Tamoxifen is the first line drug used in the treatment of estrogen receptor-positive (ER+) breast cancer. The development of multidrug resistance (MDR) to tamoxifen remains a major challenge in the treatment of cancer. One of the mechanisms related to MDR is decrease of drug influx via overexpression of drug efflux transporters such as P-glycoprotein (P-gp/MDR1), multidrug resistance associated protein (MRP), or BCRP (breast cancer resistance protein). We aimed to investigate whether the sensitivity of tamoxifen to the cells is maintained through the short period and whether the expressions of several drug efflux transporters have been upregulated. We exposed MCF7 breast cancer cells with tamoxifen 1 μM for 10 passages (MCF7 (T)). The result showed that MCF7 began to lose their sensitivity to tamoxifen from the second passage. MCF7 (T) also showed a significant increase in all transporters examined compared with MCF7 parent cells. The result also showed a significant increase of CC50 in MCF7 (T) compared to that in MCF7 (97.54 μM and 3.04 μM, resp.). In conclusion, we suggest that the expression of several drug efflux transporters such as P-glycoprotein, MRP2, and BCRP might be used and further studied as a marker in the development of tamoxifen resistance.

Background and Aim: Chronic hyperglycemia in prediabetic individuals would progress to diabetes and lead to several systemic disruptions, including hematological parameters. This study aimed to investigate the correlation between prediabetes and hematological indices in a prediabetic rat model. Materials and Methods: Eighteen male rats were randomly divided into two groups of nine. Prediabetes was induced in nine rats by a 3-week high-fat and high-glucose diet, followed by low-dose streptozotocin (STZ) injection (30 mg/ kg body weight). The oral glucose tolerance test was performed, and the fasting blood glucose (FBG) and insulin levels were measured 72 h after STZ administration. The control group of nine rats was given standard diets. At the end of the 3rd week, the animals fasted overnight before blood collection. Blood samples were drawn and used for the analysis of the FBG and fasting insulin levels and glycated albumin to define prediabetes criteria before hematology analysis. Results: We found a significant increase in the FBG and insulin levels in the prediabetic versus the control group. There were decreases in red blood cells, hemoglobin, and hematocrit levels and red cell distribution in prediabetic rats versus the control. At the same time, a significant increase in the platelet count was observed in the prediabetic group. There was a positive correlation between FBG and lymphocytes and neutrophil-lymphocyte ratio in prediabetic rats. On the other hand, we found a negative correlation between white blood cell count and glycated albumin. Conclusion: Correlations were found in several hematological parameters in the prediabetic rat models. The changes in hematological indices in prediabetic rats may be further used as a valuable indicator of glycemic control.

The Avian influenza virus is an infectious agent that may cause global health problem issues in poultry and potentially zoonotic. In recent decades, bacterial-derived sialidases have been extensively studied for their ability to inhibit avian influenza virus infections. In this study the antiviral activity of NanB sialidase from Pasteurella multocida was investigated through in vitro analysis using MDCK cells. NanB sialidase was purified from P. multocida for testing its toxicity and its ability to hydrolyze its sialic acid receptors on MDCK cells. H9N2 challenge virus was propagated in MDCK cells until cytopathic effects (CPE) appeared. Antiviral activity of NanB sialidase was conducted using MDCK cells, and then observed based on cell morphology, viral copy number, and expression of apoptosis-mediating genes. NanB sialidase effectively hydrolyzes Neu5Acα(2-6)Gal sialic acid at the dose of 129 mU/ml, while at 258 mU/ml it cause toxicity on MDCK cells. Antiviral activity of sialidase is evident based on the significantly decrease in viral copy number at all doses administrated. The increase of p53 and caspase-3 expression was observed in infected cells without sialidase. Our study demonstrates the ability of NanB sialidase to inhibit H9N2 virus replication based on observations of sialic acid hydrolysis, reduction in viral copy number, and expression of apoptosis-related genes. The future application of sialidase may be considered as an antiviral strategy against avian influenza H9N2 virus infections.

Hypercholesterolemia is a common metabolic disorder found worldwide, which is associated with dyslipidemia and cardiovascular disease incidence. Among the first line choices drugs is gemfibrozil but it has side effect gastrointestinal disorder. The aim of this study is to investigate anti hypercholesterolemia effect of ethanol extract of Acalypha indica roots (AI Extract) on plasma lipid profile and fatty liver tissue, compared to gemfibrozil. Male Sprague-Dawley rats were assigned to five groups (n = 6) and give the intervention for 4 weeks. One normal group receive normal feed, one group still induce with high fructose-cholesterol diet (HFCD), while the others were supplemented with 250 mg/kgBW AI extract, 10 mg/kgBW gemfibrozil and combination between 250 mg/kgBW AI extract + 10 mg/kgBB gemfibrozil. Total cholesterol were analyzed with Kruskal Wallis test and post hoc Mann-Whitney test. Meanwhile, HDL, LDL, triglycerides and atherogenic index were analyzed with One Way ANOVA test and post hoc Mann-Whitney test. There are statistically significant difference results in all lipid plasma profile: Total Cholesterol, (p < 0, 0001), triglyseride (p = 0, 0002) HDL (p = 0, 0276), LDL (p < 0, 0001) and Atherohenic index (p < 0, 0001) in administration of Ai extract+gemfibrozil group compared to control groups. Hypercholesterolemia.liver tissues were assessed using Clinical Research Network Scoring for Non Alcoholic Steatohepatitis (NASH). Gemfibrozil and AI gemfibrozil are significantly reduced lipid deposition in fatty liver tissue (p < 0.05), compare with control group. In conclusion, the result of this study indicated that the extract of AI extract can be used as alternative therapy for anti hypercholesterolemia.

Background Indonesia is one of the countries that is endemic to avian influenza virus subtype H9N2. This study aims to compare the molecular characteristics of avian influenza virus (AIV) subtype H9N2 from West Java. Methods Specific pathogen-free (SPF) embryonated chicken eggs were used to inoculate samples. RNA extraction and RT–qPCR confirmed the presence of H9 and N2 genes in the samples. RT–PCR was employed to amplify the H9N2-positive sample. Nucleotide sequences were obtained through Sanger sequencing and analyzed using MEGA 7. Homology comparison and phylogenetic tree analysis, utilizing the neighbor-joining tree method, assessed the recent isolate’s similarity to reference isolates from GenBank. Molecular docking analysis was performed on the HA1 protein of the recent isolate and the A/Layer/Indonesia/WestJava-04/2017 isolate, comparing their interactions with the sialic acids Neu5Ac2-3Gal and Neu5Ac2-6Gal. Results RT–qPCR confirmed the isolate samples as AIV subtype H9N2. The recent virus exhibited 11 amino acid residue differences compared to the A/Layer/Indonesia/WestJava-04/2017 isolate. Phylogenetically, the recent virus remains within the h9.4.2.5 subclade. Notably, at antigenic site II, the recent isolate featured an amino acid N at position 183, unlike A/Layer/Indonesia/WestJava-04/2017. Molecular docking analysis revealed a preference of HA1 from the 2017 virus for Neu5Ac2-3Gal, while the 2023 virus displayed a tendency to predominantly bind with Neu5Ac2-6Gal. Conclusion In summary, the recent isolate displayed multiple mutations and a strong affinity for Neu5Ac2-6Gal, commonly found in mammals.