PMID: 

Nutrients. 2019 Oct 7 ;11(10). Epub 2019 Oct 7. PMID: 31591345

Abstract Title: 

The Role of Dietary Fiber in Rheumatoid Arthritis Patients: A Feasibility Study.

Abstract: 

Short-chain fatty acids are microbial metabolites that have been shown to be key regulators of the gut-joint axis in animal models. In humans, microbial dysbiosis was observed in rheumatoid arthritis (RA) patients as well as in those at-risk to develop RA, and is thought to be an environmental trigger for the development of clinical disease. At the same time, diet has a proven impact on maintaining intestinal microbial homeostasis. Given this association, we performed a feasibility study in RA patients using high-fiber dietary supplementation with the objective to restore microbial homeostasis and promote the secretion of beneficial immunomodulatory microbial metabolites. RA patients (= 36) under routine care received daily high-fiber bars or cereals for 28 days. Clinical assessments and laboratory analysis of immune parameters in blood and stool samples from RA patients were done before and after the high-fiber dietary supplementation. We observed an increase in circulating regulatory T cell numbers, favorable Th1/Th17 ratios, as well as decreased markers of bone erosion in RA patients after 28 days of dietary intervention. Furthermore, patient-related outcomes of RA improved. Based on these results, we conclude that controlled clinical studies of high-fiber dietary interventions could be a viable approach to supplement or complement current pharmacological treatment strategies.

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PMID: 

Z Gerontol Geriatr. 2019 Oct 10. Epub 2019 Oct 10. PMID: 31602508

Abstract Title: 

Administration of alpha-lipoic acid could maintain bone mass and bone strength in senile female rats with alcohol consumption.

Abstract: 

Previous studies have demonstrated the damaging effect of alcohol (ALH) consumption on bone tissue and bone metabolism. Alpha-lipoic acid (ALA) promotes osteoblast proliferation and inhibits osteoclast proliferation, and positively affects bone regeneration; however, reports about effects of ALA on bone loss for aged female rats with ALH consumption are limited. This study was designed to investigate the impact of treatment with ALA on bone loss for aged female rats with ALH consumption. In this study 30 female Sprague-Dawley rats (22 months old), weighing approximately 520 g, were incorporated. The animals were randomly divided into three groups: group CON, group ALH and group ALH + ALA and received saline, ALH, ALH plus ALA treatment until death at 16 weeks, respectively. The results of maintaining bone mass and bone strength in senile female rats with ALH consumption were evaluated by histology, microcomputerized tomography, gene expression analysis and biomechanical tests. Results from this study indicated that ALH + ALA had stronger effects on the prevention and treatment of osteoporosis in senile female rats with ALH consumption. The ALH + ALA produced stronger effects on the bone volume ratio (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp), BMD and strength of distal femurs, and regulation of osteogenesis and bone resorption-related gene expression. These results seem to indicate thatALA intervention prevents bone loss in senile female rats with ALH consumption.

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PMID: 

Am J Transl Res. 2019 ;11(2):696-708. Epub 2019 Feb 15. PMID: 30899372

Abstract Title: 

Sequential treatment of phenethyl isothiocyanate increases sensitivity of Temozolomide resistant glioblastoma cells by decreasing expression of MGMT via NF-κB pathway.

Abstract: 

BACKGROUND: Existence of acquired or intrinsic resistance to Temozolomide (TMD) remains a point of concern in treating glioblastoma (GBM). Here we established mechanism by which Phenethyl isothiocyanate (PEITC) reverses TMD resistance in T98G cell lines bothand.METHODS: For the study TMD-resistant cell lines were generated by stepwise exposing the parental cell lines (U87 and U373) to TMD. The 50% inhibitory concentration (IC) values were established. MTT assay was done for cell survival studies, apoptosis assay by FITC Annexin V/PI staining, luciferase reporter assay for NF-transcription activity, cell colony survival and cell invasion assay, protein expression by western blot was done. Forstudies nude mouse model of GBM was established, TUNEL assay was done for apoptosis in tumor specimens.RESULTS: We established that T98G, U87-R and U373-R showed higher NF-κB activity and exhibited higher ICof TMD with significantly increased MGMT expression compared to untreated cells. Next, we found that PEITC suppressed proliferation of resistant GBM cells, inhibited NF-κB activity, decreased expression of MGMT and reversed the resistance in U373-R, U87-R and T98G cells. Exposure to PEITC followed by sequential treatment of TMD produced synergistic effect. In U373-R grafted xenografts mouse model PEITC suppressed cell growth and enhanced cell death.CONCLUSION: Altogether, the present research established that combination of PEITC with TMD could enhance its clinical efficacy in resistant GBM by suppressing MGMT via inhibiting NF-κB activity.

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PMID: 

Life Sci. 2019 Aug 15 ;231:116589. Epub 2019 Jun 19. PMID: 31226416

Abstract Title: 

Cytoprotective effects of galacto-oligosaccharides on colon epithelial cells via up-regulating miR-19b.

Abstract: 

AIMS: Despite the protective effect of galacto-oligosaccharides (GOS) on human colon has been widely-reported, the mechanism of its beneficial effect is still unclear. This paper aims to reveal the internal mechanism underlined the anti-colitis effect of GOS by studying its regulatory effect on miRNAs.MAIN METHODS: An in vitro model of colitis was constructed by using human colon epithelial FHC cells and lipopolysaccharide (LPS). An in vivo colitis model was established as well, by injecting Rag2Sprague-Dawley (SD) rats with helicobacter hepaticus. The effects of GOS pre-treatment on these two models were tested, and the miRNAs involved in these effects were studied.KEY FINDINGS: The expression of miR-19b, miR-590-5p and miR-495 was up-regulated, and the expression of miR-29a, miR-31 and miR-142-5p was down-regulated by GOS treatment in both normal and LPS-stimulated FHC cells. Among which, miR-19b was the most varied miRNA. GOS pre-treatment significantly attenuated LPS-induced cell injury, as evidenced by the increase of cell viability, the decrease of apoptosis, as well as the suppressed release of TNF-α, IFN-γ and IL-1β. GOS pre-treatment could also prevent Rag2rats against helicobacter hepaticus injection induced diarrhea and inflammation, as the body weight and colon organ weight were recovered, diarrhea score was declined, and the release of pro-inflammatory cytokines was inhibited. The in vitro and in vivo effects of GOS abovementioned were all impeded when miR-19b was silenced.SIGNIFICANCE: In vitro and in vivo experiments showed that GOS have certain anti-colitis effect, and this effect may be achieved by up-regulating miR-19b.

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PMID: 

BMJ Open Ophthalmol. 2019 ;4(1):e000217. Epub 2019 May 28. PMID: 31245609

Abstract Title: 

Protective effects of blue light-blocking shades on phototoxicity in human ocular surface cells.

Abstract: 

Objective: Blue light hazards for retina and ocular surface have been repeatedly described and many protective methods are introduced for retina; however, no study has been conducted on ocular surface protection. The purpose of this in vitro study was to examine phototoxicity and shade protection after blue light irradiation in primary human cells of corneal surface origin.Methods and analysis: Primary human cells of corneal surface origin were obtained from eye bank eyes. After blue light irradiation (405 nm) of these cells for 3 min, and a further 24 hours' incubation, surviving viable cells were assessed by the methyl thiazolyl tetrazolium assay. Simultaneously, cell viability was determined in wells covered by ultraviolet and blue light shades.Results: Under subconfluent conditions, viable cells decreased by around 50% after blue light irradiation, compared with control cells without irradiation. The blue light phototoxicity was not blocked by the control shade, but the ultraviolet-blocking and blue light-blocking shades protected the cells from phototoxicity, producing a 30%-40% reduction (ultraviolet) and 15%-30% reduction (blue light) in viable cells.Conclusion: These results indicate that blue light injures ocular surface cells and the cells are protected from damage by a shade. We recommend blue light protection to maintain ocular health, especially in high-risk populations, such as people with dry eye, contact lens users, the malnourished and the elderly.

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PMID: 

J Nutr. 2019 Oct 5. Epub 2019 Oct 5. PMID: 31586202

Abstract Title: 

Dietary Supplementation with Galactooligosaccharides Attenuates High-Fat, High-Cholesterol Diet-Induced Glucose Intolerance and Disruption of Colonic Mucin Layer in C57BL/6 Mice and Reduces Atherosclerosis in Ldlr-/- Mice.

Abstract: 

BACKGROUND: A Western-type diet (WD), rich in fat and cholesterol but deficient in fiber, induces development of diabetes and atherosclerosis. Colonic bacteria use the gut's mucous lining as an alternate energy source during periods of fiber deficiency, resulting in intestinal barrier erosion.OBJECTIVE: We hypothesized that supplementing a WD with galactooligosaccharide (GOS) fiber would attenuate WD-induced mucin layer disruption and attenuate development of metabolic diseases.METHODS: C57BL/6 mice (both sexes, 8-10 wk of age) were fed a standard rodent diet (TD7012, reference) or a high-fat, high-cholesterol-containing WD (TD88137, 21% fat, 0.15% cholesterol, 19.5% caesin) or a WD supplemented with 5% GOS fiber (TD170432, WD + GOS) for 16 wk. WD-fed mice that were gavaged daily with curcumin (100 mg/kg) served as positive controls. Glucose tolerance, colonic mucin layer, gene expression, and circulating macrophage/neutrophil levels were determined. Hyperlipidemic Ldlr-/- mice (both sexes, 8-10 wk of age) fed a WD with or without GOS supplementation (for 16 wk) were used to assess plasma LPS and atherosclerosis. Effects of dietary supplementation on different parameters were compared for each genotype.RESULTS: Compared with a WD, glucose tolerance was significantly improved in male C57BL/6 mice fed a WD + GOS (mean ± SEM: AUC = 53.6 ± 43.9 compared with 45.4 ± 33.3 g ⋅ min/dL; P = 0.015). Continuity of colonic mucin layer (MUC-2 expression) was improved in mice receiving GOS supplementation, indicating improved intestinal barrier. GOS supplementation also reduced circulating macrophages (30% decrease) and neutrophils (60% decrease), suggesting diminished systemic inflammation. In Ldlr-/- mice, GOS supplementation significantly reduced plasma LPS concentrations (mean ± SEM: 0.81 ±  0.43 EU/mL compared with 0.32 ± 0.26 EU/mL, P   

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PMID: 

Nutrients. 2019 Mar 7 ;11(3). Epub 2019 Mar 7. PMID: 30866564

Abstract Title: 

Vitamin D Deficiency is Associated with Increased Use of Antimicrobials among Preschool Girls in Ethiopia.

Abstract: 

Preschool children in Addis Ababa, Ethiopia, are highly exposed to influenza viruses. Factors related to infections, nutrition, and environmental conditions that might explain the burden of influenza among these children were investigated. Ninety-five preschool children, 48 girls and 47 boys, were followed clinically for 12 months. Illness and immune responses to influenza; three other respiratory viruses; five airway pathogenic bacteria; and levels of vitamins D, A, and B12 were assessed. Most of the children had antibodies to numerous respiratory viral and bacterial agents at study start, and many were infected during follow-up. Twenty-five girls and 25 boys fell ill during the study, and were treated with one or more courses of systemic antimicrobials. Ninety percent of both girls and boys had 25-hydroxyvitamin D [25(OH)D] levels below the recommended levels. While there was no overall difference in the levels of vitamins D, A, and B12 between girls and boys, treated girls had significantly lower 25(OH)D levels than non-treated girls and treated boys. There was a considerable number of short for age children, but only the short treated girls had significantly lower 25(OH)D levels than the non-treated children. Preschool girls with low 25(OH)D levels were more vulnerable to pathogenic microbes than boys.

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PMID: 

Infect Disord Drug Targets. 2019 Jun 26. Epub 2019 Jun 26. PMID: 31241441

Abstract Title: 

Therapeutic value of Vitamin D as an adjuvant therapy in neonates with sepsis.

Abstract: 

: Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. Vitamin D is a fat-soluble steroid hormone that contributes to the maintenance of normal calcium homeostasis and skeletal mineralization. Vitamin D has an important role in the regulation of both innate and adaptive immune systems.AIM OF THE WORK: Current study aimed to evaluate the therapeutic value of vitamin D supplementation as an adjuvant therapy in neonates with sepsis.SUBJECTS AND METHOD: This study included 60 neonates with sepsis who were divided into 2 equal groups; group I: 30 neonates with sepsis who received antibiotic only, Group II: 30 neonates with sepsis who received antibiotic therapy and vitamin D. This study included also 30 healthy neonates as a control group. Serum level of 25 (OH) vitamin D and highly sensitive C reactive protein (hs-CRP) were immunoassayed.RESULTS: There is no significant difference between group I, II and controls as regard weight, gestational age, sex and mode of delivery. There were significant differences between group I and group II in sepsis score and hs-CRP after 3, 7, 10 days of treatment (p values for sepsis score were 0.009, 0.006, 0.004 respectively and for hs-CRP were 0.015,0.001,0.001 respectively).There was significance difference in immature /total (I/T) ratio after 7,10 days of treatment (p value= 0.045, 0.025 respectively) while there was no significance difference in immature /total (I/T) ratio after 3 days of treatment (p value = 0.624). Serum 25(OH) vitamin D levels was significantly lower in neonates with sepsis (group I and II) than controls (p value

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PMID: 

Crit Care. 2019 10 21 ;23(1):324. Epub 2019 Oct 21. PMID: 31639033

Abstract Title: 

Rescue fecal microbiota transplantation for antibiotic-associated diarrhea in critically ill patients.

Abstract: 

BACKGROUND: Antibiotic-associated diarrhea (AAD) is a risk factor for exacerbating the outcome of critically ill patients. Dysbiosis induced by the exposure to antibiotics reveals the potential therapeutic role of fecal microbiota transplantation (FMT) in these patients. Herein, we aimed to evaluate the safety and potential benefit of rescue FMT for AAD in critically ill patients.METHODS: A series of critically ill patients with AAD received rescue FMT from Chinese fmtBank, from September 2015 to February 2019. Adverse events (AEs) and rescue FMT success which focused on the improvement of abdominal symptoms and post-ICU survival rate during a minimum of 12 weeks follow-up were assessed.RESULTS: Twenty critically ill patients with AAD underwent rescue FMT, and 18 of them were included for analysis. The mean of Acute Physiology and Chronic Health Evaluation (APACHE) II scores at intensive care unit (ICU) admission was 21.7 ± 8.3 (range 11-37). Thirteen patients received FMT through nasojejunal tube, four through gastroscopy, and one through enema. Patients were treated with four (4.2 ± 2.1, range 2-9) types of antibiotics before and during the onset of AAD. 38.9% (7/18) of patients had FMT-related AEs during follow-up, including increased diarrhea frequency, abdominal pain, increased serum amylase, and fever. Eight deaths unrelated to FMT occurred during follow-up. One hundred percent (2/2) of abdominal pain, 86.7% (13/15) of diarrhea, 69.2% (9/13) of abdominal distention, and 50% (1/2) of hematochezia were improved after FMT. 44.4% (8/18) of patients recovered from abdominal symptoms without recurrence and survived for a minimum of 12 weeks after being discharged from ICU.CONCLUSION: In this case series studying the use of FMT in critically ill patients with AAD, good clinical outcomes without infectious complications were observed. These findings could potentially encourage researchers to set up new clinical trials that will provide more insight into the potential benefit and safety of the procedure in the ICU.TRIAL REGISTRATION: ClinicalTrials.gov, Number NCT03895593 . Registered 29 March 2019 (retrospectively registered).

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PMID: 

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2019 Sep ;31(9):1102-1107. PMID: 31657333

Abstract Title: 

[Fecal microbiota transplantation regulates the cholinergic anti-inflammatory pathway in cerebral cortex of septic rats through intestinal microbiota].

Abstract: 

OBJECTIVE: To investigate the effects of fecal microbiota transplantation on septic gut flora and the cortex cholinergic anti-inflammatory pathway in rats.METHODS: Sixty clean grade male Sprague-Dawley (SD) rats were divided into normal saline (NS) control group, sepsis model group and fecal microbiota transplantation group by random number table, with 20 rats in each group. The rat model of sepsis was reproduced by injection of 10 mg/kg lipopolysaccharide (LPS) via tail vein, the rats in the NS control group was given the same amount of NS. The rats in the fecal microbiota transplantation group received nasogastric infusion of feces from healthy donor on the 1st day, 2 mL each time, for 3 times a day, the other two groups were given equal dose of NS by gavage. Fecal samples were collected on the 7th day after modeling, the levels of intestinal microbiota composition was determined using the 16SrDNA gene sequencing technology. The brain function was evaluated by electroencephalogram (EEG), and the proportion of each waveform in EEG was calculated. After sacrifice of rats, the brain tissues were harvested, the levels of protein expression ofα7 nicotinic acetylcholine receptor (α7nAChR) were determined by Western Blot, and positive cells of Iba-1 in brain tissue were detected by immunohistochemistry method. The levels of interleukins (IL-6 and IL-1β) and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbentassay (ELISA).RESULTS: Seven days after the reproduction of the model, all rats in the NS control group survived, while 10 rats and 8 rats died in the sepsis model group and fecal microbiota transplantation group, respectively, with mortality rates of 50% and 40% respectively. Finally, there were 20 rats in the NS control group, 10 in the sepsis model group and 12 in the fecal microbiota transplantation group. Compared with the NS control group, the diversity and composition of intestinal flora were changed, the incidence of abnormal EEG increased significantly, the expression ofα7nAchR in the cortex decreased significantly, and the levels of Iba-1, TNF-α, IL-6 and IL-1β were significantly increased in the model group, suggested that the intestinal flora was dysbiosis, and severe inflammatory reaction occurred in the cerebral cortex, and brain function was impaired. Compared with the model group, the diversity of intestinal flora in the fecal microbiota transplantation group was significantly increased (species index: 510.24±58.76 vs. 282.50±47.42, Chao1 index: 852.75±25.24 vs. 705.50±46.50, both P

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