Non-nutritional and disease-related anemia in Indone-sia: A systematic review.

Non-nutritional anemia, the second most common type of anemia worldwide after nutritional anemia, includes the anemia of inflammation (AI) and that due to helminthiasis. In this review, we examine the contribution that non-nutritional anemia makes to incidence in Indonesia. Anemia due to helminthiasis is a common problem in Indonesia and contributes to prevalence, particularly in children under 5 years. We conducted a systematic literature review based on Google Scholar and Pubmed for non-nutritional anemia. We supplemented this with hemoglobin and chronic disease data in Makassar where prevalence and type of anemia were available. To effectively reduce anemia prevalence in Indonesia, interventions should address both nutritional and non-nutritional contributing factors, in-cluding infection and genetic predisposition.

Cytotoxicity and Apoptosis Studies of Brucein D against T24 Bladder Cancer Cells.

OBJECTIVE: Brucein D (BrD), a quassinoid isolated from Brucea javanica fruit, reportedly demonstrates anti-cancer activity. This study's objective is to evaluate the cytotoxicity of Brucein D and its ability to induce apoptosis in T24 bladder cancer cells. METHODS: We investigated the cytotoxic activity of BrD against the T24 cell through the induction of apoptosis in vitro. This cytotoxic activity was evaluated with ΜΤΤ assay and followed by Calcein-AM/PI viability staining. Apoptotic activity was determined with Hoechst 33342 nuclear staining and DNA fragmentation. Doxorubicin and docetaxel were used as a positive control. Evaluation of apoptotic-related gene expression, Bax, Bak, Bcl2, and p53 was also performed using semi-quantitative PCR analysis. Statistical analysis was conducted using One-way ANOVA followed by post hoc test Turkey's HSD (Honestly Significance Difference). RESULTS: Results show that BrD had high toxicity against T24 bladder cancer cells with an IC50 value of 7.65 ± 1.2 µg/mL but relatively less toxic to 1BR3 normal skin fibroblast cells compared to the doxorubicin and docetaxel treated cells. The viability assay shows that BrD significantly increases the percentage of dead cells relative to control in a dose-dependent manner. Furthermore, the percentage of cells with apoptotic appearance was significantly higher in group treated with BrD IC50 (56.04±3.09%) compared to control (9.42±2.88). The result was similar to doxorubicin IC50 (58.97±12.31) but lower than docetaxel IC50 (74.42±9.79). DNA fragmentation in gel electrophoresis was also observed in T24 cells treated with BrD. Apoptosis was also verified by an alteration in the expression of apoptosis-related genes, upregulation of Bax, Bak, and p53, and downregulation of Bcl-2. CONCLUSION: BrD has shown a cytotoxic effect against T24 bladder cancer cells. Hence, it is a promising natural compound for the management of bladder cancer by induction of apoptosis through activation of the intrinsic pathway, with low toxicity to normal cells.

Evaluation of Blended Learning in Terms of the Perceptions of Medical Students: A Mixed Method Study.

Introduction: The ongoing 4.0 industrial evolution, characterized by the rise of digital technology, has had a massive impact on human lifestyles worldwide. Faculty members in medical school are expected to respond to this industrial revolution by implementing teaching strategies, one of which is Blended learning as a suitable solution to overcome the limitations of space and time in the teaching process. For effective utilization of blended learning, it is important to conduct extensive studies on its implementation. The aim of this study was to assess the effectiveness and efficiency of implementing blended learning in the faculty of medicine in Hasanuddin University from the students' perspective. Methods: This study used a sequential explanatory mixed method approach, combining quantitative and qualitative methods. The quantitative part involved 782 undergraduate medical students from the first, second, and third years. Data were collected through a questionnaire survey distributed among the students. The qualitative part of the research was conducted through focus group discussions involving 13 students based on the questionnaire scores, representing both high and low scores. The results of the quantitative and qualitative research were collected and integrated. Results: Based on the results, the majority of students agreed that blended learning provided many advantages to their learning (Mean±SD: 3.79±0.78). Also, they reported e-learning platform significantly contributed to their learning process (Mean±SD: 3.88±0.67). The workload of blended learning method was still considered quite heavy by students, and good time management was highly needed (Mean±SD: 3.45±0.84). As for qualitative part, some positive results were obtained; they reported that it increased motivation for learning, enhanced the efficiency of learning and gaining adaptability, while the negative opinions were the network error in e-learning, erratic e-learning display, and video quality problem. Conclusion: Most of the students expressed positive opinions about the advantages of blended learning; according to them, learning was more efficient and effective, it enhanced learning motivation, and it provided comprehensive accessible learning materials.

Healthcare Quality Received by Insured Patients in Two Indonesian Regional Public Hospitals.

Background: Hospitals are required to improve the quality of health services provided to patients. Purpose: Evaluating and comparing the healthcare quality received by insured patients hospitalized in two Indonesian regional public hospitals. Methods: Secondary data analysis used the 2019 and 2020 Indonesian National Health Insurance e-claim databases of Hospital A and Hospital B. Descriptive and crosstabs analyses were used to determine INA-CBGs diagnoses that were categorized as high volume, high risk, and high cost. Results: The admissions that caused financial loss at the Hospital A were 21.1% in 2019 and 19.8% in 2020, while 30.3% in 2019 and 27.5% at the Hospital B. More than 60% of these admissions were placed in the 3rd class of inpatient wards of the two hospitals. Of these admissions, < 5% at the Hospital A and >5% at the Hospital B were readmitted within 30 days, although more than 90% were previously discharged based on physicians' approval. Conclusions: Inadequate healthcare quality received by insured patients. Hence, an integrated clinical pathways based professional nursing practice model is highly recommended to increase patient outcomes and decrease 30 days hospital readmission rates.

Vertebral destruction in tuberculous spondylitis correlates with Toll-like Receptor 4 (TLR-4) levels: a cross-sectional study.

Background: Tuberculous (TB) spondylitis is a hazardous infectious disease causing significant spinal deformity. Increased toll-like receptor-4 (TLR-4) activity promotes more extensive infections in patients with TB spondylitis, so it has the potential to be used as a biomarker to predict the severity. This study aims to determine the relationship between TLR-4 levels and the degree of vertebral destruction in TB spondylitis patients. Materials and methods: A cross-sectional study was conducted from May to October 2023. A total of 27 TB spondylitis samples were then measured for TLR-4 serum levels. Vertebral destruction is assessed based on the Spine At Risk Signs (SARS) criteria on X-ray and MRI examinations. Moreover, the degree of sensory and motor impairment was also assessed in this study. The Spearman correlation test assessed the correlation between TLR-4 levels and vertebral destruction. Results: Most of the samples in this study were less than 30 years old (10 people, 37%), female (14 people, 51.9%), had spinal destruction at 1 level (11 people, 40.7%), had paraplegia (8 people, 29.6%), and had hypoesthesia (11 people, 40.7%). TLR-4 levels had a mean value of 8254.1±1076.1 ng/ml. TLR-4 levels were positively correlated with the degree of vertebral destruction (r=0.599, P=0.001), motor disorders (r=0.632.x, P=0.000), and sensory disorders (r=0.574, P=0.002). Conclusion: TLR-4 levels are associated with the severity of vertebral destruction in TB spondylitis, so it has the potential to be used as a prognostic biomarker.

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.

Analysis of interleukin 7 and platelet-derived growth factor-BB mRNA expression as potential markers in erythema nodosum leprosum.

Erythema nodosum leprosum (ENL) is an immunological complication of leprosy characterized by acute inflammation of the skin, nerves, and other organs. Identifying laboratory parameters is important for early diagnosis of leprosy reactions. Various cytokine biomarkers have been examined and only a few studies have reported on angiogenesis in leprosy. This study aims to understand the pathomechanism of ENL by examining IL-7 and platelet-derived growth factor (PDGF)-BB mRNA expression that can be the development and consideration of new effective therapies to prevent reactions, recurrences, and defects in leprosy. The study used a cross-sectional analytic design. Sampling was done by peripheral blood from the patient and measuring mRNA expression with specific primers RT-PCR. The expression of mRNA IL-7 and PDGF-BB was significantly different between multibasilar patients without reaction and with ENL reaction, where there was an increased expression in ENL patients. This could be used as the development of potential biomarkers in ENL and development of new therapeutic intervention pathways in ENL.

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.

Association between angiotensin-converting enzyme (ACE) gene I/D polymorphism with the risk of knee OA: A systematic review, meta-analysis, and meta-regression.

Background: Previous studies have linked genetics to knee osteoarthritis. Angiotensin-converting enzyme (ACE) gene I/D polymorphism may cause OA. However, evidence remains inconsistent. This study examines knee OA risk and ACE gene I/D polymorphism. Methods: We explored Europe PMC, Medline, Scopus, and Cochrane Library using keywords. Three assessment bias factors were assessed using the Newcastle-Ottawa Scale (NOS). Criteria for inclusion: (1) Split the study population into knee OA patients and healthy controls; (2) Analysed the ACE gene I/D polymorphism; (3) Case-control or cross-sectional surveys. Studies with non-knee OA, incomplete data, and no full-text were excluded. The odds ratio (OR) and 95% confidence intervals (95% CI) were calculated using random-effect models. Results: A total of 6 case-control studies consist of 1,226 patients with knee OA and 1,145 healthy subjects as controls were included. Our pooled analysis revealed that a significant association between ACE gene I/D polymorphism and risk of knee OA was only seen in the dominant (DD + ID vs. II) [OR 1.69 (95% CI 1.14 - 2.50), p = 0.009, I2 = 72%], and ID vs. II [OR 1.37 (95% CI 1.01- 1.86), p = 0.04, I2 = 43%] genotype models. Other genotype models, including recessive (DD vs. ID + II), alleles (D vs. I), DD vs. ID, and DD vs. II models did not show a significant association with knee OA risk. Further regression analysis revealed that ethnicity and sex may influence those relationships in several genotype models. Conclusions: Dominant and ID vs. II ACE gene I/D polymorphism models increased knee OA risk significantly. More research with larger samples and different ethnic groups is needed to confirm our findings. After ethnicity subgroup analysis, some genetic models in our study showed significant heterogeneities, and most studies are from Asian countries with Asian populations, with little evidence on Arabs.

Effectiveness of Topical Cyclosporin-A 0.1% Compared to Combined Topical Cyclosporin-A 0.1% with Topical Sodium Hyaluronate on Interleukin-6 Levels in the Tears of Patients with Dry Eye Disease.

INTRODUCTION: Pro-inflammatory cytokines are important contributors to dry eye disease (DED). The cytokine interleukin (IL)-6 has become a therapeutic target in several DED drug studies. This randomized controlled trial aimed to determine the effectiveness of topical cyclosporin-A 0.1% compared to the combination of topical cyclosporin-A 0.1% and sodium hyaluronate in reducing tear IL-6 levels in DED patients. METHODS: The participants were 20 patients, each with two eyes, who had moderate-to-severe DED. Before and after treatment, the clinical degree of DED was examined in each group, using ocular surface disease index (OSDI) scores, tear break-up time (TBUT), fluorescent tests, and Schirmer I tests. In addition, tear samples were taken to examine IL-6 levels through the ELISA method. The results were analyzed using the t-test, Wilcoxon test, and Mann-Whitney test. The correlation between tear IL-6 levels and the severity of DED was analyzed using the Spearman correlation test. RESULTS: The study showed a significantly lower tear IL-6 level, OSDI score, and degree of ocular staining after either topical cyclosporin-A 0.1% or a combination of topical cyclosporin-A 0.1% and sodium hyaluronate (all values p < 0.05). CONCLUSIONS: The combination therapy was superior in reducing tear IL-6 levels. In addition, a correlation existed between tear IL-6 levels and the severity of DED based on the TBUT, although it was weak and not statistically significant.

Randomized controlled trial of vitamin d supplementation on toll-like receptor-2 (tlr-2) and toll-like receptor-4 (tlr-4) in tuberculosis spondylitis patients.

BACKGROUND: Tuberculosis spondylitis accounts for approximately 50% of all cases of skeletal tuberculosis. Vitamin D plays a role in the immune system. Vitamin D helps in the activation of TLR-2 and TLR-4, which play a role in the process of tuberculosis infection. The objective of this study was to investigate the effect of oral supplementation with vitamin D on TLR-2 and TLR-4 levels in tuberculosis spondylitis patients. METHODS: The true Experiment Design Pretest-Posttest with Control Group (Pretest-Posttest with Control Group) was used for this research. TLR-2 and TLR-4 were measured by ELISA. Repeated ANOVA, ANOVA tests, and Kolmogorov-Smirnov normality tests on the SPSS program were used to statistically analyze the results. RESULT: In the dose groups of 10,000 IU and 5000 IU, significant increases in the levels of vitamin D, TLR-2, and TLR-4 were observed at weeks 4 and 8 (p < 0.05). In the control group, there was no significant increase. CONCLUSIONS: Vitamin D supplements can significantly increase TLR-2 and TLR-4 levels. Supplementation with vitamin D 10,000 IU/day for 8 weeks can increase vitamin D levels > 50 ng/dl to optimally act as an immunomodulator.

Dynamic interaction of obesity, age, MCP-1 Level, and ACE-1 gene with the severity of knee osteoarthritis: a cross-sectional study.

The risk factors most strongly associated with knee osteoarthritis (OA) are old age and obesity. However, few studies have evaluated the interaction between aging and obesity in conjunction with inflammatory markers and knee OA severity as part of a complete assessment of knee OA management. Therefore, this study aims to evaluate the interaction between obesity, age, inflammation [including the I/D polymorphism of angiotensin converting enzyme-1 (ACE-1)], and the severity of knee OA. Methods: A total of 80 knee OA patients were included in this cross-sectional study. The severity of knee OA was determined based on the Kellgren-Lawrence system. All patients underwent physical and radiological examination; monocyte chemoattractant protein 1 (MCP-1) markers were measured. The parameters of the ACE-1 gene were examined with sequencing DNA. Results: There was a significant relationship between age and severity of knee OA (P=0.007), with subjects aged greater than or equal to 65 having a 3.56-fold higher risk of developing moderate to severe OA than subjects aged less than 65. There was a significant difference between body weight and knee OA severity (P=0.026), in which subjects weighing greater than or equal to 60 kg had 3.14 times the risk of experiencing severe knee OA. Multivariate regression analysis indicated that age was the strongest independent variable for knee OA severity compared with body weight. MCP-1 levels were significantly higher in mild knee OA than in moderate to severe knee OA. The DD genotype of the ACE-1 gene increases the risk of severe knee OA by four times in subjects aged greater than or equal to 65 compared to subjects aged less than 65. However, the DD genotype of the ACE-1 gene does not increase the risk of severe knee OA in subjects weighing greater than or equal to 60 kg. Conclusion: While obesity and age were found to be associated with the severity of knee OA, age emerged as the independent risk factor for knee OA severity. Furthermore, MCP-1 levels were significantly higher in cases of mild knee OA compared to severe knee OA. It was observed that the DD genotype of the ACE-1 gene increases the risk of severe knee OA in individuals aged 65 years or older.

The level of ratio between matrix metalloproteinase-1 (MMP-1) and tissue inhibitor matrix metalloproteinase-1 (TIMP-1) after prolotherapy intervention and the functional outcome in patient with frozen shoulder: A randomized controlled trial.

OBJECTIVE: To determine the effect of prolotherapy on functional outcome changes, along with ratio of matrix metalloproteinase-1 (MMP-1)/tissue inhibitor matrix metalloproteinase-1 (TIMP-1) as an indicator of tissue repair in the glenohumeral joint in frozen shoulder patients. DESIGN: Single-blinded randomized controlled trial. SUBJECTS/PATIENTS: Participants with frozen shoulder. METHODS: The prolotherapy group is the study group, and the normal saline (NS) group is the control group. Each group was given injections at weeks 0, 2, 4, and 6. Level of biomarker levels was measured at week 6 and week 12 after there. Functional outcomes were measured at weeks 0, 6, and 12. RESULTS: A significant difference in week 6 and week 12 was demonstrated in the ratio of MMP-1/TIMP-1 level between the prolotherapy group and the normal saline group (P value = .002). Both groups performed well regarding the Numerical Rating Scale score and functional outcome. Compared to the normal saline group, prolotherapy changed the mean range of motion in flexion and internal rotation. CONCLUSION: Prolotherapy is considered to play a role in repairing cartilage based on biomarker assessment, particularly the ratio of MMP-1/TIMP-1-prolotherapy effectiveness in improving functional outcome and Numerical Rating Scale score.

Anti-inflammatory effects of banana (Musa balbisiana) peel extract on acne vulgaris: In vivo and in silico study.

Objective: Acne vulgaris (AV) is a common problem with a relatively high incidence rate among Asian people. The potential antimicrobial and anti-inflammatory properties of banana peels have been demonstrated in previous studies but have not been studied in cases of AV. Therefore, this study was aimed at investigating the protective effects of banana (Musa balbisiana) peel extract (MBPE) against AV. Methods: Thirty rats were divided into five groups (n = 6 rats per group): an AV group, AV group treated with 0.15% MBPE, AV group administered 0.30% MBPE, AV group administered 0.60% MBPE, and AV group administered clindamycin (the standard drug treatment). We assessed nodule size, bacterial count, histopathology, and cytokine levels (IL-1α, IFN-γ, tumor necrosis factor (TNF)-α, and IL-8). Enzyme linked immunoassays were used to measure the cytokine levels. In addition, we performed molecular docking studies to determine the interactions between phytochemicals (trigonelline, vanillin, ferulic acid, isovanillic acid, rutin, and salsolinol) via the Toll-like receptor 2 (TLR2) and nuclear factor-kappa B (NF-κB) pathways. Results: All MBPE treatment groups, compared with the AV group, showed suppression of both bacterial growth and proinflammatory cytokine production, as well as resolved tissue inflammation. The nodule size was significantly suppressed in the groups receiving the two highest doses of MBPE, compared with the AV group. However, the pharmacological action of MBPE remained inferior to that of clindamycin. Docking studies demonstrated that rutin was the phytocompound with the most negative interaction energy with TLR2 or NF-κB. Conclusions: Our results indicated that MBPE has anti-inflammatory effects against AV, by suppressing nodule formation, inhibiting bacterial growth, and decreasing proinflammatory cytokine production.

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.

Serum iron levels in tuberculosis patients and household contacts and its association with natural resistance-associated macrophage protein 1 polymorphism and expression.

BACKGROUND: Iron deficiency can impair immune function, increasing tuberculosis (TB) susceptibility and severity. The research aimed to investigate iron deficiency anemia in TB patients and household contacts and its association with natural resistance-associated macrophage protein 1 (NRAMP1) polymorphism and expression. METHODS: The levels of iron, ferritin, and transferrin were measured in the serum by ELISA (Enzyme-Linked Immunosorbent Assay). NRAMP1 polymorphisms were determined by polymerase chain reaction (PCR) and sequencing. NRAMP1 gene expression was measured by real-time PCR. Interferon-gamma release assay (IGRA) checked on household contacts to screen household contacts with positive IGRA as the control. RESULTS: This study involved 35 TB cases and 35 TB contacts. The results showed that the serum Fe levels were found to be lower in the TB case group (median 149.6 µmol/L) than in the positive IGRA household contacts group (median 628.53 µmol/L) with a p-value <0.001. Meanwhile, ferritin levels in TB cases tended to be higher, in contrast to transferrin, which was found to tend to be lower in TB cases than household contacts but did not show a significant difference. This study found no association between the polymorphism of exon 15 D543 and active TB. However, NRAMP1 gene expression was lower in TB cases than in positive IGRA household contacts (p = 0.011). Besides, there was a positive correlation between NRAMP1 gene expression and serum Fe levels (r = 0.367, p = 0.006). TB was associated with decreased NRAMP1 gene expression (OR 0.086 95% CI 0.02-0.366, p = 0.001). Besides, TB was associated with low Fe levels (OR 0.533 95% CI 0.453-0.629, p < 0.001). CONCLUSION: Comparing the TB case to the household contacts group, decreased serum Fe levels were discovered in the TB case group. This study also shows a correlation of NRAMP1 gene expression to Fe levels in TB patients and household contacts and describes that TB may lead to decreased Fe levels by downregulating NRAMP1 expression.

Comparison between Neutralization Capacity of Antibodies Elicited by COVID-19 Natural Infection and Vaccination in Indonesia: A Prospective Cohort.

BACKGROUND: To fight the COVID-19 pandemic, immunity against SARS-CoV-2 should be achieved not only through natural infection but also by vaccination. The effect of COVID-19 vaccination on previously infected persons is debatable. METHODS: A prospective cohort was undergone to collect sera from unvaccinated survivors and vaccinated persons-with and without COVID-19 pre-infection. The sera were analyzed for the anti-receptor binding domain (RBD) titers by ELISA and for the capacity to neutralize the pseudovirus of the Wuhan-Hu-1 strain by luciferase assays. RESULTS: Neither the antibody titers nor the neutralization capacity was significantly different between the three groups. However, the correlation between the antibody titers and the percentage of viral neutralization derived from sera of unvaccinated survivors was higher than that from vaccinated persons with pre-infection and vaccinated naïve individuals (Spearman correlation coefficient (r) = -0.8558; 95% CI, -0.9259 to -0.7288), p < 0.0001 vs. -0.7855; 95% CI, -0.8877 to -0.6096, p < 0.0001 and -0.581; 95% CI, -0.7679 to -0.3028, p = 0.0002, respectively), indicating the capacity to neutralize the virus is most superior by infection alone. CONCLUSIONS: Vaccines induce anti-RBD titers as high as the natural infection with lower neutralization capacity, and it does not boost immunity in pre-infected persons.

Colorectal cancer patients' outcome in correlation with dietary and nutritional status: a systematic review.

Colorectal cancer (CRC) is one of the most common cancers worldwide and it involves various biomolecular and cellular levels. CRC has possibly happened due to aging, urbanization, and diet. Different foods have varying effects on the gastrointestinal cells, that's why additional research is necessary to create effective medical interventions. This review aimed to evaluate the correlation between dietary and nutritional status on the outcome of CRC patients. Study results showed that a healthy diet such as fruit and vegetables is the best diet for improving colorectal cancer outcomes. Moreover, nutritional status affected CRC patients' outcomes, where high BMI increases the risk of having CRC. However, low BMI was associated with CRC progression and poor quality of life.

Decreasing mRNA HMGB1 expression in Klebsiella pneumoniae infection treated by Miana (Coleus scutellarioides (L.) Benth): a cohort experimental study.

Pneumonia is one of the most common infections caused by the bacterium Klebsiella pneumoniae. During the initiation of an infection, the immune system recognizes the pathogen through the release of high mobility group box 1 (HMGB1), thereby triggering the inflammation process. Miana has demonstrated potent inhibitory effects on the inflammatory process during infection in animal models. The aim of this study was to determine the effect of Miana leaf extract on mRNA HMGB1 expression in Balb/c mice infected with K. pneumoniae. Methods: This study comprised a cohort experiment using 20 Balb/c mice divided into four groups. Balb/c mice in each group were intraperitoneally injected with K. pneumoniae. Group 1 was given a placebo; Group 2 was given Miana; Group 3 was given levofloxacin; and Group 4 was given both levofloxacin and Miana. The levels of mRNA HMGB1 expression were measured using real-time PCR before, during, and after the infection as well as after the treatments. Results: The initial examination results showed that the average level of mRNA HMGB1 expression was 5.51 fc. The mRNA HMGB1 expression in mice after being challenged with K. pneumoniae was 9.64 fc. Group 1 that was given a placebo had a mean mRNA HMGB1 expression level of 14.99 fc. Group 2 that was given Miana had a mean mRNA HMGB1 expression level of 13.95 fc. Group 3 that was given levofloxacin had an average mRNA HMGB1 expression level of 6.45 fc, and Group 4 that was given levofloxacin and Miana together had an average mRNA HMGB1 expression level of 5.59 fc. Conclusion: Miana (Coleus scutellarioides (L.) Benth) increased mRNA HMGB1 expression at the initial administration via regulation of the immune system. Administration of Miana following K. pneumoniae infection inhibited the increase in mRNA HMGB1 expression. Treatment with levofloxacin reduced the level of mRNA HMGB1 expression, and the effect was optimized by the administration of Miana leaf extract as a supplement.

Serum concentration and mRNA expression of Transforming Growth Factor-Beta 1 (TGF-ß1) in stunted and non- stunted toddlers.

BACKGROUND AND AIMS: West Nusa Tenggara Province has the fifth-highest prevalence of stunting cases in Indonesia. So far, limited research is available to understand the likelihood of stunting in this region. Transforming Growth Factor-Beta 1 (TGF-ß1), an immunoregulatory cytokine, may affect the stunting progression. Knowledge of messenger mRNA expression in the TGF-ß1 gene in stunted toddlers could help to determine therapeutic targets to catch up on their growth. OBJECTIVE: This study compared the expression of TGF- ß1 mRNA and TGF-ß1 concentrations in the stunted and the non-stunted toddlers. The nutritional status of all participants was also gathered and linked to the stunting issue. METHODS: A cross-sectional study was conducted on 48 toddlers aged 12-36 months. The stunting case was defined as a Z-Score of less than -2 of length/height for age according to WHO. The serum TGF-ß1 and TGF-ß1 gene mRNA were measured using ELISA and RT-PCR, respectively. The nutritional status data were collected through interviewer-administered structured questionnaire to the toddlers' parents and 48-h food recalls. Descriptive analyses were applied to determine the distribution of participants' macronutrient and micronutrient levels. RESULTS: Results show that there were significant differences in expressions of the TGF- ß1 gene mRNA of the stunted and the non-stunted toddlers. The expression of the TGF- ß1 mRNA gene in the non-stunted toddlers was also higher with 13.7 ± 0.859 fold change than those of the stunted toddlers with 9.01 ± 1.76 fold change with a p-value <0.001. The serum TGF-ß1 concentrations in the stunted toddler (6.20 ± 3.60 pg/ml) were significantly lower than the ones in the non-stunted toddlers (14.3 ± 1.05 pg/ml) with p-value <0.001. However, there was no clear relationship between the likelihood of stunting and the nutritional status from the obtained data. CONCLUSION: Overall findings demonstrate the significantly lower both the TGF-ß1 gene mRNA expression and serum TGF-ß1 for the stunted toddlers than the non-stunted toddlers, impacting bone formation and resorption. The outcomes of this study encourage the development of interventional therapy for stunted toddlers by increasing the serum TGF-ß1 concentrations.