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Correlation of miR-150, hsa-let-7e, and miR-146a and gene expression of IL-6, IL-8, IP-10, and MIP-1β during dengue virus infection Sri Masyeni; Kuntaman Kuntaman; Aryati Aryati; Muchlis AU Sofro; Usman Hadi; Gondo Mastutik; Windu Purnomo; Agus Santosa; Benediktus Yohan; Erni Juwita Nelwan; R. Tedjo Sasmono
Narra J Vol. 1 No. 1 (2021): April 2021
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narraj.v1i1.31

Growing evidence suggests that microRNAs (miRNAs) play a pivotal role in viral infection. The objective of this study was to assess the association between the expression of miR-150, hsa-let-7e, and miR-146a on cytokine expression during dengue infection. Dengue virus (DENV) strain SJN-006, a serotype 2 DENV strain of the Cosmopolitan genotype, isolated in Bali, Indonesia, was used to infect peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals. The relative gene expressions of miR-150, hsa-let-7e, and miR-146a as well as the gene expression of cytokines (IL-6, IL-8, IP-10, and MIP-1β) were determined using quantitative real time - polymerase chain reaction (qRT-PCR) at 6, 12 and 24 hours post infection (hpi). Correlations between the microRNAs and cytokines were analyzed by means of causality tests. Our data suggests that miR-150 and hsa-let-7e were significantly higher in infected-PBMCs after 12 hpi compared to the uninfected-PBMCs (p<0.05). The causality tests demonstrated that miR-150 and hsa-let-7e were negatively correlated with IL-8 expression, meanwhile miR-146a was the contrast. DENV infection was negatively and positively correlated with miR-150 and hsa-let-7e, respectively, after 24 hpi. In conclusion, our data demonstrates the vital role of miR-150, hsa-let-7e, and miR-146a in regulating IL-8 expression with possible different pathways.

Epstein-Barr Virus and Malaria Interactions: Immunology Perspective Insani Budiningsih; Jaap M. Middeldorp; Yoes Prijatna Dachlan; Usman Hadi
HAYATI Journal of Biosciences Vol. 29 No. 6 (2022): November 2022
Publisher : Bogor Agricultural University, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.4308/hjb.29.6.824-833

Epstein-Barr Virus can cause various diseases, from acute inflammatory diseases such as fatal or chronic EBV infection, infectious mononucleosis as well as lymphoid and epithelial cancer, various autoimmune diseases, and also could interact with malaria. As EBV infects 95% of the world population, and more than 30% are infected with the protozoan parasite, with more than 500,000 deaths due to malaria cases. It is important to understand how EBV dysregulates the immune system, especially when the virus is interacting with other pathogens such as malaria parasites, causing more severe conditions in certain people like Burkitt Lymphoma. This review will be informative about the mechanism of how EBV interacts with malaria parasites and how it affects the immune system. Knowledge of various cytokines triggering the immune system which may provide links to control/minimize malaria disease severity.

PROBLEM OF ANTIBIOTIC USE AND ANTIMICROBIAL RESISTANCE IN INDONESIA: ARE WE REALLY MAKING PROGRESS? Hadi, Usman; Kuntaman, Kuntaman; Qiptiyah, Mariyatul; Paraton, Hari
Indonesian Journal of Tropical and Infectious Disease Vol. 4 No. 4 (2013)
Publisher : Institute of Topical Disease Universitas Airlangga

Background: Based on the results Antimicrobial Resistance in Indonesia: prevalence and prevention-study (AMRIN-study), the Ministry of Health of Indonesia in 2005 began a program antibiotic resistance control (PPRA) in some government hospitals, and is currently developing to all government teaching hospitals in Indonesia. Aim: The core activities of the PPRA are to implement standardized surveillance emergence of antibiotic resistant bacteria, and the surveillance of antibiotic use in terms of quantity and quality. Method: Our research in the years 2003 showed the proportion of antibiotic use 84% of patients in a hospital. The use of inappropriate antibiotics was very high, 42% no indication. Result: In 2012 the results of surveillance showed decline of inappropriate use of antibiotic, but prevalence extended-spectrum b-lactamase (ESBL)-producing K.pneumoniae (58%), and E.coli (52%) andmethicillin-resistant S.aures (MRSA) (24%) were increasing. Conclusion: It was needed to implement the most appropriate programs to prevent the growth and development of bacteria resistant to antibiotics.

Medical Audit of the Management of Patients with Sepsis in the Intermediate Care Unit of Department Internal Medicine School of Medicine Airlangga University/Dr. Soetomo Hospital Hadi, Usman; Triyono, Erwin Astha
Indonesian Journal of Tropical and Infectious Disease Vol. 1 No. 1 (2010)
Publisher : Institute of Topical Disease Universitas Airlangga

Sepsis and septic shock is one of the highest causes of death in patients treated in hospitals. Research Objectives: to evaluate the quality of the management of sepsis patients in Intermediate Care Unit, Department of Internal Medicine Dr. Soetomo Hospital Surabaya, Indonesia. This study was a retrospective study to re-evaluate the patient medical record. The number of patients treated: 275 patients, sepsis patients: 80 patients, the number of patients who entered the study 50 patients, 30 (60%) female and 20 (40%) men, most age groups aged 60 -70 years (32%), Mean 54 Median 56. Diagnostic accuracy according to the criteria of sepsis 45 (90%) patients, compliance with taking blood culture 2 (4%) patients, appropriate antibiotic selection 49 (98%) patients, the number of patients who should not be given antibiotics (4 patients), but given the antibiotic is 3 (75%) patients, the number of patients who should be given antibiotics (46 patients) but were not given antibiotics 1 (2%) patient. The reason of patients discharged: 27 had died (54%), 13 cured (26%), not yet recovered 10 (20%). The reason of patients discharged forcibly: to feel recovered 2 (20%), the condition gets worse 3 (30%), no cost 2 (20%), not clear 3 (30%). Patients with sepsis remain a big problem, and it still needs to improve the management of sepsis on existing guidelines.

EXPRESSION OF FOUR CYTOKINE/CHEMOKINE GENES IN PERIPHERAL BLOOD MONONUCLEAR CELLS INFECTED WITH DENGUE VIRUS Sri Masyeni, Dewa Ayu Putri; Hadi, Usman; Kuntaman, Kuntaman; Yohan, Benediktus; Margyaningsih, Nur Ita; Sasmono, R Tedjo
Indonesian Journal of Tropical and Infectious Disease Vol. 7 No. 4 (2019)
Publisher : Institute of Topical Disease Universitas Airlangga

Overproduction of numerous pro-inflammatory cytokines, during dengue virus (DENV) infection, has been related to plasma leakage in the vascular endothelium and studied elsewhere with conflicting results. The current study objective is to evaluate the expression of four cytokine/chemokine genes following DENV-2 infection within peripheral blood mononuclear cells (PBMC) isolated from a healthy donor. Venous blood was drawn, and PBMCs were isolated using Ficoll density gradient centrifugation. Cells were maintained in culture medium and infected with Indonesian isolate of DENV-2. Cells were harvested and followed by total RNA extraction and reverse-transcription into cDNA using oligo d(T) primers and Reverse Transcriptase enzyme system. The SYBR Green-based quantitative qRT-PCR was used to calculate the relative expression of IL-6, IL-8, IP-10 and MIP-1β- encoding genes during infection time points, compared to uninfected cell controls. The observation of the cytokine was on the 6 and 18 hours post-infection. The different expression profiles of cytokines/chemokines were observed. The up-regulation of gene expression was observed for IL-8 and IP-10. In contrast, the down-regulatory of IL-6 and MIP-1β genes expression was documented during the infection period. The cytokine IL-8 and IP-10 are potent chemoattractants in the recruitment of neutrophil, basophil, and lymphocytes in response to an infection. The highlight of this study is on the up-regulation of IL-8 and IP-10 genes expression which may confirm the roles of these chemokines in the pathogenesis of dengue infection.

Correlation of miR-150, hsa-let-7e, and miR-146a and gene expression of IL-6, IL-8, IP-10, and MIP-1β during dengue virus infection Masyeni, Sri; Kuntaman, Kuntaman; Aryati, Aryati; Sofro, Muchlis AU; Hadi, Usman; Mastutik, Gondo; Purnomo, Windu; Santosa, Agus; Yohan, Benediktus; Nelwan, Erni Juwita; Sasmono, R. Tedjo
Narra J Vol. 1 No. 1 (2021): April 2021
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narraj.v1i1.31

Growing evidence suggests that microRNAs (miRNAs) play a pivotal role in viral infection. The objective of this study was to assess the association between the expression of miR-150, hsa-let-7e, and miR-146a on cytokine expression during dengue infection. Dengue virus (DENV) strain SJN-006, a serotype 2 DENV strain of the Cosmopolitan genotype, isolated in Bali, Indonesia, was used to infect peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals. The relative gene expressions of miR-150, hsa-let-7e, and miR-146a as well as the gene expression of cytokines (IL-6, IL-8, IP-10, and MIP-1β) were determined using quantitative real time - polymerase chain reaction (qRT-PCR) at 6, 12 and 24 hours post infection (hpi). Correlations between the microRNAs and cytokines were analyzed by means of causality tests. Our data suggests that miR-150 and hsa-let-7e were significantly higher in infected-PBMCs after 12 hpi compared to the uninfected-PBMCs (p<0.05). The causality tests demonstrated that miR-150 and hsa-let-7e were negatively correlated with IL-8 expression, meanwhile miR-146a was the contrast. DENV infection was negatively and positively correlated with miR-150 and hsa-let-7e, respectively, after 24 hpi. In conclusion, our data demonstrates the vital role of miR-150, hsa-let-7e, and miR-146a in regulating IL-8 expression with possible different pathways.

Challenges and adversities among doctors in the era of healthcare disruption: Reflection from COVID-19 pandemic Sugiyatmi, Tri A.; Hadi, Usman; Chalidyanto, Djazuly; Pathak, Yashwant; Miftahussurur, Muhammad
Narra J Vol. 3 No. 2 (2023): August 2023
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v3i2.134

The doctor's profession is noble and tied up with quite strict rules, both in terms of ethics as well as discipline. Naturally, there is a problem of asymmetrical information between doctors and patients, often leading to misunderstandings. The purpose of this review is to map the available evidence related to the challenges and difficulties faced by doctors in the era of disruption. The evidence indicate that disruption of health services has both positive and negative effects. Many aspects related to the use of technology in the medical practices including innovation, cost-effectiveness, and quality improvement. However, psychologically, the doctors often get frustrated by internal or external triggers. The external factors, ranges from the equipment and work procedures, for instance, using high technology, communication with management, inter-professional relationships, patients, and their families. Volatility, uncertainty, complexity, and ambiguity (VUCA) could cause stress and burnout. In this case, doctors are highly vulnerable, and consequently, have the potential to make mistakes. Therefore, the adversity faced by doctors ought to be mapped. Resilience is a barrier against stress and burnout and the ability to adapt in resilience among doctors is important factor in dealing with the disruption era.

The role of mediator suppressor of cytokine signaling (SOCS), toll-like receptor 3 (TLR-3) and nuclear factor kappa B (NFκB) on cytokine production during dengue virus infection Masyeni, Sri; Kuntaman, Kuntaman; Aryati , Aryati; Sofro, Muchlis AU.; Hadi, Usman; Mastutik, Gondo; Purnomo, Windu; Santosa, Agus; Iqhrammullah, Muhammad; Yohan, Benediktus; Nelwan, Erni J.; Sasmono, R. Tedjo
Narra J Vol. 3 No. 2 (2023): August 2023
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v3i2.167

Inability to understand the pathogenesis of severe dengue, in particular the control mechanism of immune responses, has led to high mortality rate for patients with dengue shock syndrome (DSS). The aim of this study was to determine the control mechanism of cytokine production by mediator suppressor of cytokine signaling (SOCS), toll-like receptor 3 (TLR-3) and nuclear factor kappa B (NFκB) during DENV infection. Peripheral blood mononuclear blood cells (PBMC), isolated from healthy individuals, were infected with dengue virus (DENV)-2 strain SJN-006 Cosmopolitan genotype (isolated from Bali, Indonesia). The relative gene expression of SOCS-3, TLR-3, NFκB, and the cytokine genes (interleukin (IL)-6, IL-8, interferon inducible protein 10 (IP-10), and macrophage inflammatory protein-1 beta (MIP-1β)) were measured using qRT-PCR at 6, 12 and 24 hours post infection (hpi). Student t-test and Mann-Whitney test were used to compare the gene expressions while causal correlations were analyzed using regression test and path analyses. DENV-2 infection increased the gene expression of SOCS-3, TLR-3, and NFκB after 12 and 24 hpi. The expression of IL-6, IL-8, IP-10, and MIP-1β genes was increased and peaked at different times post-infection. NFκB and SOCS-3 genes likely have role in the upregulation of IL-8 and IL-6 gene expression, respectively. MIP-1β gene expression was significantly induced by both NFκB and SOCS-3. In conclusion, our study suggested that SOCS-3, TLR-3, and NFκB are important in regulating the production of IL-6, IL-8, IP-10, MIP-1β during early phase of DENV-2 infection. This enriches our understanding on pathogenesis pathway of DENV-associated cytokine storm.

Effector function and neutrophil cell death in the severity of sepsis with diabetes mellitus Margalin, Brilliant; Arfijanto, Muhammad V.; Hadi, Usman
Narra J Vol. 4 No. 1 (2024): April 2024
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v4i1.532

Sepsis, a life-threatening condition resulting from immune dysregulation, is typically triggered by bacterial infections and commonly coexists with diabetes mellitus. Neutrophils are the first responders to infection and require regulated activation to control pathogen and damage-associated molecular patterns. Dysregulation of neutrophil activation leads to uncontrolled inflammatory responses, often observed in both sepsis and diabetes patients. Neutrophil dysregulation, characterized by effector dysfunction and inadequate cell death processes, can serve as a biomarker for assessing sepsis severity, particularly in diabetic patients. This review article provides information on the relationship between effector function, neutrophil cell death, and the severity of sepsis in individuals with diabetes mellitus, aiming to shed light on the mechanisms underlying sepsis progression. Topics covered in the review include an overview of effector function of neutrophil cells, mechanisms of neutrophil cell death, and dysregulation of effectors and neutrophil cell death processes in sepsis severity with diabetes mellitus.

Association Between Neopterin Levels and Outcome in 30 Day HIV/AIDS Naive Patients Juanita, Lydia; Hadi, Usman; Arfijanto, Vitanata
Biomolecular and Health Science Journal Vol. 2 No. 2 (2019): Biomolecular and Health Science Journal
Publisher : Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia

Introduction: HIV/AIDS is still a major problem throughout the world even in Indonesia. Some markers can provide information regarding the description of immune activity in HIV/AIDS. Neopterin produced by macrophages as a catabolic result of Guanosine Triphosphate (GTP) is one of them. Neopterin has been widely studied as a prognostic indicator of the course in HIV/AIDS. Until now there have been no studies examine the association between neopterin levels and outcomes in 30 days of HIV/AIDS patients.Methods: A prospective longitudinal analytic study involved 56 samples of HIV/AIDS naive patients from January to April 2019. Serum neopterin levels were measured by the Enzyme Linked Immunosorbent Assay (ELISA) method. Outcome is a living condition or death within the first 30 days of the patient being treated. Discriminant function analysis was used to determine the association between variable and controlling confounding factors using the "R" program. Outputs of p value was significant if <0.05.Results: The average age of the study subjects was 39.7 ± 11 years old with predominantly male gender (71.4%). The median serum neopterin level of the study subjects was 168.13 nmol/L with the lowest levels of 11.78 nmol/L and the highest level of 196.95 nmol/L. Outcomes were grouped live and died, each group at 50%. There was a significant positive association between serum neopterin levels and outcomes in 30 days (p=0.02)Conclusion: Role of neopterin levels still need to be proven as a prognostic factor by evaluating other factors that influence the outcome of HIV/AIDS patients.

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