Chronic wounds may lead to the development of various pathological conditions such as diabetic foot ulcers and pressure sores. The current study evaluated wound healing and anti-inflammatory potentials of methanolic extract of Ephedra ciliata using series of in vivo models. Methanolic extract of Ephedra ciliata was prepared by maceration (Ec.Me). Qualitative and quantitative (HPLC) phytochemical and metal analyses were conducted to explore the chemical and metal profiles of Ec.Me. Safety profile (behavioural) and, antimicrobial, antioxidant, wound healing, anti-inflammatory and anti-angiogenic potentials of Ec.Me were evaluated using well-established in vitro and in vivo models. ELISA assay was performed to estimate the effects of Ec.Me treatment on serum levels of TNF-α. HPLC analysis identified quercetin as one of the major compounds in Ec.Me. Safety study data showed that Ec.Me was safe up to the dose of 2000 mg/kg. Antimicrobial assay data showed that Ec.Me was active against bacterial (Staphylococcus aureus) as well as fungal (Candida albicans and Aspergillus niger) strains. Ec.Me showed modertate antioxidant potential in in vitro and in vivo models. Data of excision and burn wound healing models showed that Ec.Me, promoted wound closure in a dose and time-dependent manner. Treatment with 20% Ec.Me cream and heparin showed almost the same effects with no statistical differences (p > 0.05). Ec.Me also showed time-dependent anti-inflammatory activities in both acute and chronic models. In carrageenan model, treatment with 200 mg/kg of Ec.Me showed comparable anti-inflammatory effects (p > 0.05) with quercetin and indomethacin throughout the study. In cotton pellet granuloma model treatment with 200 mg/kg of Ec.Me and indomethacin inhibited granuloma formation significantly better (p < 0.05) as compared with the rest of the treatment groups. Histopathological examination of skin samples showed marked improvement in architecture with minimal infiltration of inflammatory cells. Data of in vivo angiogenesis assay showed marked improvement in vessels length, density, branching points, total segments and total nets after treatment with Ec.Me, indicating no toxic effects towards vasculature development. Significant (p < 0.05) downregulation of TNF-α was observed in serum samples of animals treated with Ec.Me. Based on data of the current study, it is concluded that quercetin-rich extract of Ephedra ciliata has wound healing and anti-inflammatory potentials via downregulation of TNF-α. Moreover, it is suggested that the antimicrobial activity of Ec.Me prevented microbial invasion, thus promoted natural wound healing mechanisms as well.

Intrahepatic cholangiocarcinoma (ICC) arises from cholangiocytes in the intrahepatic bile duct and is the second most common type of liver cancer. Cholangiocytes express both oestrogen receptor-α and -β, and oestrogens positively modulate cholangiocyte proliferation. Studies in women and men have reported higher circulating oestradiol is associated with increased ICC risk, further supporting a hormonal aetiology. However, no observational studies have examined the associations between exogenous hormone use and reproductive factors, as proxies of endogenous hormone levels, and risk of ICC.

Schizophrenia (SCZ) is a psychiatric disorder characterized by both positive and negative symptoms, including cognitive dysfunction, decline in motivation, delusion and hallucinations. Antipsychotic agents are currently the standard of care treatment for SCZ. However, only about one-third of SCZ patients respond to antipsychotic medications. In the current study, we have performed a meta-analysis of publicly available whole-genome expression datasets on Brodmann area 46 of the brain dorsolateral prefrontal cortex in order to prioritize potential pathways underlying SCZ pathology. Moreover, we have evaluated whether the differentially expressed genes in SCZ belong to specific subsets of cell types. Finally, a cross-tissue comparison at both the gene and functional level was performed by analyzing the transcriptomic pattern of peripheral blood mononuclear cells of SCZ patients. Our study identified a robust disease-specific set of dysfunctional biological pathways characterizing SCZ patients that could in the future be exploited as potential therapeutic targets.

Studies have shown the effects of chocolate-based products on appetite-related indicators; however, the results of these studies are equivocal. Thus, the aim of the present study was to conduct a systematic review of studies investigating the acute and long-term response of appetite-related hormones to chocolate intake in adults. A systematic search of MEDLINE and EMBASE for published studies, in English, was performed from inception up to November 2018. It appears that ghrelin and leptin are not responsible for the satiating effect of chocolate products. Gastric infusion of milk chocolate elicited a greater increase in cholecystokinin (CCK), in comparison with oral ingestion of milk chocolate and gastric infusion of non-caloric products. Moreover, viscosity seems to have no effect on active CCK and glucagon-like peptide-1. Due to the heterogeneity between studies, limited sample, low quality of evidence, and substantial variation in methods and chocolate products, caution is suggested in interpreting these results.

Shenxian-Shengmai (SXSM) Oral Liquid is a CFDA-approved patent Chinese Herbal medicine, which has been clinically used for the treatment of bradycardia. However, its active components and action mechanism remain to be established. The present study aimed to evaluate the efficacy of SXSM on bradycardia and to identify the possible active components and their pharmacological targets for this action.

The Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) is among long non-coding RNAs (lncRNAs) which has disapproved the old term of "junk DNA" which was used for majority of human genome which are not transcribed to proteins. An extensive portion of literature points to the fundamental role of this lncRNA in tumorigenesis process of diverse cancers ranging from solid tumors to leukemia. Being firstly identified in lung cancer, it has prognostic and diagnostic values in several cancer types. Consistent with the proposed oncogenic roles for this lncRNA, most of studies have shown up-regulation of MALAT1 in malignant tissues compared with non-malignant/normal tissues of the same source. However, few studies have shown down-regulation of MALAT1 in breast cancer, endometrial cancer, colorectal cancer and glioma. In the current study, we have conducted a comprehensive literature search and provided an up-date on the role of MALAT1 in cancer biology. Our investigation underscores a potential role as a diagnostic/prognostic marker and a putative therapeutic target for MALAT1.

Defence priming by organismal and non-organismal stimulants can reduce effects of biotic stress in plants. Thus, it could help efforts to enhance the sustainability of agricultural production by reducing use of agrochemicals in protection of crops from pests and diseases. We have explored effects of applying this approach to both Arabidopsis plants and seeds of various crops in meta-analyses. The results show that its effects on Arabidopsis plants depend on both the priming agent and antagonist. Fungi and vitamins can have strong priming effects, and priming is usually more effective against bacterial pathogens than against herbivores. Moreover, application of bio-stimulants (particularly vitamins and plant defence elicitors) to seeds can have promising defence priming effects. However, the published evidence is scattered, does not include Arabidopsis, and additional studies are required before we can draw general conclusions and understand the molecular mechanisms involved in priming of seeds' defences. In conclusion, defence priming of plants has clear potential and application of bio-stimulants to seeds may protect plants from an early age, promises to be both labour- and resource-efficient, poses very little environmental risk, and is thus both economically and ecologically promising.

Several studies have demonstrated that metformin (MTF) acts with variable efficiency as an anticancer agent. The pleiotropic anticancer effects of MTF on cancer cells have not been fully explored yet. By interrogating the Gene Expression Omnibus (GEO) for microarray expression data, we identified eight eligible submissions, representing five different studies, that employed various conditions including different cell lines, MTF concentrations, treatment durations, and cellular components. A compilation of the data sets of 13 different conditions contained 443 repeatedly up- and 387 repeatedly down-regulated genes; the majority of these 830 differentially expressed genes (DEGs) were associated with higher MTF concentrations and longer MTF treatment. The most frequently upregulated genes include DNA damage inducible transcript 4 (DDIT4), chromodomain helicase DNA binding protein 2 (CHD2), endoplasmic reticulum to nucleus signaling 1 (ERN1), and growth differentiation factor 15 (GDF15). The most commonly downregulated genes include arrestin domain containing 4 (ARRDC4), and thioredoxin interacting protein (TXNIP). The most significantly (p-value < 0.05, Fisher's exact test) overrepresented protein class was entitled, nucleic acid binding. Cholesterol biosynthesis and other metabolic pathways were specifically affected by downregulated pathway molecules. In addition, cell cycle pathways were significantly related to the data set. Generated networks were significantly related to, e.g., carbohydrate and lipid metabolism, cancer, cell cycle, and DNA replication, recombination, and repair. A second compilation comprised genes that were at least under one condition up- and in at least another condition down-regulated. Herein, the most frequently deregulated genes include nuclear paraspeckle assembly transcript 1 (NEAT1) and insulin induced gene 1 (INSIG1). The most significantly overrepresented protein classes in this compilation were entitled, nucleic acid binding, ubiquitin-protein ligase, and mRNA processing factor. In conclusion, this study provides a comprehensive list of deregulated genes and biofunctions related to in vitro MTF application and individual responses to different conditions. Biofunctions affected by MTF include, e.g., cholesterol synthesis and other metabolic pathways, cell cycle, and DNA replication, recombination, and repair. These findings can assist in defining the conditions in which MTF exerts additive or synergistic effects in cancer treatment.

Background: Approximately, one-third of adult patients with acute myeloid leukemia (AML) are refractory to initial induction chemotherapy and relapse occurs in most patients who achieve remission. This study evaluates the efficacy of decitabine in the management of refractory or relapsed AML. Methods: After literature search in electronic databases (Google Scholar, Embase, Ovid, and PubMed) studies were selected by following pre-determined eligibility criteria. Random-effects meta-analyses were performed to achieve effect sizes of complete remission (CR) rate, response rate (RR), and median survival after therapy. Subgroup analyses were performed with regards to use of decitabine with either epigenetics-based therapy, molecular therapy or chemotherapy. Results: Twenty studies were included (310 patients; age 55.1 years [95% confidence interval (CI): 43.8, 66.4]; 57% [52%, 63%] males). Overall RR was 46.1% [95% CI: 36.1%, 56.1%]. Overall CR rate was 23.5% [95% CI: 22.1%, 24.9%] but was 14.85% [95% CI: 3.8%, 25.9%] for decitabine with epigenetics-based therapies, 15.4% [95% CI: 6.7%, 24.0%] for decitabine with immunotherapy or molecular therapy, 34.8% [95% CI: 18.7%, 50.9%] for decitabine with chemotherapy, and 37.5% [36.4%, 38.7%] for decitabine with chemotherapy and molecular therapy. Median survival was 7.2 months [95% CI: 5.17, 9.3]. Major adverse events were neutropenia, nausea/vomiting, infections, fatigue, febrile neutropenia, diarrhea, thrombocytopenia, anemia, anorexia, leukopenia, hemorrhage, and hyperglycemia. Conclusion: Decitabine in combination with chemotherapy or molecular therapy has shown efficacious properties in refractory or relapsed AML patients.

Schizophrenia (SZ) is a debilitating mental illness with a multigenic aetiology and significant heritability. Despite extensive genetic studies, the molecular aetiology has remained enigmatic. A recent systems biology study suggested a protein-protein interaction network for SZ with 504 novel interactions. The onset of psychiatric disorders is predominant during adolescence, often accompanied by subtle structural abnormalities in multiple regions of the brain. The availability of BrainSpan Atlas data allowed us to re-examine the genes present in the SZ interactome as a function of space and time. The availability of genomes of healthy centenarians and nonpsychiatric Exome Aggregation Consortium database allowed us to identify the variants of criticality. The expression of the SZ candidate genes responsible for cognition and disease onset was studied in different brain regions during particular developmental stages. A subset of novel interactors detected in the network was further validated using gene expression data of post-mortem brains of patients with psychiatric illness. We have narrowed down the list of drug targets proposed by theprevious interactome study to 10 proteins. These proteins belonging to 81 biological pathways are targeted by 34 known Food and Drug Administration-approved drugs that have distinct potential for the treatment of neuropsychiatric disorders. We also report the possibility of targeting key genes belonging to celecoxib pharmacodynamics, Gα signalling and cGMP-PKG signalling pathwaysthat are not known to be specific to SZ aetiology.

The standard treatment of rectal cancer is surgery along with preoperative radiotherapy, administered alone or in combination with chemotherapy. Preoperative chemoradiotherapy (preCRT) is widely used as it allows better local control and the use of sphincter-saving surgery. Pathological response after preCRT has been shown to be a significant prognostic factor of rectal cancer recurrence and survival. In this review we will assess the value of Hypoxia Induced Factor 1α (HIF-1α), Carbonic Anhydrase IX (CA-9) and Glucose Transporter 1 (GLUT-1) genes as predictive markers of the course of local advanced rectal cancer in patients who underwent pre-CRT.

Conflicting findings on the effects of garlic supplementation on inflammatory biomarkers have been observed in randomized clinical trials (RCTs).

Myelodysplastic syndromes (MDS) are characterized by variable degrees of clinical outcomes. Until now, hypomethylating agents (HMAs) are the only drugs that have been approved by FDA in remedying this complicated prognosis disease, but without satisfactory outcome. So, biomarkers of better clinical outcome are of great significance. Many studies have already reported the potential prognostic value of DNA methylation pathway related gene (TET2/DNMT3 A/IDH) mutations in demethylation therapy patients, with controversial results. Therefore, a meta-analysis was performed to investigate their prognostic impact on HMAs treated MDS.

Current evidence suggests that age-associated inflammation, a strong risk factor for the health status of elderly individuals, is closely associated with gut microbiota. Previous animal studies have demonstrated a benefit of microbiota-driven therapy in decreasing low-grade chronic inflammation in elderly individuals; however, it remains controversial in clinical studies. Therefore, the present systematic review and meta-analysis were designed to assess the effects of microbiota-driven therapy on inflammatory markers in elderly individuals. PubMed, EMBASE, and the Cochrane Library were searched with no language restrictions from the inception of the database to November 11th, 2018 to identify all existing literature. We calculated pooled standard mean difference (SMD) using fixed effect model or random effect model to assess the effects of microbiota-driven therapy on elderly individuals. The methodological quality of the studies was determined according to the Cochrane Handbook. The publication bias was evaluated by funnel plot and Egger regression test. Ten randomized controlled studies, with 689 elderly individuals (347 individuals in the microbiota-driven therapy group and 342 individuals in the placebo group), were included in the analysis. Compared with placebo, microbiota-driven therapy did not decrease the levels of tumor necrosis factor-α (SMD, -0.24; 95% CI, -0.69 to 0.21; p = 0.30; I2 = 82.7%), interleukin-6 (SMD, -0.13; 95% CI, -0.74 to 0.49; p = 0.69; I2 = 90.7%) and interleukin-10 (SMD, 1.00; 95% CI, -0.15 to 2.15; p = 0.09; I2 = 96.3%). In addition, the microbiota-driven therapy also did not decrease the levels of C reactive protein (SMD, -1.28; 95% CI, -2.62 to 0.06; p = 0.06; I2 = 96.2%), interleukin-1β (SMD, -0.22; 95% CI, -0.81 to 0.37; p = 0.46; I2 = 73.8%), interleukin-8 (SMD, -0.03; 95% CI, -0.67 to 0.61; p = 0.93; I2 = 88.0%) and monocyte chemoattractant protein-1 (SMD, -0.11; 95% CI, -0.41 to 0.20; p = 0.49; I2 = 0%) when compared with placebo. No obvious publication bias was observed (p>0.05). In conclusion, the present meta-analysis of available randomized controlled studies did not suggest any significant benefit of microbiota-driven therapy in decreasing the inflammatory responses of elderly individuals.

Bromodomain and extra-terminal (BET) inhibitors, acting via epigenetic mechanisms, have been developed recently as potential new treatments for cancer, including prostate cancer, and inflammatory conditions. Some BET inhibitors, such as RVX-208, also raise high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 levels. A recent meta-analysis of three small trials (n = 798) found that RVX-208 protected against major adverse cardiovascular events (MACE), raising the question as to whether this protective effect was an artefact, a chance finding, or mediated by HDL-C, anti-inflammatory pathways, or other factors. Notably, the effect of RVX-208 on MACE was largely driven by revascularizations, but fewer interventions in the treatment arm could have arisen accidently from favorable effects of RVX-208 on HDL-C and C-reactive protein influencing decisions about patient care. A larger (n = 2400) trial of RVX-208, BETonMACE (NCT02586155), with a more restricted definition of MACE, excluding hospitalizations, will shortly provide clarity. A successful BETonMACE trial would raise the question as to whether RVX-208 operates via lipids, inflammation, or other means, because several previous HDL-C modulators and anti-inflammatories have not provided effective means of treating cardiovascular disease and reducing overall mortality. Re-conceptualizing cardiovascular disease within the well-established evolutionary biology theory that growth and specifically reproduction trade-off against longevity might provide a more comprehensive explanation. Drivers of the gonadotropic axis, particularly androgens, suppress both HDL-C and the immune system while promoting ischemic heart disease and stroke. As such, any effects of RVX-208 on cardiovascular disease might be the result of reducing androgens, of which higher HDL-C and reduced inflammation are biomarkers. Notably, several other effective treatments for cardiovascular disease, such as statins and spironolactone, are known anti-androgens. Results of the BETonMACE trial, and corresponding insight about the mechanism of BET inhibitors in cardiovascular disease, are eagerly awaited.

Newly published results of clinical trials has demonstrated immune checkpoint inhibitors as robust antitumor agents for urothelial carcinoma patients. However, searching for predictive biomarkers is still on the way. Previous clinical trials used PD-L1 as biomarkers, however, whether it can predict the objective response rate and overall survival is controversial. This is the first and latest study to pool the newest data in order the evaluate PD-L1 biomarker.

Vitamin A is considered as a supplement that effect on autoimmune diseases. We aimed to systematically review the effect of vitamin A on cytokines in patients with autoimmune disease.

This meta-analysis systematically evaluated the efficacy and safety of anti-PD-1/PD-L1 antibodies for pretreated advanced or metastatic nonsmall cell lung cancer (NSCLC) and investigated the correlation between PD-L1 expression levels and effectiveness of anti-PD-1/PD-L1 antibody.

Ample evidence indicates that insulin resistance (IR) is closely related to white adipose tissue (WAT), but the underlying mechanisms of IR pathogenesis are still unclear. Using 352 microarray datasets from seven independent studies, we identified a meta-signature which comprised of 1,413 genes. Our meta-signature was also enriched in overall WAT in in vitro and in vivo IR models. Only 12 core enrichment genes were consistently enriched across all IR models. Among the meta-signature, we identified a drug signature made up of 211 genes with expression levels that were co-regulated by thiazolidinediones and metformin using cross-species analysis. To confirm the clinical relevance of our drug signature, we found that the expression levels of 195 genes in the drug signature were significantly correlated with both homeostasis model assessment 2-IR score and body mass index. Finally, 18 genes from the drug signature were identified by protein-protein interaction network cluster. Four core enrichment genes were included in 18 genes and the expression levels of selected 8 genes were validated by quantitative PCR. These findings suggest that our signatures provide a robust set of genetic markers which can be used to provide a starting point for developing potential therapeutic targets in improving IR in WAT.

The role of nesfatin-1 in glucose homeostasis has been investigated previously. However, although numerous studies have examined the relationships between circulating nesfatin-1 levels and type 2 diabetes, the conclusions are contradictory. We aimed to probe the relationship between circulating nesfatin-1 levels and type 2 diabetes by meta-analysis. Seven studies including 328 type 2 diabetes patients and 294 control subjects were included. Although there was no obvious difference in circulating nesfatin-1 levels between patients with type 2 diabetes and the control group (MD = -0.04; 95% CI = -0.32 to -0.23), subgroup analysis showed higher nesfatin-1 levels in newly diagnosed type 2 diabetes patients (MD = 0.59; 95% CI = 0.45 to 0.74) and significantly lower nesfatin-1 levels in type 2 diabetes patients receiving antidiabetic treatment (MD = -0.26; 95% CI = -0.33 to -0.20). In conclusion, the analysis supports a relationship between circulating nesfatin-1 levels and type 2 diabetes, where newly diagnosed type 2 diabetes was associated with an elevated Nesfatin-1 level, and type 2 diabetes patients receiving antidiabetic treatment showed lower circulating nesfatin-1 levels.