Free radicals are produced in the body during normal cellular metabolic activities, and their excessive accumulation can overwhelm the natural antioxidant mechanisms. This leads to oxidative stress, which is associated with the development and progression of non-communicable diseases (NCDs) such as liver and kidney diseases, cardiovascular diseases, neurodegenerative diseases, cancer, and diabetes. Enzymes play a significant role in maintaining a balance between antioxidants and free radicals by either enhancing the production of antioxidants or slowing down the generation of free radicals in the body. There is no up-to-date review on how antioxidant-enzyme interactions modulate the development and progression of NCDs. This review, therefore, discusses the mechanisms of antioxidant-enzyme interactions in the control of oxidative stress, as well as the implications and prospects of these interactions in the management of NCDs. Therapeutic strategies targeting antioxidant-enzyme interactions in the natural defense mechanisms of the body against oxidative stress can provide targeted benefits in the management of various NCDs. The mechanisms of interaction of some antioxidants with catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase, glutathione S-transferases, thioredoxin protein, and thioredoxin reductase suggest their strong involvement in mitigating the development and progression of NCDs. Moreover, understanding the specific interactions and signaling pathways involved in antioxidant-enzyme interactions could facilitate the emergence of novel and effective therapeutic strategies for the management of NCDs and should be considered a primary goal of future studies. This study provides the necessary template, encourages discussion, and creates more opportunities for the next stage in the development of antioxidant therapies.

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.

The performance of neurodegenerative biomarkers—neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1)—in diagnosing minimal hepatic encephalopathy (MHE) has not been systematically evaluated, simultaneously, nor have their associations with the development of overt hepatic encephalopathy (OHE). This study aimed to evaluate the performance of plasma NfL, GFAP, tau, and UCHL1 in diagnosing MHE and predicting the development of OHE in Chinese patients with hepatic cirrhosis.

In this prospective study, 124 patients with hepatic cirrhosis were recruited. The Psychometric Hepatic Encephalopathy Score was used to diagnose MHE, and OHE development was observed during a 30-day follow-up period. Plasma levels of NfL, GFAP, tau, and UCHL1 were measured using the highly sensitive single-molecule array when MHE was diagnosed. Additionally, serum interleukin-6 (IL-6) levels and the model for end-stage liver disease (MELD) and MELD-Na scores were also measured.

MHE was diagnosed in 57 (46.0%) patients. Patients with MHE had significantly higher plasma levels of NfL and GFAP (34.2 vs. 22.4 pg/mL and 173 vs. 97.6 pg/mL, respectively; both p < 0.001) and lower tau levels (8.4 vs. 11.6 pg/mL, p = 0.048) compared to those without MHE. Plasma NfL (odds ratios = 1.027, 95% confidence interval [CI]: 1.006–1.048; p = 0.013) and serum ammonia levels (odds ratios = 1.021, 95% CI: 1.006–1.036; p = 0.007) were independently associated with MHE occurrence. A combination of NfL, GFAP, tau, and UCHL1 was effective in diagnosing MHE in all cirrhotic patients (area under the receiver operating characteristic curve [hereinafter referred to as AUROC]: 0.748, 95% CI: 0.662–0.821), with an accuracy, sensitivity, and specificity of 71.0%, 71.9%, and 71.6%, respectively. In patients without previous OHE, the combination had an AUROC of 0.764 (95% CI: 0.673–0.840), with an accuracy, sensitivity, and specificity of 72.5%, 71.7%, and 73.0%, respectively. Furthermore, GFAP (hazard ratio (HR) = 1.003, 95% CI: 1.000–1.005; p = 0.044), IL-6 (HR = 1.003, 95% CI: 1.001–1.004; p < 0.001), and MELD score (HR = 1.139, 95% CI: 1.072–1.210; p < 0.001)—but not NfL, tau, and UCHL1—were identified as risk factors for 30-day OHE development.

The combination of plasma levels of NfL, GFAP, tau, and UCHL1 performs well in diagnosing MHE. Additionally, MELD score, IL-6, and GFAP appear to be significant predictors of OHE development in patients with hepatic cirrhosis.

Drug-induced liver injury (DILI) is a harmful reaction to medications, herbs, and dietary supplements that results in liver dysfunction. Based on the distinct clinical patterns of liver damage, DILI can be categorized into hepatocellular, cholestatic, and mixed types. Hepatocellular DILI is linked to inflammation, apoptosis, and necrosis, while cholestatic DILI is commonly associated with bile plugs and, in rare cases, ductopenia. Ursodeoxycholic acid (UDCA) is the therapeutic agent most widely used for the treatment of cholestatic hepatopathies of diverse etiologies and has been mainly used as a supportive treatment in cholestatic DILI. In this review, we presented a more structured and systematic framework for the potential application of this hepatoprotective agent across a broader range of DILI scenarios. A MEDLINE search of the literature from 1995 to the present retrieved 41 preliminary clinical studies suggesting that UDCA may offer curative and preventive benefits for hepatocellular DILI as well. This aligns with preclinical studies in rodents, showing beneficial effects of UDCA in experimental DILI irrespective of the clinical patterns of injury involved. This could be due to the broad range of potentially beneficial effects of UDCA, which may address the various types of liver damage with different causes and mechanisms seen in all forms of DILI. UDCA’s beneficial properties include anticholestatic, antioxidant, anti-inflammatory, anti-apoptotic, anti-necrotic, mitochondrial protective, endoplasmic reticulum stress-relieving, and immunomodulatory effects. Controlled studies with systematic use of standardized causality assessments are eagerly awaited to properly validate the use of UDCA in DILI. Meanwhile, we hope this article helps clarify and systematize the use of this versatile and safe hepatoprotective medication for different types of liver toxicity.

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.

Fluorescence navigation is a novel technique for accurately identifying hepatocellular carcinoma (HCC) lesions during hepatectomy, enabling real-time visualization. Indocyanine green-based fluorescence guidance has been commonly used to demarcate HCC lesion boundaries, but it cannot distinguish between benign and malignant liver tumors. This review focused on the clinical applications and limitations of indocyanine green, as well as recent advances in novel fluorescent probes for fluorescence-guided surgery of HCC. It covers traditional fluorescent imaging probes such as enzymes, reactive oxygen species, reactive sulfur species, and pH-sensitive probes, followed by an introduction to aggregation-induced emission probes. Aggregation-induced emission probes exhibit strong fluorescence, low background signals, excellent biocompatibility, and high photostability in the aggregate state, but show no fluorescence in dilute solutions. Design strategies for these probes may offer insights for developing novel fluorescent probes for the real-time identification and navigation of HCC during surgery.

Organic anion-transporting polypeptides (OATPs) play a crucial role in the transport of bile acids and bilirubin. In our previous study, interleukin 6 (IL-6) reduced OATP1B3 levels in cholestatic disease. However, it remains unclear whether IL-6 inhibits OATP1B1 expression in cholestatic diseases. This study aimed to investigate whether IL-6 can inhibit OATP1B1 expression and explore the underlying mechanisms.

The effect of stimulator of interferon genes (STING) signaling on inflammatory factors was investigated in a cholestatic mouse model using RT-qPCR and enzyme-linked immunosorbent assay. To assess the impact of inflammatory factors on OATP1B1 expression in hepatocellular carcinoma, we analyzed OATP1B1 expression by RT-qPCR and Western Blot after treating PLC/PRF/5 cells with TNF-α, IL-1β, and IL-6. To elucidate the mechanism by which IL-6 inhibits OATP1B1 expression, we examined the expression of the OATP1B1 regulator TCF4 in PLC/PRF/5 and HepG2 cells using RT-qPCR and Western Blot. The interaction mechanism between β-catenin/TCF4 and OATP1B1 was investigated by knocking down β-catenin/TCF4 through siRNA transfection.

The STING inhibitor decreased inflammatory factor levels in the cholestatic mouse model, with IL-6 exhibiting the most potent inhibitory effect on OATP1B1. IL-6 downregulated β-catenin/TCF4, leading to decreased OATP1B1 expression. Knocking-down β-catenin/TCF4 counteracted the β-catenin/TCF4-mediated repression of OATP1B1.

STING-mediated IL-6 up-regulation may inhibit OATP1B1, leading to reduced transport of bile acids and bilirubin by OATP1B1. This may contribute to altered pharmacokinetics in patients with diseases associated with increased IL-6 production.

Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality and carries a high risk of recurrence. Given the substantial healthcare burden and the evolving nature of CDI, understanding the role of emerging treatment strategies is essential. While oral vancomycin remains a mainstay of CDI treatment, the past decade has brought several notable advances in agents and practices that may be used for CDI treatment and prevention. Fidaxomicin or vancomycin are now recommended for an initial episode of CDI, with several guidelines giving preference to fidaxomicin based on its demonstrated ability to reduce recurrent CDI. Promising developments have emerged regarding the use of fecal microbiota-based therapies in the management of CDI, including conventional fecal microbiota transplantation and the approved live biotherapeutic products, Rebyota and Vowst. These therapies help restore the microbiota of the colon to treat severe CDI and prevent recurrence in select patients. Several strategies have emerged to prevent recurrent CDI, including bezlotoxumab, a single-dose, weight-based IgG1 monoclonal antibody that may be given to patients at high risk of recurrence. Additional pipeline therapies, such as vaccines, beta-lactamases, and bacteriophages, may provide future opportunities for CDI management. This narrative review aimed to summarize societal guideline recommendations for CDI management, describe the evidence for key therapies used in CDI treatment, and review recent updates on emerging treatment modalities.