Search Results (14)

NSAID-induced small intestinal injury is a clinically significant complication among chronic NSAID and aspirin users, yet effective treatment options remain limited. This systematic review evaluated natural products, functional foods, and probiotics for preventing or treating NSAID-induced small intestinal injury. PubMed, Embase, CENTRAL, and CNKI were searched from inception to January 2026 for randomized studies involving adults with NSAID- or aspirin-induced enteropathy assessed using capsule endoscopy or intestinal permeability testing. Risk of bias was assessed using RoB 2 and ROBINS-I. Due to substantial clinical and methodological heterogeneity, meta-analysis was not performed, and findings were synthesized narratively. Twenty-two studies were included: 21 randomized controlled trials and one quasi-randomized study. Geranylgeranylacetone demonstrated protective effects in three of four capsule endoscopy studies. Lactoferrin, zinc carnosine, and fish protein hydrolysate reduced indomethacin-induced intestinal hyperpermeability. Probiotic effects appeared outcome-dependent, with more consistent benefits observed for capsule endoscopy-based mucosal injury outcomes than for intestinal permeability outcomes. Among randomized trials, three were rated as having low risk of bias, 15 had some concerns, and three had high risk. Overall, preliminary evidence suggests that selected natural-origin interventions may protect against NSAID/aspirin-induced small intestinal injury. However, because the certainty of evidence was generally low or very low, these findings should be interpreted as hypothesis-generating and require confirmation in larger, methodologically rigorous trials. Full article

Central venous catheters are a major risk factor for Candida albicans vascular infections, which remain challenging to manage. Although antifungal therapy is standard, the host pathways shaping vascular responses—particularly the Notch signaling pathway (NSP)—are not well characterized in this context. In addition, the potential influence of the prostaglandin pathway on vascular NSP-related responses during infection remains unclear. In this study, a rat model of central venous catheter-associated C. albicans infection was used to evaluate microbiological outcomes and vascular NSP-related protein expression. Immunohistochemical analyses were performed to assess Candida immunostaining alongside the expression of Notch receptors (Notch1–3) and ligands (DLL1/4, Jagged1/2) in vascular tissues. Experimental groups included sham, infected control, antifungal-treated (fluconazole, caspofungin, liposomal amphotericin B), and prostaglandin pathway-intervention groups (sulprostone and sulprostone followed by indomethacin). C. albicans infection was associated with higher vascular NSP-related protein expression compared with sham animals. Antifungal-treated groups showed lower NSP-related protein expression, while fungicidal agents were associated with absence of fungal growth in catheter and kidney cultures. In the sulprostone–indomethacin-treated group, NSP-related protein expression levels were lower than those in the sulprostone-treated group despite persistent fungal burden. In conclusion, central venous catheter-associated C. albicans infection was associated with altered vascular NSP-related protein expression. Differences in NSP-related protein expression patterns were observed across antifungal- and prostaglandin pathway-intervention groups. These findings are descriptive and do not allow causal inference but may provide a basis for future studies exploring the role of NSP in vascular responses to C. albicans infection. Full article

Intraventricular hemorrhage (IVH) is a common complication of prematurity and continues to represent a considerable threat due to its association with significant short- and long-term morbidity and mortality. Despite the advances in neonatal care, the prevalence of IVH, particularly in the extremely preterm neonates, remains high. Therefore, it is imperative to recognize and implement in clinical practice preventive strategies, non-pharmacological or pharmacological, to reduce IVH effectively. The aim of this narrative review is to provide an overview of novel and debatable preventive measures for IVH that are promising for clinical use and could potentially improve outcomes for very preterm neonates. IVH prevention bundles (IVHPBs) consist of strategies that aim to minimize hemodynamic and cerebral perfusion fluctuations, which are a crucial component of IVH pathogenesis. Early postnatal prophylactic indomethacin, erythropoietin, and insulin-growth factor-1 administration have shown encouraging results on IVH prevention; however, the literature is still inconclusive. Stem-cell-based interventions represent novel and promising techniques with the potential to contribute to the prevention of IVH. The prevention of IVH remains a field of investigation, and there is a requirement for conclusive evidence and recommendations. The necessity for further large-scale prospective studies is therefore evident. Full article

Background/Objectives: Male infertility is a prevalent issue impacting numerous couples worldwide. This review aims to evaluate the effectiveness of empirical therapies for male infertility, focusing on both lifestyle modifications and medical treatments. This study provides a comprehensive overview of interventions aimed at improving male fertility outcomes. Methods: A thorough review of the existing literature was conducted, encompassing studies on lifestyle changes such as dietary changes, smoking cessation, alcohol moderation, and exercise. Additionally, medical treatments including selective estrogen receptor modulators, gonadotropins, aromatase inhibitors, phosphodiesterase-5 inhibitors, antioxidants, dopamine agonists, kallikrein, indomethacin, low-dose corticosteroids, alpha-blockers, and nitric oxide donors were evaluated. The study population included males diagnosed with infertility, focusing on various underlying causes. Results: Lifestyle modifications were found to have a positive impact on sperm quality. Evidence shows that a healthy diet, smoking cessation, moderate alcohol consumption, and regular exercise improve fertility outcomes. Medical treatments demonstrated significant improvements in sperm production and quality. Selective estrogen receptor modulators and gonadotropins enhanced sperm parameters. Aromatase inhibitors and phosphodiesterase-5 inhibitors specifically improved sperm motility and increased pregnancy rates. Antioxidants, such as vitamins E and C and coenzyme Q10, reduced oxidative stress and enhanced sperm counts, motility, and morphology. Dopamine agonists, particularly cabergoline, normalized prolactin levels and improved fertility outcomes. Kallikrein therapy improved sperm parameters and increased pregnancy rates. Indomethacin treatment was associated with increased sperm concentrations and motility. Low-dose corticosteroids and alpha-blockers showed variable results, and nitric oxide donors like L-arginine enhanced sperm counts and motility. Conclusions: Empirical therapies, including lifestyle modifications and medical treatments, significantly enhance sperm quality and reproductive potential. These integrated approaches are essential in improving fertility outcomes in males. However, further extensive randomized trials are necessary to definitively establish the most effective treatments. Full article

Berberine is a natural isoquinoline alkaloid with low toxicity, which exists in a wide variety of medicinal plants. Berberine has been demonstrated to exhibit potent prevention of indomethacin-induced gastric injury (GI) but the related mechanism remains unclear. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied for the first time to investigate the alteration of serum metabolites in the protection of berberine against indomethacin-induced gastric injury in rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-GI effect of berberine. The pharmacodynamic data indicated that berberine could ameliorate gastric pathological damage, inhibit the level of proinflammatory factors in serum, and increase the level of antioxidant factors in serum. The LC-MS-based metabolomics analysis conducted in this study demonstrated the presence of 57 differential metabolites in the serum of rats with induced GI caused by indomethacin, which was associated with 29 metabolic pathways. Moreover, the study revealed that berberine showed a significant impact on the differential metabolites, with 45 differential metabolites being reported between the model group and the group treated with berberine. The differential metabolites were associated with 24 metabolic pathways, and berberine administration regulated 14 of the 57 differential metabolites, affecting 14 of the 29 metabolic pathways. The primary metabolic pathways affected were glutathione metabolism and arachidonic acid metabolism. Based on the results, it can be concluded that berberine has a gastroprotective effect on the GI. This study is particularly significant since it is the first to elucidate the mechanism of berberine’s action on GI. The results suggest that berberine’s action may be related to energy metabolism, oxidative stress, and inflammation regulation. These findings may pave the way for the development of new therapeutic interventions for the prevention and management of NSAID-induced GI disorders. Full article

Hydrogen sulfide (H₂S) emerged recently as an anti-oxidative signaling molecule that contributes to gastrointestinal (GI) mucosal defense and repair. Indomethacin belongs to the class of non-steroidal anti-inflammatory drugs (NSAIDs) and is used as an effective intervention in the treatment of gout- or osteoarthritis-related inflammation. However, its clinical use is strongly limited since indomethacin inhibits gastric mucosal prostaglandin (PG) biosynthesis, predisposing to or even inducing ulcerogenesis. The H₂S moiety was shown to decrease the GI toxicity of some NSAIDs. However, the GI safety and anti-oxidative effect of a novel H₂S-releasing indomethacin derivative (ATB-344) remain unexplored. Thus, we aimed here to compare the impact of ATB-344 and classic indomethacin on gastric mucosal integrity and their ability to counteract the development of oxidative gastric mucosal injuries. Wistar rats were pretreated intragastrically (i.g.) with vehicle, ATB-344 (7–28 mg/kg i.g.), or indomethacin (5–20 mg/kg i.g.). Next, animals were exposed to microsurgical gastric ischemia-reperfusion (I/R). Gastric damage was assessed micro- and macroscopically. The volatile H₂S level was assessed in the gastric mucosa using the modified methylene blue method. Serum and gastric mucosal PGE₂ and 8-hydroxyguanozine (8-OHG) concentrations were evaluated by ELISA. Molecular alterations for gastric mucosal barrier-specific targets such as cyclooxygenase-1 (COX)-1, COX-2, heme oxygenase-1 (HMOX)-1, HMOX-2, superoxide dismutase-1 (SOD)-1, SOD-2, hypoxia inducible factor (HIF)-1α, xanthine oxidase (XDH), suppressor of cytokine signaling 3 (SOCS3), CCAAT enhancer binding protein (C/EBP), annexin A1 (ANXA1), interleukin 1 beta (IL-1β), interleukin 1 receptor type I (IL-1R1), interleukin 1 receptor type II (IL-1R2), inducible nitric oxide synthase (iNOS), tumor necrosis factor receptor 2 (TNFR2), or H₂S-producing enzymes, cystathionine γ-lyase (CTH), cystathionine β-synthase (CBS), or 3-mercaptopyruvate sulfur transferase (MPST), were assessed at the mRNA level by real-time PCR. ATB-344 (7 mg/kg i.g.) reduced the area of gastric I/R injuries in contrast to an equimolar dose of indomethacin. ATB-344 increased gastric H₂S production, did not affect gastric mucosal PGE₂ content, prevented RNA oxidation, and maintained or enhanced the expression of oxidation-sensitive HMOX-1 and SOD-2 in line with decreased IL-1β and XDH. We conclude that due to the H₂S-releasing ability, i.g., treatment with ATB-344 not only exerts dose-dependent GI safety but even enhances gastric mucosal barrier capacity to counteract acute oxidative injury development when applied at a low dose of 7 mg/kg, in contrast to classic indomethacin. ATB-344 (7 mg/kg) inhibited COX activity on a systemic level but did not affect cytoprotective PGE₂ content in the gastric mucosa and, as a result, evoked gastroprotection against oxidative damage. Full article

We aimed to evaluate how feeding a high-fat–low-fiber (F) diet to rats and dietary intervention with the implementation of a standard-fat-and-fiber (S) diet affects the response of the cardiovascular system to chromium (III) picolinate (Cr–Pic) and, alternatively, chromium nanoparticles (Cr–NPs). Young male Wistar Han rats (n/group = 12) from either the fatty group (18 weeks on F diet) or the intervention group (9 weeks on F diet + 9 weeks on S diet) received a pharmacologically relevant dose of 0.3 mg Cr/kg body weight in the form of Cr–Pic or Cr–NPs for 9 weeks. Our study on rats confirmed the pro-inflammatory effect of an F diet administered for 18 weeks. In the intervention group, both Cr–Pic and Cr–NPs decreased heart glutathione ratio (GSH+GSSG), enhanced participation of nitric oxide (NO) derived from inducible NO synthase (iNOS) in vascular relaxation to acetylcholine (ACh), increased the vasodilator net effect of cyclooxygenase-2 (COX-2)-derived prostanoids, and increased the production of superoxide anion (O₂^.−) in aortic rings. Meanwhile, in the fatty group, there was increased heart superoxide dismutase (SOD), decreased heart catalase (CAT), and reduced sensitivity in pre-incubated aortic rings to endogenous prostacyclin (PGI₂). The factors that significantly differentiated Cr–NPs from Cr–Pic were (i) decreased blood antioxidant capacity of water-soluble compounds (0.75-fold, p = 0.0205), (ii) increased hydrogen peroxide (H₂O₂) production (1.59-fold, p = 0.0332), and (iii) modified vasodilator response due to PGI₂ synthesis inhibition (in the intervention group) vs. modified ACh-induced vasodilator response due to (iv) COX inhibition and v) PGI₂ synthesis inhibition with thromboxane receptor blockage after 18 weeks on F diet (in the fatty group). Our results show that supplementation with Cr–Pic rather than with Cr–NPs is more beneficial in rats who regularly consumed an F diet (e.g., for 18 weeks). On the contrary, in the intervention group (9 weeks on F diet + 9 weeks of dietary fat normalization (the S diet)), Cr–Pic and Cr–NPs could function as pro-oxidant agents, initiating free-radical reactions that led to oxidative stress. Full article

As is the case with most eucaryotic cells, cancer cells are able to secrete extracellular vesicles (EVs) as a communication means towards their environment and surrounding cells. EVs are represented by microvesicles and smaller vesicles called exosomes, which are known for their involvement in cancer aggressiveness. The release of such EVs requires the intervention of trafficking-associated proteins, mostly represented by the RAB-GTPases family. In particular, RAB27A is known for its role in addressing EVs-to-be secreted towards the the plasma membrane. In this study, shRNAs targeting RAB27A were used in colorectal (CRC) and glioblastoma (GB) cell lines in order to alter EVs secretion. To study and monitor EVs secretion in cell lines’ supernatants, nanoparticle tracking analysis (NTA) was used through the NanoSight NS300 device. Since it appeared that NanoSight failed to detect the decrease in the EVs secretion, we performed another approach to drop EVs secretion (RAB27A-siRNA, indomethacin, Nexihnib20). Similar results were obtained i.e., no variation in EVs concentration. Conversely, NTA allowed us to monitor EVs up-secretion following rotenone treatment or hypoxia conditions. Therefore, our data seemed to point out the insufficiency of using only this technique for the assessment of EVs secretion decrease. Full article

The effect of dietary fibres on intestinal barrier function has not been well studied, especially in the elderly. We aimed to investigate the potential of the dietary fibres oat β-glucan and wheat arabinoxylan to strengthen the intestinal barrier function and counteract acute non-steroid anti-inflammatory drug (indomethacin)-induced hyperpermeability in the elderly. A general population of elderly subjects (≥65 years, n = 49) was randomised to a daily supplementation (12g/day) of oat β-glucan, arabinoxylan or placebo (maltodextrin) for six weeks. The primary outcome was change in acute indomethacin-induced intestinal permeability from baseline, assessed by an in vivo multi-sugar permeability test. Secondary outcomes were changes from baseline in: gut microbiota composition, systemic inflammatory status and self-reported health. Despite a majority of the study population (85%) showing a habitual fibre intake below the recommendation, no significant effects on acute indomethacin-induced intestinal hyperpermeability in vivo or gut microbiota composition were observed after six weeks intervention with either dietary fibre, compared to placebo. Full article

Clinically, high cyclooxygenase-2 expression in malignant glioma correlates well with poor prognosis and the use of aspirin is associated with a reduced risk of glioma. To extend the current understanding of the apoptotic potential of aspirin in most cell types, this study provides evidence showing that aspirin induced glioma cell apoptosis and inhibited tumor growth, in vitro and in vivo. We found that the human H4 glioma cell-killing effects of aspirin involved mitochondria-mediated apoptosis accompanied by endoplasmic reticulum (ER) stress, Noxa upregulation, Mcl-1 downregulation, Bax mitochondrial distribution and oligomerization, and caspase 3/caspase 8/caspase 9 activation. Genetic silencing of Noxa or Bax attenuated aspirin-induced viability loss and apoptosis, while silencing Mcl-1 augmented the effects of aspirin. Data from genetic and pharmacological studies revealed that the axis of ER stress comprised an apoptotic cascade leading to Noxa upregulation and apoptosis. The apoptotic programs and mediators triggered by aspirin in H4 cells were duplicated in human U87 glioma cell line as well as in tumor-bearing BALB/c nude mice. The involvement of ER stress in indomethacin-induced Mcl-1 downregulation was reported in our previous study on glioma cells. Therefore, the aforementioned phenomena indicate that ER stress may be a valuable target for intervention in glioma apoptosis. Full article

Background: To evaluate the efficacy and the safety of subthreshold micropulse yellow laser (SMYL) in the treatment of chronic postoperative cystoid macular edema (PCME), which is refractory to standard therapies. Methods: A retrospective chart review of ten eyes of ten patients affected by refractory PCME who underwent SMYL was performed. Five PCME cases were subsequent to uncomplicated cataract surgery (CS), two cases to complicated CS (CCS) with posterior capsule rupture and three cases occurred after retinal detachment surgery (RD). All conditions were refractory to conventional treatments prior to SMYL interventions for at least 4 months, including nonsteroidal anti-inflammatory eyedrops, topical steroids, oral indomethacin, sub-Tenon’s triamcinolone injections and Dexamethasone intravitreal implants. All patients underwent one or more treatments with 577 nm SMYL photo-stimulation, with 7 × 7 grids with confluent spots and a 5% duty cycle covering the whole edematous retina, including the foveal center. Best corrected visual acuity (BCVA) and central macular thickness (CMT) were obtained using OCT, and evaluated before and after the treatment at 1, 2, 3 and 6-month follow-ups. Results: A complete subfoveal macular edema resolution was observed in all of the eyes, with statistically significant improvements in terms of BCVA and CMT in all of the follow-up timelines (at 6 months, p = 0.002 and p = 0.005, respectively). The mean number of laser treatments was 1.3. At the final follow-up, a complete subfoveal edema reabsorption was observed in all patients with visual acuity improvement. No complications were observed in any case. Conclusions: SMYL seems to be a safe and effective treatment for the long-term resolution of refractory PCME and may be a useful alternative to expensive and invasive therapeutic options. Full article

Obesity is associated with microvascular dysfunction. While low-fat diet improves cardiovascular risk, its contributions on microvascular function, independent of weight loss, is unknown. We tested the hypothesis that nitric oxide (NO)-dependent vasodilation in microvessels is improved by low-fat diets designed for weight loss (LFWL) compared to low-fat weight maintenance (LFWM) diet. Obese adults were randomly assigned to either a LFWL diet (n = 11) or LFWM diet (n = 10) for six weeks. Microvessels were obtained from gluteal subcutaneous fat biopsies before and after the intervention for vascular reactivity measurements to acetylcholine (Ach) and flow, with and without L-NAME or indomethacin. Vascular and serum NO and C-reactive protein (CRP) were also measured. LFWL diet increased flow-induced (FID) and ACh-induced dilation (AChID); an effect that was inhibited by L-NAME. Conversely, LFWM diet did not affect FID or AChID. Indomethacin improved FID and AChID in the baseline and this effect was minimized in response to both diets. Serum NO or CRP did not change in response to either diet. In conclusion, LFWL diet improves microvascular reactivity compared to LFWM diet and increased vascular NO contribution to the improved microvascular dilation. These data suggest that weight reduction on low fat diet is critical for microvascular health. Full article

Sphingolipids (SPLs) are biologically important molecules, but the structural diversity and complexity of SPLs brings significant analytical challenges for their study. In this paper, we have developed an UPLC-Q-TOF-MS-based sphingolipidomic approach for the comprehensive identification and quantification of SPLs in rat serum. A total of 120 SPLs covering seven subcategories were identified for the first time. Method validations including linearity, sensitivity, reproducibility, and recovery were also evaluated. This method was exemplarily applied to characterize the SPL alterations in rheumatoid arthritis (RA) rats and the intervention effects of indomethacin (IDM). Partial least squares-discriminant analysis (PLS-DA) showed that the model group was well separated from the control group, whereas the IDM-treated group exhibited a trend to recover the controls. Twenty-six significantly changed SPL markers were explored, and the levels of ceramides (Cers) and their metabolites were found to be reversed by IDM treatment. These results indicate that IDM exerts anti-arthritic effects through the suppression of Cer-mediated COX-2 activation and resulting PEG₂ liberation. The present study demonstrates a promising potential of this method for the understanding of RA and the anti-arthritic mechanisms of relevant drugs. Full article

Deregulation in uterine contractility can cause common pathological disorders of the female reproductive system, including preterm labor, infertility, inappropriate implantation, and irregular menstrual cycle. A better understanding of human myometrium contractility is essential to designing and testing interventions for these important clinical problems. Robust studies on the physiology of human uterine contractions require in vitro models, utilizing a human source. Importantly, uterine contractility is a three-dimensionally (3D)-coordinated phenomenon and should be studied in a 3D environment. Here, we propose and assess for the first time a 3D in vitro model for the evaluation of human uterine contractility. Magnetic 3D bioprinting is applied to pattern human myometrium cells into rings, which are then monitored for contractility over time and as a function of various clinically relevant agents. Commercially available and patient-derived myometrium cells were magnetically bioprinted into rings in 384-well formats for throughput uterine contractility analysis. The bioprinted uterine rings from various cell origins and patients show different patterns of contractility and respond differently to clinically relevant uterine contractility inhibitors, indomethacin and nifedipine. We believe that the novel system will serve as a useful tool to evaluate the physiology of human parturition while enabling high-throughput testing of multiple agents and conditions. Full article