Long-term efficacy of a recombinant hepatitis E vaccine in adults: 10-year results from a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Hepatitis E virus (HEV) is a frequently overlooked causative agent of acute hepatitis. Evaluating the long-term durability of hepatitis E vaccine efficacy holds crucial importance. METHODS: This study was an extension to a randomised, double-blind, placebo-controlled, phase-3 clinical trial of the hepatitis E vaccine conducted in Dontai County, Jiangsu, China. Participants were recruited from 11 townships in Dongtai County. In the initial trial, a total of 112 604 healthy adults aged 16-65 years were enrolled, stratified according to age and sex, and randomly assigned in a 1:1 ratio to receive three doses of hepatitis E vaccine or placebo intramuscularly at month 0, month 1, and month 6. A sensitive hepatitis E surveillance system including 205 clinical sentinels, covering the entire study region, was established and maintained for 10 years after vaccination. The primary outcome was the per-protocol efficacy of hepatitis E virus vaccine to prevent confirmed hepatitis E occurring at least 30 days after administration of the third dose. Throughout the study, the participants, site investigators, and laboratory staff remained blinded to the treatment assignments. This study is registered with ClinicalTrials.gov (NCT01014845). FINDINGS: During the 10-year study period from Aug 22, 2007, to Oct 31, 2017, 90 people with hepatitis E were identified; 13 in the vaccine group (0·2 per 10 000 person-years) and 77 in the placebo group (1·4 per 10 000 person-years), corresponding to a vaccine efficacy of 83·1% (95% CI 69·4-91·4) in the modified intention-to-treat analysis and 86·6% (73·0 to 94·1) in the per-protocol analysis. In the subsets of participants assessed for immunogenicity persistence, of those who were seronegative at baseline and received three doses of hepatitis E vaccine, 254 (87·3%) of 291 vaccinees in Qindong at the 8·5-year mark and 1270 (73·0%) of 1740 vaccinees in Anfeng at the 7·5-year mark maintained detectable concentrations of antibodies. INTERPRETATION: Immunisation with this hepatitis E vaccine offers durable protection against hepatitis E for up to 10 years, with vaccine-induced antibodies against HEV persisting for at least 8·5 years. FUNDING: National Natural Science Foundation of China, Fujian Provincial Natural Science Foundation, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and the Fundamental Research Funds for the Central Universities.

Risk factors for lumbar disc herniation recurrence after percutaneous endoscopic lumbar discectomy: a meta-analysis of 58 cohort studies.

Recurrent lumbar disc herniation (rLDH) is one of the most serious complications and major causes of surgical failure and paralysis following percutaneous endoscopic lumbar discectomy (PELD). There are reports in the literature on the identification of risk factors associated with rLDH; however, the results are controversial. Therefore, we conducted a meta-analysis to identify risk factors for rLDH among patients following spinal surgery. PubMed, EMBASE, and the Cochrane Library were searched without language restrictions from inception to April 2018 for studies reporting risk factors for LDH recurrence after PELD. MOOSE guidelines were followed in this meta-analysis. We used a random effects model to aggregate odds ratios (ORs) with 95% confidence intervals (CIs). The evidence of observational studies was classified into high quality (class I), medium quality (class II/III), and low quality (class IV) based on the P value of the total sample size and heterogeneity between studies. Fifty-eight studies were identified with a mean follow-up of 38.8 months. Studies with high-quality (class I) evidence showed that postoperative LDH recurrence after PELD was significantly correlated with diabetes (OR, 1.64; 95% CI, 1.14 to 2.31), the protrusion type LDH (OR, 1.62; 95% CI, 1.02 to 2.61), and less experienced surgeons (OR, 1.54; 95% CI, 1.10 to 2.16). Studies with medium-quality (class II or III) evidence showed that postoperative LDH recurrence was significantly correlated with advanced age (OR, 1.11; 95% CI, 1.05 to 1.19), Modic changes (OR, 2.23; 95% CI, 1.53 to 2.29), smoking (OR, 1.31; 95% CI, 1.00 to 1.71), no college education (OR, 1.56; 95% CI, 1.05 to 2.31), obesity (BMI ≥ 25 kg/m2) (OR, 1.66; 95% CI, 1.11 to 2.47), and inappropriate manual labor (OR, 2.18; 95% CI, 1.33 to 3.59). Based on the current literature, eight patient-related and one surgery-related risk factor are predictors of postoperative LDH recurrence after PELD. These findings may help clinicians raise awareness of early intervention for patients at high risk of LDH recurrence after PELD.

Effects of Cynaroside on Cell Proliferation, Apoptosis, Migration and Invasion though the MET/AKT/mTOR Axis in Gastric Cancer.

The Chinese medicine monomer cynaroside (Cy) is a flavonoid glycoside compound that widely exists in plants and has a variety of pharmacological effects, such as its important role in the respiratory system, cardiovascular system and central nervous system. Studies have reported that Cy has varying degrees of anticancer activity in non-small cell lung cancer, cervical cancer, liver cancer, esophageal cancer and other cancers. However, there are no relevant reports about its role in gastric cancer. The MET/AKT/mTOR signaling pathway plays important roles in regulating various biological processes, including cell proliferation, apoptosis, autophagy, invasion and tumorigenesis. In this study, we confirmed that Cy can inhibit the cell growth, migration and invasion and tumorigenesis in gastric cancer. Our finding shows that Cy can block the MET/AKT/mTOR axis by decreasing the phosphorylation level of AKT, mTOR and P70S6K. Therefore, the MET/AKT/mTOR axis may be an important target for Cy. In summary, Cy has anti-cancer properties and is expected to be a potential drug for the treatment of gastric cancer.

[Effects of tetrandrine on proliferation, migration, and invasion of glioblastoma cells].

Glioblastoma is the most common intracranial primary malignant tumor, which leads to the poor quality of life of patients and has a high recurrence rate. Chemotherapy is a vital part in the treatment of this disease. Tetrandrine(Tet) is an active ingredient extracted from the root of the Chinese medicinal plant Stephania tetrandra, which has been proved with a wide range of pharmacological effects including anti-tumor. However, there are few studies regarding the effect of Tet on glioma. In this study, MTT and BrdU assays were employed to detect the effect of Tet on the proliferation of LN229 glioblastoma cells; flow cytometry was used to analyze the cycle distribution and apoptosis; plate cloning assay and soft agar colony formation assay were performed to study the colony formation ability of LN229 cells exposed to Tet; scratch assay and Transwell assay were conducted to detect the ability of migration and invasion; Western blot was adopted to the exploration of the molecular mechanism. The MTT and BrdU assays showed that Tet inhibited the proliferation of LN229 cells in a time-and dose-dependent manner. The plate cloning assay and soft agar colony formation assay showed that Tet weakened the colony formation of LN229 cells in vitro; cytometry assay showed that Tet blocked cells in the G_1 phase and promoted cell apoptosis; scratch and Transwell assays proved that Tet inhibited the migration and invasion of LN229 cells; Western blot results showed that Tet down-regulated the expression levels of CDK2, CDK6, cyclin D1, cyclin E1, snail, slug, vimentin, and N-cadherin, while up-regulated the level of E-cadherin. The results indicate that Tet has a certain inhibitory effect on the proliferation, migration, and invasion of LN229 glioblastoma cells, and such effect may be related to the participation of Tet in the regulation of c-Myc/p27 axis and snail signaling pathway.

Long-term efficacy of a hepatitis E vaccine.

BACKGROUND: Hepatitis E virus (HEV) is a leading cause of acute hepatitis. The long-term efficacy of a hepatitis E vaccine needs to be determined. METHODS: In an initial efficacy study, we randomly assigned healthy adults 16 to 65 years of age to receive three doses of either a hepatitis E vaccine (vaccine group; 56,302 participants) or a hepatitis B vaccine (control group; 56,302 participants). The vaccines were administered at 0, 1, and 6 months, and the participants were followed for 19 months. In this extended follow-up study, the treatment assignments of all participants remained double-blinded, and follow-up assessments of efficacy, immunogenicity, and safety were continued for up to 4.5 years. RESULTS: During the 4.5-year study period, 60 cases of hepatitis E were identified; 7 cases were confirmed in the vaccine group (0.3 cases per 10,000 person-years), and 53 cases in the control group (2.1 cases per 10,000 person-years), representing a vaccine efficacy of 86.8% (95% confidence interval, 71 to 94) in the modified intention-to-treat analysis, rather than (95% confidence interval, 71 to 84) [corrected]. Of the participants who were assessed for immunogenicity and were seronegative at baseline, 87% of those who received three doses of the hepatitis E vaccine maintained antibodies against HEV for at least 4.5 years; HEV antibody titers developed in 9% in the control group. The rate of adverse events was similar in the two groups. CONCLUSIONS: Immunization with this hepatitis E vaccine induced antibodies against HEV and provided protection against hepatitis E for up to 4.5 years. (Funded by the Chinese Ministry of Science and Technology and others; ClinicalTrials.gov number, NCT01014845.).

Risk factors of postoperative delirium following spine surgery: A meta-analysis of 50 cohort studies with 1.1 million participants.

Objectives: Postoperative delirium (POD) is considered to be a common complication of spine surgery. Although many studies have reported the risk factors associated with POD, the results remain unclear. Therefore, we performed a meta-analysis to identify risk factors for POD among patients following spinal surgery. Methods: We systematically searched the PubMed, Embase and the Cochrane Library for relevant articles published from 2006 to February 1, 2023 that reported risk factors associated with the incidence of POD among patients undergoing spinal surgery. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed, and random effects models were used to estimate pooled odds ratio (OR) estimates with 95 % confidence intervals (CIs) for each factor. The evidence from observational studies was classified according to Egger's P value, total sample size, and heterogeneity between studies. Results: Of 11,329 citations screened, 50 cohort studies involving 1,182,719 participants met the inclusion criteria. High-quality evidence indicated that POD was associated with hypertension, diabetes mellitus, cardiovascular disease, pulmonary disease, older age (>65 years), patients experiencing substance use disorder (take drug ≥1 month), cerebrovascular disease, kidney disease, neurological disorder, parkinsonism, cervical surgery, surgical site infection, postoperative fever, postoperative urinary tract infection, and admission to the intensive care unit (ICU). Moderate-quality evidence indicated that POD was associated with depression, American Society of Anesthesiologists (ASA) fitness grade (>II), blood transfusion, abnormal potassium, electrolyte disorder, length of stay, inability to ambulate and intravenous fluid volume. Conclusions: Conspicuous risk factors for POD were mainly patient- and surgery-related. These findings help clinicians identify high-risk patients with POD following spinal surgery and recognize the importance of early intervention.

Histone demethylase KDM4B accelerates the progression of glioblastoma via the epigenetic regulation of MYC stability.

BACKGROUND: Glioblastoma (GBM) is the most malignant and invasive human brain tumor. Histone demethylase 4B (KDM4B) is abnormally expressed in GBM, but the molecular mechanisms by which KDM4B affects the malignant tumor progression are not well defined. METHODS: GBM cell lines and xenograft tumor samples were subjected to quantitative PCR (qPCR), Western blot, immunohistochemical staining (IHC), as well as ubiquitination, immunoprecipitation (IP), and chromatin immunoprecipitation (ChIP) assays to investigate the role of KDM4B in the progression of GBM. RESULTS: Here, we report that KDM4B is an epigenetic activator of GBM progression. Abnormal expression of KDM4B is correlated with a poor prognosis in GBM patients. In GBM cell lines, KDM4B silencing significantly inhibited cell survival, proliferation, migration, and invasion, indicating that KDM4B is essential for the anchorage-independent growth and tumorigenic activity of GBM cells. Mechanistically, KDM4B silencing led to downregulation of the oncoprotein MYC and suppressed the expression of cell cycle proteins and epithelial-to-mesenchymal transition (EMT)-related proteins. Furthermore, we found that KDM4B regulates MYC stability through the E3 ligase complex SCFFBXL3+CRY2 and epigenetically activates the transcription of CCNB1 by removing the repressive chromatin mark histone H3 lysine 9 trimethylation (H3K9me3). Finally, we provide evidence that KDM4B epigenetically activates the transcription of miR-181d-5p, which enhances MYC stability. CONCLUSIONS: Our study has uncovered a KDM4B-dependent epigenetic mechanism in the control of tumor progression, providing a rationale for utilizing KDM4B as a promising therapeutic target for the treatment of MYC-amplified GBM.

Risk factors of epidural hematoma in patients undergoing spinal surgery: a meta-analysis of 29 cohort studies.

OBJECTIVE: The authors conducted this meta-analysis to identify risk factors for spinal epidural haematoma (SEH) among patients following spinal surgery. METHODS: The authors systematically searched Pub: Med, Embase, and the Cochrane Library for articles that reported risk factors associated with the development of SEH in patients undergoing spinal surgery from inception to 2 July 2022. The pooled odds ratio (OR) was estimated using a random-effects model for each investigated factor. The evidence of observational studies was classified as high quality (Class I), moderate quality (Class II or III) and low quality (Class IV) based on sample size, Egger's P value and between-study heterogeneity. In addition, subgroup analyses stratified by study baseline characteristics and leave-one-out sensitivity analyses were performed to explore the potential sources of heterogeneity and the stability of the results. RESULTS: Of 21 791 articles screened, 29 unique cohort studies comprising 150 252 patients were included in the data synthesis. Studies with high-quality evidence showed that older patients (≥60 years) (OR, 1.35; 95% CI, 1.03-1.77) were at higher risk for SEH. Studies with moderate-quality evidence suggested that patients with a BMI greater than or equal to 25 kg/m² (OR, 1.39; 95% CI, 1.10-1.76), hypertension (OR, 1.67; 95% CI, 1.28-2.17), and diabetes (OR, 1.25; 95% CI, 1.01-1.55) and those undergoing revision surgery (OR, 1.92; 95% CI, 1.15-3.25) and multilevel procedures (OR, 5.20; 95% CI, 2.89-9.37) were at higher risk for SEH. Meta-analysis revealed no association between tobacco use, operative time, anticoagulant use or American Society of Anesthesiologists (ASA) classification and SEH. CONCLUSIONS: Obvious risk factors for SEH include four patient-related risk factors, including older age, obesity, hypertension and diabetes, and two surgery-related risk factors, including revision surgery and multilevel procedures. These findings, however, must be interpreted with caution because most of these risk factors had small effect sizes. Nonetheless, they may help clinicians identify high-risk patients to improve prognosis.

Sensory-guided isolation and identification of new sweet-tasting dammarane-type saponins from Jiaogulan (Gynostemma pentaphyllum) herbal tea.

The purpose of this study was to elucidate the chemical basis for the sweet property produced by Gynostemma pentaphyllum and find new natural high-potency (HP) sweeteners. Sixteen new compounds (gypenosides YN 1-16) were obtained by sensory-guided isolation and identification, in which fifteen of them were sweet-tasting constituents with sweetness intensities 10-100 times higher than that of sucrose evaluated by human sensory panel test. Their structures were established by 1D and 2D nuclear magnetic resonance spectra, mass spectroscopy, infrared spectroscopy, UV-visible spectroscopy, and chemical method. Gypenoside YN 4 was the sweetest compound with a concentration of 15.504 ± 1.343 mg/kg, while gypenoside YN 12 has the highest concentration (1397.674 ± 12.948 mg/kg), as shown by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Structure-activity relationship analysis implied that the compounds' sweetness intensity was associated with side-chain substitutions at C-20 or the number of glucosyl groups at C-3. These new plant-derived natural products may be potential natural sweeteners.

Recent advances of the mammalian target of rapamycin signaling in mesenchymal stem cells.

Mammalian target of rapamycin (mTOR) is a serine/threonine kinase involved in a variety of cellular functions, such as cell proliferation, metabolism, autophagy, survival and cytoskeletal organization. Furthermore, mTOR is made up of three multisubunit complexes, mTOR complex 1, mTOR complex 2, and putative mTOR complex 3. In recent years, increasing evidence has suggested that mTOR plays important roles in the differentiation and immune responses of mesenchymal stem cells (MSCs). In addition, mTOR is a vital regulator of pivotal cellular and physiological functions, such as cell metabolism, survival and ageing, where it has emerged as a novel therapeutic target for ageing-related diseases. Therefore, the mTOR signaling may develop a large impact on the treatment of ageing-related diseases with MSCs. In this review, we discuss prospects for future research in this field.

Transcriptomic profiling of mice brain under Bex3 regulation.

BEX family genes are expressed in various tissues and play significant roles in neuronal development. A mouse model of Bex3 gene knock-out was generated in this study, using the CRISPR-Cas9 system. Transcriptomic analysis of the brain was performed to identify genes and pathways under Bex3 regulation. Essential biological functions under the control of Bex3 related to brain development were identified. Ninety-five genes were differentially expressed under Bex3-/- regulation, with 53 down and 42 up. Among down-regulated genes, LOC102633156 is a member of zf-C2H2, Xlr3a is an X-linked lymphocyte regulated gene, LOC101056144 is a hippocampal related gene, 2210418O10Rik and Fam205a3 are cortex related genes. Among the upregulated genes, Zfp967 is a zf protein, Tgtp2 is a T cell-specific regulator, Trpc2 is a neuron-related gene, and Evi2 is related to NF1. A total of 34 KEGG disease terms were identified under the Bex3-/- regulation. The most prominent is non-syndromic X-linked mental retardation, where Fgd1 is enriched. Similarly, IRF, MBD, SAND, zf-BED, and zf-C2H2 were significantly enriched transcription factors. A further study is required to confirm and explain each aspect that has been identified in this study.

ZC3H15 promotes gastric cancer progression by targeting the FBXW7/c-Myc pathway.

Zinc finger CCCH-type containing 15 (ZC3H15), a highly conserved eukaryotic protein, which was associated with several cellular processes and was ubiquitously expressed in various human tissues. Recent studies indicated that ZC3H15 was involved in tumorigenesis and may be a potential biomarker in hepatocellular carcinoma (HCC) and acute myeloid leukemia (AML). However, the biological function and molecular mechanism of ZC3H15 in gastric cancer (GC) have not been studied. In this study, we revealed that ZC3H15 was highly expressed in GC and high ZC3H15 expression was closely linked to poor survival of patients with GC. We found that ZC3H15 promoted cell proliferation, migration, and invasion by increasing c-Myc expression. Next, we found that ZC3H15 could modulate c-Myc protein stability by suppressing the transcription of FBXW7, which was mainly responsible for c-Myc degradation. Moreover, silencing of FBXW7 in ZC3H15-knockdown GC cells could partly abrogate the effects induced by ZC3H15 downregulation. Taken together, our data unearth the important roles of ZC3H15 in GC development and suggest that ZC3H15 may be a potential target for the treatment of GC.

Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial.

BACKGROUND: Seroprevalence data suggest that a third of the world's population has been infected with the hepatitis E virus. Our aim was to assess efficacy and safety of a recombinant hepatitis E vaccine, HEV 239 (Hecolin; Xiamen Innovax Biotech, Xiamen, China) in a randomised, double-blind, placebo-controlled, phase 3 trial. METHODS: Healthy adults aged 16-65 years in, Jiangsu Province, China were randomly assigned in a 1:1 ratio to receive three doses of HEV 239 (30 microg of purified recombinant hepatitis E antigen adsorbed to 0.8 mg aluminium hydroxide suspended in 0.5 mL buffered saline) or placebo (hepatitis B vaccine) given intramuscularly at 0, 1, and 6 months. Randomisation was done by computer-generated permuted blocks and stratified by age and sex. Participants were followed up for 19 months. The primary endpoint was prevention of hepatitis E during 12 months from the 31st day after the third dose. Analysis was based on participants who received all three doses per protocol. Study participants, care givers, and investigators were all masked to group and vaccine assignments. This trial is registered with ClinicalTrials.gov, number NCT01014845. FINDINGS: 11,165 of the trial participants were tested for hepatitis E virus IgG, of which 5285 (47%) were seropositive for hepatitis E virus. Participants were randomly assigned to vaccine (n=56,302) or placebo (n=56,302). 48,693 (86%) participants in the vaccine group and 48,663 participants (86%) in the placebo group received three vaccine doses and were included in the primary efficacy analysis. During the 12 months after 30 days from receipt of the third dose 15 per-protocol participants in the placebo group developed hepatitis E compared with none in the vaccine group. Vaccine efficacy after three doses was 100.0% (95% CI 72.1-100.0). Adverse effects attributable to the vaccine were few and mild. No vaccination-related serious adverse event was noted. INTERPRETATION: HEV 239 is well tolerated and effective in the prevention of hepatitis E in the general population in China, including both men and women age 16-65 years. FUNDING: Chinese National High-tech R&D Programme (863 programme), Chinese National Key Technologies R&D Programme, Chinese National Science Fund for Distinguished Young Scholars, Fujian Provincial Department of Sciences and Technology, Xiamen Science and Technology Bureau, and Fujian Provincial Science Fund for Distinguished Young Scholars.

The Diverse Roles of Histone Demethylase KDM4B in Normal and Cancer Development and Progression.

Histone methylation status is an important process associated with cell growth, survival, differentiation and gene expression in human diseases. As a member of the KDM4 family, KDM4B specifically targets H1.4K26, H3K9, H3K36, and H4K20, which affects both histone methylation and gene expression. Therefore, KDM4B is often regarded as a key intermediate protein in cellular pathways that plays an important role in growth and development as well as organ differentiation. However, KDM4B is broadly defined as an oncoprotein that plays key roles in processes related to tumorigenesis, including cell proliferation, cell survival, metastasis and so on. In this review, we discuss the diverse roles of KDM4B in contributing to cancer progression and normal developmental processes. Furthermore, we focus on recent studies highlighting the oncogenic functions of KDM4B in various kinds of cancers, which may be a novel therapeutic target for cancer treatment. We also provide a relatively complete report of the progress of research related to KDM4B inhibitors and discuss their potential as therapeutic agents for overcoming cancer.

[Anti-tumor activity of tigecycline: a review].

Tigecycline is a novel glycylcycline antibacterial drug, which shows both antibiotic function and anti-tumor activity. This review summarizes the single and combined use of tigecycline for tumor treatment and the underpinning mechanisms. As an inhibitor for mitochondrial DNA translation, tigecycline affects the proliferation, migration, and invasion of tumor cells mainly through inhibiting mitochondrial protein synthesis and inducing mitochondrial dysfunction. Although the effect of tigecycline monotherapy is controversial, the efficacy of combined use of tigecycline is satisfactory. Therefore, it is important to explore the molecular mechanisms underpinning the anti-tumor activity of tigecycline, with the aim to use it as a cheap and effective new anti-tumor drug.

Molecular Mechanisms of MYCN Dysregulation in Cancers.

MYCN, a member of MYC proto-oncogene family, encodes a basic helix-loop-helix transcription factor N-MYC. Abnormal expression of N-MYC is correlated with high-risk cancers and poor prognosis. Initially identified as an amplified oncogene in neuroblastoma in 1983, the oncogenic effect of N-MYC is expanded to multiple neuronal and nonneuronal tumors. Direct targeting N-MYC remains challenge due to its "undruggable" features. Therefore, alternative therapeutic approaches for targeting MYCN-driven tumors have been focused on the disruption of transcription, translation, protein stability as well as synthetic lethality of MYCN. In this review, we summarize the latest advances in understanding the molecular mechanisms of MYCN dysregulation in cancers.

Bruceine D inhibits Cell Proliferation Through Downregulating LINC01667/MicroRNA-138-5p/Cyclin E1 Axis in Gastric Cancer.

Objective: Gastric cancer is one of the most common malignant tumors. Bruceine D (BD) is one of the extracts of Brucea javanica. In recent years, it has been reported that BD has anti-tumor activity in some human cancers through different mechanisms. Here, this study try to explore the effect of BD on gastric cancer and its regulatory mechanism. Methods: Cell proliferation ability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays, 5-bromo-2-deoxyuridine (BrdU) staining and soft agar colony formation assay, respectively. The tumor xenograft model was used to verify the effect of BD on the tumorigenicity of gastric cancer cells in vivo. Flow cytometry analysis and Western blot assay were performed to detect cell cycle and apoptosis. Gastric cancer cells were analyzed by transcriptome sequencing. The interaction between LINC01667, microRNA-138-5p (miR-138-5p) and Cyclin E1 was verified by dual luciferase experiment and RT-PCR assays. Results: We found that BD significantly inhibited cell proliferation and induced cell cycle arrest at S phase in gastric cancer cells. Transcriptome analysis found that the expression of a long non-coding RNA, LINC01667, were significantly down-regulated after BD treatment. Mechanically, it was discovered that LINC01667 upregulated the expression of Cyclin E1 by sponging miR-138-5p. Furthermore, BD enhanced the chemosensitivity of gastric cancer cells to doxorubicin, a clinically used anti-cancer agent. Conclusion: BD inhibit the growth of gastric cancer cells by downregulating the LINC01667/miR-138-5p/Cyclin E1 axis. In addition, BD enhances the chemosensitivity of gastric cancer cells to doxorubicin. This study indicates that BD may be used as a candidate drug for the treatment of patients with gastric cancer.

Molecular characterization of new described kobuvirus in dogs with diarrhea in China.

Canine kobuvirus (CaKVs) was a newly described virus detected in dogs in the US and Italy. To learn more about CaKVs, 5 of 106 fecal samples from diarrhea dogs were positive with CaKVs in China, and the full genome of CaKVs strain CH-1 isolated from dog with diarrhea was sequenced. The genome consists of 8186 nucleotides, excluding the 3' poly (A) tail, and an open reading frame that maps between nucleotide positions 601 and 7943 which encodes a 2446 amino acid polyprotein. Based on the complete amino acid sequence of polyprotein, phylogenetic analysis showed that CH-1 was grouped along with other canine kobuvirus strains detected in the USA (US-PC0082, AN211D).

Monoclonal Antibody to Bone Marrow Stromal Cell Antigen 2 Protein of Swine.

The bone marrow stromal cell antigen 2 (BST-2) protein was identified as a novel virus restriction factor that potently restricts the replication and egress of enveloped viruses. In this study, we generated monoclonal antibodies (MAbs) against porcine BST-2 encoding 34-112 aa of porcine BST-2, which was cloned and inserted into the prokaryotic expression vector pCold-I to construct a recombinant plasmid pCold-pBST-2. The recombinant porcine BST-2 protein (rpBST-2 protein) was induced by isopropyl-ß-D-thiogalactoside in Escherichia coli BL21 (DE3). Then, BALB/c mice were immunized with the purified rpBST-2 protein to prepare MAbs of BST-2. After subcloning, one strain of hybridoma cells named 1B2 secreting porcine BST-2 protein monoclonal antibody (MAb) was obtained. Indirect immunofluorescence assay and western blot analysis showed that the MAb was specifically reacted with the overexpressed porcine BST-2 protein in Vero cells. The specific MAb of porcine BST-2 provides a valuable tool for further studies of BST-2 to restrict virus infection.