Despite advancements in diagnostic and therapeutic strategies, hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality. Antioxidant-1 (ATOX1) has been implicated in oncogenic processes across various cancer types; however, its specific role in HCC remains unclear. This study aimed to investigate the function of ATOX1 and its underlying molecular mechanisms in HCC.

Immunohistochemical analysis was conducted to assess ATOX1 expression in HCC tissues. Cell Counting Kit-8, colony formation, Transwell migration, flow cytometry, and reactive oxygen species (ROS) assays were employed to evaluate the malignant behaviors of tumor cells. A xenograft mouse model was employed to assess the effects of ATOX1 knockdown on tumor growth in vivo. DCAC50 treatment was performed to inhibit the copper transport function of ATOX1. RNA sequencing was conducted to explore the potential molecular mechanisms of ATOX1 in HCC.

ATOX1 expression was significantly elevated in HCC tumor tissues. ATOX1 promoted cell proliferation, colony formation, and migration. Knockdown of ATOX1 suppressed tumor growth in vivo. Mechanistically, ATOX1 activated c-Myb, and thus enhanced the malignant phenotype of HCC cells via activation of the PI3K/AKT signaling pathway. Additionally, ATOX1 reduced intracellular copper accumulation and inhibited ROS production and apoptosis. Inhibition of ATOX1 by DCAC50 decreased cell proliferation while increasing ROS levels and apoptosis in HCC cells. Notably, acetylcysteine reversed the reduction in c-Myb expression induced by ATOX1 knockdown.

ATOX1 may promote HCC carcinogenesis through the activation of the c-Myb/PI3K/AKT pathway and the inhibition of copper accumulation and oxidative stress.

Potential celiac disease (PCD) is defined as elevated celiac serology with a preserved small intestinal mucosa. This study aimed to identify baseline characteristics and the outcomes of children with PCD consuming a gluten-containing diet.

This was a retrospective cohort study of pediatric PCD patients diagnosed between 12/2018 and 10/2024. Baseline data included demographics, anthropometrics, clinical symptoms and signs, celiac serology, and biopsy results. Follow-up data included repeat serology and biopsy results when performed.

PCD was diagnosed in 75/517 (14.5%) children undergoing upper endoscopy for suspected celiac disease (CeD). Baseline anti-transglutaminase IgA (TTG) was above 10× the upper limit of normal (ULN) in 18 (24%), between 3–10× ULN in 52 (69.3%), and <3× ULN in five (6.6%). Anti-endomysial antibody was positive in 57 (76%). Among 48 children (64%) with at least one year of follow-up, TTG normalized in 26 (54.1%), decreased to <3× ULN in 13 (27.1%), was between 3–10× ULN in six (12.5%), and was above 10× ULN in three (6.3%). Nine children had a repeat endoscopy, and six (66.7%) were diagnosed with CeD, while three remained PCD. Among the 11 children with TTG >10× ULN and at least one year of follow-up, TTG normalized in three, declined in five, and increased or remained above 10× ULN in three.

PCD is common and may be found in children with TTG above 10× ULN; approximately half will normalize TTG. The omission of biopsies may result in an erroneous diagnosis of CeD.

Artificial intelligence (AI) is transforming the diagnosis, treatment, monitoring, and research of soft tissue disorders, which include muscles, tendons, ligaments, fascia, nerves, and blood vessels. Traditional diagnostic methods often rely on imaging, histopathology, and clinical evaluation, which can be time-consuming and prone to human error. This review aims to explore the impact of AI on enhancing soft tissue care. The review examines the application of deep learning algorithms in medical imaging, pathology, predictive analytics, and treatment planning. It also evaluates AI’s role in monitoring and rehabilitation, as well as its contributions to research in soft tissue disorders. AI significantly improves the accuracy of medical imaging analysis, facilitating the detection of abnormalities such as tumors and tears. AI-powered pathology tools automate slide analysis, enhancing diagnostic consistency and efficiency. Predictive analytics enable early risk assessment and personalized patient management. In surgical contexts, AI supports preoperative simulations and robotic-assisted procedures, leading to improved outcomes. Additionally, AI enhances patient monitoring through wearable devices and telemedicine. The integration of AI into soft tissue diagnostics and therapeutics presents transformative potential for personalized and efficient healthcare. However, challenges related to data security, algorithm bias, interpretability, and ethical considerations must be addressed. Overall, AI holds promise for improving patient outcomes and advancing medical science in the field of soft tissue disorders.

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.

Despite significant advances in Parkinson’s disease (PD) treatment, it remains incurable, with limited therapeutic options. Currently, repurposing already tested, safe drugs has emerged as an effective therapeutic strategy against various neurodegenerative diseases, including PD. Using a drug-repurposing approach, the current study investigated the neuroregenerative potential of polysialic acid mimicking compounds, 5-nonyloxytryptamine oxalate (5-NOT) and Epirubicin (Epi), an anti-cancer drug, in 1-methyl-4-phenylpyridinium (MPP+)-treated human neuroblastoma SH-SY5Y cells as a PD model.

The excitotoxic model was established by exposing SH-SY5Y cells to 500 µM of MPP+ and subsequently treating them with the test compounds. The effect of MPP+-induced toxicity on cellular and nuclear morphology, as well as on the expression of neuroplasticity and cell survival proteins, were studied by immunostaining, gelatin zymogram, and Western blot assays.

Treatment with 5-NOT and Epi significantly promoted the survival of MPP+-challenged SH-SY5Y cells and prevented changes in their cellular and nuclear morphology by regulating the expression of microtubule-associated protein (MAP-2) and polysialylated-neural cell adhesion molecule (PSA-NCAM) and NCAM synaptic plasticity proteins. Further, 5-NOT and Epi treatment also protected SH-SY5Y cells by restoring levels of nitric oxide, matrix metalloproteinase, and stress response proteins. Interstingly, 5-NOT attenuated MPP+-induced toxicity in SH-SY5Y cells by regulating the intrinsic protein kinase AKT/BAD apoptotic pathway and the P-38 MAP kinase synaptic plasticity pathway.

These preliminary findings suggest that 5-NOT, as a potential polysialic acid glycomimetic, may serve as a promising drug candidate for targeting neurodegeneration of dopaminergic neurons, a hallmark feature of PD.

Leishmaniasis is a dangerous yet neglected tropical disease affecting a vast population of the world. Several medicinal plants and their constituents (natural products/phytochemicals) have been considered of prime importance for the management of leishmaniasis over the years. The present review sheds light on the molecular mechanisms of the constituents obtained from medicinal plants that are pre-clinically effective against leishmaniasis. Various mechanisms by which medicinal plant-derived natural products elicit their action against leishmaniasis are illustrated in the literature. The mechanisms identified include: disruption of cytoplasmic and mitochondrial membranes, induction of apoptosis and autophagy, modulation of gene expression and immunological pathways, pro-oxidant effects (disrupting redox balance) with mitochondrial dysfunction, cell cycle arrest, impaired cellular bioenergetics, i.e., adenosine triphosphate production and coagulation of cellular contents within Leishmania parasites. Future phytochemical and pharmacological (especially clinical) studies are necessary to further understand the mechanistic details of medicinal plant-derived natural compounds and to develop new phytotherapeutic entities from nature against leishmaniasis.

It is established that administration of the COVID-19 vaccine may be associated with an exaggerated immune response leading to enlargement of several lymph nodes. Although most cases are benign and self-limiting, some have been reported in the literature as B-cell or T-cell lymphomas, with no reported cases of chronic lymphocytic leukaemia (CLL). We report two cases of follicular lymphoma and CLL that occurred a few weeks after COVID-19 vaccination. Case 1 is a 48-year-old woman who noticed two significantly palpable masses, one in each axilla, 48 h after receiving the first dose of the Pfizer-BioNTech BNT162b2 vaccine for COVID-19. Seven days later, she noticed another mass on the right side of her neck, which was biopsied within 48 hours. Case 2 is a 75-year-old man who presented with localized swellings in the axilla and on the neck, noted 24 h after the first dose of the Moderna messenger RNA-1273 COVID-19 vaccine. Neither patient reported any constitutional or associated symptoms. Surgical biopsy of the axillary lymph node in case 1 revealed a non-Hodgkin lymphoma, confirmed via immunohistochemistry as CD20-positive B-cell follicular lymphoma. The patient also had multiple pre- and para-aortic lymph nodes. In case 2, complete blood count showed lymphocytosis (total white blood cell – 148 × 109/L; lymphocyte differential – 92%), while peripheral blood film showed lymphocytosis with a predominance of small, mature-looking lymphocytes, both suggesting CLL. Although requested, immunophenotyping and molecular testing were not performed due to patient-related challenges. Although a chance occurrence is possible, lymphoid malignancies should be considered a strong differential. The vaccination history of patients presenting with clinical manifestations suggestive of a lymphoid malignancy should be thoroughly investigated, while ruling out other possible differentials such as a benign, self-limiting inflammatory process.

Emergency department (ED) presentations are associated with higher cancer mortality. This study aimed to investigate the prevalence, frequency, and risk factors in Australian patients diagnosed with malignant skin cancers.

This data-linkage cohort study examined adult patients presenting to the ED at the Royal Melbourne and Western Health hospitals within 12 months of a malignant skin cancer diagnosis. Multivariable logistic and Poisson regressions were used to analyze factors influencing the prevalence and frequency of ED presentations.

A total of 3,873 patients were diagnosed with skin malignancies between 2010 and 2018, of which 631 were diagnosed with melanoma. The prevalence of ED presentation was 29%, representing 2,119 episodes of care (median: 0; range: 0–14). Risk factors for a higher prevalence and frequency included: age ≥75 years (odds ratio (OR) = 1.78 [95% confidence interval 1.47–2.15]; incidence risk ratio (IRR) = 1.52 [1.35–1.70]); male (OR = 1.17 [1.01–1.36]; IRR = 1.23 [1.12–1.35]); socioeconomic status levels of 0–30% (OR = 1.59 [1.24–2.03]; IRR = 1.69 [1.45–1.96]) and 71–100% (OR = 1.30 [1.07–1.58]; IRR = 1.27 [1.12–1.45]); preferred language other than English (OR = 1.47 [1.17–1.84]; IRR = 1.49 [1.32–1.69]); and experience with any systemic therapy or radiotherapy (OR = 3.77 [2.12–6.71]; IRR = 2.36 [1.82–3.05]). Age < 65 years was protective (OR = 0.72 [0.59–0.89]; IRR = 0.78 [0.68–0.90]). Other preferred languages and cancer treatment experience were also risk factors in the sub-cohort with melanoma.

This study reports the prevalence and frequency of ED presentations following a skin cancer diagnosis and their association with socioeconomic and linguistic factors in Australia. Increased awareness of these factors could help address health inequities and potentially reduce the need for ED presentations.

Drug-induced liver injury (DILI) represents a prevalent adverse event associated with medication use. However, the exact mechanisms underlying DILI remain incompletely understood, and the lack of specific diagnostic and prognostic biomarkers poses significant challenges to the clinical diagnosis and treatment of this condition. Consequently, our study aimed to endeavor to identify serum and fecal metabolic biomarkers, enabling more accurate DILI diagnosis and improved prediction of chronic progression.

Untargeted metabolomics analysis was performed on serum and fecal samples obtained from a cohort of 32 DILI patients (causality confirmed via the updated Roussel Uclaf Causality Assessment Method) and 36 healthy controls. Utilizing techniques such as partial least squares-discriminant analysis modeling and t-tests, we identified significantly differentially expressed metabolites and metabolite sets. Causality assessment was performed using the updated Roussel Uclaf Causality Assessment Method.

The findings from the analysis of serum and fecal metabolomics association pathways suggested that perturbations in bile acid metabolism might serve as potential mechanisms underlying the progression of DILI. Our study revealed 22 overlapping differential metabolites between serum and feces, displaying significant concentration differences between the DILI and healthy control groups. Notably, we identified chenodeoxycholic acid and deoxycholic acid as promising markers that not only distinguished DILI patients from healthy individuals but also exhibited predictive potential for DILI chronicity.

The integrated analysis of serum and fecal metabolites uncovers the significant disruption of bile acid metabolites as a key contributing factor in the pathogenesis of DILI. Our study offers promising potential biomarkers for the diagnosis and prognosis of DILI, paving the way for a novel perspective in the realm of DILI diagnosis and treatment.