Abstract: Human papillomavirus (HPV) infection remains a major global health concern due to its strong association with cervical and other anogenital and oropharyngeal cancers. The outcome of HPV infection is largely determined by complex interactions between the virus and host immune responses. This review summarizes current knowledge on the immune landscape of HPV infection, focusing on innate immune recognition, adaptive immune responses, and viral immune evasion strategies. HPV is sensed by host pattern recognition receptors, yet it efficiently suppresses interferon signaling and cytokine responses to establish persistent infection. Adaptive immunity, including HPV-specific CD4⁺ and CD8⁺ T-cell responses and neutralizing antibodies, plays a critical role in viral clearance, while defects in these responses contribute to persistence and disease progression. The virus employs multiple immune evasion mechanisms, such as downregulation of antigen presentation and modulation of cytokine signaling, facilitating immune escape and oncogenesis. The review also highlights immune correlates of protection, vaccine-induced immunity, and emerging immunotherapeutic strategies targeting HPV-associated diseases. A comprehensive understanding of HPV–host immune interactions is essential for optimizing vaccine design, improving therapeutic interventions, and reducing the global burden of HPV-related malignancies.

Abstract: The Mediator complex is a central regulator of eukaryotic transcription, functioning as a dynamic molecular bridge between gene-specific transcription factors and RNA polymerase II (Pol II). Although decades of research have established its modular architecture and fundamental role in transcriptional control, recent advances have significantly expanded our understanding of its structural conformations, subunit-specific functions, and links to human disease. This review provides a comprehensive overview of the Mediator complex, highlighting key structural and functional discoveries from the past decade and synthesizing its diverse roles in transcriptional regulation. We further discuss emerging concepts and future directions for therapeutically targeting Mediator, particularly in cancer. Together, these insights position the Mediator complex as a highly conserved yet adaptable, signal-responsive regulatory hub with broad implications for both normal physiology and disease pathogenesis.

Abstract: Sports science is rapidly changing with new discoveries in molecular biology and artificial intelligence. Modern “omics” tools, such as genomics, proteomics, and metabolomics along with AI-based analytics, help us understand how a child’s body builds muscle, responds to training, and recovers after exercise. These technologies also help identify factors that may increase the risk of injury. Simple genetic tests, including variations like ACE I/D and ACTN3 R577X, provide insights into traits linked to endurance, strength, and muscle performance. Protein and metabolite testing, supported by AI models, can reveal how efficiently the body uses energy or repairs tissues after activity. This review article provides the most recent and up-to-date knowledge regarding modern technologies used for performance enhancement. These scientific tools are not meant to label or limit children. Instead, they help parents and coaches understand each child’s individual needs and support healthier training decisions. AI-driven interpretations can guide choices about training intensity, rest, recovery, and nutrition in a safe and personalized manner. Overall, this paper offers practical guidance for using molecular and AI-driven sportomics responsibly. Our goal is to empower parents and coaches with informed, balanced, and child-centric strategies for enhancing performance.

Abstract: Background: Epigenetic regulation must preserve stable functional states under molecular stochasticity and changing environments, yet an operational model linking context-level signals to measurable chromatin remodeling is limited. Method: This study proposes Epigenetic Teleonomy, a stochastic control framework in which epigenomic observables relax toward an empirically estimated within-subject baseline regime (reference distribution) with lagged mediator-driven inputs and feedback. Results: A local approximation yields mean-reverting dynamics. Simulations illustrate that without effective feedback, diffusion-like drift leads to increasing dispersion, whereas sufficient regulation gain yields bounded fluctuations and recovery. In the isotropic local Ornstein–Uhlenbeck (OU) regime, stationary fluctuations scale with effective diffusion and inversely with return rate (gain). Conclusion: The framework is testable in longitudinal designs by (i) estimating a subject-specific baseline from a stable run-in window, (ii) quantifying deviation using reduced-dimensional proxies, and (iii) fitting gain and diffusion from return-to-baseline statistics.

Abstract: Background: TNXB-related classical-like Ehlers-Danlos syndrome (clEDS) is caused by biallelic pathogenic variants in TNXB, encoding the extracellular matrix glycoprotein tenascin-X. Although traditionally classified as a connective tissue disorder based on joint hypermobility and skin findings, accumulating clinical, electrophysiological, and imaging data indicate prominent neuromuscular involvement that likely reflects a central disease mechanism. Methods: A qualitative evidence synthesis was conducted following PRISMA 2020 guidelines. A comprehensive search of PubMed, OMIM, and GeneReviews was performed on January 5, 2026. Data from 18 studies representing 56 individuals with biallelic TNXB variants were synthesized narratively, with findings stratified by assessment method and zygosity. Due to heterogeneity in study designs, assessment methods, and outcome definitions, quantitative meta-analysis was not feasible. Results: Among 56 individuals with biallelic TNXB variants, subjective muscle weakness was reported in only 37% of cases. However, systematic neuromuscular assessment demonstrated objective muscle weakness in 85% of patients examined. Electromyography revealed mixed neurogenic-myopathic patterns in 60%, and muscle imaging abnormalities were present in approximately 50%. A clear dose-effect relationship was observed, with heterozygous individuals exhibiting milder phenotypes correlating with reduced serum tenascin-X levels. Conclusion: Neuromuscular involvement in TNXB-related disorders is frequent, progressive, and mechanistically linked to dysfunction at the muscle-extracellular matrix interface. These findings support the reclassification of TNXB-related disease alongside myopathic Ehlers-Danlos syndrome as a muscle-ECM interface disorder.

Abstract: Introduction of livestock into tropical and subtropical forest areas has displaced the orig-inal forest vegetation. Posterior surge of secondary vegetation has served as a source of al-ternative forage to cattle during scarcity periods. The objective of the study was to determine the botanical composition of the diet (BCD) and the productive performance of lac-tating Brown Swiss cows during the dry season. The BCD was determined through microhistological analysis of fecal samples of grazing cows. Grazing areas were sampled to determine morphological and botanical composition (BCP). Forages were sampled to determine their chemical composition. Cow's productive variables were recorded during March, April, and May of 2012. The BCP and BCD consisted of Cynodon plectostachyus and the woody species were Vachellia farnesiana, with smaller proportions of Pithecellobium dulce, Guazuma ulmifolia, and Ficus sp. These forages contributed with 63, 48, and 47% of the dry matter, metabolizable energy, and metabolizable protein requirements of the cows. Therefore, it is concluded that alternative forages contributed significantly to the nutri-tional requirements during periods of pasture scarcity. Understanding the botanical composition of the diet of grazing cows allows for the development of management strat-egies based on the efficient use of local resources.

Abstract: Introduction: Stunting is associated with poor nutritional intake during early childhood. This study evaluated the effect of a daily intake of 510 mL of an oral nutritional supplement for 180 days on linear growth among children with stunting and at-risk of stunting aged 12–36 months. Methods: A community-based, single arm intervention was conducted among 91 children in Kelantan, Malaysia. The children at enrolment had height-for-age Z-scores (HAZ) between <-1.0 SD to >-3 SD based on WHO Growth Standards. Anthropometric measurements were taken at baseline (T0), day-90 (mid-intervention), and day-180 (post-intervention). Nutrient intake was assessed using 24-hour dietary recalls, and compliance was monitored via returned empty sachets. Results: The mean age of the children at baseline was 26.7 ± 6.5 months, with 37 (41%) being stunted and 54 (59%) were at-risk of stunting. After intervention, the linear growth (height-for-age Z-score) was significantly improved over time (p < 0.001) in both stunted and at-risk children. A significant time-by-group interaction (p = 0.014) indicated differential effects between the stunted and at-risk groups. Post-hoc analysis showed HAZ improvements from baseline (T0) to 180 days in stunted and at-risk groups (p < 0.001) with the stunted group having greater mean differences. The number of stunted children declined by 37.8% (p = 0.003). Nutrient intakes of protein, vitamins D, vitamin C, vitamin B-complex, calcium, phosphorus, magnesium, and iron improved significantly. Conclusion: Daily intake of 510 mL of oral nutrition supplement improved linear growth and nutrient intakes. These findings support the potential of targeted supplementation in addressing child growth faltering and micronutrient inadequacies.

Abstract: Milk is a primary source of vital nutrients and bioactive components fundamental for the growth and development of both newborn animals and humans. Produced by economi-cally significant livestock species (including cattle, buffaloes, goats, sheep and camels) milk is a complex matrix rich in caseins, vitamins, fats and proteins. In addition to its nu-tritional profile, milk serves as a vehicle for milk-derived extracellular vesicles (mEVs), a specialized class of food-derived EVs (fEVs) that exert pleiotropic effects aligned with the One Health concept, relating animal health, human nutrition, and ecosystem stability. mEVs offer unique advantages, such as high biocompatibility and gastrointestinal stabil-ity, rendering them also potential therapeutic tools, as drug delivery systems. However, challenges remain regarding the standardization of mEVs and the variability of their mo-lecular cargo. This review provides a comparative analysis of mEVs across diverse spe-cies, including bovines, water buffaloes, yaks, camels, goats, pigs, horses, donkeys, and humans, with a focus on their unique functional profiles. Indeed, a critical issue in mEVs research is the isolation process: recommendations to minimize contamination from milk fat globules and casein micelles (which can cover EV signals) are given. Finally, current detection methods and instrumentation, with a specific focus on advancing Flow Cytom-etry (FC) approaches are discussed. Key insights include the use of Conventional FC (with fluorescence triggering, the necessity of rigorous controls and calibration, and the utility of Bead-Based Assays to overcome resolution limits) and of Imaging Flow Cytometry (IFC). In both technical approaches, the application of different EVs generic fluorescent markers and the strategic selection of tetraspanins (i.e. CD9, CD63, CD81), is mandatory, empha-sizing the importance of selecting appropriate antibody clones or considering cross-reactivity when targeting these antigens across different mammalian species.

Abstract:

B vitamins are essential micronutrients for human health with prominent antioxidant properties, capable of scavenging reactive oxygen species (ROS) and maintaining redox homeostasis, protecting cells from oxidative damage. To address global nutrient deficiencies and identify plant-based antioxidant sources, this study quantified seven B vitamins (B₁, B₂, B₃, B₅, B₆, B₉, B₁₂) in seeds, leaves, and seedlings of five oilseeds (sesame, peanut, soybean, rapeseed, perilla) and two leafy vegetables (spinach, lettuce) via LC-MS/MS, revealing distinct species- and tissue-specific patterns. Notably, sesame seeds exhibited exceptional vitamin B₃ (niacin, 39.3 μg/g), surpassing other oilseeds by 1.6-8.2-fold; its leaves contained outstanding vitamin B₆ (2.88 μg/g), with 2.57–8.31-fold higher than spinach (1.12 μg/g) and lettuce (0.34μg/g), whereas, vitamin B₁₂ (0.44 μg/g), with levels of ~13–20 times higher than other leaves samples. Sesame seedlings recorded high vitamin B₆ (1.6 μg/g) and B₁₂ (0.1 μg/g) among the oilseed crops seedlings. These findings highlight sesame as a multifunctional B vitamin resource for antioxidant nutrition, supporting dietary optimization, crop biofortification, and mitigation of global B vitamin inadequacies via plant-based solutions.

Abstract: Recombinogenic DNA damage can initiate chromosomal rearrangements that can alter gene expression or accelerate cancer progression in higher eukaryotes. Thus, there is a critical need to identify genes that suppress chromosomal rearrangements and environmental exposures that promote genetic instability. Cell cycle checkpoints modulate the cell cycle so that DNA repair occurs before the replication or segregation of damaged chromosomes. Saccharomyces cerevisiae (budding yeast) RAD9 was the first cell cycle checkpoint gene identified, which initiated intensive research studies into the mechanisms of checkpoint activation and the phenotypes of checkpoint mutants. The budding yeast Rad9 protein serves as both an adaptor and scaffold that facilitates downstream effector activation to orchestrate a DNA damage response at multiple stages of the cell cycle, which facilitate double-strand break (DSB) repair by sister chromatid recombination. However, the role of RAD9 in homologous recombination and in suppressing gross chromosomal rearrangements (GCRs) is not completely understood. In this review we discuss how RAD9 can promote genome instability resulting from aberrant DNA replication intermediates, while suppressing DSB-associated rearrangements. We also discuss possible mechanisms accounting for the synergistic increase in genomic instability in double mutants defective in both RAD9 and recombinational repair. We emphasize that while there is an overlap between checkpoint and recombinational repair pathways, RAD9 and checkpoint pathways can function independently to suppress chromosomal instability. These studies thus elucidate checkpoint mechanisms that control homologous recombination between repeated sequences.

Abstract: Background: Fibromyalgia is a chronic disease that predominantly affects women and lasts over several months, causing problems both to individuals and society. While several studies have demonstrated the potential of electroacupuncture (EA) to alleviate fibromyalgia pain in mice, further research is needed to investigate its underlying mechanisms. Programmed cell death ligand-1 (PD-L1)/PD-1 was first identified to be involved in cancer immunotherapy, but its application to pain management has not been yet investigated. Methods: This study aimed to explore the mechanism underlying action of PD-L1 on PD-1 pathway in a mouse model of fibromyalgia. Results: We established such a mouse model using intermittent cold stress (ICS) and confirmed mechanical (D4: 2.02 ± 0.13 g, n = 9) and thermal (D4: 4.28 ± 0.21 s, n = 9) hyperalgesia. We found that EA, intracerebral ventricle (ICV) PD-L1 injection, or transient receptor potential vanilloid 1 (Trpv1) knockout effectively counteracted hyperalgesia. We observed low PD-1 expression in the cerebellum of fibromyalgia mice but increased expression of TRPV1 and pain-related kinases. These phenomena could be further reversed by EA, ICV PD-L1 injection, and Trpv1 knockout. To confirm that these effects were caused by PD-L1 release, we added PD-L1 neutralizing antibodies to the EA and PD-L1 treatment. The analgesic effects and EA and PD-L1 mechanisms were inhibited. Conclusions: Our results elucidate the role of the PD-L1/PD-1 pathway in EA treatment of fibromyalgia and reveal its potential value for fibromyalgia.

Abstract:

While industrial scale dairy fermentations often employ pasteurized milk as the substrate, many farmhouse and traditional production practices apply raw milk derived from a variety of mammals. Certain artisanal production systems rely on the autochthonous microbiota of the milk, fermentation vessels, equipment and/or environment to initiate milk coagulation. While the technological properties of lactic acid bacteria associated with dairy fermentations are well described, their interactions with other organisms during fermentation and cheese ripening are poorly investigated. This study presents an overview of the microbial ecology of raw and pasteurized milk used in the production of cheeses. Furthermore, we report on the motility phenotype, lactose utilization ability and metabolic products of isolates of Hafnia paralvei and Hafnia alvei, and determine that these strains could grow in a non-antagonistic manner on plates with strains of Lactococcus lactis and Streptococcus thermophilus. As artisanal and farmhouse production systems are often associated with protected or regionally significant products, it is essential to develop a clear understanding of the microbial communities within and the complex relationships between the community members.

Abstract: Penicillium expansum inflicts significant economic damage in the fruit and vegetable industry due to its wide distribution and ability to infect a diverse range of hosts. Therefore, developing safe and environmentally sustainable strategies to suppress the growth of this pathogen is of critical importance. Bacillus subtilis, recognized for its broad antimicrobial activity and widespread occurrence, has been widely utilized in the biological management of plant diseases. This research seeks to assess the inhibitory potential of B. subtilis against P. expansum. The cell-free supernatant (CFS) derived from B. subtilis significantly suppresses the germination spores, germ tube extension, and hyphal development of P. expansum. It also reduces disease incidence in grapes and citrus and suppresses the expansion of lesions. Further investigate had shown that it can induced mycelium reactive oxygen species (ROS) accumulation, destroyed the cell membrane integrity, led to leakage of cytoplasmic contents and induced membrane lipid peroxidation. Moreover, exposure to high concentrations of CFS results in mycelial contraction and morphological abnormalities, triggering the disintegration of intracellular organelles and markedly upregulating the expression of apoptosis-associated genes. The self-protective response elicited by 5% CFS is insufficient to counteract the extent of cellular damage, ultimately driving cells toward a dynamic, multistage, and disintegrative form of cell death. The findings of this study offer a theoretical foundation for managing P. expansum after harvest.

Abstract: Docosahexaenoic acid (DHA), an omega-3 fatty acid essential for human health, is highly prone to oxidation in nanoemulsions due to their large interfacial area and presence of transition metal ions. This study investigated macroalgal chelators for stabilizing DHA-rich nanoemulsions. Sequential enzymatic–alkaline extraction using Alcalase® produced an extract with the strongest Fe2+-chelating activity (IC50 = 1.22 mg/mL), protein content of 10.11 ± 0.15%, and total phenolics ≈17 µg GAE/mL. This extract was incorporated into nanoemulsions (5 wt% DHA oil, 1 wt% Tween® 20) at 0.61, 1.22, and 2.44 mg/mL and compared with controls containing EDTA (0.025 mg/mL) or no antioxidant. Droplet size remained stable (D3,2 ≈ 77-80 nm; D4,3 ≈ 199-215 nm) and zeta potential averaged -17 to -19 mV, confirming physical stability. Confocal microscopy revealed concentration-dependent interfacial adsorption of extract components. During iron-accelerated storage, extract-treated nanoemulsions slowed hydroperoxide formation and delayed tocopherol depletion compared to the control, while reducing volatile oxidation markers such as 1-penten-3-ol by up to 40%. However, EDTA consistently provided superior protection against oxidation. These findings highlight the potential of macroalgal extracts as clean-label, natural chelators for mitigating metal-driven oxidation in DHA nanoemulsions, though synthetic chelators remain more effective under severe prooxidant conditions.

Abstract: Mutations in leucine-rich repeat kinase 2 (LRRK2) are among the most common genetic causes of Parkinson’s disease (PD), yet substantial heterogeneity exists among pathogenic variants. How mutations in distinct functional domains of LRRK2 differentially perturb cellular homeostasis remains incompletely understood. Here, we compared two pathogenic LRRK2 mutations—G2019S in the kinase domain and I1371V in the GTPase domain—across multiple cellular models, including SH-SY5Y and U87 cells, and healthy human iPSC-derived floor plate cells. We demonstrate that the I1371V mutation induces markedly more severe cellular dysfunction than G2019S. I1371V-expressing cells exhibited elevated LRRK2 autophosphorylation at S1292 and robust hyperphosphorylation of Rab8A and Rab10, indicating enhanced downstream signaling. These alterations impaired sterol trafficking, leading to selective depletion of plasma membrane cholesterol without changes in total cellular cholesterol. Consequently, I1371V cells displayed increased membrane fluidity, disrupted microdomain organization, altered membrane topology, reduced Caveolin-1 expression, and impaired dopamine transporter surface expression and dopamine uptake. Lipidomic profiling further revealed broad disruption of lipid homeostasis, including reductions in cholesteryl esters, sterols, sphingolipids, and glycerophospholipids, whereas G2019S cells showed comparatively modest changes. Pharmacological intervention revealed mutation-specific responses, with the non-selective LRRK2 modulator GW5074 outperforming the kinase-selective inhibitor MLi-2 in restoring Rab8A phosphorylation, membrane integrity, and dopaminergic function. Collectively, these findings identify membrane lipid dysregulation as a central cell-biological mechanism in LRRK2-associated PD and underscore the importance of variant-specific therapeutic strategies.

Abstract:

Background: Diabetes among adults is becoming a major public health crisis in the United States. Numerous authors have documented the rising prevalence of diabetes, with notable variations found within the United States at the census level, state, and county levels. Yet, there is a need to understand whether diabetes prevalence varies between urban centers within a particular state. Methods: This ecological study provides a longitudinal investigation of the prevalence of adult diabetes across five major metropolitan urban areas in Texas (Austin, Dallas, Fort Worth, Houston, and San Antonio) from 2011 to 2023. By utilizing data from the Behavioral Risk Factor Surveillance System (BRFSS) and statistical testing, we evaluate both the temporal trajectory and city-level geographic disparities of diabetes prevalence. Findings: Upon aggregating all five urban centers, the findings demonstrate a significant statewide increase (β=0.12, P=0.026) in diabetes prevalence over the thirteen-year study period. Furthermore, profound regional variations were observed, with San Antonio having a significantly (P<0.05) higher prevalence than Austin, Dallas, and Fort Worth, with the San Antonio area exhibiting the highest mean prevalence at 12.1% and the Austin area maintaining the lowest at 9%. Interpretation: This research emphasizes the necessity for synchronized public health policies that account for localized contexts while addressing the broader metabolic crisis facing the Texas urban corridor.

Abstract: Potyviruses express their genome as a single large open reading frame, translated into a polyprotein that is post-translationally cleaved by three virus-encoded proteases into 10 functional proteins. Several of these potyviral proteins, including nuclear inclusion protein b (NIb), are multifunctional. Here, using the classic GFP silencing in Nicotiana benthamiana gfp-transgenic plants model, we show that NIb, in addition to its canonical role as the viral RNA-dependent RNA polymerase (RdRP), functions as a suppressor of RNA silencing. Mutational analyses revealed a previously unreported NIb nuclear localization signal (NLS) consisting of a triple-lysine motif, and NIb suppression of RNA silencing activity was lost when this novel NLSs were mutated, suggesting that nuclear localization is required for NIb suppression of RNA silencing activity. Analysis of sequenced GFP siRNAs revealed three prominent siRNA hotspots at ≈nt 175, ≈320–330, and 560–700 nt. These data showed that there were differences in the positional distribution of the siRNAs between samples expressing NIb and those expressing NIbDel3x2, the NIb null mutant that does not suppress RNA silencing. However, there was no increase in the transcript‑wide siRNA burden between the two treatments. Furthermore, NIb was found to interact with four key RNA silencing pathway proteins—AGO4, HSP70, HSP90, and SGS3. Except for HSP90, each of these proteins showed degradation products that were absent in NIb mutants that did not suppress RNA silence. These findings support a role for NIb in countering host defense during virus infection.

Abstract:

This study aimed to analyze the effect of reduced water potential on the imbibition curve and triphasic pattern of seeds in several Solanaceae species. The experiment was conducted at the Seed Physiology and Health Laboratory and the Seed Biology and Biophysics Laboratory, Department of Agronomy and Horticulture, Faculty of Agriculture, Bogor Agricultural University, from April to September 2025. The study used seeds from three Solanaceae crops—chili (Capsicum annuum L., varieties Simpatik and Sempurna), tomato (Solanum lycopersicum L., varieties Niki and Rempai), and eggplant (Solanum melongena L., varieties Tangguh and Provita). The seeds were subjected to various levels of osmotic stress using polyethylene glycol (PEG 6000) to simulate water potentials of 0.00, –0.30, –1.90, and –4.10 MPa. Lower water potential in the growing medium reduced the seed’s ability to absorb the water. The triphasic pattern consistently appeared only in chili seeds, whereas in tomatoes and eggplants, it varied across varieties and water potential conditions. The lower water potential made the later the phase I ended, and the longer the phase II lasted. These findings confirm that the standard imbibition pattern cannot be generalized to all seeds, and therefore, the imbibition response is specific to seed type, variety, and germination environment.

Abstract: Background: Benign prostatic hyperplasia (BPH) is a significant health issue among ageing men, with ongoing research focused on elucidating its underlying mechanisms and improving experimental models. Testosterone Propionate (TP) is the first line of choice for the induction of BPH in experimental rodent models. However, TP's controlled status as a Schedule III drug in the United States and a Class C drug in the UK presents challenges in obtaining TP for experimental use, giving preference to the sulpiride model since it is easily obtained as an alternative for the induction and study of BPH. Method: A comprehensive literature search was conducted across multiple electronic databases, including PubMed/MEDLINE, Embase, and Web of Science. The primary PubMed search strategy included combinations of Medical Subject Headings (MeSH) and free-text terms: (“Benign prostatic hyperplasia induction” OR ‘’ and rodent models’’) AND (“Testosterone Propionate model” ) AND (“sulpiride model”). Studies were included if they induced BPH (using testosterone or sulpiride models). Titles and abstracts were screened for relevance; eligible articles underwent full-text review, with data extracted thematically. No formal risk-of-bias scoring was used due to the narrative approach; instead, studies were appraised by design, rigor, plausibility, and evidence. This study reviewed published and publicly available data, so no ethical approval was required. Results: Although both TP and sulpiride induce BPH via various mechanisms, this review provides a comparative analysis of these two commonly utilised models for studying BPH. In the TP approach, castrated rodents receive daily subcutaneous injections for 4 weeks, resulting in dihydrotestosterone (DHT)-mediated epithelial hyperplasia predominantly affecting the ventral prostate lobes. Conversely, the sulpiride model is non-invasive, employs intact animals treated with sulpiride, and induces hyperprolactinemia-mediated BPH via interactions with androgen and oestrogen receptor pathways that stimulate prostatic stromal and epithelial proliferation, particularly in the lateral and dorsal lobes, representing an alternative method. We also highlight the strengths and limitations of TP and sulpiride in replicating clinical symptoms and examine the toxicological effects of sulpiride on the kidney, testis, liver, and brain. Conclusions: we recommend the sulpiride model for the induction and studying of BPH, as it is readily accessible and closely mimics the pathogenesis of BPH in humans, unlike the TP model, which requires castration.

Abstract: Stroke has been a topic of extensive research due to its debilitating consequences and high mortality. New findings offer a deeper understanding of specific factors that affect post-stroke recovery and identify therapies that may facilitate this process. One such factor was microglia, neuronal immune cells that are highly reactive to cytokines in the neuroenvironment and can, in turn, affect the inflammatory cascades that originate after stroke, making them ideal candidates for immunomodulation in the brain. Many FDA-approved immunotherapies have been found to target distinct inflammatory signaling molecules and responders, including IL-6 inhibitors, IL-13 inhibitors, IL-12/IL-23 inhibitors, B-cell modulators, Type I interferon inhibitors, CAR T-cell therapy, Calcineurin inhibitors, Complement inhibitors, and JAK-STAT pathway inhibitors. The FDA-approved immunotherapies discussed in this review demonstrate potential in modulating the immune response after stroke by targeting key inflammatory pathways involved in secondary brain injury. Future research should focus on defining optimal therapeutic windows, identifying suitable patient populations, determining the most appropriate timing of therapy, and targeting specific immune mechanisms to balance the attenuation of harmful inflammation with the preservation of reparative processes.