To be remembered: B cell memory response against SARS-CoV-2 and its variants in vaccinated and unvaccinated individuals.

COVID-19 disease has plagued the world economy and affected the overall well-being and life of most of the people. Natural infection as well as vaccination leads to the development of an immune response against the pathogen. This involves the production of antibodies, which can neutralize the virus during future challenges. In addition, the development of cellular immune memory with memory B and T cells provides long-lasting protection. The longevity of the immune response has been a subject of intensive research in this field. The extent of immunity conferred by different forms of vaccination or natural infections remained debatable for long. Hence, understanding the effectiveness of these responses among different groups of people can assist government organizations in making informed policy decisions. In this article, based on the publicly available data, we have reviewed the memory response generated by some of the vaccines against SARS-CoV-2 and its variants, particularly B cell memory in different groups of individuals.

Comparison of the Effect of Kaolin and Bentonite Clay (Raw, Acid-Treated, and Metal-Impregnated) on the Pyrolysis of Waste Tire.

This study investigates the effectiveness of kaolin and bentonite catalysts in improving liquid hydrocarbon yields during the pyrolysis of waste tires. Raw clay, nitric acid-treated clay, and mono- or bimetal-impregnated clay were used as catalysts in the pyrolysis of waste tire. Acid-treated kaolin produced a higher yield of liquid hydrocarbons (43.24-47%) compared to acid-treated bentonite (35.34-41.85%). This improvement in the liquid yield can be attributed to the higher specific surface area and pore diameter of the acid-treated clay in comparison to raw kaolin (39.48%) and raw bentonite (31.62%). Moreover, the use of metal-impregnated catalysts, such as Fe/kaolin and Ni/Fe/kaolin, resulted in higher liquid yields (47%) compared to the 3 M HNO3-treated kaolin catalyst (43.24%). Gas chromatography-mass spectrometry (GC-MS) analysis confirmed the presence of limonene, a crucial ingredient for commercial perfume production, in the liquid products. The calorific values of oil obtained through kaolin and bentonite catalysis were measured at 13,922 and 10,174 kcal/kg, respectively, further highlighting the potential of these catalysts in waste tire valorization.

Identification of dual active sites in Caenorhabditis elegans GANA-1 protein: an ortholog of the human α-GAL a and α-NAGA enzymes.

Fabry disease (FD) is caused by a defective α-galactosidase A (α-GAL A) enzyme responsible for breaking down globotriaosylceramide (Gb3). To develop affordable therapeutics, more effort is needed to obtain insights into the underlying mechanism of FD and understanding human α-GAL A structure and function in related animal models. We adopted C. elegans as a model to elucidate the sequence and 3D structure of its GANA-1 enzyme and compared it to human α-GAL A. We constructed GANA-1 3D structure by homology modelling and validated the quality of the predicted GANA-1 structure, followed by computational docking of human ligands. The GANA-1 protein shared sequence similarities up to 42.1% with the human α-GAL A in silico and had dual active sites. GANA-1 homology modelling showed that 11 out of 13 amino acids in the first active site of GANA-1 protein overlapped with the human α-GAL A active site, indicating the prospect for substrate cross-reaction. Computational molecular docking using human ligands like Gb3 (first pocket), 4-nitrophenyl-α-D-galactopyranoside (second pocket), α-galactose (second pocket), and N-acetyl-D-galactosamine (second pocket) showed negative binding energy. This revealed that the ligands were able to bind within both GANA-1 active sites, mimicking the human α-GAL A and α-NAGA enzymes. We identified human compounds with adequate docking scores, predicting robust interactions with the GANA-1 active site. Our data suggested that the C. elegans GANA-1 enzyme may possess structural and functional similarities to human α-GAL A, including an intrinsic capability to metabolize Gb3 deposits.Communicated by Ramaswamy H. Sarma.

Translation and validation study of Quality of Life Questionnaire for Physiological Pregnancy at Sandeman Provincial Hospital, Quetta, Pakistan.

OBJECTIVE: To examine the psychometric properties of the Urdu version of Quality of Life Questionnaire for Physiological Pregnancy. METHODS: The cross-sectional study was conducted from August 1 to October 31, 2020, at the Obstetrics and Gynaecology department of Sandeman Provincial Hospital, Quetta, Pakistan. The Quality of Life Questionnaire for Physiological Pregnancy was translated into Urdu by using a forward-backward procedure. The test-retest reliability was assessed through Cronbach's alpha reliability analysis. The validity of the translated questionnaire was constructed by using exploratory factor analysis through principal axis factoring extraction and Oblique rotation with Kaiser Normalisation. The constructs were retained based on extracted communalities. Data was analysed using SPSS v 21. RESULTS: The Urdu version of the questionnaire exhibited acceptable test-retest alpha values of 0.780 and 0.812 at two-time points, with an overall value of 0.790. All items showed good stability with intraclass correlation coefficient values of >0.80. The Kaiser-Meyer-Olkin measure for factor analysis was 0.812. Barlett's Test of Sphericity was significant (p<0.05). Three factors explaining the variance were extracted and the loading values for all nine constructs were acceptable (>0.40). All items of the translated version were retained, proving the validity of the Urdu version of the questionnaire. CONCLUSIONS: The translated version of Quality of Life Questionnaire for Physiological Pregnancy was found to be a valid and reliable instrument for the assessment of quality of life for pregnant women in regions where Urdu is the prime language of communication.

Embelin Protects Against Acute Pentylenetetrazole-Induced Seizures and Positively Modulates Cognitive Function in Adult Zebrafish.

Purpose of the research: Epilepsy is a continuous process of neurodegeneration categorized by an enduring tendency to generate uncontrolled electrical firing known as seizures causing involuntary movement all over the body. Cognitive impairment and behavioral disturbances are among the more alarming co-morbidities of epilepsy. Anti-epileptic drugs (AEDs) were found to be successful in controlling epilepsy but are reported to worsen cognitive status in patients. Embelin (EMB) is a benzoquinone derived from the plant Embelia ribes and is reported to have central nervous system (CNS) activity. This study aims to evaluate the effectiveness of EMB against pentylenetetrazole (PTZ) induced acute seizures and its associated cognitive dysfunction. This was done via docking studies as well as evaluating neurotransmitter and gene expression in the zebrafish brain. The principal results: Behavioral observations showed that EMB reduced epileptic seizures and the T-maze study revealed that EMB improved the cognitive function of the fish. The docking study of EMB showed a higher affinity toward gamma-aminobutyric acid (GABAA) receptor as compared to the standard diazepam, raising the possibility of EMB working via the alpha subunit of the GABA receptor. EMB was found to modulate several genes, neurotransmitters, and also neuronal growth, all of which play an important role in improving cognitive status after epileptic seizures. Healthy zebrafish treated with EMB alone were found to have no behavioral and biochemical interference or side effects. The immunohistochemistry data suggested that EMB also promotes neuronal protection and neuronal migration in zebrafish brains. Major Conclusions: It was perceived that EMB suppresses seizure-like behavior via GABAA receptor pathway and has a positive impact on cognitive functions. The observed effect was supported by docking study, T-maze behavior, neurotransmitter and gene expression levels, and immunohistology study. The apparatus such as the T-maze and seizure scoring behavior tank were found to be a straightforward technique to score seizure and test learning ability after acute epileptic seizures. These research findings suggest that EMB could be a promising molecule for epilepsy induced learning and memory dysfunction.

In vivo anticlastogenic effect of silymarin from milk thistle Silybum marianum L.

OBJECTIVE: Silymarin, extracted from the seeds of Silybum marianum L. (Milk thistle), is traditionally used for treating various illnesses such as diabetes, cancer, inflammation, hepatitis, liver cirrhosis, and renal problems. Acute cytotoxicity and genotoxicity studies have been reported with ambiguous outcomes; however, its relevant anticlastogenic potential is not yet evaluated. This study was aimed to evaluate in vivo subacute anticlastogenic properties of silymarin to validate its use as a medicinal agent. MATERIALS AND METHODS: Silymarin was isolated from seeds of milk thistle. Various genotoxicity bioassays of silymarin were performed using mice. First, the bone marrow cell proliferation was estimated by calculating mitotic index. Second, the chromosomal abnormalities in mice bone marrow cells were studied. Third, micronucleated polychromatic erythrocytes (MPE) test and in vivo activation of sister chromatid exchanges (SCEs) were carried out in mice bone marrow cells. Finally, primary spermatocytes were analyzed to estimate genotoxic effect of silymarin on germ cells. RESULTS: We found that silymarin is capable of inducing a significant increase (P ≤ 0.05) in cell proliferation of bone marrow cells. There is no increase in chromosomal aberrations following silymarin treatments. Results clearly showed that it significantly (P ≤ 0.05) decreased the MPE. Likewise, it was found to be a negative inducer of SCEs. It decreased in total abnormal metaphase, SCEs, MPE, and aberrant diakinesis. CONCLUSION: The results demonstrated that silymarin has a strong anticlastogenic activity upon mice genome in somatic and germ cells, indicating its safe use as a medicinal substance. Furthermore, it is not only safe but also has protective effect from clastogens.

Maslinic acid modulates secreted phospholipase A2-IIA (sPLA2-IIA)-mediated inflammatory effects in macrophage foam cells formation.

Secretory phospholipase A2-IIA (sPLA2-IIA) is one of the key enzymes causing lipoprotein modification and vascular inflammation. Maslinic acid is a pentacyclic triterpene which has potential cardioprotective and anti-inflammatory properties. Recent research showed that maslinic acid interacts with sPLA2-IIA and inhibits sPLA2-IIA-mediated monocyte differentiation and migration. This study elucidates the potential of maslinic acid in modulating sPLA2-IIA-mediated inflammatory effects in THP-1 macrophages. We showed that maslinic acid inhibits sPLA2-IIA-mediated LDL modification and suppressed foam cell formation. Further analysis revealed that sPLA2-IIA only induced modest LDL oxidation and that inhibitory effect of maslinic acid on sPLA2-IIA-mediated foam cells formation occurred independently of its anti-oxidative properties. Interestingly, maslinic acid was also found to significantly reduce lipid accumulation observed in macrophages treated with sPLA2-IIA only. Flow cytometry analysis demonstrated that the effect observed in maslinic acid might be contributed in part by suppressing sPLA2-IIA-induced endocytic activity, thereby inhibiting LDL uptake. The study further showed that maslinic acid suppresses sPLA2-IIA-induced up-regulation of PGE2 levels while having no effects on COX-2 activity. Other pro-inflammatory mediators TNF-a and IL-6 were not induced in sPLA2-IIA-treated THP-1 macrophages. The findings of this study showed that maslinic acid inhibit inflammatory effects induced by sPLA2-IIA, including foam cells formation and PGE2 production.

Effect of socio-demographic factors on endogenous biomarkers (cystatin C and creatinine) among elderly chronic kidney disease patients: a cross-sectional study.

PURPOSE: Creatinine is normally used to evaluate kidney function among elderly patients in clinical practice, which has been reported to be affected by socio-demographic factors like BMI and age. Cystatin C a newly introduced biomarker may be more efficient in identifying kidney function in obese and aged CKD patients. The aim of the current study was to assess the effect of BMI on endogenous biomarkers (cystatin C and creatinine) among elderly CKD patients in Malaysia, a first such study in the country. METHODS: The current study was conducted at the Hospital University Sains Malaysia, Kelantan. A total of 300 elderly Malay participants ≥ 65 years, with CKD, were taken in study. Demographic data, blood pressure, weight, and height were documented. Serum creatinine was assayed by Chemistry Analyzer Model Architect-C8000 (Jaffe Method), while serum cystatin C was examined by Human cystatin C ELISA kit (Sigma-Aldrich) using Thermo Scientific Varioskan Flash ELISA reader. RESULTS: The study participants were divided into three groups on the basis of age. There was a statistically significant difference at the p value < 0.05 in serum creatinine level for the three age groups [F (2, 297) = 1.98, p value 0.045]. Patients were divided into four groups on the basis of BMI. The results of one-way ANOVA revealed a statistically significant difference at the p value < 0.05 in the mean serum creatinine level for the four groups [F (3, 396) = 2.99, p value 0.032]. However, no statistically significant differences between mean serum cystatin C levels were observed on the basis of patient's age and BMI. CONCLUSION: Cystatin C is not related to BMI and age among elderly chronic kidney disease patients. The study clearly evaluates the role of serum cystatin C as a good competitor of creatinine among the elderly CKD patients.

Differential effects of sPLA2-GV and GX on cellular proliferation and lipid accumulation in HT29 colon cancer cells.

Secretory phospholipase A2 (sPLA2) group of enzymes have been shown to hydrolyze phospholipids, among which sPLA2 Group V (GV) and Group X (GX) exhibit high selectivity towards phosphatidylcholine-rich cellular plasma membranes. The enzymes have recently emerged as key regulators in lipid droplets formation and it is hypothesized that sPLA2-GV and GX enhanced cell proliferation and lipid droplet accumulation in colon cancer cells (HT29). In this study, cell viability and lipid droplet accumulation were assessed by Resazurin assay and Oil-Red-O staining. Interestingly, both sPLA2-GV and GX enzymes reduced intracellular lipid droplet accumulation and did not significantly affect cell proliferation in HT29 cells. Incubation with varespladib, a pan-inhibitor of sPLA2-Group IIA/V/X, further suppressed lipid droplets accumulation in sPLA2-GV but have no effects in sPLA2-GX-treated cells. Further studies using catalytically inactive sPLA2 enzymes showed that the enzymes intrinsic catalytic activity is required for the net reduction of lipid accumulation. Meanwhile, inhibition of intracellular phospholipases (iPLA2-γ and cPLA2-α) unexpectedly enhanced lipid droplet accumulation in both sPLA2-GV and GX-treated cells. The findings suggested an interconnected relationship between extracellular and intracellular phospholipases in lipid cycling. Previous studies indicated that sPLA2 enzymes are linked to cancer development due to their ability to induce release of arachidonic acid and eicosanoids as well as the stimulation of lipid droplet formation. This study showed that the two enzymes work in a distinct manner and they neither confer proliferative advantage nor enhanced the net lipid droplet accumulation in HT29 cells.

Docking Based 3D-QSAR Study of Tricyclic Guanidine Analogues of Batzelladine K As Anti-Malarial Agents.

The Plasmodium falciparum Lactate Dehydrogenase enzyme (PfLDH) catalyzes inter-conversion of pyruvate to lactate during glycolysis producing the energy required for parasitic growth. The PfLDH has been studied as a potential molecular target for development of anti-malarial agents. In an attempt to find the potent inhibitor of PfLDH, we have used Discovery studio to perform molecular docking in the active binding pocket of PfLDH by CDOCKER, followed by three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of tricyclic guanidine batzelladine compounds, which were previously synthesized in our laboratory. Docking studies showed that there is a very strong correlation between in silico and in vitro results. Based on docking results, a highly predictive 3D-QSAR model was developed with q2 of 0.516. The model has predicted r2 of 0.91 showing that predicted IC50 values are in good agreement with experimental IC50 values. The results obtained from this study revealed the developed model can be used to design new anti-malarial compounds based on tricyclic guanidine derivatives and to predict activities of new inhibitors.

Inhibition of Human Group IIA-Secreted Phospholipase A2 and THP-1 Monocyte Recruitment by Maslinic Acid.

Maslinic acid is a natural pentacyclic triterpenoid which has anti-inflammatory properties. A recent study showed that secretory phospholipase A2 (sPLA2) may be a potential binding target of maslinic acid. The human group IIA (hGIIA)-sPLA2 is found in human sera and their levels are correlated with severity of inflammation. This study aims to determine whether maslinic acid interacts with hGIIA-sPLA2 and inhibits inflammatory response induced by this enzyme. It is shown that maslinic acid enhanced intrinsic fluorescence of hGIIA-sPLA2 and inhibited its enzyme activity in a concentration-dependent manner. Molecular docking revealed that maslinic acid binds to calcium binding and interfacial phospholipid binding site, suggesting that it inhibit access of catalytic calcium ion for enzymatic reaction and block binding of the enzyme to membrane phospholipid. The hGIIA-sPLA2 enzyme is also responsible in mediating monocyte recruitment and differentiation. Results showed that maslinic acid inhibit hGIIA-sPLA2-induced THP-1 cell differentiation and migration, and the effect observed is specific to hGIIA-sPLA2 as cells treated with maslinic acid alone did not significantly affect the number of adherent and migrated cells. Considering that hGIIA-sPLA2 enzyme is known to hydrolyze glyceroacylphospholipids present in lipoproteins and cell membranes, maslinic acid may bind and inhibit hGIIA-sPLA2 enzymatic activity, thereby reduces the release of fatty acids and lysophospholipids which stimulates monocyte migration and differentiation. This study is the first to report on the molecular interaction between maslinic acid and inflammatory target hGIIA-sPLA2 as well as its effect towards hGIIA-sPLA2-induced THP-1 monocyte adhesive and migratory capabilities, an important immune-inflammation process in atherosclerosis.

Prolonged morphometric study of barnacles grown on soft substrata of hydrogels and elastomers.

A long-term investigation of the shell shape and the basal morphology of barnacles grown on tough, double-network (DN) hydrogels and polydimethylsiloxane (PDMS) elastomer was conducted in a laboratory environment. The elastic modulus of these soft substrata varied between 0.01 and 0.47 MPa. Polystyrene (PS) (elastic modulus, 3 GPa) was used as a hard substratum control. It was found that the shell shape and the basal plate morphology of barnacles were different on the rigid PS substratum compared to the soft substrata of PDMS and DN hydrogels. Barnacles on the PS substratum had a truncated cone shape with a flat basal plate while on soft PDMS and DN gels, barnacles had a pseudo-cylindrical shape and their basal plates showed curvature. In addition, a large adhesive layer was observed under barnacles on PDMS, but not on DN gels. The effect of substratum stiffness is discussed in terms of barnacle muscle contraction, whereby the relative stiffness of the substratum compared to that of the muscle is considered as the key parameter.

Synthesis and biological evaluation of tricyclic guanidine analogues of batzelladine K for antimalarial, antileishmanial, antibacterial, antifungal, and anti-HIV activities.

Fifty analogues of batzelladine K were synthesized and evaluated for in vitro antimalarial (Plasmodium falciparum), antileishmanial (Leishmania donovani), antimicrobial (panel of bacteria and fungi), antiviral (HIV-1) activities. Analogues 14h and 20l exhibited potential antimalarial activity against chloroquine-sensitive D6 strain with IC(50) 1.25 and 0.88 µM and chloroquine-resistant W2 strain with IC(50) 1.64 and 1.07 µM, respectively. Analogues 12c and 14c having nonyl substitution showed the most potent antileishmanial activity with IC(50) 2.39 and 2.78 µM and IC(90) 11.27 and 12.76 µM, respectively. Three analogues 12c, 14c, and 14i were the most active against various pathogenic bacteria and fungi with IC(50) < 3.02 µM and MIC/MBC/MFC <6 µM. Analogue 20l having pentyl and methyl substituents on tricycle showed promising activities against all pathogens. However, none was found active against HIV-1. Our study demonstrated that the tricyclic guanidine compounds provide new structural class for broad spectrum activity.

Synthesis and biological evaluation of tricyclic guanidine analogues of batzelladine K for antimalarial, antileishmanial, antibacterial, antifungal and anti-HIV activities.

Fifty analogues of batzelladine K were synthesized and evaluated for in vitro antimalarial (Plasmodium falciparum), antileishmanial (Leishmania donovani), antimicrobial (panel of bacteria and fungi), antiviral (HIV-1) activities. Analogues 14h and 20l exhibited potential antimalarial activity against chloroquine-sensitive D6 strain with IC50 1.25 and 0.88 µM and chloroquine-resistant W2 strain with IC50 1.64 and 1.07 µM, respectively. Analogues 12c and 14c having nonyl substitution showed the most potent antileishmanial activity with IC50 2.39 and 2.78 µM and IC90 11.27 and 12.76 µM respectively. Three analogues 12c, 14c and 14i were the most active against various pathogenic bacteria and fungi with IC50 <3.02 µM and MIC/MBC/MFC <6 µM. Analogue 20l having pentyl and methyl substituents on tricycle showed promising activities against all pathogens. However, none was found active against HIV-1. Our study demonstrated that the tricyclic guanidine compounds provide new structral class for broad spectrum activity. © 2012 John Wiley & Sons A/S.

iView: a feature clustering framework for suggesting informative views in volume visualization.

The unguided visual exploration of volumetric data can be both a challenging and a time-consuming undertaking. Identifying a set of favorable vantage points at which to start exploratory expeditions can greatly reduce this effort and can also ensure that no important structures are being missed. Recent research efforts have focused on entropy-based viewpoint selection criteria that depend on scalar values describing the structures of interest. In contrast, we propose a viewpoint suggestion pipeline that is based on feature-clustering in high-dimensional space. We use gradient/normal variation as a metric to identify interesting local events and then cluster these via k-means to detect important salient composite features. Next, we compute the maximum possible exposure of these composite feature for different viewpoints and calculate a 2D entropy map parameterized in longitude and latitude to point out promising view orientations. Superimposed onto an interactive track-ball interface, users can then directly use this entropy map to quickly navigate to potentially interesting viewpoints where visibility-based transfer functions can be employed to generate volume renderings that minimize occlusions. To give full exploration freedom to the user, the entropy map is updated on the fly whenever a view has been selected, pointing to new and promising but so far unseen view directions. Alternatively, our system can also use a set-cover optimization algorithm to provide a minimal set of views needed to observe all features. The views so generated could then be saved into a list for further inspection or into a gallery for a summary presentation.

Anti-HIV activity of Indian medicinal plants.

Acquired immunodeficiency syndrome patients face great socio-economic difficulties in obtaining treatment. There is an urgent need for new, safe, and cheap anti-HIV agents. Traditional medicinal plants are a valuable source of novel anti-HIV agents and may offer alternatives to expensive medicines in future. Various medicinal plants or plant-derived natural products have shown strong anti-HIV activity and are under various stages of clinical development in different parts of the world. The present study was directed towards assessment of anti-HIV activity of various extracts prepared from Indian medicinal plants. The plants were chosen on the basis of similarity of chemical constituents with reported anti-HIV compounds or on the basis of their traditional usage as immunomodulators. Different extracts were prepared by Soxhlet extraction and liquid-liquid partitioning. Ninety-two extracts were prepared from 23 plants. Anti-HIV activity was measured in a human CD4+ T-cell line, CEM-GFP cells infected with HIV-1NL4.3. Nine extracts of 8 different plants significantly reduced viral production in CEM-GFP cells infected with HIV-1NL4.3. Aegle marmelos, Argemone mexicana, Asparagus racemosus, Coleus forskohlii, and Rubia cordifolia demonstrated promising anti-HIV potential and were investigated for their active principles.

Antifouling properties of hydrogels.

Marine sessile organisms easily adhere to submerged solids such as rocks, metals and plastics, but not to seaweeds and fishes, which are covered with soft and wet 'hydrogel'. Inspired by this fact, we have studied long-term antifouling properties of hydrogels against marine sessile organisms. Hydrogels, especially those containing hydroxy group and sulfonic group, show excellent antifouling activity against barnacles both in laboratory assays and in the marine environment. The extreme low settlement on hydrogels in vitro and in vivo is mainly caused by antifouling properties against the barnacle cypris.

Synthesis and evaluation of beta-carboline derivatives as inhibitors of human immunodeficiency virus.

A series of beta-carboline derivatives were synthesized by utilizing aromatization and chemoselective alkylation method recently reported from our laboratory. Synthesized derivatives were evaluated for anti-HIV activity in human CD4+ T cell line (CEM-GFP) infected with HIV-1 NL(4.3) virus. 1-Formyl-beta-carboline-3-carbxylic acid methyl ester (15) showed inhibition of human immunodeficiency virus at IC(50)=2.9 microM.