Combination chemotherapy and immunotherapy have failed to achieve breakthroughs in pancreatic ductal adenocarcinoma (PDAC). Chemotherapy-induced senescence is a potential solution for this problem. This study integrates clinical samples with single-cell transcriptomic sequencing, proteomics, and RNA sequencing and reveals that FOLFIRINOX (a combination regimen of 5-fluorouracil, oxaliplatin, irinotecan, and leucovorin) treatment induces a higher proportion of senescent tumor cells (senTCs). This phenomenon is principally attributed to the presence of cCCT2, which inhibits SLX4 condensate-mediated DNA damage repair pathways by regulating small ubiquitin-like modifier conjugation, thereby promoting tumor cell senescence. In the tumor immune microenvironment, cCCT2-overexpressing senTCs exhibit a senescence-associated secretory phenotype (SASP) with preferential secretion of CXCL10, which induces chemotaxis of CD8⁺ T-cells. Based on the pro-senescence and immune-microenvironment-remodeling effects of cCCT2, an engineered exosome-loaded circRNA system, SenExo-cCCT2 is developed. When combined with SenExo-cCCT2, the FOLFIRINOX regimen enhances the capacity of pancreatic cancer cells to induce senescence. Subsequently, anti-PD-L1 therapy facilitates the immune-mediated clearance of senTCs, markedly improving the therapeutic efficacy of combined chemotherapy and immunotherapy for pancreatic cancer.

Diabetes patients have reduced basal cognitive abilities like learning, memory, and perceptual quickness, as well as a 65 percent higher risk of acquiring AD. AD and diabetes share a number of risk factors, including elevated cholesterol, Aβ deposition, degeneration, inflammation, oxidative stress, cardiovascular diseases, dysmetabolism syndrome, τ-protein phosphorylation, glycogen synthesis kinase 3, apoptosis and apolipoprotein E4. This study explores the potential inhibitory effects of imatinib at doses of 1 and 5 mg/kg, with a particular emphasis on the role of c-Abl in amyloidogenesis, a common mechanism that underlies T2DM and AD. Induction of T2DM induced AD by HFD-STZ-Aβ_25-35 model. Assessment of behavioural parameters like polydipsia, polyphagia, morris water maze & passive avoidance test; biochemical estimation of glucose, insulin, oxidative stress (SOD, GSH, Cat, TBARS), neuroinflammation (IL-1β, IL-6, TNF-α, NF-κβ), Aβ levels, c-Abl through ELISA technique. Imatinib (1 & 5 mg/kg) results in a reduction in food and water intake, as well as a reduction in memory impairment in the Morris water maze and passive avoidance test. Further, it normalises glucose, insulin, and anti-oxidant elements (SOD, GSH, Cat) levels, while decreasing TBARS levels. Additionally, ELISA data demonstrated a reduction in neuroinflammation (downregulation of IL-1β, IL-6, TNF-α, and NF-κβ), Aβ accumulation, and c-Abl levels by imatinib (1 & 5 mg/kg). Consequently, c-Abl can play a crucial role in the mediation of amyloidogenesis induced by T2DM, thereby establishing a connection between T2DM and AD. Therefore, Imatinib has the potential to treat and prevent the progression of T2DM to AD.

Survival analysis consists of a set of statistical methods used to analyse data where the outcome variable is the time until an event occurs. When such data are collected across distinct spatial regions, incorporating spatial information into survival models can be beneficial. A common approach is to apply an intrinsic Conditional Autoregressive (CAR) prior to an area-level frailty term to account for spatial correlation between regions. We extend the Bayesian Cox semi-parametric model by incorporating a spatial frailty term using the Leroux CAR prior. The aim was to improve the model's ability to describe stroke hospitalisations at the Stroke Centre Hospital in Makassar, Indonesia with a focus on understanding the geographic distribution of hospitalisations, Length of Stay (LOS) and factors influencing patient outcomes. The dataset was obtained from medical records of stroke patients admitted to this hospital (April 2021-June 2024). Variables included LOS, discharge outcomes, sex, age, stroke type, uric acid levels, hypertension, hypercholesterolemia, and diabetes mellitus. Our findings indicate that diabetes, stroke type and the presence of hypercholesterolemia significantly influence recovery rates in stroke patients. Specifically, patients with diabetes had lower recovery, while those with hypercholesterolemia and ischemic stroke patients had faster recovery compared to those with haemorrhagic strokes.

Wumei Pills, a classic traditional Chinese medicine(TCM) formula, are widely used in the treatment of biliary ascariasis and diarrhea. In recent years, studies have shown that Wumei Pills have advantages in the treatment of type 2 diabetes mellitus(T2DM), while there are no relevant reports that systematically evaluate the efficacy of Wumei Pills in the treatment of T2DM. This study addresses this issue by systematically evaluating the efficacy and safety of Wumei Pills, aiming to provide an evidence-based basis for clinical practice. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, and VIP were researched for the randomized controlled trial(RCT) involving Wumei Pills for the treatment of T2DM that were published from inception to September 2024. RevMan 5.3 was used for the Meta-analysis of the data. A total of 18 RCTs were included, with a total of 1 437 patients. Meta-analysis produced the following results.(1)Treatment group outperformed control group in terms of overall response rate(RR=1.28, 95%CI[1.14, 1.43], P<0.000 1), fasting blood glucose(FPG)(WMD=-0.69, 95%CI[-0.93,-0.46], P<0.000 01), two-hour postprandial plasma glucose(2hPG)(WMD=-0.74, 95%CI[-1.17,-0.31], P<0.000 7), glycated hemoglobin(HbA1c)(WMD=-0.39, 95%CI[-0.60,-0.18], P=0.000 3), high-density lipoprotein(HDL)(WMD=0.38, 95%CI[0.28, 0.48], P<0.000 01), and body mass index(BMI)(WMD=-1.41, 95%CI[-2.40,-0.42], P=0.005).(2)The two groups had comparable effects regarding total cholesterol(TC)(WMD=-0.53, 95%CI[-1.13, 0.08], P=0.09) and low-density lipoprotein(LDL)(WMD=-0.25, 95%CI[-0.56, 0.06], P=0.12).(3)Triglycerides(TG)(WMD=-0.28,95%CI [-0.59,0.03],P=0.08), sensitivity analysis showed potential reduction effect(WMD=-0.20,95%CI[-0.36,-0.04],P=0.01). Occurrence of adverse drug reaction(RR=0.43,95%CI [0.23,0.80],P=0.007), sensitivity analysis showed significant disappearance(RR=0.56,95%CI[0.26,1.22],P=0.14), suggesting that the efficacy of treatment group was not better than that of control group. The results indicate that the treatment of T2DM with Wumei Pills is greatly related to the improvement of glucose metabolism, lipid metabolism, and clinical efficacy. The findings provide a basis for clinical application of Wumei Pills in treating T2DM, while the conclusion remains to be verified by clinical studies with higher quality.

Nutritional and immune status are emerging as systemic factors that may influence the onset and course of optic nerve disorders. Recognising their potential role in neuro-ophthalmology can enhance preventive strategies and support holistic patient management in clinical practice.

Non-arteritic anterior ischaemic optic neuropathy (NAION) is a common cause of sudden, painless vision loss in older adults. Although vascular and systemic risk factors such as diabetes mellitus and hypertension are well-documented, emerging evidence suggests that nutritional and immune status may also play a role in its development.

A retrospective case-control study was conducted involving 50 NAION patients and 50 age-matched ophthalmologically healthy controls. The Prognostic Nutritional Index (PNI) was calculated as 10 × serum albumin (g/dL) + 0.005 × lymphocyte count (per mm³). Controlling Nutritional Status (CONUT) scores were derived from serum albumin, total cholesterol, and lymphocyte counts. Group differences were assessed using the Mann-Whitney U and Chi-square tests. Logistic regression identified independent predictors of NAION, with significance set at p < 0.05.

PNI values were significantly lower in NAION patients than in controls (42.32 ± 5.05 vs. 46.87 ± 1.95, p < 0.001), while CONUT scores were significantly higher (1.24 ± 1.62 vs. 0.22 ± 0.50, p < 0.001). Both PNI (OR = 0.657, 95% CI: 0.531-0.812, p < 0.001) and CONUT (OR = 3.102, 95% CI: 1.236-7.789, p = 0.009) independently predicted NAION. Diabetes mellitus and hypertension were also more prevalent in the NAION group (p < 0.05).

PNI and CONUT scores may serve as non-invasive, independent biomarkers for assessing NAION risk. These findings underscore the contribution of systemic nutritional and immune factors to NAION pathogenesis and support their integration into comprehensive patient evaluations. Prospective studies are needed to confirm these results and explore clinical applications.

Motor signs are frequently observed over the clinical course of Alzheimer's disease (AD). We explored the potential clinical associations of motor manifestations in AD.

Our sample consisted of older adults (≥ 60 years) with AD from NACC. Individuals with Parkinson's disease or other Parkinsonian syndrome or under anti-parkinsonian agents were excluded. UPDRS III was used to assess motor signs in nine domains: hypophonia; masked facies; resting tremor; action/postural tremor; rigidity; bradykinesia; impaired chair rise; impaired posture/gait; postural instability. A global motor variable assessed the presence of at least one motor sign. Binary logistic models were estimated for the global (primary) and individual motor domain variables (secondary outcomes).

A total of 4771 older, predominantly female, well-educated participants were analysed: 3556 without (75.4 ± 7.6 years, 45.6% males) and 1215 with motor manifestations (79.4 ± 7.8 years, 44.4% males). The most influential risk factor for motor manifestations in AD was the Clinical Dementia Rating stage: stage one increased the odds of motor signs by ~ 44%, stage two by ~ 168% and stage three by ~ 437%. Each additional point on the Geriatric Depression Scale elevated the odds of motor manifestations by ~ 5%, whereas each additional point on the Mini-Mental State Examination decreased these odds by ~ 2.5%. Cerebrovascular disease (by ~ 44%), diabetes mellitus (by ~ 25%), traumatic brain injury (by ~ 30%), alcohol abuse (by ~ 33%), anxiolytics (by ~ 36%), antidepressants (by ~ 31%), antipsychotics (by ~ 48%) and β-blockers (by ~ 33%) elevated the odds of motor manifestations. Angiotensin II receptor blockers decreased the odds of motor manifestations (by ~ 33%).

Disease progression constitutes the most crucial clinical risk factor for motor manifestations in AD.

Diabetes mellitus, particularly type 2 diabetes (T2DM), is a major global health challenge characterized by persistent hyperglycemia resulting from insulin resistance. Protein tyrosine phosphatase 1B (PTP1B) has emerged as a key enzyme involved in regulating insulin signaling, making it a promising target for therapeutic interventions aimed at improving insulin sensitivity. However, the development of effective PTP1B inhibitors has been hindered by issues such as poor bioavailability and off-target effects. This study presents an integrated approach combining machine learning (ML), molecular docking, and molecular dynamics (MD) simulations to identify novel PTP1B inhibitors. An ML-based predictive model was developed using a dataset of over 2183 known PTP1B inhibitors to guide the selection of compounds with high inhibitory potential. Molecular docking was applied to a compound database of 1.6 million molecules, identifying 1057 promising candidates, which were then refined using the ML model to select the top five compounds. Additionally, the same strategy was applied to a natural product-derived compound database containing 160,000 molecules, leading to the identification of two additional PTP1B inhibitors. This comprehensive approach, combining ML with computational predictions, accelerates the drug discovery process and enhances the reliability of the findings, offering a promising pathway for the development of novel treatments for T2DM and related metabolic disorders.

Type 2 diabetes mellitus (T2DM) is a global health concern with significant mortality rate associated with comorbidities like diabetic kidney disease (DKD) and cardiovascular disease (CVD). Thus, treatment guidelines recommend first-line treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2Is) and/or glucagon-like peptide 1 (GLP-1) agonists for T2DM with comorbidities. However, in patients when these treatments are not tolerated, contraindicated, or considered expensive, dipeptidyl peptidase 4 inhibitors (DPP4Is) serve as an add-on or alternative for glycemic control without hypoglycemia risk. This study aimed to understand patients' preferences in three South Asian countries between SGLT2I (medication A) and DPP4I (medication B) and the reasons influencing their preference for effective management of T2DM.

In this cross-sectional study (November 2021 to November 2022) across India, Taiwan, and the Philippines, patients with T2DM on both SGLT2I and DPP4I or neither completed the survey to identify their medication preferences. Differences in baseline characteristics and preferred medication (chi-squared/Fisher's exact tests) and potential attributes influencing preferences (logistic regression) were analyzed.

Among 1224 participants, SGLT2I (64.5%) was significantly preferred over DPP4I (35.5%). Mean age of participants was 59.3 years and the majority were female patients/individuals (52.5%), overweight/obese (56.6%), with glycated hemoglobin levels ≥ 7% (57.6%). Common comorbidities included hypertension (62.7%) and dyslipidemia (75.5%); the majority were without history of CVD (83.7%) or CKD (84%). The most prescribed T2DM medication was biguanide (83.9%), followed by combination of SGLT2Is and DPP4Is (51.3%). The most influential attributes were blood sugar reduction (56.9%), reduced heart failure hospitalization (14.4%), and kidney disease risk reduction (12.1%). SGLT2I users showed a higher preference for heart failure hospitalization reduction (16.5%) or weight reduction (11.1%). Country of residence, thiazolidinedione use, and SGLT2I/DPP4I use were significant factors in logistic regression analyses.

Asian patients with T2DM preferred medication profile resembling SGLT2Is over DPP4Is. Understanding patient preferences may aid optimal glycemic control while reducing cardiovascular and renal risks.

In this review, we explore the under-recognized burden of fractures in diabetes, focusing on resource-constrained healthcare systems. We examine the epidemiology, assessment methodologies, and management approaches to osteoporosis in diabetes and discuss strategies to improve skeletal health outcomes.

Public healthcare strategies for fracture risk reduction in diabetes include educating healthcare providers, empowering patients, and integrating fracture liaison services for secondary prevention. Community-based awareness programs, digital health solutions, and screening tools such as FRAX® (with diabetes-specific adjustments) facilitate early identification and management. Policies supporting insurance coverage and cost-effective management strategies are likewise crucial. Diabetes-related bone fragility, characterized by altered bone quality and increased fracture risk despite relatively preserved bone density, creates a significant yet underrecognized health burden. Fracture prevention in diabetes is both a clinical necessity and an economic imperative. In this expanding cohort, multidisciplinary, policy-supported strategies can reduce morbidity, mortality, and costs associated with fragility fractures.

Diabetes Mellitus (DM) is a common metabolic disorder that requires ongoing treatment. While oral hypoglycemic drugs are commonly used, they do not provide a permanent cure and can have adverse effects. In order to find more effective treatments with fewer adverse effects, researchers are focusing on herbal sources. Saffron extract, known for its therapeutic and aromatic qualities, has shown promising antidiabetic effects in numerous in vivo and clinical studies. This study aims to explore the antidiabetic potential of safranal, an active constituent of saffron, with a specific focus on its ability to protect against diabetes-related endothelial damage.

In this study, five groups of four-month-old male Wistar albino rats were utilized. A diabetes model was induced using streptozotocin. Relax responses were assessed by various parameters, including blood glucose levels, weight, HbA1c, insulin levels, immunohistochemical analysis for aorta and pancreatic tissues, and relevant genes.

In this study, safranal treatment in three different doses did not affect weight but significantly reduced blood glucose levels depending on the dosage and duration of administration. HbA1c levels decreased, while insulin levels increased in treated rats. Insulin antibody staining in pancreatic tissues increased. Safranal treatment also reduced VCAM-1 gene expression and increased eNOS gene expression in thoracic aortic tissues. Additionally, safranal improved acetylcholine relaxation responses in isolated organ bath examinations.

Safranal demonstrates antidiabetic properties in streptozotocin-induced diabetic rats and has the potential to protect against diabetes-induced endothelial dysfunction.