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Effect of SARS-CoV-2 spike protein exposure on ACE2 and interleukin 6 productions in human adipocytes: An in-vitro study
Get PDFSince adipocytes play a crucial role in pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection due to their interaction with angiotensin-converting enzyme 2 (ACE2) and interleukin 6 (IL-6), obesity is associated with an increased risk of coronavirus disease 2019 (COVID-19) mortality. Discovery of ACE2 as a SARS-CoV-2 receptor raises a controversy about whether to use ACE inhibitors (ACEIs) could be an optional therapy to prevent cytokine storms. Studies assessing the expressions of ACE2 and IL-6 upon exposure to SARS‑CoV‑2 is therefore important as a basis for therapeutical trials in the future. The aim of this study was to determine the effect of SARS-CoV-2 spike protein exposure on the production of ACE2 and IL-6 in adipocyte cells. Adipocytes were collected from abdominal adipose tissues of healthy and obese 45-year-old male donor having neither a history of SARS‑CoV‑2 infection nor COVID-19 vaccination. After being stained using the oil red O protocol, the viable adipocytes were then exposed to S1 subunit of SARS-CoV-2 spike protein. The levels of ACE2 and IL-6 were then examined using the enzyme-linked immunosorbent assay (ELISA). The results showed significant increase of ACE2 (90.22 µg/mL) and IL-6 level (60.01 µg/mL) in human adipocytes upon exposure compared to unexposed control cells (ACE2 13.33 µg/mL; IL-6 21.33 µg/mL), both comparisons had p<0.001). This study provides insight into the basic mechanism of severe COVID-19 symptoms in obese patients and provides a basic information of the potential of ACE inhibitors as an optional therapy for COVID-19 patients with obesity
Vitamin D3 induces stem cell activation via Lgr5-Bmi1 expression and improving mouse colitis histology index
Get PDFConventional therapy for inflammatory bowel disease using long-term anti-inflammatory drugs does not seem to provide optimal results. Adjuvant therapy using vitamin D3 is believed to have an essential role in repairing the colonic mucosa through the activation of colonic stem cells. The aim of this study was to demonstrate the effect of vitamin D3 in mucosal repair through stem cell activation, marked by leucin-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and B lymphoma Mo-MLV insertion region 1 (Bmi1) expression and decrease the mouse colitis histology index (MCHI) score. In this study, 50 Mus musculus strain BALB/c were divided into five groups: negative control group, colitis group, and colitis groups with vitamin D3 administration of 0.2 mcg, 0.4 mcg, and 0.6 mcg per 25 g body weight for seven days. Dextran sulfate sodium (DSS) 5% was used to induce colitis. Lgr5-Bmi1 expression was measured using immunodoublestain fluorescent labeling method. Our data suggested that administration of vitamin D3 significantly increased expression of Lgr5-Bmi1 in the colonic mucosa. The colitis group treated with the highest dose of vitamin D3 (0.6 mcg/25 gram) showed the lowest MCHI score (3.60±0.64) while the lowest dose of vitamin D3 had the highest MCHI score (12.60±1.47). In conclusion, stimulating stem cells, vitamin D3 administration stimulates mucosal regeneration, as demonstrated by upregulated expression of Lgr5-Bmi-1
Factors associated with small airway obstruction in COVID-19 survivors: A cross-sectional study among health-care providers
Get PDFCoronavirus disease 2019 (COVID-19) has been identified for more than two years, yet studies assessing post-infection lung function are limited. Reports on lung function in COVID-19 patients indicate that patients have restrictive defects and small airway dysfunction that can persist and are not necessarily related to the severity of the disease. The aim of this study was to assess the incidence of small airway obstruction and its incidence-associated factors among COVID-19 survivors to better describe the long-term effects of COVID-19. A cross-sectional study was conducted among COVID-19 survivors who less than 50 years at Medan Adventist Hospital between 2020–2022. The data were collected through interview, direct assessment and respiratory examination. A total of 89 COVID-19 survivors were recruited of which the majority of them were female with a mean age of 32.6-year-old with the largest group was 19–30 years. The comorbidities found among the survivors were heart and thyroid disorders, with the most common symptom of post-COVID-19 was fatigue. Most of them had mild COVID-19. The mean forced mid-expiratory flow (FEF25–75%) was 96.3±20.22, with an incidence rate of small airway obstruction was 19.1%. Univariate and multivariate analyses indicated no significant association between age, gender, comorbidities, history of oxygenation during COVID-19 treatment, COVID-19 severity and the type of post COVID-19 syndrome symptoms with the incidence of small airway obstruction. In conclusion, among COVID-19 survivors who were less than 50 years old, those studied variables seems have less association with the incidence of small airway obstruction. Nevertheless, a further study with a bigger sample size is important to be conducted
Neurological manifestations of COVID-19 in Indonesia: Assessment of the role of sex and age
Get PDFCoronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest in multiple organs. While the primary manifestations of COVID-19 occur in the respiratory system, other organ systems are also involved, including nervous systems that cause neurological symptoms. The aim of this study was to determine the neurological manifestations of COVID-19 patients and to assess the role of age and sex on neurological manifestation incidence. A cross-sectional study was conducted at Pelamonia Hospital, Makassar, Indonesia, among inpatient COVID-19 cases, using a total sampling method. Demographic data and neurological manifestations of the COVID-19 patients were collected. The associations between age and sex with the incidence of neurological symptoms were analyzed using the Chi-squared test. Out of 424 inpatients with COVID-19 cases, 62.3% were females, with the highest age group was 20–40 years (42.7%). The neurological symptoms were reported in 232 patients, accounting for approximately 54.7%. The most frequently reported neurological symptom was headache (n=104, 44.8%), followed by anosmia (n=44, 18.9%), ageusia (n=48, 20.6%), myopathy (n=14, 6%), stroke (n=10, 4.3%), seizure (n=5, 2.1%), and altered consciousness (n=7, 3%). An association was found between sex and the incidence of headache, myopathy, stroke, and altered consciousness. There was also an association between age and the incidence of headache and stroke. The study highlights that COVID-19 patients commonly exhibit neurological implications affecting the central nervous system and peripheral nervous system. Therefore, it is crucial for the early detection of neurological symptoms in COVID-19 cases to have better management
Effectiveness of smartphone application in increasing knowledge on COPD and its non-pharmacological management in COPD patients
Get PDFChronic obstructive pulmonary disease (COPD) is among top ten of the world's causes of death. The development of the “Paru Sehat” smartphone application is a positive initiative and might have the potential to improve the disease management of COPD, improve patient’s quality of life, and reduce complications associated with COPD. However, its effectiveness in improving the knowledge of the COPD patients is unknown. The aim of this study was to determine the effectiveness of “Paru Sehat” in increasing knowledge on COPD and its non-pharmacological management in COPD patients. A quasi-experimental study with a one-group pretest-posttest was conducted among stable COPD patients at Prof. Chairuddin Panusunan Lubis Hospital, Medan, Indonesia. Bristol COPD knowledge questionnaire (BCKQ) was used to assess the knowledge scores of the patients before and after exposure to the “Paru Sehat” twice a week for four weeks. A dependent Student t-test was used to compare the knowledge scores between pre- and post-intervention for both knowledge domains (i.e., knowledge on the disease and non-pharmacological management). Student t-test or one-way ANOVA were used to determine the association between patients’ characteristics and the knowledge scores within pre- and post-treatment. Our data indicated a significant improvement of the knowledge scores on disease between pre- and post-treatment (15.92±3.79 vs 19.56±3.68, p<0.001). The knowledge score on non-pharmacological management also increased significantly post-treatment (7.52±2.02) compared to pre-treatment (10.08±2.379), p<0.001. In addition, this study found that educational attainment was associated with the scores of both knowledge domains of which individuals with senior high school or higher education level had significantly improvement of knowledge scores. This study highlights that although “Paru Sehat” application could improve the knowledge on COPD and its non-pharmacological management, its effects are less effective among individuals with low educational attainment
Polymyositis concomitant with hepatitis B virus infection: Treatment challenges
Get PDFPolymyositis is a chronic autoimmune disease that presents with symmetrical progressive proximal muscle weakness. The cause of this disease due to abnormal activation of macrophages that might be associated with systemic diseases such as other autoimmune diseases, malignancy or viral infections including hepatitis B virus. The aim of this case report was to highlight treatment challenges in a patient with polymyositis concomitant with hepatitis B. A 28-years-old man with history of completed hepatitis B treatment with negative viral load presented with symmetrical progressive weakness on both inferior proximal extremities. The patient complained of pain predominantly in both tights and calves. No dermatological manifestation was observed. Elevated muscle enzymes and liver function were observed. Along with the course of the disease, hepatitis B reactivation was discovered as hepatitis B virus DNA was re-detected. Treatment options of this patient (polymyositis concomitant with hepatitis B viral infection) remain challenging. The main treatment of polymyositis consists of high dose methylprednisolone and this immunosuppressant could worsen the hepatitis B virus infection. The patient was finally treated with combination of mycophenolic acid and methylprednisolone for polymyositis and entecavir for hepatitis B. After one month of treatment, the patient showed a clinical improvement. This case highlights that viral screening must be done prior to starting polymyositis treatment as it could concomitant with viral infections such as hepatitis B. Antiviral prophylaxis must be given 1–2 weeks before immunosuppression starts. Management for both polymyositis and hepatitis B is important with entecavir or tenofovir as the optimal agents against hepatitis B virus
Phytocompounds of Nigella sativa seeds extract and their neuroprotective potential via EGR1 receptor inhibition: A molecular docking study
Get PDFBioactivity of Nigella sativa seed extract has the potential as a neuro-protector, offering its promising utility in the clinical setting for brain injury management. This study aimed to identify the phytocompounds contained in the extract of N. sativa seeds and further screen their respective neuronal anti-inflammatory activities in silico. The extract of N. sativa seeds was prepared through successive maceration using non-polar to polar solvents (n-hexane and ethanol, respectively). The phytocompounds in the ethanolic extract were initially identified through qualitative analysis and further analyzed with gas chromatography-mass spectrometry (GC-MS). The spectral data were compared with the compound library for identification. The identified phytocompounds were then simulated computationally for their binding affinities toward the active pocket of early growth response-1 (EGR1) receptor (PDB: 14r2a). We found that the ethanolic extract of N. sativa seeds were predominantly constituted of hexadecanoic acid, ethyl ester (17.15%); linoleic acid ethyl ester (15.0%); octadecanoic acid (13.26%); and ethyl oleate (10.38%). The binding affinity of the phytocompounds ranged from -7.49 kcal/mol (methyl palmitoleate) to -14.31 kcal/mol (9-hexadecanoic acid, methyl ester), with 12 compounds having binding affinity < -10 kcal/mol. In conclusion, ethanolic extract of N. sativa seeds are rich with fatty acids that have active as anti-inflammatory and may exert neuronal protection by inhibiting EGR1 receptor. Studies using animal models to confirm the activity are warranted
Non-alcoholic fatty liver disease (NAFLD) and COVID-19 outcomes: A systematic review, meta-analysis, and meta-regression
Get PDFIt is important to identify risk factors for poor outcomes of coronavirus disease 2019 (COVID-19) patients. Currently, the correlation between non-alcoholic fatty liver disease (NAFLD) and COVID-19 outcomes has not been established. This study was conducted to determine the association between NAFLD and in-hospital outcomes of COVID-19 patients. The systematic searches were conducted by using PubMed and the Europe PMC databases and particular keywords were used as of December 10, 2020. Further searches were conducted up to 2022. All articles that include data about COVID-19 and fatty liver disease were collected. Statistical analysis was performed by using Review Manager 5.4 and Comprehensive Meta-Analysis version 3 software. A total of 7,210 COVID-19 patients from 18 studies were included in the final analysis. Meta-analysis revealed that NAFLD increased the risk of developing poor in-hospital outcome (pooled both severe disease and death) in COVID-19 patients (RR 1.42; 95%CI: 1.17–1.73, p<0.001, I2=84%, random-effect modeling). Subgroup analysis however found that having NAFLD only increased the chance of getting severe COVID-19 (RR 1.67; 95%CI: 1.32–2.13, p<0.001, I2=86%, random-effect modeling) and not mortality (RR 1.00; 95%CI: 0.68–1.47, p=0.98, I2=80%, random-effect modeling). Meta-regression suggested that age (p=0.001) and diabetes (p=0.029) were significantly influenced the relationship between NAFLD and in-hospital outcomes of COVID-19 (pooled both severe disease and mortality). The weaker association of NAFLD and in-hospital outcomes of COVID-19 was found for studies with median age ≥45 years old (RR 1.29) when compared to studies with median age <45 years old (RR 2.96). In addition, studies with the prevalence of diabetes ≥25% (RR 1.29) had a weaker association with in-hospital outcomes when compared to studies with diabetes prevalence <25% (RR 1.85). In conclusion, NAFLD increased the risk of chance of getting severe COVID-19 and therefore it should be evaluated closely to reduce the chance of getting severe COVID-19
Phenotypical and molecular assessments on the pharmacological effects of curcumin in Drosophila melanogaster
Get PDFCurcumin, a dietary polyphenol derived from turmeric's rhizome, exhibits a range of pharmacological activities, such as antioxidant, analgesic, antipyretic, and anti-inflammatory effects. It has been investigated for its therapeutic potential in chronic obstructive pulmonary disease (COPD) due to its ability to inhibit nuclear factor kappa B (NF-κB), modulate oxidative stress, impact cell viability, and regulate gene expression. However, most studies have been limited to in vitro conditions. To address this gap, we conducted in vivo experiments using the fruit fly Drosophila melanogaster to explore the antioxidant activities and biological significance of curcumin. Several parameters were assessed using different assays, including curcumin toxicity assay, fly survival, locomotor response to curcumin treatment (with or without cigarette smoke), trypan blue staining, larval crawling assays, and gene expression analysis. Our data revealed no significant differences in toxicity and locomotor tests across various curcumin concentrations. D. melanogaster tolerated curcumin at concentrations of 0.5 µM, 5 µM, 50 µM, and 500 µM, suggesting its safety without negatively impacting locomotor. Furthermore, curcumin at 5 µM extended the lifespan of D. melanogasterexposed to cigarette smoke, while reversing the negative effects of smoke exposure on gut cell viability and larval locomotor activity. In conclusion, curcumin administration appeared safe for D. melanogaster, with potential benefits for longevity and locomotory function. These findings support the idea that curcumin possesses in vivo antioxidant properties and may serve as a promising pharmacological agent. However, further study is needed to explore its potential applications in human health and disease management, particularly in the context of COPD
Effectiveness of Zingiber officinale to reduce inflammation markers and the length of stay of patients with community-acquired pneumonia: An open-label clinical trial
Get PDFExamination of the interleukin 6 (IL-6) and procalcitonin levels, and neutrophil-lymphocyte ratio (NLR) might could help to diagnosis and predict the duration of therapy and prognosis of pneumonia cases. Zingiber officinale var rubrum could be used as an adjunct therapy in infectious diseases as it has anti-inflammatory activity. The aim of study was to assess the effect of Z. officinale on levels of IL-6 dan procalcitonin, NLR, and the length of hospitalization of patients with community-acquired pneumonia (CAP). An open-label clinical trial was conducted among CAP cases regardless of the etiology at Dr Moewardi Hospital and Universitas Sebelas Maret Hospital, Surakarta, Indonesia from July to September 2022. A total of 30 inpatient CAP cases were recruited and were randomly divided into two groups: (1) received Z. officinale capsule 300 mg daily for five days in addition to CAP standard therapy; and (2) received CAP standard therapy only, as control group. The data were compared using a paired Student t-test, Chi-squared test, Mann-Whitney test and Wilcoxon signed-rank test as appropriate. In Z. officinale group, the mean difference between post- and pre-treatment as follow: IL-6 level was 9.93 pg/mL, procalcitonin level -471.31 ng/mL, and NLR value -4.01. In control group, the difference was 18.94 pg/mL for IL-6, 339.39 ng/mL for procalcitonin, and 1.56 for NLR. The change of IL-6 was not statistically significant between treatment and control groups with p=0.917. The changes of procalcitonin level and NLR were significant between treatment and control group with p=0.024 and p=0.007, respectively, of which the treatment had better improvement. In addition, our data indicated that the length of stay was not statistically significant between the treatment and control groups (4.13 vs 4.47 days, p=0.361). In conclusion, Z. officinale could reduce serum inflammatory markers such as procalcitonin and NLR but it has little impact in reducing IL-16 level and the length of hospitalization of CAP patients