2-(3-(Chloromethyl)benzoyloxy)benzoic Acid reduces prostaglandin E-2 concentration, NOX2 and NFKB expression, ROS production, and COX-2 expression in lipopolysaccharide-induced mice.

INTRODUCTION: Inflammation is a fundamental response to various insults, including microbial invasion and tissue injury. While aspirin (ASA) has been widely used for its anti-inflammatory properties, its adverse effects and limitations highlight the need for novel therapeutic alternatives. Recently, a novel salicylic acid derivative, 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid (3-CH2Cl), has emerged as a potential substitute for ASA, offering a simpler, environmentally friendly synthesis and a promising safety profile. AIM OF THE STUDY: This research aims to evaluate the anti-inflammatory mechanism of 3-CH2Cl in a lipopolysaccharide (LPS)-induced mouse model, focusing on its effects on prostaglandin E-2 (PGE-2) concentration, NOX2 and NFkB expression, ROS production, and COX-2 expression. MATERIAL AND METHODS: Utilizing BALB/C mice subjected to LPS-induced inflammation, we investigated the therapeutic potential of 3-CH2Cl. The study included synthesis and tablet preparation, experimental design, peripheral blood plasma PGE-2 measurement, splenocyte isolation and COX-2 expression analysis, nitric oxide and ROS measurement, and immunohistochemical analysis of NOX2 and NFkB expression. RESULTS: 3-CH2Cl significantly reduced PGE-2 levels (p = 0.005), NO concentration in liver homogenates (p = 0.005) and plasma (p = 0.0011), and expression of NOX2 and NFkB in liver (p < 0.0001) and splenocytes (p = 0.0036), demonstrating superior anti-inflammatory activity compared to ASA. Additionally, it showed potential in decreasing COX-2 expression in splenocytes. CONCLUSION: 3-CH2Cl exhibits potent anti-inflammatory properties, outperforming ASA in several key inflammatory markers in an LPS-induced inflammation model. The reduction of COX-2 expression, alongside the reduction of pro-inflammatory cytokines and oxidative stress markers, suggest it as a promising therapeutic agent for various inflammatory conditions.

Anti-inflammatory effect of Faloak (Sterculia quadrifida R. Br) stem bark on TNF-α, IL-1ß, and IL-6 in DENV-3-infected Wistar rats.

Background: Dengue infection can trigger an immunological response that results in an inflammatory reaction, which acts as a defensive mechanism to protect the host. Dengue infection leads to an elevation in the release of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). These three cytokines have been shown to correlate with the development of thrombocytopenia and plasma leakage, which is related to the severity of the disease. Aim: This study aims to investigate the effect of faloak (Sterculia quadrifida R. Br) stem bark on TNF-α, IL-1ß, and IL-6 levels in Wistar rats infected with dengue, specifically DENV-3. Methods: A group of 27 male Wistar rats (Rattus norvegicus) aged 2-3 months and weighting 200-300 g were divided into three distinct groups: healthy, dengue, and treatment (dengue infection and extract) groups. The rats in both the dengue and treatment groups were administered an injection of DENV-3 with a titer of 105 pfu at a dosage of 0.8 cc via the intraperitoneal route. The propagation of DENV-3 was initiated using C6/36 cells, and it underwent four passages. The extract was administered orally via a nasogastric tube at a dosage of 1,500 mg/kg body weight once daily for 7 days. The healthy group underwent blood sampling on the first day, whereas the dengue and therapy groups underwent blood sampling on the fifth and eighth, respectively. Results: Compared with the healthy group, TNF-α levels in the dengue and treatment groups showed significant differences on day 5 post-infection. The post hoc analysis revealed a statistically significant difference between the dengue-treatment and dengue-healthy groups. The IL-1ß levels in the dengue and healthy groups significantly differed on days 5 and 8 post-infection compared to the healthy group. The treatment group had less of a decrease in IL-6 levels on days 5 and 8 than the dengue group. However, no statistically significant differences were observed. Conclusion: The stem bark of S. quadrifida shows potential as an anti-inflammatory agent in dengue infections, particularly in its ability to decrease levels of TNF-α and IL-1ß.

The sodium does not affect joint pain and functional activity of knee osteoarthritis patients.

Background: The sodium may aggravate synovial inflammation and cartilage thinning. This incidence can cause joint pain and reduce functional activity. Not many people know the effect of sodium on the incidence of osteoarthritis. Objective: This study aims to determine the relationship between sodium in the body and knee joint pain which results in functional activity. Methods: The quantitative descriptive study used accidental sampling. The study was conducted at three outpatient polyclinic orthopedics of hospitals and was approved by the Health Ethics Committee. All data were collected during the interview. The Semi-Quantitative Food Frequency Questionnaire and the Nutrisurvey Indonesia 2007 application were used as a tool to collect daily sodium intake (mg). Knee joint pain score was measured using the Visual Analog Scale (VAS), while functional body activity was measured using the Western Ontario McMaster Osteoarthritis Index (WOMAC). The Pearson and Spearman test (P<0.05) were used as a correlation test. Results: 80 subjects were recruited according to the inclusion criteria. Characteristics of the subjects were pre-elderly (32, 40%), women (74, 92.5%), body mass index ≥30 kg/m2 (54, 67.5%) and occupation (43, 53.75%). Average sodium intake = 2090.78±1084.33 mg, VAS score = 6.28±1.95 and WOMAC score = 32.65±14.88. The correlation sodium, VAS, and WOMAC were not significant (P=0.196, P=0.372). Conclusions: Increased sodium intake is not associated with knee joint pain and functional body activity.

Antioxidant Role in Critically Ill Patients with Vasodilatory Shock: Does Glutathione Peroxidase Correlate to Severity of Tissue Hypoxia and Organ Failure.

Purpose: We aimed to evaluate the antioxidant role in critically ill patients with vasodilatory shock as it relates to severity of tissue hypoxia and organ failure. Patients and Methods: An observational and prospective study was conducted in critically ill patients with vasodilatory shock. Glutathione peroxidase (GPx) levels as antioxidants were measured based on their levels in the patient's serum. Tissue hypoxia as micro-hemodynamic status was represented by lactate levels, the macro-hemodynamic status was represented by vasoactive inotropic score (VIS) and mean arterial pressure (MAP), while organ dysfunction severity was represented by the shock index (SI), the sequential organ failure assessment (SOFA) score, and the acute physiology and chronic health evaluation (APACHE) II score. Results: Thirty-four critically ill patients with vasodilatory shock met the eligibility criteria. The mortality rate was 41.2%. Glutathione peroxidase levels did not show a significant difference between survivors and non-survivors at baseline or after 24 hours. At the initial measurement, there was a correlation between GPx and lactate levels, GPx and SOFA scores. The macrohemodynamic status was represented by VIS and MAP, which were correlated with SI. Conclusion: Glutathione peroxidase as antioxidant is related to severity of tissue hypoxia and organ failure in critically ill patients with vasodilatory shock.

Levels of SARS-COV-2 anti-spike protein receptor-binding domain (S-RBD) IgG in Indonesian-vaccinated healthcare workers: experimental research.

Studies evaluating the levels of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike protein receptor-binding domain (S-RBD) immunoglobulin G (IgG) antibodies in vaccinated healthcare workers in Indonesia are limited. Objectives: Evaluating time-dependent levels of anti-IgG S-RBD antibodies and monitoring the response of healthcare workers in a tertiary hospital in Indonesia after vaccination. Materials and methods: This prospective cohort observational study was conducted from January to December 2021. A total of 50 healthcare workers participated in the study. Blood samples were collected at five time points. Antibody levels were measured using a CL 1000i analyzer (Mindray Bio-Medical Electronics Co., Ltd., Shenzhen, China). Antibody levels between groups were analyzed using the Wilcoxon signed-rank test with P less than 0.05. Results: The median levels of SARS-CoV-2 anti-S-RBD IgG antibody on days 14, 28, 90, and 180 were significantly higher than the levels on day 0 (P<0.001). After the second dose, peak levels were observed on day 14; the levels decreased gradually after day 28. Despite receiving two doses of the vaccine, 10 out of 50 participants (20%) were infected with COVID-19 (coronavirus disease 2019). However, symptoms were mild, and antibody levels were significantly higher than in noninfected participants (P<0.001). Conclusion: SARS-CoV-2 anti-S-RBD IgG antibody levels increased significantly until day 14 after the second dose; the levels decreased gradually after day 28. Ten participants (20%) were infected with SARS-CoV-2, with mild symptoms.

Molecular Mechanism of Fucoidan Nanoparticles as Protector on Endothelial Cell Dysfunction in Diabetic Rats' Aortas.

Antioxidants have an important role in protecting against diabetes complications such as vascular endothelial cell damage. Fucoidan has strong antioxidant properties, therefore the aim of this study was to investigate the protective mechanism of fucoidan nanoparticles through the pathway of antioxidant activity against streptozotocin-induced diabetic aortic endothelial cell dysfunction in rats. Fucoidan nanoparticles are made utilizing high-energy ball milling. This research consists of five groups, namely: control rats, rats were administered aquadest; diabetic rats, rats were administered streptozotocin (STZ); fucoidan nanoparticle rats, rats were administered STZ and fucoidan nanoparticles. Aortic tissue was collected for the evaluation of ROS (reactive oxygen species), Malondialdehyde (MDA), superoxide Dismutase (SOD), Glutathione Peroxidase (GPx), Nuclear factor erythroid-2-related factor 2 (Nrf2), Nitric Oxide (NO), cyclic Guanosine Monophosphate (cGMP), relaxation response of acetylcholine (Ach), and the diameter of the aorta. The size distribution of the fucoidan nanoparticles was 267.2 ± 42.8 nm. Administration of fucoidan nanoparticles decreased the levels of ROS and MDA, and increased the levels of SOD, levels of GPx, Nrf2 expression, NO levels, cGMP expression, the relaxation response of Ach, and lumen diameter of the aorta, which are significantly different when compared with diabetic rats, p < 0.05. In this study, we concluded that the mechanism pathway of fucoidan nanoparticles prevents aortic endothelial cell dysfunction in diabetic rats through antioxidant activity by reducing ROS and MDA and incrementing SOD levels, GPx levels, and Nrf2 expression. All of these can lead to an elevated relaxation response effect of Ach and an increase in the lumen diameter of the aorta, which indicates a protective effect of fucoidan nanoparticles on aortic endothelial cells.

How Effective is Angiotensin II in Decreasing Mortality of Vasodilatory Shock? A Systematic Review.

Background: Patients with severe vasodilation accompanied by refractory hypotension despite high doses of vasopressors were associated with a high mortality rate. The Ang-2 for the Treatment of High-Output Shock (ATHOS) 3 trial demonstrated that angiotensin 2 (Ang-2) could effectively increase MAP and blood pressure in vasodilatory shock patients. This systematic review aims to summarize the impact of Ang-2 for the treatment of vasodilatory shock on clinical outcomes, including length of stay, MAP level (before and after), and mortality also Ang-2 dose needed. Methods: A systematic search in PubMed, Sage, ScienceDirect, Scopus and Gray literature was conducted to obtain studies about the use of Ang-2 in vasodilatory shock patients. Results: In all of the studies that we obtained, there were different results regarding mortality in patients with vasodilatory shock with Ang-2. Mortality was significantly lower when Ang-2 was administered to patients with elevated renin. The initial dose of Ang-2 can be started at 10-20 ng/kg/min, but there is no agreement on the maximum dose. Ang-2 may be considered a third-line vasopressor if the targeted MAP has not been achieved after administration of norepinephrine >200 ng/kg/min for more than 6 hours. Although not statistically significant, the use of Ang-2 can reduce the length of stay in the ICU and in the hospital when compared to patients without Ang-2 therapy, in addition to reducing the dose of vasopressor. Conclusion: Overall, the use of Ang-2 has potential to be a regimen for patients with vasodilatory shock. Further study is needed to obtain more data.

Effect of MTHFR A1298C Gene Polymorphism on Acute Coronary Syndrome.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Acute coronary syndrome is a manifestation of CVD. In Indonesia, limited studies have been conducted on genetics as a potential risk factor for acute coronary syndrome (ACS). Consequently, this study aimed to examine the effect of the methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism on the incidence of ACS. METHOD: The study employed a case-control design. Outpatients from the cardiology and internal medicine clinics at the University of Airlangga (UNAIR) Hospital in Surabaya, Indonesia, constituted the study population. The case group comprised 60 patients with a history of ACS, while the control group consisted of 30 patients without a history of cardiovascular complaints. MTHFR A12980C gene polymorphism examination was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP) method at the Tropical Disease Center UNAIR Laboratory. RESULTS: Among the ACS group, 29 (48.1%), 13 (21.7%), and 18 (30%) of the individuals had AA, AC, and CC genotype patterns, respectively. In the control group, 16 individuals had AA (53.3%), 6 AC (20%), and 8 CC (26.7%). The C allele variant was identified in 41% of the ACS group and 37% of the control group. The odds ratio (OR) for the incidence of ACS was 1.195 (95% confidence interval [CI]; 0.381-3.752), 1.241 (95% CI; 0.481-3.486), and 1.222 (95% CI; 0.381-3.752). Chi-square analysis revealed no association between MTHFR A1298C gene polymorphism and the incidence of ACS (P > 0.05). CONCLUSIONS: MTHFR A1298C gene polymorphism did not significantly affect ACS incidence.

Chest wall tumor tuberculosis in Indonesian adolescent: A rare case.

BACKGROUND: Extrapulmonary tuberculosis has increased in the last few decades, and establishing a diagnosis is still challenging. CASE PRESENTATION: A 15 years old Indonesian adolescent complained of a lump on the right lung. The patient and his mother had a history of pulmonary tuberculosis and received the anti-tuberculosis drug. Chest inspection showed a soft consistency mass, smooth surface, poorly defined borders, and size of 7 × 7 cm in the posterolateral dextra region. Radiological examination showed a mass of 2 × 2.5 × 5.3 cm in the right anterior mediastinum. FNAB lymph nodes showed granulomatous inflammation consistent with tuberculosis. The patient had a wide excision tumor, and a GeneXpert MTB/RIF examination of the tumor excision material showed that Mycobacterium tuberculosis was detected very low. The patient received an anti-tuberculosis drug and had a good prognosis. DISCUSSION: Patients with a family history of tuberculosis should be examined for tuberculosis. Although in a patient with lung carcinoma signs and symptoms, it does not rule out chest wall tuberculosis. CONCLUSION: Enforcement of the correct diagnosis can increase the prognosis of extrapulmonary tuberculosis.

Kinetics of anti-SARS-CoV-2 responses post complete vaccination with coronavac: A prospective study in 50 health workers.

Background: COVID-19 pandemic causes severe acute respiratory syndrome and requires rapid action. The development of effective safe vaccines become a global priority for achieving herd immunity. Vaccination is expected to form specific antibodies against the SARS-CoV-2 spike protein which can neutralize the virus, preventing the virus from binding with ACE 2 receptors. Objective: Evaluating and to know if there any differences of kinetics antibody levels from recipient's anti-IgG S-RBD and NAb with complete second dose CoronaVac Vaccine, to determine the antibody response in preventing SARS-CoV-2. Method: A prospective-cohort study using observational analytics was conducted from January-April 2021 at Dr. Soetomo Hospital, Surabaya. A total of 50 subjects are healthcare workers who received two doses of CoronaVac. The IgG S-RBD and NAb levels were measured on Maglumi 800 device (SNIBE, China). Differences in IgG S-RBD and NAb levels before vaccination and after second dose CoronaVac vaccination on 14th day, on 28th day, ware tested using Friedman and Wilcoxon tests. Result: Mean values of IgG S-RBD and NAb have fluctuated. There was a significant difference between IgG S-RBD and NAb levels on day-0 (0.090 vs 18.630; p < 0.001) and day-28 (141.266 vs 116.640; p = 0.037). The median value showed the IgG S-RBD level on day-28 was much better than NAb value (141,266 v 116,640). Conclusion: CoronaVac will form persistent antibodies. Despite antibody development, the acquired humoral immunity decreased at 28 days after full CoronaVac immunization. Kinetics of antibody NAb decreased more rapidly than IgG S-RBD.

Antioxidative Stress and Anti-Inflammatory Activity of Fucoidan Nanoparticles against Nephropathy of Streptozotocin-Induced Diabetes in Rats.

Oxidative stress and inflammation have been shown to interact and have the role of importance in causing diabetic nephropathy complications. Fucoidan has a strong antioxidant and anti-inflammation effect, so the aim of this research was to evaluate the antioxidative stress and anti-inflammatory effect of fucoidan nanoparticles against nephropathy of streptozotocin-induced diabetes in rats. Fucoidan nanoparticles are characterized using dynamic light scattering (DLS) and scanning electron microscope (SEM). The rats were randomized into the control group (were given with aquadest), streptozotocin group (were injected with streptozotocin at a dose of 55 mg/kg BW i.p.), and fucoidan nanoparticle group (were given orally with fucoidan at doses 75, 150, and 300 mg/kg BW and then injected streptozotocin at a dose of 55 mg/kg BW i.p.). The blood was taken to evaluate the level of blood urea nitrogen (BUN) and creatinine. The kidney tissues were collected to measure malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) by ELISA; superoxide dismutase (SOD), and glutathione peroxidase (GPx) by immunohistochemical staining and histological observation by Hematoxylin & Eosin (H&E) staining. The DLS demonstrated that the fucoidan nanoparticle size was 330.6 ± 58.8 nm, and the SEM showed an irregular shape with a rough surface image. The administration of streptozotocin significantly increased BUN, creatinine, MDA, IL-6, and TNF-α levels, whereas expression of SOD and GPx decreased as compared with the control group (p < 0.05). The administration of fucoidan nanoparticles only at a dose of 300 mg/kg BW significantly decreases BUN, creatinine, MDA, IL-6, and TNF-α levels. However, fucoidan nanoparticles at a dose of 300 mg/kg BW significantly increase SOD and GPx expression as compared with the streptozotocin group (p < 0.05). The administration of streptozotocin caused the loss of normal kidney cell structure and necrosis, while treatment with fucoidan nanoparticles improved renal cell necrosis. It can be concluded that fucoidan nanoparticles are promising agents in terms of the protection afforded against streptozotocin-induced nephropathy through antioxidative stress by decreasing MDA and increasing SOD and GPx and through anti-inflammatory effect by decreasing levels of IL-6 and TNF-α.

Antioxidative Stress and Antiapoptosis Effect of Chitosan Nanoparticles to Protect Cardiac Cell Damage on Streptozotocin-Induced Diabetic Rat.

The antioxidant can inhibit oxidative stress and apoptosis, which has a role in an important mechanism on diabetic-induced cardiac cell damage. The research goal was to prove the antioxidative stress and antiapoptosis effect of chitosan nanoparticles as a cardioprotector in streptozotocin-induced diabetic rats. Scanning electron microscope (SEM) and dynamic light scattering (DLS) characterize the chitosan nanoparticles. This research is a laboratory experiment which consists of the control group (rats were given distilled water), the streptozotocin group (rats were injected streptozotocin at dose of 55 mg/kg BW i.p), and the chitosan nanoparticle group (rats were given streptozotocin at dose 55 mg/kg BW i.p, and then given chitosan nanoparticles at dose 75 mg/kg BW, 150 mg/kg BW, and 300 mg/kg BW peroral). Creatine kinase-myoglobin (CK-MB) and lactate dehydrogenase (LDH) were measured from the blood sample. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) from cardiac tissue were examined by ELISA; nuclear factor erythroid 2-related factor 2 (Nrf2) was evaluated by western blotting; B-cell lymphoma 2 (Bcl-2) and Caspase-3 expression were investigated by immunohistochemical staining and also were evaluated histological preparation by hematoxylin & eosin (H&E) staining. The chitosan nanoparticles have a rough surface and an irregular shape. Its size is 247.3 ± 38.1 µm. Streptozotocin injection significantly increased the levels of CK-MB, LDH, MDA, and expression of caspase-3. In contrast, the levels of SOD, GPx, Nrf2, and expression of Bcl-2 decreased as compared with the control group (p < 0.05). This is accompanied by the loss of normal cardiac cell structure and necrosis. The administration of chitosan nanoparticles significantly reduced levels of CK-MB, LDH, MDA, and expression of Caspase-3. However, the levels of SOD, GPx, Nrf2, and expression of Bcl-2 increased as compared with the streptozotocin group (p < 0.05). And also, chitosan nanoparticles inhibited cell necrosis in diabetic rats. This study suggests that the administration of chitosan nanoparticles can protect cardiac cell damage in diabetic rats through antioxidative stress by decreasing ROS and increasing Nrf2 expression, level of SOD, and GPx and through antiapoptosis by increasing expression of Bcl-2 and decreasing expression of Caspase-3.

Molecular docking and dynamic simulation of conserved B cell epitope of SARS-CoV-2 glycoprotein Indonesian isolates: an immunoinformatic approach.

Background: An immunoinformatic approach may be useful to investigate the conserved region in the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Indonesia isolates. The aim of this study was to investigate Indonesian SARS-CoV-2 isolates based on B cell epitopes by targeting the conserved regions in the spike glycoprotein to trigger increased multi-variant virus neutralization and memory response for the development of vaccine seed candidates. Methods: SARS-CoV-2 spike glycoprotein gene sequences originating from Indonesia were compared with Wuhan (China), the United Kingdom, South Africa, India, the United States, and Brazil isolates obtained from the NCBI and GISAID databases. The recognition of antigens was carried out directly using B cells through the B cell receptor (BCR). An indirect B cell activation by Cluster of Differentiation (CD)4+ T cells and major histocompatibility complex (MHC)-II was predicted through the binding with human leukocyte antigen (HLA) based on IC 50 value. In addition, vaccine allergenicity and toxicity were investigated. During the molecular complex examination, the 3D peptide structure was investigated and the lowest amount of energy formed when the vaccine candidate peptide bound to BCR and MHC-II was calculated. Results: As a result, the spike glycoprotein sequences of Indonesian SARS-CoV-2 isolates had conserved regions which were very similar to reference countries such as China, the United Kingdom, South Africa, India, the United States, and Brazil. Conclusion: It was predicted that the conserved regions could be identified as the epitope of B and T CD4+ cells that produced the peptides for vaccine candidate with antigenic, non-allergen, and non-toxic properties.

Characterization of SARS-CoV-2 East Java isolate, Indonesia.

Background: Incidents of SARS-CoV-2 in East Java increased steadily, and it became the second epicenter in Indonesia. The COVID-19 pandemic caused a dire multisectoral crisis all around the world. This study investigates and characterizes local isolates from East Java, Indonesia.   Methods: There were 54 patients suspected with SARS-COV-2 infection and 27 patients were COVID-19 positive. Virus isolates were obtained from COVID-19 inpatients' nasopharyngeal swabs at the Dr Soetomo Teaching Hospital, Surabaya. There were only three isolates (#6, #11, #35) with good growth characteristics. Serial blind passage and cytopathic effect observation in the Vero E6 cell line were performed for virus isolation. Confirmation of the SARS-CoV-2 infection was proven by means of reverse transcriptase-polymerase chain reactions using SARS-CoV-2 specific primers, scanning electron microscopy, and scanning transmission electron microscopy examination. Whole genome sequencing was performed using ARTIC protocol. Furthermore, SARS-CoV-2 characterization was identified through a western blot using rabbit serum immunized with inactive SARS-CoV-2 vaccine and human natural COVID-19 infection serum.   Results: Spike gene analysis of three samples (#6, #11, #35) found that the D614G mutation was detected in all isolates, although one isolate exhibited the D215Y and E484D mutation. Based on whole genome analysis, those three isolates were included in clade 20A, and two isolates were included in lineage B.1.6 with one isolate belongs to lineage B.1.4.7.   Conclusion: Based on molecular characterization and immunogenicity of SARS-CoV-2 East Java, Indonesia showed high titer and it has mutation in some regions.

Comparison of IL-17 and FOXP3+ Levels in Maternal and Children Leprosy Patients in Endemic and Nonendemic Areas.

Leprosy, a chronic infection caused by M. leprae, has a complex transmission problem that makes eradication programs difficult. New cases and ongoing transmission of leprosy in endemic areas make individuals living in endemic environments vulnerable to leprosy. This can be caused by the dysregulation of immune system in individuals living in leprosy-endemic areas. Although the number of male leprosy patients is higher, female leprosy patients have more impact on the family health status due to close contact with family members, roles in the household, and parenting. This could cause the increased number of children leprosy patients. We investigated the dysregulation of immune system by comparing IL-17 and FOXP3+ levels occurring in maternal and child leprosy patients in endemic and nonendemic areas. The results of the study found a statistically significant difference in IL-17 levels between the MB leprosy patient group and the control group (p=0.048), where higher levels of IL-17 are observed in the control group. A significant difference also was found in FOXP3+ levels between the group of healthy children living in endemic and those living in nonendemic areas (p=0.047), where higher FOXP3+ is observed in the healthy children living in endemic areas group.

A decrease in PPD specific CD4 T cell CD38 and HLA-DR expression in pulmonary tuberculosis patients after 8 weeks of therapy correlates with successful anti-tuberculosis treatment.

Tuberculosis (TB) is a major health problem in Indonesia with a million new cases each year. The CD4 T cell adaptive immune response against Mycobacterium tuberculosis (MTB) is central to the control of this disease. We investigated whether standard therapy of TB causes changes to these cells in the early stages of treatment. To do this we took blood samples from 2 groups of TB patients in Banda Aceh, Indonesia; one from a group of patients before treatment, and the other from a group who become smear negative after 8 weeks treatment. MTB specific CD4 T cells were identified by ex vivo stimulation with PPD and flow cytometric measurement of intracellular cytokines and surface markers. We found no difference in total PPD specific CD4 T cells between the groups, but that the proportion of these cells CD38 + HLA-DR+ was significantly lower in the treatment group. This decrease was not specific to Interferon gamma (IFNg), Interleukin-2 (IL-2) or Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) producing cells. Our findings show that anti-MTB treatment affects the adaptive immune response, and that measuring the decrease of the PPD specific CD4 T cell CD38+HLA-DR+ phenotype could be a useful parameter for determination of treatment success.

The Association of FLT3-ITD Gene Mutation with Bone Marrow Blast Cell Count, CD34, Cyclin D1, Bcl-xL and hENT1 Expression in Acute Myeloid Leukemia Patients.

BACKGROUND & OBJECTIVE: FLT3-ITD has been recently used as a molecular prognostic marker for risk classification in acute myeloid leukemia (AML) therapy. In this study we aimed to investigate the association of FLT3-ITD gene mutation with bone marrow blast cell count, CD34 expression as malignant cell burden, cyclin D1 and Bcl-xL expressions as indexes of cell proliferation and anti-apoptosis and human equilibrative nucleoside transporter 1 (hENT1) expression as cytarabine transporter during AML treatment. METHODS: We investigated FLT3-ITD mutations, bone marrow blast cell count, CD34, cyclin D1, Bcl-xL and hENT1 expression in bone marrow aspirates from 22 de novo AML patients in a cross sectional study. RESULTS: FLT3-ITD mutations were observed in 5 out of 22 de novo AML patients (22.7%). Patient with FLT3-ITD mutations had higher blast cell counts (79.5% vs 56.1%, P=0.004). In patients with FLT3-ITD mutations, CD34 and cyclin D1 expressions were higher (MFI 328.80 vs 25.78, P=0.003 and MFI 74.51 vs 57.15 P=0.005) than the patients without mutations. hENT1 expression in AML with FLT3-ITD mutation was lower (MFI 29.64 versus 56.32, P=0.0000) than in mutation-free AML. There was no significant difference in Bcl-xL expression between patients with and without mutations (P=0.61). CONCLUSION: A significant association was found between FLT3-ITD gene mutations in AML patients with bone marrow blast cell count, CD34, cyclin D1 and hENT1 expressions, however no association was obtained with Bcl-xL expression. These findings support the role of such mutation in pathogenesis of AMLand its contribution in rearrangement of standard therapy with cytarabine in management of AML.

TLR10 and Its Unique Anti-Inflammatory Properties and Potential Use as a Target in Therapeutics.

TLRs are pattern recognition receptors (PRRs) whose cytoplasmic signalling domain is similar to that of IL-1. The extracellular domain of TLRs serve as the binding site of pathogen associated molecular patterns. TLRs are found on both plasma and endosomal membranes and they mainly exert their function by activating genes which lead to production of inflammatory factors. The latest TLR to be discovered, TLR10 is a unique TLR which exhibit anti-inflammatory properties. TLR10 is found on the plasma membrane with other TLRs namely TLR1, TLR2, TLR4, TLR5 and TLR6. Studies have revealed that TLR10 is found on the same gene cluster with TLR1 and TLR6 and is also a coreceptor of TLR2. Up to date, TLR10 is the only TLR which exhibit anti-inflammatory property. Previously, TLR10 was thought to be an "orphan receptor" but much recent studies have identified ligands for TLR10. Currently there is no review article on TLR10 that has been published. In this narrative review, we are going to give an account of TLR10, its functions mainly as an anti-inflammatory PRR and its possible applications as a target in therapeutics.

Changes of serum adenosine deaminase level in new cases of pulmonary tuberculosis before and after intensive phase treatment.

BACKGROUND AND OBJECTIVES: Tuberculosis (TB) continues to be a public health crisis with an estimated 10 million people developing TB disease in 2017. Adenosine deaminase (ADA) level in serum and pleural fluid as a biomarker may be used to diagnose pulmonary TB (PTB), but it is not always easy to obtain those samples at the end of treatment. This study was conducted to analyze the changes of serum ADA level in the new case of PTB patients with acid-fast bacilli (AFB) smear-positive sputum and sputum conversion status as treatment monitoring in PTB patients. MATERIALS AND METHODS: This was a prospective observational analytic study conducted in Dr. Soetomo General Hospital, Surabaya, from January 2018 to May 2018. Participants were all new cases of PTB patients with AFB smear-positive sputum, and a positive rapid molecular test for Mycobacterium tuberculosis. Blood serums were taken at the same time on the 1st day of TB treatment and also taken at the end of intensive phase treatment to analyze the changes of serum ADA level. RESULTS: There were 26 TB patients and 26 healthy control people. Serum ADA level at the beginning of TB treatment was higher than the level at the end of intensive phase treatment. There was a significant difference between serum ADA level before and after the intensive phase of TB treatment (P < 0.001). CONCLUSIONS: The examination of serum ADA levels can be used to evaluate the PTB treatment response.

Metformin associated inflammation levels regulation in type 2 diabetes mellitus-tuberculosis coinfection patients - A case report.

IFN-γ elevation is one of the indicators of successful treatment in active tuberculosis (TB) infection due to macrophage and Th-1 activation in inducing autophagy process. However, IL-10 also inhibits interferon-mediated mycobactericid activities by blocking IFN-γ; signaling pathways in autophagy. Therefore, ratio IFN-γ/IL-10 has to be greater than 1 (>1) then IFN-γ remains has anti-mycobacterium. Metformin (MET) is a potent combination drug to elevate anti-TB efficacy and able to regulate inflammation. In this study, an observational clinical study was done in diabetes mellitus (DM)-TB co-infection outpatients at Surabaya Paru Hospital. This study evaluated how MET therapy; affected inflammation. MET was used at least 2 months, accompanying with insulin and; anti-TB and as comparison to non MET group. The result in this study MET increased both pro-inflammatory and anti-inflammatory cytokines, thus MET may consider as adjunct therapy in DM-TB coinfection patients due; to its ability in Th-1 and Th-2 immuno-regulating response, especially to enhance IFN-γ; and to reduce insulin associated IL-10 upregulation.