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Breast cancer and diabetes are significant health challenges, and effective treatments for both diseases are lacking. Proton pump inhibitors (PPIs) have demonstrated anticancer and hypoglycemic effects, but their mechanisms of action are not yet fully understood. We used the GeneCards and PharmMapper databases to identify therapeutic targets for diabetes, breast cancer and PPIs. We identified common targets and constructed a regulatory network of diseases and drugs using the STRING database and Cytoscape software. We also explored the binding between small molecule ligands and protein receptors using Discovery Studio software. We identified 33 shared targets for breast cancer, diabetes, and PPIs including lansoprazole, omeprazole, and pantoprazole, which play a critical role in fatty acid transport, insulin resistance, apoptosis, and cancer-related signaling pathways. Our findings demonstrated that PPIs had a strong affinity for AKT1 and MMP9. This study provides insights into the mechanisms of action of PPIs in breast cancer and diabetes and identifies AKT1 and MMP9 as critical targets for future drug development. Our findings highlight the potential of PPIs as a novel therapeutic approach for these challenging diseases. [ABSTRACT FROM AUTHOR]

The public and social health burdens of ischemic stroke have been increasing worldwide. Hyperglycemia leads to a greater risk of stroke. This increased risk is commonly seen among patients with diabetes and is in connection with worsened clinical conditions and higher mortality in patients with acute ischemic stroke (AIS). Therapy for stroke focuses mainly on restoring cerebral blood flow (CBF) and ameliorating neurological impairment caused by stroke. Although choices of stroke treatment remain limited, much advance have been achieved in assisting patients in recovering from ischemic stroke, along with progress of recanalization therapy through pharmacological and mechanical thrombolysis. However, it is still necessary to develop neuroprotective therapies for AIS to protect the brain against injury before and during reperfusion, prolong the time window for intervention, and consequently improve neurological prognosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are broadly regarded as effective drugs in the treatment of type 2 diabetes mellitus (T2DM). Preclinical data on GLP-1 and GLP-1 RAs have displayed an impressive neuroprotective efficacy in stroke, Parkinson's disease (PD), Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), and other neurodegenerative diseases. Based on the preclinical studies in the past decade, we review recent progress in the biological roles of GLP-1 and GLP-1 RAs in ischemic stroke. Emphasis will be placed on their neuroprotective effects in experimental models of cerebral ischemia stroke at cellular and molecular levels. [ABSTRACT FROM AUTHOR]

Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) for ESRD. Single glomerular proteomics and immunohistochemistry were used to identify differentially expressed proteins and enriched pathways in glomeruli. During the median follow-up period of 24 months, 144 (45%) patients progressed to ESRD. In multivariable models, the Renal Pathology Society classification failed to predict ESRD, although the solidified glomerulosclerosis (score 1: HR 1.65, 95% confidence interval [CI] 1.04–2.60; score 2: HR 2.48, 95% CI 1.40–4.37) and extracapillary hypercellularity (HR 2.68, 95% CI 1.55–4.62) were identified as independent risk factors. Additionally, single glomerular proteomics, combined with immunohistochemistry, revealed that complement C9 and apolipoprotein E were highly expressed in solidified glomerulosclerosis. Therefore, solidified glomerulosclerosis and extracapillary hypercellularity predict diabetic ESRD in Chinese patients. Single glomerular proteomics identified solidified glomerulosclerosis as a unique pathological change that may be associated with complement overactivation and abnormal lipid metabolism. [ABSTRACT FROM AUTHOR]

Objective: To determine the relationship between ATP7B mutations and diabetes in Wilson disease (WD).Research Design and Methods: A total of 21 exons and exon-intron boundaries of ATP7B were identified by Sanger sequencing.Results: Two novel compound heterozygous mutations (c.525 dupA/ Val176Serfs*28 and c.2930 C>T/ p.Thr977Met) were detected in ATP7B. After d-penicillamine (D-PCA) therapy, serum aminotransferase and ceruloplasmin levels in this patient were normalized and levels of HbA1c decreased. However, when the patient ceased to use D-PCA due to an itchy skin, serum levels of fasting blood glucose increased. Dimercaptosuccinic acid capsules were prescribed and memory recovered to some extent, which was accompanied by decreased insulin dosage for glucose control by 5 units.Conclusions: This is the first report of diabetes caused by WD. [ABSTRACT FROM AUTHOR]

This article discusses findings of a study which evaluated and compared the epidemiological and clinical features of the metabolic syndrome in the Uygur and Kazak ethnic populations. The metabolic syndrome, which has been defined as a clustering of insulin resistance, hypertension, and dyslipidemia, has become a major public health issue worldwide. Previous studies have shown that the prevalence of hypertension and diabetes was significantly different between the Uygur and Kazak populations, the two major minorities in Xinjiang. The study reported a difference in distributions of the metabolic syndrome among ethnicities that was similar to previous studies. African Americans had a higher age-adjusted prevalence of hypertension, and Mexican-Americans had a higher age-adjusted prevalence of hyperglycemia. It is interesting that the different prevalence of hypertension and diabetes in the two ethnic populations with the same body-mass index (BMI) levels does not seem to be associated with obesity. Further analysis suggested that even with the same BMI, both Uygur males and females had a significantly greater waist-to-hip ratio than Kazak people.

Objective: To evaluate the cutoff value of HbA1c for predicting diabetes and prediabetes in a Chinese high risk population aged over 45.Methods: A total of 619 people aged over 45 without diabetes were randomly recruited to complete Finnish Diabetes Risk Score (FINDRISC) questionnaire. 208 high-risk individuals (defined by Diabetes Risk Score >=9) had OGTT and HbA1c determined at the same time.Results: In a Chinese population aged over 45, the best cutoff value of HbA1c for detecting diabetes and prediabetes was 5.8% and 5.4% respectively. The area under the receiver operating characteristic (AUROC) curve of HbA1c for detecting diabetes was 0.85 (95% CI: 0.80-0.90) and prediabetes was 0.62 (95% CI: 0.54-0.70). The combined use of HbA1c and fasting blood glucose (FPG) had larger AUROC than HbA1c alone (0.88, 95%CI: 0.83-0.92 in detecting diabetes vs 0.75, 95% CI: 0.67-0.82 in prediabetes), and had a higher sensitivity in predicting diabetes and higher specificity and positive predictive value (PPV) in predicting prediabetes. However, the AUROC between HbA1c alone and combined use in predicting diabetes was not significantly different (p=0.173).Conclusions: FINDRISC is feasible tool to screen people who are at high risk of diabetes. The cutoff values of HbA1c to diagnose diabetes and prediabetes in a Chinese high risk population aged over 45 were 5.8% and 5.4%, respectively. The sensitivity and specificity of HbA1c for detecting diabetes and prediabetes was relatively low, so that the combined use of HbA1c and FPG may be more effective in prediction. [ABSTRACT FROM AUTHOR]