Metrics details one of the most common autoimmune diseases and the leading cause of hypothyroidism is linked to metabolic and cellular dysfunctions that contribute to disease aetiopathogenesis This case-control study aimed to identify potent metabolic biomarkers of HT employing machine learning techniques 62 euthyroid patients with HT and 58 healthy individuals were included from the metabolic biomarkers in Hashimoto’s thyroiditis and psoriasis (METHAP) clinical trial Quantification of 73 metabolites was performed using gas-chromatography/mass spectrometry in plasma and urine samples of fasted participants microbiome and lipid metabolism were identified in the HT group Ordinary least squares and beta regression modeling associated the presence of HT with methylmalonic acid myristoleic acid and total saturated fatty acids Artificial neural network analysis had good predictive accuracy with an AUC of 0.8 while debiased sparse partial correlation network analysis identified metabolite-metabolite interactions distinct for HT These findings provide insights into novel biomarkers associated with HT and we discuss their biological relevance and clinical significance Hashimoto’s thyroiditis is associated with mitochondrial dysfunction and carbohydrate and fatty acids dysfunctional metabolism Considering the large number of studies demonstrating distinct metabolic imbalances and cellular dysfunctions in HT this study aimed to define the metabolic imprint of HT using a comprehensive panel of metabolites as markers There is a pressing need to seek sensitive biomarkers that capture the metabolic state of patients with HT and reflect the underlying metabolic disturbances Metabolism is a complex network of thousands of metabolites that might be a marker of specific metabolic blocks we analyzed the changes of metabolites participating in key cellular metabolism and function pathways we measured the levels of urine organic acids and plasma fatty acids in human samples of patients with HT and compared them to age and sex-matched healthy individuals a total of 200 individuals were recruited at the Heraklion University Hospital in Crete and the Health Clinic for Autoimmune and Chronic Diseases in Athens with the contribution from private practices in Athens to reach the required number of participants For the purpose of this case-control study 62 patients with HT and 58 age and sex-matched healthy individuals were included Potential participants were first screened by an endocrinologist to assess whether the patients met the following criteria: Inclusion criteria for all participants: 18–60 years old non-lactating or pregnant women and non-athletes Inclusion criteria for Hashimoto’s thyroiditis: Presence of anti-thyroid antibodies and gray-scale findings Exclusion criteria for Hashimoto’s thyroiditis: Individuals having undergone complete thyroidectomy with malignant or congenital goiter Exclusion criteria for the control group: Participants with acute or chronic disease receiving medication Participants were verbally informed of the study objectives they were requested to read and sign the informed consent Baseline measurements include TSH levels for both groups and FT3 participants were requested to fill in a form to record demographic data alcohol consumption (number of glasses/week) while their dietary habits were recorded through the Mediterranean Diet Score (MDS) Metabolomic profiling was performed in both groups using targeted metabolomics and the study conformed to the EU General Data Protection Regulation (GDPR) Research was performed in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards The present study has received approval by the Research Ethics Committee of the University of Crete (AP 147/10072020) An informed consent was obtained from all participants.This research received no external funding Fasted participants were requested to collect urine samples in a sterilized container Peripheral blood was collected on the same day and time to ensure minimal day-to-day or daytime metabolite fluctuations using a K2-ethylene diamino tetra-acetic EDTA-containing vacuum blood collection tube Plasma isolation was performed by centrifuge at 1500×g at 4 °C Urine and plasma samples were aliquoted and then stored at − 80 °C and − 20 °C until analysis and up to 24 h to ensure minimal metabolite degradation Concentrations of organic acids are reported in relation to creatinine levels we estimated the ratio of product metabolite to reactant metabolite to assess the function of specific enzymes The ANN model employed was a feed-forward neural network trained using the error backpropagation algorithm The receiver operating characteristic (ROC) curve was utilized to evaluate the model’s accuracy which aligns with established methods for assessing model performance a Debiased sparse partial correlation (DSPC) network analysis was employed in both groups DSPC enables the computation of partial correlation coefficients and their p values while facilitating the identification of underlying connectivity patterns among numerous metabolic features Main central tendency measures were also estimated such as the degree of centrality and the betweenness In the present study, 120 participants were analyzed, including 62 patients with Hashimoto’s thyroiditis and 58 individuals in the control group who were matched for age and gender. The population characteristics are summarized in Table 1 The two groups exhibited similar characteristics in terms of demographics TSH levels were within the normal range for both groups with no statistical significance between them Differential metabolite expression in HT patients: Up: fold change analysis of the organic acid metabolic compounds Corrected false discovery rate (Wilcoxon test Colored dots indicate significantly different variables which estimates the group variable and age as statistically significant factors at 90% and 95% levels of significance It has to be noted that the interpretation of coefficients within the beta regression framework diverges from that of a conventional linear model the exponentiation of coefficients in this context yields the odds ratios for a one-unit increase in a given predictor variable All the models used had a slight positive autocorrelation (DW < 2) but the collinearity diagnostics revealed a lack of multicollinearity The graphical examination of the standardized residuals revealed that the hypothesis of normality and homoscedasticity was held in all the models above Receiver operating characteristics (ROC) curve for the ability of a specific combination of biomarkers to identify patients with Hashimoto’s disease. “0” represents the control group; “1” represents the HT cases. Neural network architecture used as a predictive model A debiased sparse partial correlation (DSPC) network of OA and TFA metabolites of Hashimoto's disease while the edges symbolize the association measures between them The thickness of the edges corresponds to the strength of these associations providing a visual indication of their relative importance The network employs color coding to differentiate between positive (red lines) and negative (blue lines) there is an increasing need to define the metabolic imbalances of HT to provide early detection and targeted treatment in addition to thyroid hormone replacement therapy The present study identified differentially expressed urine organic acids and plasma fatty acids in euthyroid patients with HT compared to healthy individuals 3-hydroxybutyric acid and fumaric: succinic ratio were markedly different between case and control groups adjusting for confounding variables dihomo-gamma-linolenic acid (C20:3n6) and total saturated fatty acids (SFA) were all higher in the HT group compared to control we discuss our findings by grouping the tested metabolites according to their biological relevance given the underlying metabolic interconnections the present study validates these findings in the population of euthyroid patients with HT using MMA which is regarded as a more sensitive biomarker for functional vitamin B12 insufficiency preliminary findings indicated a possible change in 4-hydroxyphenylpyruvic acid (4-HPPA) levels among individuals with HT the statistical significance of this hypothesis was not confirmed in the regression model potentially due to the limited sample size Further research with a larger sample size is needed to investigate the relationship between 4-HPPA and HT more comprehensively and determine its clinical significance considering the central role of antioxidants in the fine-tuning of the immune system and the findings of this study attention should be given to the marginal micronutrient deficiencies of HT patients and the use of sensitive biomarkers for their detection we assessed SDH activity by measuring the fumaric acid: succinic acid ratio and found it was significantly lower in the HT group indicating a reduced enzymatic activity and accumulation of the reactant succinic acid Riboflavin (vitamin B2) acts as an important cofactor for ETC and the function of SDH in particular suggesting a potential role of marginal vitamin B2 deficiency in HT the two groups had similar adherence scores to the Mediterranean Diet suggesting a disrupted metabolism of endogenous fatty acids in the HT group rather than an increased intake of SFA reduced sensitivity in capturing inter-individual differences Another parameter to assess the non-difference in fatty acids intake was the levels of the essential fatty acids linoleic acid and a-linoleic acid which are exclusively obtained through diet and were similar between the two groups (p = 0.248 and 0.475 respectively) indicating that more sophisticated techniques could be employed without compromising the primary results’ generality Factors such as patient heterogeneity and variability in other parameters influence these estimations studies often include 30–50 patients per treatment group which aligns closely with the sample size utilized in the present investigation the implementation of ANN analytical techniques in this study demonstrates their applicability to targeted metabolomics data careful consideration of sample size and strategies to address overfitting are essential to optimize their effectiveness in medical research contexts this study provides a detailed report of the differences between organic and fatty acids between Hashimoto and healthy individuals generating a novel hypothesis that needs further exploration we applied more stringent approaches in predictive modeling and regression analysis to explore the potency of certain metabolites as predictive biomarkers and identified an improved combination that reached fairly good predictive accuracy the present study identified certain borderline significant metabolites participating in central metabolic pathways A possible explanation for the mild differences observed is that these metabolic networks are supplied by numerous metabolic pathways to maintain cellular function and counterbalance metabolic dysfunctions at different stages the interpretation of metabolomic findings needs to be done with caution assessing them within the context of metabolic networks rather than as single markers such as DSPC and others employed in the present and previous studies are expected to shed light on these borderline significance differences and especially their association with related phenotypical traits such as dysfunctional TCA with fatigue in Hashimoto although patients’ medical history was obtained and individuals with severe acute or chronic disease were excluded routine biochemical and blood count testing would clarify potential clusters within the group Age and BMI were different in females with HT compared to control and although these variables did not affect the detected association between HT and the selected metabolic biomarkers subgroup analysis using a larger sample size would provide in-depth insight into these associations An in-depth subgroup analysis could reveal essential heterogeneities within the analyzed dataset a comprehensive separate subgroup analysis was not conducted in this study OLS regression with age and gender as predictors was performed to provide preliminary insights into potential subgroup effects a complete subgroup analysis would necessitate either separate data analysis for each gender and age group or the generation of a regression model with interaction terms (age_group x Gender) An additional limitation of this study is the absence of analyses pertaining to population differences across regions or ethnic groups which may restrict the generalizability of our findings to broader populations it is suggested that a more comprehensive population-specific analysis for distinct groups (Caucasians people of African descent etc.) could be the focus of future research the above points limit the generalizability of the present study’s findings to other populations Hashimoto’s thyroiditis is characterized by metabolic complications affect the patient’s overall health and quality of life we identified markers of mitochondrial dysfunction carbohydrate and fatty acids metabolism malfunction and microbiome imbalance in HT Early detection and monitoring of the underlying metabolic dysfunctions are critical in the decision-making process to achieve low levels of thyroid destruction and hormonal regulation targeted strategies can significantly contribute to the alleviation of the pro-inflammatory status and the metabolic burden of HT The dataset is available upon reasonable request from the corresponding authors Is a normal TSH synonymous with ‘euthyroidism’ in levothyroxine monotherapy? An update on the pathogenesis of Hashimoto’s thyroiditis Enhanced oxidative stress in Hashimoto’s thyroiditis: Inter-relationships to biomarkers of thyroid function Metabolic characteristics of Hashimoto’s thyroiditis patients and the role of microelements and diet in the disease management—An overview and inflammatory factors in patients with autoimmune thyroid disease Metabolic pressure and the breach of immunological self-tolerance The association of subclinical insulin resistance with thyroid autoimmunity in euthyroid individuals The relationships between the gut microbiota and its metabolites with thyroid diseases Thyroid-gut-axis: How does the microbiota influence thyroid function? Immunomodulatory actions of vitamin D in various immune-related disorders: A comprehensive review Immunomodulatory function of vitamin D and its role in autoimmune thyroid disease Five serum fatty acids are associated with subclinical hypothyroidism in a Chinese pregnant population Serum metabolomic patterns in patients with autoimmune thyroid disease Metabolic profiling of organic and fatty acids in chronic and autoimmune diseases Targeted metabolomic analysis of serum fatty acids for the prediction of autoimmune diseases Prediction of autoimmune diseases by targeted metabolomic assay of urinary organic acids Classification of some test of normality techniques into UMP and LMP using Monte Carlo simulation technique James-Stein type estimators in beta regression model: Simulation and application Autoimmune comorbidities in Hashimoto’s thyroiditis: Different patterns of association in adulthood and childhood/adolescence Autoimmune mechanisms in pernicious anaemia and thyroid disease Relationship of tobacco smoking with serum vitamin B12 folic acid and haematological indices in healthy adults Exploring the impact of cigarette smoke extracts on vitamin B12: Insights into the transformation of methylcobalamin and hydroxycobalamin to cyanocobalamin through in vitro evaluation Mechanism of enzymic formation of homogentisate from p-hydroxyphenylpyruvate Metabolomic profile overlap in prototypical autoimmune humoral disease: A comparison of myasthenia gravis and rheumatoid arthritis and zinc in benign thyroid diseases and of selenium in malignant thyroid diseases: Low selenium levels are found in subacute and silent thyroiditis and in papillary and follicular carcinoma Effect of micronutrients on thyroid parameters Assessment of vitamin concentrations in patients with Hashimoto’s thyroiditis and their relationships with thyroid function and anthropometric parameters—A preliminary study Martínez-Reyes, I. & Chandel, N. S. Mitochondrial TCA cycle metabolites control physiology and disease. Nat. Commun. 11(1), 1–11. https://doi.org/10.1038/s41467-019-13668-3 (2020) “Ferrocrinology”—Iron Is an important factor involved in gluco- and lipocrinology Mechanisms of insulin resistance in humans and possible links with inflammation Succinate-to-fumarate ratio as a new metabolic marker to detect the presence of SDHB/D-related paraganglioma: Initial experimental and ex vivo findings Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages Structure and function of biotin-dependent carboxylases Influence of intestinal flora on the elimination of phenylacetic acid in urine Intestinal microbiota regulates the gut-thyroid axis: The new dawn of improving Hashimoto thyroiditis Serotonin: A potent immune cell modulator in autoimmune diseases The dopaminergic system in autoimmune diseases Mitochondrial functions modulate neuroendocrine and transcriptional responses to acute psychological stress Effects of thyroid hormones on lipid metabolism pathologies in non-alcoholic fatty liver disease Fatty acid status in infancy is associated with the risk of type 1 diabetes-associated autoimmunity The association between serum palmitic acid and thyroid function ER stress contributes to high-fat diet-induced decrease of thyroglobulin and hypothyroidism Palmitic acid downregulates thyroglobulin (Tg) and thyroperoxidase (TPO) in human primary thyrocytes: A potential mechanism by which lipotoxicity affects thyroid? The influence of nutritional intervention in the treatment of Hashimoto’s thyroiditis—A systematic review Logistic regression and artificial neural network classification models: A methodology review Artificial neural networks for small dataset analysis MetSizeR: Selecting the optimal sample size for metabolomic studies using an analysis based approach Trivedi, D. K., Hollywood, K. A. & Goodacre, R. Metabolomics for the masses: The future of metabolomics in a personalized world. New Horiz. Transl. Med. 3(6), 294–305. https://doi.org/10.1016/j.nhtm.2017.06.001 (2017) Multiple-testing correction in metabolome-wide association studies and transformations: Improving the biological information content of metabolomics data Critical evaluation of the questionnaires assessing adherence to the Mediterranean diet that are based on servings Download references The authors would like to thank all the administrative technical and medical staff of the Laboratory of Toxicology of the University of Crete the University Hospital of Heraklion and the Metabolomic Medicine health clinic for their dedicated involvement in this study The study was supported by Metabolomic Medicine and European Institute of Molecular Medicine Laboratory of Toxicology and Forensic Sciences Evangelia Sarandi & Aristidis Tsatsakis Health Clinics for Autoimmune and Chronic Diseases Evangelia Sarandi & Dimitris Tsoukalas Clinic of Endocrinology and Metabolic Disorders Laboratory of Health Economics and Management (LabHEM) National and Kapodistrian University of Athens Efstathia Paramera & Evangelos Papakonstantinou SK and AT conceived and designed the present study as part of a PhD ES and CL collected patient data and samples of the participants EvP and AT were responsible for the methodological and experimental procedures statistical analysis and preparation of figures and tables were performed by ES and VF DT and GR and was critically reviewed by CL All authors have read and reviewed the final manuscript is the scientific director at Metabolomic Medicine There is no further financial relationship between the study investigators The rest of the authors declare no competing interest Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Below is the link to the electronic supplementary material Download citation DOI: https://doi.org/10.1038/s41598-025-89600-1 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology The Sarandí canal in Argentina turned blood red last week Officials suspect a toxic substance used in dyes has entered the waterway A canal in Argentina turned blood red last week and started producing a foul smell Officials are still investigating the incident but early reports suggest that a toxic substance used in dyes may have entered the waterway "It looks like a stream of blood; we have never seen it like this," María Ducomls The neighborhood along the canal hosts tanneries and other industries that turn animal skin into leather. Parts of the Sarandí also border a nature reserve, German broadcaster GW News reported Related: Earth from space: Golden river of toxic waste spills out from deadly mining disaster in South Africa Get the world’s most fascinating discoveries delivered straight to your inbox —Earth from space: Pakistan's 'bleeding ink' lagoon brings life to harsh desert environment —Earth from space: Crimea's 'putrid sea' creates beautiful rainbow of color but smells like rotten eggs The department said it sent a mobile analysis lab to Sarandí and collected 0.4 gallons (2 liters) of water for chemical analysis and liquid chromatography which separates components in a mixture — in this case the department thought a colorant was responsible for the water's red hue "It is thought to be some kind of organic colouring," the department said Officials continue to investigate the source of the incident Patrick PesterSocial Links NavigationTrending News WriterPatrick Pester is the trending news writer at Live Science His work has appeared on other science websites such as BBC Science Focus and Scientific American Patrick retrained as a journalist after spending his early career working in zoos and wildlife conservation He was awarded the Master's Excellence Scholarship to study at Cardiff University where he completed a master's degree in international journalism He also has a second master's degree in biodiversity evolution and conservation in action from Middlesex University London Patrick investigates the sale of human remains you will then be prompted to enter your display name Corryvreckan whirlpool: Scotland's 'raging cauldron' that is named after a Norse king and said to house a witch Atlantic ocean currents are weakening — and it could make the climate in some regions unrecognizable Science news this week: International blackouts and 'T Videos from a suburb of Argentina’s capital of Buenos Aires showing a bright red river has drawn international attention and reignited local fears of chemical dumping Local residents told Argentinian news outlet C5N that this is not the first time an odd color has been seen in the Sarandí River which use chemicals to turn animal skins into leather “My husband left our house and said that it was all red," one local woman told C5N with an acidic smell that hurts our throat." The Argentinian Environment Ministry said they have taken water samples from the river to determine the cause of the water’s color change on Thursday, according to the BBC Officials from the Avellaneda municipality suspect the presence of aniline in water samples taken on Friday morning, according to LA NACION Aniline is a toxic substance that is used in dyes and medicines Officials said they had lodged a complaint to the Buenos Aires province water authority Maria Ducomls told LA NACION the water has been tainted in various colors many times “It's been brown and all types of oils show up at the top [of the water].” Ducomls also said residents have been lodging complaints regarding the contaminated river but have been repeatedly been told there is no reason to worry Images show the Sarandi River's water with an intense color red flowing into an estuary Reach him at fernando.cervantes@gannett.com and follow him on X @fern_cerv_ Please enable JS and disable any ad blocker A small town outside of Buenos Aires, Argentina woke up to a blood red sight on Feb. 6, 2025, when the Sarandí Canal appeared bright red. Officials in the Buenos Aires neighborhood of Avellaneda worried that the color change may have been the result of a toxic spill Unfortunately for residents and the creatures that call the area home this isn't the first time the Sarandí Canal has undergone a dramatic color change Keep reading to learn more about what is going on with the Argentina canal that turned red, and what locals say is behind the water's macabre hue Residents of Avellaneda were left reeling after discovering that the canal that ran along their homes had turned crimson It's important to note the location is in a mixed residential and industrial area of Buenos Aires The residents spoke to the Associated Press about the terrifying scene in their backyards, explaining they were frightened by the waterway's awful smell and peculiar color "It looks like a stream of blood; we have never seen it like this," a woman named María Ducomls told the publication Folks like Ducomls feared the worst after getting a look at the water, assuming that the change had been brought about by a toxic chemical spill. That's likely due to the Sarandí's proximity to massive industrial buildings that serve as tanneries, and even one that processes toxic waste Officials are still searching for answers after retrieving samples from the water According to initial testing performed by a mobile lab that collected samples on-site it appeared that the blood red color was the result of a dye that had been added to the water According to the New York Post, locals believe this may have been the result of factories along the canal dumping chemicals or dyes into the canal which flows into the larger body of water known as the Río de la Plata Despite the shock from some residents, others say this isn't the first time they've seen the Sarandí change colors. According to the BBC, A woman who went by the name Silvia said that while the canal was currently red, "other times it was yellow, with an acidic smell that makes us sick even in the throat." Ducomls told the DW News something similar, claiming that local industrial companies had been known to dump waste in the canal you don't have to be an inspector to see how much pollution the poor Sarandí River suffers from," she continued Unfortunately, it doesn't seem like Ducomls is exaggerating. A report from Infobae revealed that Buenos Aires had seen a 30% increase in accidents where toxic chemicals had been spilled Given that DW News states that the Sarandí also runs along portions of a nature reserve it seems even more important than ever that officials figure out a way to determine the cause of all of these spills so they can start working on a way to prevent them Here’s How Fracking Causes Water Pollution So It's Too Late to Clean up the Ocean, Scientists Say — What Happens Now? Avoid These PFAS Chemicals, or "Forever Chemicals" At All Costs Link to XLink to InstagramContact us by EmailOpt-out of personalized ads People may receive compensation for some links to products and services on this website Offers may be subject to change without notice A stream winding through a populous area on the outskirts of Buenos Aires has turned crimson red in recent hours sparking fears of industrial chemical dumping images shared by residents on social media showed Friday is home to tanneries and other industries that transform animal skins into leather using chemicals Images of the blood-red waterway captured by residents quickly spread on social media described waking early one recent morning to powerful odors we already had a special and hazardous waste incinerator spewing pollutants into the air,” she told The Associated Press “It looks like a stream of blood; we have never seen it like this,” she said Officials from the municipality of Avellaneda about 15 kilometers (9 miles) south of the Argentine capital a toxic substance used in dyes and medicines Get Tri-state area news delivered to your inbox with NBC New York's News Headlines newsletter they filed a complaint with the Buenos Aires province ministry of infrastructure and public services Residents report that the stream has exhibited various unusual colors in the past — gray blue and brown — often with an oily surface They say they have been filing complaints against local businesses since the 1990s with several cases of alleged environmental contamination still open Follow AP’s coverage of Latin America and the Caribbean at https://apnews.com/hub/latin-america Source:  TOI  Context: The Sarandí Stream near Buenos Aires turned crimson red raising concerns over industrial chemical contamination Google Map+ Google Map+ Google Map+ Google Map+ Google Map+ Google Map+ Insights IAS: Simplifying UPSC IAS Exam Preparation Contact Us: Call us at 080 69405205 (toll-free) Don't miss out on this amazing opportunity to participate in the Scholarship Test A stream winding through a densely populated area on the outskirts of Buenos Aires has turned a shocking crimson red in recent hours depicting the Sarandi stream’s eerie transformation A normally unremarkable stream in Argentina has taken on an alarming appearance leaving residents shocked and environmentalists concerned which is a tributary of the Rio de la Plata runs alongside numerous tanneries and other industries involved in processing animal hides into leather and many believe they are responsible for the disturbing discolouration of the water While the Sarandi stream has been known to exhibit unusual colours in the past—sometimes appearing oily or even violet—the vivid red hue has struck an especially alarming chord with residents and environmental activists described the overwhelming pollution in the area “It looks like a stream of blood; we have never seen it like this,” she added ALSO READ: Would You Try Snake Meat? This $7 Soup Packs Protein, Low Fat, And A Shocking Flavor! DETAILS INSIDE Industrial Pollution Strikes Sarandi Stream Again This incident is not the first time the Sarandi stream has raised environmental concerns The region has long struggled with pollution with industrial waste frequently contaminating the waterway Environmental groups have repeatedly called for stricter regulations and enforcement against industries that discharge untreated waste into local water sources Experts warn that the presence of hazardous chemicals in the water could pose severe risks to human health and local wildlife Given that the stream feeds into the Río de la Plata there is also concern about broader ecological consequences Authorities are expected to conduct water tests to determine the exact cause of the discolouration and whether it poses a health hazard environmental activists and local organisations are urging the government to enforce stricter pollution controls to prevent further contamination of the Sarandi stream and other vulnerable waterways ALSO READ: Mali Shocker: Over 50 People Killed In Gao City After Armed Assailants Ambushed Convoy And Army Escort The images of the blood-red stream have reignited public outcry over Argentina’s industrial pollution crisis Many hope that the shocking visuals will spur decisive action from both the government and industries to ensure that such environmental disasters do not become the norm Jagran English brings you all the latest and breaking news from India and around the world Follow english.jagran.com to stay updated with the latest English news The water of a stream in an industrial area in Argentina has turned red The Ministry of the Environment of the province of Buenos Aires has taken water samples to determine the cause of the discoloration of the Sarandí stream an official told the local television station Canal 13 Local residents have been complaining about the water pollution for years The stream is located in the municipality of Avellaneda on the outskirts of the capital Buenos Aires and flows into the River Río de la Plata There are numerous industrial plants in the area According to the Ministry of the Environment chemical analyses are to clarify which pollutants caused the discoloration Local residents compared the deep red color of the stream to a "river of blood" The drinking water also constantly comes out of the tap dirty and smelly Foul odors from the stream are now also normal the stream had already had different colors You don't have permission to access the page you requested What is this page?The website you are visiting is protected.For security reasons this page cannot be displayed Massive floods in Brazil’s southern Rio Grande do Sul state have killed at least 75 people over the last seven days At least 155 people were injured, while damage from the rains forced more than 88,000 people from their homes Approximately 16,000 took refuge in schools The floods left a wake of devastation, including landslides, washed-out roads and collapsed bridges across the state. Operators reported electricity and communications cuts. More than 800,000 people are without a water supply, according to the civil defense agency, which cited figures from water company Corsan. Get top local stories delivered to you every morning with NBC DFW's News Headlines newsletter. A rescue team pulled an elderly man in serious medical condition into a helicopter from a remote area in the Bento Gonçalves municipality, according to footage from military firefighters. Torrents of brown water poured over a nearby dam. On Saturday evening, residents in the town of Canoas stood up to their shoulders in muddy water and formed a human chain to pull boats carrying people to safety, according to video footage shared by local UOL news network. The Guaiba river reached a record level of 5.33 meters (17.5 feet) on Sunday morning at 8 a.m. local time, surpassing levels seen during a historic 1941 deluge, when the river reached 4.76 meters. “I repeat and insist: the devastation to which we are being subjected is unprecedented,” state Gov. Eduardo Leite said Sunday morning. He had previously said the state will need a “kind of ‘Marshall Plan’ to be rebuilt.” Brazilian President Luiz Inácio Lula da Silva visited Rio Grande do Sul for a second time on Sunday, accompanied by Defense Minister José Múcio, Finance Minister Fernando Haddad and Environment Minister Marina Silva, among others. The leftist leader and his team surveyed the flooded streets of Porto Alegre from a helicopter. “We need to stop running behind disasters. We need to see in advance what calamities might happen and we need to work,” Lula told journalists afterwards. During Sunday mass at the Vatican, Pope Francis said he was praying for the state’s population. “May the Lord welcome the dead and comfort their families and those who had to abandon their homes,” he said. The downpour started Monday and was expected to last through Sunday. In some areas, such as valleys, mountain slopes and cities, more than 300 millimeters (11.8 inches) of rain fell in less than a week, according to Brazil’s National Institute of Meteorology, known by the Portuguese acronym INMET, on Thursday. The heavy rains were the fourth such environmental disaster in the state in a year, following floods in July, September and November 2023 that killed 75 people. Weather across South America is affected by the climate phenomenon El Niño, a periodic, naturally occurring event that warms surface waters in the Equatorial Pacific region. In Brazil, El Niño has historically caused droughts in the north and intense rainfall in the south. This year, the impacts of El Niño have been particularly dramatic, with a historic drought in the Amazon. Scientists say extreme weather is happening more frequently due to human-caused climate change. “These tragedies will continue to happen, increasingly worse and more frequent,” said Suely Araújo, a public policy coordinator at the Climate Observatory, a network of dozens of environmental and social groups. Brazil needs to adjust to the effects of climate change, she said in a Friday statement, referring to a process known as adaptation. Volume 10 - 2023 | https://doi.org/10.3389/fmolb.2023.1201912 Psoriasis is a common inflammatory disease that affects mainly the skin the moderate to severe forms have been associated with several comorbidities metabolic syndrome and cardiovascular disease Keratinocytes and T helper cells are the dominant cell types involved in psoriasis development via a complex crosstalk between epithelial cells peripheral immune cells and immune cells residing in the skin Immunometabolism has emerged as a potent mechanism elucidating the aetiopathogenesis of psoriasis offering novel specific targets to diagnose and treat psoriasis early The present article discusses the metabolic reprogramming of activated T cells tissue-resident memory T cells and keratinocytes in psoriatic skin presenting associated metabolic biomarkers and therapeutic targets keratinocytes and activated T cells are glycolysis dependent and are characterized by disruptions in the TCA cycle the amino acid metabolism and the fatty acid metabolism Upregulation of the mammalian target of rapamycin (mTOR) results in hyperproliferation and cytokine secretion by immune cells and keratinocytes Metabolic reprogramming through the inhibition of affected metabolic pathways and the dietary restoration of metabolic imbalances may thus present a potent therapeutic opportunity to achieve long-term management of psoriasis and improved quality of life with minimum adverse effects Since different subsets of helper cells have been considered key players in psoriasis’ immunological pathways interest has increasingly been focused on elucidating the impact of metabolism on the immune system’s function of psoriasis patients could provide critical points for investigating how metabolic cellular reactions and processes may control immunity and inflammation offering novel tools for monitoring and managing immune-mediated diseases Given that emerging evidence suggests targeting specific metabolic events as a strategy to limit cutaneous inflammation this review will first focus on the potential mechanisms underlying the association between the metabolic reprogramming of the critical cell players and inflammatory skin responses of psoriasis Potential metabolic biomarkers and therapeutic anti-psoriatic approaches integrating immune/metabolic responses from the published literature are also summarized Psoriasis is widely regarded as a multifactorial immune-related disease triggered by environmental factors in the background of genetic predisposition Although the precise pathogenetic mechanisms have yet to be deciphered psoriasis seems to be controlled by endogenous and exogenous factors Although the exact role of HLA-C in psoriasis development remains unclear there seems to be an interplay/relation between HLA-Cw6 status and immune dysregulation in psoriasis patients While genetic factors are well documented in psoriasis such as mechanical skin trauma and inflammation the lack of adequate data and the specific role of autoantibodies in the inflammatory cascade that initiate psoriasis have stalled the unwinding progression to the disease etiology Metabolic derangements in T cells (top) and keratinocytes (bottom) in psoriasis Metabolic derangements in activated T cells aim to cover their needs in energy and substrates (enhanced glycolysis and downstream energy metabolism pathways T cells residing in the skin (such as memory T cells) rely on the uptake of lipids from the lipid-rich and low-glucose microenvironment Damaged keratinocytes upregulate glycolytic pathways to cover their proliferative demands as well (shown in bold) Activation of the mammalian target of the rapamycin (mTOR) pathway via the increased amino acid availability and the abundance of pro-inflammatory mediators facilitates the high proliferation and cytokine secretion by activated T cells and keratinocytes Increased influx of glucose and amino acids is facilitated by the overexpression of the respective transporters on the cell membrane of T cells and keratinocytes (shown in bold) Only primary substrates are shown for each transporter Gut microbiome deregulation and the aberrant production of microbial metabolites result in intestinal permeability activation of pro-inflammatory Th-17 cells and suppression of Tregs while it promotes the disruption of the epidermis integrity odium-coupled neutral amino acid transporter; TCA tissue-resident memory cells [Modified from (21)] GLUT1 might thus serve as an attractive therapeutic target in hyperproliferative skin diseases LAT-2 and LAT-3 transporters, responsible for transporting several other amino acids, support LAT-1 function by forming heterodimers with CD-98. Inhibition of the LAT-1 transporter in the IMQ animal model did not suppress epidermal proliferation indicating the compensatory role for other transporters of the LAT family (Cibrian et al., 2020b) our improved understanding of skin and T cell immunometabolism coupled with the interplay between metabolic and inflammatory pathways has led to significant progress in biomarker discovery paving the way for novel targeted treatments which will be discussed in the following sections Studies focusing on the metabolism of psoriasis have yielded insightful findings prompting researchers to investigate potential biomarkers that will deepen our knowledge of the complex relationship between metabolism and immune responses and serve as prognostic tools The field focused on the study of metabolism is metabolomics which as part of the other -omics sciences such as genomics and proteomics has multiple applications in basic research and biomarker discovery Metabolic biomarkers in psoriasis related to energy metabolism inflammation and insulin resistance and the gut microbiome 2-Ketoglutaric acid has been found to be higher in the serum of patients with psoriasis compared to healthy individuals but lower compared to psoriatic arthritis patients (Armstrong et al., 2014) 2-Ketoglutaric acid has a dual role as a TCA cycle intermediate and as a precursor of glutamate which is further metabolized to proline for collagen synthesis increasing 2- ketoglutaric acid may be due to an increased need for glutamine given the central role of this metabolite in multiple pathways a causal relationship has not been established requiring additional markers Metabolism of free fatty acids is mediated by carnitine, an amine that functions as a transporter of long-chain fatty acids to mitochondria for beta-oxidation. Carnitine also acts as a scavenger contributing to the clearance of amino acid metabolism intermediates. The binding of fatty acids to carnitine is mediated by carnitine palmitoyl transferase-1 (CPT-1). CPT-1 pharmacological suppression resulted in reduced production and survival of the skin TRM (Pan et al., 2017) Longitudinal studies of healthy populations with present metabolic dysfunctions will validate the predictive value of such biomarkers in psoriasis and reinforce the role of metabolic reprogramming in psoriasis Other studies on circulating levels of amino acids have identified downstream metabolites of the glutamine/glutamate pathway, the urea cycle, and the metabolism of tryptophan and phenylalanine, which, according to researchers, are implicated in the development of psoriatic lesions (Koussiouris et al., 2021) Qualitative and quantitative analysis of the metabolites related to gut dysbiosis would open a new path in biomarker discovery of psoriasis through the involvement of gut microbiota and novel metabolic therapeutic targets Current treatment approaches for psoriasis are mainly based on disease severity and the presence of psoriatic arthritis. In mild to moderate cases, treatment mainly includes topical anti-psoriatic agents, i.e., topical steroids, topical calcineurin inhibitors, vitamin D analogs, and retinoids), while, in severe cases, systemic, classical or biological therapies are usually required (Armstrong and Read, 2020) Several therapies targeting immunometabolism exist, including pharmacological agents with known anti-inflammatory properties that target metabolism, such as metformin, dimethyl fumarate and methotrexate, reviewed by Pålsson-McDermott and O’Neill (2020) novel targeted therapies are emerging based on immune cells’ and keratinocytes’ different metabolic demands The distinctive advantage of these therapeutic strategies lies in the selectivity of the drug against cells undergoing metabolic reprogramming which leaves normal cells unaffected and preserves tissue homeostasis (dietary) supplementation with n-3 fatty acids might be a helpful adjuvant in psoriasis treatment restoration of the microbial community can directly or indirectly benefit patients receiving therapy while gut microbiome biomarkers may serve as predictive markers of treatment selection Available study results on the efficacy of metabolic targeting of psoriasis can be grouped into four categories; Energy metabolism Targeting specific metabolic networks of affected cells in psoriasis to reprogram pro-inflammatory cells to their normal state is an attractive approach to increase efficacy and reduce relapse and side effects Therapeutic opportunities for psoriasis targeting metabolic pathways through pharmacological agents and supportive dietary recommendations Our understanding of the intertwined processes of metabolism cell function and immune responses in psoriasis is still growing metabolic disruptions in energy production pathways amino acids and lipids metabolism and dysbiosis seem to be common prompting us to look for novel diagnostic and therapeutic tools up-to-date studies have identified several metabolic biomarkers associated with the distinct metabolic fingerprint of psoriasis or associated metabolic complications such as IR These metabolic pathways can also be targeted through drug inhibitors to limit the immune response and keratinocyte hyperproliferation tailor-made nutritional plans to restore metabolic imbalances thus protecting unaffected cells and promoting anti-inflammatory and resolution pathways can contribute to the long-term control of psoriasis metabolomic studies have several limitations including the variability between studies due to the lack of a standardized method and study design that hampers reproducibility and interpretation of the findings different population characteristics and lack of validation datasets significantly stall the biomarker discovery process The metabolic rewiring of cells that promote inflammation and psoriasis progression to their normal state to resolve inflammation is an exciting yet growing field and future clinical trials are needed to investigate their application in human real life settings monitoring metabolic fluctuations as part of the early diagnosis of metabolic comorbidities prevention and treatment optimization has emerged as a powerful strategy for psoriasis and ongoing ventures report encouraging findings With the use of metabolic biomarkers to close monitor the response to treatment and overall metabolic health clinicians will be able to provide long-term therapy for psoriasis and prevention early diagnosis and treatment of related comorbidities Future studies in this direction should focus on longitudinal interventional studies to validate these biomarkers and large metabolomics studies to report differences across populations Supervision and editing of the final manuscript ES All authors contributed to the article and approved the submitted version The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential 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Krueger-Krasagakis, Tsoukalas, Sidiropoulou, Evangelou, Sifaki, Rudofsky, Drakoulis and Tsatsakis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Aristidis Tsatsakis, dHNhdHNha2FAdW9jLmdy; Evangelia Sarandi, ZXNhcmFuZGk2QGhvdG1haWwuY29t Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish (adsbygoogle = window.adsbygoogle || []).push({}); Joel Sonora has officially joined Argentina Primera Division side Arsenal de Sarandi on loan for the 2019-20 season The club announced on Thursday they’ve signed Sonora from 2 Sonora totaled 56 appearances for Stuttgart’s second team over three seasons #ArsenalFútbolClub Los mediocampistas Joel Soñora (@Sojoel1) y Diego Núñez firmaron sus respectivos contratos con el club y ya forman parte del plantel. Felicitaciones y éxitos !!! pic.twitter.com/vj7i6ttTrk — Arsenal Fútbol Club (@ArsenalOficial) August 1, 2019 The midfielder spent last season on loan as well with fellow Argentina top-flight side Talleres de Cordoba In 21 combined appearances between league and cup play Sonora scored one goal and registered two assists U-20 Men’s National Team at the 2015 FIFA U-20 World Cup He is the son of former Boca Juniors and later MLS player Diego Sonora His brother Alan is also playing domestically in Argentina with Independiente The brothers are expected to meet in league play on Sept Arsenal gained promotion back into the top-flight last season and are currently fourth in the Primera Division table after one matchday was wondering the same thing…..definitely an opportunity missed for that age group to continue to develop and gel together before Olympic Qualifying smh Dynamo had a player from there a decade ago who could only manage 10 appearances before leaving to bounce around between Argentine teams you’ve never heard of and the Italian Serie C/D Δdocument.getElementById( "ak_js_1" ).setAttribute( "value"