Breast cancer is one of the leading causes of mortality among women worldwide. Tumor necrosis factor α-induced protein 3-interacting protein 1 (TNIP1) is a ubiquitin-binding protein that is widely expressed, but its function in breast cancer cells remains unknown. This study aimed to elucidate the molecular mechanism of TNIP1 regulation in the proliferation and apoptosis of breast cancer cells.

A colony formation assay was conducted on MCF-7 and T47D cells stably transfected with TNIP1/cyclin G1 (CCNG1) short hairpin RNAs. Quantitative polymerase chain reaction was performed to assess the relative abundances of TNIP1, CCNG1, and cyclin D1 (CCND1) messenger RNAs. Immunoprecipitation and immunoblotting were used to detect the expression of TNIP1, CCNG1, CCND1, and related proteins. A dual-luciferase reporter assay was employed to explore the molecular mechanism of TNIP1 in signal transduction. Caspase activity in MCF-7 and T47D cells transfected with TNIP1 short hairpin RNAs was measured using the Caspase-Glo 3/7 assay.

Ablation of TNIP1 induced growth arrest in breast cancer cells. TNIP1 directly interacted with CCNG1, and TNIP1 knockdown increased the ubiquitination of CCNG1. CCNG1 knockdown also induced growth arrest in MCF-7 and T47D cells. Furthermore, TNIP1 knockdown activated the NF-κB pathway and induced apoptosis in these cells.

TNIP1 regulates the proliferation and apoptosis of breast cancer cells, suggesting that TNIP1 may serve as a potential biomarker for breast cancer.

Ferroptosis plays an essential role in chronic liver diseases, and cyclooxygenase-2 (COX-2) affects liver fibrosis through multiple mechanisms. However, research on COX-2 regulation of ferroptosis in chronic liver injury remains limited. This study aimed to investigate whether and how COX-2 regulates ferroptosis in chronic liver injury.

In vivo, a thioacetamide (TAA)-induced chronic liver injury model, characterized by significant liver lipid peroxidation and oxidative stress, was used. COX-2+/+ and COX-2–/– mice were treated with TAA or normal saline. In vitro, primary mouse hepatocytes were isolated and treated with dimethyl sulfoxide (DMSO), erastin+DMSO, etoricoxib+erastin+DMSO, and tBHQ+erastin+DMSO. Mitochondrial morphology, iron metabolism, lipid peroxidation, and oxidative stress were assessed to verify ferroptosis. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway was measured to investigate the relationship between COX-2 and ferroptosis.

TAA-treated COX-2–/– mice presented milder liver fibrosis, whereas TAA-treated COX-2–/– mice livers and etoricoxib+erastin+DMSO-treated primary hepatocytes exhibited alleviated mitochondrial damage compared with TAA-treated COX-2+/+ littermates and erastin+DMSO-treated primary hepatocytes, respectively. The knockout of COX-2 decreased ferrous ion concentration (p < 0.01) and mitigated lipid peroxidation in TAA-treated livers (p < 0.05). Furthermore, both COX-2 knockout and etoricoxib restored reduced glutathione (p < 0.05) and glutathione peroxidase 4 (p < 0.05), while decreasing malondialdehyde levels (p < 0.05). Additionally, COX-2 inhibition upregulated Nrf2, which helped alleviate erastin+DMSO-induced ferroptosis (p < 0.01).

Ferroptosis contributes to the progression of chronic liver injury. Inhibition of COX-2 upregulates Nrf2, mitigating hepatocyte ferroptosis in chronic liver injury.

Gastrointestinal complications are common in patients after ischemic stroke. Gastric motility is regulated by gastric pace-making activity (also called gastric myoelectrical activity (GMA)) and autonomic function. The aim of this study was to evaluate GMA, assessed by noninvasive electrogastrography (EGG), and autonomic function, measured via spectral analysis of heart rate variability derived from the electrocardiogram in patients with ischemic stroke.

EGG and electrocardiogram were simultaneously recorded in both fasting and postprandial states in 14 patients with ischemic stroke and 11 healthy controls. Multi-channel surface EGG was used to measure GMA, and autonomic function was evaluated by heart rate variability spectral analysis.

Compared to healthy subjects, patients with ischemic stroke, especially those with a modified Rankin scale ≥ 4, had impaired GMA in both fasting and postprandial states. This included a lower percentage of normal gastric slow waves (the basic rhythmic waves of GMA) and a higher percentage of tachygastria, bradygastria, or arrhythmia. Patients with ischemic stroke also showed a decrease in the dominant frequency and power of the gastric slow waves. Autonomic functions were altered in ischemic stroke patients with a modified Rankin scale ≥ 4, as reflected by increased sympathetic activity and reduced parasympathetic activity.

Gastric pace-making activity is impaired in patients with severe ischemic stroke, as evidenced by a reduced percentage of normal gastric slow waves and a lower frequency of gastric slow waves, likely due to impaired autonomic functions.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and highly aggressive embryonal tumor that predominantly affects infants and young children. This malignancy arises from primitive neuroectodermal cells and exhibits heterogeneous differentiation into various embryonic tissues. Due to its rarity and complexity, diagnosing and managing AT/RT present significant challenges. Recent studies have summarized the key features of cerebellar and supratentorial AT/RT cases; however, critical gaps remain in understanding their diffuse leptomeningeal variants and long-term functional outcomes. Here, we report a case of a two-year-old child diagnosed with cerebellar AT/RT, who presented with vomiting and gait instability. The patient underwent a gross total resection followed by adjuvant radiotherapy and chemotherapy. Despite achieving radiological remission, the patient survived for only eight months and experienced severe neurological deficits, including persistent ataxia and recurrent infections. This case highlights the disconnect between surgical success and long-term quality of life. It underscores the importance of integrating molecular diagnostics and palliative care to address the multifaceted burden of AT/RT.

Acute coronary syndrome (ACS) in patients with SARS-CoV-2 infection is primarily driven by inflammation-induced myocardial injury through both direct and indirect mechanisms. Effective clinical management requires a dual approach: addressing cardiovascular lesions while also mitigating virus-induced local and systemic inflammation. This comprehensive approach is essential for improving the diagnosis and treatment of SARS-CoV-2-associated ACS. Emerging evidence highlights the potential of myocardial protective agents, including angiotensin-converting enzyme 2-modulating drugs and traditional Chinese medicine, which not only stabilize plaques and improve endothelial function but also confer cardioprotective effects. Furthermore, advancements in nanotechnology offer promising strategies for targeted therapy—particularly through angiotensin-converting enzyme 2 receptor modulation—by enhancing the precision and efficacy of herbal medicine delivery. This review explores the complex interplay between SARS-CoV-2 infection and ACS pathogenesis, and evaluates the therapeutic potential of pharmacological, herbal, and nanotechnology-based interventions in managing this multifaceted condition.

Chronic hepatitis B virus (HBV)-infected patients may exhibit liver fibrosis and other pathological changes despite normal alanine aminotransferase (ALT). This study aimed to assess the efficacy and safety of tenofovir amibufenamide (TMF) in chronic HBV-infected patients with normal ALT levels.

The ongoing PROMOTE study (NCT05797714) is the first prospective, multicenter, randomized, open-label, blank-controlled clinical trial involving chronic HBV-infected patients with normal ALT levels. Participants were randomized in a 1:1 ratio to receive either TMF (TMF group) or no treatment (blank control group). The primary efficacy endpoint was the proportion of participants achieving HBV DNA levels <20 IU/mL at 48 weeks.

A total of 197 participants were enrolled, with 95 in the TMF group and 102 in the blank control group. At 48 weeks, a significantly greater proportion of participants in the TMF group achieved HBV DNA levels <20 IU/mL compared with the control group (74.2% vs. 9.0%, P < 0.001). The TMF group demonstrated more pronounced reductions in HBV DNA (−2.63 vs. −0.22 log10 IU/mL, P < 0.001), HBsAg (−0.07 vs. −0.04 log10 IU/mL, P = 0.02), and ALT levels (−14.09% vs. 0%, P = 0.003) compared with the blank control. In the TMF group, the proportion of participants with high-normal ALT levels (20–40 IU/L) was reduced. No significant differences were observed between the groups in creatinine, glomerular filtration rate, bone turnover biomarkers, lipid profiles, or phosphorus levels.

TMF treatment demonstrates significant efficacy in chronic HBV-infected patients with normal ALT levels and shows a favorable safety profile regarding bone, renal, and lipid parameters. The PROMOTE study is ongoing, and further results at 96 and 144 weeks are expected to provide additional insights.

Malignant mixed Müllerian tumor (MMMT) or carcinosarcoma of the female genital tract is a rare but highly aggressive malignancy.

We report a unique case of primary ovarian MMMT with poorly differentiated angiosarcoma as its homologous sarcomatous component in a 53-year-old woman with a known germline BRCA1 mutation who presented with a pelvic mass. She underwent staging cytoreduction surgery including total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic and para-aortic lymph node dissections. The removed right ovarian tumor formed a 2.5 cm nodular to cystic mass replacing the entire organ. Microscopic examination revealed two distinct tumor components: high-grade serous carcinoma and poorly differentiated angiosarcoma. The proliferating sarcomatous cells were diffusely positive for CD31 and Factor VIII, but were negative for 100, SOX10 and cytokeratin. Both the serous carcinoma and angiosarcoma components demonstrated aberrant strong and diffuse p53 nuclear positivity. KRAS mutation analysis revealed guanine-adenine-thymine point mutation at codon 12 in both tumor components. Metastatic tumor was found involving the contralateral left ovary with the cellular composition of pure angiosarcomatous component.

This is the first report of an ovarian MMMT with angiosarcoma as its homologous sarcoma component. The presence of aberrant p53 expression and identical KRAS mutation in both the serous carcinoma and angiosarcoma components supports the theory of malignant mesenchymal transition/metaplasia in the development of MMMT.

Exophiala, a genus of saprotrophic black fungi commonly found in the environment, is typically associated with cutaneous infections in immunocompromised hosts and rarely manifests as pneumonia. Here, we report the first case of Exophiala pneumonia in Pakistan, occurring in an immunocompetent, middle-aged female with interstitial lung disease.

A 56-year-old female presented with a two-week history of malaise and a cough productive of black sputum. On auscultation, fine crackles were heard in the bilateral posterior middle and lower lung fields. Chest radiography showed features of usual interstitial pneumonia with patchy and dense reticular opacities in the middle and lower lung lobes bilaterally. Bronchoscopy was performed, and bronchoalveolar lavage was sent to the microbiology laboratory for culture. Gram stain findings revealed numerous pus cells, primarily neutrophils, along with septate hyphae, which were also confirmed on potassium hydroxide smear. The results were communicated to the treating physician, and the patient was started on intravenous voriconazole. After four days of incubation at 25°C and 37°C, colonies of mold were observed on the culture, which were identified as Exophiala jeanselmei on Lactophenol Cotton Blue staining. After one week of treatment, the patient showed clinical improvement and was discharged on oral voriconazole with outpatient follow-up.

Our findings suggest that bronchoalveolar lavage with an elevated neutrophil count and abnormal pulmonary imaging should be evaluated as signs of both fungal and bacterial pneumonia. Additionally, fungal culture should be considered in such cases, as it employs specific techniques and prolonged incubation for the isolation of fungi. Since Exophiala jeanselmei is a rare yet severe cause of pneumonia, early detection and the knowledge gained from treated infections are crucial for effective management.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with marked phenotypic differences observed among its major histological subtypes, adenocarcinoma (ADC), squamous cell carcinoma (SCC), and small cell lung cancer (SCLC), in both clinical presentation and therapeutic response. In recent years, metabolomics has emerged as a powerful tool for studying cancer metabolic reprogramming, providing new insights into the metabolic distinctions among lung cancer subtypes. This review summarizes recent research advances in the metabolomics of ADC, SCC, and SCLC. Studies have revealed that ADC and SCC display distinct metabolic profiles in lipid metabolism, amino acid metabolism, and cell membrane synthesis, while SCLC demonstrates a unique metabolic pattern. Through metabolomic technologies, particularly mass spectrometry and liquid chromatography, it is possible to effectively differentiate lung cancer subtypes and identify potential biomarkers for early diagnosis and personalized treatment. This review also explores the clinical potential of metabolomics in lung cancer, emphasizing its critical role in early diagnosis and subtype stratification. These methodological advances establish a robust foundation for precision oncology paradigms in thoracic malignancies.

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.