Allogeneic islet cells implant on poly-l-lactide matrix to reduce hyperglycaemia in streptozotocin-induced diabetic rat.

OBJECTIVE: To demonstrate the effects of allogeneic islet cell matrix implants for glycaemic control in rats with induced diabetes. METHOD: Sprague-Dawley rats were used as allogeneic donors of islet cells. Cells were seeded on three-dimensional proprietary poly-(l-lactide) matrices. Animals were rendered diabetic and a week later a matrix seeded with islet cells (IMI group) or a control matrix (placebo group) was implanted in the small bowel mesentery. Blood glucose levels were measured weekly for 12 weeks. After sacrifice, implant sections were Gomori stained for beta-cells and immuno-stained for insulin 3, 4, 5, and 6 months post implantation. RESULTS: 82% of seeded islet cells attached to the matrices. In the IMI group blood glucose levels were significantly reduced after implantation compared with before implantation across several time points. In the IMI group beta-cells and insulin-positive cells were identified at the implant site. CONCLUSION: The islet cell matrix implant reduced the blood glucose levels although complete normo-glycaemia was not established. The islet cell matrix implant may serve as an additional option for islet cell transplantation using 3D scaffold platforms for better survival and function of the islet cells.

Interleukin-6 and interleukin-10 plasma levels and mRNA expression in polytrauma patients.

PURPOSE: Host response to polytrauma occasionally has unpredictable outcomes. Immune response is a major factor influencing patient's outcome. This study evaluated the interaction of two main cytokines in immune response after major trauma, specifically interleukin-6 (IL-6) and interleukin-10 (IL-10). Plasma level of these cytokines is determined by mRNA expression of these cytokines genes which may decide the outcome of polytrauma patients. METHODS: This prospective multicenter trial held at four trauma centers enrolled 54 polytrauma patients [Injury Severity Score (ISS) ≥ 16]. Plasma levels and mRNA expression of IL-6 and IL-10 were measured for 5 days after trauma. Clinical evaluation was conducted to observe whether patients endured multiple organ dysfunction syndrome (MODS) and death. MODS evaluation was performed using sequential organ failure assessment (SOFA). Trauma load which in this study is represented with ISS, plasma level, expression of cytokine genes and patient's outcome were examined with correlation test and statistical analysis. RESULTS: The elevated IL-6/IL-10 ratio indicated increased activity of systemic inflammation response, especially pro-inflammation response which bears higher probability of progressing to MODS and death. The decline of IL-6/IL-10 ratio with heavy trauma load (ISS > 30) showed that compensatory anti-inflammation response syndrome (CARS) state was more dominant than systemic inflammatory response syndrome (SIRS), indicating that malfunction and failure of immune system eventually lead to MODS and deaths. The statistical significance in plasma level of cytokines was found in the outcome group which was defined as bearing a low trauma load but mortality. CONCLUSION: The pattern of cytokine levels in inflammation response has great impact on the outcome of polytrauma patients. Further study at the genetic level is needed to investigate inflammation process which may influence patient's outcome.

Secretome of Hypoxia-Preconditioned Mesenchymal Stem Cells Promotes Liver Regeneration and Anti-Fibrotic Effect in Liver Fibrosis Animal Model.

<b>Background and Objective:</b> Liver fibrosis (LF) is a most common pathological process characterized by the activation of hepatocytes leading to the accumulation of extracellular matrix (ECM). Hypoxia precondition treated in MSCs (H-MSCs) could enhance their immunomodulatory and regeneration capability, through expressing robust anti-inflammatory cytokines and growth factors, known as H-MSCs secretome (SH-MSCs) that are critical for the improvement of liver fibrosis. However, the study regarding the efficacy and mechanism of action of SH-MSCs in ameliorating liver fibrosis is still inconclusive. In this study, the therapeutic potential and underlying mechanism for SH-MSCs in the treatment of liver fibrosis were investigated. <b>Materials and Methods:</b> A rat model with liver fibrosis induced by CCl₄ was created and maintained for 8 weeks. The rats received intravenous doses of SH-MSCs and secretome derived from normoxia MSCs (SN-MSCs), filtered using a tangential flow filtration (TFF) system with different molecular weight cut-off categories, both at a dosage of 0.5 mL. The ELISA assay was employed to examine the cytokines and growth factors present in both SH-MSCs and SN-MSCs. On the ninth day, the rats were euthanized and liver tissues were collected for subsequent histological examination and analysis of mRNA expression. <b>Results:</b> The ELISA test revealed that SH-MSCs exhibited higher levels of VEGF, PDGF, bFGF, IL-10, TGF-ß and IL-6 compared to SN-MSCs. <i>In vivo</i>, administration of SH-MSCs notably decreased mortality rates. It also demonstrated a reduction in liver fibrosis, collagen fiber areas, α-SMA positive staining and relative mRNA expression of TGF-ß. Conversely, SN-MSCs also contributed to liver fibrosis improvement, although SH-MSCs demonstrated more favorable outcomes. <b>Conclusion:</b> Current findings suggested that SH-MSCs could improve CCl₄-induced liver fibrosis and decrease α-SMA and TGF-ß expression.

The Effects of High Fat Diet on the Incidence of Obesity and Monocyte Chemoattractant Protein-1 Levels on Histological Changes in Prostate Wistar Rats.

Introduction: Benign prostatic hyperplasia (BPH) is a histopathological diagnosis characterized by the increase in stromal cells and epithelial cells of the prostate gland in the transitional zone surrounding the urethra. Obesity is the risk factor of BPH. The most frequent cause of obesity is a high-fat diet (HFD). Obesity and HFD lead to pro-inflammatory conditions. One of the pathomechanisms for the occurrence of BPH is a low-degree inflammatory factor, one of which is the level of monocyte chemoattractant protein-1/MCP-1. This study aims to determine the influence of HFD on the incidence of obesity and inflammatory factors (monocyte chemoattractant protein-1/MCP-1 levels) on the histopathological picture of the prostate. Methods: Experimental research was performed on male Wistar rats with each of the 6 rats given normal fat (ND) and HFD intake and terminated at 8 weeks and 6 rats given each ND and HFD were terminated at 16 weeks. The determination of obesity was determined based on Lee's criteria which were categorized as obese if the Lee index >0.3 and non-obese if ≤0.3. Examination of circulating MCP-1 was carried out by the ELISA method and determination of prostatic hyperplasia was done by calculating the percentage of prostate glands that had a large per-field cystic dilatation on light microscopy examination. All data are analyzed statistically with the Fisher Exact Test and Spearman Correlation Test. Results: Of the 12 rats that were given ND, none of them became obese according to Lee's criteria, on the other hand, of the 12 rats that were given HFD 8 became obese (66.7%, p = 0.001). Serum MCP-1 levels and the percentage of prostate glands that had cystic dilatation were significantly higher in mice receiving HFD than ND; both at week-8 (MCP-1; 18.87 vs 15.66) and (prostate gland experiencing cystic dilatation; 63.46% vs 47.24%) and week-16 (MCP-1; 21.27 vs 21.27) and (prostate gland experiencing cystic dilatation; 67.79% vs 56.39%). Spearman correlation analysis showed that only circulating MCP-1 levels were significantly correlated (p < 0.05) to the percentage of the prostate gland that had cystic dilatation; especially in week 16 (r = 0.713 and p < 0.001). At 8 weeks, it was not statistically significant (r = 0.406 and p = 0.095). Conclusion: High fat intake has been shown to increase the risk of obesity, but obesity does not increase inflammatory status and the incidence of prostate glands with cystic dilatation. On the other hand, high-fat intake increases inflammatory status which in turn causes prostate glands to develop cystic dilatation.

Circulating miR-221/222 expression as microRNA biomarker predicting tamoxifen treatment outcome: a case-control study.

The high mortality rate in breast cancer (BC) patients is generally due to metastases resistant to systemic therapy. Two causes of systemic therapy resistance in BC patients are circulating miRNAs-221 and miR-222, leading to improved BC cell proliferation, survival, and reduced cell apoptosis. This study investigated the miRNA expression changes associated with cancer cell resistance to tamoxifen therapy and is expected to be clinically meaningful before providing endocrine therapy to luminal-type BC patients who express them. Methods: This case-control research included individuals with the luminal subtype of BC who had received tamoxifen medication for around one year. Furthermore, the case group contained 15 individuals with local recurrence or metastases, while the control group comprised 19 patients without local recurrence or metastases. Plasma miR-221/222 quantification was performed with real-time PCR using transcript-specific primers. Results: A significant difference was found in circulating miR-221 expression between cases and controls (P=0.005) but not in miR-222 expression (P=0.070). There were no significant differences between miR-221/222 expression, progesterone receptor, Ki67 protein levels, lymphovascular invasion, and stage. However, receiver operator characteristic curve analyses showed miR-221/222 expressions predictive of tamoxifen resistance (P=0.030) with a sensitivity of 60.00 and a specificity of 83.33%. Conclusion: The use of circulating miR-221/222 expression can predict relapse as well as resistance to tamoxifen treatment in BC patients, and their testing is recommended for luminal subtype BC patients who will undergo tamoxifen therapy to determine their risk of tamoxifen resistance early, increasing treatment effectiveness.

Correlation expression Toll-like receptor 4 with multidrugs resistant tuberculosis in diabetes mellitus condition.

BACKGROUND: Toll-like receptor (TLR) are ligand homologous protein in the APC cell membrane that has functions as a receptor to triger leukocytes and innate immune responses. When there is a Microbacterium tuberculosis (MTB) infection enters from droplets to the lungs, the alveolar macrophages perform a phagocytic function. The interaction between M. tuberculosis and the TLR macrophage receptors produces chemokines which induce migration of monocytes and dendrite cells for destruction. Diabetes militus (DM) has become risk factor for developing tuberculosis. DM condition will reduce immunity and the ability of immune cell phagocytes bactery and triger severe infections. The consequences of more severe infection and metabolic disorders that occur make a person more likely to experience Multidrugs resistant MTB. Not much data that reports on the expression of TLR4 as a ligand that triggers an immune response in conditions of MDR and DM. We try to find out correlation between TLR-4 in MDR MTB, diabetes and level of MTB bacteria in experimental animals. METHODS: We conducted an experimental study on 30 experimental mice weighing 25 grams consisting of negative control grub, infected with MTB, infected with MDR MTB, negative control diabetes, MTB DM, MDR MTB DM. DM animals were induced by streptozosin to experience DM, then in the treatment of infection, intraperitoneal MTB and MDR MTB bacterial injections were given. Termination was carried out on day 14. We count number of bacteria level in the lungs and perform evaluation TLR4 from blood sampel. RESULTS: The negative control group had mean TLR value of 1.47 (± 0.46) while the MTB group showed an increase in TLR 9.22 (± 0.39) followed by MDR MTB 9.50 (± 0.29), DM negative control 9, 21 (± 0.24) and more increasing in conditions of DM MTB 13.36 (± 0.32) and DM MDR MTB 13.35 (± 0.34). ANOVA analysis showed a significant difference (P = 0.00). pearson correlation analysis find strong correlation TLR4 in MTB and MDR MTB with diabetes. CONCLUSION: there were a significant difference level TLR4 between MTB and MDR TB infection with diabetes. higher TLR4 level higher in DM MTB, DM MDR MTB. TLR 4 strong correlates with an increase in the number of MTB bacteria.

Topical Curcumin as Chemoprotector Against Photoproducts Production: The Role of Cyclobutyl Pyrimidine Dimers, 8-Hydroxy2'Deoxyguanosine Expression and Epidermal Hyperplasia in Acute and Chronic UVB-Induced Mice.

Background: Ultraviolet B (UVB) exposure leads to formation of photoproducts leading to cellular damage. Prevention using sunscreen can sometimes be inadequate and can be an economic burden. Recent studies have suggested the photoprotective effect of curcumin. Objective: To examine the acute and chronic photoprotective effect of topical curcumin, using cyclobutyl pyrimidine dimers (CPD) and 8-hydroxy2'deoxyguanosine (8-OHdG) expression as markers of DNA-induced damage, and epidermal hyperplasia on UVB-induced mice. Methods: Three treatment groups were established. Group A (negative control) consisted of 5 mice, Group B and C were further divided into two categories to assess acute and chronic effects of topical curcumin and UVB radiation. Each consisted of six subgroups of five mice. Subgroup 1; UVB exposure only (positive control) subgroup 2; acetone and UVB exposure, subgroup 3-6; topical curcumin application of 100nM, 1µM, 10µM, and 100µM concentrations, respectively. In Group C, there were two categories that received 3x/week UVB exposure for three weeks which effects were being observed at 24 hours and 10 days after the last exposure. The topical curcumin dose was 2mg/mL/cm2 applied 30 minutes prior to 343mJ/cm2/day UVB irradiation. Skin biopsy was done one hour after the last UVB exposure for immunohistochemical and histopathology examinations. Results: Topical curcumin showed a limited yet robust protective effect against CPD and 8-OHdG expression in Group B, while in Group C all concentrations showed significant CPD and 8-OHdG inhibition after 10 days of UVB exposure. The 10µM and 100µM concentrations showed the best epidermal hyperplasia inhibition effect (p<0.05). No significant differences were found in terms in efficacy either in single nor daily application. Conclusion: Topical curcumin can prevent the formation of the photoproducts CPD and 8-OHdG and epidermal hyperplasia in both acute and chronic exposure in UVB-induced mice.

Correlation between innate and adaptive immunity response in TB children post BCG vaccination. Is it effective or not?: Cross-sectional study.

Background: How far the role of innate immunity and adaptive immunity do in children who have been BCG vaccinated in controlling the course and the severity of the TB disease has not been completely known. Mycobacterium tuberculosis entry to the body will be recognized by Toll-like receptors found on macrophages, neutrophils, and dendritic cells as part of the innate immune response, after which the dendritic cells will then present the antigen to lymphocyte T0 cells and initiate the adaptive immune response (of which CD4 T cells have an important role in). Was one or were both of these immune responses function well or not in a BCG Vaccinated Children with TB? Objective: This study aim to find a better understanding of the role of innate immune response assessed by TLR2/TLR4 mRNA gene expression and serum TLR2/TLR4 levels, while the role of adaptive immune response is assessed by analyzing serum CD4 level in children with TB who have had BCG vaccination. Methods: This cross-sectional study was conducted among children with TB at the outpatient and inpatient wards at Bhakti Medicare and Jakarta Islamic Hospital. Expression of mRNA gene was measured using the Boom method and protein serum levels were measured using the ELISA method. The results were analyzed by using the SPSS v.23 program. Results: Sixty-nine children were recruited as subjects. In this study, 68.1% of whom had BCG scars. TLR4 mRNA gene expression was found to be higher than TLR2 mRNA gene expression. Serum CD4 level was found to be highest out of TLR2 and TLR4 level, but serum TLR2 level was higher than TLR4 level. TLR2/TLR4 mRNA gene expression, serum TLR2/TLR4 levels, and CD4 levels in subjects with BCG scar were also found to be significantly higher than in subjects without BCG scar (p < 0.001). There was a significant positive correlation between TLR2/TLR4 mRNA gene expression and serum TLR2/TLR4 levels (r = 0.860; r = 0.864; p < 0.001) and between serum levels TLR2/TLR4 with serum CD4 levels (r = 0.822; r = 0.832 p < 0.001). Conclusion: As early as possible, BCG vaccine administration is needed in endemic countries, but it must be ensured that scars can be formed. It is also important to control Latent TB Infection (LTBI) to prevent transmission and relapse of disease.

Choroidal Thickness in Correlation with Axial Length and Myopia Degree.

Background: Myopia is a condition in which the visual images come to a focus in front of the retina of the eye. This disease is a major cause of visual disability, which presents in 108 million persons globally. Purpose: This study aims to determine the relationship between the degree of myopia, the axial length, and the choroidal thickness (CT). Methods: This is an observational analytical study that made use of a cross-sectional design. A total of 59 participants with refractive errors underwent treatment at Hasanuddin University Hospital and 116 eyes were measured and analyzed. The choroidal thickness was measured using the Enhance Depth Imaging OCT (EDI-OCT) tool, which is divided into nine observational areas. Furthermore, all data obtained were compared using statistical analysis, such as the one-way ANOVA and Pearson correlation test (p < 0.05). Results: There was a significant relationship between the choroidal thickness with axial length (p < 0.05) and myopia degrees (p < 0.05). Conclusions: The thickness of the choroid decreases with an increase in the axial length and degree of myopia, which further indicates that the higher the myopia degree, the thinner the choroidal vasculature.

In vivo and in vitro inhibition effect of propolis on Klebsiella pneumoniae: A review.

For centuries, propolis has been used to treat various diseases in traditional medicine due to its biological and pharmacological activities. It remains popular because of its potentially beneficial role in human health due to its well-known broad multispectrum properties, including antiviral, anti-inflammatory, antibacterial, anesthetic, antioxidant, anticancer, antifungal, antiprotozoal, antihepatotoxic, antimutagenic, and antiseptic activity. Numerous studies have examined the antibacterial activity of propolis and its derivatives, which include many natural antimicrobial compounds with broad spectrum activity against different bacterial types. In vitro studies have shown propolis's antibacterial activity against Gram-positive and Gram-negative bacteria. Many studies have examined propolis's effect on inhibiting bacterial growth. Several studies examining propolis's inhibition of Gram-positive and Gram-negative bacteria have shown it to be an effective antimicrobial agent. Klebsiella pneumoniae is a Gram-negative bacterium commonly associated with respiratory infections, particularly in hospital settings. Inappropriate antibiotic use may contribute to the increasing number of bacterial strains resistant to available drugs. This review summarizes the findings of previous studies on propolis and its potential mechanisms in inhibiting K. pneumoniae growth in animals.

microRNA-221 and tamoxifen resistance in luminal-subtype breast cancer patients: A case-control study.

BACKGROUND: Around 70% of breast cancers (BCs) are estrogen receptor-α (ERα)-positive. Adjuvant endocrine therapy is used to reduce estrogen levels and inhibit signal transduction through the ER. The anti-estrogen drugs that are most commonly used in endocrine therapy belong to the selective ER modulator (SERM) class and include tamoxifen. Although it has been used for three decades in cases of early-stage and ERα-positive BC, resistance to tamoxifen is a common problem. microRNAs (miRNAs) have a potential role in demonstrating BC resistance to tamoxifen therapy. Hence, there is a need to investigate the expression of miRNA-221 (miR-221) in luminal-subtype BC patients receiving tamoxifen therapy. METHODS: This case-control study investigated luminal-subtype BC patients who had undergone endocrine therapy for at least 1 year. The case group comprised patients with local or metastatic recurrence, and the control group comprised patients without local or metastatic recurrence. RESULTS: There was a significant difference in miR-221 expression (p = 0.005) between the case and control groups. There were no significant differences between the groups that were positive and negative for the progesterone receptor (PR) (p = 0.25), had high and low marker of proliferation Ki-67 levels (p = 0.60), were positive and negative for lymphovascular invasion (p = 0.14), and had stage 2 and stage 3 cancer (p = 0.25). CONCLUSION: miR-221 expression was higher in tamoxifen-resistant BC cases. miR-221 is a potential biomarker of tamoxifen resistance.

Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinants.

Background: The host immune system plays an important role in hepatitis B virus (HBV) infection manifestation. Genetic polymorphisms of several inflammatory cytokines, including TNF-α and IL-10, have been associated with chronic hepatitis B (CHB) progression, although with contradicting results. CHB progression can be categorized into four phases, immune tolerance (IT), immune clearance (IC), low/no replicative (LR), and e-negative hepatitis (ENH), with HBeAg seroconversion as an important milestone. Here, we determined the association of TNF-α (rs1800629) and IL-10 (rs1800896 and rs1800872) SNPs in the context of CHB natural history progression, particularly to HBeAg seroconversion, in Indonesian CHB patients. Methods: A total of 287 subjects were recruited and categorized into distinct CHB phases based on HBeAg, viral load, and ALT levels. TNF-α and IL-10 SNPs were determined using PCR-RFLP and confirmed with direct sequencing. The association between SNP genotypes with CHB dynamics was determined using logistic regression presented as odds ratio (OR) with 95% CI. Results: No significant association was found between IL-10 -592A/C polymorphism and progression of IT and IC to LR, IT and IC to ENH, and LR to ENH phases in all the gene models. IL-10 rs1800896 and TNF-α rs1800629 could not be analyzed using logistic regression. Subjects' age (≥40 years old) was significantly associated with IT and IC to LR (OR: 2.191, 95% CI 1.067-4.578, P = 0.034), IT and IC to ENH (OR: 7.460, 95% CI 3.316-18.310, P < 0.001), and LR to ENH (OR: 5.252, 95% CI 2.010-14.858, P = 0.001). Male gender was associated with LR to ENH (OR: 4.077, 95% CI 1.605-11.023, P = 0.004). Conclusions: Age and male gender were associated with CHB phase progression instead of the TNF-α and IL-10 polymorphisms. It would be beneficial to study not only the effect of host determinants but also the viral factor to understand the mechanisms of CHB phase progression.

Systemic lidocaine administration influences NF-kß gene expression, NF-kß and TNF- α protein levels on BALB/c mice with musculoskeletal injury.

BACKGROUND: The immune system can produce various inflammatory mediators to protect the body from stress and surgical trauma. However, this excessive inflammatory response will interfere with the body's immune system, causing systemic inflammatory response syndrome and multi-organ failure if allowed to continue. Lidocaine as an anti-inflammatory is used to treat surgical pain and pain arising from the disease process and treat ventricular arrhythmias. This study aims to prove the efficacy of systemic lidocaine injection as an anti-inflammatory drug in BALB/c mice with sterile musculoskeletal injuries. METHODS: This study used a prospective experimental laboratory study on experimental animals of BALB/c mice using a simple randomized design. Sixteen adult white BALB/c mice (male, healthy, 10-12 weeks old, 35-40 g body weight, and no disability) were selected and randomly divided into two groups: the group given lidocaine (2 mg/kg body weight) and a group that was given sterile distilled water. NF-kß and TNF-α protein levels were detected by ELISA, while mRNA expression of NF-kß was analyzed and determined by quantitative real-time PCR. RESULTS: Musculoskeletal injury significantly increased the expression of both mRNA and protein levels of NF-kß and TNF-α protein level. In addition, the NF-kß (protein and mRNA) and TNF-α (protein) levels in rats experiencing inflammation due to musculoskeletal injury were significantly decreased in the lidocaine group (p < 0.001). CONCLUSIONS: The administration of systemic lidocaine injection was able to inhibit the expression of mRNA NF-kß, the protein levels of NF-kß, and protein levels of TNF-α in mice with musculoskeletal injuries.

Exercise adaptations and TGF-ß1 levels in recreational cyclists.

BACKGROUND: Cycling is a physical exercise that is widely performed to improve physical fitness. Regular physical exercise will lead to adaptations to exercise. This adaptation is useful in suppressing the production of reactive oxygen stress (ROS) generated in response to cellular metabolism that uses oxygen. Transforming growth factor beta-1 (TGF-ß1) plays a role in increasing the production of ROS, thus, when the concentration is low, it would lead to an improvement in physical fitness. This study aims to compare levels of TGF-ß1 between recreational cyclists and sedentary groups. In addition, this research also compares several other parameters, which are fasting blood sugar levels and lipid profiles (triglycerides, total cholesterol, HDL cholesterol, and LDL cholesterol) between cyclists and sedentaries. METHODS: This was an observational analytical study with a cross-sectional design. The research subjects consisted of 2 groups, each consisting of 21 participants, namely the recreational cyclist and the sedentary group. Anthropometric examinations were carried out, including body weight, height, body mass index, waist circumference, and body fat percentage. Fasting blood glucose concentration and lipid profile (Triglyceride - TG, Total Cholesterol - Total C, HDL Cholesterol - HDL-C, and LDL Cholesterol - LDL-C) were determined by the enzymatic colorimetric methods, and TGF-ß1 levels were determined using the fluorescence of specific antibodies for TGF-ß1 (pg/ml) using ELISA method. Statistical analysis was performed using IBM SPSS v. 25. RESULTS: The anthropometric variables, other than body height, did not differ significantly between the two groups, so did the fasting blood glucose concentration. Nevertheless, the lipid profile (TG, Total C, HDL-C and LDL-C) were found to be significantly better in the cyclist group (p < 0.05).The mean level of TGF-ß1 in recreational cyclists was 8, 908.48 pg/ml, lower than the control group, 10, 229.28 pg/ml. The results of the unpaired t-test showed significant mean differences between the two groups, (p = 0.001; p < 0.05). CONCLUSION: The levels of TGF-ß1 in the recreational cyclist group were lower than the sedentary group. Regular physical exercise will trigger exercise adaptations that can suppress latent TGF-ß1 activation.

Comparison TLR2 and TLR4 serum levels in children with pulmonary and extrapulmonary tuberculosis with and without a Bacillus Calmette-Guérin (BCG) scar.

The formation of a scar after Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccination influences the effectiveness of protection against Mycobacterium tuberculosis (MTB) infection. The innate immunity plays a critical role both in the pathophysiology of tuberculosis (TB) and BCG vaccination protection mechanism. Parts of innate immunity: macrophages, dendritic cells, and neutrophils, have microbial recognition surface receptors called Toll-like receptors (TLR) 2 and 4. The objective of this study is to compare the serum levels of TLR2 and TLR4 in BCG-vaccinated pediatric patients with pulmonary and extrapulmonary TB. This cross-sectional study included children aged less than 18 years old with contracted TB disease and had received BCG vaccination. The subjects were recruited by convenience sampling from both outpatient and inpatient care at Bhakti Medicare and Jakarta Islamic Hospital, from November 2018 to December 2019. Serum TLR2 and TLR4 levels measured using ELISA of the two groups of subjects: children with pulmonary TB (PTB) and extrapulmonary TB (EPTB), were then compared. The presence of BCG scars was included in the analysis. Independent T-test, ANOVA test, and Kolmogorov-Smirnov normality tests on the SPSS program were used to statistically analyze the results. Serum TLR2 and TLR4 levels were higher in EPTB group, but the difference was not significant (TLR2 p = 0.758 and TLR4 p = 0.646, respectively). Subjects with BCG scars in both groups have significantly higher serum TLR2 and TLR4 levels than those without BCG scars in the EPTB group (EPTB p = 0.001 and p = 0.004, respectively); (PTB p < 0.001 and p < 0.001, respectively). BCG vaccination and MTB infection stimulate better innate immune response in EPTB than in PTB and serum TLR2 and TLR4 levels in those with BCG scars were higher when compared to those without BCG scars.

Comparison of 2% deoxyarbutin and 4% hydroquinone as a depigmenting agent in healthy individuals: A double-blind randomized controlled clinical trial.

BACKGROUND: Hydroquinone, which is considered the gold standard skin depigmenting agent, has been associated with multiple side effects. Lately, deoxyarbutin has been suggested to be an alternative of hydroquinone with better safety profile. OBJECTIVE: To compare the depigmenting effect of 2% deoxyarbutin and 4% hydroquinone sera. METHODS: This double-blind randomized controlled study was done on the right and left arms of healthy participants. Subjects were instructed to apply either 2% deoxyarbutin or 4% hydroquinone serum on each arm, which were randomly labeled as group A and B, every day for 12 weeks. Chromameter and mexameter analysis were done every 2 weeks to assess the color change. Paired and independent t-tests were used to assess the color change within and between both groups, respectively. RESULTS: A total of 59 females participated in this study. Both groups showed significant improvement in skin depigmentation as shown by the chromameter (increase in L* value) and mexameter (decrease in melanin index) analysis at the end of the study (p < 0.05). No significant difference in both parameters was observed between both groups (p > 0.05). No side effects were reported in either groups. CONCLUSION: 2% deoxyarbutin and 4% hydroquinone sera showed comparable depigmenting efficacy.

Relationship between expression mRNA gene Treg, Treg, CD4+, and CD8+ protein levels with TST in tuberculosis children: A nested case-control.

BACKGROUND: The ability of Mycobacterium tuberculosis to survive intracellularly, provides a cellular adaptive immune response played by specific T cells to defend against tuberculosis. The adaptive immune response to Bacillus of Calmette and Guerin (BCG) immunization is responded to by B cells, T Follicular B helper, T regulatory, restriction CD1, CD8+, CD4+, Th1, Th2, and Th17. BCG immunization can cause a tuberculin test reaction to being positive. The tuberculin test is a method for diagnosing TB infection and for screening individuals for latent infection and assessing the rate of TB infection in a given population. METHODS: a nested case-control survey was conducted on patients with a diagnosis of TB and parents 0-18 years of age from 3 hospitals in Indonesia during September-November 2019 with a total sample of 69 people undergoing clinical examinations, supporting and diagnosing subjects, blood sampling 1-2 cc for examination mRNA gene Treg, Treg, CD 4+, and CD 8+, then centrifuged at 3000 rpm for 10 min to support blood cells and serum. RESULTS: There was a significant relationship between expression of mRNA gene Treg with TST (p = 0,000), Treg with TST (p = 0,000), and CD4+ with TST (p = 0,000). Meanwhile, CD8 + was not significantly associated with TST (p = 0.118). CONCLUSIONS: It is necessary to check the expression of mRNA gene Treg, Treg, CD4+, and CD8+ with more samples to find the mean value that shows the protective value of further TB.

Analysis of CD4 and CD8 expression in multidrug-resistant tuberculosis infection with diabetes mellitus: An experimental study in mice.

BACKGROUND: Tuberculosis (TB) remains a major global health problem, in the top 10 causes of death. As a regulator of the immune response, T-helper (Th) cells activate other lymphocytes from the immune system, such as B cells, to destroy the TB pathogen by releasing CD4 and CD8 Th cells. Diabetes mellitus (DM) is a known cause of developing active pulmonary TB. Few studies have examined the biomolecular expression affecting Mycobacterium tuberculosis (MTB) and multidrug-resistant (MDR) MTB, which are associated with low immunity represented by TB in diabetes and CD4 and CD8 levels. MATERIALS AND METHODS: This animal study used a post-test control group design. We performed an experimental study using 30 BALB/c mice, each weighing 25 g. It included six experimental animal groups, of which three had a diabetes condition induced using intraperitoneal streptozotocin, and all were infected with MTB or MDR TB. We evaluated the CD4 and CD8 levels in each group and analyzed the differences. RESULTS: We found a significant difference in CD4 and CD8 levels in MTB and MDR TB conditions. CONCLUSION: This study shows that acute infection in experimental mice with MTB and MDR TB with or without diabetes had the highest levels of both CD4 and CD8 cells, which can be a sign of increased cellular immunity in a mice model.

Karnofsky Performance Scale and Neurological Assessment of Neuro-Oncology Scale as Early Predictor in Glioma.

OBJECTIVE: Glioma is one of the most frequent and disabling primary brain tumour. Patients are not only dealing with survival, but also quality of life, which remains another major concern. Karnofsky Performance Scale (KPS) is one of the most commonly used scale to assess patients' quality of life. A recent scale, known as Neurological Assessment of Neuro-Oncology Scale, has surfaced to examine neurological disability caused by brain tumour. Previous study showed this scale to be superior to KPS in predicting survival. However, these scales have never been used to foresee functional scale improvement during disease progression. We sought to determine whether initial KPS and NANO Scale can predict functional scale improvement 2 months after surgery. METHODS: Patients with glioma grade II-IV were included in the study. IDH mutation and MGMT methylation were tested. KPS and NANO scale were examined before surgery and 2 months after surgery. Favorable outcome (FO) was defined as improvement in functional scale 2 months after surgery. Patients initial functional scales were analyzed towards favorable outcome. RESULTS: Glioma WHO grade II, III and IV was found in 17 patients (36.2%), 3 patients (6.4%) and 27 patients (57.4%) respectively. Median KPS before and 2 months after surgery were 50 (30-80) and 60 (0-100), whereas median NANO scale before and 2 months after surgery were 5 (0-12) and 3 (0-12). Favorable outcome was found in 63.8% (KPS) and 78.7% (NANO Scale). Patients initial functional scales were significantly related to FO. CONCLUSION: Good initial functional scales are 4 to 5 times likely of having a favorable outcome 2 months after surgery.

Metformin improves FOXP3 mRNA expression through suppression of interferon gamma levels in pristane-induced murine models of lupus.

Background:  A recent study has indicated the potential of metformin therapy for lupus in animal models, but there has been no study evaluating the effect on pristane-induced lupus. This study aims to evaluate the effect of intraperitoneal versus oral metformin on interferon (IFN)-γ levels and FOXP3 mRNA expression on pristane-induced female BALB/c mice. Methods: In total, 31 female BALB/c mice, aged 6 weeks, were intraperitoneally induced with 0.5 ml of pristane (2,6,10,14-tetramethylpentadecane). After 120 days, the mice were grouped and treated with various treatments: normal saline 100 mcl, oral metformin 100mg/kgBW, or intraperitoneal metformin 100mg/kgBW. After 60 days of treatment, all treatment groups were sacrificed, and kidney specimens prepared and stained using hematoxylin and esosin. Results: IFNγ levels of saline controls vs. oral metformin group was 309.39 vs. 292.83 pg/mL (mean difference 16.56 pg/mL; 95% CI 0.74-32.37; p=0.042), and saline control vs. intraperitoneal metformin group was 309.39 vs. 266.90 pg/mL (mean difference 42.49 pg/mL; 95% CI 29.24-55.73 pg/mL; p<0.004). FOXP3 mRNA expression changes in saline controls vs. oral metformin group was 6.90 vs. 7.79-fold change (mean difference -0.89-fold change; 95% CI -1.68-(-0.11); p=0.03)  and in saline controls vs. intraperitoneal metformin group was 6.90 vs. 9.02-fold change (mean difference -2.12-fold change; 95% CI -2.99-(-1.25); p=<0.001). Correlation analysis of FOXP3 mRNA expression and IFNγ level changes revealed a Pearson correlation of -0.785 (p=0.001) and R2 value of 0.616 (p=0.001). Conclusion: Metformin is a potential new therapy to reduce the levels of IFNγ and increase FOXP3 mRNA expression in mice models of systemic lupus erythematosus. Intraperitoneal metformin, i.e intravenous administration in human, could provide a novel route of administration to improve the effect of metformin for lupus patients.