Type 2 diabetes (T2D) is a metabolic disorder characterized by insulin resistance (IR), inflammation, and dysregulation in glucose metabolism. The disease is spreading globally, partly due to aging, which can damage the immune system and speed up the progression of the metabolic disorder. This review primarily delves into the triggers for T2D within the framework of the ominous octet, which emphasizes 8 principal factors under the “ominous octet” framework that contribute to high blood glucose and associated metabolic disorders. The article studies the interplay of hyperinsulinemia, mitochondrial dysfunction (MD), and endoplasmic reticulum (ER) stress with immune aging in driving disease progression affecting each component of the octet. MD and ER stress can result in defects in insulin signaling, ultimately leading to β-cell death. Chronic inflammation associated with aging, also known as inflammaging, especially affects older adults by worsening IR and glucose regulation, which creates a continuous sequence of metabolic problems. Thus, the “ominous octet” framework provides fundamental knowledge to develop personalized treatment approaches that target metabolic dysfunction together with ER stress, MD, and immune system imbalances. These strategies show promising potential to improve treatments for T2D and may lead to better health outcomes for older adults dealing with this condition.

The proto-oncogene c-Fos is known as a reliable marker of cell activation, which is immediately induced after a new stimulus in specific brain regions, depending on the nature of the stimulus applied. However, the expression of c-Fos is increased in Alzheimer’s disease (AD) and contributes to amyloid β-peptide-induced neurotoxicity. This review attempted to focus on the role of c-Fos in learning and memory in both healthy brain and AD, emphasizing on possible mechanisms. Comparing the available findings, regarding learning and memory, c-Fos expression leads to memory formation through ERK (extracellular signal-regulated kinase)/CREB (cAMP response element-binding protein) and long-term potentiation, while it is down regulated after the repetition and habituation of stimuli. However, its overexpression in neurons and glia of AD, contributes to cognitive deficits and neuronal loss, which represents a defect in its ability to habituate to repeated stimuli. Also, expression pattern in glial is associated with constitutive CREB activation following increasing amyloid beta (Aβ), activation transcription factor (ATF3), and cytochrome c in apoptosis pathways. Thus, two contradictory roles of c-Fos in the healthy brain and AD, reveal more complexity in c-Fos up and down stream signaling pathways, bioavailability, and sensitivity. Future studies focusing on c-Fos modulation, might offer promising strategies to mitigate cognitive decline in AD.

Chronic subdural hematoma (CSDH) is a common disease in neurosurgery, with epidemiological characteristics showing an overall annual incidence of 1.7–20.6 per 100,000 people and a higher prevalence in the elderly. However, despite the increased disease burden, there have been limited breakthroughs in treatment options over the past 20 years. A significant gap exists in our understanding of the exact pathophysiological mechanism of CSDH, leading to a lack of specific clinical treatment options based on a clear pathological mechanism. Current research suggests that the development of CSDH involves dual mechanisms of trauma and inflammation, and that these pathologic processes together promote pathological changes such as angiogenesis, inflammatory response, and neovascularization. Therapies for CSDH encompass both surgical (e.g., twist-drill drainage, burr-hole drainage, craniotomy) and non-surgical approaches (e.g., clinical observation, medication, intracranial pressure monitoring, anticoagulation). Meanwhile, middle meningeal artery embolization, as an emerging minimally invasive interventional technique, has shown good prospects for clinical application. This review aims to bridge the gap between current treatment options and the need for effective strategies by providing a comprehensive summary of the epidemiological trends, pathophysiological advances, and optimization of therapeutic strategies for CSDH.

Type 1 diabetes (T1D) develops when the immune system targets and destroys pancreatic β-cells responsible for insulin production, ultimately resulting in reduced insulin levels. Islet transplantation has garnered significant attention as a potential treatment, but it presents numerous challenges that hinder its effectiveness for T1D patients. A primary issue is the immune system’s tendency to reject transplanted islets, leading to a gradual decline in their functionality. Furthermore, many individuals remain reliant on additional insulin therapy. These challenges are exacerbated by the global shortage of organ donors, which limits the availability of pancreata for transplantation. This review outlines several innovative strategies to regenerate insulin-producing β-cells for the treatment of T1D, with a primary focus on pancreatic progenitor and stem cells. The strategy of converting non-β cells, particularly pancreatic α-cells, into functional β-cells continues to show promise. Moreover, α-cells, which are less vulnerable to autoimmune attacks, present a distinct opportunity for β-cell regeneration in individuals with T1D. While the use of progenitor or stem cells for β-cell regeneration appears encouraging, various hurdles, such as immune rejection, suboptimal differentiation, and other challenges, still impede the implementation of this strategy. Nonetheless, this approach may ultimately pave the way for long-lasting treatment and potential cures for T1D.

Gastrointestinal (GI) health is essential for maintaining systemic balance, influencing digestion, immunity, and neuroendocrine signaling. However, GI disorders such as irritable bowel syndrome, inflammatory bowel disease, gastroesophageal reflux disease, peptic ulcers, and constipation are increasingly prevalent, significantly affecting global health and healthcare economics. Although conventional pharmacological treatments offer symptomatic relief, their long-term use is often associated with adverse effects, resistance, and limited efficacy, prompting a shift toward alternative and complementary therapies. Traditional systems of medicine, such as Ayurveda, Traditional Chinese Medicine, Unani, and Siddha, emphasize holistic approaches, including herbal formulations that target underlying causes rather than just symptoms. This review provides a comprehensive analysis of the role of natural products and traditional herbals in GI health. It discusses key bioactive constituents, flavonoids, alkaloids, terpenoids, and polyphenols, known for their anti-inflammatory, antimicrobial, gastroprotective, and prebiotic properties. Widely used herbal remedies such as Triphala, licorice root, peppermint oil, turmeric, and psyllium are highlighted for their proven therapeutic actions. Additionally, the review documents more than 300 medicinal plants traditionally used in diverse cultures worldwide for managing GI conditions, based on ethnopharmacological evidence. While the therapeutic promise is substantial, challenges such as formulation standardization, herb-drug interactions, and limited clinical data remain. The review underscores the need for integrating traditional wisdom with modern scientific validation, offering a path forward for safe, effective, and personalized GI healthcare.

Thrombocytopenia in cirrhosis presents significant challenges in clinical practice. To help clinicians rapidly understand and standardize the diagnosis and treatment of this condition, the Liver Fibrosis, Cirrhosis, and Portal Hypertension Group under the Chinese Society of Hepatology, Chinese Medical Association, convened experts across relevant fields to formulate the Expert Consensus for the Management of Thrombocytopenia in Cirrhosis. This consensus aimed to provide evidence-based guidance for clinical diagnosis and treatment.

Acute liver failure (ALF) is a disorder with various etiologies. Although the causes leading to this disruptive condition are well documented in published ALF cohorts, there is significant concern among patients who experience ALF with indeterminate causes, an issue requiring thorough analysis. This review aimed to analyze cohort studies on ALF with a focus on unknown causes leading to classification as indeterminate ALF. The analysis revealed that, among 67 worldwide adult and pediatric ALF cohorts, indeterminate causes of ALF ranged from 2% to 100%, with an average of 30%. Among the 13 pediatric ALF cohorts, the corresponding range was 22% to 100%, with an average of 47%, while among the 55 adult ALF cohorts, the range was 2% to 78%, with an average of 26%. The percentage values were higher in pediatric cohorts due to the higher incidence of rare genetic causes compared to adult patients. Notably, higher rates of indeterminate causes were found in cohorts studied before the availability of diagnostic serologic screening parameters and polymerase chain reaction techniques for various hepatitis virus infections. Patients with indeterminate ALF may not have received a specific treatment that, if effective, could have helped prevent liver transplantation. It is concluded that, in future cases, all efforts must be undertaken to clearly establish the cause of severe liver injury, enabling effective therapy when available and helping reduce the risk of progression to ALF and the need for liver transplantation.

Persistent liver injury halts the regenerative capacity of hepatocytes and activates mechanisms that result in the replacement of normal hepatic parenchyma with extracellular matrix deposits. As liver fibrosis develops, the liver undergoes architectural changes and alterations in microcirculation that lead to increased intrahepatic vascular resistance and portal hypertension. Thrombocytopenia is a prevalent condition in patients with chronic liver disease and portal hypertension. Multiple mechanisms related to increased platelet destruction or decreased platelet production contribute to thrombocytopenia. Increased platelet destruction occurs due to splenic sequestration caused by hypersplenism or immune-mediated conditions. Decreased platelet production results from a decline in thrombopoietin production, bone marrow suppression by medications, or toxic insults. Therapies aimed at improving thrombocytopenia are controversial, and individual factors must be considered. Although hepatic venous pressure gradient measurement is the gold standard for diagnosing portal hypertension, non-invasive tests show adequate correlation with hepatic venous pressure gradients. Various clinical risk scores consider platelet counts as independent predictors of adverse liver outcomes, such as the development of esophageal varices and the presence of advanced fibrosis. Nonselective beta-blockers are the cornerstone of long-term management for clinically significant portal hypertension. Indications for transjugular intrahepatic portosystemic shunt placement include failure to control portal hypertension-related bleeding, early rebleeding, and refractory or recurrent ascites. Ultimately, liver transplantation is the only definitive cure for portal hypertension and its major complications, including thrombocytopenia. Understanding the mechanisms underlying thrombocytopenia in patients with portal hypertension and chronic liver disease is essential for accurate diagnosis and effective patient management. This review aimed to evidence on the pathophysiological mechanisms linking chronic liver disease, portal hypertension, and thrombocytopenia, and to discuss their diagnostic and therapeutic implications.

Recent advancements in cancer immunotherapy have highlighted glypican-3 (GPC3) as a prominent target for treating hepatocellular carcinoma (HCC). However, approximately 10% to 30% of HCC patients exhibit low or absent GPC3 expression on the surface of tumor cells, which limits the feasibility of GPC3-targeted therapies. Consequently, it is essential for patients to undergo pre-diagnostic assessments of GPC3 expression in tumor cells to evaluate their suitability for GPC3-directed therapy. Although various methods have been developed to specifically detect GPC3 as a biomarker for treatment and prognosis, the diagnostic approaches currently employed in clinical studies remain relatively limited. Here, we provide a comprehensive overview of the clinical development of GPC3-targeted therapeutics, clinical trials in GPC3-positive HCC, and current methods for detecting GPC3 expression, highlighting their advantages and limitations. Furthermore, we explore the potential of integrating targeted therapy with various GPC3 detection modalities tailored to different pathological stages. This integration not only provides insights into the selection of effective methods for detecting GPC3 expression but also has the potential to significantly improve the clinical outcomes of patients with liver cancer. By simultaneously assessing the advantages and disadvantages of these methods, this review aims to establish a theoretical foundation for the clinical selection of appropriate GPC3 detection strategies for targeted therapy.

Chronic hepatitis B virus (HBV) infection remains a major cause of liver diseases, including cirrhosis and hepatocellular carcinoma. Reliable biomarkers for assessing viral replication, liver damage, and predicting clinical outcomes are essential for effective patient management. This review focuses on two promising biomarkers: serum HBV RNA and hepatitis B core-related antigen, both of which show strong correlations with viral replication and disease progression. Serum HBV RNA levels reflect the quantity and transcriptional activity of intrahepatic covalently closed circular DNA, providing insights into viral replication. They also correlate with other markers of replicative activity and have predictive value for key clinical outcomes, including hepatitis B e antigen and hepatitis B surface antigen seroconversion, relapse after therapy cessation, and liver fibrosis. Similarly, hepatitis B core-related antigen is closely associated with covalently closed circular DNA levels, correlates with markers of viral replication, and shows promise in predicting liver fibrosis, cirrhosis, and the risk of hepatocellular carcinoma. This review highlights the potential of both biomarkers for monitoring disease progression and guiding therapeutic decisions, particularly in the context of personalized treatment strategies and risk assessment for liver-related complications.