British Journal of Biomedical Science最新文献

Background: Hypertension is a major risk factor for cardiovascular diseases and premature death worldwide. Less than half of adults with hypertension are not properly diagnosed and treated indicating a need for better diagnostic and treatment strategies. Exosomal miRNAs have been implicated in hypertension development and show potential as non-invasive disease biomarkers. Therefore, this study aimed to investigate potential exosomal miRNA biomarkers of hypertension to enhance early detection.

Methods: Plasma exosomes from newly identified, stage I essential hypertensive adults and their controls were isolated and characterised. The miRNA profiles were compared using small RNA sequencing, then validated with quantitative PCR (qPCR). Enriched pathways and gene ontologies of predicted miRNA targets were compared against systemically dysregulated pathways to validate its biological function.

Results: Hypertensives showed preferential release of exosomes larger than 150 and significantly reduced expression of exosomal CD9. After qPCR validation, a unique hypertensive exosomal miRNA profile consisting of three downregulated and one upregulated miRNA was identified. The combination of this miRNA signature (hsa-miR-184, hsa-miR-432-5p, hsa-miR-1-3p, and hsa-miR-1246) with BMI demonstrated the highest diagnostic value. Predicted target pathways of the miRNA signature and systemically dysregulated proteomics pathways highlighted the convergence of aberrant metabolic pathways in the development of hypertension.

Conclusion: This study identified a unique hypertensive exosomal miRNA profile when used combination with BMI. The miRNA signature provided insights into the mechanisms involved in the early stages of hypertension and offers leads for further validation in biomarker discovery to alleviate the burden of cardiovascular diseases.

FIT-PNAs (forced intercalation-Peptide Nucleic Acids) are promising RNA sensors due to the enhanced fluorescence gained by such molecules upon RNA hybridization. In this report we describe a chemical approach that leads to unprecedented brightness for a FIT-PNA where the neighbouring Guanine base (G) to the fluorophore (a.k.a. surrogate base) is chemically modified with a cyclopentane (cp) backbone and is N-methylated, leading to a positively charged (G⁺) base. A series of G modified bases (G⁺, cpG, and cpG⁺) were introduced as the neighbouring base to BisQ (surrogate base) in 15-mer FIT-PNAs designed to sense the oncogenic long-noncoding RNA, colon cancer associated transcript 1 (lncRNA CCTA-1). Using synthetic RNA, the combination denoted as cpG⁺ led to a two-fold increase in brightness (BR = 16.9) compared to the unmodified G base (BR = 8.4). Introducing a G mismatch in RNA sequence that is opposite to the G base (G, G⁺, cpG, or cpG⁺) in the FIT-PNA, led to an increase in fluorescence that was not observed for synthetic DNA. Molecular simulations confirmed these observations and further correlated fluorescence data for FIT-PNAs with synthetic DNA and RNA with/out mismatches. Importantly, in ovarian cancer cells overexpressing CCAT1, only the cpG⁺ modified FIT-PNA produced a bright fluorescent signal, confirmed by FACS and confocal microscopy. Our results demonstrate that strategic chemical modifications of the neighboring G base in FIT-PNA significantly enhance their brightness and specificity for RNA detection in biological systems.

In the UK, there are approximately 650,000 babies born each year. The pregnancy journey is not only unique to each woman, but for each individual pregnancy that may be experienced. Pregnancy complications, miscarriage, and stillbirths are still a huge problem with maternity services, highlighting the need for more research to understand the underlying causes, earlier detection or even prevention of conditions such as pre-eclampsia, gestational diabetes, restricted fetal growth and the impact of infection during pregnancy. One area of interest which transcends these conditions is the functioning of the placenta. The placenta is the lifeline for the fetus to the mother. It is a unique organ, crucial for survival, but also known to have impacts on the lifelong health of the fetus. Aberrant development, as well as in utero exposure to infections and environmental chemicals are known to have multiple impacts on the functioning of the placenta, and the fetus it supports. The placental environment is a fascinating organ to study with much still to be learned about its development, role in pregnancy complications, as well as its impact on long term offspring health. The placental environment is abundant with immune cells and mediators. There is a need within medical and biomedical practice for a good understanding of the complex relationship between immune cells, the decidua and placenta, and doing so will aid in development of better diagnostic tests and treatments for placenta-driven pregnancy complications and infections. This review will summarise the placenta as an immunological environment through description of key decidual immune cells, the expression of innate recognition receptors and it will provide an update on the placental immune response to infections of importance during pregnancy.

Tablets are the most commonly used dosage form due to their low manufacturing cost and ease of administration. Incorporating mesoporous silica microparticles offers enhanced control over drug release and bioavailability; however, formulation remains challenging due to poor compressibility and disintegration characteristics. This study explores dynamic formulation strategies to enable successful incorporation of SYLOID XDP 3150 (SYLOID) into oral tablet formulations. Tablets were prepared via direct compression using varying ratios of Avicel PH 102 (MCC: microcrystalline cellulose) and lactose monohydrate (25:75, 50:50, and 75:25) with SYLOID incorporated at 0%, 20%, and 40% (w/w). A 500 mg tablet mass was maintained throughout, and SYLOID alone was also compressed to assess baseline behaviour. Key tablet properties including porosity, tensile strength, friability, and disintegration time were evaluated. Direct compression of SYLOID alone failed due to poor compactability and particle fragmentation at 221.72 MPa. Increased Avicel content led to reduced porosity and enhanced tensile strength, while higher SYLOID levels increased porosity but compromised mechanical strength and friability. Disintegration was faster in lactose-rich formulations but delayed with increased SYLOID due to its hydrophobicity. Incorporating a superdisintegrant and binder enabled the final formulations to meet USP requirements for disintegration and friability. Overall, SYLOID was shown to significantly affect tablet architecture and performance, necessitating excipient support to overcome its inherent limitations. These findings support further evaluation of drug-loaded SYLOID tablets to assess their impact on drug release profiles and oral bioavailability.

Context: Immunohistochemical (IHC) testing of estrogen receptors (ER), progesterone receptors (PR), HER2 and Ki-67 on breast cancer samples is carried out in the majority of clinical departments to predict response to therapies and to determine prognosis. Issues surrounding the reproducibility of testing are well documented and guidelines recommend laboratories participate in external quality assessment (EQA) in order to ensure reliability of results.

Objective: To assess the reproducibility of IHC testing for these markers in hospitals from the south, north, and centre of Vietnam, estimated to be approximately half of all clinical hospitals in the country performing these tests.

Design: As cases are referred for testing between hospitals, an EQA ring study was designed that included the testing of samples from all participating laboratories. Participants were provided with unstained slides of invasive breast carcinomas with different expression levels for ER, PR, HER2 and Ki-67.

Results: There was a significant level of reproducibility for all four biomarkers, with ER testing giving the least variation in results (kappa 0.822, coefficient of variation [CV] 4.8%) and Ki-67 the greatest variation (kappa 0.647 CV 17%). However, 328/392 (84%) and 317/392 (81%) of the Ki-67 evaluations were in agreement when employing the clinically relevant cut points of ≥30% and ≥20%, respectively. The reproducibility of testing for HER2-low expression was relatively poor (kappa 0.323, 95% CI 0.223-0.424), compared to overall agreement for HER2 testing (kappa 0.794, 95% CI 0.753-0.836).

Conclusion: This is the first EQA ring study held within Vietnam for ER, PR, HER2 and Ki-67 and sets the base line as to the current level of reproducibility in the country. Continued participation in the program will help ensure the reliability of testing for clinical use.

Non-malignant disorders of granulocytes and monocytes include a range of conditions characterized by either quantitative issues (such as cytopenias or cytophilias) or qualitative defects in innate immune cells. These disorders encompass neutropenias, monocytopenias, eosinophilic syndromes, and defects in granulocyte maturation. They can result from genetic mutations (including ELANE, HAX1, GATA2, and CSF3R), autoimmune dysregulation, or idiopathic mechanisms. The clinical manifestations of these disorders vary and can include recurrent infections, inflammatory complications, and organ damage. These issues arise from disrupted granulopoiesis, abnormal apoptosis, or dysfunctional chemotaxis. Recent innovations underscore how molecular diagnostics inform both mutation detection and risk stratification in congenital neutropenias. Take ELANE-associated severe congenital neutropenia: such variants not only establish the disorder but also highlight the subsequent hazard of myelodysplastic progression. In contrast, GATA2 deficiency generates isolated monocytopenia, correlating with a broadened window for opportunistic pathogens. Frontline practice now advocates for prompt, integrative assessment using next-generation sequencing alongside quantitative flow cytometry, thereby parsing mild benign states from early clonal hematopoiesis. Management hurdles persist, especially in patients with refractory neutropenia and the calibrated use of immunosuppression in autoimmune etiologies. The COVID-19 pandemic incidentally reiterated the extent of infectious susceptibility within this cohort, prompting the refinement of absolute, personalized prophylactic strategies. This review synthesizes the molecular mechanisms, genetic basis, and therapeutic innovations in non-malignant granulocyte/monocyte disorders, offering a roadmap for personalized management. By bridging mechanistic insights with clinical practice, it addresses unmet needs in diagnostics, risk prediction, and novel biologics, ultimately improving outcomes for these underrecognized yet impactful conditions.

Health disparities that are seen in underserved and underrepresented communities are a pressing issue in healthcare. These disparities are embedded into our society through structural inequalities that lead to poorer health outcomes in those from minoritised communities. In its place as the heart of modern healthcare, the biomedical science workforce has the potential to play a crucial role in mitigating these disparities by fostering greater cultural competence, improving patient outcomes and driving innovative solutions. This study reviewed the current literature on the impact of diversity within the biomedical science workforce on health disparities in underserved communities. The review demonstrated where embedded inequities in healthcare lead to worse health outcomes for underserved communities. These disparities are found across healthcare education, diagnostic processes as well as within research and innovation, and this work uses the COVID-19 Pandemic as an example of where health disparities have significant consequences for the communities impacted. This review demonstrates that a diverse biomedical science workforce can not only contribute to better health outcomes, but also to inclusive research agendas and clinical studies by ensuring that research priorities are more representative of a broader population. A more diverse biomedical science workforce can serve as role models and mentors, inspiring the next-generation of biomedical scientists from underrepresented backgrounds creating a continuous cycle of inclusion and representation, helping to reduce health disparities over time. Therefore, a key strategy in promoting health equity is by increasing diversity in the biomedical science field. After review of current published works, the authors have proposed a list of recommendations that outline steps institutions, professional bodies and policymakers could take to a strategic and sustained commitment to improving biomedical science workforce diversity in an effort to reduce health disparities.

Background: Artificial intelligence (AI) is increasingly playing important roles in healthcare diagnosis, treatment, monitoring, and prevention of diseases. Despite this widespread implementation of AI in biomedical sciences, it has yet to be characterized.

Aim: The aim of this scoping review is to explore AI in biomedical sciences. Specific objectives are to synthesize six scopes addressing the characteristics of AI in biomedical sciences and to provide in-depth understanding of its relevance to education.

Methods: This scoping review has been developed according to Arksey and O'Malley frameworks. PubMed, Embase, and Web of Science databases were searched using broad search terms without restrictions. Citations were imported into EndNote for screening and extraction. Data were categorized and synthesized to define six scopes discussing AI in biomedical sciences.

Results: A total of 2,249 articles were retrieved for screening and extraction, and 192 articles were included in this review. Six scopes were synthesized from the extracted data: Scope (1): AI in biomedical sciences by decade, highlighting the increasing number of publications on AI in biomedical sciences. Scope (2): AI in biomedical sciences by region, showing that publications on AI in biomedical sciences mainly originate from high-income countries, particularly the USA. Scope (3): AI in biomedical sciences by model, identifying machine learning as the most frequently reported model. Scope (4): AI in biomedical sciences by discipline, with microbiology the discipline most commonly associated with AI in biomedical sciences. Scope (5): AI in biomedical sciences education, which was limited to only six studies, indicating a gap in research on the educational application of AI in biomedical sciences. Scope (6): Opportunities and limitations of AI in biomedical sciences, where major reported opportunities include efficiency, accuracy, universal applicability, and real-world application. Limitations include; model complexity, limited applicability, and algorithm robustness.

Conclusion: AI has generally been under characterized in the biomedical sciences due to variability in AI models, disciplines, and perspectives of applicability.

Background: Although mRNA-based vaccines have been in development for over two decades, their widespread use only emerged during the COVID-19 pandemic. The success of these vaccines has brought mRNA technology to the forefront of efforts to develop novel vaccines. However, as this is a rapidly evolving field, there is a need for a comprehensive and up-to-date overview of the current evidence base to guide further research and development. This study, therefore, systematically reviewed the literature on clinical trials using mRNA vaccines for infectious diseases other than COVID-19.

Methods: A systematic review of the literature, following the PRISMA 2020 guidelines, identified clinical trials in infectious diseases other than COVID-19. PubMed and ClinicalTrials.gov were screened for such clinical trials using search terms related to mRNA vaccines, and the results of the two independent searches were combined. Clinical trials using mRNA vaccines against either COVID-19 or non-communicable diseases were removed, as were duplicated studies. The remaining clinical trials were then stratified based on pathogen, status, and phase.

Results: Nine hundred and seventy-six clinical trials were identified, of which 83 met the inclusion criteria. These included candidate mRNA vaccines against 14 viral, two bacterial and one protozoan infection. Of these, 43 trials have concluded, 21 are active, and a further 12 are recruiting, with the remaining not yet recruiting, enrolling by invitation, or withdrawn. Of the 43 completed clinical trials, 26 were phase I trials, eight were phase I/II trials, three were phase II trials, and six were phase III trials. The clinical trials captured in this systematic review included combined vaccines, with two or more vaccines administered at the same time, and mRNA vaccines designed to encode pathogen structural components, in addition to pathogen-specific antibodies.

Conclusion: This systematic review identified clinical trials investigating mRNA vaccine candidates against multiple infectious diseases, other than COVID-19, with the majority targeting viral infections. Despite the lack of long-term data, this systematic review suggests that these mRNA vaccine candidates are safe and effective with the potential to shape the field of preventive medicine. Beyond the prevention of infectious diseases, mRNA vaccines are showing promise against cancer and potential applications in autoimmune and other diseases.