Lung cancer (LC) remains the leading cause of cancer-related deaths worldwide, characterized by high mortality rates and limited treatment options. MicroRNAs (miRNAs) are critical regulators of gene expression and play significant roles in the development of LC. This review aimed to provide a comprehensive analysis of oncogenic miRNAs involved in LC, focusing on their dysregulation, functional roles, and potential implications for diagnosis and therapy. In this review, we collected data from published literature, specifically selecting English articles closely related to the topic. We conducted a thorough review of studies published between 2013 and 2023, utilizing prominent academic databases such as PubMed, Scopus, and Google Scholar to gather relevant data. Our investigation highlights several oncogenic miRNAs that have been shown to play critical roles in lung cancer biology, including miR-9-5p, miR-21, and miR-31. These miRNAs are known to facilitate various key processes, such as tumor cell proliferation, enhanced migratory capabilities, and the development of resistance to chemotherapeutic agents. Additionally, miRNAs present significant diagnostic and therapeutic potential. In conclusion, the unique roles and regulatory networks of miRNAs in LC warrant extensive further research. Further research is essential to uncover the complex networks of miRNAs and to develop innovative miRNA-based therapies for lung cancer.

Metabolic dysfunction-associated steatotic liver disease has emerged as a leading cause of chronic liver disease and cirrhosis in the Western world. With rising rates of obesity, the prevalence of metabolic dysfunction-associated steatohepatitis (MASH)-related cirrhosis is expected to increase. MASH is associated with chronic hepatic inflammation and progressive liver fibrosis, and significant research is focused on developing pharmacological therapies to reverse these downstream complications. Recent trials have explored various therapeutic targets across metabolic, inflammatory, and fibrogenic pathways aimed at decreasing liver triglycerides, inflammation, lipotoxicity, and fibrosis. Some of these drugs show promise in reversing biomarkers and/or histologic markers of steatohepatitis and fibrosis, although most have been primarily studied in non-cirrhotic patients. However, in the context of the significant unmet medical need of patients with MASH-associated cirrhosis, growing interest in targeting compensated cirrhosis has prompted renewed investment in numerous early clinical and late-stage programs evaluating novel investigational agents in this population. This review summarizes current therapies under evaluation in phase 2 and 3 clinical trials for MASH-related cirrhosis, highlighting drug mechanisms, outcomes, and future research directions.

Patients with acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) are at high risk of bleeding with traditional artificial liver support systems. To address the bleeding risk in liver failure patients, the safety of regional mesylate anticoagulation (RMA) in centrifugation artificial liver support systems (cALSS) is proposed for study.

In this prospective single-arm study, ALF and ACLF patients were treated with cALSS using RMA. Coagulation function was monitored, and the predictors of mesylate dose were analyzed using the area under the curve (AUC). Blood ammonia, model for end-stage liver disease scores, and survival rates at 28 and 90 days were assessed.

All 57 patients showed no new bleeding within 24 h post-cALSS. Most disseminated intravascular coagulation indicators improved at 0.5 h and 24 h post-cALSS. Thromboelastography showed hypocoagulability at 0.5 h post-cALSS. Univariate and multivariate analyses identified pre-R and pre-MA as key factors for R exceeding 10 m at 0.5 h post-cALSS, with odds ratios of 0.91 (95% confidence interval (CI): 0.84–0.98) and 2.03 (95% CI: 1.05–3.90), respectively, P < 0.05. The predictive values were pre-MA ≤ 38 mm (AUC = 0.817, 95% CI [0.690–0.907], P < 0.001) and pre-R > 6.3 m (AUC = 0.790, 95% CI [0.661–0.888], P < 0.001). Patients showed improvements in blood ammonia and model for end-stage liver disease scores after the last session, especially those with high initial levels (>80 µmol/L and >30). The 28-day and 90-day survival rates of ALF patients were similar to those of ACLF patients.

cALSS with RMA is safe for liver failure patients with a high risk of bleeding. Adjusting the mesylate dose based on pre-R and pre-MA enhances safety.

Hepatocellular carcinoma (HCC) represents the most prevalent malignancy in Egypt and globally. However, non-invasive diagnostic/prognostic biomarkers for early detection of HCC are still lacking. Circular RNAs (circRNAs) are one of the promising biomarkers. They are considered stable, long-stranded non-coding RNAs in a sealed circular form held together by covalent bonds. circRNAs have been observed in several genetic studies to play a vital role in the initiation and progression of malignancy. Our current cross-sectional study aimed to evaluate the potential role of serum-derived hsa_circ_101555 as a diagnostic biomarker for HCC, in addition to comparing its prognostic significance and predicting the response to therapy.

The serum expression level of hsa_circ_101555 was measured using real-time polymerase chain reaction in 62 clinically/radiologically diagnosed Egyptian HCC patients at baseline and three months after HCC treatment. These results were compared to those of 30 healthy subjects.

Our data showed that the mean circRNA value was highest in HCC cases (7.66 ± 3.74) compared to healthy controls (1.21 ± 0.96). Furthermore, the circRNA value showed excellent diagnostic accuracy in differentiating HCC patients from healthy controls at a cutoff point of 1.966, as indicated by an area under the curve of 0.984. In addition, it showed a prognostic role in differentiating between HCC progression and regression in these patients based on response evaluation criteria in solid tumors (RECIST)/ modified- RECIST (mRECIST) response categories at the cutoff point 5.1150, with an area under the curve of 0.891 and a standard error of 0.058. Interestingly, positive correlations between post-intervention circRNA levels and laboratory measurements were observed in our HCC patients, including the albumin-bilirubin score (r = 0.424, P = 0.001**), the neutrophil-to-lymphocyte ratio (r = 0.410, P = 0.001**), alpha-fetoprotein (r = 0.273, P = 0.032*), the aspartate aminotransferase/alanine aminotransferase ratio (r = 0.284, P = 0.025*), fibrosis-4 (r = 0.501, P = 0.000**), and the aspartate aminotransferase to platelet ratio score (r = 0.436, P = 0.000**), indicating an association with worsening liver inflammation, fibrosis, and disease progression. Lastly, post-intervention circRNA values were significantly correlated with clinical/pathological tumor key features, including larger tumors (>5 cm) (P = 0.019), multiplicity (tumor numbers > 3) (P = 0.031), vascular invasion (P = 0.030), Barcelona Clinic Liver Cancer stage C (P = 0.007), and advanced Tomur, Node, Metastasis stage (P = 0.012).

To our knowledge, this is the first study to highlight the expression levels of serum-derived hsa_circ_101555 in Egyptian HCC patients. Our data showed its upregulation in HCC cases compared to healthy subjects. Additionally, its increased levels were associated with tumor progression according to the RECIST/mRECIST categories. Furthermore, its significant correlation with markers/scores of liver inflammation, dysfunction, and tumor pathological features underscores its potential as a promising diagnostic/prognostic biomarker, aiding in better clinical decision-making for the management of hepatocellular carcinoma.

Extrahepatic portosystemic shunts (EPS) are abnormal connections between the portal and systemic circulations. Acquired EPS occur most commonly in adults and are usually associated with portal hypertension due to cirrhosis. Acquired EPS cases can be further subdivided into two types: variceal (pre-existing) EPS and non-variceal EPS (NVEPS). Variceal EPS arise from originally small vessels with pre-existing dual portal and systemic drainage. Due to elevated portal pressure, these vessels dilate and undergo a reversal of flow, sending blood back to the systemic circulation. A much less common and, therefore, underappreciated subset of acquired EPS is NVEPS, which consists of aberrant connections that did not previously exist between the portal vein and large systemic vessels, usually in the presence of portal hypertension. Neoangiogenesis results in the development of abnormal anastomoses between the portal vein and other large veins, resulting in splenorenal, gastrorenal, portocaval, and mesocaval shunts. While not uncommon, they are frequently overlooked in the diagnosis and treatment of portal hypertension and can pose significant diagnostic and therapeutic challenges. Because the treatment of variceal EPS and NVEPS can differ markedly, it is important to correctly diagnose NVEPS and institute appropriate management. The aim of this article was to review acquired EPS, with particular attention to NVEPS, updating the pathogenesis, diagnosis, and treatment.

Metabolic dysfunction-associated steatotic liver disease (MASLD), is the most common form of chronic liver disease worldwide. This study aimed to explore the role of TM6SF2 in high-fat diet (HFD)-induced MASLD through the gut-liver axis.

The TM6SF2 gut-specific knockout (TM6SF2 GKO) mouse was constructed using CRISPR/Cas9 technology. TM6SF2 GKO and wild-type (CON) mice were fed either a HFD or a control diet for 16 weeks to induce MASLD. Blood, liver, and intestinal lipid content, as well as gut microbiota and serum metabolites, were then analyzed.

TM6SF2 GKO mice fed an HFD showed elevated liver and intestinal lipid deposition compared to CON mice. The gut microbiota of HFD-fed TM6SF2 GKO mice exhibited a decreased Firmicutes/Bacteroidetes ratio compared to HFD-fed CON mice. The HFD also reduced the diversity and abundance of the microbiota and altered its composition.Aspartate aminotransferase, alanineaminotransferase, and total cholesterol levels were higher in HFD-fed TM6SF2 GKO mice compared to CON mice, while triglyceride levels were lower. Serum metabolite analysis revealed that HFD-fed TM6SF2 GKO mice had an increase in the expression of 17 metabolites (e.g., LPC [18:0/0-0]) and a decrease in 22 metabolites (e.g., benzene sulfate). The differential metabolites of LPC (18:0/0-0) may serve as HFD-fed TM6SF2 serum biomarkers, leading to MASLD exacerbation in GKO mice.

TM6SF2 GKO aggravates liver lipid accumulation and liver injury in MASLD mice. TM6SF2 may play an important role in regulating intestinal flora and the progression of MASLD through the gut-liver axis.

Heme oxygenase 1 (HO-1) has an influential yet insufficiently investigated effect on Sirtuin 1 (SIRT1), a histone deacetylase activated by nicotinamide adenine dinucleotide, which may impact the transforming growth factor-β (TGF-ß)/Smad3 pathway in nonalcoholic fatty liver disease (NAFLD)-related liver fibrosis. This study aimed to elucidate the regulation of NAFLD-related liver fibrosis induced by HO-1 through the SIRT1/TGF-ß/Smad3 pathway.

HO-1 induction and inhibition were established in C57BL/6J mice fed a methionine- and choline-deficient (MCD) diet. Additionally, wild-type mice were fed either a normal diet or an MCD diet. Hematoxylin and eosin, Masson’s trichrome, and Sirius Red staining were used to assess hepatic steatosis, inflammation, and fibrosis. In vitro, plasmid overexpression and small interfering RNA silencing of HO-1 were performed in LX-2 cells. Cell viability was assessed using the Cell Counting Kit-8, and apoptosis was evaluated via terminal deoxynucleotidyl transferase dUTP nick-end labeling and immunofluorescence. Flow cytometry was employed to assess apoptosis and reactive oxygen species production. Western blot and real-time quantitative reverse transcription polymerase chain reaction were used to analyze the mRNA and protein expression of genes related to HO-1, SIRT1, the TGF-ß signaling pathway, and fibrosis.

MCD-fed mice developed significant liver damage, including steatosis, inflammatory infiltration, and pericellular fibrosis. Zinc protoporphyrin treatment exacerbated these conditions. Corroborating these findings, silencing HO-1 in LX-2 cells increased the expression of fibrosis-related genes. Furthermore, HO-1 overexpression not only increased SIRT1 expression but also reduced the activity of key regulatory factors in the TGF-ß signaling pathway, suggesting a potential interaction between HO-1 and the SIRT1/TGF-ß pathway.

HO-1 inhibits the activation of the TGF-ß/Smad3 pathway in NAFLD-related liver fibrosis through SIRT1. These findings provide insights into new therapeutic strategies for treating NAFLD-associated liver fibrosis.

Therapy-related B-lymphoblastic leukemia (B-ALL) following treatment for multiple myeloma is a rare occurrence. Despite its rarity and the lack of recognition by the World Health Organization as a distinct disease entity, previous publications indicate its possible emergence following myeloma treatment.

The patient is a 65-year-old gentleman with a history of IgG kappa multiple myeloma, status post multiple lines of therapy. The patient presented with a fever, and a complete blood count showed cytopenia. Bone marrow morphologic evaluation revealed numerous blasts. Immunophenotypic analysis demonstrated that these blasts were B lymphoblasts, despite MYC and unusual surface kappa light chain expression. A diagnosis of B-ALL with surface kappa light chain expression post-myeloma treatment was made. Ancillary studies indicated that the B-ALL and the previous myeloma were clonally unrelated. Next-generation gene sequencing revealed pathogenic mutations in KDM6A and KRAS.

This case highlights the potential for therapy-related B-ALL following myeloma treatment, a phenomenon deserving further investigation. The expression of surface light chain in blasts can present a diagnostic pitfall.

Since the adoption of novel prognostic scores, such as the iterative model for end-stage liver disease (MELD 3.0) and the gender-equity model for liver allocation (GEMA), their utility has markedly expanded to diverse clinical scenarios. However, data concerning their prognostic value in more generalized cirrhotic populations are scarce. In this study, we aimed to elucidate the MELD 3.0/GEMA-Na for long-term mortality risk stratification and refine their usage scope.

This study retrospectively reviewed 310 hospitalized patients with decompensated cirrhosis. Discrimination and stratification were compared between MELD 3.0/GEMA-Na and other scores. Validation was performed in another 120 subjects.

In the investigated cohort, the median MELD-Na, MELD 3.0, and GEMA-Na were 9 (7, 12), 12 (10, 17), and 12 (9, 17), respectively. Compared to their predecessors, both MELD 3.0 and GEMA-Na models exhibited consistently better discriminative ability, especially in relation to long-term mortality. This effect was more pronounced for GEMA-Na, which was the only score to present an area under the receiver operating characteristic curve greater than 0.8 up to two years (0.807). Statistical analysis indicated that a MELD 3.0 score of 18 and a GEMA-Na score of 20 were the most optimal cutoffs to rank the risk of death, both of which were independently associated with two-year all-cause transplant-free mortality (MELD 3.0: hazard ratio: 1.13, 95% confidence interval: 1.10, 1.17; GEMA-Na: hazard ratio: 1.12, 95% confidence interval: 1.10, 1.17, both P < 0.001). Similar findings were affirmed in the validation cohort.

MELD 3.0 is superior to other MELD-based scores for long-term prognostication in hospitalized patients with cirrhosis, while GEMA-Na demonstrated even better accuracy and performance.

There are no intraepithelial eosinophils present in the normal esophageal mucosa. It is well established that gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) individually can result in esophageal eosinophilia and that the two disorders frequently coexist in the same patient. Nevertheless, the first step in the diagnostic algorithm for patients with esophageal symptoms associated with esophageal eosinophilia is to exclude non-EoE disorders that can cause esophageal eosinophilia, including GERD. While it is clear that GERD without EoE can cause low-level esophageal eosinophilia, it is less clear whether GERD alone can induce EoE-level esophageal eosinophilia (i.e., ≥15 eosinophils per high-power field). In this report, we have reviewed mechanisms by which reflux might induce eosinophilia in the esophagus and assessed studies suggesting that GERD alone can induce EoE-level esophageal eosinophilia. Studies on the latter issue have suffered from numerous shortcomings, including the use of outmoded or dubious methods for identifying GERD. Many of these studies were published prior to the realization that EoE can respond to proton pump inhibitor treatment. Our review of these studies suggests that GERD alone rarely, if ever, causes EoE-level eosinophilia (perhaps <1% of cases). For patients with definitive evidence of GERD associated with EoE-level esophageal eosinophilia but without endoscopic or clinical features of EoE, it is impossible to determine whether the eosinophilia is caused solely by GERD, by underlying but unrelated EoE that does not manifest typical features, or by EoE driven by GERD-induced defects, such as impaired esophageal barrier function. Until better diagnostic tests for EoE become available, this situation will remain a clinical conundrum.