Bhaumik Patel

CD24 is an emerging innate immune checkpoint that regulates inflammatory and antiviral immune responses through interactions with Siglec family receptors. Although CD24 has been extensively studied in immune regulation and has recently gained attention as a therapeutic target in infectious and inflammatory diseases, its role in cancer remains incompletely understood. CD24 is overexpressed in multiple human malignancies, where accumulating evidence suggests that it promotes tumor progression and immune evasion through activation of diverse intracellular and extracellular signaling pathways. However, the importance of its subcellular localization and associated signaling remains poorly defined. Here, we investigated CD24 expression, localization, signaling associations, immune-cell infiltration, and clinical outcomes using publicly available cancer datasets, focusing on breast cancer (BRCA), cervical squamous cell carcinoma (CESC), and glioblastoma multiforme (GBM). Our analyses revealed prominent membrane-associated CD24 localization in BRCA and CESC, whereas CD24 was predominantly cytoplasmic in GBM. BRCA and CESC exhibited increased integrin β1 expression and distinct associations between CD24 and components of integrin β1/SRC and TGFβ-associated signaling networks, including MEK1 and SMAD7. In addition, we identified a structurally consistent and energetically favorable predicted interface between CD24 and Siglec-10, suggesting a mechanism by which CD24 may suppress anti-tumor immunity. Elevated CD24 expression was associated with immune-infiltration patterns consistent with an immunosuppressive tumor microenvironment in BRCA and CESC, including negative associations with M1 macrophage, CD8⁺ T-cell, and NK-cell infiltration. Importantly, high CD24 expression was associated with unfavorable overall survival in BRCA and CESC, whereas the opposite relationship was observed in GBM. Collectively, these findings suggest that the subcellular distribution of CD24 may be associated with distinct tumor signaling, the immune microenvironment, and prognostic profiles, highlighting the potential importance of CD24 localization in determining its tumor-type-specific biological functions.

Postbiotics, which are preparations of inanimate microorganisms and their components, have emerged as a promising functional ingredient in animal health and nutrition. Postbiotics are primarily composed of microbial cell fractions, metabolites, enzymes, vitamins, polysaccharides, and short-chain fatty acids. Unlike probiotics, postbiotics do not contain live microorganisms, which strengthens their greater stability and safety in feed/food formulations. Postbiotics offer several beneficial effects, including antioxidant, anti-inflammatory, immune-modulatory, and antimicrobial actions. They enhance antioxidant enzymes, neutralize reactive oxygen species, and inhibit lipid peroxidation, thereby protecting tissues from oxidative damage. Postbiotics also inhibit pro-inflammatory molecules like TNF-α and IL-6, while enhancing the anti-inflammatory cytokine IL-10, promoting the maturation and function of immune cells, and increasing secretory IgA production. They suppress a variety of pathogenic bacteria, including Escherichia coli, Salmonella, Staphylococcus, Campylobacter, etc., both in vitro and in vivo. Moreover, they increase beneficial gut bacteria and improve the digestion and integrity of the intestine. This article outlines the beneficial effects of postbiotics in animals including poultry, swine, canine, feline, horses, and ruminant animals, either as feed/food or as a supplement. The integration of postbiotics into animal feed improves growth performance, feed conversion ratios, and disease resistance in animals. Thus, the multifunctional benefits of postbiotics make them a valuable tool for healthy companion animals and sustainable livestock production, supporting both animal welfare and productivity without the drawbacks associated with antibiotic growth promoters.

Viral infection is a significant cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (Allo-HSCT), largely due to its impact on and interaction with immune reconstitution. Both innate and adaptive immunity are essential for effective viral control, yet their recovery post-transplant is often delayed or functionally impaired. Emerging evidence suggests genetic variation, particularly polymorphisms in the IL28B gene (encoding IFN-λ3), as a critical factor influencing the quality and timing of immune responses during the early post-transplant period. This review explores the role of IL28B polymorphisms in shaping antiviral immunity, in general, as well as after Allo-HSCT. IL28B variants have been implicated in modulating interferon-stimulated gene (ISG) expression, natural killer (NK) cell activity, and type I/III interferon signaling, all central components of innate immune defense against viral infections. Furthermore, IL28B polymorphisms, particularly rs12979860, have been shown in both general populations and limited HSCT cohorts to alter T cell response and interferon production, affecting reactivation and clearance of multiple viruses such as cytomegalovirus (CMV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein–Barr virus (EBV), COVID-19, and BK polyomavirus (BKPyV) as well as Graft vs. Host disease, thereby affecting adaptive immune reconstitution and long-term viral control. Understanding how IL28B genotype alters immune dynamics in transplant recipients could enhance risk stratification for CMV and other diseases and inform personalized prophylactic or therapeutic strategies. Therefore, this review highlights IL28B as a promising biomarker and potential immunoregulatory target in the management of viral infection post-Allo-HSCT.

Background/Objectives: CD318 (also known as CDCP1) is a transmembrane protein that is overexpressed in many cancers and contributes to tumor progression, invasion, and metastasis by activating SRC family kinases through phosphorylation. Emerging evidence also suggests that CD318 plays a role in modulating the tumor immune microenvironment, although its precise mechanism in tumor progression is still not well understood. Methods: To investigate this, we analyzed the expression and immune-related functions of CD318 using the publicly available data from The Cancer Genome Atlas (TCGA) across colorectal adenocarcinoma (COAD), cervical squamous cell carcinoma (CESC), lung adenocarcinoma (LUAD), and pancreatic adenocarcinoma (PAAD). Results: All four cancers exhibited a high level of CD318 expression. Notably, in CESC, LUAD, and PAAD, plasmin-mediated cleavage of CD318 leads to phosphorylation of SRC and protein kinase C delta (PKCδ), which activates HIF1α and/or p38 MAPK. These downstream effectors translocate to the nucleus and promote the transcriptional upregulation of TGFβ1, fostering an immunosuppressive tumor microenvironment through Treg cell recruitment. In contrast, this signaling cascade appears to be absent in COAD. Instead, our analysis indicate that intact CD318 in COAD interacts with the surface receptors CD96 and CD160, which are found on CD8⁺ T cells and NK cells. Conclusions: This interaction enhances cytotoxic immune responses in COAD by promoting CD8⁺ T cell and NK cell activity, offering a possible explanation for the favorable prognosis associated with high CD318 expression in COAD, compared to the poorer outcomes observed in CESC, LUAD, and PAAD.

Ovotransferrin (OVT) is one of the major proteins of egg white and is known to bind and transport irons in animals. OVT exerts bacteriostatic and bactericidal activities due to its iron-binding capacity. OVT effectively controls the growth of various pathogenic microorganisms, including Pseudomonas, E. coli, Staphylococcus, Proteus, and Klebsiella species, as well as inhibiting the replication of viruses. OVT also has antioxidant, anti-inflammatory, anti-hypertensive, anticancer, and immuno-stimulating properties. For instances, OVT quenches free radicals, induces antioxidant enzymes, suppresses pro-inflammatory cytokines, increases immune cells, reduces angiotensin-converting enzymes, and inhibits the proliferation of cancer cells. In this review, the beneficial effects of OVT in both in vitro and in vivo, particularly livestock, are described. Because of its antimicrobial properties, OVT supplementation in livestock feed would be an excellent alternative to antibiotics, which reducing the development of antibiotic-resistant pathogenic microorganisms. Thus, OVT could be a game-changing protein for the growth, performance, and healthy life of animals.

Cranberries are a distinctive source of bioactive compounds, containing polyphenols such as flavonoids, anthocyanins, phenolic acids, and triterpenoids. Cranberries are often associated with potential health benefits for the urinary tract and digestive system due to their high antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties. Cranberry induces the production of antioxidant enzymes, suppresses lipid peroxidation, reduces inflammatory cytokines, modulates immune cells, maintains gut microbiota, and inhibits bacterial adhesion and growth. Cranberry polyphenols also have metal-binding motifs that bind with metals, particularly zinc and iron. The combination of cranberry polyphenols and metals displays increased biological activity. In this review, an attempt is made to describe the physiological properties and health benefits of cranberries for livestock, including poultry, swine, canine, feline, and ruminant animals, as either feed/food or as supplements. Cranberry, and/or its components, has the capability to potentially control infectious diseases like diarrhea, urinary tract infection, gut integrity, and intestinal probiotic health. Moreover, cranberries show efficacy in suppressing the growth of pathogenic microorganisms such as Salmonella species, Campylobacter species, Streptococcus species, and Enterococcus species bacteria. Thus, cranberry could be considered as a potential natural feed additive or food supplement for animal health improvement.

Background: CD59, a GPI-anchored membrane protein, protects cancer cells from complement-dependent cytotoxicity (CDC) by inhibiting the formation of the membrane attack complex (MAC). It has been demonstrated to be overexpressed in most solid tumors, where it facilitates tumor cell escape from complement surveillance. The role of CD59 in cancer growth and interactions between CD59 and immune cells that modulate immune evasion has not been well explored. Methods: Using cancer patient database from The Cancer Genome Atlas (TCGA) and other public databases, we analyzed CD59 expression, its prognostic significance, and its association with immune cell infiltration in the tumor microenvironment, identifying associated genomic and functional networks and validating findings with invitro cell-line experimental data. Results: This article describes the abundant expression of CD59 in multiple tumors such as cervical squamous cell carcinoma (CESC), kidney renal cell carcinoma (KIRC), glioblastoma multiforme (GBM), head and neck squamous cell carcinoma (HNSC), and stomach adenocarcinoma (STAD), as well as in pan-cancer, using The Cancer Genome Atlas (TCGA) database and confirmed using multiple cancer cell lines. The expression of CD59 significantly alters the overall survival (OS) of patients with multiple malignancies such as CESC, GBM, HNSC, and STAD. Further, the correlation between CD59 and Treg and/or MDSC in the tumor microenvironment (TME) has shown to be strongly associated with poor outcomes in CESC, GBM, HNSC, and STAD as these tumors express high FOXP3 compared to KIRC. Moreover, unfavorable outcomes were strongly associated with the expression of CD59 and M2 tumor-associated macrophage infiltration in the TME via the IL10/pSTAT3 pathway in CESC and GBM but not in KIRC. In addition, TGFβ1-dominant cancers such as CESC, GBM, and HNSC showed a high correlation between CD59 and TGFβ1, leading to suppression of cytotoxic T cell activity. Conclusion: Overall, the correlation between CD59 and immune cells predicts its prognosis as unfavorable in CESC, GBM, HNSC, and STAD while being favorable in KIRC.

The role of the most common TP53 single-nucleotide polymorphism (SNP) at codon 72, which encodes for proline (P72) or arginine (R72), in the regulation of the immune system has not yet been thoroughly explored. We found that this SNP contributes to aggravated inflammatory response in COVID-19 patients resulting from biased macrophage activation. R72-P53 inhibits mitochondrial manganese superoxide dismutase, leading to impaired reactive oxygen species scavenging, oxidation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and, consequently, its inhibition. Reduced PTEN activity causes constitutive activation of the PI3K/Akt pathway, which restricts proinflammatory (M1) and promotes anti-inflammatory (M2) phenotypes through NF-κB and p53 inhibition. In contrast, PTEN-reduced PI3K/Akt activity, in P72 carrying cells, favors M1 phenotypes. LPS-stimulated R72 macrophages fail to reduce tumor growth in a mouse model of cancer, in contrast with P72 macrophages, which preserve M1 phenotype in vivo and reduce tumor growth by enhancing antitumor T cell responses, consistent with antitumor functions of M1 macrophages. In addition, P72 macrophages contributed to increased mortality in a mouse model of LPS-induced endotoxemia. Therefore, given the high frequency of P72 in African Americans, cell signaling alterations driven by codon 72 of TP53 SNP may potentially contribute to differences in clinical outcomes and health disparities in common diseases associated with dysregulated macrophage activation.

Cardiovascular diseases are a leading cause of mortality across the globe, and transplant surgeries are not always successful since it is not always possible to replace most of the damaged heart tissues, for example in myocardial infarction. Chitosan, a natural polysaccharide, is an important biomaterial for many biomedical and pharmaceutical industries. Based on the origin, degree of deacetylation, structure, and biological functions, chitosan has emerged for vital tissue engineering applications. Recent studies reported that chitosan coupled with innovative technologies helped to load or deliver drugs or stem cells to repair the damaged heart tissue not just in a myocardial infarction but even in other cardiac therapies. Herein, we outlined the latest advances in cardiac tissue engineering mediated by chitosan overcoming the barriers in cardiac diseases. We reviewed in vitro and in vivo data reported dealing with drug delivery systems, scaffolds, or carriers fabricated using chitosan for stem cell therapy essential in cardiac tissue engineering. This comprehensive review also summarizes the properties of chitosan as a biomaterial substrate having sufficient mechanical stability that can stimulate the native collagen fibril structure for differentiating pluripotent stem cells and mesenchymal stem cells into cardiomyocytes for cardiac tissue engineering.