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Gut Microbiota of Sarawak's "Orang Ulu" Indigenous Community in East Malaysia Reveals Vanish Microbes: A Comparison With Urban Communities. 马来西亚东部沙捞越“Orang Ulu”土著社区的肠道微生物群揭示了消失的微生物:与城市社区的比较。
IF 4.6 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2026-01-21 eCollection Date: 2025-01-01 DOI: 10.3389/bjbs.2025.15378
Farhat Abjani, Yi Xian Er, Soo Ching Lee, Priya Madhavan, Anthony Rhodes, Yvonne Ai Lian Lim, Pei Pei Chong, Karuthan Chinna

Introduction: Urbanization often correlates with reduced diversity in human gut microbiota, with notable variations observed between the gut microbiota among the Indigenous communities in rural villages and urban citizens residing in modern settings. Although research has been conducted on the gut microbiota of healthy adults in Malaysia, there has been no study characterising the gut microbiota of Sarawak's Indigenous communities to date. This study aims to fill this gap by examining the gut microbiota profile of the Sarawak Indigenous groups (specifically Orang Ulu subethnic groups Kayan and Kenyah), comparing them with semi-urbanized Selangor Indigenous communities from Peninsular Malaysia (represented by Proto Malay subtribe Temuan) and Urban communities from Kuala Lumpur.

Methods: We conducted a cross-sectional study and collected stool samples from 86 Indigenous participants from Sarawak and compared them with published data from 45 Malaysian Indigenous participants from Selangor and 18 Urban citizens living in Kuala Lumpur City. DNA was extracted from the stool samples, and subsequently, the V4 hypervariable region of the 16S rRNA gene was sequenced. The raw sequence data were analyzed using the Quantitative Insights into Microbial Ecology 2 (QIIME2) bioinformatics platform.

Results and discussion: Analysis revealed that the Sarawak Indigenous community exhibited the highest gut microbial diversity, followed by the Peninsular Indigenous and Urban groups. The Prevotella/Bacteroides (P/B) ratio revealed that the Sarawak Indigenous community showed the highest presence of Prevotella at 88.3%, while Kuala Lumpur Urban residents had a predominantly Bacteroides composition at 61%. The Selangor Indigenous community also exhibited a Prevotella-dominant profile at 75.5%. VANISH microbes (Prevotella, Faecalibacterium, and Succinivibrio) were identified as dominant genera in the Sarawak Indigenous gut microbiota, contrasting with the BIoSSUM microbe (Bacteroidaceae) found in the Kuala Lumpur cohort.

Conclusion: This study sheds light on the distinct gut microbiota composition of Sarawak's Indigenous community, which has not been previously explored. It highlights the impact of urbanization on gut microbiota composition during lifestyle transitions.

城市化通常与人类肠道菌群多样性的减少有关,在农村农村的土著社区和居住在现代环境中的城市居民之间观察到肠道菌群的显著差异。虽然已经对马来西亚健康成年人的肠道微生物群进行了研究,但迄今为止还没有对砂拉越土著社区的肠道微生物群进行表征的研究。本研究旨在通过检查砂拉越土著群体(特别是奥朗乌鲁亚族群Kayan和Kenyah)的肠道微生物群概况来填补这一空白,将它们与来自马来西亚半岛的半城市化的雪兰莪土著社区(以原马来亚部落Temuan为代表)和吉隆坡的城市社区进行比较。方法:我们进行了一项横断面研究,收集了来自沙捞越的86名土著参与者的粪便样本,并将其与来自雪兰莪的45名马来西亚土著参与者和居住在吉隆坡市的18名城市居民的公开数据进行了比较。从粪便样本中提取DNA,随后对16S rRNA基因的V4高变区进行测序。原始序列数据使用Quantitative Insights into Microbial Ecology 2 (QIIME2)生物信息学平台分析。结果和讨论:分析显示,沙捞越土著社区的肠道微生物多样性最高,其次是半岛土著和城市群体。普雷沃氏菌/拟杆菌(P/B)比值显示,砂拉越土著社区的普雷沃氏菌最高,为88.3%,而吉隆坡城市居民以拟杆菌为主,为61%。雪兰莪土著社区也以普雷沃菌为主,占75.5%。与吉隆坡队列中发现的BIoSSUM微生物(拟杆菌科)相比,VANISH微生物(Prevotella, Faecalibacterium和Succinivibrio)被确定为砂拉越本地肠道微生物群中的优势属。结论:这项研究揭示了沙捞越土著社区独特的肠道微生物群组成,这是以前没有探索过的。它强调了城市化对生活方式转变期间肠道微生物群组成的影响。
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引用次数: 0
S100 Protein and Interleukin Biomarkers Among COVID-19 Subjects With and Without Pneumonia: A Systematic Review and Meta-Analysis. S100蛋白和白细胞介素生物标志物在伴有和不伴有肺炎的COVID-19受试者中:一项系统综述和荟萃分析
IF 4.6 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2026-01-08 eCollection Date: 2025-01-01 DOI: 10.3389/bjbs.2025.15355
Haily Liduin Koyou, Vasudevan Ramachandran, Mohd Nazil Salleh, Wan Aliaa Wan Sulaiman, Mohd Hazmi Mohamed, Mohd Jaamia Qaadir Mohd Badrin, Caroline Satu Jelemie

Background: The global spread of COVID-19, caused by SARS-CoV-2, has resulted in a wide spectrum of clinical manifestations, ranging from asymptomatic cases to severe complications, such as pneumonia, acute respiratory distress syndrome (ARDS), and multiple organ failure. Identifying effective biomarkers is essential for predicting disease severity and improving patient management.

Objectives: This meta-analysis aims to assess the significance of S100 proteins (S100A4, S100A8, S100A9, S100A12, S100B, S100P) and interleukins (IL) (IL-6, IL-8, IL-10, IL-17, IL-1β) in COVID-19 patients, comparing those with and without pneumonia or organ failure.

Methods: A systematic literature search was conducted on different databases, yielding 47 relevant studies published between 2020 and 2024. Data on the prevalence of IL and S100 protein levels were extracted and analyzed using pooled standardized mean differences (SMD) and heterogeneity (I2) to evaluate their associations with disease severity.

Results: IL-6 and IL-10 levels were significantly elevated in COVID-19 patients suffering from pneumonia or organ failure. IL-6 levels were notably higher in pneumonia patients compared to those without (SMD = 0.34 [95% CI: 0.17, 0.52], I2 = 29%). Similarly, elevated S100B levels were observed in severe cases (SMD = 0.51 [95% CI: 0.19, 0.83], I2 = 0%). While IL-10 levels showed high variability (I2 = 90%), they remained consistently linked with worse outcomes.

Conclusion: This meta-analysis underscores the potential of IL-6, IL-10, and S100 proteins as important biomarkers in evaluating COVID-19 severity, offering valuable insights to help clinical management.

背景:由SARS-CoV-2引起的COVID-19全球传播导致了广泛的临床表现,从无症状病例到严重并发症,如肺炎、急性呼吸窘迫综合征(ARDS)和多器官衰竭。识别有效的生物标志物对于预测疾病严重程度和改善患者管理至关重要。目的:本荟萃分析旨在评估S100蛋白(S100A4、S100A8、S100A9、S100A12、S100B、S100P)和白细胞介素(IL-6、IL-8、IL-10、IL-17、IL-1β)在COVID-19患者中的意义,并与有无肺炎或器官衰竭患者进行比较。方法:对不同数据库进行系统文献检索,获得2020 - 2024年间发表的相关研究47篇。提取IL患病率和S100蛋白水平的数据,并使用合并标准化平均差异(SMD)和异质性(I2)进行分析,以评估其与疾病严重程度的相关性。结果:肺炎或器官衰竭患者IL-6、IL-10水平明显升高。肺炎患者IL-6水平明显高于无肺炎患者(SMD = 0.34 [95% CI: 0.17, 0.52], I2 = 29%)。同样,在重症患者中观察到S100B水平升高(SMD = 0.51 [95% CI: 0.19, 0.83], I2 = 0%)。虽然IL-10水平表现出很高的可变性(I2 = 90%),但它们始终与较差的结果相关。结论:该荟萃分析强调了IL-6、IL-10和S100蛋白作为评估COVID-19严重程度的重要生物标志物的潜力,为帮助临床管理提供了有价值的见解。
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引用次数: 0
An Analysis of the Readability of Public-Facing Information Relating to Prevention of Infectious Diseases by Vaccination. 面向公众的传染病预防接种信息的可读性分析。
IF 4.6 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-12-22 eCollection Date: 2025-01-01 DOI: 10.3389/bjbs.2025.15435
Beverley C Millar, Callum Peters, John E Moore

Purpose: The readability of public-facing vaccine-related information is an important aspect of health literacy particularly regarding vaccine uptake. The aims of this study were to analyse the readability of such written literature and to provide recommendations, for improvement.

Methods: Readability of vaccine-related information (ntotal = 240) from publicly available sources (n = 20 per category), including PubMed Abstracts, Expert Review of Vaccines (ERV) and Cochrane Reviews (CR), paired plain language and scientific abstracts, public health materials, clinical trial summaries and vaccine patient information leaflets, were assessed using the Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), SMOG and Gunning Fog readability metrics using the readability software tool readable.com.

Results: Vaccine-related information for all sources had poor readability across all readability metrics with 90.8% and 94.6% not reaching the target FKGL (≤8) (mean 12 ± 3.2 sd) and FRE (≥60) (mean 34 ± 17 sd). Plain language summaries had improved readability, but did not reach reference targets. Scientific abstract and plain language scores for the CR were FRE (mean 25 ± 7.2 sd; median 25) versus (mean 37 ± 8.6 sd; median 36) p < 0.0001), respectively and for ERV FRE the scientific abstract (mean 18 ± 11 sd; median 17) versus the plain language score (mean 26 ± 11 sd; median 28) p = 0.002), respectively, indicating an improvement in readability scores for plain language summaries but again not reaching reference targets.

Conclusion: The readability of public-facing vaccination materials is currently not optimum. The readability can be improved through the employment of readability calculators and ensuring, where possible, the use of mono-syllable words and less than fourteen words per sentence. The preparation of public-facing materials with improved readability scores will help aid in the promotion of health literacy and in turn promote vaccination uptake.

目的:面向公众的疫苗相关信息的可读性是卫生素养的一个重要方面,特别是在疫苗接种方面。本研究的目的是分析这些书面文献的可读性,并提出改进建议。方法:使用Flesch Reading Ease (FRE)、Flesch- kincaid Grade Level (FKGL)、Flesch- kincaid Grade Level (FKGL)和Cochrane Reviews (CR)等公开来源的疫苗相关信息(ntotal = 240)的可读性进行评估,包括PubMed摘要、疫苗专家评论(ERV)和Cochrane评论(CR)、配对的通俗语言和科学摘要、公共卫生材料、临床试验摘要和疫苗患者信息单页。结果:所有来源的疫苗相关信息在所有可读性指标上的可读性都很差,分别有90.8%和94.6%未达到目标FKGL(≤8)(平均12±3.2 sd)和FRE(≥60)(平均34±17 sd)。简单的语言摘要提高了可读性,但没有达到参考目标。CR的科学摘要和通俗语言评分分别为FRE(平均25±7.2 sd;中位数25)和(平均37±8.6 sd;中位数36)p < 0.0001), ERV的科学摘要(平均18±11 sd;中位数17)和通俗语言评分(平均26±11 sd;中位数28)p = 0.002),表明通俗语言摘要的可读性得分有所提高,但仍未达到参考目标。结论:目前面向公众的疫苗接种资料的可读性尚不理想。可通过使用可读性计算器来提高可读性,并在可能的情况下确保使用单音节单词和每句少于14个单词。编写具有更高可读性分数的面向公众的材料将有助于促进卫生知识普及,从而促进疫苗接种。
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引用次数: 0
Molecular Effects of Glucose on MIR503HG-Regulated Genes in Triple-Negative Breast Cancer. 葡萄糖对三阴性乳腺癌中mir503hg调控基因的分子作用
IF 4.6 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-12-17 eCollection Date: 2025-01-01 DOI: 10.3389/bjbs.2025.15206
Victoria A Reid, Barbara Yang, Kyle Russo, Melina J Sedano, Ramesh Choudhari, Enrique I Ramos, Shrikanth S Gadad

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, characterized by a lack of key hormone receptors in tumor cells. As there are limited treatment options for these patients, it is crucial to understand the underlying mechanisms by which TNBC constantly evolves and evades treatments. In this regard, the pervasive nature of transcription provides a potential reservoir of transcripts, including both coding and noncoding, that TNBC leverages to sustain a proliferative advantage and support tumor growth. TNBC is affected by energy sources such as glucose, which can have a profound impact on gene expression regulation mediated by various molecules, including noncoding RNAs, at the cellular level. In this study, we demonstrate that glucose modulates the gene expression profile mediated by the microRNA-503 host gene (MIR503HG), which has been previously implicated in TNBC. To comprehensively characterize the impact of glucose on MIR503HG-regulated genes and cellular pathways, we sequenced total RNA, performed gene set enrichment analyses, and determined the relation between gene expression and patient outcomes. Analysis of gene subsets specific to various glucose environments identified clinical outcomes for breast cancer patients across different molecular subtypes. Our findings indicate that MIR503HG has potential as a diagnostic marker and may be useful in the clinical management of TNBC.

三阴性乳腺癌(TNBC)是最具侵袭性的乳腺癌亚型,其特征是肿瘤细胞中缺乏关键激素受体。由于这些患者的治疗选择有限,因此了解TNBC不断演变和逃避治疗的潜在机制至关重要。在这方面,转录的普遍性提供了一个潜在的转录库,包括编码和非编码,TNBC利用这些转录库来维持增殖优势并支持肿瘤生长。TNBC受葡萄糖等能量来源的影响,可在细胞水平上对包括非编码rna在内的各种分子介导的基因表达调控产生深远影响。在这项研究中,我们证明了葡萄糖调节由microRNA-503宿主基因(MIR503HG)介导的基因表达谱,该基因先前与TNBC有关。为了全面表征葡萄糖对mir503hg调控基因和细胞通路的影响,我们对总RNA进行了测序,进行了基因集富集分析,并确定了基因表达与患者预后之间的关系。对不同葡萄糖环境特异性基因亚群的分析确定了不同分子亚型乳腺癌患者的临床结果。我们的研究结果表明,MIR503HG具有作为诊断标志物的潜力,可能在TNBC的临床管理中有用。
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引用次数: 0
Epidemiological Analysis of Antinuclear Antibodies Positivity and Pattern Distribution in a Taiwanese Hospital-Based Cohort. 台湾医院人群抗核抗体阳性及分布的流行病学分析。
IF 4.6 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-12-15 eCollection Date: 2025-01-01 DOI: 10.3389/bjbs.2025.15625
Yu-Wei Tseng, Cheng-Li Lin, Si-Yu Chen, Tze-Kiong Er

Background: Autoimmune diseases pose an increasing global health burden. The detection of antinuclear antibodies (ANA) via indirect immunofluorescence (IIF) is central to diagnosing systemic autoimmune conditions. This study aimed to assess the prevalence and distribution of ANA patterns in a Taiwanese population.

Methods: We conducted a retrospective, cross-sectional study of 8,299 patients who underwent ANA testing at Asia University Hospital between January 2021 and December 2023. ANA patterns were classified based on fluorescence staining characteristics. Demographic variables, including age and gender, were analyzed.

Results: ANA positivity was observed in 35.3% of patients. The most frequent pattern was homogeneous (33.0%), followed by speckled (24.1%). Female patients had a significantly higher positivity rate (female-to-male ratio 2.7:1), and the ≥66-year age group accounted for 34.6% of ANA-positive cases. Mixed ANA patterns were identified in 22.8% of ANA-positive patients, with homogeneous-speckled being the most common combination (27.4%).

Conclusion: This large-scale study provides valuable epidemiological data on ANA prevalence and pattern distribution in Taiwan. The predominance of homogeneous and speckled patterns, particularly among older female patients, aligns with established trends in autoimmune diseases. The high proportion of mixed ANA patterns suggests the need for further investigation into their clinical significance and diagnostic value.

背景:自身免疫性疾病造成越来越大的全球健康负担。通过间接免疫荧光(IIF)检测抗核抗体(ANA)是诊断全身自身免疫性疾病的核心。本研究旨在评估台湾人群中ANA型态的流行与分布。方法:我们对2021年1月至2023年12月期间在亚洲大学医院接受ANA检测的8299例患者进行了回顾性横断面研究。基于荧光染色特征对ANA模式进行分类。人口统计变量,包括年龄和性别,进行了分析。结果:ANA阳性占35.3%。最常见的是均匀型(33.0%),其次是斑点型(24.1%)。女性患者的阳性率明显高于男性(男女比为2.7:1),且≥66岁年龄组占ana阳性病例的34.6%。在22.8%的ANA阳性患者中发现混合ANA模式,其中均匀斑点是最常见的组合(27.4%)。结论:本研究为台湾ANA的流行病学研究提供了有价值的资料。均匀和斑点型的优势,特别是在老年女性患者中,与自身免疫性疾病的既定趋势一致。混合ANA模式的高比例提示需要进一步研究其临床意义和诊断价值。
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引用次数: 0
Nasopharyngeal Carcinoma in Southeast Asia: Current Landscape and Future Priorities. 东南亚鼻咽癌:现状和未来重点。
IF 4.6 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-12-12 eCollection Date: 2025-01-01 DOI: 10.3389/bjbs.2025.15902
Suat Ming Chan, Ian C Paterson, Lee Fah Yap

Nasopharyngeal carcinoma (NPC) remains a major public health concern with a geographically skewed distribution. The disease is endemic in East Asia (particularly China), Southeast Asia (SEA) and South-Central Asia. Although China contributes the largest share of global NPC cases, several SEA countries consistently report high incidence rates. Despite this substantial burden, NPC remains a neglected disease across much of the region. This review synthesizes and appraises the available evidence on the epidemiology, incidence trends and disease burden of NPC in SEA. High-incidence hotspots persist in Indonesia, Malaysia, Singapore, Vietnam, the Philippines, and Thailand, with particularly striking rates among indigenous populations of East Malaysia. Late-stage presentation is common and survival outcomes in many SEA countries lag behind those observed in better-resourced endemic regions. Socioeconomic disparities in many SEA communities also amplify exposure to key NPC risk factors. This review outlines key region-specific challenges and identifies priority areas for coordinated health system strengthening. We emphasize the urgent need for regionally tailored strategies to mitigate the growing burden of NPC throughout SEA.

鼻咽癌(NPC)仍然是一个主要的公共卫生问题,其地理分布不均匀。该病在东亚(特别是中国)、东南亚(SEA)和中南亚流行。尽管中国占全球NPC病例的最大份额,但几个东南亚国家的发病率一直很高。尽管有如此沉重的负担,但在该地区的大部分地区,NPC仍然是一种被忽视的疾病。本文对东南亚地区鼻咽癌流行病学、发病率趋势和疾病负担的现有证据进行综合评价。印度尼西亚、马来西亚、新加坡、越南、菲律宾和泰国的高发热点地区仍然存在,东马来西亚土著人口的发病率尤其惊人。晚期表现是常见的,许多东南亚国家的生存结果落后于资源较好的流行地区。许多东南亚社区的社会经济差异也扩大了对关键NPC风险因素的暴露。本审查概述了针对特定区域的主要挑战,并确定了协调加强卫生系统的优先领域。我们强调迫切需要制定适合区域的战略,以减轻整个东南亚地区NPC日益增长的负担。
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引用次数: 0
Influence of Reference Gene Selection on miRNA Quantification by RT-qPCR in Human Placental Samples. 内参基因选择对RT-qPCR测定人胎盘miRNA的影响。
IF 4.6 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-12-04 eCollection Date: 2025-01-01 DOI: 10.3389/bjbs.2025.15354
Ankica Sekovanić, Tatjana Orct, Adrijana Dorotić, Daria Pašalić, Zorana Kljaković-Gašpić, Sandra Stasenko, Tatjana Mioč, Martina Piasek, Jasna Jurasović

The gold standard for assessing expression of miRNAs, small molecules involved in numerous biological processes, is reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The reliability of RT-qPCR analysis results largely depends on accurate data normalization and the selection of an appropriate reference gene. This study evaluated the stability of five candidate reference genes-miR-525, miR-520c, SNORD48, miR-135b, and miR-143-in human placental samples. GeNorm, NormFinder, BestKeeper, and the delta Ct-method were used to evaluate gene expression stability. The effect of reference gene selection for normalization of target miRNAs (miR-1537, miR-190b, miR-16, miR-21, and miR-146a) expression in term placental samples from smokers and non-smokers was also investigated. All statistical tools identified miR-525, miR-520c, and SNORD48 as the three most stable reference genes, except for GeNorm, which recommends the combination of the first two genes. Normalization using SNORD48 and miR-525 produced comparable results for miR-21 expression in the placental samples, both in smokers and non-smokers, whereas normalization with miR-143 yielded markedly different outcomes compared to SNORD48 and miR-525. These findings highlight the considerable impact of reference gene selection on RT-qPCR results, emphasizing the importance of careful validation to avoid misinterpretation of gene expression data.

mirna是参与许多生物过程的小分子,评估mirna表达的金标准是逆转录-定量聚合酶链反应(RT-qPCR)。RT-qPCR分析结果的可靠性很大程度上取决于准确的数据归一化和选择合适的内参基因。本研究评估了人类胎盘样本中五个候选内参基因——mir -525、miR-520c、SNORD48、miR-135b和mir -143的稳定性。采用GeNorm、NormFinder、BestKeeper和delta ct法评价基因表达稳定性。我们还研究了内参基因选择对吸烟者和非吸烟者足月胎盘样本中靶mirna (miR-1537、miR-190b、miR-16、miR-21和miR-146a)表达正常化的影响。除了GeNorm推荐前两个基因的组合外,所有统计工具都认为miR-525、miR-520c和SNORD48是三个最稳定的内参基因。在吸烟者和非吸烟者的胎盘样本中,使用SNORD48和miR-525进行归一化对miR-21的表达产生了相似的结果,而使用miR-143进行归一化与使用SNORD48和miR-525相比,产生了明显不同的结果。这些发现突出了内参基因选择对RT-qPCR结果的巨大影响,强调了仔细验证以避免基因表达数据误解的重要性。
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引用次数: 0
Corrigendum: Reproducibility of Immunohistochemical Testing of Estrogen Receptors, Progesterone Receptors, Human Epidermal Growth Factor Receptor-2 (HER2) and Ki-67 in Vietnam. 更正:越南雌激素受体、孕激素受体、人表皮生长因子受体-2 (HER2)和Ki-67免疫组化检测的可重复性。
IF 4.6 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-12-02 eCollection Date: 2025-01-01 DOI: 10.3389/bjbs.2025.15864
Thai Anh Tu, Nguyen Van Tin, Anthony Rhodes, Dinh Bui Quynh Anh, Le Thi Hong Dao, Nguyen Thi Truc Linh, Dinh Thi Khanh Nhu, Nguyen Thi Hong Nhung, Lam Thanh Cam, Ngo Thi Minh Hanh, Pham Nguyen Cuong, Nguyen Thanh Toan, Nguyen Khac Tuyen, Do Dinh Khanh, Tran Thi Truc Ngan, Lam Kieu Mong Thy, Nguyen Van Thanh, Nguyen Quang Tuan, Vo Ngoc Nguyen, Le Thi Thuy Nhu, Nguyen Dam Chau Bao

[This corrects the article DOI: 10.3389/bjbs.2025.15455.].

[这更正了文章DOI: 10.3389/bjbs.2025.15455.]。
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引用次数: 0
Formulation and In Vitro Characterisation of Withaferin A-Loaded Liposomal Gels for the Topical Management of Chronic Inflammatory Skin Conditions. 局部治疗慢性炎症性皮肤状况的负载Withaferin a脂质体凝胶的配方和体外表征。
IF 4.6 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-12-01 eCollection Date: 2025-01-01 DOI: 10.3389/bjbs.2025.14847
Mandeep Kaur Marwah, Hala Shokr, Karan Singh Rana, Yukta Sameer Hindalekar, Rosie Kainth, Parmida Babaei, Shakil Ahmad

Chronic inflammatory skin conditions such as psoriasis, eczema, and acne are driven by sustained inflammation, oxidative stress, and impaired tissue repair. Current treatments often lead to adverse effects with prolonged use highlighting the need for safer, targeted alternatives. Withaferin-A, a bioactive compound derived from Withania somnifera, has demonstrated potent anti-inflammatory and antioxidant properties in various disease models. This study explored the potential of Withaferin-A liposome-loaded gels for topical delivery, testing their efficacy in an inflamed skin model. Withaferin-A liposomes were prepared using the ethanol injection method and incorporated into hydroxypropyl methylcellulose (HPMC) gels. In vitro release studies using a permeable insert system were used to compare release profiles of Withaferin-A from liposomal gels. Cytotoxicity was assessed via XTT assay on human umbilical vein endothelial cells (HUVEC) and human dermal fibroblasts (HDFa). Inflammation was induced with tumour necrosis factor-alpha (TNF-α), and anti-inflammatory effects measured using enzyme-linked immunosorbent assays for interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP9). Reactive oxygen species (ROS) levels were quantified using the DCFDA assay. Cytotoxicity studies using the XTT assay on HUVEC and HDFa cells revealed good biocompatibility at lower Withaferin-A concentrations (0-1 µM), though reduced viability was observed at 5 µM. In vitro release studies revealed sustained release of Withaferin-A from liposomal gels, with significantly slower release over 6 h compared to solution at 99.53% ± 3.47% and 48.87% ± 4.51% respectively. Anti-inflammatory effects were evaluated following TNF-α-induced inflammation, with Withaferin-A loaded gels significantly reducing IL-6 secretion in a dose-dependent manner in both HUVECs (38.90 ± 5.34 to 19.15 ± 3.56 pg/mL) and HDFa cells (40.05 ± 2.23 to 10.42 ± 2.02 pg/mL). Withaferin-A treatment also reduced ROS levels and lowered MMP-9 secretion in HDFa cells from 408.80 ± 13.05 pg/mL to 195.00 ± 7.55 pg/mL, indicating potential for tissue remodelling. In summary, WA-loaded liposomal gels demonstrated effective anti-inflammatory activity and sustained drug release while maintaining biocompatibility at therapeutic concentrations. These findings support their potential as a novel strategy for managing inflammatory skin diseases by improving drug bioavailability and promoting tissue repair.

慢性炎症性皮肤病,如牛皮癣、湿疹和痤疮,是由持续的炎症、氧化应激和组织修复受损引起的。目前的治疗方法往往导致长期使用的不良反应,强调需要更安全,有针对性的替代品。Withaferin-A是一种从Withania somnifera中提取的生物活性化合物,在多种疾病模型中显示出有效的抗炎和抗氧化特性。本研究探索了负载Withaferin-A脂质体凝胶局部递送的潜力,测试了它们在炎症皮肤模型中的功效。采用乙醇注射法制备了Withaferin-A脂质体,并将其掺入羟丙基甲基纤维素(HPMC)凝胶中。使用渗透性插入系统进行体外释放研究,以比较Withaferin-A从脂质体凝胶中的释放谱。采用XTT法测定人脐静脉内皮细胞(HUVEC)和人真皮成纤维细胞(HDFa)的细胞毒性。用肿瘤坏死因子-α (TNF-α)诱导炎症,用白细胞介素-6 (IL-6)和基质金属蛋白酶-9 (MMP9)的酶联免疫吸附法测定抗炎作用。采用DCFDA法定量测定活性氧(ROS)水平。XTT法对HUVEC和HDFa细胞的细胞毒性研究显示,在较低的Withaferin-A浓度(0-1µM)下具有良好的生物相容性,但在5µM时活性降低。体外释放研究表明,与溶液相比,Withaferin-A在6 h内的缓释速度显著减慢,分别为99.53%±3.47%和48.87%±4.51%。在TNF-α-诱导炎症后评估抗炎作用,负载Withaferin-A凝胶在HUVECs(38.90±5.34至19.15±3.56 pg/mL)和HDFa细胞(40.05±2.23至10.42±2.02 pg/mL)中均以剂量依赖性方式显著降低IL-6分泌。Withaferin-A处理也降低了HDFa细胞的ROS水平和MMP-9分泌,从408.80±13.05 pg/mL降至195.00±7.55 pg/mL,表明了组织重塑的潜力。总之,负载wa的脂质体凝胶显示出有效的抗炎活性和持续的药物释放,同时保持治疗浓度下的生物相容性。这些发现支持了它们作为一种通过提高药物生物利用度和促进组织修复来管理炎症性皮肤病的新策略的潜力。
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引用次数: 0
Mitochondrial DNA Mutations and Epigenetic Regulation in Type 2 Diabetes Mellitus Development. 线粒体DNA突变和2型糖尿病的表观遗传调控。
IF 4.6 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-11-27 eCollection Date: 2025-01-01 DOI: 10.3389/bjbs.2025.15375
Mei Xin Koh, Timothy Simpson, Shamsul Mohd Zain, Qasim Ayub, Hong Leong Cheah, Yan Pan, Shi Hui Cheng, Yuh-Fen Pung

The global prevalence of type 2 diabetes mellitus (T2DM) has increased significantly over the past decade and is projected to rise further. While genetic and lifestyle factors are well-established contributors to T2DM pathogenesis, mitochondria have also gained attention as the key players. Many studies suggested that mitochondrial DNA (mtDNA) mutations and epigenetic modifications were implicated in the development and progression of T2DM. This review aimed to provide a comprehensive analysis of mtDNA mutations and epigenetic modifications associated with T2DM. Based on data from 30 published studies, a total of 117 mtDNA mutations were identified to be associated with T2DM, with D-loop region being the mutation hotspot. However, it was reported that the majority of D-loop mutations were also more frequently observed in healthy populations compared to mutations in other mtDNA regions, suggesting their potential non-pathogenic characteristic. Thus, mtDNA mutations found to be associated with T2DM but with lower occurrence in healthy populations may play a more significant role in influencing T2DM susceptibility. Regarding epigenetic modifications, mtDNA methylation was commonly reported in the D-loop and ND6 regions across seven studies. These findings suggested that these regions may play critical roles in the regulation of mitochondrial gene expression under diabetic conditions. Lastly, this review also discussed the technical challenges and limitations of detecting mtDNA mutations and methylation changes. In addition, relevant ethical considerations surrounding mitochondrial genetic research were also addressed. In conclusion, mtDNA mutations and methylation changes could potentially serve as biomarkers for the development and progression of T2DM. These molecular modifications may offer valuable insights for early diagnosis and preventive strategies. However, further research and validation are essential to establish their clinical significance and diagnostic utility.

2型糖尿病(T2DM)的全球患病率在过去十年中显著增加,预计还会进一步上升。虽然遗传和生活方式因素是T2DM发病的重要因素,但线粒体作为关键因素也受到了关注。许多研究表明,线粒体DNA (mtDNA)突变和表观遗传修饰与T2DM的发生和进展有关。本综述旨在提供与T2DM相关的mtDNA突变和表观遗传修饰的全面分析。基于30篇已发表的研究数据,共鉴定出117个mtDNA突变与T2DM相关,其中D-loop区是突变热点。然而,据报道,与其他mtDNA区域的突变相比,大多数d环突变在健康人群中也更频繁地观察到,这表明它们具有潜在的非致病性特征。因此,发现与T2DM相关但在健康人群中发生率较低的mtDNA突变可能在影响T2DM易感性方面发挥更重要的作用。关于表观遗传修饰,在七项研究中,mtDNA甲基化通常在D-loop和ND6区域被报道。这些发现表明,这些区域可能在糖尿病患者线粒体基因表达的调控中发挥关键作用。最后,本文还讨论了检测mtDNA突变和甲基化变化的技术挑战和局限性。此外,还讨论了围绕线粒体基因研究的相关伦理问题。总之,mtDNA突变和甲基化变化可能是T2DM发生和发展的潜在生物标志物。这些分子修饰可能为早期诊断和预防策略提供有价值的见解。然而,进一步的研究和验证是必要的,以建立其临床意义和诊断的效用。
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引用次数: 0
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