A gut-derived hormone regulates cholesterol metabolism.

The reciprocal coordination between cholesterol absorption in the intestine and de novo cholesterol synthesis in the liver is essential for maintaining cholesterol homeostasis, yet the mechanisms governing the opposing regulation of these processes remain poorly understood. Here, we identify a hormone, Cholesin, which is capable of inhibiting cholesterol synthesis in the liver, leading to a reduction in circulating cholesterol levels. Cholesin is encoded by a gene with a previously unknown function (C7orf50 in humans; 3110082I17Rik in mice). It is secreted from the intestine in response to cholesterol absorption and binds to GPR146, an orphan G-protein-coupled receptor, exerting antagonistic downstream effects by inhibiting PKA signaling and thereby suppressing SREBP2-controlled cholesterol synthesis in the liver. Therefore, our results demonstrate that the Cholesin-GPR146 axis mediates the inhibitory effect of intestinal cholesterol absorption on hepatic cholesterol synthesis. This discovered hormone, Cholesin, holds promise as an effective agent in combating hypercholesterolemia and atherosclerosis.

Biological performance of a bioabsorbable magnesium-magnesium phosphate cement interbody fusion cage in a porcine lumbar interbody fusion model: a feasibility study.

PURPOSE: The aim of the study was to evaluate the feasibility of a bioabsorbable cage consisting of magnesium and magnesium phosphate cement (MPC) in a porcine lumbar interbody fusion model. METHODS: Twelve male Ba-Ma mini pigs underwent lumbar discectomy and fusion with an Mg-MPC cage or a PEEK cage at the L3/L4 and L4/L5 level. Computed tomography (CT) scans were made to evaluate the distractive property by comparing average disc space height (DSH) before and at 6, 12, and 24 weeks after the operation. After the lumbar spines were harvested at 6 or 24 weeks after the operation, micro-CT examination was conducted to analyze the fusion rate, and stiffness of motion segments was investigated through mechanical tests. A histological study was performed to evaluate the tissue type, inflammation, and osteolysis in the intervertebral space. RESULTS: CT scans showed no significant difference between the two groups in average DSH at each time point. Micro-CT scans revealed an equal fusion rate in both groups (0% at 6 weeks, 83.3% at 24 weeks). Both groups showed time-dependent increases in stability, the Mg-MPC cages achieved an inferior stiffness at 6 weeks and a comparable stiffness at 24 weeks. Histologic evaluation showed the presence of newly formed bone in both groups. However, empty spaces were observed at the interface or around the Mg-MPC cages. CONCLUSION: Compared with the PEEK cages, the Mg-MPC cages achieved comparable distraction, fusion rate, and spinal stability at 24 weeks after the operation. However, due to inferior stiffness at the early stage and fast degradation, further modification of material composition and design are necessary.

Effects of Dl-3-n-butylphthalide on neurological function, hemodynamics and Hcy concentration in cerebral hemorrhage: a systematic review and meta-analysis.

Background: Dl-3-n-Butylphthalide (NBP) has emerged as a potential therapeutic agent for cerebral hemorrhage, despite not being included in current guideline recommendations. Investigating the underlying physiological and pathological mechanisms of Dl-3-n-Butylphthalide in cerebral hemorrhage treatment remains a critical area of research. Objective: This review aims to evaluate the efficacy of Dl-3-n-Butylphthalide in cerebral hemorrhage treatment and elucidate its potential biological mechanisms, thereby providing evidence to support treatment optimization. Methods: A comprehensive search of seven electronic databases (PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP, and Wanfang Database) was conducted for studies published up to September 2023. Screening and data extraction were performed by a team of researchers. The Cochrane collaboration tool was utilized for risk bias assessment, and Revman 5.3 along with Stata 17.0 were employed for statistical analysis. Outcomes: We searched 254 literature, and 19 were included in this meta-analysis. The results showed that Dl-3-n-Butylphthalide improved the clinical efficacy rate (RR = 1.25, 95% CI 1.19-1.31; p = 0.00), quality of life (MD = 13.93, 95% CI: 11.88-15.98; p = 0.000), increased cerebral blood flow and velocity, reduced cerebral edema volume, Hcy concentration, and did not have obvious adverse reactions (RR = 0.68, 95% CI: 0.39-1.18; p = 0.10). Conclusion: This meta-analysis is the first to demonstrate the potential of Dl-3-n-Butylphthalide in treating cerebral hemorrhage. It suggests that Dl-3-n-Butylphthalide may alleviate clinical symptoms by modulating neurological function and improving hemodynamics. Our findings provide robust evidence for incorporating Dl-3-n-Butylphthalide into cerebral hemorrhage treatment strategies, potentially guiding future clinical practice and research. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/ display_record.php?RecordID=355114, Identifier CRD42022355114.

Association of blood urea nitrogen to creatinine ratio with incident type 2 diabetes mellitus: A retrospective cohort study in the Chinese population.

Renal dysfunction can lead to insulin resistance and increase the incidence of type 2 diabetes mellitus (T2DM). The blood urea nitrogen to creatinine ratio (NCR) is a frequently used indicator to assess renal dysfunction and differentiate between prerenal and intrinsic renal injury. However, the association between NCR and T2DM in the Chinese population remains unclear. Hence, this study aimed to investigate the association between NCR and the incidence of T2DM in the Chinese population. The relationship between NCR and T2DM was examined using the Cox proportional hazards model and curve fitting techniques. In addition, a comprehensive set of sensitivity and subgroup analyses were performed. All results were presented as hazard ratios (HRs) and 95% confidence intervals (CIs). Between 2010 and 2016, 189,416 Chinese people were recruited from the Rich Healthcare Group for this retrospective cohort study. Of the participants, 3755 (19.8%) were diagnosed with T2DM during the follow-up period. After full adjustment, the Cox proportional hazards model revealed a positive connection between NCR and the incidence of T2DM (HR = 1.03, 95% CI: 1.02-1.04, P < .001). Compared with individuals with lower NCR Q1 (≤13.536), the multivariate HR for NCR and T2DM in Q2 (13.536-16.256), Q3 (16.256-19.638), Q4 (>19.638) were 1.08 (0.98-1.19), 1.16 (1.05-1.28), 1.39 (1.26-1.53). The higher NCR groups (≥20) had a higher ratio of T2DM (HR = 1.28, 95% CI: 1.18-1.38, P < .001) than the lowest NCR group (<20). These findings were validated using sensitivity and subgroup analyses. In conclusion, this study found a positive and independent association between NCR and the incidence of T2DM after adjusting for confounding variables.

DNAzyme-RCA-based colorimetric and lateral flow dipstick assays for the point-of-care testing of exosomal m5C-miRNA-21.

Methylation of microRNAs (miRNAs) is a post-transcriptional modification that affects miRNA activity by altering the specificity of miRNAs to target mRNAs. Abnormal methylation of miRNAs in cancer suggests their potential as a tumor marker. However, the traditional methylated miRNA detection mainly includes mass spectrometry, sequencing and others; complex procedures and reliance on large instruments greatly limit their application in point-of-care testing (POCT). Based on this, we developed DNAzyme-RCA-based gold nanoparticle (AuNP) colorimetric and lateral flow dipstick (LFD) assays to achieve convenient detection of exosomal 5-methylcytosine miRNA-21 (m5C-miRNA-21) for the first time. The two assays achieved specific recognition and linear amplification of m5C-miRNA-21 through the DNAzyme triggered RCA reaction and color output with low background interference through AuNP aggregation induced by base complementary pairing. The lowest concentration of m5C-miRNA-21 visible to the naked eye of the two assays can reach 1 pM and 0.1 pM, respectively. Detection of exosomal m5C-miRNA-21 in clinical blood samples showed that the expression level of m5C-miRNA-21 in colorectal cancer patients was significantly higher than that in healthy individuals. This approach not only demonstrates a new strategy for the detection of colorectal cancer but also provides a reference for the development of novel diagnostic tools for other miRNA methylation-related diseases.