Suggestion of active 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents using predictive QSAR model based on the combination of ALASSO with an ANN model.

The novel severe acute respiratory syndrome coronavirus (SARS CoV-2) was introduced as an epidemic in 2019 and had millions of deaths worldwide. Given the importance of this disease, the recommendation and design of new active compounds are crucial. 3-chymotrypsin-like protease (3 CLpro) inhibitors have been identified as potent compounds for treating SARS-CoV-2 disease. So, the design of new 3 CLpro inhibitors was proposed using a quantitative structure-activity relationship (QSAR) study. In this context, a powerful adaptive least absolute shrinkage and selection operator (ALASSO) penalized variable selection method with inherent advantages coupled with a nonlinear artificial neural network (ANN) modelling method were used to provide a QSAR model with high interpretability and predictability. After evaluating the accuracy and validity of the developed ALASSO-ANN model, new compounds were proposed using effective descriptors, and the biological activity of the new compounds was predicted. Ligand-receptor (LR) interactions were also performed to confirm the interaction strength of the compounds using molecular docking (MD) study. The pharmacokinetics properties and calculated Lipinski's rule of five were applied to all proposed compounds. Due to the ease of synthesis of these suggested new compounds, it is expected that they have acceptable pharmacological properties.

Ridge regression and its applications in genetic studies.

With the advancement of technology, analysis of large-scale data of gene expression is feasible and has become very popular in the era of machine learning. This paper develops an improved ridge approach for the genome regression modeling. When multicollinearity exists in the data set with outliers, we consider a robust ridge estimator, namely the rank ridge regression estimator, for parameter estimation and prediction. On the other hand, the efficiency of the rank ridge regression estimator is highly dependent on the ridge parameter. In general, it is difficult to provide a satisfactory answer about the selection for the ridge parameter. Because of the good properties of generalized cross validation (GCV) and its simplicity, we use it to choose the optimum value of the ridge parameter. The GCV function creates a balance between the precision of the estimators and the bias caused by the ridge estimation. It behaves like an improved estimator of risk and can be used when the number of explanatory variables is larger than the sample size in high-dimensional problems. Finally, some numerical illustrations are given to support our findings.

Pattern of cigarette smoking effect on periodontal pocketing and attachment loss: a retrospective study.

AIM: The aim of the present retrospective study was to evaluate the local effects of smoking on periodontium and to assess the patterns of periodontitis (pocket depths and attachment loss) in smokers and non-smokers. METHODS: In this study, records of 126 non-smokers and 51 smokers (≥ 5 cigarettes/day) periodontitis patients were evaluated and probing pocket depth (PPD), clinical attachment level (CAL) and bleeding on probing (BOP) data were collected from clinical patients records. Patients' data were subject to two sample t-tests to assess the difference between the groups and to analysis of variance using the generalized linear model to seek associations between smoking and site positions, age and clinical parameters. RESULTS: The difference between CAL of smokers and non-smokers was greatest at the anterior maxillary palatal sites (P = 0.002) and reached 1 mm. When the effect of different site positions as well as smoking as a between subject variable and age as a co-variate on the attachment level measurements were assessed using analysis of variance, significant effects for smoking, jaw (lower versus upper) and anterior-posterior position as well as age were detected. No significant interactions were found between smoking and any of the three position variables. CONCLUSION: Lack of interaction between smoking and any of the three position variables indicates that the destructive effects of smoking on the periodontal tissues maybe mainly from systemic side-effects and almost independent of the site position within the mouth, although some additional local effects may be present in areas such as anterior palatal sites.

Jejunal carcinoid tumor mimicking leiomyosarcoma: preoperative diagnosis by endoscopic biopsy.

Primary carcinoid tumor of the jejunum is rare, and is an unusual cause of massive gastrointestinal bleeding. A case of primary jejunal carcinoid tumor in a 39-year-old woman who presented with massive hematochezia is described. Both upper and lower gastrointestinal endoscopies showed no abnormalities. An abdominal computed tomographic scan, small-bowel barium contrast studies, and small-bowel endoscopy showed a subserosal mass, of 5 x 4 cm, with a cavity suggesting central necrosis, and a deep mucosal ulceration, located in the proximal jejunum. Although these clinical presentations were strongly suggestive of a leiomyosarcoma, histologic examination of biopsy samples obtained by enteroscopy confirmed the diagnosis of jejunal carcinoid tumor. The patient underwent radical jejunal resection and recovered uneventfully. In spite of the large size of the tumor, there was one solitary lymph node metastasis, but no evidence of liver metastases. This kind of jejunal carcinoid tumor, presenting with massive gastrointestinal bleeding and a subserosal bulky growth mimicking a leiomyosarcoma, has not been reported previously. Moreover, this is a rare case of a jejunal carcinoid which was diagnosed preoperatively by small bowel-endoscopic biopsy.

Chemotactic properties of rat immunoglobulins and immune complexes.

The effect of rat immunoglobulins and immune complexes on the locomotor function of rat polymorphonuclear leukocytes (PMN) was investigated in vitro. Rat immunoglobulin G1 (IgG1), IgG2a, IgG2b, and IgA monoclonal antibodies specific for the dinitrophenyl hapten were used. Both monomeric and polymeric IgA showed chemotactic activity in a dose-dependent manner. IgG1 and IgG2b also induced a dose-dependent locomotor response of PMN, but the nature of the induced migration was chemokinetic (enhancing random migration). IgG2a was chemotactic and induced maximal migration at a relatively low concentration. IgG1- and IgG2b-immune complexes induced stronger migration than antibody alone; however, IgA- and IgG2a-immune complexes did not. IgA was shown to modify the chemotactic movement of PMN induced by N-formylmethionyl-leucyl-phenylalanine (FMLP). In the presence of both IgA and FMLP in the lower chamber, the migration towards suboptimal concentrations of FMLP was enhanced. By contrast, IgA in the upper chamber decreased migration towards the optimal or higher concentrations of FMLP. These findings suggest that IgA may work synergistically with luminal chemoattractants to mobilize PMN to the locus of infection on the mucosal surface. In addition, the intense activity of IgG2a alone and IgG1- or IgG2b-immune complexes in inducing PMN migration may play an important role in inflammatory processes. The data indicate that immunoglobulins have a direct effect on PMN mobility.

Molecular forms of IgA produced by various lymphoid tissues--analysis using high speed liquid chromatography.

Molecular forms of immunoglobulin A (IgA) produced by cultured cells from various human lymphoid tissues were analyzed using high speed liquid chromatography (HLC). IgA secreted into culture media was easily separated into polymeric and monomeric forms by HLC. HLC has the advantages of high resolution, reproducibility, rapidity and technical simplicity in the separation of polymeric and monomeric IgA. Peripheral blood lymphocytes and cells from gut-associated lymphoid tissues, such as mesenteric lymph nodes or large bowel mucosa, secreted predominantly polymeric IgA, whereas lymphoid cells from bone marrow produced mainly monomeric IgA. Spleen cells and tonsillar cells produced nearly equal proportions of polymeric and monomeric IgA. These results suggest that with regard to IgA in serum, the polymer may originate from the gut-associated lymphoid tissues and the monomer may mostly derive from the bone marrow.

Distribution of secretory component in non-cancerous human gastric mucosa.

Immunological detection of secretory component (SC) in non-cancerous human gastric mucosa was carried out by the peroxidase-anti-peroxidase (PAP) method using several fixatives. SC was detected in the generative zone or mucous neck of normal gastric mucosa without intestinal metaplasia (IM) and in absorptive cells of IM of the stomach. The deep part of complete type IM showed a larger amount of SC than the superficial part. These findings suggested that the appearance of SC in gastric mucosa would be relevant to the immunity of glandular epithelium. In addition, SC was also detected in pyloric gland cells in specimens fixed with cold 95% ethanol. From these results, SC was considered to be a normal constituent and one of the developmental proteins in the gastric mucosa.