Two years of SARS-CoV-2 infection (2019–2021): structural biology, vaccination, and current global situation

The deadly SARS-CoV-2 virus has infected more than 259,502,031 confirmed cases with 5,183,003 deaths in 223 countries during the last 22 months (Dec 2019–Nov 2021), whereas approximately 7,702,859,718, vaccine doses have been administered (WHO: https://covid19.who.int/) as of the 24th of Nov 2021. Recent announcements of test trial completion of several new vaccines resulted in the launching of immunization for the common person around the globe highlighting a ray of hope to cope with this infection. Meanwhile, genetic variations in SARS-CoV-2 and third layer of infection spread in numerous countries emerged as a stronger prototype than the parental. New and parental SARS-CoV-2 strains appeared as a risk factor for other pre-existing diseases like cancer, diabetes, neurological disorders, kidney, liver, heart, and eye injury. This situation requires more attention and re-structuring of the currently developed vaccines and/or drugs against SARS-CoV-2 infection. Although a decline in COVID-19 infection has been reported globally, an increase in COVID-19 cases in the subcontinent and east Mediterranean area could be alarming. In this review, we have summarized the current information about the SARS-CoV-2 biology, its interaction and possible infection pathways within the host, epidemiology, risk factors, economic collapse, and possible vaccine and drug development.

Aluminum Poisoning with Emphasis on Its Mechanism and Treatment of Intoxication

Aluminum poisoning has been reported in some parts of the world. It is one of the global health problems that affect many organs. Aluminum is widely used daily by humans and industries. Residues of aluminum compounds can be found in drinking water, food, air, medicine, deodorants, cosmetics, packaging, many appliances and equipment, buildings, transportation industries, and aerospace engineering. Exposure to high levels of aluminum compounds leads to aluminum poisoning. Aluminum poisoning has complex and multidimensional effects, such as disruption or inhibition of enzymes activities, changing protein synthesis, nucleic acid function, and cell membrane permeability, preventing DNA repair, altering the stability of DNA organization, inhibition of the protein phosphatase 2A (PP2A) activity, increasing reactive oxygen species (ROS) production, inducing oxidative stress, decreasing activity of antioxidant enzymes, altering cellular iron homeostasis, and changing NF-kB, p53, and JNK pathway leading to apoptosis. Aluminum poisoning can affect blood content, musculoskeletal system, kidney, liver, and respiratory and nervous system, and the extent of poisoning can be diagnosed by assaying aluminum compounds in blood, urine, hair, nails, and sweat. Chelator agents such as deferoxamine (DFO) are used in the case of aluminum poisoning. Besides, combination therapies are recommended.

Analysis of HIV quasispecies and virological outcome of an HIV D+/R+ kidney–liver transplantation

Introduction Transplantation among HIV positive patients may be a valuable therapeutic intervention. This study involves an HIV D+/R+ kidney–liver transplantation, where PBMC-associated HIV quasispecies were analyzed in donor and transplant recipients (TR) prior to transplantation and thereafter, together with standard viral monitoring. Methods The donor was a 54 year of age HIV infected woman: kidney and liver recipients were two HIV infected men, aged 49 and 61. HIV quasispecies in PBMC was analyzed by ultra-deep sequencing of V3 env region. During TR follow-up, plasma HIV-1 RNA, HIV-1 DNA in PBMC, analysis of proviral integration sites and drug-resistance genotyping were performed. Other virological and immunological monitoring included CMV and EBV DNA quantification in blood and CD4 T cell counts. Results Donor and TR were all ART-HIV suppressed at transplantation. Thereafter, TR maintained a nearly suppressed HIV-1 viremia, but HIV-1 RNA blips and the increase of proviral integration sites in PBMC attested some residual HIV replication. A transient peak in HIV-1 DNA occurred in the liver recipient. No major changes of drug-resistance genotype were detected after transplantation. CMV and EBV transient reactivations were observed only in the kidney recipient, but did not require specific treatment. CD4 counts remained stable. No intermixed quasispecies between donor and TR was observed at transplantation or thereafter. Despite signs of viral evolution in TR, HIV genetic heterogeneity did not increase over the course of the months of follow up. Conclusions No evidence of HIV superinfection was observed in the donor nor in the recipients. The immunosuppressive treatment administrated to TR did not result in clinical relevant viral reactivations.

Antioxidant and Inflammatory Effects of Nelumbo nucifera Gaertn. Leaves

This study is aimed at identifying the bioactive components in lotus leaf flavonoid extract (LLFE) and analyzing the antioxidant and anti-inflammatory activities of LLFE in vitro and in vivo. The flavonoids in LLFE were determined by UHPLC-MS/MS. The effect of LLFE on damaged 293T cells (H2O2, 0.3 mmol/L) was determined by MTT assay, and the activity of antioxidant enzymes was measured by kits. We studied the antioxidant and anti-inflammatory effects of LLFE on D-Gal/LPS (30 mg/kg·bw and 3 μg/kg·bw)-induced aging mice. We also evaluated the main organ index, pathological changes in the liver, lung, and kidney, liver function index, biochemical index, cytokine level, and mRNA expression level in serum and liver. The results showed that LLFE contains baicalein, kaempferol, kaempferid, quercetin, isorhamnetin, hyperoside, lespenephryl, and rutin. LLFE reduced the oxidative damage sustained by 293T cells, increased the levels of SOD, CAT, GSH, and GSH-Px, and decreased the level of MDA. The animal studies revealed that LLFE reduced oxidative damage and inflammation in injured mice, inhibited increases in AST, ALT, MDA, and NO, increased SOD, CAT, GSH, and GSH-Px levels, upregulated anti-inflammatory cytokines IL-10 and IL-12, and downregulated proinflammatory cytokines IL-6, IL-1β, TNF-α, and IFN-γ. Furthermore, the expression of antioxidant- and anti-inflammatory-related mRNA was consistent with the above results.

DNA methylation clocks tick in naked mole rats but queens age more slowly than nonbreeders

Naked mole rats (NMRs) live an exceptionally long life, appear not to exhibit age-related decline in physiological capacity and are resistant to age-related diseases. However, it has been unknown whether NMRs also evade aging according to a primary hallmark of aging: epigenetic changes. To address this question, we profiled n = 385 samples from 11 tissue types at loci that are highly conserved between mammalian species using a custom array (HorvathMammalMethylChip40). We observed strong epigenetic aging effects and developed seven highly accurate epigenetic clocks for several tissues (pan-tissue, blood, kidney, liver, skin clocks) and two dual-species (human–NMR) clocks. The skin clock correctly estimated induced pluripotent stem cells derived from NMR fibroblasts to be of prenatal age. The NMR epigenetic clocks revealed that breeding NMR queens age more slowly than nonbreeders, a feature that is also observed in some eusocial insects. Our results show that despite a phenotype of negligible senescence, the NMR ages epigenetically.

The History of Solid Organ Transplantation

This chapter provides a brief history of solid organ transplantation. Although the focus is on the living donor, the history of living donor solid organ transplantation is intertwined with the history of deceased donor solid organ transplantation. This is particularly true in the early years of solid organ transplantation when the earliest success for some solid organ transplants began with living donors, e.g. kidney, and began with deceased donors for other solid organ transplants, e.g. liver. The history of each solid organ in which living donors have supplied grafts (kidney, liver, lung, pancreas, intestines, and uterus) is described even though some are rarely if ever performed today, e.g. lung, intestine, pancreas. We also discuss the living domino donor—a candidate-recipient (most commonly the recipient of a deceased donor liver or heart) whose own organ is not discarded but is transplanted into another person.

Preliminary sub-acute toxicological assessment of methanol leaves extract of Culcasia angolensis (Araceae) in Wistar rats

Background The plant Culcasia angolensis (Araceae) has diverse ethnomedicinal uses, including the management of rheumatic pain, healing of cuts, dislocations, and bruises. Despite its potential therapeutic uses, the toxicity profile of Culcasia angolensis has not been evaluated. This study assessed the sub-acute toxicity effects of Culcasia angolensis leaves extract (CAE). The phytochemical determination of the CAE was conducted as per the standard protocols. The median lethal dose (LD50) was determined using the Organization for Economic Cooperation and Development (OECD) 423 guideline. Besides, the sub-acute toxic effects of the CAE (125, 250, and 500 mg/kg) were investigated following administration of the CAE daily for 28 consecutive days as per the OECD 407 guideline. The weekly body weights were recorded. The animals were euthanized on the 29th day, and blood samples were obtained for haematological and biochemical investigations. The heart, kidney, liver, and lungs were collected for histological examinations. Besides, the relative organ weights (ROW) were determined. Results The CAE contains cardiac glycosides, alkaloids, tannins, flavonoids, steroids, saponins, and terpenoids. The oral LD50 was above 5 g/kg. There was a remarkable decline in the weekly body weight at all the CAE doses. The CAE increased the lymphocytes, aspartate transaminase, and urea. However, the levels of alanine transaminase and alkaline phosphatase were elevated remarkably. The histological studies did not reveal any serious organs abnormalities. Conclusion The CAE is relatively safe on acute administration. However, it may be slightly toxic on sub-acute administration, especially to the liver and kidney.

Potential Toxicity Evaluation of Protopine in Macleaya cordata (Willd.) R. Br.—A Bioactivity Guided Approach

Macleaya cordata (Willd.) R. Br. (M. cordata) is a perennial herb known for its chemotherapeutic properties, strong feeding additive, and potential antidiarrheal drug. Despite its therapeutic potentials, its clinical applications are hindered by an apparent lack of toxicity data. In this study, the toxic ingredients of this plant were investigated using a bioactivity-guided approach. Two compounds, protopine and allocryptopine, were purified and elucidated by LC-MS, 1H-NMR, and 13C-NMR. Protopine, a primary component in M. cordata, had an LD50 of 313.10 mg/kg i.e., which was considered toxic. An autopsy was performed on protopine-administered mice, and the histopathology of the kidney, liver, brain, heart, lung, and spleen was determined. Autopsy findings included hemorrhage in the respiratory system, lung congestion, and hemorrhage and edema in the parenchymatous organs (heart, liver, kidney, and brain). Histopathology confirmed the pathological changes in the brain, liver, and kidney. Protopine is one of the principal bioactive constituents of many phytopreparations used in veterinary and human medicine, such as Sangrovit and Iberogast. Our findings indicated that phytopreparations containing protopine might pose a serious health threat to humans and animals.

Antibody-Mediated Rejection and Recurrent Primary Disease: Two Main Obstacles in Abdominal Kidney, Liver, and Pancreas Transplants

The advances in acute phase care have firmly established the practice of organ transplantation in the last several decades. Then, the next issues that loom large in the field of transplantation include antibody-mediated rejection (ABMR) and recurrent primary disease. Acute ABMR is a daunting hurdle in the performance of organ transplantation. The recent progress in desensitization and preoperative monitoring of donor-specific antibodies enables us to increase positive outcomes. However, chronic active ABMR is one of the most significant problems we currently face. On the other hand, recurrent primary disease is problematic for many recipients. Notably, some recipients, unfortunately, lost their vital organs due to this recurrence. Although some progress has been achieved in these two areas, many other factors remain largely obscure. In this review, these two topics will be discussed in light of recent discoveries.

SARS-COV2 Associated Oral Lesions- A Review

Introduction: COVID-19 disease is caused by SARS-CoV-2 virus and it was declared pandemic by World Health Organization (WHO) on March 11,2020. The coronavirus infection has an affinity for ACE2 receptors and by attaching to them, the virus enters the host cells. Along with many body organs like lungs, kidney, liver, upper respiratory tract, nervous system, skeletal muscles, ACE2 concentration is also found in abundance in epithelial cells of tongue and salivary glands. Materials and Methods: Recent studies, researches, documents and case reports published in the world medical literature in the year 2020-2021 were searched and documented in our study. The search engines used were PUBMED, google scholar, WEB OF SCIENCE etc. Results: Dysgeusia, xerostomia, sore throat, aphthous and herpetiform ulcers, candidiasis, enanthema, Kawasaki like lesions were the most common among various oral manifestations. Others includes plaque like changes, gingival inflammation, necrotizing gingivitis, erythema -multiforme, angina-bullosa like lesions, Melkersson-Rosenthal Syndrome, Oral mucormycosis etc.The sites of infection mainly include tongue, gingiva, hard and soft palate, buccal and labial mucosa etc. Conclusion: The etiopathogenesis of such lesions cannot be directly corelated with COVID-19 and factors such as stress, immunosuppression, co-infections, secondary lesions, opportunistic infections, systemic diseases, poor oral hygiene etc. must be considered. Management of stress is an important factor. In this review article various oral lesions are discussed in COVID-19 infection states in detail. The importance of earliest diagnosis of oral lesions is to be kept in mind to prevent further complications.