Nutritional intervention is promising in alleviating liver injury during tuberculosis treatment: a review.

Liver injury is a main adverse effect of first-line tuberculosis drugs. Current management of tuberculosis-drug-induced liver injury (TBLI) mainly relies on withdrawing tuberculosis drugs when necessary. No effective treatment exists. Various nutrients and functional food ingredients may play a protective role in TBLI. However, a comprehensive review has not been conducted to compare the effects of these nutrients and functional food ingredients. We searched Pubmed and Web of Science databases from the earliest date of the database to March 2023. All available in-vitro, animal and clinical studies that examined the effects of nutritional intervention on TBLI were included. The underlying mechanism was briefly reviewed. Folic acid, quercetin, curcumin, Lactobacillus casei, spirulina and Moringa oleifera possessed moderate evidence to have a beneficial effect on alleviating TBLI mostly based on animal studies. The evidence of other nutritional interventions on TBLI was weak. Alleviating oxidative stress and apoptosis were the leading mechanisms for the beneficial effects of nutritional intervention on TBLI. In conclusion, a few nutritional interventions are promising for alleviating TBLI including folic acid, quercetin, curcumin, L. casei, spirulina and M. oleifera, the effectiveness and safety of which need further confirmation by well-designed randomized controlled trials. The mechanisms for the protective role of these nutritional interventions on TBLI warrant further study, particularly by establishing the animal model of TBLI using the tuberculosis drugs separately.

The role and advantage of traditional Chinese medicine in the prevention and treatment of COVID-19.

The global coronavirus disease 2019 (COVID-19) pandemic has had a massive impact on global social and economic development and human health. By combining traditional Chinese medicine (TCM) with modern medicine, the Chinese government has protected public health by supporting all phases of COVID-19 prevention and treatment, including community prevention, clinical treatment, control of disease progression, and promotion of recovery. Modern medicine focuses on viruses, while TCM focuses on differential diagnosis of patterns associated with viral infection of the body and recommends the use of TCM decoctions for differential treatment. This differential diagnosis and treatment approach, with its profoundly empirical nature and holistic view, endows TCM with an accessibility advantage and high application value for dealing with COVID-19. Here, we summarize the advantage of and evidence for TCM use in COVID-19 prevention and treatment to draw attention to the scientific value and accessibility advantage of TCM and to promote the use of TCM in response to public health emergencies. Please cite this article as: Huang M, Liu YY, Xiong K, Yang FW, Jin XY, Wang ZQ, Zhang JH, Zhang BL. The role and advantage of traditional Chinese medicine in the prevention and treatment of COVID-19. J Integr Med. 2023; 21(5): 407-412.

Folic acid protects against tuberculosis-drug-induced liver injury in rats and its potential mechanism by metabolomics.

Observational study indicated that folic acid (FA) supplementation may protect against tuberculosis-drug-induced liver injury (TBLI). The aim is to investigate the effect and mechanism of FA on TBLI in rats. Liver injury was induced by a daily gavage of isoniazid (INH) and rifampicin (RIF) in the model and FA groups. Rats in the FA group were also treated with 2.5 mg/kg body weight FA. Rats in the control group were not treated. Eight rats were used in each group. The severity of liver injury was measured by the serum levels of hepatic enzymes and histological score. The metabolites in serum and liver tissues were analyzed by HPLC-Q-TOF-MS/MS. FA treatment significantly reduced alanine aminotransferase and liver necrosis. Seventy-nine differential metabolites in the serum and liver tissues were identified among the three groups. N-acylethanolamines, INH and RIF metabolites, phosphatidylcholines, lysophosphatidylcholines, monoglycerides, diglycerides and bile acids were regulated by FA treatment, involving key metabolic pathways, such as N-acylethanolamine metabolism, INH and RIF metabolism, liver regeneration, inflammation alleviation and bile acid metabolism. RT-PCR and western blotting results confirmed the altered N-acylethanolamine metabolism and improved drug metabolism by FA. In conclusion, FA was protective against TBLI, which may be related to the regulation of N-acylethanolamine metabolism and drug detoxification by FA.

Decoding the Key Functional Combined Components Group and Uncovering the Molecular Mechanism of Longdan Xiegan Decoction in Treating Uveitis.

Objective: Longdan Xiegan Decoction (LXD) is a famous herbal formula in China. It has been proved that LXD has been shown to have a significant inhibitory effect on suppresses the inflammatory cells associated with uveitis. However, the key functional combination of component groups and their possible mechanisms remain unclear. Methods: The community detecting model of the network, the functional response space, and reverse prediction model were utilized to decode the key components group (KCG) and possible mechanism of LXD in treating uveitis. Finally, MTT assay, NO assay and ELISA assay were applied to verify the effectiveness of KCG and the accuracy of our strategy. Results: In the components-targets-pathogenic genes-disease (CTP) network, a combination of Huffman coding and random walk algorithm was used and eight foundational acting communities (FACs) were discovered with important functional significance. Verification has shown that FACs can represent the corresponding C-T network for treating uveitis. A novel node importance calculation method was designed to construct the functional response space and pick out 349 effective proteins. A total of 54 components were screened and defined as KCG. The pathway enrichment results showed that KCG and their targets enriched signal pathways of IL-17, Toll-like receptor, and T cell receptor played an important role in the pathogenesis of uveitis. Furthermore, experimental verification results showed that important KCG quercetin and sitosterol markedly inhibited the production of nitric oxide and significantly regulated the level of TNF-α and IFN-γ in Lipopolysaccharide-induced RAW264.7 cells. Discussion: In this research, we decoded the potential mechanism of the multi-components-genes-pathways of LXD's pharmacological action mode against uveitis based on an integrated pharmacology approach. The results provided a new perspective for the future studies of the anti-uveitis mechanism of traditional Chinese medicine.

Modulation of hyperglycemia by sodium alginate is associated with changes of serum metabolite and gut microbiota in mice.

Previous studies showed that sodium alginates of different molecular weights reduced postprandial glucose differently. We hypothesize that the differential modulation of hyperglycemia by sodium alginates with different molecular weights may be associated with their differential regulations of serum metabolites and gut microbiota. In this work, high-fat diet-fed mice were supplemented with high- and low-molecular-weight sodium alginate (H-SA, 3350 kDa; L-SA, 131 kDa). Blood glucose/lipid parameters, serum metabolites and gut microbiota were measured. Compared with L-SA, H-SA more significantly reduced fasting blood glucose, HOMA-IR, total cholesterol and body fat; H-SA more significantly enriched serum metabolites, including certain lipids, branched-chain amino acids, and vitamin D and E derivatives. These changes were correlated with the differential modulation of gut microbiota by H-SA and L-SA. In conclusion, the differential effects of sodium alginates with different molecular weights in alleviating hyperglycemia were associated with their differential modulations of serum metabolites and gut microbiota.

Astaxanthin supplementation mildly reduced oxidative stress and inflammation biomarkers: a systematic review and meta-analysis of randomized controlled trials.

Previous in vitro and animal studies showed that astaxanthin improved oxidative stress and inflammation biomarkers. We hypothesized the same effects of astaxanthin in humans and conducted a systematic review and meta-analysis of previous randomized controlled trials to test this hypothesis. The literature search was performed on PubMed, Cochrane Library, and Scopus databases from January 1970 to April 2021. Main eligibility criteria include: intervention using astaxanthin for at least 1 week; inclusion of placebo control; and measuring at least 1 of the common oxidative stress and inflammation biomarkers before and after intervention. Twelve randomized controlled trials including 380 participants were included. Compared with placebo, astaxanthin significantly reduced blood malondialdehyde concentration (standardized mean difference [SMD]: -0.95; 95% CI, -1.67 to -0.23; P = .01). The lowering effect of astaxanthin supplementation on malondialdehyde was particularly significant in type 2 diabetes mellitus (T2DM) patients (SMD: -0.64; 95% CI, -1.26 to -0.01; P < .05). A limited number of trials were available for the effects of astaxanthin on other oxidative stress biomarkers. Astaxanthin supplementation appeared to improve superoxide dismutase activity and reduce serum isoprostane concentration in overweight subjects. Astaxanthin significantly reduced blood interleukin-6 concentration in T2DM patients (weighted mean difference: -0.70 pg/mL; 95% CI, -1.29 to -0.11 pg/mL; P = .02). The effects of astaxanthin on blood C-reactive protein and tumor necrosis factor-α concentrations were not significant. The current work indicated that astaxanthin supplementation may be beneficial for improving oxidative stress and certain inflammation biomarkers, particularly in T2DM patients. Future work should investigate the effects of astaxanthin on T2DM.

Adjunctive vitamin A and D for the glycaemic control in patients with concurrent type 2 diabetes and tuberculosis: a randomised controlled trial.

The objective of this study is to investigate the effects of vitamin A, D and their interaction on the glycaemic control in patients with both diabetes and tuberculosis. Tuberculosis infection and its treatment induce hyperglycaemia and complicate the glycaemic control in patients with diabetes. A randomised controlled trial with a 2 × 2 factorial design was conducted in a tuberculosis-specialised hospital in Qingdao, China. A total of 279 patients who have both diabetes and tuberculosis were included in this analysis. The patients received standard anti-tuberculosis treatment alone (control group), or together with a dose of vitamin A (600 µg RAE/d) or vitamin D (10 µg/d) or a combination of vitamin A (600 µg RAE/d) and vitamin D (10 µg/d) for 2 months. The effects of the intervention on fasting plasma glucose and 2-h postprandial blood glucose were investigated by ANCOVA. The analysis was adjusted for baseline values, age, sex, smoking, drinking and antidiabetic treatment as covariates. No significant effect was observed for vitamin A and D supplementation on fasting plasma glucose, 2-h postprandial blood glucose, BMI and related blood parameters. No interaction was observed between vitamin A and D supplementation for these endpoints. Vitamin A and D supplementation showed a null effect on the glycaemic control for patients with concurrent diabetes and tuberculosis. Future work should evaluate the effect of vitamin A and D supplementation on insulin-related indices for these patients and investigate the effect of vitamin D receptor genotypes.

Detecting Critical Functional Ingredients Group and Mechanism of Xuebijing Injection in Treating Sepsis.

Sepsis is a systemic inflammatory reaction caused by various infectious or noninfectious factors, which can lead to shock, multiple organ dysfunction syndrome, and death. It is one of the common complications and a main cause of death in critically ill patients. At present, the treatments of sepsis are mainly focused on the controlling of inflammatory response and reduction of various organ function damage, including anti-infection, hormones, mechanical ventilation, nutritional support, and traditional Chinese medicine (TCM). Among them, Xuebijing injection (XBJI) is an important derivative of TCM, which is widely used in clinical research. However, the molecular mechanism of XBJI on sepsis is still not clear. The mechanism of treatment of "bacteria, poison and inflammation" and the effects of multi-ingredient, multi-target, and multi-pathway have still not been clarified. For solving this issue, we designed a new systems pharmacology strategy which combines target genes of XBJI and the pathogenetic genes of sepsis to construct functional response space (FRS). The key response proteins in the FRS were determined by using a novel node importance calculation method and were condensed by a dynamic programming strategy to conduct the critical functional ingredients group (CFIG). The results showed that enriched pathways of key response proteins selected from FRS could cover 95.83% of the enriched pathways of reference targets, which were defined as the intersections of ingredient targets and pathogenetic genes. The targets of the optimized CFIG with 60 ingredients could be enriched into 182 pathways which covered 81.58% of 152 pathways of 1,606 pathogenetic genes. The prediction of CFIG targets showed that the CFIG of XBJI could affect sepsis synergistically through genes such as TAK1, TNF-α, IL-1ß, and MEK1 in the pathways of MAPK, NF-κB, PI3K-AKT, Toll-like receptor, and tumor necrosis factor signaling. Finally, the effects of apigenin, baicalein, and luteolin were evaluated by in vitro experiments and were proved to be effective in reducing the production of intracellular reactive oxygen species in lipopolysaccharide-stimulated RAW264.7 cells, significantly. These results indicate that the novel integrative model can promote reliability and accuracy on depicting the CFIGs in XBJI and figure out a methodological coordinate for simplicity, mechanism analysis, and secondary development of formulas in TCM.

Effects of resistant starch supplementation on oxidative stress and inflammation biomarkers: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Animal experiments showed that resistant starch (RS) had an antioxidant and antiinflammatory effect. However, clinical studies showed both insignificant and significant effects of RS on inflammation and oxidative stress. The purpose of this work is to conduct a systematic review and meta-analysis of previous randomized controlled trials (RCTs) to investigate these effects. METHODS AND STUDY DESIGN: A systematic literature search was conducted on Web of Science, Scopus, PubMed and Cochrane electronic databases, which included studies from the earliest date of the database to September 2021. Key inclusion criteria were: RCTs; reporting at least one inflammatory or oxidative stress biomarker as endpoint; more than seven day intervention. Key exclusion criteria were: using a mixture of RS and other functional food ingredients as intervention substance; inappropriate controls. RESULTS: A total of 16 RCTs including 706 subjects were included. RS supplementation significantly improved total antioxidant capacity [standard mean difference (SMD) (95% CI): 2.64 (0.34, 4.94), p=0.03], and significantly reduced blood malondialdehyde concentration [SMD (95% CI): -0.55 (- 0.94, -0.17), p=0.01]. RS supplementation significantly reduced blood C-reactive protein concentration in type 2 diabetes mellitus (T2DM) patients [SMD (95% CI): -0.35 (-0.65, -0.05), p=0.02]. RS consumption significantly reduced blood interlukin-6 and tumor necrosis factor- concentration if removing one distinct trial. CONCLUSIONS: RS supplementation may significantly reduce a few oxidative-stress and inflammation biomarkers such as malondialdehyde and C-reactive protein, particularly in T2DM patients. Future work should investigate the optimal dosage of RS supplementation for modulating oxidative stress and inflammation biomarkers related to T2DM.

Intake of Fish and Marine n-3 Polyunsaturated Fatty Acids and Risk of Cardiovascular Disease Mortality: A Meta-Analysis of Prospective Cohort Studies.

Previous epidemiological studies have investigated the association of fish and marine n-3 polyunsaturated fatty acids (n-3 PUFA) consumption with cardiovascular disease (CVD) mortality risk. However, the results were inconsistent. The purpose of this meta-analysis is to quantitatively evaluate the association between marine n-3 PUFA, fish and CVD mortality risk with prospective cohort studies. A systematic search was performed on PubMed, Web of Science, Embase and MEDLINE databases from the establishment of the database to May 2021. A total of 25 cohort studies were included with 2,027,512 participants and 103,734 CVD deaths. The results indicated that the fish consumption was inversely associated with the CVD mortality risk [relevant risk (RR) = 0.91; 95% confidence intervals (CI) 0.85-0.98]. The higher marine n-3 PUFA intake was associated with the reduced risk of CVD mortality (RR = 0.87; 95% CI: 0.85-0.89). Dose-response analysis suggested that the risk of CVD mortality was decreased by 4% with an increase of 20 g of fish intake (RR = 0.96; 95% CI: 0.94-0.99) or 80 milligrams of marine n-3 PUFA intake (RR = 0.96; 95% CI: 0.94-0.98) per day. The current work provides evidence that the intake of fish and marine n-3 PUFA are inversely associated with the risk of CVD mortality.

Effects of cranberry beverages on oxidative stress and gut microbiota in subjects with Helicobacter pylori infection: a randomized, double-blind, placebo-controlled trial.

Helicobacter pylori-induced oxidative stress plays an important role in gastric diseases. H. pylori disturbs gut microbiota. The objective is to investigate the effects of cranberry beverages on oxidative stress biomarkers and gut microbiota in H. pylori positive subjects. 171 H. pylori positive participants were randomly assigned to one of the three groups: high-dose (HCb; 480 mL cranberry beverage), low-dose (LCb; 240 mL cranberry beverage plus 240 mL placebo) and placebo (480 mL). Subjects consumed the beverages daily for 4 weeks. Fasting blood samples were analyzed for oxidative stress biomarkers. The intestinal microbiome was analyzed by 16S rRNA sequencing. Compared with the placebo, HCb resulted in a significantly higher increase of total antioxidant capacity (mean ± SD: 1.39 ± 1.69 IU mL-1vs. 0.34 ± 1.73 IU mL-1; p < 0.001) and a higher decrease of the lipid peroxidation product malondialdehyde (-7.29 ± 10.83 nmol mg-1vs. -0.84 ± 15.66 nmol mg-1; p = 0.025). A significant dose-dependent effect on the elevation of superoxide dismutase was observed (p < 0.001). Microbiome data showed that consuming HCb and LCb led to a significant reduction of Pseudomonas (p < 0.05). In conclusion, the current research showed that consuming cranberry beverages significantly improved the antioxidant status in H. pylori positive subjects, which may be related to the reshaping of gut microbiota.

Vitamins A and D fail to protect against tuberculosis-drug-induced liver injury: A post hoc analysis of a previous randomized controlled trial.

OBJECTIVES: Vitamins A and D provided protection from xenobiotic-induced liver injury in previous animal studies. We conducted a post hoc analysis of our previous randomized controlled trial to investigate the effects of vitamin A and D supplementation on tuberculosis-drug-induced liver injury. METHODS: The trial was conducted in a hospital in Qingdao, China, from October 2012 to March, 2015. The control group received only tuberculosis treatment. The vitamin A, vitamin D, and vitamins A & D groups received, respectively, additional supplementation of 2000 IU/d vitamin A, 400 IU/d vitamin D, and a combination of 2000 IU/d vitamin A and 400 IU/d vitamin D. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, γ-glutamyltransferase, and cholinesterase were monitored throughout the treatment. Liver injury was defined as ALT or AST three times higher than the upper limit of normal, which was defined for AST, ALT, alkaline phosphatase, γ-glutamyltransferase, and cholinesterase, respectively, as 40 U/L, 40 U/L, 150 U/L, 40 U/L, and 10 500 U/L. RESULTS: Among the 753 participants, 11% exhibited liver injury. No significant effect of vitamin A or D supplementation was observed on the incidence of liver injury or on elevated liver indices including ALT, AST, alkaline phosphatase, γ-glutamyltransferase, and cholinesterase. The interaction between vitamin A and D supplementation was not significant. CONCLUSIONS: Vitamin A and D supplementation did not protect against tuberculosis-drug-induced liver injury. Future work should evaluate the effects of higher dosages of vitamins A and D and the effects of different genotypes for vitamin A and D metabolic enzymes or receptors.

Increased vegetable and fruit intake is associated with reduced failure rate of tuberculosis treatment: a hospital-based cohort study in China.

Increased intake of vegetables and fruits has been associated with reduced risk of tuberculosis infection. Vegetables and fruits exert immunoregulatory effects; however, it is not clear whether vegetables and fruits have an adjuvant treatment effect on tuberculosis. Between 2009 and 2013, a hospital-based cohort study was conducted in Linyi, Shandong Province, China. Treatment outcome was ascertained by sputum smear and chest computerised tomography, and dietary intake was assessed by a semi-quantitative FFQ. The dietary questionnaire was conducted at the end of month 2 of treatment initiation. Participants recalled their dietary intake of the previous 2 months. A total of 2309 patients were enrolled in this study. After 6 months of treatment, 2099 patients were successfully treated and 210 were uncured. In multivariate models, higher intake of total vegetables and fruits (OR 0·70; 95 % CI 0·49, 0·99), total vegetables (OR 0·68; 95 % CI 0·48, 0·97), dark-coloured vegetables (OR 0·61; 95 % CI 0·43, 0·86) and light-coloured vegetables (OR 0·67; 95 % CI 0·48, 0·95) were associated with reduced failure rate of tuberculosis treatment. No association was found between total fruit intake and reduced failure rate of tuberculosis treatment (OR 0·98; 95 % CI 0·70, 1·37). High intake of total vegetables and fruits, especially vegetables, is associated with lower risk of failure of tuberculosis treatment in pulmonary tuberculosis patients. The results provide important information for dietary guidelines during tuberculosis treatment.

Effects of resistant starch on glycaemic control: a systematic review and meta-analysis.

The effects of resistant starch on glycaemic control are controversial. In this study, a systematic review and meta-analysis of results from nineteen randomised controlled trials (RCT) was performed to illustrate the effects of resistant starch on glycaemic control. A literature search was conducted on PubMed, Scopus and Cochrane electronic databases for related publications from inception to 6 April 2020. Key inclusion criteria were: RCT; resistant starch as intervention substances and reporting glucose- and insulin-related endpoints. Exclusion criteria were: using type I resistant starch or a mixture of resistant starch and other functional food ingredients as intervention; using substances other than digestible starch as controls. The effect of resistant starch on fasting plasma glucose was significant (effect size (ES) -0·09 (95 % CI -0·13, -0·04) mmol/l, P = 0·001) compared with digestible starch. Subgroup analyses revealed that the ES was larger when the dosage of resistant starch was more than 28 g/d (ES -0·16 (95 % CI -0·24, -0·08) mmol/l, P < 0·001) or the intervention period was more than 8 weeks (ES -0·12 (95 % CI -0·18, -0·06) mmol/l, P < 0·001). The effect on homoeostatic model assessment (HOMA)-insulin resistance (IR) was significant (ES -0·33 (95 % CI -0·51, -0·14), P = 0·001). However, the effects on other insulin-related endpoints were not significant, including fasting plasma insulin, four endpoints from the frequently sampled intravenous glucose tolerance test (insulin sensitivity index, acute insulin response, disposition index and glucose effectiveness) and HOMA-ß. The current study indicated moderate effects of resistant starch on improving glycaemic control.

Association of Dietary Micronutrient Intake with Pulmonary Tuberculosis Treatment Failure Rate: ACohort Study.

Malnutrition is associated with an increased risk of pulmonary tuberculosis (PTB) treatment failure. Currently, there is no effective adjunctive nutritional therapy. The current objective is to investigate the association of dietary micronutrient intake with PTB treatment outcome.A cohort study including 1834 PTB patients was conducted in Linyi, China. The dietary micronutrient intake was assessed through a three-day 24 h dietary recall questionnaire. The treatment outcome was assessed by combinations of sputum smear and computerized tomography results. A multivariate binary regression model was used to assess the associations. The final model was adjusted for potential confounding factors. A low intake of vitamin C (adjusted OR (95% CI): 1.80 (1.07, 3.04), Ptrend = 0.02) and Zn (adjusted OR (95% CI): 2.52 (1.25, 5.08), Ptrend = 0.02) was associated with a high treatment failure rate. In addition, a low intake of vitamin C and Mn was associated with a severe tuberculosis symptom, as indicated by a high TB score. A supplementation of vitamin C and Zn may be beneficial in PTB treatment. Previous meta-analysis of randomized controlled trials (RCTs) reported a null effect of Zn supplementation on PTB treatment. The effect of vitamin C supplementation should be investigated by RCTs.

Adjunctive vitamin A and D during pulmonary tuberculosis treatment: a randomized controlled trial with a 2 × 2 factorial design.

BACKGROUND AND OBJECTIVE: Vitamin A and D have immunoregulatory effects and may improve the response to pulmonary tuberculosis treatment. The interaction of vitamin A and D on pulmonary tuberculosis treatment has not been studied. The objective is to investigate the effects of adjunctive supplementation of vitamin A, D and their interaction on the outcome of pulmonary tuberculosis treatment, primarily time to sputum smear conversion. METHODS: We conducted a randomized controlled trial with a 2 × 2 factorial design in Qingdao, China. Eight hundred patients were enrolled to receive standard pulmonary tuberculosis therapy alone (control), or together with vitamin A (2000 IU d-1), or vitamin D (400 IU d-1) or a combination of vitamin A (2000 IU d-1) and D (400 IU d-1) during the intensive-phase of pulmonary tuberculosis treatment. RESULTS: 761 patients were included in the tuberculosis symptom analysis; 521 patients with positive baseline sputum smear results were included in the sputum smear analysis. The allocation to vitamin A or D did not significantly influence the time to sputum smear conversion [vitamin A: adjusted hazard ratio: 1.021, 95% CI: (0.821, 1.271); vitamin D: adjusted hazard ratio: 0.949, 95% CI: (0.760, 1.185)]. No significant interaction was observed between vitamin A and D supplementation (p = 0.660). Vitamin D supplementation significantly relieved the tuberculosis symptoms as indicated by decreased TBscore [mean difference: -0.2, 95% CI: (-0.4, 0)] in week 2 to 4. CONCLUSIONS: Adjunctive supplementation of vitamin A and/or D did not improve the time to smear conversion in pulmonary tuberculosis patients. However vitamin D supplementation significantly improved tuberculosis symptoms during the first month of pulmonary tuberculosis treatment.

Recent advances in the anti-aging effects of phytoestrogens on collagen, water content, and oxidative stress.

Skin undergoes degenerative changes as it ages, which include the loss of elasticity, reductions in the epidermal thickness and collagen content, elastic fiber degeneration, and increased wrinkling and dryness. Skin aging can be significantly delayed by the administration of estrogen. Estrogen deficiency following menopause results in atrophic skin changes and the acceleration of skin aging. Estrogen administration has positive effects on human skin by delaying or preventing skin aging manifestations, but the use of estrogen replacement is a risk factor for breast and uterine cancer. Phytoestrogens are a large family of plant-derived molecules possessing various degrees of estrogen-like activity; they exhibit agonist or antagonist estrogenic properties depending on the tissue. These molecules could be ideal candidates to combat skin aging and other detrimental effects of hypoestrogenism. In this paper, we review the effects of phytoestrogens on human skin and the mechanisms by which phytoestrogens can alleviate the changes due to aging.

SNX17 (Sorting Nexin 17) Mediates Atrial Fibrillation Onset Through Endocytic Trafficking of the Kv1.5 (Potassium Voltage-Gated Channel Subfamily A Member 5) Channel.

BACKGROUND: Kv1.5 (Potassium voltage-gated channel subfamily A member 5) has been regarded as a promising target of interventions for atrial fibrillation (AF). SNX17 (sorting nexin 17), a member of the SNXs (sorting nexin family), regulates the intracellular trafficking of membrane proteins through its FERM (four-point-one, ezrin, radixin, moesin) domain. However, whether SNX17 regulates the trafficking process of Kv1.5 remains unknown. METHODS: A SNX17 knockout rat line was generated to test the role of SNX17 in atrial electrophysiology. The protein expression of SNX17 and membrane ion channels was detected by Western blotting. Electrophysiology changes in the atrial tissue and myocytes were analyzed by optical mapping and patch clamp, respectively. Acetylcholine and electrical stimulation were used to induce AF, and ECG recording was adopted to assess the influence of SNX17 deficiency on AF susceptibility. The spatial relationship between Kv1.5 and SNX17 was evaluated by immunostaining and confocal scanning, and the functional region of SNX17 regulating Kv1.5 trafficking was identified using plasmids with truncated SNX17 domains. RESULTS: Embryonic death occurred in homozygous SNX17 knockout rats. SNX17 heterozygous rats survived, and the level of the SNX17 protein in the atrium was decreased by ≈50%. SNX17 deficiency increased the membrane expression of Kv1.5 and atria-specific ultrarapid delayed rectifier outward potassium current ( IKur) density, resulting in a shortened action potential duration, and eventually contributing to AF susceptibility. Mechanistically, SNX17 facilitated the endocytic sorting of Kv1.5 from the plasma membrane to early endosomes via the FERM domain. CONCLUSIONS: SNX17 mediates susceptibility to AF by regulating endocytic sorting of the Kv1.5 channel through the FERM domain. SNX17 could be a potential target for the development of new drugs for AF.

[Electroacupuncture plus Gastrodin Improves Learning-memory Ability Possibly by Up-regulating Expression of SIRT 1 and PGC-1 ɑ in Hippocampal CA 1 Region of Alzheimer's Disease Rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with Gastrodin on learning-memory ability and expression of silent information regulator 2 homologous protein 1(SIRT 1) and peroxisome proliferator activated receptor γ coactivator (PGC-1 ɑ) of hippocampal CA 1 region in Alzheimer's disease(AD) rats, so as to explore its mechanism under-lying improvement of AD. METHODS: Sixty male SD rats were randomly divided into normal control (normal), sham operation (sham), model, EA, Gastrodin and EA＋ Gastrodin groups (n＝10 in each). The AD model was established by intraperitoneal injection of D-Galactose (120 mg•kg－1•d－1) combined with bilateral hippocampal injection of ß amyloid 1-40(Aß 1-40). EA was applied at "Baihui"(GV 20), "Dazhui"(GV 14) and "Zusanli"(ST 36) for 30 min, once daily for 4 weeks. For rats of the Gastro-din group and EA＋ Gastrodin group, intraperitoneal injection of gastrodin(10 mg/kg) was conducted once daily for 4 weeks. Morris water maze tests were used to assess the rat's learning-memory ability. Nissl staining was used to assess the morphological changes of neurons in the hippocampal CA 1 area. The expression of SIRT 1 and PGC-1 ɑ of hippocampal CA 1 region was mea-sured by immunohistochemical staining. RESULTS: 1) Morris water maze tests showed that, compared with the normal and sham group, the escape latency was significantly prolonged (P<0.05), and the percentage of platform quadrant residence duration and the platform crossing times were considerably decreased in the model group (P<0.05). After the intervention, the escape latency was obviously shortened (P<0.05), and the percentage of platform quadrant residence duration and the platform crossing times were markedly increased in the EA, Gastrodin and EA＋Gastrodin groups relevant to the model group (P<0.05). 2) Nissl staining showed that, in comparison with the normal group or sham group, the number of cells in the hippocampal CA 1 area was decreased and the arrangement was disorganized in the model group. The number of cells in CA 1 area was relatively higher in the 3 treatment groups than in the model group. 3) The expression levels of SIRT 1 and PGC-1 ɑ proteins in the hippocampal CA 1 area were significantly down-regulated in the model group than in the normal and sham groups (P<0.05). After the intervention, the expression levels of SIRT 1 and PGC-1 ɑ in the EA, Gastrodin and EA＋Gastrodin groups were significantly up-regulated compared with the model group (P<0.05). The effects of EA＋Gastrodin were significantly superior to those of simple EA and simple Gastrodin in shortening the escape latency, up-regulating the expression levels of SIRT 1 and PGC-1 ɑ as well as in increasing the percentage of platform quadrant residence time and platform crossing times (P<0.05). CONCLUSION: Both EA and Gastrodin can improve the learning-memory ability of AD rats, which may be related to their effects in up-regulating the expression of SIRT 1 and PGC-1 ɑ and reducing neuronal injury in the CA 1 region of hippocampus, suggesting a protective role of EA on hippocampal neurons. The effect of EA combined with Gastrodin is markedly better than that of EA and Gastrodin alone.