Search Results (647)

Early prevention of pathological changes underlying gastric cancer (GC) development is a critical strategy, offering the most effective opportunity to limit malignant progression and improve patient outcomes. We have previously demonstrated that Helicobacter pylori (Hp) (cagA⁺vacA⁺) contributes to GC development by activating gastric fibroblasts toward CAF-like phenotype, eliciting aggressive, cancer stem cells (CSCs)-related malignant transformation of LGR5⁺ normal epithelial cells. A key mediator of these processes appears to be the NF-κB/STAT3 axis. Therefore, our aim was to investigate the protective role of hydrogen sulfide (H₂S) as a potential novel strategy for counteracting Hp-induced fibroblast reprogramming. Human fibroblasts were infected with Hp (cagA+vacA+) for 120 h. The fast-releasing H₂S donor NaHS (50, 100, 200 and 400 µM) was added every 24 h. Activation markers, corresponding signaling pathways, H₂S release and activities of H₂S-metabolizing enzymes were determined. NaHS reduced Hp-induced fibroblast activation and their pro-inflammatory, pro-tumorigenic markers, which was associated with the inhibition of NF-κB/STAT3 axis and Twist expression. Additionally, it modulated sulfur metabolism while preserving sulfur-enzyme homeostasis. NaHS limited Hp adhesion (high doses), reduced reinfection-induced activation and increased sensitivity of Hp to metronidazole. These findings suggest that H₂S signaling may represent a modulatory factor of NF-κB/STAT3-driven inflammatory responses during Hp infection and warrant further investigation. Full article

Background: Ischemia–reperfusion injury is a major contributor to early graft dysfunction after kidney transplantation and is associated with endothelial damage, reflected by circulating soluble thrombomodulin (sTM). This exploratory study aimed to assess very early graft-level changes in renal vein sTM during reperfusion using a paired-kidney design, in which kidneys from the same donor were preserved using different strategies: static cold storage (SCS) and hypothermic machine perfusion (HMP). Methods: Renal vein blood samples were collected intraoperatively at 1 and 30 min after reperfusion. Plasma sTM concentrations were determined using ELISA. Early graft function was monitored during the first 7 days post-transplantation. Results: Cold ischemia time was longer in the HMP group than in the SCS group (20 ± 8 h vs. 13 ± 6 h, p < 0.05). At 1 min post-reperfusion, sTM levels were comparable between groups. In the HMP group, sTM decreased significantly between 1 and 30 min after reperfusion, whereas no change was observed in the SCS group. Between-group differences at either time point did not reach statistical significance. Early renal function parameters improved in both groups, with no significant inter-group differences. No cases of delayed graft function or graft thrombosis occurred. Conclusions: Kidney preservation strategy may modulate very early graft-level endothelial responses during reperfusion, reflected by renal vein sTM dynamics. Although a limited sample size may have reduced the ability to detect between-group differences, very early renal vein sTM measurements may provide insight into ischemia–reperfusion injury. Clinical relevance requires validation in larger studies. Full article

Dacarbazine (DTIC) is a clinically important anticancer drug whose photosensitivity poses challenges for its stability and interactions with supramolecular hosts. Here, we investigate its complexation with the host 1,10-N,N′-bis-(β-D-ureidocellobiosyl)-4,7,13,16-tetraoxa-1,10-diazacyclooctadecane (TN), a hybrid urea–carbohydrate–diazacrown system, using combined experimental and computational approaches. While TN has been studied as a host molecule, its specific interactions with DTIC and the associated thermodynamic characteristics had not been characterized. Computational results (obtained at the density functional theory level (DFT)) indicate that TN primarily forms non-inclusion complexes, with DTIC engaging in hydrogen bonding with sugar units, urea bridges, and diazacrown ether moieties. Experimental ¹H NMR studies in D₂O confirmed these interaction patterns, showing notable chemical shifts for sugar protons. Conductometric measurements between 293 and 313 K allowed for the determination of formation constants and thermodynamic parameters. The results demonstrate that TN:DTIC complexation is spontaneous, exothermic, and enthalpy-driven, accompanied by decreased system entropy. Comparison with previous studies on cyclodextrin complexes shows that TN forms strong associations with DTIC, owing to its abundant donor–acceptor groups, which facilitate extensive hydrogen-bonding networks. These findings provide new insights into DTIC stabilization and highlight TN’s potential as a multifunctional platform for drug delivery. Full article

Background: Frostbite injury is a thermal injury where ice crystals form in skin tissues and subsequently lead to damage due to prolonged exposure to cold temperatures below 0 °C. The extremities are mostly affected, leading to potential amputation. As there is no pharmacological treatment of frostbite injury, we recently reported that non-clinically viable hydrogen sulfide (H₂S) donors promote frostbite wound healing in mice. In this study, we investigated whether commonly used cosmetic creams supplemented with sodium thiosulfate (STS), a clinically viable H₂S donor drug, also promote healing of frostbite wounds. Methods: Frozen magnets (−80 °C) were placed on the dorsal skin of 40 C57BL/6 mice for 3 min to induce frostbite injury. Next, commercially available cosmetic creams (Aveeno, Dove, Neutrogena, and Nivea) were topically applied on frostbite wounds daily for 14 days with or without 150 µM of STS supplementation. The mice were sacrificed on day 15 after induction of frostbite injury, and samples of the injured dorsal skin tissue were collected for analysis. Results: Addition of STS enhanced frostbite wound healing, as evidenced by progressive and significantly reduced wound area by about 50% and inflammation (p < 0.05), and markedly increased granulation tissue formation by >45%, fibroblast maturation by >28%, and re-epithelialization by >63% compared to control groups (p < 0.05), with Nivea producing a superior wound-healing effect. Also, STS supplementation significantly upregulated the expression of CD31 (by >25%), KI-67 (by >25%), CD163 (by >20%), fibronectin (by >14%), and cytokeratin (by >50%) in frostbite wounds compared to control groups, with Aveeno and Nivea producing a better wound-healing effect than Dove and Neutrogena creams. Conclusions: In conclusion, STS accelerated healing of frostbite wounds. Therefore, it could be considered as a novel pharmacological treatment of clinical frostbite. Full article

Hydrogen sulfide (H₂S) is a gasotransmitter that plays a crucial role in regulating pathological processes following injury to the central and peripheral nervous systems. This review systematizes current data on various classes of H₂S donors and inhibitors of its biosynthesis in neurotrauma and related experimental models. Inorganic donors (e.g., NaHS, Na₂S, and STS) rapidly suppress oxidative stress and inflammation, supporting the recovery of synaptic plasticity and cognitive function. Organic donors (e.g., GYY4137, ACS67, ACS84, SPRC, ADT-OH and its derivatives, S-memantine, and MTC) provide sustained H₂S release, stabilize the blood–brain barrier, and exhibit antiapoptotic activity. Natural donors (e.g., DADS, DATS, and SAMe) demonstrate high biocompatibility, inhibit pyroptosis, and enhance antioxidant defense mechanisms. Hybrid systems—including nanoparticles and hydrogels—enable targeted delivery and prolonged action, thereby stimulating regeneration and angiogenesis. Thiol-activated donors (e.g., COS/H₂S and AlaCOS) allow controlled H₂S release, offering broad opportunities for precise modulation of its concentration within target tissues. Inhibitors (e.g., AOAA, PAG, oxamic hydrazide 1, L-aspartic acid, benserazide, and NSC4056) of H₂S biosynthesis underscore the physiological importance of this gasotransmitter, as their administration enhances neuroinflammation and diminishes neuroprotection. The analysis reveals a general pattern: all classes of H₂S donors effectively modulate key pathological mechanisms, differing in their rate, duration, and specificity of action. These findings highlight the therapeutic promise of H₂S-based pharmacological agents in clinical neurotraumatology, while emphasizing the need for further research to optimize delivery systems, enhance efficacy, and minimize adverse effects. Full article

Nitrate contamination of water resources poses significant ecological and public health risks. This study developed a cobalt-immobilized microplastic catalyst (Co–MP) capable of activating peroxymonosulfate (PMS) and facilitating formic-acid-assisted catalytic denitrification of nitrate. Characterization via Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), Energy-Dispersive X-ray Spectroscopy (EDX), and X-ray diffractometry (XRD) confirmed successful Co deposition, with the surface cobalt content reaching 5.2%. The system’s performance was optimized using Response Surface Methodology (RSM), identifying catalyst dosage and Co(II) concentration as the most significant factors. Under the optimized conditions (pH 5.5, reaction time 120 min, catalyst dosage 1.5 g L⁻¹, and Co(II) concentration 60 mg L⁻¹), the system achieved a nitrate removal efficiency of 90.6%, in excellent agreement with the model prediction (90.93%), along with an 86.7% reduction in total nitrogen, confirming stepwise denitrification to gaseous nitrogen species (N₂). The Co(II)/Co(III) redox cycle, sustained by PMS-assisted regeneration and driven by formic acid as the electron donor, ensured stable performance with minimal cobalt leaching (0.05 mg L⁻¹). This coupled oxidative–reductive system offers a sustainable dual-remediation strategy that simultaneously achieves selective nitrate conversion and valorizes microplastic waste for catalytic environmental applications. Full article

Vitamin A deficiency (VAD) remains a severe health issue in sub-Saharan Africa, causing blindness, illness, and child mortality. In Mozambique, about 69% of children under five are affected, highlighting the short-term impact and donor dependence of supplementation programs. Mangoes (Mangifera indica L.), rich in provitamin A carotenoids, offer a sustainable, food-based strategy to reduce VAD, but their high perishability and postharvest losses of 20–40% limit their impact. This review combined analysis of 21 studies on solar drying of mangoes in Africa with interviews from health directors in three districts of Inhambane Province, Mozambique, to assess both technical and practical aspects of mango utilization. Findings show that improved solar dryers reduce drying time by up to 40 h compared with open-sun drying, achieve safe moisture content below 12%, and retain 60–90% of β-carotene—significantly higher than the 40–55% typical of open-sun methods. One hundred grams of solar-dried mango can meet 60–100% of a child’s or 50–70% of a woman’s daily vitamin A needs. Despite these advantages, interviews revealed limited community adoption and persistent dependence on supplementation. To bridge this gap, initiatives must enhance training, access to affordable dryers, and policy integration to turn seasonal mango surpluses into sustainable, year-round nutrition solutions. Full article

Background: Uncontrolled donation after circulatory death (uDCD) remains underutilized globally, despite critical organ shortages. We report outcomes from Israel’s uDCD kidney transplant program compared with the matched donation after brain death (DBD) recipients. Methods: This retrospective cohort study analyzed all uDCD kidney transplants performed at the Rabin Medical Center between January 2018 and December 2024, compared with DBD transplants during the same period. Propensity score matching (1:3 ratio) was performed using recipient demographics, comorbidities, and donor characteristics. Primary outcomes included delayed graft function (DGF), graft failure, and patient survival. Results: Among 92 kidney transplants, 21 (22.8%) were from uDCD donors. After propensity-matching (21 uDCD, 63 DBD), significant baseline differences persisted: uDCD recipients were younger (47.2 ± 11.8 vs. 57.5 ± 10.9 years, p < 0.001) despite a similar dialysis vintage (7.2 ± 3.2 vs. 7.7 ± 3.7 years, p = 0.569). Warm ischemia time was 58.5 ± 12.3 vs. 3.0 ± 0.0 min (p < 0.001), and cold ischemia time was longer in uDCD (13.7 ± 5.9 vs. 8.4 ± 2.5 h, p < 0.001). DGF occurred in 90.5% of uDCD versus 54.1% of DBD recipients (p = 0.006). Graft failure was markedly higher in uDCD (28.6% vs. 1.6%, p = 0.001), yet mortality was lower (14.3% vs. 27.9%, p = 0.339). After a median follow-up of 60 months (IQR 48–72) for both groups, the death-censored 5 year graft survival rate was 71.4% for uDCD versus 98.4% for DBD (p < 0.001). Conclusions: Despite higher rates of DGF and graft failure, uDCD kidney transplantation demonstrated an acceptable 5 year patient survival rate in carefully selected younger recipients. These findings support cautious expansion of uDCD programs with rigorous recipient selection criteria and realistic outcome expectations. Full article

This review integrates the biology and clinical translation of hydrogen sulfide (H₂S) in balneology. It frames H₂S as a gasotransmitters with dual chemical and biological actions and summarizes the H₂S/HS⁻ equilibrium as a function of pH, temperature, and oxygenation, which governs bioaccessibility in sulfurous waters. Endogenous and exogenous sources, transport, and mitochondrial catabolism are outlined, together with core cellular mechanisms: protein persulfidation; activation of Nrf2/ARE; modulation of NF-κB; regulation of ion channels; and engagement of PI3K/Akt, MAPK/ERK, and Wnt pathways, plus epigenetic interactions with HDACs and sirtuins. Preclinical and clinical evidence in dermatology, musculoskeletal disease, and respiratory care is synthesized, alongside metabolic, cardiovascular, gastrointestinal, and renal effects. Technical aspects that preserve the bioactive fraction of H₂S while meeting environmental safety limits are highlighted. Routes of administration (bathing, peloids, inhalation, and drinking cures) and key operational parameters are described. Overall, the review links physicochemical and molecular foundations with clinical indications for sulfurous waters and derivatives and identifies opportunities for research and development in H₂S donors and thermal cosmetics without extrapolating beyond the available data. Full article

Prebiotics are selectively utilized substrates that modulate gut microbiota and host health, yet different prebiotic structures may elicit distinct ecological and metabolic responses. In this study, we investigated the effects of five structurally diverse prebiotics—isomaltooligosaccharides (IMO), arabinogalactans (AG), pectin, inulin, and stachyose—on human gut microbiota via a 24 h in vitro anaerobic culture with healthy donors’ gut microbiota. Microbial community dynamics were profiled by 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) production was analyzed. All treatments resulted in decreased α-diversity compared with baseline, with pectin most effectively preserving microbial richness and evenness, whereas stachyose led to the greatest reduction. Community composition and functional profiles shifted in a substrate-specific manner, with AG promoting Bacteroidaceae, IMO stimulating Lachnospiraceae and Faecalibacterium, and pectin supporting balanced microbial structures and SCFA production. Pectin, IMO, and inulin enhanced butyrate levels, whereas AG and pectin promoted propionate formation. These findings demonstrate that prebiotic structural differences strongly shape gut microbial ecology and metabolism, providing a mechanistic basis for rationally selecting and combining prebiotics to beneficially modulate the gut microbiota. Full article

Purpose: Cisplatin chemotherapy is complicated by acute kidney injury (cis-AKI), driven by regulated cell death pathways, including apoptosis and pyroptosis. However, the temporal relationship between apoptosis and pyroptosis in cis-AKI remains unclear. This study investigated the roles of these pathways and evaluated the renoprotective effect of the hydrogen sulfide (H₂S) donor GYY4137. Method: Cis-AKI was modeled in mice and HK2 cells, divided into control, cisplatin, and cisplatin + GYY groups. Kidney function parameters, histopathology, and cell death were evaluated. Markers of apoptosis and pyroptosis, along with the H₂S-producing enzyme, were analyzed. Results: Renal impairment progressed from BUN elevation to increased Scr, coupled with aggravated renal tissue damage. Apoptotic signaling peaked at 24 h, evidenced by a raised Bax/Bcl-2 ratio and caspase-3 cleavage. Pyroptosis pathways, via both NLRP3/caspase-1/GSDMD and caspase-3/GSDME axes, were activated later at 72 h, with concurrent rises in IL-1β and IL-18. GYY4137 treatment significantly ameliorated renal dysfunction, reducing serum creatinine and BUN levels by 22.64% and 22.5%, respectively. It suppressed both the early apoptotic and delayed pyroptosis cascades without reversing CBS downregulation. Conclusions: GYY4137 mitigated both apoptosis and pyroptosis, offering a promising multi-targeted therapy for cis-AKI. Full article

Background: Arterial stiffness assessed by measuring pulse wave velocity (PWV) is a well-established predictor of cardiovascular mortality. To our knowledge, no studies on arterial stiffness in kidney transplant recipients (KTRs) from Tunisia have been conducted. The present study aimed to assess arterial stiffness in Tunisian KTRs and to identify the key predictors associated with its increase. Methods: We conducted a cross-sectional, single-center study enrolling Tunisian KTRs aged 18 years or older with a minimum post-transplant follow-up of six months. Arterial stiffness was measured as pulse carotid–femoral PWV (CF-PWV) by a Complior device. A CF-PWV ≥ 10 m/s was defined as elevated. Results: Fifty-four KTRs were included (mean age: 42.55 ± 10.61 years). Among them, 19 (35.2%) had a CF-PWV ≥ 10 m/s. The univariate analysis showed a significant association between elevated CF-PWV and the following parameters: age, hypertension prior to transplantation, dyslipidemia, donor age, parameters obtained through office blood pressure measurement (systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP)), central SBP recorded by the Complior device, nocturnal SBP obtained through 24 h ambulatory blood pressure monitoring (ABPM), and fasting blood glucose. A multivariable analysis with CF-PWV ≥ 10 m/s as a dependent variable retained the following independent factors: dyslipidemia (p = 0.015; OR = 60.32), donor age (p = 0.014; OR = 1.16), SBP obtained through office blood pressure measurement (p = 0.015; OR = 1.25), and fasting blood glucose (p = 0.034; OR = 22.35). Conclusions: Given the major impact of cardiovascular disease on post-transplant outcomes, understanding the determinants of arterial stiffness is crucial for improving patient care. Routine PWV assessment may not be feasible in all centers due to cost or limited equipment availability. Therefore, identifying the clinical and biological markers associated with arterial stiffness offers a low-cost and widely accessible alternative for evaluating cardiovascular risk. These findings may support the development of a simple risk score to help nephrologists detect and manage high-risk KTRs more effectively. Full article

The key to proper implant integration in bone replacement is to orchestrate the complex interactions between materials and tissues. Moreover, due to the rapid demographic shift towards aging societies and the increase in elderly and osteoporotic patients, it is of great importance that implant materials are osteointegrative in not only healthy but also compromised bone tissues. Here, titanium (Ti) scaffolds were subjected to shifted laser surface texturing (sLST) using a nanosecond pulsed laser to create an open pore macrotopography with micro-and nano-Ti droplets. In contrast to conventional laser texturing, which leads to high heat accumulation; in sLST, the frequency of laser pulses is low, allowing for resolidification, thereby creating a surface with abundant coverage micro-/nanodroplets. The main objective was to compare the cellular responses of human mesenchymal stromal cells (hMSCs) on sLST-textured Ti surfaces (LT-Ti) for the first time with standard sand-blasted, acid-etched surfaces (SLA-Ti). In-depth analyses of cell survival, proliferation, shape, mineralization, and gene expression were performed. Cell survival/proliferation was found to be similar on both surfaces; however, SEM imaging revealed differences in hMSC morphology. On LT-Ti, cells adopted well-rounded shapes, whereas on SLA-Ti they assumed more planar shapes. Bulk RNA sequencing performed after short-term culture on both surfaces disclosed expression changes in genes such as DUSP6, TNFSF12-TNFSF13 and SULT1A4. Remarkably, the osteogenic differentiation capacity of hMSCs was significantly enhanced on LT-Ti compared to SLA-Ti. Furthermore, aged/osteoporotic donor cohorts showed significantly enhanced matrix mineralization on LT-Ti. In conclusion, our novel results demonstrate that sLST-Ti surfaces are safe, highly biocompatible, can rescue patient-cohort-specific mineralization behavior, and therefore hold great potential for the development into next-generation implants, which are suitable for both the elderly and bone-compromised populations. Full article

Background/Objectives: The aim of this study was to evaluate the effects of sodium trimetaphosphate (TMP) and fluoride (F) on the surface free energy (SFE) of enamel coated with human salivary pellicle in vitro, both after treatment with the gels and after an erosive challenge. Methods: Bovine enamel discs (n = 10/group) were randomly allocated into seven treatment groups (gels): placebo (without any actives), low-fluoride gels (4500 ppm F—“4500F”) supplemented or not with microparticulate TMP (5%) or nanoparticulate (2.5% or 5%) TMP, 9000 ppm F (positive control), and 12,300 ppm F (acid gel, commercial control); a negative control group (i.e., untreated enamel) was included. Discs were exposed to human saliva (2 h), treated with the gels (1 min) and subjected to a 1-min acid challenge. Three probing liquids were used to assess enamel SFE. Data were submitted to two-way, repeated-measures ANOVA followed by Tukey’s test, and by Mann–Whitney’s test (p < 0.05). Results: SFE was significantly altered after exposure to saliva, changing from hydrophobic to slightly hydrophilic; gel treatment further increased enamel hydrophilicity (i.e., electron-donor properties), without significant differences among gels. After the erosive challenge, the enamel surface became significantly less hydrophilic for all groups; the highest values were observed for both gels containing nanoparticulate TMP. As for the overall SFE, the best performance was achieved by the gel containing 5% nanometric TMP. Conclusions: SFE of salivary-coated enamel was significantly influenced by the treatment gels, which promoted increases in hydrophilicity. Gels containing TMP, especially at nanoscale, promoted higher resistance to changes in hydrophilicity after an erosive challenge. Full article

Thiotaurine (2-aminoethane thiosulfonate) is a naturally occurring sulfur-based compound featuring a thiosulfonate group, enabling it to act as a biologically relevant donor of hydrogen sulfide (H₂S) through thiol-dependent persulfidation. H₂S levels are known to be reduced in individuals with osteoarthritis, where it plays roles in modulating inflammation, oxidative stress, and pain. This study investigated the anti-inflammatory effects of Thiotaurine in human primary chondrocytes exposed to a pro-inflammatory cytokine. Cells were pre-treated with Thiotaurine prior to stimulation with TNF-α, and the expression levels of key interleukins were assessed at both the mRNA and protein levels. TNF-α stimulation led to upregulation of IL-6, IL-8, and IL-1β, which was significantly attenuated by Thiotaurine pre-treatment. Additionally, immunofluorescence analysis showed that Thiotaurine inhibited the phosphorylation and nuclear translocation of p65, indicating suppression of NF-κB pathway activation. Persulfide detection assays confirmed an increase in intracellular persulfide levels following Thiotaurine treatment. In summary, due to its anti-inflammatory activity and ability to release H₂S, Thiotaurine emerges as a promising and potentially safe therapeutic option for osteoarthritis and other inflammation-related conditions. Full article