Protein In Relation Research Articles

DETERMINED BIOCHEMICAL CONTENT IN Epinephelus malabaricus AND Lutjanus argentimaculatus ARE ECONOMICALLY IMPORTANT FINFISHES IN NAGAPATTINAM COAST, SOUTH INDIA

The finfishes Epinephelus malabaricus and Lutjanus argentimaculatus are cost-effectively imperative, so selected for divergent sizes, proximate compositions like crude protein, carbohydrate, lipids, ash and gross energy in relation to dissimilar seasons, size and sex groups with the vision of assessing the nutritive values and their % contributions, Indeterminates (IM), females (F), males (M) are selected for these studies. In the current studies results are showed different parameters; in E. malabaricus the utmost crude protein amount was observed (20-30 cm; 73.86%) post-monsoon from IM followed by same season in IM showed (10-20 cm; 73.85%), crude carbohydrate uppermost content was noticed in post-monsoon from F (50-60 cm; 72.15%) followed by same post-monsoon in M showed (50-60 cm; 71.31%). superior amount of lipid content maximum amount was observed in F (40-50 cm; 7.75%) in post-monsoon followed by same season in F (50-60 cm; 7.11%), the highest ash content was obtained from IM (20-30 cm; 8.12%) observed in post-monsoon followed by same season in IM (10-20 cm; 8.11%), highest cross energy was noticed in post-monsoon of F (50-60 cm; 18.39%) followed by same season in M showed (50-60 cm; 18.35%). In L. argentimaculatus premier amount of crude protein in IM was observed (10-25 cm; 75.05%) in summer followed by same season in IM showed (25-40 cm; 75.02%), crude carbohydrate high content was noticed from M & F (70-85 cm; 4.75%) in summer, followed by in F showed (70-85 cm; 4.45%) in monsoon and post-monsoon. Uppermost lipid content was observed from F in summer (55-70 cm; 7.21% & 70-85 cm; 7.20%) followed by post-monsoon in F was obtained (70-85 cm; 6.98%), utmost ash content was expressed in IM (10-25 cm; 7.25%) pre-monsoon followed by same season IM (25-40 cm; 7.05%), highest energy content was noticed in summer in F (70-85 cm; 18.34 MJ/kg) followed by same season M showed (70-85 cm; 18.04 MJ/kg), based on different parameters it concluded that selected finfishes are potentially functional for the human societies.

In silico docking analysis of beta-defensin 20 against cation channel sperm-associated protein 1-4 to predict its role in the sperm maturation.

Beta-defensin 20 (DEFB20) is widely expressed in the epididymis with gene features involved in epididymal sperm maturation. However, the action mechanism and function of DEFB20 in sperm maturation are still unclear. One of the important roles of beta-defensin is the ion channel activity. The cation channel sperm-associated protein (CatSper) alpha is an ion channel protein found on the sperm surface. This study aimed to investigate the interaction between DEFB20 and CatSper1-4 protein in relation to the sperm maturation process. Protein sequences were obtained from the National Center for Biotechnology Information (NCBI). Protein modeling and validation were carried out by using the Robetta modeling server and the Ramachandran plot method. Rosetta web server was used for the docking analysis. The results revealed a natural interaction between DEFB20 and CatSper1-4. The interaction occurred at the cation channel (close to the casein kinase II), ion transport protein, and kinase c phosphorylation of the CatSper1-4 active site. The DEFB20 region interacting with CatSper2-4 was the beta-defensin domain, while with CatSper1 was the non-beta-defensin domain. Based on the analysis, DEFB20 may interact with CatSper α subunits, particularly CatsSper1, to affect ion channel activity during sperm maturation.

Impaired fasting glucose levels among perinatally HIV-infected adolescents and youths in Dar es Salaam, Tanzania.

This study assessed impaired fasting glucose and associated factors among perinatally HIV-infected adolescents and youths in Dar es salaam Tanzania. Impaired fasting glucose is a marker of heightened risk for developing type 2 diabetes among perinatally HIV-infected individuals. Therefore, identifying individuals at this stage is crucial to enable early intervention. Therefore, we assessed impaired fasting glucose (IFG) and associated factors among perinatally HIV-infected population in Dar es salaam Tanzania. A cross-sectional study was conducted among 152 adolescents and youth attending HIV clinic at Muhimbili National Hospital and Infectious Disease Centre from July to August 2020. Fasting blood glucose (>8 hours) was measured using one-touch selects LifeScan, CA, USA. We also examined C-Reactive Protein and interleukin-6 inflammatory biomarkers in relation to impaired fasting glucose (IFG). Associations between categorical variables were explored using Chi-square, and poison regression with robust variance was used to calculate the prevalence ratios. Of the 152 participants, the majority were male (n=83[54.6%]), and the median age was 15(14-18) years. Overweight or obesity was prevalent in 16.4%, while more than one in ten (13.2%) had high blood pressure (≥149/90mmHg). All participants were on antiretroviral therapy (ART); 46% had used medication for over ten years, and about one in three had poor medication adherence. Among the recruited participants, 29% had impaired fasting glucose. The odds of IFG were two times higher in males compared to females (PR, 2.07, 95% CI 1.19 -3.59 p=0.001). Moreover, we found with every increase of Interleukin 6 biomarker there was a 1.01 probability increase of impaired fasting glucose (PR, 1.01, 95% CI 1.00 - 1.02 p=0.003). About one in three perinatally HIV-infected youths had impaired fasting glucose in Dar es Salaam, Tanzania, with males bearing the biggest brunt. Moreover, with every increase of 1.101 of the probability of having IFG increased. This calls for urgent measures to interrupt the progression to diabetes disease and prevent the dual burden of disease for this uniquely challenged population.

Abstract #1321565: Evaluation of High Sensitive C-Reactive Protein in Relation With Dyslipidemia in Patients With Subclinical Hypothyroidism

Subclinical hypothyroidism is a common health problem when compared with overt hypothyroidism, with an incidence of 3% to 8%, both associated with an increased cardiovascular risk. The aim of the study is to determine the association between high sensitive C-reactive protein and subclinical hypothyroidism in comparison with controlled patients with hypothyroidism under treatment, and also investigate the association between high sensitive C-reactive protein and dyslipidemia in subclinical hypothyroidism.

Characteristics of the Isu1 C-terminus in relation to [2Fe-2S] cluster assembly and ISCU Myopathy.

Mitochondrial [2Fe-2S] cluster biosynthesis is driven by the coordinated activities of the Iron-Sulfur Cluster (ISC) pathway protein machinery. Within the ISC machinery, the protein that provides a structural scaffold on which [2Fe-2S] clusters are assembled is the ISCU protein in humans; this protein is referred to as the "Scaffold" protein. Truncation of the C-terminal portion of ISCU causes the fatal disease "ISCU Myopathy", which exhibits phenotypes of reduced Fe-S cluster assembly in cells. In this report, the yeast ISCU ortholog "Isu1" has been characterized to gain a better understanding of the role of the scaffold protein in relation to [2Fe-2S] assembly and ISCU Myopathy. Here we explored the biophysical characteristics of the C-terminal region of Isu1, the segment of the protein that is truncated on the human ortholog during the disease ISCU Myopathy. We characterized the role of this region in relation to iron binding, protein stability, assembly of the ISC multiprotein complex required to accomplish Fe-S cluster assembly, and finally on overall cell viability. We determined the Isu1 C-terminus is essential for the completion of the Fe-S cluster assembly but serves a function independent of protein iron binding.

Protein and amino acid intakes in relation to prostate cancer risk and mortality-A prospective study in the European Prospective Investigation into Cancer and Nutrition.

The association between protein intake and prostate cancer risk remains unclear. To prospectively investigate the associations of dietary intakes of total protein, protein from different dietary sources, and amino acids with prostate cancer risk and mortality. In 131,425 men from the European Prospective Investigation into Cancer and Nutrition, protein and amino acid intakes were estimated using validated dietary questionnaires. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean follow-up of 14.2 years, 6939 men were diagnosed with prostate cancer and 914 died of the disease. Dairy protein was positively associated with overall prostate cancer risk in the three highest fifths compared to the lowest (HRQ3 =1.14 (95% CI 1.05-1.23); HRQ 4=1.09 (1.01-1.18); HRQ5 =1.10 (1.02-1.19)); similar results were observed for yogurt protein (HRQ3 =1.14 (1.05-1.24); HRQ4 =1.09 (1.01-1.18); HRQ5 =1.12 (1.04-1.21)). For egg protein intake and prostate cancer mortality, no association was observed by fifths, but there was suggestive evidence of a positive association in the analysis per standard deviation increment. There was no strong evidence of associations with different tumour subtypes. Considering the weak associations and many tests, the results must be interpreted with caution. This study does not provide strong evidence for an association of intakes of total protein, protein from different dietary sources or amino acids with prostate cancer risk or mortality. However, our results may suggest some weak positive associations, which need to be confirmed in large-scale, pooled analyses of prospective data.

Tumoral PD-L1 does not impact time to treatment discontinuation in EGFR mutated non-small cell lung cancer patients treated with EGFR tyrosine kinase inhibitor-a Danish cohort study.

BackgroundNot all non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations respond equally to therapy with tyrosine kinase inhibitors (TKIs). Programmed death ligand-1 (PD-L1) has previously been speculated as a possible biomarker for treatment outcome because of its positive correlation with these mutations in cell lines, but clinical studies have yielded conflicting results. We investigate the predictive potential of this surface protein in relation to clinical benefit in patients as measured by time to treatment discontinuation (TTD).MethodsWe screened 516 Danish patients with EGFR mutations for inclusion based on a history of TKI treatment and a PD-L1 status that was assessed no earlier than three months prior to treatment initiation. Patients were stratified according to their expression of the potential biomarker as either negative (0%), low (1–49%) or high (≥50%). We employed the Kaplan-Meier method and the log rank test to test for a difference in treatment duration according to PD-L1 expression.ResultsWe included 111 Danish patients. The median follow-up time from inclusion until death or censoring at the end of the study was 670 days (range, 32–1,664 days, 95% CI: 502–897 days). Fifty-seven patients (51%) categorized as PD-L1 expression negative, 32 (29%) as low and 22 (20%) as high. We tested for differences in treatment duration between the three groups. Our tests did not yield statistically significant P values.ConclusionsIn our cohort of 111 Danish patients with NSCLC harboring mutations in the epidermal growth factor receptor gene, expression levels of PD-L1 did not significantly impact the duration of clinical benefit from tyrosine kinase treatment.

Effects of Detergents on the Spectral Features of B820 Bacteriochlorophyll a in Light-Harvesting Complex 3.

Excitonic coupling of bacteriochlorophyll (BChl) a in light-harvesting (LH) proteins of purple photosynthetic bacteria is key for efficient photon capture and energy transfer. Environmental factors can affect the spectral features of these BChl a pigments and investigating these effects can provide insight into the molecular mechanisms underlying the photosynthetic spectral tuning. The present study analyzes the spectral alterations of the Qy band of B820 BChl a within the LH3 protein in relation to the type and concentration of detergents in the buffer. Changing the detergent from lauryl dimethylamine N-oxide (LDAO) to n-dodecyl-β-d-maltoside (DDM) caused a red shift in the B820 Qy band accompanied by hyperchromism; these spectral alterations were completely reversed by exchanging back from DDM to LDAO. These results reflect the different effects of harsh vs mild detergents on the perturbation of LH3. The B820 Qy band did not change when LDAO or NaCl concentration was altered, suggesting that electrostatic effects by external components have little influence on the spectral features of B820 BChl a in LH3.

Sensitivity of three antibody assays to SARS-CoV-2 nucleocapsid protein in relation to timing since diagnosis

The sensitivity of immunoassay for antibodies to SARS-CoV-2 may decrease over time. We compared three serology assays against SARS-CoV-2 nucleocapsid protein using serum samples of 20 health care workers with a history of mild PCR-confirmed coronavirus disease 2019 (COVID-19) at various timing since diagnosis. Overall, the sensitivity (95% confidence interval) was 95.0 (75.1-99.9), 60.0 (36.1-81.0), and 45.0 (23.1-68.5) for the Roche, Sysmex, and Abbott assays, respectively. The sensitivity of all these assays exceeded 80 for those diagnosed within 6 months, whereas it varied considerably for those diagnosed more than 6 months ago: 88.9 (Roche) versus 0 (Abbott). The present data provide a reference for researchers planning serological studies and interpreting these data. Such assay difference in terms of detection durability can be used, if used in combination, for the estimation of the timing of previously undetected infection.

Plasma glial fibrillary acidic protein and neurofilament light chain in relation to disability worsening in multiple sclerosis

Background: Predicting disability worsening in multiple sclerosis (MS) remains an important challenge. Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) seem promising biomarkers. Studies investigating blood GFAP in relation to longitudinal outcome measures in MS are scarce. Objective: To compare plasma-GFAP (p-GFAP) and plasma-NfL (p-NfL) levels in relation to sustained disability worsening. Methods: We measured baseline p-GFAP and p-NfL in a prospective cohort of 115 individuals with MS and 30 matched controls, using Single Molecule Array (Simoa). Disability worsening was defined as an increase in at least one of three measures (Expanded Disability Status Scale, Timed 25-foot walk, 9-Hole Peg test), confirmed after 6 months and persistent upon data closure. Results: In a multivariable Cox proportional-hazards model, p-GFAP was not significantly associated with sustained disability worsening after 4.40 ± 0.82 years, while p-NfL (HR = 1.046, p = 0.001), EDSS (HR = 1.24, p = 0.039), and disease duration (HR = 1.048, p = 0.017) were. Area under the curve of ROC curves in relation to worsening was 0.61 for p-GFAP (p = 0.031) and 0.63 for p-NfL (p = 0.015). Kaplan–Meier curves showed similar patterns for both proteins. Conclusion: p-NfL emerged as a significant explanatory variable for worsening in Cox regression analysis, and p-GFAP did not. Both p-GFAP and p-NfL were related to worsening based on ROC curves.

Studies of IGF-I and Klotho Protein in Relation to Anabolic-Androgenic Steroid and Growth Hormone Administrations.

It has been suggested to longitudinally monitor Insulin-like growth factor I (IGF-I) as a biomarker for the detection of recombinant growth hormone (GH). Subsequently, it is of interest to understand any confounders of endogenous IGF-I. Herein we have studied if serum IGF-I concentration is affected by the intake of anabolic androgenic steroids (AAS) and the potential connection between IGF-I and klotho protein. Moreover, the usefulness of klotho as a biomarker for recombinant GH intake was assessed in healthy male volunteers. An ongoing administration of AAS did not affect the levels of IGF-I. Klotho protein was ~30% higher in men with an ongoing AAS use compared to those with previous (>2 months ago) AAS use, and the serum klotho protein correlated negatively with luteinizing hormone (LH) (rs = −0.38, p = 0.04) and follicle stimulating hormone (FSH) (rs = −0.35, p = 0.05) levels. Serum IGF-I and klotho concentrations showed no correlation in the AAS using population but showed a strong negative correlation in healthy volunteers (rs = −0.86, p = 0.006). The intake of recombinant GH did not affect the serum concentrations of the klotho levels. In conclusion, IGF-I was not affected by supra-physiological AAS doses in men. Interestingly, an association between AAS intake and serum klotho was seen. The usefulness of klotho as an androgen biomarker warrants further studies, whereas klotho can be discarded as a promising biomarker for GH doping.

Meta-analysis of the response of elephant grass and panicum grass to nitrogen fertilization

Nitrogen fertilization is an efficient practice to improve pasture productivity and quality. However, the efficiency of Nitrogen (N) application depends on favorable climatic conditions. Thus, in the present work, a metanalytic study was used to summarize and analyze data on nitrogen fertilization in forage species: elephant grass (Pennisetum purpureum) and panicum grass [Megathyrsus maximus (Syn. Panicum maximum)], in order to determine the critical levels and recommended doses of nutrients for the rational use of fertilizers in forage plants, whether in pastures or weeds. Therefore, in this study, a systematic review was used, which is a type of investigation, for which research works carried out in Brazil between 2010 and 2020 were considered, including only scientific articles and dissertations. Based on the data from these studies, the relative increments of dry matter and crude protein in relation to the control treatment and the efficiency of nitrogen use in the production of dry matter and crude protein were calculated. All data collected were submitted to analysis of variance for linear and quadratic effects on each of the variables and, in case of significance, regression analysis was performed. Nitrogen fertilization in Pennisetum purpureum and Megathyrsus maximus provides consistent increases in dry matter and crude protein production, however above 1000 kg of nitrogen ha-1 there is a compromise in the efficiency of dry matter production. With a view to reducing losses due to the lower efficiency in crude protein production, it is important to verify that above 500 kg of nitrogen, there is a drastic reduction in the efficiency of crude protein production by Pennisetum purpureum. For all nitrogen doses, there is a drastic reduction in crude protein production efficiency by Megathyrsus maximus in relation to the control.

Evaluating type and amount of dietary protein in relation to metabolic syndrome among Iranian adults: cross-sectional analysis of Fasa Persian cohort study

Background and aimMetabolic syndrome is characterized by several conditions including abdominal obesity, dyslipidemia, impaired glucose levels, and hypertension; which all are directly associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. This study aimed to evaluate the association of the amount and source of dietary protein with the risk of metabolic syndrome and its components in adult men and women.Material and methodThis study was performed using Persian cohort data, Fasa branch, which included 3660 men and 5262 women. Individuals were divided into five groups for total dietary proteins, plant proteins, and animal proteins using the quintiles, and the odds of incidence for metabolic syndrome and each component was evaluated.ResultsA higher intake of total protein was associated with lower odds of having metabolic syndrome (OR: 0.24 95% CI 0.18–0.33, P-trend < 0.001 in men, OR: 0.42 95% CI 0.34–0.51, P-trend < 0.001 in women) and all of its components. men (OR: 0.35 95% CI 0.25–0.48, P-trend < 0.001) and women (OR: 0.41 95% CI 0.33–0.52, P-trend < 0.001) in the highest quintile of plant protein intake had a reduced prevalence of metabolic syndrome and its components. An increased animal protein intake was associated with a lower prevalence of metabolic syndrome (P-trend < 0.001), a declined risk of having elevated triglycerides (P-trend = 0.016) in men, and a reduced risk of having abdominal obesity in men (P-trend < 0.001) and women (P-trend < 0.001).ConclusionA higher consumption of total protein and plant protein was associated with a lower prevalence of metabolic syndrome and its components. Increased consumption of animal protein seemed to be related to a lower prevalence abdominal obesity. Also, only in men, animal protein was associated with decreased risk of having metabolic syndrome.

The Isocaloric Substitution of Plant-Based and Animal-Based Protein in Relation to Aging-Related Health Outcomes: A Systematic Review

Plant-based and animal-based protein intake have differential effects on various aging-related health outcomes, but less is known about the health effect of isocaloric substitution of plant-based and animal-based protein. This systematic review summarized current evidence of the isocaloric substitutional effect of plant-based and animal-based protein on aging-related health outcomes. PubMed and Embase databases were searched for epidemiologic observational studies published in English up to 15 March 2021. Studies that included adults ≥18 years old; use of a nutritional substitution model to define isocaloric substitution of plant protein and animal protein; health outcomes covering mortality, aging-related diseases or indices; and reported association estimates with corresponding 95% confidence intervals were included. Nine cohort studies and 3 cross-sectional studies were identified, with a total of 1,450,178 subjects included in this review. Consistent and significant inverse association of substituting plant protein for various animal proteins on all-cause mortality was observed among 4 out of 5 studies with relative risks (RRs) from 0.54 to 0.95 and on cardiovascular disease (CVD) mortality among all 4 studies with RRs from 0.58 to 0.91. Among specific animal proteins, the strongest inverse association on all-cause and CVD mortality was identified when substituting plant protein for red and/or processed meat protein, with the effect mainly limited to bread, cereal, and pasta protein when replacing red meat protein. Isocaloric substitution of plant-based protein for animal-based protein might prevent all-cause and CVD-specific mortality. More studies are needed on this topic, particularly for cancer incidence and other specific aging-related diseases.

A genomic approach identifies sRAGE as a putatively causal protein for asthma

Asthma is a complex respiratory condition caused by environmental and genetic factors. Although lower concentrations of the anti-inflammatory protein soluble receptor for advanced glycation end products (sRAGE) have been associated with asthma in humans and mouse models, it is uncertain whether sRAGE plays a causal role in asthma. We designed a 2-stage study of sRAGE in relation to asthma with association analysis in FHS participants as well as causal inference testing using Mendelian randomization (MR). We measured plasma levels of sRAGE and performed cross-sectional analysis to examine the association between plasma sRAGE concentration and asthma status in 6546 FHS participants. We then used sRAGE protein advanced glycation end products (pQTLs) derived from a genome-wide association study of plasma sRAGE levels in ∼7000 FHS participants with UK Biobank asthma genome-wide association study in MR to consider sRAGE as a putatively causal protein for asthma. We also performed replication MR using an externally derived sRAGE pQTL from the INTERVAL study. Last, we conducted colocalization using cis-pQTL variants at the advanced glycosylation end-product specific receptor (AGER) locus with variants from the UK Biobank asthma genome-wide association study. Association analysis revealed that each 1 SD increment in sRAGE concentration was associated with a 14% lower odds of asthma in FHS participants (95% CI 0.76-0.96). MR identified sRAGE as putatively causal for and protective against asthma on the basis of self-reported (odds ratio [per 1 SE increment in inverse-rank-normalized sRAGE]= 0.97, 95% CI 0.95-0.99; P= .005) and doctor-diagnosed asthma (odds ratio= 0.97, 95% CI 0.95-0.99; P= .011). Through this genomic approach, we identified sRAGE as a putatively causal, biologically important, and protective protein in relation to asthma. Functional studies incell/animal models are needed to confirm our findings.

Body composition and composition of gain of growing beef bulls fed rations with varying energy concentrations

Data on chemical body composition of cattle serve as a basis for recommendations on energy and nutrient requirements. Relevant data of growing dual-purpose Fleckvieh (German Simmental) bulls are scarce and originate from old trials, covering low rates of gain and live weights. Hence, the aim of the study was to analyze the body tissue distribution, chemical composition, and composition of body weight gain of growing Fleckvieh bulls within a 120–780 kg live weight range. Results showed that body composition changed during growth but was not affected by dietary energy concentration. Changes in body composition were characterized by increasing shares of fat tissue and ether extract. Body tissues as blood, organs, gastrointestinal tract, and bone proportionately decreased during growth, while muscle and tendon proportions remained constant. The bulls featured enhanced growth potential and high muscle and protein gain throughout the described weight range. The requirements for metabolizable protein in relation to energy decrease with increasing live weight of the animals.

Neutrophils Contribute to Severity of Tuberculosis Pathology and Recovery From Lung Damage Pre- and Posttreatment.

BackgroundDespite microbiological cure, about 50% of tuberculosis (TB) patients have poor lung recovery. Neutrophils are associated with lung pathology; however, CD16/CD62L-defined subsets have not been studied in TB. Using flow cytometry, we monitored frequencies, phenotype, and function of neutrophils following stimulation with Mycobacterium tuberculosis (Mtb) whole cell lysate (WCL) and ESAT-6/CFP-10 fusion protein (EC) in relation to lung pathology.MethodsFresh blood from 42 adult, human immunodeficiency virus (HIV)–negative TB patients were analyzed pre- and post-therapy, with disease severity determined using chest radiography and bacterial load. Flow cytometry was used to monitor frequencies, phenotype, and function (generation of reactive oxygen species [ROS], together with CD11b, tumor necrosis factor, and interleukin 10 [IL-10] expression) of neutrophils following 2-hour stimulation with Mtb-specific antigens.ResultsTotal neutrophils decreased by post-treatment compared to baseline (P = .0059); however, CD16brCD62Lbr (segmented) neutrophils increased (P = .0031) and CD16dimCD62Lbr (banded) neutrophils decreased (P = .038). Banded neutrophils were lower in patients with severe lung damage at baseline (P = .035). Following WCL stimulation, ROS from segmented neutrophils was higher in patients with low Mtb loads even after adjusting for sex (P = .038), whereas IL-10–expressing CD16dimCD62Llo cells were higher in patients with mild damage (P = .0397) at baseline. ConclusionsHigh ROS generation, low levels of banded neutrophils, and high levels of IL-10–expressing CD16dimCD62Llo neutrophils are associated with reduced lung pathology at diagnosis. Hence, neutrophils are potential early indicators of TB severity and promising targets for TB host-directed therapy.

Genomic Analysis of 71 Cardiovascular Proteins in the Framingham Heart Study Identifies Regulatory Networks for Cardiometabolic Risk

Aims: Cardiometabolic risk factors often cluster and their coexistence increases cardiovascular disease (CVD) risk. Unraveling molecular mechanisms for the clustering of risk factors and their links to CVD may highlight promising therapeutic approaches. Methods and Results: We performed a multi-stage integrative genomic study of 71 CVD-related proteins in relation to ten CVD risk factors including lipids, adiposity, dysglycemia and blood pressure traits. Leveraging 16,000 protein expression quantitative trait loci (pQTL) with GWAS signals for CVD risk factors, we identified pQTLs on Chromosome 2 (GCKR region), 9 (ABO region), and 12 (SH2B3 region) that colocalized with at least three risk factors. By integrating pQTLs with tissue specific expression quantitative trait loci (eQTLs), we identified complex three-way regulatory relations of proteins with CVD risk factors via expression of transcripts that were distant (trans from the protein coding gene, including the trans-regulation of APOB (protein) in relation to LDL cholesterol (risk factor) through SORT1 (transcript) expression and ANGPTL3 in relation to triglycerides through PCSK7 expression. Using Mendelian randomization, we identified 13 putatively causal proteins for seven risk factors and found three circulating proteins (ANGPTL13, APOB, and NTproBNP) whose levels were associated with the corresponding risk factor when tested cross-sectionally and longitudinally in ~7000 Framingham Heart Study participants. Conclusions: Results of this integrative approach may provide a broader view of network biology underlying cardiometabolic risk and highlight promising therapeutic targets for prevention and treatment of CVD.

PD-L1 Expression Associated with Epstein-Barr Virus Status and Patients' Survival in a Large Cohort of Gastric Cancer Patients in Northern Brazil.

Simple SummaryThe programmed death ligand 1 (PD-L1) tumor expression is a manifestation of immune evasion and is used as a biomarker for treatment by immunotherapy and appears as a promising therapeutical option for Gastric Cancer (GC). The aim of this study was to evaluate the correlation between EBV status, PD-L1 expression and overall survival in a cohort of a thousand GC patients. Of the thousand tumors, 190 were EBV-positive and presented a high relative expression of PD-L1. the PD-L1 low expression was a characteristic of GC patients EBV-negative. We also show that the high expression of PD-L1 impacts on the survival probability and increase overall survival in GC patients. No EBV-negative GC patients had expression of PD-L1 protein, which suggests that the low expression is related to low overall survival. Patients with GC positive for EBV, presenting PD-L1 overexpression can benefit from immunotherapy treatments and performing the quantification of PD-L1 in gastric neoplasms should be adopted as routine.Gastric cancer (GC) is a worldwide health problem, making it one of the most common types of cancer, in fifth place of all tumor types, and the third highest cause of cancer deaths in the world. There is a subgroup of GC that consists of tumors infected with the Epstein–Barr virus (EBV) and is characterized mainly by the overexpression of programmed cell death protein-ligand-1 (PD-L1). In the present study, we present histopathological and survival data of a thousand GC patients, associated with EBV status and PD-L1 expression. Of the thousand tumors analyzed, 190 were EBV-positive and the vast majority (86.8%) had a high relative expression of mRNA and PD-L1 protein (p < 0.0001) in relation to non-neoplastic control. On the other hand, in EBV-negative samples, the majority had a low PD-L1 expression of RNA and protein (p < 0.0001). In the Kaplan–Meier analysis, the probability of survival and increased overall survival of EBV-positive GC patients was impacted by the PD-L1 overexpression (p < 0.0001 and p = 0.004, respectively). However, the PD-L1 low expression was correlated with low overall survival in those patients. Patients with GC positive for EBV, presenting PD-L1 overexpression can benefit from immunotherapy treatments and performing the quantification of PD-L1 in gastric neoplasms should be adopted as routine.

Identification of protein related to dietary vitamin B3 deficiency in Mediterranean fruit fly larvae.

Mediterranean fruit fly (medfly), Ceratitis capitata, is among the most destructive agricultural pest. The sterile insect technique (SIT) can effectively control medfly populations. To rear healthy medflies for the purpose of SIT, it is essential to supplement B vitamins in the diet. However, the function of the dietary B vitamins in C. capitata larvae is not known. With the microscopic analysis, several organs in the head were examined and the spiracle formation and sensory organs were normally formed between the niacin-supplied and niacin-absent groups. However, formation of the ocular depression was differently developed between the two groups, although the hypostomal sclerite was formed properly. These results signify that niacin deficiency maybe interrupt development of medfly larvae ocular depression. Proteomic analyses using LC MS/MS detected a total of 1845 proteins in two flies. A total of 607 of the 1845 proteins were overexpressed and one third (598 proteins) were downexpressed in the niacin-deficient larvae, while about one third were similarly expressed. Overexpressed proteins in the niacin-deficient larvae included ryanodine receptor 44 F, intergrin-PS, spalt-major homeotic protein, and chiffon protein. One of important overexpressed proteins was optomotor-blind protein in relation to wing development in the niacin-deficient medfly larvae.