Drug-induced hepatotoxicity is a significant clinical issue worldwide. Given the limited treatment options for these liver injuries, understanding the mechanisms and modes of cell death is crucial for identifying novel therapeutic targets. For the past 60 years, reactive oxygen species and iron-dependent lipid peroxidation (LPO) have been hypothesized to be involved in many models of acute drug-induced liver injury. However, this mechanism of toxicity was largely abandoned when apoptosis became the primary focus of cell death research. More recently, ferroptosis—a novel, non-apoptotic form of cell death—was identified in NRAS-mutant HT-1080 fibrosarcoma cells exposed to erastin and other NRLs. Ferroptosis is characterized by glutathione depletion and the impairment of glutathione peroxidase 4 activity, which hinders the detoxification of lipid hydroperoxides. These hydroperoxides then serve as substrates for iron-dependent LPO propagation. This cell death mechanism is now receiving widespread attention, extending well beyond its original identification in cancer research, including in the field of drug-induced liver injury. However, concerns arise when such mechanisms are applied across different cell types and disease states without sufficient validation. This review critically evaluated the historical evidence for iron-dependent LPO as a mechanism of drug-induced hepatotoxicity and explored how these earlier findings have led to the current concept of ferroptosis. Overall, the published data support the idea that multi-layered endogenous antioxidant defense mechanisms in the liver limit the occurrence of pathophysiologically relevant LPO under normal conditions. Only when these defense mechanisms are severely compromised does ferroptosis become a significant mode of drug-induced cell death.

The brain, traditionally regarded as immune-privileged due to the blood-brain barrier, harbors a sophisticated immune system crucial for maintaining neural health and resilience against various challenges. Microglia, the resident immune cells of the central nervous system, actively monitor their environment, participating in immune surveillance, synaptic pruning, and neuroprotection. Astrocytes also play vital roles by regulating neurotransmitter levels, supporting metabolism, and maintaining the blood-brain barrier integrity. Recent research underscores the involvement of T cells and monocytes in modulating neuroinflammation and immune responses within the brain. Neurological disorders such as Alzheimer’s and Parkinson’s disease highlight the brain’s vulnerability to immune dysregulation. This review aimed to elucidate the role of neuroimmune cells in brain health and the progression of neurological diseases. It aimed to identify critical mechanisms to enhance therapeutic strategies and improve outcomes. Understanding these interactions is essential for developing targeted therapies to mitigate neuroinflammation and preserve cognitive functions. This review critically examines neuroinflammation related to aging and disease, with a focus on neuroimmune cells and their underlying mechanisms. It highlights how chronic inflammation, driven by activated microglia and astrocytes, exacerbates neuronal damage, synaptic dysfunction, and cognitive decline. The disruption of immune privilege in these conditions involves complex pathways that trigger inflammatory responses, impairing essential neural functions. Despite its immune-privileged status, the brain’s immune system, primarily involving microglia and astrocytes, is crucial for maintaining homeostasis and managing illness. Our review strongly suggests that neurological diseases, influenced by genetic, environmental, and aging factors, often involve heightened neuroinflammation. Targeted therapies are needed to address infections, chronic inflammation, and environmental impacts. Additionally, research into mental health disorders and advancements in imaging techniques are critical for understanding immune dysfunction and enhancing treatment strategies.

The diagnostic value of primary biliary cholangitis (PBC)-specific antibodies in patients with elevated alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels, and other identifiable causes, was unclear. Our study aimed to determine whether etiological treatments in PBC-specific antibody-positive patients could improve liver biochemical tests, thereby distinguishing them from individuals with PBC.

We enrolled patients who were positive for PBC-specific antibodies and elevated ALP and/or GGT levels but with other identifiable etiologies. Changes in liver biochemistry following non-ursodeoxycholic acid etiological treatments were monitored.

A total of 155 patients with positive PBC-specific antibodies and elevated ALP and/or GGT levels due to non-PBC diseases were enrolled. Among them, 100 patients were diagnosed with non-PBC liver diseases, mainly metabolic-associated fatty liver disease, drug-induced liver injury, and autoimmune hepatitis. Additionally, 55 patients had non-liver diseases, predominantly connective tissue diseases. The median follow-up duration was 15.9 (4.7–25.6) months. Among 141 patients who completed follow-up after receiving etiological treatments, 85.1% (120/141) showed improvement in ALP and/or GGT levels, with 51.8% (73/141) achieving normalization of both ALP and GGT. However, 68 patients continued to exhibit elevated ALP and/or GGT, with 55 patients displaying isolated GGT elevation and 11 patients showing liver histological changes not consistent with PBC.

PBC-specific antibodies, along with elevated ALP and GGT levels, may occur in various non-PBC diseases. Etiological treatments may improve or even resolve cholestatic biochemistry. For these patients, initiating etiological treatment rather than immediately starting ursodeoxycholic acid therapy would be justified.

Cancer continues to pose a substantial public health problem in Nigeria, characterized by rising rates of occurrence and mortality. While there is increasing interest in using natural products for cancer treatment, comprehensive data on the specific bioactive compounds in these plants and how they modulate different types of cancer are still lacking. Additionally, although traditional knowledge about these food plants is rich and valuable, it has not been fully integrated with modern scientific research to create standardized treatment protocols. Scientific databases like PubMed, ScienceDirect, Google Scholar, and ResearchGate were explored to retrieve empirical data. The key plants discussed are Spondias mombin, Xanthosoma sagittifolium, Elaeis guineensis, Irvingia gabonensis, Allium cepa, Blighia sapida, Dioscorea dumetorum, Psidium guajava, and Talinum triangulare. These plants demonstrate a wide range of anticancer properties, including the ability to induce apoptosis (cell death), halt the cell cycle, inhibit angiogenesis, and regulate inflammatory responses. They contain a variety of phytochemicals, such as flavonoids, tannins, terpenoids, alkaloids, and organosulfur compounds, which contribute to their anticancer effects. For example, Spondias mombin contains flavonoids that inhibit the formation of tumors, whereas Xanthosoma sagittifolium exhibits cytotoxic effects against leukemia cells. Additionally, Elaeis guineensis exhibits antioxidant properties that counteract oxidative stress, a crucial factor in cancer progression. This review highlights the significance of these plants in developing complementary cancer therapies that can be used alongside conventional treatments. By combining traditional knowledge with contemporary scientific methods, these medicinal plants have the potential to provide innovative approaches to cancer prevention and treatment, addressing the pressing demand for safer and more efficient therapeutic alternatives.

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and primarily includes ulcerative colitis and Crohn’s disease. As the number of patients suffering from IBD increases, diagnosis and treatment have become pressing yet challenging tasks. A major challenge is that patients with IBD often do not exhibit characteristic symptoms, making it difficult to distinguish IBD from other intestinal abnormalities. Endoscopy is the most conventional method used to diagnose IBD; however, this technique is invasive and costly. Therefore, there is a need to develop affordable, non-invasive diagnostic methods, which underscores the importance of identifying biomarkers specific to IBD. It is now well established that the gut microbiome plays a significant role in the development of IBD, and changes in the abundance of various gut organisms have been widely studied to identify microbial signatures associated with the disease. This review discusses the current state of knowledge regarding biomarkers in IBD, with a primary focus on the gut microbiome, associated metabolic signatures, and their links with immunological biomarkers. These biomarkers will help propose an integrative model to better understand the pathophysiology of this complex disease. Such an integrated approach also offers insights into potential therapeutic targets for designing more effective treatment strategies for patients.

Large granular lymphocytic leukemias (LGLLs), including T-cell LGLL and natural kill (NK)-cell LGLL variants, are rare lymphoproliferative disorders characterized by the chronic proliferation of cytotoxic lymphocytes. Despite recent advancements, challenges remain in distinguishing these entities from one another and from related disorders, such as T-cell prolymphocytic leukemia, adult T-cell leukemia/lymphoma, Sézary syndrome, and aggressive NK-cell leukemia, owing to overlapping clinical and morphologic features. This article aims to review the role of molecular and immunophenotypic markers in guiding diagnosis and prognosis of LGLLs, with brief review of their clinical and morphologic features by synthesizing current advances in molecular pathogenesis, immunophenotypic profiling, and updated World Health Organization (WHO) classification criteria in order to enhance diagnostic precision, improve prognostic assessment, and inform personalized treatment strategies for these challenging disorders.

Literature was searched through Pubmed and the recently published 5th WHO classification criteria. Articles were reviewed and analyzed with emphasis on recent molecular and cytogenetic insights.

A total of 106 publications were reviewed, and the recent molecular insights—focusing on those concerning STAT3 mutations in T-cell LGLL and TET2 mutations in NK-cell LGLL which have refined diagnostic frameworks, though gaps persist in understanding their clinical relevance and variability.

By providing a comparative analysis of large granular lymphocytic leukemias and their differential diagnoses in cooperation of the current advances in molecular pathogenesis, immunophenotypic profiling, and updated WHO classification criteria, this work aimed to enhance diagnostic precision, improve prognostic assessment, and inform personalized treatment strategies for these challenging LGLLs.

Imbalanced autonomic function has been reported in gastrointestinal (GI) disorders. The vagus nerve is a major component in the regulation of upper GI motility. Vagal nerve stimulation (VNS) has been shown to improve symptoms of various GI disorders by enhancing parasympathetic activity. This review aims to summarize the clinical efficacy of transcutaneous VNS for GI disorders, focusing on abdominal pain, other GI symptoms, and GI motility, and to discuss the mechanisms of action of transcutaneous VNS. Randomized clinical trials investigating transcutaneous VNS in several major GI disorders, including functional dyspepsia, gastroparesis, constipation, irritable bowel syndrome, and inflammatory bowel disease, were reviewed and discussed. The forms of transcutaneous VNS covered in this review include transcutaneous auricular VNS, transcutaneous cervical VNS, and percutaneous electrical nerve field stimulation. Transcutaneous VNS has been shown to relieve abdominal pain, improve GI symptoms, and accelerate GI motility by enhancing vagal activity in patients with various GI disorders. Transcutaneous VNS is an innovative, effective, and safe therapy for patients with GI disorders; however, large-scale clinical trials are necessary to establish optimal treatment modalities and efficacy.

T-cell receptor (TCR) sequencing provides a novel platform for insight into and characterization of intricate T-cell profiles, advancing the understanding of tumor immune heterogeneity. Recently, transarterial chemoembolization (TACE) combined with systemic therapy has become the recommended regimen for advanced hepatocellular carcinoma. The regulation of the immune microenvironment after TACE and its impact on tumor progression and recurrence has been a focus of research. By examining and tracking fluctuations in the TCR repertoire following combination treatment, novel perspectives on the modulation of the tumor microenvironment post-TACE and the underlying mechanisms governing tumor progression and recurrence can be gained. Clarifying the distinctive metrics and dynamic alterations of the TCR repertoire within the context of combination therapy is imperative for understanding the mechanisms of anti-tumor immunity, assessing efficacy, exploiting novel treatments, and further advancing precision oncology in the treatment of hepatocellular carcinoma. In this review, we initially summarized the fundamental characteristics of TCR repertoire and depicted immune microenvironment remodeling after TACE. Ultimately, we illustrated the prospective applications of TCR repertoires in TACE combined with systemic therapy.

Microscopic colitis is a chronic inflammatory disease of the colon that describes patients who present with watery diarrhea, normal or minimal endoscopic findings, and chronic inflammation identified on colonic biopsy. As the name suggests, microscopic colitis requires histologic evaluation for diagnosis. The two most well-established histologic patterns are collagenous colitis and lymphocytic colitis. In this review, we highlighted the key histologic features of microscopic colitis on biopsy specimens, along with its endoscopic findings, pathogenesis, and underlying molecular mechanisms. We also discussed important mimickers—including amyloidosis, collagenous colitis, ischemic colitis, and radiation colitis—emphasizing their distinguishing histopathologic characteristics. Recognizing these mimickers is crucial, as their treatment strategies are significantly different.