PMID: 

Transl Oncol. 2019 Dec 31 ;13(2):401-409. Epub 2019 Dec 31. PMID: 31901552

Abstract Title: 

Enhanced Anticancer Effect of Adding Magnesium to Vitamin C Therapy: Inhibition of Hormetic Response by SVCT-2 Activation.

Abstract: 

l-Ascorbic acid (vitamin C, AA) is known as an antioxidant, but at high concentrations, AA can kill cancer cells through a prooxidant property. Sodium-dependent vitamin C transporter family-2 (SVCT-2) determines the cellular uptake of AA, and the activity of SVCT-2 is directly related to the anticancer activity of AA. Cancer cells that showed high SVCT-2 expression levels were more sensitive to AA treatment than cancer cells with low SVCT-2 expression levels. Cells with low SVCT-2 expression showed a hormetic response to a low dose of AA. Magnesium ions, which are known to activate SVCT-2, could increase the Vvalue of SVCT-2, so we investigated whether providing magnesium supplements to cancer cells with low SVCT-2 expression that had shown a hormetic response to AA would elevate the Vvalue of SVCT-2, allowing more AA to accumulate. To evaluate the effects of magnesium on cancer cells, MgSOand MgClwere screened as magnesium supplements; both forms showed synergistic anticancer effects with AA. Taken together, the results of this study suggest that magnesium supplementation enhanced the anticancer effect of AA by inhibiting the hormetic response at a low dose. This study has also demonstrated that AA treatment with magnesium supplementation provided more effective anticancer therapy than AA treatment alone.

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PMID: 

Oxid Med Cell Longev. 2019 ;2019:5120275. Epub 2019 Dec 2. PMID: 31885798

Abstract Title: 

Melatonin Protects Intervertebral Disc from Degeneration by Improving Cell Survival and Function via Activation of the ERK1/2 Signaling Pathway.

Abstract: 

Melatonin, a neuroendocrine hormone secreted by the pineal body, has a positive effect on intervertebral disc degeneration. The present study is aimed at investigating the biological role of melatonin in intervertebral disc degeneration and its underlying mechanism. A human nucleus pulposus cell (NPC) line was exposed to melatonin at different concentrations. Cell proliferation was measured by CCK-8 assay. Cell cycle and apoptosis were analyzed by flow cytometry. Western blot was performed to measure the protein expression of indicated genes. A rabbit model of intervertebral disc degeneration was established to detect the role and mechanism of melatonin on intervertebral disc degeneration. Our study showed that melatonin promoted NPC viability and inhibited cell arrest. Furthermore, melatonin treatment led to the upregulation of collagen II and aggrecan and downregulation of collagen X. Moreover, melatonin significantly elevated the activity of the ERK signaling pathway. Inhibition of the ERK1/2 signals reversed the role of melatonin in the regulation of NPCs bothand. Melatonin increased NPC viability through inhibition of cell cycle arrest and apoptosis. Moreover, melatonin promoted the secretion of functional factors influencing the nucleus pulposus cell physiology and retarded cell degeneration. Our results suggest that melatonin activated the ERK1/2 signaling pathway, thereby affecting the biological properties of the intervertebral disc degeneration.

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PMID: 

J Diabetes Metab Disord. 2019 Dec ;18(2):543-549. Epub 2019 Dec 2. PMID: 31890680

Abstract Title: 

Efficacy of melatonin in restoring the antioxidant status in the lens of diabetic rats induced by streptozotocin.

Abstract: 

Background: Melatonin is a well-known free radical scavenger. The present study aimed to investigate the effects of melatonin treatment on the antioxidant status in the lenticular tissue of streptozotocin (STZ)-induced diabetic rats.Methods: Thirty-four male rats were randomly divided into four groups as follows: healthy control rats (group 1, = 10); diabetic control rats (group 2, = 10); melatonin-treated (5 mg/kg·day) diabetic rats (group 3, = 10) and melatonin-treated (5 mg/kg·day) healthy rats (group 4, = 4). Diabetes was induced by injection of streptozotocin (50 mg/kg, ip). Following 8-weeks of melatonin treatment, all rats were killed and the blood plasma and their lenses were stored at -70 °C for antioxidant enzyme activities assay and biochemical determination.Results: The plasma glucose and lens malondialdehyde (MDA) increased significantly in the rats of group 2 as compared to the group 1. Also, a significant decrease in the levels of catalase (CAT) and glutathione reductase (GR) activities in the lenses and plasma reduced glutathione (GSH) was found. However, the levels of lenticular MDA (not significant) and the plasma glucose significantly decreased in the rats of group 3 compared to the group 2. Besides, the levels of CAT, GR in the rats lens and plasma GSH increased significantly.Conclusion: Diabetes mellitus induced hyperglycemia and oxidative stress, whereas melatonin decreased the blood glucose levels and lipid peroxidation and increased the activities of antioxidant enzymes in diabetic rat lenses.

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PMID: 

Mol Med Rep. 2019 Dec 23. Epub 2019 Dec 23. PMID: 31894324

Abstract Title: 

Melatonin suppresses epithelial‑to‑mesenchymal transition in the MG‑63 cell line.

Abstract: 

Epithelial‑to‑mesenchymal transition (EMT) is a major process involved in tumor progression and metastasis. Melatonin is secreted by the pineal gland and has been documented as a potential therapeutic agent for multiple tumors. However, the effects of melatonin on EMT during osteosarcoma (OA) developmentremain undefined. The present study explored the biological functions and effects of melatonin on EMT induced by transforming growth factor β1 (TGF‑β1) and its underlying mechanisms in MG‑63 cells. Using western‑blotting and immunofluorescence, it was found that the switch in E‑cadherin/N‑cadherin and vimentin expression was induced by TGF‑β1, which was reversed by melatonin through the suppression of Snail and matrix metalloproteinase 9 (MMP‑9), through hypoxia‑inducible factor 1α (HIF‑1α) inhibition. These findings demonstrated that the anticancer effects of melatonin against OA MG‑63 cells is through the suppression of EMT via HIF‑1α/Snail/MMP‑9 signaling.

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n/a

PMID: 

Br J Pharmacol. 2020 Jan 3. Epub 2020 Jan 3. PMID: 31900938

Abstract Title: 

Melatonin rescues osteoporosis by upregulating BMMSCs' osteogenic ability but suppressing BMMSC-mediated osteoclastogenesis via MT2-inactivated NF-

Abstract: 

BACKGROUND AND PURPOSE: Melatonin is a neurohormone involved in many biological activities, especially bone homeostasis. However, how melatonin directs bone remodelling and the role of bone marrow mesenchymal stem cells (BMMSCs) in the regulating melatonin-mediated bone formation-resorption balance remain undefined.
EXPERIMENTAL APPROACH: Osteoporosis models were established, and bone tissue and serum were collected to test the effects of melatonin on bone homeostasis. Melatonin receptors (MT receptors) were knocked down, the NF-κB signalling pathway and receptor activator of nuclear factor-κB ligand (RANKL) expression were investigated, and communication between BMMSCs and osteoclasts was detected with direct-contact or indirect-contact system.
KEY RESULTS: Bone loss and microstructure disorder in mice were profoundly reversed after melatonin treatment, as an integrated result of anabolic and anti-resorptive effects. In vitro, a low physiological melatonin concentration selectively promoted the BMMSCs' osteogenic lineage commitment and extracellular mineralization, but had no impact on extracellular matrix synthesis. After MT knockdown, especially MT2 knockdown, the positive effects of melatonin on osteogenesis were attenuated. The canonical NF-κB signalling pathway was the first discovered downstream signalling pathway after MT receptor activation and was found to be downregulated by melatonin during osteogenesis. Melatonin suppressed BMMSC-mediated osteoclastogenesis by inhibiting RANKL production in BMMSCs, and this effect only occurred when BMMSCs and osteoclast precursors were co-cultured in an indirect-contact manner.
CONCLUSION AND IMPLICATIONS: Our work suggests that melatonin plays a crucial role in bone balance, significantly accelerates the osteogenic differentiation of BMMSCs by suppressing the MT2-dependent NF-κB signalling pathway, and downregulates osteoclastogenesis via RANKL paracrine secretion.

PMID: 

Neuropeptides. 2019 Dec 25:102002. Epub 2019 Dec 25. PMID: 31902595

Abstract Title: 

Melatonin exerts neuroprotective effects by attenuating astro- and microgliosis and suppressing inflammatory response following spinal cord injury.

Abstract: 

Reactive gliosis and inflammatory reaction are common pathological change to spinal cord injury (SCI). Whereas, the effects of melatonin (MT) on the astro- and microgliosis and their related inflammatory response in the injured spinal cord are not fully understood. In this study, MT's effects on the accumulation and proliferation of microglia and astrocytes and their related inflammatory response were investigated in an acute SCI model. The effects of MT on oxidative stress, neuronal survival and behavioral performance were also tested. It was found that MT treatment significantly suppressed the accumulation and the proliferation of microglia and astrocytes. Quantitative PCR data showed that MT significantly down-regulated the pro-inflammatory markers iNOS, IL-1β and TNF-α expressions. The data showed that MT led to the rise in SOD, CAT and GSH-Px contents and the decrease in MDA content. Western blotting analysis verified that MT significantly down-regulated caspase-3, Bax and GFAP expressions, up-regulated Bcl-2 expression. Compared with the SCI vehicle-treated group, the SCI MT-treated group exhibited a greater Basso Mouse Scale (BMS) locomotor rating score. On the whole, these findings implied that MT exerts its neuroprotective effects by suppressing the accumulation and the proliferation of microglia and astrocytes and reducing the release ofpro-inflammatory cytokines, which might be one of the underlying mechanisms of the MT's neuroprotective effect after SCI. Accordingly, MT may be a promising therapeutic candidate for acute SCI.

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PMID: 

J Psychopharmacol. 2020 Jan 7:269881119895536. Epub 2020 Jan 7. PMID: 31909680

Abstract Title: 

Effects of acute cannabidiol administration on anxiety and tremors induced by a Simulated Public Speaking Test in patients with Parkinson's disease.

Abstract: 

BACKGROUND: Cannabidiol (CBD) is one of the main components ofand has anxiolytic properties, but no study has been conducted to evaluate the effects of CBD on anxiety signs and symptoms in patients with Parkinson's disease (PD). This study aimed to evaluate the impacts of acute CBD administration at a dose of 300 mg on anxiety measures and tremors induced by a Simulated Public Speaking Test (SPST) in individuals with PD.METHODS: A randomised, double-blinded, placebo-controlled, crossover clinical trial was conducted. A total of 24 individuals with PD were included and underwent two experimental sessions within a 15-day interval. After taking CBD or a placebo, participants underwent the SPST. During the test, the following data were collected: heart rate, systemic blood pressure and tremor frequency and amplitude. In addition, the Visual Analog Mood Scales (VAMS) and Self-Statements during Public Speaking Scale were applied. Statistical analysis was performed by repeated-measures analysis of variance (ANOVA) while considering the drug, SPST phase and interactions between these variables.RESULTS: There were statistically significant differences in the VAMS anxiety factor for the drug; CBD attenuated the anxiety experimentally induced by the SPST. Repeated-measures ANOVA showed significant differences in the drug for the variable related to tremor amplitude as recorded by the accelerometer.CONCLUSION: Acute CBD administration at a dose of 300 mg decreased anxiety in patients with PD, and there was also decreased tremor amplitude in an anxiogenic situation.

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PMID: 

Molecules. 2019 Dec 27 ;25(1). Epub 2019 Dec 27. PMID: 31892132

Abstract Title: 

β-Caryophyllene, a CB2-Receptor-Selective Phytocannabinoid, Suppresses Mechanical Allodynia in a Mouse Model of Antiretroviral-Induced Neuropathic Pain.

Abstract: 

Neuropathic pain associated with nucleoside reverse transcriptase inhibitors (NRTIs), therapeutic agents for human immunodeficiency virus (HIV), responds poorly to available drugs. Smoked cannabis was reported to relieve HIV-associated neuropathic pain in clinical trials. Some constituents of cannabis () activate cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptors. However, activation of the CB1 receptor is associated with side effects such as psychosis and physical dependence. Therefore, we investigated the effect ofβ-caryophyllene (BCP), a CB2-selective phytocannabinoid, in a model of NRTI-induced neuropathic pain. Female BALB/c mice treated with 2'-3'-dideoxycytidine (ddC, zalcitabine), a NRTI, for 5 days developed mechanical allodynia, which was prevented by cotreatment with BCP, minocycline or pentoxifylline. A CB2 receptor antagonist (AM 630), but not a CB1 receptor antagonist (AM 251), antagonized BCP attenuation of established ddC-induced mechanical allodynia. β-Caryophyllene prevented the ddC-induced increase in cytokine (interleukin 1 beta, tumor necrosis factor alpha and interferon gamma) transcripts in the paw skin and brain, as well as the phosphorylation level of Erk1/2 in the brain. In conclusion, BCP prevents NRTI-induced mechanical allodynia, possibly via reducing the inflammatory response, and attenuates mechanical allodynia through CB2 receptor activation. Therefore, BCP could beuseful for prevention and treatment of antiretroviral-induced neuropathic pain.

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PMID: 

Clin Infect Dis. 2020 Jan 4. Epub 2020 Jan 4. PMID: 31900476

Abstract Title: 

Smoking as a risk factor of invasive fungal disease: Systematic review and meta-analysis.

Abstract: 

To investigate the association between smoking and invasive fungal disease (IFD), we searched MEDLINE and Web of Science for studies published until September 2018. Two authors independently performed study selection and data extraction. Relative risks (RRs) were pooled using random-effects meta-analysis. We included 25 studies (18,171 participants; 2,527 IFD cases). The meta-analysis showed an increased risk of IFD in smokers (RR 1.41 [95%CI 1.09-1.81]; P = 0.008). The risk of IFD was higher in retrospective than in prospective studies (RR 1.93 [1.28-2.92] vs. 1.02 [0.78-1.34]; P = 0.04), in studies with multivariate adjustment compared to studies with univariate analysis (RR 2.15 [1.27-3.64] vs. 1.15 [0.88-1.51]; P = 0.06), and in studies published after 2002 (RR 2.08 [1.37-3.15] vs. 0.95 [0.75-1.22]; P = 0.008); other subgroup characteristics did not significantly influence the association in meta-regression. Smoking cessation strategies should be implemented, especially in patients who are already at risk for IFD.

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PMID: 

Acta Physiol Hung. 2015 Mar ;102(1):1-22. PMID: 25804386

Abstract Title: 

Cycle training induces muscle hypertrophy and strength gain: strategies and mechanisms.

Abstract: 

Cycle training is widely performed as a major part of any exercise program seeking to improve aerobic capacity and cardiovascular health. However, the effect of cycle training on muscle size and strength gain still requires further insight, even though it is known that professional cyclists display larger muscle size compared to controls. Therefore, the purpose of this review is to discuss the effects of cycle training on muscle size and strength of the lower extremity and the possible mechanisms for increasing muscle size with cycle training. It is plausible that cycle training requires a longer period to significantly increase muscle size compared to typical resistance training due to a much slower hypertrophy rate. Cycle training induces muscle hypertrophy similarly between young and older age groups, while strength gain seems to favor older adults, which suggests that the probability for improving in muscle quality appears to be higher in older adults compared to young adults. For young adults, higher-intensity intermittent cycling may be required to achieve strength gains. It also appears that muscle hypertrophy induced by cycle training results from the positive changes in muscle protein net balance.

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