Branched-chain amino acids supplementation has beneficial effects on the progression of liver cirrhosis: A meta-analysis.

BACKGROUND: Liver cirrhosis (LC) is currently the 11th most common cause of death and 15th cause of morbidity globally. The treatment of LC is mainly aimed at etiological intervention, lifestyle intervention, prevention and treatment of complications and nutritional treatment. Nutritional treatment of LC mainly includes increasing dietary intake, food intake time and branched-chain amino acids (BCAAs). Despite the recommendation of BCAAs in some guidelines, adverse effects have been reported in studies so the efficacy and safety of BCAAs remain controversial. Currently, BCAAs have been widely used in chronic liver disease, while the summary of the effect of BCAAs on long-term prognosis is rare. AIM: To determine the effects of BCAAs in patients with LC. METHODS: The PubMed, Cochrane Library, Embase and Web of Science databases were searched. The retrieval deadline was 1 October 2021 and there were no language restrictions set in the retrieval. The study was performed in strict accordance with the inclusion and exclusion criteria. Nine studies were finally included. The primary outcome was complications of LC. The secondary outcomes were nutritional status and liver function. This meta-analysis used the Review Manager, version 5 statistical package (Cochrane Collaboration, Oxford, England) for analysis. RESULTS: The analysis included nine studies that consisted of 1080 patients (554 in the BCAA groups and 526 in the control groups). The nine studies were randomized control trials (RCTs). The quality of the studies was assessed using the risk of bias method recommended by the Cochrane Collaboration. BCAAs reduced the rate of complications in LC patients [Risk ratio: 0.70, 95% confidence interval (CI): 0.56-0.88, P = 0.002] and improved patients' albumin levels [std mean difference SMD: 0.26, 95%CI: 0.12-0.40, P = 0.0002]. Meanwhile, BCAAs significantly ameliorated the levels of alanine transaminase (SMD: -2.03, 95%CI: -2.52 to -1.53, P < 0.00001) and aspartate aminotransferase (SMD: -1.8, 95%CI: -2.14 to -1.46, P < 0.00001). Meanwhile, glucose in the LC was significantly increased in BCAA-treated patients (MD: 13.04, 95%CI: 6.81-19.89, P = 0.0002). CONCLUSION: BCAAs reduce the incidence of complications in patients with LC and ameliorate nutritional status.

Randomized controlled trial for time-restricted eating in overweight and obese young adults.

Time-restricted eating (TRE) is known to improve metabolic health, whereas very few studies have compared the effects of early and late TRE (eTRE and lTRE) on metabolic health. Overweight and obese young adults were randomized to 6-h eTRE (eating from 7 a.m. to 1 p.m.) (n = 21), 6-h lTRE (eating from 12 p.m. to 6 p.m.) (n = 20), or a control group (ad libitum intake in a day) (n = 19). After 8 weeks, 6-h eTRE and lTRE produced comparable body weight loss compared with controls. Compared with control, 6-h eTRE reduced systolic blood pressure, mean glucose, fasting insulin, insulin resistance, leptin, and thyroid axis activity, whereas lTRE only reduced leptin. These findings shed light on the promise of 6-h eTRE and lTRE for weight loss. Larger studies are needed to assess the promise of eTRE to yield better thyroid axis modulation and overall cardiometabolic health improvement.

The association study of Apolipoprotein E polymorphisms and chronic obstructive pulmonary disease in the Chinese population: A case-control study.

Chronic obstructive pulmonary disease (COPD) patients have increased cardiovascular morbidity and mortality. Apolipoprotein E (ApoE) is involved in chronic inflammation which is the common characteristic of emphysema and cardiovascular disease. ApoE polymorphisms are associated with cardiovascular disorders and atherosclerosis. There is no report about the association between ApoE polymorphism and COPD.A total of 480 COPD patients and 322 controls who were unrelated Chinese Han individuals were enrolled. Rs429358 and rs7412 were genotyped and the associations between ApoE polymorphisms and COPD risk were analyzed by logistic regression analysis. Online software SHEsis were applied to perform linkage disequilibrium (LD) and haplotypes analysis. The interactions of ApoE and environmental factor on COPD susceptibility was analyzed by software MDR3.0.2.No significant association was found between rs429358, rs7412 and COPD under different genetic models. Rs429358 and smoking formed the best model in the MDR analysis. The frequency of E2/E2 phenotype was the lowest in 2 groups. E3/E3 was the most common phenotype, accounting for 69.8% of COPD patients and 68.9% of controls. No statistically difference was identified between the cases and controls under different phenotypes.This was the first genetic association study between ApoE and COPD. No positive association was found in the Chinese Han population. Rs429358 and smoking status existed significant interaction, indicating that both of ApoE and smoking may be involved in the development of COPD disease.

[Effects of epidermal growth factor receptor on airway inflammation in a rat asthmatic model].

OBJECTIVE: To explore the possible roles of epidermal growth factor receptor (EGFR) in the process of acute and chronic airway inflammation in a rat asthmatic model. METHODS: Forty-five Sprague-Dawley (SD) rats were randomly divided into control groups (subgroups A1, A2, A4), asthmatic groups (subgroups B1, B2, B4) and treatment groups (subgroups C1, C2, C4), with 5 mice in each subgroup. Mice in the asthmatic and treatment groups were exposed to OVA challenge for 1 week, 2 weeks and 4 weeks. Rats in the treatment groups received intraperitoneal injection of a tyrosine kinase inhibitor Genistein (Rongli China) with the dose of 20 mg/kg 1 hour before OVA exposure. Total cell counts and cell differentials in bronchoalveolar lavage fluid (BALF) were performed. A semi-quantified method of airway inflammation score was used to evaluate airway inflammation by hematoxylin-eosin (HE) staining. Expression of EGFR and tyrosine phosphorylation (EGFR activation) in airway epithelium at different times of OVA exposure were evaluated by immunohistochemical and immunofluorescence. All data were expressed as mean +/- SD. One-way ANOVA was used for comparison between 2 groups and post-hoc multiple comparisons of means were performed by using Least Significant Difference. RESULTS: (1) The total cell counts and cell differentials in the BALF of subgroups B1, B2 and B4 were higher than those of subgroups A1, A2 and A4. The total cell counts and eosinophils (EOS) in the BALF of subgroups C1, C2, and C4 [Total cells (48 +/- 6) x 10(5), (51 +/- 9) x 10(5), (57 +/- 12) x 10(5); EOS (2.5 +/- 0.5) x 10(5), (2.7 +/- 0.6) x 10(5), (2.6 +/- 0.5) x 10(5), respectively] decreased significantly as compared to those of subgroups B1, B2 and B4 [Total cells (70 +/- 10) x 10(5), (88 +/- 8) x 10(5), (72 +/- 10) x 10(5); EOS (5.6 +/- 0.8) x 10(5), (6.6 +/- 0.6) x 10(5), (4.3 +/- 0.4) x 10(5)], all P < 0.05. There was no significant difference in the counts of neutrophils and lymphocytes in BALF between the treatment groups and the asthmatic groups. The count of epithelial cells in group C1 [(2.5 +/- 0.5) x 10(5)] was lower than that in group B1[(4.9 +/- 0.7) x 10(5)], q = 4.671, P < 0.05. But that in group C4[(5.7 +/- 1.2) x 10(5)] was higher than that in group B4 [(4.3 +/- 0.4) x 10(5)], q = 4.012, P < 0.05. (2) The airway inflammation score in group C4(3.6 +/- 0.6) was less than that in group B4(5.1 +/- 0.6), q = 4.923, P < 0.05. The scores of group C1 and C2 were less than those of group B1 and B2, but the differences did not reach statistical significance. (3) The expression of EGFR and tyrosine phosphorylation in airway epithelium of the OVA sensitized subgroups were increased statistically as compared to the control subgroups (all P < 0.05). Genistein decreased tyrosine phosphorylation of EGFR in subgroups C1, C2 and C4[(3.12 +/- 0.24), (3.00 +/- 0.28), (2.69 +/- 0.54)] as compared to subgroups B1, B2 and B4[(3.69 +/- 0.43), (3.57 +/- 0.29), (4.46 +/- 0.47), respectively] (all P < 0.05). (4) There were positive correlations between expression and activation of EGFR in airway epithelium and total cell counts, EOS counts, neutrophil and lymphocyte counts in BALF, and airway inflammation scores (all P < 0.05). CONCLUSIONS: EGFR is involved in airway inflammation of asthmatic rats. Tyrosine kinase inhibitor Genistein inhibits acute and chronic airway inflammation in the asthmatic model.

[The role of 12-alkylated chitosans/plasmid-encoding antisense endothelin converting enzyme complex nanoparticles in immunomodulation of allergic airway inflammation].

OBJECTIVE: To explore a novel nonspecific immunomodulation for the treatment of allergic airway inflammation by RNA interference for endothelin converting enzyme (ECE) using 12-alkylated chitosans/plasmid-encoding antisense ECE complex nanoparticles. METHODS: Forty BALB/c mice were randomly divided into Group N (normal control), Group NM (OVA + 12-ACSs/antisense-ECE plasmid), Group As (OVA) and Group DNA (OVA + antisense-ECE plasmid), and sensitized by intraperitoneal injection of OVA at day 1 and day 14, followed by challenge with aerosol of 1% OVA at day 24, 25 and 26, but with saline as a control (N). Supernatants from cultured splenocytes and lung homogenates were subjected to detection of the levels of interleukin-4, 5, 10, 13 (IL-4, 5, 10, 13), interferon-gamma (IFN-gamma) and endothelin-1 (ET-1) by using ELISA. Lung tissues were embedded, sliced and HE stained for histopathologic examination. The cultured splenocytes were subjected to flow cytometry detection (IL-4, IL-10 and IFN-gamma). RESULTS: Mice in group NM showed a lower level of cell count than that in either group AS or group DNA. Compared with N group, the lung tissues taken from the mice in As and DNA groups displayed allergic inflammation with eosinophil infiltration, while the pulmonary inflammation was decreased significantly in group NM. The levels of ET-1, IL-4, IL-13 and IL-5 were down regulated in group NM compared to As and DNA groups (P < 0.05 or P < 0.01). After stimulation by OVA, the splenocytes from the mice in NM group produced a higher level of IL-10 than that from As and DNA groups (P < 0.05 or P < 0.01). The number of Th2 lymphocytes (CD(4)(+) T cells with IL-4 expression) was significantly elevated in the mice of As, DNA and NM groups respectively, while the number of Th2 lymphocytes was lower in the mice of group NM than in the mice of group As or group DNA. The number of CD(4)(+)CD(25)(+) cells with IL-10 expression was up-regulated in the mice of As, DNA and NM groups respectively compared to the control. The percentage of T regulating cells was higher in the mice of group NM compared with that in the mice of group As or group DNA. No detectable difference in the level of Th1 cells (CD(4)(+) T cells with IFN-gamma expression) was found among the 4 groups. CONCLUSION: 12-ACSs can encapsulate and deliver antisense-ECE expression plasmid into bronchial epithelial cells in vitro and 12-ACSs/antisense ECE plasmid complex nanoparticles have the capability to down regulate the synthesis of ET-1 and thus decrease the allergic airway inflammation in OVA-sensitized mice.

Clinical observation and mechanism study on treatment of senile dementia with Naohuandan.

OBJECTIVE: To observe the therapeutic effect and mechanism of Naohuandan (NHD) in treating senile dementia (SD). METHODS: Clinical study: Fifty-eight patients with SD, whose diagnosis conforms to the Diagnostic Standard of DSM-IV issued by American Association of Psychiatry, were enrolled and randomly assigned into two groups. The 30 patients in the treated group were treated with NHD, 4 capsules each time, 3 times daily. The 28 patients in the control group were treated with Piracetam, 1.6 g each time, 3 times daily. The therapeutic course for both groups was 3 months. The therapeutic efficacy was estimated and compared by comprehensive scores of memory and cognition, scores of Mini-mental State Examination (MMSE) and Activities of Daily Living (ADL). Experimental study: Rats were divided into the control group, the model group and the high-dosage and low-dosage NHD treated groups. The protective effect of NHD on the per-oxidative damage of hippocampal neurons in beta-amyloid protein induced SD model was observed and the related criteria were determined. RESULTS: Clinical study showed that both NHD and Piracetam could improve the clinical symptoms of patients, the two medicines showing insignificant difference in total effective rate. But NHD was better in elevating MMSE score and lowering ADL score in patients than Piracetam (P < 0.05 and P < 0.01). Experimental study showed that (1) 24 and 72 hrs after modeling, the activity of SOD and GSH were lower and the level of MDA higher in the model group than those in the control group (P < 0.05 or P < 0.01). Compared with the model group at the corresponding time points, in the high-dosage NHD group, SOD and GSH were higher, MDA was lower (P < 0.05 or P < 0.01); but in the low-dosage NHD group, SOD at the 72nd hr was higher (P < 0.05) and MDA at 24th and 72nd hrs was lower (P < 0.01). And most of the criteria in the high-dosage NHD group was improved better than that in the low-dosage NHD group. (2) The survival rates of neurons in various groups were not different significantly (P > 0.05) 24 hrs after modeling, but that in the high-dosage NHD group was significantly higher than that in the model group (P < 0.01) and in the low-dosage NHD group 72 hrs after modeling (P < 0.05). CONCLUSION: NHD is an effective Chinese herbal preparation for treatment of SD, and its mechanism is related with its inhibition on peroxidative injury and protection on neurons.