Myocardial ischemia is a major global contributor to mortality. While reperfusion therapy remains the most effective treatment, it paradoxically leads to myocardial ischemia–reperfusion (MI/R) injury, resulting in irreversible cardiac damage for which no effective interventions currently exist. This underscores the pressing need to unravel the pathogenesis of MI/R injury and devise new therapeutic strategies. In this study, supervised machine learning models, including logistic regression (LR), support vector machines (SVM), random forests (RF), neural networks (NN), and k-nearest neighbors (kNN), were utilized to predict treatment response. The models incorporated molecular and biochemical features to evaluate three drugs: trans-Anethole (TNA), pentoxifylline (PTX), and cyanidin-3-O-glucoside (Cy3G). The sequential forward selection (SFS) method was employed to select the most relevant features for prediction. To assess model performance, metrics such as precision, accuracy, recall (sensitivity), specificity, and the Matthews Correlation Coefficient (MCC) were analyzed for both reduced and complete models. Among the classifiers, kNN demonstrated notable performance, achieving an accuracy of 0.9156 ± 0.0242 and an average area under the ROC curve (AUC) of 0.90 across three cross-validation iterations surpassing all other classifiers. This observed performance is in line with recent literature that employs advanced computational methods in similar domains. A key advantage of our study is the use of a two-layer framework—integrating molecular signatures with biochemical markers—which can provide improved robustness and biological relevance. This multi-layer integration enhances interpretability and better reflects the multifactorial nature of MI/R injury, while supporting model generalization. Feature selection identified one molecular marker (SOX5) and two biochemical markers (dP/dtmax and cTnT) as significant predictors of drug response. This integrative approach has the potential to enhance personalized therapy for myocardial ischemia by enabling precise drug response predictions and guiding the development of targeted treatment strategies.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-18620-8.

The aim of this study (PTX-trial) is to determine the optimal dose of pentoxifylline (PTX) in preterm neonates (gestational age < 30 weeks) with (suspected) late onset sepsis (LONS). The PTX-trial is a prospective multicentre open-label sequential dose-optimization study with an adapted continual reassessment method. An up-and-down dose-response design was used, with dose step-up and step-down titration per three patients with a PTX dose of 30 mg/kg/day in 6 h for 3 days in the first group. The primary outcome was an ED75, which was defined as a both clinical and chemical effective dose for 75% of preterm neonates with LONS. In total, 30 neonates were included in the study. As an effective dose was only observed in 27% of the patients, the ED75 could not be determined. There were no significant differences in biochemical and clinical response between the different dosage groups. The largest decrease in nSOFA score after start of PTX was observed in the dosage group of 30 mg/kg/day in 6 h. In this dose-finding trial for PTX in preterm neonates, our findings reveal no discernible clinical advantage associated with either increasing or decreasing the PTX dosage. The relatively high variability in sepsis severity and patients' post-natal ages increase the uncertainty of our findings, but the standardly used dosage of 30 mg/kg/day (5 mg/kg/h for 6 h) has consistently demonstrated safe tolerability without any reported severe adverse events.

Chronically Trypanosoma cruzi-infected mice show signs of behavioral and cognitive changes, resembling aspects of Chagas disease patients. Inflammatory mediators, such as cytokines and nitric oxide (NO) have been linked to mental disorders. Preclinical studies showed the partial effects of the trypanossomicidal drug benznidazole (Bz) on mnemonic alterations. Here, we investigated the participation of the parasite and systemic inflammatory profile in behavioral and cognitive changes, using Bz combined with the immunoregulator pentoxifylline (PTX). Chronically T. cruzi-infected C57BL/6 mice were treated with Bz (25 mg/Kg/day) and PTX (20 mg/Kg/day) as mono or combined therapies, submitted to behavioral tests, and canonical biological stressors were analyzed. Bz therapy had no effects on anxiety, but partially ameliorated innate compulsive behavior, depression, and memory loss, while PTX and, mainly, Bz + PTX had a broader beneficial effect on these changes. Bz and Bz + PTX reduced parasitemia. The three therapies decreased the parasite burden in the brain. Bz and Bz + PTX therapies reduced oxidative stress in the brain tissue, while PTX and Bz + PTX therapies efficiently controlled the elevated concentrations of GABA/glutamate in the cerebral cortex. Even after parasite control, serum concentrations of NO and tumor necrosis factor (TNF) enhanced as the disease progressed. Bz and, mainly, Bz + PTX treatments reduced NO levels. The three therapeutic schemes hamper the progressive increase of TNF levels. Reanalysis of available data on the systemic miRNA transcriptome supports the beneficial role of Bz + PTX therapy on pivotal hubs involved in inflammation of the central nervous system and neurodegenerative disorders. Moreover, principal components analysis (PCA-2D and 3D projections) underlined the distinction between the noninfected and vehicle-treated infected groups, while Bz + PTX-treated infected mice were closer to noninfected controls. The combined Bz + PTX therapy reduced parasite load and regulated pivotal neurochemical changes in the brain and the systemic inflammatory profile, improving behavioral and cognitive changes in a model of Chagas disease.

Introduction: The prevalence of executive dysfunctions and attention deficits is increasingly recognized among patients with atherosclerotic cardiovascular disease (ASCVD). Cilostazol (CLZ) and pentoxifylline (PTX) are two potential therapeutic agents that may help reduce the risk of cognitive decline in these patients, likely due to their anti-inflammatory, vasodilatory and endothelial protective effects. However, their comparative efficacy remains unknown. Research Question: CLZ or PTX, which drug is effective in reducing cognitive dysfunctions in ASCVD patients? Methods: A systematic review (SR) was conducted following a comprehensive literature search including RCTs, narrative review, retrospective, and prospective studies. The individual effects of both therapies were evaluated with respect to their potential to reduce vascular stress and improve cognitive dysfunction. Results: This SR compares CLZ versus PTX in 19,966 subjects across 6 studies carried out in 4 countries including Brazil, Japan, Taiwan, and the United States. PTX significantly reduced C-reactive protein (CRP) (P=0.04), Tumor Necrosis Factor-alpha (TNF-α) (P&lt;0.01) levels, and attenuated the decline in Interleukin-10 (IL-10) compared to placebo (P&lt;0.01), thereby suggesting a potential anti-inflammatory effect (Fernandes et al). Additionally, it enhances blood flow by promoting fibrinolysis, improving erythrocyte flexibility, and reducing neutrophil activation (McCarty et al). On the contrary, CLZ was associated with a 25% reduction in dementia risk (HR 0.75; 95%CI, 0.61–0.92) (Tai et al), and significantly reduced the risk of ischemic (OR 0.68; 95%CI, 0.57–0.81; P&lt;0.0001) and hemorrhagic (OR 0.43; 95%CI, 0.29–0.64; P=0.0001) stroke with a lower risk of bleeding (McHutchison et al). However, RCTs showed no significant improvement in Mini-Mental State Examination (MMSE) scores with cilostazol over 96 weeks (Saito et al). Additionally, post-stroke cognition did not improve significantly, with elevated M1 macrophages potentially contributing to neurological decline (Huang et al). While both drugs show promising effects, CLZ has more supportive cognitive data. Conclusion: Based on current evidence, CLZ and PTX show potential in mitigating cognitive dysfunctions in ASCVD. CLZ has more data linking to reduced dementia and stroke risk, while PTX shows strong anti-inflammatory benefits. If confirmed by future trials, both therapies could be integrated into guidelines as adjuncts for selected patients.

Amikacin (AMK), a potent aminoglycoside antibiotic, is clinically valuable for severe Gram-negative infections but is limited by its nephrotoxic and hepatotoxic effects, primarily mediated through oxidative stress and inflammation. This study investigated the protective role of pentoxifylline (PTX), a methylxanthine derivative with antioxidant and anti-inflammatory properties, against AMK-induced organ damage in male BALB/c mice. Thirty mice were divided into six groups: control, AMK (100mg/kg/day), PTX monotherapy (50 or 100mg/kg/day), and AMK combined with PTX (50 or 100mg/kg/day). After 28 days, biochemical, oxidative stress, inflammatory, and histopathological analyses were conducted. AMK administration significantly elevated renal (BUN and creatinine) and hepatic (ALT, AST and ALP) markers, increased oxidative stress (MDA), and upregulated inflammatory cytokines (IL-17), alongside histopathological damage in kidney and liver tissues. Co-treatment with PTX, particularly at 100mg/kg, normalized these parameters, restored antioxidant defenses, reduced inflammation, and preserved tissue architecture. PTX demonstrated dose-dependent efficacy, with the higher dose offering complete protection against AMK-induced toxicity. These findings highlighted PTX's potential as an adjunctive therapy to mitigate AMK-associated nephrotoxicity and hepatotoxicity, suggesting its clinical utility in optimizing aminoglycoside safety without compromising efficacy.

Chronic Chagas cardiomyopathy (CCC) is a major public health issue in endemic areas of Latin America, representing one of the leading causes of heart failure and sudden death. The hallmark histopathological lesion of CCC is low-intensity, persistent myocarditis associated with cytokine production. Long-term use of pentoxifylline (PTX) may serve as an effective pharmacological intervention for immunomodulation, reducing inflammation and, consequently, diminishing myocardial perfusion abnormalities and thus preserving left ventricular systolic function. We investigated 38 patients with CCC, randomly assigned to PTX (n = 19), 400 mg 3 times a day for 6 months, or placebo (PLC) (n = 19). At baseline and post-treatment, patients underwent cytokine measurements, quality of life assessment, 2D echocardiography, and myocardial perfusion scintigraphy. After treatment, TNF-α levels in the PTX group decreased from 10.14 ± 5.5 to 8.32 ± 3.6 and from 9.12 ± 4.4 to 10.32 ± 8.5 in the PLC group (p = 0.06). Additionally, IL-10 levels increased from 2.74 ± 0.7 to 5.61 ± 8.6 in the PTX group, while in the placebo group, they decreased from 6.96 ± 11.8 to 5.50 ± 8.3 (p = 0.09); neither of these findings reached statistical significance. Also, no significant changes were observed in the echocardiographic variables after treatment. LVEF showed a modest change from 46.2% ± 7.9 to 47.4% ± 7.0 in the PTX group and from 48.2% ± 6.6 to 48.0% ± 6.9 in the PLC group (p = 0.37). No significant positive effects on myocardial perfusion were noted. However, the quality-of-life assessment documented a significant improvement of functional capacity in the PTX group. The results of this study suggest a potential positive effect of PTX in modulating the inflammatory profile of CCC patients. However, use of pentoxifylline in these patients did not attenuate the degree of ventricular dysfunction or reduce myocardial perfusion defects.

Targeting the p38MAPK/STAT3/NF-κB65 pathway modulates the hepatoprotective effect of pentoxifylline against sodium valproate-induced liver injury in rats; A study based on integrating network pharmacology and experiment validation.

Pentoxifylline (PTX), a methylxanthine derivative, has been recognized as a potential anti-inflammatory treatment across various conditions, yet its effects on inflammatory markers remain inconsistent. This systematic review/meta-analysis evaluated the impact of PTX on serum levels and gene expression of key inflammatory markers in randomized controlled trials (RCTs). A systematic search was conducted in PubMed, Scopus, Embase, Web of Science, and ProQuest up to May 2025. Search results were screened in two stages by two independent reviewers. Data was extracted and the quality of the studies included was assessed using the Cochrane Risk of Bias (RoB) tool. Statistical analysis was performed using STATA -17. The present study was conducted in accordance with the PRISMA guidelines. This study included 81 RCTs involving 7,058 participants. PTX treatment significantly reduced serum levels of CRP (SMD = -0.30, 95% CI: -0.47 to -0.13), IL-6 (SMD = -0.51, 95% CI: -0.81 to -0.22), TNF-α (SMD = -0.72, 95% CI: -0.95 to -0.48), and IL-8 (SMD = -1.14, 95% CI: -1.94 to -0.33) compared to controls. No statistically significant effects were observed for IL-1β, ESR, IL-10, or TNFR. High heterogeneity was noted in most outcomes, partly attributed to variations in age, treatment duration, dosage, geographic region, and health conditions. Subgroup analyses revealed that younger patients, shorter interventions, and lower PTX doses were associated with stronger anti-inflammatory responses. PTX reduces TNF-α, IL-6, IL-8, and CRP, supporting its role in chronic inflammatory diseases. Efficacy varies by age, dose, duration, geography, and disease, requiring personalized treatment. Contradictory biomarker effects and study limitations warrant high-quality trials with standardized protocols.

Background/objectivesChronic kidney disease (CKD) is a highly prevalent, irreversible, and progressive disease associated with a high cardiovascular risk. We aimed to clinically investigate the extra-therapeutic effect of adding therapeutic doses of pentoxifylline (PTX) and/or folic acid (FA) for CKD patients to the standard care on their health-related quality.MethodsA randomized, prospective, parallel, and controlled clinical trial of CONSORT 80 patients diagnosed with CKD stages 3–5 were stratified by simple randomization into four groups (20 patient/group) and followed up for 6 months. Control group: received standard usual care therapy only; PTX group: received therapeutic dose of PTX added to standard usual care therapy; FA group: received FA added to standard usual care therapy; and PTX and FA group: received both PTX and FA added to their standard usual care therapy. The primary objective was to compare the renal function biochemical parameters for the intervention groups compared to the control group. Meanwhile, the secondary objective was to compare the incidence of readmission to hospitalization with cardiovascular events, incidence of peripheral vascular diseases and Fatigue Assessment Scale (FAS) for the intervention groups compared to the control group.Clinical trial registrationThis study’s research was granted authorization by the Research Ethics Committee (REC), Faculty of Medicine, Ain Shams University, No. (FMASU MS UNIV 15/2022) dated to 15/12/2022, and the Ethical Committee in the Faculty of Pharmacy (Girls), Al-Azhar University, No. (313) dated to 22/12/2022. This study was authorized by https://clinicaltrials.gov/ (NCT05284656) and the first date of registration was 16/02/2022. All patients were assigned to write an informed consent.ResultsThere was a significant improvement in renal function biochemical parameters and a significant reduction in the FAS for the intervention groups compared to the control group.ConclusionsOur results demonstrated that administration of therapeutic doses of PTX and/or FA in CKD patients delayed the progression of advanced chronic kidney disease and has been used successfully improved their health-related quality of life.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12882-025-04399-3.

Melanoma is a highly aggressive skin cancer with limited therapeutic response. Targeting intracellular signaling pathways and promoting tumor cell differentiation are promising therapeutic strategies. Pentoxifylline (PTX) and norcantharidin (NCTD) have demonstrated antitumor properties, but their combined mechanisms of action in melanoma remain poorly understood. The effects of PTX (30 and 60 mg/kg) and NCTD (0.75 and 3 mg/kg), administered alone or in combination, in a DBA/2J murine B16-F1 melanoma model via intraperitoneal and intratumoral (IT) routes were evaluated. Tumor growth was monitored, and molecular analyses included RNA sequencing and immunofluorescence quantification of PI3K, AKT1, mTOR, ERBB2, BRAF, and MITF protein levels, and molecular docking simulations were performed. In the final stage of the experiment, combination therapy significantly reduced tumor volume compared to monotherapies, with the relative tumor volume decreasing from 18.1 ± 1.2 (SD) in the IT Control group to 0.6 ± 0.1 (SD) in the IT combination-treated group (n = 6 per group; p < 0.001). RNA-seq revealed over 3000 differentially expressed genes in intratumoral treatments, with enrichment in pathways related to oxidative stress, immune response, and translation regulation (KEGG and Reactome analyses). Minimal transcript-level changes were observed for BRAF and PI3K/AKT/mTOR genes; however, immunofluorescence showed reduced total and phosphorylated levels of PI3K, AKT1, mTOR, BRAF, and ERBB2. MITF protein levels and pigmentation increased, especially in PTX-treated groups, indicating enhanced melanocytic differentiation. Docking analyses predicted direct binding of both drugs to PI3K, AKT1, mTOR, and BRAF, with affinities ranging from -5.7 to -7.4 kcal/mol. The combination of PTX and NCTD suppresses melanoma progression through dual mechanisms: inhibition of PI3K/AKT/mTOR signaling and promotion of tumor cell differentiation.

Epilepsy is a persistent neurological condition that impacts millions of individuals globally. Neuroinflammation is regarded as a key contributor to the process of epileptogenesis. Several preclinical studies investigated the protective role of pentoxifylline (PTX) in an experimental model of epilepsy. This study aimed to investigate the fundamental role of pentoxifylline and its protective pathways in generalized epilepsy patients. In this controlled parallel randomized clinical study, 66 patients with generalized epilepsy were randomly assigned to two groups: group 1 (the control group; n = 33) received 100mg of phenytoin three times daily (t.i.d.) for 6months, while group 2 (the pentoxifylline group; n = 33) received 100mg of phenytoin t.i.d. and 400mg of pentoxifylline twice daily for 6months. Participants were evaluated at baseline and 6months after treatment to assess the serum levels of high mobility group box-1 protein (HMGB-1), toll-like receptor-4 (TLR-4), nuclear factor kappa-B (NF-κB), amyloid beta (Aβ), and nuclear factor erythroid 2-related factor 2 (Nrf2). The clinical outcome was assessed through a mini-mental state examination (MMSE), quality of life questionnaire (QOLIE-31), and seizure frequency. After treatment, the pentoxifylline group demonstrated a significant decrease in serum levels of HMGB1 (P = 0.016), TLR-4 (P = 0.007), NF-κB (P = 0.008), and Aβ (P = 0.012) and a significant increase in serum Nrf2 (P = 0.007). Additionally, the pentoxifylline group showed a significant increase in both the MMSE score (P = 0.001) and QOLIE-31 score (P = 0.001), which was associated with a significant decrease in the frequency of seizures (P = 0.025). Pentoxifylline may be considered a promising adjuvant therapy for generalized epilepsy patients. Trial registration number: NCT05637086, registration date: 27-11-2022.

Hodgkin lymphoma (HL) is a common neoplasm in adolescents and young adults, primarily treated with doxorubicin (DOX) and bleomycin (BLM), which may cause severe adverse effects. The cure rate decreases to 75% in advanced-stage disease, highlighting the need for improved treatment strategies. Pentoxifylline (PTX), an NF-κB pathway inhibitor, enhances chemotherapy-induced apoptosis in cancer cells, making it a promising candidate for HL therapy. This study assessed the effects of PTX, DOX, and BLM on apoptosis, proliferation, and senescence in Hs-445 HL cells. Cell viability and clonogenicity were measured by spectrophotometry and spectrofluorimetry, while apoptosis, caspase activity, cell cycle, mitochondrial membrane potential (ΔΨm), proliferation, and senescence were analyzed via flow cytometry. Gene expression was assessed by qPCR. PTX significantly induced apoptosis, especially when combined with BLM or BLM+DOX (triple therapy), and modulated gene expression by upregulating proapoptotic and downregulating antiapoptotic markers. PTX increased caspase-3, -8, and -9 activity and disrupted the ΔΨm, particularly with BLM or triple therapy. Furthermore, PTX abolished DOX-induced G2 cell cycle arrest, reduced proliferation, and clonogenicity, and reversed DOX- and BLM-induced senescence. In conclusion, PTX induces apoptosis in HL cells, enhances DOX and BLM cytotoxicity synergistically, and reverses senescence, suggesting its potential as an adjunct therapy for HL.

BackgroundRecent infectious disease outbreaks, notably COVID-19, have significantly affected society. Despite initial preventive measures and vaccination efforts, COVID-19 persist, requiring effective treatments. Commonly used corticosteroids face debate over their efficacy, with studies questioning their impact on COVID-19 outcomes and their association with hyperglycemia, particularly in diabetic patients. This complex interaction between COVID-19, diabetes, and corticosteroid use underscores the need for alternative treatments like pentoxifylline (PTXF) to manage inflammation and mitigate corticosteroid-induced hyperglycemia in diabetic patients.MethodThis study aimed to assess the effectiveness of PTXF in diabetic COVID-19 patients through a randomized, controlled trial. Patients with specific criteria were recruited from two academic hospitals in Yazd, Iran and randomized to receive PTXF or dexamethasone along with other medications. Outcome measures included inflammatory markers, clinical symptoms, adverse events, and hyperglycemic-related risks.ResultThe clinical trial, involving 47 diabetic patients, revealed that on the seventh day, the PTXF group exhibited lower mean levels of WBC, neutrophil, lymphocyte, IL6, and CRP compared to the dexamethasone group (p-value < 0.05). In addition, the rise in blood sugar during the illness was significantly lower in the PTXF group due to great importance and interest.ConclusionsPTXF may present promising evidence in improving COVID-19 patients by reducing inflammatory parameters, especially in diabetic patients.Trial Registration: Trial registry date: 2024-10-12, Trial Registry number: IRCT20190810044500N29

Combined quercetin with phosphodiesterase inhibitors; sildenafil and pentoxifylline alleviated CCl4-induced chronic hepatic fibrosis: Role of redox-sensitive pathways.

Psoriasis is one of the dermatological autoimmune diseases that involve cracking, redness, bleeding and inflammation on the surface of the skin. Sulfasalazine (SUL) is an immunity suppressing and anti-phlogistic drug. Pentoxifylline (PTN) is an immunosuppressant and vasodilator. So, the two drugs are co-administered together in the treatment protocol for psoriasis. No chromatographic analytical method was developed in the literature for the quantitative determination of SUL and PTN in their binary mixture and spiked human plasma. So, this work’s goal is to establish an environmentally friendly and selective TLC method for quantitative assay of sulfasalazine and pentoxifylline in their common mixture and spiked human plasma samples. The separation was successfully obtained using a developing system consisting of ethanol: ethyl acetate (7: 3, v/v) and 270 nm as UV scanning wavelength. Paracetamol was chosen as an internal standard to correct sampling minute variations. The obtained retardation factor values were 0.02, 0.43, 0.68 and 0.8 for plasma, pentoxifylline, sulfasalazine and paracetamol, in the same order. The resulting LLOQ for SUL and PTN were 0.3 and 0.2 µg/band, respectively. Three environmental friendliness assessment tools including analytical greenness metric approach (AGREE), eco-scale assessments, and green analytical procedure index (GAPI) were applied to evaluate the environmental safety characters of the suggested method. Validation parameters were within the accepted ranges when checked according to US-FDA guidelines to for bioanalytical method validation.

Background and aimsRecent studies have shown wound-healing properties of systemic pentoxifylline (PTX). This study aimed to investigate the effectiveness of PTX 10% topical gel in the healing of pressure ulcer (PU).MethodsThe patients with stages 2 or 3 PU were randomly divided to PTX and control groups (n = 35 in each). For the first group, 10% PTX gel was used topically, along with common treatments, once a day for two weeks, while for the control group, a novel dressing along with the common wound care were applied. At the end of the first and second weeks, the wound size change and healing rate were compared between the groups.ResultsThere was a significant decrease in wound size at the first and second weeks in PTX group compared to the control (P < 0.05). Furthermore, the number of cases showing complete wound healing in PTX group (n = 16; 45.71%) was more than control group (n = 9; 25.71%); however, the difference was not statistically significant (P = 0.081).ConclusionThis study demonstrated that PTX 10% topical gel can be a promising treatment option to accelerate wound healing in patients with PU.

Abstract Objective/Hypothesis Stereotactic ablative radiation therapy (SABR) is becoming an increasingly popular treatment for patients with recurrent non-small cell lung cancer. Thoracic reirradiation, however, can be toxic, with some institutions reporting grade 3 pneumonitis in upward of 30% of reirradiated patients. Pentoxifylline (PTX) and vitamin E (VE) have mitigated toxicity in standard breast treatment and may be beneficial in the reduction of radiation-induced pneumonitis. The objective of this study is to prospectively evaluate the efficacy of PTX and VE in reducing grade 3 pneumonitis in patients undergoing SABR with locoregionally recurrent lung cancer or new lung primary tumors in the setting of prior thoracic radiation. We hypothesize that these patients will experience rates of grade 3 pneumonitis lower than 30% at 3, 6, and 12 months post-treatment. Materials and Methods Patients who received radiation for a prior thoracic malignancy with a diagnosis of a recurrent or new NSCLC were recruited from our institution. PTX and VE were administered at the time of simulation, approximately 1 week prior to starting treatment, and were continued for 12 weeks post-treatment. SABR was delivered using standard stereotactic techniques to a dose of 50 Gy at 10 Gy per fraction over 2 weeks. Clinical and radiographic assessment of pneumonitis was conducted at 3, 6, and 12 months post-treatment. Demographic information was collected before treatment. Results The rate of grade 3 pneumonitis in our PTX- and VE-treated cohort was significantly lower than 30% at 3 months (0%, 95% CI 0%-11%, P = .001), 6 months (5%, 95% CI 0%-20%, P = .004), and 12 months (0%, 95% CI 0%-21%, P = .010) post-treatment. Also, 92% of participants were medication compliant. Conclusion PTX and VE are safe interventions that may reduce rates of grade 3 pneumonitis for patients undergoing reirradiation for locoregionally recurrent and/or new lung primary tumors.

Aims: Major depressive disorder (MDD) may be linked to broader pathophysiological pathways such as oxidative stress, inflammation, vascular dysfunction, and neuroplasticity alterations. Pentoxifylline (PTX), a pleiotropic drug, targets all these pathways through non-specific phosphodiesterase (PDE) inhibition. This is the first systematic review and meta-analysis to examine the role of PTX in major depressive disorder.Methods: A comprehensive search of electronic databases, including PubMed, Scopus, Cochrane, and Web of Science, was performed in October 2024. We included only randomized controlled trials (RCTs), and their data were extracted and analysed using Reman 5.4 software. The inclusion criteria as follows: adult patients diagnosed with MDD were included as the population. The intervention considered was pentoxifylline, either alone or in combination with selective serotonin reuptake inhibitors. Comparators included placebo, either alone or combined with SSRIs. Eligible studies needed to report outcomes such as the Hamilton Depression Rating Scale (HAM-D).Results: Four RCTs with 318 patients were included in the study. PTX showed a statistically significant improvement in HAM-D scores at the primary endpoint compared with the placebo (MD=−3.84, 95% CI [−4.87 to −2.81], p&lt;0.00001). Moreover, PTX showed a statistically significant increase in serotonin and BDNF levels (MD=20.76 ng/mL, 95% CI [5.49 to 36.04], p=0.008; and MD=10.83 ng/mL, 95% CI [−0.22 to 21.88], p=0.05, respectively) and a statistically significant decrease in TNF-α and IL-6 levels (MD=−3.24 pg./mL, 95% CI [−4.12 to −2.36], p&lt;0.00001; and MD=−2.64 pig/mL, 95% CI [−3.79 to −1.48], p&lt;0.00001, respectively). There was no statistically significant difference between the PTX and placebo in any of the reported side effects including nausea, vomiting, headache, diarrhoea, increased appetite, and sexual dysfunction.Conclusion: The study findings suggest that PTX may be effective and safe as an adjuvant antidepressant agent in patients with MDD, demonstrating a significant reduction in HAM-D scores. The results of this study need to be interpreted with caution considering several limitations.

Abstract Study question How does the combination of pentoxifylline and tocopherol affect endometrial proliferation or vascularization in patients with recurrent implantation failure (RIF) or recurrent pregnancy loss(RPL)? Summary answer Treatment with pentoxifylline (PTX) and tocopherol (vitamin E) significantly reduced endometrial vascularization and proliferation disorders, improving pregnancy rates (PR), as assessed by luteal phase ultrasound. What is known already Ultrasound assessment of endometrial receptivity allowed to assess endometrial vascularization and proliferation. There is no consensus on the treatment proposed for women with endometrial vascularization and/or proliferative disorders; however, pregnancy chances are decreased. The combination of PTX and vitamin E was initially studied in patients with radiation-induced damage to increase the endometrial thickness and improve uterine vascularization. After that, this combined treatment was studied in the context of embryo transfers in women with thin endometrium and oovocyte donation, showing a significant increase in endometrial volume. Study design, size, duration This retrospective, single-center study was conducted at the ART Center of the University of Liège, Belgium, from January 2020 to December 2023. A total of 621 patients were referred for RIF, RPL, or atrophic endometrium, and underwent ultrasound endometrial receptivity testing. After applying exclusion criteria, 52 patients were analyzed and compared to a control group (n= ?) of women with similar characteristics (age, previous embryo transfers, and miscarriages) who did not receive PTX/vitamin E. Participants/materials, setting, methods Fifty-two women with RIF or RPL were included in this study. Endometrial proliferation and vascularization were assessed by ultrasound during the implantation window (days 21–24 of a 28-day cycle or progesterone +7 in an artificial cycle). Abnormal findings (endometrial volume &amp;lt; 2cm3, uterine artery PI &amp;gt; 2.8, sub-endometrial VFI &amp;lt;0.25) prompted treatment with PTX (400 mg 2x/d) and Vitamin E (500 IU 2x/d) for 3 months before a follow-up ultrasound. Main results and the role of chance The aim of our single-center retrospective study was to evaluate the benefit of treatment with PTX 400 mg 2x/d and Vitamin E 500 IU 2x/d administered for at least 3 months in 52 patients presenting abnormal ultrasound criteria (endometrial volume &amp;lt; 2cm3 and/or uterine artery PI &amp;gt; 2,8 and/or sub-endometrial VFI &amp;lt;0,25). We observed a significant increase in endometrial volume of 0.32 cm3 (p = 0.0054), as well as a significant increase in VFI of 0.49 (p = 0.041) after treatment. The PI of the right uterine artery decreased significantly by 0.25 (p = 0.029) and the PI of the left uterine artery decreased by 0.27 but not significantly after treatment. The second outcome was to evaluate the benefit of the treatment on the PR. Clinical pregnancy rate following the first embryo transfer, after at least 3 months of treatment, was observed in 38.2% of patients. In the control group, PR was 23,5% at the first embryo transfer (p = 0,17). Within 6 months following the first embryo transfer, 50% of patients in the treated group achieved at least one clinical pregnancy, compared to 35.3% of patients in the control group (p = 0.17). Limitations, reasons for caution The results of our study are promising. To strengthen their validity, it is essential to conduct a larger study including a larger number of patients, to improve statistical power, particularly regarding pregnancy rates. Additionally, these finding should be corroborated by a larger prospective study. Wider implications of the findings Managing patients who repeatedly suffer of RPL or RIF remains a challenge. These results highlight the role of the endometrium in successful implantation, which should not be underestimated. It is essential to establish a consensus on the treatment for patients with endometrial vascular or proliferative disorders to improve their PR. Trial registration number No

First insight on the effective removal of pentoxifylline drug under visible-light-driven irradiation with ZnO catalyst obtained via precipitation.