Treatment of COVID-19 patients with quercetin: a prospective,single center,randomized, controlled trial

Scientific research continues on new preventive and therapeutic strategies against severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). So far, there is no proven curative treatment, and a valid alternative therapeutic approach needs to be developed. This study is designed to evaluate the effect of quercetin in COVID-19 treatment. This was a single-centre, prospective randomized controlled cohort study. Routine care versus QCB (quercetin, vitamin C, bromelain) supplementation was compared between 429 patients with at least one chronic disease and moderate-to-severe respiratory symptoms. Demographic features, signs, laboratory results and drug administration data of patients were recorded. The endpoint was that QCB supplementation was continued throughout the follow-up period from study baseline to discharge, intubation, or death. The most common complaints at the time of hospital admission were fatigue (62.4%), cough (61.1%), anorexia (57%), thirst (53.7%), respiratory distress (51%) and chills (48.3%). The decrease in CRP and ferritin levels was higher in the QCB group (all Ps were < 0.05). In the QCB group, the increase in platelet and lymphocyte counts was higher (all Ps were < 0.05). QCB did not reduce the risk of events during follow-up. Adjustments for statistically significant parameters, including the lung stage, use of favipiravir and presence of comorbidity did not change the results. While there was no difference between the groups in terms of event frequency, the QCB group had more advanced pulmonary findings. QCB supplement is shown to have a positive effect on laboratory recovery. While there was no difference between the groups in terms of event frequency, QCB supplement group had more advanced pulmonar findings, and QCB supplement is shown to have a positive effect on laboratory recovery/results. Therefore, we conclude that further studies involving different doses and plasma level measurements are required to reveal the dose/response relationship and bioavailability of QCB for a better understanding of the role of QCB in the treatment of SARS CoV-2.     

Glutathione S-transferase gene polymorphisms in Turkish patients with diabetes mellitus

Glutathione S-transferases (GSTs) are enzymes involved in the metabolism of many disease-causing electrophilic substrates and protect the cells against oxidative stress. In the present study, we investigated the GSTM1, GSTT1 and GSTP1 gene polymorphisms in diabetic patients and healthy individuals and searched whether polymorphisms in GST genes are associated with diabetes mellitus (DM) in the Turkish population. The study population consisted of 98 unrelated healthy individuals and 98 patients with DM. Genotyping of GSTM1, GSTT1 and GSTP1 genes was performed using real time polymerase chain reaction with a Light Cycler instrument. Patients had a higher frequency of the GSTM1 null genotype than the control group (Odds ratios, OR = 3.7; 95% confidence intervals, CI = 2.05-6.70). However, there was no significant difference in the frequencies of the GSTT1 and GSTP1 gene polymorphisms between the patients and control group. The combined analysis of these three GST genotypes showed a further DM risk increase (OR = 5.7, 95% CI = 1.51-31.07). This is the first study to determine the association of diabetes with GST gene polymorphism in the Turkish population. These results show that GSTM1 null genotype may play a significant role in the aetiopathogeneses of DM and the GSTM1 gene may be a useful marker in the prediction of DM susceptibility of the Turkish population.     

Cell wall-bound invertase limits sucrose export and is involved in symptom development and inhibition of photosynthesis during compatible interaction between tomato and Xanthomonas campestris pv vesicatoria

Cell wall-bound invertase (cw-Inv) plays an important role in carbohydrate partitioning and regulation of sink-source interaction. There is increasing evidence that pathogens interfere with sink-source interaction, and induction of cw-Inv activity has frequently been shown in response to pathogen infection. To investigate the role of cw-Inv, transgenic tomato (Solanum lycopersicum) plants silenced for the major leaf cw-Inv isoforms were generated and analyzed during normal growth and during the compatible interaction with Xanthomonas campestris pv vesicatoria. Under normal growth conditions, activities of sucrolytic enzymes as well as photosynthesis and respiration were unaltered in the transgenic plants compared with wild-type plants. However, starch levels of source leaves were strongly reduced, which was most likely caused by an enhanced sucrose exudation rate. Following X. campestris pv vesicatoria infection, cw-Inv-silenced plants showed an increased sucrose to hexose ratio in the apoplast of leaves. Symptom development, inhibition of photosynthesis, and expression of photosynthetic genes were clearly delayed in transgenic plants compared with wild-type plants. In addition, induction of senescence-associated and pathogenesis-related genes observed in infected wild-type plants was abolished in cw-Inv-silenced tomato lines. These changes were not associated with decreased bacterial growth. In conclusion, cw-Inv restricts carbon export from source leaves and regulates the sucrose to hexose ratio in the apoplast. Furthermore, an increased apoplastic hexose to sucrose ratio can be linked to inhibition of photosynthesis and induction of pathogenesis-related gene expression but does not significantly influence bacterial growth. Indirectly, bacteria may benefit from low invertase activity, since the longevity of host cells is raised and basal defense might be dampened.     

Prediction of protein-protein interactions: unifying evolution and structure at protein interfaces

The vast majority of the chores in the living cell involve protein-protein interactions. Providing details of protein interactions at the residue level and incorporating them into protein interaction networks are crucial toward the elucidation of a dynamic picture of cells. Despite the rapid increase in the number of structurally known protein complexes, we are still far away from a complete network. Given experimental limitations, computational modeling of protein interactions is a prerequisite to proceed on the way to complete structural networks. In this work, we focus on the question 'how do proteins interact?' rather than 'which proteins interact?' and we review structure-based protein-protein interaction prediction approaches. As a sample approach for modeling protein interactions, PRISM is detailed which combines structural similarity and evolutionary conservation in protein interfaces to infer structures of complexes in the protein interaction network. This will ultimately help us to understand the role of protein interfaces in predicting bound conformations.     

Architectures and functional coverage of protein-protein interfaces

The diverse range of cellular functions is performed by a limited number of protein folds existing in nature. One may similarly expect that cellular functional diversity would be covered by a limited number of protein-protein interface architectures. Here, we present 8205 interface clusters, each representing a unique interface architecture. This data set of protein-protein interfaces is analyzed and compared with older data sets. We observe that the number of both biological and crystal interfaces increases significantly compared to the number of Protein Data Bank entries. Furthermore, we find that the number of distinct interface architectures grows at a much faster rate than the number of folds and is yet to level off. We further analyze the growth trend of the functional coverage by constructing functional interaction networks from interfaces. The functional coverage is also found to steadily increase. Interestingly, we also observe that despite the diversity of interface architectures, some are more favorable and frequently used, and of particular interest, are the ones that are also preferred in single chains.     

The Association Between Polymorphic Genotypes of Glutathione S-Transferases and COPD in the Turkish Population

Although smoking is regarded as the most important causal factor in chronic obstructive pulmonary disease (COPD), only 10–20% of smokers develop symptomatic COPD, which indicates the presence of genetic predisposing factors in its pathogenesis. This study investigates the association between gene polymorphysims of glutathione S-transferases (GSTs) and COPD. Blood samples were taken from 149 patients and 150 healthy controls. Polymorphisms of GSTT1, GSTM1, and GSTP1 were genotyped using Real-Time PCR. Multivariate logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals between specific genotypes and COPD. There was no difference in the frequencies of the genotypes of GSTM1 and GSTT1 between the groups, but the GSTP1 Ile/Ile genotype was significantly higher in the patients than in the controls (61.1% vs. 38%). GSTP1 Ile/Val and Val/Val genotypes were associated with a decreased risk of COPD when compared to the Ile/Ile genotype (2.12-fold and 4-fold, respectively). Thus we suggest that the Val allele of GSTP1 may have a protective effect for development of COPD. Furthermore, when we evaluated the association between GSTP1 genes and smoking status, smokers with the GSTP1 Ile allele had an increased risk for the development of COPD. Among the combinations of the genotypes, the combination of GSTM1, GSTT1 null, and GSTP1 Val/Val was associated with the maximal increased risk (12-fold) of COPD. Thus to explain the ethiopathogenesis of COPD, investigation of a single gene family is inadequate. Based on our results and the previous data, further studies should be focused on the GSTP1 gene and the interactions with other genes such as polymorphisms of N-acetyltransferases, GSTM1 and GSTT1, microsomal epoxide hydrolase, and allelic variants of cytochrome P450.     

An Ethnobotanical Survey of Inner-West Anatolia, Turkey

This study is focused on ethnobotanical usages of wild plants growing within the Afyonkarahisar province districts of Sinanpaşa, Hocalar and Dazkırı. Ninety local informants in 11 villages were interviewed. A total of 129 different usages of wild plants in the study area were recorded. Out of 650 plant species commonly present, 93 plant taxa (14.3%) belonging to 43 families were used for medicinal (52 citations), foodstuff (37 citations), fodder (14 citations), dye (six citations), firewood (five citations), construction materials (four citations) and miscellaneous purposes (11 citations). At least 15% of the information regarding ethnobotanical uses of wild plants was obtained by showing herbarium voucher samples to the informants. It was noted that Sideritis leptoclada and Verbascum stenostachyum are endemic to Turkey and their endangered status has markedly increased in recent years because of increased collecting for ethnobotanical purposes. Informants indicate that members of the younger generation have a much reduced interest in ethnobotanical knowledge and that this is a danger to the continued use of local plants.     

A computational approach to the polymerizabilities of diallylamines

Some selected diallylamine monomers have been studied with the semiempirical PM3 method as model compounds for N,N-dialkyl-N-2-(alkoxycarbonyl)allylammonium salts, in order to build up a quantitative and qualitative relationship between the experimental cyclopolymerizabilities of the monomers and calculated parameters such as charge, energy, geometrical features, bond orders, local softness values and HOMO-LUMO gaps. The charges on nitrogen, vinyl and allyl carbons, the activation barriers, the local softness values and the HOMO-LUMO gaps are found to represent the polymerizability trend of the monomers in general. Three-dimensional structures have been proposed for the reactants and their transition states by geometry optimizations with PM3.     

Zinc-induced alterations in contractile properties of rat diaphragm muscle in vitro

The effect of zinc ions on the isometric contraction of rat diaphragm muscles in the presence and in the absence of external calcium was studied. Using a transducer, the isometric force was measured as a function of supramaximal electrical stimulation, either directly or indirectly applied to the muscle. The following parameters were measured: peak twitch tension, PT, twitch contraction time, CT, relaxation half-time, RT-1/2, and peak rates of tension increase and decrease, +dP/dt and -dP/dt. The following zinc-induced alterations were observed: an increase of the PT; a decrease of the RT-1/2; an increase in the +dP/dt and -dP/dt. The CT was not changed significantly. Our results suggest that zinc ions have a positive inotropic effect on isolated diaphragm muscle. The increase in PT may be explained by a zinc-activated Ca²⁺ uptake by sarcoplasmic reticulum. This was followed by an increase in the rate of rise of tension development, which was secondary to increased -dP/dt. The mechanism(s) by which extracellular Ca²⁺ contributes to this action of zinc is not known.