Methotrexate is a widely utilized chemotherapeutic agent known to induce neurotoxic effects, thereby constraining its therapeutic potential across various malignancies. While Moringa leaf extract has demonstrated significant antioxidants and anti-inflammatory properties, its role in mitigating Methotrexate-induced neurotoxicity remains inadequately explored. This study seeks to elucidate the protective effects of Moringa leaf extract on Methotrexate-mediated damage within the dentate gyrus of the hippocampus. Male rats were administered Moringa leaf extract at 300 mg/kg body weight via oral gavage bi-weekly over four weeks. Concurrently, select groups received intraperitoneal injections of 0.5 mg/kg Methotrexate twice weekly for the study. The administration of Methotrexate elicited oxidative stress, as evidenced by elevated levels of malondialdehyde and diminished activity of superoxide dismutase. Histopathological assessments revealed that Methotrexate treatment induced significant alterations in the dentate gyrus, characterized by an inflammatory response marked by the upregulation of Toll-like receptor 4. Activation of the Toll-like receptor 4 signalling pathway consequently led to an increased expression of the Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3-inflammasome and enhanced caspase-1 activation. Importantly, co-administration of Moringa leaf extract with Methotrexate substantially reduced both inflammatory and oxidative stress markers while restoring the dentate gyrus's structural integrity. Moringa leaf extract demonstrates potent antioxidant and anti-inflammatory properties that effectively counteract Methotrexate-induced neurotoxicity by modulating the brain's TLR4/NLRP3/caspase-1 signalling axis.

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Rabies is still a serious public health problem globally, especially where there is high dog-to-human contact and low vaccination coverage. In this paper, a fractional-order mathematical model is developed to explain the transmission dynamics of rabies in dogs and humans. The model is established by adopting the Caputo-Fabrizio fractional-order derivative (CFFROD), which suits the memory effects and non-locality properties of disease progression. The model has compartments for susceptible, exposed, infected, and recovered members of both species, as well as the viral load in the environment. Existence and uniqueness of solutions are proven via fixed-point theory to ensure mathematical consistency of the model. Numerical computations via the Adams-Bashforth method are performed to analyse the dynamics of the system for a range of fractional orders. Numerical computations provide evidence that fractional-order dynamics have a considerable impact on disease progression, ensuring the significance of memory in infectious disease modelling. Based on verified experimental data, a comparison between the fractional-order and classical models is presented. The results show that the fractional model provides greater insight into transmission and control timing patterns and best fits real-world data. This study supports the use of fractional modelling in the well-informed creation of successful rabies prevention initiatives and improved comprehension of disease dynamics.

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Infertility remains a significant global health concern, with endometrial receptivity recognized as a critical factor influencing successful implantation. Granulocyte‑Colony Stimulating Factor (G‑CSF), a hematopoietic cytokine, has recently emerged as a potential therapeutic agent for enhancing endometrial function and modulating immune responses during assisted reproductive procedures. This study aims to investigate the effect of intrauterine infusion versus subcutaneous injection of G‑CSF on immunological and angiogenic markers related to endometrial receptivity in infertile women undergoing intrauterine insemination (IUI). A total of 75 infertile females were enlisted in this prospective interventional comparative trial and were equally divided into three groups: the intrauterine infusion group, the subcutaneous injection group, and the control group (no G‑CSF administration). Baseline demographic and hormonal characteristics, as well as ultrasound and immunological parameters, were recorded before and after G‑CSF administration. Statistical analysis showed no significant differences in demographic and baseline clinical, hormonal, and biochemical characteristics across the groups. Post‑intervention, both G‑CSF groups demonstrated significant improvements in endometrial vascularity indices (pulsatility index, resistance index, and V1/V2 ratio) compared to the control group, despite the endometrial thickness not differing significantly. Serum levels of TNF‑α significantly decreased, while VEGF levels increased significantly post‑G‑CSF in all groups; IL‑10 levels increased but reached significance only in the subcutaneous and control groups. These outcomes indicate that G‑CSF may enhance endometrial receptivity via improved vascular and immunological parameters, although the effect remains inconclusive and requires further validation.

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In cancer treatments, the efficacy of Chimeric Antigen Receptor T (CAR-T) cell therapy is affected in heterogeneous tumors due to ambiguous tumor boundaries, morphological variability, and similarity between tumor and non-tumor tissues in medical imaging. Accurate tumor localization and classification are crucial for optimizing CAR-T targeting and therapeutic success. Traditional segmentation networks struggle with intensity similarity, shape variability, and contextual complexity in heterogeneous tumors. Further, robust classification of tumor regions using limited medical data remains a key challenge. We propose a dual-component Computational Perception Architecture composed of a novel segmentation-classification framework. The segmentation backbone is a U-Net enhanced with a Visual Perception Module (VPM) for ROI-level feature refinement. Multi-Head Self-Dilated Attention (MHSDA) in the encoder to capture multi-scale dependencies. ResNet50 with Dense Attention Modules in skip connections for improved feature continuity. Group Receptive Large Kernel (GRLK) Blocks for diverse receptive field decoding. The classification network utilizes edge-perception, morphological, and positional images, and segmentation maps. Deep ensemble learning for decision robustness and transfer learning to boost generalization on breast cancer labeled datasets. The proposed method is tested on the publicly available PBC and CAR-T datasets from Kaggle. The research model achieved a Dice Score of 0.901, an IoU of 0.856, a Precision of 0.882, a Classification Accuracy of 93.7%, and an F1-Score of 0.915. These outcomes show the superior capacity for precision tumor detection and classification, thus offering a potent computational aid in enhancing the targeting precision of CAR-T therapies.

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The Tumor Microenvironment (TME) resists conventional treatments by sending out signals that weaken the immune system. Tumor cells vary significantly, and treatments can lead to resistance. This paper focuses on constructing an effective module for reprogramming the tumor ecosystem using Computational Intelligence-Guided Nanoplatforms. It hypothesizes that computationally optimized fuzzy deep learning, integrated with nanoplatform-mediated drug delivery, can dynamically reprogram tumor-infiltrating T-cells to overcome immunosuppression in the TME, thereby enhancing cytotoxicity and therapeutic response. A novel nanotechnology-integrated deep fuzzy learning framework—Seagull Optimized Sugeno Fuzzy Deep Learning (SgOSF-DL)—is proposed to reprogram T-cell behavior in real-time. Multi-omic data from tumor-infiltrating T-cells are encoded and analyzed using fuzzy logic to determine their immune state (suppressed, exhausted, or active), guided by key biomarkers such as Granzyme B and PD-1. The optimized model governs the release of IL-21 and checkpoint inhibitors via nanoplatforms composed of PLGA, gold nanoshells, and iron oxide particles. Fuzzy rules are formulated using optimized parameters to evaluate the TME. Simulation results confirm that the proposed SgOSF-DL model accurately distinguishes between cancer and healthy cells. It alters cancer behavior by reducing tumor burden, lowering PD-1, and boosting Granzyme B expression. The model achieves 96.5% accuracy in classifying T-cell states, reduces tumor count by 69.2%, and decreases PD-1 expression by 61% for active immune function. It also offers faster therapeutic classification (0.017 seconds) with an activation consistency of 92.8%. Fuzzy logic enables transparent decision-making, aiding clinicians in understanding the treatment rationale.

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The deep integration of AI and immunotherapy is reshaping the paradigm of cancer diagnosis and treatment. From biomarker discovery to personalised treatment, from adverse reaction warnings to empowering grassroots communities, despite bottlenecks such as data silos, algorithm transparency, and ethical controversies, the technical potential of AI has already begun to emerge. This paper examines the evolution of global AI medical device policies and product release trends over the past decade, identifying the issues and challenges posed by the current regulatory landscape, including: first, the structural imbalance between the regulatory system and the rate of technological innovation; second, the double-standardisation dilemma between risk classification and clinical validation; and third, the ethical paradox of data governance and algorithmic transparency. The challenges faced include: first, Technology Fusion: AI at the Crossroads with Synthetic Biology and Nanotechnology. Second, Algorithm Transparency and Ethical Paradox. Third, In-Depth Application of Regulatory Technology. Fourth, Collaborative Innovation in Industrial Ecology. Based on this, this paper provides systematic recommendations for addressing the regulation of AI medical devices: first, Building a Dynamic Adaptive Technology Supervision System. Second, Perfecting the Full Life Cycle Clinical Evidence Chain. Third, Create an Open and Collaborative Industrial Innovation Ecosystem. Fourth, Deepen International Regulatory Coordination and Cooperation. Recommendations for the regulation of AI medical devices in the field of immunotherapy: First, Multi-Modality Imaging and Treatment Integrated Platform. Second, Intelligent Empowerment of Primary Care. Third, Global Collaboration and Data Sharing.

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One of the key links of the immune system, which plays a crucial role in maintaining homeostasis and lung function, is T-regulatory cells (Treg). Their suppressive effect on the immune system predetermines the potential of various modulating effects, taking into account the pathogenetic features of the pathology, which underlie innovative methods of therapy, including in pulmonology. However, awareness of them remains insufficient and, in some cases, contradictory, which requires appropriate consideration and analysis, which became the purpose of this work. An analysis of 69 literary sources selected from different databases of biomedical scientific information was carried out. The analysis showed that targeted methods for the treatment of inflammation and tumors are developed based on the generally accepted paradigm about Treg and are aimed at their modulation. In inflammation, activation of Treg, exerting a suppressive effect on T-effector cells, reduces it. In tumors, their depletion, promoting the expression of T-effector cells, including antitumor cells, slows their growth. This is achieved by various direct or indirect methods of influence. Along with this, some researchers suggest using a depleting effect on Tregs in inflammation, and similarly, in both tumor and inflammatory processes, which contradicts the generally accepted paradigm regarding Tregs. Thus, a modulating effect on Tregs can have a therapeutic effect on both inflammation and tumors, with a differentiated consideration of the mechanisms of their development. Methods of treating inflammation that contradict the generally accepted paradigm regarding Tregs remain unsupported by a sufficient evidence base and are untenable.

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The lack of awareness among the general medical audience about the central link in the lung immune system―T-regulatory cells (Treg) and the existing contradictions on this issue necessitate consideration and analysis, which is the purpose of this work. An analysis of 63 full-text literary sources, selected from the primary information databases, was conducted. An assessment of Treg in maintaining immune status is provided, indicating that they play a central role in balancing proinflammatory and anti-inflammatory cytokines, thereby maintaining the body's homeostasis. Their primary function is reflected in the generally accepted paradigm underlying the diagnosis and treatment of immune system disorders, which consists of an immunosuppressive effect with complex, ambivalent manifestations. This effect limits inflammatory reactions, especially hyperergic ones, but simultaneously contributes to the suppression of the antitumor immune response and stimulation of carcinogenesis processes. A decrease in Tregs is associated with opposite effects that depend on the nature of the relationship between the tumor and inflammation, and requires immunoprecise therapeutic effects. By influencing Tregs, it is possible to target and effectively modulate the processes of inflammation and carcinogenesis in the lungs. The depletion of the T-regulatory cell population is directly proportional to antitumor activity and inflammation intensity, and inversely proportional to tumor progression and inflammation regression. The opinion of some researchers that depletion of Treg cells reduces inflammation is unfounded and contradicts the generally accepted paradigm.

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Millions of people worldwide suffer from diabetes, and many develop chronic wounds like diabetic foot ulcers that struggle to heal. Traditional wound dressings often fall short. They cannot effectively control infections or create the ideal conditions for healing. This is where gelatin-based biofilms come in. Made from collagen, gelatin is naturally compatible with the human body and can be tailored to meet the specific needs of diabetic wounds. This overview explores how gelatin-based biofilms are revolutionising wound care. Recent advances in gelatin-based biomaterials demonstrate significant promise for improving wound healing outcomes. Studies show these materials achieve 50–100% wound closure within 12–18 days, with gelatin-QAS/PCL/bioglass nanofibers and GelMA/graphene oxide composites showing remarkably rapid healing. The materials exhibit strong antibacterial properties against common pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA)and E. coli, while maintaining excellent cell viability above 80%. Mechanical testing reveals favourable properties, including compressive strength of up to 412 kPa and porous structures that are ideal for tissue regeneration. Key findings include enhanced granulation tissue formation (reaching a thickness of 1.6 mm), reduced wound areas (remaining at just 4.9% after treatment), and promotion of neurovascular regeneration. The evidence suggests gelatin-based biomaterials are ready for more extensive clinical validation, with future research needed to optimise degradation rates and transition these promising results into clinical practice. They are paving the way for real-world solutions that could transform the lives of people with diabetes. By combining nature’s building blocks with cutting-edge science, these advanced dressings offer hope for faster, safer, and more effective wound healing.

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Hyperthyroidism is a medical condition characterized by the excessive production and release of thyroid hormones by the thyroid gland. It has diverse etiologies, clinical manifestations, and treatment options. Among the contributing factors to the development of thyroid disease are cytokines, which influence both the immune system and thyroid follicular cells. Notably, cytokines such as IL-17 and IL-33 play critical roles in autoimmune thyroid diseases by promoting inflammation and modulating immune responses. This study aimed to evaluate the serum levels of IL-17 and IL-33 in Iraqi individuals diagnosed with hyperthyroidism. A total of  60 hyperthyroid patients (21 males and 39 females, aged 17–40 years) and 30 healthy controls (8 males and 22 females) were enrolled. Blood samples were collected, and serum levels of IL-17 and IL-33 were measured using standard ELISA techniques. The results demonstrated a statistically significant increase in IL-17 concentrations in patients with hyperthyroidism (39.480 ± 9.665 ng/L) compared to controls (25.695 ± 4.448 ng/L) (p ≤ 0.01). Similarly, IL-33 levels were significantly elevated in the patient group (1247.745 ± 966.963 ng/L) compared to the control group (32.788 ± 47.741 ng/L) (p ≤ 0.01). These findings suggest a potential role for IL-17 and IL-33 in the immunopathogenesis of hyperthyroidism, highlighting their value as possible biomarkers for disease progression.

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Cigarette smoke (CS) contains a complex combination of thousands of different chemicals that increase oxidative stress. Inhaling CS causes an inflammatory response, which leads to several diseases linked to tobacco. Ashitaba has various derivatives that serve as intermediates in the biosynthesis of one type of bioactive flavonoid antioxidant, which is thought to neutralize oxidative stress events. Ashitaba has also been shown to inhibit platelet aggregation, exhibit vasorelaxant effects, and suppress the differentiation of preadipocytes. Safety studies indicate that administering ashitaba chalcone orally to male Wistar rats for 28 days showed no signs of toxicity. Similarly, gavage administration of ashitaba extract in male ICR mice demonstrated safe absorption and metabolism of 4-hydroxyderricin and xanthoangelol without adverse effects. Additionally, a related compound, xanthohumol, a prenylated chalcone found in hops, was given to female BALB/c mice at approximately 1000 mg/kg daily for three weeks without toxic effects. This study proves that Ashitaba contains antioxidants that can help prevent oxidative stress and inflammation induced by CS. Flavonoids isolated from ashitaba were found to have a flavonoid content of 38.115 ± 0.124 ppm, which was then implemented in in-vivo studies The ability of these antioxidants to decrease the level of pro-inflammatory cytokines in rat blood serum and lung tissue after exposure to CS was investigated. In this study, we isolated flavonoids from ashitaba and obtained a flavonoid, then implemented it for in vivo studies, and the ability of antioxidants in Angelica keiskei to prevent inflammatory events was proved.

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Despite great progress in understanding the mechanism of action of influenza and SARS-CoV-2 viruses, there is currently no effective prevention and treatment for the complications of influenza and COVID-19. The Transmembrane Protease Serine S1 subtype 2 (TMPRSS2) and NOD-like receptor protein 3 inflammasome (NLRP3-I) are the main targets for the prevention and treatment of COVID-19 and influenza. The TMPRSS2 is responsible for the penetration of the SARS-CoV-2 and influenza viruses into the cell, while the hyperactivation of the NLRP3 inflammasome can lead to a cytokine storm, multiorgan failure, and death. The correct strategy for preventing illness from COVID-19 and influenza is to block the TMPRSS2 preemptively. Preventing the cytokine storm in COVID-19 and influenza is only effective when inhibiting NLRP3-I. Long-term prophylaxis with the TMPRSS2 inhibitor bromhexine hydrochloride (BRH) proves sufficient to prevent SARS-CoV-2 and influenza infection largely. Treatment with high doses of colchicine, which is able to inhibit the NLRP3-I, leads to inhibition of the cytokine storm (CS) and significantly decreases mortality. Combined application of BRH and colchicine is a very effective, safe, and inexpensive method against the spread and complications of COVID-19 and influenza.

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The SARS-2 virus, responsible for the COVID-19 epidemic in early 2020, persists in posing a hazard to public health through the emergence of new mutations and surges in prevalence across several nations. Immunosuppressive medications treat both short-term and long-term inflammatory illnesses. The classification of these medications into various types is based on their action mechanisms. It is important to review the most recent data on the effectiveness and side effects of administering these drugs to patients because of the risk of severe inflammatory repercussions in COVID-19 patients, including acute respiratory failure and cytokine storm. This article presents accurate data on the advantages and disadvantages of using immunosuppressive medications in COVID-19 patients, while also providing a concise overview of the various types of these medications. Taken together, anti-inflammatory drugs and immune response inhibitors seem to be associated with better outcomes, such as shorter hospital stays and less need for mechanical ventilation, faster recovery from acute symptoms, and lower mortality rates, especially in the critically ill. However, one must consider the possibility of increasing treatment duration and vulnerability to fungal and bacterial infections. To minimize the negative effects of these medications, it is important to carefully balance their dosage and administration timing. Overall, the utilization of immunosuppressive medications, whether administered recently during illness or consistently for non-COVID-19 reasons, appears to have a beneficial impact on managing inflammation, expediting recovery, and decreasing mortality. However, it is crucial to exercise caution and avoid prescribing these drugs without proper consideration.

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The diverse community of microorganisms residing in the human digestive tract, known as the intestinal microbiome, plays a crucial role in the development and progression of various liver diseases. Disruptions in the gut-liver axis have been associated with various liver conditions, including non-alcoholic fatty liver disease, alcoholic liver disease, viral hepatitis, cirrhosis of liver, and hepatocellular carcinoma. Intestinal dysbiosis can worsen liver disease by promoting systemic inflammation, influencing immune responses, and altering metabolic pathways. This review explores the intricate connection between gut microbiome and liver diseases, highlighting fecal microbiome transplantation as a potential therapeutic approach. Considering search through databases using keywords including “liver disease” AND “microbiome” we found 62 clinical trials out of total 3,303 articles on microbiome changes to find promising treatment of liver disease. Totally 55 articles were assessed, of which most of the studies were about using probiotics, the diet and exercise, and finally FMT. NAFLD was the most predominant liver disease targeted for intervention and treatment. Most of studies (47/55: 85.45%) reported targeting microbiome as an effective and promising treatment. Probiotics and prebiotics also show promise in mitigating liver dysfunction by modulating gut microbiome and influencing adipokines, key regulators in metabolic and inflammatory processes. Despite advancements, significant gaps persist, particularly regarding FMT applications in chronic viral hepatitis and HCC. Further clinical trials are essential to optimize gut microbiome-targeted therapies for liver disease management. This review emphasizes the need for a multidisciplinary approach to bridge the gap between microbial science and therapeutic innovations in hepatology.

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Research indicates that immunization is the most efficacious approach for stopping the transmission of COVID-19. This study aims to offer immunization recommendations for patients with autoimmune/autoinflammatory rheumatological disorders, immunodeficiencies, cancer, diabetes, chronic respiratory, and cardiovascular diseases. The intended audience includes doctors, medical personnel, and patients. This review study involved conducting a search in scholarly electronic databases, including ISI, Google Scholar, Scopus, and PubMed. The issue of COVID-19 vaccinations and the vaccination of patients with certain disorders was informed by the latest and pertinent authoritative publications published between 1980 and 2024. When autoimmune illness patients effectively manage their disease activity and there is no concurrent infection, they should receive the COVID-19 vaccination. Low-intensity immunosuppression does not reduce the antibody response to vaccinations. Immunization using all forms of vaccination, excluding live attenuated vaccines, is efficacious for all individuals with cancer, except for those undergoing anti-B cell therapy. Additionally, it is recommended to administer vaccinations to individuals who have underlying conditions such as obesity, cardiovascular diseases, respiratory diseases, and diabetes, as these conditions heighten the chance of developing severe cases of COVID-19. To combat the COVID-19 virus, the most effective approach is to increase vaccination coverage in order to stimulate immune responses. This paper provides a thorough examination of the latest developments and existing challenges in the area of COVID-19 vaccines against cancer. Additionally, it explores the prospective future uses of vaccines in cancer immunotherapies.

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The microbiota plays an essential role in the regulation of the natural immune system, influencing both innate and adaptive immunological responses. This review extracted information from available observational studies that explore the intricate cooperation between gut microbiota and immune system regulation across various health conditions, including Crohn’s disease, respiratory infections, autoimmune diseases, cancer, metabolic disorders, and infectious diseases. Key findings highlight how dysbiosis, a rotation in the microbiome composition or microbial imbalance, contributes to disease pathogenesis and immune dysregulation, while specific microbial taxa and their metabolites can serve as potential biomarkers and therapeutic targets. By analyzing these studies, the paper aims to provide a comprehensive understanding of the gut microbiota’s impact on immune function and its potential implications for disease prevention and management. In conclusion, this review comprehensively elucidates the complex relationship between gut flora and immune system regulation across various health conditions. The synthesized findings underscore the profound impact of microbiota composition on immune responses, from influencing disease susceptibility and severity to potential therapeutic interventions. Key insights include the identification of microbiota-based biomarkers for predicting treatment outcomes and disease risks, highlighting the potential for personalized medicine approaches. However, the few available observational studies, such as study design variability and the complex nature of microbiota dynamics, necessitate further mechanistic research to validate causal relationships and optimize clinical applications. Moving forward, integrating microbiota-targeted therapies and dietary interventions tailored to individual microbial profiles holds promise for mitigating immune dysregulation and improving overall health outcomes.

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Autoimmune disorders comprise a broad category of illnesses marked by abnormal immune reactions against self‑antigens, resulting in persistent inflammation and tissue damage. This comprehensive review examines the complex mechanisms underlying the development of autoimmune disease, focusing on immunopathogenesis. We discuss the interplay between genetic predispositions, environmental triggers, and pathogens in the initiation and perpetuation of autoimmunity. Key cytokines and inflammatory pathways are highlighted to illustrate their roles in disease progression. We then explore the distinct pathogenic mechanisms of organ‑speciϐic autoimmune disorders, including autoimmune thyroid diseases, autoimmune hemolytic anemia, neuromyelitis optica, idiopathic inflammatory myopathies, and inflammatory bowel disease, while also reviewing the influence of gut microbiome dysbiosis on immune function. Lastly, we address biomarker identiϐication for early detection, current therapeutic strategies, and emerging treatments that target novel pathways. By integrating ϐindings from diverse studies, this review provides a holistic understanding of the immunological landscape of autoimmune disorders, paving the way for improved diagnostic and therapeutic options

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