Intrahepatic cholangiocarcinoma (iCCA) is the second most prevalent primary liver cancer, characterized by insidious onset and high malignancy. Many patients are diagnosed at an inoperable stage, and the effectiveness of chemotherapy and radiotherapy remains limited. This study aimed to provide a comprehensive review of the histological classification, genetic alterations, molecular subtypes, and corresponding imaging signatures of iCCA, highlighting its heterogeneity and offering insights into targeted therapy and personalized treatment. The heterogeneity of iCCA poses significant challenges to both targeted therapy and immunotherapy, necessitating in-depth exploration at the molecular and subtyping levels. Investigating genetic variations, signaling pathway alterations, and molecular subtypes can aid in patient stratification. Stratifying iCCA patients allows for more precise treatment selection, ultimately improving survival outcomes. Imaging, as a non-invasive tool, holds substantial potential for predicting subtypes and molecular profiles. It is possible to infer histological and molecular features from imaging, or to interpret imaging signatures in light of known histological and molecular data. This integrative approach, combining external imaging with internal molecular insights, fosters a comprehensive understanding of iCCA’s characteristics and enhances clinical management.

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.

The diagnosis of hepatic precancerous lesions (HPC) and early hepatocellular carcinoma (HCC) has significant public health implications and holds the potential to reduce the global burden of HCC. This study aimed to identify molecular features and biomarkers associated with HPC progression and early HCC development.

RNA sequencing was used to identify differentially expressed genes in mouse HPC tissues and normal liver tissues. Cyclin E1 (CCNE1) expression in HPC tissues and HCC cells was assessed using immunohistochemistry, Western blotting, and real-time polymerase chain reaction. The effects of CCNE1 on HCC cell proliferation, migration, invasion, and apoptosis were evaluated using colony formation, wound healing, Transwell assays, and flow cytometry. The mechanism of CCNE1 was explored through Kyoto Encyclopedia of Genes and Genomes pathway analysis and gene set enrichment analysis and further validated through in vitro experiments. The interaction between CCNE1 and tumor-associated macrophages (TAMs) was investigated by co-culturing HCC cells with macrophages.

RNA sequencing and TCGA database analysis showed that CCNE1 expression was significantly elevated in mouse HPC tissues and human HCC samples and was associated with reduced survival rates. In vitro assays demonstrated that CCNE1 promoted HCC cell proliferation, migration, invasion, and survival by activating the PI3K/Akt signaling pathway. Additionally, CCNE1 induced TAM polarization toward the M2 phenotype by promoting the expression of CCL2 and CCL5 in HCC cells.

CCNE1 promotes HPC progression and HCC cell proliferation, migration, invasion, and survival by activating the PI3K/Akt signaling pathway. Furthermore, CCNE1 enhances the secretion of CCL2 and CCL5 by HCC cells, promoting TAM infiltration and M2 polarization, thereby contributing to tumor progression.

Tumors are complex systems characterized by variations across genetic, transcriptomic, phenotypic, and microenvironmental levels. This study introduced a novel framework for quantifying cancer cell heterogeneity using single-cell RNA sequencing data. The framework comprised several scores aimed at uncovering the complexities of key cancer traits, such as metastasis, tumor progression, and recurrence.

This study leveraged publicly available single-cell transcriptomic data from three human breast cancer subtypes: estrogen receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative. We employed a quantitative approach, analyzing copy number alterations (CNAs), entropy, transcriptomic heterogeneity, and diverse protein-protein interaction networks (PPINs) to explore critical concepts in cancer biology.

We found that entropy and PPIN activity related to the cell cycle could distinguish cell clusters with elevated mitotic activity, particularly in aggressive breast cancer subtypes. Additionally, CNA distributions varied across cancer subtypes. We also identified positive correlations between the CNA score, entropy, and the activities of PPINs associated with the cell cycle, as well as those linked to basal and mesenchymal cell lines.

This study addresses a gap in the current understanding of breast cancer heterogeneity by presenting a novel quantitative approach that offers deeper insights into tumor biology, surpassing traditional marker-based methods.

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.

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.

Memory loss is a symptom of several neurological disorders, including dementia and Alzheimer’s disease (AD). It can significantly impact individuals, their loved ones, and society as a whole. Current pharmaceutical interventions have shown some improvement in individuals’ quality of life, but more needs to be done to reduce the burden of memory loss and AD. This paper investigates herbal remedies for memory loss, with a particular focus on the mechanisms underlying their effects. By consulting several South Asian printed books, numerous traditionally used medicinal plants with memory-enhancing properties were identified. A review of published studies showed that many of these plants have reported properties related to memory enhancement and the treatment of AD. Some of the relevant mechanistic actions reported for these plants include acetylcholinesterase inhibition, anti-inflammatory activity, antioxidant effects, and neuroprotective properties. There is also evidence that some plants exhibit a combination of different mechanisms, making them especially promising as therapeutic agents for memory loss. Our review shows the existence and potential of medicinal plants in addressing memory loss. Additionally, some reports provide a scientific basis for the use of these plants in conditions characterized by memory decline, such as AD. This study underscores the importance of further research to evaluate the efficacy of traditionally used medicinal plants in the management of memory loss.

Mucinous cystic neoplasms (MCNs) are rare pancreatic lesions that often go undiagnosed due to their asymptomatic nature. Though typically benign, they can harbor malignant potential, making early detection and treatment essential. This case report presents a 32-year-old female with intermittent epigastric pain, who was found to have a cystic lesion in the pancreatic tail, diagnosed as an MCN through endoscopic ultrasound and fine-needle aspiration. The patient underwent a spleen-sparing distal pancreatectomy, which was complicated by a peri-pancreatic abscess that required drainage. This case highlights the importance of distinguishing MCNs from other pancreatic cystic lesions, as misdiagnosis or delayed intervention can lead to adverse outcomes. It underscores the need for vigilant diagnostic imaging and individualized treatment strategies, particularly in young patients, to avoid unnecessary morbidity and ensure optimal outcomes. The report contributes to the growing understanding of MCNs, emphasizing early diagnosis, tailored surgical management, and the significance of postoperative care.

Cardiovascular diseases (CVDs) remain the leading cause of global morbidity and mortality, highlighting the urgent need for innovative diagnostic and prognostic approaches to address their complex pathophysiology. Recent advances in molecular cardiology have unveiled immune-derived microRNAs (miRNAs), or immuno-miRs, as pivotal regulators in the interplay between immune responses and cardiovascular pathology. Secreted by immune cells such as T lymphocytes, macrophages, and neutrophils, these small non-coding RNAs modulate critical signaling pathways by regulating gene expression. Immuno-miRs influence essential processes, including inflammation, endothelial dysfunction, and fibrotic remodeling—core mechanisms underlying conditions such as atherosclerosis, myocardial infarction, and heart failure. Moreover, their presence in systemic circulation within extracellular vesicles underscores their role in intercellular communication, impacting both immune and non-immune cardiovascular cells, such as cardiomyocytes and endothelial cells. This dual functionality renders immuno-miRs promising candidates as diagnostic biomarkers for early disease detection and as prognostic tools for assessing disease progression and therapeutic efficacy. Furthermore, emerging miRNA-based interventions—such as miRNA mimics and inhibitors—show considerable promise in modulating immune dysregulation in CVDs, although clinical translation remains a significant challenge. In this review, we comprehensively examine the regulatory roles of immuno-miRs in both innate and adaptive immune responses and explore recent advancements in miRNA-based therapies. By consolidating current knowledge and identifying existing gaps, we provide a comprehensive overview of the transformative potential of immuno-miRs in CVD management. Integrating these molecules into personalized medicine may pave the way for more effective, targeted, and minimally invasive strategies to combat one of the world’s most pressing health challenges.

Fat mass and obesity-associated protein (FTO) has been linked to various cancers, though its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate FTO expression, its clinical relevance, functional role in HCC progression, and the underlying molecular mechanisms.

Quantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis were used to assess FTO expression in HCC. Functional assays, including proliferation, invasion, and epithelial-mesenchymal transition studies, were conducted using HCC cell lines with FTO knockdown. N6-methyladenosine (m6A) RNA immunoprecipitation and RNA stability assays further elucidated the role of FTO in BUB1 mRNA methylation and stability. Co-immunoprecipitation studies were employed to confirm the interaction between BUB1 and TGF-βR1. In vivo studies in nude mice were conducted to evaluate tumor growth following FTO knockdown.

FTO was significantly upregulated in HCC tissues compared to normal liver tissues, with higher expression observed in advanced tumor-node-metastasis stages and metastatic HCC. Elevated FTO correlated with poor overall survival in patients. Silencing FTO decreased HCC cell proliferation, colony formation, invasion, epithelial-mesenchymal transition, and tumor growth in nude mice. Mechanistically, FTO downregulation led to increased m6A modification of BUB1 mRNA, thereby promoting its degradation via the YTH domain family 2-dependent pathway and reducing BUB1 protein levels. Additionally, BUB1 physically interacted with TGF-βR1, activating downstream TGF-β signaling.

FTO is overexpressed in HCC and is associated with poor clinical outcomes. Mechanistically, FTO promotes HCC progression by stabilizing BUB1 mRNA through an m6A-YTH domain family 2–dependent pathway, which activates TGF-β signaling. Targeting the FTO–BUB1–TGF-βR1 regulatory network may offer a promising therapeutic strategy for HCC.

Hepatocellular carcinoma (HCC) remains challenging to treat in advanced stages, primarily due to the development of resistance to sorafenib. There is an urgent need for novel therapeutic strategies to overcome this resistance. This study aimed to investigate the potential of oleanolic acid (OA), a natural hepatoprotective compound, in mitigating sorafenib resistance and elucidate its underlying molecular mechanisms.

Sorafenib-resistant Huh7 and HepG2 cell lines were established to mimic the resistant phenotype. The effects of OA on these cells were evaluated by assessing cell invasion, migration, and sensitivity to sorafenib. Gene expression analysis was conducted to identify molecular changes induced by OA treatment, with a focus on fabp3 expression.

Oleanolic acid significantly inhibited the invasive and migratory capabilities of sorafenib-resistant Huh7 and HepG2 cells (p < 0.01). Furthermore, OA treatment downregulated fabp3 expression and restored the cells’ sensitivity to sorafenib.

Oleanolic acid shows promise as an adjunct therapy for overcoming sorafenib resistance in HCC. By reducing cell aggressiveness and restoring drug sensitivity, OA may enhance the therapeutic efficacy of current treatments for advanced HCC.

This review explores the complex interplay between the microbiome and human aging, highlighting how dysbiosis impacts host physiology and health, particularly in relation to genomic stability and telomere attrition. Recent advances in cellular and molecular biology have underscored the role of both intrinsic and extrinsic factors in human aging, with the microbiome emerging as a key determinant of host physiology and health. Dysbiosis—disruptions in microbiome composition—is linked to various age-related diseases and impacts genomic stability and telomere attrition, the progressive shortening of telomeres that limits cell division and contributes to aging. This review examines how microbiome dynamics influence aging by triggering inflammation, oxidative stress, immune dysregulation, and metabolic dysfunction, all of which affect two primary hallmarks of aging: genomic instability and telomere attrition. Understanding these interactions is essential for developing targeted interventions to restore microbiome balance and promote healthy aging, offering potential treatments to extend healthspan and alleviate aging-related diseases. The convergence of microbiome and aging research promises transformative insights and new avenues for improving global population well-being.

Chronic obstructive pulmonary disease (COPD) is an irreversible inflammatory lung disease. Studies have shown that macrophages and estrogen receptors play a pivotal regulatory role in the development of COPD. Ejiao (Colla Corii Asini, CCA, or donkey-hide gelatin), a traditional Chinese medicine, has anti-inflammatory and lung function-protective effects, but its specific mechanism in COPD remains unclear. This study aimed to explore the immunomodulatory effects of Ejiao on COPD, focusing on its impact on inflammatory pathways and macrophages.

This study is the first to apply a network pharmacology approach to explore the potential mechanisms underlying Ejiao’s therapeutic effects on COPD. We collected the peptides and chemical components of Ejiao and used the STRING database to screen for COPD-related targets of Ejiao components, constructing a drug-molecular network. Additionally, we established cigarette smoke extract (CSE) and lipopolysaccharide-induced cell injury models and treated them with Ejiao-containing serum. Western blot (WB) analysis was used to detect the expression of related proteins, enabling a preliminary exploration of Ejiao’s effects and regulatory mechanisms. In further experiments, a mouse COPD model was established, and eight weeks of Ejiao intervention were conducted. We assessed lung function, pathological changes in lung tissue, monitored cytokine levels in serum and bronchoalveolar lavage fluid, performed flow cytometry to evaluate abdominal macrophage levels, and conducted WB to analyze protein expression, providing an in-depth study of Ejiao’s regulatory effects on the mouse COPD model.

The findings from the network pharmacology analysis suggest a potential regulatory role of the estrogen receptor pathway in COPD. CSE stimulation of RAW264.7 cells resulted in elevated tumor necrosis factor-α levels, decreased interleukin-10 levels, reduced expression of estrogen receptors (ERs) α and β, decreased inhibitor of NF-κB levels, and increased p-AKT levels. Following Ejiao intervention, interleukin-10, ERα+β, and inhibitor of NF-κB levels increased, while p-AKT levels decreased. Ejiao significantly improved lung function in CSE/lipopolysaccharide-induced COPD mice, reduced the number of macrophages, lowered the levels of inflammatory factors in bronchoalveolar lavage fluid, and increased estradiol levels in serum. WB results indicated that Ejiao may ameliorate lung injury in COPD by modulating the ER/AKT/NF-κB pathway.

The results suggest that Ejiao may improve lung injury and inflammation in CSE/ lipopolysaccharide-induced COPD by regulating the ER/AKT/NF-κB pathway.

Lung Squamous cell carcinoma (LSCC) represents the second most common non-small cell lung cancer. Although studies identified adenocarcinoma-like driver mutations in LSCC using next-generation sequencing (NGS), the disease is challenging to treat due to the limited number of detectable mutations for targeted drug therapy. This study aimed to evaluate the mutation profiles of LSCC detected by NGS to assess the relationships between different driver mutations and clinicopathological parameters.

NGS with a panel of 72 cancer-related genes was used to evaluate the driver mutation profiles of 41 lung resection specimens from patients with LSCC at the Molecular Pathology Laboratory of Aydın Adnan Menderes University in Türkiye. Clinical and histopathological features were recorded for analysis.

Detection of 94 mutations in 23 genes in DNA extracted from the tissue samples of 36 patients revealed that the most prevalent mutations were TP53 (30.85%), NF1 (20.20%), PTEN (11.70%), PIK3CA (5.31%), FBXW7 (4.25%), KRAS (3.20%), respectively. We identified statistically significant relationships between PIK3CA and lower mean age (p = 0.007) and between PTEN and mild inflammatory reaction (p = 0.004). PTEN was associated with central localization (p = 0.13), NF1 with visceral pleural involvement (p = 0.09), and PIK3CA with severe inflammatory reaction (p = 0.053), as well as with advanced pathological T stage (p = 0.09) and pathological N stage (p = 0.057) according to the TNM staging system.

Our study highlights the importance of assessing mutation profiles in LSCC patients to identify driver mutations as potential therapeutic targets. Certain histopathological features are associated with these mutations, serving as indicators for treatment and follow-up decisions.

Surgical management of supratentorial spontaneous intracerebral hemorrhage (sICH) remains controversial. Craniotomy (CT) reduces mortality but offers limited functional benefits. Neuroendoscopic surgery (NE) has emerged as a viable alternative, providing improved outcomes. Recent randomized controlled trials (RCTs) strengthen ongoing comparisons between these approaches. This meta-analysis systematically evaluates the efficacy and safety of NE versus CT for supratentorial sICH.

RCTs comparing NE versus CT for supratentorial sICH were systematically identified through comprehensive searches of PubMed, Embase, Cochrane Library, and Web of Science databases. Evaluated outcomes included functional outcome (favorable or unfavorable), hematoma evacuation rate, mortality, intraoperative blood loss, operation time, rebleeding, infection (including pulmonary and intracranial), and total complications. Cochrane’s Risk of Bias-2 tool was employed to assess the risk of bias across the included studies.

Eight RCTs were included, comprising 1,354 patients. NE demonstrated a significant advantage in achieving a favorable functional outcome (risk ratio: 1.43; 95% confidence interval (CI) 1.22, 1.68; p < 0.001) and a notably higher hematoma evacuation rate (mean difference (MD): 7.60; 95% CI 3.59, 11.61; p < 0.001). Additionally, NE was associated with a marked reduction in intraoperative blood loss (MD: −152.95; 95% CI −261.68, −44.22; p = 0.006) and a substantial reduction in operative time (MD: −118.49; 95% CI −147.30, −89.67; p < 0.001). The incidences of unfavorable functional outcome and total complications, including pulmonary infection, were significantly lower in the NE group. However, NE did not lead to an improvement in the mortality rate, and there were no significant differences in the incidences of postoperative rebleeding or intracranial infection between the two groups.

These findings suggest that NE offers distinct advantages in terms of functional outcomes and surgical efficiency for patients with supratentorial sICH. Future studies should involve larger, higher-quality RCTs, and neuroendoscopic techniques should be continuously optimized.

With the increasing use of artificial intelligence (AI) in diagnostics, AI algorithms have shown great potential in aiding diagnostics. As more of these algorithms are developed, there is overwhelming enthusiasm for implementing digital and artificial intelligence-based pathology (DAIP), but doubts and pitfalls are also emerging. However, few original or review articles address the limitations and practical aspects of implementing DAIP. In this review, we briefly examine the evidence related to the benefits and pitfalls of DAIP implementation and argue that DAIP is not suitable for every clinical laboratory.

We searched the PubMed database using the following keywords: “digital pathology,” “digital AI pathology,” and “AI pathology.”. Additionally, we incorporated personal experiences and manually searched related papers.

Ninety-two publications were found, of which 24 met the inclusion criteria. Many advantages of DAIP were discussed, including improved diagnostic accuracy and equity. However, several limitations of implementing DAIP exist, such as financial constraints, technical challenges, and legal/ethical concerns.

We found a generally favorable but cautious outlook for the implementation of DAIP in the pathology workflow. Many studies have reported promising outcomes in using AI for diagnosis and analysis; however, there are also several noteworthy limitations in implementing DAIP. Therefore, a balance between the benefits and pitfalls of DAIP must be thoroughly articulated and examined in light of the institution’s needs and goals before making the decision to implement DAIP. Approaches for mitigating machine learning biases were also proposed, and the adaptation and growth of the pathology profession were discussed in light of DAIP development and advances.

This review explores how the gut microbiome influences aging, particularly examining the effects of microbiome imbalances (dysbiosis) on immune system function, inflammation, and the integrity of genetic material. As we age, there is a noticeable decline in cellular and physiological capabilities, which heightens the risk of diseases and diminishes the body’s resilience to stress. A significant contributor to this decline is the change in the gut microbiome, which affects immune reactions, triggers chronic inflammation, and worsens DNA damage. The review is structured into several key areas: first, the connection between dysbiosis and age-related ailments such as rheumatoid arthritis, Crohn’s disease, and systemic lupus erythematosus; second, how aging influences immune tolerance, especially regarding dendritic cells, and its link to autoimmune diseases; third, the acceleration of immunosenescence and the prolonged inflammatory responses associated with aging; and fourth, the impact of senescent cells and oxidative stress on increasing inflammation and damaging DNA. We also underscored the significance of short-chain fatty acids produced by beneficial gut bacteria in modulating immune responses and facilitating DNA repair. The discussion includes the potential use of probiotics and other microbiome-related interventions as treatment options to promote healthy aging. Ultimately, we stressed the necessity for additional research to deepen our comprehension of the microbiome’s effect on DNA damage and to create personalized therapeutic strategies for fostering healthier aging and enhancing longevity.