A more accurate relationship between serum androgen and metabolism among healthy, nonobese, reproductive-age women based on liquid chromatography-tandem mass spectrometry.

This study explored a more precise association between androgens and glycolipid metabolism in healthy women of different ages. Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio were used as body fat indicators. High-density lipoprotein (HDL), low-density lipoprotein, triglycerides, and total cholesterol were used as lipid markers. Fasting blood glucose (FBG), fasting insulin, and the homeostatic model assessment of insulin resistance were used to assess insulin resistance and glucose metabolism. Liquid chromatography-tandem mass spectrometry was used to measure androgen indicators, including testosterone, sex hormone-binding globulin (SHBG), free testosterone (FT), dihydrotestosterone (DHT), androstenedione (A4), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS). DHEAS levels varied across age groups. Correlation analyses with Spearman's coefficient showed that the free androgen index correlated positively with WC (p = 0.040), FT correlated positively with BMI (p = 0.033) and WC (p = 0.049), SHBG correlated positively with HDL (p = 0.013), and A4 correlated positively with FBG (p = 0.017). Multiple linear regression analysis showed that among healthful women aged 36-40 years, A4 increased with FBG, and SHBG increased with HDL. Even within healthy, nonobese women, lipid and glucose metabolism were robustly correlated with androgens. Yearly metabolic assessments are necessary, particularly for FBG and HDL, since these markers can predict the likelihood of hyperandrogenemia, enabling timely interventions.

Promotion Effect of Coexposure to a High-Fat Diet and Nano-Diethylnitrosamine on the Progression of Fatty Liver Malignant Transformation into Liver Cancer.

Overconsumption of high-fat foods increases the risk of fatty liver disease (FLD) and liver cancer with long pathogenic cycles. It is also known that the intake of the chemical poison nitrosamine and its nanopreparations can promote the development of liver injuries, such as FLD, and hepatic fibrosis, and significantly shorten the formation time of the liver cancer cycle. The present work confirmed that the coexposure of a high-fat diet (HFD) and nano-diethylnitrosamine (nano-DEN) altered the tumor microenvironment and studied the effect of this coexposure on the progression of fatty liver malignant transformation into liver cancer. Gene transcriptomics and immunostaining were used to evaluate the tumor promotion effect of the coexposure in mice. After coexposure treatment, tumor nodules were obviously increased, and inflammation levels were elevated. The liver transcriptomics analysis showed that the expression levels of inflammatory, fatty, and fibrosis-related factors in the coexposed group were increased in comparison with the nano-DEN- and high-fat-alone groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that coexposure aggravated the high expression of genes related to the carcinomatous pathway and accelerated the formation of the tumor microenvironment. The immunohistochemical staining results showed that the coexposure significantly increased the abnormal changes in proteins related to inflammation, proliferation, aging, and hypoxia in mouse liver tissues. The coexposure of high fat and nano-DEN aggravated the process of steatosis and carcinogenesis. In conclusion, the habitual consumption of pickled foods containing nitrosamines in a daily HFD significantly increases the risk of liver pathology lesions progressing from FLD to liver cancer.

Clinical Efficacy and Safety of Mechanical Ventilation Combined with Fiberoptic Bronchoalveolar Lavage in Patients with Severe Pulmonary Infection.

BACKGROUND The aim of this study was to assess the clinical efficacy and safety of mechanical ventilation combined with fiberoptic bronchoalveolar lavage in patients with severe pulmonary infection. MATERIAL AND METHODS We randomly divided 81 patients with severe pulmonary infection into a control group (n=40) and an observation group (n=41). Both groups were treated using mechanical ventilation, and observation group additionally received assistive fiberoptic bronchoalveolar lavage. RESULTS The cure rate and effectiveness rate in the observation group were higher than in the control group (P<0.05, χ²=3.2), and the incidence of ventilator-associated pneumonia in the observation group was significantly lower than that in the control group (P<0.05, χ²=9.4). The partial pressure of oxygen (PaO2) and oxygen saturation (SaO2) were higher in the observation group than in the control group (P<0.05, t=3.862, t=33.595), whereas the partial pressure of carbon dioxide (PaCO2) and respiratory rate were lower in the observation group than in the control group (P<0.05, t=3.307, t=5.043). The levels of C-reactive protein (CRP), tumor necrosis factor-a (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8) in the 2 groups were lower after treatment than before treatment (all P<0.05), and the levels in the observation group were lower than those in the control group (all P<0.05). Hospital stay, infection control window appearance time, invasive mechanical ventilation time, and total mechanical ventilation time in the observation group were shorter than those in the control group (P<0.05, t=13.990, t=8.643, t=9.717, t=8.980). CONCLUSIONS Mechanical ventilation combined with fiberoptic bronchoalveolar lavage can effectively improve the curative effects and the blood gas and inflammation indicators in patients.

A novel external catheter fixation method for chemotherapy using inferior epigastric arterial catheterization for cervical cancer.

The aim of this randomized controlled study was to investigate the effects of a novel external catheter fixation method for chemotherapy using inferior epigastric arterial catheterization for cervical cancer.Patients diagnosed with cervical cancer were randomly divided into a control group (n = 32) and a treatment group (n = 33). Patients in the control group underwent a traditional fixation method using a haemostat, elastic band and abdominal bandage. Patients in the treatment group underwent an improved fixation method using an indwelling needle and membrane cover. We used a visual analogue scale (VAS) to evaluate each patient's comfort score and also recorded the incidence of needlestick injury and the length of injection time in each group. The VAS scores measured before and after chemotherapy in the treatment group were lower than in the control group. The incidence of needlestick injury in the treatment group was significantly lower than in the control group. The length of injection time in treatment group was significantly lower than in the control group. Compared with the traditional fixation method, the improved fixation method not only increased patient comfort but also reduced both the risk of needlestick injury and the length of injection time. This improved technique deserves increased clinical use.

Sinularin stabilizes FOXO3 protein to trigger prostate cancer cell intrinsic apoptosis.

Sinularin, a natural product that purified from soft coral, exhibits anti-tumor effects against various human cancers. However, the mechanisms are not well understood. In this study, we demonstrated that Sinularin inhibited the viability of human prostate cancer cells in a dose-dependent manner and displayed significant cytotoxicity only at high concentration against normal prostate epithelial cell RWPE-1. Flow cytometry assay demonstrated that Sinularin induced tumor cell apoptosis. Further investigations revealed that Sinularin exerted anti-tumor activity through intrinsic apoptotic pathway along with up-regulation of pro-apoptotic protein Bax and PUMA, inhibition of anti-apoptotic protein Bcl-2, mitochondrial membrane potential collapses, and release of mitochondrial proteins. Furthermore, we illustrated that Sinularin induced cell apoptosis via up-regulating PUMA through inhibition of FOXO3 degradation by the ubiquitin-proteasome pathway. To explore how Sinularin suppress FOXO3 ubiquitin-proteasome degradation, we tested two important protein kinases AKT and ERK that regulate FOXO3 stabilization. The results revealed that Sinularin stabilized and up-regulated FOXO3 via inhibition of AKT- and ERK1/2-mediated FOXO3 phosphorylation and subsequent ubiquitin-proteasome degradation. Our findings illustrated the potential mechanisms by which Sinularin induced cell apoptosis and Sinularin may be applied as a therapeutic agent for human prostate cancer.

MiR-29c-3p inhibits proliferation and migration in rat primary cardiac fibroblasts via interacting with STAT3.

BACKGROUND: The aim of this study was to elucidate the influence and molecular mechanism of microRNA-29c-3p (miR-29c-3p) on cell functions of cardiac fibroblasts. METHODS: Rat primary cardiac fibroblasts were induced with high-level glucose (HG), followed by determination of miR-29c-3p and signal transducer and activator of transcription 3 (STAT3) levels. The regulatory effects of miR-29c-3p and STAT3 (AG490) on proliferative and migratory potentials in HG-induced cardiac fibroblasts were examined by cell counting kit-8 (CCK-8) and Transwell assay, respectively. The interaction between miR-29c-3p and STAT3 was assessed by bioinformatics analysis and dual-luciferase reporter assay. RESULTS: MiR-29c-3p was downregulated, and STAT3 was upregulated in HG-induced cardiac fibroblasts. HG induction stimulated proliferative and migratory potentials in cardiac fibroblasts, which were attenuated by overexpression of miR-29c-3p. STAT3 was the target gene binding miR-29c-3p. Application of AG490, the STAT3 inhibitor, was able to reverse the promoted proliferative and migratory potentials in HG-induced cardiac fibroblasts with miR-29c-3p knockdown. CONCLUSIONS: MiR-29c-3p weakens the over-proliferative and over-migratory potentials in HG-induced cardiac fibroblasts via inactivating the STAT3 signaling.

Whole course of treatment of autoimmune progesterone dermatitis that had spontaneously resolved during pregnancy: A case report and review of the literature.

Anaphylaxis due to autoimmune progesterone dermatitis is a rare but severe allergic disease in women. The clinical manifestations of APD are diverse, and a proper understanding of the disease can help even diagnose and treat it. A case of autoimmune progesterone dermatitis related in our department is reported as follows. She developed a rash with severe pruritus that was highly consistent with her menstrual cycle without any trigger 10 years ago. Laboratory tests were unremarkable. But all the symptoms disappeared during her pregnancy and resurfaced after the miscarriage. Two years ago, after a positive progesterone intradermal test confirmed the diagnosis of PH, she was given mifepristone, contraceptives(OCPs), and skin embedding treatment, and her symptoms improved.

Understanding the experiences of patients with cancers in hospitals during COVID-19 pandemic in China: A qualitative research study.

AIM: To explore the experiences of patients with cancers in hospitals during the COVID-19 pandemic. DESIGN: A qualitative research study. METHODS: Using a phenomenological approach, we enrolled 22 patients with cancers in the Hunan Cancer Hospital from 20 February 2020 to 10 April 2020. The interviews were conducted face-to-face and were analysed by Colaizzi's 7-step method. This study aligns with the COREQ checklist. RESULTS: The experiences of patients with cancers in hospitals during the COVID-19 pandemic can be categorized into four major themes: (1) emotional changes; (2) delays in visiting hospital; (3) barriers to accessing medical care services, and (4) inconvenience related to logistics services.

Chinese Herbal Medicine for Type 2 Diabetes Mellitus With Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Objectives: To evaluate the efficacy and safety of Chinese herbal medicine (CHM) for type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD) with current evidence. Methods: This study was registered in PROSPERO as CRD42021271488. A literature search was conducted in eight electronic databases from inception to December 2021. The primary outcomes were lipid indices and liver functions, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine transaminase (ALT), and aspartate transaminase (AST). Review Manager 5.2 and Stata v14.0 were applied for analysis. Results: The research enrolled 18 RCTs with 1,463 participants. Results showed CHM combined with western medicine (WM) was more effective than WM alone in TG (weighted mean differences (WMD) = -0.35.95% confidence interval (CI) [-0.51, -0.19], p < 0.0001), TC (WMD = -0.58.95%CI [-0.80, -0.36], p < 0.00001), LDL-C (WMD = -0.37, 95%CI [-0.47, -0.26], p < 0.00001), HDL-C (WMD = 0.20, 95%CI [0.10, 0.29], p < 0.0001), ALT (WMD = -4.99, 95%CI [-6.64, -3.33], p < 0.00001), AST (WMD = -4.76, 95%CI [-6.35, -3.16], p < 0.00001), homeostatic model assessment of insulin resistance (WMD = -1.01, 95%CI [-1.22, -0.79], p < 0.00001), fasting blood glucose (WMD = -0.87, 95%CI [-1.13, -0.61], p < 0.00001), 2-h postprandial glucose (WMD = -1.45.95%CI [-2.00, -0.91], p < 0.00001), body mass index (WMD = -0.73.95%CI [-1.35, -0.12], p = 0.02), and overall effective rate (risk ratio (RR) = 1.37.95%CI [1.29, 1.46], p < 0.00001). Conclusion: The CHM in combination with WM seems to be more beneficial in T2DM with NAFLD patients in improving lipid and glucose metabolism, liver function, and insulin resistance as well as improving overall efficiency and reducing body weight. Given the poor quality of reports from these studies and uncertain evidence, these findings should be interpreted cautiously. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021271488, identifier CRD42021271488.

Inhibition of sphingomyelin synthase 2 relieves hypoxia-induced cardiomyocyte injury by reinforcing Nrf2/ARE activation via modulation of GSK-3ß.

Sphingomyelin synthase 2 (SMS2) is a vital contributor to tissue injury and affects various pathological processes. However, whether SMS2 participates in the modulation of cardiac injury in myocardial infarction has not been determined. This study aimed to evaluate the potential role of SMS2 in the regulation of cardiomyocyte injury induced by hypoxia, an in vitro model for studying myocardial infarction. Our data revealed that SMS2 expression was significantly upregulated in cardiomyocytes in response to hypoxia. Loss-of-function experiments revealed that knockdown of SMS2 markedly restored the viability of cardiomyocytes impaired by hypoxia, and attenuated hypoxia-evoked apoptosis and reactive oxygen species (ROS) generation. In contrast, cardiomyocytes that highly expressed SMS2 were more sensitive to hypoxia-induced injury. Moreover, SMS2 deficiency enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling through inactivation of glycogen synthase kinase-3ß. Notably, suppression of Nrf2 markedly abrogated SMS2 knockdown-mediated cardioprotective effects on hypoxia-exposed cardiomyocytes. Our results illustrate that downregulation of SMS2 exerts a cardioprotective function by protecting cardiomyocytes from hypoxia-induced apoptosis and oxidative stress through enhancement of Nrf2 activation. Our study indicates a potential role of SMS2 in the modulation of cardiac injury, which may contribute to the progression of myocardial infarction.

Thymosin as a possible therapeutic drug for COVID-19: A case report.

BACKGROUND: There are no effective antiviral therapies for coronavirus disease 2019 (COVID-19) at present. Although most patients with COVID-19 have a mild or moderate course of disease, up to 5%-10% of patients may have a serious and potentially life-threatening condition, indicating an urgent need for effective therapeutic drugs. The therapeutic effect of thymosin on COVID-19 has not been previously studied. In this paper, for the first time we report a case of thymosin treatment of COVID-19. CASE SUMMARY: A 51-year-old man with imported COVID-19 was admitted with definite symptoms of chest tightness, chest pain, and fatigue. The polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 were negative. The antibody test was positive, confirming the diagnosis of COVID-19. As many orally administered drugs were not well tolerated due to gastrointestinal symptoms, an emergency use of thymosin, a polypeptide consisting of 28 amino acids, was administered by injection. Finally, after the implementation of the treatment program, symptoms and lung imaging improved significantly. CONCLUSION: In this case report, it is confirmed that thymosin may help alleviate the severity of COVID-19 symptoms.

Research Advances in the Roles of Circular RNAs in Pathophysiology and Early Diagnosis of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) refers to different degrees of glucose tolerance abnormalities that occur during pregnancy or are discovered for the first time, which can have a serious impact on the mother and the offspring. The screening of GDM mainly relies on the oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. The early diagnosis and intervention of GDM can greatly improve adverse pregnancy outcomes. However, molecular markers for early prediction and diagnosis of GDM are currently lacking. Therefore, looking for GDM-specific early diagnostic markers has important clinical significance for the prevention and treatment of GDM and the management of subsequent maternal health. Circular RNA (circRNA) is a new type of non-coding RNA. Recent studies have found that circRNAs were involved in the occurrence and development of malignant tumors, metabolic diseases, cardiovascular and cerebrovascular diseases, etc., and could be used as the molecular marker for early diagnosis. Our previous research showed that circRNAs are differentially expressed in serum of GDM pregnant women in the second and third trimester, placental tissues during cesarean delivery, and cord blood. However, the mechanism of circular RNA in GDM still remains unclear. This article focuses on related circRNAs involved in insulin resistance and ß-cell dysfunction, speculating on the possible role of circRNAs in the pathophysiology of GDM under the current research context, and has the potential to serve as early molecular markers for the diagnosis of GDM.

Up-regulation of CTRP12 ameliorates hypoxia/re-oxygenation-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling.

C1q/TNF-related protein 12 (CTRP12) has been reported to play a key role in coronary artery disease. However, whether CTRP12 plays a role in the regulation of myocardial ischemia-reperfusion injury is not fully understood. The goals of this work were to assess the possible relationship between CTRP12 and myocardial ischemia-reperfusion injury. Here, we exposed cardiomyocytes to hypoxia/re-oxygenation (H/R) to establish an in vitro cardiomyocyte injury model of myocardial ischemia-reperfusion injury. Our results showed that H/R treatment resulted in a decrease in CTRP12 expression in cardiomyocytes. The up-regulation of CTRP12 ameliorated H/R-induced cardiomyocyte injury via the down-regulation of apoptosis, oxidative stress, and inflammation. In contrast, the knockdown of CTRP12 enhanced cardiomyocyte sensitivity to H/R-induced cardiomyocyte injury. Further investigation showed that CTRP12 enhanced the levels of nuclear Nrf2 and increased the expression of Nrf2 target genes in cardiomyocytes exposed to H/R. However, the inhibition of Nrf2 markedly diminished CTRP12-overexpression-mediated cardioprotective effects against H/R injury. Overall, these data indicate that CTRP12 protects against H/R-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling. This work suggests a potential role of CTRP12 in myocardial ischemia-reperfusion injury and proposes it as an attractive target for cardioprotection.

Modified Predictive Model and Nomogram by Incorporating Prebiopsy Biparametric Magnetic Resonance Imaging With Clinical Indicators for Prostate Biopsy Decision Making.

PURPOSE: The purpose of this study is to explore the value of combining bpMRI and clinical indicators in the diagnosis of clinically significant prostate cancer (csPCa), and developing a prediction model and Nomogram to guide clinical decision-making. METHODS: We retrospectively analyzed 530 patients who underwent prostate biopsy due to elevated serum prostate specific antigen (PSA) levels and/or suspicious digital rectal examination (DRE). Enrolled patients were randomly assigned to the training group (n = 371, 70%) and validation group (n = 159, 30%). All patients underwent prostate bpMRI examination, and T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) sequences were collected before biopsy and were scored, which were respectively named T2WI score and DWI score according to Prostate Imaging Reporting and Data System version 2 (PI-RADS v.2) scoring protocol, and then PI-RADS scoring was performed. We defined a new bpMRI-based parameter named Total score (Total score = T2WI score + DWI score). PI-RADS score and Total score were separately included in the multivariate analysis of the training group to determine independent predictors for csPCa and establish prediction models. Then, prediction models and clinical indicators were compared by analyzing the area under the curve (AUC) and decision curves. A Nomogram for predicting csPCa was established using data from the training group. RESULTS: In the training group, 160 (43.1%) patients had prostate cancer (PCa), including 128 (34.5%) with csPCa. Multivariate regression analysis showed that the PI-RADS score, Total score, f/tPSA, and PSA density (PSAD) were independent predictors of csPCa. The prediction model that was defined by Total score, f/tPSA, and PSAD had the highest discriminatory power of csPCa (AUC = 0.931), and the diagnostic sensitivity and specificity were 85.1% and 87.5%, respectively. Decision curve analysis (DCA) showed that the prediction model achieved an optimal overall net benefit in both the training group and the validation group. In addition, the Nomogram predicted csPCa revealed good estimation when compared with clinical indicators. CONCLUSION: The prediction model and Nomogram based on bpMRI and clinical indicators exhibit a satisfactory predictive value and improved risk stratification for csPCa, which could be used for clinical biopsy decision-making.

Broad Impact of Exchange Protein Directly Activated by cAMP 2 (EPAC2) on Respiratory Viral Infections.

The recently discovered exchange protein directly activated by cAMP (EPAC), compared with protein kinase A (PKA), is a fairly new family of cAMP effectors. Soon after the discovery, EPAC has shown its significance in many diseases including its emerging role in infectious diseases. In a recent study, we demonstrated that EPAC, but not PKA, is a promising therapeutic target to regulate respiratory syncytial virus (RSV) replication and its associated inflammation. In mammals, there are two isoforms of EPAC-EPAC1 and EPAC2. Unlike other viruses, including Middle East respiratory syndrome coronavirus (MERS-CoV) and Ebola virus, which use EPAC1 to regulate viral replication, RSV uses EPAC2 to control its replication and associated cytokine/chemokine responses. To determine whether EPAC2 protein has a broad impact on other respiratory viral infections, we used an EPAC2-specific inhibitor, MAY0132, to examine the functions of EPAC2 in human metapneumovirus (HMPV) and adenovirus (AdV) infections. HMPV is a negative-sense single-stranded RNA virus belonging to the family Pneumoviridae, which also includes RSV, while AdV is a double-stranded DNA virus. Treatment with an EPAC1-specific inhibitor was also included to investigate the impact of EPAC1 on these two viruses. We found that the replication of HMPV, AdV, and RSV and the viral-induced immune mediators are significantly impaired by MAY0132, while an EPAC1-specific inhibitor, CE3F4, does not impact or slightly impacts, demonstrating that EPAC2 could serve as a novel common therapeutic target to control these viruses, all of which do not have effective treatment and prevention strategies.

MicroRNA-29c Acting on FOS Plays a Significant Role in Nonalcoholic Steatohepatitis Through the Interleukin-17 Signaling Pathway.

Nonalcoholic fatty liver disease is the most common hepatic disease in western countries and is even more ubiquitous in Asian countries. Our study determined that TH17/Treg cells were imbalanced in animal models. Based on our interest in the mechanism underlying TH17/Treg cell imbalance in nonalcoholic fatty liver mice, we conducted a joint bioinformatics analysis to further investigate this process. Common gene sequencing analysis was based on one trial from one sequencing platform, where gene expression analysis and enrichment analysis were the only analyses performed. We compared different sequencing results from different trials performed using different sequencing platforms, and we utilized the intersection of these analytical results to perform joint analysis. We used a bioinformatics analysis method to perform enrichment analysis and map interaction network analysis and predict potential microRNA sites. Animal experiments were also designed to validate the results of the data analysis based on quantitative polymerase chain reaction (qPCR) and western blotting. Our results revealed 8 coexisting differentially expressed genes (DEGs) and 7 hinge genes. The identified DEGs may influence nonalcoholic steatosis hepatitis through the interleukin-17 pathway. We found that microRNA-29c interacts with FOS and IGFBP1. Polymerase chain reaction analyses revealed both FOS and microRNA-29c expression in NASH mice, and western blot analyses indicated the same trend with regard to FOS protein levels. Based on these results, we suggest that microRNA-29c acts on FOS via the interleukin-17 signaling pathway to regulate TH17/Treg cells in NASH patients.

Guided ion beam and theoretical studies of sequential bond energies of water to sodium cysteine cation.

Absolute bond dissociation energies of water to sodium cysteine (Cys) cations and cysteine to hydrated sodium cations are determined experimentally by collision-induced dissociation of Na(+)Cys(H(2)O)(x), where x = 1-4, complexes with xenon in a guided ion beam mass spectrometer. Experimental results show that the binding energies of water and cysteine to the complexes decrease monotonically with increasing number of water molecules. Quantum chemical calculations at three different levels show reasonable agreement with the experimental bond energies. The calculations indicate that the primary binding site for Na(+) changes from charge-solvated tridentate chelation at the amino nitrogen, carbonyl oxygen, and sulfur side-chain for x = 0 and 1 to the C terminus of zwitterionic cysteine for x = 4, whereas different levels of theory provide conflicting predictions for x = 2 and 3. The first solvent shell of Na(+)Cys is found to be complete at four waters. This is fewer than needed for the aliphatic amino acid glycine, because the functionalized side-chain of Cys provides an internal solvation site, a binding motif that probably applies for most other functionalized amino acids.

Synergistic effects of Lactobacillus rhamnosus culture supernatant and bone marrow mesenchymal stem cells on the development of alcoholic steatohepatitis in mice.

The gut microbiota has been shown to play an important role in chronic liver disease. It has been found that both Lactobacillus rhamnosus and its culture supernatant have the potential to mitigate alcoholic steatohepatitis. However, the exact mechanism is still not fully understood. Bone marrow mesenchymal stem cells have immunosuppressive effects with few side effects. The synergistic effect between Lactobacillus rhamnosus culture supernatant and bone marrow mesenchymal stem cells (BMMSCs) deserves further observation. In this study, a mouse model of chronic alcoholic hepatitis was established by eight weeks of Lieber-DeCarli liquid diet feeding; and LGG-s, BMMSCs or a combination of the two were used to explore a new therapeutic method for alcoholic liver disease and to study the mechanism. The results showed that the combined LGG-s and BMMSC treatment might have a synergistic effect and could improve the symptoms of alcoholic hepatitis by regulating inflammation, autophagy and lymphocyte subsets through the PI3k/NF-kB and PI3K/mTOR pathways. With the treatment, the autophagy rate accelerated, and alcohol-induced natural killer B (NKB) cell and follicular helper T (TFH) cell numbers decreased. These findings suggest that the development of alcoholic hepatitis may occur via PI3K/NF-kB and PI3K/mTOR pathway overactivation as well as through NKB and TFH cell imbalances. Moreover, LGG-s and BMMSCs can regulate these factors and alleviate the disease.

Detection of Nuclear Protein Profile Changes by Human Metapneumovirus M2-2 Protein Using Quantitative Differential Proteomics.

Human metapneumovirus (hMPV) is a leading cause of lower respiratory infection in pediatric populations globally. This study examined proteomic profile changes in A549 cells infected with hMPV and two attenuated mutants with deleted PDZ domain-binding motif(s) in the M2-2 protein. These motifs are involved in the interruption of antiviral signaling, namely the interaction between the TNF receptor associated factor (TRAF) and mitochondrial antiviral-signaling (MAVS) proteins. The aim of this study was to provide insight into the overall and novel impact of M2-2 motifs on cellular responses via an unbiased comparison. Tandem mass tagging, stable isotope labeling, and high-resolution mass spectrometry were used for quantitative proteomic analysis. Using quantitative proteomics and Venn analysis, 1248 common proteins were detected in all infected samples of both technical sets. Hierarchical clustering of the differentiated proteome displayed distinct proteomic signatures that were controlled by the motif(s). Bioinformatics and experimental analysis confirmed the differentiated proteomes, revealed novel cellular biological events, and implicated key pathways controlled by hMPV M2-2 PDZ domain-binding motif(s). This provides further insight for evaluating M2-2 mutants as potent vaccine candidates.

Moraxella catarrhalis Macrolide-Resistant Isolates Are Highly Concentrated in Two MLST Clonal Complexes -CCN10 and CC363.

To gain some insights into the molecular evolution of Moraxella catarrhalis macrolide resistance, PCR and sequencing analysis of the 23S rRNA gene, copB typing and multilocus sequence typing (MLST) were performed on 181 M. catarrhalis isolates. The isolates were obtained from children (n = 47) and adults (n = 134) presenting with respiratory disease in the years 2010-2014. Macrolide resistance was highly age-related, and nucleotide position alterations at A2330T could be detected in all macrolide-resistant isolates. copB 0 and copB NT (non-typable) were only found in macrolide-susceptible isolates from adults. Furthermore, copB I/III was the main type in adult or macrolide-susceptible isolates, while copB II was the most common type in children or macrolide-resistant isolates. Twenty-two different MLST clusters (sharing 7 of the 8 identical loci) were detected and only four likely primary founders (ST224, ST363, STN08, and STN10) which belong to clonal complex (CC) 224, CC363, CCN08, and CCN10, were detected, respectively. Macrolide-resistant M. catarrhalis isolates were highly concentrated in two CCs (CCN10 and CC363), which indicates some potential evolutionary advantage or co-evolution to some extent. However, further studies are needed to fully elucidate the evolution of CCN10 and CC363 in macrolide resistance.