Zingiber officinale Roscoe (ginger) is traditionally used as a culinary spice worldwide. In folklore medicine, raw and fresh ginger has been used for treating nausea and vomiting, to improve liver function and digestion, antidiarrheal, to treat menstrual cramps, and as an aphrodisiac. Zingerone [4-(4-hydroxy-3-methoxyphenyl)-2-butanone] is the major bioactive ingredient present in ginger. Zingerone has shown a wide-range of pharmacological activities in vitro and in vivo studies. While zingerone is present in small amount in fresh ginger, but its level is increased during drying or heating during cooking. The amount of zingerone increases significantly due to the conversion of gingerol into zingerone through retro-aldol reaction. Owing to its strong antioxidant and anti-inflammatory properties, zingerone has the ability to scavenge reactive oxygen species and to assist in curing a wide array of non-communicable diseases associated with oxidative stress such as diabetes mellitus, obesity, cardiometabolic and cardiovascular disorders, neurological abnormalities, osteoarthritic, and certain cancer types. For this review, extensive literature searches were performed using PubMed, Google Scholar, Science Direct, and other search engines. The major aims of our review are to describe the chemical characteristics of zingerone as well as the various in vitro and in vivo studies reported regarding the pharmacological effects of zingerone and the mechanism of action observed at the cellular and molecular levels. The results of published preclinical and few clinical studies suggest that zingerone has several promising therapeutic applications due to its strong antioxidant, anti-inflammatory and anti-proliferative activities without any serious side effects. However, well-designed, randomized, placebo-controlled, and multi-center clinical studies are needed to determine the optimal therapeutic doses, and long-term safety of zingerone.
The human immune system functions across a vast spectrum of biological scales, from nanometer-sized signaling molecules to meter-long organ systems. This scale diversity underpins the ability to maintain homeostasis while confronting pathogens of markedly different sizes. To explore how the size of pathogens and host defense mechanisms shape infection susceptibility, immune strategies, and evolutionary host-microbe dynamics, this narrative review synthesizes evidence from immunology, microbiology, and evolutionary biology to examine the influence of size at molecular, cellular, and anatomical levels. Key themes include pathogen niche specialization, structural and immune barriers, size mismatches leading to invasion, and evolutionary implications for infection control. Pathogen size dictates strategies of entry, persistence, and immune evasion - from the nanometric replication of viruses to the chronic modulation of immunity by helminths. Host defenses, including molecular mediators, phagocytes, and large-scale anatomical barriers, are scaled to counter these challenges. Disruptions in this hierarchy, such as barrier breaches or immunodeficiencies, predispose to characteristic infections. Moreover, evolutionary pressures linked to size drive microbial adaptation, including antimicrobial resistance, while shaping host tolerance and immunity. Recognizing the role of size as a determinant in host-pathogen interactions reframes infection as a scale-dependent dialogue. Integrating this perspective may inform precision medicine, microbiome engineering, and strategies to mitigate emerging threats such as antimicrobial resistance.
BACKGROUND IgE plays a critical role in allergic inflammation and asthma pathogenesis. This study investigates the involvement of IgE cells in asthma exacerbation and evaluates the effectiveness of targeted interventions. AIM To evaluate the role of IgE in the exacerbation of allergic asthma and to determine the clinical efficacy of anti-IgE therapy in improving disease outcomes. Specifically, the study investigates changes in serum IgE levels, lung function, asthma control scores, and the frequency of acute exacerbations among patients receiving standard therapy with or without anti-IgE intervention. METHODS A total of 200 patients diagnosed with moderate to severe asthma were enrolled in this experimental study conducted from April 2024 to April 2025. Participants were randomized to receive either standard asthma therapy or therapy combined with anti-IgE agents. IgE levels and asthma control parameters were monitored. RESULTS Participants receiving anti-IgE treatment demonstrated a significant reduction in serum IgE levels (P < 0.001), improved Forced expiratory volume in one second scores, and fewer exacerbation episodes compared to the control group. CONCLUSION IgE cells significantly contribute to asthma severity, and targeted therapy against IgE can improve disease outcomes. These findings underscore the importance of immunomodulatory strategies in asthma management.
The immune system, host brain development, and general metabolism are all influenced by the gut bacteria. Bacteria make up the majority of the gut microbiota in mammals. The mouse has been the most often used animal model in preclinical biological research. In mice, Firmicutes and Clostridiales are prominent. On the other hand, Bacteroidaceae , Prevotellaceae , and Firmicutes are commonly found in humans. In this review, we performed a detailed study by focusing on a comparison between human and murine gut microbiomes, role of the microbiome and their secreted metabolites in regulating gut immunity to maintain homeostasis, and changes in the microbial composition in the dysbiotic state.
Stem cell-like memory T (TSCM) cells possess stem cell properties including multipotency and self-renewal and are being recognized as emerging players in various human diseases. Advanced technologies such as multiparametric flowcytometry and single cell sequencing have enabled their identification and molecular characterization. In case of chronic viral diseases such as human immunodeficiency virus-1, CD4+ TSCM cells, serve as major reservoirs of the latent virus. However, during immune activation and functional exhaustion of effector T cells, these cells also possess the potential to replenish the pool of functional effector cells to curtail the infection. More recently, these cells are speculated to play important role in protective immunity following acute viral infections such as coronavirus disease 2019 and might be amenable for therapeutics by ex vivo expansion. Similarly, studies are also investigating their pathological role in driving autoimmune responses. However, there are several gaps in the understanding of the role of TSCM cells in viral and autoimmune diseases to make them potential therapeutic targets. In this minireview, we have attempted an updated compilation of the dyadic role of these complex TSCM cells during such human diseases along with their biology and transcriptional programs.
To control the pandemic, efficient vaccines must be applied to the population,including patients with autoimmune diseases. Therefore, one can expect that coronavirus disease 2019（COVID-19） vaccines may influence the underlying autoimmune processes in these patients. Additionally, it is essential to understand whether COVID-19 vaccines would be effective, safe, and provide long-lasting immunological protection and memory. However, the currently available and approved COVID-19 vaccines turned out to be safe, effective, and reliable in patients with autoimmune inflammatory and rheumatic diseases. Furthermore,most patients said they felt safer after getting vaccinations for COVID-19 and reported enhanced overall quality of life and psychological wellbeing. In general,the COVID-19 vaccines have been highly tolerated by autoimmune patients. Such findings might comfort patients who are reluctant to use COVID-19 vaccines and assist doctors in guiding their patients into receiving vaccinations more easily and quickly.
Co-stimulatory molecules are key mediators in the regulation of immune responses and knowledge of its different families, structure, and functions has improved in recent decades. Understanding the role of co-stimulatory molecules in pathological processes has allowed the development of strategies to modulate cellular functions. Currently, modulation of co-stimulatory and co-inhibitory molecules has been applied in clinical applications as therapeutic targets in diseases and promising results have been achieved.
Free radicals（reactive oxygen species, superoxides and hydroxyl radicals） lead to the development of oxidative stress because of imbalance in the amount of antioxidants. Continued development of oxidative stress leads to chronic diseases in humans. The instability in the antioxidant activities and accumulation of oxidative stress due to free radicals may occur in diseases like inflammatory bowel disease（IBD）. Antioxidants are substances that inhibit or delay the mechanism of oxidation of molecules mediated by free radicals and also transform into lesseractive derivatives. Probiotics are defined as live microorganisms that show beneficial effects on inflamed intestine and balance the inflammatory immune responses in the gut. Probiotic strains have been reported to scavenge hydroxyl radicals and superoxide anions that are abundantly produced during oxidative stress. The most widely studied probiotic strains are Streptococcus, Bifidobacterium and Lactobacillus. Probiotics cultured in broth have shown some amount of antioxidant activities. Fermented milk and soy milk, which possess starter microorganisms（probiotics）, tends to increase the antioxidant activities manyfold. This review aims to discuss the in vivo and in vitro antioxidant activities of specific probiotics with various assays with respect to IBD.
Advanced therapy medicinal products are human medical therapies based on genes, cells, or tissues, and due to their characteristics, they offer new innovative opportunities for the treatment of diseases and injuries, especially for diseases beyond the reach of traditional approaches. These therapies are at the forefront of innovation and have historically been very controversial, although in the last decade they have gained prominence while the number of new advanced therapies has increased every year. In this regard, despite the controversy they may generate, they are expected to dominate the market in the coming decades. Technologies based on advanced therapies are the present and future of medicine and bring us closer to the long-awaited precision medicine. Here we review the field as it stands today, with a focus on the molecular mechanisms that guided the different advanced therapies approved by the European Medicines Agency, their current status, and their legal approval.
In liver transplant patients, solid tumors and post-transplant lymphoproliferative disorders have emerged as significant long-term mortality causes. In addition, it is assumed that de novo malignancy after liver transplantation（LT） is the secondleading cause of death after cardiovascular complications. Well-established risk factors for post-transplant lymphoproliferative disorders and solid tumors are calcineurin inhibitors, tacrolimus, and cyclosporine, the cornerstones of all immunosuppressive therapies used after LT. The loss of immunocompetence facilitated by the host immune system due to prolonged immunosuppressive therapy leads to cancer development, including LT patients. Furthermore, various mechanisms such as bacterial dysbiosis, activation through microbe-associated molecular patterns, leaky gut, and bacterial metabolites can drive cancerpromoting liver inflammation, fibrosis, and genotoxicity. Therefore, changes in human microbiota composition may contribute further to de novo carcinogenesis associated with the severe immunosuppression after LT.
The mammalian protein kinase C-interacting cousin of thioredoxin （PICOT; also termed glutaredoxin 3） is a multi-domain monothiol glutaredoxin that is involved in a wide variety of signaling pathways and biological processes. PICOT is required for normal and transformed cell growth and is critical for embryonic development. Recent studies in T lymphocytes demonstrated that PICOT can translocate to the nucleus and interact with embryonic ectoderm development, a polycomb group protein and a core component of the polycomb repressive complex 2, which contributes to the maintenance of transcriptional repression and chromatin remodeling. Furthermore, PICOT was found to interact with chromatin-bound embryonic ectoderm development and alter the extent of histone 3 lysine 27 trimethylation at the promoter region of selected polycomb repressive complex 2 target genes. PICOT knockdown in Jurkat T cells led to increased histone 3 lysine 27 trimethylation at the promoter region of CCND2, a cell cycle-regulating gene which encodes the cyclin D2 protein. As a result, the expression levels of CCND2 mRNA and protein levels were reduced,concomitantly with inhibition of the cell growth rate. Analysis of multiple data sets from the Cancer Genome Atlas revealed that a high expression of PICOT correlated with a low expression of CCND2 in a large number of human cancers.In addition, this parameter correlated with poor patient survival, suggesting that the ratio between PICOT/CCND2 mRNA levels might serve as a predictor of patient survival in selected types of human cancer.
On the immunological limitations of hibernation and synthetic torpor as a supporting technique for astronauts’ radioprotection in deep space missions
The immune system plays a pivotal role in defending our body from invading pathogens and in surveillance against cancer. While most cells that acquire mutations are detected and destroyed by immunocytes, a small number of transformed cells succeed in evading immune destruction by inhibiting immune checkpoint regulatory pathways, leading to suppression of anti-cancer immune responses. Under normal conditions, immune checkpoint receptors maintain selftolerance, prevent immunopathology, and regulate overall immune homeostasis.However, their skewed activation by cancer cells may lead to the suppression of nascent anti-tumor immunity and the promotion of tumor growth. Discovering the role of immune checkpoints in cancer and understanding their mode of operation has led to the development of novel strategies for cancer immunotherapy, which are based on the intervention or blockade of immune checkpoint-regulated pathways. Clinical studies have demonstrated that immune checkpoint co-inhibitory receptor-blocking antibodies can revert tumor-induced immunosuppression and augment overall anti-tumor immunity. These antibodies induced durable clinical responses and unprecedented therapeutic benefits in multiple types of malignancies. Although immune checkpoint inhibitors have revolutionized cancer therapy, the clinical benefits of these drugs have been limited to subsets of cancer patients and treatments frequently associated with a unique spectrum of toxicities, termed immune-related adverse events. Future discoveries of novel immune checkpoint receptors, identification of new prognostic and predictive biomarkers, and improvement of combination therapies are likely to boost the success rate of cancer immunotherapy and increase the survival rates of patients with different types of cancers.
Drug induced lupus is an established and recognised entity,and penicillamine is one of the drugs that induce it.But the uncertainty remains:Could penicillamine trigger autoimmunity in a broad-spectrum or in a particular way?
The ability of CD4 T cells to differentiate into various effector or regulatory T cell subsets explains the successful adaptation of immune responses to different types of infectious pathogens. Immune responses in the context of cancer are also shaped by CD4 T cells, which can directly affect cancer prognosis in patients. While the proinflammatory mediator interleukin（IL）-1β was initially shown to enhance Th2 cell responses, recent findings support a predominant role of two other members of the IL-1 family, IL-18 and IL-33, on the production of Th1 and Th2-derived cytokines. In addition, IL-1β was found to profoundly affect the biology of two recently identified CD4 T cell subsets, Th17 and Th9 cells. IL-1β is critical for Th17 cell differentiation and it enhances the production of IL-9 and IL-21 by Th9 cells, thus increasing their anticancer properties. We will here review the mechanisms accounting for the ability of IL-1 cytokines to affect the differentiation of CD4 effector T cells with a focus on Th17 and Th9 cells. The physiopathological relevance of IL-1-driven effects on CD4 T cells will also be discussed.
Holistic paradigm in carcinogenesis: Genetics, epigenetics, immunity, inflammation and oral infections
Macrophages are key players in various immune responses. In addition to functions in innate immunity such as antigen phagocytosis and cytokine production, antigen presentation by macrophage represents a link between innate and acquired immunity. During inflammatory processes, na?ve monocytes differentiate into proinflammatory M1 and anti-inflammatory M2 macrophages. Resident monocytes/macrophages contribute to immune response that maintains tissue-specific homeostasis. In the target organs of autoimmune diseases, macrophages have dual functions in both the induction and suppression of autoimmune responses, which are mediated by production of various cytokines and chemokines, or by interaction with other immune cells. This review focuses on selected autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, and Sj?gren’s syndrome, to illustrate the key roles of macrophages in the cellular or molecular pathogenesis of autoimmunity. In addition, the contribution of macrophages to each autoimmune disease is compared.
Mammalian chitinases and the related chilectins（Chi Ls） belong to the GH18 family, which hydrolyse the glycosidic bond of chitin by a substrate-assisted mechanism. Chitin the fundamental component in the coating of numerous living species is the most abundant natural biopolymer. Mounting evidence suggest that the function of the majority of the mammalian chitinases is not exclusive to catalyze the hydrolysis of chitin producing pathogens, but include crucial role specific in the immunologic activities. The chitinases and chitinaselike proteins are expressed in response to different proinflammatory cues in various tissues by activated macrophages, neutrophils and in different monocytederived cell lines. The mechanism and molecular interaction of chitinases in relation to immune regulation embrace bacterial infection, inflammation, dismetabolic and degenerative disease. The aim of this review is to update the reader with regard to the role of chitinases proposed in the recent innate and adaptive immunity literature. The deep scrutiny of this family of enzymes could be a useful base for further studies addressed to the development of potential procedure directing these molecules as diagnostic and prognostic markers for numerous immune and inflammatory diseases.
The classical view of signaling between cells of immune system includes two major routes of intercellular communication:Through the release of extracellular molecules or a direct interaction between membrane bound receptor and its membrane bound ligand,which initiate a cascade of signaling in target cell.However,recent studies indicate that besides these canonical modes of signaling there are also noncanonical routs of intercellular communications through membrane stripping/membrane exchange/trogocytosis,extracellular traps,exosomes and ectososmes/microparticles.In this review we discuss what are the components of noncanonical pathways of signaling and what role they play in immune cells interactions.
