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Promising candidate drug target genes for repurposing in cervical cancer: A bioinformatics-based approach
Get PDFCervical cancer is the fourth most common cancer among women globally, and studies have shown that genetic variants play a significant role in its development. A variety of germline and somatic mutations are associated with cervical cancer. However, genomic data derived from these mutations have not been extensively utilized for the development of repurposed drugs for cervical cancer. The objective of this study was to identify novel potential drugs that could be repurposed for cervical cancer treatment through a bioinformatics approach. A comprehensive genomic and bioinformatics database integration strategy was employed to identify potential drug target genes for cervical cancer. Using the GWAS and PheWAS databases, a total of 232 genes associated with cervical cancer were identified. These pharmacological target genes were further refined by applying a biological threshold of six functional annotations. The drug target genes were then cross-referenced with cancer treatment candidates using the DrugBank database. Among the identified genes, LTA, TNFRSF1A, PRKCZ, PDE4B, and PARP were highlighted as promising targets for repurposed drugs. Notably, these five target genes overlapped with 12 drugs that could potentially be repurposed for cervical cancer treatment. Among these, talazoparib, a potent PARP inhibitor, emerged as a particularly promising candidate. Talazoparib is currently being investigated for safety and tolerability in other cancers but has not yet been studied in the context of cervical cancer. Further clinical trials are necessary to validate this finding and explore its potential as a repurposed drug for cervical cancer
Sleep quality and cognitive function on self-rated health status among the elderly: Findings from the Indonesian family life survey (IFLS-5)
Get PDFCognitive decline poses a significant challenge for the elderly population globally. The aim of this study was to determine the prevalence of cognitive function and its associated factors among the elderly in the Indonesian family life survey’s fifth wave (IFLS-5) conducted from 2014 to 2015. The study included elderly individuals aged 60 and above, excluding proxy respondents and those with missing data. Various socio-demographic, cognitive function and health-related variables were analyzed, including age, sex, education level, marital status, residence, region, economic status, current employment, self-rated health status, happiness, sleep quality, depression, loneliness, and chronic conditions. Multivariate logistic regression analysis was used to identify the factors associated with cognitive functions among the 2,929 elderly respondents. The results revealed that 44.6% of the respondents reported poor cognitive function. In the unadjusted model, residence (OR: 0.81; 95%CI: 0.70–0.94), region of other islands (OR: 0.66; 95%CI: 0.54–0.81), sleep quality (OR: 0.53; 95%CI: 0.42–0.68), self-rated health status (OR: 1.38; 95%CI: 1.19–1.61), happiness (OR: 1.48; 95%CI: 1.22–1.79), and depression (OR: 1.22; 95%CI: 1.04–1.44) showed significant associations with cognitive function. After adjusting for confounding factors, the association remained significant for residence (OR: 0.77; 95%CI: 0.66–0.89), regions other than Java, Bali, and Sumatra (OR: 0.61; 95%CI: 0.50–0.76), self-rated health (OR: 1.28; 95%CI: 1.09–1.51), happiness (OR: 1.30; 95%CI: 1.06–1.59), and sleep quality (OR: 0.60; 95%CI: 0.47–0.78). These findings emphasize the necessity of interventions aimed at enhancing sleep quality and overall health in order to preserve cognitive function among the elderly, thus potentially improving their quality of life. Implementing comprehensive health programs could significantly enhance the overall quality of life for the aging population, especially the elderly population
Comprehensive in silico analysis of single nucleotide polymorphism and molecular dynamics simulation of human GATA6 protein in ventricular septal defect
Get PDFCongenital heart disease (CHD) represents nearly one-third of congenital birth defects annually, with ventricular septal defect (VSD) being the most common type. The aim of this study was to explore the role of specific GATA binding protein 6 gene (GATA6) mutations as a potential etiological factor in the development of VSD through an in silico approach. Data were collected from the human gene databases: DisGeNET and GeneCards, with protein-protein interaction networks constructed via STRING and Cytoscape. Gene ontology and pathway enrichment analyses were conducted using DAVID, with data analysis in R with significance set at FDR p<0.05. Target single nucleotide polymorphisms (SNPs) of GATA6 were obtained from NCBI dbSNP, and non-synonymous single nucleotide polymorphism (nsSNP) effects were predicted using SIFT, PolyPhen-2, I-Mutant 2.0, Fathmm, MutPred 2.0, SNP&GO, and PON-P2. Conserved regions of GATA6 were analyzed using ConSurf, with functional classification, variant conservation, and stability changes evaluated in Google Colab. Multiple sequence alignment was performed using ClustalW. Mutation modeling and molecular dynamics analysis, using GROMACS, revealed that among 87 intersecting genes, 16 proteins were interconnected with GATA6, showing a centrality value of 0.4378. Gene ontology analysis highlighted atrioventricular canal development, protein-DNA complexes, and transcription factor regulation as key processes for cardiac development, especially in the ventricular septum. NsSNP and molecular dynamics analyses identified rs387906818 and rs387906820 as having the highest pathogenic potential for VSD due to amino acid structural changes
Psoriasis severity assessment: Optimizing diagnostic models with deep learning
Get PDFPsoriasis is a chronic skin condition with challenges in the accurate assessment of its severity due to subtle differences between severity levels. The aim of this study was to evaluate deep learning models for automated classification of psoriasis severity. A dataset containing 1,546 clinical images was subjected to pre-processing techniques, including cropping and applying noise reduction through median filtering. The dataset was categorized into four severity classes: none, mild, moderate, and severe, based on the Psoriasis Area and Severity Index (PASI). It was split into 1,082 images for training (70%) and 463 images for validation and testing (30%). Five modified deep convolutional neural networks (DCNN) were evaluated, including ResNet50, VGGNet19, MobileNetV3, MnasNet, and EfficientNetB0. The data were validated based on accuracy, precision, sensitivity, specificity, and F1-score, which were weighted to reflect class representation; Pairwise McNemar's test, Cochran's Q test, Cohen’s Kappa, and Post-hoc test were performed on the model performance, where overall accuracy and balanced accuracy were determined. Findings revealed that among the five deep learning models, ResNet50 emerged as the optimum model with an accuracy of 92.50% (95%CI: 91.2–93.8%). The precision, sensitivity, specificity, and F1-score of this model were found to be 93.10%, 92.50%, 97.37%, and 92.68%, respectively. In conclusion, ResNet50 has the potential to provide consistent and objective assessments of psoriasis severity, which could aid dermatologists in timely diagnoses and treatment planning. Further clinical validation and model refinement remain required
Phytochemistry and antifatigue activities of Carica papaya leaf from geothermal, coastal and urban areas, Indonesia
Get PDFFatigue, a condition of lack of energy and motivation resulting in the feeling of extreme tiredness or exhaustion, is usually prevented and treated with ergogenic aids, such as in the form of nutritional supplements. Papaya (Carica papaya) may be a potential candidate for ergogenic aids, considering its healthy secondary metabolite properties and number of metabolite compounds that could be affected by the location where the plant growing. The aim of this study was to identify the phytochemicals of papaya leaves from three different locations: geothermal, coastal, and urban areas in Aceh province, Indonesia. Concentrations of papaya leaf with the highest number of secondary metabolite compounds were tested in rats to measure blood lactate acid concentrations after strenuous exercise. The number of chemical compounds identified from the three locations was 24 compounds; 23 compounds and 17 compounds, respectively. The highest concentration of chemical compounds that have antifatigue activity contained in all papaya leaf samples were neophytadiene, linolenic acid, gamma tocopherol, hexadecanoic acid, vitamin E, carpaine, octadecatrienoic acid, nor lean-12-ene, squalene, and phytol. Furthermore, most of the compounds' highest concentrations were found in papaya leaves from the coastal area and, therefore, tested on the animal model. Treatment was provided in 12 male rats with different doses of papaya powder supplements for 15 days. The results showed that lactic acid levels of rats received a dose of 400 mg/kg of papaya leaf extract reduced the lactic acid concentration (p=0.014) compared with the control group. This study highlights that papaya leaves from the coastal area have the most potential activities as ergogenic herbal aid and were able to reduce lactic acid levels in rats after strenuous exercise
Relationship between G protein level with left ventricular systolic function in children with acyanotic heart disease
Get PDFHeart failure is a pediatric emergency caused by the heart's inability to adequately meet the body metabolic needs and the most common cause is congenital heart disease (CHD). The G protein is the most prominent family of membrane-bound protein known to act in major regulatory events of the cardiovascular system, one of which is heart failure. The aim of this study was to determine the level of G protein and its relationship with left ventricular systolic function in children with acyanotic CHD. A cross-sectional study was conducted in Dr. Zaionel Abidin Hospital, Banda Aceh, Indonesia. The patients aged 0 to 18 years and had acyanotic CHD diagnosis by echocardiography were included. Anthropometry measurement was performed according to standard WHO procedures and G protein level was measured using the ELISA method. The Chi-squared test was used to measure the relationship between G protein level and left ventricular systolic function. Out of a total of 38 children with acyanotic CHD, the mean level of G protein was 36.25 ng/mL and the mean of left ventricular systolic function was 73.1%. There was no relationship between G protein and left ventricular systolic function in children with acyanotic CHD. However, further study with a larger sample size and considering other variables are needed to confirm this finding
Weil’s disease with multiple organ dysfunction, community-acquired pneumonia and septic shock: The role of rapid diagnosis and management
Get PDFLeptospirosis is an uncommon infectious illness – a spirochetal zoonosis – caused by Leptospira species and the primary cause of human leptospirosis is exposure to the urine of infected rodents. Clinical manifestations of human leptospirosis are diverse, ranging from asymptomatic infection to severe life-threatening with multiorgan dysfunction. The severe condition is known as Weil's disease, which is characterized by feverish illness with jaundice, acute kidney damage, and bleeding. The aim of this case report was to present a Weil's disease which occurred simultaneously with a community-acquired pneumonia (CAP) resulting in serious complications. A 41-year-old man with Weil's disease, as well as CAP caused by Streptococcus pneumoniae, and septic shock was presented. The patient was treated accordingly after establishing the diagnosis through history taking, physical examination, and laboratory tests. In this instance, the score for diagnosing leptospirosis based on Modified Faine's Criteria was calculated resulting possible diagnoses; and therefore, therapeutic management was initiated. Despite presenting with severe symptoms, the patient recovered completely after receiving antibiotics and supportive care. This study highlights that when a patient has Weil’s disease and a CAP infection, which could cause unfavorable consequence, a prompt diagnosis and proper treatment could result satisfied patient recovery
Factors associated with cognitive impairment and the quality-of-life among COVID-19 survivors working as healthcare workers
Get PDFProlonged physical and mental health changes, known as post-COVID conditions (PCC), could impair the quality-of-life (QoL) of healthcare workers. The aim of this study was to identify factors that contribute to cognitive impairments and QoL among COVID-19 survivors working as healthcare workers. This cross-sectional study involved healthcare workers at Prof. Dr. Chairuddin P. Lubis Universitas Sumatera Utara Hospital, Medan, Indonesia. The Montreal Cognitive Assessment (MoCA) was used to assess the cognitive function, while the World Health Organization Quality-of-Life Brief Version (WHOQOL-BREF) questionnaire was used to evaluate the QoL. Factors associated with cognitive and QoL status were examined using Mann-Whitney and Chi-squared tests. A total of 100 COVID-19 survivors were included in the study, most of whom were female (74%), aged ≤35 years (95%), and were doctors (62%). Only 22% of the participants had a normal BMI, 93% had a history of mild COVID-19, and 54% had one comorbidity. The Overall MoCA score averaged 24.18±2.86, indicating mild cognitive impairment among the groups. The distribution of MoCA scores had similar patterns with no significant differences based on age, gender, comorbidities, BMI, COVID-19 severity, and frequency of infection. Interestingly, the number of vaccine doses received by the participants had a statistically significant associated with MoCA scores of which those receiving more than two doses had higher cognitive scores than those with only two doses (p=0.008). Based on categorized MoCA scores (normal vs cognitive impairment), none assessed factors were not significantly associated with cognitive outcomes. The WHOQOL-BREF scores ranged from 62.5 to 95.5, with a mean of 83.67±7.03. None of the assessed factors were associated with WHOQOL-BREF scores among COVID-19 survivors. These findings highlight the need for further study to explore the protective role of vaccination frequency in cognitive impairment and the factors underlying the resilience in QoL among survivors
Role of antioxidants in reducing oxidative stress and seizure frequency in drug-resistant epileptic patients
Get PDFDrug-resistant epilepsy presents significant challenges in treating epileptic patients, leading to recurrent seizures and necessitating the use of polypharmacy with anti-epileptic drugs. Both of these conditions contribute to increased oxidative stress, which is detrimental to the brain. The aim of this study was to determine the role of vitamins C and E in reducing oxidative stress and seizure frequency in drug-resistant epileptic patients. This was a double-blinded, randomized clinical trial with a placebo, parallel design, and block randomization. The subjects were drug-resistant epileptic patients aged 1–18 years who received routine treatment. Randomization was performed on 100 patients who were divided into the treatment or placebo groups. The patients received a combination of vitamin C (100 mg/day) and vitamin E (200 IU/day for those <5 years or 400 IU/day for those ≥5 years) or a placebo for eight weeks. Malondialdehyde (MDA) levels and seizure frequency were measured prior to and after the intervention. A total of 42 and 46 patients were followed till the end of the study in the intervention and placebo groups, respectively. Our data indicated that the MDA levels prior to treatment were not significantly different between the treatment and placebo groups (0.901 vs 0.890 mmol/mL, p=0.920) and were significantly reduced after the treatment in both the treatment group (p<0.001) and placebo group (p=0.028). The changes in MDA levels (between post- and pre-treatment) were also not significantly different between the two groups (p=0.181). Our per-protocol analysis indicated that the reduction in seizure frequency was significantly higher in the treatment group compared to the placebo group (95% vs 35%, p<0.001), with 92% and 60% relative and absolute risk reduction, respectively. The intention-to-treat analysis also indicated that the reduction in seizure frequency was significantly higher in the intervention group than in the control group (80% vs 32%, p<0.001), with relative and absolute risk reduction of 70% and 48%, respectively. There was no significant relationship between changes in MDA levels and seizure frequency in either group. In conclusion, vitamins C and E could reduce seizure frequency and, therefore, could be considered as adjuvant therapy in drug-resistant epileptic patients
Acute toxicity, secondary metabolites, and antioxidant activity of Macaranga tanarius from post-coal mining and non-mining areas in East Kalimantan, Indonesia
Get PDFCoal plays a crucial role in Indonesia’s foreign exchange and East Kalimantan’s revenue sharing, yet its environmental impacts, including soil acidification, raises concerns. Reclamation measures involve revegetation with pioneer plants such as Macaranga sp., known for their medicinal properties. However, the pharmacological properties of these plants are influenced by secondary metabolites, which depend on soil parameters such as pH and nutrient levels. The aim of this study was to evaluate the acute toxicity, secondary metabolites, and antioxidant activities of Macaranga tanarius leaf extracts from post-coal mining area (MTPCMA) and non-mining area (MTNMA) alongside soil parameters. Acute toxicity of M. tanarius leaf extracts and soils were assessed using the brine shrimp lethality test (BSLT). Phytochemical screening was done using thin-layer chromatography (TLC), determining total phenolic (TPC) and flavonoid content (TFC). The DPPH radical scavenging assay was used to assess the antioxidant activity. A comparative analysis between MTPCMA and MTNMA was conducted using Student t-test. The data showed no significant difference in toxicity between MTPCMA and MTNMA leaf extracts (LC50 of 100–1000 µg/mL) (p=0.062), and soils from both areas were non-toxic (LC50 of >1000 µg/mL). Although heavy metal concentrations were higher in PCMA than in NMA soil (p<0.001), secondary metabolite compounds and TFC in both extracts were not significantly different (p=0.076). Both extracts contained flavonoids and polyphenols with antioxidant activity and terpenoids without antioxidant activities. The DPPH radical scavenging test suggested insignificant antioxidant activity between MTPCMA and MTNMA extracts (p=0.237). In conclusion, non-toxic soils in post-mining land and insignificant differences between MTPCMA and MTNMA extracts suggest good soil nutrient availability, highlighting the success of land recovery after 10 years of revegetation with M. tanarius