharmaceutical CBD may be an effective and safe adjunctive therapy in refractory ES and may also be associated with improvements in electrographic findings.


greenmedinfo--2020-03-21--Cannabidiol exerts protective effects in an in vitro model of Parkinson's disease activating AKT/mTO

Cannabidiol exerts protective effects in an in vitro model of Parkinson's disease activating AKT/mTOR pathway.

Parkinson 's disease ( PD ) is a neurodegenerative disorder characterized by the degeneration of the nigrostriatal dopaminergic pathway with loss of substantia nigra pars compacta neurons and dopamine depletion .
Various natural compounds showed protective actions against PD .
In this work , the protective effects of cannabidiol ( CBD ) , obtained from Cannabis sativa , were evaluated in retinoic acid differentiated SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium ( MPP ) , an in vitro PD model .
In order to evaluate which receptor is involved in CBD actions CB1 , CB2 and TRPV1 receptor antagonists were used .
@ @ @ @ @ @ @ caused by MPP , reducing apoptosis as demonstrated by the reduction of Bax and caspase 3 .
Moreover , CBD reduced the nuclear levels of PARP-1 .
The protective effects of CBD seem to be mediated by the activation of ERK and AKT/mTOR pathways .
The treatment with AKT1/2 inhibitor and the mTOR inhibitor rapamycin abolished CBD protective effects .
The CBD-induced ERK activation may be mediated by CBD interaction with CB2 and TRPV1 .
We also investigated the protein levels of the autophagic proteins LC3 and beclin 1 .
CBD reduced the @ @ @ @ @ @ @ TRPV1 receptors .
These data suggested the involvement of ERK in the modulation of autophagy .
However , beclin 1 levels were not modified neither by MPPnor by CBD .
These results indicated that CBD may exert preventive and protective actions in PD .

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of the nigrostriatal dopaminergic pathway with loss of substantia nigra pars compacta neurons and dopamine depletion. Various natural compounds showed protective actions against PD. In this work, the protective effects of cannabidiol (CBD), obtained from Cannabis sativa, were evaluated in retinoic acid differentiated SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium (MPP), an in vitro PD model. In order to evaluate which receptor is involved in CBD actions CB1, CB2 and TRPV1 receptor antagonists were used. CBD counteracted the loss of cell viability caused by MPP, reducing apoptosis as demonstrated by the reduction of Bax and caspase 3. Moreover, CBD reduced the nuclear levels of PARP-1. The protective effects of CBD seem to be mediated by the activation of ERK and AKT/mTOR pathways. The treatment with AKT1/2 inhibitor and the mTOR inhibitor rapamycin abolished CBD protective effects. The CBD-induced ERK activation may be mediated by CBD interaction with CB2 and TRPV1. We also investigated the protein levels of the autophagic proteins LC3 and beclin 1. CBD reduced the MPP-induced increase of LC3 by CB2 and TRPV1 receptors. These data suggested the involvement of ERK in the modulation of autophagy. However, beclin 1 levels were not modified neither by MPPnor by CBD. These results indicated that CBD may exert preventive and protective actions in PD.


greenmedinfo--2020-03-21--Vitamin C ameliorated cardiac autonomic neuropathy in type 2 diabetic rats.

BACKGROUND : Vitamin C ( VC ) is a common antioxidant with cell protection potentials .
However , its possible protective effect on cardiac autonomic nerves from diabetic induced insults is yet to be explored .
AIM : To investigate the effects of VC on diabetic cardiac autonomic neuropathy .
METHODS : Thirty male Wistar rats were equally grouped into control , diabetic and diabetic + VC .
Type 2 diabetes was induced with fructose diet and alloxan .
VC ( 1 g/kg ) was administered for 4 wkoral canula .
Blood pressure and heart rate were measured non-invasively using @ @ @ @ @ @ @ analysis of heart rate variability ( HRV ) was used to assess cardiac autonomic neuropathy .
Blood was collected from the ocular sinus for biochemical analysis .
Urethane ( 1 g/kg-ip ) was used for anaesthesia prior to HRV and cervical dislocation to harvest hearts .
Intracardiac autonomic nerve was assessed using tyrosine hydroxylase immunohistochemistry on fixed heart sections .
RESULTS : Results were analysed using ANOVA atαUnlike VC and control groups , diabetic rats showed significantly ( < 0.0001 ) reduced HRV , increased heart-rate and blood pressure , initial increase in @ @ @ @ @ @ @ sparse activity at week-4 of diabetes .
Furthermore , apolipoprotein B , Oxidative stress and inflammatory markers were significantly ( < 0.01 ) reduced in VC treated rats .
CONCLUSION : VC possesses cardio-autonomic nerve protective potential and ameliorates the symptoms of cardiac autonomic neuropathy in type 2 diabetes .
The possible mechanismswhich VC exert these effects may bedownregulation of oxidative stress , inflammation and apolipoprotein B .

BACKGROUND: Vitamin C (VC) is a common antioxidant with cell protection potentials. However, its possible protective effect on cardiac autonomic nerves from diabetic induced insults is yet to be explored.
AIM: To investigate the effects of VC on diabetic cardiac autonomic neuropathy.
METHODS: Thirty male Wistar rats were equally grouped into control, diabetic and diabetic + VC. Type 2 diabetes was induced with fructose diet and alloxan. VC (1 g/kg) was administered for 4 wkoral canula. Blood pressure and heart rate were measured non-invasively using tail flick blood pressure monitor. Spectral analysis of heart rate variability (HRV) was used to assess cardiac autonomic neuropathy. Blood was collected from the ocular sinus for biochemical analysis. Urethane (1 g/kg-ip) was used for anaesthesia prior to HRV and cervical dislocation to harvest hearts. Intracardiac autonomic nerve was assessed using tyrosine hydroxylase immunohistochemistry on fixed heart sections.
RESULTS: Results were analysed using ANOVA atαUnlike VC and control groups, diabetic rats showed significantly (<0.0001) reduced HRV, increased heart-rate and blood pressure, initial increase in cardiac tyrosine hydroxylase activities at week-2 and sparse activity at week-4 of diabetes. Furthermore, apolipoprotein B, Oxidative stress and inflammatory markers were significantly (<0.01) reduced in VC treated rats.
CONCLUSION: VC possesses cardio-autonomic nerve protective potential and ameliorates the symptoms of cardiac autonomic neuropathy in type 2 diabetes. The possible mechanismswhich VC exert these effects may bedownregulation of oxidative stress, inflammation and apolipoprotein B.


greenmedinfo--2020-03-21--Vitamin C restricts the emergence of acquired resistance to EGFR-targeted therapies in colorectal ca

Vitamin C restricts the emergence of acquired resistance to EGFR-targeted therapies in colorectal cancer.

The long-term efficacy of the Epidermal Growth Factor Receptor ( EGFR ) -targeted antibody cetuximab in advanced colorectal cancer ( CRC ) patients is limited by the emergence of drug-resistant ( persister ) cells .
Recent studies in other cancer types have shown that cells surviving initial treatment with targeted agents are often vulnerable to alterations in cell metabolism including oxidative stress .
Vitamin C ( VitC ) is an antioxidant agent which can paradoxically trigger oxidative stress at pharmacological dose .
Here we tested the hypothesis that VitC in combination with cetuximab could restrain the emergence of secondary resistance @ @ @ @ @ @ @ We found that addition of VitC to cetuximab impairs the emergence of drug persisters , limits the growth of CRC organoids , and significantly delays acquired resistance in CRC patient-derived xenografts .
Mechanistically , proteomic and metabolic flux analysis shows that cetuximab blunts carbohydrate metabolism by blocking glucose uptake and glycolysis , beyond promoting slow but progressive ROS production .
In parallel , VitC disrupts iron homeostasis and further increases ROS levels ultimately leading to ferroptosis .
Combination of VitC and cetuximab orchestrates a synthetic lethal metabolic cell death program triggered by ATP @ @ @ @ @ @ @ limits the emergence of acquired resistance to anti-EGFR antibodies .
Considering that high-dose VitC is known to be safe in cancer patients , our findings might have clinical impact on CRC patients treated with anti-EGFR therapies .

The long-term efficacy of the Epidermal Growth Factor Receptor (EGFR)-targeted antibody cetuximab in advanced colorectal cancer (CRC) patients is limited by the emergence of drug-resistant (persister) cells. Recent studies in other cancer types have shown that cells surviving initial treatment with targeted agents are often vulnerable to alterations in cell metabolism including oxidative stress. Vitamin C (VitC) is an antioxidant agent which can paradoxically trigger oxidative stress at pharmacological dose. Here we tested the hypothesis that VitC in combination with cetuximab could restrain the emergence of secondary resistance to EGFR blockade in CRCwild-type models. We found that addition of VitC to cetuximab impairs the emergence of drug persisters, limits the growth of CRC organoids, and significantly delays acquired resistance in CRC patient-derived xenografts. Mechanistically, proteomic and metabolic flux analysis shows that cetuximab blunts carbohydrate metabolism by blocking glucose uptake and glycolysis, beyond promoting slow but progressive ROS production. In parallel, VitC disrupts iron homeostasis and further increases ROS levels ultimately leading to ferroptosis. Combination of VitC and cetuximab orchestrates a synthetic lethal metabolic cell death program triggered by ATP depletion and oxidative stress, which effectively limits the emergence of acquired resistance to anti-EGFR antibodies. Considering that high-dose VitC is known to be safe in cancer patients, our findings might have clinical impact on CRC patients treated with anti-EGFR therapies.


greenmedinfo--2020-03-21--Dietary melatonin supplementation may have beneficial effects in the management of metabolic syndrom

Dietary melatonin supplementation may have beneficial effects in the management of metabolic syndrome.

BACKGROUND : Metabolic syndrome is a complex pattern of disorders which occur jointly and is associated with increased risk of cardiovascular and cerebrovascular disease .
Therefore the need for more-efficient options of treatment has become imperative .
OBJECTIVE : This study examined the effect of dietary-melatonin in the management of behavioural , metabolic , antioxidant and organ changes due to high-fat/high-sugar ( HFHS ) diet- induced metabolic syndrome in mice .
METHODOLOGY : Mice were randomly-assigned into five groups of ten animals each .
Groups were normal control [ fed standard diet ( SD ) ] , HFHS control , @ @ @ @ @ @ @ HFHS at 2.5 , 5 and 10 mg/kg of feed .
Mice were fed for seven weeks , and body weight was assessed weekly .
Open-field behaviours , radial-arm and Y-maze spatial memory were scored at the end of the experimental period .
Twenty-four hours after the last behavioural test , blood was taken for estimation of blood glucose levels after an overnight fast .
Animals were then euthanised , and blood was taken for estimation of plasma insulin , leptin and adiponectin levels , and serum lipid profile .
The liver , @ @ @ @ @ @ @ for general histology , while homogenates of the liver and whole brain were used to assess oxidative stress parameters .
RESULTS : Results showed that dietary melatonin ( compared to HFHS diet ) was associated with a decrease in body weight , food intake and novelty-induced behaviours ; and an increase in spatial-working memory scores .
A decrease in glucose , insulin , leptin and malondialdehyde levels ; and an increase in adiponectin levels and superoxide dismutase activity were also observed .
Histomorphological/histomorphometric examination revealed evidence of organ injury with HFHS diet , @ @ @ @ @ @ @ supplemented diet .
CONCLUSION : In conclusion , dietary melatonin supplementation may have beneficial effects in the management of metabolic syndrome .

BACKGROUND: Metabolic syndrome is a complex pattern of disorders which occur jointly and is associated with increased risk of cardiovascular and cerebrovascular disease. Therefore the need for more-efficient options of treatment has become imperative.
OBJECTIVE: This study examined the effect of dietary-melatonin in the management of behavioural, metabolic, antioxidant and organ changes due to high-fat/high-sugar (HFHS) diet- induced metabolic syndrome in mice.
METHODOLOGY: Mice were randomly-assigned into five groups of ten animals each. Groups were normal control [fed standard diet (SD)], HFHS control, and 3 groups of melatonin incorporated into HFHS at 2.5, 5 and 10 mg/kg of feed. Mice were fed for seven weeks, and body weight was assessed weekly. Open-field behaviours, radial-arm and Y-maze spatial memory were scored at the end of the experimental period. Twenty-four hours after the last behavioural test, blood was taken for estimation of blood glucose levels after an overnight fast. Animals were then euthanised, and blood was taken for estimation of plasma insulin, leptin and adiponectin levels, and serum lipid profile. The liver, kidneys and brain were excised and processed for general histology, while homogenates of the liver and whole brain were used to assess oxidative stress parameters.
RESULTS: Results showed that dietary melatonin (compared to HFHS diet) was associated with a decrease in body weight, food intake and novelty-induced behaviours; and an increase in spatial-working memory scores. A decrease in glucose, insulin, leptin and malondialdehyde levels; and an increase in adiponectin levels and superoxide dismutase activity were also observed. Histomorphological/histomorphometric examination revealed evidence of organ injury with HFHS diet, and varying degrees of amelioration with melatonin- supplemented diet.
CONCLUSION: In conclusion, dietary melatonin supplementation may have beneficial effects in the management of metabolic syndrome.


greenmedinfo--2020-03-21--Melatonin and oxidative stress in melasma - an unexplored territory; a prospective study.

BACKGROUND : Melasma , an acquired disorder of hyperpigmentation , is the most common pigmentary disorder in India .
Many factors are implicated in the pathogenesis , and recently the role of oxidative damage including melatonin has been postulated .
This study was undertaken to evaluate the role of oxidative stress and serum melatonin in pathogenesis of melasma .
METHODS : Seventy-five patients with melasma and an equal number of age and sex-matched controls were included in the study .
Clinical characteristics were noted , and baseline severity assessment using modified Melasma Area and Severity Index ( MASI ) was @ @ @ @ @ @ @ , catalase , protein carbonyl , and nitric oxide levels were measured and compared between cases and controls .
RESULTS : The serum levels of melatonin and catalase were significantly lower among the cases as compared to controls , while the serum levels of protein carbonyl and nitric oxide were significantly higher in cases compared to controls .
There was no statistically significant correlation between these markers of oxidative stress and severity of the disease .
CONCLUSIONS : Oxidative stress is increased in patients with melasma compared to the control group in this @ @ @ @ @ @ @ also exists in patients with melasma .
No correlation between the oxidative stress and severity of the disease was found .
Further and larger studies including therapeutic trials with powerful antioxidants are warranted .

BACKGROUND: Melasma, an acquired disorder of hyperpigmentation, is the most common pigmentary disorder in India. Many factors are implicated in the pathogenesis, and recently the role of oxidative damage including melatonin has been postulated. This study was undertaken to evaluate the role of oxidative stress and serum melatonin in pathogenesis of melasma.
METHODS: Seventy-five patients with melasma and an equal number of age and sex-matched controls were included in the study. Clinical characteristics were noted, and baseline severity assessment using modified Melasma Area and Severity Index (MASI) was done in all patients. Serum melatonin, catalase, protein carbonyl, and nitric oxide levels were measured and compared between cases and controls.
RESULTS: The serum levels of melatonin and catalase were significantly lower among the cases as compared to controls, while the serum levels of protein carbonyl and nitric oxide were significantly higher in cases compared to controls. There was no statistically significant correlation between these markers of oxidative stress and severity of the disease.
CONCLUSIONS: Oxidative stress is increased in patients with melasma compared to the control group in this study. A state of melatonin deficit also exists in patients with melasma. No correlation between the oxidative stress and severity of the disease was found. Further and larger studies including therapeutic trials with powerful antioxidants are warranted.


greenmedinfo--2020-03-21--Melatonin for the treatment of sepsis: the scientific rationale

Sepsis affects 30 million people worldwide , leading to 6 million deaths every year ( WHO ) , and despite @ @ @ @ @ initiatives are drastically needed .
According to the current literature , oxidative imbalance and mitochondrial @ @ @ @ @ septic patients that can cause multiorgan failure and death .
Melatonin , alongside its traditionally @ @ @ @ @ hormonal regulator of the circadian rhythm , is a promising adjunctive drug for sepsis through @ @ @ @ @ powerful antioxidant properties .
Several animal models of sepsis have demonstrated that melatonin can prevent @ @ @ @ @ through restoring mitochondrial electron transport chain ( ETC ) function , inhibiting nitric oxide synthesis @ @ @ @ @ The purpose of this article is to review the current evidence for the role of @ @ @ @ @ its pharmacokinetic profile and virtual absence of side effects .
While clinical data is limited @ @ @ @ @ use of melatonin is patients with severe sepsis and septic shock .

Sepsis affects 30 million people worldwide, leading to 6 million deaths every year (WHO), and despite decades of research, novel initiatives are drastically needed. According to the current literature, oxidative imbalance and mitochondrial dysfunction are common features of septic patients that can cause multiorgan failure and death. Melatonin, alongside its traditionally accepted role as the master hormonal regulator of the circadian rhythm, is a promising adjunctive drug for sepsis through its anti-inflammatory, antiapoptotic and powerful antioxidant properties. Several animal models of sepsis have demonstrated that melatonin can prevent multiorgan dysfunction and improve survival through restoring mitochondrial electron transport chain (ETC) function, inhibiting nitric oxide synthesis and reducing cytokine production. The purpose of this article is to review the current evidence for the role of melatonin in sepsis, review its pharmacokinetic profile and virtual absence of side effects. While clinical data is limited, we propose the adjunctive use of melatonin is patients with severe sepsis and septic shock.


greenmedinfo--2020-03-21--Green Tea Helps Cystitis Sufferers and Prevents Antibiotic Resistance


greenmedinfo--2020-03-22--The genetic basis of high-carbohydrate and high-monosodium glutamate diet related to the increase of

The genetic basis of high-carbohydrate and high-monosodium glutamate diet related to the increase of likelihood of type 2 diabetes mellitus.

Diabetes is one of the most common metabolic diseases .
Aside from the genetic factor , previous studies stated that other factors such as environment , lifestyle , and paternal-maternal condition play critical roles in diabetes through DNA methylation in specific areas of the genome .
One of diabetic cases is caused by insulin resistance and changing the homeostasis of blood glucose control so glucose concentration stood beyond normal rate ( hyperglycemia ) .
High fat diet has been frequently studied and linked to triggering diabetes .
However , most Asians consume rice ( or food with high carbohydrate ) @ @ @ @ @ @ @ ) .
This habit could lead to pathophysiology of type 2 diabetes mellitus ( T2D ) .
Previous studies showed that high-carbohydrate or high-MSG diet could change gene expression or modify protein activity in body metabolism .
This imbalanced metabolism can lead to pleiotropic effects of diabetes mellitus .
In this study , the authors have attempted to relate various changes in genes expression or protein activity to the high-carbohydrate and high-MSG-induced diabetes .
The authors have also tried to relate several genes that contribute to pathophysiology of T2D and proposed several ideas @ @ @ @ @ @ @ curing people with T2D .
These are done by investigating altered activities of various genes that cause or are caused by diabetes .
These genes are selected based on their roles in pathophysiology of T2D .

Diabetes is one of the most common metabolic diseases. Aside from the genetic factor, previous studies stated that other factors such as environment, lifestyle, and paternal-maternal condition play critical roles in diabetes through DNA methylation in specific areas of the genome. One of diabetic cases is caused by insulin resistance and changing the homeostasis of blood glucose control so glucose concentration stood beyond normal rate (hyperglycemia). High fat diet has been frequently studied and linked to triggering diabetes. However, most Asians consume rice (or food with high carbohydrate) and food with monosodium glutamate (MSG). This habit could lead to pathophysiology of type 2 diabetes mellitus (T2D). Previous studies showed that high-carbohydrate or high-MSG diet could change gene expression or modify protein activity in body metabolism. This imbalanced metabolism can lead to pleiotropic effects of diabetes mellitus. In this study, the authors have attempted to relate various changes in genes expression or protein activity to the high-carbohydrate and high-MSG-induced diabetes. The authors have also tried to relate several genes that contribute to pathophysiology of T2D and proposed several ideas of genes as markers and target for curing people with T2D. These are done by investigating altered activities of various genes that cause or are caused by diabetes. These genes are selected based on their roles in pathophysiology of T2D.


greenmedinfo--2020-03-22--Medical Martial Law? DOJ Requests Suspension of Certain Constitutional Rights During Coronavirus Eme

Medical Martial Law? DOJ Requests Suspension of Certain Constitutional Rights During Coronavirus Emergency

A concerning new report published in Rolling Stone titled , “ DOJ Wants to Suspend Certain Constitutional Rights During Coronavirus Emergency , ” reveals that the Department of Justice , under the auspices of protecting the public health from the threat of COVID-19 , is attempting to suspend some of the most basic protections upon which the United States Constitution and our civil rights are founded .
As summarized in the Rolling Stone article , The story first broke through the Hill , which reported in greater depth on the topic : “ Documents obtained by the publication revealed several @ @ @ @ @ @ @ changes would give the attorney general the power to ask top district judges to stop court proceedings `` whenever the district court is fully or partially closed by virtue of any natural disaster , civil disobedience , or other emergency situation.
” These top judges would also gain the power to the stop court proceedings during a national emergency .
In addition , the DOJ has asked for the ability to ask chief judges to permanently detain an individual without trial during emergencies .
Another proposal would reportedly waive the statute of limitations @ @ @ @ @ @ @ trials during an emergency and could last up to `` one year following the end of the national emergency . ''
First , please share this article with others .
Social media has been severely restricting our distribution of content like this , but if enough share it organically , it will gain greater reach .
Also , please use email to forward our content to others , as it is less likely to be censored .
Second , join Stand For Health Freedom , a 501c4 whose sole mission is to help @ @ @ @ @ @ @ to elected officials , government decision makers , and lawmakers .
Learn more here : https : //www.standforhealthfreedom.com To learn more about the growing threat to our Constitutionally-protected freedoms watch independent investigative journalist James Cobett 's latest report on Medical Martial Law 2020 .
Video Summary : `` As the lockdowns go into place and the military takes to the streets in country after country , the decades of preparation for medical martial law are finally paying off for the pandemic planners .
Today on this emergency edition of The Corbett Report podcast @ @ @ @ @ @ @ have led us to the brink of martial law and the steps that are being taken to implement it now .
Please help to spread this important information and to raise awareness of the crisis that we are facing . ''

Visit our Re-post guidelines This article is copyrighted by GreenMedInfo LLC, 2020
A concerning new report published in Rolling Stone titled, “DOJ Wants to Suspend Certain Constitutional Rights During Coronavirus Emergency,” reveals that the Department of Justice, under the auspices of protecting the public health from the threat of COVID-19, is attempting to suspend some of the most basic protections upon which the United States Constitution and our civil rights are founded.
As summarized in the Rolling Stone article,
“The Department of Justice has secretly asked Congress for the ability to detain arrested people “indefinitely” in addition to other powers that one expert called “terrifying.”
The story first broke through the Hill, which reported in greater depth on the topic:
“Documents obtained by the publication revealed several different proposals. One of the proposed changes would give the attorney general the power to ask top district judges to stop court proceedings "whenever the district court is fully or partially closed by virtue of any natural disaster, civil disobedience, or other emergency situation.” These top judges would also gain the power to the stop court proceedings during a national emergency. In addition, the DOJ has asked for the ability to ask chief judges to permanently detain an individual without trial during emergencies. Another proposal would reportedly waive the statute of limitations for criminal investigations as well as civil trials during an emergency and could last up to "one year following the end of the national emergency."
CALL TO ACTION
First, please share this article with others. Social media has been severely restricting our distribution of content like this, but if enough share it organically, it will gain greater reach. Also, please use email to forward our content to others, as it is less likely to be censored. Second, join Stand For Health Freedom, a 501c4 whose sole mission is to help you communicate your health freedom related concerns to elected officials, government decision makers, and lawmakers. Learn more here: https://www.standforhealthfreedom.com
LEARN MORE ABOUT MEDICAL MARTIAL LAW
To learn more about the growing threat to our Constitutionally-protected freedoms watch independent investigative journalist James Cobett's latest report on Medical Martial Law 2020.
Video Summary: "As the lockdowns go into place and the military takes to the streets in country after country, the decades of preparation for medical martial law are finally paying off for the pandemic planners. Today on this emergency edition of The Corbett Report podcast, James lays out the steps that have led us to the brink of martial law and the steps that are being taken to implement it now. Please help to spread this important information and to raise awareness of the crisis that we are facing."


greenmedinfo--2020-03-23--Apigenin regulates Th1/Th2 balance via suppression in expressions of Th2 response.

Background : Allergic rhinitis ( AR ) is an immunoglobulin E ( IgE ) -mediated immune-inflammatory response mainly affecting nasal mucosa .
Apigenin , a flavonoid , has been documented to possess promising anti-allergic potential .
Aim : To determine the potential mechanism of action of apigenin against ovalbumin ( OVA ) -induced AR by assessing various behavioral , biochemical , molecular , and ultrastructural modifications .
Materials and Methods : Allergic rhinitis was induced in BALB/c mice ( 18-22 grams ) by sensitizing it with OVA ( 5 % , 500μL , intraperitoneal [ IP ] on each consecutive @ @ @ @ @ @ @ by intranasal challenge with OVA ( 5 % , 5 μL per nostril on day 21 ) .
Animals were treated with either vehicle ( distilled water , 10 mg/kg , IP ) or apigenin ( 5 , 10 , and 20 mg/kg , IP ) .
Conclusion : Apigenin regulates Th1/Th2 balance via suppression in expressions of Th2 response ( IgE , histamine , ILs , GATA3 , STAT6 , SOCS1 , and NF-κB ) and activation of Th1 response ( IFN-γ and T-bet ) to exert its anti-allergic potential in a @ @ @ @ @ @

Background: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated immune-inflammatory response mainly affecting nasal mucosa. Apigenin, a flavonoid, has been documented to possess promising anti-allergic potential.
Aim: To determine the potential mechanism of action of apigenin against ovalbumin (OVA)-induced AR by assessing various behavioral, biochemical, molecular, and ultrastructural modifications.
Materials and Methods: Allergic rhinitis was induced in BALB/c mice (18-22 grams) by sensitizing it with OVA (5%, 500μL, intraperitoneal [IP] on each consecutive day, for 13 days) followed by intranasal challenge with OVA (5%, 5 μL per nostril on day 21). Animals were treated with either vehicle (distilled water, 10 mg/kg, IP) or apigenin (5, 10, and 20 mg/kg, IP).
Results: Intranasal challenge of OVA resulted in significant induction (<.05) of AR reflected by an increase in nasal symptoms (sneezing, rubbing, and discharge), which were ameliorated significantly (<.05) by apigenin (10 and 20 mg/kg) treatment. It also significantly inhibited (<.05) OVA-induced elevated serum histamine, OVA-specific IgE, total IgE, and IgG1 andβ-hexosaminidase levels. Ovalbumin-induced increased levels of interleukin (IL)-4, IL-5, IL-13, and interferon (IFN)-γ in nasal lavage fluid were significantly decreased (<.05) by apigenin. Ovalbumin-induced alterations in splenic GATA binding protein 3 (ie, erythroid transcription factor) (GATA3), T-box protein expressed in T cells (T-bet), signal transducer and activator of transcription-6 (STAT6), suppressor of cytokine signaling 1 (SOCS1), nuclear factor-kappa B (NF-κB), and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha messenger RNA, as well as protein expressions were significantly inhibited (<.05) by apigenin. It also significantly ameliorated (<.05) nasal and spleen histopathologic and ultrastructure aberration induced by OVA.
Conclusion: Apigenin regulates Th1/Th2 balance via suppression in expressions of Th2 response (IgE, histamine, ILs, GATA3, STAT6, SOCS1, and NF-κB) and activation of Th1 response (IFN-γ and T-bet) to exert its anti-allergic potential in a murine model of OVA-induced AR.