ABSTRACT
AIM: This study aimed to explore the benefits of different antiviral regimens in pregnant women with hepatitis B virus (HBV) infection in an attempt to provide scientific reference for clinically relevant interventions. METHODS: The study cohort comprised 64 pregnant women with HBV infection who presented to our hospital from May 2018 to July 2020. The women were grouped according to the treatment administered: a control group consisting of 32 pregnant women who received routine intervention and an observation group consisting of 32 pregnant women who received routine intervention plus tenofovir disoproxil fumarate (TDF) tablets. The two groups were compared in terms of liver function; HBV load (HBV DNA); neonatal characteristics (hepatitis B surface antigen and HBV DNA positivity); levels of interleukin (IL)-2, IL-4, and IL-6; neonatal growth and development; Apgar scores; incidence of adverse events; and incidence of maternal adverse effects during treatment. RESULTS: The observation group had lower levels of alanine aminotransferase, glutamic acid aminotransferase, IL-4, IL-6, and HBV DNA and higher levels of IL-2 than the control group after 1 month of treatment (p < 0.05). There was no significant difference in the incidence of adverse events between the two groups (p > 0.05). CONCLUSION: The administration of TDF tablets significantly reduced the HBV DNA levels and did not increase the physiological burden or adverse effects in pregnant women with HBV infection.
Subject(s)
Hepatitis B , Pregnancy Complications, Infectious , Antiviral Agents/adverse effects , Child , DNA, Viral , Female , Hepatitis B/drug therapy , Hepatitis B e Antigens/therapeutic use , Hepatitis B virus , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnant Women , Treatment Outcome , Viral LoadABSTRACT
IMPORTANCE: This was the first study evaluating the performance of the Xpert Xpress group B Streptococcus (GBS) test using rectovaginal swabs from Chinese pregnant women. Compared to the other three assays, the Xpert Xpress GBS test demonstrated high sensitivity and specificity when screening 939 pregnant women for GBS in rectovaginal specimens. Additionally, its reduced time to obtain results makes it valuable for the rapid detection of GBS.
Subject(s)
Pregnancy Complications, Infectious , Streptococcal Infections , Pregnancy , Female , Humans , Pregnant Women , Pregnancy Complications, Infectious/diagnosis , Vagina , Streptococcal Infections/diagnosis , Streptococcus agalactiae/geneticsABSTRACT
The knee joint has long been considered a closed system. The pathological effects of joint diseases on distant organs have not been investigated. Herein, our clinical data showed that post-traumatic joint damage, combined with joint bleeding (hemarthrosis), exhibits a worse liver function compared with healthy control. With mouse model, hemarthrosis induces both cartilage degeneration and remote liver damage. Next, we found that hemarthrosis induces the upregulation in ratio and differentiation towards Th17 cells of CD4+ T cells in peripheral blood and spleen. Deletion of CD4+ T cells reverses hemarthrosis-induced liver damage. Degeneration of cartilage matrix induced by hemarthrosis upregulates serological type II collagen (COL II), which activates CD4+ T cells. Systemic application of a COL II antibody blocks the activation. Furthermore, bulk RNAseq and single-cell qPCR analysis revealed that the cartilage Akt pathway is inhibited by blood treatment. Intra-articular application of Akt activator blocks the cartilage degeneration and thus protects against the liver impairment in mouse and pig models. Taken together, our study revealed a pathological joint-liver axis mediated by matrikine-activated CD4+ T cells, which refreshes the organ-crosstalk axis and provides a new treatment target for hemarthrosis-related disease. Intra-articular bleeding induces cartilage degradation through down-reulation of cartilage Akt pathway. During this process, the soluble COL II released from the damaged cartilage can activate peripheral CD4+ T cells, differention into Th17 cells and secretion of IL-17, which consequently induces liver impairment. Intra-articular application of sc79 (inhibitor of Akt pathway) can prevent the cartilage damage as well as its peripheral influences.
Subject(s)
CD4-Positive T-Lymphocytes , Liver , Animals , Mice , Humans , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/pathology , Liver/pathology , Liver/metabolism , Hemarthrosis/genetics , Hemarthrosis/pathology , Male , Disease Models, Animal , Th17 Cells/immunology , Th17 Cells/pathology , Collagen Type II/genetics , Elapid Venoms/pharmacology , Female , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
Platelet-rich plasma (PRP) has gained significant attention in the field of regenerative medicine due to its potential therapeutic applications. However, few studies have reported the components, especially anti-ageing-related components, of PRP derived from umbilical cord blood (UCB). It is essential to understand the influence of age on the composition and efficacy of PRP to optimize its clinical use. The present study compared the concentrations of bioactive components in PRP from healthy female adults and UCB-derived PRP. PRP was obtained from blood samples from females in four age groups (12 per group): neonates (UCB donors) and adults aged 18-25, 26-45, and 46-65 years, respectively. The concentrations of epidermal growth factor, basic fibroblast growth factor-2 (FGF-2), insulin-like growth factor-1, platelet-derived growth factor-AA (PDGF-AA), PDGF-AB/BB, vascular endothelial growth factor A, RANTES, TIMP-1, TIMP-2, GDF11, and clusterin and activity of superoxide dismutase, catalase, and glutathione peroxidase (GPx) in the PRP samples were determined and compared among groups. Pairwise comparisons between the groups showed statistically significant differences in the concentrations of some bioactive components of PRP, such as FGF-2, PDGF-AB/BB, and clusterin, and GPx activity. UCB-derived PRP contains various active ingredients such as VEGF-A, CAT activity, and TIMP-2. Contrary to expectations, UCB-derived PRP did not show higher concentrations of the anti-ageing protein GDF11. Because UCB is a rich source of bioactive components with low immunogenicity, its use in PRP preparation is an important research direction for future studies.
Subject(s)
Platelet-Rich Plasma , Vascular Endothelial Growth Factor A , Infant, Newborn , Humans , Adult , Female , Adolescent , Young Adult , Clusterin , Tissue Inhibitor of Metalloproteinase-2 , Fetal Blood , Fibroblast Growth Factor 2 , Becaplermin , Bone Morphogenetic Proteins , Growth Differentiation FactorsABSTRACT
OBJECTIVE: Self-sampling with proper instruction in 35-37 weeks' gestation is an option to clinician sampling to prevent early-onset invasive group B streptococcal disease of infants. We aimed to assess the accuracy of self-sampling and influencing factors of preference for collection method in Chinese women. METHODS: We compared the screening results of self-sampling with clinician collection in a sample of 520 women in late pregnancy. We collected their demographics, clinical information and preference for collection method. A multi-nominal logistic regression model was used to measure the association between the influencing factors and these participants' preference. RESULTS: A good agreement between the two collection methods was found with a Cohen's Kappa coefficient 0.83 (95%CI = 0.71-0.95). The prevalence of GBS infection in the two methods is statistically different in this low-risk group when self-sampling presented a better outcome in terms of detecting positive cases. Self-sampling is preferable by 20.9% of the participants. No less pain during self-sampling and age older than 35 years old was statistically related to preference for clinician collection. CONCLUSION: The accuracy of self-sampling is no worse than clinician collection. It could be an option for those younger than 35 years old, especially for those who report low pain threshold. Pregnant women are able to collect rectovaginal samples prior to their antenatal visit. Self-sampling followed by appropriate transportation of the sample to an advanced laboratory could eliminate the effects of local laboratory capacity. There are implications in increasing GBS screening participation in resource-limited settings.
Subject(s)
Pregnancy Complications, Infectious , Streptococcal Infections , Infant , Female , Pregnancy , Humans , Adult , Cross-Sectional Studies , Streptococcal Infections/epidemiology , Streptococcus agalactiae , Specimen Handling/methods , Mass Screening , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiologyABSTRACT
BACKGROUND: Osteoarthritis (OA), a prevalent degenerative disease characterized by degradation of extracellular matrix (ECM), still lacks effective disease-modifying therapy. Mesenchymal stem cells (MSCs) transplantation has been regarded as the most promising approach for OA treatment while engrafting cells alone might not be adequate for effective regeneration. Genetic modification has been used to optimize MSC-based therapy; however, there are still significant limitations that prevent the clinical translation of this therapy including low efficacy and safety concerns. Recently, chemically modified mRNA (modRNA) represents a promising alternative for the gene-enhanced MSC therapy. In this regard, we hypothesized that adipose derived stem cells (ADSCs) engineered with modRNA encoding insulin-like growth factor 1 (IGF-1) were superior to native ADSCs on ameliorating OA development. METHODS: Mouse ADSCs were acquired from adipose tissue and transfected with modRNAs. First, the kinetics and efficacy of modRNA-mediated gene transfer in mouse ADSCs were analyzed in vitro. Next, we applied an indirect co-culture system to analyze the pro-anabolic potential of IGF-1 modRNA engineered ADSCs (named as IGF-1-ADSCs) on chondrocytes. Finally, we evaluated the cell retention and chondroprotective effect of IGF-1-ADSCs in vivo using fluorescent labeling, histology and immunohistochemistry. RESULTS: modRNA transfected mouse ADSCs with high efficiency (85 ± 5%) and the IGF-1 modRNA-transfected ADSCs facilitated burst-like production of bio-functional IGF-1 protein. In vitro, IGF-1-ADSCs induced increased anabolic markers expression of chondrocytes in inflammation environment compared to untreated ADSCs. In a murine OA model, histological and immunohistochemical analysis of knee joints harvested at 4 weeks and 8 weeks after OA induction suggested IGF-1-ADSCs had superior therapeutic effect over native ADSCs demonstrated by lower histological OARSI score and decreased loss of cartilage ECM. CONCLUSIONS: These findings collectively supported the therapeutic potential of IGF-1-ADSCs for clinical OA management and cartilage repair.
Subject(s)
Insulin-Like Growth Factor I , Osteoarthritis , Adipose Tissue , Animals , Chondrocytes/metabolism , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/metabolism , Mice , Osteoarthritis/genetics , Osteoarthritis/metabolism , Osteoarthritis/therapy , RNA, Messenger/genetics , RNA, Messenger/metabolism , Stem Cells/metabolismABSTRACT
Mesenchymal stem cells (MSCs) have been widely used as functional components in tissue engineering. However, the immunogenicity and limited pro-angiogenic efficacy of MSCs greatly limited their pro-regenerative ability in allogenic treatment. Herein, utilizing a chemically defined cocktail in the culture system, including cytokines, small molecules, structural protein, and other essential components, we generated the immunoprivileged and pro-angiogenic cells (IACs) derived from human adipose tissues. Conventional adipose-derived MSCs (cADSCs) were used as a control in all the experiments. IACs show typical MSC properties with enhanced stemness capacity and a robust safety profile. IACs induce a significantly milder immune response of allogenic peripheral blood mononuclear cells in an H3K27me3-HLA axis-dependent manner. IACs, through superior paracrine effects, further promote nitric oxide production, anti-apoptotic ability, and the tube formation of human vein endothelial cells. Embedded in a photo-reactive hydrogel (Gel) termed as GelMA/HA-NB/LAP for tissue engineering treatment, IACs promote faster tissue regeneration in a xenogeneic full-thickness skin defect model, eliciting a milder immune response and enhanced blood vessel formation in IACs-treated defect areas. Together with its excellent pro-regenerative potential and robust safety, our findings suggest that IACs may be a promising candidate for clinically relevant stem cell and tissue engineering therapeutics.
Subject(s)
Endothelial Cells , Mesenchymal Stem Cells , Adipose Tissue , Cells, Cultured , Humans , Leukocytes, Mononuclear , Neovascularization, Physiologic , Wound HealingABSTRACT
Rho GTPase-activating protein 26 (ARHGAP26) is a negative regulator of the Rho family that converts the small GTP-binding protein RhoA (GTP-RhoA) to its inactive GDP-bound form and is a putative tumor suppressor gene associated with cell growth and migration. Here, the involvement of ARHGAP26 in ovarian cancer cell proliferation and migration was investigated. In this study, low ARHGAP26 expression was observed in ovarian cancer tissues and was associated with a poor overall survival and higher ß-catenin expression in patients with ovarian cancer. A2780 and HEY cells with ARHGAP26 upregulation showed decreased cell proliferation, migration, and invasion, along with decreased GTP-RhoA, ß-catenin, VEGF, MMP2, and MMP7 expression. ARHGAP26 upregulation in A2780 cells also inhibited lung metastasis in vivo. SKOV3 cells with ARHGAP26 downregulation demonstrated an inverse effect, which was inhibited by ARHGAP26 overexpression or DKK1, an antagonist of the ß-catenin pathway. SMURF1, an E3 ubiquitin ligase, interacted with and induced ubiquitination of ARHGAP26. ARHGAP26 upregulation in SKOV3 cells significantly inhibited SMURF1 upregulation-induced cell migration and invasion. Overall, SMURF1-mediated ubiquitination of ARHGAP26 may promote invasion and migration of ovarian cancer cells via the ß-catenin pathway.
Subject(s)
GTPase-Activating Proteins/metabolism , Ovarian Neoplasms/metabolism , Ubiquitin-Protein Ligases/metabolism , Blotting, Western , Cell Line, Tumor , Cell Movement/genetics , Cell Movement/physiology , Cell Proliferation/genetics , Cell Proliferation/physiology , Female , GTPase-Activating Proteins/genetics , Humans , Ovarian Neoplasms/genetics , Real-Time Polymerase Chain Reaction , Signal Transduction/genetics , Signal Transduction/physiology , Ubiquitin-Protein Ligases/genetics , Ubiquitination/genetics , Ubiquitination/physiologyABSTRACT
The balance of inflammation is critical to the repair of spinal cord injury (SCI), which is one of the most devastating traumas in human beings. Inflammatory cytokines, the direct mediators of local inflammation, have differential influences on the repair of the injured spinal cord. Some inflammatory cytokines are demonstrated beneficial to spinal cord repair in SCI models, while some detrimental. Various animal researches have revealed that local delivery of therapeutic agents efficiently regulates inflammatory cytokines and promotes repair from SCI. Quite a few clinical studies have also shown the promotion of repair from SCI through regulation of inflammatory cytokines. However, local delivery of a single agent affects only a part of the inflammatory cytokines that need to be regulated. Meanwhile, different individuals have differential profiles of inflammatory cytokines. Therefore, future studies may aim to develop personalized strategies of locally delivered therapeutic agent cocktails for effective and precise regulation of inflammation, and substantial functional recovery from SCI.