Macrophage modulation with dipeptidyl peptidase-4 inhibitors:A new frontier for treating diabetic cardiomyopathy?

This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy(DCM)treatment by dipeptidyl peptidase-4(DPP-4)inhibitors.Zhang et al studied teneligliptin,a DPP-4 inhibitor used for diabetes management,and its potential cardioprotective effects in a diabetic mouse model.They suggested teneligliptin administration may reverse established markers of DCM,including cardiac hypertrophy and compromised function.It also inhibited the NLRP3 inflammasome and reduced inflammatory cytokine production in diabetic mice.Macrophages play crucial roles in DCM pathogenesis.Chronic hyperglycemia disturbs the balance between pro-inflammatory(M1)and antiinflammatory(M2)macrophages,favoring a pro-inflammatory state contributing to heart damage.Here,we highlight the potential of DPP-4 inhibitors to modulate macrophage function and promote an anti-inflammatory environment.These compounds may achieve this by elevating glucagon-like peptide-1 levels and potentially inhibiting the NLRP3 inflammasome.Further studies on teneligliptin in combination with other therapies targeting different aspects of DCM could be suggested for developing more effective treatment strategies to improve cardiovascular health in diabetic patients.

Aryl hydrocarbon receptor dynamics in esophageal squamous cell carcinoma:From immune modulation to therapeutic opportunities

Esophageal squamous cell carcinoma(ESCC)is a substantial global health burden.Immune escape mechanisms are important in ESCC progression,enabling cancer cells to escape the surveillance of the host immune system.One key player in this process is the Aryl Hydrocarbon Receptor(AhR),which influences multiple cellular processes,including proliferation,differentiation,metabolism,and immune regulation.Dysregulated AhR signaling participates in ESCC development by stimulating carcinogenesis,epithelial-mesenchymal transition,and immune escape.Targeting AhR signaling is a potential therapeutic approach for ESCC,with AhR ligands showing efficacy in preclinical studies.Additionally,modification of AhR ligands and combination therapies present new opportunities for therapeutic intervention.This review aims to address the knowledge gap related to the role of AhR signaling in ESCC pathogenesis and immune escape.

Altered expression of miR-125a and dysregulated cytokines in systemic lupus erythematosus: Unveiling diagnostic and prognostic markers

BACKGROUND Systemic lupus erythematosus(SLE)is a chronic autoimmune disorder impacting multiple organs,influenced by genetic factors,especially those related to the immune system.However,there is a need for new biomarkers in SLE.MicroRNA-125a(miR-125a)levels are decreased in T cells,B cells,and dendritic cells of SLE patients.MiR-125a plays a regulatory role in controlling the levels of tumor necrosis factor-alpha(TNF-α)and interleukin 12(IL-12),which are crucial pro-inflammatory cytokines in SLE pathogenesis.AIM To assess the levels of miR-125a,IL-12,and TNF-αin SLE patients’plasma,evaluating their diagnostic and prognostic value.METHODS The study included 100 healthy individuals,50 newly diagnosed(ND),and 50 SLE patients undergoing treatment.The patients were monitored for a duration of 24 wk to observe and record instances of relapses.MiR-125a expression was measured using real-time reverse transcription polymerase chain reaction,while ELISA kits were used to assess IL-12 and TNF-αproduction.RESULTS The results showed significantly reduced miR-125a expression in SLE patients compared to healthy individuals,with the lowest levels in ND patients.TNF-αand IL-12 expression levels were significantly elevated in SLE patients,especially in the early stages of the disease.Receiver operating characteristic curve analyses,and Cox-Mantel Log-rank tests indicated miR-125a,TNF-α,and IL-12 as proper diagnostic biomarkers for SLE.A negative correlation was found between plasma miR-125a expression and IL-12/TNF-αlevels in SLE patients.CONCLUSION Decreased miR-125a levels may be involved in the development of SLE,while elevated levels of IL-12 and TNF-αcontribute to immune dysregulation.These findings offer new diagnostic and prognostic markers for SLE.Moreover,the negative correlation observed suggests an interaction between miR-125a,TNF-α,and IL-12.Further research is necessary to uncover the underlying mechanisms that govern these relationships.

Resveratrol downregulates TGF-β1 and Smad3 expression and attenuates oxidative stress in CCl_4-induced kidney damage in rats

Objective:To evaluate the effect of resveratrol against CCl4-induced nephrotoxicity.Methods:Forty-two male Wistar rats were divided into seven groups randomly.After six weeks,kidney weight,body weight,blood urea,serum creatinine,oxidative stress markers,and gene expression of renal transforming growth factor-beta1(TGF-β1),TGF-βreceptor type 1(TGF-βR1)and Smad3 were determined.In addition,the protein level of TGF-β1 in the tissue lysate was measured.Results:Resveratrol had a protective role in renal tissue by the improvement of antioxidant balance and reduction of renal parameters such as creatinine and urea(P<0.001).In addition,the renal m RNA level of TGF-β1,TGF-βR1,Smad3,as well as the protein level of TGF-β1 were decreased in rats treated with resveratrol(P<0.001),compared to the CCl4 group.Conclusions:Overall,resveratrol shows a protective effect against nephrotoxicity in CCl4 treated rats by reducing oxidative stress status and modulating the TGF-βsignaling.

A New Insight into Energy Distribution of Electrons in Fuel-Rod Gap in VVER-1000 Nuclear Reactor

In order to calculate the electron energy distribution in the fuel rod gap of a VVER- 1000 nuclear reactor, the Fokker-Planck equation （FPE） governing the non-equilibrium behavior of electrons passing through the fuel-rod gap as an absorber has been solved in this paper. Besides, the Monte Carlo Geant4 code was employed to simulate the electron migration in the fuel-rod gap and the energy distribution of electrons was found. As for the results, the accuracy of the FPE was compared to the Geant4 code outcomes and a satisfactory agreement was found. Also, different percentage of the volatile and noble gas fission fragments produced in fission reactions in fuel rod, i.e. Krypton, Xenon, Iodine, Bromine, Rubidium and Cesium were employed so as to investigate their effects on the electrons＇ energy distribution. The present results show that most of the electrons in the fuel rod＇s gap were within the thermal energy limitation and the tail of the electron energy distribution was far from a Maxwellian distribution. The interesting outcome was that the electron energy distribution is slightly increased due to the accumulation of fission fragments in the gap. It should be noted that solving the FPE for the energy straggling electrons that are penetrating into the fuel-rod gap in the VVER-1000 nuclear reactor has been carried out for the first time using an analytical approach.

Synthesis and Characterization of Indium Niobium Oxide Thin Films via Sol—Gel Spin Coating Method

In the present study, niobium-doped indium oxide thin films were prepared by sol-gel spin coating technique. The effects of different Nb-doping contents on structural, morphological, optical, and electrical properties of the films were characterized by means of X-ray diffraction （XRD）, field emission scanning electron microscopy （FESEM）, atomic force microscopy （AFM）, UV-Vis spectroscopy, and four point probe methods. XRD analysis confirmed the formation of cubic bixbyite structure of In203 with a small shift in major peak position toward lower angles with addition of Nb. FESEM micrographs show that grain size decreased with increasing the Nb-doping content. Optical and electrical studies revealed that optimum opto-electronic properties, including minimum electrical resistivity of 119.4 × 10^-3 Ω cm and an average optical transmittance of 85% in the visible region with a band gap of 3.37 eV were achieved for the films doped with Nb-doping content of 3 at.%. AFM studies show that addition of Nb at optimum content leads to the formation of compact films with smooth surface and less average roughness compared with the prepared ln2O3 films.

Factor XIII VaU34Leu polymorphism and risk of recurrent pregnancy loss in Iranian population： a case control study

BACKGROUND： Recurrent pregnancy loss （RPL） is a heterogeneous condition and thrombophilias have been considered as a probable cause. OBJECTIVE： The aim of this study was to investigate the prevalence of the coagulation factor XIII Va134Leu polymorphism among women with unexplained RPL. METHODS： A total of 140 women with a history of unexplained RPL and 100 age-matched healthy fertile women were recruited. The presence of FXIII Va134Leu polymorphism among the cases and controls was investigated using PCR-RFLP method. RESULTS： Genotype analyses of the subjects revealed that the patients had a significantly higher prevalence of V/L and L/L than the controls （P〈 0.05）： 33.5% vs. 15%, and 9.2% vs. 2%, respectively. CONCLUSION： These results indicate a significant association between FXIII Va134Leu polymorphism and unexplained RPL in the Iranian patient.