Salivary transforming growth factor beta in oral submucous fibrosis: A diagnostic and predictive marker.

CONTEXT: Growth factors and cytokines like transforming growth factor beta (TGF-ß) play a key role in the pathogenesis of oral submucous fibrosis. AIMS: To elucidate the role of Salivary TGF-ß isoforms as a predictive and diagnostic marker for oral submucous fibrosis. SETTINGS AND DESIGN: A total of 30 OSMF and 10 control patients were included in this study, and their clinic-epidemiological data was recorded. METHODOLOGY: The expression of TGF-ß genes-TGF-ß1, TGF-ß2, TGF-ß3-was studied by a real-time polymerase chain reaction in tissue and saliva. Patients were given medicinal intervention for 12 weeks along with jaw-opening exercises. Expression of salivary TGF-ß genes was studied at 12 weeks. STATISTICAL ANALYSIS USED: SPSS software version 20. RESULT: Expression of salivary TGF beta isoforms in OSMF was more than in the control group. There was an increase in salivary TGF-ß1, ß2, ß3 expressions with increasing clinical grades of OSMF and advancing the stage of the disease. Expression of all the TGF beta isoforms was decreased after treatment with statistically significant results. Statistically significant correlations were found between the mean difference of TGF-ß1 and the mean difference between mouth opening and tongue protrusion. CONCLUSION: Salivary TGF-ß isoforms may be used in diagnosis, risk assessment, and screening of the entire population at risk of OSMF after its clinical validation. However, adequate sample size and segmental assessment of the expression of TGF-ß isoforms are needed for further evaluation.

Amino acid pattern reveals multi-functionality of ORF3 protein from HEV.

The smallest open reading frame (ORF) encoded protein ORF3 of hepatitis E virus (HEV), recently, has been demonstrated to perform multiple functions besides accessory roles. ORF3 could act as a target for vaccine against HEV infections. The IDR (intrinsically disordered region); IDP (ID protein)/IDPR (ID protein region), plays critical role in various regulatory functions of viruses. The dark proteome of HEV-ORF3 protein including its structure and function was systematically examined by computer predictors to explicate its role in viral pathogenesis and drug resistance beyond its functions as accessory viral protein. Amino acid distribution showed ORF3 enrichment with disorder-promoting residues (Ala, Pro, Ser, Gly) while deficiency in order-promoting residues (Asn, Ile, Phe, Tyr and Trp). Initial investigation revealed ORF3 as IDP (entirely disordered protein) or IDPR (proteins consisting of IDRs with structured globular domains). Structural examination revealed preponderance of disordered regions interpreting ORF3 as moderately/highly disordered protein. Further disorder predictors categorized ORF3 as highly disordered protein/IDP. Identified sites and associated-crucial molecular functions revealed ORF3 involvement in diverse biological processes, substantiating them as targets of regulation. As ORF3 functions are yet to completely explored, thus, data on its disorderness could help in elucidating its disorder related functions.

Structure based docking and biological evaluation towards exploring potential anti-cancerous and apoptotic activity of 6-Gingerol against human prostate carcinoma cells.

BACKGROUND: 6-Gingerol (6-G) is the primary active phytocomponent of ginger and has been shown to regulate multiple targets against cancer and its treatment. Androgen receptors (ARs) remain critical in the progression of prostate cancer (PCa). This study focuses on investigating 6-G as a promising anti-cancerous agent that inhibits AR activity significantly. METHODS: In this study, molecular docking simulation was done to investigate the binding affinity of 6-G and control drug Bicalutamide (BT) against oncogenic AR and tumor suppressor estrogen receptor ß (ERß). The crystal structure of AR and ERß was retrieved from Protein Data Bank (PDB) and docked with 3D Pubchem structures of 6-G using iGEMDOCK and AutoDock. Further in vitro study was done to evaluate the antioxidant, anti-cancerous, apoptotic, and wound healing potential of 6-G. RESULTS: The result displays that 6-G shows good binding affinity with AR and ERß. Condensation of the nucleus, change in mitochondrial membrane potential (MMP) and the ability to induce reactive oxygen species (ROS) were done in human PCa PC-3 cells. Results from the MTT assay demonstrated that 6-G and control drug BT showed significant (p < 0.01) dose and time dependent inhibition of human PCa PC-3 cells. 6-G increased the ROS generation intracellularly and decreased the MMP, and cell migration in treated PCa PC-3 cells. 6-G treated cells showed fragmented, condensed chromatin and nuclear apoptotic bodies. CONCLUSIONS: Thus, this study validates 6-G as a potential drug candidate against human PCa. However, further study of the anticancer potency of 6-G has to be done before its use for PCa treatment.

Correction: Yadav et al. PLGA-Quercetin Nano-Formulation Inhibits Cancer Progression via Mitochondrial Dependent Caspase-3,7 and Independent FoxO1 Activation with Concomitant PI3K/AKT Suppression. Pharmaceutics 2022, 14, 1326.

In the published publication [...].

Fabrication, structural, and enhanced mechanical behavior of MgO substituted PMMA composites for dental applications.

The most common denture material used for dentistry is poly-methyl-methacrylate (PMMA). Usually, the polymeric PMMA material has numerous biological, mechanical and cost-effective shortcomings. Hence, to resolve such types of drawbacks, attempts have been made to investigate fillers of the PMMA like alumina (Al2O3), silica (SiO2), zirconia (ZrO2) etc. For the enhancement of the PMMA properties a suitable additive is required for its orthopedic applications. Herein, the main motive of this study was to synthesize a magnesium oxide (MgO) reinforced polymer-based hybrid nano-composites by using heat cure method with superior optical, biological and mechanical characteristics. For the structural and vibrational studies of the composites, XRD and FT-IR were carried out. Herein, the percentage of crystallinity for all the fabricated composites were also calculated and found to be 14.79-30.31. Various physical and optical parameters such as density, band gap, Urbach energy, cutoff energy, cutoff wavelength, steepness parameter, electron-phonon interaction, refractive index, and optical dielectric constant were also studied and their values are found to be in the range of 1.21-1.394 g/cm3, 5.44-5.48 eV, 0.167-0.027 eV, 5.68 eV, 218 nm, 0.156-0.962, 4.273-0.693, 1.937-1.932, and 3.752-3.731 respectively. To evaluate the mechanical properties like compressive strength, flexural strength, and fracture toughness of the composites a Universal Testing Machine (UTM) was used and their values were 60.3 and 101 MPa, 78 and 40.3 MPa, 5.85 and 9.8 MPa-m1/2 respectively. Tribological tests of the composites were also carried out. In order to check the toxicity, MTT assay was also carried out for the PM0 and PM15 [(x)MgO + (100 - x) (C5O2H8)n] (x = 0 and 15) composites. This study provides a comprehensive insight into the structural, physical, optical, and biological features of the fabricated PMMA-MgO composites, highlighting the potential of the PM15 composite with its enhanced density, mechanical strength, and excellent biocompatibility for denture applications.

Potential role of microRNAs in personalized medicine against hepatitis: a futuristic approach.

MicroRNAs (miRNAs) have been the subject of extensive research for many years, primarily in the context of diseases such as cancer. However, our appreciation of their significance in viral infections, particularly in hepatitis, has increased due to the discovery of their association with both the host and the virus. Hepatitis is a major global health concern and can be caused by various viruses, including hepatitis A to E. This review highlights the key factors associated with miRNAs and their involvement in infections with various viruses that cause hepatitis. The review not only emphasizes the expression profiles of miRNAs in hepatitis but also puts a spotlight on their potential for diagnostics and therapeutic interventions. Ongoing extensive studies are propelling the therapeutic application of miRNAs, addressing both current limitations and potential strategies for the future of miRNAs in personalized medicine. Here, we discuss the potential of miRNAs to influence future medical research and an attempt to provide a thorough understanding of their diverse roles in hepatitis and beyond.

Enhanced therapeutic efficacy of Piperlongumine for cancer treatment using nano-liposomes mediated delivery.

Piperlongumine (PL) is a well-known bioactive alkaloid that has been reported as a potent anticancer molecule but has failed to provide potential activity in translational and clinical applications due to some drawbacks like low bioavailability, hydrophobicity, and rapid degradation. However, nano-formulation is a good choice to increase the bioavailability and enhance cellular uptake of PL. In this study, PL loaded nano-liposomes (NPL) were formulated using the thin-film hydration method and analyzed by Response Surface Methodology (RSM) in order to treat cervical cancer. The NPL were thoroughly characterized using particle size, PDI, zeta potential, drug loading capacity, encapsulation efficiency, SEM, AFM and FTIR. Different assays viz. MTT, AO/PI, DAPI, MMP, cell migration, DCFDA and apoptotic assay using Annexin V-FITC/PI were performed for anticancer potential of NPL in human cervical carcinoma cells (SiHa and HeLa). NPL showed enhanced cytotoxicity, diminished cell proliferation, reduced cell viability, enhanced nuclear condensation, reduction in mitochondrial membrane potential, inhibited cell migration, increased ROS level and promoted more apoptosis in both human cervical cancer cell lines. These findings demonstrated that NPL may be a potential therapeutic option for cervical cancer.

Synergetic effects of boron nitride with waste zirconia: Evaluation of instantaneous fingerprint detection and mechanical properties for biomedical applications.

Herein, present study mainly focuses on the synthesis and characterizations of boron nitride reinforced waste zirconia (wZrO2) with different concentrations. Composites were prepared via a scalable solid-state reaction method. Various physical parameters such as density, ionic concentration, polaron radius, and field strength were evaluated. XRD results reveal crystalline nature with a major phase of tetragonal zirconia and as boron nitride is reinforced, the tetragonal transforms into a monoclinic zirconia. Interconnected spherical grains and nanosheets were observed using FESEM. Mechanical characterizations revealed the highest compressive strength of 266 MPa. The latent fingerprints were visualized using a composite on different surfaces, implementing the powder dusting and solution techniques. MTT assay was performed and revealed good biocompatible nature. These results reveal that composite is suitable for fabrication of bioceramics with acceptable mechanical and biological performances. The composite can also be utilized for latent fingerprint detection in forensic science.

TNF-α and MMPs mediated mucus hypersecretion induced by cigarette smoke: An in vitro study.

Cigarette smoke is one of the leading causes of oxidative stress due to high levels of free radicals, which in turn leads to the degradation of alveolar cell walls and development of emphysema. Cigarette smoking has been linked to chronic bronchitis, Chronic Obstructive Pulmonary Disease (COPD) and lung cancer as well. The aim of the present study was to observe the effect of cigarette smoke extract (CSE) on TNF-α and MMPs mediated mucus hypersecretion in A549 cell line. The MTT experiments showed that CSE caused a dose-dependent decline in the level of viability of A549 cells. In addition, AO/PI and Mitotracker Red staining assays demonstrated that CSE caused the A549 cells to undergo apoptosis. This was determined by observing the reduction in mitochondrial membrane potential. CSE was found to be responsible for the formation of intracellular ROS, which was observed by DCFDA staining through fluorescence microscopy. Approximately 65% migration rate was decreased in 20% CSE exposed cells. CSE exposure led to the significantly increased mRNA levels of TNF-α, MMP-7, and MMP-12, in comparison to the control cells. Additionally, the expression of MUC5AC and MUC5B was provoked by CSE as well. Human epithelial cells are stimulated by TNF-α and MMPs secreted mucus, as shown by expression of MUC5AC and MUC5B. CSE could induce mucus in lungs through TNF-α and MMPs mediated pathways.

Global and local evolutionary dynamics of Dengue virus serotypes 1, 3, and 4.

Evolutionary studies on Dengue virus (DENV) in endemic regions are necessary since naturally occurring mutations may lead to genotypic variations or shifts in serotypes, which may lead to future outbreaks. Our study comprehends the evolutionary dynamics of DENV, using phylogenetic, molecular clock, skyline plots, network, selection pressure, and entropy analyses based on partial CprM gene sequences. We have collected 250 samples, 161 in 2017 and 89 in 2018. Details for the 2017 samples were published in our previous article and that of 2018 are presented in this study. Further evolutionary analysis was carried out using 800 sequences, which incorporate the study and global sequences from GenBank: DENV-1 (n = 240), DENV-3 (n = 374), and DENV-4 (n = 186), identified during 1944-2020, 1956-2020, and 1956-2021, respectively. Genotypes V, III, and I were identified as the predominant genotypes of the DENV-1, DENV-3, and DENV-4 serotypes, respectively. The rate of nucleotide substitution was found highest in DENV-3 (7.90 × 10-4 s/s/y), followed by DENV-4 (6.23 × 10-4 s/s/y) and DENV-1 (5.99 × 10-4 s/s/y). The Bayesian skyline plots of the Indian strains revealed dissimilar patterns amongst the population size of the three serotypes. Network analyses showed the presence of different clusters within the prevalent genotypes. The data presented in this study will assist in supplementing the measures for vaccine development against DENV.

Correlation between different retinal layers with visual acuity in diabetic retinopathy patients with clinically significant macular edema.

Purpose: To study the corelation between outer retinal layer thickness (ORL), outer photoreceptor segment thickness (PROS), and central macular thickness (CMT) with best-corrected visual acuity (BCVA) in patients having clinically significant macular edema (CSME) and compare these parameters with normal patients. Methods: This was a prospective, nonrandomized, observational, comparative study done during the period of January to May 2019. The study included 60 eyes of 36 patients. The patient population was segregated into two Groups: Group I (30 normal eyes of 15 normal patients) and Group II (30 eyes of 21 diabetic patients) with CSME. The comparison between ORL, PROS, and CMT was made between both the groups, and the correlation between ORL thickness, PROS thickness, and CMT with BCVA in Group II was studied. Results: The mean age in Group I was 52.6+10.66 years, and 53.42+8.15 years in Group II. The male/female ratio was 1.1:1 in Group I and 4:3 in Group II. The mean CMT was greater in Group II (330.13 ± 37.01) than in Group I (222.20 ± 12.30). The mean ORL thickness was greater in Group I (97.73 ± 6.92) than in Group II (80.63 ± 9.03). The PROS thickness was statistically significant in Group I (35.05 ± 3.4) than in Group II (28.57 ± 3.53). There was a strong correlation between BCVA and ORL thickness (r = -0.580, P < 0.001) and more strong correlation between BCVA and PROS thickness in Group II (r = -0.611, P < 0.000). There was a moderate correlation between BCVA and CMT (r = 0.410, P < 0.025), and all results were statistically significant. Conclusion: Both ORL and PROS thickness were greater in healthy normal eyes than in eyes with CSME. BCVA was strongly correlated with PROS and ORL thickness and moderately associated with CMT.

Intrinsic disorder in the open reading frame 2 of hepatitis E virus: a protein with multiple functions beyond viral capsid.

BACKGROUND: Hepatitis E virus (HEV) is the cause of a liver disease hepatitis E. The translation product of HEV ORF2 has recently been demonstrated as a protein involved in multiple functions besides performing its major role of a viral capsid. As intrinsically disordered regions (IDRs) are linked to various essential roles in the virus's life cycle, we analyzed the disorder pattern distribution of the retrieved ORF2 protein sequences by employing different online predictors. Our findings might provide some clues on the disorder-based functions of ORF2 protein that possibly help us in understanding its behavior other than as a HEV capsid protein. RESULTS: The modeled three dimensional (3D) structures of ORF2 showed the predominance of random coils or unstructured regions in addition to major secondary structure components (alpha helix and beta strand). After initial scrutinization, the predictors VLXT and VSL2 predicted ORF2 as a highly disordered protein while the predictors VL3 and DISOPRED3 predicted ORF2 as a moderately disordered protein, thus categorizing HEV-ORF2 into IDP (intrinsically disordered protein) or IDPR (intrinsically disordered protein region) respectively. Thus, our initial predicted disorderness in ORF2 protein 3D structures was in excellent agreement with their predicted disorder distribution patterns (evaluated through different predictors). The abundance of MoRFs (disorder-based protein binding sites) in ORF2 was observed that signified their interaction with binding partners which might further assist in viral infection. As IDPs/IDPRs are targets of regulation, we carried out the phosphorylation analysis to reveal the presence of post-translationally modified sites. Prevalence of several disordered-based phosphorylation sites further signified the involvement of ORF2 in diverse and significant biological processes. Furthermore, ORF2 structure-associated functions revealed its involvement in several crucial functions and biological processes like binding and catalytic activities. CONCLUSIONS: The results predicted ORF2 as a protein with multiple functions besides its role as a capsid protein. Moreover, the occurrence of IDPR/IDP in ORF2 protein suggests that its disordered region might serve as novel drug targets via functioning as potential interacting domains. Our data collectively might provide significant implication in HEV vaccine search as disorderness in viral proteins is related to mechanisms involved in immune evasion.

Intrinsically disordered regions in the rodent hepevirus proteome.

Hepatitis E virus (HEV) is the causative agent of Hepatitis E infections across the world. Intrinsically disordered protein regions (IDPRs) or intrinsically disordered proteins (IDPs) are regions or proteins that are characterized by lack of definite structure. These IDPRs or IDPs play significant roles in a wide range of biological processes, such as cell cycle regulation, control of signaling pathways, etc. IDPR/IDP in proteins is associated with the virus's pathogenicity and infectivity. The prevalence of IDPR/IDP in rat HEV proteome remains undetermined. Hence, we examined the unstructured/disordered regions of the open reading frame (ORF) encoded proteins of rat HEV by analyzing the prevalence of intrinsic disorder. The intrinsic disorder propensity analysis showed that the different ORF proteins consisted of varying fraction of intrinsic disorder. The protein ORF3 was identified with maximum propensity for intrinsic disorder while the ORF6 protein had the least fraction of intrinsic disorder. The analysis revealed ORF6 as a structured protein (ORDP); ORF1 and ORF4 as moderately disordered proteins (IDPRs); and ORF3 and ORF5 as highly disordered proteins (IDPs). The protein ORF2 was found to be moderately as well as highly disordered using different predictors, thus, was categorized into both IDPR and IDP. Such disordered regions have important roles in pathogenesis and replication of viruses.

Circulation of DENV-3 Genotype 3 during 2017 to 2018 in Delhi: A Single-Center Hospital-Based Study.

Introduction Delhi is hyperendemic for dengue virus (DENV) where all the four DENV have previously been reported. A constant vigilance of circulating DENV serotypes is important in surveillance, since the introduction of a new variant to areas affected by preexisting serotypes constitutes a risk factor for dengue hemorrhagic fever and dengue shock syndrome. Objectives This retrospective study was performed with an objective to determine the circulating serotype and genotype of DENV in acute phase blood samples of patients who have reported to a tertiary liver care hospital in New Delhi during the last 2 years (2017-2018). Methods The data of clinician-initiated testing for dengue nonstructural protein 1 (NS1) antigen (Ag) was searched in the institutional hospital information system. The serum sample of dengue NS1 Ag-positive cases confirmed by enzyme-linked immunosorbent assay (ELISA; PANBIO, Gyeonggi-do, ROK) and a fever duration of less than 5 days were retrieved from the laboratory archive. The DENV serotyping on these sample was performed by reverse transcriptase polymerase chain reaction (RT-PCR). Sequencing and phylogenetic analysis was done for the capsid premembrane (CprM) region to determine the genotype. Results A total of 440 acute-phase samples were received. Twenty one (4.77%) were positive for dengue NS1 Ag with a mean age of 35.1 years and male-to-female ratio of 1.1:1. Eight cases (38.09%) were positive by dengue RT-PCR and all belonged to DENV-3 serotypes. Phylogenetic tree analysis revealed DENV-3 clustered to genotype III with 100% homology with 2008 Indian subcontinent strain. Conclusion This study revealed circulation of DENV-3, genotype III in Delhi from 2017 to 2018, similar to the 2008 viral type. Virological surveillance is an important exercise to be done for viral infections with public threat and outbreak potential.

Innate Immune Response and Inflammasome Activation During SARS-CoV-2 Infection.

The novel coronavirus SARS-CoV-2, responsible for the COVID-19 outbreak, has become a pandemic threatening millions of lives worldwide. Recently, several vaccine candidates and drugs have shown promising effects in preventing or treating COVID-19, but due to the development of mutant strains through rapid viral evolution, urgent investigations are warranted in order to develop preventive measures and further improve current vaccine candidates. Positive-sense-single-stranded RNA viruses comprise many (re)emerging human pathogens that pose a public health problem. Our innate immune system and, in particular, the interferon response form an important first line of defense against these viruses. Flexibility in the genome aids the virus to develop multiple strategies to evade the innate immune response and efficiently promotes their replication and infective capacity. This review will focus on the innate immune response to SARS-CoV-2 infection and the virus' evasion of the innate immune system by escaping recognition or inhibiting the production of an antiviral state. Since interferons have been implicated in inflammatory diseases and immunopathology along with their protective role in infection, antagonizing the immune response may have an ambiguous effect on the clinical outcome of the viral disease. This pathology is characterized by intense, rapid stimulation of the innate immune response that triggers activation of the Nod-like receptor family, pyrin-domain-containing 3 (NLRP3) inflammasome pathway, and release of its products including the pro-inflammatory cytokines IL-6, IL-18, and IL-1ß. This predictive view may aid in designing an immune intervention or preventive vaccine for COVID-19 in the near future.

Mathematical modeling in perspective of vector-borne viral infections: a review.

Background: Viral diseases are highly widespread infections caused by viruses. These viruses are passing from one human to other humans through a certain medium. The medium might be mosquito, animal, reservoir and food, etc. Here, the population of both human and mosquito vectors are important. Main body of the abstract: The main objectives are here to introduce the historical perspective of mathematical modeling, enable the mathematical modeler to understand the basic mathematical theory behind this and present a systematic review on mathematical modeling for four vector-borne viral diseases using the deterministic approach. Furthermore, we also introduced other mathematical techniques to deal with vector-borne diseases. Mathematical models could help forecast the infectious population of humans and vectors during the outbreak. Short conclusion: This study will be helpful for mathematical modelers in vector-borne diseases and ready-made material in the review for future advancement in the subject. This study will not only benefit vector-borne conditions but will enable ideas for other illnesses.

Development of Highly Sensitive Sandwich ELISA for the Early-Phase Diagnosis of Chikungunya Virus Utilizing rE2-E1 Protein.

Introduction: Chikungunya is caused by an alpha virus transmitted to humans by an infected mosquito. Infection is generally considered to be self-limiting and non-critical. Chikungunya infection may be diagnosed by severe joint pain with fever, but it is difficult to diagnose because the symptoms of chikungunya are common to many pathogens, including dengue fever. Diagnosis mainly depends on viral culture, reverse transcriptase polymerase chain reaction (RT-PCR), and IgM ELISA. Early and accurate diagnosis of the virus can be achieved by the application of PCR methods, but the high cost and the need for a thermal cycler restrict the use of such methods. On the other hand, antibody-based IgM ELISA is considered to be inexpensive, but antibodies against chikungunya virus (CHIKV) only develop after 4 days of infection, so it has limited application in the earlier diagnosis of viral infection and the management of patients. Because of these challenges, a simple antigen-based sensitive, specific, and rapid detection method is required for the early and accurate clinical diagnosis of chikungunya. Methods: The amino acid sequence of CHIKV ectodomain E1 and E2 proteins was analyzed using bioinformatics tools to determine the antigenic residues, particularly the B-cell epitopes and their characteristics. Recombinant E2-E1 CHIKV antigen was used for the development of polyclonal antibodies in hamsters and IgG was purified. Serological tests of 96 CHIKV patients were conducted by antigen-capture ELISA using primary antibodies raised against rCHIKV E2-E1 in hamsters and human anti-CHIKV antibodies. Results: We observed high specificity and sensitivity, of 100% and 95.8%, respectively, and these values demonstrate the efficiency of the test as a clinical diagnostic tool. There was no cross-reactivity with samples taken from dengue patients. Discussion: Our simple and sensitive sandwich ELISA for the early-phase detection of CHIKV infection may be used to improve the diagnosis of chikungunya.

Identification of the Key miRNAs and Genes Associated with the Regulation of Non-Small Cell Lung Cancer: A Network-Based Approach.

Lung cancer is the major cause of cancer-associated deaths across the world in both men and women. Lung cancer consists of two major clinicopathological categories, i.e., small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Lack of diagnosis of NSCLC at an early stage in addition to poor prognosis results in ineffective treatment, thus, biomarkers for appropriate diagnosis and exact prognosis of NSCLC need urgent attention. The proposed study aimed to reveal essential microRNAs (miRNAs) involved in the carcinogenesis of NSCLC that probably could act as potential biomarkers. The NSCLC-associated expression datasets revealed 12 differentially expressed miRNAs (DEMs). MiRNA-mRNA network identified key miRNAs and their associated genes, for which functional enrichment analysis was applied. Further, survival and validation analysis for key genes was performed and consequently transcription factors (TFs) were predicted. We obtained twelve miRNAs as common DEMs after assessment of all datasets. Further, four key miRNAs and nine key genes were extracted from significant modules based on the centrality approach. The key genes and miRNAs reported in our study might provide some information for potential biomarkers profitable to increased prognosis and diagnosis of lung cancer.

Sequence to structural analysis of ORF5 protein in Norway rat Hepatitis E Virus.

Hepatitis E virus (HEV) is a major causative agent of acute hepatitis in developing countries. The Norway rat HEV genome consists of six open reading frames (ORFs), i.e., ORF1, ORF2, ORF3, ORF4, ORF5 and ORF6. The additional reading frame encoded protein ORF5 is attributed to life cycle of rat HEV. The ORFF5 protein's function remains undetermined. Therefore, it is of interest to analyze the ORF5 protein for its physiochemical properties, primary structure, secondary structure, tertiary structure and functional characteristics using bioinformatics tools. Analysis of the ORF5 protein revealed it as highly unstable, hydrophilic with basic pI. The ORF5 protein consisted mostly of Arg, Pro, Ser, Leu and Gly. The 3D structural homology model of the ORF5 protein generated showed mixed α/ß structural fold with predominance of coils. Structural analysis revealed the presence of clefts, pores and a tunnel. This data will help in the sequence, structure and functional annotation of ORF5.

Analysis of codon usage patterns in open reading frame 4 of hepatitis E viruses.

Background: Hepatitis E virus (HEV) is a member of the family Hepeviridae and causes acute HEV infections resulting in thousands of deaths worldwide. The zoonotic nature of HEV in addition to its tendency from human to human transmission has led scientists across the globe to work on its different aspects. HEV also accounts for about 30% mortality rates in case of pregnant women. The genome of HEV is organized into three open reading frames (ORFs): ORF1 ORF2 and ORF3. A reading frame encoded protein ORF4 has recently been discovered which is exclusive to GT 1 isolates of HEV. The ORF4 is suggested to play crucial role in pregnancy-associated pathology and enhanced replication. Though studies have documented the ORF4's importance, the genetic features of ORF4 protein genes in terms of compositional patterns have not been elucidated. As codon usage performs critical role in establishment of the host-pathogen relationship, therefore, the present study reports the codon usage analysis (based on nucleotide sequences of HEV ORF4 available in the public database) in three hosts along with the factors influencing the codon usage patterns of the protein genes of ORF4 of HEV. Results: The nucleotide composition analysis indicated that ORF4 protein genes showed overrepresentation of C nucleotide and while A nucleotide was the least-represented, with random distribution of G and T(U) nucleotides. The relative synonymous codon usage (RSCU) analysis revealed biasness toward C/G-ended codons (over U/A) in all three natural HEV-hosts (human, rat and ferret). It was observed that all the ORF4 genes were richly endowed with GC content. Further, our results showed the occurrence of both coincidence and antagonistic codon usage patterns among HEV-hosts. The findings further emphasized that both mutational and selection forces influenced the codon usage patterns of ORF4 protein genes. Conclusions: To the best of our knowledge, this is first bioinformatics study evaluating codon usage patterns in HEV ORF4 protein genes. The findings from this study are expected to increase our understanding toward significant factors involved in evolutionary changes of ORF4. Supplementary Information: The online version contains supplementary material available at 10.1186/s43088-022-00244-w.