Persistent hyperglycemia and uncontrolled type 2 diabetes contribute significantly to diabetes- related mortality by causing multiorgan and systemic injuries, particularly in vital organs such as the heart and kidneys, leading to both microvascular and macrovascular complications. The auto-oxidation of glucose increases oxidative stress, which in turn affects gene modulation and immune responses through the activation of four major pathways: (1) the polyol pathway, (2) the protein kinase C (PKC) pathway, (3) the advanced glycation end-product-receptor for advanced glycation end-product (AGE-RAGE) pathway, and (4) the hexosamine pathway. Oxidative stress and microRNAs (miRNAs) are closely related. These small non-coding RNAs bind to the 3' untranslated regions (3' UTRs) of target mRNAs, leading to mRNA degradation and translational repression. Although numerous studies have identified microRNAs (miRNAs) as important regulators of oxidative stress and diabetic complications, the available evidence remains fragmented. Therefore, this review aims to discuss the roles of miRNAs in oxidative stress-activated pathways and in the generation and detoxification of reactive oxygen species. It also highlights the potential of miRNAs as novel therapeutic targets in type 2 diabetes mellitus and outlines the challenges associated with their clinical application.

Statin-associated immune-mediated necrotizing myopathy (IMNM) is a distinct idiopathic inflammatory myopathy (IIM) associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies. The present study determined all-cause mortality among patients with statin-associated IMNM.

In this retrospective cohort study of 142 adult patients with IIM evaluated at a tertiary academic medical center, statin-associated IMNM was defined by IMNM with recent statin exposure. IIM was defined by standard criteria. The primary outcome was all-cause mortality. Age-adjusted Cox proportional hazards models were the primary analyses with additional adjustments for age, diabetes mellitus, and hyperlipidemia with propensity score-weighted Cox models.

Among 142 patients with IIM, 41 were statin-associated IMNM who were older and had shorter disease duration (p < 0.05). All-cause mortality was higher in statin-associated IMNM (31.7%, 13/41) than in IIM (23.8%, 24/101) (unadjusted HR 2.55, 95% CI 1.24-5.24; p = 0.011), with cardiopulmonary events and infections the major causes of death. In unadjusted analysis, statin-associated IMNM was associated with higher mortality (hazard ratio [HR] 2.55, 95% CI 1.24-5.24) and attenuated after age adjustment (HR 1.98, 95% CI 0.97-4.03) and was no longer statistically significant after adjustment for diabetes and hyperlipidemia (HR 1.70, 95% CI 0.71-4.08). Joint stratification by anti-HMGCR status and age (cutoff 60 years) demonstrated that older patients with statin-associated IMNM had the lowest survival among the four strata (log-rank P = 0.036).

Statin-associated IMNM is associated with higher mortality than other myositis subtypes; this excess attenuates after adjustment for age and cardiometabolic comorbidity, indicating these pre-existing conditions identify a higher-risk clinical phenotype.

To compare ⌀3.3 mm and ⌀4.1 mm hydrophilic titanium-zirconium implants supporting fixed dental prostheses (FDPs) in mandibular distal-extension situations among participants with varying degrees of hyperglycaemia.

Participants were stratified according to HbA1c (5.8%-< 7.0% vs. ≥ 7.0%) and subsequently randomized within each stratum to receive either ⌀3.3 mm or ⌀4.1 mm titanium-zirconium implants. Each participant received a two-implant-supported multi-unit FDP. The primary outcome was marginal bone level (MBL) change at 12 months after prosthesis delivery. Secondary outcomes included implant stability quotient (ISQ), peri-implant indices, Healing Index and patient-reported outcomes.

Of 88 enrolled participants, 83 (166 implants) were evaluated. Implant survival was 100%, with no peri-implantitis. At 12 months, MBL did not differ significantly between the ⌀3.3 mm [0.27 mm (IQR, 0.07-0.68)] and ⌀4.1 mm groups [0.27 mm (IQR, -0.04 to 0.54); p = 0.078]. Participants with HbA1c ≥ 7% had approximately sevenfold higher odds of MBL ≥ 0.5 mm than those with HbA1c < 7%. Secondary ISQ was significantly higher with ⌀4.1 mm implants (79.6 vs. 76.1; p < 0.001), whereas early healing was better with ⌀3.3 mm implants (p = 0.005). Chewing ability improved significantly from baseline to 12 months irrespective of implant diameter or HbA1c category (p < 0.0001).

At 1 year, ⌀3.3 mm and ⌀4.1 mm hydrophilic Ti-Zr implants demonstrated no statistically significant difference in MBL although ⌀4.1 mm implants demonstrated higher stability. Patient-reported chewing ability improved substantially following rehabilitation for both implant diameters. Higher HbA1c was associated with greater odds of clinically relevant MBL.

The trial was registered prospectively with the Clinical Trials Registry-India (CTRI/2017/08/009315).

Emerging evidence indicates that hypoxia- and cuproptosis-related molecular alterations may contribute to diabetic retinopathy (DR). This study aimed to identify biomarkers associated with these processes and investigate their biological relevance in DR.

The DR-related datasets GSE189005 and GSE221521 were sourced from public databases, while hypoxia-related and cuproptosis-related genes were extracted from published studies. Genes consistently differentially expressed across both datasets were intersected with those associated with hypoxia- and cuproptosis-related expression scores to derive candidate genes. Selection of candidate biomarkers was performed using machine-learning algorithms and expression consistency analysis, with diagnostic performance assessed via receiver operating characteristic (ROC) curves. Functional enrichment, immune cell infiltration, regulatory network analysis, candidate compound prediction, and reverse transcription quantitative PCR (RT-qPCR) were also conducted.

Intersection screening yielded 13 candidate genes. Machine-learning analysis identified three candidate biomarkers. Notably, MED19 and CA11 were consistently downregulated in DR, exhibiting area under the curve (AUC) values exceeding 0.70 in both datasets, thus qualifying as biomarkers. Functional enrichment analysis suggested MED19's involvement in "proteasome" and "spliceosome" pathways, while CA11 was linked to "regulation of autophagy" and "basal cell carcinoma" pathways. Differential infiltration of three immune cell populations (eosinophils, M2 macrophages, activated natural killer cells) was noted between DR and control groups in GSE189005, with M2 macrophages demonstrating a significant negative correlation with both biomarkers. Regulatory network analysis highlighted several candidate transcriptional regulators for MED19 and CA11, including ELF1-MED19 and KDM5B-CA11. Thirty candidate compounds/interventions were identified, including schizandrin B and pirinixic acid. RT-qPCR confirmed the significant downregulation of MED19 and CA11 in DR samples, providing preliminary support.

MED19 and CA11 were identified as biomarkers, presenting a potential framework for therapeutic intervention in DR.

Klotho, an anti-ageing protein involved in metabolic regulation, is downregulated in type 2 diabetes mellitus (T2DM). Prior studies suggest that enhancing Klotho expression may help manage diabetes and its complications. Yoga, with its systemic effects, may offer a promising non-pharmacological approach. The present study aimed to evaluate the effect of a 15-day structured yoga lifestyle (SYL) programme on serum Klotho levels and glycaemic parameters in individuals with T2DM.

This single-arm, open-label exploratory study was conducted on 74 adults (30-65 years) with T2DM. The SYL programme included asanas, pranayama, meditation, kriyas, a satvik diet, and spiritual sessions. Pre- and post-assessments included serum Klotho, fasting blood glucose (FBG), postprandial blood glucose (PPBG), and blood pressure (BP). The Wilcoxon signed-rank test was used.

Serum Klotho levels increased significantly by 14.65% (P < 0.001). FBG and PPBG were reduced by 5.97% and 3.68%, respectively (P < 0.001). Systolic BP was reduced modestly (P = 0.025); diastolic BP showed no change. Subgroup analysis showed greater Klotho increase in those aged > 55 years, females, non-hypertensives, and those with a longer duration of diabetes (P < 0.05).

The findings support SYL as a potential adjunct therapy. Longer controlled trials are needed to further establish these results.

Retinal ganglion cells (RGCs) degeneration is an early event in diabetic retinopathy (DR), tightly coupled to mitochondrial dysfunction. While the mitochondrial gatekeeper voltage-dependent anion channel 1(VDAC1) is a known mediator of apoptosis, its regulation and therapeutic targeting in diabetic RGCs remain unclear.

We examined VDAC1 expression in human donor retinas, streptozotocin-induced diabetic mice, and high glucose-treated SH-SY5Y cells. VDAC1-knockdown SH-SY5Y cells were established to explore its functional role in the context. Using virtual screening and molecular docking, we identified resveratrol (RSV) as a potential VDAC1 inhibitor, which was further validated by surface plasmon resonance binding assays and RSV-based pull-down experiments. The effects of RSV were assessed by RGCs survival, retinal electrophysiological function, and mitochondrial quality control. Tripartite motif-containing 23 (TRIM23)-VDAC1 interaction along with ubiquitination modifications were confirmed by co-immunoprecipitation. Finally, combination therapy involving RSV and adeno-associated virus serotype 2 (AAV2) carrying the γ-synuclein (SNCG) promoter mediated Trim23 overexpression was applied in both DR and acute ocular hypertension (AOH) animal models.

VDAC1 was upregulated in diabetic RGCs, and its knockdown was protective. We further discovered that RSV recruits the E3 ligase TRIM23 to VDAC1, inducing a K27-linked ubiquitination switch that promotes mitophagy instead of apoptosis. We propose that RSV binding acts as an allosteric switch, reconfiguring VDAC1 to favor this protective ubiquitination pathway. Consequently, RSV restored mitochondrial health and RGCs viability. Therapeutically, enhancing this axis via RSV and RGCs-targeted Trim23 overexpression synergistically protected against RGCs loss in both DR and AOH models.

Our study unveils a pharmacologically inducible switch wherein RSV, via direct VDAC1 binding, redirects its function toward TRIM23-mediated K27-linked ubiquitination and mitophagy. The TRIM23-VDAC1 allosteric axis represents a novel therapeutic paradigm for neuroprotective intervention in DR and beyond.

Cancer centers are required to facilitate interventions that engage communities in reducing the cancer burden in their catchment area. Tools exist to visualize catchment area data, but none integrate multiple factors for targeting interventions. The Community Need Priority Index-Breast Cancer Screening (CNPI-BCS) was created to approximate population-level need on the basis of characteristics associated with low adherence to routine screening guidelines. This study demonstrates program-specific utility of CNPI-BCS, by describing alignment between the index and patients reached by the mobile van.

Patients screened for breast cancer through mobile mammography were extracted from the electronic health record. Between 2021 and 2025, 3,662 patients were screened, across 418 mobile events, held with 176 community partners. Data were stratified by CNPI-BCS quintile, and Spearman rank correlation was used to evaluate trends by subgroup. Concordance between patient residential and screening locations was assessed. Multilevel logistic regression was used to estimate correlation of CNPI-BCS and underscreening (rarely/never screened) among mobile screening unit patients. Model performance was evaluated for discrimination and calibration.

The top CNPI-BCS quintile (n = 243 tracts) represented the highest-need communities, where the most events were held (n = 188, 45%) and the most patients were screened (n = 1,616, 44%). Underscreening rates increased monotonically from the lowest-need quintile (27%) to the highest-need quintile (47%). Forty-four percent were screened in the same quintile in which they lived. CNPI-BCS was positively associated with higher odds of underscreening (odds ratio, 1.20 per 0.1-unit [95% CI, 1.08 to 1.33]; P < .001). Receiver operating characteristic analysis showed satisfactory discrimination (corrected AUC = 0.692; apparent AUC = 0.735 [95% CI, 0.718 to 0.752]).

Findings demonstrate that CNPI-BCS accurately identifies screening need among a mobile mammography patient cohort, offering an evidence-based framework for identifying priority areas for breast cancer screening interventions.

Phlegmasia cerulea dolens (PCD) is a rare but serious complication of extensive venous thromboembolism (VTE) that can lead to limb ischemia and significant morbidity if not treated promptly. We describe a 69-year-old man with metastatic non-small cell lung cancer and hemorrhagic brain metastases who developed rapidly progressive PCD despite recent negative imaging and an existing inferior vena cava filter. He presented with bilateral lower extremity discoloration, absent Doppler signals, and signs of end-organ involvement. The patient underwent urgent mechanical thrombectomy with rapid clinical improvement and restoration of venous flow. This case highlights how quickly PCD can develop in high-risk patients and supports thrombectomy as a useful option for the resolution of extensive VTE and PCD.

A hallmark of glioblastoma (GBM) is disease recurrence that occurs in all patients despite resection, radiation, and chemotherapy. A critical challenge in GBM treatment is the management of recurrent disease for which no standard of care exists. Predicting the location of GBM recurrence may improve the efficiency of advanced-stage therapies. We present an artificial intelligence (AI)-based model to predict the recurrence risk of unprocessed surgical tissues at initial resection. AI-informed label-free optical microscopy was used to generate a normalized tumor infiltration value (AI-infiltration) for optical images of samples taken from resection cavity margins. These values, in combination with clinical, radiographic, and molecular variables, were used to build a predictive model of focal recurrence. In a cohort of 80 patients, comprising 367 samples and 133,454 unique images, GBM infiltration was significantly higher in margin samples from recurrent sites (P = 0.03) compared with those from nonrecurrent sites. A random forest machine learning classifier predicted site recurrence with an average area under the receiver operating characteristic curve of 87% ± 10.0 for the training cohort and 80% (95% confidence interval: 0.64 to 0.97) for the validation cohort. AI-infiltration was the strongest contributor to recurrence prediction, outperforming tumor molecular features. Model performance remained high regardless of tumor location, resulting in random forest model predictions of recurrence at 5 and 10 millimeters of each sample. These findings represent the potential of AI to predict sites of tumor recurrence, thereby improving accessibility to targeted, precision, and multimodal therapy for the highest-risk areas of disease.

The link between insulin resistance (IR) and hepatocellular carcinoma (HCC), especially in relation to HCV genotype-3 infection, is still poorly understood. In South Asian countries and among the peoples of the United States, this problem remains a major public health concern. According to previous studies, metabolic and viral interactomes have not been analyzed together, and hence this is a limitation of the study. This cross-sectional observational study involved 110 people, categorized into control (n=20), chronic hepatitis C (CHC) (n=45), and hepatocellular carcinoma (HCC) (n=45) groups. Clinical, biochemical, and metabolic parameters-HOMA-IR and HbA1c-were measured. The appropriate statistical tests were used for group comparisons. We performed molecular docking to investigate the interaction between the HCV genotype-3 core protein and human IRS-1 using ClusPro. HCC was independently associated with stage III-V fibrosis (AOR: 24.18), elevated HOMA-IR >4, a key indicator of insulin resistance (AOR: 3.53), and AFP >10 ng/mL (AOR: 3.71). Moreover, HbA1c >7% greater GGT and low albumin level were significantly higher in HCC group (P<0.05). Obese patients had higher IR markers, but CHC-to-HCC progression depended more on combined fibrosis and metabolic dysregulation than obesity alone. Docking analysis, there was a strong hydrophobic and electrostatic interaction between HCV core protein and IRS-1, with a binding energy of -1196.0 kcal/mol, indicating a strong and stable interaction between the two proteins. According to this study, it is possible that the presence of insulin resistance, advanced fibrosis, and viral persistence may interact biochemically and molecularly to contribute to hepatocellular carcinoma in cases of HCV genotype-3 infection.