miR-939-3p induces sarcoma proliferation and poor prognosis via suppressing BATF2.

Background: Sarcoma is a rare and aggressive malignancy with poor prognosis, in which oncogene activation and tumor suppressor inactivation are involved. Accumulated studies suggested basic leucine zipper transcription factor ATF-like 2 (BATF2) as a candidate tumor suppressor, but its specific role and mechanism in sarcoma remain unclear. Methods: The expression levels of BATF2 and miR-939-3p were evaluated by using human sarcoma samples, cell lines and xenograft mouse models. Bioinformatics analysis, qPCR, Western blot, cell proliferation assay, overexpression plasmid construction, point mutation and dual luciferase reporter assay were utilized to investigate the role and mechanism of miR-939-3p in sarcoma. Results: In this study, we demonstrated that the expression of BATF2 was downregulated in human sarcoma tissues and cell lines. The downregulation of BATF2 was negatively associated with the prognosis of sarcoma patients. Subsequent bioinformatic prediction and experimental validations showed that BATF2 expression was reduced by microRNA (miR)-939-3p mimic and increased by miR-939-3p inhibitor. Additionally, miR-939-3p was upregulated in sarcoma tissues and cells, correlating with a poor prognosis of sarcoma patients. Moreover, miR-939-3p overexpression suppressed sarcoma cell proliferation, which was significantly attenuated by the restoration of BATF2, while siRNA-mediated knockdown of BATF2 aggravated the miR-939-3p-induced promotion of sarcoma cell proliferation. Further computational algorithms and dual-luciferase reporter assays demonstrated that miR-939-3p repressed BATF2 expression via directly binding to its 3' untranslated region (3' UTR). Conclusion: Collectively, these findings identified miR-939-3p as a novel regulator of BATF2, as well as a prognostic biomarker in sarcoma, and revealed that suppressing miR-939-3p or inducing BATF2 expression may serve as a promising therapeutic strategy against sarcoma.

Regulatory roles of SP-A and exosomes in pneumonia-induced acute lung and kidney injuries.

Introduction: Pneumonia-induced sepsis can cause multiple organ dysfunction including acute lung and kidney injury (ALI and AKI). Surfactant protein A (SP-A), a critical innate immune molecule, is expressed in the lung and kidney. Extracellular vesicles like exosomes are involved in the processes of pathophysiology. Here we tested one hypothesis that SP-A regulates pneumonia-induced AKI through the modulation of exosomes and cell death. Methods: Wild-type (WT), SP-A knockout (KO), and humanized SP-A transgenic (hTG, lung-specific SP-A expression) mice were used in this study. Results: After intratracheal infection with Pseudomonas aeruginosa, KO mice showed increased mortality, higher injury scores, more severe inflammation in the lung and kidney, and increased serum TNF-α, IL-1ß, and IL-6 levels compared to WT and hTG mice. Infected hTG mice exhibited similar lung injury but more severe kidney injury than infected WT mice. Increased renal tubular apoptosis and pyroptosis in the kidney of KO mice were found when compared with WT and hTG mice. We found that serum exosomes from septic mice cause ALI and AKI through mediating apoptosis and proptosis when mice were injected intravenously. Furthermore, primary proximal tubular epithelial cells isolated from KO mice showed more sensitivity than those from WT mice after exposure to septic serum exosomes. Discussion: Collectively, SP-A attenuates pneumonia-induced ALI and AKI by regulating inflammation, apoptosis and pyroptosis; serum exosomes are important mediators in the pathogenesis of AKI.

Detection of melanocyte lineage-specific genes in vitiligo lesions.

Vitiligo is an acquired pigmentary disorder characterized by the loss of skin color and functional melanocytes. The pathogenesis of vitiligo remains unclear, which means that effective clinical treatment is difficult. However, if melanocyte linkage-specific genes are identified in vitiligo lesions, the appropriate treament for melanocytes may be implemented. The current study aimed to detect the expression of melanocyte lineage-specific genes in vitiligo lesion needle biopsies and to predict the occurrence of perifollicular repigmentation in depigmented macules. A total of 6 patients with stable vitiligo and 4 healthy volunteers were recruited from the Department of Dermatology, Wuhan Third Hospital. Total RNA was extracted from skin tissue needle biopsies from the periphery and center of depigmented macules, and adjacent normal skin. The expression of dopachrome tautomerase (Dct), tyrosinase (Tyr) and ß-actin (ACTB) genes were detected using a reverse transcription (RT)-semi quantitative polymerase chain reaction (PCR) assay. RNA extracted from 7 mg of skin samples was sufficient to amplify all three genes. The expression profile of each patient was then observed in the center of vitiligous lesions and were deemed to be Dct+Tyr-ACTB+, Dct-Tyr-ACTB+ or Dct+Tyr+ACTB+. At 5 months, patient follow-up indicated that perifollicular repigmentation was efficaciously induced by 308 nm eximer light radiation in a patient who had a Dct+Tyr-ACTB+ gene expression. The results demonstrated that needle skin biopsy and RT-semi quantitative PCR may be used as a less traumatic and reliable method to detect the expression profiles of melanocyte lineage-specific genes in needle biopsies, which may have the potential to predict the occurrence of perifollicular repigmentation in vitiligo.

Collagen type III glomerulopathy: case report and review of the literature
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To summarize the clinical and pathological features of collagen type III glomerulopathy, the present report describes a case of collagen type III glomerulopathy and reviewed more than 60 cases recorded by other groups in English literature over the last few years. A 24-year-old female patient was admitted because of lower limbs edema, without any other discomforts. The lab examination of the patient reported proteinuria (2.42 g/24 h urine), microscopic hematuria, and the serum creatinine was 71 µmol/L. She received renal biopsy. The immunofluorescence staining results showed that collagen type III expression was positive. The electron microscopy examination showed that the mesangial regions were widened, with visible fine fibers in it. The periodic stripes of collagen fibers could be seen on some fine fiber-like substance under a high-magnification microscope, the diameters of the fiber-like substances were 40 - 70 nm. Serum collagen type III N-peptide (PIIIP N-P) was 97.94 ng/mL. After the patient received benazepril 10 mg per day and symptomatic treatments (Chinese drug, Cordyceps Capsules 0.5 g per day), her proteinuria resolved (~ 0.5 g/24 hour urine).

Acute postinfectious glomerulonephritis with a large number of crescents caused by Mycoplasma pneumoniae.

Mycoplasma pneumoniae-induced acute postinfectious glomerulonephritis has various pathological changes and relatively poor prognosis. It often occurs in children, barely in adults. Currently, no clear treatment guidelines have been established for its treatment using glucocorticoid and immunosuppressive. In this study, we report an adult who admitted to our hospital due to fever and gross hematuria. The patient presented with nephritic syndrome and renal failure and confirmed to have M. pneumoniae infection by serum detection and acute postinfectious glomerulonephritis with a large number of crescents by renal biopsy. He was given glucocorticoid, immunosuppressive agent combined with hemodialysis as well as other supportive treatment. Three months later, his renal function became normal, urine protein level decreased to 0.4 g/24 h, and the C3 complement increased to normal level. In conclusion, glucocorticoid and immunosuppressive treatment should be given to patients with M. pneumoniae-infection induced glomerulonephritis after confirmed to have a large number of crescents by renal biopsy and the treatment could improve the prognosis.

Self-control study of combination treatment of 308 nm excimer laser and calcipotriene ointment on stable psoriasis vulgaris.

OBJECTIVE: This study aims to compare the differences of clinical efficacy and safety of treatment of stable psoriasis vulgaris with calcipotriene ointment in combination with 308 nm excimer laser to 308 nm excimer laser alone. METHODS: Randomized, open and self-control trial was conducted in 36 selected patients. The skin lesions from these patients with stable psoriasis vulgaris were divided into two sides along the midline of torso, one side was treated with 308 nm excimer laser, 2 times/week, at meantime Calcipotriene was applied externally, 2 times/day (treatment group); the other side was given 308 nm excimer laser alone, 2 times/week, the treatment period was 6 weeks (control group). Skin lesion area, PASI scores and cumulative doses of 308 nm excimer laser in patients with psoriasis were assessed before treatment and on weeks 2, 4 and 6 after treatment. RESULTS: 32 of 36 patients with stable psoriasis vulgaris completed study, effective rates in two groups were better on week 6 (84.37%, 56.25%) than on week 4 (53.12%, 37.5%) and on week 2 (31.25%, 18.75%) (P < 0.05). Effective rate on week 6 in control group (56.25%) was lower than treatment group (84.37%) (P < 0.05). The two groups showed that PASI scores on weeks 2 and 4 after treatment were significantly lower than before treatments (P < 0.05), and PASI scores on week 6 in treatment group was significantly lower than control group (P < 0.05). The average cumulative laser doses in treatment group at the end of trial was 4.69 (2.03) J/cm(2), which was significantly lower than in control group 8.41 (2.42) J/cm (P < 0.05). Treatment efficacies in the head, folds, back, abdomen and limbs were similar and no serious adverse effects, however the number of treatment and irradiation doses in the head and folds were significantly less than in back, abdomen and limbs (P < 0.05). CONCLUSIONS: Treatment of psoriasis vulgaris with 308 nm excimer laser in combination with external application of Calcipotriene ointment can improve long-term treatment efficacy, decrease cumulative laser doses, and reduce adverse effects induced by laser irradiations.