Search Results (344)

Protein-losing nephropathy (PLN) involves a heterogeneous group of pathologies leading to selective glomerular damage and development of renal disease. ICGN, the main cause of PLN, requires immunosuppressive treatment. However, the scientific evidence in veterinary medicine on immunosuppressive therapeutic schemes in this condition is limited. The aim of this study is to describe the clinical and paraclinical evolution of five dogs with PLN, presumably associated with ICGN, treated with chlorambucil as immunosuppressive monotherapy. Suspected IGCN was established by the presence of a urine protein–creatinine ratio (UPC) ≥ 3 without response to standard therapy, hypoalbuminemia < 2, or progressive azotemia. Patients were treated with a dosage range of chlorambucil from 0.16 to 0.4 mg/kg (mean 0.25 mg/kg) every 24 h as the sole immunosuppressant. In the end, 4/5 patients showed significant clinical improvement, 3/3 had resolution of the nephrotic syndrome, 5/5 had a sustained decrease in UPC values during follow-up and no relevant adverse effects were observed. In this report, chlorambucil proved to be a well-tolerated and potentially effective monotherapy for immune-mediated PLN in dogs. Full article

This study investigated the immunonutritional potential of high-molecular-weight (Mw~85 kDa), non-degraded chitosan (NCS) and gamma-radiation-degraded, low-molecular-weight chitosan (RCS) incorporated into aquafeeds for Nile tilapia (Oreochromis niloticus). RCS was produced by γ-irradiation (10 kGy) in the presence of 0.25% (w/v) H₂O₂, yielding low-viscosity, colloidally stable nanoparticles with Mw ranging from 10 to 13 kDa. Five diets were formulated: a control, NCS at 0.50%, and RCS at 0.025%, 0.050%, and 0.075%. No adverse effects on growth were observed, confirming safety. Immune gene expression (e.g., ifng1, nfκb, tnf), antioxidant markers (e.g., reduced MDA, increased GSH and GR), and nonspecific humoral responses (lysozyme, IgM, and bactericidal activity) were significantly enhanced in the NCS-0.50, RCS-0.050, and RCS-0.075 groups. Notably, these benefits were achieved with RCS at 10-fold lower concentrations than NCS. Following challenge with Edwardsiella tarda, fish fed RCS-0.050 and RCS-0.075 diets exhibited the highest survival rates and relative percent survival, highlighting robust activation of innate and adaptive immunity alongside redox defense. These results support the use of low-Mw RCS as a biologically potent, cost-effective alternative to traditional high-Mw chitosan in functional aquafeeds. RCS-0.050 and RCS-0.075 show strong potential as immunonutritional agents to enhance fish health and disease resistance in aquaculture. Full article

Background: Advanced and recurrent vulvar squamous cell carcinoma (VSCC) presents a major therapeutic challenge with limited treatment options and poor outcomes. Immune checkpoint inhibitors (ICIs) have shown efficacy in other HPV-associated malignancies, but their role in VSCC remains poorly defined due to the rarity of the disease and limited clinical trial data. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines and registered in PROSPERO (CRD420251067565). A comprehensive literature search identified prospective clinical trials evaluating ICIs in patients with advanced, unresectable, recurrent, or metastatic VSCC. The primary outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Risk of bias was assessed using the MINORS tool. Meta-analyses were performed using random-effects models, with subgroup analyses based on PD-L1 status and treatment regimens (monotherapy vs. combination therapy). Results: Six non-randomized single-arm trials involving 181 patients were included. The pooled ORR was 21%, with higher response rates observed in combination therapy (46%) compared to monotherapy (11%), though not statistically significant. Median PFS and OS were 2.2 months and 6.4 months, respectively. ORRs were similar between PD-L1-positive and PD-L1-negative subgroups. A safety analysis showed treatment-related adverse events (AEs) in 73% of patients and grade ≥ 3 AEs in 23%. The incidence of treatment-related death was 3%. Conclusions: ICIs demonstrate modest but durable efficacy and an acceptable safety profile in advanced VSCC. The current evidence supports their use in selected patients. However, response variability and the lack of reliable predictive biomarkers, such as PD-L1 or HPV status, underscore the need for biomarker-driven clinical trials and improved patient selection strategies. Full article

The advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, significantly improving patient outcomes across multiple malignancies. Nonetheless, these therapies are associated with immune-related adverse effects, including cardiotoxicity, which remains a critical concern. This review provides a comprehensive analysis of ICI-related cardiotoxicity, encompassing its pathophysiological mechanisms, risk factors, diagnostic modalities, and management strategies. The onset of cardiotoxicity varies widely, ranging from acute myocarditis to long-term cardiovascular complications. Early identification through clinical assessment, biomarkers, and advanced imaging techniques is crucial for timely intervention. Management strategies include high-dose corticosteroids, other immunosuppressive agents, and supportive therapies, with a focus on balancing oncologic efficacy and cardiovascular safety. Additionally, rechallenging patients with ICIs following cardiotoxic events remains a complex clinical decision requiring multidisciplinary evaluation. As immunotherapy indications expand to include high-risk populations in a curative setting too, optimizing screening, prevention, and treatment strategies is essential to mitigate cardiovascular risks. A deep understanding of the molecular and clinical aspects of ICI-related cardiotoxicity will enhance patient safety and therapeutic decision-making, underscoring the need for ongoing research in this rapidly evolving field. Full article

Background and Objectives: Immune checkpoint inhibitors (ICIs) have emerged as groundbreaking agents in cancer therapy; however, their immune-related adverse effects, especially pulmonary toxicity, significantly limit their use. This study aimed to determine the incidence and risk factors associated with ICI-induced pulmonary toxicity. Materials and Methods: We conducted a prospective observational study involving 126 patients aged ≥18 years with malignancies treated with ICIs between April 2022 and April 2024. Patients were followed every six months over a two-year period. Clinical, laboratory, and radiological data were collected to assess pulmonary toxicity. Results: The mean age of our patients was 62.93 ± 12.94 years, and 81% were male. The ICI-related pulmonary toxicity rate was 16.7%, and the all-cause mortality rate was 68.3%. In the analysis, the conditions associated with pulmonary toxicity were the type of malignancy, the presence of lung cancer, COPD, long-term ICI use, dyspnea, cough and sputum, the pre-ICI lung nodule mass, and high blood monocyte levels. Our regression analysis results for the determination of risk factors showed a 7.70-fold increase in the presence of cough symptoms, a 4.57-fold increase in the presence of COPD, a 0.998-fold increase for every 1 unit decrease in lymphocyte count, and an 11.75-fold increase in risk for a monocyte count of 130 or less. Conclusions: Our study’s findings suggest that patients with identifiable risk factors for pulmonary toxicity should undergo closer monitoring and early diagnostic evaluation during ICI therapy to reduce morbidity and mortality. Full article

Background: Allogeneic hematopoietic stem cell transplant (Allo-HSCT) recipients are still at increased risk of severe COVID-19 infection. Vaccination is a critical strategy to protect this population. This real-world prospective cohort study aimed to evaluate the immune response and clinical outcomes of COVID-19 vaccines in Allo-HSCT recipients. Methods: Allo-HSCT recipients (median age: 48 years) who received either the BNT162b2 or CoronaVac vaccines were included. Antibodies against the SARS-CoV-2 spike protein were quantitatively measured using the chemiluminescent microparticle immunoassay. Patient- and vaccine-related factors affecting antibody responses were analyzed. Adverse events, including graft-versus-host disease (GVHD) and post-vaccine infections, were recorded. Results: Among 95 Allo-HSCT recipients, 86.3% achieved adequate antibody responses following COVID-19 vaccination. Patients receiving ≥3 vaccine doses showed significantly higher antibody titers compared to those with only 2 doses (OR: 0.11; 95% CI: 0.02–0.53; p = 0.006 **). The use of Ruxolitinib or Ibrutinib was associate with increased odds of low antibody response (OR: 38.39; 95% CI: 3.14–468.95; p = 0.004 **). Hypogammaglobulinemia (low serum IgG levels) was associated with a reduced antibody response (OR: 0.17; 95% CI: 0.03–0.96; p = 0.045 *), while no significant correlation was found between serum IgA levels and antibody responses (p = 0.672). Three cases of post-vaccine GVHD were observed, and no fatalities related to COVID-19 occurred during the study. Conclusions: COVID-19 vaccination is safe and effective in Allo-HSCT recipients, with stronger responses especially following ≥3 vaccine doses. Patients receiving GVHD treatment or with hypogammaglobulinemia exhibited impaired responses, emphasizing the need for tailored vaccination strategies and close monitoring in this population. Full article

Background: The combined diphtheria–tetanus–acellular pertussis (three-component), Haemophilus influenzae type b (Hib, conjugate), and ACYW135 meningococcal (conjugate) vaccine (DTaP-Hib-MCV4) offers a promising alternative to single-component vaccines, potentially simplifying immunization schedules and improving vaccination coverage. Methods: We evaluated the safety, immunogenicity, and protective efficacy of DTaP-Hib-MCV4 in animal models. Acute and long-term toxicity studies were conducted in Sprague-Dawley (SD) rats with equal numbers of male and female animals. Immunogenicity was assessed in female NIH mice and SD rats using a three-dose regimen at 14-day intervals. Orbital blood was collected 14 days post-immunization to measure IgG titers against pertussis, diphtheria, tetanus, Hib, and meningococcal antigens. The protective efficacy was determined using potency tests for the pertussis, diphtheria, and tetanus components; passive protection studies for Hib; and serum bactericidal antibody (SBA) titers against A/C/Y/W135 meningococcal serogroups. Results: Acute and repeated-dose toxicity studies in SD rats showed no signs of abnormal toxicity or irritation at either high (three doses/rat) or low (one dose/rat) doses levels. The no-observed-adverse-effect level (NOAEL) for DTaP-Hib-MCV4 was established at three doses/rat after 8 weeks of repeated intramuscular administration and a 4-week recovery period. Specific IgG antibodies against all the vaccine components were detected in animal sera at both one and three doses/rat, with no evidence of immunotoxicity. Following two-dose primary immunization in murine models, the combined vaccine elicited robust antigen-specific antibody responses, with geometric mean titers (GMTs) as follows: 1,280,000 for pertussis toxin (PT); 761,093 for filamentous hemagglutinin (FHA); 1,159,326 for pertactin (PRN); 1,659,955 for diphtheria toxoid (DT); 1,522,185 for tetanus toxoid (TT); 99 for Haemophilus influenzae type b (Hib); and 25,600, 33,199, 8300, and 9051 for serogroups A, C, Y, and W135 of Neisseria meningitidis, respectively. In the rat models, three-dose primary immunization also elicited robust antigen-specific antibody responses. Protection studies demonstrated efficacy against pertussis, tetanus toxin, and diphtheria toxin challenges. In the Hib challenge study, none of the 10 animals given anti-DTaP-Hib-MCV4 antiserum developed bacteremia after the live Hib challenge (vs. 5814/0.1 mL in the negative control, p < 0.001). In addition, the SBA titers against meningococcal serogroups exceeded the protective threshold (≥1:8) in 92.2% of the immunized mice and 100% of the immunized rats. Crucially, the combined vaccine induced potent immune responses and protective efficacy, with antibody levels and protection against each component antigen comparable to or greater than those of the individual components: DTaP, Hib, and MCV4. Conclusions: These findings demonstrate that the DTaP-Hib-MCV4 combined vaccine is both safe and immunogenic, supporting its potential as a viable alternative to individual vaccines. This combined vaccine may streamline immunization programs and enhance vaccination coverage. Full article

Adjuvant treatment for resectable non-small cell lung cancer (NSCLC) has seen significant advancements following the introduction of immune checkpoint inhibitors (ICIs). These therapies, which enhance the immune system’s ability to recognize and target cancer cells, have demonstrated substantial improvements in disease-free survival (DFS) following surgical resection. Recent studies have shown that ICIs can extend DFS, particularly for patients with high Programmed Death-Ligand 1 (PD-L1) expression but also for those with lower levels of PD-L1, suggesting a broader potential for their application. In the IMpower010 trial, atezolizumab improved DFS compared to best supportive care (BSC) in resected stage II–IIIA NSCLC, with a hazard ratio (HR) of 0.66 (95% CI 0.50–0.88) for patients with PD-L1 expression ≥1% and 0.79 (95% CI 0.64–0.96) for the overall stage II–IIIA population. In the PEARLS/KEYNOTE-091 trial, pembrolizumab also demonstrated a DFS benefit over a placebo for patients with stage IB–IIIA disease (HR 0.76; 95% CI 0.63–0.91), with a median DFS of 53.6 months versus 42.0 months. Despite these promising results, challenges remain regarding the optimal selection of patients, particularly in identifying the most effective biomarkers and determining the ideal duration of treatment. While ICIs are generally well-tolerated, immune-related adverse events, although manageable, require careful monitoring, especially when ICIs are used in combination with chemotherapy. Ongoing research is focused on optimizing treatment duration and exploring combination therapies, with the objective of further improving long-term survival outcomes. The integration of immunotherapy in the adjuvant setting represents a significant advancement in the management of resectable NSCLC. This review aims to provide an overview of the current evidence supporting the use of ICIs in the adjuvant treatment of NSCLC, focusing on treatment efficacy, safety profiles, and ongoing research into biomarkers and combination therapies. Full article

Background/Objectives: Coeliac disease is an immune-mediated disorder of the gastrointestinal tract that may result in significant nutritional deficiencies. Effective management requires strict, lifelong adherence to a gluten-free diet. Both underdiagnosis and unnecessary dietary restrictions can adversely affect patients’ health and quality of life. To assess adherence to the current recommendations for the laboratory diagnosis of coeliac disease and promote evidence-based practices while reducing inter-laboratory variability, the Spanish Group on Autoimmunity of the Spanish Society of Immunology conducted a nationwide survey. Methods: A thirty-item survey was distributed to fifty autoimmune laboratories across Spain. Data were collected through a structured Excel-based questionnaire comprising multiple-choice items, which was distributed via email to the participating laboratories. It explored practices related to the diagnosis of coeliac disease in the general population and among at-risk groups as well as approaches to patient follow-up and demand management. Results: Thirty-five laboratories completed the electronic questionnaire. For the serological screening of coeliac disease, all the respondents reported using IgA anti-tissue transglutaminase (tTG-IgA) antibody testing together with total IgA measurement to assess IgA competence. However, consistent use of anti-endomysial antibody testing and HLA genotyping and adherence to pre-analytical recommendations for accurate interpretation of results were not uniform across centres. Conclusions: At the time these data were collected (the third trimester of 2021), the 2020 ESPGHAN guidelines for the diagnosis of coeliac disease in the paediatric population had not yet been fully implemented in most of the laboratories surveyed. For diagnosing adults, most laboratories adhered to local and European guidelines. Full article

Background: The introduction of biological drugs into clinical practice for the treatment of children with systemic juvenile idiopathic arthritis (sJIA) allows disease control but increases the risk of infectious events. Infectious events cause immunosuppressive therapy interruptions, leading to disease flare and life-threatening complications, namely macrophage activation syndrome. Our study aimed to evaluate the efficacy and safety of simultaneous vaccination against pneumococcal and Haemophilus influenzae type b (Hib) in children with sJIA. Methods: This study included 100 sJIA patients receiving immunosuppressive therapy who were simultaneously vaccinated against pneumococcal and Haemophilus influenzae type b (Hib) infections. The mean age of disease onset was 5.5 years. The median age at vaccination was 10 ± 4.5 years. Clinical and laboratory parameters of sJIA activity, immunization efficacy, and safety, including anti-SP and anti-Hib IgG antibodies, as well as all vaccination-related adverse events (AEs), were recorded in every patient before, 3 weeks after, and 6 months after vaccination. Results: At the time of vaccination, 29% of patients did not meet the criteria for the inactive disease stage, as defined by C. Wallace: active joints were present in 34.5% of patients, systemic manifestations (rash and/or fever) were present in 41.3%, and 24.2% of patients had solely inflammatory laboratory activity. The protective titer of anti-SP and anti-Hib IgG antibodies was detected in the majority of patients 3 weeks after vaccination (100% and 93%, respectively). The results remained unchanged (99% and 92%, respectively) for 6 months of follow-up, compared to the baseline (91% and 37%, p = 0.000001). Anti-SP IgG and anti-Hib titers raised from 48.3 (18.2; 76.5) and 0.64 (0.3; 3.2) U/mL at the baseline to 103.5 (47.3; 185.4) and 4 (3.5; 4.2) U/mL at D22 and 105 (48.7; 171.8) and 4 (3.8; 4) U/mL (EOS), respectively. Immunosuppressive therapy regimens (combined therapy or biological disease-modifying antirheumatic drug monotherapy) did not influence the immunogenic efficacy of vaccination. The incidence of infectious complications (p = 0.0000001) and antibiotic prescriptions (p = 0.0000001) decreased by more than two times, to 29.9 and 13.8 events per 100 patient months, respectively, within 6 months after vaccination—the average duration of acute infectious events was reduced by five times after immunization (p = 0.0000001). Vaccination did not lead to disease flare: the number of patients with active joints decreased by half compared to the baseline, and the number of patients with systemic manifestations decreased by six times. All vaccine-associated adverse events were considered mild and resolved within 1–2 days. Conclusions: Simultaneous vaccination against pneumococcal and Hib infections in sJIA children is an effective and safe tool that reduces the number and duration of infectious events and does not cause disease flare-ups. Full article

The 3rd International Electronic Conference on Biomedicines (ECB 2025) was an online event held from 12 to 15 May 2025, by the journal Biomedicines MDPI. The goal of this conference was to enable scientists to present their latest research in the field of biomedicines, especially on the discovery and characterization of new therapeutic targets in the era of precise medicine, and to engage in discussions with the scientific community worldwide. Recent advances in biomedical research have provided an advanced insight into the biological background of human disease, setting the groundwork for the development of new therapeutic strategies. The agenda of the conference included, but was not limited to, the following topics: insulin resistance or hyperinsulinemia; immunotherapy and adverse effects; the tumor microenvironment; the immune system, tumor immunology, and autoimmune disease; biomedicine in cardiovascular diseases; diabetes, obesity, and metabolic diseases; gene therapy and gene editing; rare diseases; and molecular mechanisms of neurodegeneration. Full article

Background/Objectives: The emergence of multidrug-resistant Acinetobacter baumannii (MDR A. baumannii) as a leading cause of fatal hospital-acquired infections underscores the urgent need for effective vaccines. While oral vaccines using live Bacillus subtilis spores expressing A. baumannii TonB-dependent receptor (TBDR) show promise, biosafety concerns regarding recombinant spore persistence necessitate alternative strategies. Here, we evaluated chemically inactivated B. subtilis spores displaying TBDR as a safer yet immunogenic vaccine candidate. Methods: Recombinant spores were inactivated using iron-ethanol sporicidal solution and administered to BALB/c mice (8–12 weeks old) to assess safety and immunogenicity. Toxicity was evaluated through clinical monitoring, serum biochemistry, and histopathology. Immune responses were characterized by T/B cell activation, IgG/IgA titers, and mucosal sIgA levels. Protective efficacy was determined by challenging immunized mice with MDR A. baumannii Ab35 and quantifying bacterial loads and examining tissue pathology. Results: The inactivated spores exhibited an excellent safety profile, with no adverse effects on clinical parameters, organ function, or tissue integrity. Immunization induced robust systemic and mucosal immunity, evidenced by elevated CD4+/CD8+ T cells, B cells, and antigen-specific IgG/IgA in serum and mucosal secretions. Following the challenge, vaccinated mice showed significantly reduced pulmonary bacterial burdens (>90% reduction), and preserved lung and spleen architecture compared to controls, which developed severe inflammation and tissue damage. Conclusions: These findings demonstrate that inactivated B. subtilis spores expressing TBDR are a safe, orally administrable vaccine platform that elicits protective immunity against MDR A. baumannii. By addressing biosafety concerns associated with live spores while maintaining efficacy, this approach represents a critical advance toward preventing high-risk nosocomial infections. Full article

Dairy cows are suffering from heat stress (HS) worldwide, and this has become a continual challenge in dairy production systems. The objective of this study was to investigate the effects of the shade of poplar trees on alleviating HS via measuring milk production, nutrient digestibility, immunity, and antioxidant capability in the serum of dairy cows in open cowsheds. A total of 540 lactating Holstein cows were assigned to 2 groups (3 cowsheds per group, 90 cows per cowshed), including the treatment group with poplar trees on the west side of sheds and the control group without trees. This study was carried out in the early-hot season, hot season, and late-hot season. The results showed the following: (1) During the hot season, shaded cows exhibited lower respiration rate (p < 0.05) and higher dry matter intake (p < 0.05) and daily milk yield (p < 0.05), compared with the control. Also, apparent digestibility of crude protein, acid detergent fiber, and neutral detergent fiber demonstrated an increase (p < 0.05) in shaded cows during the hot season. (2) Total antioxidant capacity and superoxide dismutase activity in the serum of shaded cows increased (p < 0.05) during the hot season and late-hot season, compared with the control. (3) Serum interleukin-4, immunoglobulin G, and immunoglobulin M concentrations of shaded cows were greater (p < 0.05) than the control during the hot season. Additionally, serum concentrations of HSP60, HSP70, and HSP90 in shaded cows showed a decrease (p < 0.05) during the hot season. In conclusion, shade from poplar trees can mitigate the adverse impact of high-temperature environments on cows in open cowsheds. Full article

Background/Objectives: Equine rhinopneumonia, caused by equine herpesvirus types 1 and 4 (EHV-1 and EHV-4), continues to be a significant health and economic concern in the global equine industry, particularly in Kazakhstan. While vaccines targeting EHV-1 are available, there is currently no licensed monovalent vaccine for EHV-4, and existing formulations offer limited protection against this serotype. This study aimed to develop and evaluate a freeze-dried, live-attenuated EHV-4 vaccine with improved safety, stability, and immunogenicity. Methods: A field isolate of EHV-4 was attenuated through serial passaging in primary lamb testicle (LT-KK49) cell cultures. Viral biomass was concentrated and formulated with various stabilizers before freeze-drying. The most effective stabilizer composition—sucrose, gelatin, and lactalbumin hydrolysate—was selected based on viral titer retention. Safety and immunogenicity were assessed in mice, guinea pigs, rabbits, donkeys, and horses. A guinea pig reproductive challenge model was used to evaluate protective efficacy. Results: The optimized lyophilized vaccine retained infectivity (>6.0 log₁₀ TCID_50/cm³) for at least six months at 4 °C. No adverse clinical signs were observed in any test species. Immunization induced robust neutralizing antibody responses in both small animals and equines. In the guinea pig model, vaccinated females demonstrated 100% pregnancy retention and fetal viability following challenge with a virulent EHV-4 strain. Conclusions: This freeze-dried, live-attenuated EHV-4 vaccine candidate is safe, immunogenic, and thermostable. It offers a promising platform for the targeted prevention of EHV-4 infection, particularly in young horses and in regions with limited cold-chain infrastructure. Full article

Janus kinase inhibitors, including tofacitinib, filgotinib, and upadacitinib, have emerged as effective therapeutic options for the management of inflammatory bowel diseases (IBDs). By targeting the JAK-STAT signaling pathway, these agents modulate immune responses and reduce inflammation. However, concerns regarding the potential risk of malignancy associated with their use have gained significant attention. The JAK-STAT pathway is not only critical for inflammatory signaling but also plays a pivotal role in cellular growth, differentiation, and tumor surveillance. Observational studies and clinical trial data in rheumatoid arthritis have reported malignancies, including non-melanoma skin cancer and solid tumors, in patients receiving JAK inhibitors, with evidence suggesting variable risks depending on the selectivity of the agent. Current evidence does not suggest an increased risk of oncogenesis in patients with IBDs. Balancing therapeutic efficacy with long-term safety requires ongoing vigilance; patient stratification based on risk factors; and tailored monitoring strategies to mitigate potential adverse effects, including malignancies, during JAK inhibitor therapy. Long-term follow-up data of up to 10 years offer reassuring evidence that JAK inhibitor therapy in IBD patients does not confer an increased risk of malignancies, supporting their continued use within appropriate clinical settings. Full article