PMID: 

Oxid Med Cell Longev. 2019 ;2019:4569614. Epub 2019 Dec 14. PMID: 31949878

Abstract Title: 

Folic Acid Supplementation Suppresses Sleep Deprivation-Induced Telomere Dysfunction and Senescence-Associated Secretory Phenotype (SASP).

Abstract: 

Sleep deprivation is reported to cause oxidative stress and is hypothesized to induce subsequent aging-related diseases including chronic inflammation, Alzheimer's disease, and cardiovascular disease. However, how sleep deprivation contributes to the pathogenesis of sleep deficiency disorder remains incompletely defined. Accordingly, more effective treatment methods for sleep deficiency disorder are needed. Thus, to better understand the detailed mechanism of sleep deficiency disorder, a sleep deprivation mouse model was established by the multiple platform method in our study. The accumulation of free radicals and senescence-associated secretory phenotype (SASP) was observed in the sleep-deprived mice. Moreover, our mouse and human population-based study both demonstrated that telomere shortening and the formation of telomere-specific DNA damage are dramatically increased in individuals suffering from sleeplessness. To our surprise, the secretion of senescence-associated cytokines and telomere damage are greatly improved by folic acid supplementation in mice. Individuals with high serum baseline folic acid levels have increased resistance to telomere shortening, which is induced by insomnia. Thus, we conclude that folic acid supplementation could be used to effectively counteract sleep deprivation-induced telomere dysfunction and the associated aging phenotype, which may potentially improve the prognosis of sleeplessness disorder patients.

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PMID: 

Nutr Res. 2019 Dec 23 ;75:1-14. Epub 2019 Dec 23. PMID: 31955011

Abstract Title: 

Postischemic supplementation of folic acid improves neuronal survival and regeneration in vitro.

Abstract: 

Supplementation of folic acid (FA) is beneficial to several neurological diseases because it promotes notch signaling and neurogenesis and reduces blood homocysteine levels. We hypothesized that postischemic supplementation of FA is beneficial for neuronal survival and regeneration. The objective of the present study was to determine the postischemic neuroprotective and neuroregenerative efficacy of FA supplementation and its effects on various cellular processes in vitro. This work benefited from the use of FA and glucose-free media to better assess the ischemic neuroprotection provided by FA supplementation. The postischemic supplementation of FA significantly improved cell viability, and the improvement was primarily by obstructing the oxygen-glucose deprivation (OGD)-activated apoptosis. Furthermore, postischemic treatment with FA significantly reduced the mitochondrial membrane depolarization and the formation of acidic organelles triggered by OGD. Moreover, FA's effect on neuroregeneration following OGD was evaluated by measuring the cell proliferation and neurite outgrowth length. Treatment with FA enhanced cell proliferation and neurite outgrowth significantly. Thus, these results revealed some of the mechanisms by which FA supplementation provided neuroprotection and neuroregeneration following ischemic injury and highlighted the need for further research into the potential of folic acid as a clinical drug for ischemic stroke.

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PMID: 

Nutr Metab (Lond). 2020 ;17:6. Epub 2020 Jan 14. PMID: 31956332

Abstract Title: 

Folic acid and melatonin mitigate diabetic nephropathy in rats via inhibition of oxidative stress.

Abstract: 

Background: Diabetes mellitus is a global epidemic leads to multiple serious health complications, including nephropathy. Diabetic nephropathy is a serious kidney-related complication of type 1 or 2 diabetes that is prevalent in almost 40% of the people with diabetes. We examined whether folic acid and melatonin can reduce progression of nephropathy in rats of type 1 diabetes mellitus by controlling the level of oxidative stress, glucose, lipids, and cytokines.Methods: Forty-two male albino rats were distributed into six groups, ( = 7 per group). Five of the groups were induced with diabetes by a single intraperitoneal injection of freshly prepared streptozotocin at a dose of 50 mg/kg body weight. After the induction of diabetes, the rats were treated with folic acid (100 mg/kg) and melatonin (10 mg/kg) separately and in combination daily for 6 weeks, whereas, the other diabetic group was treated with glibenclamide (5 mg/kg). One of the diabetic groups served as a positive control. One-way ANOVA was used to compare those five subfields ability followed by LSD multiple comparisons.Results: The data indicated that diabetes significantly altered the body weight, lipids and kidney function. Diabetic rats exhibited a significant increase in plasma levels of urea, uric acid, creatinine, sodium, tumor necrosis factor alpha (TNF-α), interleukin-6(IL-6), cholesterol, triglycerides, and low-density lipoprotein (LDL). In contrast, plasma total protein, potassium, high-density lipoprotein (HDL) and interleukin-10 (IL-10) decreased significantly in diabetic rats compared to the control rats. Moreover, levels of renal malondialdehyde (MDA) and nitric oxide (NO) were significantly increased while the levels of renal glutathione(GSH), superoxide dismutase(SOD), and catalase (CAT) were significantly decreased in diabetic rats comparison to those in the control rats. Hence, diabetic rats treated with folic acid and melatonin alone as well as in combination showed improvements with respect to the indices in addition to a significant recovery observed via histopathology when compared to the diabetic group.Conclusions: These results revealed that treatment with folic acid in combination with melatonin in diabetic rats was more effective than treatment with either of folic acid or melatonin alone to alleviate the symptoms of diabetic nephropathy.

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PMID: 

Int J Environ Res Public Health. 2020 01 19 ;17(2). Epub 2020 Jan 19. PMID: 31963813

Abstract Title: 

Dietary Folate Intake and Folic Acid Supplements among Pregnant Women from Southern Italy: Evidence from the"Mamma&Bambino"Cohort.

Abstract: 

Folate requirement among women who plan to become pregnant should be raised to 600μg/day during the periconceptional period. To meet this need, several countries began to promote the use of folic acid supplements before and during pregnancy. Here, we investigated prevalence and determinants of dietary folate intake and folic acid supplement use among 397 pregnant women (aged 15-50 years old, median = 37 years old). We also investigated their effects on neonatal outcomes in a subgroup of women who completed pregnancy. For doing that, we used data from the"Mamma&Bambino"project, an ongoing mother-child cohort settled in Catania (Italy). Inadequate folate intake was evaluated using a Food Frequency Questionnaire and defined as an intake

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PMID: 

Ann Neurosci. 2019 Apr ;26(2):60-65. Epub 2019 Apr 1. PMID: 31975775

Abstract Title: 

Folic Acid Modulates Matrix Metalloproteinase-9 Expression Following Spinal Cord Injury.

Abstract: 

Background: Treatment of spinal cord injury (SCI) induced neuropathic pain (NP) proves to be extremely clinically challenging as the mechanism behind SCINP is poorly understood. Matrix metalloproteinase (MMP) is largely responsible for the early disruption of the blood spinal cord barrier. This system initiates macrophage infiltration and degradation of myelin, which plays a pivotal role in how NP occurs. In a recent study, we demonstrated that folic acid (FA) treatment to cSCI rats reduced NP and improved functional recovery by repressing MMP-2 expression. We hypothesize that MMP-2 expression is suppressed because FA actively methylates the DNA sequence that encodes for the MMP-2 protein. However, modulation of MMP-2 expression for alleviation of NP is only pertinent to the mid- to late-phase of injury. Therefore, we need to explore alternate therapeutic methods to target the early- to mid-phase of injury to wholly alleviate NP.Purpose: Furthering our previous findings on inhibiting MMP-2 expression by FA in mid- and late- phase following cSCI in rats, we hypothesized that FA will methylate and suppress MMP-9 expression during the early- phase, day 1, 3, 7 post cSCI and mid- phase (day 18 post cSCI), in comparison with MMP-2 expression during mid- and the late-phase of cSCI.Methods: Adult male Sprague Dawley rats (250-270g) underwent cSCI, using a NYU impactor, with 12.5 gm/cm injury. The spinal cord-injured animals were treated intraperitoneally (i.p.) with a standardized dose of FA (80μg/kg body weight) on day 1, 2, 3, prior to cSCI, followed by daily injection up to 14 or 17 days post-cSCI in different experiments. Animals were euthanized on day 1, 3, 7 post cSCI (early- phase), day 18 post cSCI (mid- phase), and day 42 post cSCI (late-phase) and the epicenter region of injuredspinal cord were harvested for MMP-9 and MMP-2 expression analysis by Western blots technique.Results: i) During early-phase on day 1, 3, and 7, the quantitation displayed no statistical significance in MMP-9 expression, between water- and FA- injected rats. ii) On day 18 post-cSCI, FA significantly modulates the expression of MMP-9 (p = 0.043) iii) Comparing results with MMP-2 expression and inhibition, FA significantly modulates the expression of MMP-2 on day 18 post cSCI (FA- and water-injected rats (p = 0.003). iv) In addition, FA significantly modulates the expression of MMP-2 on day 42 post-cSCI comparing FA- and water- injected rat groups (p = 0.034).Conclusion: We report that FA administration results in alleviating cSCI-induced NP by inhibiting MMP-9 in the proposed mid- phase of cSCI. However, FA administration resulted in MMP-2 decline during both mid- through late- phase following cSCI. Our study elucidates a new phase of cSCI, the mid-phase. We conclude that further investigation on discovering and quantifying the nature of the mid- phase of SCI injury is needed.

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PMID: 

Pregnancy Hypertens. 2020 Jan 14. Epub 2020 Jan 14. PMID: 31987769

Abstract Title: 

The effect of folic acid throughout pregnancy among pregnant women at high risk of pre-eclampsia: A randomized clinical trial.

Abstract: 

BACKGROUND: Pre-eclampsia is a serious hypertension disease that occurs during pregnancy. Folic acid (FA) supplementation has been reported to reduce pre-eclampsia risk in pregnant women. Here, we aimed to assess whether treatment of high doses of FA in pregnant women with high pre-eclampsia risk could prevent the onset of pre-eclampsia.METHODS: We conducted a randomized clinical trial in 1576 women who had pre-eclampsia or eclampsia in their last pregnancy and had a pregnancy plan. Subjects were randomized into two groups. The low dose (LD) group (n = 788) received 0.4 mg of FA daily from the first 3 months of pregnancy until the entire pregnancy, and the high dose (HD) group (n = 788) received 4 mg of FA per day. We followed up the subjects until production.RESULTS: The plasma homocysteine (homocysteine) and FA levels were significantly higher in the HD group that in the LD group. Severe gestational hypertension, early onset pre-eclampsia (

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PMID: 

Molecules. 2020 Jan 22 ;25(3). Epub 2020 Jan 22. PMID: 31979082

Abstract Title: 

Preclinical Pharmacological Activities of Epigallocatechin-3-gallate in Signaling Pathways: An Update on Cancer.

Abstract: 

Epigallocatechin gallate (EGCG) is the main bioactive component of catechins predominantly present in svarious types of teas. EGCG is well known for a wide spectrum of biological activity as an anti-oxidative, anti-inflammatory, and anti-tumor agent. The effect of EGCG on cell death mechanisms via the induction of apoptosis, necrosis, and autophagy has been documented. Moreover, its anti-proliferative and chemopreventive action has been demonstrated in many cancer cell lines. It was also involved in the modulation of cyclooxygenase-2, in oxidative stress and inflammation of different cell processes. EGCG has been reported as a promising target for plasma membrane proteins, such as epidermal growth factor receptor (EGFR). In addition, it has been demonstrated a mechanism of action relying on the inhibition of ERK1/2, p38 MAPK, NF-κB, and vascular endothelial growth factor (VEGF). EGCG and its derivatives were used in proteasome inhibition and they were involved in epigenetic mechanisms. In summary, EGCG is the most predominant and bioactive constituent of teas and it has a pivotal role in cancer prevention. Its preclinicalpharmacological activities are associated with complex molecular mechanisms that involve numerous signaling pathways.

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PMID: 

Curr Drug Discov Technol. 2020 Jan 26. Epub 2020 Jan 26. PMID: 31985382

Abstract Title: 

The potential role of tea in periodontal therapy: An updated review.

Abstract: 

Periodontal diseases are highly prevalent and can affect high percentage of the world population. Oxidative stress and inflammation plays an important role in the pathogenesis of periodontal diseases. Nowadays, more attention has been focused on the herbal remedies in the field of drug discovery. Green tea is an important source of polyphenol antioxidants, it has long been used as a beverage worldwide. The most interesting polyphenol components of green tea leaves that are related with health benefits are the catechins. Taken together this review suggested that green tea with its wide spectrum of activities could be a healthy alternative for controlling the damaging reactions seen in periodontal diseases.

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PMID: 

J Microbiol Biotechnol. 2019 Dec 30. Epub 2019 Dec 30. PMID: 31893612

Abstract Title: 

Phloretin protects macrophages from-induced inflammation through the TLR4 signaling pathway.

Abstract: 

Macrophages are the cells of the first-line defense system, which protect the body from foreign invaders such as bacteria. However, Gram-negative bacteria have always been the major challenge for macrophages due to the presence of lipopolysaccharides on their outer cell membrane. In the present study, we evaluated the effect of phloretin, a flavonoid commonly found in apple, on the protection of macrophages frominfection. RAW 264.7 cells infected with standard, or virulentK1 21 strain were treated with phloretin in a dose- dependent manner to examine its efficacy in protection of macrophages. Our results revealed that phloretin treatment reduced the production of nitric oxide (NO) and generation of reactive oxygen species along with reducing the secretion of proinflammatory cytokines induced by theandK1 21 strains in a concentration-dependent manner. Additionally, treatment of phloretin downregulated the expression of-induced major inflammatory markers i.e. cyclooxygenase-2 (COX-2) and hemeoxygenase-1 (HO-1), in a concentration dependent manner. Moreover, the TLR4-mediated NF-κB pathway was activated in-infected macrophages but was potentially downregulated by phloretin at the transcriptional and translational levels. Collectively, our data suggest that phloretin treatment protects macrophages from infection of virulentK1 strain by downregulating the TLR4-mediated signaling pathway and inhibiting NO and cytokine production, eventually protecting macrophages from-induced inflammation.

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PMID: 

Biosci Biotechnol Biochem. 2020 Jan 27:1-10. Epub 2020 Jan 27. PMID: 31987005

Abstract Title: 

Fig (L.) leaf tea suppresses allergy by acceleration disassembly of IgE-receptor complexes.

Abstract: 

In this study, I investigated the allergy suppressive effect of tea made from fig (L.) leaves. In the rat basophil cell line RBL-2H3, degranulation was significantly suppressed by treatment with fig tea at the same time as addition of IgE antibodies (sensitization). IgE bound to the cell surface was liberated in the medium depending on the treatment time with fig tea. Therefore, it was suggested that the mechanism of action of fig tea is promotion of dissociation of IgE from FcεRI receptors. Such a mechanism is novel in food materials. On oral administration to mice, fig tea showed an inhibitory effect on allergic dermatitis. Furthermore, in tests using an atopic dermatitis model in NC/Nga mice, continued administration of fig tea suppressed symptom exacerbation after antigen administration.AD: atopic dermatitis;β-Hex: β-hexosaminidase; FCM: flow cytometory; OA: oral administration; TA: transdermal administration.

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