BCSC-1 (breast cancer suppressor candidate-1), the official gene symbol VWA5A (von Willebrand factor A domain containing 5 A), is downregulated in a variety of cancer types including breast cancer. The role of BCSC-1 in tumorigenesis and the underlying mechanisms are poorly understood. One of the ways to predict a spectrum of functions of an unknown protein is to identify the protein-protein interaction network involving it. Flag-pLV-Neo-BCSC1 or the empty vector were stably transfected into breast cancer cells MCF-7. The levels of BCSC1 expression were identified by Western blotting. Co-immunoprecipitation assay coupled with liquid chromatography with tandem mass spectrometry (Co-IP-MS) and bioinformatic analysis were done to study protein-protein interactions. A subset of interacting proteins was validated by immunofluorescence (IF). IF was also conducted to determine the cell migration of BCSC-1. The pEGFP-C3 plasmids with full-length and truncated BCSC-1 were transiently transfected into breast cancer cells to identify domains of BCSC-1 guiding the subcellular location. 341 interacting partners of BCSC-1 were significantly enriched in Flag-BCSC-1 against negative control. These interactors included the lysosome and the proteasome related to proteostatic pathways, the peroxisome involved in lipid metabolism, endocytosis components in the vesicle transport pathway, and the regulation of actin cytoskeleton. STAT1, STAT3, and CDC42, identified among the interacting partners, co-localized with BCSC-1. In addition, BCSC-1 distributed to the leading edge of migrating breast cancer cells. VIT (vault protein inter-α-trypsin) domain of BCSC-1 is required in the regulation of cell migration. BCSC-1 might exert diverse functions through protein-protein interactions.

PACT (encoded by the PRKRA gene) is a double-stranded RNA binding protein with defined antiviral defense and cytoplasmic RNA-induced silencing actions in mammals. We previously described a further role for PACT as a modulator of nuclear receptor (NR)-regulated gene expression. Here, we investigated the role of PACT in prostate cancer (PCa) using a loss-of-function approach. Depletion of PACT in multiple PCa cell lines resulted in a reduction in cell proliferation, but viability was maintained. RNA-sequencing analysis of LNCaP PCa cells ± PACT revealed a depletion of biological processes involved in cell cycle, mitochondrial function, and NR-response pathways in the PACT knockout (KO) cells. In the PACT KO cells, downregulated genes included the androgen-regulated KLK3 (prostate specific antigen, PSA), together with H2AFJ, PSMD5, AQP3, TMEM45B, and SLC22A3, and siRNA-mediated knockdown of these genes reduced cell growth and proliferation in LNCaP cells. Further, reducing PACT or PSA induced cell cycle arrest at G0/G1. Additionally, the hormone-mediated upregulation and AR antagonist-driven downregulation of PSA gene expression were respectively attenuated and enhanced in PACT KO cells. Taken together, these data support a pro-proliferative role for PACT in PCa, and siRNA therapeutic targeting of PACT, or downregulated genes with PACT KO, could represent a new therapeutic approach.

MicroRNA (miRNA) dysregulation is implicated in testicular germ cell tumor (TGCT) pathogenesis. Here, we characterized miRNA expression profiles across TGCT histologic subtypes using miRNA-sequencing on 43 formalin-fixed paraffin-embedded (FFPE) tissue samples (31 primary, 12 metastases) from 29 patients to identify diagnostic markers and their regulatory functions. From 20 seminomas (SEM), 14 non-seminomatous germ cell tumors (N-SEM), and 9 teratomas, we profiled a total of 2606 miRNAs. Compared to teratomas, 154 miRNAs (targeting 657 genes) were enriched in SEM, and 141 miRNAs (targeting 358 genes) in N-SEM. miR-200-3p, targeting the DNA methyltransferase DNMT3B, was enriched in N-SEM versus SEM. Our findings showed high concordance with The Cancer Genome Atlas (TCGA)-TGCT data (Pearson R > 0.66, p < 1e-10). miRNA expression was largely similar between primary and metastatic tissues and between chemotherapy-treated and untreated teratomas, reflecting teratoma chemo-resistance. Using novel candidates, miRNA-based logistic regression classifiers distinguished viable GCT (SEM/N-SEM) from teratoma (Area Under the Curve [AUC] > 0.96) and SEM from N-SEM (AUC = 0.81), outperforming well-known miRNA markers. Target gene analysis implicated FOXO and RUNX1 regulation, somatotroph signaling, and height-related pathways. Overall, our comprehensive tissue-level miRNA profiling in TGCTs identified potential diagnostic biomarkers for histologic subtypes, offering insights into miRNA-mediated transcriptional dysregulation.

The deubiquitinating enzyme USP14, which belongs to the ubiquitin-specific protease family, is highly expressed in various malignant tumors. The regulatory mechanisms in tumors are complex and diverse, encompassing a range of cellular processes such as proliferation, apoptosis, inflammation, autophagy, and drug resistance. However, the functional role of USP14 in gastric cancer remains unclear. In the current investigation, a significant upregulation of USP14 expression was observed in gastric cancer, and its overexpression was associated with an unfavorable prognosis among patients. The involvement of USP14 is indispensable for promoting the growth, motility, and infiltration of gastric cancer cells, as revealed by our findings. Further investigations revealed that USP14 interacts with KPNA2 and is responsible for deubiquitinating it by removing ubiquitin. Moreover, the deubiquitylation process mediated by USP14 was found to be critically dependent on the K48 residue of ubiquitin. The knockdown of USP14 significantly suppressed the proliferation, migration, and invasion of gastric cancer cells. This effect was attributed to the regulation of c-MYC nuclear translocation through KPNA2 deubiquitination. The findings underscore the imperative for further evaluation of the potential therapeutic significance of USP14 in gastric cancer.

Ubiquitination is integral to the pathogenesis of various tumors. This study sought to elucidate the role and underlying mechanisms of BTRC-mediated ubiquitination and degradation in glioma.

The expression levels of beta-transduced in repeat containing E3 ubiquitin protein ligase (BTRC), nuclear factor of activated T cells 5 (NFAT5) and aquaporin-4 (AQP4) were assessed by RT-qPCR/Western blot. The association and underlying mechanisms of BTRC, NFAT5, and AQP4 were examined through co-immunoprecipitation, cycloheximide chase, and chromatin immunoprecipitation assays. The influence of the BTRC/NFAT5/AQP4 axis on the malignant biological functions of glioma cells and tumor growth was evaluated through a series of in vitro and in vivo experiments.

In glioma cells, BTRC expression was observed to be downregulated. Overexpression of BTRC inhibits proliferation, migration and invasion, while promoting apoptosis in glioma cells. Mechanically, BTRC overexpression facilitates ubiquitination and degradation of NFAT5, thereby inhibiting NFAT5-mediated transcriptional activation of AQP4. Functional recovery assays demonstrated that the overexpression of either AQP4 or NFAT5 counteracted the intervention effect of upregulation of BTRC on the malignant behavior of glioma cells. In vivo animal experiments further confirmed the results of the in vitro experiments, indicating that the overexpression of BTRC inhibits tumor growth through the NFAT5/AQP4 axis.

BTRC negatively modulates the transcription of AQP4 via NFAT5 in glioma cells, thereby influencing their malignant biological functions and tumor growth.

Ocular surface tumors, originating from either the conjunctiva or the cornea, primarily fall into three categories of malignant or premalignant neoplasms: ocular surface squamous neoplasia (OSSN), ocular surface melanocytic tumors, and conjunctival lymphoid tumors. These neoplasms can originate from either the conjunctiva or the cornea. Exposure to space radiation, particularly galactic cosmic rays, and solar particle events, poses a significant threat to astronaut health, including the development of ocular malignancies. As such, the objective of this study was to describe the exposure risk for ocular surface malignancies, current mitigation strategies, and management considerations for a mission to Mars. The current mitigation strategies for space radiation include physical and structural shielding along with dietary interventions. Additionally, management of ocular health during a Mars mission can include holoportation, AI-powered diagnostics, newest in-space surgical technology, optical coherence tomography (OCT), and more. Conclusively, further research and collaboration amongst space and healthcare professionals is necessary to ensure the safety and well-being of astronauts during future space exploration endeavors.

Bladder cancer was commonly diagnosed cancer, which has a high disease burden in China and the world. This study aims to better assess the epidemiological situation of bladder cancer in China.

Data for bladder cancer mortality were observed based on the data from the National Mortality Surveillance System. We analyzed the number of deaths, years of life lost(YLL), the age-standardized mortality rates(ASMR) and the age-standardized YLL rates due to bladder cancer in China during 2005-2020. We calculated the reduction in life expectancy due to bladder cancer.

In 2020, bladder cancer accounted for 29 730 deaths and 492 859 YLL in China. The ASMR and the age-standardized YLL rate of males were consistently higher than that of females. From 2005 to 2020, the reduction in life expectancy due to bladder cancer increased from 0.018 to 0.021 years. The reduction in life expectancy caused by bladder cancer in urban areas was consistently higher than that in rural areas, since this increased from 0.013 years in 2005 to 0.018 years in 2020 in rural areas. The reduction in life expectancy caused by bladder cancer in males was higher than that in females, and increased from 0.024 to 0.029 years in males between 2005 and 2020.

The number of deaths for bladder cancer in China has been increasing in recent years. Although the loss of life expectancy caused by bladder cancer in China was relatively small, the gradually increasing trend warrants attention, especially in economically developed regions.

Gestational trophoblastic disease, characterised by abnormal proliferation of trophoblastic tissue in the placenta during pregnancy, contributes to maternal morbidity and mortality. This study aimed to estimate the pooled prevalence and histopathological patterns of gestational trophoblastic disease in Africa, where previous studies have reported inconsistent findings.

Systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines.

We searched PubMed, ScienceDirect, Hinari and Google Scholar for studies published between January 2000 and January 2024.

Institution-based observational studies from African countries reporting the prevalence and/or histopathological patterns of gestational trophoblastic disease, using total deliveries as the denominator.

Data were extracted into Excel and analysed using Stata V.17. Pooled estimates were calculated using a random-effects model with Knapp-Hartung adjustment. Heterogeneity was assessed with Cochran's Q test and the I² statistic, and study quality was evaluated using the Joanna Briggs Institute tool.

Of the 2252 studies identified, 33 were included, comprising 2885 gestational trophoblastic disease cases from eight countries. The pooled prevalence of gestational trophoblastic disease in Africa was 4.35 per 1000 deliveries (95% CI 3.26 to 5.45, I²=99.8%). The pooled prevalence of hydatidiform mole, invasive mole and choriocarcinoma in Africa was 3.49 per 1000 deliveries (95% CI 2.45 to 4.52, I²=99.7%), 0.47 per 1000 deliveries (95% CI 0.14 to 0.79, I²=72.2%) and 0.97 per 1000 deliveries (95% CI 0.54 to 1.40, I²=99.1%), respectively.

This review indicated the prevalence of gestational trophoblastic disease was high. Hydatidiform mole was the predominant histopathological pattern observed. Routine antenatal screening is needed for early detection. Further research should be conducted to identify risk factors and evaluate strategies for the prevention and management of the disease.

CRD42024504268.

The pandemic associated restrictions hastened adoption of telemedicine. We used a mixed methods approach to evaluate the frequency, patterns and determinants of telemedicine use for persons with epilepsy (PWE) in a low middle income country.

We carried out an explanatory sequential QUAN◊qual study of PWE on telemedicine use. We collected socio-demographic and epilepsy related data, and estimated satisfaction with telemedicine. For the qualitative part we purposively sampled 30 PWE and conducted 4 focus group discussions and 6 interviews. For the physician perspective we surveyed 49 physicians from 5 allied departments and conducted a focus group discussion and 5 key informant interviews. We explored domains of knowledge, technology, organisation, environment, innovation and health care specific factors using expert validated guides. We analysed the survey descriptively using STATA ver 14.2, STATA Corp, USA. We coded transcripts both inductively and deductively using Nvivo 12, USA. Joint displays were generated.

Telemedicine was used by 386 (50.1%; 95%CI: 46.5-53.7%) of 770 surveyed PWE. Higher education, living farther away and lower income were significantly associated with telemedicine use. Most PWE needed help to use telemedicine. Physicians and PWE agreed appropriate selection was a facilitator for telemedicine use. Physicians were most concerned about communication while PWE were most concerned about medications.

Telemedicine reached about half of PWE during the pandemic. Lack of awareness including digital literacy among PWE and lack of training and/or opportunity for providers were important barriers. Selection of appropriate provider and PWE are key factors in ensuring an optimal telemedicine encounter.

This retrospective cohort study aimed to examine the association between blood eosinophil counts and in-hospital mortality among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to the intensive care unit (ICU).

Data were retrieved from the MIMIC-IV 2.2 database. AECOPD patients with blood eosinophil counts measured within the first 24 h following ICU admission were included. Kaplan-Meier (KM) survival analysis compared in-hospital mortality across eosinophil thresholds (0.10, 0.15, 0.20, and 0.30 × 10⁹/L). Four Cox regression models adjusted for confounders, with patients categorized into three eosinophil groups: eosinophil counts < 0.1 × 10⁹/L (Group I), 0.1 × 10⁹/L ≤ eosinophil counts < 0.3 × 10⁹/L (Group II), and eosinophil counts ≥ 0.3 × 10⁹/L (Group III), with the Group I serving as the reference group. Restricted cubic spline (RCS) analysis based on a Cox proportional hazards model was used to assess the non-linear relationship between eosinophil counts and in-hospital mortality.

A total of 1,855 patients were analyzed. KM survival curves showed significant mortality differences at eosinophil thresholds of 0.10, 0.15, and 0.20 × 10⁹/L. Compared with Group I, Group II consistently exhibited a significantly lower risk of in-hospital mortality across all Cox models. Group III showed a mortality reduction only in the unadjusted model, which lost statistical significance after adjustment. RCS analysis revealed an "L"-shaped association, with an inflection point around 0.042 × 10⁹/L.

Lower eosinophil counts were associated with increased in-hospital mortality among critically ill AECOPD patients. Absolute eosinophil counts may serve as a prognostic biomarker to support personalized ICU management. Prospective studies are needed to validate these findings and inform clinical decision-making.