Search

Aim: To estimate if MSH2 polymorphisms, viz. rs63749993, rs2303425, rs2303426, rs4987188, rs2303428 and rs17217772, have any association with clinical outcomes in North Indian lung cancer patients. Materials & methods: PCR-RFLP was used for genotyping 500 cases. Logistic regression and survival analysis was performed by utilizing MedCalc software. Results & conclusion: Our study concluded, adenocarcinoma subjects having heterozygous genotype for rs2303425 have increased survival time (MST = 12.43, p = 0.03). In lung cancer patients undergoing paclitaxel therapy, heterozygous carriers for the rs17217772 polymorphism have reduced survival time (MST = 7.96 vs 2.63 months; HR = 2.09; p = 0.02). For rs63749993 polymorphism undergoing irinotecan therapy, subjects having mutant genotype showed poor survival (13.26 vs 6.06 months; HR = 5.37; p = 0.0004). The results suggest that MSH2 polymorphisms are involved in decreasing overall survival for patients undergoing platinum-based chemotherapy.

In the last 45 years, ebolaviruses have periodically caused epidemics in the African continent. In Dec 2019, approval of a recombinant vector-based EBOV vaccine, named Ervebo, came as an encouraging news; still, there is a long way to go in development of an accessible, global and pan-ebolavirus vaccine. In the current study, we expanded our previous in silico work which was conducted on ebolavirus glycoprotein and resulted in identification of three potentially immunogenic peptides (P1 - FKRTSFFLWVIILFQRTFSIPL, P2 - LANETTQALQLF and P3 - RATTELRTFSILNRKAIDF). An analysis to estimate the number of expected human leukocyte antigen (HLA) responders revealed that P1, P2 and P3 can potentially interact with 2540, 2150 and 2802 HLA alleles respectively. Further, these peptides were subject to in vitro analysis wherein human peripheral blood mononuclear cell (PBMC) proliferation and Interferon-gamma (IFN-γ) production by peptide stimulated cells was studied in ten healthy human blood samples with the help of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and sandwich enzyme-linked immunosorbent assay (ELISA) respectively. P3 presented the best results, a significant (p

Recognizing and monitoring students’ attention during learning is crucial to successful knowledge acquisition since it influences cognitive function. As a result, gaining a precise picture of a learner’s mental state may enable interactive learning systems to alter tutoring content, devise effective help tactics, and improve learning outcomes. In computer-based learning environments, keeping track of students’ mental states is vital. Investigating the feasibility of utilizing active learning in enhancing student engagement index when exposed to various visual stimuli is the genesis of this work. The research includes collecting EEG data from 20 participants (ten males, ten females) while resting and being subjected to various virtual infotainment/educational content. The EEG data were collected using the Allengers Neuro PLOT, a 40-channel wet electrode system. The work includes raw and pre-processed EEG data under quiescent and audio-visual continuous cues. The recorded data is accommodated by a sophisticated EEG data pre-processing pipeline and will be available to the research community for usage.Specifications Table

Dengue virus (DENV) is endemic in 100 countries with the ability to impact nearly 50% of world population. DENV envelope (E) protein is responsible for viral attachment to host cells and has been target of various countermeasure development efforts. The current study focuses on a consensus computational approach to identify cross-reactive, immunogenic DENV-2 E peptides displaying promiscuity with a wide array of human leukocyte antigen (HLA) molecules. Four conserved peptides (FP-1, FP-2, FP-3 and FP-4) containing multiple CD8

Identifying immunogenic targets of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is critical to advance diagnostic and disease control strategies. We analyzed humoral (ELISA) and T-cell (ELISpot) immune responses to spike (S) and nucleocapsid (N) SARS-CoV-2 proteins as well as to human endemic coronavirus (eCoV) peptides in serum from convalescent coronavirus disease 2019 (COVID-19) patients from Tatarstan, Russia. We identified multiple SARS-CoV-2 peptides that were reactive with serum antibodies and T cells from convalescent COVID-19. In addition, age and gender associated differences in the reactivity to S and N protein peptides were identified. Moreover, several SARS-CoV-2 peptides tested negatively correlated with disease severity and lung damage. Cross-reactivity to eCoV peptides was analyzed and found to be lower in COVID-19 compared to controls. In this study, we demonstrate the changing pattern of immunogenic peptide reactivity in COVID-19 serum based on age, gender and previous exposure to eCoVs. These data highlight how humoral immune responses and cytotoxic T cell responses to some of these peptides could contribute to SARS-CoV-2 pathogenesis.

Early indications of the likelihood of severe coronavirus disease 2019 COVID-19 can influence treatments and could improve clinical outcomes. However, knowledge on the prediction markers of COVID-19 fatality risks remains limited. Here, we analyzed and quantified the reactivity of serum samples from acute (non-fatal and fatal) and convalescent COVID-19 patients with the spike surface glycoprotein (S protein) and nucleocapsid phosphoprotein (N protein) SARS-CoV-2 peptide libraries. Cytokine activation was also analyzed. We demonstrated that IgM from fatal COVID-19 serum reacted with several N protein peptides. In contrast, IgM from non-fatal serum reacted more with S protein peptides. Further, higher levels of pro-inflammatory cytokines were found in fatal COVID-19 serum compared to non-fatal. Many of these cytokines were pro-inflammatory and chemokines. Differences in IgG reactivity from fatal and non-fatal COVID-19 sera were also demonstrated. Additionally, the longitudinal analysis of IgG reactivity with SARS-CoV-2 S and N protein identified peptides with the highest longevity in humoral immune response. Finally, using IgM antibody reactivity with S and N SARS-CoV-2 peptides and selected cytokines, we have identified a panel of biomarkers specific to patients with a higher risk of fatal COVID-19 compared with that of patients who survive. This panel could be used for the early prediction of COVID-19 fatality risk.

Ebolaviruses are at the forefront of emerging viruses and present a very perceptible threat to global peace and harmony. In the last decade, Ebola virus disease has claimed more than 90% of total lives since its inception in 1976. Owing to multiple host immune evasion methods employed by the virus and the limitations of traditional vaccine development approaches, finding a globally effective and reliable counter measure against Ebola virus remains a challenge. Highly conserved peptide fragments belonging to critical viral proteins and containing multiple epitopes which have the capacity to interact with a wide array of HLA molecules present a viable solution. Immunoinformatics or computational immunology enables rapid screening and shortlisting of plausible epitopes with a high immunogenic potential, thus, supporting expeditious elucidation of efficacious vaccine candidates. In light of above facts, we describe a computational methodology in this chapter for identification of potent peptide vaccine candidates against human infecting viruses. By applying this stringent methodology, we were able to identify multiple, immunogenic ebolavirus peptide fragments which, after verification in animal models, might be considered as part of future synthetic Ebola vaccine.

In this study, we have done structural and functional analysis of rs1800932 rs1042821 polymorphisms and tried to estimate any association of these polymorphisms with clinical outcomes in north Indian lung cancer patients.Genotyping of 500 lung cancer patients was completed utilizing PCR-RFLP (Polymerase chain reaction- Restriction fragment length polymorphism). MedCalc statistical software was used to calculate adjusted and unadjusted odds ratios. Various computational tools like SIFT PROVEAN are used for functional analysis. Structural analysis was completed via MODELLER and CHIMERA.In our study, patients suffering from small cell lung cancer (SCLC) and harboring heterozygous genotype (AG) for MSH6 (rs1800932) polymorphism have reported a significant increase in median survival time (MST) (20.6 vs. 7.6 months, p = 0.03). Furthermore, for MSH6 rs1042821 polymorphism, patients undergoing docetaxel and carbo/cisplatin combination chemotherapeutic regimen and carrying heterogeneous genotype (CT) reported a significant increase in MST (16.6 vs.8.36 months, p = 0.03) and a corresponding decrease in hazard ratio 0.42 (95% CI= 0.18-1.03). Structural and Functional analysis of rs1042821 polymorphism revealed that it is present in the non-coding region of MSH6 protein and is significantly associated with increased overall survival.These results suggest that MSH6 rs1800932 rs1042821 polymorphisms are involved in increasing the overall survival of lung cancer patients, further confirmed by computational analysis.

Several species of microalgae have been known to produce exopolysaccharides (EPS) with potential immune activity. In the present investigation, ethyl acetate fraction of crude EPS secreted by Dunaliella salina was explored for immunomodulatory activity against peripheral blood mononuclear cells (PBMC) and RAW 264.7 macrophages. Effect of EPS on cell growth and cytokines production were measured using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and ELISA respectively. Griess reagent was used for measuring the nitric oxide production in RAW 264.7 macrophages. FTIR analysis and mass spectroscopy were carried out for the characterization. Ethyl acetate fraction exhibited dose dependent increase in proliferative index and cytokines production (IFN-γ, TNF-α, TGF-β). At low concentration (250 and 500 µg/mL), it showed growth inhibition and at higher concentration (1000 and 1500 µg/mL), it enhanced the cell growth. Interestingly, the pronounced increased TNF-α production was observed in ethyl acetate fraction treated PBMC cells at higher concentration (750 and 1000 µg/mL) indicating the immunostimulatory effect. In RAW cells, concentration dependent diminished cell growth (IC50 = 691 µg/mL) and nitric oxide production (IC50 = 630 µg/mL) was observed. FTIR analysis showed the presence of polysaccharides due to the detection of hydroxyl (–OH), Carbonyl (C–O) and alkyl (C–H) groups. Mass spectroscopy results revealed ethyl acetate fraction as penta-saccharide (m/z = 887.56 and 886.54) which are confirmed to be hetero-polysaccharides consisting of hexoses and pentoses along with association of ions. These results suggest that penta-saccharide (ethyl acetate fraction) isolated from D. salina may have the potential to be used for therapeutic purpose as immunomodulatory agent.

Nephropathia Epidemica (NE), endemic to several Volga regions of Russia, including the Republic of Tatarstan (RT) and the Republic of Mordovia (RM), is a mild form of hemorrhagic fever with renal syndrome caused by infection with rodent-borne orthohantaviruses. Although NE cases have been reported for decades, little is known about the hantavirus strains associated with human infection in these regions. There is also limited understanding of the pathogenesis of NE in the RT and the RM. To address these knowledge gaps, we conducted comparative analyses of patients with NE in the RT and the RM. Clinical symptoms were more severe in patients with NE from the RM with longer observed duration of fever symptoms and hospitalization. Analysis of patient sera showed changes in the levels of numerous cytokines, chemokines, and matrix metalloproteases (MMPs) in patients with NE from both the RT and the RM, suggesting leukocyte activation, extracellular matrix degradation, and leukocyte chemotaxis. Interestingly, levels of several cytokines were distinctly different between patients NE from the RT when compared with those from the RM. These differences were not related to the genetic variation of orthohantaviruses circulating in those regions, as sequence analysis showed that Puumala virus (PUUV) was the causative agent of NE in these regions. Additionally, only the “Russia” (RUS) genetic lineage of PUUV was detected in the serum samples of patients with NE from both the RT and the RM. We therefore conclude that differences in serum cytokine, chemokine, and MMP levels between the RT and the RM are related to environmental factors and lifestyle differences that influence individual immune responses to orthohantavirus infection.

Copper is an essential trace mineral that plays an important role in various physiological processes of human body and also possesses excellent antimicrobial properties, however its high dose results in the formation of free-radicals, which can induce cytotoxicity through chromosomal and DNA damage. Therefore, cytotoxicity of colloidal copper nanoparticles (CuNPs) on murine macrophage cell line (RAW 264.7) was studied to understand the correlation between the cytotoxicity and the nanoparticle yield. Three identical sets of CuNPs with similar physical properties having hydrodynamic particle size of 11–14 nm were prepared by chemical reduction method with target yield of 0.2 g, 0.3 g and 0.4 g. CuNPs exhibited dose-dependent (0.001–100 μg/mL) cytotoxicity due to the mitochondrial damage as indicated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) assay. Oxidative stress induced by reactive oxygen species (ROS) in RAW 246.7 macrophage cell lines exposed to CuNPs was the primary cause of observed cytotoxicity in all CuNPs test samples. Morphological changes in cells also indicated strong dose-dependent oxidative damage by CuNPs. IC50 (half maximal inhibitory concentration) values of CuNPs were independent of nanoparticle yield. This suggests that per batch variation in CuNPs yield from 0.2 g to 0.4 g had no negative correlation with their toxicity that makes CuNPs a potential candidate for further development of nanotherapeutics and anticancer drugs.

Exopolysaccharides (EPS) isolated from microalgae are promising immune cell proliferation agents, that could be potentially used as immunostimulants. In the current study, Scenedesmus acutus (S. acutus) was grown under varying nutrient (sulphur and phosphorus) concentrations to enhance the EPS production, and the isolated EPS were assessed for their effect on cell proliferation using peripheral blood mononuclear cells (PBMC). Five different concentrations of MgSO4 (0, 0.25, 0.5, 1.0 and 1.25 g/L) and K2HPO4 (0, 0.2, 0.6, 0.8 and 1.0 g/L) were taken as compared to the normal culture conditions (0.75 g/L MgSO4 and 0.4 g/L K2HPO4) with the intention to enrich EPS secretion. LC–MS, FTIR and NMR analysis revealed that isolated EPS have the characteristic spectrum of hetero-polysaccharides (octa-saccharides). Immunostimulatory property of EPS was demonstrated by their ability to augment PBMC proliferation as measured by MTT assay. Further, increase in the glucose content and proliferative index was observed for EPS obtained under higher concentrations of MgSO4 (1 and 1.25 g/L) and K2HPO4 (0.6 and 0.8 g/L) relative to normal culture conditions. Effects of the generated EPS under varying concentration of MgSO4 (r = 0.84–0.99) and K2HPO4 (r = 0.76–0.97) remained strongly correlated with cell count, chlorophyll content, total biomass, glucose, proliferative index and its scavenging activity. Collectively, our data not only showed that EPS generated by S. acutus under higher concentration of K2HPO4 and MgSO4 possess improved immunostimulatory properties, but also provides convincing evidence towards nutritional optimization of alga for enhanced EPS production with better bioactivities. Supplementary Information The online version contains supplementary material available at 10.1007/s13205-021-02720-z.

Ebolaviruses are at the forefront of emerging viruses and present a very perceptible threat to global peace and harmony. In the last decade, Ebola virus disease has claimed more than 90% of total lives since its inception in 1976. Owing to multiple host immune evasion methods employed by the virus and the limitations of traditional vaccine development approaches, finding a globally effective and reliable counter measure against Ebola virus remains a challenge. Highly conserved peptide fragments belonging to critical viral proteins and containing multiple epitopes which have the capacity to interact with a wide array of HLA molecules present a viable solution. Immunoinformatics or computational immunology enables rapid screening and shortlisting of plausible epitopes with a high immunogenic potential, thus, supporting expeditious elucidation of efficacious vaccine candidates. In light of above facts, we describe a computational methodology in this chapter for identification of potent peptide vaccine candidates against human infecting viruses. By applying this stringent methodology, we were able to identify multiple, immunogenic ebolavirus peptide fragments which, after verification in animal models, might be considered as part of future synthetic Ebola vaccine.

Background. Multiple sclerosis (MS) is a chronic debilitating disorder characterized by persisting damage to the brain caused by autoreactive leukocytes. Leukocyte activation is regulated by cytokines, which are readily detected in MS serum and cerebrospinal fluid (CSF). Objective. Serum and CSF levels of forty-five cytokines were analyzed to identify MS diagnostic markers. Methods. Cytokines were analyzed using multiplex immunoassay. ANOVA-based feature and Pearson correlation coefficient scores were calculated to select the features which were used as input by machine learning models, to predict and classify MS. Results. Twenty-two and twenty cytokines were altered in CSF and serum, respectively. The MS diagnosis accuracy was ≥92% when any randomly selected five of these biomarkers were used. Interestingly, the highest accuracy (99%) of MS diagnosis was demonstrated when CCL27, IFN-γ, and IL-4 were part of the five selected cytokines, suggesting their important role in MS pathogenesis. Also, these binary classifier models had the accuracy in the range of 70-78% (serum) and 60-69% (CSF) to discriminate between the progressive (primary and secondary progressive) and relapsing-remitting forms of MS. Conclusion. We identified the set of cytokines from the serum and CSF that could be used for the MS diagnosis and classification.

Ebolaviruses, discovered in 1976, belongs to the Filoviridae family, which also includes Marburg and Lloviu viruses. They are negative-stranded RNA viruses with six known species identified to date. Ebola virus (EBOV) is a member of Zaire ebolavirus species and can cause the Ebola virus disease (EVD), an emerging zoonotic disease that results in homeostatic imbalance and multi-organ failure. There are three EBOV outbreaks documented in the last six years resulting in significant morbidity (>32,000 cases) and mortality (>13,500 deaths). The potential factors contributing to the high infectivity of this virus include multiple entry mechanisms, susceptibility of the host cells, employment of multiple immune evasion mechanisms and rapid person-to-person transmission. EBOV infection leads to cytokine storm, disseminated intravascular coagulation, host T cell apoptosis as well as cell mediated and humoral immune response. In this review, a concise recap of cell types targeted by EBOV and EVD symptoms followed by detailed run-through of host innate and adaptive immune responses, virus-driven regulation and their combined effects contributing to the disease pathogenesis has been presented. At last, the vaccine and drug development initiatives as well as challenges related to the management of infection have been discussed.

Copper is known for its bactericidal properties since ancient time. Development of copper nanoparticle (CNP) based antimicrobial products has generated interest in studying their toxicological properties. In this article, we have investigated the ROS (reactive oxygen species)–induced cytotoxicity of colloidal CNPs on MCF-7 human breast cancer cells. To understand the dependence of nanoparticle’s anticancer potential on their per batch yield, three identical sets of CNPs with similar physical properties with hydrodynamic size (11–14 nm) were prepared by chemical reduction method with per batch yield of 0.2 g, 0.3 g, and 0.4 g. Dose-dependent toxicity of as-synthesized (i.e., without any post preparation treatment) CNPs was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay for CNP concentrations of 0.001–100 μg/mL. Strong dose-dependent toxicity was observed in all CNPs batches, which was because of the mitochondrial damage in MCF-7. Cytotoxicity in MCF-7 exposed to CNPs was observed due to rupture of cell membrane and shrinkage as well as oxidative stress induced by reactive oxygen species (ROS). IC50 values of CNPs were independent of per batch yield of CNPs. This confirms that increase in CNPs yield from 0.2 to 0.4 g has no negative correlation with their cytotoxic response. The ability to scale up the nanoparticle yield with strong dose-dependent cytotoxicity makes CNPs potential candidate for the development of anticancer drugs.

SARS-CoV-2 has spread very quickly from its first reported case on January 19th, 2020 in the United Stated of America, leading WHO to declare pandemic by March 11th, 2020. RNA viruses accumulate mutations following replication and passage in human population, which prompted us to determine the rate and the regions (hotspots) of the viral genome with high rates of mutation. We analyzed the rate of mutation accumulation over a period of 11 weeks (submitted between 19th January to 15th April 2020) in USA SARS-CoV-2 genome. Our analysis identified that majority of the viral genes accumulated mutations, although with varying rates and these included NSP2, NSP3, RdRp, helicase, Spike, ORF3a, ORF8, and Nucleocapsid protein. Sixteen mutations accumulated in Spike protein in which four mutations are located in the receptor binding domain. Intriguingly, we identified a fair number of viral proteins (NSP7, NSP9, NSP10, NSP11, Envelop, ORF6, and ORF7b proteins), which did not accumulate any mutation. Limited changes in these proteins may suggest that they have conserved functions, which are essential for virus propagation. This provides a basis for a better understanding of the genetic variation in SARS-CoV-2 circulating in the US, which could help in identifying potential therapeutic targets for controlling COVID-19.

Peptide-based vaccines are an appealing strategy which involves usage of short synthetic peptides to engineer a highly targeted immune response. These short synthetic peptides contain potential T- and B-cell epitopes. Experimental approaches in identifying these epitopes are time-consuming and expensive; hence immunoinformatics approach came into picture. Immuninformatics approach involves epitope prediction tools, molecular docking, and population coverage analysis in design of desired immunogenic peptides. In order to overcome the antigenic variation of viruses, conserved regions are targeted to find the potential epitopes. The present chapter demonstrates the use of immunoinformatics approach to select potential peptide containing multiple T- (CD8+ and CD4+) and B-cell epitopes from Avian H3N2 M1 Protein. Further, molecular docking (to analyse HLA-peptide interaction) and population coverage analysis have been used to verify the potential of peptide to be presented by polymorphic HLA molecules. In silico approach of epitope prediction has proven to be successful methodology in screening the putative epitopes among numerous possible vaccine targets in a given protein.

Peptide-based vaccines are an appealing strategy which involves usage of short synthetic peptides to engineer a highly targeted immune response. These short synthetic peptides contain potential T- and B-cell epitopes. Experimental approaches in identifying these epitopes are time-consuming and expensive; hence immunoinformatics approach came into picture. Immuninformatics approach involves epitope prediction tools, molecular docking, and population coverage analysis in design of desired immunogenic peptides. In order to overcome the antigenic variation of viruses, conserved regions are targeted to find the potential epitopes. The present chapter demonstrates the use of immunoinformatics approach to select potential peptide containing multiple T- (CD8+ and CD4+) and B-cell epitopes from Avian H3N2 M1 Protein. Further, molecular docking (to analyse HLA-peptide interaction) and population coverage analysis have been used to verify the potential of peptide to be presented by polymorphic HLA molecules. In silico approach of epitope prediction has proven to be successful methodology in screening the putative epitopes among numerous possible vaccine targets in a given protein.

Cinnamomum verum plant is widely used in traditional medicine to reduce inflammation. In the present study, water-soluble polysaccharides were isolated from Cinnamomum verum bark followed by sequential separation from four solvent extracts (hexane, dichloromethane, chloroform and methanol) and analysed for the presence of sugar, protein and different phytochemicals. Crude and purified ethyl acetate fractions of soluble polysaccharides were analysed in vitro using mouse leukemic macrophage (RAW 264.7) cell line and human peripheral blood mononuclear cells (PBMCs). Water-soluble (crude and ethyl acetate purified fractionation) polysaccharides contained glucose, whereas proteins and phytochemicals were absent. Water-soluble polysaccharide fraction had less antioxidant activity as compared to all four solvent extracts. Also, water-soluble polysaccharides (250 μg/ml) did not affect the cell growth, while all other four extracts (250 μg/ml) inhibited the growth of RAW 264.7 cells. Cell growth inhibition was detected when concentration of crude and ethyl acetate fraction polysaccharides was increased, where IC50 values were 1120 ± 27 and 1780 ± 227 μg/mL, respectively. Interestingly, crude and ethyl acetate polysaccharides showed concentration-dependent increase of the cell growth in PBMCs, indicating immunostimulating effect. Our data suggests that the immunological properties of cinnamon may be associated with the presence of polysaccharides.

SputnikV is a vaccine against SARS-CoV-2 developed by the Gamaleya National Research Centre for Epidemiology and Microbiology. The vaccine has been shown to induce both humoral and cellular immune responses, yet the mechanisms remain largely unknown. Forty SputnikV vaccinated individuals were included in this study which aimed to demonstrate the location of immunogenic domains of the SARS-CoV-2 S protein using an overlapping peptide library. Additionally, cytokines in the serum of vaccinated and convalescent COVID-19 patients were analyzed. We have found antibodies from both vaccinated and convalescent sera bind to immunogenic regions located in multiple domains of SARS-CoV-2 S protein, including Receptor Binding Domain (RBD), N-terminal Domain (NTD), Fusion Protein (FP) and Heptad Repeats (HRs). Interestingly, many peptides were recognized by immunized and convalescent serum antibodies and correspond to conserved regions in circulating variants of SARS-CoV-2. This breadth of reactivity was still evident 90 days after the first dose of the vaccine, showing that the vaccine has induced a prolonged response. As evidenced by the activation of T cells, cellular immunity strongly suggests the high potency of the SputnikV vaccine against SARS-CoV-2 infection.

Ebola virus (EBOV), member of genus Ebolavirus, family Filoviridae, have a non-segmented, single-stranded RNA that contains seven genes: (a) nucleoprotein (NP), (b) viral protein 35 (VP35), (c) VP40, (d) glycoprotein (GP), (e) VP30, (f) VP24, and (g) RNA polymerase (L). All genes encode for one protein each except GP, producing three pre-proteins due to the transcriptional editing. These pre-proteins are translated into four products, namely: (a) soluble secreted glycoprotein (sGP), (b) Δ-peptide, (c) full-length transmembrane spike glycoprotein (GP), and (d) soluble small secreted glycoprotein (ssGP). Further, shed GP is released from infected cells due to cleavage of GP by tumor necrosis factor α-converting enzyme (TACE). This review presents a detailed discussion on various functional aspects of all EBOV proteins and their residues. An introduction to ebolaviruses and their life cycle is also provided for clarity of the available analysis. We believe that this review will help understand the roles played by different EBOV proteins in the pathogenesis of the disease. It will help in targeting significant protein residues for therapeutic and multi-protein/peptide vaccine development.

Influenza vaccine development is considered to be complicated and challenging. Constantly evolving influenza viruses require continuous global monitoring and reformulation of the vaccine strains. Peptides that are conserved among different strains and subtypes of influenza A virus are strongly considered to be attractive targets for development of cross protective influenza vaccines that stimulate cellular responses. In this study, three highly conserved (>90%) matrix 1 peptides that contain multiple T cell epitopes, ILGFVFTLTVPSERGLQRRRF (PM 1), LIRHENRMVLASTTAKA (PM 2) and LQAYQKRMGVQMQR (PM 3), were assessed for their immunogenic potential in vitro by subjecting peripheral blood mononuclear cells from healthy volunteers to repetitive stimulation with these chemically synthesised peptides and measuring their IFN-γ concentrations, proliferation by ELISA, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, respectively. Seven samples were screened for immunogenicity of PM 1 and PM 2, and six for that of PM 3. All six samples had positive responses (IFN-γ secretion) to PM 3 stimulation, as did five and three for PM 2 and PM 1 respectively. In contrast, seven (PM 1 and PM 2) and four (PM 3) samples showed proliferative response as compared with unstimulated cells. The encouraging immunogenic response generated by these highly conserved matrix 1 peptides indicates they are prospective candidates for development of broadly reactive influenza vaccines.

An endophytic fungus (strain T1) isolated from Taxus baccata was studied for the production of metabolites with anticancer and antioxidant activities. This fungus was identified as Diaporthe sp. based on rDNA-internal transcribed spacer (ITS) sequence analysis. The crude extract showed cytotoxic activity against MCF-7 and HeLa cancer cell lines, with IC50 (concentration inhibiting 50% of growth rate) values of 1058 ± 44 and 1257 ± 80 μg ml−1, respectively. The scavenging activity of fungal extract increased significantly with increasing concentration [IC50 (concentration required to scavenge 50% of free radicals) 482 ± 9 μg ml−1]. Ultra-high-performance liquid chromatography-quadrupole-time of flight analysis revealed the presence of three trichalasins (trichalasin E, F and H) in the crude extract of T1 which are known to have antitumour and antioxidant activities. These results suggest that Diaporthe sp. has the potential to be used for therapeutic purposes because of its antiproliferative and antioxidant potential and also for the production of cytochalasins.

Multiple sclerosis (MS) is a neurodegenerative disease characterized by lesions in the central nervous system (CNS). Inflammation and demyelination are the leading causes of neuronal death and brain lesions formation. The immune reactivity is believed to be essential in the neuronal damage in MS. Cytokines play important role in differentiation of Th cells and recruitment of auto-reactive B and T lymphocytes that leads to neuron demyelination and death. Several cytokines have been found to be linked with MS pathogenesis. In the present study, serum level of eight cytokines (IL-1β, IL-2, IL-4, IL-8, IL-10, IL-13, IFN-γ, and TNF-α) was analyzed in USA and Russian MS to identify predictors for the disease. Further, the model was extended to classify MS into remitting and non-remitting by including age, gender, disease duration, Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) into the cytokines datasets in Russian cohorts. The individual serum cytokines data for the USA cohort was generated by Z score percentile method using R studio, while serum cytokines of the Russian cohort were analyzed using multiplex immunoassay. Datasets were divided into training (70%) and testing (30%). These datasets were used as an input into four machine learning models (support vector machine, decision tree, random forest, and neural networks) available in R programming language. Random forest model was identified as the best model for diagnosis of MS as it performed remarkable on all the considered criteria i.e., Gini, accuracy, specificity, AUC, and sensitivity. RF model also performed best in predicting remitting and non-remitting MS. The present study suggests that the concentration of serum cytokines could be used as prognostic markers for the prediction of MS.

Altered expression of many genes and proteins is essential for cancer development and progression. Recently, the affected expression of metadherin (MTDH), also known as AEG-1 (Astrocyte Elevated Gene 1) and Lyric, has been implicated in various aspects of cancer progression and metastasis. Elevated expression of MTDH/AEG-1 has been reported in many cancers including breast, prostate, liver, and esophageal cancers, whereas its expression is low or absent in non-malignant tissues. These expression studies suggest that MTDH may represent a potential tumor associated antigen. MTDH also regulates multiple signaling pathways including PI3K/Akt, NF-κB, Wnt/β-catenin, and MAPK which cooperate to promote the tumorigenic and metastatic potential of transformed cells. Several microRNA have also been found to be associated with the increased MTDH expression in different cancers. Increased MTDH levels were linked to the tumor chemoresistance making it an attractive novel therapeutic target. In this review, we summarize data on MTDH function in various cancers.