SEARCH · Search PubMed

Results for “cord blood mononuclear cells”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

680 records · Page 9Linked to original sources

PubMed2026

The effectiveness of digital health interventions for type 2 diabetes in underserved populations: A systematic review and meta-analysis.

This systematic review and meta-analysis of 12 randomized controlled trials (1835 participants) evaluated whether digital health interventions (DHIs) improve glycemic control among underserved adults with type 2 diabetes (T2D), including racial/ethnic minority, low-income, Medicaid-insured, rural, and low-health-literacy populations. Searches of PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to December 20, 2025 identified eligible parallel-group randomized controlled trials reporting change in hemoglobin A1c (HbA1c). Two reviewers independently screened studies, extracted data, and assessed risk of bias using the revised Cochrane Risk of Bias 2 tool. Random-effects meta-analysis showed that DHIs produced a modest but statistically significant HbA1c reduction versus control (mean difference, -0.37 %age points; 95% CI, -0.44 to -0.30; P < .0001; equivalent to -4.0 mmol/mol). Heterogeneity was moderate-to-substantial (I² = 69.9%). Subgroup analyses suggested directionally similar effects by population group and intervention modality, but interpretation was limited by study-level data and the small number of trials. Funnel-plot inspection and Egger's test (P = .31) did not suggest major small-study effects, although power was limited. Overall certainty for HbA1c was moderate. DHIs may support more equitable diabetes care when implemented with cultural tailoring, language access, digital-literacy support, and technology-access safeguards.

Humans↗

PubMed2026

Plasma proteomics: considerations for preanalytical variability; a systematic review with narrative synthesis.

BACKGROUND: The plasma proteome (PP) is a dynamic system subject to pathology-associated changes and a focus for novel disease biomarker discovery. Disease-related PP research assumes protein concentrations in test specimens accurately reflect the in vivo milieu. However, measures to maintain the physicochemical integrity of the proteome before assay are often rudimentary, poorly described, or lacking standardisation in published studies. Contrastingly, in laboratory medicine, there is an expectation that errors in the so-called "preanalytical phase" (PAP) that impact patient results are understood, monitored, and mitigated against, while also being well described in research publications. There is therefore scope for good practice from laboratory medicine to inform PP research workflows. This review considers factors in the PAP which may impact the validity of PP results. CONTENT: A systematic review was conducted per PRISMA guidelines, limited to English-language peer-reviewed studies (2014-2024). Candidate studies were imported, screened, and managed using Covidence systematic review software. SUMMARY: 15 eligible studies were reviewed, covering many relevant processes. 11 studies reported statistically significant differences in PP due to factors in the PAP. Temperature and time-to-processing were the most commonly reported factors affecting the PP, with significant effects reported in 8 studies. OUTLOOK: PAP variability can significantly affect results in PP studies. Careful consideration of the effect of each stage of the PAP is needed when working with the PP. In multicenter studies, pre-defined and research question-specific sample processing workflows are essential for reducing PAP variability, which helps ensure the validity of PP studies.

Humans↗

PubMed2026

Flexible ureteroscopy with a flexible and negative suction ureteral access sheath versus traditional sheath for treatment of infectious upper urinary tract stones: A prospective, randomized controlled study.

To evaluate the efficacy and safety of the flexible ureteroscopy (fURS) with a flexible and negative suction ureteral access sheath (FANS) versus traditional sheath for patients with infectious upper urinary tract stones (IUUTS). A total of 185 patients were enrolled, with 93 assigned to the FANS group and 92 to the traditional UAS group. The primary outcome was the stone-free rate (SFR) at the first postoperative day. Secondary outcomes included the SFR at 30 days postoperatively, operative time, hemoglobin reduction, length of hospital stay, quality of life (QoL) improvement, incidence of ureteral stricture at 3 months, and surgery-related complications. No significant differences were observed between the two groups in baseline demographics or preoperative clinical characteristics (P > 0.05). The FANS group had significantly lower white blood cell count, C-reactive protein, and procalcitonin levels at 6 and 24 h postoperatively (all P < 0.05). Mean operative time was significantly shorter (P < 0.001), QoL improvement was obviously greater (P < 0.001), and average hospital stay was shorter in the FANS group (P < 0.001). The SFRs on postoperative day 1 and at 30 days were both significantly higher in the FANS group (both P < 0.05). At 3 months, ureteral strictures occurred in three patients in the traditional UAS group and one in the FANS group, a difference that was not statistically significant (P > 0.05). The overall complication rate was significantly lower in the FANS group (P < 0.05). For patients with IUUTS, fURS combined with FANS effectively improves stone clearance efficiency and reduces the risk of postoperative infection.

Humans↗

PubMed2026

Systemic biomarkers of treatment response to methotrexate in people with painful knee osteoarthritis: A biological substudy of the PROMOTE randomised controlled clinical trial.

OBJECTIVE: Stratification of therapeutic responses may help identify efficacious therapies for osteoarthritis (OA). In the PROMOTE randomised trial, participants with elevated baseline high-sensitivity C-reactive protein (hs-CRP) showed greater pain reduction after methotrexate treatment. We set out to interrogate a broader panel of serum/plasma inflammatory response markers relevant to methotrexate actions as potential biomarkers of therapeutic effect. Our objectives were to: (i) characterize changes in these systemic markers during methotrexate treatment; determine whether (ii) baseline levels or (iii) changes in any marker during treatment were associated with treatment response; and (iv) compare these findings with the more established clinical inflammatory marker, hs-CRP. DESIGN: Plasma/serum samples from participants in PROMOTE's biological substudy were analysed for 35 inflammatory markers at baseline (pre-treatment) and at 6-months (post-treatment), by MesoScale V-plex multiplex assay. Those with paired biological and clinical data at both baseline and 6-months were included in the substudy analysis set. Relationships between markers and overall data structure were assessed by Pearson correlation and Principal Component analysis. Associations between markers (baseline levels or change over time) and change in average knee pain severity in past week (numerical rating scale, NRS) were evaluated by univariable linear regression, adjusting for baseline age, sex, and body mass index. Least Absolute Shrinkage and Selection Operator (LASSO) regression with bootstrap resampling enabled marker selection. Benjamini-Hochberg correction adjusted for multiple testing (Padj). RESULTS: 87 participants with paired blood marker and clinical data were eligible for substudy analysis. 18/35 markers were quantifiable and analysed. Systemic IL-8 and TNF-α levels decreased (Padj=0.015, 0.048 respectively) while IL-15 increased (Padj=0.033) with methotrexate treatment over 6-months. Analysing within this active treatment randomised arm, higher baseline IFN-γ was associated with greater reduction in NRS pain change (0.66 [0.01, 1.31], P=0.047), as was decreasing TNF-α over 6-months (2.25 [0.00, 4.5], P=0.049). LASSO identified higher IFN-γ, lower plasma IL-15 and IL-16, and younger age as the most important baseline predictors of pain improvement. hs-CRP was highly selected by LASSO for treatment response in both arms. In a secondary univariate treatment arm-by-biomarker interaction analysis, of the 19 markers, only hs-CRP showed consistent effects in adjusted models (at baseline, coeffic. 2.34 [0.53, 4.15], P=0.001; change over 6-months, (0.36 [0.06, 0.66], P=0.018). CONCLUSIONS: Blood measurement of IFN-γ, TNF-α, IL-15 and IL-16 as well as hs-CRP could act as potential markers to stratify the treatment response by average knee pain to methotrexate in knee osteoarthritis.

Humans↗

PubMed2026

Closed-loop vasopressor systems for hemodynamic control in perioperative and critical care settings: a systematic review and meta-analysis.

Maintaining mean arterial pressure (MAP) within a predefined target is central to haemodynamic management in surgical and critically ill adults receiving vasopressors. Closed-loop vasopressor (CLV) systems automate titration to optimise blood pressure control, but their clinical effectiveness remains uncertain. We performed a systematic review and meta-analysis comparing CLV with manual titration. This PRISMA 2020-compliant review was prospectively registered in PROSPERO (CRD420250655697). MEDLINE, Embase, Scopus, Web of Science, CENTRAL, and the Cochrane Library were searched (January 2000-June 2025). Randomised controlled trials enrolling adults receiving vasopressors in perioperative or intensive care settings were included. Primary outcomes were time within the MAP target range and time spent in hypotension or hypertension. Risk of bias was assessed using RoB 2.0 and certainty of evidence using GRADE. Random- or fixed-effects models were selected according to heterogeneity. Six randomized controlled trials (215 patients) were included in the systematic review, whereas five perioperative trials contributed to the meta-analysis of haemodynamic control outcomes, and one ICU-based study was summarized narratively because it did not report comparable MAP control endpoints. CLV increased time within the MAP target range (mean difference [MD] 33.94%, 95% CI 20.41-47.46; I2 = 77%) and reduced time in hypotension (MD - 18.24%, 95% CI - 28.95 to - 7.53; I2 = 73%). There was no significant difference in time in hypertension, cumulative norepinephrine dose, or major/minor adverse events. ICU length of stay was not pooled because of clinical and methodological heterogeneity. Certainty of evidence ranged from low to high (moderate for haemodynamic control outcomes). CLV systems improved haemodynamic control, primarily in perioperative settings, but heterogeneity and small samples limit confidence in effect size and generalisability. Evidence in critically ill populations remains limited, and larger trials are needed to determine whether improvements in these physiological surrogate endpoints translate into meaningful patient-centred outcomes.

Humans↗

PubMed2026

Duration and characteristics of hypoglycemia with once-weekly insulin efsitora alfa versus once-daily basal insulins in adults with type 2 diabetes: Exploratory safety analysis of QWINT 2-4.

AIMS: Efsitora is a novel once-weekly basal insulin. Efsitora demonstrated similar efficacy and safety compared with once-daily basal insulin comparators across four phase 3 clinical trials for type 2 diabetes. This exploratory safety analysis further characterizes hypoglycemia events in the efsitora and once-daily treatment groups in three of these trials (QWINT-2, -3, and -4). METHODS: Median duration of hypoglycemia events was assessed with masked continuous glucose monitoring. Incidence of persistent-recurrent (PR) hypoglycemia was assessed by investigators and by a pre-specified algorithm using SMBG e-diary data. Factors contributing to hypoglycemia, characteristics of hypoglycemia, and treatment methods were reported by participants and assessed across groups. RESULTS: Across the three trials, durations of hypoglycemic events for efsitora vs once-daily basal insulin comparators were: Level 1 and 2 [<70 mg/dL]: 40-42.5 vs 40 min; Level 2 [<54 mg/dL]: 35-39.9 vs 35 min. Few incidences of PR hypoglycemia were reported for efsitora or once-daily comparators. No major descriptive differences were observed between hypoglycemia contributing factors, characteristics, or treatment methods in efsitora and once-daily treatment groups. CONCLUSIONS: No clinically relevant differences were observed between the duration or characteristics of hypoglycemic events in efsitora and once-daily treatment groups in the QWINT-2, -3, and -4 trials.

Adult↗

PubMed2026

Glycemic and safety outcomes of the insulin-only bionic pancreas in older adults and individuals with impaired awareness of Hypoglycemia: a post hoc analysis of a randomized pivotal trial.

AIMS: Evaluate the efficacy and safety of iLet Bionic Pancreas (BP) in older adults and individuals with impaired awareness of hypoglycemia (IAH). METHODS: This post hoc analysis used individual participant-level data from the Insulin-Only Bionic Pancreas Pivotal Trial (n = 440; NCT04200313). Eligible participants (n = 96) with type 1 diabetes, aged ≥ 60 years and/or had IAH (Clarke score ≥ 4), were randomized to BP with aspart/lispro (BP-Asp/Lis; n = 45), BP with fast-acting aspart configuration (BP-Fiasp; n = 31), or standard care (SC; n = 20) for 13 weeks. RESULTS: Compared with SC, time-in-range (70-180 mg/dL) significantly increased by 7.49 % (95 % CI: 2.61 to 12.38; ∼1.8 h/day) with BP-Asp/Lis and by 8.28 % (95 % CI: 3.15 to 13.41; ∼2.0 h/day) with BP-Fiasp, driven by reduced hyperglycemia. No significant differences were observed in hypoglycemia exposure. Severe hypoglycemia occurred in four participants (four events) on BP-Asp/Lis and one participant (two events) on SC. One diabetic ketoacidosis event occurred on BP-Fiasp due to an infusion set failure. CONCLUSIONS: In high-risk, clinically vulnerable populations, the BP system significantly improved glycemic control while maintaining safety parity with respect to hypoglycemia risk, providing a resilient therapeutic alternative for vulnerable cohorts.

Humans↗

PubMed2026

Measurement of low-density lipoprotein cholesterol and other circulating lipids in Brazil: a systematic literature review.

Accurate laboratory assessment of circulating lipids underpins cardiovascular risk stratification, yet clinical interpretation depends not only on the assays but on the formula chosen to estimate low-density lipoprotein cholesterol (LDL-C). This review integrates the 2019-2025 evidence on laboratory methods for triglycerides (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDLC), and on the formulas estimating LDL-C, VLDL-C, and non-HDL cholesterol, to determine how these should be measured, reported, and harmonized in Brazil, where lipid thresholds are adapted from international consensus. A PRISMA 2020 systematic search (PROSPERO CRD420251241064) of PubMed/MEDLINE, Scopus, SciELO, LILACS, Web of Science, and Embase retrieved 57,915 records; after removing 38,210 duplicates, 19,705 titles/abstracts were screened, 312 full texts assessed, and 25 sources included. Enzymatic colorimetric assays remain standard for TG, TC, and HDLC. For LDL-C, Martin/Hopkins classifies more accurately than Friedewald (89.6% vs 83.2% correct categorization in 5,051,467 patients), particularly at high TG and low LDL-C, while Sampson/NIH and modified Sampson/NIH extend reliable estimation into hypertriglyceridemia and very low LDL-C; direct measurement is reserved for TG beyond the validated range. Although the review centers on the Friedewald, Martin/Hopkins, and Sampson/NIH families that dominate guideline practice, other published equations exist and are addressed in context. In Brazil, atherogenic-lipid thresholds are risk-based decision limits rather than reference intervals; national surveys describe lipid distributions but were not designed to establish them. Analytical standardization through traceability programs, multicenter validation of formulas, and-where the distribution-based construct applies (HDLC, pediatrics)-nationally derived reference intervals are priorities for equitable cardiovascular risk assessment in Brazil.

Humans↗

PubMed2026

Factors Impacting Overall Survival Post-Relapse in High-Risk Neuroblastoma: Children's Oncology Group Outcomes From 2000 to 2019.

PURPOSE: Prior studies of features impacting post-relapse survival in high-risk neuroblastoma (HRNB) evaluated patient cohorts that did not receive contemporary high-risk or relapse therapies. We describe overall survival (OS) after first progression or first relapse of HRNB in a modern cohort. METHODS: Patients with HRNB enrolled on COG ANBL00B1(NCT00904241) between 2000 and 2019, who had relapsed or progressive disease were eligible. Clinical and molecular risk factors at diagnosis, therapy era, clinical trial enrollment, and clinical features at relapse, including site of and time to relapse, were evaluated. OS post-relapse was compared between groups using log-rank tests and Cox models. RESULTS: Among 4253 eligible HRNB patients, 1616 had relapse or progression as a first event. Five-year OS post-relapse was 19.1 ± 1.1%. The risk group with the lowest post-relapse survival was observed in patients with INSS Stage 4 or 4S disease < 18 months of age at diagnosis with MYCN amplified (MYCN-A) tumors. The other significant most unfavorable factors at diagnosis included diagnosis 2000-2004, tumor MYCN-A, 1p loss of heterozygosity (LOH), and elevated LDH or ferritin. Unfavorable factors at relapse included the time to relapse < 36 months from diagnosis, and combined local and metastatic disease at relapse. Multivariable analysis indicated that those with tumors harboring 1p LOH, age ≤ 5 years at diagnosis, or earlier treatment therapy era (2000-2004) had a higher risk of post-relapse death. CONCLUSIONS: While the 5-year OS rate was low in this cohort, there are subsets of patients with relapsed HRNB who demonstrate long-term survival. TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT00904241.

Humans↗

PubMed2026

Identification of molecular subtypes in clear cell renal cell carcinoma based on chromatin regulators and tumor immune microenvironment profiling.

In the histological classification of renal cell carcinoma, clear cell renal cell carcinoma (ccRCC) accounts for the highest proportion and is the most common subtype. Despite advances in management, it continues to be associated with considerable incidence and mortality. Although surgery and systemic therapies are available, their efficacy is constrained by pronounced intratumoral heterogeneity and treatment resistance. Identifying robust biomarkers and clarifying the underlying biological mechanisms are therefore essential to improving diagnosis, risk stratification and therapeutic decision-making. In this work, we identified two ccRCC molecular subtypes displaying divergent chromatin regulator (CR) profiles and different clinical prognoses. Using the genes differentially expressed between these subgroups, we constructed a CR-related score (CRS) that effectively stratified patients according to survival. More analysis concluded that the low expression of CR was more linked with the immune-activated tumors, which encompassed the immune pathway enrichment, as well as the elevation of numerous immune cell subtypes. Moreover, elevated CRS was associated with improved immunotherapy responsiveness. Drug-sensitivity analyses nominated several candidate agents, and SMARCD3 knockdown in 786-O cells inhibited proliferation and migration and reduced sensitivity to masitinib. Collectively, these findings support the prognostic and therapeutic relevance of CR-related states in ccRCC and provide a framework for future experimental validation of chromatin-regulated tumor-immune interactions.

Humans↗

PubMed2026

Harnessing Endogenous Plasticity Rather than Reprogramming of Mature Cells Will Advance Regenerative Medicine, Cancer Treatment and Rejuvenation.

The successful culture of human embryonic stem (hES) cells from inner cell mass cells of blastocyst stage 'spare' embryos in 1998, followed by induced pluripotent stem (iPS) cells in 2006, which allowed somatic cells to be reprogrammed to pluripotency using the Yamanaka factors, transformed regenerative biology and inspired extensive global efforts towards developing pluripotent stem cell-based applications. However, hES and iPS cells, as well as organoids generated from them, largely retain fetal-like characteristics, which limits their relevance for clinical translation. Concurrently, the prevailing assumption published in leading journals that adult tissues lack endogenous stem cells has led to the belief that mature cells dedifferentiate and reprogram during in vivo regeneration upon chronic injury, and that the appearance of embryonic/fetal markers in diabetes, heart failure, cancer, and many other chronic disease states reflects dedifferentiation of mature cells. We suggest that the prevailing concepts of dedifferentiation and reprogramming, both in vitro and in vivo, require careful re-evaluation. Adult somatic cells possibly do not truly dedifferentiate, neither in vitro nor in vivo. Instead, tissue-resident, pluripotent, very small embryonic-like stem cells (VSELs) in multiple organs account for the observed biology. In vitro "reprogramming" responses to Yamanaka factors likely reflect selective activation and expansion of VSELs/early progenitors rather than the dedifferentiation/ reprogramming of mature adult somatic cells. Likewise, the embryonic/fetal-like signatures reported in multiple disease states including cancer reflect expansion of immature tissue-specific progenitors that arise from VSELs but fail to differentiate normally due to a damaged microenvironment in vivo. Therapeutic strategies involving transplantation of MSCs, MUSE cells, or their secreted exosomes improve disease outcomes, possibly by restoring the damaged niche that supports functional tissue repair by VSELs. Although direct evidence to support this is lacking at present, recognising the central role of VSELs/progenitors and their niche in maintaining tissue homeostasis in vivo could resolve existing roadblocks and guide more effective endogenous regenerative therapies for diseased tissues and age-related dysfunctions.

Humans↗

PubMed2026

Opposite metabolic and gut responses to oral glutamine in male and female mice with diet-induced obesity.

Obesity is often associated with sex-dependent metabolic complications, to which altered intestinal barrier function and gut microbiota contribute. Glutamine supplementation has previously shown beneficial effects on gut barrier function and glycemic control. We thus aimed to characterize, in male and female mice, the effects of oral glutamine supplementation during high-fat-diet-induced obesity. Male and female C57BL/6 mice received a standard (SD) or high-fat diet (HFD; 60 % kcal from fat) for 14 weeks (W14). From W12 onward, mice received glutamine in drinking water (2 g/kg/day) or no supplementation. Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic inflammatory response, cecal microbiota and inflammatory/endocrine adipose response were assessed. In both male and female mice, glutamine supplementation failed to improve body weight and body composition. However, glutamine reduced glucose intolerance in HFD-fed males (AUC reduced by 14.57 %) that was associated with a partial restoration of plasma resistin and insulin and a trend toward limiting adipose inflammatory response. In males, glutamine did not affect gut microbiota composition and colonic response. Conversely, in HFD-fed females, glutamine supplementation led to gut microbiota changes (increase in Bacteroidota and Pseudomonadota phyla; increase in Muribaculaceae and Tannerellaceae families), increased colonic inflammatory markers (Il1b, Tlr4, Myd88, Irf3), increased inflammatory response in subcutaneous adipose tissue and increased HOMA-IR. Finally, HFD-fed mice exhibited sex-specific responses to glutamine supplementation with protective effects in males and harmful effects in females that need to be further deeply explored.

Animals↗

PubMed2026

Deciphering CD8+ T cell exhaustion in human cancers through single-cell and spatial transcriptomics.

Exhausted CD8+ T cells (Tex) within the tumor microenvironment (TME) represents a critical barrier limiting anti-tumor immune responses. Tex cells are characterized by upregulated inhibitory immune checkpoint receptors, reduced cytotoxicity, and functional heterogeneity. Their genomic features and regulatory networks remain poorly defined, and only a minority of patients respond to immune checkpoint blockade (ICB) therapy. Single-cell RNA sequencing (scRNA-seq), through high-resolution transcriptomic profiling, has revealed diverse Tex subpopulations, identified subpopulation-specific marker genes and regulatory pathways. Spatial transcriptomics has further mapped the spatial distribution of Tex and their interaction networks with immune cells, tumor cells, and stromal cells, elucidating the impact of spatial heterogeneity on Tex functionality. Current studies indicate that the exhausted state of Tex is dynamic and modifiable, with functional differences among subpopulations closely associated with tumor progression and therapeutic response. However, the genomic characteristics, epigenetic regulation, and spatial interaction mechanisms of Tex require further exploration. This review summarizes recent advances in high-resolution omics technologies for precisely dissecting Tex heterogeneity, functional features, and interactions with other cells. It emphasizes the central value of optimizing Tex-targeted tumor immunotherapy strategies, providing theoretical foundations and directional guidance for developing more effective anti-tumor immunotherapies.

Humans↗

PubMed2026

In vivo genome-wide CRISPR screens identify FOXR1 as a suppressor of CD8+ T cell antitumor immunity.

T cell dysfunction critically limits the efficacy of T cell-based immunotherapies in solid tumors, yet the intrinsic regulators of T cell dysfunction remain incompletely understood. Through an in vivo genome-wide CRISPR screen in tumor-infiltrating CD8+ T cells, we identified Forkhead Box R1 (FOXR1) as a potent transcriptional suppressor of CD8+ T cell effector functions. Genetic ablation of FOXR1 significantly enhanced cytokine production and cytotoxic capacity in both murine and human CD8+ T cells, whereas its overexpression impaired T cell activation and effector molecule expression. Mechanistically, multiomics integration of RNA-seq, CUT&Tag-seq, and ATAC-seq revealed that FOXR1 binds directly to promoter regions of key effector genes, including IL2, GZMB, and PRF1, and represses their expression. Importantly, FOXR1 deletion in human anti-CD19 CAR T cells improved their efficacy against solid tumors, demonstrating that FOXR1 is a checkpoint of T cell effector function and targeting FOXR1 is a promising strategy to enhance CAR T cell efficacy against solid tumors.

Animals↗

PubMed2026

Effect of SGLT2 inhibitor drugs on triglyceride-glucose (TyG) index in adults: A systematic review and meta-analysis.

BACKGROUND: Insulin resistance is a serious public health concern. The triglyceride-glucose (TyG) index is a simple, cheap, and reproducible surrogate of insulin resistance, and sodium-glucose cotransporter-2 (SGLT2) inhibitors have reshaped cardio-metabolic care beyond glycemic control. METHODS: We followed PRISMA and registered the protocol in PROSPERO (CRD420251056341). We searched PubMed, Scopus, Web of Science, EMBASE, and Cochrane from inception to May 31st, 2026, including observational studies and clinical trials reporting baseline and follow-up TyG in adults. Two reviewers screened records, a third resolved disagreements, data were extracted with a standardized form, and quality was assessed with Cochrane RoB 2.0, the Newcastle-Ottawa Scale, and the JBI checklists. The primary outcome was within-group change in TyG pooled with random-effects (Hartung-Knapp); tests were two-sided with a significance threshold of 0.05. RESULTS: Twelve studies comprising thirteen study arms were included, with a total of 1845 participants. Follow-up ranged from 12 weeks to 5 years. Across studies, SGLT2 inhibitor therapy was associated with a significant reduction in TyG index (mean difference = -0.28, 95% confidence interval [-0.41; -0.14], I2 = 99.5%). Egger's test suggested possible small-study effects, whereas Begg's test and trim-and-fill analysis did not show clear evidence of publication bias; leave-one-out analyses showed that no single study materially influenced the pooled estimate. CONCLUSION: Despite heterogeneity in populations, drug choice, and follow-up duration, SGLT2 inhibitors were associated with a significant decrease in TyG, although small-study effects cannot be excluded.

Humans↗

PubMed2026

Overcoming Immunological Barriers in MSC-Derived Insulin-Producing Cells through CRISPR-Based Hypoimmunogenic Engineering and Translational Perspectives for Type 1 Diabetes.

Mesenchymal stromal cell (MSC)-derived insulin-producing cells (IPCs) represent an emerging strategy for β-cell replacement in type 1 diabetes mellitus (T1DM) owing to their differentiation potential, intrinsic immunomodulatory properties, and lower tumorigenic risk compared with pluripotent stem cell-derived platforms. However, accumulating evidence indicates that differentiation-associated immunogenicity, context-dependent immune recognition, and recurrent autoimmune responses may substantially limit long-term graft survival and therapeutic durability following transplantation. This review critically examines the immunological barriers associated with MSC-derived IPCs, including altered MHC expression, susceptibility to alloimmune and autoimmune-mediated rejection, and potential reactivation of autoreactive immune memory. We discuss the application of CRISPR-based hypoimmunogenic engineering strategies targeting antigen presentation pathways, NK-cell activation, and immune checkpoint modulation to generate more immune-evasive MSC-derived IPCs while preserving β-cell functionality. By integrating insights from T1DM immunopathogenesis, MSC biology, genome editing, and translational immunology, we propose a framework linking immune engineering with controlled differentiation, functional maturation, and long-term safety evaluation. In parallel, we comparatively position MSC-derived IPCs alongside clinically advancing iPSC-derived β-cell platforms to highlight their distinct translational niche, including potential advantages related to safety, immunomodulatory capacity, manufacturing accessibility, and scalability, while acknowledging the superior functional maturity and clinical progression currently demonstrated by iPSC-derived systems. Finally, we discuss key translational challenges, including genomic stability, immune-evasion durability, GMP-compliant manufacturing, and the need for rigorous functional and immunological benchmarking prior to clinical application of hypoimmunogenic MSC-derived IPC therapies in T1DM.

Humans↗

PubMed2026

Proteomic profiling reveals that DPP4 overexpression increases cell adhesion, inhibits cell migration, and restores androgen sensitivity in prostate cancer.

Dipeptidyl peptidase-4 (DPP4), a serine protease with both enzymatic and non-enzymatic roles, has emerged as a context-dependent modulator of tumor progression. In the present study, we investigated the expression and function of DPP4 in androgen-sensitive and castration-resistant prostate cancer (CRPC) models. Proteomic analysis of androgen-resistant prostate cells overexpressing DPP4 identified the involvement of the cellular adhesion molecules pathway. In prostate cells, lentiviral-mediated DPP4 overexpression restored androgen receptor signaling, inhibited epithelial-to-mesenchymal transition, and reduced cell migration, whereas DPP4 silencing produced the opposite effects. We demonstrate that DPP4 expression is down-regulated in CRPC cells and that treatment with capsaicin (CAP), a bioactive compound derived from red peppers, restores DPP4 expression. Moreover, DPP4 restoration by CAP suppresses prostate tumorigenesis in the TRAMP mice in vivo model of prostate cancer. Our results suggest that DPP4 could be a new target for CRPC.

Male↗

PubMed2026

Effects of short-bout accumulated exercise on postprandial metabolism in adults: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the acute effects of short-bout accumulated exercise (SBAE) interrupting prolonged sedentary behaviour on postprandial glucose, insulin, and triglycerides in adults. METHODS: Systematic searches in PubMed, Web of Science, Embase, Cochrane Library, CINAHL, SPORTDiscus, and CNKI (inception to 10 December 2025) identified randomised crossover trials comparing SBAE (≤10 min/bout, inter-bout interval ≥30 min or adequate recovery) with continuous sedentary behaviour. Outcomes included postprandial glucose, insulin, and triglyceride AUCs. Standardised mean differences (SMD) were pooled using random-effects models. RESULTS: Thirty-one publications reporting data from 29 independent cohorts involving 573 unique participants (mean age 47.8 ± 20.3 years; 47.5% female; mean BMI 29.0 ± 5.1 kg/m²) were included. Compared with continuous sedentary behaviour, SBAE significantly reduced glucose AUC (SMD = -0.53, 95% CI: -0.71 to -0.34, P < 0.001) and insulin AUC (SMD = -0.58, 95% CI: -0.85 to -0.31, P < 0.001), but not triglyceride AUC (SMD = -0.17, 95% CI: -0.48 to 0.15, P = 0.306).Exploratory subgroup analyses showed statistically significant reductions in glucose and insulin for walking and for inter-bout intervals < 60 min, but not for standing alone or intervals ≥ 60 min. A statistically significant insulin-lowering effect was observed in obese individuals. CONCLUSION: SBAE acutely improves postprandial glucose and insulin control. Exploratory subgroup analyses showed statistically significant effects for walking and for inter-bout intervals < 60 min, but these comparisons are observational and no formal interaction test was conducted. These findings provide preliminary evidence for acute SBAE in sedentary populations, though long-term health effects and real-world generalisability require further investigation.

Adult↗