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.

Spinal cord injury (SCI) significantly impacts the central nervous system, with limited effective treatments available. Brain-derived neurotrophic factor (BDNF) plays a crucial role in neuronal growth, survival, and regeneration after SCI. MicroRNAs, particularly miR-124-3p, have been implicated in SCI pathophysiology. However, the relationship between miR-124-3p and BDNF in the context of SCI remains unclear. This study aimed to investigate the correlation between miR-124-3p expression and BDNF levels in a rat model of spinal cord injury and to assess how the timing of injury affects this relationship.

This study included 72 male Wistar rats divided into three groups: intact (n = 8), sham (n = 32), and SCI (n = 32). SCI diagnosis was confirmed through behavioral-motor function analysis using the Basso, Beattie & Brenham score and histological examination with crystal violet staining. The expression levels of miR-124-3p and BDNF were assessed using real-time polymerase chain reaction in all groups at four time points (one hour, one day, three days, and seven days post-injury).

In the SCI group, a marked reduction in miR-124-3p expression was observed relative to both the sham and intact groups. Conversely, there was a substantial elevation in BDNF expression within the SCI group in comparison to the sham and intact groups. The findings underscore a negative association between miR-124-3p expression and BDNF messenger RNA levels.

The downregulation of miR-124-3p and concurrent upregulation of BDNF suggest a potential regulatory role of miR-124-3p in modulating BDNF expression during SCI. These findings provide new insights into the molecular mechanisms underlying SCI and suggest that miR-124-3p and BDNF could serve as potential therapeutic targets. Further research is needed to explore the translational potential of these findings for developing novel diagnostic and therapeutic strategies for SCI.

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.

This review presents the latest evidence on the link between genetic single nucleotide polymorphisms and dental caries, highlighting key genes and pathways involved, introducing foundational concepts, and discussing essential methodological considerations for future research. Several genes have been identified as significantly associated with caries experience, including those related to tooth mineral tissues, taste perception, salivary composition and flow, and immune response. Epistatic interactions appear to be crucial in explaining genetic influence. Inconsistencies in the literature are attributed to variations in caries classification, age groups, ethnic backgrounds, limited statistical power, and linkage disequilibrium. Population stratification often confounds results, and few studies adequately control for genetic ancestry. Ensuring Hardy-Weinberg equilibrium and accounting for linkage disequilibrium are essential to avoid bias. Bonferroni corrections for multiple comparisons are fundamental but rarely applied, contributing to inconsistent findings. In conclusion, genetic epidemiology studies suggest that dental caries has a genetic component, accounting for significant individual differences in disease risk.

The COVID-19 pandemic profoundly impacted university students, presenting multifaceted challenges including the abrupt transition to virtual learning and significant disruptions to emotional well-being and dietary habits. This study aimed to investigate the dietary and nutritional characteristics associated with academic stress among Mexican university students during the COVID-19 lockdown.

This cross-sectional study was conducted with a sample of 114 university students in Mexico. Participants completed a self-reported questionnaire assessing dietary patterns, nutritional intake, and academic stress levels. Informed consent was obtained from all participants prior to data collection.

Among study participants (n = 114), 57.8% experienced moderate academic stress, while 25.7% reported high academic stress during the COVID-19 lockdown. Notably, 13.5% of students demonstrated food cravings that were significantly associated with increased consumption of red and fatty meats (P = 0.030) and sausages (P = 0.017). A negative virtual education experience was associated with food cravings towards high-calorie and saturated-fat foods (P = 0.014), as well as elevated academic stress levels (P = 0.009). Furthermore, high academic stress levels were positively associated with food cravings (P = 0.020), particularly towards carbohydrate-rich foods (P = 0.037).

The COVID-19 lockdown substantially disrupted the dietary habits and nutritional status of university students, with academic stress serving as a significant mediating factor.

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.

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.

Huo Xue Tong Luo Capsule (HXTL) has been clinically used to treat osteonecrosis of the femoral head, osteoporosis, and other bone and joint diseases with promising effects. Our previous study has shown that HXTL can promote osteogenesis in mesenchymal stem cells by inhibiting lncRNA-Miat expression through histone modifications. However, the mechanism by which HXTL treats postmenopausal osteoporosis (PMOP) remains unclear. In this study, we used network pharmacology-based mechanism prediction, molecular docking, and pharmacological validation to investigate the mechanism of HXTL in treating PMOP.

The key candidate targets and relevant signaling pathways of HXTL for PMOP treatment were predicted using network pharmacology and molecular docking analysis. RAW264.7 cells were used for Western blot to validate the predicted mechanistic pathways. The ovaries of mice were surgically removed to simulate PMOP. The effect of HXTL on PMOP was evaluated using tartrate-resistant acid phosphatase staining and immunohistochemical assays in vivo.

Network pharmacology analysis suggested that HXTL interacted with 215 key targets linked to PMOP, primarily affecting the PI3K-AKT signaling pathway. Molecular docking showed that the main components of HXTL exhibited strong binding affinity to NFATc1, p-PI3K, and p-AKT1. Furthermore, our in vitro results confirmed that HXTL suppressed the PI3K-AKT signaling pathway. In vivo, HE and tartrate-resistant acid phosphatase staining results showed that HXTL inhibited osteoclast formation and protected bone mass.

This research demonstrated that HXTL could inhibit osteoclast formation and prevent bone loss induced by ovariectomy in mice by inhibiting the PI3K-AKT signaling pathway. These findings provide important evidence for the clinical application of HXTL in treating PMOP.