Long Noncoding RNA LINC02249 Is a Prognostic Biomarker and Correlates with Immunosuppressive Microenvironment in Skin Cutaneous Melanoma.

Skin cutaneous melanoma (SKCM) is one of the most aggressive and life-threatening tumors. It has a high incidence rate, as well as significant metastasis and fatality rates. To successfully treat SKCM and to increase the overall survival rate, early identification and risk stratification are both absolutely necessary. Long noncoding RNAs (lncRNAs) play a significant regulatory role in a variety of cancers. However, the expression and function of many lncRNAs have not been investigated. We evaluated the expression profile of the long noncoding RNA LINC02249 (LINC02249) in pan-cancers by using data on gene expression obtained from TCGA and GTEx. The biological function of LINC02249 was determined by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The prognostic value of LINC02249 expression in SKCM patients was statistically analyzed. Besides, the ssGSEA approach was utilized in order to investigate the degree to which LINC02249 expression is correlated with tumor immune infiltration. In this study, the expression of LINC02249 was found to be abnormally high in a variety of tumors, according to our findings. When compared with nontumor specimens, the level of expression of LINC02249 was shown to be significantly elevated in SKCM samples. GO and KEGG assays revealed LINC02249 may be involved in tumor progression. High expression of LINC02249 was associated with shorter overall survival and disease-specific survival of SKCM patients. More importantly, multivariate methods revealed that LINC02249 expression was an independent prognostic factor for SKCM cases. Using ssGSEA, we found that the expression of LINC02249 was negatively associated with different tumor-infiltrating immune cells, especially aDC, Treg, and macrophages. Overall, our findings suggested that LINC02249 can serve as a novel biomarker to predict the prognosis and immune infiltration in SKCM.

Efficacy and Safety of Tacrolimus in the Treatment of Pediatric Henoch-Schönlein Purpura Nephritis.

BACKGROUND: Children with severe Henoch-Schönlein purpura nephritis (HSPN) may progress to end-stage renal disease without appropriate treatment. OBJECTIVE: This study aimed to investigate the efficacy and safety of tacrolimus combined with glucocorticoids in the treatment of pediatric HSPN. METHODS: A total of 87 HSPN patients with urinary protein ≥ 0.75 g/24 h received standard of care, including angiotensin II receptor blockers/angiotensin-converting enzyme inhibitors and glucocorticoids. Patients were divided into three groups and additionally received tacrolimus (n = 30), cyclophosphamide (n = 31), or mycophenolate mofetil (MMF) (n = 26). We monitored outcome measures, including proteinuria, hematuria, and renal function and analyzed the efficacy and side effects in each group. RESULTS: At 2-month follow-up, the overall efficacy was 93.3%, 83.9%, and 61.5% for tacrolimus, cyclophosphamide, and MMF, respectively (P < 0.05). Urinary protein significantly decreased for all groups. Urinary red blood cell counts significantly decreased for patients treated with tacrolimus (P < 0.001) and cyclophosphamide (P < 0.05), whereas no significant decrease was seen for those receiving MMF (P = 0.09). Although urine ß2-microglobulin significantly decreased following 2 months of treatment with all medications, efficacy was greater with tacrolimus than with cyclophosphamide and MMF (P < 0.001). Major adverse events were respiratory and urinary infections, with MMF having the highest infection rate. The cyclophosphamide group also experienced additional adverse events, including arrhythmia, hemorrhagic cystitis, leukocytosis, thrombocytopenia, and hyperglycemia. CONCLUSIONS: These results indicate that tacrolimus is more effective at reducing proteinuria and hematuria and improving renal function, with relatively milder side effects, in the treatment of pediatric HSPN. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2200055323, retrospectively registered on January 7, 2022.

Targeting Antibacterial Effect and Promoting of Skin Wound Healing After Infected with Methicillin-Resistant Staphylococcus aureus for the Novel Polyvinyl Alcohol Nanoparticles.

INTRODUCTION: Topical agents typically remain in the wound site for time duration that are too short to effectively eradicate MRSA tradition formation of BZK that can be maintained within the wound site for longer time periods, should be more effective. METHODS: The novel chitosan and poly (D,L-lactide-co-glycoside) nanoparticles loaded with benzalkonium bromide (BZK) were designed, for the promotion wound healing after MRSA infection. The physical characterization of these nanoparticles, as well as their antibacterial activity in vitro, release profile in simulated wound fluid, cell toxicity, anti-biofilm activity, and their ability to improve the skin wound healing in a mouse model were also studied. RESULTS: These novel nanoparticles were found to have a significant antibacterial activity (p<0.01), both in vitro and in vivo test. The stronger anti-biofilm ability of the nanoparticles to inhibit the formation of bacterial biofilms, at a concentration of 3.33 µg/mL, and clear existing bacterial biofilms, at a concentration of 5 mg/mL, compared with its water solution. In addition, significant damage to bacterial cell walls also was found, providing insight into the mechanism of antibacterial activity. CONCLUSION: Taken together, these results demonstrated the ability of BZK-loaded nanoparticles in the promotion of skin wound healing with MRSA infection. The current findings open a new avenue for nanomedicine development and future clinical applications in the treatment of wounds.

Aloe-emodin inhibits the proliferation, migration, and invasion of melanoma cells via inactivation of the Wnt/beta-catenin signaling pathway.

BACKGROUND: Aloe-emodin is reported as a potential cancer therapeutic agent due to its inhibition of the proliferation, migration, and invasion of cancer cells. This study aimed to confirm the effects of aloe-emodin on the progression of melanoma and identify the underlying molecular mechanisms. METHODS: The effects of aloe-emodin treatment (concentrations ranging from 0 to 25 µg, 48 h) on proliferation, apoptosis, distribution of cell cycle, migration, and invasion were detected by performing Cell Counting Kit-8 (CCK-8) assay, colony formation assay, flow cytometry, wound healing assay, and Transwell invasion experiments. Rescue experiments were carried out by overexpression of ß-catenin to verify the role of ß-catenin in the inhibition of melanoma by aloe-emodin. The analysis was carried out at the animal level by constructing tumor-bearing nude mice model. RESULTS: The results showed that aloe-emodin prominently reduced the proliferation, migration, and invasion of melanoma cells. Additionally, it was found that aloe-emodin significantly enhanced the cell apoptosis and induced G2 phase arrest of melanoma cells via enhancing the expressions of cleaved-caspase3, bax, and reducing cyclinD1, c-myc, and bcl-2. In addition, aloe-emodin could also inhibit Wnt3a levels, and promote GSK3-beta and beta-catenin phosphorylation. In vivo experiments also showed that overexpression of beta-catenin reversed the effects of aloe-emodin on tumor growth. CONCLUSIONS: In conclusion, our findings indicated that aloe-emodin might prominently inhibit the tumor growth and metastasis of melanoma via the Wnt/beta-catenin signaling pathway in vitro. Therefore, aloe-emodin may serve as a potential drug for the clinical treatment of melanoma.

LncRNA GAS5 suppresses CD4+ T cell activation by upregulating E4BP4 via inhibiting miR-92a-3p in systemic lupus erythematosus.

Increasing evidence reveals that long noncoding RNAs (lncRNAs) are associated with autoimmune and inflammatory diseases, such as systemic lupus erythematosus (SLE). In this study, we aimed to explore the role of lncRNA growth arrest specific 5 (GAS5) in the pathogenesis of SLE. We found that lncRNA GAS5 was decreased in CD4+ T cells and plasma from SLE patients. Overepression of GAS5 inhibited activation of normal CD4+ T cells and attenuated the self-reactivity of SLE CD4+ T cells. Additionally, we demonstrated that adenovirus E4 binding protein 4 (E4BP4) was involved in lncRNA GAS5-mediated inhibition of CD4+ T cell activation. GAS5 could upregulate E4BP4 by inhibiting miR-92a-3p. Taken together, our results indicate that the GAS5/miR-92a-3p/E4BP4 pathway plays an important role in inhibiting CD4+ T cell activation in SLE, thus providing a potential therapeutic target for SLE treatment.

A Case of Congenital Nephrogenic Diabetes Insipidus Caused by Thr108Met Variant of Aquaporin 2.

Congenital nephrogenic diabetes insipidus (CNDI) is a rare renal disorder caused by mutations in arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 (AQP2). The clinical signs of CNDI include polyuria, compensatory polydipsia, dehydration, electrolyte disorder, and developmental retardation without prompt treatment. In this study we report a rare case of CNDI caused by a single base transition in AQP2 gene. A 4.5 years old male patient suffered from oral dryness, polydipsia, and polyuria for more than 3 years. Laboratory examinations showed hypernatremia, hyperchloremia, and decreased urine osmolality and specific gravity. Ultrasound and MRI found bilateral upper ureteral dilatation and hydronephrosis. Furthermore, sequencing analysis found a C>T transition leading to a T108M missense mutation of AQP2. The patient was given low sodium diet and treated with hydrochlorothiazide followed by amiloride with indomethacin. The patient's clinical course improved remarkably after 1 year of treatment. This study reports the first case of CNDI featuring T108M missense mutation alone. These findings demonstrate a causative role of T108M mutation for CNDI and contribute to the mechanistic understanding of CNDI disease process.

Case Report: Complete Remission of C1q Nephropathy Treated With a Single Low-Dose Rituximab, a Reality or Coincidence?

C1q nephropathy is a glomerulopathy that is characterized by large amount of C1q deposits in the glomerular mesangium. It is a diagnosis of exclusion after ruling out systemic lupus erythematosus and membranoproliferative glomerulonephritis by systemic and serological examination. The pathogenesis of C1q nephropathy is unclear. In addition, there is very little generalizability in the treatment and prognosis for pediatric C1q nephropathy due to diversities in clinical manifestations and pathological types. Rituximab is a human/mouse chimeric monoclonal antibody against CD20, which is primarily used for treating lymphomas and, most recently, has been used to treat certain kidney diseases including C1q nephropathy. In this report, we used one quarter of the typical dose of rituximab for lymphoma treatment to achieve complete remission in a C1q nephropathy patient, significantly reducing deposition of immune complexes and glomerular damage. This case indicates that dosage reconsiderations may be necessary for rituximab in treatment of pediatric C1q nephropathy.