The inflammation process of gout arthritis and its treatment.

Gout arthritis is an inflammatory condition that occurs suddenly in joints affected by high uric acid levels (hyperuricemia). The uric acid levels in this disease fluctuate throughout its various phases, resulting in frequent or recurrent attacks. This study aims to review some aspects of gout arthritis, such as its pathophysiology, treatment goals, and adverse drug reactions. This study employs review literature using articles published between 2017 and 2022 as the research methodology. Furthermore, articles under 2017 are used as references if they are relevant to the study's subject matter. The findings showed the importance of the pathogenesis of inflammation in the treatment of gout arthritis. It is also recommended to use anti-inflammatories such as colchicine and uric acid-lowering medications starting at a specific time to prevent unintended risks. Hence, pharmacotherapy management's adverse effects include nausea, vomiting, myalgia, neuropathy, and stomach pain.

UNAS-Net: A deep convolutional neural network for predicting Covid-19 severity.

We present a study on Covid-19 detection using deep learning algorithms that help predict and detect Covid-19. Chest X-ray images were used as the input dataset to prepare and train the proposed model. In this context, deep learning architecture (DLA) and optimisation strategies have been proposed and explored to support the automated detection of Covid-19. A model based on a convolutional neural network was proposed to extract features of images for the feature-learning phase. Data augmentation and fine-tuning with deep-feature-based methods were applied to improve the model. Image enhancement and saliency maps were used to enhance visualisation and estimate the disease severity level based on two parameters; degree of opacity and geographic extent. Contrast-limited adaptive histogram equalization and Otsu thresholding were employed with several parameters to investigate the effects on the visualisation results. An experimental investigation was performed between the proposed method and other pretrained DLAs. The proposed work obtained excellent classification accuracy and sensitivity of 97.36% and 95.24% respectively. In addition, the input parameters for image enhancement significantly affected the results. The overall performance metrics were perfect for DenseNet and adequately high for the proposed work which is comparable to other models. Data augmentation and fine-tuning successfully handed the networks to enhance the overall performance, especially in our case with limited datasets.

Effect of supplementation of Rhodomyrtus tomentosa fruit juice in preventing hypercholesterolemia and atherosclerosis development in rats fed with high fat high cholesterol diet.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Nutraceuticals, mainly based on natural products, have been proven to control the risk factors of CVDs effectively. Rhodomyrtus tomentosa is an underutilized fruit that is rich in phenolic compounds and has antioxidant activities. Scientific investigation was needed to verify the pharmacological properties of R. tomentosa fruit juice in Sprague-Dawley rats fed with high fat high cholesterol (HFHC) as antihypercholesterolemic and antiatherosclerotic agents. The experiments were carried out using male albino rats fed with HFHC diet for 75 days and at the same time orally supplemented with R. tomentosa fruit juice (RTFJ) in doses of 0.5, 1, and 2 g/kg body weight (BW) daily for 75 days. Simvastatin was used as a positive control. At the end of the experiment, the blood was collected, and the serum was assayed for total triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C). The histopathology of coronary and aorta arteries was observed under the light microscope. The results demonstrated that the supplementation of RTFJ significantly prevented the increase of total triglycerides, total cholesterol, low-density lipoprotein, and the decrease of high-density lipoprotein in serum. Supplementation of RTFJ also prevents atherosclerosis development by preventing the thickening of the blood vessel wall, deposition of lipid formation, and foam cells in the tunica intima of the aorta and coronary arteries. These findings suggested that supplementation of R. tomentosa fruit juice prevents hypercholesterolemia and atherosclerosis.

Prediction of human-Streptococcus pneumoniae protein-protein interactions using logistic regression.

Streptococcus pneumoniae is a major cause of mortality in children under five years old. In recent years, the emergence of antibiotic-resistant strains of S. pneumoniae increases the threat level of this pathogen. For that reason, the exploration of S. pneumoniae protein virulence factors should be considered in developing new drugs or vaccines, for instance by the analysis of host-pathogen protein-protein interactions (HP-PPIs). In this research, prediction of protein-protein interactions was performed with a logistic regression model with the number of protein domain occurrences as features. By utilizing HP-PPIs of three different pathogens as training data, the model achieved 57-77 % precision, 64-75 % recall, and 96-98 % specificity. Prediction of human-S. pneumoniae protein-protein interactions using the model yielded 5823 interactions involving thirty S. pneumoniae proteins and 324 human proteins. Pathway enrichment analysis showed that most of the pathways involved in the predicted interactions are immune system pathways. Network topology analysis revealed ß-galactosidase (BgaA) as the most central among the S. pneumoniae proteins in the predicted HP-PPI networks, with a degree centrality of 1.0 and a betweenness centrality of 0.451853. Further experimental studies are required to validate the predicted interactions and examine their roles in S. pneumoniae infection.

Hepatoprotective effect of Pandanus odoratissimus seed extracts on paracetamol-induced rats.

CONTEXT: Pandanus odoratissimus Linn. (Pandanaceae) seed extract is known to have antioxidant activities. However, the potential hepatoprotective effect is still unclear. OBJECTIVE: To investigate the hepatoprotection aspect of P. odoratissimus methanol extract towards paracetamol-induced rats. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were randomly divided into six equal groups: one group served as the healthy control and five groups with hepatotoxicity (hepatotoxic control and 4 treatment groups). The oral treatment of paracetamol-induced hepatotoxicity of 3 g/kg using three different concentrations of P. odoratissimus (300, 600 and 900 mg/kg), and silymarin (200 mg/kg) groups were administered once a day for 14 days. Enzyme activities and protein levels in serum were determined in rats at the end of the treatments. The histopathology of rat livers was observed under an electron microscope with 10× magnification. RESULTS: Pandanus odoratissimus significantly decreased the serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT) activities in induced-paracetamol rat serum (p < 0.05). Moreover, P. odoratissimus significantly decreased total bilirubin and direct bilirubin levels (p < 0.05). It significantly blocked the decline of serum albumin and protein levels (p < 0.05). Histopathological changes amplified paracetamol-induced liver damage and the hepatoprotective effect of P. odoratissimus in the liver. DISCUSSION AND CONCLUSIONS: Pandanus odoratissimus improved the hepatoprotective effect in a concentration-dependent manner by reducing related hepatic enzyme and protein markers, suggesting as a useful agent in hepatotoxicity treatment, and it can be generalized to a broader study population in different hepatotoxic animal models.

Structure-based discovery of novel inhibitors of Mycobacterium tuberculosis CYP121 from Indonesian natural products.

Tuberculosis (TB) continues to be a serious global health threat with the emergence of multidrug-resistant tuberculosis (MDR-TB) and extremely drug-resistant tuberculosis (XDR-TB). There is an urgent need to discover new drugs to deal with the advent of drug-resistant TB variants. This study aims to find new M. tuberculosis CYP121 inhibitors by the screening of Indonesian natural products using the principle of structure-based drug design and discovery. In this work, eight natural compounds isolated from Rhoeo spathacea and Pluchea indica were selected based on their antimycobacterial activity. Derivatives compound were virtually designed from these natural molecules to improve the interaction of ligands with CYP121. Virtual screening of ligands was carried out using AutoDock Vina followed by 50 ns molecular dynamics simulation using YASARA to study the inhibition mechanism of the ligands. Two ligands, i.e., kaempferol (KAE) and its benzyl derivative (KAE3), are identified as the best CYP121 inhibitors based on their binding affinities and adherence to the Lipinski's rule. Results of molecular dynamics simulation indicate that KAE and KAE3 possess a unique inhibitory mechanism against CYP121 that is different from GGJ (control ligand). The control ligand alters the overall dynamics of the receptor, which is indicated by changes in residue flexibility away from CYP121 binding site. Meanwhile, the dynamic changes caused by the binding of KAE and KAE3 are isolated around the binding site of CYP121. These ligands can be developed for further potential biological activities.

Peptide-Based Subunit Vaccine Design of T- and B-Cells Multi-Epitopes against Zika Virus Using Immunoinformatics Approaches.

The Zika virus disease, also known as Zika fever is an arboviral disease that became epidemic in the Pacific Islands and had spread to 18 territories of the Americas in 2016. Zika virus disease has been linked to several health problems such as microcephaly and the Guillain-Barré syndrome, but to date, there has been no vaccine available for Zika. Problems related to the development of a vaccine include the vaccination target, which covers pregnant women and children, and the antibody dependent enhancement (ADE), which can be caused by non-neutralizing antibodies. The peptide vaccine was chosen as a focus of this study as a safer platform to develop the Zika vaccine. In this study, a collection of Zika proteomes was used to find the best candidates for T- and B-cell epitopes using the immunoinformatics approach. The most promising T-cell epitopes were mapped using the selected human leukocyte antigen (HLA) alleles, and further molecular docking and dynamics studies showed a good peptide-HLA interaction for the best major histocompatibility complex-II (MHC-II) epitope. The most promising B-cell epitopes include four linear peptides predicted to be cross-reactive with T-cells, and conformational epitopes from two proteins accessible by antibodies in their native biological assembly. It is believed that the use of immunoinformatics methods is a promising strategy against the Zika viral infection in designing an efficacious multiepitope vaccine.

Enhancement of drug absorption through the blood-brain barrier and inhibition of intercellular tight junction resealing by E-cadherin peptides.

E-cadherin-mediated cell-cell interactions in the zonula adherens play an important role in the formation of the intercellular tight junctions found in the blood-brain barrier. However, it is also responsible for the low permeation of drugs into the brain. In this study, HAV6 peptide derived from the EC1 domain of E-cadherin was found to enhance the permeation of ¹4C-mannitol and [³H(G)]-daunomycin through the blood-brain barrier of the in situ rat brain perfusion model. In addition, HAV6 peptide and verapamil have a synergistic effect in enhancing the BBB permeation of daunomycin. A new intercellular-junction resealing assay was also developed using Caco-2 monolayers to evaluate new peptides (BLG2, BLG3, and BLG4) derived from the bulge regions of the EC2, EC3, and EC4 domains of E-cadherin. BLG2 and BLG4 peptides but not BLG3 peptides were found to be effective in blocking the resealing of the intercellular junctions. The positive control peptides (ADT10, ADT6, and HAV10) block the resealing of the intercellular junctions in a concentration-dependent manner. All these findings suggest that E-cadherin-derived peptides can block E-cadherin-mediated cell-cell interactions. These findings demonstrate that cadherin peptides may offer a useful targeted permeation enhancement of therapeutic agents such as anticancer drugs into the brain.

Effects of an E-cadherin-derived peptide on the gene expression of Caco-2 cells.

PURPOSE: The goal of this study was to determine the effects of exposure to an HAV peptide (Ac-SHAVSS-NH2) on the protein and gene expression in Caco-2 cells, a model for the intestinal mucosa. METHODS: Caco-2 cells were incubated with either 100 or 500 microM of the hexapeptide then evaluated over a 48-h time period. RESULTS: Cell detachment from the monolayer was seen only after 48 h of exposure to the peptide, with the greatest effects occurring with a peptide concentration of 500 microM. Total protein expression of E-cadherin showed a decrease of nearly 20% at the 24-h time point for each concentration examined, whereas no significant changes were detected at the other time points studied. Short term exposure to a 500 microM solution of Ac-SHAVSS-NH2 caused few changes in gene expression as determined by Affymetrix GeneChip microarrays; however, longer exposure periods produced numerous changes in the treated cells. The variations in mRNA expression indicate that this HAV peptide has an effect in the E-cadherin signaling pathways. The greatest increases in mRNA expression were found in genes regulating excretion or degradation of the peptide. CONCLUSIONS: This work suggests that this HAV peptide produces effects that reach beyond modulation of adhesion.

Increasing paracellular porosity by E-cadherin peptides: discovery of bulge and groove regions in the EC1-domain of E-cadherin.

PURPOSE: The objective of this work is to evaluate the ability of peptides derived from the bulge (HAV-peptides) and groove (ADT-peptides) regions of E-cadherin EC1-domain to increase the paracellular porosity of the intercellular junctions of Madin-Darby canine kidney (MDCK) cell monolayers. METHODS: Peptides were synthesized using a solid-phase method and were purified using semi-preparative HPLC. MDCK monolayers were used to evaluate the ability of cadherin peptides to modulate cadherin-cadherin interactions in the intercellular junctions. The increase in intercellular junction porosity was determined by the change in transepithelial electrical resistance (TEER) values and the paracellular transport of 14C-mannitol. RESULTS: HAV- and ADT-peptides can lower the TEER value of MDCK cell monolayers and enhance the paracellular permeation of 14C-mannitol. HAV- and ADT-decapeptides can modulate the intercellular junctions when they are added from the basolateral side but not from the apical side; on the other hand. HAV- and ADT-hexapeptides increase the paracellular porosity of the monolayers when added from either side. Conjugation of HAV- and ADT-peptides using omega-aminocaproic acid can only work to modulate the paracellular porosity when ADT-peptide is at the N-terminus and HAV-peptide is at the C-terminus; because of its size, the conjugate can only modulate the intercellular junction when added from the basolateral side. CONCLUSIONS: Peptides from the bulge and groove regions of the EC1 domain of E-cadherin can inhibit cadherin-cadherin interactions, resulting in the opening of the paracellular junctions. These peptides may be used to improve paracellular permeation of peptides and proteins. Furthermore, this work suggests that both groove and bulge regions of EC-domain are important for cadherin-cadherin interactions.