WTAP regulates stem cells via TRAF6 to maintain planarian homeostasis and regeneration.

WTAP, a highly conserved Wilms' tumor 1 interacting protein, is involved in a variety of biological processes. However, functional studies of WTAP in planarians have not been reported. In this study, we examined the spatiotemporal expression pattern of planarian DjWTAP and investigated its functions in planarians regeneration and homeostasis. Knocking-down DjWTAP resulted in severe morphological defects leading to lethality within 20 days. Silencing DjWTAP promoted the proliferation of PiwiA+ cells but impaired the lineage differentiation of epidermal, neural, digestive, and excretory cell types, suggesting a critical role for DjWTAP in stem cell self-renewal and differentiation in planarian. To further investigate the mechanisms underlying the defective differentiation, RNA-seq was employed to determine the transcriptomic alterations upon DjWTAP RNA interference. Histone 4 (H4), Histone-lysine N-methyltransferase-SETMAR like, and TNF receptor-associated factor 6 (TRAF6), were significantly upregulated in response to DjWTAP RNAi. Knocking-down TRAF6 largely rescued the defective tissue homeostasis and regeneration resulted from DjWTAP knockdown in planarians, suggesting that DjWTAP maintains planarian regeneration and homeostasis via TRAF6.

The Efficacy and Safety of Infliximab in Refractory Noninfectious Uveitis: A Meta-Analysis of Observational Studies.

Background: Although infliximab has been recommended for the second-line treatment of seronegative spondyloarthropathy- or juvenile idiopathic arthritis-related uveitis, the issue of its systemic efficacy and safety in a broader diversity of refractory noninfectious uveitis is debatable. To assess the short-term and relatively long-term efficacy of infliximab in refractory noninfectious uveitis, we performed a systematic review and meta-analysis of observational studies. Methods: PubMed, Cochrane Library, EMBASE, and Wanfang Med Online were systematically searched from January 2005 to March 2020. Two investigators independently assessed eligibility. Data were independently collected by two investigators. The pooled proportions were estimated with patients for intraocular inflammation control and improvement of visual acuity. Pooled proportions with 95% credible intervals were computed. Study homogeneity was investigated using I 2 statistics to quantify the percentage of variation across studies. To pool the results, the Mantel-Haenszel fixed-effects or random-effects models were used. Results: Of 2316 studies identified, 16 unique studies with 509 unique participants were included in the meta-analysis. The pooled proportions of intraocular inflammation control reached 92% (95% CI: 87%-98%; I 2: 1%; p=0.42) and 95% (95% CI: 93%-97%; I 2: 0%; p=0.91) in groups of ≤6- and ≥12-month follow-up durations. During the relatively long follow-up period, the pooled proportions of maintaining visual acuity stable or increasing at least one line reached 99% (95% CI: 96%-100%; I 2: 0%; p=0.54) in the involved eyes. The corticosteroid-sparing effect of infliximab was also well demonstrated, with the proportion of corticosteroid-sparing success reaching 85.5% (112/131). Besides, about serious adverse events, 2.6% (13/500) of patients experienced hypersensitivity reactions, 2.4% (12/500) of patients experienced serious infections, 1.8% (9/500) of patients experienced autoimmune diseases, and 0.6% (3/500) of patients experienced neoplasia. Conclusions: This meta-analysis provided evidence that infliximab might be a promising choice in controlling inflammatory activity, gaining visual acuity, and sparing corticosteroid use with relatively few side effects when applied in treating refractory noninfectious uveitis. Systematic Review Registration: [website], identifier [registration number].

Rituximab in the treatment of immune-mediated necrotizing myopathy: a review of case reports and case series.

Immune-mediated necrotizing myopathy (IMNM) is a group of immune-related myopathies characterized by progressive proximal muscle weakness, extremely high serum creatine kinase (CK) levels, and necrotic muscle fibers with a relative lack of inflammation. Treatment of IMNM is challenging, with most cases refractory to high-dose steroids in combination with multiple immunotherapies. The role of rituximab (RTX) for IMNM has been explored in isolated case reports and small series. The aim of this article was to perform a literature review of patients with IMNM treated with RTX and to evaluate RTX efficacy and safety. A total of 34 patients with IMNM were reviewed: 52.9% (18/34) with anti-signal recognition particle (SRP) antibodies and 47.1% (16/34) with anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies. Patient age at onset varied from 11 years to 81 years (mean 41 years). The majority of patients presented as a severe proximal muscle weakness and the peak level of CK varied from 3900 IU/L to 56,000 IU/L (mean 18,440 IU/L). Prior to RTX administration, all patients were treated with high-dose steroids and most were treated with multiple immunotherapies. The reason for initiating RTX was that 64.7% (22/34) of patients showed no improvement after previous treatments, and 35.3% (12/34) of patients relapsed when attempting to wean steroids or other immunosuppressive agents. With regard to RTX efficacy, 61.8% (21/34) of patients presented a response to RTX. Our data may support the use of RTX as an effective treatment strategy against IMNM resistant to steroids and multiple immunotherapies. Meanwhile, RTX as a first-line therapy could be a choice in IMNM, particularly in African Americans with anti-SRP antibody-positive subsets. ANA, antinuclear antibody; CK, creatine kinase; HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase; IMNM, immune-mediated necrotizing myopathy; MAC, membrane attack complex; MHC-I, major histocompatibility complex-I; RTX, rituximab; SRP, signal recognition particle.

The Role of Mycophenolate Mofetil for the Induction of Remission in ANCA-Associated Vasculitis: A Meta-Analysis.

Objectives: The successful introduction of mycophenolate mofetil (MMF) as a treatment for renal allograft reduced the incidence of acute rejection. The inspiring effects obtained by the MMF have led to an evaluation of its therapeutic potency on ANCA-associated vasculitis (AAV). However, there is little evidence of the MMF's efficacy on the AAV. The meta-analysis is carried out to evaluate the efficacy of MMF as a remission induction therapy in AAV. Methods: Up to June 30th, 2020, PubMed, Cochrane Library, and Embase have been searched comprehensively. According to heterogeneity, the pooled remission rates are synthesized by either fixed-effect or random-effect models. Results: The eight included studies comprising 230 patients who were treated with MMF as induction therapy are included in our analysis. The pooled overall remission rate is 74% (95% CI: 0.68-0.80). The remission rate, the infection rate and the rate of leukopenia of four randomized controlled trials aimed at comparing the effects of MMF with cyclophosphamide (CYC) during induction therapy for AAV have no statistical significance (P > 0.05). Conclusion: MMF may be an alternative to CYC for remission induction therapy in AAV with MPO-ANCA, mild to moderate renal involvement and non-life-threatening state. Whether to observe the effect of MMF in AAV or to compare the difference between MMF and CYC in the future studies, risk stratification and subgrouping of AAV patients should be first carried out to correctly identify the AAV subgroup suitable for MMF.