首页 > 最新文献

Narra J最新文献

英文 中文
Fecal ingestion rate based on worker activity patterns during stool handling in a ruminant farm. 反刍动物养殖场粪便处理过程中基于工人活动模式的粪便摄入率。
Pub Date : 2025-08-01 Epub Date: 2025-06-20 DOI: 10.52225/narra.v5i2.1989
Yudith V Paramitadevi, Cindy R Priadi, Iftita Rahmatika, Andriansjah Rukmana

Farm workers who handle livestock stools face an increased risk of infection by pathogenic bacteria, such as Escherichia coli O157 and Salmonella spp., leading to millions of severe health issues and thousands of fatalities annually. The aim of this study was to assess the impact of these pathogens by measuring their concentrations, determining rates of unintentional fecal consumption, and conducting a quantitative assessment of microbial risk. An integrated farm in Sukabumi City, Indonesia, was examined for E. coli O157 and Salmonella spp. in livestock stools. Additionally, the study monitored the rate of incidental fecal ingestion among farm workers. Stool samples were collected (n= 40) from ruminants and analyzed following ISO 16649-1:2018, ISO 9308-1:2014, and ISO 6579-1:2017/Amd.1:2020. The study tracked worker's behavior daily to determine the contact time. The fecal ingestion rate was calculated by multiplying the estimated stool weight ingested by the contact time workers spent cleaning livestock stools in the barn each day. Microbial analysis revealed that the highest concentration of E. coli O157 in beef cattle stools was 2.49 log10 CFU/g. The study determined mean fecal ingestion rates during the dry season (8.64 mg/day) and rainy season (6.84 mg/day). Results from the quantitative microbial risk assessment showed that stool from beef cattle posed a higher risk of E. coli O157 infection compared to other ruminants, with an estimated disease burden of 9.8 × 10-3 pppy. This study represents the first comprehensive quantitative evaluation of fecal ingestion by farm workers during animal husbandry. The findings underscore the need for improved worker safety measures, such as enhanced sanitation practices and protective equipment, to mitigate the risks of handling livestock stools.

处理牲畜粪便的农场工人面临着感染致病菌的风险增加,如大肠杆菌O157和沙门氏菌,每年导致数百万人出现严重的健康问题和数千人死亡。本研究的目的是通过测量这些病原体的浓度、确定非故意粪便消耗率和对微生物风险进行定量评估来评估这些病原体的影响。印度尼西亚Sukabumi市的一个综合农场在牲畜粪便中检查了大肠杆菌O157和沙门氏菌。此外,该研究还监测了农场工人偶然摄入粪便的比率。从反刍动物中收集粪便样本(n= 40),并按照ISO 16649-1:2018、ISO 9308-1:2014和ISO 6579-1:2017/Amd.1:2020进行分析。该研究每天跟踪员工的行为,以确定接触时间。粪便摄取率的计算方法是将估计的粪便重量乘以工人每天在畜棚中清洁牲畜粪便所花费的接触时间。结果表明,肉牛粪便中大肠杆菌O157的最高浓度为2.49 log10 CFU/g。该研究确定了旱季(8.64 mg/天)和雨季(6.84 mg/天)的平均粪便摄取率。定量微生物风险评估结果显示,肉牛粪便感染大肠杆菌O157的风险高于其他反刍动物,估计疾病负担为9.8 × 10-3 pppy。这项研究首次对农场工人在畜牧业中摄入的粪便进行了全面的定量评估。研究结果强调需要改进工人安全措施,例如加强卫生习惯和防护设备,以减轻处理牲畜粪便的风险。
{"title":"Fecal ingestion rate based on worker activity patterns during stool handling in a ruminant farm.","authors":"Yudith V Paramitadevi, Cindy R Priadi, Iftita Rahmatika, Andriansjah Rukmana","doi":"10.52225/narra.v5i2.1989","DOIUrl":"10.52225/narra.v5i2.1989","url":null,"abstract":"<p><p>Farm workers who handle livestock stools face an increased risk of infection by pathogenic bacteria, such as <i>Escherichia coli</i> O157 and <i>Salmonella spp</i>., leading to millions of severe health issues and thousands of fatalities annually. The aim of this study was to assess the impact of these pathogens by measuring their concentrations, determining rates of unintentional fecal consumption, and conducting a quantitative assessment of microbial risk. An integrated farm in Sukabumi City, Indonesia, was examined for <i>E. coli</i> O157 and <i>Salmonella spp</i>. in livestock stools. Additionally, the study monitored the rate of incidental fecal ingestion among farm workers. Stool samples were collected (n= 40) from ruminants and analyzed following ISO 16649-1:2018, ISO 9308-1:2014, and ISO 6579-1:2017/Amd.1:2020. The study tracked worker's behavior daily to determine the contact time. The fecal ingestion rate was calculated by multiplying the estimated stool weight ingested by the contact time workers spent cleaning livestock stools in the barn each day. Microbial analysis revealed that the highest concentration of <i>E. coli</i> O157 in beef cattle stools was 2.49 log<sub>10</sub> CFU/g. The study determined mean fecal ingestion rates during the dry season (8.64 mg/day) and rainy season (6.84 mg/day). Results from the quantitative microbial risk assessment showed that stool from beef cattle posed a higher risk of <i>E. coli</i> O157 infection compared to other ruminants, with an estimated disease burden of 9.8 × 10<sup>-3</sup> pppy. This study represents the first comprehensive quantitative evaluation of fecal ingestion by farm workers during animal husbandry. The findings underscore the need for improved worker safety measures, such as enhanced sanitation practices and protective equipment, to mitigate the risks of handling livestock stools.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e1989"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mortality and associated factors among community-acquired pneumonia patients: A cross-sectional study in a provincial referral hospital in Indonesia. 社区获得性肺炎患者的死亡率及相关因素:印度尼西亚一家省级转诊医院的横断面研究
Pub Date : 2025-08-01 Epub Date: 2025-06-04 DOI: 10.52225/narra.v5i2.1649
Dani Rosdiana, Fajri M Siregar, Nabila C Ediwi, Rahmi T Putri, Zuyyina Er Nurrahma, Adinda Elisabet, Rosantia Sarassari, Dodi Safari, Cimi Ilmiawati, Aisyah Elliyanti

Community-acquired pneumonia (CAP) poses a significant impact on the healthcare system due to rehospitalization and mortality. About one-third of hospitalized CAP patients died within one year. In addition to advanced age, vulnerable groups with comorbidities such as cancer, diabetes, and cerebrovascular disease (CVD) are more likely to suffer from severe CAP. The aim of this study was to investigate the factors linked to mortality in adult hospitalized CAP patients. The study extracted the medical records of patients aged ≥18 years, admitted to a referral hospital in Riau Province, who were diagnosed with CAP between January and December 2023. Multiple logistic regression step-wise analysis was employed to determine the factors associated with mortality in CAP patients. The study involved 334 patients with a median age of 58 years. Based on the confusion, urea, respiratory rate, blood pressure, and age ≥65 years (CURB-65) score, 11.9% of patients had severe CAP (CURB-65 scores 3 and 4). Age was a significant predictor of severe CAP (p≤0.001). The most prevalent comorbidities were malignancy (33.2%), CVD (30.2%), and diabetes (28.4%). Mortality incidence during hospitalization reached 35.9%. Significant factors associated with mortality in hospitalized CAP patients included renal dysfunction/elevated serum urea levels (p=0.031), CURB-65 score (p=0.023), vasopressor use (p≤0.001), mechanical ventilator use (p≤0.01) and steroid use (p=0.029). However, CVD was associated with a decreased risk of mortality (p=0.019). Gram-negative bacteria predominated, accounting for 50.6% of all positive isolates. Several significant factors were associated with mortality in adult patients hospitalized with CAP at referral Hospital in Riau, including renal dysfunction, CURB-65 score, vasopressor use, mechanical ventilator use, and steroid use. This finding underscored the importance of early identification factors in CAP patients.

社区获得性肺炎(CAP)由于再住院和死亡率对医疗保健系统产生重大影响。大约三分之一的CAP住院患者在一年内死亡。除高龄外,患有癌症、糖尿病和脑血管疾病(CVD)等合并症的弱势群体更容易发生严重的CAP。本研究的目的是调查与成年住院CAP患者死亡率相关的因素。该研究提取了2023年1月至12月期间在廖内省一家转诊医院被诊断为CAP的年龄≥18岁患者的医疗记录。采用多元逻辑回归逐步分析确定与CAP患者死亡率相关的因素。该研究涉及334名患者,中位年龄为58岁。根据混淆、尿素、呼吸频率、血压和年龄≥65岁(CURB-65)评分,11.9%的患者有严重的CAP (CURB-65评分3和4)。年龄是严重CAP的显著预测因子(p≤0.001)。最常见的合并症是恶性肿瘤(33.2%)、心血管疾病(30.2%)和糖尿病(28.4%)。住院期间死亡率为35.9%。与住院CAP患者死亡率相关的显著因素包括肾功能不全/血清尿素水平升高(p=0.031)、CURB-65评分(p=0.023)、血管加压药使用(p≤0.001)、机械呼吸机使用(p≤0.01)和类固醇使用(p=0.029)。然而,心血管疾病与死亡风险降低相关(p=0.019)。革兰氏阴性菌占多数,占阳性菌株的50.6%。廖内省转诊医院CAP住院成人患者的死亡率与几个重要因素相关,包括肾功能不全、CURB-65评分、血管加压药的使用、机械呼吸机的使用和类固醇的使用。这一发现强调了CAP患者早期识别因素的重要性。
{"title":"Mortality and associated factors among community-acquired pneumonia patients: A cross-sectional study in a provincial referral hospital in Indonesia.","authors":"Dani Rosdiana, Fajri M Siregar, Nabila C Ediwi, Rahmi T Putri, Zuyyina Er Nurrahma, Adinda Elisabet, Rosantia Sarassari, Dodi Safari, Cimi Ilmiawati, Aisyah Elliyanti","doi":"10.52225/narra.v5i2.1649","DOIUrl":"10.52225/narra.v5i2.1649","url":null,"abstract":"<p><p>Community-acquired pneumonia (CAP) poses a significant impact on the healthcare system due to rehospitalization and mortality. About one-third of hospitalized CAP patients died within one year. In addition to advanced age, vulnerable groups with comorbidities such as cancer, diabetes, and cerebrovascular disease (CVD) are more likely to suffer from severe CAP. The aim of this study was to investigate the factors linked to mortality in adult hospitalized CAP patients. The study extracted the medical records of patients aged ≥18 years, admitted to a referral hospital in Riau Province, who were diagnosed with CAP between January and December 2023. Multiple logistic regression step-wise analysis was employed to determine the factors associated with mortality in CAP patients. The study involved 334 patients with a median age of 58 years. Based on the confusion, urea, respiratory rate, blood pressure, and age ≥65 years (CURB-65) score, 11.9% of patients had severe CAP (CURB-65 scores 3 and 4). Age was a significant predictor of severe CAP (<i>p≤</i>0.001). The most prevalent comorbidities were malignancy (33.2%), CVD (30.2%), and diabetes (28.4%). Mortality incidence during hospitalization reached 35.9%. Significant factors associated with mortality in hospitalized CAP patients included renal dysfunction/elevated serum urea levels (<i>p</i>=0.031), CURB-65 score (<i>p</i>=0.023), vasopressor use (<i>p≤</i>0.001), mechanical ventilator use (<i>p≤</i>0.01) and steroid use (p=0.029). However, CVD was associated with a decreased risk of mortality (<i>p</i>=0.019). Gram-negative bacteria predominated, accounting for 50.6% of all positive isolates. Several significant factors were associated with mortality in adult patients hospitalized with CAP at referral Hospital in Riau, including renal dysfunction, CURB-65 score, vasopressor use, mechanical ventilator use, and steroid use. This finding underscored the importance of early identification factors in CAP patients.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e1314"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spectrum of rare EGFR mutations in Indonesian lung adenocarcinoma: Findings from an 8-year analysis of 4,778 cases highlighting the need for advanced targeted therapies. 印度尼西亚肺腺癌中罕见EGFR突变的谱:来自4778例病例的8年分析结果,强调需要先进的靶向治疗。
Pub Date : 2025-08-01 Epub Date: 2025-04-21 DOI: 10.52225/narra.v5i2.1721
Didik S Heriyanto, Ika Trisnawati, Lisnawati Rachmadi, Jeffry B Tenggara, Vincent Lau, Andrew N Gunawan, Brigitta N Halim, Fara S Yuliani, Vincent Laiman, Soehartati Gondhowiardjo, Hsiao-Chi Chuang

Lung cancer patients in Indonesia exhibit a high prevalence of epidermal growth factor receptor (EGFR) mutations, with a substantial proportion attributed to rare or uncommon variants. The clinical significance of rare EGFR mutations lies in their differential sensitivity to tyrosine kinase inhibitors (TKIs). While they are frequently resistant to first- and second-generation TKIs, they often respond to third-generation TKIs, necessitating tailored treatment options. The need for improving access to advanced targeted therapies in Indonesia also highlights the importance of conducting research on rare EGFR mutations. The aim of this study was to identify the spectrum and frequency of EGFR mutations in patients with lung adenocarcinoma in Indonesia. A cross-sectional observational study with total sampling was conducted from January 2016 to April 2024 to investigate EGFR mutation profiles in lung adenocarcinoma patients. Samples were acquired from patients with a confirmed anatomical pathology diagnosis from various healthcare centers across Indonesia. A total of 4,778 samples were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) on various specimen types to determine EGFR mutation prevalence and patterns. Associations between demographic data and EGFR mutation status were assessed. EGFR mutations were detected in 54.6% of samples, with common mutations (exon 19 deletions/insertions and point mutation L858R) comprising 76.2% of positive cases and rare mutations (exon 20 insertions, point mutation G719X, S768I, T790M, and L861Q) accounted for 20.3%. Significant associations were found between geographic origin, age, and sex with EGFR mutation status. This study confirms substantial genetic variability and geographical differences in EGFR mutations among Indonesian lung adenocarcinoma patients, emphasizing the urgent need for further research to prompt enhanced molecular diagnostics and targeted therapies in the region.

印度尼西亚的肺癌患者表皮生长因子受体(EGFR)突变的患病率很高,其中很大一部分归因于罕见或不常见的变异。罕见的EGFR突变的临床意义在于它们对酪氨酸激酶抑制剂(TKIs)的不同敏感性。虽然他们经常对第一代和第二代tki有耐药性,但他们通常对第三代tki有反应,因此需要量身定制的治疗方案。印度尼西亚需要改善先进靶向治疗的可及性,这也突出了开展罕见EGFR突变研究的重要性。本研究的目的是确定印尼肺腺癌患者EGFR突变的频谱和频率。我们于2016年1月至2024年4月进行了一项全抽样的横断面观察性研究,以调查肺腺癌患者的EGFR突变谱。样本来自印度尼西亚各医疗中心确诊解剖病理诊断的患者。采用实时定量聚合酶链反应(RT-qPCR)对各种标本类型进行分析,共4778份样本,以确定EGFR突变的患病率和模式。评估了人口统计数据与EGFR突变状态之间的关系。54.6%的样本检测到EGFR突变,其中常见突变(第19外显子缺失/插入和点突变L858R)占阳性病例的76.2%,罕见突变(第20外显子插入,点突变G719X、S768I、T790M和L861Q)占20.3%。发现地理来源、年龄和性别与EGFR突变状态之间存在显著关联。本研究证实了印度尼西亚肺腺癌患者中EGFR突变的遗传变异性和地理差异,强调迫切需要进一步研究以促进该地区增强分子诊断和靶向治疗。
{"title":"Spectrum of rare <i>EGFR</i> mutations in Indonesian lung adenocarcinoma: Findings from an 8-year analysis of 4,778 cases highlighting the need for advanced targeted therapies.","authors":"Didik S Heriyanto, Ika Trisnawati, Lisnawati Rachmadi, Jeffry B Tenggara, Vincent Lau, Andrew N Gunawan, Brigitta N Halim, Fara S Yuliani, Vincent Laiman, Soehartati Gondhowiardjo, Hsiao-Chi Chuang","doi":"10.52225/narra.v5i2.1721","DOIUrl":"10.52225/narra.v5i2.1721","url":null,"abstract":"<p><p>Lung cancer patients in Indonesia exhibit a high prevalence of epidermal growth factor receptor (<i>EGFR</i>) mutations, with a substantial proportion attributed to rare or uncommon variants. The clinical significance of rare <i>EGFR</i> mutations lies in their differential sensitivity to tyrosine kinase inhibitors (TKIs). While they are frequently resistant to first- and second-generation TKIs, they often respond to third-generation TKIs, necessitating tailored treatment options. The need for improving access to advanced targeted therapies in Indonesia also highlights the importance of conducting research on rare <i>EGFR</i> mutations. The aim of this study was to identify the spectrum and frequency of <i>EGFR</i> mutations in patients with lung adenocarcinoma in Indonesia. A cross-sectional observational study with total sampling was conducted from January 2016 to April 2024 to investigate <i>EGFR</i> mutation profiles in lung adenocarcinoma patients. Samples were acquired from patients with a confirmed anatomical pathology diagnosis from various healthcare centers across Indonesia. A total of 4,778 samples were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) on various specimen types to determine <i>EGFR</i> mutation prevalence and patterns. Associations between demographic data and <i>EGFR</i> mutation status were assessed. <i>EGFR</i> mutations were detected in 54.6% of samples, with common mutations (exon 19 deletions/insertions and point mutation L858R) comprising 76.2% of positive cases and rare mutations (exon 20 insertions, point mutation G719X, S768I, T790M, and L861Q) accounted for 20.3%. Significant associations were found between geographic origin, age, and sex with <i>EGFR</i> mutation status. This study confirms substantial genetic variability and geographical differences in <i>EGFR</i> mutations among Indonesian lung adenocarcinoma patients, emphasizing the urgent need for further research to prompt enhanced molecular diagnostics and targeted therapies in the region.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e1721"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the potential effects of Lactococcus lactis D4 on the proliferation, apoptosis, and inflammatory responses in colorectal cancer cells. 探讨乳酸乳球菌D4对结直肠癌细胞增殖、凋亡及炎症反应的潜在影响。
Pub Date : 2025-08-01 Epub Date: 2025-04-28 DOI: 10.52225/narra.v5i2.1596
Muhammad I Rivai, Ronald E Lusikooy, Andani E Putra, Aisyah Elliyanti, Ade Sukma

Lactococcus lactis D4 is a probiotic produced through the fermentation of buffalo milk in bamboo, namely "dadih", a traditional food from West Sumatera, Indonesia. To the best of our knowledge, no specific research has investigated the effects of L. lactis D4, derived from dadih extraction, on colorectal cancer or its potential clinical applications. Therefore, the aim of this study was to evaluate the potential of L. lactis D4 from dadih to inhibit colorectal cancer growth in rat models, with a focus on its effects on cell proliferation, apoptosis, and inflammatory responses. An in vivo study was conducted using 37 male Sprague-Dawley rats, allocated into five groups: (1) control (no treatment), (2) dysplasia (induced with 1,2-dimethylhydrazine until dysplasia developed), (3) dysplasia + L. lactis D4 (induced with 1,2-dimethylhydrazine, then treated with L. lactis D4 after dysplasia confirmation), (4) cancer (induced with 1,2-dimethylhydrazine until cancer was confirmed), and (5) cancer + L. lactis D4 (induced with 1,2-dimethylhydrazine until cancer was confirmed, then treated with L. lactis D4 for 15 days). The effects of L. lactis D4 on cancer progression were assessed through immunohistochemical analysis of cell proliferation (cyclin D1, Bcl-2), apoptosis (p53, caspase-3), and inflammation (nuclear factor-κB (NF-κB) and cyclooxygenase-2 (COX-2)). This study found that L. lactis D4 treatment reduced adenocarcinoma and dysplasia severity in colorectal cancer models through significant reduction in cyclin D1, Bcl-2, NF-κB, and COX-2 expression observed across all groups (p<0.01), although changes in dysplasia and cancer subgroups were not statistically significant (p>0.05). No statistically significant change was noted in p53 expression (p=0.518), whereas caspase-3 expression varied significantly across groups (p=0.010). In conclusion, L. lactis D4 reduces the expression of cyclin D1, Bcl-2, NF-κB, and COX-2 proteins, offering insights into its potential to modulating proliferation and inflammation in colorectal cancer growth.

乳酸乳球菌D4是一种由水牛奶发酵而成的益生菌,即印度尼西亚西苏门答腊岛的传统食品“大竹”。据我们所知,目前还没有专门的研究调查从大黄提取物中提取的乳杆菌D4对结直肠癌的影响或其潜在的临床应用。因此,本研究的目的是在大鼠模型中评估大黄乳杆菌D4抑制结直肠癌生长的潜力,重点研究其对细胞增殖、凋亡和炎症反应的影响。选取雄性Sprague-Dawley大鼠37只,分为5组:(1)对照(未处理),(2)发育不良(1,2-二甲基肼诱导至发育不良),(3)发育不良+乳酸菌D4(1,2-二甲基肼诱导至发育不良,确诊后再用乳酸菌D4治疗),(4)癌变(1,2-二甲基肼诱导至确诊),(5)癌变+乳酸菌D4(1,2-二甲基肼诱导至确诊为癌变,再用乳酸菌D4治疗15天)。通过免疫组化分析细胞增殖(cyclin D1, Bcl-2),凋亡(p53, caspase-3)和炎症(核因子-κB (NF-κB)和环氧化酶-2 (COX-2))来评估乳杆菌D4对癌症进展的影响。本研究发现乳杆菌D4通过显著降低各组cyclin D1、Bcl-2、NF-κB和COX-2的表达,降低结直肠癌模型的腺癌和不典型增生严重程度(p < 0.05)。p53表达差异无统计学意义(p=0.518), caspase-3表达差异有统计学意义(p=0.010)。综上所述,L. lactis D4可降低cyclin D1、Bcl-2、NF-κB和COX-2蛋白的表达,为其调节结直肠癌增殖和炎症的潜力提供了新的见解。
{"title":"Exploring the potential effects of <i>Lactococcus lactis</i> D4 on the proliferation, apoptosis, and inflammatory responses in colorectal cancer cells.","authors":"Muhammad I Rivai, Ronald E Lusikooy, Andani E Putra, Aisyah Elliyanti, Ade Sukma","doi":"10.52225/narra.v5i2.1596","DOIUrl":"10.52225/narra.v5i2.1596","url":null,"abstract":"<p><p><i>Lactococcus lactis</i> D4 is a probiotic produced through the fermentation of buffalo milk in bamboo, namely \"<i>dadih</i>\", a traditional food from West Sumatera, Indonesia. To the best of our knowledge, no specific research has investigated the effects of <i>L. lactis</i> D4, derived from <i>dadih</i> extraction, on colorectal cancer or its potential clinical applications. Therefore, the aim of this study was to evaluate the potential of <i>L. lactis</i> D4 from <i>dadih</i> to inhibit colorectal cancer growth in rat models, with a focus on its effects on cell proliferation, apoptosis, and inflammatory responses. An in vivo study was conducted using 37 male Sprague-Dawley rats, allocated into five groups: (1) control (no treatment), (2) dysplasia (induced with 1,2-dimethylhydrazine until dysplasia developed), (3) dysplasia + <i>L. lactis</i> D4 (induced with 1,2-dimethylhydrazine, then treated with <i>L. lactis</i> D4 after dysplasia confirmation), (4) cancer (induced with 1,2-dimethylhydrazine until cancer was confirmed), and (5) cancer + <i>L. lactis</i> D4 (induced with 1,2-dimethylhydrazine until cancer was confirmed, then treated with <i>L. lactis</i> D4 for 15 days). The effects of <i>L. lactis</i> D4 on cancer progression were assessed through immunohistochemical analysis of cell proliferation (cyclin D1, Bcl-2), apoptosis (p53, caspase-3), and inflammation (nuclear factor-κB (NF-κB) and cyclooxygenase-2 (COX-2)). This study found that <i>L. lactis</i> D4 treatment reduced adenocarcinoma and dysplasia severity in colorectal cancer models through significant reduction in cyclin D1, Bcl-2, NF-κB, and COX-2 expression observed across all groups (<i>p</i><0.01), although changes in dysplasia and cancer subgroups were not statistically significant (<i>p</i>>0.05). No statistically significant change was noted in p53 expression (<i>p</i>=0.518), whereas caspase-3 expression varied significantly across groups (<i>p</i>=0.010). In conclusion, <i>L. lactis</i> D4 reduces the expression of cyclin D1, Bcl-2, NF-κB, and COX-2 proteins, offering insights into its potential to modulating proliferation and inflammation in colorectal cancer growth.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e1596"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Striving for smoke-free families: Wives' role in Gayo Lues, Aceh-Indonesia. 争取无烟家庭:妻子在印度尼西亚亚齐加约卢伊斯的角色。
Pub Date : 2025-08-01 Epub Date: 2025-04-30 DOI: 10.52225/narra.v5i2.1960
Hasrizal Saffutra, Mustanir Yahya, Rizanna Rosemary, Rosaria Indah, Dedy Syahrizal

Smoking remains a prevalent habit in many households, particularly in regions where cultural norms strongly accept tobacco use. The aim of this study was to examine the influential role of wives in Gayo Lues, Aceh, Indonesia, in promoting smoking cessation within their families. Amidst cultural norms that widely accept smoking, these wives employed both persuasive and, occasionally, coercive methods to encourage healthier behaviors among family members. Utilizing a qualitative approach with Participatory Action Research (PAR), data were collected through in-depth interviews with seven wives who have firsthand experience with smoking behaviors in their families. The findings revealed that wives in Gayo Lues act as both health monitors and guardians, balancing emotional support with firm boundaries to foster a smoke-free home environment. Their roles extended beyond traditional caregiving, as they actively shape family health outcomes. In conclusion, this study underscored the importance of empowering wives as health advocates in public health efforts, particularly in culturally conservative settings. Future research could further explore the broader socio-cultural dynamics influencing wives' health advocacy roles and assess the sustainability of these behaviors over time.

吸烟在许多家庭中仍然是一种普遍的习惯,特别是在文化规范强烈接受烟草使用的地区。本研究的目的是检查印度尼西亚亚齐加约卢埃斯的妻子在促进家庭戒烟方面的影响作用。在广泛接受吸烟的文化规范中,这些妻子们采用劝说和偶尔强制的方法来鼓励家庭成员采取更健康的行为。采用参与性行动研究(PAR)的定性方法,通过对7位有家庭吸烟行为第一手经验的妻子进行深入访谈来收集数据。调查结果显示,加约卢斯的妻子既是健康监督者,也是监护人,在情感支持和严格的界限之间取得平衡,以营造一个无烟的家庭环境。她们的作用超出了传统的照料,因为她们积极影响家庭健康结果。总之,这项研究强调了在公共卫生工作中赋予妻子权利作为健康倡导者的重要性,特别是在文化保守的环境中。未来的研究可以进一步探索影响妻子健康倡导角色的更广泛的社会文化动态,并评估这些行为的可持续性。
{"title":"Striving for smoke-free families: Wives' role in Gayo Lues, Aceh-Indonesia.","authors":"Hasrizal Saffutra, Mustanir Yahya, Rizanna Rosemary, Rosaria Indah, Dedy Syahrizal","doi":"10.52225/narra.v5i2.1960","DOIUrl":"10.52225/narra.v5i2.1960","url":null,"abstract":"<p><p>Smoking remains a prevalent habit in many households, particularly in regions where cultural norms strongly accept tobacco use. The aim of this study was to examine the influential role of wives in Gayo Lues, Aceh, Indonesia, in promoting smoking cessation within their families. Amidst cultural norms that widely accept smoking, these wives employed both persuasive and, occasionally, coercive methods to encourage healthier behaviors among family members. Utilizing a qualitative approach with Participatory Action Research (PAR), data were collected through in-depth interviews with seven wives who have firsthand experience with smoking behaviors in their families. The findings revealed that wives in Gayo Lues act as both health monitors and guardians, balancing emotional support with firm boundaries to foster a smoke-free home environment. Their roles extended beyond traditional caregiving, as they actively shape family health outcomes. In conclusion, this study underscored the importance of empowering wives as health advocates in public health efforts, particularly in culturally conservative settings. Future research could further explore the broader socio-cultural dynamics influencing wives' health advocacy roles and assess the sustainability of these behaviors over time.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e1960"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Thymoquinone and madecassoside improve motor function in a rotenone-induced mouse model of early Parkinson's disease: Role of dopamine, alpha-synuclein and mBDNF. 百里醌和马尾皂苷改善鱼藤酮诱导的早期帕金森病小鼠模型的运动功能:多巴胺、α -突触核蛋白和mBDNF的作用
Pub Date : 2025-08-01 Epub Date: 2025-05-09 DOI: 10.52225/narra.v5i2.2439
Shinta Kusumawati, Agustina T Endharti, Farhad Balafif, Shahdevi N Kurniawan, Aris Rosidah, Rabjhany Anaqah, Izzunazel A Barqillah, Husnul Khotimah

Parkinson's disease is a progressive, incurable neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and pathological aggregation of α-synuclein in the midbrain, leading to motor dysfunction. Thymoquinone (TQ), an active compound from Nigella sativa, has demonstrated antioxidant properties that may reduce dopamine degradation, while madecassoside (MA), a triterpenoid component of Centella asiatica, exhibits neuroprotective effects. To date, no study has investigated the combined effects of TQ and MA in a Parkinson's disease model. The aim of this study was to evaluate the synergistic neuroprotective potential of TQ and MA on motor function, dopamine levels, α-synuclein accumulation, and mature brain-derived neurotrophic factor (mBDNF) expression in a rotenone (ROT)-induced mouse model of early Parkinson's disease. Rotenone (2.5 mg/kg BW) was administered subcutaneously for two weeks to induce Parkinson's disease, while TQ alone, MA alone and combination of TQ and MA at various doses, as well as a reference drug (pramipexole) were given every 48 hours concurrently with rotenone. Motor symptoms were assessed through behavioral tests, including the open field test (OFT), beam walking test, and hanging wire test; midbrain dopamine levels were quantified via enzyme-linked immunosorbent assay (ELISA), α-synuclein expression was assessed using Western blotting, and immunohistochemistry was used to detect mBDNF-positive cells in the cerebral cortex. The combination of TQ and MA significantly increased midbrain dopamine levels and improved locomotor activity, as shown by increased total distance traveled and mean velocity in ROT-induced mice. Biochemically, this combined treatment reduced α-synuclein expression, suggesting attenuation of early pathological aggregation typically observed in Parkinson's disease. Although the increase in mBDNF expression in the cerebral cortex was not statistically significant, it was higher in the TQ-MA treatment group compared to controls and other groups. Collectively, these results highlight the therapeutic potential of TQ and MA in combination to counteract both motor deficits and early neurochemical disruptions in a ROT-induced model of Parkinson's disease.

帕金森病是一种进行性、无法治愈的神经退行性疾病,其特点是多巴胺能神经元变性,α-突触核蛋白在中脑内病理聚集,导致运动功能障碍。百里醌(TQ)是黑草(Nigella sativa)中的一种活性化合物,具有抗氧化特性,可以减少多巴胺的降解,而积雪草(Centella asiatica)中的三萜成分马尾草皂苷(MA)具有神经保护作用。迄今为止,还没有研究调查了TQ和MA在帕金森病模型中的联合作用。本研究的目的是评估TQ和MA对鱼藤酮(ROT)诱导的早期帕金森病小鼠模型的运动功能、多巴胺水平、α-突触核蛋白积累和成熟脑源性神经营养因子(mBDNF)表达的协同神经保护潜力。鱼藤酮(2.5 mg/kg BW)皮下注射2周诱导帕金森病,TQ单用、MA单用及不同剂量TQ和MA联用,每48小时与鱼藤酮同时服用一种参比药物(普拉克索)。通过行为测试评估运动症状,包括空地测试(OFT)、梁行走测试和吊丝测试;采用酶联免疫吸附法(ELISA)测定大鼠中脑多巴胺水平,Western blotting检测α-突触核蛋白表达,免疫组化检测大脑皮层mbdnf阳性细胞。TQ和MA联合使用显著增加了中脑多巴胺水平,改善了运动活动,这可以通过增加rot诱导小鼠的总行进距离和平均速度来证明。从生物化学角度看,这种联合治疗降低了α-突触核蛋白的表达,表明帕金森病典型的早期病理聚集减弱。虽然脑皮层mBDNF表达增加无统计学意义,但TQ-MA治疗组mBDNF表达高于对照组和其他组。总的来说,这些结果强调了TQ和MA联合治疗在rot诱导的帕金森病模型中抵消运动缺陷和早期神经化学破坏的治疗潜力。
{"title":"Thymoquinone and madecassoside improve motor function in a rotenone-induced mouse model of early Parkinson's disease: Role of dopamine, alpha-synuclein and mBDNF.","authors":"Shinta Kusumawati, Agustina T Endharti, Farhad Balafif, Shahdevi N Kurniawan, Aris Rosidah, Rabjhany Anaqah, Izzunazel A Barqillah, Husnul Khotimah","doi":"10.52225/narra.v5i2.2439","DOIUrl":"10.52225/narra.v5i2.2439","url":null,"abstract":"<p><p>Parkinson's disease is a progressive, incurable neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and pathological aggregation of α-synuclein in the midbrain, leading to motor dysfunction. Thymoquinone (TQ), an active compound from <i>Nigella sativa</i>, has demonstrated antioxidant properties that may reduce dopamine degradation, while madecassoside (MA), a triterpenoid component of <i>Centella asiatica</i>, exhibits neuroprotective effects. To date, no study has investigated the combined effects of TQ and MA in a Parkinson's disease model. The aim of this study was to evaluate the synergistic neuroprotective potential of TQ and MA on motor function, dopamine levels, α-synuclein accumulation, and mature brain-derived neurotrophic factor (mBDNF) expression in a rotenone (ROT)-induced mouse model of early Parkinson's disease. Rotenone (2.5 mg/kg BW) was administered subcutaneously for two weeks to induce Parkinson's disease, while TQ alone, MA alone and combination of TQ and MA at various doses, as well as a reference drug (pramipexole) were given every 48 hours concurrently with rotenone. Motor symptoms were assessed through behavioral tests, including the open field test (OFT), beam walking test, and hanging wire test; midbrain dopamine levels were quantified via enzyme-linked immunosorbent assay (ELISA), α-synuclein expression was assessed using Western blotting, and immunohistochemistry was used to detect mBDNF-positive cells in the cerebral cortex. The combination of TQ and MA significantly increased midbrain dopamine levels and improved locomotor activity, as shown by increased total distance traveled and mean velocity in ROT-induced mice. Biochemically, this combined treatment reduced α-synuclein expression, suggesting attenuation of early pathological aggregation typically observed in Parkinson's disease. Although the increase in mBDNF expression in the cerebral cortex was not statistically significant, it was higher in the TQ-MA treatment group compared to controls and other groups. Collectively, these results highlight the therapeutic potential of TQ and MA in combination to counteract both motor deficits and early neurochemical disruptions in a ROT-induced model of Parkinson's disease.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e2439"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mesenchymal stem cell-derived secretome accelerates third-degree burn wound healing: Effects on proliferation, angiogenesis, and fibrosis regulation. 间充质干细胞衍生的分泌组加速三度烧伤创面愈合:对增殖、血管生成和纤维化调节的影响。
Pub Date : 2025-08-01 Epub Date: 2025-05-19 DOI: 10.52225/narra.v5i2.1828
Bayu T Dirja, Agung Putra, Nur D Amalina

Mesenchymal stem cell-derived secretome (MSC-derived secretome) has shown promise in regenerative medicine; however, research specifically evaluating its efficacy in third-degree burn wounds remains scarce. The aim of this study was to investigate the effects of MSC-derived secretome on cellular proliferation, angiogenesis, myofibroblast activity, and collagen synthesis in a third-degree burn wound model. A total of 20 Wistar rats were randomly assigned to four groups: a healthy control group, a negative control group with untreated third-degree burn wounds, and two treatment groups receiving MSC-derived secretome at doses of 100 µL and 200 µL for 14 days. The wound healing was assessed 14 days post-treatment. Proliferating cell nuclear antigen (PCNA) protein expression was quantified via Western blot to assess cell proliferation; vascular endothelial growth factor (VEGF) gene expression was analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) to examine angiogenesis; alpha-smooth muscle actin (α-SMA) expression was assessed through immunohistochemistry to evaluate myofibroblast activity; and collagen density was measured using Masson's trichrome staining to determine tissue remodeling. Our data indicated that MSC-derived secretome treatment significantly enhanced multiple aspects of the healing process in a dose-dependent manner. PCNA expression increased by 2.8-fold in the 200 µL MSC-derived secretome group compared to the negative control (p<0.05). VEGF gene expression was upregulated by 2.14-fold in the 200 µL secretome group compared to the negative control (p<0.05). α-SMA protein expression increased by 12.67% in the 200 µL secretome group, while collagen density demonstrated the most pronounced improvement at the 200 µL dose, reaching an increase of 81.26% (p<0.05). In conclusion, MSC-derived secretome significantly accelerates burn wound healing by promoting cell proliferation, enhancing angiogenesis, and increasing collagen synthesis while modulating myofibroblast activity. This highlights the potential of MSC-derived secretome as a therapeutic option for optimizing burn wound repair and reducing fibrotic complications.

间充质干细胞衍生分泌组(MSC-derived secretome)在再生医学中显示出前景;然而,专门评估其在三度烧伤创面疗效的研究仍然很少。本研究的目的是研究间质干细胞衍生分泌组对三度烧伤模型中细胞增殖、血管生成、肌成纤维细胞活性和胶原合成的影响。将20只Wistar大鼠随机分为4组:健康对照组、未治疗三度烧伤创面的阴性对照组、2个治疗组分别给予100µL和200µL剂量的间质干细胞衍生分泌组,持续14 d。治疗14天后评估伤口愈合情况。Western blot检测增殖细胞核抗原(PCNA)蛋白表达,评价细胞增殖;采用定量逆转录聚合酶链式反应(qRT-PCR)检测血管内皮生长因子(VEGF)基因表达;免疫组化法检测α-平滑肌肌动蛋白(α-SMA)表达,评价肌成纤维细胞活性;用马松三色染色法测定胶原蛋白密度,测定组织重塑。我们的数据表明,骨髓间质干细胞衍生的分泌组治疗以剂量依赖的方式显著增强了愈合过程的多个方面。与阴性对照组相比,200µL mscs衍生分泌组PCNA表达增加2.8倍(200µL分泌组pVEGF基因表达上调2.14倍)
{"title":"Mesenchymal stem cell-derived secretome accelerates third-degree burn wound healing: Effects on proliferation, angiogenesis, and fibrosis regulation.","authors":"Bayu T Dirja, Agung Putra, Nur D Amalina","doi":"10.52225/narra.v5i2.1828","DOIUrl":"10.52225/narra.v5i2.1828","url":null,"abstract":"<p><p>Mesenchymal stem cell-derived secretome (MSC-derived secretome) has shown promise in regenerative medicine; however, research specifically evaluating its efficacy in third-degree burn wounds remains scarce. The aim of this study was to investigate the effects of MSC-derived secretome on cellular proliferation, angiogenesis, myofibroblast activity, and collagen synthesis in a third-degree burn wound model. A total of 20 Wistar rats were randomly assigned to four groups: a healthy control group, a negative control group with untreated third-degree burn wounds, and two treatment groups receiving MSC-derived secretome at doses of 100 µL and 200 µL for 14 days. The wound healing was assessed 14 days post-treatment. Proliferating cell nuclear antigen (PCNA) protein expression was quantified via Western blot to assess cell proliferation; <i>vascular endothelial growth factor</i> (<i>VEGF</i>) gene expression was analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) to examine angiogenesis; alpha-smooth muscle actin (α-SMA) expression was assessed through immunohistochemistry to evaluate myofibroblast activity; and collagen density was measured using Masson's trichrome staining to determine tissue remodeling. Our data indicated that MSC-derived secretome treatment significantly enhanced multiple aspects of the healing process in a dose-dependent manner. PCNA expression increased by 2.8-fold in the 200 µL MSC-derived secretome group compared to the negative control (<i>p</i><0.05). <i>VEGF</i> gene expression was upregulated by 2.14-fold in the 200 µL secretome group compared to the negative control (<i>p</i><0.05). α-SMA protein expression increased by 12.67% in the 200 µL secretome group, while collagen density demonstrated the most pronounced improvement at the 200 µL dose, reaching an increase of 81.26% (<i>p</i><0.05). In conclusion, MSC-derived secretome significantly accelerates burn wound healing by promoting cell proliferation, enhancing angiogenesis, and increasing collagen synthesis while modulating myofibroblast activity. This highlights the potential of MSC-derived secretome as a therapeutic option for optimizing burn wound repair and reducing fibrotic complications.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e1828"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapeutic potential of hUC-MSC secretome preconditioned with IFN-γ and/or TNF-α: An in vitro study on Alzheimer's neuronal cell models. IFN-γ和/或TNF-α预处理hUC-MSC分泌组的治疗潜力:阿尔茨海默病神经元细胞模型的体外研究
Pub Date : 2025-08-01 Epub Date: 2025-05-24 DOI: 10.52225/narra.v5i2.2281
Edhijanto Widaja, Jeanne A Pawitan, Yetty Ramli

Alzheimer's disease is a progressive neurodegenerative disease that is characterized by toxic Amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). Treatment options include the use of human umbilical cord mesenchymal stem cell (hUC-MSC)-based therapy. Its secretome contains healing substances such as neprilysin (CD10), which breaks down Aβ42; anti-inflammatory cytokines, which lower inflammation; and growth factors, which promote neuronal regeneration. The aim of this study was to produce hUC-MSC secretomes preconditioned with tumor necrosis factor-alpha (TNF-α) and/or interferon-gamma (IFN-γ) to enhance the secretion of these healing substances. hUC-MSCs were sub-cultured in T-25 flasks at a seeding density of 5×103 cells/cm2 in 10 mL xeno-free medium. hUC-MSCs were preconditioned with TNF-α only, IFN-γ only, and a combination of TNF-α and IFN-γ. This study used 10 ng/mL TNF-α and 20 ng/mL IFN- γ. The secretome was harvested after 48 hours of preconditioning and then filtered through a 0.22 µm filter. In vitro tests were conducted to assess the effects of the secretome on neuronal survival using the neuroblastoma SH-SY5Y cell line. These cells were differentiated with retinoic acid (RA) and then exposed to Aβ42 to mimic Alzheimer's disease neurons. Secretome therapy was applied at concentrations of 5%, 10%, and 20% to evaluate neuroprotective effects. Four types of secretome were tested: unpreconditioned, TNF-α preconditioned, IFN-γ preconditioned, and a combination of TNF-α and IFN-γ. High levels of CD10 (neprilysin) expression were observed in hUC-MSCs treated with IFN-γ and TNF-α, although they did not release sufficient soluble neprilysin (sNEP). Viability results indicated that secretomes preconditioned with IFN-γ at 10% and 20% concentrations provided the highest increase in cell viability after 72 hours post-therapy. The combination of TNF-α and IFN-γ preconditioned secretome exhibited synergistic effects, particularly at 5% and 10% doses at 24- and 72-hours post- therapy. In conclusion, preconditioned hUC-MSC secretome represents a promising therapeutic approach for Alzheimer's disease, as it enhances neuronal cell viability and promotes neuronal regeneration. However, further studies are required to optimize sNEP release and maximize therapeutic efficacy in in vivo models.

阿尔茨海默病是一种进行性神经退行性疾病,其特征是毒性淀粉样蛋白-β (a β)斑块和神经原纤维缠结(nft)。治疗方案包括使用人脐带间充质干细胞(hUC-MSC)为基础的治疗。它的分泌组含有愈合物质,如neprilysin (CD10),它可以分解Aβ42;抗炎细胞因子,可以降低炎症;以及促进神经元再生的生长因子。本研究的目的是制备经肿瘤坏死因子-α (TNF-α)和/或干扰素-γ (IFN-γ)预处理的hUC-MSC分泌组,以增强这些愈合物质的分泌。hUC-MSCs在10 mL无xeno培养基中以5×103 cells/cm2的播种密度在T-25烧瓶中传代培养。分别用TNF-α、IFN-γ和TNF-α和IFN-γ联合预处理hUC-MSCs。本研究使用10 ng/mL TNF-α和20 ng/mL IFN- γ。预处理48小时后收获分泌组,然后通过0.22µm过滤器过滤。利用神经母细胞瘤SH-SY5Y细胞系进行体外试验,评估分泌组对神经元存活的影响。这些细胞用视黄酸(RA)分化,然后暴露于Aβ42以模拟阿尔茨海默病神经元。采用浓度为5%、10%和20%的分泌组治疗来评估神经保护作用。测试了四种类型的分泌组:未预处理、TNF-α预处理、IFN-γ预处理以及TNF-α和IFN-γ的组合。在IFN-γ和TNF-α处理的hUC-MSCs中观察到高水平的CD10 (neprilysin)表达,尽管它们没有释放足够的可溶性neprilysin (sNEP)。活性结果表明,在治疗后72小时,用10%和20%浓度的IFN-γ预处理的分泌组细胞活性提高最高。TNF-α和IFN-γ预处理分泌组的联合表现出协同作用,特别是在治疗后24小时和72小时,5%和10%的剂量。总之,预处理的hUC-MSC分泌组是一种很有前途的治疗阿尔茨海默病的方法,因为它可以增强神经元细胞的活力并促进神经元再生。然而,在体内模型中优化sNEP释放和最大化治疗效果还需要进一步的研究。
{"title":"Therapeutic potential of hUC-MSC secretome preconditioned with IFN-γ and/or TNF-α: An in vitro study on Alzheimer's neuronal cell models.","authors":"Edhijanto Widaja, Jeanne A Pawitan, Yetty Ramli","doi":"10.52225/narra.v5i2.2281","DOIUrl":"10.52225/narra.v5i2.2281","url":null,"abstract":"<p><p>Alzheimer's disease is a progressive neurodegenerative disease that is characterized by toxic Amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). Treatment options include the use of human umbilical cord mesenchymal stem cell (hUC-MSC)-based therapy. Its secretome contains healing substances such as neprilysin (CD10), which breaks down Aβ42; anti-inflammatory cytokines, which lower inflammation; and growth factors, which promote neuronal regeneration. The aim of this study was to produce hUC-MSC secretomes preconditioned with tumor necrosis factor-alpha (TNF-α) and/or interferon-gamma (IFN-γ) to enhance the secretion of these healing substances. hUC-MSCs were sub-cultured in T-25 flasks at a seeding density of 5×103 cells/cm<sup>2</sup> in 10 mL xeno-free medium. hUC-MSCs were preconditioned with TNF-α only, IFN-γ only, and a combination of TNF-α and IFN-γ. This study used 10 ng/mL TNF-α and 20 ng/mL IFN- γ. The secretome was harvested after 48 hours of preconditioning and then filtered through a 0.22 µm filter. In vitro tests were conducted to assess the effects of the secretome on neuronal survival using the neuroblastoma SH-SY5Y cell line. These cells were differentiated with retinoic acid (RA) and then exposed to Aβ42 to mimic Alzheimer's disease neurons. Secretome therapy was applied at concentrations of 5%, 10%, and 20% to evaluate neuroprotective effects. Four types of secretome were tested: unpreconditioned, TNF-α preconditioned, IFN-γ preconditioned, and a combination of TNF-α and IFN-γ. High levels of CD10 (neprilysin) expression were observed in hUC-MSCs treated with IFN-γ and TNF-α, although they did not release sufficient soluble neprilysin (sNEP). Viability results indicated that secretomes preconditioned with IFN-γ at 10% and 20% concentrations provided the highest increase in cell viability after 72 hours post-therapy. The combination of TNF-α and IFN-γ preconditioned secretome exhibited synergistic effects, particularly at 5% and 10% doses at 24- and 72-hours post- therapy. In conclusion, preconditioned hUC-MSC secretome represents a promising therapeutic approach for Alzheimer's disease, as it enhances neuronal cell viability and promotes neuronal regeneration. However, further studies are required to optimize sNEP release and maximize therapeutic efficacy in in vivo models.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e2281"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Peptide-based drug as atherosclerosis multitarget therapy from Lytechinus variegatus spine: An in silico study. 以多肽为基础的药物作为动脉粥样硬化的多靶点治疗:一项计算机研究。
Pub Date : 2025-08-01 Epub Date: 2025-04-21 DOI: 10.52225/narra.v5i2.1152
Dessy Arisanty, Salsabila P Khairani, Kevin N Cuandra, Dhyani P Wahyudi, Isna C Kamila, Malya Cs Maharani, Eillen Theodora, Raymond E Budianto, Alifya R Shofiy, Ikwandi C Nugraha, Zaki S Aaliyya, Awalil Rk Rahman, Al H Ariouso

Atherosclerosis is a leading cardiovascular disease characterized by the buildup of plaques within arterial walls. The aim of this study was to investigate the potential of peptides derived from Lytechinus variegatus spines as novel therapeutic agents for atherosclerosis using an in silico approach. Key proteins involved in atherosclerosis were selected as target proteins: vascular endothelial growth factor receptor (VEGFR), protein kinase B (AKT1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 8 (MAPK8), and endothelin-1 (ET-1). Comprehensive analysis involving ligand and protein preparation, toxicity, and allergenicity assessments, absorption, distribution, metabolism and excretion (ADME) predictions, and molecular docking were conducted to evaluate the safety, pharmacokinetic properties, binding affinity (kcal/mol), root mean square deviation (RMSD) (Å), as well as a 2D and 3D visualization. Toxicity predictions revealed that peptide 9 was non-toxic and non-allergenic, with a lethal dose 50 (LD50) of 3,000 mg/kg, indicating its safety. Peptide 9 demonstrated the most promising results, effectively inhibiting VEGFR2 (-10,90 kcal/mol), AKT1 (-10,56 kcal/mol), EGFR (-9,82 kcal/mol), MAPK8 (-9,64 kcal/mol), and ET-1 (-11,41 kcal/mol) with strong binding affinities and specificity. These interactions suggested that peptide 9 from Lytechinus variegatus spines may serve as a competitive multitarget inhibitor, offering potential multitarget therapeutic activity against atherosclerosis. Peptide 9 also had high water solubility and did not affect the concentration or excretion of other drugs or compounds, minimizing the risk of drug-drug interactions.

动脉粥样硬化是一种主要的心血管疾病,其特征是动脉壁内斑块的积聚。本研究的目的是利用计算机方法研究从缬草棘中提取的肽作为动脉粥样硬化新型治疗剂的潜力。选择与动脉粥样硬化相关的关键蛋白为靶蛋白:血管内皮生长因子受体(VEGFR)、蛋白激酶B (AKT1)、表皮生长因子受体(EGFR)、丝裂原活化蛋白激酶8 (MAPK8)和内皮素-1 (ET-1)。综合分析包括配体和蛋白质制备、毒性和致敏性评估、吸收、分布、代谢和排泄(ADME)预测和分子对接,以评估安全性、药代动力学特性、结合亲和力(kcal/mol)、均方根偏差(RMSD) (Å),以及2D和3D可视化。毒性预测显示肽9无毒、无致敏性,致死剂量50 (LD50)为3000 mg/kg,表明其安全性。Peptide 9表现出最有希望的结果,有效抑制VEGFR2 (-10,90 kcal/mol)、AKT1 (-10,56 kcal/mol)、EGFR (-9,82 kcal/mol)、MAPK8 (-9,64 kcal/mol)和ET-1 (-11,41 kcal/mol),具有很强的结合亲和力和特异性。这些相互作用表明,从Lytechinus variegatus棘肽9可能作为一个竞争性的多靶点抑制剂,提供潜在的多靶点治疗活性动脉粥样硬化。肽9还具有高水溶性,不影响其他药物或化合物的浓度或排泄,最大限度地降低了药物相互作用的风险。
{"title":"Peptide-based drug as atherosclerosis multitarget therapy from <i>Lytechinus variegatus</i> spine: An in silico study.","authors":"Dessy Arisanty, Salsabila P Khairani, Kevin N Cuandra, Dhyani P Wahyudi, Isna C Kamila, Malya Cs Maharani, Eillen Theodora, Raymond E Budianto, Alifya R Shofiy, Ikwandi C Nugraha, Zaki S Aaliyya, Awalil Rk Rahman, Al H Ariouso","doi":"10.52225/narra.v5i2.1152","DOIUrl":"10.52225/narra.v5i2.1152","url":null,"abstract":"<p><p>Atherosclerosis is a leading cardiovascular disease characterized by the buildup of plaques within arterial walls. The aim of this study was to investigate the potential of peptides derived from <i>Lytechinus variegatus</i> spines as novel therapeutic agents for atherosclerosis using an in silico approach. Key proteins involved in atherosclerosis were selected as target proteins: vascular endothelial growth factor receptor (VEGFR), protein kinase B (AKT1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 8 (MAPK8), and endothelin-1 (ET-1). Comprehensive analysis involving ligand and protein preparation, toxicity, and allergenicity assessments, absorption, distribution, metabolism and excretion (ADME) predictions, and molecular docking were conducted to evaluate the safety, pharmacokinetic properties, binding affinity (kcal/mol), root mean square deviation (RMSD) (Å), as well as a 2D and 3D visualization. Toxicity predictions revealed that peptide 9 was non-toxic and non-allergenic, with a lethal dose 50 (LD<sub>50</sub>) of 3,000 mg/kg, indicating its safety. Peptide 9 demonstrated the most promising results, effectively inhibiting VEGFR2 (-10,90 kcal/mol), AKT1 (-10,56 kcal/mol), EGFR (-9,82 kcal/mol), MAPK8 (-9,64 kcal/mol), and ET-1 (-11,41 kcal/mol) with strong binding affinities and specificity. These interactions suggested that peptide 9 from <i>Lytechinus variegatus</i> spines may serve as a competitive multitarget inhibitor, offering potential multitarget therapeutic activity against atherosclerosis. Peptide 9 also had high water solubility and did not affect the concentration or excretion of other drugs or compounds, minimizing the risk of drug-drug interactions.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e1152"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Determinants of safety performance in healthcare settings: A meta-analysis. 医疗环境中安全表现的决定因素:一项荟萃分析。
Pub Date : 2025-08-01 Epub Date: 2025-05-12 DOI: 10.52225/narra.v5i2.1654
Septyani Prihatiningsih, Tri Martiana, Noeroel Widajati, Jonny K Fajar

Safety performance among healthcare workers is an important issue, and currently, the factors related to it remain unclear. The aim of this study was to identify the factors related to safety performance among the healthcare worker population. This meta-analysis study was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) standards. Data on the factors affecting safety performance in the healthcare population were collected from each article to determine pooled point estimates. Data heterogeneity was evaluated using the Q statistic. Numerical data were analyzed using the inverse variance test, and the Mantel-Haenszel test was used for categorical data analysis. Pooled point estimates were presented as mean difference (MD) or odds ratio (OR) along with a 95% confidence interval (95%CI). Fifty articles were included in this study. Our results showed that nurses had lower safety performance compared to other professions (OR: 0.66; 95%CI: 0.56-0.79; p-Egger: 0.3739; p-Heterogeneity <0.0001; p<0.0001). On the other hand, it was also identified that housekeepers were associated with better safety performance compared to other professions (OR: 1.90; 95%CI: 1.08-3.35; p-Egger: 0.1577; p-Heterogeneity: 0.0950; p=0.0220). Furthermore, our findings revealed that healthcare workers who had undergone work safety training had better safety performance compared to those who had not (OR: 1.40; 95%CI: 1.01-1.95; p-Egger: 0.6124; p-Heterogeneity <0.0001; p=0.0430). In conclusion, this study has identified the factors contributing to safety performance in the healthcare population. These findings can inform policymakers in developing regulatory improvements regarding safety performance in healthcare workers.

卫生保健工作者的安全绩效是一个重要的问题,目前,与之相关的因素尚不清楚。本研究的目的是确定卫生保健工作者人群中与安全表现相关的因素。本荟萃分析研究按照系统评价和荟萃分析的首选报告项目(PRISMA)标准进行。从每篇文章中收集影响医疗保健人群安全性能因素的数据,以确定汇总点估计值。使用Q统计量评估数据异质性。数值数据分析采用方差反检验,分类数据分析采用Mantel-Haenszel检验。合并点估计值表示为平均差(MD)或优势比(or)以及95%置信区间(95% ci)。本研究纳入了50篇文章。结果显示,与其他职业相比,护士的安全绩效较低(OR: 0.66; 95%CI: 0.56-0.79; p- egger: 0.3739; p- egger: 0.1577; p-异质性:0.0950;p=0.0220)。此外,我们的研究结果显示,接受过安全生产培训的医护人员比没有接受过安全生产培训的医护人员有更好的安全绩效(OR: 1.40; 95%CI: 1.01-1.95; p- egger: 0.6124; p异质性p=0.0430)。总之,本研究确定了影响医疗保健人群安全性能的因素。这些发现可以为决策者提供信息,以制定有关卫生保健工作者安全绩效的监管改进措施。
{"title":"Determinants of safety performance in healthcare settings: A meta-analysis.","authors":"Septyani Prihatiningsih, Tri Martiana, Noeroel Widajati, Jonny K Fajar","doi":"10.52225/narra.v5i2.1654","DOIUrl":"10.52225/narra.v5i2.1654","url":null,"abstract":"<p><p>Safety performance among healthcare workers is an important issue, and currently, the factors related to it remain unclear. The aim of this study was to identify the factors related to safety performance among the healthcare worker population. This meta-analysis study was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) standards. Data on the factors affecting safety performance in the healthcare population were collected from each article to determine pooled point estimates. Data heterogeneity was evaluated using the Q statistic. Numerical data were analyzed using the inverse variance test, and the Mantel-Haenszel test was used for categorical data analysis. Pooled point estimates were presented as mean difference (MD) or odds ratio (OR) along with a 95% confidence interval (95%CI). Fifty articles were included in this study. Our results showed that nurses had lower safety performance compared to other professions (OR: 0.66; 95%CI: 0.56-0.79; <i>p</i>-Egger: 0.3739; <i>p</i>-Heterogeneity <0.0001; <i>p</i><0.0001). On the other hand, it was also identified that housekeepers were associated with better safety performance compared to other professions (OR: 1.90; 95%CI: 1.08-3.35; <i>p</i>-Egger: 0.1577; <i>p</i>-Heterogeneity: 0.0950; <i>p</i>=0.0220). Furthermore, our findings revealed that healthcare workers who had undergone work safety training had better safety performance compared to those who had not (OR: 1.40; 95%CI: 1.01-1.95; <i>p</i>-Egger: 0.6124; <i>p</i>-Heterogeneity <0.0001; <i>p</i>=0.0430). In conclusion, this study has identified the factors contributing to safety performance in the healthcare population. These findings can inform policymakers in developing regulatory improvements regarding safety performance in healthcare workers.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e1654"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Narra J
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1