Liver failure profoundly affects the immune system, leading to dysregulation of innate and adaptive immune response. This review explores the intricate relationship between liver function and immune homeostasis. The role of the liver as a central hub in immune response initiation is elucidated, emphasizing its involvement in hepatic inflammation induction and subsequent systemic inflammation. Cytokines, chemokines, growth factors, and lipid mediators orchestrate these immune processes, serving as both prognostic biomarkers and potential therapeutic targets in liver failure-associated immune dysregulation, which might result from acute-on-chronic liver failure (ACLF) and cirrhosis. Furthermore, the review delves into the mechanisms underlying immunosuppression in liver failure, encompassing alterations in innate immune cell functions such as neutrophils, macrophages, and natural killer cells (NK cells), as well as perturbations in adaptive immune responses mediated by B and T cells. Conclusion: Understanding the immunological consequences of liver failure is crucial for developing targeted therapeutic interventions and improving patient outcomes in liver disease management.

Photodynamic therapy (PDT) has emerged as a promising therapeutic approach owing to its non-invasive nature and minimal toxicity. PDT involves the administration of a photosensitizing agent (PS), which, upon light activation, induces a photodynamic reaction (PDR), leading to targeted cell destruction. However, developing resistance to PDT poses a significant challenge to its effectiveness. Various factors, including properties and administration of PSs, mediate this resistance. Despite the widespread use of substances like 5-aminolevulinic acid (5-ALA) and protoporphyrin, their efficacy is limited due to restricted tumor penetration and a lack of tumor targeting. To address these limitations, nano-delivery techniques and newer PSs like Aza-BODIPY and its derivatives, which offer enhanced tissue penetration, are being explored. In this paper, we provide an overview of resistance mechanisms in PDT and discuss novel methods, substances, and technologies to overcome resistance to improve clinical outcomes in tumor treatment.

Caffeine, one of the most widely consumed bioactive compounds worldwide, is gaining recognition for its potential anticancer properties beyond its well-known neurological and metabolic effects. Mechanistically, caffeine exerts anti-tumor activity by modulating key cellular pathways involved in carcinogenesis, including the inhibition of phosphodiesterases, antagonism of adenosine A2A receptors, and disruption of the DNA damage response through ATR-Chk1 pathway inhibition. These actions collectively promote apoptosis, suppress tumor cell proliferation, and impair metastatic spread. In vitro and in vivo studies have demonstrated that caffeine can enhance the cytotoxic effects of chemotherapeutic agents and radiation therapy, suggesting a synergistic role in conventional cancer treatments. Epidemiological data further supports an inverse association between habitual caffeine consumption and the incidence of several cancers, notably liver, colorectal, breast, and prostate cancers. Among these, the most consistent experimental and clinical evidence exists for liver and colorectal cancer, where caffeine’s modulatory effects on inflammation and cell proliferation have been repeatedly observed. Additionally, caffeine’s anti-oxidant and anti-inflammatory properties may contribute to a microenvironment less conducive to tumor initiation and progression. While promising, the anticancer effects of caffeine are influenced by factors such as dosage, individual genetic variability, and cancer type, underscoring the need for further clinical investigation. This review explores the emerging role of caffeine as a potential chemopreventive and adjuvant therapeutic agent in oncology.

The mismatch repair system is critical for correcting base–base mismatches and insertion-deletion loops during DNA replication. Deficiencies in MMR (due to mutations in MLH1, MSH2, MSH6, or PMS2) lead to microsatellite instability and contribute to the development of various cancers, such as Lynch syndrome-related colorectal cancer and sporadic tumors. This review will delve into the molecular basis of MMR deficiency. Additionally, the review will cover diagnostic approaches for detecting MSI and MMR deficiency, including next-generation sequencing and PCR-based methods. The implications for treatment will be discussed, emphasizing immune checkpoint inhibitors (e.g., pembrolizumab) that target tumors with high mutational burdens due to MMR deficiency, as well as novel therapeutic approaches like synthetic lethality exploiting DNA repair vulnerabilities.

Systemic lupus erythematosus (SLE) is a chronic, autoimmune inflammatory disease with a multisystem manifestation and a variety of clinical symptoms. Over the last decades, the prognosis and life expectancy of patients with SLE improved significantly due to the implementation of corticosteroids combined with immunosuppressive agents. Nevertheless, the use of these medications is often associated with the occurrence of serious side effects and additional deterioration of organ function. Therefore, developing and implementing novel therapies that are both safer and more effective in managing disease is crucial. For a long time, European Alliance of Associations for Rheumatology (EULAR) recommended only 2 biological agents in the treatment of SLE: belimumab and rituximab. However, in 2023, anifrolumab, an interferon (IFN) receptor inhibitor, and voclosporin, a novel calcineurin inhibitor, appeared in new SLE treatment guidelines. In addition, several biological agents are targeting different cells or cytokines that are being evaluated in phase II and III clinical trials. Apart from that, experimental therapies such as targeting of plasma cells, chimeric antigen receptor T-cell therapy (CAR-T) or stem cell transplantation appear promising in the treatment of the severe forms of SLE.

Background: Liver failure profoundly affects the immune system, leading to dysregulation of innate and adaptive immune responses. Body: This review explores the intricate relationship between liver function and immune homeostasis. The role of the liver as a central hub in immune response initiation is elucidated, emphasizing its involvement in hepatic inflammation induction and subsequent systemic inflammation. Cytokines, chemokines, growth factors, and lipid mediators orchestrate these immune processes, serving as both prognostic biomarkers and potential therapeutic targets in liver failure-associated immune dysregulation. Furthermore, the review delves into the mechanisms underlying immunosuppression in liver failure, encompassing alterations in innate immune cell functions such as neutrophils, macrophages, and natural killer cells (NK cells), as well as perturbations in adaptive immune responses mediated by B and T cells. Conclusion: Understanding the immunological consequences of liver failure is crucial for developing targeted therapeutic interventions and improving patient outcomes in liver disease management.