Ahmed Yaseen

Colorectal cancer (CRC) remains a major global health burden, with rising incidence and mortality, particularly in developing countries. The tumor microenvironment (TME) plays a critical role in CRC progression by facilitating angiogenesis, immune evasion, and metastasis through complex intercellular communication. Among the key mediators of this communication are exosomes—nano-sized extracellular vesicles—that transport a variety of bioactive molecules, including competing endogenous RNAs (ceRNAs). These ceRNAs, such as long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and mRNAs, act as molecular sponges for microRNAs (miRNAs), thereby regulating gene expression and influencing cancer-related pathways like Wnt/β-catenin and PI3K/Akt. This review explores the emerging role of exosomal ceRNAs derived from the TME in CRC progression, emphasizing their involvement in promoting tumor cell proliferation, invasion, metastasis, and resistance to therapy. By elucidating the intricate crosstalk between exosomal ceRNAs and the TME, we highlight their potential as novel biomarkers and therapeutic targets, offering new avenues for personalized treatment strategies in colorectal malignancies. Despite growing interest in exosomes and non-coding RNAs in colorectal cancer (CRC), limited attention has been given to the specific role of exosomal ceRNAs derived from the tumor microenvironment (TME). Existing reviews have predominantly addressed broader aspects of exosomal non-coding RNAs (e.g., miRNAs, lncRNAs, and circRNAs in general CRC progression, metastasis, or as biomarkers) or focused on exosomal communication in other malignancies. However, the intricate mechanisms by which TME-derived exosomal ceRNAs establish regulatory networks to drive CRC pathology—particularly through miRNA sponging in stromal-tumor crosstalk—remain underexplored and insufficiently synthesized. This review addresses these critical gaps by uniquely emphasizing exosomal ceRNAs sourced from the TME (including CAFs, macrophages, and other stromal components), elucidating their convergent roles in orchestrating proliferation, invasion, immune evasion, and chemoresistance. By integrating recent evidence into a TME-centric framework, we provide novel insights into potential diagnostic and therapeutic applications, advancing beyond general exosomal RNA overviews toward targeted strategies for CRC.

Cancer stem cells (CSCs) represent a critical subpopulation within tumors, driving progression, metastasis, and, notably, resistance to conventional therapies. This inherent recalcitrance underscores an urgent need for targeted eradication strategies. Chimeric Antigen Receptor (CAR)-based cellular immunotherapies, including CAR-T, CAR-NK, and CAR-NKT cells, have revolutionized the treatment of hematological malignancies and are now emerging as potent tools against CSCs in solid tumors. This review provides a comprehensive overview of CSC biology, the foundational principles of CAR engineering, and the current clinical landscape of these cellular immunotherapies. It delves into the specific challenges encountered when targeting CSCs, such as tumor heterogeneity, the pervasive immunosuppressive tumor microenvironment, and the risk of on-target/off-tumor toxicities. Furthermore, the report explores advanced engineering strategies, including dual-targeting and logic-gated CARs, the strategic modulation of CSC metabolism, and the transformative potential of multi-omics integration and artificial intelligence. By synthesizing current knowledge and highlighting innovative approaches, this review aims to illuminate the path toward overcoming stem-like resistance and achieving durable cancer remission through engineered cellular immunotherapies.

Purpose Sex hormone-binding globulin (SHBG), which regulates androgen and estrogen bioavailability, has been linked to cognitive decline, but its relationship with temporal lobe changes—an area vulnerable in early Alzheimer’s disease (AD)—remains unclear. This study aimed to investigate whether plasma SHBG levels are associated with temporal lobe volume and cognitive performance across the cognitive spectrum from normal aging to AD. Methods Participants included individuals with AD (n = 85), mild cognitive impairment (MCI; n = 304), and cognitively normal controls (CN; n = 50). Cognitive performance was assessed using the ADAS-Cog 11, MMSE, and CDR-SB. Temporal lobe volumes were derived from MRI scans using tensor-based morphometry (TBM), and plasma SHBG levels were measured using a validated immunoassay. Multiple regression analyses adjusted for age, sex, education, handedness, and APOE ε4 status were conducted, followed by mediation analysis to test indirect effects through temporal lobe volume. Results After covariate adjustment, elevated plasma SHBG levels were significantly associated with reduced temporal lobe volume in the MCI group. Across both MCI and AD participants, greater temporal lobe volume correlated with better cognitive performance on all tests. Mediation analysis indicated that in MCI, the relationship between higher plasma SHBG and poorer cognitive outcomes was significantly mediated by reduced temporal lobe volume. Conclusion These findings suggest that elevated SHBG may contribute to early cognitive impairment in MCI through its impact on temporal lobe integrity, highlighting SHBG as a potential target in the prodromal stages of AD.

Macrophage migration inhibitory factor (MIF) is one of several pivotal cytokines that contribute to orchestrate immune regulation, inflammation, and cell survival, acting as both a mediator of host defense and a factor that viruses can exploit. This comprehensive review delineates MIF’s multifaceted roles across diverse viral families—including Retroviridae, Herpesviridae, Hepadnaviridae, Orthomyxoviridae, Flaviviridae, Paramyxoviridae, and Picornaviridae—highlighting the mechanisms by which viruses manipulate MIF signaling to promote replication, evade immune responses, and induce tissue damage. Viral strategies often involve upregulating MIF expression or leveraging its receptor pathways, such as CD74, CXCR2, and CXCR4, to enhance viral persistence, disrupt barrier integrity, and skew immune polarization toward pro-viral or immunosuppressive states. Conversely, MIF-driven inflammation can worsen pathogenic processes, including cytokine storms, neuroinvasion, and fibrosis, contributing to disease severity. Notably, pharmacologic inhibition of MIF has shown promise in preclinical models, reducing viral replication and mitigating tissue damage, thereby positioning MIF as one of the compelling targets for host-directed antiviral therapies. Understanding the complex, context-dependent functions of MIF in viral infections provides transformative insights for innovative treatment strategies that aim to disrupt virus-host interactions, control inflammation, and improve clinical outcomes in infectious diseases. Future research exploring MIF’s molecular interactions, genetic variations, and therapeutic modulation will be crucial for harnessing its potential for personalized, effective antiviral interventions.