An immuno-informatics approach for annotation of hypothetical proteins and multi-epitope vaccine designed against the Mpox virus.

A worrying new outbreak of Monkeypox (Mpox) in humans is caused by the Mpox virus (MpoxV). The pathogen has roughly 28 hypothetical proteins of unknown structure, function, and pathogenicity. Using reliable bioinformatics tools, we attempted to analyze the MpoxV genome, identify the role of hypothetical proteins (HPs), and design a potential candidate vaccine. Out of 28, we identified seven hypothetical proteins using multi-server validation with high confidence for the occurrence of conserved domains. Their physical, chemical, and functional characterizations, including molecular weight, theoretical isoelectric point, 3D structures, GRAVY value, subcellular localization, functional motifs, antigenicity, and virulence factors, were performed. We predicted possible cytotoxic T cell (CTL), helper T cell (HTL) and linear and conformational B cell epitopes, which were combined in a 219 amino acid multiepitope vaccine with human ß defensin as a linker. This multi-epitopic vaccine was structurally modelled and docked with toll-like receptor-3 (TLR-3). The dynamical stability of the vaccine-TLR-3 docked complexes exhibited stable interactions based on RMSD and RMSF tests. Additionally, the modelled vaccine was cloned in-silico in an E. coli host to check the appropriate expression of the final vaccine built. Our results might conform to an immunogenic and safe vaccine, which would require further experimental validation.Communicated by Ramaswamy H. Sarma.

Seasonal variation, contamination and ecological risk assessment of heavy metals in sediments of coastal wetlands along the Bay of Bengal.

Functioning of coastal wetland habitats is essential for the ecosystem integrity and sustainability of coastal development that enables human progress along transitional waterways. However, these habitats are continuously being affected by a variety of pollutants including metallic elements. In this study, seasonal variation, pollution status and ecological risks of heavy metals (Cr, Mn, Co, Ni, As, Cu, Zn and Pb) in surface sediment of the several types of coastal wetlands (estuaries, mudflats, sandy beaches, mangroves, and saltmarshes) were detected by using X-ray fluorescence (EDXRF) spectrometry. The results showed that the mean concentration level of metals in the surficial sediment samples followed the order of Cu (84.06 ± 8.60 µg/g) > Zn (51.00 ± 8.97 µg/g) > Mn (38.25 ± 11.34 µg/g) > Cr (3.52 ± 0.91 µg/g) > Pb (0.27 ± 0.13 µg/g) > Co (0.24 ± 0.13 µg/g) > As (0.21 ± 0.12 µg/g) > Ni (0.16 ± 0.08 µg/g). In comparison to the pre-monsoon period, the post-monsoon season had higher concentrations of heavy metals while the overall accumulation level of metals in the wetlands exhibited a pattern of estuarine wetland (28.47 ± 31.35 µg/g) > mangrove (22.23 ± 30.79 µg/g) > mudflat (21.79 ± 29.71 µg/g) > sandy beach (21.47 ± 28.15 µg/g) > saltmarsh (21.28 ± 30.02 µg/g). Although, the pollution assessment indices e.g., contamination factor (CF), degree of contamination (CD), geoaccumulation index (Igeo) and pollution load index (PLI) showed minimal levels of contamination in the studied sites, enrichment factor (EF) suggested greater enrichment of the metals in the pre-monsoon season but with the lowest ecological risk (RI < 40) in both seasons. Cluster analysis, principal component analysis (PCA), and Pearson's correlation were performed to determine the sources of heavy metals in collected samples which specified that Pb, As, Co and Ni predominantly came from natural sources whereas Cu, Mn, Zn and Cr emerged from anthropogenic sources such as industrial effluents, domestic wastewater, fertilizer or pesticide consumption on farmland along the riverbank, vessel emissions, and the confluence of tributary rivers.

Erratum: Publisher Correction: Additive manufacturing for biomedical applications: a review on classification, energy consumption, and its appreciable role since COVID-19 pandemic.

[This corrects the article DOI: 10.1007/s40964-022-00373-9.].

A Multidisciplinary Approach and Current Perspective of Nonalcoholic Fatty Liver Disease: A Systematic Review.

In recent times, nonalcoholic fatty liver disease (NAFLD) has been considered one of the major causes of liver disease across the world. NAFLD is defined as the deposition of triglycerides in the liver and is associated with obesity and metabolic syndrome. Hyperinsulinemia, insulin resistance (IR), fatty liver, hepatocyte injury, unbalanced proinflammatory cytokines, mitochondrial dysfunction, oxidative stress, liver inflammation, and fibrosis are the main pathogenesis in NAFLD. Recent studies suggest that the action of intestinal microbiota through chronic inflammation, increased intestinal permeability, and energy uptake plays a vital role in NAFLD. Moreover, polycystic ovarian syndrome also causes NAFLD development through IR. Age, gender, race, ethnicity, sleep, diet, sedentary lifestyle, and genetic and epigenetic pathways are some contributing factors of NAFLD that can exacerbate the risk of liver cirrhosis and hepatocellular carcinoma (HCC) and eventually lead to death. NAFLD has various presentations, including fatigue, unexplained weight loss, bloating, upper abdominal pain, decreased appetite, headache, anxiety, poor sleep, increased thirst, palpitation, and a feeling of warmth. Some studies have shown that NAFLD with severe coronavirus disease 2019 (COVID-19) has poor outcomes. The gold standard for NAFLD diagnosis is liver biopsy. Other diagnostic tools are imaging tests, serum biomarkers, microbiota markers, and tests for extrahepatic complications. There are no specific treatments for NAFLD. Therefore, the main concern for NAFLD is treating the comorbid conditions such as anti-diabetic agents for type 2 diabetes mellitus, statins to reduce HCC progression, antioxidants to prevent hepatocellular damage, and bariatric surgery for patients with a BMI of >40 kg/m2 and >35 kg/m2 with comorbidities. Lifestyle and dietary changes are considered preventive strategies against NAFLD advancement. Inadequate treatment of NAFLD further leads to cardiac consequences, sleep apnea, chronic kidney disease, and inflammatory bowel disease. In this systematic review, we have briefly discussed the risk factors, pathogenesis, clinical features, and numerous consequences of NAFLD. We have also reviewed various guidelines for NAFLD diagnosis along with existing therapeutic strategies for the management and prevention of the disease.

Role of Prophylactic Steroids in Differentiation Syndrome.

Acute promyelocytic leukemia (APML) is defined as a balanced chromosomal translocation between chromosomes 15 and 17 t(15;17)(q24;q21), which results in the formation of promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARA) fusion protein. A widespread recommendation for APML treatment is combined all-trans retinoic acid (ATRA)/arsenic trioxide (ATO) therapy. Differentiation syndrome (DS), or retinoic acid syndrome, is one of the well-known complications of APML treated with ATRA or ATO. The presenting symptoms of APML-induced DS are diverse, and rare symptoms are easily misdiagnosed. However, unexplained fever, dyspnea, weight gain > 5 kg, leukocytosis, acute renal failure, and a chest radiograph demonstrating pleural or pericardial effusion are the most common manifestations of DS. Early recognition and prompt initiation of corticosteroids are key factors in the management of DS. As soon as ATRA/ATO therapy is started, prophylactic treatment with steroids has been recommended to minimize the severity of DS. It is proposed that ATRA/ATO should be stopped or held once the signs and symptoms of DS develop. This case report describes a 45-year-old male who was diagnosed with APML after he developed episodes of hematuria and nose bleeding at home. The patient was also given an empiric steroid along with ATRA/ATO to lessen the intensity of DS. Our study suggests that early initiation of prophylactic steroid treatment can improve the prognosis and mortality of patients with APML-induced DS.

Rapid Turn From Cirrhosis to Encephalopathy Following COVID-19 Infection: A Cautionary Tale.

The coronavirus disease 2019 (COVID-19) infection has most commonly led to patients presenting with pulmonary disease, including severe acute respiratory syndrome. However, in about 14-53% of patients with a newly diagnosed COVID-19 infection, the liver is the organ most drastically affected, as opposed to the lungs. In patients with preexisting liver damage, the first symptom of a COVID-19 infection may come from worsening liver failure such as hepatic encephalopathy or worsening ascites. This case report highlights this unusual presentation of a COVID-19 infection in a patient with preexisting alcoholic liver cirrhosis. We report this case to heed warning that acutely worsening liver failure may be the first presenting symptom of a superimposed COVID-19 infection on preexisting liver disease.

Additive manufacturing for biomedical applications: a review on classification, energy consumption, and its appreciable role since COVID-19 pandemic.

The exponential rise of healthcare problems like human aging and road traffic accidents have developed an intrinsic challenge to biomedical sectors concerning the arrangement of patient-specific biomedical products. The additively manufactured implants and scaffolds have captured global attention over the last two decades concerning their printing quality and ease of manufacturing. However, the inherent challenges associated with additive manufacturing (AM) technologies, namely process selection, level of complexity, printing speed, resolution, biomaterial choice, and consumed energy, still pose several limitations on their use. Recently, the whole world has faced severe supply chain disruptions of personal protective equipment and basic medical facilities due to a respiratory disease known as the coronavirus (COVID-19). In this regard, local and global AM manufacturers have printed biomedical products to level the supply-demand equation. The potential of AM technologies for biomedical applications before, during, and post-COVID-19 pandemic alongwith its relation to the industry 4.0 (I4.0) concept is discussed herein. Moreover, additive manufacturing technologies are studied in this work concerning their working principle, classification, materials, processing variables, output responses, merits, challenges, and biomedical applications. Different factors affecting the sustainable performance in AM for biomedical applications are discussed with more focus on the comparative examination of consumed energy to determine which process is more sustainable. The recent advancements in the field like 4D printing and 5D printing are useful for the successful implementation of I4.0 to combat any future pandemic scenario. The potential of hybrid printing, multi-materials printing, and printing with smart materials, has been identified as hot research areas to produce scaffolds and implants in regenerative medicine, tissue engineering, and orthopedic implants.