Racial Differences in Mental Stress-Induced Transient Endothelial Dysfunction and Its Association With Cardiovascular Outcomes.

OBJECTIVE: This study aimed to investigate differences in transient endothelial dysfunction (TED) with mental stress in Black and non-Black individuals with coronary heart disease (CHD), and their potential impact on cardiovascular outcomes. METHODS: We examined 812 patients with stable CHD between June 2011 and March 2016 and followed through February 2020 at a university-affiliated hospital network. Flow-mediated vasodilation (FMD) was assessed before and 30 minutes after mental stress. TED was defined as a lower poststress FMD than prestress FMD. We compared prestress FMD, post-stress FMD, and TED between Black and non-Black participants. In both groups, we examined the association of TED with an adjudicated composite end point of cardiovascular death or nonfatal myocardial infarction (first and recurring events) after adjusting for demographic, clinical, and socioeconomic factors. RESULTS: Prestress FMD was lower in Black than non-Black participants (3.7 [2.8] versus 4.9 [3.8], p < .001) and significantly declined with mental stress in both groups. TED occurred more often in Black (76%) than non-Black patients (67%; multivariable-adjusted odds ratio = 1.6, 95% confidence interval = 1.5-1.7). Over a median (interquartile range) follow-up period of 75 (65-82) months, 142 (18%) patients experienced either cardiovascular death or nonfatal myocardial infarction. Black participants had a 41.9% higher risk of the study outcome than non-Black participants (95% confidence interval = 1.01-1.95). TED with mental stress explained 69% of this excess risk. CONCLUSIONS: Among CHD patients, Black individuals are more likely than non-Black individuals to develop endothelial dysfunction with mental stress, which in turn explains a substantial portion of their excess risk of adverse events.

Sesquiterpenoids isolated from davana (Artemisia pallens Wall. ex DC) mitigates parkinsonism in Caenorhabditis elegans disease model.

Parkinson's disease (PD) is a multifactorial ailment that severely affects the viability of dopaminergic neurons leading to progressive loss of motor control. The current regimen for PD treatment includes synthetic drugs that lack efficacy and cause serious side effects. Consequently, recent drug development studies are focusing on alternative medicines from plant sources. Artemisia pallens Wall. ex DC, commonly known as davana, is an annual aromatic herb cultivated in southern India. Given the diverse traditional and scientifically documented therapeutic effects of A. pallens, the pharmacological potential of the isolates of the plant, namely bicyclogermacrene (D1), cis-davanone (D3), and cis-hydroxy davanone (D5), was tested for anti-Parkinson's activity in Caenorhabditis elegans model. The tested compounds alleviated α-synuclein (α-syn) aggregation and maximum decline was observed in 25 µM D1 supplemented worms. Additionally, D1 modulated dopamine regulated nonanol-1 repulsion and locomotory behaviour of C. elegans validating its future use as a dopamine-enhancing agent. The genetic regulation mediating the above effects validated through the qPCR study showed that D1 supplementation displayed its anti-Parkinson's effect through upregulation of the antioxidant defence system genes (superoxide dismutase (sod)-1, sod-2, and sod-4) and PD associated pdr-1 gene that maintains the mitochondrial proteostasis. The molecular docking studies of C. elegans PDR-1 with D1 further confirmed its contribution in D1 induced abridgment of Parkinson disease linked pathologies in C. elegans disease model. Hence, this article proposes D1 as an effective regimen for curtailing the Parkinson disease linked pathologies through mechanism of maintaining cellular redox state and proteostasis.

A Clinician's Guide to Smartwatch "Interrogation".

PURPOSE OF REVIEW: Wearable technology is rapidly evolving and the data that it can provide regarding an individual's health is becoming increasingly important for clinicians to consider. The purpose of this review is to help inform health care providers of the benefits of smartwatch interrogation, with a focus on reviewing the various parameters and how to apply the data in a meaningful way. RECENT FINDINGS: This review details interpretation of various parameters found commonly in newer smartwatches such as heart rate, step count, ECG, heart rate recovery (HRR), and heart rate variability (HRV), while also discussing potential pitfalls that a clinician should be aware of. Smartwatch interrogation is becoming increasingly relevant as the continuous data it provides helps health care providers make more informed decisions regarding diagnosis and treatment. For this reason, we recommend health care providers familiarize themselves with the technology and integrate it into clinical practice.

Role of the Pangolin in Origin of SARS-CoV-2: An Evolutionary Perspective.

After the recent emergence of SARS-CoV-2 infection, unanswered questions remain related to its evolutionary history, path of transmission or divergence and role of recombination. There is emerging evidence on amino acid substitutions occurring in key residues of the receptor-binding domain of the spike glycoprotein in coronavirus isolates from bat and pangolins. In this article, we summarize our current knowledge on the origin of SARS-CoV-2. We also analyze the host ACE2-interacting residues of the receptor-binding domain of spike glycoprotein in SARS-CoV-2 isolates from bats, and compare it to pangolin SARS-CoV-2 isolates collected from Guangdong province (GD Pangolin-CoV) and Guangxi autonomous regions (GX Pangolin-CoV) of South China. Based on our comparative analysis, we support the view that the Guangdong Pangolins are the intermediate hosts that adapted the SARS-CoV-2 and represented a significant evolutionary link in the path of transmission of SARS-CoV-2 virus. We also discuss the role of intermediate hosts in the origin of Omicron.

MMP-7 derived peptides with MHC class-I binding motifs from canine mammary tumor tissue elicit strong antigen-specific T-cell responses in BALB/c mice.

Matrix Metalloproteinases (MMPs)-induced altered proteolysis of extracellular matrix proteins and basement membrane holds the key for tumor progression and metastasis. Matrix metalloproteinases-7 (Matrilysin), the smallest member of the MMP family also performs quite alike; thus serves as a potential candidate for anti-tumor immunotherapy. Conversely, being an endogenous tumor-associated antigen (TAA), targeting MMP-7 for immunization is challenging. But MMP-7-based xenovaccine can surmount the obstacle of poor immunogenicity and immunological tolerance, often encountered in TAA-based conventional vaccine for anti-tumor immunotherapy. This paves the way for investigating the potential of MMP-7-derived major histocompatibility complex (MHC)-binding peptides to elicit precise epitope-specific T-cell responses towards their possible inclusion in anti-tumor vaccine formulations. Perhaps it also ushers the path of achieving multiple epitope-based broad and universal cellular immunity. In current experiment, an immunoinformatics approach has been employed to identify the putative canine matrix matelloproteinases-7 (cMMP-7)-derived peptides with MHC class-I-binding motifs which can elicit potent antigen-specific immune responses in BALB/c mice. Immunization with the cMMP-7 DNA vaccine induced a strong CD8+ cytotoxic T lymphocytes (CTLs) and Th1- type response, with high level of gamma interferon (IFN-γ) production in BALB/c mice. The two identified putative MHC-I-binding nonameric peptides (Peptide32-40 and Peptide175-183) from cMMP-7 induced significant lymphocyte proliferation along with the production of IFN-γ from CD8+ T-cells in mice immunized with cMMP-7 DNA vaccine. The current observation has depicted the immunogenic potential of the two cMMP-7-derived nonapeptides for their possible exploitation in xenovaccine-mediated anti-tumor immunotherapy in mouse model.

Alveolar Regeneration in COVID-19 Patients: A Network Perspective.

A viral infection involves entry and replication of viral nucleic acid in a host organism, subsequently leading to biochemical and structural alterations in the host cell. In the case of SARS-CoV-2 viral infection, over-activation of the host immune system may lead to lung damage. Albeit the regeneration and fibrotic repair processes being the two protective host responses, prolonged injury may lead to excessive fibrosis, a pathological state that can result in lung collapse. In this review, we discuss regeneration and fibrosis processes in response to SARS-CoV-2 and provide our viewpoint on the triggering of alveolar regeneration in coronavirus disease 2019 (COVID-19) patients.

A study of hepatitis A virus seropositivity among children aged between 1 and 5 years of age: Implications for universal immunization.

BACKGROUND: Hepatitis A virus (HAV) causes an enterically transmitted viral disease mainly affecting children and endemic in many developing countries, including India. There is an epidemiological shift with an increased incidence of symptomatic cases among children. This study was conducted to assess the seroprevalence of HAV among young children aged below 5 years and the need for universal immunization. METHOD: This cross-sectional study was conducted at two tertiary care hospitals in Northern India, from Apr 2014 to Jul 2015, among healthy children aged between 1 and 5 years. The sample size was calculated based on the prevalence of HAV seropositivity of 40% among children aged <10 years [16-60%] and alpha error of 5%. Analysis of serum IgG against HAV was performed by enzyme-linked immunosorbent assay method, and results were analyzed. RESULTS: A total of 1084 children aged between 12 and 60 months were enrolled, with male-to-female ratio of 1.86:1. A total of 471 children (43.5%) were found to be positive for IgG against HAV. The seroprevalence of HAV was lower among younger children aged 12-23 months (odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.52-0.87, p = 0.03), which was statistically significant. Seropositivity of HAV was lower among boys and families consuming safe drinking water and having improved sanitation facilities. CONCLUSION: The study observed lower seropositivity against HAV among younger children, making them susceptible of contracting the disease. Possible underlying risk factors were younger age, unsafe drinking water, poor sanitation, and low education status of parents. Therefore, vaccination may be recommended as optional vaccine at one year of age, along with improved public health efforts for safe drinking water, hygiene practices, and food safety.

Delay in antibiotic therapy results in fatal disease outcome in murine pneumococcal pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) remains a major cause of death worldwide. Mechanisms underlying the detrimental outcome despite adequate antibiotic therapy and comorbidity management are still not fully understood. METHODS: To model timely versus delayed antibiotic therapy in patients, mice with pneumococcal pneumonia received ampicillin twice a day starting early (24 h) or late (48 h) after infection. Clinical readouts and local and systemic inflammatory mediators after early and late antibiotic intervention were examined. RESULTS: Early antibiotic intervention rescued mice, limited clinical symptoms and restored fitness, whereas delayed therapy resulted in high mortality rates. Recruitment of innate immune cells remained unaffected by antibiotic therapy. However, both early and late antibiotic intervention dampened local levels of inflammatory mediators in the alveolar spaces. Early treatment protected from barrier breakdown, and reduced levels of vascular endothelial growth factor (VEGF) and perivascular and alveolar edema formation. In contrast, at 48 h post infection, increased pulmonary leakage was apparent and not reversed by late antibiotic treatment. Concurrently, levels of VEGF remained high and no beneficial effect on edema formation was evident despite therapy. Moreover, early but not late treatment protected mice from a vast systemic inflammatory response. CONCLUSIONS: Our data show that only early antibiotic therapy, administered prior to breakdown of the alveolar-capillary barrier and systemic inflammation, led to restored fitness and rescued mice from fatal streptococcal pneumonia. The findings highlight the importance of identifying CAP patients prior to lung barrier failure and systemic inflammation and of handling CAP as a medical emergency.

Poly (I:C) enhances the anti-tumor activity of canine parvovirus NS1 protein by inducing a potent anti-tumor immune response.

The canine parvovirus NS1 (CPV2.NS1) protein selectively induces apoptosis in the malignant cells. However, for an effective in vivo tumor treatment strategy, an oncolytic agent also needs to induce a potent anti-tumor immune response. In the present study, we used poly (I:C), a TLR3 ligand, as an adjuvant along with CPV2.NS1 to find out if the combination can enhance the oncolytic activity by inducing a potent anti-tumor immune response. The 4T1 mammary carcinoma cells were used to induce mammary tumor in Balb/c mice. The results suggested that poly (I:C), when given along with CPV2.NS1, not only significantly reduced the tumor growth but also augmented the immune response against tumor antigen(s) as indicated by the increase in blood CD4+ and CD8+ counts and infiltration of immune cells in the tumor tissue. Further, blood serum analysis of the cytokines revealed that Th1 cytokines (IFN-γ and IL-2) were significantly upregulated in the treatment group indicating activation of cell-mediated immune response. The present study reports the efficacy of CPV2.NS1 along with poly (I:C) not only in inhibiting the mammary tumor growth but also in generating an active anti-tumor immune response without any visible toxicity. The results of our study may help in developing CPV2.NS1 and poly (I: C) combination as a cancer therapeutic regime to treat various malignancies.

HN protein of Newcastle disease virus sensitizes HeLa cells to TNF-α-induced apoptosis by downregulating NF-κB expression.

Hemagglutinin neuraminidase (HN) is a membrane protein of Newcastle disease virus (NDV) with the ability to induce apoptosis in many transformed cell lines. TNF-α is a multi-factorial protein that regulates cell survival, differentiation and apoptosis. In a previous study, we reported that HN protein induces apoptosis by downregulating NF-κB expression. Further, we speculated that downregulation of NF-κB expression might sensitize HeLa cells to TNF-α-mediated apoptosis. Therefore, the present study was undertaken to investigate if HN protein could sensitize HeLa cells to TNF-α and to examine the apoptotic potential of the HN protein and TNF-α in combination. The results revealed that the pro-apoptotic effects were more pronounced with the combination of HN and TNF-α than with HN or TNF-α alone, which indicates that the HN protein indeed sensitized the HeLa cells to TNF-α-induced cell death. The results of the study provide a mechanistic insight into the apoptotic action of HN protein along with TNF-α, which could be valuable in treating tumor types that are naturally resistant to TNF-α.

Viral genes as oncolytic agents for cancer therapy.

Many viruses have the ability to modulate the apoptosis, and to accomplish it; viruses encode proteins which specifically interact with the cellular signaling pathways. While some viruses encode proteins, which inhibit the apoptosis or death of the infected cells, there are viruses whose encoded proteins can kill the infected cells by multiple mechanisms, including apoptosis. A particular class of these viruses has specific gene(s) in their genomes which, upon ectopic expression, can kill the tumor cells selectively without affecting the normal cells. These genes and their encoded products have demonstrated great potential to be developed as novel anticancer therapeutic agents which can specifically target and kill the cancer cells leaving the normal cells unharmed. In this review, we will discuss about the viral genes having specific cancer cell killing properties, what is known about their functioning, signaling pathways and their therapeutic applications as anticancer agents.

Scrutinizing the immune defence inventory of Camponotus floridanus applying total transcriptome sequencing.

BACKGROUND: Defence mechanisms of organisms are shaped by their lifestyle, environment and pathogen pressure. Carpenter ants are social insects which live in huge colonies comprising genetically closely related individuals in high densities within nests. This lifestyle potentially facilitates the rapid spread of pathogens between individuals. In concert with their innate immune system, social insects may apply external immune defences to manipulate the microbial community among individuals and within nests. Additionally, carpenter ants carry a mutualistic intracellular and obligate endosymbiotic bacterium, possibly maintained and regulated by the innate immune system. Thus, different selective forces could shape internal immune defences of Camponotus floridanus. RESULTS: The immune gene repertoire of C. floridanus was investigated by re-evaluating its genome sequence combined with a full transcriptome analysis of immune challenged and control animals using Illumina sequencing. The genome was re-annotated by mapping transcriptome reads and masking repeats. A total of 978 protein sequences were characterised further by annotating functional domains, leading to a change in their original annotation regarding function and domain composition in about 8% of all proteins. Based on homology analysis with key components of major immune pathways of insects, the C. floridanus immune-related genes were compared to those of Drosophila melanogaster, Apis mellifera, and other hymenoptera. This analysis revealed that overall the immune system of carpenter ants comprises many components found in these insects. In addition, several C. floridanus specific genes of yet unknown functions but which are strongly induced after immune challenge were discovered. In contrast to solitary insects like Drosophila or the hymenopteran Nasonia vitripennis, the number of genes encoding pattern recognition receptors specific for bacterial peptidoglycan (PGN) and a variety of known antimicrobial peptide (AMP) genes is lower in C. floridanus. The comparative analysis of gene expression post immune-challenge in different developmental stages of C. floridanus suggests a stronger induction of immune gene expression in larvae in comparison to adults. CONCLUSIONS: The comparison of the immune system of C. floridanus with that of other insects revealed the presence of a broad immune repertoire. However, the relatively low number of PGN recognition proteins and AMPs, the identification of Camponotus specific putative immune genes, and stage specific differences in immune gene regulation reflects Camponotus specific evolution including adaptations to its lifestyle.

Administration of IκB-kinase inhibitor PS1145 enhances apoptosis in DMBA-induced tumor in male Wistar rats.

Nuclear factor kappa-B (NF-κB), a key anti-apoptotic factor, plays a critical role in tumor cell growth, metastasis, and angiogenesis. The transcriptional activity of NF-κB is normally suppressed in the cytoplasm due to its association with a natural inhibitor molecule IκB. Phosphorylation of the IκB at Ser 32 and Ser 36 by the IκB kinase complex (IKK) marks the degradation of the molecule by 26S proteasome. As NF-κB is constitutively activated in most of the tumor cells, inhibition of the activities of IKK may significantly sensitize the tumor cells to apoptosis. In the present study, we investigated the effect of IκB kinase-specific blocker PS1145 on DMBA-induced skin tumor of male Wistar rats. We examined the apoptotic effect of PS1145 on DMBA-induced tumor by various histopathological and molecular techniques. Our results demonstrate the significant expression of major pro-apoptotic genes like caspases 2, 3, 8, 9, and p53 in PS1145-treated tumor bearing group at mRNA levels as well as significant (P < 0.05) down regulation in the expression levels of NF-κB and VEGF, the major pro-inflammatory and pro-angiogenic factors, respectively. The histopathological examination showed that the tumor progression, mitotic, AgNOR, and PCNA indices were significantly reduced in PS1145 treatment groups as compared to PBS control on day 28 of post-treatment. Furthermore, significant increase in TUNEL positive nuclei and observation of peculiar apoptotic nuclei in transmission electron microscopy were seen in PS1145 treatment group. We conclude that intravenous application of PS1145 promotes direct apoptosis in DMBA-induced skin tumor in male Wistar rats by blocking NF-κB and VEGF activities.

In-vitro characterization and evaluation of apoptotic potential of bicistronic plasmid encoding HN gene of Newcastle disease virus and human TNF-α.

The viral gene oncotherapy in combination with cytokines emerges as an exciting strategy for cancer therapy due to its minimal side effects and tumor specificity. HN is the surface protein of NDV which is involved in virus infectivity and is known to kill many cancerous cell types. TNF-α, a multifactorial cytokine has direct anti-tumor activity by activating the extrinsic pathways of apoptosis. In the present study, HN gene of NDV and TNF-α of human were cloned at multiple cloning sites (MCS) 1 and 2 of bicistronic expression vector pVIVO2. Expression pattern of recombinant clone was checked on transcriptional and translational level by RT-PCR, Immunofluorescence assay and flow cytometry. On flow cytometric analysis HN gene expression was found to be 28.30 ± 1.21; 5.22 ± 0.60%, and TNF-α gene expression was found to be 15.44 ± 0.42; 6.51 ± 0.757%, in HeLa cells transfected with pVIVO.nd.hn.hu.tnf and pVIVO2 empty vector control, respectively. These assays confirm that HN and TNF-α act synergistically in the induction of apoptosis in HeLa cells.

Development of dog mammary tumor xenograft in immunosuppressed Swiss albino mice.

Development and study of dog mammary tumour xenograft in immunosuppressed Swiss Albino Mice adds a new dimension in cancer research as dog tumors have many similarities with human tumors regarding progression, histopathology, molecular mechanism, immune response and therapy. Failure of the immune system to recognize and eliminate cancer cells leads to cancer progression and the fight between immune cells and cancer cells has a great role in understanding the mechanism of cancer progression and elimination. Rejection and acceptance of tumour xenograft depends on efficiency of CD4+, CD8+ and NK cell populations. In the present investigation, dog mammary tumor xenograft in cyclosporine-A and gamma-irradiated, immunosuppressed Swiss Albino mice was developed and the immune cell status of graft accepted and rejected mice was assessed. It was observed that all the major immune cells (CD4+, CD8+ and NK cells) play an equal role in tumour rejection.

Role of the plant-specific calcium-binding C2-DOMAIN ABSCISIC ACID-RELATED (CAR) protein family in environmental signaling.

Many signaling processes rely on information decoding at the plasma membrane, and membrane-associated proteins and their complexes are fundamental for regulating this process. Still many questions exist as to how protein complexes are assembled and function at membrane sites to change identity and dynamics of membrane systems. Peripheral membrane proteins containing a calcium and phospholipid-binding C2-domain can act in membrane-related signaling by providing a tethering function so that protein complexes form. C2 domain proteins termed C2-DOMAIN ABSCISIC ACID-RELATED (CAR) proteins are plant-specific, and the functional relevance of this C2 domain protein subgroup is just emerging. The ten Arabidopsis CAR proteins CAR1 to CAR10 have a single C2 domain with a plant-specific insertion, the so-called "CAR-extra-signature" or also termed "sig domain". Via this "sig domain" CAR proteins can bind signaling protein complexes of different kinds and act in biotic and abiotic stress, blue light and iron nutrition. Interestingly, CAR proteins can oligomerize in membrane microdomains, and their presence in the nucleus can be linked with nuclear protein regulation. This shows that CAR proteins may play unprecedented roles in coordinating environmental responses and assembling required protein complexes to transmit information cues between plasma membrane and nucleus. The aim of this review is to summarize structure-function characteristics of the CAR protein family and assemble findings from CAR protein interactions and physiological functions. From this comparative investigation we extract common principles about the molecular operations that CAR proteins may fulfill in the cell. We also deduce functional properties of the CAR protein family based on its evolution and gene expression profiles. We highlight open questions and suggest novel avenues to prove and understand the functional networks and roles played by this protein family in plants.

Assessment of Cardiovascular Risk for Noncardiac and Nonsurgical Activities.

Cardiovascular risk stratification is a frequent evaluation performed by health professionals. Not uncommonly, requests for risk stratification involve activities or procedures that fall outside of the scope of current evidence-based guidelines. Estimating risk and providing guidance for these requests can be challenging due to limited available evidence. This review focuses on some of these unique requests, each of which are real examples encountered in our practice. We offer guidance by synthesizing the available medical literature and formulating recommendations on topics such as the initiation of testosterone and erectile dysfunction therapy, SCUBA and skydiving, polygraphy, and electroconvulsive therapy.

Outcomes of Transcatheter Aortic Valve Replacement in Patients With Coexisiting Amyloidosis: Mortality, Stroke, and Readmission.

Background: Cardiac amyloidosis can coexist in patients with severe aortic stenosis. There are limited outcomes data on whether this impacts the risk of transcatheter aortic valve replacement (TAVR). Objectives: The authors aimed to investigate the effect of amyloidosis on outcomes of TAVR. Methods: We used the Nationwide Readmissions Database to identify hospitalizations for TAVR between 2016 and 2019. The presence of a diagnosis of amyloidosis was identified. Propensity score-weighted regression analysis was used to identify the association of amyloidosis with in-hospital mortality, acute ischemic stroke, and 30-day readmission rate after TAVR. Results: We identified 245,020 hospitalizations for TAVR, including 273 in patients with amyloidosis. The mean age was 79.4 ± 8.4 years. There was no difference in in-hospital mortality or 30-day readmission rate in patients with and without amyloidosis (1.8% vs 1.5%, P = 0.622; and 12.9% vs 12.5%, P = 0.858; respectively). However, there was a higher rate of acute ischemic stroke in patients with amyloidosis (6.2% vs 1.8%, P < 0.001). Propensity score-weighted logistic regression analysis showed the presence of amyloidosis was associated with greater odds of acute ischemic stroke (odds ratio: 3.08, 95% CI: 1.41-6.71, P = 0.005), but no difference in mortality (odds ratio: 0.79, 95% CI: 0.28-2.27, P = 0.666) or 30-day readmission rate after TAVR (HR: 0.72, 95% CI: 0.41-1.25, P = 0.241). Conclusions: This analysis suggests amyloidosis may be associated with a higher thromboembolic risk after TAVR that merits further investigation.

Signaling network analysis reveals fostamatinib as a potential drug to control platelet hyperactivation during SARS-CoV-2 infection.

Introduction: Pro-thrombotic events are one of the prevalent causes of intensive care unit (ICU) admissions among COVID-19 patients, although the signaling events in the stimulated platelets are still unclear. Methods: We conducted a comparative analysis of platelet transcriptome data from healthy donors, ICU, and non-ICU COVID-19 patients to elucidate these mechanisms. To surpass previous analyses, we constructed models of involved networks and control cascades by integrating a global human signaling network with transcriptome data. We investigated the control of platelet hyperactivation and the specific proteins involved. Results: Our study revealed that control of the platelet network in ICU patients is significantly higher than in non-ICU patients. Non-ICU patients require control over fewer proteins for managing platelet hyperactivity compared to ICU patients. Identification of indispensable proteins highlighted key subnetworks, that are targetable for system control in COVID-19-related platelet hyperactivity. We scrutinized FDA-approved drugs targeting indispensable proteins and identified fostamatinib as a potent candidate for preventing thrombosis in COVID-19 patients. Discussion: Our findings shed light on how SARS-CoV-2 efficiently affects host platelets by targeting indispensable and critical proteins involved in the control of platelet activity. We evaluated several drugs for specific control of platelet hyperactivity in ICU patients suffering from platelet hyperactivation. The focus of our approach is repurposing existing drugs for optimal control over the signaling network responsible for platelet hyperactivity in COVID-19 patients. Our study offers specific pharmacological recommendations, with drug prioritization tailored to the distinct network states observed in each patient condition. Interactive networks and detailed results can be accessed at https://fostamatinib.bioinfo-wuerz.eu/.

In silico proteomic characterization of human epidermal growth factor receptor 2 (HER-2) for the mapping of high affinity antigenic determinants against breast cancer.

Multiple different approaches are being used to activate the immune system against breast cancer. Vaccine therapy in general follows the principle that injections of various substances ultimately result in the presentation of tumor peptides to the patient's immune system. We proposed a potential in silico DNA vaccine against breast cancer by integrating high affinity T cell (MHC-I and MHC-II) and B cell (continuous and discontinuous) epitopes. The matching of the HLA haplotype and antigen was performed to provide the appropriate peptide epitope suitable for majority of the patients. The immunogenic nature of the antigenic construct was also enhanced by the administration of consensus epitopes. The potency of DNA vaccines depends on the efficient expression and presentation of the encoded antigen of interest and the chances of efficient expression of our antigenic construct in host organism was also verified by in silico approaches. An attempt was made to overcome the limited potency of the DNA vaccine by targeting DNA to professional antigen-presenting cells (APCs). A higher immune response theoretically corresponds to a higher survival rate of patients. Therefore, optimization studies were also employed to enhance the immunogenicity of proposed in silico DNA vaccine.