Skeletal muscle-derived FSTL1 starting up angiogenesis by regulating endothelial junction via activating Src pathway can be upregulated by hydrogen sulfide.

Hydrogen sulfide (H2S) promotes microangiogenesis and revascularization after ischemia. Neovascularization starts with the destruction of intercellular junctions and is accompanied by various endothelial cell angiogenic behaviors. Follistatin-like 1 (FSTL1) is a cardiovascular-protective myokine that works against ischemic injury. The present study examined whether FSTL1 was involved in H2S-induced angiogenesis and explored the underlying molecular mechanism. We observed that H2S accelerated blood perfusion after ischemia in the mouse hindlimb ischemia model. Western blot analysis showed that H2S stabilized FSTL1 transcript and increased FSTL1 and Human antigen R (HuR) levels in skeletal muscle. RNA-interference HuR significantly inhibited the H2S-promoted increase in FSTL1 levels. Exogenous FSTL1 promoted the wound-healing migration of human umbilical vein endothelial cells (HUVECs) and increased monolayer endothelial barrier permeability. Immunostaining showed that FSTL1 increased interendothelial gap formation and decreased VE-Cadherin, Occludin, Connexin-43, and Claudin-5 expression. In addition, FSTL1 significantly increased the phosphorylation of Src and VEGFR2. However, the Src inhibitor, not the VEGFR2 inhibitor, could block FSTL1-induced effects in angiogenesis. In conclusion, we demonstrated that H2S could upregulate the expression of FSTL1 by increasing the HuR levels in skeletal muscle, and paracrine FSTL1 could initiate angiogenesis by opening intercellular junctions via the Src signaling pathway.NEW & NOTEWORTHY The myocyte-derived paracrine protein FSTL1 acts on vascular endothelial cells and initiates the process of angiogenesis by opening the intercellular junction via activating Src kinase. H2S can significantly upregulate FSTL1 protein levels in skeletal muscles by increasing HuR expression.

Extracellular vesicles produced by human-induced pluripotent stem cell-derived endothelial cells can prevent arterial stenosis in mice via autophagy regulation.

Intravascular transplantation of human-induced pluripotent stem cells (hiPSCs) demonstrated a significant therapeutic effect in the treatment of restenosis by the paracrine function of extracellular vesicles (EVs). However, the risk of tumorigenicity and poor cell survival limits its clinical applications. In this study, we for the first time applied a highly efficient and robust three-dimensional (3D) protocol for hiPSC differentiation into endothelial cells (ECs) with subsequent isolation of EVs from the derived hiPSC-EC (ECs differentiated from hiPSCs), and validated their therapeutic effect in intimal hyperplasia (IH) models. We found that intravenously (iv) injected EVs could accumulate on the carotid artery endothelium and significantly alleviate the intimal thickening induced by the carotid artery ligation. To elucidate the mechanism of this endothelial protection, we performed miRNA expression profiling and found out that among the most conserved endothelial miRNAs, miR-126 was the most abundant in hiPSC-EC-produced EVs (hiPSC-EC-EV). MiR-126 depletion from hiPSC-EC-EV can hinder its protective effect on human umbilical vein endothelial cells (HUVECs) in an inflammatory process. A variety of functional in vitro studies revealed that miR-126 was able to prevent endothelial apoptosis after inflammatory stimulation, as well as promote EC migration and tube formation through autophagy upregulation. The latter was supported by in vivo studies demonstrating that treatment with hiPSC-EC-EV can upregulate autophagy in mouse carotid artery ECs, thereby preventing IH and modulating vascular homeostasis via remodeling of the vascular intima. Our findings suggest a regulatory mechanism for the therapeutic effect on arterial restenosis by autophagy regulation, and provide a potential strategy for clinical treatment of the disease.

Spontaneous regression of central nervous system posttransplant lymphoproliferative disease: A case report.

RATIONALE: Primary central nervous system (CNS) posttransplant lymphoproliferative disease (PTLD) is a very rare entity. Patients may respond to reduction of immunosuppression or other therapies, but the prognosis is still pessimistic. PATIENT CONCERNS: Herein, we report a 40-year-old female with a history of renal transplantation developed brain masses 4 years ago. Although brain biopsy was performed, PTLD was underdiagnosed then. No relevant treatment was administered. However, the lesions resolved spontaneously. After 4 years, new lesion appeared in a different brain region. DIAGNOSES: The history of renal transplantation raised the suspicion of PTLD. Reexamination of previous brain sections confirmed the diagnosis of polymorphic PTLD (P-PTLD). A second biopsy of the new lesion also demonstrated P-PTLD. INTERVENTIONS: She was referred to hematology department to receive rituximab. OUTCOMES: After 4 rounds of treatment, the lesion resolved satisfactorily. LESSONS: This case demonstrates the natural history of primary CNS P-PTLD. Although self-remission and recurrence is possible, aggressive measures should be taken to this condition.

Solitary juxtacortical lesion associated with anti-N-methyl-D-aspartate receptor encephalitis: a case report.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a severe autoimmune encephalitis mediated by anti-NMDA receptor antibodies. Brain MRI manifestations vary and are non-specific. If there are any lesions, they tend to be diffusely or multifocally distributed. Solitary lesion is relatively rare. CASE PRESENTATION: We report a 16-year-old girl who initially presented with focal seizures but developed severe psychiatric and extrapyramidal symptoms later on. Brain MRI revealed a solitary juxtacortical demyelinating lesion in the left frontal lobe. No enhancement was noted. Electroencephalogram captured epileptiform discharges in the same region. NMDAR IgGs were tested positive in the serum and cerebrospinal fluid. Corticosteroid and intravenous IgG were administered and the patient completely recovered. Brain MRI revealed a fainter lesion in the left frontal lobe. CONCLUSION: In very rare instances, anti-NMDA receptor encephalitis can present with a solitary brain lesion. A full panel of antibodies for autoimmune encephalitis is the key leading to the diagnosis.

Monoclonal gammopathies regardless of subtypes are associated with poor prognosis of diffuse large B-cell lymphoma: A STROBE-compliant article.

Monoclonal gammopathy (MG), a positive result of serum immunofixation electrophoresis (SIFE), has been reported in cases of diffuse large B-cell lymphoma (DLBCL). We performed this study to further investigate the prognostic value of MG in DLBCL.We retrospectively reviewed patients diagnosed with DLBCL between January 2007 and December 2014, and identified 37 patients with MG. The clinical characteristics of these patients were then reviewed. A 1:2 case-control analysis was conducted on 74 matched controls, who were patients with DLBCL and without MG. Both cases and controls were age-matched and were diagnosed within the same year.Among 37 DLBCL patients with MG, the monoclonal component of IgM was the most frequent compared to the other subtypes. Laboratory tests showed that the presence of MG was correlated with a decreased platelet-to-lymphocyte ratio (PLR). Survival analysis showed that MG-secreting DLBCL patients had an inferior overall survival (OS) and progression-free survival (PFS), compared with MG-nonsecreting patients, regardless of MG subtype. However, treatment response analysis showed that MG was not a good indicator for tumor relapse. When patients with DLBCL were grouped by immunophenotype, we found that MG was associated with poor prognosis in the non-germinal center B-cell-like (GCB) type, rather than GCB type in OS analysis. Meanwhile, there was no statistical significance upon PFS analysis in both immunophenotypes. Furthermore, our study found that the appearance of MG during treatment did make prognostic sense compared to nonsecretors.Overall, MG can serve as a prognostic factor for DLBCL. We hypothesize that its presence in DLBCL may reflect the immune microenvironment in tumor progression and warrants further study to unveil the underlying molecular pathogenesis.