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Despite the recent progress in emotion recognition, state-of-the-art systems are unable to achieve improved performance in cross-language settings. In this article we propose a Multimodal Dual Attention Transformer (MDAT) model to improve cross-language multimodal emotion recognition. Our model utilises pre-trained models for multimodal feature extraction and is equipped with dual attention mechanisms including graph attention and co-attention to capture complex dependencies across different modalities and languages to achieve improved cross-language multimodal emotion recognition. In addition, our model also exploits a transformer encoder layer for high-level feature representation to improve emotion classification accuracy. This novel construct preserves modality-specific emotional information while enhancing cross-modality and cross-language feature generalisation, resulting in improved performance with minimal target language data. We assess our model's performance on four publicly available emotion recognition datasets and establish its superior effectiveness compared to recent approaches and baseline models.

BackgroundRespiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause of LRTI in the elderly. The available treatments and FDA-approved vaccines for RSV only lessen the severity of the infection and are recommended for infants and elderly people.MethodsWe focused on developing a broad-spectrum vaccine that activates the immune system to directly combat RSV. The objective of this study is to identify CD4+ and CD8+ T-cell epitopes using an immunoinformatics approach to develop RSV vaccines. The efficacy of these peptides was validated through in-vitro and in-vivo studies involving healthy and diseased animal models. ResultsFor each major histocompatibility complex (MHC) class-I and II, we found three epitopes of RSV proteins including F, G, and SH with an antigenic score of >0.5 and a projected SVM score of

Background: Melanoma is the most fatal kind of skin cancer. Among its various types, cutaneous melanoma is the most prevalent one. Melanoma cells are thought to be highly immunogenic due to the presence of distinct tumor-associated antigens (TAAs), which includes carcinoembryonic antigen (CEA), cancer/testis antigens (CTAs) and neo-antigens. The CTA family is a group of antigens that are only expressed in malignancies and testicular germ cells. Methods: We used integrative framework and systems-level analysis to predict potential vaccine candidates for cutaneous melanoma involving epitopes prediction, molecular modeling and molecular docking to cross-validate the binding affinity and interaction between potential vaccine agents and major histocompatibility molecules (MHCs) followed by molecular dynamics simulation, immune simulation and in silico cloning. Results: In this study, three cancer/testis antigens were targeted for immunotherapy of cutaneous melanoma. Among many CTAs that were studied for their expression in primary and malignant melanoma, NY-ESO-1, MAGE1 and SSX2 antigens are most prevalent in cutaneous melanoma. Cytotoxic and Helper epitopes were predicted, and the finest epitopes were shortlisted based on binding score. The vaccine construct was composed of the four epitope-rich domains of antigenic proteins, an appropriate adjuvant, His tag and linkers. This potential multi-epitope vaccine was further evaluated in terms of antigenicity, allergencity, toxicity and other physicochemical properties. Molecular interaction estimated through protein-protein docking unveiled good interactions characterized by favorable binding energies. Molecular dynamics simulation ensured the stability of docked complex and the predicted immune response through immune simulation revealed elevated levels of antibodies titer, cytokines, interleukins and immune cells (NK, DC and MA) population. Conclusion: The findings indicate that the potential vaccine candidates could be effective immunotherapeutic agents that modify the treatment strategies of cutaneous melanoma.

Introduction: Nipah (NiV) is the zoonotic deadly bat-borne virus that causes neurological and respiratory infections which ultimately lead to death. There are 706 infected cases reported up till now especially in Asia, out of which 409 patients died. There is no vaccine and effective treatment available for NiV infections and we have to timely design such strategies as world could not bear another pandemic situation.Methods: In this study, we screened viral proteins of NiV strains based on pangenomics analysis, antigenicity, molecular weight, and sub-cellular localization. The immunoproteomics based approach was used to predict T-cell epitopes of MHC class-I and II as potential vaccine candidates. These epitopes are capable to activate CD4+, CD8+, and T-cell dependent B-lymphocytes.Results: The two surface proteins including fusion glycoprotein (F) and attachment glycoprotein (G) are antigenic with molecular weights of 60 kDa and 67 kDa respectively. Three epitopes of F protein (VNYNSEGIA, PNFILVRNT, and IKMIPNVSN) were ranked and selected based on the binding affinity with MHC class-I, and 3 epitopes (VILNKRYYS, ILVRNTLIS, and VKLQETAEK) with MHC-II molecules. Similarly, for G protein, 3 epitopes each for MHC-I (GKYDKVMPY, ILKPKLISY, and KNKIWCISL) and MHC-II (LRNIEKGKY, FLIDRINWI, and FLLKNKIWC) with substantial binding energies were predicted. Based on the physicochemical properties, all these epitopes are non-toxic, hydrophilic, and stable.Conclusion: Our vaccinomics and system-level investigation could help to trigger the host immune system to prevent NiV infection.

The study aimed to understand the molecular evolution of the pathogen recognition peptidoglycan (PGN) proteins and their role in regulating the immune response against infectious diseases in Drosophila melanogaster. D. melanogasterWe obtained the PGRP proteins from 11 different species of Drosophila and analyzed the different evolutionary trends that might be associated with them. We were able to identify the evidence of strong positive selection taking place for these proteins. We investigated the diversity and function of the PGN proteins in D. melanogaster and related species through a combination of bioinformatics approaches. They found that the PGN proteins have undergone rapid and diverse evolution, with some undergoing positive selection and others experiencing gene duplication and loss. The study also revealed that different PGN proteins play distinct roles in regulating the immune response to bacterial infections, with some responding specifically to certain types of bacteria. The research provides valuable insights into the evolution and function of the PGN proteins in the immune response of D. melanogaster. It highlights their potential relevance to pathogen recognition and immune defence in other organisms.

Introduction: We describe a case of remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome following administration of the ChAdOx1-S/nCoV-19 [recombinant] vaccine, suggesting a possible causal link. Case Description: A 72-year-old man presented to his general practitioner with swollen, oedematous hands and legs 2 weeks after receiving a coronavirus vaccine. He had raised inflammatory markers but remained systemically well. He was initially presumed to have cellulitis, but his symptoms persisted despite several courses of antibiotics. Deep vein thromboses, cardiac failure, renal failure and hypoalbuminaemia were ruled out. Upon Rheumatology review, he was diagnosed as having RS3PE syndrome with the Covid vaccine suspected of being an immunogenic trigger. Following initiation of steroid therapy, his symptoms improved dramatically, as is characteristic of RS3PE syndrome. Discussion: The pathophysiology of RS3PE is unclear. It is known to have various triggers and associations including infections, certain vaccines and malignancy. This case highlights that a coronavirus vaccine (ChAdOx1-S/nCoV-19 [recombinant] vaccine) is also a possible trigger. Factors that make the diagnosis likely include an acute onset of symptoms including pitting oedema in a typical distribution, age above 50, and unremarkable autoimmune serology. Other learning points from this case include the importance of antibiotic stewardship and the need to explore non-infectious causes of illness when antibiotics do not improve symptoms. Conclusion: The ChAdOx1-S/nCoV-19 [recombinant] vaccine is a possible trigger of RS3PE. However, the benefits of vaccines against coronavirus outweigh the risks in the majority of patients.

Objective(s): Alpha-amylase and alpha-glucosidase enzyme inhibition is an effective and rational approach for controlling postprandial hyperglycemia in type II diabetes mellitus (DM). Several inhibitors of this therapeutic class are in clinical use but are facing challenges of safety, efficacy, and potency. Keeping in view the importance of these therapeutic inhibitors, in this study we are reporting 10 new oxadiazole analogs 5 (a-g) & 4a (a-c) as antidiabetic agents. Materials and Methods: The newly synthesized derivatives 5 (a-g) & 4a (a-c) were characterized using different spectroscopic techniques including FTIR,1HNMR, 13CNMR, and elemental analysis data. All compounds were screened for their in vitro α-amylase and α-glucosidase enzyme inhibitory potential, while two selected compounds (5a and 5g) were screened for cytotoxicity using MTT assay.Results: Two analogues 5a and 4a (a) exhibited strong inhibitory potential against α-glucosidase enzyme, i.e., IC50 value=12.27±0.41 µg/ml and 15.45±0.20 µg/ml, respectively in comparison with standard drug miglitol (IC50 value=11.47±0.02 µg/ml) whereas, one compound 5g demonstrated outstanding inhibitory potential (IC50 value=13.09±0.06 µg/ml) against α-amylase enzyme in comparison with standard drug acarbose (IC50 value=12.20±0.78 µg/ml). The molecular interactions of these active compounds in the enzymes’ active sites were evaluated following molecular docking studies. Conclusion: Our results suggested that these new oxadiazole derivatives (5a, 5g & 4a (a)) may act as promising drug candidates for the development of new alpha-amylase and alpha-glucosidase inhibitors. Therefore, we further recommend in vitro and in vivo pharmacological evaluations and safety assessments.

In an attempt to find new targets for α-amylase and α-glucosidase for the treatment of type 2 diabetes mellitus, the present study aims in determining the anti-diabetic potential of synthesized dihydropyrimidinone derivatives. The in vitro α-glucosidase and α-amylase inhibitory activity was performed and the molecular docking analysis of the ligand in the active binding site of target protein was determined. The results revealed significant percent inhibition of α-glucosidase by the compound 6-benzyl-4-(4-hydroxyphenyl)-3,4,6,7-tetrahydro-1H-pyrrolo[3,4-d]pyrimidine-2,5-dione (compound A). The active compound showed 81.99% inhibition when compared to standard ascorbic acid having percent inhibition 81.18%. The IC50 of active compound (A) showed to be 1.02 µg/ml. The molecular docking analysis revealed that the ligand bound to the active binding site of protein with the lowest binding energy of -7.9 kcal/mol that was also significantly similar to standard having -7.8 kcal/mol binding energy. The molecular dynamic simulation studies also revealed stable binding of ligand in the active binding site of protein with low RMSD of 1.7 Å similar to the protein RMSD 1.6Å In conclusion, the study revealed a potential new target against α-glucosidase to treat type 2 diabetes mellitus.

Lung cancer is one of the deadliest types of cancer responsible for thousands of cancer-related deaths. Its treatment has remained a challenge for researchers, but an increase in the knowledge of molecular pathways and biology of lung cancer has dramatically changed its management in recent decades. Immunotherapies and immunomodulation of lung cancer have previously failed for a long time but thanks to continuous research work and enthusiasm, now, this field is emerging as a novel effective therapy. Now, it is hope with potential benefits and promising results in the treatment of lung cancer. This review article focuses on immune checkpoints inhibitors: CTLA-4 inhibitors (ipilimumab and tremelimumab) and PDL-1 inhibitors (durvalumab and atezolizumab) that can be blocked to treat lung carcinoma. It is also focused on critically analyzing different studies and clinical trials to determine the potential benefits, risks, and adverse events associated with immunotherapeutic treatment.

Abstract Background Because of the highly heterogeneous nature of breast cancer, each subtype differs in response to several treatment regimens. This has limited the therapeutic options for metastatic breast cancer disease requiring exploration of diverse therapeutic models to target tumor specific biomarkers. Methods Differentially expressed breast cancer genes identified through extensive data mapping were studied for their interaction with other target proteins involved in breast cancer progression. The molecular mechanisms by which these signature genes are involved in breast cancer metastasis were also studied through pathway analysis. The potential drug targets for these genes were also identified. Results From 50 DEGs, 20 genes were identified based on fold change and p-value and the data curation of these genes helped in shortlisting 8 potential gene signatures that can be used as potential candidates for breast cancer. Their network and pathway analysis clarified the role of these genes in breast cancer and their interaction with other signaling pathways involved in the progression of disease metastasis. The miRNA targets identified through miRDB predictor provided potential miRNA targets for these genes that can be involved in breast cancer progression. Several FDA approved drug targets were identified for the signature genes easing the therapeutic options for breast cancer treatment. Conclusion The study provides a more clarified role of signature genes, their interaction with other genes as well as signaling pathways. The miRNA prediction and the potential drugs identified will aid in assessing the role of these targets in breast cancer.

Abstract Background Type 2 diabetes mellitus (T2DM) is a worldwide disease that have an impact on individuals of all ages causing micro and macro vascular impairments due to hyperglycemic internal environment. For ultimate treatment to cure T2DM, association of diabetes with immune components provides a strong basis for immunotherapies and vaccines developments that could stimulate the immune cells to minimize the insulin resistance and initiate gluconeogenesis through an insulin independent route. Methodology Immunoinformatics based approach was used to design a polyvalent vaccine for T2DM that involved data accession, antigenicity analysis, T-cell epitopes prediction, conservation and proteasomal evaluation, functional annotation, interactomic and in silico binding affinity analysis. Results We found the binding affinity of antigenic peptides with major histocompatibility complex (MHC) Class-I molecules for immune activation to control T2DM. We found 13-epitopes of 9 amino acid residues for multiple alleles of MHC class-I bears significant binding affinity. The downstream signaling resulted by T-cell activation is directly regulated by the molecular weight, amino acid properties and affinity of these epitopes. Each epitope has important percentile rank with significant ANN IC50 values. These high score potential epitopes were linked using AAY, EAAAK linkers and HBHA adjuvant to generate T-cell polyvalent vaccine with a molecular weight of 35.6 kDa containing 322 amino acids residues. In silico analysis of polyvalent construct showed the significant binding affinity (− 15.34 Kcal/mol) with MHC Class-I. This interaction would help to understand our hypothesis, potential activation of T-cells and stimulatory factor of cytokines and GLUT1 receptors. Conclusion Our system-level immunoinformatics approach is suitable for designing potential polyvalent therapeutic vaccine candidates for T2DM by reducing hyperglycemia and enhancing metabolic activities through the immune system.

Abstract Background Colorectal cancer is known to be the most common type of cancer worldwide with high disease-related mortality. It is the third most common cancer in men and women and is the second major cause of death globally due to cancer. It is a complicated and fatal disease comprising of a group of molecular heterogeneous disorders. Results This study identifies the potential biomarkers of CRC through differentially expressed analysis, system biology, and proteomic analysis. Ten publicly available microarray datasets were analyzed and seven potential biomarkers were identified from the list of differentially expressed genes having a p value

Nanobiotechnology is the intersection of nanotechnology and biology, where nano systems are applied to help study biological systems. There is a growing interest of researchers in the application of nanotechnology in improving the efficacy of photodynamic therapy. In this study, the antioxidant, photodynamic, anticancer, and antibacterial potential of plant extracts and silver nanoparticles (AgNPs) were investigated. In order to synthesize AgNPs, 10 g of dried powder of Tecoma stans and Narcissus tazetta was boiled in deionized water (100 ml) and mixed with aqueous solution of silver metals, resulting in the formation of AgNPs. The synthesized AgNPs were spherical having size in a range of 15–100 nm. The application of extract (50 µl) and AgNPs to rhabdomyosarcoma cell line showed a decreased cell viability (%). Photodynamic study revealed an improvement in photosensitizer efficacy on introducing AgNPs. Both plant extracts and AgNPs had significant effect against methicillin resistant Staphylococcus aureus (MRSA) as well as sensitive Staphylococcus aureus with minimum inhibitory concentration (MIC) values of AgNPs lower (32–256 µg/ml) than the plant extracts. According to the current findings, these AgNPs have an enhancing effect on the photodynamic cytotoxic potential of plant extracts. Because of biological efficacy, these AgNPs may play a crucial role in determining therapeutic potential of Tecoma stans and Narcissus tazetta.

BackgroundType 2 diabetes mellitus (T2DM) is a heterogeneous, metabolic, and chronic condition affecting vast numbers of the world’s population. The related variables and T2DM associations have not been fully understood due to their diverse nature. However, functional genomics can facilitate understanding of the disease. This information will be useful in drug design, advanced diagnostic, and prognostic markers.AimTo understand the genetic causes of T2DM, this study was designed to identify the differentially expressed genes (DEGs) of the disease.MethodsWe investigated 20 publicly available disease-specific cDNA datasets from Gene Expression Omnibus (GEO) containing several attributes including gene symbols and clone identifiers, GenBank accession numbers, and phenotypic feature coordinates. We analyzed an integrated system-level framework involving Gene Ontology (GO), protein motifs and co-expression analysis, pathway enrichment, and transcriptional factors to reveal the biological information of genes. A co-expression network was studied to highlight the genes that showed a coordinated expression pattern across a group of samples. The DEGs were validated by quantitative PCR (qPCR) to analyze the expression levels of case and control samples (50 each) using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as the reference gene.ResultsFrom the list of 50 DEGs, we ranked three T2DM-related genes (p < 0.05): SRR, NFKB1, and PDE4B. The enriched terms revealed a significant functional role in amino acid metabolism, signal transduction, transmembrane and intracellular transport, and other vital biological functions. DMBX1, TAL1, ZFP161, NFIC (66.7%), and NR1H4 (33.3%) are transcriptional factors associated with the regulatory mechanism. We found substantial enrichment of insulin signaling and other T2DM-related pathways, such as valine, leucine and isoleucine biosynthesis, serine and threonine metabolism, adipocytokine signaling pathway, P13K/Akt pathway, and Hedgehog signaling pathway. The expression profiles of these DEGs verified by qPCR showed a substantial level of twofold change (FC) expression (2−ΔΔCT) in the genes SRR (FC ≤ 0.12), NFKB1 (FC ≤ 1.09), and PDE4B (FC ≤ 0.9) compared to controls (FC ≥ 1.6). The downregulated expression of these genes is associated with pathophysiological development and metabolic disorders.ConclusionThis study would help to modulate the therapeutic strategies for T2DM and could speed up drug discovery outcomes.

Background: Hypertension is one of the most devastating human health problems with a higher incidence of both mortality and morbidity. The prevalence of this disease is more pronounced in underdeveloped countries as compared to developed countries. Drug discovery and development is a complex, time-consuming process, associated with increased failure risk. Therefore, the drug development process declined to the lowest in the history of the pharmaceutical industry during the past several years Therefore, drug reprofiling could be a lucrative approach for the novice in the field of new drug discovery and development. Methods: In this study in silico drug repurposing method was used to find the best drug candidate for hypertension using the differential expression genes (DEGs) approach. We performed a molecular docking analysis of 2500 drugs from FDA-approved databases against the selected DEGs for lead identification. Furthermore, molecular docking (MD) simulation was performed to analyze the stability of the interacting complexes. Results: We screened FDA-approved drugs against the four selected overexpressed DEGs using the molecular operating environment (MOE). These DEGs were adrenomedullin (ADM), ubiquitin-specific peptidase-8 (USP-8), angiopoietin-like-4 (ANGPTL-4), and endothelin-1 (EDN1). The three top-ranked drug candidates against each target protein were shortlisted. Moreover, these twelve complexes after docking were validated by the molecular dynamics (MD) simulation for 100 ns with the active sites of the target. Conclusions: Based on the high binding affinity and stability of the drug complexes, we demonstrated here that these molecules could be investigated further as a potential drug candidate for hypertension.

Human papilloma virus (HPV) causes cervical and many other cancers. Recent trend in vaccine design is shifted toward epitope-based developments that are more specific, safe, and easy to produce. In this study, we predicted eight immunogenic peptides of CD4+ and CD8+ T-lymphocytes (MHC class I and II as M1 and M2) including early proteins (E2 and E6), major (L1) and minor capsid protein (L2). Male and female Sprague Dawly rats in groups were immunized with each synthetic peptide. L1M1, L1M2, L2M1, and L2M2 induced significant immunogenic response compared to E2M1, E2M2, E6M1 and E6M2. We observed optimal titer of IgG antibodies (>1.25 g/L), interferon-γ (>64 ng/L), and granzyme-B (>40 pg/mL) compared to control at second booster dose (240 µg/500 µL). The induction of peptide-specific IgG antibodies in immunized rats indicates the T-cell dependent B-lymphocyte activation. A substantial CD4+ and CD8+ cell count was observed at 240 µg/500 µL. In male and female rats, CD8+ cell count for L1 and L2 peptide is 3000 and 3118, and CD4+ is 3369 and 3484 respectively compared to control. In conclusion, we demonstrated that L1M1, L1M2, L2M1, L2M2 are likely to contain potential epitopes for induction of immune responses supporting the feasibility of peptide-based vaccine development for HPV.

Published in August 2021

Abstract Background Alopecia or hair loss is a complex polygenetic and psychologically devastating disease affecting millions of men and women globally. Since the gene annotation and environmental knowledge is limited for alopecia, a systematic analysis for the identification of candidate biomarkers is required that could provide potential therapeutic targets for hair loss therapy. Results We designed an interactive framework to perform a meta-analytical study based on differential expression analysis, systems biology, and functional proteomic investigations. We analyzed eight publicly available microarray datasets and found 12 potential candidate biomarkers including three extracellular proteins from the list of differentially expressed genes with a p-value

Background The coronavirus SARS-CoV-2 is a member of the Coronaviridae family that has caused a global public health emergency. Currently, there is no approved treatment or vaccine available against it. The current study aimed to cover the diversity of SARS-CoV-2 strains reported from all over the world and to design a broad-spectrum multi-epitope vaccine using an immunoinformatics approach. Methods For this purpose, all available complete genomes were retrieved from GISAID and NGDC followed by genome multiple alignments to develop a global consensus sequence to compare with the reference genome. Fortunately, comparative genomics and phylogeny revealed a significantly high level of conservation between the viral strains. All the Open Reading Frames (ORFs) of the reference sequence NC_045512.2 were subjected to epitope mapping using CTLpred and HLApred, respectively. The predicted CTL epitopes were then screened for antigenicity, immunogenicity and strong binding affinity with HLA superfamily alleles. HTL predicted epitopes were screened for antigenicity, interferon induction potential, overlapping B cell epitopes and strong HLA DR binding potential. The shortlisted epitopes were arranged into two multi-epitope sequences, Cov-I-Vac and Cov-II-Vac, and molecular docking was performed with Toll-Like Receptor 8 (TLR8). Results The designed multi-epitopes were found to be antigenic and non-allergenic. Both multi-epitopes were stable and predicted to be soluble in an Escherichia coli expression system. The molecular docking with TLR8 also demonstrated that they have a strong binding affinity and immunogenic potential. These in silico analyses suggest that the proposed multi-epitope vaccine can effectively evoke an immune response.

An amendment to this paper has been published and can be accessed via the original article.

A novel thermophilic bacterial strain of the genus Aeribacillus was isolated from Thar Dessert Pakistan. This strain showed significant antibacterial activity against Micrococcus luteus, Staphylococcus aureus, and Pseudomonas aeruginosa. The strain coded as ‘SAT4’ resembled with Aeribacillus pallidus in the morphological, biochemical and molecular tests. The production of antibacterial metabolites by SAT4 was optimized. These active metabolites were precipitated by 50% ammonium sulphate and purified through sephadex G-75 gel permeation chromatography and reverse phase HPLC. The molecular weight of 37 kDa was examined by SDS-PAGE. The structural elucidation of the purified product was studied by FTIR, 1H and 13C NMR. The X-ray diffractions study showed that the crystals belonged to the primitive orthorhombic lattice (a = 12.137, b = 13.421, c = 14.097 Å) and 3D structure (proposed name: Aeritracin) was determined. This new peptide antibacterial molecule can get a position in pharmaceutical and biotechnological industrial research.

Klebsiella pneumoniae is an opportunistic gram-negative bacterium that causes nosocomial infection in healthcare settings. Despite the high morbidity and mortality rate associated with these bacterial infections, no effective vaccine is available to counter the pathogen. In this study, the pangenome of a total of 222 available complete genomes of K. pneumoniae was explored to obtain the core proteome. A reverse vaccinology strategy was applied to the core proteins to identify four antigenic proteins. These proteins were then subjected to epitope mapping and prioritization steps to shortlist nine B-cell derived T-cell epitopes which were linked together using GPGPG linkers. An adjuvant (Cholera Toxin B) was also added at the N-terminal of the vaccine construct to improve its immunogenicity and a stabilized multi-epitope protein structure was obtained using molecular dynamics simulation. The designed vaccine exhibited sustainable and strong bonding interactions with Toll-like receptor 2 and Toll-like receptor 4. In silico reverse translation and codon optimization also confirmed its high expression in E. coli K12 strain. The computer-aided analyses performed in this study imply that the designed multi-epitope vaccine can elicit specific immune responses against K. pneumoniae. However, wet lab validation is necessary to further verify the effectiveness of this proposed vaccine candidate.

Invasive candidiasis is potentially life-threatening systemic fungal infection caused by Candida albicans (C. albicans). Candida enters the blood stream and disseminate throughout the body and it is often observed in hospitalized patients, immunocompromised individuals or those with chronic diseases. This infection is opportunistic and risk starts with the colonization of C. albicans on mucocutaneous surfaces and respiratory epithelium. MicroRNAs (miRNAs) are small non-coding RNAs which are involved in the regulation of virtually every cellular process. They regulate and control the levels of mRNA stability and post-transcriptional gene expression. Aberrant expression of miRNAs has been associated in many disease states, and miRNA-based therapies are in progress. In this study, we investigated possible variations of miRNA expression profiles of respiratory epithelial cells infected by invasive Candida species. For this purpose, respiratory epithelial tissues of infected individuals from hospital laboratory were accessed before their treatment. Invasive Candida infection was confirmed by isolation of Candia albicans from the blood cultures of the same infected individuals. The purity of epithelial tissues was assessed by flow cytometry (FACSCalibur cytometer; BD Biosciences, Heidelberg, Germany) using statin antibody (S-44). TaqMan quantitative real-time PCR (in a TaqMan Low Density Array format) was used for miRNA expression profiling. MiRNAs investigated, the levels of expression of 55 miRNA were significantly altered in infected tissues. Some miRNAs showed dramatic increase (miR-16-1) or decrease of expression (miR-17-3p) as compared to control. Gene ontology enrichment analysis of these miRNA-targeted genes suggests that Candidal infection affect many important biological pathways. In summary, disturbance in miRNA expression levels indicated the change in cascade of pathological processes and the regulation of respiratory epithelial functions following invasive Candidal infection. These findings contribute to our understanding of host cell response to Candidal systemic infections.

The existing aromatase inhibitors produced unwelcome effects impose the discovery of novel drugs with privileged selectivity, a reduced amount of toxicity and humanizing potency. In this study, we illuminate the binding mode of polyketide azaphilanoid pigments monascin, ankaflavin, monascorubrin and monascorubramine isolated from Monascus fungus to the aromatase by molecular docking. The 3-dimensional structure of aromatase enzyme (PDB: 4KQ8) was obtained from the Protein Data Bank. PatchDock docking software was used to analyze structural complexes of the aromatase with monascus pigments. Comparatively, the AutoGrid model presented the most briskly constructive binding mode of monascin to aromatase. Docked energies in kcal/mol are: monascin;-13.2; monascorubramine:-12.8, monascorubrin:-12.3; ankaflavin: -10.5. These outcomes exposed these ligands could be potential drugs to treat hormone dependent breast cancer.

Background: Rheumatoid arthritis is an inflammatory and chronic disease of the joints affecting 1% of the world’s population. Women are three times more likely to be affected than men. Many drugs are being used for the treatment of rheumatoid arthritis but they often have severe side effects. C-C motif chemokine ligand 28 (CCL28) recruits leukocytes and other proinflammatory factors to the site of joint inflammation. The purpose of the present research is the computational evaluation of astragalin, a natural flavonoid extracted from black tea, as an inhibitor of CCL28 by in silico docking. Methods: The three-dimensional structure of CCL28 to act as a molecular target was obtained from the Protein Data Bank (PDB ID: 6CWS). The quality of the CCL28 structure was assessed using Phyre 2 and Molecular Operating Environment (MOE) software was used for binding affinity analysis. Astragalin served as a ligand for docking and naproxen, a known drug for rheumatoid arthritis, was used as a standard for comparison. Results: In molecular docking, astragalin showed significant binding affinity with the CCL28 target molecule, with a binding energy of -5.40 kcal/mol, in comparison with naproxen which has a binding energy of -4.87 kcal/mol. Astragalin has strong binding affinity for CCL28 as compared to standard naproxen. Conclusion: This study revealed that astragalin could have the potential to serve as an inhibitor of CCL28 for the treatment of rheumatoid arthritis.