Yumna Khan

T cell activation is a central mechanism in adaptive immunity, modulating immune surveillance, host defense, and immune-mediated pathology. It is a highly coordinated mechanism including antigen recognition, co-stimulatory and co-inhibitory signaling, and cytokine-mediated regulation. This work aims to synthesize existing knowledge on the molecular mechanisms modulating T cell activation, with emphasis on integrated signaling cascades, experimental models, and therapeutic implications. A narrative review of the literature was conducted, focusing on key signaling cascades, regulatory mechanisms, and experimental methods used to analyze T cell activation in both basic and translational immunology. T cell activation is orchestrated via the mediation of T cell receptor (TCR) signaling with co-stimulatory and co-inhibitory cascades, alongside cytokine-mediated cues that collectively determine T cell fate and function. Critical intracellular signaling cascades, offer pivotal function in transcriptional and metabolic reprogramming. Experimental models such as in vitro stimulation systems, flow cytometry-based analyses, and advanced imaging approaches have significantly improved mechanistic knowledge of T cell responses. These insights have informed therapeutic approaches targeting T cell activation in cancer immunotherapy, autoimmune diseases, and infectious conditions. Although, obstacles in clinical translation remain. A comprehensive understanding of T cell activation needs integration of molecular, experimental, and clinical perspectives. Importantly, this review emphasizes the comparative strengths and limitations of contemporary experimental models and discusses how multi-omics integration and computational modeling can improve reproducibility, physiological relevance, and translational predictability in T cell research. Advancements in this field continue to offer opportunities for the development of targeted immunotherapies and enhanced disease intervention approaches.

Bullous pemphigoid (BP) is an autoimmune blistering disease that especially presents in elderly patients, but recently, its incidence has increased in patients treated with inhibitors of dipeptidyl peptidase-4 (DPP-4), among which teneligliptin is widely prescribed as an antidiabetic drug for the treatment of type 2 diabetes mellitus (T2DM). Recent studies describe the association of teneligliptin with the onset of BP, hypothesizing that DPP-4 inhibition could induce immune dysregulation able to trigger autoimmune responses against skin antigens BP180 and BP230. This mini-review discusses the immunomodulatory effects of teneligliptin, immune responses, and chronic inflammation associated with diabetes that predispose patients to BP. It also discusses the clinical implications, such as monitoring for BP in T2DM patients on teneligliptin therapy. Elucidation of this relationship may help in optimizing management strategies by highlighting discontinuation or alternative therapies in the case of a high risk of development of BP.

We performed an updated systematic review and meta-analysis to evaluate tenecteplase 0.25 mg/kg in the extended time window. MEDLINE was searched via PubMed, Scopus, and Web of Science from inception to February 2026, with trial registries also screened. Eligible trials were RCTs of adults treated beyond 4.5 h from last known well or with wake-up stroke, comparing IV tenecteplase 0.25 mg/kg with placebo or standard care. Primary efficacy outcomes were 90-day mRS 0-1 and mRS 0-2, and primary safety outcomes were symptomatic intracranial hemorrhage and death. RoB 2 and GRADE were used to assess risk of bias and certainty. Risk ratios were pooled using a random effects model. Nine RCTs, including 4,000 participants, met eligibility criteria. Tenecteplase was associated with a modest increase in excellent functional outcome (9 studies, 4000 patients, RR 1.12, 95% CI 1.027 to 1.22, p = 0.01, I²: 14.9%) and favorable functional outcome (9 studies, 4000 patients, RR 1.06, 95% CI 1.01 to 1.11, p = 0.0091, I²: 10.6%). Tenecteplase showed a significantly higher risk of sICH (9 studies, 4000 patients, RR 1.86, 95% CI 1.065 to 3.24, p = 0.029, I²: 21.8%), while no difference was found in death (9 studies, 4000 patients, RR 1.006, 95% CI 0.85 to 1.19, p = 0.95, I²: 35.5%). GRADE certainty was high for favorable outcome and death, and moderate for excellent outcome, sICH, reperfusion, and parenchymal hematoma type 2. In extended window acute ischemic stroke, tenecteplase 0.25 mg/kg improved 90-day functional outcomes and increased reperfusion, but it increased intracranial hemorrhage, including sICH. These findings support careful use in imaging selected patients, with attention to bleeding risk.

Breast cancer (BC) continues to be the most prevalent cause of death from cancer on a global scale, requiring novel and targeted therapeutic strategies. Peptide-loaded nanoparticles (NPs) have been established as a prospective platform for precision drug delivery in BC treatment, providing enhanced cancer selectivity, improved drug stability, and reduced systemic toxicity. This article explores the multifaceted utilizations of peptide-loaded NPs in BC therapeutics, highlighting advancements in targeted drug delivery, combination therapy, and vaccine development. Peptideloaded NPs have demonstrated superior efficacy in delivering chemotherapeutic agents, overcoming drug resistance, and minimizing adverse effects. Studies on tumor-homing peptides, such as F3- functionalized liquid crystalline NPs and tLyP-1-modified reconstituted high-density lipoprotein NPs, have shown significant improvements in drug accumulation at tumor sites, reduction in metastasis, and prolonged circulation time. Additionally, the creation of peptide-based vaccines targeting tumor-associated antigens, including HER2/neu and heat shock protein 90 (HSP90), is reshaping BC immunotherapy, stimulating strong immune responses against tumors. Despite these advancements, obstacles persist in ensuring NP stability, mitigating immunogenicity, and scaling up manufacturing for clinical translation. Future directions include the integration of peptide-loaded NPs with CRISPR/Cas9 for gene-editing applications, the development of peptide nanovaccines, and the use of personalized nanomedicine approaches tailored to the molecular profiles of individual tumors. This review underscores the potential of peptide-loaded NPs as a next-generation therapeutic strategy, facilitating the development of more efficient and personalized treatments for BC.

Colorectal cancer (CRC) continues to be a substantial cause of cancer-related fatality globally, necessitating improved diagnostic and therapeutic strategies. Exosomes, small extracellular vesicles that facilitate intercellular communication, as key mediators in CRC progression by transporting bioactive molecules, including non-coding RNAs (ncRNAs). These exosomal ncRNAs (exo-ncRNAs) participate in regulating gene expression, tumor proliferation, metastasis, chemoresistance, and immune escape. ExoncRNAs show distinct patterns in CRC, making them potential non-invasive indicators for early detection and prognosis. Additionally, the potential of exosome-based therapies, including engineered exosomal RNA delivery, offers new avenues for precision oncology. However, addressing challenges, such as standardization of exosome isolation methods, clinical validation, and mechanistic elucidation, is necessary before their full clinical implementation. This article offers a comprehensive synthesis of the recent knowledge of exo-ncRNAs in CRC, emphasizing their biological functions, molecular mechanisms, and translational potential in diagnostics and therapeutics. Future research integrating artificial intelligence and multi-omics approaches may further enhance the clinical utility of exo-ncRNAs, advancing precision medicine in CRC management.

Cytokine Release Syndrome (CRS) is a hyperinflammatory condition triggered by infections, immunotherapies, and systemic immune dysregulation. PANoptosis, a unique form of programmed inflammatory cell death that integrates pyroptosis, apoptosis, and necroptosis, has emerged as a key contributor to CRS pathogenesis. This review explores the mechanistic role of PANoptosis in CRS, with particular emphasis on immunotherapy-induced toxicity and viral infections such as SARS-CoV-2 and influenza. PANoptosis exacerbates cytokine storms through ZBP1, NLRP3, and CASP8-mediated pathways, creating a pathological feedback loop that intensifies inflammation and promotes multi-organ damage. Current evidence suggests that modulating PANoptotic pathways, including targeting TNF-α, IFN-γ, and inflammasome components, may mitigate cytokine-driven tissue injury. Despite growing interest, the therapeutic potential of PANoptosis remains underexplored. Advancing our understanding of PANoptosis and its interaction with cytokine signaling will be critical for developing effective interventions for CRS and improving outcomes in patients undergoing immunotherapy or battling severe infections.

The detection of cancer remains a significant challenge due to limitations of current screening approaches, where usually several procedures and imprecise information are required. Liquid biopsy has emerged as an appealing method that makes it unnecessary to use invasive procedures. It depicts the biology of tumors at first sight based on circulating tumor cells (CTCs), cell-free DNA (cfDNA), and exosomes in the blood of the patient. This paper provides a review of the likelihood of the integration of liquid biopsy with medical imaging methods, such as MRI, CT, PET, and ultrasound, to enhance the accuracy of tumor identification. We expand on how liquid biopsy might improve healthcare imaging by defining tumor characterization more accurately and precisely, avoiding false positive and negative values, and providing genetic integration information that is often useful when interpreting imaging scans. Case examples are employed to demonstrate the seamless combination of liquid biopsy data with imaging outcomes, which can help expand the understanding of cancer pathophysiology and treatment sensitivity. However, artificial intelligence and machine learning should be used to support the execution of this supposed synergistically integrated strategy. The article also explains the problems concerning the integration of these two diagnostic methods and stresses the importance of standardizing the procedures and cooperation between the disciplines. This aggregation could result in earlier detection, improved monitoring, as well as individual approaches to cancer patients, hence leading to a significant increase in positive clinical outcomes.

Alzheimer's disease (AD) is a progressive condition that causes the degeneration of nerve cells, leading to a decline in cognitive abilities and memory impairment, significantly affecting millions around the globe. The primary pathological feature of AD is the buildup of amyloid-β (Aβ) plaques in the brain, which has become a major target for therapeutic strategies. This thorough review examines the progress made in next-generation therapies that concentrate on monoclonal antibodies (mAbs) aimed at Aβ. We explore how these antibodies function, their effectiveness in clinical settings, and their safety profiles, specifically discussing notable mAbs, such as aducanumab, donanemab, lecanemab, etc. This review also addresses the difficulties related to Aβ- targeted treatments. Furthermore, it examines the advancing field of biomarker development and tailored medicine strategies designed to improve the accuracy of AD treatment. By integrating the latest findings from clinical trials and new research, this review offers an in-depth evaluation of the possibilities and challenges associated with mAbs in modifying the progression of AD. Future considerations regarding combination therapies and novel drug delivery methods are also examined, emphasizing the necessity for ongoing research to achieve significant advancements in managing AD. Through this review, we seek to provide clinicians, researchers, and policymakers with insights into the current landscape and future directions of Aβ-targeted therapies, promoting a deeper understanding of their role in addressing AD.