Dysregulated expression of long non-coding RNA X-inactive specific transcript (lncRNA-XIST) has been indicated in various cancer types. In the present study, a meta-analysis was conducted to evaluate the potential role of lncRNA-XIST in predicting the clinicopathological parameters of patients with cancer. Eligible studies were obtained through a systematic search of PubMed, Web of Science, Embase and the Cochrane Library, of articles published prior to January 2019. The combined odds ratio and 95% confidence interval were calculated to determine the association between lncRNA-XIST expression and patient outcome. In addition, 45 pairs of osteosarcoma (OS) tissues and adjacent healthy tissues from a single institution were analyzed for the expression of lncRNA-XIST, and its association with clinicopathological features; ultimately, a total of 1,869 cancer patients from 25 studies were assessed. The results demonstrated that high expression levels of lncRNA-XIST were significantly associated with lymphatic metastasis, larger tumor size, advanced cancer stage and distant metastasis. However, sex was not associated with lncRNA-XIST expression level. In the OS patient cohort, it was demonstrated that lncRNA-XIST was highly expressed in OS tissues, which negatively correlated with patient prognosis. The present study indicated that lncRNA-XIST may serve as a potential biomarker for advanced clinical parameters in human cancer.

Glioma is a common brain malignancy with high mortality. The competing endogenous RNA (ceRNA) networks may play key roles in cancer progression. This study was conducted to probe the role of long noncoding RNA (lncRNA) NCK1-AS1 in glioma progression and the involved mechanisms.

Mastitis is the most commonly diagnosed infectious disease reducing milk yield and quality and is accompanied by mammary tissue damage in both humans and animals. Mastitis incurs welfare and economic costs as well as environmental concerns regarding treatment. Staphylococcus aureus (S. aureus) is a prevalent Gram-positive bacteria and a major cause of mastitis, however, pathogenesis of the intrinsic anti-inflammatory response in mammary tissues is still principally unknown. Our aim, in combatting the S. aureus induced inflammatory response in mammary tissues, was to elucidate the intrinsic anti-inflammatory role of MerTK signaling. Here, we demonstrate that Mer receptor tyrosine kinase (MerTK) regulates an intrinsic negative feedback to balance the over-reaction of the host defense system. S. aureus elicits toll-like receptors 2 and 6 (TLR2/TLR6) signaling pathways, subsequently recruiting TRAF6, whose ubiquitination is intricate to the downstream signaling including MAPKs and NF-κB. We observed that TLR2/TLR6 activation, in response to S. aureus, was concomitant with induced MerTK activation, leading to raised expression of suppressor of cytokine signaling 1 and 3 (SOCS1, SOCS3) in wild type mice mammary tissues and epithelial cells. Meanwhile, S. aureus infection in MerTK-/- mice showed significant increased phosphorylation of p65, IκBα, p38, JNK and ERK along with production of pro-inflammatory cytokines. Moreover, MerTK-/- evidently inhibited S. aureus induced phosphorylation of STAT1 and subsequent SOCS1/SOCS3 expression which are pivotal in the negative feedback mechanism for targeting TRAF6 to inhibit the TLR2/TLR6 mediated immune response. Taken together, our findings demonstrate the importance of MerTK in the regulation of the intrinsic feedback during the inflammatory response induced by S. aureus through STAT1/SOCS1/SOCS3 in mice mammary tissues and mice mammary epithelial cells (MMECs).

Natural products play vital roles against infectious diseases since ancient times and most drugs in use today are derived from natural sources. Worldwide, multi-drug resistance becomes a massive threat to the society with increasing mortality. Hence, it is very crucial to identify alternate strategies to control these 'super bugs'. Pseudomonas aeruginosa is an opportunistic pathogen reported to be resistant to a large number of critically important antibiotics. Quorum sensing (QS) is a cell-cell communication mechanism, regulates the biofilm formation and virulence factors that endow pathogenesis in various bacteria including P. aeruginosa. In this study, we identified and evaluated quorum sensing inhibitors (QSIs) from plant-based natural products against P. aeruginosa. In silico studies revealed that catechin-7-xyloside (C7X), sappanol and butein were capable of interacting with LasR, a LuxR-type quorum sensing regulator of P. aeruginosa. In vitro assays suggested that these QSIs significantly reduced the biofilm formation, pyocyanin, elastase, and rhamnolipid without influencing the growth. Especially, butein reduced the biofilm formation up to 72.45% at 100 µM concentration while C7X and sappanol inhibited the biofilm up to 66% and 54.26% respectively. Microscale thermophoresis analysis revealed that C7X had potential interaction with LasR (KD = 933±369 nM) and thermal shift assay further confirmed the biomolecular interactions. These results suggested that QSIs are able to substantially obstruct the P. aeruginosa QS. Since LuxR-type transcriptional regulator homologues are present in numerous bacterial species, these QSIs may be developed as broad spectrum anti-infectives in the future.

Osteosarcoma is the most common type of malignant bone tumor, which has an overall survival rate of only 15-30%. The present study aimed to investigate the effects of 15-hydroxy-6α,12-epoxy-7β,10αH,11βH-spiroax-4-ene-12-one (HESEO), a compound extracted from the endophytic fungus Penicillium sp. FJ-1 isolated from Avicennia marina, on the proliferation of osteosarcoma cells and to explore its underlying mechanisms of action. Cell number was counted to measure the cell proliferation. JC-1 reagent was used to measure mitochondrial membrane potential. ELISA was used to measure the cytochrome c level and caspase activities. Apoptosis was detected by Annexin V-Propidium Iodide staining. Gene and protein expression were measured by reverse-transcription-PCR and western blot analysis, respectively. Additionally, the anti-tumor effects of HESEO were explored within a syngeneic osteosarcoma tumor model. The results suggested that HESEO significantly inhibited the proliferation of osteosarcoma cells and induced apoptosis of MG-63 cells, evidenced by their decreased mitochondrial membrane potential, and increased cytochrome c release, caspase activities and percentage of apoptotic cells. In addition, HESEO increased the expression of pro-apoptotic genes and proteins compared with control cells. The results indicated that HESEO may act through increasing p53 upregulated modulator of apoptosis expression. Furthermore, HESEO treatment significantly increased the survival time and decreased the tumor burden of osteosarcoma tumor-bearing mice compared with vehicle treatment. Furthermore, combined treatment with HESEO enhanced the effects of the chemotherapeutic agent methotrexate on a lung metastasis osteosarcoma model. These data suggested that HESEO could be developed as a potential anti-tumor agent against osteosarcoma.

The beneficial functions of bone marrow mesenchymal stem cells (BM-MSCs) decline with decreased cell survival, limiting their therapeutic efficacy for myocardial infarction (MI). Irisin, a novel myokine which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), is believed to be involved in a cardioprotective effect, but little was known on injured BM-MSCs and MI repair yet. Here, we investigated whether FNDC5 or irisin could improve the low viability of transplanted BM-MSCs and increase their therapeutic efficacy after MI.

Adenosine triphosphate (ATP), as a key substance for regulating tumor progression in the tumor microenvironemnt (TME), is an emerging target for tumor theranostics. Herein, we report a minimalist but versatile nanoplatform with simultaneously TME-responsive drug release, TME-enhanced imaging, ATP-depletion sensitized chemotherapy and photothermal therapy for intelligent tumor theranostics. Methods: The Fe3+ and tannic acid (TA) coordination were self-deposited on doxorubicin (Dox) in a facile method to prepare Dox-encapsulated nanoparticles (DFTNPs). Results: When irradiated by a near infrared laser, the DFTNPs could elevate the temperature in the tumor region efficiently. Subsequently, the Dox could be released by the disassembly of Fe3+/TA in the TME to initiate chemotherapy. Particularly, the smart nanoagent not only enabled ATP-depletion and enhanced the therapeutic effect of chemotherapy, but also acted as photothermal transduction agent for photothermal therapy. Moreover, the nanoagent also acted as T1-weighted MR imaging,photoacoustic imaging and photothermal imaging contrast agent. The mice treated by DFTNPs plus laser showed a complete tumor eradication in 14d observation. Conclusion: This as-prepared versatile nanoplatform offers new insights toward the application of smart nanoagents for improved tumor theranostics.

Endometritis is a postnatal reproductive disorder disease, which leads to great economic losses for the modern dairy industry. Emerging evidence indicates that microRNAs (miRNAs) play a pivotal role in a variety of diseases and have been identified as critical regulators of the innate immune response. Recent miRNome profile analysis revealed an altered expression level of miR-148a in cows with endometritis. Therefore, the present study aims to investigate the regulatory role of miR-148a in the innate immune response involved in endometritis and estimate its potential therapeutic value. Here, we found that miR-148a expression in lipopolysaccharide (LPS)-stimulated endometrial epithelial cells was significantly decreased. Our results also showed that overexpression of miR-148a using agomiR markedly reduced the production of pro-inflammatory cytokines, such as IL-1β and TNF-α. Moreover, overexpression of miR-148a also suppressed NF-κB p65 activation by targeting the TLR4-mediated pathway. Subsequently, we further verified that miR-148a repressed TLR4 expression by binding to the 3'-UTR of TLR4 mRNA. Additionally, an experimental mouse endometritis model was employed to evaluate the therapeutic value of miR-148a. In vivo studies suggested that up-regulation of miR-148a alleviated the inflammatory conditions in the uterus as evidenced by H&E staining, qPCR and Western blot assays, while inhibition of miR-148a had inverse effects. Collectively, pharmacologic stabilization of miR-148a represents a novel therapy for endometritis and other inflammation-related diseases.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia, with metabolic disturbances resulting from defects in insulin secretion, insulin resistance (IR), or both. Chinese hamsters have potential value as non-obese animal models of spontaneous T2DM for studying the pathogenesis and molecular characteristics of diabetes. In this study, the molecular characteristics of the Chinese hamster diabetes animal model were investigated through small intestine proteomics and serum metabolomics. A total of 213 differentially abundant proteins and 14 differentially abundant metabolites were identified through liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-time of flight mass spectrometry (GC-TOF/MS) analysis, respectively. Annotation by bioinformatics analysis revealed that these differentially abundant proteins in the small intestine were commonly associated with abnormal glucose and lipid metabolism, IR, impaired insulin secretion, amino acid metabolism disorders, and inflammatory dysregulation. Moreover, differentially abundant metabolites in the serum were amino acids and were related to diabetic IR. Through the analysis of small intestine proteomics and serum metabolomics in the Chinese hamster diabetes model, we provide a preliminary understanding of the diabetic characteristics of this model from a molecular perspective. This study provides data incentivizing the popularization and application of Chinese hamsters in T2DM research. SIGNIFICANCE: Spontaneous rodent models of diabetes, such as Chinese hamsters, effectively summarizes the clinical characteristics of type 2 diabetes and has high applicative value for studying the pathophysiology of diabetes. In order to explore the potential value of the Chinese hamster diabetes animal model in the study of the T2DM molecular mechanism, we performed small intestine proteomic analysis and serum metabolomic analysis in Chinese hamsters for the first time. After an integrated analysis of proteomics and metabolomics, we have a preliminary understanding of the diabetic characteristics of this model from a molecular perspective. Further, we found that in the occurrence and development of T2DM, the metabolic abnormalities of this model are particularly prominent, especially the metabolism of amino acids. These findings not only provide basic data in support of the popularization and application of the current model in T2DM research, but also provide a new perspective for the exploration of mechanisms related to T2DM.

Curcumin is a potential drug for the treatment of colorectal cancer (CRC). Its mechanism of action has not been elucidated. This study aims to investigate the mechanism of action of curcumin in the treatment of CRC via bioinformatics methods such as network pharmacology and molecular docking.

Colorectal cancer (CRC) ranks the second most common cause of cancer-related mortality worldwide. Ferroptosis, a recently discovered form of programmed cell death different from other, raises promising novel opportunities for therapeutic intervention of CRC. This study intended to systematically assess the prognosis value and multiple roles of the ferroptosis-related genes in the tumor immune microenvironment of CRC.

Id3, an inhibitor of DNA binding protein, plays important roles in the function and homeostasis of effector and memory T cells. Recent evidence has shown that Id3 is also implicated in CD8 T cell exhaustion. However, whether and how Id3 might regulate effector function or exhaustion of CD8 T cells, especially in the tumor setting, is still unknown. Here, we first showed that Id3 expression was impaired in tumor-infiltrating CD8 T cells as liver cancer progressed, especially in PD-1 +Tim-3 + exhausted CD8 T cells. Enforced expression of Id3 in CD8 T cells resulted in repressed development of anti-tumor CTLs exhaustion, which offered better tumor control. And partially depletion of Id3 in CD8 T cells promoted the development of exhausted CD8 T cells. Furthermore, Id3hi CD8 T cells could respond to PD-1 blockade. Collectively, Id3 exerts protective functions in CD8 T cells for liver cancer.

Vibrio fluvialis is a food-borne pathogen with epidemic potential that causes cholera-like acute gastroenteritis and sometimes extraintestinal infections in humans. However, research on its genetic diversity and pathogenicity-related genetic elements based on whole genome sequences is lacking. In this study, we collected and sequenced 130 strains of V. fluvialis from 14 provinces of China, and also determined the susceptibility of 35 of the strains to 30 different antibiotics. Combined with 52 publicly available V. fluvialis genomes, we inferred the population structure and investigated the characteristics of pathogenicity-related factors. The V. fluvialis strains exhibited high levels of homologous recombination and were assigned to two major populations, VflPop1 and VflPop2, according to the different compositions of their gene pools. VflPop2 was subdivided into groups 2.1 and 2.2. Except for VflPop2.2, which consisted only of Asian strains, the strains in VflPop1 and VflPop2.1 were distributed in the Americas, Asia and Europe. Analysis of the pathogenicity potential of V. fluvialis showed that most of the identified virulence-related genes or gene clusters showed high prevalence in V. fluvialis, except for three mobile genetic elements: pBD146, ICEVflInd1 and MGIVflInd1, which were scattered in only a few strains. A total of 21 antimicrobial resistance genes were identified in the genomes of the 182 strains analysed in this study, and 19 (90%) of them were exclusively present in VflPop2. Notably, the tetracycline resistance-related gene tet(35) was present in 150 (95%) of the strains in VflPop2, and in only one (4%) strain in VflPop1, indicating it was population-specific. In total, 91% of the 35 selected strains showed resistance to cefazolin, indicating V. fluvialis has a high resistance rate to cefazolin. Among the 15 genomes that carried the previously reported drug resistance-related plasmid pBD146, 11 (73%) showed resistance to trimethoprim-sulfamethoxazole, which we inferred was related to the presence of the dfr6 gene in the plasmid. On the basis of the population genomics analysis, the genetic diversity, population structure and distribution of pathogenicity-related factors of V. fluvialis were delineated in this study. The results will provide further clues regarding the evolution and pathogenic mechanisms of V. fluvialis, and improve our knowledge for the prevention and control of this pathogen.

Although pertussis cases globally have been controlled through the Expanded Programme on Immunization (EPI), the incidence of pertussis has increased significantly in recent years, with a "resurgence" of pertussis occurring in developed countries with high immunization coverage. Attracted by its fast-developing economy, the population of Shenzhen has reached 14 million and has become one of the top five largest cities by population size in China. The incidence of pertussis here was about 2.02/100,000, far exceeding that of the whole province and the whole country (both < 1/100,000). There are increasing numbers of reports demonstrating variation in Bordetella pertussis antigens and genes, which may be associated with the increased incidence. Fifty strains of Bordetella pertussis isolated from 387 suspected cases were collected in Shenzhen in 2018 for genotypic and molecular epidemiological analysis.

Atherosclerosis emerges as a result of multiple dynamic cell processes including endothelial damage, inflammatory and immune cell infiltration, foam cell formation, plaque rupture, and thrombosis. Animal experiments have indicated that cathepsins (CTSs) mediate the antigen transmission and inflammatory response involved in the atherosclerosis process, but the specific signal pathways and target cells of the CTSs involved in atherosclerosis are unknown.

The incidence of breast cancer (BC) ranks first among all kinds of female malignancies. Its invasion, migration, apoptosis and resistance to chemotherapeutic drugs are the focus of current research. Nuclear receptor binding protein 1 (NRBP1) and spalt-like transcription factor 4 (SALL4), which are observed to be abnormally expressed in BC, are investigated herein to identify their involvement in invasion, migration, apoptosis and chemotherapeutic drug sensitivity of BC and to elucidate the underlying mechanism. After NRBP1 was overexpressed by cell transfection, wound healing and Transwell experiments were used to detect the abilities of cell invasion and migration, and western blotting was used to detect the expression of MMP2 and MMP9. Cell viability and apoptosis were detected by Cell Counting Kit-8 assay, TUNEL staining and western blotting, in which Doxorubicin (DOX) and cis-platinum (Cis) were administrated after overexpression of NRBP1. Finally, after overexpression of NRBP1 and SALL4, the cell invasion, migration and apoptosis, and the sensitivity to DOX and Cis, were detected to explore the underlying mechanism. Overexpression of NRBP1 inhibited the invasion and migration, promoted the apoptosis, and enhanced the chemotherapeutic effect of chemotherapy drugs in BC cells. Overexpression of SALL4 in cells blocked the effects of NRBP1 overexpression on invasion, migration, apoptosis and DOX and Cis drug sensitivity of BC cells. In conclusion, NRBP1 negatively regulated SALL4 to reduce the invasion and migration capacities, promote apoptosis and increase the sensitivity to chemotherapeutic drugs of BC cells.

B cells contribute to the pathogenesis of polycystic ovary syndrome (PCOS). Clinically, metformin is used to treat PCOS, but it is unclear whether metformin exerts its therapeutic effect by regulating B cells. Here, we showed that the expression level of tumor necrosis factor-alpha (TNF-α) in peripheral blood B cells from PCOS patients was increased. Metformin used in vitro and in vivo was able to reduce the production of TNF-α in B cells from PCOS patients. Administration of metformin improved mouse PCOS phenotypes induced by dehydroepiandrosterone (DHEA) and also inhibited TNF-α expression in splenic B cells. Furthermore, metformin induced metabolic reprogramming of B cells in PCOS patients, including the alteration in mitochondrial morphology, the decrease in mitochondrial membrane potential, Reactive Oxygen Species (ROS) production and glucose uptake. In DHEA-induced mouse PCOS model, metformin altered metabolic intermediates in splenic B cells. Moreover, the inhibition of TNF-α expression and metabolic reprogramming in B cells of PCOS patients and mouse model by metformin were associated with decreased mTOR phosphorylation. Together, TNF-α-producing B cells are involved in the pathogenesis of PCOS, and metformin inhibits mTOR phosphorylation and affects metabolic reprogramming, thereby inhibiting TNF-α expression in B cells, which may be a new mechanism of metformin in the treatment of PCOS.

To investigate the protective effect and mechanism of genipin (GE) on mitochondrial damage in retinal pigment epithelial (RPE) cells induced by high glucose.

Bronchiectasis is a highly heterogeneous chronic airway disease with marked geographic and ethnic variations. Most influential cohort studies to date have been performed in Europe and USA, which serve as the examples for developing a cohort study in China where there is a high burden of bronchiectasis. The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China) is designed to: (1) describe the clinical characteristics and natural history of bronchiectasis in China and identify the differences of bronchiectasis between the western countries and China; (2) identify the risk factors associated with disease progression in Chinese population; (3) elucidate the phenotype and endotype of bronchiectasis by integrating the genome, microbiome, proteome, and transcriptome with detailed clinical data; (4) facilitate large randomized controlled trials in China.

Propofol is a general anesthetic option for deep brain stimulation (DBS) of the subthalamic nucleus (STN) of patients with Parkinson's disease (PD). However, its effects on STN activity and neuropsychological outcomes are controversial. The optimal propofol anesthesia for asleep DBS is unknown. This study investigated the safety and effectiveness of an optimized propofol anesthesia regimen in asleep DBS.