Narra J (Journal)
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Perindopril decreases angiotensin-converting enzyme 2 (ACE2) expression in human adipocytes exposed to SARS-CoV-2 S1 spike protein
Get PDFThe expression of angiotensin-converting enzyme 2 (ACE2) in the adipose tissues of obese patients needs further study, as it may aid infection and serve as a viral reservoir. There has been controversy over whether to use ACE inhibitors to prevent coronavirus disease 2019 (COVID-19) severity. Perindopril, an ACE2 inhibitor, has been proposed; however, its relationship with COVID-19 has not yet been clear. The aim of this study was to investigate the effect of perindopril to reduce the expression of ACE2 and pro-inflammatory cytokine in adipocytes exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Enzymatic isolation of adipose tissues was performed from obese male donor patients aged 30–50 years, then exposed it with SARS-CoV-2 S1 spike protein. This study also included human recombinant ACE2 (hrsACE2) as a comparison to perindopril. The expression of ACE2 was evaluated using ELISA. Our data indicated that SARS-CoV-2 Spike protein exposure increased ACE2 expression significantly. Administration of perindopril decreased ACE2 expression (43.37 µg/mL) significantly compared to the positive group (80.31 µg/mL) (p<0.001). Perindopril administration also decreased IL-6 levels significantly compared to positive group(p<0.001). This study highlights that perindopril could reduce the ACE2 expression and pro-inflammatory cytokine levels in adipocytes exposed to SARS-CoV-2 S1 spike protein
Transcriptomic analysis of profibrinolytic and fibrinolytic inhibitor genes in COVID-19 patients
Get PDFThe immunopathogenesis of COVID-19 infection is initiated by the entry of the SARS-CoV-2 virus into the human body through droplets, entering the lungs and binding to the ACE-2 receptor. Activated macrophages stimulate an immune and inflammatory response, leading to the activation of the coagulation cascade, including profibrinolytic and fibrinolytic inhibitor processes. One of the proteins involved in profibrinolytic is encoded by the PLAUR gene, while fibrinolytic inhibitor proteins are encoded by the A2M and SERPINE1 genes. This research aims to assess the transcriptomic analysis of genetic expression data of profibrinolytic genes, fibrinolytic inhibitor genes and their correlation with serum D-dimer levels, which describe the clinical condition of coagulation in COVID-19 patients. This cross-sectional study included 25 patients each for mild and moderate-to-severe COVID-19 at Dr. M. Djamil Padang General Hospital, Padang, Indonesia. Inter-group gene expression comparisons will be analyzed using log2 folds change, and bivariate tests will be analyzed using correlation. The results show that the PLAUR gene has higher expression in moderate-to-severe compared to mild cases. Similarly, the SERPINE1 and A2M genes expressions are higher in moderate-to-severe compared to mild cases. Furthermore, there is a significant correlation between serum D-dimer levels and profibrinolytic factor (PLAUR gene) expression in COVID-19 patients. The correlation between serum D-dimer levels with fibrinolytic inhibitor factor (SERPINE1 and A2M genes) expression was found. These conclude that there is a significant difference in the expression of the profibrinolytic and fibrinolytic inhibitor genes between mild and moderate-to-severe cases in COVID-19, demonstrating COVID-19 infection affects coagulation activities
A fruit fly-based approach to unraveling enteropathy-causing pharmaceuticals
Get PDFEnteropathy is a gastrointestinal disorder characterized by inflammation in the small intestine and one of the causes of enteropathy is the side effects of certain drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs). The mechanism of NSAIDs, such as indomethacin, could inhibit prostaglandin synthesis, leading to a decrease in mucus production and small intestine integrity. To test the effects of a drug, it is necessary to undergo preclinical testing using animal models. Commonly used animal models such as mice and rats have several drawbacks including high cost, ethical issues, and long lifespan. Therefore, alternatives such as using invertebrate animals like Drosophila melanogaster as a more economical in vivo platform with genetic similarity to mammals and devoid of ethical concerns are needed. The aim of this study was to evaluate Drosophila melanogaster as an in vivo model organism in testing the side effects of pharmaceuticals that cause enteropathy. In this study, flies aged 3–5 days were starved and then placed into treatment vials comprising untreated control and indomethacin-treated (3.75 mM, 7.5 mM, and 15 mM). Survival analysis was conducted during the treatment period, followed by a Smurf assay test after seven days of treatment. Subsequently, the expression of pro-inflammatory cytokine-related genes (drs and totA), mitochondria stability-related genes (tom40), and endogenous antioxidant-related genes (sod1, sod2, and cat) was performed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Our data indicated that indomethacin did not impact lifespan or cause intestinal damage. However, we observed increased expression of pro-inflammatory cytokine-related genes, including drs, and a twofold increase in totA gene expression. Furthermore, there was a significant upregulation of mitochondrial stability gene tom40, endogenous antioxidant genes sod1 and cat, and a threefold increase in sod2 at 15 mM indomethacin. Although no phenotypical changes in gut integrity were detected, the increased expression of pro-inflammatory cytokine genes suggests the occurrence of inflammation in the indomethacin-treated flies
The ethanol extract of Sargassum duplicatum as an ovicidal agent against Aedes aegypti
Get PDFDengue hemorrhagic fever (DHF) is a major health concern in tropical and subtropical countries. Indonesia has DHF cases perennially every year. On the other hand, Indonesia is abundant with seaweed (Sargassum duplicatum), which can be found across its seashore. The macroalgae contains secondary metabolites with ovicidal activity; hence, it has the potential to be utilized in suppressing the Aedes aegypti. The aim of this study was to determine the ovicidal activity of S. duplicatum against the Ae. aegypti eggs. The algae were macerated with ethanol 70% before being subjected to qualitative phytochemical screenings. The ovicidal tests were conducted with an extract concentration of 50 ppm, 100 ppm, 500 ppm, 1000 ppm, and 1500 ppm, while distilled water was used as the control. The hatchability of Ae. aegypti was observed 24 hours a day for 4 days and the larval development was investigated under a microscope. Phytochemical screenings revealed that the extract was positive containing alkaloids, flavonoids, steroids, saponins, and phenols. The hatchability of Ae. aegypti eggs were significantly reduced following the S. duplicatum extract exposure for four days (p=0.000). The extract had LC50 of 828.653 ppm and LC50 of 1786.09 ppm for the ovicidal activity against Ae. aegypti eggs. The concentration of ethanol extract of S. duplicatum did not affect the mosquito development from larvae to adult stage (p=0.263). Further research is needed to explore the effect of specific compounds contained in the S. duplicatum and investigate their ovicidal potential
Could fasciotomy prevent amputation in patients with electrical burn injuries? Insights from a cross-sectional study in Indonesia
Get PDFThe amputation rate resulting from electrical burn injuries remains high, yet no study has investigated whether early fasciotomy may reduce the amputation rate. The aim of this study was to analyze the success rate of fasciotomy in preventing amputation and determine the optimal timing for fasciotomy in electrical burn injuries. This study was conducted at Dr. Soetomo Hospital from January 2020 to July 2023. Total sampling was employed to recruit the patients. Clinical data, voltage characteristics, burn location, affected total body surface area, burn depth, hospital arrival time, and time interval from incident to fasciotomy were assessed. Chi-squared test was used to assess factors associated with the fasciotomy incidence and factors associated with amputation after fasciotomy. A total of 45 patients were included of which 97.8% were male with a mean age of 37.60-year-old. Approximately 73% of patients had full-thickness burn injuries, with the left upper extremity being the most affected (80%). There are seven patients (15.6%) had fasciotomy and five (11.1%) patients had an amputation. Our data indicated a significant association between voltage characteristics and fasciotomy incidence (p=0.034). Additionally, our data indicated that earlier arrival to the hospital (p=0.002) and timely fasciotomy conducted upon arrival (p<0.001) were associated with a reduced rate of amputation. This study highlights that prompt arrival to the hospital and early fasciotomy may prevent amputation in patients with electrical burn injuries
Nearly catastrophe coronary perforation: Is it second drug-eluting stent effective?
Get PDFCoronary artery perforation (CAP) is an uncommon yet serious complication. Although severe perforations (Ellis III) have become more frequent, the overall mortality rate associated with perforations (7.5%) has decreased in recent years. Unfortunately, our medical facility cannot always access a cover stent. The aim of this case report was to demonstrate the effectiveness of using a second drug-eluting stent as an alternative and successful treatment approach in a CAP patient. This is the case of a 67-year-old female with stable angina pectoris Canadian Cardiovascular Society classification III (CCS III), three-vessel coronary artery disease (CAD), who declined CABG (Syntax score of 44) and had type II diabetes mellitus. The patient underwent elective percutaneous coronary intervention (PCI), and we identified diffuse stenosis in the proximal to distal portions of the left anterior descending artery (LAD) with extensive calcification. Furthermore, there was a chronic total occlusion (CTO) in obtuse marginal (OM) 2, as well as critical stenosis in OM3, 80% stenosis in the proximal part of right coronary artery (RCA), 90% stenosis in the middle of the RCA, 90–95% in the distal RCA, and diffuse stenosis ranging from 70–80% in the distal posterolateral. During the procedure to alleviate the stenosis in the left circumflex artery (LCx), we encountered a coronary perforation classified as Ellis type III while using a 2.5/20 mm NC balloon inflated to 12 atm for 12 seconds. In response, we performed stent placement from the proximal LCx to OM2 using the Xience Xpedition drug-eluting stent (DES) measuring 2.5/28 mm. Subsequently, we conducted extended balloon inflation (intermittent) for five minutes. Despite these efforts, the coronary perforation, still classified as Ellis type III, persisted. We decided to employ intrastent stenting (a second DES strategy) with the Coroflex Isar DES measuring 2.5/28 mm, followed by prolonged balloon inflation. The outcome revealed no remaining perforation, Thrombolysis in Myocardial Infarction (TIMI) III flow, and no complications such as pericardial effusion after 48 hours of monitoring. The implantation of a second DES proved to be a practical approach for managing a significant CAP
A comparative analysis between next-generation sequencing and conventional culture method to detect empyema-associated microorganisms: A systematic review
Get PDFEmpyema poses a significant global health concern, yet identifying responsible bacteria remains elusive. Recent studies question the efficacy of conventional pleural fluid culture in accurately identifying empyema-causing bacteria. The aim of this study was to compare diagnostic capabilities of next-generation sequencing (NGS) with conventional pleural fluid culture in identifying empyema-causing bacteria. Five databases (Google Scholar, Science Direct, Cochrane, Research Gate, and PubMed) were used to search studies comparing conventional pleural fluid culture with NGS for identifying empyema-causing bacteria using keywords. Positive results identified through conventional pleural fluid culture and NGS were extracted. In addition, bacterial profiles identified by NGS were also documented. Joanna-Briggs Institute (JBI) critical appraisal tool was employed to assess quality of included studies. Descriptive analysis was employed to present outcome of interests. From five databases, three studies, with 354 patients, were included. Findings from three studies showed that NGS outperformed conventional pleural fluid culture in detecting empyema-causing bacteria even in culture-negative samples. Moreover, dominant bacterial profiles identified through NGS included Streptococcus pneumoniae, Staphylococcus aureus, and anaerobic bacteria. In conclusion, NGS outperforms conventional pleural fluid culture in detection empyema-causing bacteria, yet further studies with larger samples and broader bacterial profiles are needed to increase confidence and urgency in its adoption over conventional pleural fluid culture
Effect of moringa extract on parasitemia, monocyte activation and organomegaly among Mus musculus infected by Plasmodium berghei ANKA
Get PDFIn Indonesia, malaria remains a problem, with 94,610 active cases in 2021 and its current therapy includes chloroquine and artemisinin; however, resistance has been commonly reported. To overcome this problem, studies about potential medicinal plants that can be used as antimalaria, such as moringa (Moringa oleifera) started to receive more attention. The aim of this study was to investigate the effects of moringa in parasitemia, monocyte activation, and organomegaly on animal model malaria. This experimental study used male Mus musculus, infected by Plasmodium berghei ANKA, as an animal malaria model. The extract was made by maceration of dry moringa leaves, which were then divided into three concentrations: 25%, 50%, and 75%. Dihydroartemisinin-piperazine was used as a positive control treatment, and distilled water as a negative control treatment. The animals were observed for six days to assess the parasitemia count and the number of monocyte activation. On day 7, the animals were terminated, and the liver, spleen, and kidney were weighed. The results showed that the effective concentrations in reducing parasitemia and inducing monocyte activation were 50% and 25% of moringa leaf extract, respectively. The smallest liver and spleen enlargement was observed among animals within the group treated with a 50% concentration of M. oleifera extract. In contrast, the smallest kidney enlargement was observed in the group treated with 25% of M. oleifera extract. Further analysis is recommended to isolate compounds with antimalarial properties in moringa leaves
Effectiveness of Tai Chi as a non-invasive intervention for mild cognitive impairment in the elderly: A comprehensive review and meta-analysis
Get PDFThe aging population warrants the increase of mild cognitive impairment (MCI) prevalence, a condition that could progress to dementia. Efforts have been made to improve the MCI and prevent its progression, including the introduction of Tai Chi, a Chinese traditional exercise. The aim of this systematic review and meta-analysis was to evaluate the efficacy of Tai Chi in attenuating MCI among the elderly population. Records investigating the effect of Tai Chi exercise intervention on cognitive function among elderly patients were searched systematically from PubMed, ScienceDirect, Google Scholar, and Europe PMC as of April 13, 2023. The risk of bias (RoB 2.0) quality assessment was employed in the quality appraisal of the studies included. Review Manager 5.4.1 was used for data extraction and meta-analysis, where the standard mean difference (SMD) and 95% confidence interval (95%CI) were computed. Eight randomized control trials with a total of 1379 participants were included in this meta-analysis. Six trials assessed Montreal Cognitive Assessment scores, where its pooled analysis suggested that Tai Chi was as effective as conventional exercise (SMD=0.15, 95%CI: -0.11 to 0.40, p=0.26). However, pooled analysis of the Mini-Mental Status Examination suggested that Tai Chi intervention more effectively improved cognitive function and reduced the rate of cognitive impairment in elderly patients (SMD=0.36, 95%CI: 0.18 to 0.54, p<0.01) as compared to the control group. This systematic review and meta-analysis suggest that, in some extent, Tai Chi is efficacious in improving cognitive function and slowing down the rate of cognitive impairment among elderly patients
Role of preservation methods using deep-freezing and liquid nitrogen in bone allograft characteristics: An in vitro study
Get PDFBone grafting has emerged as a key solution in bone defect management such as allograft, graft of bone from another individual. However, bone allografts usually undergo rigorous preparation to eliminate immune-triggering elements. The deep-freezing methods may delay graft use, while cryopreservation using liquid nitrogen allows rapid freezing but may alter graft characteristics. The aim of this study was to investigate the post-preservation changes in bone allograft characteristics and to compare the effectiveness of deep-freezing and liquid nitrogen methods using animal model. An experimental study using a post-test only control group design was conducted. Fresh-frozen femoral cortical bone was obtained from male New Zealand white rabbits. Preservation by deep-freezing involved placing bone samples in a -80°C freezer for 30 days. For liquid nitrogen preservation, bone grafts were immersed in liquid nitrogen for 20 min, followed by a 15-min rest at room temperature and a final immersion in 0.9% sodium chloride at 30°C for 15 min. Bone samples then underwent evaluation of cell viability, compression, and bending tests. Cell viability test employed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and the compression and bending tests used the Universal Testing Machine (UTM). Independent Student t-test or Mann-Whitney U test were used to compare the methods as appropriate. Our study found that the use of deep-freezing and liquid nitrogen resulted in similar outcomes for cell viability, compression, and bending tests, with p-values of 0.302, 0.745, and 0.512, respectively. Further exploration with larger sample sizes may help to optimize the methods for specific applications