Search Results (4,249)

Bovine mastitis, particularly that caused by Staphylococcus aureus, presents a major challenge to dairy production worldwide due to its economic impact, animal welfare concerns, and zoonotic potential. This narrative review synthesizes current literature on the epidemiology, pathogenesis, resistance patterns, and control strategies related to S. aureus-associated mastitis in dairy cattle. It highlights the pathogen’s virulence mechanisms, such as biofilm formation, immune evasion, and toxin production, that facilitate persistent infections. The review compiles global prevalence data, revealing significant geographic variation and disparities between clinical and subclinical cases. Antimicrobial resistance, especially the emergence of methicillin-resistant S. aureus (MRSA), is extensively examined alongside resistance gene profiles. Diagnostic approaches, including culture, PCR, MALDI-TOF MS, and AI-based systems, are evaluated for their sensitivity and field applicability. Additionally, the review addresses public health implications, zoonotic risks, and One Health perspectives, culminating in an exploration of prevention strategies, including improved hygiene, vaccination, dry cow therapy, and AI-driven herd management. The findings emphasize the urgent need for integrated surveillance, precision diagnostics, and targeted interventions to mitigate the burden of S. aureus mastitis. Full article

Obesity, a multifactorial metabolic syndrome driven by genetic–epigenetic crosstalk and environmental determinants, manifests through pathological adipocyte hyperplasia and ectopic lipid deposition. With the limitations of conventional anti-obesity therapies, which are characterized by transient efficacy and adverse pharmacological profiles, the scientific community has intensified efforts to develop plant and fungal polysaccharide therapeutic alternatives. These polysaccharide macromolecules have emerged as promising candidates because of their diverse biological activities and often act as natural prebiotics, exerting beneficial effects through multiple pathways. Plant and fungal polysaccharides can reduce blood glucose levels, alleviate inflammation and oxidative stress, modulate metabolic signaling pathways, inhibit nutrient absorption, and reshape gut microbial composition. These effects have been shown in cellular and animal models and are associated with mechanisms underlying obesity and related metabolic disorders. This review discusses the complexity of obesity and multifaceted role of plant and fungal polysaccharides in alleviating its symptoms and complications. Current knowledge on the anti-obesity properties of plant and fungal polysaccharides is also summarized. We highlight their regulatory effects, potential intervention pathways, and structure–function relationships, thereby providing novel insights into polysaccharide-based strategies for obesity management. Full article

Triclabendazole (TCBZ) is the gold standard treatment for fascioliasis. However, reports on resistance are increasing, emphasizing the need for alternative therapy. Combining TCBZ with ivermectin (IVM) was found to be effective for treating animal fascioliasis. Building on this, we aimed to evaluate the efficacy of the TCBZ/IVM combination therapy for human fascioliasis. This study enrolled 136 patients with Fasciola from Upper Egypt, and they were divided into the first group (n = 65), who received TCBZ monotherapy, and the second group (n = 71), who received the TCBZ/IVM combination. Assessments were to evaluate treatment response based on clinical, eosinophilic, and radiological parameters. Chronic fasciolosis was diagnosed in 17 patients (12.5%). No differences were observed in age and sex. Significant improvements were noted in all parameters in both groups, with more pronounced effects observed in the second group. A significantly higher complete response, including clinical, eosinophilic, and radiological improvements, was reported in the combined therapy group, with 53.3% compared to 26.2% in the monotherapy group (p < 0.001). A high baseline eosinophilic count was significantly associated with response. The efficacy of the TCBZ/IVM combination for treating human fascioliasis suggested a possible boosting effect, which can benefit regions of TCBZ failure. Further large-scale randomized studies are warranted to confirm these findings. Full article

Albumin-binding agents enhance tumor uptake of radiopharmaceuticals targeting prostate-specific membrane antigens (PSMAs) in radiotherapy. We synthesized PSMA-NARI-56, a molecule with both PSMA targeting activity and albumin-binding moiety, labeled with ¹⁷⁷Lu as the therapeutic agent. The aim of this study was to determine the specific binding of ¹⁷⁷Lu-PSMA-NARI-56 towards PSMA, assess its biodistribution, and evaluate therapeutic effectiveness by tumor-bearing mice. The effect of ¹⁷⁷Lu-PSMA-NARI-56 viability of PSMA-positive cell (LNCaP) was evaluated. Biodistribution and endoradiotherapy studies were utilized to determine the distribution, targeting, and anti-tumor efficacy by tumor-bearing mice identified by ¹¹¹In-PSMA-NARI-56. ¹⁷⁷Lu-PSMA-NARI-56 exhibited a significant impact on the viability of the LNCaP cell. Biodistribution results revealed the maximum tumor uptake of ¹⁷⁷Lu-PSMA-NARI-56 occurring within 24 h, reaching 40.56 ± 10.01%ID/g. In radionuclide therapy, at 58 days post-injection (p.i.), ¹⁷⁷Lu-PSMA-NARI-56 demonstrated superior tumor inhibition (98%) compared to ¹⁷⁷Lu-PSMA-617 (58%), and the mouse survival rate after 90 days of radiotherapy (90%) was also higher than that of ¹⁷⁷Lu-PSMA-617 (30%) in LNCaP tumor-bearing mice. In the PSMA-positive animal model, ¹⁷⁷Lu-PSMA-NARI-56 shows higher potential radiotheranostic and prolonged accumulation (identify by ¹¹¹In-PSMA-NARI-56/nanoSPECT/CT image), offering the potential for improved treatment effectiveness and increased survival rates when compared to ¹⁷⁷Lu-PSMA-617. Full article

This review explores the biofilm architecture and drug resistance of Enterococcus faecalis in clinical and environmental settings. The biofilm in E. faecalis is a heterogeneous, three-dimensional, mushroom-like or multilayered structure, characteristically forming diplococci or short chains interspersed with water channels for nutrient exchange and waste removal. Exopolysaccharides, proteins, lipids, and extracellular DNA create a protective matrix. Persister cells within the biofilm contribute to antibiotic resistance and survival. The heterogeneous architecture of the E. faecalis biofilm contains both dense clusters and loosely packed regions that vary in thickness, ranging from 10 to 100 µm, depending on the environmental conditions. The pathogenicity of the E. faecalis biofilm is mediated through complex interactions between genes and virulence factors such as DNA release, cytolysin, pili, secreted antigen A, and microbial surface components that recognize adhesive matrix molecules, often involving a key protein called enterococcal surface protein (Esp). Clinically, it is implicated in a range of nosocomial infections, including urinary tract infections, endocarditis, and surgical wound infections. The biofilm serves as a nidus for bacterial dissemination and as a reservoir for antimicrobial resistance. The effectiveness of first-line antibiotics (ampicillin, vancomycin, and aminoglycosides) is diminished due to reduced penetration, altered metabolism, increased tolerance, and intrinsic and acquired resistance. Alternative strategies for biofilm disruption, such as combination therapy (ampicillin with aminoglycosides), as well as newer approaches, including antimicrobial peptides, quorum-sensing inhibitors, and biofilm-disrupting agents (DNase or dispersin B), are also being explored to improve treatment outcomes. Environmentally, E. faecalis biofilms contribute to contamination in water systems, food production facilities, and healthcare environments. They persist in harsh conditions, facilitating the spread of multidrug-resistant strains and increasing the risk of transmission to humans and animals. Therefore, understanding the biofilm architecture and drug resistance is essential for developing effective strategies to mitigate their clinical and environmental impact. Full article

Background/Objectives: Tamoxifen, a selective estrogen receptor modulator widely used as an adjunct in the treatment of breast cancer, has known effects on bone metabolism, although its impact on osseointegration and cellular responses during early bone healing remains unclear. Understanding these effects is essential given the increasing use of dental implants in cancer survivors. The study aimed to observe the influence of tamoxifen on human osteosarcoma (SAOS-2) cells lines, as well on the osseointegration of titanium implants in ovariectomized female rats. Methods: SAOS-2 cells were incubated with Dulbecco’s modified growth medium. Six titanium (Ti) disks were used at each time point. The samples were divided into groups with the presence (TAM, n = 36) or not (CTR, n = 36) of tamoxifen in a concentration of 2 μM. In vivo, 72 animals were divided in groups with bilateral ovariectomy or SHAM and tamoxifen administration or not (15 mg/kg). Cell viability, mineralization rate, and collagen synthesis were assessed, as well as bone/implant contact (BIC) and bone ingrowth (BIN). Results: Tamoxifen caused a decrease in SAOS-2 viability, although an increase in the mineralization rate was observed. In vivo, the TAM groups presented higher BIC and BIN when compared to their control, but a lower percentage of mature collagen cells. Conclusions: Based on our findings, in vitro, the therapy with TAM slightly reduced the viability of SAOS-2 cells while significantly increasing the mineralization rate. In vivo, the therapy positively influenced BIC and BIN during the osseointegration phase. Full article

Plant latex is a rich source of proteolytic enzymes with potential biomedical applications, particularly in hemostasis. Among them, thrombin-like enzymes (TLEs) have garnered interest in their ability to mimic thrombin by catalyzing the conversion of fibrinogen to fibrin, facilitating clot formation. While TLEs from snake venoms have been well-characterized and applied clinically, their plant-derived counterparts remain underexplored. This review critically examines the structural and functional characteristics of TLEs from plant latex, comparing them to animal-derived TLEs and evaluating their role in both procoagulant and fibrinolytic processes. Emphasis is placed on dual fibrinogenolytic and fibrinolytic activities exhibited by latex proteases, which often vary with concentration, incubation time, and protease type. In vitro coagulation assays and electrophoretic analyses are discussed as critical tools for characterizing their multifunctionality. By addressing the knowledge gaps and proposing future directions, this paper positions plant latex proteases as promising candidates for development in localized hemostatic and thrombolytic therapies. Full article

Toxoplasma gondii is an intracellular protozoan found worldwide that is capable of infecting nearly all warm-blooded animals, including humans. Its parasitic success lies in its capacity to create chronic infections while avoiding immune detection, altering host immune responses, and disrupting programmed cell death pathways. This review examines the complex relationship between T. gondii and host immunity, focusing on how the parasite influences innate and adaptive immune responses to survive in immune-privileged tissues. We present recent findings on the immune modulation specific to various parasite strains, the immunopathology caused by imbalanced inflammation, and how the parasite undermines host cell death mechanisms such as apoptosis, necroptosis, and pyroptosis. These immune evasion tactics enable prolonged intracellular survival and pose significant challenges for treatment and vaccine development. We also review advancements in therapeutic strategies, including host-directed approaches, nanoparticle drug delivery, and CRISPR-based technologies, along with progress in vaccine development from subunit and DNA vaccines to live-attenuated candidates. This review emphasizes the importance of T. gondii as a model for chronic infections and points out potential avenues for developing innovative therapies and vaccines aimed at toxoplasmosis and similar intracellular pathogens. Full article

Quercetin is a biologically active flavonoid compound that exerts numerous beneficial effects in humans and animals, including anti-diabetic activity. Its action has been explored in rodent models of type 1 and type 2 diabetes. It was revealed that quercetin mitigated diabetes-related hormonal and metabolic disorders and reduced oxidative and inflammatory stress. Its anti-diabetic effects were associated with advantageous changes in the relevant enzymes and signaling molecules. Quercetin positively affected, among others, superoxide dismutase, catalase, glutathione peroxidase, glucose transporter-2, glucokinase, glucose-6-phosphatase, glycogen phosphorylase, glycogen synthase, glycogen synthase kinase-3β, phosphoenolpyruvate carboxykinase, silent information regulator-1, sterol regulatory element-binding protein-1, insulin receptor substrate 1, phosphoinositide 3-kinase, and protein kinase B. The available data support the conclusion that the action of quercetin was pleiotropic since it alleviates a wide range of diabetes-related disorders. Moreover, no side effects were observed during treatment with quercetin in rodents. Given that human diabetes affects a large part of the population worldwide, the results of animal studies encourage clinical trials to evaluate the potential of quercetin as an adjunct to pharmacological therapies. Full article

Obesity is a multifactorial condition that influences metabolic, endocrine, inflammatory, circadian, and behavioral systems. These disruptions can adversely affect the initiation of lactogenesis II—the critical process marking the onset of copious milk secretion following childbirth. In mothers with obesity, prolonged inflammation within the mammary gland, a blunted hormonal response (notably of prolactin), altered progesterone and estrogen dynamics, high leptin levels, and misaligned circadian rhythms contribute significantly to delayed lactogenesis. In addition, mechanical difficulties and psychological factors further hinder effective breastfeeding. This report synthesizes evidence from human epidemiological studies and animal models that elucidate the diverse mechanisms linking maternal obesity to delayed lactogenesis. We review the role of obesity-associated inflammatory mediators in impairing mammary tissue remodeling, the endocrine aberrations that impair lactogenic signaling, the consequences of circadian disruption on hormonal rhythmicity, and the behavioral influences that challenge effective breastfeeding. Finally, we discuss the clinical implications of these findings and propose future research directions targeting endocrine modulation, anti-inflammatory therapy, circadian interventions, and enhanced lactation support strategies for mothers with obesity. Full article

Cardiac arrhythmias remain a major source of morbidity and mortality, often stemming from molecular and structural abnormalities that are insufficiently addressed by current pharmacologic and interventional therapies. Gene therapy has emerged as a transformative approach, offering precise and durable interventions that directly target the arrhythmogenic substrate. Across the spectrum of inherited and acquired arrhythmias—including long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, atrial fibrillation, and post-infarction ventricular tachycardia—gene-based strategies such as allele-specific silencing, gene replacement, CRISPR-mediated editing, and suppression-and-replacement constructs are showing growing translational potential. Advances in delivery platforms, including cardiotropic viral vectors, lipid nanoparticle-encapsulated mRNA, and non-viral reprogramming tools, have further enhanced the specificity and safety of these approaches. Additionally, innovative applications such as biological pacemaker development and mutation-agnostic therapies underscore the versatility of genetic modulation. Nonetheless, significant challenges remain, including vector tropism, immune responses, payload limitations, and the translational gap between preclinical models and human electrophysiology. Integration of patient-derived cardiomyocytes, computational simulations, and large-animal studies is expected to accelerate clinical translation. This review provides a comprehensive synthesis of the mechanistic rationale, therapeutic strategies, delivery platforms, and translational frontiers of gene therapy for cardiac arrhythmias. Full article

The investigation of the reward system is a fascinating domain with future applications for pain therapy and understanding addiction. We investigated interactions between tramadol use and the imidazoline system, through the modulatory effects of imidazoline receptor blockers, by behavior analysis and electroencephalography (EEG). Thirty-six male Wistar rats were placed within a conditioned place preference (CCP) setting using a three-compartment box apparatus. The transition of the six groups of subjects from one compartment to another was constantly monitored, related to preconditioning for one day, conditioning for eight days, and post-conditioning testing on day 10. During the conditioning phase, the groups received: a saline solution, efaroxan, idazoxan, tramadol, tramadol + efaroxan, and tramadol + idazoxan, respectively. The administration of efaroxan, idazoxan, or a saline solution in the non-preferred compartment did not alter the time spent by rats there. On the other hand, the administration of tramadol alone in the non-preferred compartment significantly increased the time spent by animals there (151.66 ± 11.69 s) post-conditioning as compared to preconditioning (34.5 ± 5.31 s) (p < 0.01), while the combination of efaroxan and tramadol significantly reduced its effect. After the combination with idazoxan, the effect of tramadol on increasing the time spent by the animal in the non-preferred compartment remained significantly higher than in the preconditioning phase. A significant increase in time spent in the non-preferred compartment demonstrates the existence of a CPP induction effect (by changing the preference). The effects of tramadol on the reward system can cause changes in the brain’s neuroplasticity, potentially leading to learned behaviors that promote drug seeking in previous non-preferred environments. Full article

Parkinson’s disease (PD) is a common neurodegenerative disorder with substantial global impact. Although current therapies can provide symptomatic relief, they are often associated with high costs and adverse effects. Natural compounds with a history of traditional medicinal use have emerged as promising alternatives. In this study, we investigated the therapeutic potential and underlying mechanisms of berberine in both cellular and animal models of PD. In vitro, SH-SY5Y cells exposed to 6-hydroxydopamine (6-OHDA) exhibited decreased viability and increased oxidative stress, both of which were significantly alleviated by berberine treatment based on cell viability assays and DCFH-DA staining. Western blot analysis revealed that berberine modulated the AMPK–PGC-1α–SIRT1 signaling pathway and restored the expression of autophagy-related proteins LC3B and P62, suggesting that berberine could improve mitochondrial function and autophagy balance. In vivo studies using a 6-OHDA-induced PD mouse model further confirmed these effects, showing that berberine could improve motor function and lead to molecular changes consistent with in vitro studies. Additionally, safety evaluations indicated no significant hepatotoxicity based on AST and ALT levels. Body weight also remained stable throughout treatment. Collectively, our findings suggest that berberine can not only alleviate PD-related symptoms but also target key pathological mechanisms, supporting its potential as a therapeutic candidate for PD and other neurodegenerative diseases. Full article

Chemotherapeutic agents and radiotherapy are highly effective in treating malignancies. However, they carry a significant risk of harming the gonads and may lead to endocrine dysfunction and reproductive issues. This review outlines the molecular mechanisms of gonadotoxic therapies, focusing on radiation, alkylating agents, and platinum compounds. It discusses the loss of PMFs due to gonadotoxic exposure, including DNA double-strand breaks, oxidative stress, and dysregulated signaling pathways like PI3K/PTEN/Akt/mTOR and TAp63-mediated apoptosis. Furthermore, it explores strategies to mitigate gonadal damage, including GnRH agonists, AMH, imatinib, melatonin, sphingolipid metabolites, G-CSF, mTOR inhibitors, AS101, and LH. These therapies, paired with existing fertility preservation methods, could safeguard reproductive and hormonal functions and improve the quality of life for young cancer patients. Despite the progress made in recent years in understanding gonadotoxic mechanisms, gaps remain due to questionable reliance on mouse models and the lack of models replicating human ovarian dynamics. Long-term studies are vital for wider analyses and exploration of protective strategies based on various animal models and clinical trials. It is essential to verify that these substances do not hinder the anti-cancer effectiveness of treatments or cause lasting DNA changes in granulosa cells, raising the risk of miscarriages and infertility. Full article

Background/Objectives: Limited robust data support the use of antibiotic combinations in the treatment of orthopedic infections. However, in certain situations, the combination of antibiotics seems to be beneficial. This review aims to outline the circumstances under which a combination of antibiotics may be utilized in the treatment of orthopedic infections. Methods: We reviewed the existing guidelines on orthopedic infections and focused on situations where antibiotic combinations are recommended or proposed optionally. We chose vitro and animal studies that provide evidence for the effectiveness of several widely recommended combinations. Results: The combinations serve multiple purposes: they provide empirical coverage while awaiting microbiological results, offer targeted treatment for difficult-to-treat infections, and facilitate oral treatment primarily for staphylococcal infections. The objectives include enhancing bacterial coverage against Gram-positive and Gram-negative bacteria, achieving synergistic effects with bactericidal agents, and reducing the risk of antibiotic resistance. The review outlines specific combinations for fracture-related infections, periprosthetic joint infections, spinal infections, and anterior cruciate ligament reconstruction infections, emphasizing the importance of tailoring antibiotic choices based on local epidemiology and patient history. The review also addresses potential drawbacks of combination therapy, such as toxicity, higher costs, and drug interactions, underscoring the complexity of managing orthopedic infections effectively. Conclusions: According to the guidelines, several different proposals are made, depending in part on the countries’ epidemiology. In a well-defined situation, various authors propose either monotherapy or a combination of antibiotics. When a combination is suggested, the choice of antibiotics is based on the expected effect: broadening the spectrum, enhancing bactericidal activity, achieving a synergistic effect, or reinforcing biofilm activity to optimize the treatment. Full article