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.