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Diabetes mellitus (DM) is a metabolic disorder that seriously harms human health. Notoginsenoside R1 (NGR1) can be used in various diseases. We explored consequents of NGR1 on tumour necrosis factor (TNF)-α-stimulated Min6 and rat primary islets β cells. The results were that TNF-α significantly cut down cell activity, raised cell apoptosis and iNOS expression and decreased insulin secretion in Min6 and rat primary islets β cells. NGR1 alleviated TNF-α-treated cell dysfunctions. In addition, miR-29a was positively regulated by NGR1 in TNF-α-treated Min6 and rat primary islets β cells. miR-29a knockdown damaged protection roles of NGR1 through cutting down cell activity and insulin secretion, raising apoptosis and iNOS in TNF-α-treated Min6 and rat primary islets β cells. The phosphorylation of Wnt3a, β-catenin and the rate of p/t-AKT/PI3K was all increased, while p/t-GSK3β was decreased by the administration with NGR1. In conclusion, NGR1 alleviated TNF-α-stimulated Min6 and rat primary islets β cells apoptosis and worn roles via positively regulating miR-29a. This process might be through actuation of Wnt/β-catenin and PI3K/AKT/GSK3β signal ways. [ABSTRACT FROM AUTHOR]

As an important 5-methylcytidine (m5C) methyltransferase, NOP2/Sun RNA methyltransferase family member 6 (NSUN6) has been reported to play an important role in the progression of several diseases. However, the role of NSUN6 in the progression of osteosarcoma (OS) remains unclear. This study aimed to identify the role of NSUN6 in the progression of OS and clarify the potential molecular mechanism. The present study discovered that NSUN6 was upregulated in OS and a higher NSUN6 expression was a strong indicator for poorer prognosis of patients with OS. In addition, the loss of NSUN6 led to reduced proliferation, migration and invasion of OS cells. Through bioinformatics analysis, RNA immunoprecipitation (RIP) and methylated RIP assays, eukaryotic elongation factor 1 α-2 (EEF1A2) was identified and validated as a potential target of NSUN6 in OS. Mechanistically, the expression of EEF1A2 was significantly suppressed following NSUN6 knockdown due to reduced EEF1A2 mRNA stability in an m5C-dependent manner. Meanwhile, NSUN6 deficiency inhibited m5C-dependent activation of Akt/mTOR signaling pathway. In addition, genetic overexpression of EEF1A2 or pharmacological activation of the Akt signaling pathway counteracted the suppressive effects of NSUN6 deficiency on the proliferation, invasion and migration of OS cells. The current findings suggested that NSUN6 may serve as a potential therapeutic target for OS treatment. [ABSTRACT FROM AUTHOR]

The adaptive immune response against hepatocellular carcinoma (HCC) could be a therapeutic target to restrain HCC initiation and growth. The interactions between hepatoma cells and immune cells modify the anti‐tumor immunity to influence hepatoma cell survival. To explore the potential interplay between hepatoma cells and anti‐HCC T‐cells, we conducted a HCC induction mouse model to analyze the phenotypic and functional alterations of T‐cell subsets. We found that both hepatoma tissues and hepatoma cell lines substantially produced higher leptin, which is an adipokine usually expressed in fat tissue, than normal liver tissue or hepatocytes. We also found that regulatory T‐cells (Tregs), effector CD4+ T‐cells and CD8+ T‐cells upregulated expression of leptin receptor (LEPR) in spleens and livers after HCC induction. In vitro study showed that macrophages and dendritic cells isolated from HCC livers upregulated LEPR expression on T‐cells. Leptin inhibited Treg activation and function in vitro, demonstrated by lower expression of TGF‐β, IL‐10, CTLA4 and GITR in Tregs, as wells weaker suppression of CD8+ T‐cell proliferation and production of cytotoxic mediators. In addition, silencing LEPR in Tregs favored tumor growth in a hepatoma cell line allograft model. Taken together, our study suggests that hepatoma cells could enhance anti‐HCC immunity through secreting leptin to down‐regulate Treg activity and subsequently promote CD8+ T‐cell response. [ABSTRACT FROM AUTHOR]

Objective: Diabetic nephropathy (DN) is a major microvascular complication of diabetes and the leading cause of end-stage renal disease. Early detection and prevention of DN are important. Retinol-binding protein 4 (RBP4) has been considered as a single diagnostic marker for the detection of renal impairment. However, the results have been inconsistent. The present meta-analysis aimed to determine the diagnostic potential of RBP4 in patients in type 2 diabetes mellitus (T2DM) with DN., Methods: We searched PubMed, Web of Science, Embase, Wanfang and CNKI databases from inception until January 2024. The meta-analysis was performed by Stata version 15.0, and sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were pooled. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was utilized to assess the quality of each included study. In addition, heterogeneity and publication bias were evaluated., Results: Twenty-nine studies were included in the meta-analysis. The pooled sensitivity and specificity were 0.76 [95% confidence interval (CI), 0.71-0.80] and 0.81 (95% CI, 0.76-0.85), respectively. The results showed a pooled PLR of 4.06 (95% CI, 3.16-5.21), NLR of 0.29 (95% CI, 0.24-0.36) and DOR of 13.76 (95% CI, 9.29-20.37). The area under the summarized receiver operating characteristic curve was given a value of 0.85 (95% CI, 0.82-0.88). No obvious publication bias existed in the Deeks' funnel plot asymmetry test., Conclusion: Our findings suggest that RBP4 has a promising diagnostic value with good sensitivity and specificity for patients with T2DM with DN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cao, Zhong, Jin, Hu, Wang, Shi and Wei.)

The present work aimed to explore the protective effects of curcumenol and evaluate its pharmacological mechanisms in 5/6 nephrectomy-induced chronic renal failure (CRF). Rats with CRF were administrated curcumenol and the effects on renal functions were investigated. Renal function examinations were carried out, whereas serum levels of inflammatory mediators, including NF-κB, MCP-1 and IL-1β were analyzed by ELISA. The mRNA expression levels of SIRT1, p65 and IκBα were measured by qRT-PCR, and the SIRT1 protein levels were analyzed by western blot and immunohistochemistry. Our results indicated that curcumenol significantly improved the renal functions in the CRF rats. Compared to the sham group, serum levels of NF-κB, MCP-1, IL-1β, and the mRNA expression levels of p65 were significantly increased (p < 0.01), whereas the mRNA expression level of IκBα was significantly decreased (p < 0.01) and the SIRT1 levels were dramatically down-regulated (p < 0.05) in the CRF groups. Treatment with curcumenol remarkably inhibited inflammatory responses as reflected by the reduced levels of inflammatory mediators (p < 0.01) and SIRT1 up-regulation (p < 0.05). Our findings suggested that curcumenol could improve the renal function in 5/6 nephrectomy-induced CRF rats, and the mechanisms might involve suppressing the associated inflammation and modulating the SIRT1 and NF-κB signaling pathways., (© 2022 American Association for Anatomy.)

There are still limitations in artificial bone materials used in clinical practice, such as difficulty in repairing large bone defects, the mismatch between the degradation rate and tissue growth, difficulty in vascularization, an inability to address bone defects of various shapes, and risk of infection. To solve these problems, our group designed stereolithography (SLA) 3D-printed calcium silicate artificial bone improved by a calcium sulfate-Cu 2+ delivery system. SLA technology endows the scaffold with a three-dimensional tunnel structure to induce cell migration to the center of the bone defect. The calcium sulfate-Cu 2+ delivery system was introduced to enhance the osteogenic activity of calcium silicate. Rapid degradation of calcium sulfate (CS) induces early osteogenesis in the three-dimensional tunnel structure. Calcium silicate (CSi) which degrades slowly provides mechanical support and promotes bone formation in bone defect sites for a long time. The gradient degradation of these two components is perfectly matched to the rate of repair in large bone defects. On the other hand, the calcium sulfate delivery system can regularly release Cu 2+ in the temporal and spatial dimensions, exerting a long-lasting antimicrobial effect and promoting vascular growth. This powerful 3D-printed calcium silicate artificial bone which has rich osteogenic activity is a promising material for treating large bone defects and has excellent potential for clinical application., Competing Interests: Author TZ was employed by Wuhan QISIDA Technology Development Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gao, Li, Lei, Chen, Huang, Yan, Xiao, Zhang, Wang, Wei and Hu.)

As an important 5-methylcytidine (m 5 C) methyltransferase, NOP2/Sun RNA methyltransferase family member 6 (NSUN6) has been reported to play an important role in the progression of several diseases. However, the role of NSUN6 in the progression of osteosarcoma (OS) remains unclear. This study aimed to identify the role of NSUN6 in the progression of OS and clarify the potential molecular mechanism. The present study discovered that NSUN6 was upregulated in OS and a higher NSUN6 expression was a strong indicator for poorer prognosis of patients with OS. In addition, the loss of NSUN6 led to reduced proliferation, migration and invasion of OS cells. Through bioinformatics analysis, RNA immunoprecipitation (RIP) and methylated RIP assays, eukaryotic elongation factor 1 α-2 (EEF1A2) was identified and validated as a potential target of NSUN6 in OS. Mechanistically, the expression of EEF1A2 was significantly suppressed following NSUN6 knockdown due to reduced EEF1A2 mRNA stability in an m 5 C-dependent manner. Meanwhile, NSUN6 deficiency inhibited m 5 C-dependent activation of Akt/mTOR signaling pathway. In addition, genetic overexpression of EEF1A2 or pharmacological activation of the Akt signaling pathway counteracted the suppressive effects of NSUN6 deficiency on the proliferation, invasion and migration of OS cells. The current findings suggested that NSUN6 may serve as a potential therapeutic target for OS treatment., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Hu et al.)

Objective: To explore the stability of seminal plasma miR-122-3p and miR-141-5p and their diagnostic value for idiopathic asthenospermia., Methods: Seminal plasma miR-122-3p and miR-141-5p with various incubation time, freeze-thaw cycles and incubation time were analyzed. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was used to detect the content of miR-122-3p and miR-141-5p, with U6 snRNA as the reference. The idiopathic asthenospermia group was further divided into grade I and II based on the progressive motility percent, and the content of miR-122-3p and miR-141-5p in the two grades were compared., Results: No difference was detected after incubation at room temperature and 4 degrees Celsius. But seminal plasma miR-122-3p and miR-141-5p have decreased along with the increase in freeze-thaw cycles increases. RT-PCR assayed showed that the miR-122-3p content in the idiopathic asthenospermia group was significantly lower than the control group, while miR-141-5p was significantly higher. The difference in both miR-122-3p and miR-141-5p content was statistically significant (P < 0.05). A significant difference in miR-122-3p and miR-141-5p content between a and b groups was also detected (P < 0.05). The AUC-ROC of miR-122-3p was 0.88. At the cutoff value of 1.02, the sensitivity and specificity was 83% and 84%, respectively. At the cutoff of 2.95, the AUC-ROC of miR-141-5p was 0.88. The sensitivity and specificity was 84% and 70%, respectively., Conclusion: MiR-122-3p and miR-141-5p in seminal plasma are stable and have certain value for the diagnosis of idiopathic asthenospermia.

This study aimed to examine the expression of and the relationship between CD44V6, CDH11, and β-catenin. The expression of these cell adhesion molecules was detected in 90 osteosarcoma and 20 osteochondroma specimens using immunohistochemistry. Associations between these parameters and clinicopathological data were also examined. The expression rates of CD44V6, CDH11, and β-catenin were 25.0% (5/20), 70.0% (14/20), and 20.0% (4/20) in osteochondroma specimens, respectively. Compared to osteochondromas, the proportions of expression of CD44V6 and β-catenin in osteosarcoma specimens increased to 65.6% (59/90) and 60.0% (54/90), respectively. However, the expression rate of CDH11 in osteosarcomas was reduced to 40.0% (36/90). The expression of these markers was significantly associated with metastasis and overall survival (P < 0.05). Survival analysis revealed that patients with increased expression of CD44V6 and β-catenin as well as decreased expression of CDH11 were correlated with a shorter survival time. Multivariate analysis indicated that clinical stage, metastasis status, and the expression of CD44V6, CDH11, and β-catenin were found to be associated with overall survival. Further, the expression of β -catenin and that of CD44V6 were positively correlated with each other. Thus, our results indicated abnormal expression of CD44V6, CDH11, and β-catenin in osteosarcomas and osteochondromas, which may provide important indicators for further research.