Metabolic Profile Research Articles

Comparative Ecotoxicity Assessment of highly bioactive Isomeric monoterpenes carvacrol and thymol on aquatic and edaphic indicators and communities

The growing demand for sustainable natural products to replace harmful synthetic ones requires comprehensive ecotoxicity assessments to ensure their eco-friendly nature. This study explored for the first time the changes in microbial community growth and metabolic profiles from river and natural soil samples exposed to the two structural isomers, thymol (THY) and carvacrol (CARV), utilizing Biolog EcoPlate™ assays and 16S rRNA gene sequencing for taxonomic analysis. In addition, we addressed existing ecotoxicity data gaps for these two compounds by using aquatic (Daphnia magna and Vibrio fischeri) and soil (Eisenia fetida and Allium cepa) indicators. Results show acute toxicity of both CARV and THY on all indicators. V. fischeri (LC50=0.59mg/L)>D. magna (4.75mg/L)>A. cepa (6.47mg/L) for CARV, and V. fischeri (LC50=1.71mg/L)>A. cepa (4.05mg/L)>D. magna (8.13mg/L) for THY. E. fetida showed LC50=7.68mg/kg for THY and 1.04 for CARV. River and soil microbial communities showed resilience, likely because they contain taxa capable of biodegrading these products. No significant growth inhibition effects were observed up to 100mg/L, though substrate utilization decreased at higher concentrations, particularly for polymers and amines in soil microorganisms and polymers in aquatic communities. Soil microorganisms were more affected than aquatic ones, with CARV being more toxic than THY (EC50120h=THY 94.13 and CARV 29.79mg/L in soil microorganisms). These findings suggest that an increase in the consumption of these products and their subsequent ecotoxicity effects from environmental discharge should still be monitored before being ruled out. However, long-term effects are unlikely due to microbial degradation of these natural products, potentially reducing risks to other target species and opening the way for their use as substitutes for commercial antibiotics.

Unique tau- and synuclein-dependent metabolic reprogramming in neurons distinct from normal aging.

Neuronal cells are highly specialized cells and have a specific metabolic profile to support their function. It has been demonstrated that the metabolic profiles of different cells/tissues undergo significant reprogramming with advancing age, which has often been considered a contributing factor towards aging-related diseases including Alzheimer's (AD) and Parkinson's (PD) diseases. However, it is unclear if the metabolic changes associated with normal aging predispose neurons to disease conditions or a distinct set of metabolic alterations happen in neurons in AD or PD which might contribute to disease pathologies. To decipher the changes in neuronal metabolism with age, in AD, or in PD, we performed high-throughput steady-state metabolite profiling on heads in wildtype Drosophila and in Drosophila models relevant to AD and PD. Intriguingly, we found that the spectrum of affected metabolic pathways is dramatically different between normal aging, Tau, or Synuclein overexpressing neurons. Genetic targeting of the purine and glutamate metabolism pathways, which were dysregulated in both old age and disease conditions partially rescued the neurodegenerative phenotype associated with the overexpression of wildtype and mutant tau. Our findings support a "two-hit model" to explain the pathological manifestations associated with AD where both aging- and Tau/Synuclein- driven metabolic reprogramming events cooperate with each other, and targeting both could be a potent therapeutic strategy.

Differences in cardiorespiratory fitness by gonadotropin-releasing hormone agonist treatment before and after testosterone in transgender adolescents.

There are known sex differences in cardiorespiratory fitness (CRF). Little is known about the impact of pubertal blockade with a gonadotropin-releasing hormone agonist (GnRHa) followed by hormone therapy on CRF for transgender adolescents. We aimed to 1) determine the effect of GnRHa monotherapy on CRF and mitochondrial function and associations with metabolomic profiles and 2) evaluate changes after 1 and 12 mo of testosterone therapy among transgender adolescents. Participants assigned female at birth (n = 19, baseline age of 15.0 ± 1.0 yr) from two groups: GnRHa+ (n = 8) and GnRHa- (n = 11) were examined at baseline and 1- and 12-mo post-testosterone therapy in a longitudinal observational study to assess cardiorespiratory fitness, mitochondrial respiration, and metabolic profile. Fasted morning labs included assessment of metabolomics and peripheral blood mononuclear cell mitochondrial respiration and degree of mitochondrial coupling (respiratory control ratio, RCR). A graded cycle ergometer test was performed. Baseline differences were evaluated between groups. Changes were compared with mixed linear regression models evaluating time (baseline, 1 mo, and 12 mo), group (GnRHa treatment yes/no), and their interaction. At baseline GnRHa+ individuals had higher relative V̇o2peak (30.1 ± 4.83 vs. 25.24 ± 4.47 mL/kg/min, P = 0.042) than GnRHa- individuals. In regression models, GnRHa+ individuals had a significant increase in peak watts (P = 0.011) and total exercise time (P = 0.005) after 12 mo of testosterone (P = 0.012) but not GnRHa- individuals. GnRHa+ individuals have significantly higher RCR under carbohydrate (P = 0.0007) and lipid (P = 0.0002) conditions than GnRHa+ individuals. Pretreatment with GnRHa positively influences peak CRF and mitochondrial respiration in adolescent transgender males undergoing testosterone therapy.NEW & NOTEWORTHY This study demonstrates differences in exercise capacity and mitochondrial respiration at baseline based on whether or not individuals had feminizing puberty blocked. Individuals who had puberty blocked had greater improvements in cardiopulmonary exercise testing parameters after 12 mo of testosterone than those who went through feminizing puberty.

Afatinib boosts CAR-T cell antitumor therapeutic efficacy via metabolism and fate reprogramming

BackgroundChimeric antigen receptor T (CAR-T) cell therapy has been shown remarkable efficacy in the treatment of hematological malignancies in recent years. However, a considerable proportion of patients would experience tumor recurrence and deterioration. Insufficient CAR-T cell persistence is the major reason for relapse. Multiple strategies to enhance the long-term antitumor effects of CAR-T cells have been explored and developed. In this study, we focused on tyrosine kinase inhibitors (TKIs), which have emerged immunomodulatory potential besides direct tumoricidal effects.MethodsHere, we screened 50 approved TKIs drugs and identified that afatinib (AFA) markedly enhanced the expressing of CD62L and inhibited reactive oxygen species level in T cells. And the underlying mechanisms of AFA medicating T cells were explored by detecting signal transduction, and metabolism pattern. Furthermore, we co-cultured AFA with CAR-T cells during the preparation stage and multianalyses of differentiation characteristics, metabolic profiling, and RNA sequencing revealed that AFA induce comprehensive metabolism remodeling and fate reprogramming. Based on it, we finally identified the antitumor efficacy of AFA-pretreatment CAR-T compared with negative-control CAR-T.ResultsWe identified that AFA blocked the T-cell receptor (TCR) and phosphoinositide 3-kinase-protein kinase B-mechanistic target of rapamycin signaling pathways, induced metabolic reprogramming and modulated T-cell differentiation. When combined with CAR-T cells, AFA inhibited the exhaustion and enhanced the persistence and cytotoxicity. Our results revealed that the pretreatment of AFA enables to boost CAR-T cells with strong antitumor cytotoxicity in leukemia mouse model.ConclusionsOur study systematically demonstrated that AFA pretreatment effectively enhanced CAR-T cells antitumor performance, which presents a novel optimization strategy for potent and durable CAR-T cell therapy.

Clinical Profile and Risk Factors for Complication of Type 2 Diabetes Mellitus at the National Referral Hospital, Bhutan: A Descriptive Cross-Sectional Study.

Globally, diabetes mellitus is a major public health concern affecting 10.5% of the population. Nearly 90% of these people have Type 2 diabetes mellitus (T2DM). In Bhutan, T2DM is prevalent in 5.6% of the population, and around 60% are unaware of their diagnosis of diabetes. There is no baseline information on the rate and the risk factors for complications of diabetes in Bhutan. The study assessed the clinical profile and the risk factors for complications of T2DM at the Jigme Dorji Wangchuk (JDW) National Referral Hospital, Bhutan. A descriptive cross-sectional study was conducted at the JDW National Referral Hospital, Bhutan, from January to December 2019. Patients with T2DM attending diabetic clinics were included in the study. Demographic variables and metabolic profiles were recorded using a standard pro forma. Descriptive statistics were used to express the results. The association of clinical profiles with the microvascular complication was assessed using multivariate logistic analysis with statistical significance at p < 0.05. There were 292 patients with T2DM during the study period. The rate of microvascular complication is around 25% in T2DM. Among the complications, diabetic retinopathy occurred in over 51%, followed by neuropathy (29.7%) and nephropathy (18.9%). Over 1/3rd of patients had a duration of diabetes over 10 years with a mean duration of 6.3 (5.4) years, and around 44% (127/292) of them had poor glycemic control (HbA1C ≥ 7%). The age ≥ 60 years and the duration of diabetes ≥ 10 years were independent risk factors for microvascular complications in T2DM patients. Regular exercise prevents retinopathy (OR 0.4, 95%CI 0.2-0.9, p = 0.026). There is a microvascular complication in 1 in 4 of type 2 diabetic patients. Age over 60 years and a duration of diabetes of more than 10 years are independent risk factors for microvascular complications, and regular exercise is preventive for microvascular complications.

Are subjective reports of exercise intensity accurate in recreational athletes?

Quantifying exercise intensity accurately is crucial for understanding links between cumulative exercise and cardiovascular outcomes. Exercise burden, the integral of intensity and duration is often estimated from subjective self-reports which have uncertain accuracy. We studied 40 endurance athletes (EA) 41 to 69 yrs. with >10 yrs. training history during a scripted outdoor 42 km cycling training session. Heart rate (HR) and power output (Watts) were continuously measured. Reports of perceived exertion (RPE) using a word (RPEWord) and numerical Borg scale (RPEBorg) were obtained during and 30 min. post ride and were related to cardiac (HR) and metabolic (MET·min) exercise endpoints. RPEs were highly variable, underestimating objective metrics of exercise intensity. Poor agreement was observed between either scale reported 30 minutes after exercise relative to heart rate: exercise RPEBorg vs. mean exercise HR and %HRpeak (both rs=.29, p=0.07), with no agreement between either scale vs. other objective endpoints. Agreement between RPEBorg and RPEWord was good during exercise (rs=0.86, 95% CI 0.75 to 0.92, P=0.001), but diminished post ride (rs=0.54, 95% CI 0.28 to 0.73, P=0.001). Different cardiac and metabolic profiles during exercise and a contrast between metabolic and cardiac burden was greater in less fit individuals as they accrued greater cardiac (14039±2649 vs. 11784±1132 HR·min, P<0.01) but lower metabolic (808±59 vs. 858±61 MET·min, P<0.05) burden vs. fitter EA. Caution is advised in interpreting MET·min and HR burden estimated from self-reports. Objective measurements of exercise intensity are required for detailed assessment of the risks and benefits of long-term exercise.

Taxonomic and metabolic characterisation of biofilms colonising Roman stuccoes at Baia’s thermal baths and restoration strategies

Stuccoes are very delicate decorative elements of Roman age. Very few of them survived almost intact to present days and, for this reason, they are of great interest to restorers and conservators. In this study, we combined metabarcoding and untargeted metabolomics to characterise the taxonomic and metabolic profiles of the microorganisms forming biofilms on the stuccoes located on the ceiling of the laconicum, a small thermal environment in the archaeological park of Baia (southern Italy). We found that some samples were dominated by bacteria while others by eukaryotes. Additionally, we observed high heterogeneity in the type and abundance of bacterial taxa, while the eukaryotic communities, except in one sample (at prevalence of fungi), were dominated by green algae. The metabolic profiles were comparable across samples, with lipids, lipid-like molecules and carbohydrates accounting for roughly the 50% of metabolites. In vitro and in vivo tests to remove biofilms on stuccoes using essential oils blends were successful at a 50% dilution for one hour and half. This integrative study advanced our knowledge on taxonomic and metabolic profiles of biofilms on ancient stuccoes and highlighted the potential impacts of these techniques in the field of cultural heritage conservation.

Clinical implications of dual therapy of acarbose plus myo-inositol on the thyroid profile in women with polycystic ovary syndrome

Context: Polycystic ovary syndrome (PCOS) and thyroid are the most common endocrine disorders affecting women of childbearing age, causing anovulation and infertility. There is an increased prevalence of thyroid dysfunction reported among PCOS women. Aims: To evaluate the benefits of acarbose plus myo-inositol therapy on the thyroid profile of PCOS. Methods: An open-labelled, parallel randomised clinical trial on 80 PCOS women based on inclusion and exclusion criteria was performed at the Department of Gynaecology, SRM Medical College Hospital and Research Centre, Kattankulathur. Institutional ethics committee approval and prior informed consent were obtained. The trial was registered in CTRI (No: CTRI/2022/04/041877). Group A (n = 38) received metformin 500 mg TID, and group B (n = 39) received acarbose 50 mg TID along with myoinositol 1000 mg BID. Assessment of metabolic and hormonal profile was done at baseline and at the end of six months. Results: Both groups showed significant reductions in luteinising hormone (p &lt;0.0001), total testosterone (p&lt;0.05), thyroid stimulating hormone (p&lt;0.05), fasting insulin (p&lt;0.05), and homeostatic model assessment for insulin resistance (p&lt;0.0001). The follicle-stimulating hormone was increased only in the metformin group. No significant changes in body mass index, free triiodothyronine, free tetraiodothyronine, and fasting glucose were observed in any group. Both therapies were safe, and no side effects or hypoglycaemia were recorded. Conclusions: In consideration of the beneficial effects of the study, we conclude that the administration of acarbose plus myo-inositol exerts positive effects on the thyroid and other endocrinological profiles in PCOS women.

Unravelling the Significance of Seed Proteomics: Insights into Seed Development, Function, and Agricultural Applications.

Seeds are essential for plant reproduction, ensuring species survival and dispersal while adapting to diverse environments throughout a plant's life. Proteomics has emerged as a powerful tool for deciphering the complexities of seed growth, germination, and stress responses. Advanced proteomic technologies enable the analysis of protein changes during germination, dormancy, and ageing, enhancing our understanding of seed lifespan and vitality. Recent studies have revealed detailed insights into metabolic processes and storage protein profiles across various plant species. This knowledge is crucial for improving seed storage, conserving quality, and maintaining viability. Additionally, it contributes to sustainable agriculture by identifying stress-responsive proteins and signalling pathways that can mitigate stress and enhance farming practices. This review highlights significant advancements in seed proteomics over the past decade, discussing critical discoveries related to storage proteins, protein interactions, and proteome modifications due to stress. It illustrates how these insights transform seed biology, boosting productivity, food security, and environmentally friendly practices. The review also identifies existing knowledge gaps and provides direction for future research, underscoring the need for continued interdisciplinary collaboration in this dynamic field.

Metabolic and Pharmacokinetic Profiling of an Exogenous Ketone Ester by Background SGLT2 Inhibitor Therapy in Heart Failure with Reduced Ejection

Metabolic and Pharmacokinetic Profiling of an Exogenous Ketone Ester by Background SGLT2 Inhibitor Therapy in Heart Failure with Reduced Ejection

The antisickling agent, 5-hydroxymethyl-2-furfural: Other potential pharmacological applications.

For the last two decades, the aromatic aldehyde 5-hydroxymethyl-furfural (5-HMF) has been the subject of several investigations for its pharmacologic potential. In 2004, the Safo group reported that 5-HMF has potent antisickling activity by targeting and ameliorating the primary pathophysiology of hypoxia-induced sickling of erythrocytes (red blood cells [RBC]). Following the encouraging outcome of the preclinical and phase I/II clinical studies of 5-HMF for the treatment of sickle cell disease (SCD), there have been multiple studies suggesting 5-HMF has several other biological or pharmacologic activities, including anti-allergic, antioxidant, anti-hypoxic, anti-ischemic, cognitive improvement, anti-tyrosinase, anti-proliferation, cytoprotective, and anti-inflammatory activities. The wide range of its effects makes 5-HMF a potential candidate for treating a variety of diseases including cognitive disorders, gout, allergic disorders, anemia, hypoxia, cancers, ischemia, hemorrhagic shock, liver fibrosis, and oxidative injury. Several of these therapeutic claims are currently under investigation and, while promising, vary in terms of the strength of their evidence. This review presents the research regarding the therapeutic potential of 5-HMF in addition to its sources, physicochemical properties, safety, absorption, distribution, metabolism, and excretion (ADME) profiles.

Depression in childhood to early adulthood and respiratory health in early adulthood.

Both depression and respiratory disease are common today in young populations. However, little is known about the relationship between them. This study aims to explore the association between depression in childhood to early adulthood and respiratory health outcomes in early adulthood, and the potential underlying mechanisms. A prospective study was conducted based on the Swedish BAMSE (Barn, Allergi, Miljö, Stockholm, Epidemiologi [Children, Allergy, Milieu, Stockholm, Epidemiology]) birth cohort (n = 4089). We identified clinically diagnosed depression through the dispensation of antidepressants, using national register data confirmed by self-reported diagnosis. At the 24-year follow-up, respiratory health was assessed via questionnaires and clinical evaluation. Metabolic and inflammatory profiles were analysed to explore potential mechanisms. Among the 2994 participants who provided study data, 403 (13.5%) had depression at any time point from around age 10 to 25 years. Depression was associated with higher risks of any chronic bronchitis symptoms (odds ratio = 1.58, 95% CI 1.21-2.06) and respiratory symptoms (odds ratio = 1.41, 95% CI 1.11-1.80) in early adulthood, independent of body mass index (BMI) and smoking status. Compared to individuals without depression, those with depression had a higher fat mass index (FMI (β = 0.48, 95% CI 0.22-0.74)) and increased blood levels of fibroblast growth factor 21 and Interleukin-6 in early adulthood. These markers together with FMI were found to partly mediate the association between depression and respiratory symptoms (total mediation proportion: 19.8 and 15.4%, respectively, P < 0.01). Depression in childhood to early adulthood was associated with an increased risk of respiratory ill-health in early adulthood, independently of smoking. Metabolic and inflammatory dysregulations may underlie this link.

Regional and ethnic factors of obesity and diabetes mellitus in women of re-productive age in the Pribaikal region

Introduction. Overweight is currently one of the leading global medical problems. Overweight and obesity contribute significantly to the development of diseases such as diabetes, cardiovascular disorder and can also cause premature death. Obesity has a negative impact on reproductive function; almost a quarter of women of childbearing age are overweight and about a third of them are obese.Aim. To study the characteristics of carbohydrate metabolism, hormonal indicators, and clinical-metabolic profiles, as well as to assess the potential risk of developing diabetes mellitus in women of fertile age with overweight and obesity residing in the Baikal region.Materials and methods. The study involved 60 overweight and obese women of reproductive age in the Pribaikalye region, including 33 women of Russian nationality (group 1) and 27 women of Buryat nationality (group 2). Anthropo-metric, sociodemographic and behavioural criteria were analysed, as well as questionnaires using the FINDRISC Scale. General clinical analyses of blood and urine were performed, lipid profile parameters, glucose, insulin, creatinine, transaminases, estradiol, thyroid hormone, leptin levels in blood plasma were studied. In addition, an oral glucose tolerance test was performed and the insulin resistance index (HOMA-IR) was calculated.Results. In the group of Buryat women with lower body weight as compared to Russians, higher levels of leptin, HOMA- IR index, and larger waist circumference are observed. In Buryat women, low physical activity makes a significant contribution to the development of overweight and obesity, while for Russian women, excessive caloric intake is more important. In accordance with the results of the FINDRISC scale survey, the greatest contribution to the potential development of diabetes mellitus in the Russian group is body mass index (weight), and in the Buryat group, in addition to these indicators, waist circumference and reduced physical activity.Conclusions. The results of the study will be of great help in the development of pro-grammes for the prevention of diabetes and obesity, taking into account regional and ethnic differences among the population.

Single cell atlas reveals multilayered metabolic heterogeneity across tumour types

Metabolic reprogramming plays a pivotal role in cancer progression, contributing to substantial intratumour heterogeneity and influencing tumour behaviour. However, a systematic characterization of metabolic heterogeneity across multiple cancer types at the single-cell level remains limited. We integrated 296 tumour and normal samples spanning six common cancer types to construct a single-cell compendium of metabolic gene expression profiles and identify cell type-specific metabolic properties and reprogramming patterns. A computational approach based on non-negative matrix factorization (NMF) was utilised to identify metabolic meta-programs (MMPs) showing intratumour heterogeneity. In-vitro cell experiments were conducted to confirm the associations between MMPs and chemotherapy resistance, as well as the function of key metabolic regulators. Survival analyses were performed to assess clinical relevance of cellular metabolic properties. Our analysis revealed shared glycolysis upregulation and divergent regulation of citric acid cycle across different cell types. In malignant cells, we identified a colorectal cancer-specific MMP associated with resistance to the cuproptosis inducer elesclomol, validated through in-vitro cell experiments. Furthermore, our findings enabled the stratification of patients into distinct prognostic subtypes based on metabolic properties of specific cell types, such as myeloid cells. This study presents a nuanced understanding of multilayered metabolic heterogeneity, offering valuable insights into potential personalized therapies targeting tumour metabolism. National Key Research and Development Program of China (2021YFA1300601). National Natural Science Foundation of China (key grants 82030081 and 81874235). The Shenzhen High-level Hospital Construction Fund and Shenzhen Basic Research Key Project (JCYJ20220818102811024). The Lam Chung Nin Foundation for Systems Biomedicine.

Integrative network pharmacology and multi-omics to study the potential mechanism of Niuhuang Shangqing Pill on acute pharyngitis.

Niuhuang Shangqing Pill (NSP) is a renowned Chinese medicine prescription listed in the Chinese Pharmacopoeia (Edition 2020, volume 1) and is utilized in clinical practice for treating headaches and acute pharyngitis (AP) associated with "Shanghuo". Despite its widespread use, the pharmacological mechanism and bioactive components underlying NSP in treating AP remain unclear. This study delved into evaluate the alleviation effect of NSP on AP and explore the mechanisms by analyzing multi-omics. UHPLC-Q Exactive Orbitrap HRMS was employed for the chemical ingredients of NSP. Multiple compositions, targets and pathways involved in the treatment of AP with NSP were predicted by network pharmacology. Additionally, wistar rat model of AP induced by capsaicin was established to evaluate the anti-AP activity of NSP in vivo. The potential mechanism of NSP to improve AP was investigated by real-time PCR, pharyngeal transcriptome analysis, non-targeted metabolomics, immunofluorescence and western blot. 119 compounds were identified by UHPLC-Q Exactive Orbitrap HRMS. Both clinical data of Gene Expression Omnibus (GEO) and network pharmacology demonstrated that MAPK signaling pathway and TNF signaling pathway were the critical pathway for AP treatment. In rat model of AP induced by capsaicin, NSP demonstrated the ability to reduce the levels of IL-1β, TNF-α, IL-6, CGRP, SP, PGE2, COX-2 in serum. Moreover, Transcriptomics analysis comprehensively indicated that NSP regulated the MAPK signaling pathway, TNF signaling pathway, biosynthesis of phenylalanine, tyrosine and tryptophan, arachidonic acid metabolism in AP rats. Metabolomics analysis verified that NSP could rebalance arachidonic acid metabolism, biosynthesis of phenylalanine, tyrosine and tryptophan and regulate metabolic profiles. Multi-omics Correlation analysis exhibited that the relative expression of Tnfrsf1b was significantly negatively correlated with 12(S)-HPETE. Immunofluorescence, real-time PCR and western blot of pharyngeal tissue revealed that NSP inhibited the TNF/p38-MAPK/NF-κB signaling pathway. Additionally, in vitro study on RAW264.7 cells confirmed that NSP counteract LPS-induced inflammatory by inhibiting the TNF/p38-MAPK/NF-κB signaling pathway. Overall, NSP effectively ameliorated capsaicin-induced AP by modulating the arachidonic acid metabolism and TNF/p38-MAPK/NF-κB signaling pathway. NSP effectively ameliorated capsaicin-induced AP by modulating the arachidonic acid metabolism, biosynthesis of phenylalanine, tyrosine and tryptophan, as well as the TNF/p38-MAPK/NF-κB signaling pathway.

LED lighting affects maturation, conversion and metabolic profile of somatic embryos derived from Kelussia odoratissima Mozaff

LED lighting affects maturation, conversion and metabolic profile of somatic embryos derived from Kelussia odoratissima Mozaff

Banxia Baizhu Tianma Decoction alleviates pentylenetetrazol-induced epileptic seizures in rats by preventing neuronal cell damage and apoptosis and altering serum and urine metabolic profiles

Banxia Baizhu Tianma Decoction alleviates pentylenetetrazol-induced epileptic seizures in rats by preventing neuronal cell damage and apoptosis and altering serum and urine metabolic profiles

A brief harvesting-freezing delay significantly alters the kidney metabolome and leads to false positive and negative results.

Abnormalities in distinct metabolic pathways have been associated with the pathogenesis and progression of many forms of kidney disease. Metabolomics analyses can be used to determine organ-specific metabolic fingerprints and, ideally, should represent the metabolic state of the organ at the exact moment the sample is harvested. However, conventional harvesting methods depend on posteuthanasia tissue harvest, which results in ischemia conditions and metabolome changes that could potentially introduce artifacts into the final studies. We recently optimized a modified clamp-freezing technique for rodent kidney harvesting and freezing, significantly reducing ischemia and freezing times and granting a closer snapshot of in vivo metabolism. In this study, we characterized and compared the metabolome of kidneys harvested using our modified approach versus traditional techniques to determine which metabolites are preferentially affected by a brief lapse of ischemia and freezing delay and which are more stable. We used Sprague-Dawley rats as a model of wild-type (WT) kidneys and PCK [polycystic kidney disease (PKD)] rats as a model of chronic kidney disease kidneys. Finally, we compared the metabolic profile of clamp-frozen and delayed WT and PKD kidneys to determine which metabolic changes are most likely observed in vivo in PKD and which could be subjected to false positive or negative results. Our data indicate that a short harvesting-freezing delay is sufficient to impart profound metabolic changes in WT and PKD kidneys, leading to false positive and negative differences when comparing these genotypes. In addition, we identified a group of metabolites that were more stable. Interestingly, while the delay had a similar effect between WT and PKD, there were notable differences. The data obtained indicate that the quick clamp-freezing technique for kidney metabolomics provides a more accurate interpretation of the in vivo metabolic changes associated with the disease state. NEW & NOTEWORTHY Our study shows that a brief harvesting-freezing delay associated with organ collection and freezing can significantly alter the kidney metabolic profile of both male and female wild-type and a genetic model of chronic kidney disease. Importantly, given that the effect of this delay differs among genotypes, it is not safe to assume that equally delaying harvesting-freezing in wild-type and polycystic kidney disease kidneys adequately controls this effect, ultimately leading to false positive and negative results among different renal diseases.

The loss-of-function of AtNATA2 enhances AtADC2-dependent putrescine biosynthesis and priming, improving growth and salinity tolerance in Arabidopsis.

Putrescine (Put) is a promising small molecule-based biostimulant to enhance plant growth and resilience, though its mode of action remains unclear. This study investigated the Put priming effect on Arabidopsis mutant lines (Atadc1, Atadc2, Atnata1, and Atnata2) under control conditions and salinity to understand its role in regulating plant growth. The Atadc2 mutant, characterized by reduced endogenous Put levels, showed insensitivity to Put priming without growth enhancement, which was linked to significant imbalances in nitrogen metabolism, including a high Gln/Glu ratio. Contrarily, the Atnata2 mutant exhibited significant growth improvement and upregulated AtADC2 expression, particularly under Put priming, highlighting these genes' involvement in regulating plant development. Put priming enhanced plant growth by inducing the accumulation of specific polyamines (free, acetylated, conjugated, or bound form) and improving light-harvesting efficiency, particularly in the Atnata2 line. Our findings suggest that AtNATA2 may negatively regulate Put synthesis and accumulation via AtADC2 in the chloroplast, impacting light harvesting in photosystem II (PSII). Furthermore, the Atadc2 mutant line exhibited upregulated AtADC1 but reduced AcPut levels, pointing to a cross-regulation among these genes. The regulation by AtNATA2 on AtADC2 and AtADC2 on AtADC1 could be crucial for plant growth and overall stress tolerance by interacting with polyamine catabolism, which shapes the plant metabolic profile under different growth conditions. Understanding the regulatory mechanisms involving crosstalk between AtADC and AtNATA genes in polyamine metabolism and the connection with certain SMBBs like Put can lead to more effective agricultural practices, improving plant growth, nitrogen uptake, and resilience under challenging conditions.

Multimorbidity patterns and socioeconomic conditions: Association with functional limitations in older adults

This study evaluated the association between multimorbidity patterns and socioeconomic conditions with functional limitation in individuals aged 60 years or older from the State of Minas Gerais, Brazil. This was a cross-sectional study with data from the last National Health Survey. Dependent variables were functional limitations in basic (BADL) and instrumental activities of daily living (IADL). The independent variables were multimorbidity patterns and socioeconomic conditions. Multimorbidity patterns were defined using an exploratory factor analysis. The association between multimorbidity patterns and dependent variables was tested using logistic regression models adjusted for covariates. Multimorbidity patterns were associated with limitations in BADL and IADL, except for the metabolic profile for IADL. Individuals with higher income had lower chances of being limited in BADL. Older adults with a higher level of education and income had lower chances of limitation in IADL. Multimorbidity patterns and socioeconomic conditions were associated with limitations in BADL and IADL.