Search

Abstract The adverse pregnancy outcomes, including recurrent spontaneous abortion (RSA), are strongly correlated with water-soluble vitamins, but how to predict RSA occurrence using them remains unsatisfactory. This study aims to investigate the possibility of predicting RSA based on the baseline levels of water-soluble vitamins tested by ultra-liquid chromatography-tandem mass spectrometry. A total of 918 pregnant women was consecutively enrolled in this cross-sectional study. According to the miscarriage numbers, they were divided into normal first pregnancy (NFP, n = 608), once spontaneous abortion (OSA, n = 167), and continuous spontaneous abortion (CSA, n = 143) groups. The Cox proportional-hazards regression model was employed to establish a risk model for predicting RSA. The RSA occurrence was 6.54% in overall pregnant women, with a prevalence of 12.57% in the OSA group and 27.27% in the CSA group. Significant differences were observed in baseline deficiencies of vitamin B3, B5, B6, and B9 among NFP, OSA, and CSA groups (χ2 = 12.191 ~ 37.561, all P 0.05). Our study presents a highly sensitive model based on mass spectrometry assay of baseline levels in B vitamins to predict the RSA occurrence as possible.

Abstract Chemotherapy is a commonly effective treatment for most types of cancer. However, many patients experience a relapse due to minimal residual disease (MRD) after chemotherapy. Previous studies have analyzed the changes induced by chemotherapy for specific types of cancer, but our study is the first to comprehensively analyze MRD across various types of cancer. We included both bulk and single-cell RNA sequencing datasets. We compared the expression of the entire genome and calculated scores for canonical pathway signatures and immune infiltrates before and after chemotherapy across different types of cancer. Our findings revealed that DUSP1 was the most significantly and widely enriched gene in pan-cancer MRD. DUSP1 was found to be essential for MRD formation and played a role in T cell-fibroblast communications and the cytotoxic function of CD4 + T cells. Overall, our analysis provides a comprehensive understanding of the changes caused by chemotherapy and identifies potential targets for preventing and eliminating MRD, which could lead to long-term survival benefits for patients.

Pyroptosis is a regulated cell death pathway involved in numerous human diseases, especially malignant tumors. Recent studies have identified multiple pyroptosis-associated signaling molecules, like caspases, gasdermin family and inflammasomes. In addition, increasing in vitro and in vivo studies have shown the significant linkage between pyroptosis and immune regulation of cancers. Pyroptosis-associated biomarkers regulate the infiltration of tumor immune cells, such as CD4+ and CD8+ T cells, thus strengthening the sensitivity to therapeutic strategies. In this review, we explained the relationship between pyroptosis and cancer immunology and focused on the significance of pyroptosis in immune regulation. We also proposed the future application of pyroptosis-associated biomarkers in basic research and clinical practices to address malignant behaviors. Exploration of the underlying mechanisms and biological functions of pyroptosis is critical for immune response and cancer immunotherapy.

BackgroundContinuous prevention efforts for human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) are recommended among those men who have sex with men (MSM). Creative use of e-technologies coupled with a better understanding of social networks could lead to improved health interventions among this risk population. ObjectiveThe aims of the study were to (1) compare the impact of various advertising strategies on recruiting MSM participants to an online HIV/AIDS survey, and (2) explore the feasibility of using a social network service (SNS) for study advertising. MethodsA cross-sectional online survey was conducted in 2009. South Australian men over 18 years were invited to participate if they had had sexual intercourse with men in the previous year. A short questionnaire was used to collect demographics and information on sexual behavior, HIV history, use of the Internet for dating purposes, and sources of health information. The survey was promoted in community settings and online, including advertisements through social networks. ResultsA total of 243 men completed the online survey during the 8-week data collection period. Online advertisements recruited 91.7% (220/240) of the sample. Conversely, traditional advertisements in the community recruited only 5.8% (14/240) of the sample. Ten volunteers were asked to advertise on their personal SNS application, but only 2 effectively did so. Only 18/240 (7.5%) of the respondents reported having learned of our study through the SNS application. In this sample, 19.3% (47/243) of participants had never been tested for HIV. Among the participants who had been tested, 12.8% (25/196) reported being HIV-positive. Regarding Internet use, 82.3% (200/243) of participants had dated online in the previous 6 months. Among the participants who had dated online, most (175/200, 87.5%) had found an Internet sexual partner and two-thirds (132/200, 66.0%) had had anal sex with these partner(s). Among men who had anal sex with an Internet partner, 68.2% (90/132) used a condom during sex. ConclusionsThe MSM participants in this study had high-risk profiles for HIV and other sexually transmitted diseases (STDs), which highlights the need for ongoing health interventions among this group. In this study, the SNS marketing strategy did not appear to create a viral effect and it had a relatively poor yield.

Several types of modifications have been proven to participate in the metabolism and processing of different RNA types, including non-coding RNAs (ncRNAs). N-6-methyladenosine (m6A) is a dynamic and reversible RNA modification that is closely involved in the ncRNA homeostasis, and serves as a crucial regulator for multiple cancer-associated signaling pathways. The ncRNAs usually regulate the epigenetic modification, mRNA transcription and other biological processes, displaying enormous roles in human cancers. In this review, we summarized the significant implications of m6A-ncRNA interaction in various types of cancers. In particular, the interplay between m6A and ncRNAs in cancer pathogenesis and therapeutic resistance are being widely recognized. We also discussed the relevance of m6A-ncRNA interaction in immune regulation, followed by the interference on cancer immunotherapeutic procedures. In addition, we briefly highlighted the computation tools that could identify the accurate features of m6A methylome among ncRNAs. In summary, this review would pave the way for a better understanding of the biological functions of m6A-ncRNA crosstalk in cancer research and treatment.

Abstract Ferroptosis is a cell death process caused by metabolic dysfunction with the feature of aberrant iron accumulation. Emerging studies have identified that ferroptosis is an important biological function involving in the tumorigenesis, and targeting ferroptosis could provide promising therapeutic targets for lung cancer. However, such therapeutic strategies show limited therapeutic effect owing to drug resistance and other unknown underlying mechanisms. In this study, lysine-specific demethylase 1 (LSD1/KDM1A) was found to be significantly upregulated in lung cancer cells and tissues. The patients with KDM1A downregulation displayed the good prognosis. Using gene set enrichment analysis (GSEA), we demonstrated that KDM1A-associated genes might participate in the regulation of cell ferroptosis and Myc signaling in lung cancer. Knockdown of KDM1A inhibited the level of c-Myc and increased the concentration of malondialdehyde (MDA) and irons in human lung cancer cells H1299 and A549. Downregulation of c-Myc could facilitate KDM1A knockdown-mediated ferroptosis. Our study has elucidated the effect of KDM1A/c-Myc regulatory axis in the ferroptosis resistance of lung cancer cells.

: Objective: To examine stakeholder perspectives on the factors of an effective approach to reduce Q fever risk including disease prevention, and the perceived potential benefits of a One Health framework. Methods: Semi?structured interviews were conducted with general practitioners (GPs), veterinarians, government authorities, researchers, and representatives from the farming industry. Transcripts were thematically analysed. Results: Six major themes were identified as key factors underpinning an effective approach to Q fever: understanding Q fever burden; effective surveillance; the role of general practitioners and other stakeholders; barriers and enablers of vaccination; an integrated approach; and increased Q fever awareness. Most participants perceived GPs to play a central role in disease detection, notification, treatment and prevention through health promotion and vaccination, despite GPs acknowledging limited awareness of Q fever. Participants suggested leadership is required from the Department of Health (DoH) to foster inter?sectoral communication and collaboration. Conclusions: A One Health approach holds opportunities for zoonosis prevention. We recommend that medical curricula and professional development be enhanced, zoonosis working group networks strengthened, government?industry partnerships established, and relevant stakeholders included within an integrated program. Implications for public health: Updating medical curricula, GP professional development programs and inter?sectoral collaboration led by health departments may reduce Q fever burden., Q fever caused by Coxiella burnetii is present in Australian livestock, wildlife and ticks,[sup.1,2] and is a persistent problem for high?risk occupations in Australia.[sup.3] Clinical presentation of Q fever includes [...]

: Objective: To examine the cost benefits of a heat health warning system (HHWS) in South Australia. Methods: Information from key agencies was used to estimate the costs associated with the South Australian HHWS, including for three targeted public health interventions. Health cost savings were estimated based on previously reported HHWS?attributable reductions in hospital and emergency department (ED) admissions and ambulance callouts. Results: The estimated cost for a one?week activation of the HHWS was AU$593,000. Activation costs compare favourably with the potential costs averted through HHWS?attributable reductions in hospital admissions and ambulance callouts with an estimated benefit?cost ratio of 2.0?3.3. Conclusions: On the basis of estimated cost benefit, the South Australian HHWS is a no?regret public health response to heatwaves. Implications for public health: As global temperatures rise there are likely to be significant health impacts from more frequent and intense heatwaves. This study indicates that HHWSs incorporating targeted supports for vulnerable groups are likely to be cost?effective public health interventions., The past five years have been the warmest in recorded history[sup.1] and the rise in global temperatures is exposing populations to record?breaking temperatures and more frequent heatwaves.[sup.2,3] In Australia, the [...]

Autophagy is a self-recycling and conserved process, in which the senescent cytoplasmic components are degraded in cells and then recycled to maintain homeostatic balance. Emerging evidence has suggested the involvement of autophagy in oncogenesis and progression of various cancers, such as ovarian cancer (OC). Meanwhile, the non-coding RNAs (ncRNAs) frequently regulate the mRNA transcription and other functional signaling pathways in cell autophagy, displaying promising roles in human cancer pathogenesis and therapeutic response. This article mainly reviews the cutting-edge research advances about the interactions between ncRNAs and autophagy in OC. This review not only summarizes the underlying mechanisms of dynamic ncRNA-autophagy association in OC, but also discusses their prognostic implications and therapeutic biomarkers. The aim of this review was to provide a more in-depth knowledge framework exploring the ncRNA-autophagy crosstalk and highlight the promising treatment strategies for OC patients.

Ferroptosis is a novel type of cell death associated with iron accumulation and excessive lipid peroxidation. Elucidating the underlying molecular mechanisms of ferroptosis is intensively related to the development and treatment of multiple diseases, including musculoskeletal disorders. Moreover, in vitro and in vivo studies have shown the importance of oxidative stress in musculoskeletal conditions such as osteoporosis, osteoarthritis, rheumatoid arthritis, and osteosarcoma. Ferroptosis-derived clinical management of musculoskeletal diseases offers tremendous and attractive opportunities. Notably, ferroptosis agonists have been proven to enhance the sensitivity of osteosarcoma cells to conventional therapeutic strategies. In this review, we have mainly focused on the implications of ferroptosis regulation in the pathophysiology and therapeutic response of musculoskeletal disorders. Understanding roles of ferroptosis for controlling musculoskeletal diseases might provide directions for ferroptosis-driven therapies, which could be promising for the development of novel therapeutic strategies.

Pyroptosis is a cell death pathway that plays a significant role in lung adenocarcinoma (LUAD). Also, studies regarding the correlation between the expression of long non-coding RNAs (lncRNAs) and the mechanism of LUAD has aroused concern around the world. The purpose of this paper is to explore the underlying relationship of differentially expressed lncRNAs and pyroptosis-related genes. The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression were applied to construct a prognostic risk score model from the TCGA database. A pyroptosis-related five-lncRNA signature (CRNDE, HHLA3, MIR193BHG, LINC00941, LINC01843) was considered to be correlated to the prognosis and immune response of LUAD patients. In addition, the cytological experiments revealed that aberrantly expressed HHLA3 displayed a proliferation promotion role in LUAD cells A549 and H460. Next, the forest and nomogram plots have shown this lncRNA signature could be served as an independent prognostic factor for LUAD. The ROC curves further identified the prognostic value of the five-lncRNA signature. The infiltration of immune cells, such as T cells CD8, T cells CD4 memory resting, T cells CD4 memory activated and M0 macrophages were greatly different between the high-risk group and the low-risk group. It implicated that the signature is significantly effective in immunotherapy of LUAD patients. This study has supplied a novel pyroptosis-related lncRNA signature and provided a predictive model for prognosis and immune response of LUAD patients.

B-Raf proto-oncogene serine/threonine-protein kinase (BRAF) is frequently altered in multiple cancer types, and BRAF V600 mutations act as a prime target for precision therapy. Although emerging evidence has investigated the role of BRAF, the comprehensive profiling of BRAF expression, alteration and clinical implications across various cancer types has not been reported. In this study, we used the TCGA dataset, covering 10,967 tumor samples across 32 cancer types, to analyze BRAF abnormal expression, DNA methylation, alterations (mutations and amplification/deletion), and their associations with patient survival. The results showed that BRAF expression, alteration frequency, mutation site distribution, and DNA methylation patterns varied tremendously among different cancer types. The expression of BRAF was found higher in PCPG and CHOL, and lower in TGCT and UCS compared to normal tissues. In terms of pathological stages, BRAF expression was significantly differentially expressed in COAD, KIRC, LUSC, and OV. The methylation levels of BRAF were significantly lower in LUSC, HNSC, and UCEC compared to normal tissue. The expression of BRAF and downstream gene (ETS2) was negatively correlated with methylation levels in various cancers. The overall somatic mutation frequency of BRAF was 7.7% for all cancer samples. Most fusion transcripts were found in THCA and SKCM with distinct fusion patterns. The majority of BRAF mutations were oncogenic and mainly distributed in the Pkinase_Tyr domain of THCA, SKCM, COADREAD, and LUAD. The BRAF mutations were divided into five levels according to the clinical targeted therapy implication. The results showed level 1 was mainly distributed in SKCM, COADREAD, and LUAD, while level 3B in THCA. The overall BRAF CNV frequency was about 42.7%, most of which was gain (75.9%), common in GBM, TGCT, and KIRP. In addition, the forest plot showed that increased BRAF expression was associated with poor patient overall survival in LIHC, OV, and UCEC. Taken together, this study provided a novel insight into the full alteration spectrum of BRAF and its implications for treatment and prognosis.