Metabolic Studies Research Articles

Metabolic energetic adaptation of Atlantic salmon phagocytes to changes in carbon sources and exposure to PAMPs

Phagocytic cells are pivotal for host homeostasis and infection defense, necessitating metabolic adaptations in glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation (OXPHOS). While mammalian phagocytes shift towards glycolysis and glutaminolysis during polarization, research on fish phagocyte metabolic reprogramming is limited. To address this, the Atlantic salmon phagocytic cell line, SHK-1, serves as a valuable model. Using the Seahorse XFe96 Flux Analyzer, this study compares SHK-1 bioenergetics under glucose-restricted (L-15 medium) and glucose-supplemented (PM) conditions, providing insights into metabolic characteristics and responses to Piscirickettsia salmonis bacterium Pathogen-associated molecular patterns (PAMPs). A standardized protocol for the study of real-time changes in the metabolism study of SHK-1 in PM and L-15 media, determining oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) is shown. Exhibiting metabolic adaptations, SHK-1 cells in the PM medium have higher basal and maximal OCR and spare capacity (SRC), while those grown in the L-15 medium favor OXPHOS, showing minimal glycolytic function. Despite metabolic differences, intracellular ATP levels are comparable, highlighting the metabolic plasticity and adaptability of SHK-1 cells to various carbon sources. Exposure to PAMPs from Piscirickettsia salmonis induces a metabolic shift, increasing glycolysis and OXPHOS, influencing ATP, lactate, glutamine, and glutamate levels. These findings highlight the role of mitochondrial bioenergetics and metabolic plasticity in salmon phagocytes, offering novel nutritional strategies for host-pathogen interventions based on energy metabolism.

Advances in Chiral Metabolomic Profiling and Biomarker Discovery.

Chiral metabolomics entails the enantioselective measurement of the metabolome present in a biological system. Over recent years, it has garnered significant interest for its potential in discovering disease biomarkers and aiding clinical diagnostics. D-Amino acids and D-hydroxy acids, traditionally overlooked as unnatural, are now emerging as novel signaling molecules and potential biomarkers for a range of metabolic disorders, brain diseases, kidney disease, diabetes, and cancer. Despite their significance, simultaneous measurements of multiple classes of chiral metabolites in a biological system remain challenging. Hence, limited information is available regarding the metabolic pathways responsible for synthesizing D-amino/hydroxy acid and their associated pathophysiological mechanisms in various diseases. Capitalizing on recent advancements in sensitive analytical techniques, researchers have developed various targeted chiral metabolomic methods for the analysis of chiral biomarkers. Here, we highlight the pivotal role of chiral metabolic profiling studies in disease diagnosis, prognosis, and therapeutic interventions. Furthermore, we describe cutting-edge chromatographic and mass spectrometry methods that enable enantioselective analysis of chiral metabolites. These advanced techniques are instrumental in unraveling the complexities of disease biomarkers, contributing to the ongoing efforts in disease biomarker discovery.

Efficacy and safety of apraglutide in short bowel syndrome with intestinal failure and colon–in–continuity: A multicenter, open-label, metabolic balance study

BackgroundApraglutide is a novel long-acting GLP-2 analog in development for short bowel syndrome with intestinal failure (SBS-IF). This multicenter, open-label, phase 2 study in SBS-IF and colon-in-continuity (CiC) investigates the safety and efficacy of apraglutide. MethodsThis was a 52-week phase 2 metabolic balance study (MBS) in 9 adult patients with SBS-IF-CiC receiving once-weekly subcutaneous apraglutide injections. Safety was the primary endpoint. Secondary endpoints included changes in absorption parameters (MBS at baseline, after 4 weeks with stable parenteral support (PS), and 48 weeks), PS needs (48-week PS adjustment period based on monthly 48-hour fluid balances) and intestinal morphology and motility (static and cine MRI at baseline and 4, 24 and 48 weeks). ResultsPS volume decreased by -4702mL/week (-52%; p<0.001) at week 52. Seven patients (78%) achieved ≥1 day off PS at week 52. At 4 weeks, fecal output was reduced by 253 g/day (p=0.013). At 48 weeks, increases in wet weight absorption by 316 g/day (p=0.039), energy absorption by 1134 kJ/day (p=0.041) and carbohydrate absorption by 56.1 g/day (p= 0.024) were observed. Moreover, small bowel length increased from 29.7 to 40.7 cm (p=0.012), duodenal wall thickness increased by 0.8 mm (p=0.02) and motility in the proximal colon was reduced (p=0.031). A total of 127 adverse events was reported, which were mostly mild to moderate. ConclusionApraglutide had an acceptable safety profile and was associated with significant reductions in PS needs and days off PS, improvements in intestinal absorption, and structural and functional intestinal changes in patients with SBS-IF-CiC.ClinicalTrials.gov, Number NCT04964986

Preclinical metabolism and metabolic drug-drug interaction profile of pedunculoside and rotundic acid.

Pedunculoside and rotundic acid, the most abundant components in plants of the genus Ilex L. (Aquifoliaceae), exhibit biological and pharmacological significance in the treatment of cardiovascular diseases. However, there have been few studies on their metabolism. This study performed a systematic metabolism study of pedunculoside and rotundic acid and evaluated their potential for herb-drug interaction. Pedunculoside or rotundic acid was incubated with human liver microsomes and recombinant human metabolic enzymes, and analyzed using LC-Q-TOF/MS and LC-MS/MS. Pedunculoside was found to be the most stable in human liver microsomes, whereas rotundic acid was easily metabolized. Eight pedunculoside metabolites and six rotundic acid metabolites were detected and tentatively identified through hydroxylation, glucuronidation, acetylation, and glucose conjugation. Hydroxylation of pedunculoside is mainly catalyzed by CYP3A4/5 and partly by CYP2C8. Hydroxylation of rotundic acid is almost exclusively catalyzed by CYP3A4/5, and its glucuronidation reaction is mediated by UGT1A4. Neither pedunculoside nor rotundic acid showed CYP inhibition (IC50 values > 50 μM) with the probe substrates of major CYP isoforms during incubation with human liver microsomes. This study is the first investigation into the invitro metabolism of pedunculoside and rotundic acid using human liver microsomes. It also aims to assess their potential as perpetrators of drug-drug interactions involving CYP enzymes. The comprehensive metabolism and drug interaction studies of pedunculoside and rotundic acid enable us to evaluate and manage potential risks with their use in pharmacotherapy.

A comparative study of bioenergetic metabolism on mammary epithelial cells from humans and Göttingen Minipigs

Mammary epithelial cells (MECs) of humans (h) and Göttingen Minipigs (mp) were analyzed to compare their ability to perform ATP production by oxidative phosphorylation and glycolysis. The ATP production under basal and stressor situations highlights the same metabolic potential of both primary cell lines. However, quantitively the ATP production rate of hMECs was higher than mpMECs. Conversely, oxidative cell respiration in mpMECs exploits a maximum respiratory capacity to support pathophysiological circumstances or stress conditions that could require an excessive effort of cell metabolism. Since mpMECs primarily utilize an oxidative metabolism similar to hMECs, the metabolic characterization conducted allows us to confirm that mpMECs represent a potential alternative cellular model in the translational medicine approach.

A diel multi-tissue genome-scale metabolic model of Vitis vinifera.

Vitis vinifera, also known as grapevine, is widely cultivated and commercialized, particularly to produce wine. As wine quality is directly linked to fruit quality, studying grapevine metabolism is important to understand the processes underlying grape composition. Genome-scale metabolic models (GSMMs) have been used for the study of plant metabolism and advances have been made, allowing the integration of omics datasets with GSMMs. On the other hand, Machine learning (ML) has been used to analyze and integrate omics data, and while the combination of ML with GSMMs has shown promising results, it is still scarcely used to study plants. Here, the first GSSM of V. vinifera was reconstructed and validated, comprising 7199 genes, 5399 reactions, and 5141 metabolites across 8 compartments. Tissue-specific models for the stem, leaf, and berry of the Cabernet Sauvignon cultivar were generated from the original model, through the integration of RNA-Seq data. These models have been merged into diel multi-tissue models to study the interactions between tissues at light and dark phases. The potential of combining ML with GSMMs was explored by using ML to analyze the fluxomics data generated by green and mature grape GSMMs and provide insights regarding the metabolism of grapes at different developmental stages. Therefore, the models developed in this work are useful tools to explore different aspects of grapevine metabolism and understand the factors influencing grape quality.

Novel Benzothiazole Derivatives: Synthesis, Anticancer Activity, Density Function Theory (DFT) Study, and ADMET Prediction

Benzothiazole is an amazing small molecule involved in many applications in industrial and pharmaceutical industries to prepare many candidate compounds as effective drugs. In this study, we presented some derivatives of this compound that were prepared easily and quickly with the help of microwaves to minimize time, energy, and finances. The compounds’ cytotoxicity against the two cell lines SK-GT-4 and AMGM5 was examined. The cytotoxic effect of each compound at different concentrations was measured using the MTT assay. Compounds exhibited no potent cytotoxic effects toward the SK-GT-4 cell line. Compounds B1 and B2 had a high IC50 value and good growth inhibition activity against the AMGM5 cell line. According to in silico absorption, distribution, metabolism, and excretion analysis (ADME) prediction studies, the compounds B1, B2, and B3 met Lipinski and were drug-like in most physicochemical parameters. Despite some violations, generally favorable pharmacokinetic properties. It is also assumed that it can potentially become a drug candidate in the future. Various electronic parameters were examined using DFT/WB97XD/6-31++G(d,p), and studies were conducted to support the experimental findings. To estimate the binding modes of compounds B1 and B5, we also performed in silico molecular docking studies.

In-silico Investigation of Ginseng Phytoconstituents as Novel Therapeutics Against MAO-A.

Ginseng (Panax ginseng) is a herb of medicinal and nutritional importance. Ginseng has been used since ancient times for the treatment of numerous ailments as it has many therapeutic properties. Several phytoconstituents are present in Panax ginseng that possess a variety of beneficial pharmacological properties. To explore the potential of phytoconstituents of Panax ginseng in the treatment of depression, a molecular modeling technique was utilized targeting monoamine oxidase-A (MAO-A). A total of sixty-one phytoconstituents of ginseng were drawn with the help of ChemBioDraw Ultra 12.0 software and PDBs for MAO-A enzyme were retrieved from the RCSB PDB database. The prepared ligands were screened for MAO-A properties using the software Molegro Virtual Docker (MVD 2010.4.1.0). All the prepared ligands were evaluated for drug-likeliness properties using Swiss ADME. Among the docking studies of 60 Ginseng phytochemicals including one standard, 15 phytoconstituents with the highest dock score and better binding interactions were selected further for absorption, distribution, metabolism and excretion (ADME) studies. Stachyose (-227.287, 17 interactions), Raffinose (-222.157, 14 interactions), and Ginsenoside Rg1 (-216.593, 10 interactions) were found to possess better interactions as compared to Clorgyline taken as a standard drug. Stachyose was found to be the most potent inhibitor of MAO-A enzyme under investigation and can be a potential lead molecule for the development of newer phytochemical-based treatment of depression.

A Newly Identified Protective Role of C5a Receptor 1 in Kidney Tubules against Toxin-Induced Acute Kidney Injury

Acute kidney injury (AKI) remains a major reason for hospitalization with limited therapeutic options. While complement activation is implicated in AKI, the role of C5a receptor 1 (C5aR1) in kidney tubular cells is unclear. We used aristolochic acid nephropathy (AAN) and folic acid nephropathy (FAN) models to establish the role of C5aR1 in kidney tubules during AKI in germline C5ar1-/- mice, myeloid cell-specific, and kidney tubule-specific C5ar1 knockout mice. After aristolochic acid and folic acid injection, C5ar1-/- mice had increased AKI severity and a higher degree of tubular injury. Macrophage depletion in C5ar1-/- mice or myeloid cell-specific C5ar1 deletion did not affect the outcomes of AA-induced AKI. RNA-sequencing data from RTECs showed that C5ar1 deletion was associated with the downregulation of mitochondrial metabolism and ATP production transcriptional pathways. Metabolic studies confirmedreduced mitochondrial membrane potential at baseline and increased mitochondrial oxidative stress after injury in C5ar1-/- RTECs. Moreover, C5ar1-/- RTECs had enhanced glycolysis, glucose uptake, and lactate production upon injury, corroborated by metabolomics analysis of kidneys from AAN mice. Kidney tubule-specific C5ar1 knockout mice recapitulated exacerbated AKI observed in C5ar1-/- mice in AAN and FAN. Our data indicate that C5aR1 signaling in kidney tubules exerts renoprotective effects against toxin-induced AKI by limiting overt glycolysis and maintaining mitochondrial function, revealing a novel link between the complement system and tubular cell metabolism.

Comparative Analysis of Oxidative Metabolism in Liver in Different Experimental Models of Hypothyroidism: Low Iodine Diet and Anti-Thyroid drug (Methimazole)

Objectives: On the concept of oxidative stress in hypothyroidism, which still remains ambiguous and controversial, the article emphasizes the issue of the impact of the experimental conditions on the validity of the data obtained in different methods of modeling thyroid dysfunction. Materials and Methods: Experiments were conducted on 112 white nonlinear male rats. Thyroid hormones and biomarkers of oxidative metabolism in the liver tissue were determined in rats kept for 3 months on a low-iodine diet (LID) and in rats with methimazole (MMI)-induced hypothyroidism (2,5 mg/100 g of body weight for 3 weeks). Results: In LID-rats (n=96) total serum T4 amounted 43, total T3 in liver tissue - 73% of the level found in euthyroid animal, p=0.0121 and p=0.0051, respectively), whereas in MMI-rats (n=96) both total and free serum T4 were 67% of control (p=0.0002 for both total and free T4). In LID-rats cytochrome oxidase (CcOX) activity in liver tissue was 68.5, concentration of malondialdehyde (MDA) - 58% of euthyroids (p value - 0.0202 and 0.0127, respectively), while protein carbonyls (PC) level was 116% of the control (p=0.0411). In MMI-rats liver malate dehydrogenase (MDH) activity decreased up to 70.9, but succinate dehydrogenase (SDH) activity and MDA concentration increased up to 163.6 and 154% of the level in euthyroid animals respectively (p˂0.05). Conclusion: LID-model led to the more pronounced inhibition of thyroid function, than that the MMI-hypothyroidism model used. LID-model was accompanied by a decrease in the intensity of oxidative metabolism in liver tissue, whereas MMI-hypothyroidism - by activation of the succinate oxidation pathway and an increase in the concentration of secondary lipid peroxidation products in the liver of experimental animals. The results suggest that the conflicting data obtained from studies of oxidative metabolism in hypothyroidism, among other assumptions, may be due to the different approaches used by researchers to model thyroid dysfunction.

19F qNMR based pharmacokinetics, metabolism and mass balance studies of SARS-CoV-2-3CL protease inhibitor simnotrelvir (SIM0417) in humans.

Simnotrelvir (SIM0417), an inhibitor of the 3CL protease of SARS-CoV-2, has been identified as a CYP3A sensitive substrate. This study investigated the pharmacokinetics, metabolism, and mass balance of simnotrelvir following a single oral dose of 750 mg in six healthy Chinese male subjects, co-administered with four doses of 100 mg ritonavir. Analysis using 19F qNMR combined with LC-MS/MS showed that the parent drug M0 constituted over 90% of the drug-related components in plasma. Of the administered dose, 55.4% (54.3% of M0) was recovered in urine, while 36.7% (4.57% of M0) was excreted in feces. UPLC/Q-TOF MS was used to identify metabolites in human plasma, urine and feces. Notably, oxidative metabolites catalyzed by CYP3A were scarcely detected in these matrixes. The amide hydrolyzed metabolite M9 and the cyano hydrolyzed metabolite M10 were recognized as the predominant metabolites, with the main excretion being through feces (19.0% and 12.7% of the administered dose, respectively). In vitro experiments indicated that M10 is primarily formed in the duodenum and jejunum, with further metabolism to M9 by microbiota in the large intestine. Overall, the co-administration of simnotrelvir with ritonavir led to predominant metabolism by intestinal enzymes or microbiota, resulting in hydrolyzed metabolites. These findings highlight the critical role of intestinal metabolism in the pharmacokinetics of simnotrelvir and emphasize the need to consider interactions with antibiotics and individual differences of intestinal microbiota.

Genetically Enriched Clinical Trials for Precision Development of Noncancer Therapeutics: A Scoping Review.

Genetically driven clinical trial enrichment has been proposed to accelerate and reduce the cost of developing new therapeutics. Usage of this approach has not been comprehensively reviewed. We searched Ovid MEDLINE, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, and WHO ICTRP for articles published between 2010 and 2023. Excluding absorption, distribution, metabolism, and elimination pharmacogenetic studies and anti-infectives, we found 95 completed, 4 terminated, and 22 ongoing prospective genetically enriched trials on 110 drugs for 48 nononcology, nonrare syndromic indications. Trial sizes ranged from 4 to 6,147 participants (median 72) and covered numerous disease areas, particularly neurology (30), metabolism (22), and psychiatry (17). Fifty-six completed studies (60%) met their primary end point. Overall, this scoping review demonstrates that genetically enriched trials are feasible and scalable across disease areas and provide critical information for further development, or attrition, of investigational drugs. Large, appropriately designed disease-, hospital-, or population-based biobanks will undoubtedly facilitate this type of precision drug development approach.

Emerging roles of small extracellular vesicles in metabolic reprogramming and drug resistance in cancers.

Studies of carcinogenic metabolism have shown that cancer cells have significant metabolic adaptability and that their metabolic dynamics undergo extensive reprogramming, which is a fundamental feature of cancer. The Warburg effect describes the preference of cancer cells for glycolysis over oxidative phosphorylation (OXPHOS), even under aerobic conditions. However, metabolic reprogramming in cancer cells involves not only glycolysis but also changes in lipid and amino acid metabolism. The mechanisms of these metabolic shifts are critical for the discovery of novel cancer therapeutic targets. Despite advances in the field of oncology, chemotherapy resistance, including multidrug resistance, remains a challenge. Research has revealed a correlation between metabolic reprogramming and anticancer drug resistance, but the underlying complex mechanisms are not fully understood. In addition, small extracellular vesicles (sEVs) may play a role in expanding metabolic reprogramming and promoting the development of drug resistance by mediating intercellular communication. The aim of this review is to assess the metabolic reprogramming processes that intersect with resistance to anticancer therapy, with particular attention given to the changes in glycolysis, lipid metabolism, and amino acid metabolism that accompany this phenomenon. In addition, the role of sEVs in disseminating metabolic reprogramming and promoting the development of drug-resistant phenotypes will be critically evaluated.

Novel drug sampling technique: portal vein catheterization in steers.

To determine the feasibility of catheterizing the portal vein to obtain serial portal vein blood samples in steers. We hypothesized that the portal vein catheterization would be a successful continuous sampling technique with minimal adverse effects in steers. 2 groups of steers were used: a pilot group (n = 2) and experimental group (n = 6). In both groups, steers were sedated with xylazine. The right rib spaces were clipped and aseptically prepped. The portal vein was visualized via ultrasound, and a 14-gauge catheter was placed percutaneously and advanced into the portal vein. A guide wire was passed through the catheter, followed by a tissue dilator and then a vascular balloon catheter. In the pilot group, blood chemistries were performed prior to portal vein catheterization and then again once the catheter was placed (with samples from both the jugular vein and portal catheter). The liver was also examined at necropsy for any gross lesions in both groups. All steers tolerated the portal vein catheters well, with the catheters lasting for the full length of the study period (7 days). The only observed adverse reaction was a superficial abscess at the catheter site (n = 3). On necropsy, 1 liver had gross discoloration, but no other abnormalities were noted. There were no significant changes in biochemistry profiles before or after portal vein catheterization. Portal vein catheterization is a novel and feasible serial sampling technique of the portal vein. This technique can be used in future pharmacokinetic, nutrition, metabolism, or toxicity studies.

Absorption, Distribution, Metabolism, and Excretion of Icenticaftor (QBW251) in Healthy Male Volunteers at Steady State and In Vitro Phenotyping of Major Metabolites.

Icenticaftor (QBW251) is a potentiator of the CFTR protein and is currently in clinical development for the treatment of chronic obstructive pulmonary disease and chronic bronchitis. An absorption, distribution, metabolism, and excretion (ADME) study was performed at steady state to determine the pharmacokinetics, mass balance, and metabolite profiles of icenticaftor in humans. In this open-label study, six healthy men were treated with unlabeled oral icenticaftor (400 mg b.i.d.) for 4 days. A single oral dose of [14C]icenticaftor was administered on Day 5, and unlabeled icenticaftor was administered b.i.d. from the evening of Day 5 to Day 12. Unchanged icenticaftor accounted for 18.5% of plasma radioactivity. Moderate to rapid absorption of icenticaftor was observed (median Tmax: 4 hours), with 93.4% of the dose absorbed. It exhibited moderate distribution (Vz/F: 335 L) and was extensively metabolized, principally through N-glucuronidation, O-glucuronidation, and/or O-demethylation. The metabolites M8 and M9, formed by N-glucuronidation and O-glucuronidation of icenticaftor, respectively, represented the main entities detected in plasma (35.3% and 14.5%, respectively) in addition to unchanged icenticaftor (18.5%). The apparent mean T1/2 of icenticaftor was 15.4 hours in blood and 20.6 hours in plasma. Icenticaftor was eliminated from the body mainly through metabolism followed by renal excretion, and excretion of radioactivity was complete after 9 days. In vitro phenotyping of icenticaftor showed that cytochrome P450 and uridine diphosphate glucuronosyltransferase were responsible for 31% and 69% of the total icenticaftor metabolism in human liver microsomes, respectively. This study provided invaluable insights into the disposition of icenticaftor. Significance Statement The ADME of a single radioactive oral dose of icenticaftor was evaluated at steady state to investigate the nonlinear pharmacokinetics observed previously with icenticaftor. [14C]Icenticaftor demonstrated good systemic availability after oral administration and was extensively metabolized and moderately distributed to peripheral tissues. The most abundant metabolites, M8 and M9, were formed by N-glucuronidation and O-glucuronidation of icenticaftor, respectively. Phenotyping demonstrated that [14C]icenticaftor was metabolized predominantly by UGT1A9 with a remarkably low Km value.

Urinary Stone Formation and Testosterone Supplementation: Insights from a Cross-sectional Study in Athletes

Introduction: The use of exogenous testosterone has become increasingly prevalent in sports fields, raising concerns about its potential risks and benefits. Methods &amp; Materials: This study aimed to investigate the effects of testosterone supplementation on stone formation in the urinary tract and urine composition. A total of 1080 athletes participated in a two-year cross-sectional study, with 495 individuals receiving testosterone supplementation and 585 individuals serving as non-users. Blood and urine samples were collected, and CT scans were performed to assess stone presence. Results: The results revealed a significant increase in crystalluria among testosterone users compared to non-users (38.2% vs. 2.7%, p=0.004). Imaging findings also showed a higher incidence of abnormal results in testosterone users (25.2% vs. 4.3%, p=0.0017), with kidney calcification, pelvic and calyceal stones, ureteral stones, and bladder stones observed. Conclusion: However, further metabolic studies are required to establish a definitive cause-and-effect relationship between testosterone use and stone formation. This study sheds light on the potential risks associated with exogenous testosterone use and highlights the need for evidence-based recommendations in sports and athletic performance.

The risk of dyslipidemia on PLHIV associated with different antiretroviral regimens in Huzhou

Background Dyslipidemia is increasingly common in people living with HIV (PLHIV), thereby increasing the risk of cardiovascular events and diminishing the quality of life for these individuals. The study of blood lipid metabolism of PLHIV has great clinical significance in predicting the risk of cardiovascular disease. Therefore, this study aims to examine the blood lipid metabolism status of HIV-infected patients in Huzhou before and after receiving highly active antiretroviral therapy (HAART) and to explore the impact of different HAART regimens on dyslipidemia. Method PLHIV confirmed in Huzhou from June 2010 to June 2022 was included. The baseline characteristics and clinical data during the follow-up period were collected, including some blood lipid indicators (total cholesterol and triglycerides) and HAART regimens. A multivariate logistic regression model and the generalized estimating equation model were used to analyze the independent effects of treatment regimens on the risk of dyslipidemia. Result The overall prevalence of dyslipidemia among PLHIV after HAART was 70.11%. PLHIV receiving lamivudine (3TC) + efavirenz (EFV) + zidovudine (AZT) had a higher prevalence of dyslipidemia compared to those receiving 3TC+EFV+tenofovir disoproxil fumarate (TDF). In a logistic analysis adjusted for important covariates such as BMI, age, diabetes status, etc., we found that the risks of dyslipidemia were higher with 3TC+EFV+AZT (dyslipidemia: odds ratio [OR] = 2.09, 95% confidence interval [Cl]: 1.28–3.41; TG ≥1.7: OR = 2.40, 95%Cl:1.50–3.84) than with 3TC+EFV+TDF. Furthermore, on PLHIV that was matched 1:1 by the HAART regimens, the results of the generalized estimation equation again showed that 3TC+EFV+AZT (TG ≥1.7: OR = 1.84, 95%Cl: 1.10–3.07) is higher for the risk of marginal elevations of TG than 3TC+EFV+TDF. Conclusion The prevalence of dyslipidemia varies according to different antiretroviral regimens. Using both horizontal and longitudinal data, we have repeatedly demonstrated that AZT has a more adverse effect on blood lipids than TDF from two perspectives. Therefore, we recommend caution in using the 3TC+EFV+AZT regimen for people at clinical risk of co-occurring cardiovascular disease.

Metabolic imaging in living plants: A promising field for chemical exchange saturation transfer (CEST) MRI.

Magnetic resonance imaging (MRI) is a versatile technique in the biomedical field, but its application to the study of plant metabolism in vivo remains challenging because of magnetic susceptibility problems. In this study, we report the establishment of chemical exchange saturation transfer (CEST) for plant MRI. This method enables noninvasive access to the metabolism of sugars and amino acids in complex sink organs (seeds, fruits, taproots, and tubers) of major crops (maize, barley, pea, potato, sugar beet, and sugarcane). Because of its high signal detection sensitivity and low susceptibility to magnetic field inhomogeneities, CEST analyzes heterogeneous botanical samples inaccessible to conventional magnetic resonance spectroscopy. The approach provides unprecedented insight into the dynamics and distribution of sugars and amino acids in intact, living plant tissue. The method is validated by chemical shift imaging, infrared microscopy, chromatography, and mass spectrometry. CEST is a versatile and promising tool for studying plant metabolism in vivo, with many applications in plant science and crop improvement.

Transcriptome and metabolism study reveals impact of nitrogen fertilizer on triticale

Transcriptome and metabolism study reveals impact of nitrogen fertilizer on triticale

Synthesis, characterization, in vitro and in silico studies of N, N-dimethyl phenyl chalcone-Schiff’s base hybrid

Three dissimilar N, N-dimethylphenyl chalcone Schiff's base hybrids (CSBHs) were synthesized and characterized by nuclear magnetic resonance spectroscopy (NMR), Fourier transform infrared (FT-IR) and ultraviolet-visible spectroscopic techniques by the theoretical as well as investigational methods. The molecular weights of the CSBHs were also confirmed by the Electrospray ionization Mass technique. The in vitro antidiabetic, anti-inflammatory and cytotoxicity were tested for the CSBHs using α-amylase inhibitory and protein anti-denaturation methods. The CSBHs showed good antidiabetic and anti-inflammatory activities and the percentage of inhibitions is nearer to standard drugs acarbose and diclofenac sodium. The molecular docking studies for CSBHs were investigated and their docking results are superior and also density functional theory method are performed for CSBHs to support biological and molecular docking results. The CSBHs showed very good hydrogen bonding interactions with amino acid residues of the enzymes and the CSBHs showed lower band gap and higher electrophilicity index values. In addition, (ADMET) Absorption, Distribution, Metabolism, Excretion and Toxicity study and Protox-II toxicity predictions were performed to check the pharmacological properties of CSBHs.