Search Results (947)

Objectives. Pancreatic cancer remains one of the most lethal malignancies, and the lack of effective therapies highlights the need for novel treatment strategies. In this study, we evaluated the antitumor potential of the attenuated Streptococcus pyogenes strain GURSA1—engineered to knockout the M protein completely—in a murine model of orthotopically transplanted pancreatic ductal adenocarcinoma. Methods. Female C57Bl/6 mice received intratumoral injections of GURSA1 at doses of 5 × 10⁵ or 1 × 10⁶ CFU per animal. Animal survival, body weight, tumor engraftment, metastasis intensity, tumor mass and volume, and hematological, biochemical, histological, and microbiological parameters were assessed. Results. Intratumoral administration of GURSA1 produced dose-dependent antitumor effects on tumor growth and metastatic burden, but did not result in a statistically significant survival benefit. The strain reduced tumor engraftment, the overall metastasis score, and the incidence of hemorrhagic ascites, while also decreasing tumor mass and volume, with the strongest effects observed at a dose of 1 × 10⁶ CFU. Treatment increased platelet counts and reduced urea and ALT levels toward values observed in intact mice, without affecting anemia, neutrophilia, or changes in AST, alkaline phosphatase, glucose, and total protein levels. Conclusions. These findings demonstrate that GURSA1 attenuates partial reduction in primary tumor burden in vivo and support further investigation of this strain as a potential oncolytic agent. Full article

Objectives: Existing animal models of post-traumatic stress disorder (PTSD) are often methodologically complex and produce variable outcomes. The aim of this study was to develop a modified PTSD model that accurately recapitulates the clinical progression of the disorder, incorporating both behavioral features and objective physiological parameters. Methods: We utilized a modified Single Prolonged Stress with Subsequent Stress (SPS&S) protocol, supplemented by a stress reminder phase (without re-exposure to primary stressors) and an evaluation of stress response extinction. Eighty male Wistar rats were subjected to the stress protocol, followed by comprehensive behavioral, hematological (leukocytes, hemoglobin, and hematocrit), and hormonal (corticosterone; adrenocorticotropic hormone (ACTH)) assessments 4–5 weeks post-stress. Results: The model produced a PTSD-like phenotype in 25% of animals, characterized by persistent alterations in the investigated biomarkers. The PTSD group exhibited sustained behavioral impairments (increased anxiety), hematological changes (neutrophilic leukocytosis), and endocrine dysregulation (decreased corticosterone, ACTH, and epinephrine). Conclusions: This modified SPS&S model demonstrates validity for studying the long-term consequences of stress, with PTSD markers remaining stable throughout the 28-day observation period. Full article

Background/Objectives: Male infertility, including primary and secondary infertility, is significantly influenced by oxidative stress, which disrupts sperm function and fertility. Seminal plasma, a protein-rich fluid essential for sperm protection and function, represents a valuable source for identifying biomarkers through proteomic analysis. While previous studies have explored seminal plasma proteins in fertility, the specific proteomic changes associated with oxidative stress in secondary infertility remain unclear. This study aimed to characterize these alterations by analyzing seminal plasma from three groups: men with secondary infertility, fertile donors with high oxidative stress, and fertile donors without oxidative stress. Methods: Pooled semen samples from each group underwent quantitative proteomics analysis using advanced mass spectrometry, with subsequent bioinformatic analysis using tools like DAVID, STRING, and IPA for identifying differentially expressed proteins (DEPs). Results: Quantitative proteomic analysis identified 377 DEPs in secondary infertility and 523 DEPs in fertile donors with high oxidative stress compared to controls. Bioinformatic analysis revealed seven shared pathways, including acute-phase response signaling, organismal injury, cellular movement, cell-to-cell signaling, free radical scavenging, immune cell trafficking, and Hematological system development. Notably, C3 and SERPINA3 exhibited significant alterations, along with proteins involved in sperm motility, capacitation, and fertilization, suggesting their potential roles in impaired fertility. Conclusions: These findings underscore the link between oxidative stress and secondary infertility and highlight specific seminal plasma proteins as potential biomarkers and therapeutic targets for diagnosing and treating male infertility. Full article

Background/Objectives: Dendritic cells (DCs) are key regulators of immune responses in cardiovascular disease, yet their role in platelet homeostasis and thrombopoiesis remains incompletely understood. We previously demonstrated that chronic depletion of CD11c⁺ cells accelerates atherosclerotic plaque development. The objective of this study was to determine whether sustained loss of CD11c⁺ cells alters platelet production and systemic inflammatory signaling under atherogenic conditions. Methods: CD11c-DTR bone marrow chimeric mice on ApoE⁻/⁻ background were generated and fed a high-cholesterol diet. CD11c⁺ cells were depleted by repeated diphtheria toxin administration over six weeks. Circulating platelet counts were quantified by automated hematology analysis. Systemic inflammatory changes were assessed using serum cytokine and chemokine profiling, and serum thrombopoietin (TPO) levels were measured by ELISA. Results: Chronic CD11c⁺ cell depletion resulted in a significant increase in circulating platelet counts in ApoE⁻/⁻ mice. Serum cytokine profiling revealed broad inflammatory remodeling, including increased levels of cytokines associated with megakaryopoiesis and platelet activation, such as IL-4, MCP-1, CXCL9, IL-16, and IL-1α. In parallel, serum TPO levels were significantly elevated following CD11c⁺ cell depletion. Conclusions: In the specific context of hyperlipidemic CD11c-DTR bone marrow chimeric mice, these findings demonstrate that loss of CD11c⁺ cells is associated with a pro-thrombopoietic shift, elevated platelet counts, and systemic inflammatory changes. Our data identify a CD11c⁺ cell–TPO–platelet axis linking immune regulation to platelet homeostasis and thrombo-inflammatory signaling under these specific atherogenic conditions. Full article

(1) Background: Chemotherapy-induced hematological toxicity remains a major limitation to treatment continuity. Docetaxel is widely used in solid tumors due to its clinical efficacy, despite cumulative bone marrow suppression and splenic alterations. Curcuma longa is a phytochemical with antioxidant and anti-inflammatory properties that may confer cytoprotective effects on hematopoietic tissues. (2) Methods: One hundred and five male Wistar rats were randomly allocated into five treatment groups and evaluated at 7, 14, and 21 days. Animals received placebo, docetaxel alone, or docetaxel combined with Curcuma longa at doses of 25, 50, or 500 mg/kg/day. Post-treatment hematological parameters and relative spleen weight were analyzed using one-way ANOVA and Tukey’s post hoc test. (3) Results: Docetaxel induced progressive reductions in red blood cell count, hemoglobin, hematocrit, leukocytes, and platelets, with greater severity at day 21. Curcuma longa co-treatment partially mitigated these alterations in a dose- and time-dependent manner. Intermediate doses (25–50 mg/kg) showed the most consistent hematoprotective effects. High-dose treatment (500 mg/kg) was associated with no statistically significant change in relative spleen weight. (4) Conclusions: Curcuma longa partially mitigated docetaxel-induced hematological toxicity and modulated splenic responses in this experimental model. These findings support further translational studies on chemotherapy-induced hematological toxicity to clarify the role of Curcuma longa as a low-toxicity strategy. Full article

Background: Inflammatory activity in rheumatoid arthritis can be determined by normal blood count ratios such as Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Systemic Immune Inflammation Index (SII), and C-reactive Protein (CRP). Objective: The aim of this research is to determine how these markers change after therapy and whether their pre- and post-treatment differences follow patterns that allow for simple parametric analyses. Methods: A prospective cohort of 52 RA patients (30 females and 22 males) was examined. The patients’ blood samples were tested at baseline and at the end of their 6-month Infliximab treatment. Hematologic markers such as NLR, PLR, and SII were calculated from the complete blood count (CBC), and CRP levels were measured. The statistical methods of Shapiro–Wilk (SW), Kolmogorov–Smirnov (KS), and Anderson–Darling (AD) were used, and later, paired t-tests were used to generate statistics where necessary. Results: Post-treatment measurements were consistently lower for all four biomarkers. QQ-plots and formal tests revealed that the differences between findings were essentially normal, allowing for paired t-tests. The mean decreases were as follows: NLR −1.10 (95% CI −1.48 to −0.71), PLR −43.0 (−55.4 to −30.7), SII −299 (−388 to −211), and CRP −11.36 (−13.18 to −9.54), all p < 0.001. CRP showed the greatest drop, with significant decreases in PLR and SII and a moderate decline in NLR, indicating therapy-related attenuation of systemic inflammation. Conclusions: The study shows that six months of infliximab therapy results in a consistent post-treatment decrease in all four biomarkers: NLR, PLR, SII, and CRP. Because the pre-post differences were roughly normal, CRP revealed the greatest decrease, with significant decreases in PLR and SII and a moderate decrease in NLR, consistent with systemic inflammation reduction. When combined, the CBC-derived indices track with CRP and can serve as practical, low-cost markers for monitoring therapy response in RA, despite the single-arm design. Full article

Background/Objectives: This study aimed to evaluate the prognostic value of ¹⁸F-FDG PET/CT-based secondary lymphoid organ metabolic ratios—spleen/liver (SLR), bone marrow/liver (BLR), and ileocecal region/liver (ILR)—and hematological inflammation markers (neutrophil/lymphocyte ratio [NLR] and systemic immune-inflammation index [SII]) obtained before nivolumab treatment in relation to survival in patients with advanced non-small cell lung cancer (NSCLC). Methods: This retrospective single-center study included 79 advanced NSCLC patients who were treated with nivolumab monotherapy at Marmara University Faculty of Medicine Hospital between 2022 and 2024. Pretreatment SLR, BLR, and ILR ratios were calculated from ¹⁸F-FDG PET/CT examinations; NLR and SII values were obtained from hematological data. Survival outcomes were analyzed using the Kaplan–Meier method, and prognostic factors were assessed using Cox proportional hazards regression analysis. In a subset of patients, an exploratory longitudinal analysis was performed using early follow-up PET/CT to assess follow-up-to-baseline changes in immune-organ metabolic ratios in relation to overall survival. Results: High NLR and SII levels were significantly associated with shorter progression-free survival and overall survival. In contrast, no significant associations were observed between PET/CT-derived metabolic ratios (SLR, BLR, and ILR) and survival. Multivariate analysis identified the presence of liver metastases and a high NLR as independent adverse prognostic factors for overall survival. Conclusions: In this homogeneous real-world cohort treated exclusively with single-agent nivolumab, PET/CT-derived secondary lymphoid organ metabolic ratios showed limited prognostic value at baseline and during early on-treatment assessment. In contrast, hematological inflammation markers, especially high NLR levels, are strong prognostic indicators of survival and may complement established clinical factors in risk stratification. Full article

Background: Acute kidney injury (AKI) is a frequent and clinically relevant complication in cancer patients, with highly variable incidence. AKI increases morbidity and mortality, prolongs hospitalization, and may limit access to oncologic therapies. This study evaluated the incidence, risk factors, and outcomes of AKI in hospitalized cancer patients. Methods: We retrospectively analyzed patients admitted between 1 January 2016 and 31 December 2019. Individuals with cancer were identified and categorized into three groups: hematologic malignancies, solid cancers with metastases, and solid cancers without metastases. Demographic, clinical, and laboratory data were collected, and AKI was defined and staged according to KDIGO criteria, evaluating serum creatinine changes. Results: Among 56,390 hospitalized patients, 6723 (11.9%) had a cancer diagnosis. AKI incidence was significantly higher in cancer versus non-cancer patients (30.1% vs. 19.6%). Hematologic cancers showed the highest incidence (39.3%). Among hematologic patients, ICU admission, sepsis, and diabetes were strongly associated with AKI. In non-metastatic solid cancers, more conventional factors—including female sex, older age, sepsis, and ICU admission—were significant predictors. In contrast, in metastatic solid cancers, traditional AKI risk factors did not correlate with increased AKI occurrence. In cancer patients overall, AKI per se did not increase mortality risk; however, stage 3 AKI was associated with significantly higher mortality (HR 1.37, 95% CI 1.13–1.66, p < 0.001). Conclusions: AKI is common in hospitalized cancer patients, with specific patterns and heterogeneous risk factors and impact on outcomes. Implementation of tailored preventive strategies and early recognition are necessary to mitigate progression and improve clinical trajectories. Full article

The impact of tourism on Magellanic penguins (Spheniscus magellanicus) in Patagonia is a complex issue that requires a balanced approach between conservation and sustainable tourism development. While tourism in the region can bring significant economic benefits, it can also have a negative impact on the penguins by disrupting nesting behavior and chick rearing, and even increasing the risk of disease and predation. We examined a comparative analysis of scientific papers on the impact of tourism on Magellanic penguins in two breeding colonies in Argentinean Patagonia, which have been visited for 10 to 50 years and whose visitor numbers range from 10,000 to 120,000 per year. We analyzed different physiological parameters (i.e., immunological, hematological, biochemical, and stress parameters) and behavioral respond (alternate head turns) in adult birds and chicks in these colonies. Although the results suggest that Magellanic penguins have adapted well to the presence of tourists in their breeding colonies, we documented changes in certain physiological parameters that indicate chronic stress due to high exposure to tourism. It is important to promote sustainable tourism in Patagonia that not only minimizes these negative impacts but also improves the protection of the penguins and their habitat. This includes the creation of new nature reserves, environmental education, and the regulation of tourism activities. Implementing responsible tourism practices can ensure economic benefits while protecting the well-being and health of penguin populations. The combination of increased tourist awareness and concrete conservation measures can protect not only the Magellanic penguins but also the natural wealth of the entire Patagonia region. Full article

Pseudomonas aeruginosa bloodstream infections (PABSIs) are a major clinical challenge due to their association with significant mortality and antimicrobial resistance mechanisms. The COVID-19 pandemic changed antimicrobial practices, intensive care management, and patient risk profiles, potentially influencing the epidemiology and outcomes of PABSIs. In the post-pandemic period, practices were expected to revert to normal. The objective of this scoping review was to identify and summarize reported mortality rates and risk factors for PABSIs in studies published between 2023 and 2025. Literature searches were conducted across PubMed, Web of Science, Embase, and Scopus. Screening was performed in accordance with PRISMA-ScR guidelines. Twenty-two eligible studies were included. Mortality rates varied across the study setting and populations; however, several consistent predictors were consistently identified, including carbapenem exposure, multidrug-resistant Pseudomonas aeruginosa, hematologic disease or malignancy, corticosteroid therapy, sepsis or septic shock, mechanical ventilation, and higher severity-of-illness scores. Few studies have linked molecular mechanisms to patient outcomes, highlighting important gaps in knowledge. Notably, only a small number of studies included the post-pandemic period but did not analyze the data separately. Despite limited available evidence, critically ill and immunocompromised patients remain at greatest risk of death from PABSIs. This review highlights the need for a broader comparative analysis in future. Full article

Background/Objectives: Psoriasis is a chronic immune-mediated inflammatory disease associated with systemic inflammation and comorbidities such as cardiovascular disease and metabolic syndrome. Blood-derived inflammatory indices like neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune-inflammation value (PIV) have been proposed as biomarkers of systemic inflammation and disease severity. This retrospective and prospective observational study aimed to evaluate the long-term effects of guselkumab, an IL-23 inhibitor, on these indices in moderate-to-severe psoriasis. Methods: We analyzed 208 patients with moderate-to-severe psoriasis treated with guselkumab, with hematologic evaluations available for 208 patients at baseline, 208 at week 52, 129 at week 104, and 94 at week 156. Systemic inflammatory indices were calculated from routine annual blood tests. Patients were stratified by obesity, cardiovascular comorbidities, treatment response, and prior biologic therapy. Longitudinal changes were assessed using Friedman tests with Wilcoxon post hoc comparisons, and correlations between PASI and inflammatory indices were evaluated using Spearman’s coefficients. Results: SIRI and PLR showed significant reductions at week 156 (p = 0.038 and p = 0.018, respectively), while MLR also decreased over time without reaching consistent significance. NLR and PIV showed minimal or inconsistent changes. Obese patients and those with cardiovascular disease had higher baseline SII and SIRI and less pronounced improvements. No significant differences were observed between super responders and others. Correlation between baseline PASI and most inflammatory markers was weak, except for a weak but significant correlation with PIV (ρ = 0.119, p = 0.049). Conclusions: Guselkumab treatment is associated with long-term reduction in systemic inflammatory indices, particularly SIRI. The weak correlation of these markers with skin severity highlights a dissociation between cutaneous and systemic inflammation. SIRI and SII may serve as useful biomarkers to monitor systemic inflammation and guide comprehensive management in psoriasis patients. Full article

Background: In 2019, a new virus caused by SARS-CoV-2, called COVID-19, spread throughout the world, causing a pandemic state. As the pandemic progressed and cases continued to increase, safe vaccines were developed for the entire population. In Brazil, AstraZeneca^® (ChAdOx1-S) and Pfizer^® (BNT162b2) vaccines were among those administered to the population. Objectives: The objective of this study was to analyze whether immunoglobulin G (IgG) is produced for COVID-19 in individuals immunized with two doses of AstraZeneca (ChAdOx1-S) and Pfizer (BNT162b2) vaccines and to evaluate several parameters in order to understand how our bodies respond to this immunization. Methods: The study involved the participation of 120 individuals: 49 in the control group, 44 vaccinated with the AstraZeneca vaccine, and 27 the vaccinated with Pfizer vaccine. Results: Hematological, biochemical, inflammatory, and oxidant/antioxidant parameters and the production of IgG antibodies were analyzed. An increase in some inflammatory parameters was observed in vaccinated individuals, which may have been caused by an immune reaction after vaccination. In terms of hematological parameters, the changes caused by vaccination appear to be transient and quickly resolved after immunization. In terms of biochemical parameters, an increase in IgG antibodies was observed in the group vaccinated with the Pfizer^® vaccine; however, the AstraZeneca^® and control groups also produced IgG, although to a lesser extent. In terms of the remaining parameters, there was little change after vaccination. Regarding the levels of oxidants/antioxidants, it was observed that there was a compensation by antioxidants due to the increase in oxidant parameters, which may act as corrective mechanism. Conclusions: Both the AstraZeneca^® and Pfizer^® vaccines induced anti-SARS-CoV-2 IgG production, accompanied by inflammatory, hematological, and oxidative changes. Full article

Background/Objectives: Alopecia areata is an autoimmune disorder characterized by nonscarring hair loss and systemic immune dysregulation. Hematological indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), mean platelet volume (MPV), systemic immune-inflammation index (SII), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) have been associated with inflammatory activity in dermatologic diseases. This study aimed to compare systemic inflammatory markers among patients with severe and mild alopecia areata and healthy controls, and to explore longitudinal changes in these markers in patients with severe disease who achieved clinical improvement following Janus kinase (JAK) inhibitor therapy. Methods: This retrospective cohort study included 129 participants: 43 patients with severe alopecia areata (SALT ≥ 50) treated with JAK inhibitors who achieved documented clinical improvement, 43 patients with mild disease (SALT ≤ 20), and 43 age- and sex-matched healthy controls. Hematological inflammatory markers, including red cell distribution width (RDW), MPV, MLR, NLR, PLR, SII, ESR, and CRP, were compared across groups. In patients with severe disease, longitudinal changes were assessed at baseline, three months after treatment initiation, and at the time of documented clinical improvement. Results: MLR, NLR, PLR, SII, and ESR levels were significantly higher in the severe group compared with mild cases and controls, while RDW, MPV, and CRP showed no significant differences. Among patients with severe alopecia areata who achieved clinical improvement following JAK inhibitor therapy, NLR and SII decreased significantly over time. MLR, PLR, and CRP also showed reductions during follow-up, while ESR and RDW remained unchanged. Conclusions: Systemic inflammatory markers are elevated in severe alopecia areata compared with mild disease and healthy controls. In patients who achieved clinical improvement with JAK inhibitor therapy, several inflammatory indices demonstrated longitudinal changes. These findings are exploratory and suggest an association between systemic inflammation, disease severity, and clinical improvement rather than definitive predictive biomarkers. Full article

Background/Objectives: Hypertension (HTN) remains a major global concern despite the availability of many antihypertensive medications, each with its own side effects. Lifestyle interventions, such as aerobic exercise and antioxidant-rich foods, represent promising non-pharmacological strategies for hypertension management. This study investigated the combined effects of exercise and vitamin C on anthropometric parameters, blood pressure, gut histology, biochemical markers, hematological profile, inflammatory gene expression, redox status, and stress hormones in L-nitroarginine methyl ester (L-NAME)-induced hypertensive rats. Methods: Male Wistar rats (n = 30) were randomly divided into five groups (n = 6/group): control, hypertensive (HTN), hypertensive + exercise (HTN + EX), hypertensive + vitamin C (HTN + VC), and hypertensive + exercise + vitamin C (HTN + EX + VC). Exercise consisted of treadmill training at a low intensity (50 ft/min) for 60 min daily, while vitamin C was administered orally (200 mg/kg/day) for four weeks. Blood pressure, anthropometric parameters, gut histology, inflammatory gene expression, hematological indices, serum biochemistry, oxidative stress markers, and hormonal assays were measured. Results: Both exercise and vitamin C individually reduced blood pressure (p < 0.05) and increased villi length (p < 0.05), upregulated anti-inflammatory cytokine expression in the gut, lowered oxidative stress (assessed through CRP, MDA, and catalase), and reduced stress hormones (cortisol and norepinephrine). The combined intervention (HTN + EX + VC) showed the most pronounced effects, resulting in a greater reduction in blood pressure and reversal of the changes induced by hypertension when compared to the HTN group. Conclusions: Exercise and vitamin C were beneficial in lowering blood pressure and improving the adverse changes associated with hypertension. Full article

Background: Mucormycosis, an invasive fungal infection with high morbidity and mortality rates, requires prompt surgical and antifungal therapies; however, the role of antifungal susceptibility testing (AFST) in clinical management of mucormycosis remains underexplored. We aimed to describe the experience of using AFST in the clinical management of mucormycosis. Methods: We conducted a retrospective study from 1 October 2017 to 8 February 2023. We included non-pregnant patients aged ≥ 18 years old with a positive culture for Mucorales and with proven or probable mucormycosis. We collected clinical and microbiological data using a chart review. Results: Over the study period, a total of 119 patients were included, with 36 (30%) undergoing AFST. Of all patients, the median age was 54 years, with 80 (67%) being White and not Hispanic and 73 (61%) being male. Fifty-three (45%) patients had DM, 27 (23%) had hematological malignancy, 15 (13%) had SOT, and 23 (19%) had COVID-19. Half of the cases met the criteria of proven invasive mucormycosis, with pulmonary involvement being the most common presentation (46, 39%), followed by rhino-cerebral-orbital involvement (35, 29%). The majority of Mucorales isolates were Rhizopus species (79, 66%). Among the 36 who underwent AFST, posaconazole minimal inhibitory concentrations (MICs) were lower than isavuconazole (range 0.03 to 2 µg/mL versus 0.1 to 16 µg/mL, respectively). AFST resulted in a change in antifungal therapy from isavuconazole to posaconazole in 3/36 (8%) cases. There was no statistically significant difference in the mortality between the patients whose isolates received AFST versus those who did not have AFST performed. Conclusions: AFST led to a change in antifungal therapy in a minority of mucormycosis cases. Further studies to understand the epidemiological range of antifungal MICs and the effect of AFST-informed antifungal therapy are needed. Full article