PMID: 

J Transl Med. 2020 Jan 29 ;18(1):43. Epub 2020 Jan 29. PMID: 31996227

Abstract Title: 

Lycopene and bone: an in vitro investigation and a pilot prospective clinical study.

Abstract: 

BACKGROUND: There are several effective therapies for osteoporosis but these agents might cause serious adverse events. Lycopene intake could prevent bone loss, however studies on its effects on bone are scarce. Our aim was to investigate the effects of lycopene on osteoblast cells as well as bone mineral density and bone turnover markers in postmenopausal women.METHODS: We investigated the effect of lycopene on the Wnt/β-catenin and ERK 1/2 pathways, RUNX2, alkaline phosphatase, RANKL and COL1A of Saos-2. We also carried out a pilot controlled clinical study to verify the feasibility of an approach for bone loss prevention through the intake of a lycopene-rich tomato sauce in 39 postmenopausal women.RESULTS: Lycopene 10 µM resulted in higher β-catenin and phERK1/2 protein Vs the vehicle (p = 0.04 and p = 0.006). RUNX2 and COL1A mRNA was induced by both 5 and 10 µM doses (p = 0.03; p = 0.03 and p = 0.03; p = 0.05) while RANKL mRNA was reduced (p 

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PMID: 

Free Radic Biol Med. 2020 Jan 31. Epub 2020 Jan 31. PMID: 32014502

Abstract Title: 

Natural ingredients-derived antioxidants attenuate HO-induced oxidative stress and have chondroprotective effects on human osteoarthritic chondrocytes via Keap1/Nrf2 pathway.

Abstract: 

Osteoarthritis (OA) is the most common disabling joint disease and its pathological process is closely related to oxidative stress. Recent studies have shown that antioxidants allicin, sulforaphane, and lycopene derived from natural ingredients garlic, broccoli, and tomato can reduce the degree of oxidative stress and the expression of inflammatory markers, indicating that theses antioxidants might be helpful for OA treatment. In this study, we investigated the effects of allicin, sulforaphane, and lycopene on HO-stimulated human osteochondral samples and osteoarthritic chondrocytes. Our results revealed that allicin, sulforaphane, and lycopene effectively reduced the oxidative stress-induced cell apoptosis, and increased gene expression of antioxidant enzymes. Besides, these natural ingredients-derived antioxidants reduced the expression of inflammatory factors, enhanced the chondrogenic matrix synthesis, and reduced the hypertrophic differentiation of osteoarthritic chondrocytes. These regulations were mainly through the activation of Keap1/Nrf2 pathway. Our findings suggest that these antioxidants might be a potential therapeutic strategy for OA.

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PMID: 

Neuropharmacology. 2020 Jan 27:107976. Epub 2020 Jan 27. PMID: 32001239

Abstract Title: 

Docosahexaenoic acid protects motor function and increases dopamine synthesis in a rat model of Parkinson's disease via mechanisms associated with increased protein kinase activity in the striatum.

Abstract: 

Parkinson's disease (PD) is a devastating neurodegenerative disease that leads to motor deficits and selective destruction of nigrostriatal dopaminergic neurons. PD is typically treated by dopamine replacement agents; however, dopamine replacement loses effectiveness in the later stages of the disease. Here, we describe the neuroprotective effects of the omega-3 fatty acid docosahexaenoic acid (DHA) in the medial forebrain bundle 6-hydroxydopamine (6-OHDA) model of advanced-stage PD in rats. We show that daily administration of DHA protects against core symptoms of PD, including deficits in postural stability, gait integrity, and dopamine neurochemistry in motor areas of the striatum. Our results also demonstrate that DHA increases striatal dopamine synthesis via phosphorylation of the rate-limiting catecholamine synthesizing enzyme tyrosine hydroxylase, in a manner dependent on the second messenger-linked protein kinases PKA and PKC. We also show that DHA specifically reverses dopamine loss in the nigrostriatal pathway, with no effect in the mesolimbic or mesocortical pathways. This suggests that DHA is unlikely to produce pharmacotherapeutic or adverse effects that depend on dopamine pathways other than the nigrostriatal pathway. To our knowledge, previous reports have not examined the effects of DHA in such an advanced-stage model, documented that the dopamine synthesizing effects of DHA in vivo are mediated through the activation of protein kinases and regulation of TH activity, or demonstrated specificity to the nigrostriatal pathway. These novel findings corroborate the beneficial effects of omega-3 fatty acids seen in PD patients and suggest that DHA provides a novel means of protecting patients for dopamine neurodegeneration.

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PMID: 

Biochimie. 2020 Jan 31. Epub 2020 Jan 31. PMID: 32014503

Abstract Title: 

Brain targeting with docosahexaenoic acid as a prospective therapy for neurodegenerative diseases and its passage across blood brain barrier.

Abstract: 

Docosahexaenoic acid (DHA, 22:6n-3) is the main omega-3 polyunsaturated fatty acid in brain tissues necessary for common brain growth and function. DHA can be provided to the body through two origins: an exogenous origin, from direct dietary intakes and an endogenous one, from the bioconversion of the essentialα-linolenic acid (ALA, 18:3n-3) in the liver. In humans, the biosynthesis of DHA from its precursor ALA is very low. A reduction in the cerebral amount of DHA is detected in patients suffering from neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Considering the vital functions of DHA for the brain, new methodologies to target the brain with DHA offers encouraging perceptions in the improvement of precautionary and therapeutic approaches for neurodegenerative diseases. The aim of the present review was to provide better understanding of the cerebral uptake of DHA in different form including free fatty acids, Lysophosphatidylcholines LysoPC-DHA as well as structured phospholipids. First, we explored the special structure of the blood-brain barrier BBB, BBB being a physical and metabolic barrier with restrictive properties. Then, we discussed the incorporation of DHA into the membrane phospholipids of the brain, the neuroprotective and therapeutic effect of DHA for neurological diseases.

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PMID: 

Physiol Rep. 2020 Jan ;8(2):e14262. PMID: 31997577

Abstract Title: 

The effect of acute exercise on environmentally induced symptoms of dry eye.

Abstract: 

The purpose of this study was to investigate the effects of acute exercise on environmentally induced symptoms of dry eye. Twelve participants without dry eye disease volunteered to complete three experimental visits in a randomized order; (1) control condition seated for 1 h at a relative humidity (RH) of 40% (CONT), (2) dry condition seated for 1 h at a RH of 20% (DRY), and (3) exercise condition seated for 40 min followed by 20 min of cycling exercise at a RH of 20% (EXER). Tear volume, tear matrix metalloproteinase 9 (MMP-9), perception of dry eye symptoms (frequency and severity), core temperature, and ocular surface temperature (OST) were measured at the end of each exposure. The perception of dry eye frequency and MMP-9 concentration were significantly higher in DRY compared to CONT (P 

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PMID: 

Antioxidants (Basel). 2020 Jan 19 ;9(1). Epub 2020 Jan 19. PMID: 31963866

Abstract Title: 

Cytoprotective Effects of Delphinidin for Human Chondrocytes against Oxidative Stress through Activation of Autophagy.

Abstract: 

Antioxidant enzymes are decreased in osteoarthritis (OA) patients, implying the role of oxidative stress in osteoarthritis pathogenesis. The aim of this study was to evaluate the cytoprotective effects of delphinidin, a potent antioxidant, in human chondrocytes and the underlying mechanisms. The cytoprotective mechanism induced by delphinidin against oxidative stress (HO) in human chondrocytes was investigated. Cell viability and death were evaluated using proapoptotic and antiapoptotic markers such as cleaved caspase-3 (c-caspase-3), cleaved poly(ADP-ribose) polymerase-acetylcysteine (c-PARP), Bcl-X, and transcription factors associated with redox and inflammation regulation, including nuclear factor kappa B (NF-κB) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Induction of autophagy was assessed by formation of LC3-II and autophagosome-(LC3 punctate, monodansylcadaverine (MDC) and acridine orange staining) in the presence or absence of an autophagy inhibitor. Treatment with delphinidin itself atconcentration below 50 µM for 24 h did not affect viability of chondrocytes. Delphinidin inhibited reactive oxygen species (ROS)-induced apoptosis by significantly decreasing apoptosis markers such as c-caspase-3 and c-PARP while increasing antiapoptotic marker Bcl-Xand antioxidant response NF-κB and Nrf2 pathways. Delphinidin also activated cytoprotective autophagy to protect chondrocytes during oxidative stresses. Activation of autophagy with autophagy inducer rapamycin also inhibited ROS-induced cell death and decreased proapoptotic proteins but increased antiapoptotic protein Bcl-X, NF-κB, and Nrf2. Delphinidin can protect chondrocytes against HO-induced apoptosis via activation of Nrf2 and NF-κB and protective autophagy. Thus, it can inhibit OA with protection of chondrocytes. Delphinidin can protect chondrocytes against HO-induced ROS with maintenance of homeostasis and redox. These results suggest that delphinidin could be used to protect chondrocytes against age-related oxidative stress and other oxidative stresses in the treatment of OA. Thus, delphinidin may play a critical role in preventing the development and progression of OA.

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PMID: 

J Ethnopharmacol. 2020 Jan 10 ;251:112561. Epub 2020 Jan 10. PMID: 31926988

Abstract Title: 

The antidiarrhoeal evaluation of Psidium guajava L. against enteropathogenic Escherichia coli induced infectious diarrhoea.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: The plant Psidium guajava L. (Myrtaceae), commonly used as an edible fruit is traditionally used worldwide in treatment of various gastrointestinal problems including diarrhoea. The leaves of the plant have also been evaluated for antidiarrhoeal activity in various chemical induced diarrhoea models.OBJECTIVE: The main objective of the present study was to evaluate the potency of P. guajava leaves and its major biomarker quercetin against enteropathogenic Escherichia coli (EPEC) induced infectious diarrhoea using preclinical and computational model.MATERIAL AND METHODS: P. guajava alcoholic leaf extract (PGE) was initially standardized using HPLC taking quercetin as a biomarker and was then subjected to antidiarrhoeal evaluation on rats in an EPEC induced diarrhoea rat model. The study included assessment of various behavioral parameters, initially for 6 h and then for up to 24 h of induction which was followed by estimation of stool water content, density of EPEC in stools and blood parameters evaluation. The colonic and small intestinal tissues of the treated animals were subjected to various biochemical estimations, in vivo antioxidant evaluation, estimation of ion concentration, Na/K-ATPase activity, assessment of pro-inflammatory cytokines and histopathological studies. Further, the major biomarker off PGE, quercetin was subjected to molecular docking studies with Na/K-ATPase and EPEC.RESULTS: The results demonstrated a significant antidiarrhoeal activity of quercetin (50 mg/kg), PGE at 200 and 400 mg/kg, p.o., where quercetin and PFGE at 200 mg/kg, p.o. were found to be more prominent, as confirmed through higher % protection, water content of stools and density of EPEC in stools. PGE and its biomarker quercetin also significantly recovered the WBC, Hb, platelets loss and also revealed a significant restoration of altered antioxidants level, pro-inflammatory cytokines (IL-1β and TNF-α) expression and had positive influence on Na/K-ATPase activity. The docking studies of quercetin with Na/K-ATPase showed favourable interactions and residues Glu 327, Ser 775, Asn 776, Glu 779 and Asp 804 of Na/K-ATPase were adequately similar to quercetin for donating ligands for binding, while quercetin was also found to terminate the linkage between mammalian cells and EPEC thus, preventing further infection from EPEC.CONCLUSION: Inhibition in intestinal secretion, reduced nitric oxide production and inflammatory expression along with reactivation of Na/K-ATPase activity could be attributed to the observed antidiarrhoeal potential of PGE against infectious diarrhoea, where quercetin was confirmed to be the main contributing factor.

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PMID: 

ACG Case Rep J. 2019 Aug ;6(8):e00161. Epub 2019 Aug 21. PMID: 31737700

Abstract Title: 

N-Acetylcysteine in the Management of Acute Liver Failure From Sickle Cell Hepatic Crisis.

Abstract: 

N-acetylcysteine (NAC) has been well studied in the treatment of acetaminophen-induced and select non-acetaminophen-induced liver failure. However, its role in the management of sickle cell hepatic crisis resulting in acute liver failure (ALF) is unknown. We describe and discuss the novel and beneficial use of NAC in a 25-year-old man with ALF due to sickle cell hepatic crisis. We further review ALF in sickle cell disease and NAC in the treatment of non-acetaminophen-induced liver failure. Our case highlights the promising role of NAC in sickle cell-related liver injury.

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PMID: 

Gynecol Endocrinol. 2019 Nov 21:1-7. Epub 2019 Nov 21. PMID: 31749393

Abstract Title: 

Comparison of the efficacy between NAC and metformin in treating PCOS patients: a meta-analysis.

Abstract: 

Our aim is to evaluate the clinical effectiveness and safety by comparing N-acetyl-cysteine (NAC) with metformin administrated by polycystic ovary syndrome (PCOS) patients. Systematic review and meta-analysis of randomized clinical trials (RCTs). MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure were searched for studies. 10 studies were considered eligible for inclusion. NAC significantly reduced BMI and total testosterone, there was no significant difference in pregnancy rate, serum LH level, fasting insulin, and LH/FSH ratio. In conclusions, NAC may be considered as an alternative supplement to metformin, but large-scale randomized controlled trials are needed to assess the efficacy and safety of NAC in PCOS patients.

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PMID: 

Cells. 2019 Dec 29 ;9(1). Epub 2019 Dec 29. PMID: 31905757

Abstract Title: 

Synergistic Effects of N-Acetylcysteine and Mesenchymal Stem Cell in a Lipopolysaccharide-Induced Interstitial Cystitis Rat Model.

Abstract: 

The purpose of this study was to reduce the amount of stem cells used in treating preclinical interstitial cystitis (IC model) by investigating the synergistic effects of multipotent mesenchymal stem cells (M-MSCs; human embryonic stem cell-derived) and N-acetylcysteine (NAC). Eight-week-old female Sprague-Dawley rats were divided into seven groups, i.e., sham (= 10), lipopolysaccharide/protamine sulfate (LPS/PS;= 10), LPS/PS + NAC (= 10), LPS/PS with 25K MSC (= 10), LPS/PS with 50K MSC (= 10) LPS/PS + 25K MSC + NAC (= 10), and LPS/PS + 50K MSC + NAC (= 10). To induce the IC rat model, protamine sulfate (10 mg, 45 min) and LPS (750μg, 30 min) were instilled once a week for five consecutive weeks via a transurethral PE-50 catheter. Phosphate-buffered saline (PBS) was used in the sham group. One week after the final instillation, M-MSCs with two suboptimal dosages (i.e., 2.5 or 5.0 × 10cells) were directly transplanted into the outer-layer of the bladder. Simultaneously, 200 mg/kg of NAC or PBS was intraperitoneally injected daily for five days. The therapeutic outcome was evaluated one week after M-MSC or PBS injection by awake cystometry and histological analysis. Functionally, LPS/PS insult led to irregular micturition, decreased intercontraction intervals, and decreased micturition volume. Both monotherapy and combination therapy significantly increased contraction intervals, increased urination volume, and reduced the residual volume, thereby improving the urination parameters compared to those of the LPS group. In particular, a combination of NAC dramatically reduced the amount of M-MSCs used for significant restoration in histological damage, including inflammation and apoptosis. Both M-MSCs and NAC-based therapy had a beneficial effect on improving voiding dysfunction, regenerating denudated urothelium, and relieving tissue inflammation in the LPS-induced IC/BPS rat model. The combination of M-MSC and NAC was superior to MSC or NAC monotherapy, with therapeutic efficacy that was comparable to that of previously optimized cell dosage (1000K) without compromised therapeutic efficacy.

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