Fetal Growth Retardation is Associated with High Apoptotic Cells and Low VEGF Expression in Placenta of Malarial Pregnant Mice.

Background: During pregnancy, pregnant women are susceptible to malaria, contributing significantly to maternal and infant mortality. Objective: This research was conducted to study the effect of Plasmodium berghei infection in pregnant mice on fetal growth retardation through placental cell apoptosis and the change of local vascularization. Methods: Eighteen pregnant Balb/c strain mice resulting from simultanously mating were divided into two groups those were nine pregnant mice used as non infected group and nine pregnant mice infected with Plasmodium berghei on day 9th post mating used as infected group respectively. On day 15th of post mating, all of the pregnant mice were killed. Fetal weights were measured using analytic balance. Apoptosis of placental cells and VEGF expression in the placental tissue were measured using immunohistochemistry. Results: Result showed that there was sequestration of parasite-infected red blood cells (PRBCs) in intervillous space. Statistical analysis showed that the fetal weights in infected pregnant mice group was significantly lower than non infected one (p = 0.01), and the placental cell apoptosis in placental tissue of infected pregnant mice was significantly higher than the non infected one (p=0.00).There was also a significant difference on VEGF expression between infected group and non infected group (p= 0,00). Conclusion: Plasmodium berghei infection in pregnant Balb/c mice can cause fetal growth retardation due to high of placental cell apoptosis and low VEGF expression.

Molecular docking, synthesis, and antibacterial activity of the analogs of 1-allyl-3-benzoylthiourea.

Background and purpose: The incidence of antibiotic resistance rapidly emerges over the globe. In the present study, the synthesis of thiourea derivatives as antibacterial agents and their biological evaluation are reported. Experimental approach: Preliminary studies were done by molecular docking of four analogs of 1-allyl-3-benzoylthiourea, clorobiocin, and ciprofloxacin on the DNA gyrase subunit B receptor (PDB: 1KZN). The nucleophilic substitution reaction of benzoyl chloride analogs to the allylthiourea yielded four 1-allyl-3-benzoylthiourea analogs (Cpd 1-4). The reactions were done by a modified Schotten Baumann method. The in vitro antimicrobial activities were determined using the agar dilution method against methicillin-resistant Staphylococcus aureus (MRSA), Salmonella typhi, Escherichia coli, and Pseudomonas aeruginosa. Findings/Results: The in-silico study showed that Cpd 1-4 possesses a good interaction on the DNA gyrase subunit B receptor compared to the ciprofloxacin. Cpd 3 had the best binding affinity with a rerank score of - 91.2304. Although the candidate compounds showed unsatisfactory antibacterial activity, they indicated an increasing trend of growth inhibition along with the increment of concentration. Cpd 1 and 4 exhibited in vitro antibacterial activities against MRSA with a minimum inhibitory concentration value of 1000 µg/mL, better compared to the other compounds. Conclusion and implication: Despite lacking antibacterial activity, all the synthesized compounds showed an increased trend of growth inhibition along with the increment of concentration. Therefore, additional development should be implemented to the compounds of interest in which optimization of lipophilicity and steric properties are suggested.

Nornidulin, A New Inhibitor of Plasmodium falciparum Malate: Quinone Oxidoreductase (PfMQO) from Indonesian Aspergillus sp. BioMCC f.T.8501.

This study aimed to obtain a microbial active compound as a novel antimalarial drug from Indonesian isolates. Target-based assays were used to screen for antimalarial activity against the parasite mitochondrial, Plasmodium falciparum malate:quinone oxidoreductase (PfMQO) enzyme. In total, 1600 crude extracts, composed from 800 fungi and 800 actinomycetes extracts, were screened against PfMQO, yielding six active extracts as primary hits. After several stages of stability tests, one extract produced by Aspergillus sp. BioMCC f.T.8501 demonstrated stable PfMQO inhibitory activity. Several purification stages, including OCC, TLC, and HPLC, were performed to obtain bioactive compounds from this active extract. All purification steps were followed by an assay against PfMQO. We identified the active compound as nornidulin based on its LC-MS and UV spectrum data. Nornidulin inhibited PfMQO activity at IC50 of 51 µM and P. falciparum 3D7 proliferation in vitro at IC50 of 44.6 µM, however, it had no effect on the growth of several mammalian cells. In conclusion, we isolated nornidulin from Indonesian Aspergillus sp. BioMCC f.T.8501 as a novel inhibitor of PfMQO, which showed inhibitory activity against the proliferation of P. falciparum 3D7 in vitro.

The Effects of Holothurin and Caspofungin on the Vaginal Cell Inflammation Parameters of the Rattus norvegicus Strain Post Induction of Candida albicans.

Purpose: Candida albicans (C. albicans) is a fungus that causes superficial and invasive candidiasis in its host. Caspofungin, has been widely used as a synthetic antifungal, whereas holothurin has been shown to have potential as a natural antifungal. The purpose of this study was to see how holothurin and caspofungin affected the number of C. albicans's colonies, LDH levels, and the number of inflammatory cells in vagina of Rattus norvegicus. Patients and Methods: Design of this research is using posttest only with control group design with 48 Rattus norvegicus Wistar strains used in this study were divided into six treatment groups. Each group was divided into three-time intervals of 12, 24, and 48 hours. LDH markers were tested using ELISA, inflammatory cells were counted manually, and the number of colonies was calculated using colonymetry before being diluted with NaCl 0.9% and planted in sabouraud dextrose agar (SDA). Results: According to the findings, inflammatory cells in the treatment of holothurin (48-hours) had an OR of 1.68 CI (-0.79-4.16) P = 0.09 and caspofungin had an OR of 4.18 CI (1.26-9.63) P = 0.09. Meanwhile, LDH in the holothurin (48-hour) treatment obtained OR 348, CI (286-410), P=0.03, and Caspofungin OR 393, CI (277-508), P=0.03. Colonies were obtained with zero numbers in the holothurin treatment (48 hours) and with Caspofungin OR 393, CI (273-508) P=0.00. Conclusion: Holothurin and caspofungin administration reduced the number of C. albicans colonies and the number of inflammatory cells (P 0.05), implying that holothurin and caspofungin could prevent C. albicans infection.

Cross Protectivity Analysis of 49.8 kDa Pili Subunits of S. flexneri against Vibrio cholerae Infection.

Background: Although the AMV and AMS vaccine candidates have similar characteristics as hemagglutinin and adhesive molecules, there are differences in molecular weight. Objective: The research aims to determine the immunological cross-reaction between AMS and AMV. Method: Antihemagglutination test used the anti-adhesion molecular antibody AMS. Next, we examined the immune response that has to be linked with protectivity. The model of the research uses MLIL. The sample separated the mice into four groups, and each group had five mice. The first group was the negative control group. The second group was given AMV and infected with Shigella flexneri. The third group was immunized with AMV before being exposed to Shigella flexneri. The last group was infected with Vibrio cholerae. The immune response results were evaluated by calculating the weight of MLIL and counting the colony of bacteria. We also examined other AMS immune responses, namely, ß-defensin and s-IgA levels. To get the data, we measured the number of Th17 immune effector cells, T-reg, and proinflammatory cytokine IL-17A. Data analysis was performed using ANOVA, independent t-test, Kruskal-Wallis, and Mann-Whitney tests. Results: An antihemagglutination cross immune response, intestinal weight, the number of bacterial colonies, and other findings were found to be significant (p < 0.05) for the levels of ß-defensin, s-IgA, Th17, T-reg, and IL-17A. Conclusion: The 49.8 kDa·MW protein subunit of the Shigella flexneri adhesion molecule could act as a candidate vaccine homologous for shigellosis and cholera in the future.

GENERATING RESPONSES IMMUNE IN CELLULAR AND HUMORAL TREATMENT WITH EPITOPE SPIKE, EPITOPE ENVELOPE PROTEIN, AND EPITOPE MEMBRANE PROTEIN SARS-COV-2, HONEY, SAUSSUREA LAPPA, AND NIGELLA SATIVA.

BACKGROUND: Covid-19 has become pandemic in the World, including Indonesia. Our last study showed that HSF could serve as an immunomodulator. Using the exact search, we found that the most immuno-dominant SARS-COV2 epitope, namely A spike protein epitope, B envelope protein epitope, and C membrane protein epitope, we concise to be HF. MATERIALS AND METHODS: We used to post only control design study and mice as an animal model. The research divided mice into four groups, and the first group as control received PBS as a placebo. The second, three, and last four groups gave HF, HSN, and HFHSN (combine HF and HSN). All of the regiment enters the mouth with a special sonde to reach the gastrointestinal organ. We gave HF every week three times and HSN once a day. After administration regiments for a long three weeks, we sacrificed the mice. We evaluated cellular immune responses that are Th-2, Th-17, and NK cells. We check for humoral immune response, TGF-ß,IL-17A, IL-4, IgG,IL-4, ß-defensin, and s-IgA. RESULTS: Highest profile cellular immunity HF, HSN, and HFHSN were NK cell, Th-2 and Th-17, and the last NK cell, respectively. After that which in humoral immunity, the domination response IgG and IL-4 were HF. But HSN and HFHSN dominated for s-IgA and ß-defensin production. By using the study Bio-Informatica, we found HF. CONCLUSION: If the results of this study are continued to the clinical trial level, it is necessary to recommend additional markers such as CTL (s-IgA and ß-defensin in lung tissue)and CPE assay.

Antimalarial Properties of Isoquinoline Derivative from Streptomyces hygroscopicus subsp. Hygroscopicus: An In Silico Approach.

Malaria is one of the life-threatening diseases in the world. The spread of resistance to antimalarial drugs is a major challenge, and resistance to artemisinin has been reported in the Southeast Asian region. In the previous study, the active compound of Streptomyces hygroscopicus subsp. Hygroscopicus (S. hygroscopicus), eponemycin, has been shown to have antimalarial effects. To further analyze the effects of other active compounds on the Plasmodium parasite, identifying and analyzing the effectiveness of compounds contained in S. hygroscopicus through instrumentation of liquid chromatography/mass spectrometry (LC/MS) and in silico studies were very useful. This study aimed at identifying other derivative compounds from S. hygroscopicus and screening the antimalarial activity of the compound by assessing the binding affinity, pharmacokinetic profile, and bond interaction. The derivative compounds were identified using LC/MS. Protein targets for derivative compounds were found through literature studies, and the results of identification of compounds and protein targets were reconstructed into three-dimensional models. Prediction of pharmacokinetic profiles was carried out using Swiss ADME. Screening of protein targets for the derivative compound was carried out using the reverse molecular docking method. Analyzing bond interaction was done by LigPlot. One compound from S. hygroscopicus, i.e., 6,7-dinitro-2-[1, 2, 4]triazole-4-yl-benzo[de]isoquinoline-1,3-dione, was successfully identified using LC/MS. This compound was an isoquinoline derivative compound. Through literature studies with inclusion criteria, thirteen protein targets were obtained for reverse molecular docking. This isoquinoline derivative had the potential to bind to each protein target. The pharmacokinetic profile showed that this compound had the drug-likeness criteria. Conclusion. 6,7-Dinitro-2-[1, 2, 4]triazole-4-yl-benzo[de]isoquinoline-1,3-dione has antimalarial activity as shown by reverse molecular docking studies and pharmacokinetic profiles. The best inhibitory ability of compounds based on bond affinity is with adenylosuccinate synthetase.

ß-Glucan of Candida albicans Cell Wall Extract Inhibits Salmonella Typhimurium Colonization by Potentiating Cellular Immunity (CD8 + and CD4 + T Cells).

INTRODUCTION: Antimicrobial resistance has been reported in the drugs used for the treatment of typhoid fever. The immunomodulatory substance ß-glucan can be used as an alternative therapy as it potentiates host immunity. The aims of this study are to observe the effect of Candida albicans cell wall (CCW) extract towards host immunity (TCD8+ and TCD4+ cells in spleen, intestinal sIgA) and its capacity to kill Salmonella in the intestine and liver of typhoid fever mice models. METHODS: Typhoid fever mice models were created by infecting mice with S. Typhimurium orally. Mice were divided into four groups: the Non-Infected, Infected, CCW (infected mice treated with 300 µg CCW extract/mouse once a day), and Ciprofloxacin groups (infected mice treated with 15 mg/kg BW ciprofloxacin twice a day). RESULTS: Secretory IgA (sIgA) concentrations of mice in the CCW group remained unchanged. However, their TCD4+ and TCD8+ cells increased substantially compared to those in the Non-Infected group. In the Ciprofloxacin group, sIgA concentrations increased markedly compared to those in the Non-Infected and CCW groups; TCD4+ and TCD8+ cells also increased significantly compared to those in the Infected Group, but not significant compared to those in the CCW group. Colonization of S. Typhimurium in the intestine and liver decreased significantly in the CCW and Ciprofloxacin groups compared to that in the Infected group, with the lowest reduction being found in the Ciprofloxacin group. CONCLUSIONS: The inhibition of S. Typhimurium colonization by CCW is associated with the increase in TCD4+ and TCD8+ cells.

Β-Glucan of candida albicans cell wall extract inhibits salmonella typhimurium colonization by potentiating cellular immunity (cd8 + and cd4 + t cells)

Abstract INTRODUCTION: Antimicrobial resistance has been reported in the drugs used for the treatment of typhoid fever. The immunomodulatory substance β-glucan can be used as an alternative therapy as it potentiates host immunity. The aims of this study are to observe the effect of Candida albicans cell wall (CCW) extract towards host immunity (TCD8+ and TCD4+ cells in spleen, intestinal sIgA) and its capacity to kill Salmonella in the intestine and liver of typhoid fever mice models. METHODS: Typhoid fever mice models were created by infecting mice with S. Typhimurium orally. Mice were divided into four groups: the Non-Infected, Infected, CCW (infected mice treated with 300 µg CCW extract/mouse once a day), and Ciprofloxacin groups (infected mice treated with 15 mg/kg BW ciprofloxacin twice a day). RESULTS: Secretory IgA (sIgA) concentrations of mice in the CCW group remained unchanged. However, their TCD4+ and TCD8+ cells increased substantially compared to those in the Non-Infected group. In the Ciprofloxacin group, sIgA concentrations increased markedly compared to those in the Non-Infected and CCW groups; TCD4+ and TCD8+ cells also increased significantly compared to those in the Infected Group, but not significant compared to those in the CCW group. Colonization of S. Typhimurium in the intestine and liver decreased significantly in the CCW and Ciprofloxacin groups compared to that in the Infected group, with the lowest reduction being found in the Ciprofloxacin group. CONCLUSIONS The inhibition of S. Typhimurium colonization by CCW is associated with the increase in TCD4+ and TCD8+ cells.

Rhodamine B induces oxidative stress and cervical epithelial cell proliferation in the uterus.

This study aimed to investigate the effect of Rhodamine B exposure on oxidative stress and cervical epithelial cells proliferation in the uterus. Twenty eight female Wistar albino rats were divided into four groups (n = 7 each): one control (untreated) group; and three Rhodamine B groups at several doses (4.5, 9, 18 mg/200 g body weight/day) for 36 days. Colometric analysis of malondialdehyde (MDA) level as a marker of lipid peroxidation and histological analysis of the cervical epithelial cells proliferation was performed. The MDA levels and proliferation of epithelial cells were significantly higher in all Rhodamine B groups compared to control group (P < 0.05). The MDA levels were increased in a dose-dependent manner in the Rhodamine B groups. Moreover, the proliferation of epithelial cells was also increased by Rhodamine B in a dose-dependent manner. In conclusion, subchronic Rhodamine B administration induces lipid peroxidation and cervical epithelial cells proliferation in a dose dependent manner.