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.

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 β-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, β-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 β-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 β-catenin pathway.

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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.

Depression is a global mental health problem, the worst cases of which can lead to self-injury or suicide. An automatic depression detection system is of great help in facilitating clinical diagnosis and early intervention of depression. In this work, we propose a new automatic depression detection method utilizing speech signals and linguistic content from patient interviews. Specifically, the proposed method consists of three components, which include a Bidirectional Long Short-Term Memory (BiLSTM) network with an attention layer to deal with linguistic content, a One-Dimensional Convolutional Neural Network (1D CNN) to deal with speech signals, and a fully connected network integrating the outputs of the previous two models to assess the depressive state. Evaluated on two publicly available datasets, our method achieves state-of-the-art performance compared with the existing methods. In addition, our method utilizes audio and text features simultaneously. Therefore, it can get rid of the misleading information provided by the patients. As a conclusion, our method can automatically evaluate the depression state and does not require an expert to conduct the psychological evaluation on site. Our method greatly improves the detection accuracy, as well as the efficiency.

Background Self-sampling with proper instruction in 35-37 weeks’ gestation is supplementary to clinician sampling to prevent early-onset invasive group B streptococcal disease of infants. Despite of the accuracy proved in previous studies, disputes were raised on pregnant women’s low preference and adherence to the method of swab collection. We aimed to assess the accuracy of self-sampling and influencing factors for preference on collection method in Chinese women. Methods We compared screening results of self-sampling with clinician collection in a sample of 522 women in late pregnancy. These participants needed to complete a questionnaire on their preference and demographics after self-sampling. A multi-nominal logistic regression model was then used to measure the association between the influencing factors and preference for collection method. 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. Four factors (maternal age, parity, education attainment and pain difference) were included in the final multi-nominal regression model while gestational age and vaginal suppository use were excluded. Non-elderly parturient women were 2.84 (95% CI 1.19-6.74) times more likely to prefer self-sampling compared to clinician sampling, adjusting for parity, education and pain difference. If these participants experienced more or equal pain during self-sampling compared to clinician collection, they were more likely to prefer clinician sampling controlling the other three factors’ effect. Conclusions Our study suggests high agreement between the two collection methods. Self-sampling presented a higher detection rate than physician-collected samples. Pregnant women are able to collect rectovaginal samples prior to their antenatal visit. Self-sampling is preferable by 1/5 of the participants and it could be an option for those younger than 35 years old, especially for those with low pain threshold.

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