PMID: 

Antioxidants (Basel). 2019 Dec 11 ;8(12). Epub 2019 Dec 11. PMID: 31835711

Abstract Title: 

Dietary Selenium Supplementation Ameliorates Female Reproductive Efficiency in Aging Mice.

Abstract: 

Female reproductive (ovarian) aging is distinctively characterized by a markedly reduced reproductive function due to a remarkable decline in quality and quantity of follicles and oocytes. Selenium (Se) has been implicated in playing many important biological roles in male fertility and reproduction; however, its potential roles in female reproduction, particularly in aging subjects, remain poorly elucidated. Therefore, in the current study we used a murine model of female reproductive aging and elucidated how different Se-levels might affect the reproductive efficiency in aging females. Our results showed that at the end of an 8-week dietary trial, whole-blood Se concentration and blood total antioxidant capacity (TAOC) were significantly reduced in Se-deficient (0.08 mg Se/kg; Se-D) mice, whereas both of these biomarkers were significantly higher in inorganic (0.33 mg/kg; ISe-S) and organic (0.33 mg/kg; OSe-S) Se-supplemented groups. Similarly, compared to the Se-D group, Se supplementation significantly ameliorated the maintenance of follicles and reduced the rate of apoptosis in ovaries. Meanwhile, the rate of in vitro-produced embryos resulting from germinal vesicle (GV) oocytes was also significantly improved in Se-supplemented (ISe-S and OSe-S) groups compared to the Se-D mice, in which none of the embryos developed to the hatched blastocyst stage. RT-qPCR results revealed that mRNA expression of,,,, andgenes in ovaries of aging mice was differentially modulated by dietary Se levels. A considerably higher mRNA expression of,,, andwas observed in Se-supplemented groups compared to the Se-D group. Similarly, mRNA expression ofandwas significantly lower in Se-supplemented groups. Immunohistochemical assay also revealed a significantly higher expression of GPX4 in Se-supplemented mice. Our results reasonably indicate that Se deficiency (or marginal levels) can negatively impact the fertility and reproduction in females, particularly those of an advancing age, and that the Se supplementation (inorganic and organic) can substantiate ovarian function and overall reproductive efficiency in aging females.

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Dishonesty and fraud in the health care system are significant barriers to the implementation of universal health coverage, yet this corruption is rarely if ever discussed

PMID: 

Am J Transl Res. 2019 ;11(8):5105-5113. Epub 2019 Aug 15. PMID: 31497226

Abstract Title: 

Glycyrrhizin suppresses inflammation and cell apoptosis by inhibition of HMGB1 via p38/p-JUK signaling pathway in attenuating intervertebral disc degeneration.

Abstract: 

Intervertebral disc degeneration (IDD) is associated with the nucleus pulposus (NP) cells inflammation and apoptosis. Previous studies have shown that glycyrrhizin (GL) is a valid inhibitor of the high-mobility group box-1 gene (HMGB1) which expressed much higher in an inflammatory condition. However, it is not known whether GL protects against IDD by the inhibition of HMGB1. To study the effect and mechanism of glycyrrhizin on intervertebral disc degeneration. We analyzed the expression of HMGB1 in different degree of degenerate disc tissues. Interleukin 1 beta (IL-1β) was used in stimulating the NP cells to degeneration. We used recombined human HMGB1 to resist the function of GL to explore whether GL acted via the target of HMGB1. Our study showed that the expression of HMGB1 markedly increased in severely degenerated disc tissues. IL-1β promoted the progress of IDD, and the stimulation of GL could reverse the effects of IL-1β. Moreover, p38 and p-JNK were significantly suppressed by GL stimuli. These results suggested that GL prevented NP degradation via restraining inflammation and cell apoptosis by inhibition of HMGB1 via p38/p-JNK signaling pathway. GL may become a novel cytokine for the therapy of IDD in the future.

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PMID: 

J Cell Mol Med. 2020 Jan ;24(1):214-226. Epub 2019 Oct 27. PMID: 31657123

Abstract Title: 

Glycyrrhizin mitigates radiation-induced acute lung injury by inhibiting the HMGB1/TLR4 signalling pathway.

Abstract: 

Radiation-induced lung injury (RILI) is the major complication of thoracic radiation therapy, and no effective treatment is available. This study explored the role of high-mobility group box 1 (HMGB1) in acute RILI and the therapeutic effect of glycyrrhizin, an inhibitor of HMGB1, on RILI. C57BL/6 mice received a 20 Gy dose of X-ray radiation to the whole thorax with or without administration of glycyrrhizin. Severe lung inflammation was present 12 weeks after irradiation, although only a mild change was noted at 2 weeks and could be alleviated by administration of glycyrrhizin. Glycyrrhizin decreased the plasma concentrations of HMGB1 and sRAGE as well as TNF-α, IL-1β and IL-6 levels in the bronchoalveolar lavage fluid (BALF). The expression of RAGE was decreased while that of TLR4 was significantly increased at 12 weeks, but not 2 weeks, after irradiation in mouse lung tissue. In vitro, the expression of TLR4 increased in RAW 264.7 cells after conditioning with the supernatant from the irradiated MLE-12 cells containing HMGB1 but showed no change when conditioned medium without HMGB1 was used. However, conditioned culture had no effect on RAGE expression in RAW 264.7 cells. Glycyrrhizin also inhibited the related downstream transcription factors of HMGB/TLR4, such as NF-κB, JNK and ERK1/2, in lung tissue and RAW 264.7 cells when TLR4 was activated. In conclusion, the HMGB1/TLR4 pathway mediates RILI and can be mitigated by glycyrrhizin.

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PMID: 

Transl Stroke Res. 2019 Dec 24. Epub 2019 Dec 24. PMID: 31872339

Abstract Title: 

Glycyrrhizin Prevents Hemorrhagic Transformation and Improves Neurological Outcome in Ischemic Stroke with Delayed Thrombolysis Through Targeting Peroxynitrite-Mediated HMGB1 Signaling.

Abstract: 

Peroxynitrite (ONOO) and high mobility group box 1 protein (HMGB1) are important cytotoxic factors contributing to cerebral ischemia-reperfusion injury. However, the roles of ONOOin mediating HMGB1 expression and its impacts on hemorrhagic transformation (HT) in ischemic brain injury with delayed t-PA treatment remain unclear. In the present study, we tested the hypothesis that ONOOcould directly mediate the activation and release of HMGB1 in ischemic brains with delayed t-PA treatment. With clinical studies, we found that plasma nitrotyrosine (NT, a surrogate marker of ONOO) was positively correlated with HMGB1 level in acute ischemic stroke patients. Hemorrhagic transformation and t-PA-treated ischemic stroke patients had increased levels of nitrotyrosine and HMGB1 in plasma. In animal experiments, we found that FeTmPyP, a representative ONOOdecomposition catalyst (PDC), significantly reduced the expression of HMGB1 and its receptor TLR2, and inhibited MMP-9 activation, preserved collagen IV and tight junction claudin-5 in ischemic rat brains with delayed t-PA treatment. ONOOdonor SIN-1 directly induced expression of HMGB1 and its receptor TLR2 in naive rat brains in vivo and induced HMGB1 in brain microvascular endothelial b.End3 cells in vitro. Those results suggest that ONOOcould activate HMGB1/TLR2/MMP-9 signaling. We then addressed whether glycyrrhizin, a natural HMGB1 inhibitor, could inhibit ONOOproduction and the antioxidant properties of glycyrrhizin contribute to the inhibition of HMGB1 and the neuroprotective effects on attenuating hemorrhagic transformation in ischemic stroke with delayed t-PA treatment. Glycyrrhizin treatment downregulated the expressions of NADPH oxidase p47 phox and p67 phox and iNOS, inhibited superoxide and ONOOproduction, reduced the expression of HMGB1, TLR2, MMP-9, preserved type IV collagen and claudin-5 in ischemic brains. Furthermore, glycyrrhizin significantly decreased the mortality rate, attenuated hemorrhagic transformation, brain swelling, blood-brain barrier damage, neuronal apoptosis, and improved neurological outcomes in the ischemic stroke rat model with delayed t-PA treatment. In conclusion, peroxynitrite-mediated HMGB1/TLR2 signaling contributes to hemorrhagic transformation, and glycyrrhizin could be a potential adjuvant therapy to attenuate hemorrhagic transformation, possibly through inhibiting the ONOO/HMGB1/TLR2 signaling cascades.

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PMID: 

Food Funct. 2019 Dec 17. Epub 2019 Dec 17. PMID: 31845693

Abstract Title: 

Selenium alleviates lipopolysaccharide-induced endometritis via regulating the recruitment of TLR4 into lipid rafts in mice.

Abstract: 

Selenium (Se) is an essential trace element for living organisms and plays diverse biological roles. Endometritis is a common reproductive disorder in dairy cows, causing huge economic losses. In this study, we explored the effects of Se on lipopolysaccharide (LPS)-induced endometritis in mice and expounded its underlying mechanism of action. We validated the anti-inflammatory effects of Se in vivo by establishing a mouse model of endometriosis induced by LPS. Se significantly reversed the LPS-induced uterine histopathological changes, MPO activity and inflammatory cytokine levels in vivo. Simultaneously, TLR4 and its downstream signaling pathways, lipid rafts and cholesterol levels in the tissues were also attenuated by Se under LPS stimulation. In addition, the molecular mechanism of the Se anti-inflammatory effect was clarified in mouse endometrial epithelial cells. Se inhibited TLR4-mediated NF-κB and IRF3 signal transduction pathways to reduce the production of inflammatory factors. We found that Se promoted the consumption of cholesterol to suppress the lipid rafts coming into being and inhibited the TLR4 positioning to the lipid raft to prevent the inflammatory response caused by LPS.Meanwhile, Se activated the LxRα-ABCA1 pathway to cause the outflow of cholesterol in cells. The anti-inflammatory effect of Se was disrupted by silencing LxRα. In conclusion, Se exerted anti-inflammatory effects most likely by the LxRα-ABCA1 pathway activation, which inhibited lipid rafts by depleting cholesterol and ultimately impeded the migration of TLR4 to lipid rafts.

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PMID: 

Int J Neurosci. 2019 Nov 26:1-7. Epub 2019 Nov 26. PMID: 31721620

Abstract Title: 

Melatonin attenuates nicotine-induced autophagy and neurological changes by decreasing the production of reactive oxygen species.

Abstract: 

The aim of this study was to explore the mechanism of neurological changes underlying the toxicity of nicotine.Rat pheochromocytoma 12 (PC12) cells and human neuroglia (HM) cells were used. The ROS levels of the cells were detected by the FACScan. Autophagy flux was monitored by a tandem monomeric RFP-GFP-tagged LC3 lentivirus. The autophagic proteins LC3, SQSTM1/p62 and Beclin1 were detected by western blot assay. In order to evaluate the effects of nicotine and melatonin on the morphological changes of neurons, primary cortical neurons were obtained and immunocytochemistry of TUBB3 tubulin were conducted.Nicotine increased the levels of reactive oxygen species (ROS) in PC12 and HM cells in a concentration-dependent manner. Microscopy showed increased autophagic flux in nicotine-treated PC12 cells. Subsequent western blotting results showed that nicotine induced increase in the levels of LC3B-II and Beclin1, and decreased SQSTM1/p62 in a concentration-dependent manner. Finally, nicotine treatment reduced the length of TUBB3-positive axons and dendrites. Melatonin, a mitochondrially targeted antioxidant, reduced the ROS level, and blocked autophagy activation and the morphologic structural changes induced by nicotine.Our results suggested that the role of nicotine in neuronal toxicity maybe through the induction of ROS and the subsequent activation of autophagy. These effects could be restored by melatonin.

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PMID: 

Arch Physiol Biochem. 2019 Nov 15:1-9. Epub 2019 Nov 15. PMID: 31726890

Abstract Title: 

Melatonin reverses depressive and anxiety like-behaviours induced by diabetes: involvement of oxidative stress, age, rage and S100B levels in the hippocampus and prefrontal cortex of rats.

Abstract: 

Diabetes is associated with depression and anxiety symptoms. The current investigation was designed to explore the effect of melatonin on depressive and anxiety like-behaviours, oxidative stress, levels of AGE, RAGE and S100B in streptozotocin-induced diabetic rats. The animals were divided into four groups: Normoglycemic; Normoglycemic + melatonin; diabetic; diabetic + melatonin (10 mg/kg, for 4 weeks). The malondialdehyde (MDA), reduced glutathione (GSH), AGE, RAGE and S100B were measured and the depressive and anxiety like-behaviours were assessed by forced swimming and elevated plus maze tests, respectively. Melatonin ameliorates depressive and anxiety like-behaviours. Concomitantly, melatonin reversed diabetes induced increase of MDA, AGE and decrease of GSH and S100B levels in the hippocampus and prefrontal cortex. In conclusion, our results showed that melatonin administration may exert antidepressant-likeand anxiolytic effects in diabetic rats through normalising of AGE/RAGE, S100B and oxidative stress in the prefrontal cortex and hippocampus.

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PMID: 

Front Plant Sci. 2019 ;10:1388. Epub 2019 Oct 30. PMID: 31737014

Abstract Title: 

Melatonin Is a Potential Target for Improving Post-Harvest Preservation of Fruits and Vegetables.

Abstract: 

Melatonin is a ubiquitous molecule distributed in nature and not only plays an important role in animals and humans but also has extensive functions in plants, such as delaying senescence, exerting antioxidant effects, regulating growth and development, and facilitating plant adaption to stress conditions. Endogenous melatonin is widespread in fruits and vegetables and plays prominent roles in the ripening and post-harvest process of fruits and vegetables. Exogenous application of melatonin removes excess reactive oxygen species from post-harvest fruits and vegetables by increasing antioxidant enzymes, non-enzymatic antioxidants, and enzymes related to oxidized protein repair. Moreover, exogenous application of melatonin can increase endogenous melatonin to augment its effects on various physiological processes. Many previous reports have demonstrated that application of exogenous melatonin improves the post-harvest preservation of fruits and vegetables. Although overproduction of melatonin in plants via transgenic approaches could be a potential means for improving the post-harvest preservation of fruits and vegetables, efforts to increase endogenous melatonin in plants are limited. In this review, we summarize the recent progress revealing the role and action mechanisms of melatonin in post-harvest fruits and vegetables and provide future directions for the utilization of melatonin to improve the post-harvest preservation of fruits and vegetables.

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Florida’s religious and medical rights are still under attack. It’s up to each of us standing up together that will allow us to make a difference