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Humans are a major reservoir of the hepatitis B virus (HBV), therefore promising treatment and control vaccination strategies are needed to eradicate the virus. Though promising drugs and vaccines are available against HBV, still efforts are required to enrich the therapy options. Herein, the HBV assembly protein was explored to identify novel targets for future use against HBV. Computer-aided drug designing and immune-informatics techniques were employed for the identification of putative inhibitors and vaccine ensemble against HBV using capsid assembly protein. The identified drug molecule binds with high affinity to the active pocket of the protein, and several epitopes are scanned in the protein sequence. The drug molecule, besides being a good putative inhibitor, has acceptable drug-like properties. A multi-epitope vaccine is also constructed to overcome the limitations of weakly immunogenic epitopes. In contrast to the MHC II level, the set of predicted epitopes has been recognized to interact with significant numbers of HLA alleles of MHC I. Selected epitopes are extremely virulent, antigenic, nontoxic, nonallergic, have suitable affinity to bind with the prevailing DRB*0101 allele, and also spectacle 86% mediocre population coverage. A multi-epitope peptide-based vaccine chimera having 73 amino acids was designed. It emerged as substantially immunogenic, thermally stable, robust in producing cellular as well as humoral immune responses, and had competent physicochemical properties to analyze in vitro and in vivo studies. The capsid assembly protein is a in more stable nature in the presence of the drug molecule compared to the TLR3 receptor in the vaccine presence. These particulars were confirmed by exposing the docked molecules to absolute and relative binding free energy approaches of MMGBSA/PBSA. The purpose to investigate the interactions between the vaccine and a representative TLR3 immune receptor can reveal the intermolecular affinity and possible presentation mechanism of the vaccine by TLR3 to the host immune system. It was revealed that the vaccine is showing a very good affinity of binding for the TLR3 and forming a network of hydrophobic and hydrophilic interactions. Overall, the findings of this study are promising and might be useful for further experimental validations. [ABSTRACT FROM AUTHOR]

The interaction between SARS-CoV-2 Spike protein and angiotensin-converting enzyme 2 (ACE2) is essential to viral attachment and the subsequent fusion process. Interfering with this event represents an attractive avenue for the development of therapeutics and vaccine development. Here, a hybrid approach of ligand- and structure-based virtual screening techniques were employed to disclose similar analogues of a reported antiviral phytochemical, glycyrrhizin, targeting the blockade of ACE2 interaction with the SARS-CoV-2 Spike. A ligand-based similarity search using a stringent cut-off revealed 40 FDA-approved compounds in DrugBank. These filtered hits were screened against ACE2 using a blind docking approach to determine the natural binding tendency of the compounds with ACE2. Three compounds, deslanoside, digitoxin, and digoxin, were reported to show strong binding with ACE2. These compounds bind at the H1-H2 binding pocket, in a manner similar to that of glycyrrhizin which was used as a control. To achieve consistency in the docking results, docking calculations were performed via two sets of docking software that predicted binding energy as ACE2-Deslanoside (AutoDock, −10.3 kcal/mol and DockThor, −9.53 kcal/mol), ACE2-Digitoxin (AutoDock, −10.6 kcal/mol and DockThor, −8.84 kcal/mol), and ACE2-Digoxin (AutoDock, −10.6 kcal/mol and DockThor, −8.81 kcal/mol). The docking results were validated by running molecular simulations in aqueous solution that demonstrated the stability of ACE2 with no major conformational changes in the ligand original binding mode (~ 2 Å average RMSD). Binding interactions remained quite stable with an increased potential for getting stronger as the simulation proceeded. MMGB/PBSA binding free energies were also estimated and these supported the high stability of the complexes compared to the control (~ −50 kcal/mol net MMGB/PBSA binding energy versus ~ −30 kcal/mol). Collectively, the data demonstrated that the compounds shortlisted in this study might be subjected to experimental evaluation to uncover their real blockade capacity of SARS-CoV-2 host ACE2 receptor. [ABSTRACT FROM AUTHOR]

Knowing the beneficial aspects of nanomedicine, scientists are trying to harness the applications of nanotechnology in diagnosis, treatment, and prevention of diseases. There are also potential uses in designing medical tools and processes for the new generation of medical scientists. The main objective for conducting this research review is to gather the widespread aspects of nanomedicine under one heading and to highlight standard research practices in the medical field. Comprehensive research has been conducted to incorporate the latest data related to nanotechnology in medicine and therapeutics derived from acknowledged scientific platforms. Nanotechnology is used to conduct sensitive medical procedures. Nanotechnology is showing successful and beneficial uses in the fields of diagnostics, disease treatment, regenerative medicine, gene therapy, dentistry, oncology, aesthetics industry, drug delivery, and therapeutics. A thorough association of and cooperation between physicians, clinicians, researchers, and technologies will bring forward a future where there is a more calculated, outlined, and technically programed field of nanomedicine. Advances are being made to overcome challenges associated with the application of nanotechnology in the medical field due to the pathophysiological basis of diseases. This review highlights the multipronged aspects of nanomedicine and how nanotechnology is proving beneficial for the health industry. There is a need to minimize the health, environmental, and ethical concerns linked to nanotechnology. [ABSTRACT FROM AUTHOR]

Nanotechnology, contrary to its name, has massively revolutionized industries around the world. This paper predominantly deals with data regarding the applications of nanotechnology in the modernization of several industries. A comprehensive research strategy is adopted to incorporate the latest data driven from major science platforms. Resultantly, a broad-spectrum overview is presented which comprises the diverse applications of nanotechnology in modern industries. This study reveals that nanotechnology is not limited to research labs or small-scale manufacturing units of nanomedicine, but instead has taken a major share in different industries. Companies around the world are now trying to make their innovations more efficient in terms of structuring, working, and designing outlook and productivity by taking advantage of nanotechnology. From small-scale manufacturing and processing units such as those in agriculture, food, and medicine industries to larger-scale production units such as those operating in industries of automobiles, civil engineering, and environmental management, nanotechnology has manifested the modernization of almost every industrial domain on a global scale. With pronounced cooperation among researchers, industrialists, scientists, technologists, environmentalists, and educationists, the more sustainable development of nano-based industries can be predicted in the future. [ABSTRACT FROM AUTHOR]

Background: In November 2019, the world faced a pandemic called SARS-CoV-2, which became a major threat to humans and continues to be. To overcome this, many plants were explored to find a cure. Methods: Therefore, this research was planned to screen out the active constituents from Artemisia annua that can work against the viral main protease Mpro as this non-structural protein is responsible for the cleavage of replicating enzymes of the virus. Twenty-five biocompounds belonging to different classes namely alpha-pinene, beta-pinene, carvone, myrtenol, quinic acid, caffeic acid, quercetin, rutin, apigenin, chrysoplenetin, arteannunin b, artemisinin, scopoletin, scoparone, artemisinic acid, deoxyartemisnin, artemetin, casticin, sitogluside, beta-sitosterol, dihydroartemisinin, scopolin, artemether, artemotil, artesunate were selected. Virtual screening of these ligands was carried out against drug target Mpro by CB dock. Results: Quercetin, rutin, casticin, chrysoplenetin, apigenin, artemetin, artesunate, sopolin and sito-gluside were found as hit compounds. Further, ADMET screening was conducted which represented Chrysoplenetin as a lead compound. Azithromycin was used as a standard drug. The interactions were studied by PyMol and visualized in LigPlot. Furthermore, the RMSD graph shows fluctuations at various points at the start of simulation in Top1 (Azithromycin) complex system due to structural changes in the helix-coil-helix and beta-turn-beta changes at specific points resulting in increased RMSD with a time frame of 50 ns. But this change remains stable after the extension of simulation time intervals till 100 ns. On other side, the Top2 complex system remains highly stable throughout the time scale. No such structural dynamics were observed bu the ligand attached to the active site residues binds strongly. Conclusion: This study facilitates researchers to develop and discover more effective and specific therapeutic agents against SARS-CoV-2 and other viral infections. Finally, chrysoplenetin was identified as a more potent drug candidate to act against the viral main protease, which in the future can be helpful. [ABSTRACT FROM AUTHOR]

Background. Aliarcobacter butzleri is a Gram-negative, curved or spiral-shaped, microaerophilic bacterium and causes human infections, specifically diarrhea, fever, and sepsis. The research objective of this study was to employ computer-aided drug design techniques to identify potential natural product inhibitors of a vital enzyme in this bacterium. The pyrimidine biosynthesis pathway in its core genome fraction is crucial for its survival and presents a potential target for novel therapeutics. Hence, novel small molecule inhibitors were identified (from traditional Chinese medicinal (TCM) compound library) against it, which may be used for possible curbing of infection by A. butzleri. Methods. A comprehensive subtractive genomics approach was utilized to identify a key enzyme (orotidine- 5 ′ -phosphate decarboxylase) cluster conserved in the core genome fraction of A. butzleri. It was selected for inhibitor screening due to its vital role in pyrimidine biosynthesis. TCM library (n > 36,000 compounds) was screened against it using pharmacophore model based on orotidylic acid (control), and the obtained lead-like molecules were subjected to structural docking using AutoDock Vina. The top-scoring compounds, ZINC70454134, ZINC85632684, and ZINC85632721, underwent further scrutiny via a combination of physiological-based pharmacokinetics, toxicity assessment, and atomic-scale dynamics simulations (100 ns). Results. Among the screened compounds, ZINC70454134 displayed the most favorable characteristics in terms of binding, stability, absorption, and safety parameters. Overall, traditional Chinese medicine (TCM) compounds exhibited high bioavailability, but in diseased states (cirrhosis, renal impairment, and steatosis), there was a significant decrease in absorption, Cmax, and AUC of the compounds compared to the healthy state. Furthermore, MD simulation demonstrated that the ODCase-ZINC70454134 complex had a superior overall binding affinity, supported by PCA proportion of variance and eigenvalue rank analysis. These favorable characteristics underscore its potential as a promising drug candidate. Conclusion. The computer-aided drug design approach employed for this study helped expedite the discovery of antibacterial compounds against A. butzleri, offering a cost-effective and efficient approach to address infection by it. It is recommended that ZINC70454134 should be considered for further experimental analysis due to its indication as a potential therapeutic agent for combating A. butzleri infections. This study provides valuable insights into the molecular basis of biophysical inhibition of A. butzleri through TCM compounds. [ABSTRACT FROM AUTHOR]

Background: The WHO has issued a call to action urging countries to accelerate the rollout of new WHO-recommended shorter all-oral treatment regimens for drug-resistant TB (DR-TB), which remains a public-health crisis. The all-oral, 6-month BPaL/M regimen comprises 3–4 drugs: pretomanid used in combination with bedaquiline and linezolid, with or without moxifloxacin. This regimen has been recommended by the WHO for use in DR-TB patients instead of ≥9-month (up to 24-month) regimens. This study aims to project this regimen's use, along with its components bedaquiline, pretomanid and linezolid, and other treatments for DR-TB globally through 2026. It is intended to guide global health stakeholders in planning and budgeting for DR-TB interventions. Projected usage could help estimate cost of the individual components of DR-TB regimens over time. Methods: Semi-structured interviews were conducted with national TB programme participants in key countries to gather intelligence on established plans and targets for use of various DR-TB treatment regimens from 2023 to 2026. These data informed development of projections for the global use of regimens and drugs. Results: Consistent global growth in the use of shorter regimens in DR-TB treatment was shown: BPaLM reaching 126,792 patients, BPaL reaching 43,716 patients, and the 9-11-month all-oral bedaquiline-based regimen reaching 13,119 patients by 2026. By 2026, the longer all-oral regimen is projected to be used by 19,262 patients, and individualised treatment regimens by 15,344 patients. Conclusion: The study shows BPaL/M will be used in majority of DR-TB patients by 2024, reaching 78% by 2026. However, national efforts to scale-up, case-finding, monitoring, drug-susceptibility testing, and implementation of new treatments will be essential for ensuring they are accessible to all eligible patients in the coming years and goals for ending TB are met. There is an urgent need to engage communities in capacity building and demand generation. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is one of the leading acute liver infections triggered by viral hepatitis. Patients infected with HEV usually recover and the annual death rate is negligible. Currently, there is no HEV licensed vaccine available globally. This study was carried out to design a multi-epitope HEV peptide-based vaccine by retrieving already experimentally validated epitopes from ViPR database leading to epitope prioritization. Epitopes selected as potential vaccine candidates were non-allergen, immunogenic, soluble, non-toxic and IFN gamma positive. The epitopes were linked together by AAY linkers and the linker EAAAK was used to join adjuvant with epitopes. Toll-like receptor (TLR)-4 agonist was used as an adjuvant to boost efficacy of the vaccine. Furthermore, codon optimization followed by disulfide engineering was performed to analyse the designed vaccine's structural stability. Computational modeling of the immune simulation was done to examine the immune response against the vaccine. The designed vaccine construct was docked with TLR-3 receptor for their interactions and then subjected to molecular dynamic simulations. The vaccine model was examined computationally towards the capability of inducing immune responses which showed the induction of both humoral and cell mediated immunity. Taken together, our study suggests an In-silico designed HEV based multi-epitope peptide-based vaccine (MEPV) that needs to be examined in the wet lab-based data that can help to develop a potential vaccine against HEV. [ABSTRACT FROM AUTHOR]

The two most familiar scores used for prognostication of liver cirrhosis are the Model for End-stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP), while the Glasgow-Blatchford (GB) score is used for sorting non-variceal upper gastrointestinal hemorrhage into high- or low-risk categories. This study evaluates the validity of the CTP, MELD, and GB scoring systems in prognosticating the in-hospital outcome of bleeding portal hypertensive patients. In this study, the ROC curve and Younden index determine the efficacy of three scoring systems. The results indicate that CTP was the most efficient score as the predictor of outcome (AUC = 0.9, cut-off value > 7); followed by MELD (AUC = 0.8, cut-off value > 18) and then the GB score (AUC = 0.64, cut-off value > 14) (p < 0.05). In pair-wise comparison, the difference between CTP and MELD was insignificant (p > 0.05). Patients with a CTP score of >7 had notably higher in-hospital mortality (19.8% vs. 0.9%, p < 0.0001). Similarly, mortality with a MELD score > 18 was significant (14.8% vs. 5.9% (p < 0.0001). The GB score was not a good indicator of the outcome. Platelets, albumin, CTP, and MELD scores were the independent contributors to mortality. Thus, as liver cirrhosis prognosticators, CTP and MELD scores can also both be used as predictive scores of the in-hospital outcomes of bleeding patients due to portal hypertension. Compared to the GB score, CTP and MELD scores are fairly efficient predictors in these patients. [ABSTRACT FROM AUTHOR]

In Pakistan and other developing countries, the available data on the association of T2DM and HCV is limited. We therefore made an attempt to report the association of HCV and diabetes in Pakistani population through this meta-analysis. HCV and diabetes related studies were identified using various key words, from a number of databases including CINAHL, PubMed, Web of Science and Embase. Using RevMan5, the main outcome was regarded as type 2 diabetes associations with hepatitis c virus infection in Pakistan. Independent analyses were made for "HCV in diabetic patients" and "diabetes cases in hepatitis C virus patients". Using random effect model, odds ratios were calculated with 95% CIs (dichotomous data). I2 statistics were used to calculate heterogeneity. From a total of 53 studies, we finally selected 6 studies for the meta-analysis. Using random effects model, hepatitis c virus patients in 3 studies (n = 1,902) demonstrated that HCV is a risk factor in developing diabetes, contrary to patients with no HCV infection (OR 0.01, 95% CI: 0.00-0.06, I2 = 0%; RR 0.01, 95% CI: 0.00-0.07, I2 = 0%). The remaining 3 studies (n = 13,710) had reported HCV infections in type 2 diabetic patients and patients with no diabetes. Similarly, our meta-analysis revealed higher prevalence of HCV infections in patients with type 2 diabetes (OR 0.7, 95% CI: 0.17-0.42, I2 = 32%; RR 0.30, 95% CI: 0.20-0.46, I2 = 32%) as compared to patients with no type 2 diabetes mellitus. Our meta-analysis demonstrates a significant link between HCV and T2DM. Further studies are recommended with adequate sample sizes [ABSTRACT FROM AUTHOR]

• A multiple epitope subunit vaccine designed against Colorado tick virus. • A significant amount of IgM antibodies with an increase in immunoglobulin levels was found. • Over the course of simulation, the vaccine showed robust interactions with TLR4 receptor. • Strong hydrophobic and hydrophilic contacts have been inferred with high stability over 200 ns time intervals. Despite being a medically significant tick-borne virus, little research has been done on the Colorado tick fever virus. This virus is a member of the Spinareoviridae family and is mainly spread in the western parts of the United States and southwest Canada. It is classified as a Coltivirus. The main vector of the virus, Dermacentor andersoni , a wood tick found in the Rocky Mountains, determines patterns of viral spread. Furthermore, no effective antiviral treatment or vaccine has yet been created to guard against viral infections. An alternate method of preventing viral infections is vaccination. To stop a potential pandemic in the future, a thermodynamically stable and economical vaccination should be discovered. The goal of this study was to develop a potential vaccine against the Colorado tick fever virus. We seek to identify epitopes within two critical proteins, the Colorado tick fever virus's structural protein VP9 and the RNA-directed RNA polymerase VP1, to predict the precise locations that B and T cells will recognize by using a variety of reverse vaccinology and Computational techniques. Through modelling, the epitopes were deliberately engineered to connect with their corresponding HLA molecules, serving as the foundation for a multi-epitope subunit vaccination. This meticulously crafted vaccination candidate was created by joining B and T cell epitopes that had been extensively examined and linked with the appropriate linkers. Numerous physiological characteristics, including molecular weight, instability index, and aliphatic index, were assessed for the vaccine model, it was 3D modelled to dock with TLR-4. Previous research suggested that adding human beta-defensin as an adjuvant to the vaccine sequence at the N-terminus might improve immunogenicity. Additionally, the C-IMMSIM server ran immunological simulations to confirm the final vaccine design. The immunological simulation analysis anticipated a natural immune response. E. coli was used as the host for in-silico cloning, and the 0.96 CAI value obtained indicates that the vaccine construct will express itself to its fullest extent in the E. coli host. The binding mode of vaccine construct has been investigated via molecular docking approach against TLR4 human receptor protein. Vaccine created in this study shown efficacious and immunogenic response during immune simulation. Furthermore, this was more accurately validated through molecular dynamic simulations where the receptor molecule strongly bonds to the active residues of the epitope during 200 ns simulation time intervals. No certain changes were inferred among both receptor molecules and epitope during this time interval and remains static. Thus, these investigations result in determining the effectiveness in treating infections caused by the Colorado tick fever virus, which will allow experimentalists for its further validation to tackle this disease. [ABSTRACT FROM AUTHOR]

The JCV (John Cunningham Virus) is known to cause progressive multifocal leukoencephalopathy, a condition that results in the formation of tumors. Symptoms of this condition such as sensory defects, cognitive dysfunction, muscle weakness, homonosapobia, difficulties with coordination, and aphasia. To date, there is no specific and effective treatment to completely cure or prevent John Cunningham polyomavirus infections. Since the best way to control the disease is vaccination. In this study, the immunoinformatic tools were used to predict the high immunogenic and non-allergenic B cells, helper T cells (HTL), and cytotoxic T cells (CTL) epitopes from capsid, major capsid, and T antigen proteins of JC virus to design the highly efficient subunit vaccines. The specific immunogenic linkers were used to link together the predicted epitopes and subjected to 3D modeling by using the Robetta server. MD simulation was used to confirm that the newly constructed vaccines are stable and properly fold. Additionally, the molecular docking approach revealed that the vaccines have a strong binding affinity with human TLR-7. The codon adaptation index (CAI) and GC content values verified that the constructed vaccines would be highly expressed in E. coli pET28a (+) plasmid. The immune simulation analysis indicated that the human immune system would have a strong response to the vaccines, with a high titer of IgM and IgG antibodies being produced. In conclusion, this study will provide a pre-clinical concept to construct an effective, highly antigenic, non-allergenic, and thermostable vaccine to combat the infection of the John Cunningham virus. • The JCV (John Cunningham Virus) is known to cause progressive multifocal leukoencephalopathy. • To date, there is no specific and effective treatment to completely cure or prevent John Cunningham. • In this study, the immunoinformatic tools were used to predict the high immunogenic and non-allergenic epitopes to design the highly efficient subunit vaccines. • MD simulation was used to confirm that the newly constructed vaccines are stable and properly fold. • The immune simulation analysis indicated that the human immune system would have a strong response upon the injection. [ABSTRACT FROM AUTHOR]

The continued emergence of human coronaviruses (hCoVs) in the last few decades has posed an alarming situation and requires advanced cross-protective strategies against these pandemic viruses. Among these, Middle East Respiratory Syndrome coronavirus (MERS-CoV), Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), and Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) have been highly associated with lethality in humans. Despite the challenges posed by these viruses, it is imperative to develop effective antiviral therapeutics and vaccines for these human-infecting viruses. The proteomic similarity between the receptor-binding domains (RBDs) among the three viral species offers a potential target for advanced cross-protective vaccine designs. In this study, putative immunogenic epitopes including Cytotoxic T Lymphocytes (CTLs), Helper T Lymphocytes (HTLs), and Beta-cells (B-cells) were predicted for each RBD-containing region of the three highly pathogenic hCoVs. This was followed by the structural organization of peptide- and mRNA-based prophylactic vaccine designs. The validated 3D structures of these epitope-based vaccine designs were subjected to molecular docking with human TLR4. Furthermore, the CTL and HTL epitopes were processed for binding with respective human Lymphocytes Antigens (HLAs). In silico cloning designs were obtained for the prophylactic vaccine designs and may be useful in further experimental designs. Additionally, the epitope-based vaccine designs were evaluated for immunogenic activity through immune simulation. Further studies may clarify the safety and efficacy of these prophylactic vaccine designs through experimental testing against these human-pathogenic coronaviruses. [ABSTRACT FROM AUTHOR]

As SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) continues to inflict chaos globally, a new variant officially known as B.1.1.529 was reported in South Africa and was found to harbor 30 mutations in the spike protein. It is too early to speculate on transmission and hospitalizations. Hence, more analyses are required, particularly to connect the genomic patterns to the phenotypic attributes to reveal the binding differences and antibody response for this variant, which can then be used for therapeutic interventions. Given the urgency of the required analysis and data on the B.1.1.529 variant, we have performed a detailed investigation to provide an understanding of the impact of these novel mutations on the structure, function, and binding of RBD to hACE2 and mAb to the NTD of the spike protein. The differences in the binding pattern between the wild type and B.1.1.529 variant complexes revealed that the key substitutions Asn417, Ser446, Arg493, and Arg498 in the B.1.1.529 RBD caused additional interactions with hACE2 and the loss of key residues in the B.1.1.529 NTD resulted in decreased interactions with three CDR regions (1–3) in the mAb. Further investigation revealed that B.1.1.529 displayed a stable dynamic that follows a global stability trend. In addition, the dissociation constant (K D), hydrogen bonding analysis, and binding free energy calculations further validated the findings. Hydrogen bonding analysis demonstrated that significant hydrogen bonding reprogramming took place, which revealed key differences in the binding. The total binding free energy using MM/GBSA and MM/PBSA further validated the docking results and demonstrated significant variations in the binding. This study is the first to provide a basis for the higher infectivity of the new SARS-CoV-2 variants and provides a strong impetus for the development of novel drugs against them. [ABSTRACT FROM AUTHOR]

Objective: To evaluate probiotics' effects in reducing hyperbilirubinemia in late preterm and term neonates. Study Design: Quasi-experimental study Place and Duration of Study: Department of Neonatology, Pakistan Institute of Medical Sciences (PIMS), Islamabad Pakistan, from Oct 2018 to Mar 2019. Methodology: The quasi-experimental study was conducted on 60 neonates with hyperbilirubinemia. They were randomly divided into two Groups. Group-A (n=30) received phototherapy. Group-B (n=30) received probiotics containing Lactobacillus reuteri at a dose of 5 drops daily for three days, in addition to phototherapy. Total serum bilirubin was calculated at 0, 24 and 72 hours for both Groups. Results: In Group-A, the mean total bilirubin in mg/dl at 0, 24 and 72 hours were 18.14±2.35, 15.28±2.93 and 12.31±2.29, respectively. Similarly, in Group-B, it was 19.86±5.85, 16.23±4.01 and 10.75±2.23 at 0, 24 and 72 hours, respectively. There was an insignificant statistical difference in mean total bilirubin between Groups A and B at 0 and 24 hours (p<0.001). However, when comparison was made at 72 hours, a significant statistical difference was observed in Group-B (Intervention Group) (p=0.005) Conclusion: Probiotics significantly lowered total serum bilirubin in neonates with hyperbilirubinemia. Further studies are required to evaluate its role in physiological and pathological jaundice. [ABSTRACT FROM AUTHOR]

Methods: We recruited 40 cases of advanced NSCLC, stages III and IV, aged > 18-<70 years old, and eligible to receive chemotherapy with or without radiotherapy, along with 20 healthy controls of comparable age and sex; after diagnosis and staging of patients, blood samples were collected for flow cytometric detection of Mo-MDSCs.Results: Significant accumulation of Mo-MDSCs in patients compared to their controls (p < 0.0001). Furthermore, these cells accumulated significantly in stage IV compared to stage III (p = 0.006) and correlated negatively with overall survival (r = -0.471, p = 0.002), lymphocyte to monocyte ratio (r = -0.446, p = 0.004), and mean platelet volume to platelet count ratio (MPV/PC) (r = -0.464, p = 0.003), patients with Mo-MDSCs < 13% had significantly better survival than those with Mo-MDSCs ≥ 13% (p = 0.041).Conclusion: Mo-MDSCs represent one of the key mechanisms in the immunosuppressive tumor microenvironment (TME) to play major roles not only in the carcinogenesis of lung cancer but also in disease progression and prognosis and, in addition, predict the efficacy of immune checkpoint inhibitors; our results provided some support to target Mo-MDSCs and needed to be augmented by further studies. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) is a novel respiratory disease that has led to a global pandemic and created a havoc. The COVID‐19 disease severity varies among individuals, depending on fluctuating symptoms. Many infectious diseases such as hepatitis B and dengue hemorrhagic fever have been associated with ABO blood groups. The aim of this study was to explore whether ABO blood groups might serve as a risk or a protective factor for COVID‐19 infection. Moreover, the symptomatic variations of COVID‐19 infection among the individuals with different blood groups were also analyzed. An online questionnaire‐based survey was conducted in which 305 partakers were included, who had successfully recovered from coronavirus infection. The ABO blood groups of 1294 healthy individuals were also taken as a control. The results of the current study demonstrated that antibody A containing blood groups (blood group B, p‐value: 0.049 and blood group O, p‐value: 0.289) had a protective role against COVID‐19 infection. The comparison of symptomatic variations among COVID‐19‐infected subjects showed that blood group O subjects had lower chances of experiencing severe symptoms relating to respiratory distress, while subjects with AB blood group were more prone to develop symptoms, but the differences in both groups were found to be statistically non‐significant. In conclusion, subjects who do not have anti‐A antibodies in their serum (i.e., subjects with group A and AB) are more likely to be infected with COVID‐19. The current data showed that there was no significant association of signs and symptoms variations of COVID‐19 infection among individuals with different blood groups. [ABSTRACT FROM AUTHOR]

Mammarena viruses are emerging pathogenic agents and cause hemorrhagic fevers in humans. These viruses accomplish host immune system evasion to replicate and spread in the host. There are only few available therapeutic options developed for Mammarena Virus (also called MMV). Currently, only a single candidate vaccine called Candid#1 is available against Junin virus. Similarly, the effective treatment Ribavirin is used only in Lassa fever treatments. Herein, immune-informatics pipeline has been used to annotate whole proteome of the seven human infecting Mammarena strains. The extensive immune based analysis reveals specie specific epitopes with a crucial role in immune response induction. This was achieved by construction of immunogenic epitopes (CTL "Cytotoxic T-Lymphocytes", HTL "Helper T-Lymphocytes", and B cell "B-Lymphocytes") based vaccine designs against seven different Mammarena virus species. Furthermore, validation of the vaccine constructs through exploring physiochemical properties was performed to confirm experimental feasibility. Additionally, in-silico cloning and receptor based immune simulation was performed to ensure induction of primary and secondary immune response. This was confirmed through expression of immune factors such as IL, cytokines, and antibodies. The current study provides with novel vaccine designs which needs further demonstrations through potential processing against MMVs. Future studies may be directed towards advanced evaluations to determine the efficacy and safety of the designed vaccines through further experimental procedures. • Mammarena viruses are emerging pathogenic agents and cause hemorrhagic fevers in humans. • Herein, immune-informatics pipeline has been used to annotate whole proteome of the seven human infecting Mammarena strains. • The extensive immune based analysis reveals specie specific epitopes with a crucial role in immune response induction. • Additionally, immune simulation was performed to ensure induction of primary and secondary immune response. • Future experimental procedures may determine the efficacy and safety of the designed vaccines. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) is the world's most prevalent chronic viral infection. More than 350 million individuals are chronic carriers of the virus, with an estimated 2 billion infected persons. For instance, the role of HBx protein in attachment and infection is very obvious and consequently deemed as an important druggable target. Targeting the interface and discovering novel drugs greatly advanced the field of therapeutics development. Therefore, in the current study, HBx to Bcl-xL is abrogated on high-affinity carbon nanotubes using computational structural biology tools. Our analysis revealed that among the total 62 carbon fullerenes, only 13 compounds exhibited inhibitory activity against HBx, which was further confirmed through IFD-based rescoring. Structural dynamics investigation revealed stable binding, compactness, and hydrogen bonds reprogramming. Moreover, the binding free energy calculation results revealed that the top hits1-4 possess the total binding energy of −54.36 kcal/mol (hit1), −50.81 kcal/mol (hit2), −47.09 kcal/mol (hit3), and −45.59 kcal/mol for hit4. In addition, the predicted KD values and bioactivity scores further validated the inhibitory potential of these top hits. The identified compounds need further in vitro and in vivo validation to aid the treatment process of HBV. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is one of the most prevalent inflammatory disease among non-fatal skin diseases, affecting up to one fifth of the population in developed countries. AD is characterized by recurrent pruritic and localized eczema with seasonal fluctuations. AD initializes the phenomenon of atopic march, during which infant AD patients are predisposed to progressive secondary allergies such as allergic rhinitis, asthma, and food allergies. The pathophysiology of AD is complex; onset of the disease is caused by several factors, including strong genetic predisposition, disrupted epidermal barrier, and immune dysregulation. AD was initially characterized by defects in the innate immune system and a vigorous skewed adaptive Th2 response to environmental agents; there are compelling evidences that the disorder involves multiple immune pathways. Symptomatic palliative treatment is the only strategy to manage the disease and restore skin integrity. Researchers are trying to more precisely define the contribution of different AD genotypes and elucidate the role of various immune axes. In this review, we have summarized the current knowledge about the roles of innate and adaptive immune responsive cells in AD. In addition, current and novel treatment strategies for the management of AD are comprehensively described, including some ongoing clinical trials and promising therapeutic agents. This information will provide an asset towards identifying personalized targets for better therapeutic outcomes. [ABSTRACT FROM AUTHOR]