Free Radicals, Mitochondrial Dysfunction and Sepsis-induced Organ Dysfunction: A Mechanistic Insight.

Sepsis is a complex clinical condition and a leading cause of death worldwide. During Sepsis, there is a derailment in the host response to infection, which can progress to severe sepsis and multiple organ dysfunction or failure, which leads to death. Free radicals, including reactive oxygen species (ROS) generated predominantly in mitochondria, are one of the key players in impairing normal organ function in sepsis. ROS contributing to oxidative stress has been reported to be the main culprit in the injury of the lung, heart, liver, kidney, gastrointestinal, and other organs. Here in the present review, we describe the generation, and essential properties of various types of ROS, their effect on macromolecules, and their role in mitochondrial dysfunction. Furthermore, the mechanism involved in the ROS-mediated pathogenesis of sepsis-induced organ dysfunction has also been discussed.

Nanomaterials for intelligent CRISPR-Cas tools: improving environment sustainability.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) is a desirable gene modification tool covering a wide area in various sectors of medicine, agriculture, and microbial biotechnology. The role of this incredible genetic engineering technology has been extensively investigated; however, it remains formidable with cargo choices, nonspecific delivery, and insertional mutagenesis. Various nanomaterials including lipid, polymeric, and inorganic are being used to deliver the CRISPR-Cas system. Progress in nanomaterials could potentially address these challenges by accelerating precision targeting, cost-effectiveness, and one-step delivery. In this review, we highlighted the advances in nanotechnology and nanomaterials as smart delivery systems for CRISPR-Cas so as to ameliorate applications for environmental remediation including biomedical research and healthcare, strategies for mitigating antimicrobial resistance, and to be used as nanofertilizers for enhancing crop growth, and reducing the environmental impact of traditional fertilizers. The timely co-evolution of nanotechnology and CRISPR technologies has contributed to smart novel nanostructure hybrids for improving the onerous tasks of environmental remediation and biological sustainability.

Surgical Management of Gossypiboma: A Case Report.

Gossypiboma is a rarely reported surgical complication and refers to a retained surgical textile in the body after a procedure. The surrounding inflammation and reaction often manifest as acute pain and subsequently require additional surgery. We report the case of a 33-year-old female who presented with acute abdominal pain one month after undergoing an exploratory laparotomy secondary to a gunshot wound in her home country. A diagnosis of retained foreign body was made with radiological imaging and confirmed upon the retrieval of two surgical sponges after the operation. Due to the high morbidity and mortality as well as increased healthcare costs, strict protocols must be followed to avoid such outcomes.

A Critical Review on Human Malaria and Schistosomiasis Vaccines: Current State, Recent Advancements, and Developments.

Malaria and schistosomiasis are two major parasitic diseases that remain leading causes of morbidity and mortality worldwide. Co-infections of these two parasites are common in the tropics, where both diseases are endemic. The clinical consequences of schistosomiasis and malaria are determined by a variety of host, parasitic, and environmental variables. Chronic schistosomiasis causes malnutrition and cognitive impairments in children, while malaria can cause fatal acute infections. There are effective drugs available to treat malaria and schistosomiasis. However, the occurrence of allelic polymorphisms and the rapid selection of parasites with genetic mutations can confer reduced susceptibility and lead to the emergence of drug resistance. Moreover, the successful elimination and complete management of these parasites are difficult due to the lack of effective vaccines against Plasmodium and Schistosoma infections. Therefore, it is important to highlight all current vaccine candidates undergoing clinical trials, such as pre-erythrocytic and erythrocytic stage malaria, as well as a next-generation RTS,S-like vaccine, the R21/Matrix-M vaccine, that conferred 77% protection against clinical malaria in a Phase 2b trial. Moreover, this review also discusses the progress and development of schistosomiasis vaccines. Furthermore, significant information is provided through this review on the effectiveness and progress of schistosomiasis vaccines currently under clinical trials, such as Sh28GST, Sm-14, and Sm-p80. Overall, this review provides insights into recent progress in malarial and schistosomiasis vaccines and their developmental approaches.

Therapeutic Role of ELOVL in Neurological Diseases.

Fatty acids play an important role in controlling the energy balance of mammals. De novo lipogenesis also generates a significant amount of lipids that are endogenously produced in addition to their ingestion. Fatty acid elongation beyond 16 carbons (palmitic acid), which can lead to the production of very long chain fatty acids (VLCFA), can be caused by the rate-limiting condensation process. Seven elongases, ELOVL1-7, have been identified in mammals and each has a unique substrate specificity. Researchers have recently developed a keen interest in the elongation of very long chain fatty acids protein 1 (ELOVL1) enzyme as a potential treatment for a variety of diseases. A number of neurological disorders directly or indirectly related to ELOVL1 involve the elongation of monounsaturated (C20:1 and C22:1) and saturated (C18:0-C26:0) acyl-CoAs. VLCFAs and ELOVL1 have a direct impact on the neurological disease. Other neurological symptoms such as ichthyotic keratoderma, spasticity, and hypomyelination have also been linked to the major enzyme (ELOVL1). Recently, ELOVL1 has also been heavily used to treat a number of diseases. The current review focuses on in-depth unique insights regarding the role of ELOVL1 as a therapeutic target and associated neurological disorders.

Computational insight into structural basis of human ELOVL1 inhibition.

Very long-chain fatty acids (VLCFAs) play a direct role in the development of a neurological disorder, X-linked adrenoleukodystrophy (X-ALD). Since ELOVL1 catalyzes the rate-limiting step of the synthesis of VLCFAs, it has emerged as an attractive target for the treatment of X-ALD. Recently two potent inhibitors, compound 22 (C22) and compound 27 (C27) have been reported to specifically inhibit human ELOVL1 but their structural basis of inhibition has not been explored. In the present study, we have used a homology model of human ELOVL1 to deduce the binding site and binding modes of C22 and C27. We have employed computational approaches to characterize the binding of C22 and C27. Initially, binding of hexacosanoyl-CoA (C26:0-CoA) to ELOVL1 was modelled and further validated by molecular dynamics (MD) simulation. We observed that the fatty acid tail of C26: CoA protrudes from a unique opening located at the occluded end of ELOVL1. Structural comparison of ELOVL1 with the crystal structure of ELOVL7 revealed that the unique opening was not present in human ELOVL7. Combined blind and focused molecular docking approaches revealed that C22 and C27 exhibit favourable binding in the same unique opening. Further, MD simulations and free binding energy calculations confirmed that C22 and C27 maintain the favourable binding in the unique opening of ELOVL1. Overall, our findings suggest that selective human ELOVL1 inhibitors block the binding of long tails of VLCFAs near the occluded end of ELOVL1. Present study will be helpful in the discovery and design of novel, selective and potent inhibitors of human ELOVL1.

Bacteriocin-Nanoconjugates (Bac10307-AgNPs) Biosynthesized from Lactobacillus acidophilus-Derived Bacteriocins Exhibit Enhanced and Promising Biological Activities.

The proteinaceous compounds produced by lactic acid bacteria are called bacteriocins and have a wide variety of bioactive properties. However, bacteriocin's commercial availability is limited due to short stability periods and low yields. Therefore, the objective of this study was to synthesize bacteriocin-derived silver nanoparticles (Bac10307-AgNPs) extracted from Lactobacillus acidophilus (L. acidophilus), which may have the potential to increase the bioactivity of bacteriocins and overcome the hurdles. It was found that extracted and purified Bac10307 had a broad range of stability for both temperature (20-100 °C) and pH (3-12). Further, based on Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis, its molecular weight was estimated to be 4.2 kDa. The synthesized Bac10307-AgNPs showed a peak of surface plasmon resonance at 430 nm λmax. Fourier transform infrared (FTIR) confirmed the presence of biological moieties, and transmission electron microscopy (TEM) coupled with Energy dispersive X-Ray (EDX) confirmed that AgNPs were spherical and irregularly shaped, with a size range of 9-20 nm. As a result, the Bac10307-AgNPs displayed very strong antibacterial activity with MIC values as low as 8 µg/mL for Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), when compared to Bac10307 alone. In addition, Bac10307-AgNPs demonstrated promising in vitro antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 116.04 µg/mL) and in vitro cytotoxicity against human liver cancer cells (HepG2) (IC50 = 135.63 µg/mL), more than Bac10307 alone (IC50 = 139.82 µg/mL against DPPH and 158.20 µg/mL against HepG2). Furthermore, a protein-protein molecular docking simulation study of bacteriocins with target proteins of different biological functions was also carried out in order to ascertain the interactions between bacteriocins and target proteins.

Fast Track Diagnostic Tools for Clinical Management of Sepsis: Paradigm Shift from Conventional to Advanced Methods.

Sepsis is one of the deadliest disorders in the new century due to specific limitations in early and differential diagnosis. Moreover, antimicrobial resistance (AMR) is becoming the dominant threat to human health globally. The only way to encounter the spread and emergence of AMR is through the active detection and identification of the pathogen along with the quantification of resistance. For better management of such disease, there is an essential requirement to approach many suitable diagnostic techniques for the proper administration of antibiotics and elimination of these infectious diseases. The current method employed for the diagnosis of sepsis relies on the conventional culture of blood suspected infection. However, this method is more time consuming and generates results that are false negative in the case of antibiotic pretreated samples as well as slow-growing microbes. In comparison to the conventional method, modern methods are capable of analyzing blood samples, obtaining accurate results from the suspicious patient of sepsis, and giving all the necessary information to identify the pathogens as well as AMR in a short period. The present review is intended to highlight the culture shift from conventional to modern and advanced technologies including their limitations for the proper and prompt diagnosing of bloodstream infections and AMR detection.

Evaluation of Sclerotinia sclerotiorum MTCC 8785 as a biological agent for the synthesis of silver nanoparticles and assessment of their antifungal potential against Trichoderma harzianum MTCC 801.

INTRODUCTION: Owing to loads of industrial development and advancements, there is an unmet need for green-ecosystem support as well as safe technologies. For cost-cutting and eco-friendly applications, biosynthetic pathways for nanoparticle synthesis from microbes like bacteria, and fungi have attracted the global attention of researchers. METHODS: In the present research work, silver nanoparticles (AgNPs) from fungus (mycogenic) were extracellularly synthesized with cell-free filtrates of fungal phytopathogen Sclerotinia sclerotiorum MTCC 8785 harvested from broth culture in Potato dextrose broth (CFF-PDB) and Amylase production media (CFF-AMP). The synthesis was carried out at pH 7, 28 °C under dark conditions. The synthesized AgNPs were characterized using UV spectrophotometer and transmission electron microscopy (TEM). Furthermore, the antifungal efficacy of AgNPs was evaluated against the Trichoderma harzianum MTCC 801 strain by radial inhibition assay. RESULTS: Primarily, the process of biosynthesis was inferred by the characteristic change of color and spectral peak at 420 nm recorded with UV spectrophotometer further approved the nano silver production in CFF-AMP which approves the role of amylases in reduction mediated capping process. TEM analysis revealed that the AgNPs synthesized using S. sclerotiorum MTCC 8785 grown in PDB were spherical with variable size ranges from 10 to 50 nm in diameter whereas, the AgNPs synthesized using S. sclerotiorum MTCC 8785 grown in APM were in the size ranges from 40 to 50 nm. CONCLUSIONS: This is the first investigatory concern where nano-silver from fungal phytopathogen S. sclerotiorum MTCC 8785 has been prospected as new age antifungal alternatives against evolving threats from T. harzianum strain.

Body Mass Index Trends among a Cohort of Subjects Enrolled in Medication-Assisted Treatment Programmes for Opioid Use Disorder: Racial/Ethnic, Gender, and Age Differences.

Introduction: Opioid use disorder (OUD) and obesity are two pressing public health concerns in the United States (US). However, the relationship between these two epidemics has not been well-studied. Our study aims to describe the prevalence rates of obesity in individuals with OUD from a cohort study and compare that to the expected prevalence that would be observed based upon New Jersey state and US population survey data. Additionally, we sought to study whether Body Mass Index (BMI) distribution in this cohort varied by race/ethnicity, gender, and age. Methods: Our subjects (N=151) are part of a drug user cohort study of persons enrolled in medication-assisted treatment (MAT) programmes in New Jersey. Using the New Jersey Behavioral Risk Factor Survey (NJBRFS) and the National Health Interview Survey (NHIS), we generated expected BMI distributions based on race/ethnicity, age, and sex. Expected rates were compared to observed BMI. Standardized prevalence ratios were calculated, and 95% confidence intervals were constructed. Results: Among females, obesity was more prevalent in those with OUD than in the general US population. Among persons ≤50 years old, overweight and obesity were more prevalent in those with OUD than in NJBRFS. Persons who did not inject drugs were more likely to be overweight. The prevalence of underweight was significantly higher among Black non-Hispanic minorities, males, older subjects (aged 66-85), and persons who inject drugs. Conclusion: In our study, the trends in BMI vary based on race/ethnicity, gender and age in these patients with OUD. These varying trends highlight the need for tailored screening and prevention strategies. Primary care providers should be aware that their patients with OUD have multiple health problems that need to be addressed beyond their OUD condition itself. Providers are in a pivotal role to screen and implement interventions to improve their health outcomes.

The Interplay of Oxidative Stress and ROS Scavenging: Antioxidants as a Therapeutic Potential in Sepsis.

Oxidative stress resulting from the disproportion of oxidants and antioxidants contributes to both physiological and pathological conditions in sepsis. To combat this, the antioxidant defense system comes into the picture, which contributes to limiting the amount of reactive oxygen species (ROS) leading to the reduction of oxidative stress. However, a strong relationship has been found between scavengers of ROS and antioxidants in preclinical in vitro and in vivo models. ROS is widely believed to cause human pathology most specifically in sepsis, where a small increase in ROS levels activates signaling pathways to initiate biological processes. An inclusive understanding of the effects of ROS scavenging in cellular antioxidant signaling is essentially lacking in sepsis. This review compiles the mechanisms of ROS scavenging as well as oxidative damage in sepsis, as well as antioxidants as a potent therapeutic. Direct interaction between ROS and cellular pathways greatly affects sepsis, but such interaction does not provide the explanation behind diverse biological outcomes. Animal models of sepsis and a number of clinical trials with septic patients exploring the efficiency of antioxidants in sepsis are reviewed. In line with this, both enzymatic and non-enzymatic antioxidants were effective, and results from recent studies are promising. The usage of these potent antioxidants in sepsis patients would greatly impact the field of medicine.

Unravelling the Differential Host Immuno-Inflammatory Responses to Staphylococcus aureus and Escherichia coli Infections in Sepsis.

Previous reports from our lab have documented dysregulated host inflammatory reactions in response to bacterial infections in sepsis. Both Gram-negative bacteria (GNB) and Gram-positive bacteria (GPB) play a significant role in the development and progression of sepsis by releasing several virulence factors. During sepsis, host cells produce a range of inflammatory responses including inducible nitric oxide synthase (iNOS) expression, nitrite generation, neutrophil extracellular traps (NETs) release, and pro-inflammatory cytokines production. The current study was conducted to discern the differences in host inflammatory reactions in response to both Escherichia coli and Staphylococcus aureus along with the organ dysfunction parameters in patients of sepsis. We examined 60 ICU sepsis patients identified based on the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA II) scores. Pathogen identification was carried out using culture-based methods and gene-specific primers by real-time polymerase chain reaction (RT-PCR). Samples of blood from healthy volunteers were spiked with E. coli (GNB) and S. aureus (GPB). The incidence of NETs formation, iNOS expression, total nitrite content, and pro-inflammatory cytokine level was estimated. Prevalence of E. coli, A. baumannii (both GNB), S. aureus, and Enterococcus faecalis (both GPB) was found in sepsis patients. Augmented levels of inflammatory mediators including iNOS expression, total nitrite, the incidence of NETs, and proinflammatory cytokines, during spiking, were found in response to S. aureus infections in comparison with E. coli infections. These inflammatory mediators were found to be positively correlated with organ dysfunction in both GN and GP infections in sepsis patients. Augmented host inflammatory response was generated in S. aureus infections as compared with E. coli.

Plant-associated endophytic fungi as potential bio-factories for extracellular enzymes: Progress, Challenges and Strain improvement with precision approaches.

There is an intricate network of relations between endophytic fungi and their hosts that affects the production of various bioactive compounds. Plant-associated endophytic fungi contain industrially important enzymes and have the potential to fulfil their rapid demand in the international market to boost business in technology. Being safe and metabolically active, they have replaced the usage of toxic and harmful chemicals and hold a credible application in biotransformation, bioremediation and industrial processes. Despite these, there are limited reports on fungal endophytes that can directly cater to the demand and supply of industrially stable enzymes. The underlying reasons include low endogenous production and secretion of enzymes from fungal endophytes which have raised concern for widely accepted applications. Hence, it is imperative to augment the biosynthetic and secretory potential of fungal endophytes. Modern state-of-the-art biotechnological technologies aiming at strain improvement using cell factory engineering as well as precise gene editing like Clustered Regularly Interspaced Palindromic Repeats (CRISPR) and its Associated proteins (Cas) systems which can provide a boost in fungal endophyte enzyme production. Additionally, it is vital to characterize optimum conditions to grow one strain with multiple enzymes (OSME). The present review encompasses various plants-derived endophytic fungal enzymes and their applications in various sectors. Furthermore, we postulate the feasibility of new precision approaches with an aim for strain improvement and enhanced enzyme production.

Sex differences in the fecal microbiome and hippocampal glial morphology following diet and antibiotic treatment.

Rising obesity rates have become a major public health concern within the United States. Understanding the systemic and neural effects of obesity is crucial in designing preventive and therapeutic measures. In previous studies, administration of a high fat diet has induced significant weight gain for mouse models of obesity. Interestingly, sex differences in high-fat diet-induced weight gain have been observed, with female mice gaining significantly less weight compared to male mice on the same high-fat diet. It has also been observed that consumption of a high-fat diet can increase neurogliosis, but the mechanism by which this occurs is still not fully understood. Recent research has suggested that the gut microbiome may mediate diet-induced glial activation. The current study aimed to (1) analyze changes to the gut microbiome following consumption of a high fat (HF) diet as well as antibiotic treatment, (2) evaluate hippocampal microgliosis and astrogliosis, and (3) identify sex differences within these responses. We administered a low fat (Research Diets D12450 K) or high fat diet (Research Diets D12451) to male and female C57Bl/6 mice for sixteen weeks. Mice received an antibiotic cocktail containing 0.5g/L of vancomycin, 1.0 g/L ampicillin, 1.0 g/L neomycin, and 1.0 g/L metronidazole in their drinking water during the last six weeks of the study and were compared to control mice receiving normal drinking water throughout the study. We observed a significant reduction in gut microbiome diversity for groups that received the antibiotic cocktail, as determined by Illumina next-generation sequencing. Male mice fed the HF diet (± antibiotics) had significantly greater body weights compared to all other groups. And, female mice fed the low fat (LF) diet and administered antibiotics revealed significantly decreased microgliosis and astrogliosis in the hippocampus compared to LF-fed females without antibiotics. Interestingly, male mice fed the LF diet and administered antibiotics revealed significantly increased microgliosis, but decreased astrogliosis, compared to LF-fed males without antibiotics. The observed sex differences in LF-fed mice given antibiotics brings forward questions about sex differences in nutrient metabolism, gut microbiome composition, and response to antibiotics.

Targeting COPD with PLGA-Based Nanoparticles: Current Status and Prospects.

Chronic obstructive pulmonary disease (COPD) is pulmonary emphysema characterized by blockage in the airflow resulting in the long-term breathing problem, hence a major cause of mortality worldwide. Excessive generation of free radicals and the development of chronic inflammation are the major two episodes underlying the pathogenesis of COPD. Currently used drugs targeting these episodes including anti-inflammatory, antioxidants, and corticosteroids are unsafe, require high doses, and pose serious side effects. Nanomaterial-conjugated drugs have shown promising therapeutic potential against different respiratory diseases as they are required in small quantities which lower overall treatment costs and can be effectively targeted to diseased tissue microenvironment hence having minimal side effects. Poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) are safe as their breakdown products are easily metabolized in the body. Drugs loaded on the PLGA NPs have been shown to be promising agents as anticancer, antimicrobial, antioxidants, and anti-inflammatory. Surface modification of PLGA NPs can further improve their mechanical properties, drug loading potential, and pharmacological activities. In the present review, we have presented a brief insight into the pathophysiological mechanism underlying COPD and highlighted the role, potential, and current status of PLGA NPs loaded with drugs in the therapy of COPD.

Canon CP-TX1 camera - As a screening tool for amblyogenic risk factors.

Purpose: To evaluate the Canon CP-TX1 camera as a screening tool for ARFs in a pediatric population and estimate the prevalence of ARFs. Methods: In a pediatric outpatient space, largely in the immunization clinic, after obtaining parental consent, we encouraged children to be photographed from a distance of 5 feet in a dim room by using a CP-TX1 camera with the red-eye reduction feature off. Based on the captured red reflex, children were labeled as normal (symmetrical red reflexes in the two eyes, with no visible crescents); all others were considered as abnormal or positive for ARFs. All photographed children were assessed by an optometrist/refractionist for VA by age-appropriate methods. Data were entered into a 2 × 2 contingency table on statpages.org, and diagnostic indices were calculated with 95%CI. Results: With a sample of 262 children, we obtained a sensitivity of 0.82, a specificity of 0.98, a positive predictive value of 0.92, a negative predictive value of 0.94, a positive likelihood ratio of 41.06, a negative likelihood ratio of 0.17, and a prevalence of 0.24 for ARFs. Conclusion: CP-TX1 performed well as a screening tool to identify ARFs in children. Placing such a camera in an immunization clinic offers a chance to identify children with ARFs at a time when amblyopia is eminently reversible.

Plants in Anticancer Drug Discovery: From Molecular Mechanism to Chemoprevention.

Cancer is one of the primary causes of mortality globally, and the discovery of new anticancer drugs is the most important need in recent times. Natural products have been recognized as effective in fight against various diseases including cancer for over 50 years. Plants and microbes are the primary and potential sources of natural compounds to fight against cancer. Moreover, researches in the field of plant-based natural compounds have moved towards advanced and molecular level understandings from the last few decades, leading to the development of potent anticancer agents. Also, plants have been accepted as abundant and prosperous sources for the development of novel therapeutic agents for the management and prevention of different cancer types. The high toxicity of some cancer chemotherapy drugs, as well as their unfavorable side effects and drugs resistance, drives up the demand for natural compounds as new anticancer drugs. In this detailed evidence-based mechanistic review, facts and information about various medicinal plants, their bioactive compounds with their potent anticancer activities against different cancers have been gathered, with further approach to represent the molecular mechanism behind the anticancer activity of these plants. This review will be beneficial for investigators/scientists globally involved in the development of natural, safe, effective, and economical therapeutic agents/drugs against various cancers. This might be an important contribution in the field of drug discovery, where drugs can be used alone or in combination to increase the efficacy of newly synthesized drugs.

Sex differences in response to a high fat, high sucrose diet in both the gut microbiome and hypothalamic astrocytes and microglia.

Objectives: Obesity is a major epidemic in our population and has emerged as a primary health concern. Consumption of a high fat, high sugar (HFHS) diet can specifically lead to gut dysbiosis, increased inflammation, and neuroinflammation. Interestingly, sex differences in the response to a HFHS diet are emerging. In this study, we investigated the effects of a HFHS diet compared to a low fat, low sugar (LFLS) diet in 8 week old male and female C57Bl/6 mice.Methods: The diet was administered for 14 weeks; body weights and food consumption were evaluated weekly.Results: Male and female mice fed the HFHS diet gained significantly more weight than LFLS-fed mice. However, in agreement with previous studies, males gained significantly more weight on the HFHS diet compared to females fed the same diet. Importantly, we determined significant sex and diet-induced differences to gut microbiome composition using next generation Illumina sequencing. We also observed significantly less astrocyte densitometry and no significant change to microglial morphology in the hypothalamus of Female HFHS compared to Female LFLS. On the other hand, Male HFHS revealed no change to hypothalamic astrogliosis, but increased microgliosis compared to Male LFLS.Discussion: In this study, we determined sex and diet-induced differences in both the gut and the brain, however, future studies will need to be performed in order to test the direct role of the gut microbiome to weight gain and neuroinflammation in male and female mice.

A Bioinformatics Approach for the Prediction of Immunogenic Properties and Structure of the SARS-COV-2 B.1.617.1 Variant Spike Protein.

BACKGROUND: B.1.617.1, a variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing respiratory illness is responsible for the second wave of COVID-19 and associated with a high incidence of infectivity and mortality. To mitigate the B.1.617.1 variant of SARS-CoV-2, deciphering the protein structure and immunological responses by employing bioinformatics tools for data mining and analysis is pivotal. OBJECTIVES: Here, an in silico approach was employed for deciphering the structure and immune function of the subunit of spike (S) protein of SARS-CoV-2 B.1.617.1 variant. METHODS: The partial amino acid sequence of SARS-CoV-2 B.1.617.1 variant S protein was analyzed, and its putative secondary and tertiary structure was predicted. Immunogenic analyses including B- and T-cell epitopes, interferon-gamma (IFN-γ) response, chemokine, and protective antigens for SARS-CoV 2 S proteins were predicted using appropriate tools. RESULTS: B.1.617.1 variant S protein sequence was found to be highly stable and amphipathic. ABCpred and CTLpred analyses led to the identification of two potential antigenic B cell and T cell epitopes with starting amino acid positions at 60 and 82 (for B cell epitopes) and 54 and 98 (for T cell epitopes) having prediction scores > 0.8. Further, RAMPAGE tool was used for determining the allowed and disallowed regions of the three-dimensional predicted structure of SARS-CoV-2 B.1.617.1 variant S protein. CONCLUSION: Together, the in silico analysis revealed the predicted structure of partial S protein, immunogenic properties, and possible regions for S protein of SARS-CoV-2 and provides a valuable prelude for engineering the targeted vaccine or drug against B.1.617.1 variant of SARS-CoV-2.

Neutrophil extracellular traps and organ dysfunction in sepsis.

Sepsis is a clinical syndrome resulting from infection followed by inflammation and is one of the significant causes of mortality worldwide. The underlying reason is the host's uncontrolled inflammatory response due to an infection led to multiple organ dysfunction/failure. Neutrophils, an innate immune cell, are forerunners to reach the site of infection/inflammation for clearing the infection and resolute the inflammation during sepsis. A relatively new neutrophil effector function, neutrophil extracellular traps (NETs), have been demonstrated to kill the pathogens by releasing DNA decorated with histone and granular proteins. A growing number of pieces of shreds of evidence suggest that unregulated incidence of NETs have a significant influence on the pathogenesis of sepsis-induced multiple organ damage, including arterial hypotension, hypoxemia, coagulopathy, renal, neurological, and hepatic dysfunction. Thus, excessive production and improper resolution of NETs are of significant therapeutic value in combating sepsis-induced multiple organ failure. The purpose of this review is intended to highlight the role of NETs in sepsis-induced organ failure. Furthermore, the current status of therapeutic strategies to intersect the harmful effects of NETs to restore organ functions is discussed.