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Abstract Neointimal hyperplasia is a pathological vascular remodeling caused by abnormal proliferation and migration of subintimal vascular smooth muscle cells (VSMCs) following intimal injury. There is increasing evidence that tRNA-derived small RNA (tsRNA) plays an important role in vascular remodeling. The purpose of this study is to search for tsRNAs signature of neointima formation and to explore their potential functions. The balloon injury model of rat common carotid artery was replicated to induce intimal hyperplasia, and the differentially expressed tsRNAs (DE-tsRNAs) in arteries with intimal hyperplasia were screened by small RNA sequencing and tsRNA library. A total of 24 DE-tsRNAs were found in the vessels with intimal hyperplasia by small RNA sequencing. In vitro, tRF-Glu-CTC inhibited the expression of fibromodulin (FMOD) in VSMCs, which is a negative modulator of TGF-β1 activity. tRF-Glu-CTC also increased VSMC proliferation and migration. In vivo experiments showed that inhibition of tRF-Glu-CTC expression after balloon injury of rat carotid artery can reduce the neointimal area. In conclusion, tRF-Glu-CTC expression is increased after vascular injury and inhibits FMOD expression in VSMCs, which influences neointima formation. On the other hand, reducing the expression of tRF-Glu-CTC after vascular injury may be a potential approach to prevent vascular stenosis.

Selenium (Se) and cadmium (Cd) usually co-existed in soils, especially in areas with Se-rich soils in China. The potential health consequences for the local populations consuming foods rich in Se and Cd are unknown. Cardamine hupingshanensis (HUP) is Se and Cd hyperaccumulator plant that could be an ideal natural product to assess the protective effects of endogenous Se against endogenous Cd-caused bone damage. Male C57BL/6 mice were fed 5.22 mg/kg cadmium chloride (CdCl2) (Cd 3.2 mg/kg body weight (BW)), or HUP solutions containing Cd 3.2 mg/kg BW and Se 0.15, 0.29 or 0.50 mg/kg BW (corresponding to the HUP0, HUP1 and HUP2 groups) interventions. Se-enriched HUP1 and HUP2 significantly decreased Cd-induced femur microstructure damage and regulated serum bone osteoclastic marker levels and osteogenesis-related genes. In addition, endogenous Se significantly decreased kidney fibroblast growth factor 23 (FGF23) protein expression and serum parathyroid hormone (PTH) levels, and raised serum calcitriol (1,25(OH)2D3). Furthermore, Se also regulated gut microbiota involved in skeletal metabolism disorder. In conclusion, endogenous Se, especially with higher doses (the HUP2 group), positively affects bone formation and resorption by mitigating the damaging effects of endogenous Cd via the modulation of renal FGF23 expression, circulating 1,25(OH)2D3 and PTH and gut microbiota composition.

Abstract Background Whether estimated glomerular filtration rates (eGFRs) by differing biomarkers are differentially associated with mortality or whether the associations differ by diabetes status remains unclear, especially in Chinese population. Methods We included 6995 participants without diabetes (mean age: 60.4 years) and 1543 with diabetes (mean age: 61.8 years). Each eGFR measure was divided into normal (≥90 mL/min/1.73 m2), modestly declined (60 to

To investigate the effects of organic selenium (L-selenocystine, L-selenomethionine, and L-selenomethylcysteine) on non-alcoholic fatty liver disease (NAFLD), the NAFLD mice model with hepatic steatosis and fibrosis was established via feeding with a Western diet and CCl4 injection. Compared with the model group, the intervention groups with organic selenium experienced a reduction in hepatic 5-hydroxytryptophan (5-HT) contents and downregulation in the expression of tryptophan hydroxylase 1 (TPH1) and 5-HT receptor 2A/2B/3A. Similar results were observed on TPH1/5-HT in the duodenum. In addition, organic selenium decreased the bile acid (BA) concentrations in gut contents, downregulated the expression of hepatic CYP7A1, and upregulated the expression of hepatic Farnesoid X‐activated receptor (FXR). In conclusion, our findings suggest that organic selenium ameliorates NAFLD through 5-HT/BA enterohepatic circulation in mice with NAFLD.

Abstract The Naples prognostic score (NPS) is an effective inflammatory and nutritional scoring system widely applied as a prognostic factor in various cancers. We aimed to analyze the prognostic value of the NPS in patients diagnosed with non-small-cell lung cancer (NSCLC). We prospectively collected 395 patients diagnosed with NSCLC between January 2016 and December 2018 in two university-affiliated hospitals. Patients were divided into three groups according to their pretreatment NPS (Group 0: NPS = 0; Group 1: NPS = 1–2; Group 2: NPS = 3–4). Kaplan–Meier survival curves indicated that patients with higher NPS had a poorer overall survival (OS) and progress-free survival (PFS) (both P

There is increasing evidence that obesity is associated with the occurrence and development of malignant tumors. When studying the relationship between obesity and malignant tumors, it is very important to choose an appropriate animal model. However, BALB/c nude mice and other animals commonly used to study tumor xenograft (human-derived tumor cell lines) transplantation models are difficult to induce obesity, while C57BL/6 mice and other model animals commonly used for obesity research are not suitable for tumor xenograft transplantation. Therefore, it is difficult to replicate both obesity and malignancy in animal models at the same time. This review summarizes several experimental animal models and protocols that can simultaneously induce obesity and tumor xenografts.

Lactoferrin (Lf) has been shown to benefit cognitive function in several animal models. To elucidate the underlying mechanisms, male C57BL/6J mice were randomly divided into the control (CON), Western-style diets (WD), lactoferrin (Lf), and Lf + antibiotics (AB) groups. The Lf group was intragastrically administered with Lf, and the Lf + AB group additionally drank a solution with antibiotics. After 16 weeks of intervention, Lf improved the cognitive function as indicated by behavioral tests. Lf also increased the length and curvature of postsynaptic density and upregulated the related protein expression, suggesting improved hippocampal neurons and synapses. Lf suppressed microglia activation and proliferation as revealed by immunofluorescence analysis. Lf decreased the serum levels of pro-inflammatory cytokines and downregulated their protein expressions in the hippocampus region. Lf also inhibited the activation of NF-κB/NLRP3 inflammasomes in the hippocampus. Meanwhile, Lf upregulated the expression of tight junction proteins, and increased the abundance of Bacteroidetes at phylum and Roseburia at genus, which are beneficial for gut barrier and cognitive function. The antibiotics eliminated the effects of long-term Lf intervention on cognitive impairment in the Lf + AB group, suggesting that gut microbiota participated in Lf action. Short-term Lf intervention (2 weeks) prevented WD-induced gut microbiota alteration without inducing behavioral changes, supporting the timing sequence of gut microbiota to the brain. Thus, Lf intervention alleviated cognitive impairment by inhibiting microglial activation and neuroinflammation through the microbiome-gut-brain axis.

Background: Existing evidence suggest that lactoferrin might be beneficial for Alzheimer’s disease, while precise mechanisms are not fully elucidated. Objective: To determine the effects of lactoferrin intervention on cognitive function from APPswe/PS1dE9 (APP/PS1) mice, and potential mechanisms involved. Design: Both the young and middle-aged male APP/PS1 mice were divided into the control and lactoferrin intervention groups with 16 weeks’ intervention. Results: Lactoferrin had no effects on cognitive function for both the young and middle-aged mice, and no key markers involved in Aβ, tau pathology, neuro-inflammation and synaptic plasticity were altered after lactoferrin intervention. With regards to gut microbiota profiles, in the young APP/PS1 mice, lactoferrin elevated the α diversity index including ACE and Chao 1, and reduced the relative abundance of the genera Bacteroides and Alistipes and elevated Oscillibacter; in addition, Oscillibacter, Anaerotruncus, EF096579_g, EU454405_g, Mollicutes_RF39, EU474361_g, EU774448_g, and EF096976_g were specifically abundant via linear discriminant analysis with effect size (LEfSe) analysis. In the middle-aged APP/PS1 mice, the relative abundance of the phylum Proteobacteria, as well as the genera Oscillospira, Coprococcus, and Ruminococcus was significantly reduced post lactoferrin; additionally, S24_7, Bacteroidia, Bacteroidetes, and Methylobacterium were specific via LEfSe analysis in the lactoferrin group. Conclusions: Dietary lactoferrin might be beneficial for gut microbiota homeostasis although it might have no effects on cognition.

Leptin has been found to be involved in the development and progression of many autoimmune diseases. As an organ-specific autoimmune disease, the pathogenesis of Hashimoto’s thyroiditis has not been fully elucidated. It has been reported that serum leptin level is increased in Hashimoto’s thyroiditis, but other studies have not shown any difference. We replicated a mouse model of experimental autoimmune thyroiditis (EAT) with a high-iodine diet and found that injection of the leptin receptor antagonist Allo-aca reduced thyroid follicle destruction and inflammatory cell infiltration in EAT mice, and thyroxine and thyroid autoimmune antibody levels. Further investigation revealed that Allo-aca promotes the differentiation of Treg cells and inhibits the differentiation of Th17 cells. We believe that Allo-aca can alter the differentiation of Treg/Th17 cells by inhibiting the leptin signaling pathway, thereby alleviating thyroid injury in EAT mice. Interfering with the leptin signaling pathway may be a novel new approach to treat treating and ameliorating Hashimoto’s thyroiditis.

Whey protein (WP) and whey protein hydrolysates (WPH) may have the potency to promote weight loss, preserve muscle and improve gut microbiota composition. The present study explored the effect of WPH vs WP on weight management in obese middle-aged mice in the content of changes in fat mass, muscle mass and gut microbiota composition. The present results showed that WPH significantly reduced energy intake, attenuated weight gain and improved blood lipids and glucose. Moreover, WPH reduced ectopic fat deposition and enhanced antioxidant capacity in muscle, but did not significantly affect muscle mass. WPH failed to reverse the microbial diversity reduction caused by a high-fat diet, but increased Akkermansia and Clostridium XVIII abundances and decreased Alistipes abundance. In conclusion, WPH is expected to have good prospects in weight management in middle age.

Abstract Epidemiological evidence on the relationship between serum iron and liver diseases is limited. This study aims to investigate whether serum iron is associated with nonalcoholic fatty liver disease (NAFLD) and advanced hepatic fibrosis (AHF). Cross-sectional data for adults aged ≥ 18 years who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 were analyzed. Odds ratio (ORs) and 95% confidence intervals (CIs) of NAFLD and AHF associated with serum iron were estimated using multivariable logistic regression models. A total of 18,031 males and 18,989 females were included in the analysis. After multivariable adjustment for potential confounders, serum iron was significantly and inversely associated with NAFLD in both genders (P-trend

ObjectiveGiven that the prevalence rate of type 2 diabetes mellitus (T2DM) continues to increase, it is important to find an effective method to prevent or treat this disease. Previous studies have shown that dietary intervention with a slowly digestible carbohydrate (SDC) diet can improve T2DM with almost no side effects. However, the underlying mechanisms of SDC protect against T2DM remains to be elucidated.MethodsThe T2DM mice model was established with a high-fat diet and streptozocin injection. Then, SDC was administered for 6 weeks. Bodyweight, food intake, organ indices, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), homeostasis model assessment for insulin resistance (HOMA-IR), and other biochemical parameters were measured. Histopathological and lipid accumulation analyses were performed, and the glucose metabolism-related gene expressions in the liver and skeletal muscle were determined. Lastly, colonic microbiota was also analyzed.ResultsSDC intervention alleviated the weight loss in the pancreas, lowered blood glucose and glycosylated hemoglobin levels, and improved glucose tolerance and HOMA-IR. SDC intervention improved serum lipid profile, adipocytokines levels, and lowered the lipid accumulation in the liver, subcutaneous adipose tissue, and epididymal visceral adipose tissue. In addition, SDC intervention increased the expression levels of IRS-2 and GLUT-2 in liver tissues and elevated GLUT-4 expression levels in skeletal muscle tissues. Notably, SDC intervention decreased the Bacteroidetes/Firmicutes ratio, increased Desulfovibrio and Lachnospiraceae genus levels, and inhibited the relative abundance of potentially pathogenic bacteria.ConclusionsSDC intervention can improve hyperglycemia and hyperlipidemia status in diabetic mice, suggesting that this intervention might be beneficial for T2DM.

Intestinal injury is one of the major side effects that are induced by medical radiation exposure, and has limited effective therapies. In this study, we investigated the beneficial effects of sanguinarine (SAN) on intestinal injury induced by ionizing radiation (IR) both in vitro and in vivo. Mice were exposed to whole abdominal irradiation (WAI) to mimic clinical scenarios. SAN was injected intraperitoneally to mitigate IR-induced injury. Histological examination was performed to assess the tissue injuries of the spleen and small intestine. A small intestinal epithelial cell line-6 (IEC-6) was analyzed for its viability and apoptosis in vitro under different treatments. Inflammation-related pathways and serum inflammatory cytokines were detected via Western blot analysis and ELISA, respectively. High-throughput sequencing was used to characterize the gut microbiota profile. High-performance liquid chromatography was performed to assess short-chain fatty acid contents in the colon. In vitro, SAN pretreatment protected cell viability and reduced apoptosis in IEC-6 cells. In vivo, SAN pretreatment protected immune organs, alleviated intestinal injury, and promoted intestinal recovery. SAN also reduced the levels of inflammatory cytokines, suppressed high mobility group box 1 (HMGB1)/ Toll-like receptor 4 (TLR4) pathway activation, and modulated gut microbiota composition. Our findings demonstrate that the beneficial properties of SAN alleviated intestinal radiation injury. Thus, SAN represents a therapeutic option for protecting against IR-induced intestinal injury in preclinical settings.

To investigate the effect of piperine on pancreatic β cell apoptosis, mice were fed with high-fat diet and injected with 40 mg/kg streptozotoci to establish diabetic model. The mice in the piperine group received 30 mg/kg body weight of piperine by gavage for 12 weeks. Compared with the model group, piperine intervention significantly decreased fasting blooding glucose, and increased homeostasis model assessment (HOMA)-β. Piperine also increased pancreatic superoxide dismutase and decreased malondialdehyde. Piperine significantly decreased the apoptotic rate of pancreatic β-cells, and the protein expression of Bax/Bcl-2 ratio, also up-regulated the protein expression of phosphorylated PI3K and AKT in pancreas. In addition, apoptosis was induced in mouse insulinoma 6 cells by palmitate. Piperine treatment decreased apoptosis, protein expression of Bax/Bcl-2 ratio, and cytochrome C in cells. Thus, piperine plays a beneficial role on diabetic mice by improving pancreatic β-cell dysfunction, this might be associated with regulation on PI3K/Akt-mediated anti-apoptosis signaling.

Abstract Background Emerging evidence implicates excess weight as a potential risk factor for hearing loss. However, this association remained inconclusive. Therefore, we aimed to systematically and quantitatively review the published observational study on the association between body mass index (BMI) or waist circumference (WC) and hearing loss. Methods The odds ratios (ORs) or relative risks (RRs) with their 95% confidence intervals (CIs) were pooled under a random-effects model. Fourteen observational studies were eligible for the inclusion in the final analysis. Results In the meta-analysis of cross-sectional studies, the ORs for prevalent hearing loss were 1.10 (95% CI 0.88, 1.38) underweight, 1.14 (95% CI 0.99, 1.32) for overweight, OR 1.40 (95% CI 1.14, 1.72) for obesity, 1.14 (95% CI 1.04, 1.24) for each 5 kg/m2 increase in BMI, and 1.22 (95% CO 0.88. 1.68) for higher WC. In the meta-analysis of longitudinal studies, the RRs were 0.96 (95% CI 0.52, 1.79) for underweight, 1.15 (95% CI 1.04, 1.27) for overweight, 1.38 (95% CI 1.07, 1.79) for obesity, 1.15 (95% CI 1.01, 1.30) for each 5 kg/m2 increase in BMI, and 1.11 (95% CI 1.01, 1.22) for higher WC. Conclusions In summary, our findings add weight to the evidence that elevated BMI and higher WC may be positively associated with the risk of hearing loss.

This study aimed to investigate the preventive effects of lactoferrin (Lf) on chronic alcoholic liver injury (ALI) in female mice. Female C57BL/6J mice were randomly divided into four groups: control group (CON), ethanol administration group (EtOH), low-dose Lf treatment group (LLf), and high-dose Lf group (HLf). In the last three groups, chronic ALI was induced by administering 20% ethanol ad libitum for 12 weeks. Mice in the CON and EtOH groups were fed with AIN-93G diet. Meanwhile, 0.4% and 4% casein in the AIN-93G diet were replaced by Lf as the diets of LLf and HLf groups, respectively. HLf significantly reduced hepatic triglyceride content and improved pathological morphology. HLf could inhibit cytochrome P450 2E1 overexpression and promote alcohol dehydrogenase-1 expression. HLf activated protein kinase B and AMP-activated protein kinase (AMPK), as well as upregulating nuclear-factor-erythroid-2-related factor-2 expression to elevate hepatic antioxidative enzyme activities. AMPK activation also benefited hepatic lipid metabolism. Meanwhile, HLf had no obvious beneficial effects on gut microbiota. In summary, Lf could alleviate chronic ALI in female mice, which was associated with redox balance and lipid metabolism regulation.

Objective: This study assesses the attitudes and preferences of Chinese clinicians toward their involvement in shared decision making (SDM). Methods: From May 2014 to May 2015, 200 Chinese clinicians from two hospitals were enrolled to complete a survey on their attitude towards SDM. We conducted the survey via face-to-face interviews before and after an educational intervention on SDM among young Chinese clinicians. The clinicians were asked to give the extent of agreement to SDM. They also gave the extent of difficulty in using decision aids (DAs) during the SDM process. The variation in the range of responses to each question before and after the SDM intervention was recorded. The frequency of changed responses was analyzed by using JMP 6.0 software. Data were statistically analyzed using Chi-square and Mann–Whitney U tests, as appropriate to the data type. Multiple logistic regressions were used to test for those factors significantly and independently associated with preference for an approach for each scenario. Results: Of the 200 young Chinese clinicians sampled, 59.0% indicated a preference for SDM and a desire to participate in SDM before receiving education or seeing the DA, and this number increased to 69.0% after seeing the DA with the sample video of the SDM process on Statin Choice. However, 28.5% of the respondents still reported that, in their current practice, they make clinical decisions on behalf of their patients. The clinicians who denied a desire to use the DA stated that the main barriers to implement SDM or DA use in China are lack of time and knowledge of SDM. Conclusions: Most young Chinese clinicians want to participate in SDM. However, they state the main barriers to perform SDM are lack of experience and time. The educational intervention about SDM that exposes clinicians to DAs was found to increase their receptivity. Keywords: Decision aid, Shared-decision making, Cardiovascular risk, China

Abstract Non-small cell lung cancer (NSCLC) is the most commonly diagnosed lung cancer and is associated with poor prognosis. This study aimed to analyze if serum C-reactive protein (CRP), albumin (Alb), and CRP/Alb ratio could provide prognostic information in patients with NSCLC. 387 patients with primary NSCLC were included in this analysis. Cox proportional hazards regression was used to estimate hazard ratio (HR) and 95% confidence interval (CI) of death with adjustment for some potential confounders. The multivariate regression analyses revealed the statistically significant associations of decreased survival of patients with NSCLC with elevated CRP, decreased Alb, and elevated CRP/Alb ratio. The HRs of mortality were 1.56 (95% CI: 0.80–3.04) and 2.64 (95% CI: 1.35–5.16) for patients in the second and the highest tertiles of CRP (P-trend = 0.003). For albumin, the HR was 0.50 (95% CI: 0.29–0.85) for the normal group. The CRP/Alb ratio strongly predicted the survival of patients in the highest tertile with a fourfold risk of dying compared with those in the lowest tertile (HR = 4.14, 95% CI: 2.15–7.98). The subgroup analysis according to various patient characteristics confirmed these associations. In conclusion, serum CRP, albumin, and CRP/Alb ratio are predictive of survival for Chinese patients with NSCLC.

Abstract In China, the frequency of mild hypertension cases remains prevalently high. Meanwhile, diets containing functional ingredients that control blood pressure have received considerable attention. In this randomized, controlled intervention study, 65 participants were randomly assigned to consume 30 g of whey protein or maltodextrin daily for 12 weeks. Blood pressure, body composition, biochemical analysis in plasma, and flow‐mediated dilation (FMD), an index for evaluating endothelial function, were measured. Finally, 54 participants (27 participants in each group) completed the study. At the end of the intervention, the average systolic blood pressure (SBP) was 129.5 ± 7.7 mmHg in the control group and 128.2 ± 6.9 mmHg in the whey protein group (p = 0.052). In the overweight and obese participants, the SBP was significantly lower in the whey protein group than in the control group (126.5 ± 6.9 mmHg vs. 128.8 ± 7.4 mmHg, p = 0.033), and body fat, fat percentage, and waist circumference significantly decreased in the whey protein group (p = 0.010, 0.016, 0.019, respectively). No difference was observed between the control and whey protein groups with regard to the changes in plasma lipids, inflammatory cytokines, antioxidative indexes, endothelium‐1, nitric oxide, angiotensin II, and angiotensin‐converting enzyme. The increase in FMD was significantly higher in the whey protein group than in the control group (5.2% vs. 0.3%, p = 0.040). In conclusion, whey protein significantly decreased SBP in pre‐ and mildly hypertensive adults, who are also overweight and obese. Whey protein also improved endothelial function. The lowering effect of blood pressure was probably related to body fat loss in these participants.

Abstract Background Fish intake has been postulated to reduce the risk of stroke. However, whether the beneficial effect of fish are mainly linked to fat content, as a source of omega-3 polyunsaturated fatty acids, remains unclear. We conducted a meta-analysis to compare the effect of fatty and lean fish intake on stroke risk. Methods We performed a literature search on four database (PubMed, Embase, Scopus, and Cochrane Library) through February 1, 2018 to identify prospective studies of fatty and lean fish in relation to stroke risk. A random-effects model was used to calculate the summary estimates. Results We identified five prospective studies, including 7 comparisons for fatty fish intake and 5 comparisons for lean fish intake. Compared with the highest category of intake with lowest category, the summary relative risk was 0.88 [95% confidence interval (CI), 0.74–1.04] for fatty fish intake and 0.81 (95% CI, 0.67–0.99) for lean fish intake. No heterogeneity across studies and publication bias were observed. Conclusion Our findings demonstrated that fatty and lean fish intake has beneficial effects on stroke risk, especially lean fish intake. Additional prospective studies are necessary to confirm these observations.

Purpose: The main objective is to investigate the protective effect of camel milk (CM) on radiation-induced intestinal injury. Methods: The C57BL/6 J mice in 2 experiments were assigned into control group (Con), irradiation group (IR), and CM+irradiation group (CM+IR). After receiving the CM via gavage for 14 days, the mice in the first experiment were exposed to 6 Gy X-ray whole body irradiation, and survival rate was compared among the groups. Mice in the second experiment were exposed to 4 Gy irradiation and sacrificed at day 7. The small intestines were collected to examine the histopathological changes and to determine the anti-oxidative index and HMGB1/TLR4 inflammatory pathway. Fasting blood was used to measure serum pro-inflammatory factors. Results: Compared with the IR group, the survival time was prolonged, and survival rate was increased in the CM+IR group. CM increased levels of SOD and GSH and decreased MDA in the jejunum. Furthermore, intestinal protein expression of HMGB1/TLR4 pathway (TLR4, NF-κB, and HMGB1) was up-regulated by CM intervention. CM decreased the serum levels of TNF-α and IL-1β and increased IL-10 level. Conclusions: CM extended the survival time and had a protective effect against radiation-induced jejunum injury by regulation of antioxidant capacity and HMGB1/TLR4/NF-κB/MyD88 inflammatory signaling pathway.

Purpose and Methods: To investigate the doses of total body (TBI) and whole abdominal irradiation (WAI) induced lethal intestinal injury, healthy C57BL/6 J mice were divided randomly into 7 groups: control group; 6, 7, and 8 Gy TBI groups; and 5, 10, and 15 Gy WAI groups. The survival length, general conditions, body weight, daily food and water intake of the mice and the histopathological changes of small intestine were observed. Results: Lethal injury among C57BL/6 J mice was caused by ≥6 Gy TBI and 15 Gy WAI. Their body weight and food intake decreased, the structure of their small intestinal villi was destroyed, and the number of surviving crypts per circumference of the jejunum decreased in ≥6 Gy TBI groups and 15 Gy WAI group. The mice in the 10 Gy WAI group significantly lost weight within 5 days but recovered slowly thereafter. They also had poor appetite and reversibly damaged intestinal mucosa. Conclusions: Nonlethal intestinal injury could be induced by 10 Gy WAI, whereas lethal intestinal injury could be triggered by ≥6 Gy TBI and >15 Gy WAI in mice. Our results provided a basis for establishing radiation-induced intestinal injury models with C57BL/6 J mice.

Abstract Background Several cell-based therapies for adjunctive treatment of acute myocardial infarction have been investigated in multiple clinical trials, but the timing of transplantation remains controversial. We conducted a meta-analysis of randomized controlled trials to investigate the effects of timing on bone marrow-derived cell (BMC) therapy in acute myocardial infarction (AMI). Methods A systematic literature search of PubMed, MEDLINE, and Cochrane Evidence-Based Medicine databases from January 2000 to June 2017 was performed on randomized controlled trials with at least a 3-month follow-up for patients with AMI undergoing emergency percutaneous coronary intervention (PCI) and receiving intracoronary BMC transfer thereafter. The defined end points were left ventricular (LV) ejection fraction, LV end-diastolic and end-systolic index. The data were analyzed to evaluate the effects of timing on BMC therapy. Results Thirty-four RCTs comprising a total of 2,307 patients were included; the results show that, compared to the control group, AMI patients who received BMC transplantation showed significantly improved cardiac function. BMC transplantation 3–7 days after PCI (+3.32%; 95% CI, 1.91 to 4.74; P

Background: Leucine supplementation has been reported to improve lipid metabolism. However, lipid metabolism in adipose tissues and liver has not been extensively studied for leucine supplementation in mice fed with a high-fat/cholesterol diet (HFCD). Design: C57BL/6J mice were fed a chow diet, HFCD, HFCD supplemented with 1.5% leucine (HFCD+1.5% Leu group) or 3% leucine (HFCD+3% Leu group) for 24 weeks. The body weight, peritoneal adipose weight, total cholesterol (TC), triglyceride in serum and liver, and serum adipokines were analyzed. In addition, expression levels of proteins associated with hepatic lipogenesis, adipocyte lipolysis, and white adipose tissue (WAT) browning were determined. Results: Mice in the HFCD group developed obesity and deteriorated lipid metabolism. Compared with HFCD, leucine supplementation lowered weight gain and TC levels in circulation and the liver without changing energy intake. The decrease in body fat was supported by histological examination in the WAT and liver. Furthermore, serum levels of proinflammatory adipokines, such as leptin, IL-6, and tumor necrosis factor-alpha, were significantly decreased by supplemented leucine. At the protein level, leucine potently decreased the hepatic lipogenic enzymes (fatty acid synthase and acetyl-coenzyme A carboxylase) and corresponding upstream proteins. In epididymal WAT, the reduced expression levels of two major lipases by HFCD, namely phosphorylated hormone-sensitive lipase and adipose triglyceride lipase, were reversed when leucine was supplemented. Uncoupling protein 1, β3 adrenergic receptors, peroxisome proliferator-activated receptor g coactivator-1α, and fibroblast growth factor 21 were involved in the thermogenic program and WAT browning. Leucine additionally upregulated their protein expression in both WAT and interscapular brown adipose tissue. Conclusion: This study demonstrated that chronic leucine supplementation reduced the body weight and improved the lipid profile of mice fed with a HFCD. This beneficial effect was ascribed to hepatic lipogenesis, adipocyte lipolysis, and WAT browning.

Objective: To evaluate whether stem cell transplantation improves global left ventricular ejection fraction (LVEF) in patients with acute myocardial infarction (AMI), and to determine the appropriate stem cell therapy dose as well as the effective period after stem cell transplantation for therapy. Methods: A systematic literature search included Pubmed, MEDLINE, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Cochrane Evidence-Based Medicine databases. The retrieval time limit ranged from January 1990 to June 2016. We also obtained full texts through manual retrieval, interlibrary loan and document delivery service, or by contacting the authors directly. According to our inclusion and exclusion criteria, data were extracted independently by two evaluators. In case of disagreement, a joint discussion occurred and a third researcher was utilized. Data were analyzed quantitatively using Revman 5.2. Summary results are presented as the weighted mean difference (WMD) with 95% confidence intervals (CIs). We collected individual trial data and conducted a meta-analysis to compare changes in global left ventricular ejection fraction (ÎLVEF) after stem cell therapy. In this study, four subgroups were based on stem cell dose (â¤1 Ã 107 cells, â¤1 Ã 108 cells, â¤1 Ã 109 cells, and â¤1 Ã 1010 cells) and three subgroups were based on follow-up time (

Background: Pycnogenol exhibits many biological activities, including control of blood pressure (BP). However, the reported results are inconsistent because of varied characteristics of participants and quality of studies. Thus, a meta-analysis was conducted to examine the effect of Pycnogenol supplementation on BP. Methods: This literature search of PubMed, the Web of Science and the Cochrane library was performed in May 2016 to identify eligible studies. Reference lists of the retrieved articles were also reviewed. Either a fixed-effects or, in the presence of heterogeneity, a random-effects model was used to calculate the effect of combined treatment. Results: We identified nine trials involving 549 participants who received Pycnogenol supplementation ranging from 150 mg/d to 200 mg/d. Compared with the control, the pooled estimate of change in systolic and diastolic BPs were -3.22 mmHg (95% CI: -6.20, -0.24) and -3.11 mmHg (95% CI: -4.60, -1.62), respectively. Subgroup analyses showed higher BP reduction among hypertensive participants or those who received intervention for more than 12 wk. However, this significant reduction was not observed in well-designed trials. Conclusion: This meta-analysis with nine trials provides better evidence that Pycnogenol exerts beneficial effects on BP.

Background: Several studies have reported the favorable effect of leucine supplementation on insulin resistance or insulin sensitivity. However, whether or not leucine supplementation improves leptin sensitivity remains unclear. Design: Forty-eight male Sprague-Dawley rats were fed with either a high-fat diet (HFD) or HFD supplemented with 1.5, 3.0, and 4.5% leucine for 16 weeks. At the end of the experiment, serum leptin level was measured by ELISA, and leptin receptor (ObR) in the hypothalamus was examined by immunohistochemistry. The protein expressions of ObR and leptin-signaling pathway in adipose tissues were detected by western blot. Results: No significant differences in body weight and food/energy intake existed among the four groups. Serum leptin levels were significantly lower, and ObR expression in the hypothalamus and adipose tissues was significantly higher in the three leucine groups than in the control group. These phenomena suggested that leptin sensitivity was improved in the leucine groups. Furthermore, the expressions of JAK2 and STAT3 (activated by ObR) were significantly higher, and that of SOCS3 (inhibits leptin signaling) was significantly lower in the three leucine groups than in the control group. Conclusions: Leucine supplementation improves leptin sensitivity in rats on HFD likely by promoting leptin signaling.

Whey supplementation is beneficial for human health, possibly by reducing the circulating C-reactive protein (CRP) level, a sensitive marker of inflammation. Thus, a meta-analysis of randomized controlled trials was conducted to evaluate their relationship. A systematic literature search was conducted in July, 2014, to identify eligible studies. Either a fixed-effects model or a random-effects model was used to calculate pooled effects. The meta-analysis results of nine trials showed a slight, but no significant, reduction of 0.42 mg/L (95% CI −0.96, 0.13) in CRP level with the supplementation of whey protein and its derivates. Relatively high heterogeneity across studies was observed. Subgroup analyses showed that whey significantly lowered CRP by 0.72 mg/L (95% CI −0.97, −0.47) among trials with a daily whey dose ≥20 g/day and by 0.67 mg/L (95% CI −1.21, −0.14) among trials with baseline CRP ≥3 mg/L. Meta-regression analysis revealed that the baseline CRP level was a potential effect modifier of whey supplementation in reducing CRP. In conclusion, our meta-analysis did not find sufficient evidence that whey and its derivates elicited a beneficial effect in reducing circulating CRP. However, they may significantly reduce CRP among participants with highly supplemental doses or increased baseline CRP levels.

Background: Calpain, a calcium-dependent cysteine protease, has been demonstrated to regulate osteoclastogenesis, which is considered one of the major reasons for cancer-induced bone pain (CIBP). In the present study, calpain inhibitor was applied in a rat CIBP model to determine whether it could reduce CIBP through regulation of osteoclastogenesis activity. Methods: A rat CIBP model was established with intratibial injection of Walker 256 cells. Then, the efficacy of intraperitoneal administered calpain inhibitor III (MDL28170, 1 mg/kg) on mechanical withdrawal threshold (MWT) of bilateral hind paws was examined on postoperative days (PODs) 2, 5, 8, 11, and 14. On POD 14, the calpain inhibitor′s effect on tumor bone tartrate-resistant acid phosphatase (TRAP) stain and radiology was also carefully investigated. Results: Pain behavioral tests in rats showed that the calpain inhibitor effectively attenuated MWTs of both the surgical side and contralateral side hind paws on POD 5, 8, and 11 (P < 0.05). TRAP-positive cell count of the surgical side bone was significantly decreased in the calpain inhibitor group compared with the vehicle group (P < 0.05). However, bone resorption and destruction measured by radiographs showed no difference between the two groups. Conclusions: Calpain inhibitor can effectively reduce CIBP of both the surgical side and nonsurgical side after tumor injection in a rat CIBP model. It may be due to the inhibition of receptor activator of nuclear factor-kappa B ligand-induced osteoclastogenesis. Whether a calpain inhibitor could be a novel therapeutic target to treat CIBP needs further investigation.

Metformin (Met) and lactoferrin (Lf) both exhibit beneficial effects on body weight management and lipid accumulation. However, the synergistical action of Met and Lf remains unclear. In this study, 64 mice were divided into five groups, namely, the control group, high-fat diet (HFD group), HFD with Met (Met group), Lf (Lf group), and a combination of Met and Lf (Met + Lf group). Met (200 mg/kg body weight) and Lf (2 g/100 mL) were administrated in drinking water. The experiment lasted for 12 weeks. Body weight, serum, and hepatic lipids were determined. Histology of the liver and perirenal fat was observed. Protein expression related to hepatic lipid metabolism was also measured. HFD significantly increased body weight, visceral fat weight, and lipid profiles, which lead to obesity and dyslipidemia in mice. Compared with the HFD group, the treatments significantly decreased body weight and Lee’s index (body mass index of mice) with the lowest values in the Met + Lf group. The treatments also decreased the weight of visceral fat, and improved circulating lipid profile and the ability for regulating glucose intake. The adipocyte size and serum TC level were significantly lower in the Met + Lf group as compared with those in the Met or Lf group. The treatments alleviated hepatic lipid accumulation, especially in the Met + Lf group. For protein expression, the p-AMPK/AMPK ratio, a key kinase-regulating cellular energy homeostasis, was significantly higher in the Met + Lf group than the ratio in the HFD group. Similarly, the treatments significantly downregulated the protein expression of lipogenic enzymes (FAS, ACC, and SREBP-1) and upregulated the protein expression of lipolytic enzyme (ATGL). The protein expression of HMGCoAR, which is an important rate limiting enzyme in cholesterol biosynthesis, was only significantly lower in the Met + Lf group than in the HFD group. In conclusion, Met and Lf, either alone or in combination, prevented HFD-induced obesity and improved lipid metabolism.

The association between cheese consumption and risk for major health endpoints has been investigated in many epidemiologic studies, but findings are inconsistent. As all-cause mortality can be viewed as the final net health effect of dietary intakes, we conducted a meta-analysis to examine the long-term association of cheese consumption with all-cause mortality. Relevant studies were identified by a search of the PubMed database through May 2016. Reference lists from retrieved articles were also reviewed. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using a random-effects model. Pre-specified stratified and dose-response analyses were also performed. The final analysis included nine prospective cohort studies involving 21,365 deaths. The summary RR of all-cause mortality for the highest compared with the lowest cheese consumption was 1.02 (95% CI: 0.97, 1.06), and little evidence of heterogeneity was observed. The association between cheese consumption and risk of all-cause mortality did not significantly differ by study location, sex, age, number of events, study quality score or baseline diseases excluded. There was no dose-response relationship between cheese consumption and risk of all-cause mortality (RR per 43 g/day = 1.03, 95% CI: 0.99–1.07). No significant publication bias was observed. Our findings suggest that long-term cheese consumption was not associated with an increased risk of all-cause mortality.

In the crystal structure of the title compound, C5H8N2O, molecules are linked via pairs of N—H...O hydrogen bonds, forming inversion dimers. These dimers are linked via pairs of N—H...H hydrogen bonds into zigzag chains propagating along [101].

In the crystal structure of the title compound, C14H12O3, molecules are linked via intermolecular O—H...O hydrogen bonds, resulting in dimer formation. The dihedral angle between the two phenyl rings is 76.2 (2)°.

In the title molecule, C9H9N3O5, the dihedral angle between the mean planes of the amide group and the benzene ring is 31.24 (14)°. In the crystal, N—H...O hydrogen bonds link the molecules to form one-dimensional chains propagating in [100].

There are two independent molecules in the asymmetric unit of the title compound, C22H14FN3, which differ slightly in the relative orientations of the naphthyl and phenyl groups with respect to the pyridyl ring framework. In one molecule, the naphthyl ring system and the phenyl ring form dihedral of angles 56.50 (2) and 48.23 (3)°, respectively, with the pyridyl ring plane. In the other molecule, the corresponding dihedral angles are 50.01 (2) and 51.1 (3)°, respectively. In the crystal, intermolecular N—H...N hydrogen bonds connect the independent molecules into dimers.

In crystal of the title compound, C6H4F3NO2S, molecules are linked by O—H...N and C—H...O hydrogen bonds, forming chains.

In the title compound, C5H5F3N2O, the F atoms are disordered over two sets of sites in a 0.64 (3):0.36 (3) ratio. In the crystal structure, O—H...N hydrogen bonds link the molecules into chains and a short C—H...F contact also occurs.

The asymmetric unit of the title compound, C16H20N2, contains two independent molecules. The rings in each molecule are oriented at dihedral angles of 78.94 (3) and 77.76 (3)°.