Narra J (Journal)
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Research trends in microRNA profiling as a biomarker for lung adenocarcinoma via liquid biopsy: A bibliometric analysis
Research related to the development of diagnostic biomarkers in lung adenocarcinoma in various countries is important. Research on microRNA as a biomarker in lung adenocarcinoma varies depending on the population, specimen, and technology used for profiling and validation. The aim of this study was to map and analyze bibliometric data of publications related to the topic of microRNA as a candidate biomarker in lung adenocarcinoma and to determine any potential research gaps. A total of 8,506 articles were collected from Crossref, Google Scholar, Semantic Scholar, PubMed, and Scopus databases using Harzing's Publish or Perish platform. A systematic search was conducted using four keywords: “profiling,” “validating,” “microRNA,” and “lung adenocarcinoma,” and synonyms of these keywords based on the MeSH on NCBI. The data extraction process followed the chart from PRISMA-P. The article’s elimination was conducted using Mendeley Desktop and then was analyzed based on the authors' keywords using VOSviewer and Biblioshiny. A bibliometric analysis of 692 relevant articles identified four primary research clusters: (1) microRNA (19 keywords), which highlights its potential as a biomarker for early detection and diagnosis; (2) lung adenocarcinoma (18 keywords), reflecting advancements in lung cancer research; (3) liquid biopsy (19 keywords), emphasizing the growing interest in non-invasive diagnostic methods; and (4) bioinformatics (nine keywords), underscoring the role of computational approaches in transcriptomic analysis. As a primary topic, microRNAs have become a focal point of research for diagnosing lung cancer across various stages and as biomarkers for cancer cell proliferation, invasion, migration, and metastasis. Numerous studies have demonstrated the successful application of microRNAs in lung cancer diagnosis in the last decade, although the reported types of microRNAs are inconsistent. Therefore, further research on this topic should be continuously conducted, particularly to validate the types of microRNAs and the types of environments that influence them
Genetic variations of the L2 gene in human papillomavirus (HPV) type 16 from cervical cancer patients in Sumatra region, Indonesia
The L2 protein, a minor capsid component of human papillomavirus (HPV), plays a critical role in the HPV life cycle by packaging the viral genome with the L1 protein and facilitating DNA transport to the nucleus. Identifying genetic variations in the L2 gene is essential for improving vaccine development, diagnostic accuracy, and understanding viral evolution, potentially contributing to more effective HPV vaccines. The aim of this study was to investigate the genetic variation of the L2 gene in cervical cancer specimens collected from patients in Riau Province, Indonesia. A single-center, cross-sectional study was conducted at Arifin Achmad General Hospital, Riau Province, involving cervical cancer patients with confirmed HPV16 infection between January 2018 and August 2020. Demographic, clinical, and risk factor data were collected through structured interviews and direct assessments. Cervical biopsy specimens were collected, and viral DNA was extracted for L2 gene amplification using polymerase chain reaction (PCR). Sequencing was conducted on PCR products, followed by single-nucleotide polymorphism (SNP) identification through alignment with the HPV16 reference genome. The amplification and sequencing of the HPV16 L2 gene from 22 cervical cancer specimens revealed 36 SNPs, including 31 nonsynonymous and five synonymous mutations. High-frequency mutations were observed at nucleotide positions 4,074 and 4,177, each detected in 95.45% of the samples. Notable insertions were found at positions 3,668–3,669 and 4,275–4,276, indicating substantial sequence variation. Phylogenetic analysis grouped the sequences into three clusters, with most belonging to sub-lineage A2 (European), while others aligned with A4 (Asian) and East Asian lineages. The observed genetic diversity in the HPV16 L2 gene may reflect regional viral evolution and has potential implications for future vaccine development
Effective probiotic regimens for bacterial vaginosis treatment and recurrence prevention: A systematic review
Probiotics represent a promising alternative therapy for bacterial vaginosis; however, consensus on the most effective species, strains, and doses remains lacking, and long-term safety data are limited. The aim of this study was to evaluate the effectiveness of probiotics in managing bacterial vaginosis, considering species, strain, clinical outcomes, optimal dosage, duration, and side effects. This study included randomized-controlled trials (RCTs) published in English (2014–2024) on probiotic treatment for bacterial vaginosis, assessing species, strain, dose, duration, and efficacy. A systematic search was conducted on December 20, 2024, in Scopus, Web of Science, and PubMed using the keywords "vaginosis," "bacterial vaginosis," and "probiotic." Data were extracted and synthesized, and study quality was assessed using the Risk of Bias 2 tool, while NVivo 14 software facilitated thematic analysis. The systematic search yielded 1,560 initial records, of which 16 RCTs were included. The findings revealed that Lactobacillus rhamnosus TOM 22.8 (10×10⁹ CFU/day for 10 days) was the most effective strain and dose, significantly improving Nugent scores, vaginal pH, and microbiota composition and reducing bacterial vaginosis recurrence rate. Alternative strains, including L. crispatus, L. plantarum, and L. acidophilus, showed therapeutic potential at doses of 1×10⁸ to 5.4×10⁹ CFU/day for treatment durations ranging from 6 days to 4 months. The reported side effects were mild and self-limiting. This study supports the use of probiotics as an adjunctive or alternative bacterial vaginosis treatment, emphasizing the need for a personalized approach based on patient characteristics. However, limitations such as small sample sizes and heterogeneous outcome measures necessitate further research. Larger, well-designed trials with standardized methodologies are required to refine probiotic recommendations
Effects of patin fish-based nutritional intervention on biochemical and physiological recovery in malnourished rats: An in vivo study and its implications for clinical nutrition
Malnutrition is a major global health concern, especially in developing countries. Although patin fish oil and protein offer benefits, their individual and combined effects on maternal physiology remain unclear, particularly during early pregnancy. The aim of this study was to assess the effect of patin-based nutritional intervention on total serum protein, albumin, hemoglobin levels, body weight during pregnancy, body weight during lactation, heart rate, respiratory rate, body temperature, external appearance, behavioral activity, and milk production in malnourished rats. An in vivo study was conducted using Rattus norvegicus rats. The rats were divided into six groups: (1) healthy control, receiving standard feed; (2) malnourished control, receiving an 8% low-protein diet; (3) malnourished group, receiving standard feed; (4) malnourished treated with patin oil; (5) malnourished treated with patin meat; and (6) malnourished treated with a combination of patin oil and meat. The treatment consisted of 21 days during pregnancy and 23 days during lactation, for a total of 44 days. Our data indicated that patin-based intervention significantly increased total protein (p=0.044), albumin (p=0.001), and hemoglobin levels (p=0.034) compared to malnourished control group. The malnourished animals treated with patin oil showed the highest increases in total protein (1.67%), albumin (17.75%), and hemoglobin (24.26%). Body weight gain improved significantly in patin-treated group in both pregnancy (p=0.032) and lactation (p<0.001) compared to the malnourished control, with the highest gains observed in the patin oil group. Milk production also increased significantly (p<0.05), reaching its peak in the patin oil and meat combination group (6.97 g). Physiological parameters, including heart rate (p=0.021), respiratory rate (p=0.025), and body temperature (p=0.023), were significantly different among groups, of which patin oil and meat groups had the most optimal parameters compared to malnourished control group. In conclusion, patin-based nutritional intervention effectively enhances protein metabolism, hematological parameters, and physiological health in malnourished maternal rats, with patin oil demonstrating the most pronounced effects
Impact of vitamin D supplementation on post-stroke rehabilitation outcomes: A systematic review and meta-analysis
Each year, there are approximately 12.2 million new stroke cases and 6.5 million stroke-related deaths, with low- and middle-income countries shouldering a disproportionately high financial burden. Studies have associated vitamin D deficiency with arteriosclerosis, left ventricular hypertrophy, and vascular dysfunction, contributing to an elevated risk of stroke. The aim of this study was to evaluate how vitamin D supplementation affects post-stroke outcomes. A comprehensive literature search was performed across PubMed, Scopus, the Cochrane Library, ScienceDirect, Springer Link, ProQuest, and Epistemonikos from April to May 2024. This study focused on comparing the efficacy of vitamin D supplementation versus no supplementation in stroke patients of all ages. Outcome measures included the Functional Ambulation Classification (FAC), Brunnstrom Recovery Stage (BRS), Modified Rankin Scale (mRS), and National Institutes of Health Stroke Scale (NIHSS). Case reports, reviews, and research on other cardiovascular or metabolic issues were excluded. Five authors extracted data and analyzed bias separately using the Risk of Bias Version 2 (RoB V2) algorithms. The results of continuous variables were pooled into the mean difference (MD) along with 95% confidence intervals (CI) using random-effect models. Review Manager 5.4 was used to evaluate the data. Out of the 1,152,449 papers evaluated, six met the inclusion criteria, with a sample size ranging from 42 to 123 patients. Vitamin D supplementation was found to yield better outcomes after stroke. BRS in lower extremities showed better results (MD: 0.59 (95%CI: 0.27–0.91)), NIHSS improved with an MD of -1.47 (95%CI: -2.03–(-0.90)). Furthermore, there was also an improvement in mRS, with an MD of -0.91 (95%CI: -1.25–(-0.56)). In conclusion, vitamin D improved post-stroke outcomes, which supported its supplementation as a part of stroke rehabilitation
Biomarkers for predicting COVID-19 mortality: A study at Sulianti Saroso Infectious Disease Hospital, Indonesia
The high transmissibility and mortality rates of the COVID-19 pandemic pose significant challenges. Patients can deteriorate rapidly, making it crucial to identify laboratory biomarkers for high-risk individuals. The aim of this study was to evaluate the predictive value of various laboratory parameters, including C-reactive protein (CRP), D-dimer, ferritin, neutrophil-to-lymphocyte ratio (NLR), prothrombin time (PT), and procalcitonin (PCT), in predicting COVID-19 mortality. A retrospective cohort study was conducted at Sulianti Saroso Infectious Disease Hospital, where COVID-19 patients were categorized into survivors and non-survivors. The Mann-Whitney test was used to assess group differences, while receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of each biomarker, with Youden's index (J) determining optimal cut-off values. Kaplan-Meier analysis was used to compare median survival times, and Cox regression assessed hazard rates and the relationship between biomarkers and mortality. A total of 1,598 patients were analyzed, the majority of whom were admitted with oxygen saturation levels >95% and classified as having mild to moderate disease severity. Among them, 216 patients died, resulting in a mortality rate of 13.52%. Significant variations in mortality rates were observed along the survival functions for NLR, ferritin, D-dimer, CRP, and PCT (p<0.001). The survival curves for these biomarkers demonstrated distinct trends across tertiles over time. Among hematological markers, NLR was significantly associated with mortality (p<0.001), with a 1.5–2.2% increased risk per unit increase. Biochemical markers (complete blood count) proved to be more effective than hematological parameters (NLR, ferritin, PT, D-dimer, CRP, PCT) when evaluating individual prognostic performance. Bivariate analysis of CRP, D-dimer, ferritin, NLR, PT, and PCT between survivors and non-survivors showed significant differences. Notably, NLR and PCT were highly relevant for predicting disease prognosis and mortality, with sensitivity and specificity values exceeding 80%
Synergistic mechanism of Phyllanthus emblica extract and tetracycline against multidrug-resistant Acinetobacter baumannii
The rising incidence of multidrug-resistant (MDR) Acinetobacter baumannii infections underscores the urgent need for novel antimicrobial strategies. The aim of this study was to investigate the synergistic effects between a polyphenol-rich extract from Phyllanthus emblica fruit and tetracycline against MDR A. baumannii strains. The extraction process was optimized using the Box-Behnken design approach to maximize the total phenolic content (TPC) of the P. emblica extract. Key variables, including ethanol concentration, extraction time, and solid-to-liquid ratio (w/v), were determined through single-factor experiments. The antimicrobial activity of the extract, both alone and in combination with tetracycline, was evaluated against A. baumannii. Mechanistic studies focusing on bacterial lysis and efflux pump inhibition were conducted to assess the extract's effects and its combined potential with tetracycline. The Box-Behnken design successfully optimized the extraction conditions, yielding the highest TPC at 68.92% ethanol concentration, 1.85 days of extraction time, and a 1:9.58 w/v ratio. The predicted and experimentally verified TPC values of the extract were 129.19 and 130.76±2.46 mg GAE/g samples, respectively, with no significant difference (p>0.05). The extract contained several phenolic compounds identified using liquid chromatography–high-resolution mass spectrometry (LC-HRMS). It exhibited antimicrobial activity against MDR Acinetobacter baumannii, either alone or in combination with tetracycline. The combination demonstrated a synergistic effect against MDR A. baumannii, with a fractional inhibitory concentration index (FICI) of 0.37. Moreover, the combination showed superior bacteriolytic effects against MDR A. baumannii cells, as evidenced by increased release of nucleic acid components and membrane destabilization, compared to the extract or tetracycline alone (p<0.0001 for all comparisons). Additionally, the combination significantly enhanced the efflux pump inhibition effect compared to the extract or tetracycline alone (p<0.05 for both). These findings support the potential use of polyphenol-rich P. emblica extracts as adjuncts to conventional antibiotics in treating drug-resistant bacterial infections
Effects of doxazosin as adjuvant to abiraterone on viability and apoptosis of metastatic castration-resistant prostate cells cancer (mCRPC) PC3
Prostate cancer is a leading cause of death among men worldwide, with limited therapeutic options for castration-resistant metastatic prostate cancer (mCRPC). The aim of this study was to investigate the potential role of doxazosin, an α1-blocker, as an adjunctive therapy for mCRPC in combination with abiraterone. Using mCRPC PC3 cells, the effects of doxazosin on cell viability and apoptosis were assessed. The experimental design was an in vitro study with post-test-only control design. Experimental groups were divided into four groups: control group, doxazosin group, abiraterone group, and combination group (doxazosin and abiraterone). Cell viability was analyzed using the cell counting kit-8 (CCK-8) assay, while apoptosis was analyzed using Fluorescence-activated cell sorting (FACS). This study found that the IC50 value for doxazosin was 25.42±1.42 µM (mean ± standard error). The results indicated that doxazosin significantly reduced cell viability, with effects varying based on the dose administered, and doxazosin was able to induce apoptosis in mCRPC PC3 cells. The combined treatment of doxazosin and abiraterone in mCRPC PC3 cells demonstrated a significantly higher mean apoptosis percentage compared to the control group (16.27%; 95% confidence interval (CI): 11.89–20.65; p=0.001). Furthermore, the combined treatment showed a significantly higher mean apoptosis percentage compared to abiraterone alone (4.79%; 95%CI: 0.41–9.18; p=0.029), and doxazosin alone (10.99%; 95%CI: 6.61–15.38; p=0.001). These findings suggest that doxazosin, traditionally used as an α1-blocker for lower urinary tract symptoms (LUTS), could offer a novel therapeutic approach for mCRPC patients
Blood lead levels and their association with children’s factors, nutritional status, and daily dietary intake in used lead-acid battery (ULAB) recycling area
Evidence has shown that unregulated lead battery recycling is a significant contributor to lead exposure in many countries. The aim of this study was to investigate the factors associated with blood lead levels (BLLs) among children aged 1 to 5 who reside within 250 meters of used lead-acid battery recycling areas in three metropolitan neighborhoods in Indonesia. Using a cross-sectional approach, data was collected through in-person household visitations. The assessed risk factors included socio-demographic data, nutritional status, immunization, breastfeeding status, and daily food intake. BLLs were measured using the LeadCare II portable device and confirmed with plasma mass spectrometry, then classified based on the recommendations of the Centers for Disease Control and Prevention (CDC). A multivariate multinomial logistic regression was used to analyze the association between children’s characteristics and daily eating habits as predictors of BLLs. Out of a total of 433 eligible children, 361 were included in this study. High monthly household income (adjusted odds ratio (aOR): 0.16; 95% confidence interval (95%CI): 0.04–0.67), child’s age (aOR: 0.21; 95%CI: 0.07–0.64), and being boy (aOR: 2.19; 95%CI: 1.17–4.10) were associated with medium BLLs in comparison to low BLLs. In addition, high fruit consumption (AOR: 1.91; 95%CI: 0.99–3.66) and high dairy consumption (aOR: 0.42; 95%CI: 0.27–0.76) were associated with medium BLLs in comparison to low BLLs. Our study also indicated that being a boy (aOR: 5.53; 95%CI: 1.68–18.25), completed breastfeeding history (aOR: 3.47; 95%CI: 1.18–10.23), short outdoor activity duration (aOR: 0.30; 95%CI: 0.09–0.97), high heme-rich iron consumption (aOR: 0.32; 95%CI: 0.10–1.00), and high dairy consumption (aOR: 0.13; 95%CI: 0.04–0.44) were associated with high BLLs in comparison to low BLLs. This study highlights the necessity for further investigation into the impact of various dietary groups on the BLLs of children living around used lead-acid battery recycling areas
Cytoarchitectural changes in the developing cerebellar cortex of the laggard mutant mouse
The laggard (lag) mutant mouse, which arises from a mutation in the Kif14 gene, begins to exhibit ataxia and impaired growth after the first postnatal week and subsequently dies prematurely around two weeks of age. In this mutant mouse, the layered architecture of the cerebellar cortex, cerebral cortex, dentate gyrus, and olfactory bulb is disrupted at the cellular level. The aim of this study was to identify the effect of Kif14 mutation on the development of the cerebellar cortex. Abnormalities in the cytoarchitectonics of the developing cerebellar cortex were assessed using hematoxylin-eosin (HE) staining and immunohistochemistry. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and bromodeoxyuridine (BrdU) assays were performed to identify apoptotic and proliferating cells. Macroscopic observation of the lag mutant cerebellum reveals a marked reduction in size compared to wild-type mice. HE staining displays a normal foliation and lamination pattern in the lag mutant cerebellum, but detailed analysis has shown morphological disorganization in the cytoarchitectonics of the cerebellar cortex. The mutant internal granular layer is poorly defined and contains significantly fewer granule cells. Meanwhile, Purkinje cells form multilayer arrangements instead of a monolayer arrangement, as observed in wild-type mice, with their dendritic arborization being severely underdeveloped. Some Purkinje cells exhibit multiple nuclei, suggesting that the Kif14 mutation disrupts normal cell division. These phenotypes are already recognized during early postnatal days, although no difference is determined before birth. TUNEL-positive cells are significantly more numerous in the mutant external granular layer, indicating that increased apoptotic cell death contributes to the diminished granule cell population in the lag mutant mouse. In conclusion, the lag mutant cerebellar cortex shows distinct structural abnormalities, suggesting that the Kif14-encoded protein exerts multifaceted roles in the development of the brain laminated structures as well as in myelin formation