The potential of Myrmecodia pendans in preventing complications of diabetes mellitus as an antidiabetic and antihyperlipidemic agent.

Background: Hyperglycemia in diabetes mellitus (DM) can lead to dyslipidemia, which is a risk factor for macrovascular complications such as heart disease and stroke. Aside from administering antidiabetic medications, DM treatment can also be achieved through the use of natural components, such as Myrmecodia pendans, commonly known as the ant nest plant (ANP). Aim: This study aimed to investigate the impact of administering the ANP on the lipid profile of Wistar rats. Methods: A group of 20 rats was divided into two categories: 6 rats served as healthy controls (H), while the remaining 14 rats were subjected to a high-lipid diet and streptozotocin to generate a model of type 2 diabetes mellitus (T2DM). The diabetic rats were divided into two groups: the DM group consisted of rats that did not receive any treatment, while the ANP group was administered the herb orally. Results: The results revealed significant variations in triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels among the three groups (p < 0.05). The post hoc test revealed disparities in triglyceride and LDL between those in the DM group and the ANP group (p < 0.05). Conclusion: Myrmecodia pendans demonstrated the ability to decrease triglyceride and LDL, while increasing HDL levels in rats with T2DM.

The Effect of Secreted IL-10 from Mesenchymal Stem Cell on Immune Checkpoint Molecules.

Background: Immunosuppression in sepsis is hypothesized to result from the increased expression of the immune checkpoint molecules programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1). PD-1 and PD-L1 blockade therapies have been reported to increase survival in septic animals. Currently, the interleukin (IL)-10 within mesenchymal stem cell (MSC) secretome is known for its immunomodulatory capacity. Objective: To study the effect of IL-10 within MSC secretome on the expression of immune checkpoints in the rat model of sepsis. Methods: We used 48 male Rattus norvegicus rats in this research and divided them into four groups: sham (rats without sepsis induction and treatment), control (sepsis-induced rats without treatment), T1 (sepsis-induced rats treated with 150 µL of secreted IL-10 from MSC), and T2 (sepsis-induced rats treated with 300 µL of secreted IL-10 from MSC). Forty-eight hours after sepsis induction, we terminated the rats and collected the blood to examine the PD-1 and PD-L1 expression levels. Results: We found a decrease in the relative expression of PD-1 in the septic rat group given 150 µL and 300 µL of secreted IL-10 from MSC compared to the control group, but the decrease was not significant. We also found a decrease in the relative expression of PD-L1 mRNA in the septic rat group given 150 µL and 300 µL of secreted IL-10 from MSC compared to the control group. Conclusion: Administering secreted IL-10 from MSC reduces the expression of PD-1 and PD-L1 in sepsis. These findings suggest that MSC secretome can improve the immunosuppression in sepsis.

The Role of Mesenchymal Stem Cell Secretome in the Inflammatory Mediators and the Survival Rate of Rat Model of Sepsis.

In sepsis, simultaneously elevated levels of pro-inflammatory cytokines and interleukin (IL)-10 indicate immune response dysregulation, increasing the mortality of the host. As mesenchymal stem cell (MSC) secretome is known to have immunomodulatory effects, we aim to assess the role of MSC secretome in the inflammatory mediators (NF-κB p65 and p50, TNF-α, IL-10) and the survival rate of a rat model of sepsis. In this study, forty-eight male Rattus norvegicus rats were divided into one sham group and three groups with sepsis induction: the control group and the sepsis-induced rat groups treated with 150 µL (T1) and 300 µL (T2) of secretome. The survival rate was observed per 6 h for 48 h and plotted using the Kaplan-Meier method. Compared to the control group, T2 showed a significant decrease in the relative expression of NF-κB and the serum TNF-α level, and a significant increase in the serum IL-10 level. Meanwhile, T1 showed a significant decrease in the serum TNF-α level compared to the control group. The Kaplan-Meier Log Rank test did not show significance in the distribution of survival between T1, T2, and the control group. However, from the 18th to the 36th hour, the survival rate of T2 was lower than the survival rate of the control group and T1, with a noticeable difference between T2 and the control group, as well as T1 at the 36th hour. At the 42nd hour, the survival rate of T2 was the same as the control group and remained lower than T1. In conclusion, MSC secretome regulated the inflammatory mediators in rat model of sepsis, with a dose of 150 µL being more effective.

Correction: Sari, M.I.; Ilyas, S. The Expression Levels and Concentrations of PD-1 and PD-L1 Proteins in Septic Patients: A Systematic Review. Diagnostics 2022, 12, 2004.

There was an error in the original publication [...].

Coleus Amboinicus Lour. Leaf Extract as an Antioxidant in Sepsis.

Background: As broad-spectrum antibiotics can cause antimicrobial resistance in sepsis, there is the need for a complementary therapy to combat sepsis. Oxidative stress causes an increased severity and mortality in sepsis, whereas herbal medicines have been considered as an option due to its antioxidant potential. Coleus amboinicus Lour. has been documented for its therapeutic value due to the presence of flavonoid, an antioxidant compound. Objective: To study the effect of Coleus amboinicus Lour. leaf extract on total antioxidant capacity (TAC) and hepatic catalase (CAT) levels in septic rat model. Methods: Twenty-eight male Rattus norvegicus rats were divided into four groups: control (rats without sepsis induction and treatment), group 1 (septic rats treated with antibiotics), group 2 (septic rats treated with antibiotics and 250 mg/kg body weight of Coleus amboinicus Lour. leaf extract), and group 3 (septic rats treated with antibiotics and 500 mg/kg body weight of Coleus amboinicus Lour. leaf extract). The rats were sacrificed at the end of the eighth day of observation, and blood and liver tissues were gathered for examination. Results: Compared to the septic rat groups treated with only antibiotics, there was an increase in the TAC levels and CAT expression levels in septic rat groups given antibiotics and Coleus amboinicus Lour. leaf extract. However, the increase was not significant. Conclusion: Administering Coleus amboinicus Lour. leaf extract increases TAC levels and CAT expression levels in sepsis, decreasing oxidative stress. This will exert protective effects in the cells and therefore alleviate sepsis.

The Expression Levels and Concentrations of PD-1 and PD-L1 Proteins in Septic Patients: A Systematic Review.

Sepsis is a series of life-threatening organ dysfunction caused by an impaired host response to infection. A large number of molecular studies of sepsis have revealed complex interactions between infectious agents and hosts that result in heterogeneous manifestations of sepsis. Sepsis can cause immunosuppression and increase the expression of checkpoint inhibitor molecules, including programmed death protein (PD-1) and programmed death ligand 1 (PD-L1), and thus PD-1 and PD-L1 are thought to be useful as diagnostic and prognostic tools for sepsis. PD-1 is an inhibitor of both adaptive and innate immune responses, and is expressed on activated T lymphocytes, natural killer (NK) cells, B lymphocytes, macrophages, dendritic cells (DCs), and monocytes, whereas PD-L1 is expressed on macrophages, some activated T and B cells, and mesenchymal stem cells as well as various non-hematopoietic cells. This systematic review aims to assess the PD-1 and PD-L1 protein expression levels and concentrations in septic and other infectious patients.

The Effect of Hypoxia Inducible Factor -1 Alpha and Vascular Endothelial Growth Factor Level in Type 2 Diabetes Microvascular Complications and Development.

Background: Angiogenesis in diabetic patients is often caused by hyperglycemia induced by hypoxia. Objective: The aim of this study was to analyze the serum level of Hypoxia Inducible Factor -1α (HIF-1α) and Vascular Endothelial Growth Factor (VEGF) between March until Desember 2020. Methods: This is a cross-sectional analytic methods, 135 patients with Type 2 Diabetes 48 samples with Microvascular complication and 87 samples with non-microvascular complication were recruited from the various primary health care centers in Medan city and surrounding areas in North Sumatera. VEGF levels and HIF-1α tested were done with ELISA methods in the laboratory of Medical Faculty, Universitas Sumatera Utara. Statistical analysis was performed using the IBM SPSS Statistics version 24. The significance level was set up to 0.005. Results: The median HIF-1 levels in patients with microvascular complications were lower than those without microvascular complications, with a range of HIF-1α values in non-complicated samples (0.02-13.96) ng/ml and a range of HIF-1α values in vascular complications (0.52- 8.87) mg/dL. There was a significant difference in HIF-1α levels in patients with Type-2 DM with complications compared to those without complications (p<0.05). Median VEGF levels were higher in complicated Type-2 DM. There was no difference in VEGF levels in patients with Type-2 DM with complications compared to those without complications (p > 0.005). Conclusion: HIF-1α and VEGF levels showed the development in vascularity. With the higher level of HIF-1α, an increase in VEGF levels were found, indicating the angiogenesis is occurring. Although complications have not yet occurred, it is predicted that high VEGF values will cause vascular complications in the future.

The Relation of Haplotype ATP-binding Cassette B1 and Glutathione S-transferase P1 A313G Genes with Hematological Toxicity in Indonesian Breast Cancer Patients Receiving Chemotherapy.

Objectives: Hematological toxicity induced by chemotherapy is known to be caused by multiple factors, including genetic factors such as polymorphisms. The polymorphisms may occur in drug efflux transporter proteins and enzymes involved in drug metabolism. We investigate the incidence of hematological toxicities and their relation to the haplotype ATP-binding cassette B1 (ABCB1) which were polymorphisms of C1236T, C3435T, G2677T, and glutathione S-transferase P1 (GSTP1) A313G genes in Indonesian breast cancer patients who received anthracycline during chemotherapy. Methods: This retrospective cohort study was conducted on 138 breast cancer patients who underwent three cycles of chemotherapy in H. Adam Malik Hospital, Medan, Indonesia, who satisfied the inclusion criteria. The DNA of these patients was extracted from the peripheral leukocytes. Single nucleotide polymorphism (SNP) ABCB1 and GSTP1 were examined by the polymerase chain reaction-restriction fragment length polymorphism method. Data on patient characteristics and the incidence of hematological toxicity after each of the three cycles of chemotherapy were obtained from the medical records. The variations in absolute neutrophil count (ANC) and anemia were analyzed using the Friedmann test and the Wilcoxon signed-rank test. The Kruskal-Wallis test was used to investigate the association of ABCB1 and GSTP1 polymorphisms with anemia and neutropenia. The frequency distributions of genotypes and alleles were determined using the Hardy-Weinberg Equilibrium (HWE). Results: Post the chemotherapy cycles, there was decrease in ANC (Mean±SD: 5 644.4±2 962.5 mm3 vs. 3 034.8±2 049.6 mm3) and increase in anemia (12.1±1.5 g/dL vs. 11.2± 1.3 g/dL) (p < 0.050 for each). No relation was observed between ABCB1 polymorphism, either in each SNP or in the form of haplotype (the combination of more than one SNP), and the incidence of anemia and neutropenia (p > 0.050). There was also no correlation between GSTP1 polymorphisms, anemia and neutropenia incidence (p > 0.050). The ABCB1 and GSTP1 genotypes and alleles frequency distribution showed no deviation from HWE (p > 0.050). Conclusions: Indonesia breast cancer patients who underwent three cycles of chemotherapy demonstrated susceptibility to hematological toxicity by developing side effects such as anemia and neutropenia. However, no relationship was found between hematological toxicity and ABCB1 and GSTP1 polymorphisms.

The Association between TNF-α, IL-6, and Vitamin D Levels and COVID-19 Severity and Mortality: A Systematic Review and Meta-Analysis.

BACKGROUND: An increasing number of scientific journals have proposed a connection between tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the severity of COVID-19. Vitamin D has been discussed as a potential therapy for COVID-19 due to its immunomodulatory effects. This meta-analysis aims to determine the relationship, if any, between TNF-α, IL-6, vitamin D, and COVID-19 severity and mortality. METHODS: The design of the study is a systematic review and meta-analysis. A literature search is performed using PubMed, Cochrane, ProQuest, and Google Scholar. RESULTS: TNF-α insignificantly increases the risk of COVID-19 severity (adjusted odds ratio (aOR) = 1.0304; 95% CI 0.8178-1.2983; p = 0.80) but significantly increases the risk of COVID-19 mortality (crude hazard ratio (HR) = 1.0640; 95% CI 1.0259-1.1036; p = 0.0009). IL-6 significantly increases the risk of COVID-19 severity (aOR = 1.0284; 95% CI 1.0130-1.0441; p = 0.0003) and mortality (aOR = 1.0076; 95% CI 1.0004-1.0148; p = 0.04; adjusted hazard ratio (aHR) = 1.0036; 95% CI 1.0010-1.0061; p = 0.006). There is a statistically insignificant difference of the mean vitamin D levels between patients with severe COVID-19 and non-severe COVID-19 (mean difference (MD) = -5.0232; 95% CI 11.6832-1.6368; p = 0.14). A vitamin D deficiency insignificantly increases the risk of mortality of COVID-19 patients (aOR = 1.3827; 95% CI 0.7103-2.6916; p = 0.34). CONCLUSION: IL-6 is an independent prognostic factor towards COVID-19 severity and mortality.

Association between Glycated Hemoglobin with the Levels of Serum Proinflammatory Cytokines and Antioxidants in Patients with Type 2 Diabetes Mellitus in Universitas Sumatera Utara Hospital.

BACKGROUND: Hyperglycemia condition in diabetes mellitus (DM) influences proinflammatory cytokine levels and disrupts antioxidant balances. Glycated Hemoglobin is used as a biomarker of glycemic control in DM. AIM: This study aimed to analyse the association between glycated Hemoglobin with the levels of serum proinflammatory cytokines (interleukin (IL)-6) and antioxidants (glutathione peroxidase (GPx) and glutathione (GSH)) in type 2 diabetes mellitus (T2DM) patients in Universitas Sumatera Utara (USU) Hospital. METHODS: A total of eighty-nine T2DM patients were recruited at USU Hospital. Glycated Hemoglobin levels were measured using routine laboratory tests at USU Hospital. The IL-6, GPx, and GSH levels were measured using enzyme-linked immunosorbent (ELISA) method. The statistical significance was determined using the Kruskal Wallis test, followed by Mann-Whitney test (p < 0.05). RESULTS: The mean of glycated hemoglobin (%), IL-6 (pg/ml), GPx (ng/ml), and GSH (ng/ml) levels in T2DM patients were 8.96 ± 2.28, 59.27 ± 16.04, 32.13 ± 12.10, and 7.42 ± 3.50, respectively. Regarding the glycated Hemoglobin levels, 28.09% of patients had controlled diabetes, 24.72% of patients had poorly controlled diabetes, and 47.19% of patients had uncontrolled diabetes. The IL-6 levels of the three study groups based on glycated Hemoglobin levels were related significantly (p < 0.05), but there was no statistically significant difference observed between the GPx and GSH levels (p > 0.05). CONCLUSION: The present study suggests that the glycated Hemoglobin was associated with the levels of serum IL-6 levels but not GPx and GSH levels in T2DM patients in USU Hospital.

Superoxide Dismutase Levels and Polymorphism (Ala16val) In Tuberculosis Patients with Diabetes Mellitus in Medan City.

BACKGROUND: Infectious diseases and metabolic disorders would result in oxidative stress in cells. Superoxide dismutase (SOD) is an antioxidant present inside cells that acts against oxidative stress. SOD gene polymorphism can affect the activity and levels of SOD. AIM: This study aimed to analyse SOD levels and polymorphism of gene (ala16val) that regulated SOD in tuberculosis patients with diabetes mellitus in Medan city. METHODS: A total of 40 tuberculosis patients with diabetes mellitus and 40 healthy subjects participated in the study. The levels of SOD were measured using enzyme-linked immunosorbent assay (ELISA). Analysis of SOD gene polymorphism (ala16val) was done using polymerase chain reaction-restriction fragment lengths polymorphisms (PCR-RFLP) with BsaW1 as the restriction enzyme. The statistical significance was determined using the Mann Whitney test, Fisher's exact test, and Kruskal Wallis test (p < 0.05). RESULTS: The SOD levels of tuberculosis patients with diabetes mellitus were lower than those of the healthy subjects (102.474 ± 36.07 U/L vs 294.543 ± 58.75 U/L, p < 0.05). Patients of tuberculosis with diabetes mellitus tend to have more value/Val genotypes than the healthy group (57.5% vs 50%, p > 0.05). There was no association between SOD levels and SOD gene polymorphism (ala16val) in tuberculosis patients with diabetes mellitus. CONCLUSION: In this study, there was an association between the levels of SOD and tuberculosis patients with diabetes mellitus, but not for the SOD gene polymorphism (ala16val). The SOD gene polymorphism (ala16val) was not the key role to influence the SOD levels in tuberculosis patients with diabetes mellitus in Medan city.

The Gene Polymorphisms (-308G/A) and the Tumor Necrosis Factor-alpha Levels in Type 2 Diabetic Patients with and Without Tuberculosis Infection.

BACKGROUND: The gene polymorphism (-308G/A) and tumor necrosis factor-alpha (TNF-α) levels influence development of disease in type 2 diabetic patients and tuberculosis patients. AIM: In this study, we analyze the association between the TNF-α polymorphisms (-308G/A) and the levels of TNF-α in type 2 diabetic patients with and without tuberculosis infection. METHODS: This study was an analytic observational with cross sectional approach consisting 40 type 2 diabetic patients with tuberculosis infection, 40 type 2 diabetic patients without tuberculosis infection and 40 healthy control (HC) subjects. The TNF-α gene polymorphism (-308G/A) was analyzed with polymerase chain reaction-restriction fragment lengths polymorphisms (PCR-RFLP) method. The TNF-α levels were measured using an enzyme-linked immunosorbent assay. The association between gene polymorphism (-308G/A) in study groups was analyzed by Fisher's exact test, tumor necrosis factor-alpha (TNF-α) levels in study groups was carried out using the Kruskal-Wallis test. Hardy-Weinberg Equilibrium also determined genotype deviation and allele frequencies. RESULTS: The GG and GA+AA genotypes frequency in both of patient groups and HC subjects were not differ significantly (95% and 5% vs 95% and 5% vs 92.5% and 7.5%; p > 0.05). The TNF-α levels (pg/ml) of type 2 diabetic without tuberculosis infection were higher than those of type 2 diabetic with tuberculosis infection and HC subjects (7.42 ± 0.78 vs 2.23 ± 0.51 vs 2.57 ± 0.63; p < 0.01). The TNF-α levels in the GA+AA genotypes were higher than the GG wild-type genotype (p > 0.05). There was no significant deviation of genotype frequency and allele from Hardy-Weinberg Equilibrium. CONCLUSION: The gene polymorphism (-308G/A) had no association with type 2 diabetic patients with and without tuberculosis infection and the gene polymorphism (-308G/A) was not influence the TNF-α levels but there was a significant differentiation of TNF-α levels between the groups.

Cigarette Smoking and Hyperglycaemia in Diabetic Patients.

BACKGROUND: The incidence rate of diabetes mellitus has increased throughout the year. Various studies indicate that smoking may affect glucose metabolism and cause hyperglycemia in diabetes mellitus. This study aimed to compare the blood glucose and HbA1c level in diabetic smoking patients and non-smoking diabetic patients. METHODS: This study used the cross-sectional approach. The study population consisted of 30 diabetic smoking patients and 30 non-smoking diabetic patients. The diabetes history and the smoking status of the study population obtained by questionnaire-based interview, the blood glucose and HbA1c level were measured by hexokinase and immunoturbidimetry method using cobas 6000 analyser module c501 (Roche Diagnostics, Switzerland). RESULTS: The result in this study showed the fasting blood glucose, postprandial blood glucose, and HbA1c were higher by 23.64 mg/dl (p = 0.325), 58.00 mg/dl (p = 0.016), 0.39% (p = 0.412) in smoking diabetic patients compared to non-smoking diabetic patients. After statistical analysis, there was a significant difference (p < 0.05) of postprandial glucose level between smokers group and non-smokers group, but the non-significant difference of fasting blood glucose and HbA1c. CONCLUSIONS: This study concluded that there was a significant difference in postprandial glucose level between smokers group and non-smokers group but the non-significant difference of fasting blood glucose and HbA1c.