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.

Non-invasive vagus nerve stimulation (nVNS), including transcutaneous cervical (tcVNS) and auricular (taVNS) modalities, has garnered increasing attention as a neuromodulatory therapy for various neurological and psychiatric disorders. This narrative review synthesizes findings from over 80 studies, including randomized controlled trials, meta-analyses, and observational research published up to March 2024, evaluating nVNS in epilepsy, depression, stroke rehabilitation, headache, Parkinson’s disease, and Alzheimer’s disease. Evidence suggests that taVNS can reduce seizure frequency and improve quality of life in epilepsy. In major depressive disorder, nVNS demonstrates antidepressant effects comparable to pharmacotherapy, though the optimal stimulation parameters remain unclear. For post-stroke motor rehabilitation, both tcVNS and closed-loop stimulation systems enhance neuroplasticity and motor recovery. In Parkinson’s and Alzheimer’s diseases, preliminary findings indicate possible modulation of neuroinflammatory pathways and cognitive-motor functions, although recent meta-analyses report mixed efficacy. Challenges include methodological heterogeneity, protocol variability, and difficulties in designing effective sham controls, all of which limit the generalizability of current findings. Mechanistic differences between tcVNS and taVNS remain inadequately characterized. Overall, nVNS appears to be a safe and accessible therapeutic approach with broad clinical potential, particularly for treatment-resistant or underserved populations. However, future research must prioritize standardized protocols, robust clinical endpoints, and adequately powered trials to define efficacy and optimize treatment strategies. A greater focus on long-term outcomes, biomarker-guided personalization, and clinical significance over statistical findings will be critical in translating nVNS into routine practice.

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.

Prostate cancer (PCa) often manifests insidiously, with most patients being diagnosed at an advanced stage, leading to a poor prognosis. Early detection of PCa can significantly prolong overall survival by impeding the progression of metastasis. A commonly utilized screening method for detecting PCa is the prostate-specific antigen test. However, since the prostate-specific antigen lacks specificity and sensitivity for PCa identification, there is a paramount urgency to develop precise diagnostic biomarkers for early detection. Extracellular vesicles, known as exosomes, are released by cells into body fluids. Exosomes derived from cancer cells can carry genetic information about the tumor, including DNA, RNA, and proteins, which play crucial roles in tumor initiation, invasion, metastasis, and drug resistance. Studies have indicated that exosomes (including messenger RNAs, microRNAs, long noncoding RNAs and others) can enhance the sensitivity and specificity of PCa diagnosis, indicating their potential for early detection. This review highlights the biological characteristics and functions of exosomes, as well as recent advancements in their use for the diagnosis, prognosis, and treatment of prostate cancer.

This study investigates upper gastrointestinal tract (UGIT) involvement in patients with ulcerative colitis (UC), a condition traditionally considered limited to the colon. Although extra-colonic manifestations of UC are well recognized, UGIT issues have received less attention. This research aimed to document the clinical, endoscopic, and histopathological UGIT findings in adults with UC and assess their association with disease severity and extent.

This descriptive cross-sectional study was conducted at Ain Shams University over one year. A total of 78 UC patients underwent comprehensive clinical evaluations, including assessments of gastrointestinal complaints, medication history, disease progression, surgeries, and physical examinations. Endoscopic assessments of both the UGIT and colon were performed, accompanied by biopsies for histopathological analysis.

The study population had a mean age of 35.26 years, with a nearly equal gender distribution. Endoscopic findings revealed significant UGIT involvement: 64% of patients had esophagitis and/or gastroesophageal reflux disease, 93% had gastritis, and 80% had duodenitis. Histopathological findings showed notable inflammation, basal cell hyperplasia, and ulcerations in the esophagus, with 51.3% of patients exhibiting chronic gastritis and 38.5% testing positive for Helicobacter pylori infection. Statistical analysis demonstrated a strong association between colonic disease severity and UGIT endoscopic (p < 0.0001 and p < 0.001 in the esophagus and stomach, respectively) and histopathological (p < 0.004, p < 0.001, and p <0.005 in the esophagus, stomach, and duodenum, respectively) findings, particularly in patients with UGIT symptoms.

This study concludes that UGIT endoscopic and histopathological changes are prevalent among Egyptian UC patients, suggesting a significant link between UC and these UGIT findings.

Liver fibrosis is a key process in the progression of chronic liver diseases. However, there are currently no drugs specifically designed to treat liver fibrosis. Our Phase 2 trial of hydronidone for the treatment of chronic hepatitis B (CHB)-associated liver fibrosis showed that adding hydronidone to entecavir resulted in significant reversal of liver fibrosis. To further evaluate the efficacy of a 270 mg/day dose of hydronidone for treating liver fibrosis associated with CHB, we conducted this Phase 3 trial.

This is a 52-week, randomized (1:1), double-blind, placebo-controlled, multicenter, entecavir-based Phase 3 clinical study conducted at 44 study centers across China. Adult patients aged 18 to 65 years with significant liver fibrosis (defined as an Ishak score ≥ 3 on liver biopsy) associated with CHB were included.

The primary endpoint of the trial is to demonstrate the efficacy of fibrosis reversal, defined as a decrease in the Ishak stage score of liver fibrosis by ≥1 after 52 weeks of treatment, compared to baseline.

The results of this trial are expected to further support the antifibrotic indication for this novel drug.

Ectopic or heterotopic pancreases are normal pancreatic tissues located outside the pancreas. The ectopic pancreas has its own vascular and ductal systems and does not communicate with the normal pancreas. The prevalence of ectopic pancreas ranges from 0.6% to 15% among all autopsies. Many types of tumors, including intraductal papillary mucinous neoplasms (IPMNs), have been reported in the ectopic pancreas. However, little is known about the synchronous occurrence of IPMNs in both ectopic and orthotopic pancreas. In this study, we report, for the first time, two cases of concurrent IPMNs in an ectopic pancreas and an orthotopic pancreas. One patient had IPMNs both in the pancreas and in ectopic pancreatic tissue in the jejunum. Another patient had IPMNs in both the pancreas and ectopic pancreatic tissue in the duodenum. These cases may provide valuable insights into the etiological factors of IPMNs.