Strong Association of Metabolic Parameters with ADMA and VCAM-1 in Normo-Weight Subjects with Metabolic Syndrome.

Background: Metabolic syndrome (MetS) is a risk factor for cardiovascular disease and is linked to obesity. Subjects with MetS who have normo-weight potentially show higher mortality and morbidity. Purpose: This study aims to reveal the critical essential metabolic parameters associated with endothelial dysfunction in MetS subjects with normo-weight compared to obese. Patients and Methods: The study was designed using a case-control approach. Ninety-nine MetS subjects (34 Normo-weight and 65 obese) from the urban population were enrolled in this study. The components of MetS are based on NCEP/ATP III criteria. Asymmetric dimethylarginine (ADMA) and vascular cell adhesion molecule 1 (VCAM-1) as markers for endothelial dysfunction were measured in both groups. Results: Fasting blood glucose (FBG) levels were higher in the normo-weight group (143.38 ± 79.8 mg/dL) compared to the obese group (120.89 ± 46.5 mg/dL). High-density lipoprotein cholesterol (HDL-c) levels in the normo-weight group were lower (42.82 ± 10.1 mg/dL) compared to obesity (45.74 ± 9.3 mg/dL), while triacylglycerol (TAG) levels were higher in the obese (197.25 ± 110.5 mg/dL) compared to the normo-weight group (167.03 ± 98.4 mg/dL), although the differences were statistically not significant (all p > 0.05). The difference between ADMA and VCAM-1 levels was statistically not significant in both groups. Correlation between MetS components with endothelial dysfunction parameters shows that metabolic parameters correlate strongly. Interestingly, a stronger correlation between FBG and ADMA was observed in normo-weight (r = 0.519) compared to obese groups (r = 0.445). In addition, TAG consistently shows a significant correlation with ADMA and VCAM-1 in normo-weight groups. Conclusion: Metabolic parameters, especially FBG and TAG, correlate strongly with endothelial dysfunction parameters in normo-weight subjects with metabolic syndrome.

Effect of Immunomodulating Extract and Some Isolates from Etlingera rubroloba A.D. Poulsen Fruits on Diabetic Patients with Tuberculosis.

Diabetes mellitus (DM) is a disease easily complicated by tuberculosis (TB) due to impaired function of the innate immune response. The successes of the discovery of immunomodulatory compounds needs to be continued to introduce new insights into the innate immune response. In previous studies, plant compounds of Etlingera rubroloba A.D. Poulsen (E.rubroloba) were demonstrated to have potential as an immunomodulators. This study aims to isolate and identify the structure of the compounds of E.rubroloba fruit that could effectively improve the function of the innate immune response in individuals with DM infected with TB. The isolation and purification of the compounds of the E.rubroloba extract were carried out by radial chromatography (RC) and thin-layer chromatography (TLC). Identification of the isolated compound structures was determined by measuring the proton (1H) and carbon (13C) nuclear magnetic resonance (NMR). In vitro testing was performed on the immunomodulating activity of the extracts and isolated compounds on DM model macrophages infected with TB antigens. This study succeeded at isolating and identifying the structures of two isolate compounds, namely Sinaphyl alcohol diacetat (BER-1), and Ergosterol peroxide (BER-6). The two isolates were more effective as immunomodulators than the positive controls were, which differed significantly (* p < 0.05) at the reducing interleukin-12 (IL-12) levels and Toll-like receptor-2 (TLR-2) protein expression and increasing the human leucocyte antigen-DR (HLA-DR) protein expression in DM infected with TB. The isolated compound was discovered in E. rubroloba fruits, which has been reported to have the potential to be developed as an immunomodulatory agent. Follow-up testing to determine the mechanism and effectiveness of these compounds as immunomodulators for DM patients is required so that they are not susceptible to TB infection.

Phytochemical Analysis and Immunomodulatory Potential on Diabetic-Infected Tuberculosis by Fruit Etlingera rubroloba A.D. Poulsen.

<b>Background and Objective:</b> <i> Etlingera rubroloba</i> (<i>E. rubroloba</i>) A.D. Poulsen is an endemic plant in South-East Sulawesi and is a newly discovered species. This plant is expected to have the potential as an immunomodulator in patients with diabetes mellitus (DM), which can prevent tuberculosis infection by increasing the phagocytic function of macrophage cells and interleukin-12 (IL-12) levels. <b>Materials and Methods:</b> Phytochemical analysis of the ethanolic extract of the fruit of <i>E. rubroloba</i> A.D. Poulsen using Liquid Chromatography-Mass Spectrometry (LC-MS/MS) was carried out. The immunomodulatory potential <i>in vivo</i> on BALB/c mice model DM was carried out by oral induction of TB antigen with extract dose, control positive, negative and normal groups. Furthermore, the phagocytic activity of macrophage cells can be seen with a microscope and the levels of IL-12 with the Elisa kit. <b>Results:</b> The results showed the ethanol extract of the fruit of <i>E. rubroloba</i> contained eight chemical compounds and had potential as immunomodulators in BALB/c DM mice induced by TB antigen by increasing the phagocytic activity of macrophage cells and levels of IL-12, which were significantly different from the negative control (p<0.05). <b>Conclusion:</b> The chemical composition of the ethanol extract of the fruit of <i>E. rubroloba</i> has the potential as an immunomodulator in TB antigen-induced DM <i>in vivo</i>.

Exploring alternative cytokines as potential biomarkers for latent tuberculosis infection in pregnant women.

BACKGROUND: Interferon gamma release assays (IGRAs) are widely used to determine latent tuberculosis infection status. However, its pregnancy-affected performance and cost-expensive nature warrants for different alternatives for pregnant women. This study aims to evaluate the diagnostic performance of several alternative cytokines, including interleukin 2 (IL-2), interleukin 10 (IL-10), and interferon gamma-induced protein 10 (IP-10) to identify latent tuberculosis status in pregnant women. MATERIALS AND METHODS: 123 pregnant womens were recruited for this study. The IGRA status was determined by using QuantiFERON Gold In-Tube. Meanwhile, we measured the level IL-2, IL-10, and IP-10 by using sandwich-microELISA method. We performed normality and comparison test by SPSS. In addition, receiver-operator characteristic (ROC) analyses and the optimal cutoff scores were identified using the EasyROC webtool. RESULTS: We showed that IL-2, IL-10, and IP-10 were able to discriminate between IGRA-negative and IGRA-positive pregnant women. Moreover, IP-10 showed the highest discriminatory and diagnostic performance when compared to IL-2 and IL-10 with area under the curve (AUC) of 0.96 and cutoff point of 649.65 pg/mL. CONCLUSIONS: Our study showed that IP-10 can be considered as a promising alternative biomarker for IGRAs to diagnose LTBI in pregnant women.

Cardiometabolic risk factors in adults with normal weight obesity: A systematic review and meta-analysis.

Normal weight obesity (NWO) is a new emerging phenotype of obesity, defined as a normal body mass index with a high body fat percentage. While several studies have described the impact of NWO on cardiometabolic risk factors, the association between them remains uncertain. This meta-analysis systematically evaluated cardiometabolic risk factors in adults with NWO compared to adults with normal weight lean (NWL). A systematic literature search was performed from the inception until September 21, 2021 in order to comprehensively search for all observational studies that had three important variables, including adults (age ≥18 years old), NWO and cardiometabolic risk factors including metabolic syndrome, hypertension, diabetes mellitus, dyslipidaemia or all laboratory findings related to cardiometabolic risk factors. Twenty-four cross-sectional studies with a total of 75 201 subjects are included in the qualitative and quantitative analysis. Overall, older age and female sex are more likely in NWO population. Compared to NWL, NWO is significantly associated with cardiometabolic risk factors, including metabolic syndrome (OR = 2.24 [1.74, 2.89]; p < .001; I2  = 76%, Pheterogeneity < 0.001), hypertension (OR = 1.60[1.36, 1.89]; p < .001; I2  = 76%, Pheterogeneity < 0.001), diabetes mellitus (OR = 1.72[1.54, 1.92]; p < .001; I2  = 47%, Pheterogeneity < 0.001), dyslipidaemia (OR = 1.50 [1.03, 2.18]; p = .03; I2  = 94%, Pheterogeneity < 0.001) and other laboratory findings, except for C-reactive protein in both sexes group; and adiponectin levels in female group. Our meta-analysis showed that NWO was associated with cardiometabolic risk factors. Thus, the traditional definition of obesity using the BMI criteria should be challenged, as those with NWO might still be exposed to a heightened risk of cardiometabolic disorders. Nonetheless, further prospective cohort studies are needed better to understand this syndrome.

Phytochemical Screening, Toxicity Activity and Antioxidant Capacity of Ethanolic Extract of Etlingera alba Rhizome.

<b>Background and Objective:</b> <i>Etlingera alba </i>(Blume) A.D. Poulsen is one of the plants of the genus <i>Etlingera</i> which is commonly found in Southeast Sulawesi. The research is still lacking, thus, we assumed other species related to <i>E. alba,</i> specifically from the genus<i> Etlingera</i> that provides antioxidant and radical scavenging activity, namely <i>Etlingera elatior</i> (Jack) R.M. Smith. Thus, this study aimed to assess the antioxidant and toxicity activity as well as its secondary metabolites. <b>Materials and Methods:</b> <i>Etlingera alba</i> rhizome was extracted with 96% ethanol. The radical scavenging activity was assayed with 1,1-diphenyl-2-picrylhydrazyl (DPPH) and antioxidant activity was assayed with 2,2'-azino-bis-[3-ethylbenzothiazoline sulphonate (ABTS) assay for radical cation decolourization<i> in vitro</i>. Both Ascorbic Acid (AA) and Trolox were used as positive control. The secondary metabolites were identified by Thin Layer Chromatography (TLC) and LSMS/MS analyzed the difference between compounds. According to results performed with TLC and LCMS/MS. <b>Results:</b> The extract exhibited antioxidant properties using both DPPH and ABTS method. The LC₅₀ of the extract was 608.42±18.31 mg L¹.<i> Etlingera alba </i>rhizome extract contains alkaloids, flavonoids, terpenoids and steroids. The compounds detected in the extract were E-p-Coumaric acid aschantin, 2-Methoxyanofinic acid, Chavicol-ß-D-glucoside, Myristicanol B, ent-16α,17-Hydroxy-19-kaurenoic acid, 5-Hydroxy-7,8,2'-trimethoxyflavone, Methyl ursolate and Spinasterol. <b>Conclusion:</b> <i>Etlingera alba</i> rhizome contains several compounds that might be responsible for antioxidant activity and the extract itself classified as medium toxic.

Iron Overload in Transfusion-Dependent Indonesian Thalassemic Patients.

Thalassemia is a genetic disease caused by disruption of globin chain synthesis leading to severe anemia and thus regular blood transfusion is necessary. However, there have been known transfusions-related consequences, including iron overload and multi-organ damage. The aims of this study were to evaluate liver and cardiac function in youth and adult transfusion-dependent Indonesian thalassemic patients and to assess its correlation with serum ferritin levels, as well as T2 ∗ magnetic resonance imaging (MRI). Transfusion-dependent thalassemic (TDT) outpatients (n = 66; mean age, 21.5 ± 7.2 years) were carried out for the complete assessment consisting of blood test including liver enzyme and serum ferritin, followed by electrocardiography (ECG) and echocardiography. Subjects were also divided by serum ferritin levels into three groups: < 2500 ng/mL, 2500-5000 ng/mL, and >5000 ng/mL. Additionally, subgroup analysis in patients with T2∗ MRI assessment was conducted. In terms of age of first blood transfusion, subjects with ferritin >5000 ng/mL were the youngest among others. The alanine aminotransferase (ALT) levels in group with serum ferritin >5000 ng/mL were significantly higher than those of the group with serum ferritin <2500 ng/mL. Additionally, youth and adult TDT patients whose serum ferritin >5000 ng/mL had significantly lower tricuspid annular plane systolic excursion (TAPSE) when compared with those who had serum ferritin <2500 ng/mL. Similarly, TAPSE in patients with moderate cardiac siderosis based on cardiac T2∗ MRI was significantly lower than those without cardiac siderosis. There was significant, but only moderate correlation between serum ferritin and cardiac T2∗ MRI. Based on these findings, it is important to routinely monitor iron accumulation-related complications, including liver and cardiac damage in youth and adult TDT patients.

Iron Status in Newly Diagnosed ß-Thalassemia Major: High Rate of Iron Status due to Erythropoiesis Drive.

BACKGROUND: Iron overload in severe ß-thalassemia is a serious complication that occurs during the course of the disease. Information about the iron status during initial illness with ß-thalassemia major seemed to be limited. This study is aimed at analyzing iron status, serum hepcidin, and growth differentiation factor 15 (GDF15) levels in newly diagnosed ß-thalassemia major. METHODS: A case-control study was performed at Dr. Hasan Sadikin General Hospital, which included 41 children with newly diagnosed ß-thalassemia major. Age- and sex-matched controls were enrolled. The subjects had no blood transfusion, had normal liver function, and had no sign of inflammation. The groups were compared in terms of the levels of hemoglobin (Hb), serum ferritin (SF), transferrin saturation (TS), serum hepcidin, and GDF15 as iron homeostasis parameters. RESULTS: Of the 41 newly diagnosed ß-thalassemia major patients, those who were less than 24 months old had significantly lower median Hb levels than controls (5.0 vs. 11.7 g/dL, P < 0.001). The median SF and TS levels were significantly higher than those in controls (315.0 vs. 29.0 ng/mL, P < 0.001; 70.6 vs. 16.5%, P < 0.001), and median hepcidin was at the normal limit, but the value was higher in patients (251.0 vs. 123.1 ng/mL, P < 0.001). The median GDF15 level was significantly higher in patients (2,095.3 vs. 342.4 pg/mL, P < 0.001). There was a positive correlation between SF-TS, SF-hepcidin, TS-hepcidin, SF-GDF15, TS-GDF15, and hepcidin-GDF15 (P < 0.001). CONCLUSION: In newly diagnosed ß-thalassemia major, an increase in iron status occurred. This may be caused by increased iron absorption due to massive erythropoietic activity, characterized by an increase in GDF15 levels, which does not cause hepcidin suppression. The iron homeostasis response seems to be physiologically indicated by a tendency to increase hepcidin levels.

Correlation between Serum Fatty Acid Binding Protein 4 (FABP4) Levels and Cardiac Function in Patients with Thalassemia Major.

BACKGROUND: Patients with thalassemia major may suffer from complications due to iron overload. It has been suggested that several adipokines may play a potential role in the development of complications in thalassemia. Fatty acid-binding protein 4 (FABP4) is one of the adipokines, bridging several aspects of metabolic and inflammatory pathways. Little is known about the relationship between this adipokine and cardiac and liver function, especially in patients with thalassemia major. AIMS: This study is aimed at determining serum FABP4 levels in patients with thalassemia major and whether its concentration correlated with serum ferritin levels, as well as cardiac and liver function. METHODS: Thalassemia major outpatients (n = 48) completed laboratory examination, echocardiography, and electrocardiography. RESULTS: The mean age was 21.9 ± 8.0 years. A negative and weak correlation between serum ferritin and FABP4 was observed (r = -0.291, p < 0.05). In addition, there was moderate and positive correlation between left atrial volume index (LAVI) and FABP4 (r = 0.316, p < 0.05). CONCLUSIONS: Serum FABP4 correlated with serum ferritin and cardiac function in patients with thalassemia major. FABP4 may be a potential clinical biomarker for cardiac dysfunction via metabolic and inflammatory pathways due to iron accumulation and toxicity in patients with thalassemia major.

Cytotoxic and Antimigration Activity of Etlingera alba (A.D.) Poulsen Rhizome.

Etlingera alba is one of the Etlingera plants that might have anticancer activity. This study aims to investigate the cytotoxic and antimetastatic activity of E. alba rhizome fractions and migration cell assay against MDA-MB-231 cell lines, which are used for triple-negative breast cancer (TNBC) treatment assay. The cytotoxic activity was assayed using CCK-8 assay, while the antimetastatic was assayed using migration cell assay for the fractions A-F. They were followed by LCMS/MS profiling to determine the chemical contents in the most active fraction. According to results obtained, fraction B was the most active fraction for cytotoxic activity with an IC50 value of 65.43 µg/mL, while fraction E was the most active fraction for antimetastasis activity against migration rate doses of 50, 100, and 200 ppm which were 6.80, 3.66, and 3.00%, respectively. Several compounds in fraction B, such as rengyolone, licochalcone A, sugiol, and spinasterol, might have been known to have activity against cancer cells, as well as aschantin and lirioresinol B dimethyl ether from fraction E. In conclusion, the chemical components from E. alba rhizome fractions provided potency for discovering new agents for cancer treatment, specifically for TNBC.

Traditional Herbal Medicine Candidates as Complementary Treatments for COVID-19: A Review of Their Mechanisms, Pros and Cons.

Coronavirus disease 2019 (COVID-19) is a new infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that belongs to the coronavirus family. The first case was reported in December 2019, and the disease has become a pandemic. Impaired immune regulation is one of the factors that play a role in its pathogenesis and results in poor outcomes of COVID-19 patients. There have been many studies with drug candidates used as antivirals or immunomodulators. However, the results of these investigations showed that the drug candidates were not significantly effective against the disease. Meanwhile, people believe that consuming herbal immunomodulators can prevent or even cure COVID-19. Unfortunately, specific preclinical and clinical trials to evaluate the effects of herbal immunoregulators have not been conducted. Certain natural compounds might be effective for the treatment of COVID-19 based on general concepts from previous experiments. This review discusses some herbal agents extracted from various plants, including Echinacea, Cinchona, Curcuma longa, and Curcuma xanthorrhiza, which are considered for the treatment of COVID-19. In addition, we discuss the pros and cons of utilising herbal medicine during the COVID-19 pandemic, draw some conclusions, and make recommendations at the end of the session.

Association of first trimester maternal vitamin D, ferritin and hemoglobin level with third trimester fetal biometry: result from cohort study on vitamin D status and its impact during pregnancy and childhood in Indonesia.

INTRODUCTION: The role of vitamin D in placental functions and fetal growth had been addressed in many reports with conflicting results. However, such report is limited for Indonesian population. The aim of this study was to explore the association between maternal vitamin D level in the first trimester and fetal biometry in the later stage of pregnancy with adjusted OR for other determinants like hemoglobin and ferritin level. METHODS: From July 2016 a prospective cohort study of pregnant women had begun in four cities in West Java, Indonesia. Data on maternal vitamin D, ferritin, hemoglobin level, maternal demography and fetal biometry were analyzed with linear regression. RESULTS: Among 203 recruited women, 195 (96.06%) had hypovitaminosis D. One hundred fifty two (75%) were in deficient state and 43 women (21%) were in insufficient state. Women with insufficient vitamin D had the highest proportion of anemia, while women with normal vitamin D level had the highest proportion of low ferritin level. Maternal serum vitamin D showed significant associations with biparietal diameter (ß = 0.141, p = 0.042) and abdominal circumference (ß = 0.819, p = 0.001) after adjustment with maternal age, pre-pregnancy body mass index, parity, serum ferritin level, and hemoglobin level. CONCLUSION: Our study suggested that sufficient maternal vitamin D level was an important factor to improve fetal growth and development.

Fcγ receptor III expression and morphological maturity on neutrophil are associated with higher iron level of major beta-thalassemia.

Lifetime blood transfusion experienced by major ß-thalassemia patients complicated with iron overload, therefore, may lead to their tissue injury. Ultimately, free toxic iron may alter immune response via dysregulation of immune cell activity producing prolonged effector reaction. Neutrophil as one of the vital innate immune cell despite serves as the first line of defense resulting acute inflammation has a pivotal role in chronic inflammation while releasing the toxic substance that interferes biological processes. This process is initiated by one of them by activation of Fcγ Receptor III (CD16), a neutrophil membrane-bound protein. A cross-sectional laboratory study involving lysed-erythrocyte heparinized whole blood of fifty pediatric major ß-thalassemia patients treated with monoclonal antibodies i.e. CD16, CD14, and HLA-DR, dissected into CD16+ and CD16++ population using flow cytometry. Expression of Fcγ Receptor III was measured as Median Fluorescent Intensity (MFI). Hematology and iron status were measured. A correlation analysis was done. MFI of CD16 neutrophil [509.5 (371 - 796.5)] and ferritin level [(3209 µg/L, 1862 - 4564)] was positively correlated (r = 0.4, P = 0.007). Respectively, ferritin and serum iron were found negatively correlated with segmented neutrophils (r = -0.3, P = 0.02; r = -0.3, P = 0.02). Change in CD16 expression may implicate preliminarily neutrophil activation as a response of iron-overloaded tissue and result in chronic inflammation in ß-thalassemia patients. However, the maturity of this cell may be altered.  Future study in the understanding of neutrophil-mediated inflammation, particularly related to immune complexes and functionality, is imperative to be explored.