Identification of diagnostic gene signatures and molecular mechanisms for non-alcoholic fatty liver disease and Alzheimer's disease through machine learning algorithms.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and Alzheimer's disease (AD) pose significant global health challenges. Recent studies have suggested a link between these diseases; however, the underlying mechanisms remain unclear. This study aimed to decode the shared molecular landscapes of NAFLD and AD using bioinformatic approaches. METHODS: We analyzed three datasets for NAFLD and AD from the Gene Expression Omnibus (GEO). This study involved identifying differentially expressed genes (DEGs), using weighted gene co-expression network analysis (WGCNA), and using machine learning for biomarker discovery. The diagnostic biomarkers were validated using expression analysis, receiver operating characteristic (ROC) curves, and nomogram models. Furthermore, Gene Set Enrichment Analysis (GSEA) and CIBERSORT were used to investigate molecular pathways and immune cell distributions related to GADD45G and NUPR1. RESULTS: This study identified 14 genes that are common to NAFLD and AD. Machine learning identified six biomarkers for NAFLD, four for AD, and two crucial shared biomarkers: GADD45G and NUPR1. Validation confirmed their expression patterns and robust predictive abilities. GSEA revealed the intricate roles of these biomarkers in disease-associated pathways. Immune cell profiling highlighted the importance of macrophages under these conditions. CONCLUSION: This study highlights GADD45G and NUPR1 as key biomarkers for NAFLD and AD, and provides novel insights into their molecular connections. These findings revealed potential therapeutic targets, particularly in macrophage-mediated pathways, thus enriching our understanding of these complex diseases.

Sarcopenia is an independent risk factor for all-cause mortality rate in patients with diabetic foot ulcers.

Objective: This study aimed to determine whether sarcopenia affects the all-cause mortality rate of patients with diabetic foot ulcers (DFUs). Research design and methods: The clinic-based observational study included 217 patients treated at the Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University during a 4-year period. All subjects underwent dual-energy X-ray absorptiometry to determine their body composition during hospitalization. Diagnosis of sarcopenia was based on the Baumgartner diagnostic criteria. Patients were followed up regularly by phone calls until April 1, 2019, and their survival status was recorded.Univariate and multivariate Cox risk ratio regression models were used to analyze factors influencing the all-cause mortality rate of patients with DFUs. Results: Of the 217 patients, 158 people survived (82.7%), 33 died (17.3%), and 26 were lost to follow-up. The median follow-up time was 23 (Range 11-34) months. The majority of patients were male (68.6%), with a mean age of 67.29 ± 11.14 years. The 5-year survival rate was 68.3% and 45.9% for all study patients (n = 217) and sarcopenia patients (n = 81), respectively. Multivariate Cox risk regression model showed that age (HR 1.042[95%CI:1.006, 1.078], P = 0.021), sarcopenia (HR 5.051[95%CI:1.968, 12.961], P = 0.001), and serum creatinine (HR 1.007[95%CI: 1.003, 1.010], P < 0.001) were independent risk factors for all-cause mortality rate of patients with DFUs. Kaplan-Meier survival curve indicated that the survival rate of patients with sarcopenia was significantly lower than non-sarcopenia patients (P < 0.001). Conclusions: Sarcopenia is an independent risk factor for all-cause mortality of patients with DFUs and hence an important prognostic factor for patients with DFUs. Active prevention and improvement of sarcopenia can potentially improve the survival outcomes of this patient population.

Anhuienoside C Attenuates Podocyte Injury in Diabetic Nephropathy Rats.

OBJECTIVE: The present study evaluated the nephroprotective effects of anhuienoside C (AC) against diabetic nephropathy (DN) in rats. MATERIAL AND METHODS: Diabetic nephropathy was induced by administration of a high-fat diet (HFD) for 8 weeks and intraperitoneal administration of streptozotocin (STZ; 30 mg/kg) at the end of the fourth week of this protocol. Effects of AC on blood glucose levels, renal function markers, and mediators of inflammation in the serum of DN rats were assessed. RESULTS: Anhuienoside C treatment reduced the blood glucose levels and attenuated the increased levels of renal injury markers in DN rats. Anhuienoside C also increased podocyte counts; alleviated the changes in podocin, desmin, and nephrin protein levels; and ameliorated the altered pathophysiology in the kidney tissues induced by DN. Compared with the DN group, the levels of inflammatory markers and mediators of oxidative stress were reduced in the serum and kidney tissues of the AC-treated groups. Moreover, treatment with AC ameliorates the altered expression of podocin, nephrin, and desmin proteins in the renal tissue of HFD/STZ-induced kidney-injured rats. CONCLUSION: In conclusion, AC protected against podocyte injury by regulating nuclear factor kappa-light-chain-enhancer of activated B cells/protein kinase B pathway in a rat model of DN.

Fangchinoline Protects Against Renal Injury in Diabetic Nephropathy by Modulating the MAPK Signaling Pathway.

In this study, we evaluated the nephroprotective effects of fangchinoline in rats with diabetic nephropathy (DN). DN was induced by feeding a high-fat diet for 4 weeks and administering a single dose of streptozotocin (STZ) (30 mg/kg) intraperitoneally. The rats were split into groups; one group received oral fangchinoline (3 mg/kg) per day for 8 weeks. After completion of the 8-week study period, biomedical and inflammatory markers were evaluated in serum and urine, and oxidative stress was estimated in kidney tissues. In addition, Western blot assays, reverse transcription-polymerase chain reaction, and immunohistochemical analyses were performed in the kidney tissues of DN rats. The results suggest that treatment with fangchinoline attenuated the biochemical marker changes induced by DN in blood and urine. Moreover, a significant (p<0.01) reduction in inflammatory markers in serum was found in the fangchinoline group compared to the controls. Immunohistochemical analyses also revealed that treatment with fangchinoline significantly reduced the expression of collagen IV and CD31 in the kidneys compared to the control group. The expression of p38 MAPK, TNF-α, COX-2, and MMP-9 was also attenuated by fangchinoline treatment in the kidney tissues of DN rats. Together, the results of this study suggest that fangchinoline protects against nephron damage by attenuating alterations in the p38 MAPK pathway, thereby reducing oxidative stress and inflammation in DN rats.

Diosmetin Attenuates Akt Signaling Pathway by Modulating Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κB)/Inducible Nitric Oxide Synthase (iNOS) in Streptozotocin (STZ)-Induced Diabetic Nephropathy Mice.

BACKGROUND We evaluated the nephroprotective effect of diosmetin in streptozotocin (STZ)-induced diabetic nephropathy (DN) mice. MATERIAL AND METHODS Diabetes was induced by injecting STZ (50 mg/kg) i.p. for 5 days. Biochemical parameters, such as fasting blood glucose, creatinine, BUN in the serum, and albumin in the urine, were determined in STZ-induced DN mice after the 8th week of STZ administration. The level of inflammatory mediators in the serum and oxidative stress parameters in the tissue homogenate was estimated in STZ-induced DN mice. Expressions of Akt, NF-κB, and iNOS in the tissue homogenate were assessed by Western blot analysis. RESULTS Our data reveal that treatment with diosmetin significantly reduces the fasting blood glucose (FBG), serum creatinine, and blood urea nitrogen (BUN) in the serum and albumin in urine compared to the negative control group. Treatment with diosmetin attenuated the altered level of oxidative stress parameters and inflammatory cytokines in the STZ-induced DN mice. Expression of Akt and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was significantly reduced and inducible nitric oxide synthase (iNOS) was enhanced in the tissue homogenate of diosmetin-treated mice compared to the negative control group. Data from immunohistochemical analysis suggest that the expressions of NF-κB was significantly reduced in tissues of the diosmetin-treated group compared to the negative control group. CONCLUSIONS Our study shows that diosmetin protects against renal injury in STZ-induced diabetic nephropathy mice by modulating the Akt/NF-κB/iNOS signaling pathway.