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Nevin Manimala Statistics

Anti-Inflammatory and Anti-apoptotic Effects of Phosphodiesterase Inhibitors Against Streptozocin-induced Diabetic Nephropathy

In Vivo. 2026 Jan-Feb;40(1):640-649. doi: 10.21873/invivo.14226.

ABSTRACT

BACKGROUND/AIM: A variety of actions implicated in diabetic nephropathy (DN) are attributed to inflammatory cytokines and apoptosis of tubular epithelial cells. Building on our previous research demonstrating the role of different phosphodiesterase inhibitors (PDEIs) in improving renal microcirculation, glucose lowering, and antioxidant effects in rats with DN, this study aims to further explore the anti-inflammatory and anti-apoptotic properties of PDEIs by measuring their effects on renal expression of pro-inflammatory cytokines in streptozocin (STZ)-induced diabetic nephropathic rats.

MATERIALS AND METHODS: Out of 50 adult male Sprague-Dawley rats, diabetes was induced in 40 rats by a single injection of STZ (45 mg/kg) dissolved in citrate buffer. Ten days after induction of diabetes, rats were divided into five groups (10/group): normal control, diabetic control, and 3 diabetic groups treated with pentoxifylline, sildenafil, and milrinone via drinking water for 15 successive days. Serum and kidney tissue samples were collected to evaluate the effect of treatment with PDEIs on diabetes-induced histopathological changes and expression levels of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), apoptotic marker Bcl-2 Associated X-protein (Bax) and anti-apoptotic marker B cell lymphoma-2 (Bcl-2) in rat’s kidneys.

RESULTS: A significant increase in pro-inflammatory cytokines (TNF-α and IL-6), and apoptosis marker (Bax), with a concomitant decrease in anti-apoptotic protein (Bcl-2) were observed in diabetic rats. Treatment with PDEIs resulted in a significant decrease in renal expression of Bax, TNF-α, and IL-6, with an increase Bcl-2 expression, with slight, though not statistically significant, differences among the PDEI-treated groups.

CONCLUSION: The tested PDEIs, pentoxifylline, sildenafil, and milrinone, exhibit significant anti-inflammatory and anti-apoptotic effects, highlighting their potential in slowing the progression of diabetic nephropathy.

PMID:41482414 | DOI:10.21873/invivo.14226

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Integrated Bioinformatics and Experimental Analysis of Argonaute Family Members in Pancreatic Adenocarcinoma

In Vivo. 2026 Jan-Feb;40(1):123-135. doi: 10.21873/invivo.14178.

ABSTRACT

BACKGROUND/AIM: Pancreatic adenocarcinoma (PAAD) is an aggressive cancer type with high mortality rates. The Argonaute (AGO) gene/protein family is an evolutionary conserved family, which is responsible for post-transcriptional regulation of gene expression. Despite the fact that this family members (AGO1-4) have been linked to prognosis in some cancers, they have not been comprehensively investigated in PAAD. Therefore, this study investigates the role of AGO family members on PAAD.

MATERIALS AND METHODS: In our research, bioinformatics analyses were performed to study gene, protein and methylation levels, prognostic importance, gene-gene and protein-protein interactions, enrichment analysis, and immune infiltration analysis, using online and publicly available platforms. Additionally, real-time PCR was used to check mRNA levels in the pancreatic cell line BxPC-3.

RESULTS: mRNA (p<0.05), protein (p<0.001) and methylation (p<0.001) levels of AGO2 were statistically different between normal and tumor samples in the in silico and laboratory analyses, and high AGO2 levels were found to be linked to poor prognosis (p=0.037). Additionally, immune infiltration analysis demonstrated a close relationship between AGO2 mRNA expression and immune cells. In contrast to the consistent results of AGO2, other AGO family members (AGO1, AGO3, or AGO4) differed at the protein or methylation levels but had non-significant prognostic values.

CONCLUSION: The findings of this study indicate the potential importance of AGO2 in terms of biological functions and prognostication in PAAD.

PMID:41482412 | DOI:10.21873/invivo.14178

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Slow-release L-cysteine Lozenges in Smoking Cessation: Meta-analysis of Two Randomized Controlled Trials

In Vivo. 2026 Jan-Feb;40(1):39-49. doi: 10.21873/invivo.14171.

ABSTRACT

BACKGROUND/AIM: The hypothesis that elimination of cigarette smoke-derived acetaldehyde in the saliva by slow-release L-cysteine would eliminate acetaldehyde-enhanced nicotine addiction among smokers has been tested in two randomized controlled trials (RCT) using Acetium® lozenge (Biohit Oyj, Helsinki, Finland). Both RCTs showed a similar direction and magnitude of the effect size, but only the larger study was adequately powered to reach statistical significance.

MATERIALS AND METHODS: The two published RCTs on Acetium® in smoking intervention included in this formal meta-analysis include: a cohort of 423 cigarette smokers, randomly allocated to intervention (n=212) and placebo arms (n =211) in Study 1, as well as a cohort of 1,998 smokers, with 996 and 1,002 subjects in the intervention and placebo arms, respectively, in Study 2. Both studies analyzed the results for intention-to-treat (ITT) and per protocol (PP) compliance groups. Random-effects (RE) meta-analysis was used to compute the summary effect size.

RESULTS: In the ITT group of Study 1, Acetium® was more effective than placebo, with OR=1.48 (95% CI=0.87-2.54), and in Study 2, the respective OR=1.26 (95% CI=0.99-1.59). In the PP groups, the success rates in both studies were better: OR=1.65 (95% CI=0.75-3.62) and OR=1.51 (95% CI=1.12-2.02), respectively. In RE meta-analysis, the summary estimates of Acetium® efficacy were statistically significant in both the ITT (n=2,421) and PP (n=863) analysis: OR=1.29 (95% CI=1.04-1.60, p=0.018) and OR=1.53 (95% CI=1.16-2.01, p=0.0025), respectively.

CONCLUSION: Although meta-analyses with a limited number of studies should be interpreted with caution, these data provide clear support to the concept that Acetium® lozenge significantly (1.5-fold) increases the likelihood of successful smoking cessation as compared to placebo.

PMID:41482382 | DOI:10.21873/invivo.14171

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Pregnancy Outcomes Following In Vitro Fertilization: A Multicenter Comparative Analysis Between Donor-oocyte Recipients and Self-oocyte Patients in Greece

In Vivo. 2026 Jan-Feb;40(1):452-464. doi: 10.21873/invivo.14209.

ABSTRACT

BACKGROUND/AIM: Delayed childbearing has increased the reliance on in vitro fertilization (IVF) with donor oocytes for women of advanced maternal age often facing more obstetric complications compared to younger women using self-oocytes. This study evaluated and contrasted key obstetric and perinatal parameters between these two groups.

PATIENTS AND METHODS: In this retrospective multicenter study, completed IVF embryo transfer cycles were analyzed. Clinical data including clinical pregnancy, miscarriage, ectopic pregnancy rates, and major pregnancy complications were collected. Obstetric outcomes (e.g., mode of delivery, preterm birth, and neonatal parameters such as birth weight, Apgar scores, and NICU admissions) were compared between the donor-oocyte recipients (DOR-IVF) and self-oocyte (SO-IVF) groups. Statistical analysis comprised chi-square tests, t-tests, and multivariable logistic and linear regressions to adjust for potential confounders.

RESULTS: The DOR-IVF group demonstrated a clinical pregnancy rate of 44.8% (196 cases) with an 8.8% miscarriage rate, while the SO-IVF group reported 242 clinical pregnancies with an 8.1% miscarriage rate. Overall, nine ectopic pregnancies (2%) were noted, with statistically significant differences in ectopic and miscarriage rates between the groups (p=0.008 and p=0.025, respectively). Although the mean gestational age was similar and NICU admissions did not differ significantly (p=0.125), the DOR-IVF group exhibited a higher incidence of pregnancy complications (p=0.009). Multivariable logistic regression identified DOR-IVF as an independent predictor for pregnancy complications (adjusted odds ratio 2.38; 95% confidence interval=1.53-3.70). Additionally, subgroup analyses revealed that 1-minute Apgar scores were positively associated with DOR-IVF status (p=0.048) and birth weight was inversely related to the number of babies transferred (p=0.006).

CONCLUSION: DOR-IVF patients experience significantly increased risk in obstetric complications compared to younger women using SO-IVF, although neonatal outcomes remain largely similar.

PMID:41482376 | DOI:10.21873/invivo.14209

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VEGF-C Aqueous Humor Levels in Patients With Primary Open Angle Glaucoma

In Vivo. 2026 Jan-Feb;40(1):382-388. doi: 10.21873/invivo.14202.

ABSTRACT

BACKGROUND/AIM: This study aimed to quantitatively analyze and compare aqueous humor concentrations of vascular endothelial growth factor-C (VEGF-C) in patients with primary open-angle glaucoma (POAG) versus non-glaucomatous controls while evaluating potential significant correlations.

PATIENTS AND METHODS: We conducted an observational cross-sectional study. At surgery initiation, anterior chamber paracentesis was performed under sterile conditions, and 50-100 μl of aqueous humor samples were collected. VEGF-C quantification employed a multiplex magnetic bead immunoassay platform.

RESULTS: The study involved the collection of aqueous humor samples from 76 participants: 39 samples were collected from the POAG group and 37 from the control group (age-related cataract). Quantitative analysis revealed mean VEGF-C concentrations of 26.41±26.016 pg/ml in POAG eyes compared to 16.70±8.60 pg/ml in controls (p=0.277), demonstrating no statistically significant difference. Receiver operating characteristic (ROC) curve analysis showed limited prognostic ability for POAG detection (AUC=0.60; p=0.278).

CONCLUSION: This study represents the first large-scale evaluation of aqueous humor VEGF-C levels in patients with POAG. Our results provide evidence against VEGF-C up-regulation in POAG.

PMID:41482375 | DOI:10.21873/invivo.14202

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Effects of Intravenous Laser Irradiation of Blood on Metabolic Markers in Patients With Hyperlipidemia: A Retrospective Pilot Study

In Vivo. 2026 Jan-Feb;40(1):495-501. doi: 10.21873/invivo.14213.

ABSTRACT

BACKGROUND/AIM: Hyperlipidemia is a major risk factor for cardiovascular diseases. Pharmacological treatment and lifestyle modifications are the main therapeutic approaches; however, some patients respond poorly or have limited tolerance. Intravenous laser irradiation of blood (ILIB) has recently been proposed as a potential adjunctive therapy, but its clinical efficacy remains unclear. The aim of this study was to evaluate the effects of ILIB therapy on lipid profiles and glycemic parameters in patients with chronic diseases.

PATIENTS AND METHODS: This retrospective single-group study included 60 patients with chronic diseases who received ILIB therapy at the Chang Bing Show Chwan Memorial Hospital between July 2022 and February 2024. Laboratory parameters before and after treatment, including total cholesterol, triglycerides (TG), LDL-C, fasting glucose, and HbA1c, were descriptively compared to demonstrate absolute and percentage changes. Paired t-test and Wilcoxon signed-rank test were used, with p<0.05 considered statistically significant.

RESULTS: After treatment, only TG showed a significant reduction (167.8 mg/dl vs. 118.8 mg/dl, p=0.001). Subgroup analysis revealed that patients with TG >150 mg/dL, LDL>130 mg/dl, and total cholesterol >200 mg/dl all demonstrated significant decreases after ILIB therapy (p<0.05), while no significant changes were observed in patients with normal baseline values. Fasting glucose and HbA1c showed no significant changes in any subgroup.

CONCLUSION: ILIB demonstrated significant lipid-lowering effects in patients with dyslipidemia, particularly in those with elevated TG, LDL, and total cholesterol. No changes were observed in patients with normal lipid levels, suggesting a “normalizing” rather than broadly “lowering” effect. ILIB shows promise as an adjunctive therapy for hyperlipidemia, though larger randomized controlled trials are warranted to confirm these findings.

PMID:41482358 | DOI:10.21873/invivo.14213

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Mutational Spectrum of T-Cell Large Granular Lymphocytic Leukemia: Insights From the AACR Project GENIE Consortium

Cancer Genomics Proteomics. 2026 Jan-Feb;23(1):135-143. doi: 10.21873/cgp.20566.

ABSTRACT

BACKGROUND/AIM: T-cell large granular lymphocyte leukemia (T-LGLL) is a rare, indolent lymphoproliferative disorder of cytotoxic T cells in the peripheral blood, bone marrow, and spleen. This analysis was conducted to characterize genomic alterations and highlight potential therapeutic targets, with the goal of refining the molecular landscape of T-LGLL by emphasizing population-specific biomarkers.

MATERIALS AND METHODS: This study utilized the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database to identify common gene mutations. Using the AACR GENIE database, a retrospective analysis of T-cell large granular lymphocyte leukemia (T-LGLL) samples was performed. The data was evaluated by extracting patient demographics and excluding synonymous mutations from consideration. Statistical significance was assessed using chi-squared tests and computational analyses in RStudio (R Foundation for Statistical Computing, Boston, MA, USA). Somatic mutations and chromosomal copy number variations were evaluated, with statistical significance defined as p=0.001.

RESULTS: Frequently observed somatic mutations included STAT3 (41.7%), STAT2 (20.9%), KMT2D (11.3%), SETD1B (8.7%), TP53 (7.0%), TNFAIP3 (6.1%), DNMT3A (5.2%), FAS (4.3%), SMARCA4 (3.5%), EPHB1 (2.6%), KSR2 (2.6%), ALOX12B (2.6%), EGFR (2.6%), DDX3X (7.0%), and IKZF3 (1.7%). When stratified by demographic variables, males and White patients demonstrated a higher frequency of mutations.

CONCLUSION: This study provides a comprehensive genomic profile of T-LGLL, identifying recurrent somatic mutations and commonly affected pathways. Notably, frequent alterations were observed in the FASFASL signaling pathway, underscoring its potential as a target for therapeutic development.

PMID:41482347 | DOI:10.21873/cgp.20566

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Energy Spectrum of Ultrahigh-Energy Cosmic Rays across Declinations -90° to +44.8° as Measured at the Pierre Auger Observatory

Phys Rev Lett. 2025 Dec 12;135(24):241002. doi: 10.1103/p4l5-hxlf.

ABSTRACT

The energy spectrum of cosmic rays above 2.5 EeV has been measured across the declination range -90°≤δ≤+44.8° using ∼310 000 events accrued at the Pierre Auger Observatory from an exposure of (104 900±3 100) km^{2} sr yr. No significant variations of energy spectra with declination are observed, after allowing or not for nonuniformities across the sky arising from the well-established dipolar anisotropies in the arrival directions of ultrahigh-energy cosmic rays. The instep feature in the spectrum at ≃10 EeV reported previously is now established at a significance above 5σ. Within the statistics, the energy spectra are indistinguishable across declinations so disfavoring an origin for the instep from a few distinctive sources.

PMID:41482327 | DOI:10.1103/p4l5-hxlf

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Active Quantum Flocks

Phys Rev Lett. 2025 Dec 12;135(24):248302. doi: 10.1103/rd46-hr3q.

ABSTRACT

Flocks of animals represent a prominent archetype of collective behavior in the macroscopic classical world, where the constituents, such as birds, concertedly perform motions and actions as if being one single entity. Here, we address the so far open question of whether flocks can also form in the microscopic world at the quantum level. For that purpose, we introduce the concept of active quantum matter by formulating a class of models of active quantum particles on a one-dimensional lattice. We provide both analytical and large-scale numerical evidence that these systems can give rise to quantum flocks. A key finding is that these quantum flocks exhibit distinct quantum properties by developing strong quantum coherence over long distances. We propose that quantum flocks could be experimentally observed in Rydberg atom arrays.

PMID:41482319 | DOI:10.1103/rd46-hr3q

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Nevin Manimala Statistics

Exact Non-Markovian Master Equations: A Generalized Derivation for Gaussian Systems

Phys Rev Lett. 2025 Dec 12;135(24):240401. doi: 10.1103/cb7c-5f66.

ABSTRACT

We derive an exact master equation that captures the dynamics of a quadratic quantum system linearly coupled to a Gaussian environment of the same statistics: the Gaussian master equation (GME). Unlike previous approaches, our formulation applies universally to both bosonic and fermionic setups, and remains valid even in the presence of initial system-environment correlations, allowing for the exact computation of the system’s reduced density matrix across all parameter regimes. Remarkably, the GME shares the same operatorial structure as the Redfield equation and depends on a single kernel: a dressed environment correlation function accounting for all virtual interactions between the system and the environment. This simple structure grants a clear physical interpretation and makes the GME easy to simulate numerically, as we show by applying it to an open system based on two fermions coupled via superconductive pairing.

PMID:41482302 | DOI:10.1103/cb7c-5f66