Biochemical Pathways Research Articles

An update on nonsteroidal anti-inflammatory drug-induced urticaria.

Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (HR-NSAIDs) are common adverse events related to the widespread use of over-the-counter NSAIDs for the treatment of a variety of inflammatory conditions. Urticaria is the most commonly reported immediate cutaneous clinical sign of HR-NSAIDs, but it can be a manifestation of pathophysiologically different clinical entities that require different therapeutic strategies. The aim of this study is to ease the identification of the correct phenotype of HR-NSAIDs in patients reporting urticaria associated with the intake of NSAIDs and provide updated information about their diagnosis and management. The study is a narrative review conducted by collecting the most relevant and up-to-date data related to the classification, pathophysiology, severity, and prognosis of NSAID hypersensitivity reactions. PubMed and Embase scientific databases were used as search engines to select relevant articles. Patients developing HR-NSAIDs can be divided into two categories: selective responders (SR), who develop reactions after the administration of a single specific NSAID due to an underlying IgE or T-cell mediated hypersensitivity mechanism, or cross-intolerant (CI), who develop reactions to more than one chemically unrelated NSAIDs due to abnormalities in the biochemical pathways related with prostaglandin metabolism, independently from an underlying immunological mechanism. Five major different categories of HR-NSAIDs have been identified: NSAIDs-exacerbated cutaneous disease (NECD), NSAIDs-induced urticaria/angioedema with/without respiratory and systemic symptoms of anaphylaxis (NIUAA), and NSAIDs-exacerbated respiratory disease (NERD), which are developed by CI patients, and single NSAIDs-induced urticaria, angioedema and/ or anaphylaxis (SNIUAA) and single NSAIDs-induced delayed hypersensitivity reactions (SNIDHR), which are developed by CI patients. In vivo and in vitro diagnostic tests have rarely been shown to be reliable in all these entities and therefore are not routinely used in clinical practice. The management in SR patients consists of strict avoidance of the culprit drug, while for cross-intolerance reactions oral tolerance tests with safe alternative drugs (e.g. weak COX-1 inhibitors or selective COX-2 inhibitors) can be performed. HR-NSAIDs are being observed with increasing frequency, however, the pathogenesis behind some NSAIDS-associated clinical entities is still unclear. Diagnosis is mostly based on a thorough clinical history and confirmed by a drug challenge test. Clinical management is based on strict avoidance and use of alternative tolerated medications. Overall, all therapeutic decisions depend on the correct identification of the type of reaction the patient experienced.

Influence of epinephrine reactivity to stress on meat quality in goats

Abstract The magnitude of physiological responses to a stressor can vary among individual goats within a herd; however, whether these differences can differentially affect meat quality is not known. This study was conducted to determine the influence of the magnitude of epinephrine response (ER) to acute stress on muscle metabolome and meat quality in goats. Male Spanish goats (6 mo old) were transported for 180 min. (N = 75 goats; 25 goats/day) to impose stress. Blood samples were obtained after transport for analysis of physiological responses. Goats were slaughtered using humane procedures and samples were collected for muscle metabolomics and meat quality analyses. The data obtained from blood and muscle/meat analysis were then categorized based on epinephrine concentrations into low (LE), medium (ME), and high (HE) epinephrine response groups (n = 12/ER group). The physiological and meat quality variables were analyzed as a Completely Randomized Design in SAS, and metabolomics data were analyzed using R software. Plasma glucose concentrations were significantly high in the HE group, low in the LE group, and intermediate in the ME group (P < 0.05). However, leukocyte counts and cortisol, norepinephrine, blood urea nitrogen, and creatine concentrations were not different among the ER groups. Muscle (Longissimus dorsi) glycogen concentrations (15 min postmortem) were significantly higher (P < 0.05) in the ME and LE groups than in the HE group. However, postmortem Longissimus muscle pH and temperature (15 min and 24 h), 24 h calpastatin and desmin levels, and rib chop color (L*, a*, and b*), cooking loss, and Warner-Bratzler shear force values were unaffected by ER. Targeted metabolomics analysis of Longissimus muscle (15 min) revealed that diacyl phosphatidylcholines (C38:0; 40:6) and sphingomyelin (C20:2) were significantly different (P < 0.05) among the ER groups, with the concentrations of these metabolites being consistently high in the LE group. These differential muscle metabolite concentrations suggest that ER can influence biochemical pathways associated with cell membrane integrity and signaling. Epinephrine response had a significant effect on dopamine concentrations, with the levels increasing with increasing levels of ER. The results indicate that differences in epinephrine reactivity can influence selected physiological responses and muscle metabolites; however, it does not significantly influence meat quality attributes.

Oxidative stress and dermocosmetics

Oxidative stress is quite a significant form of attack on the skin as it is considered one of the most important factors that causes skin aging. The article attempts to understand oxidative stress in the skin through in vitro studies targeting various biochemical pathways. In addition, cosmetic ingredients are described with the aim of both preventing oxidative stress on the skin as well as maintaining and enhancing the essential biological functions of the skin.

Stable isotope profiling and its potential applications to poultry sciences

Metabolomics is a bottom-up approach to studying metabolism in living cells, tissues, organoids, or even whole organisms. In conjunction with genomics and proteomics, it is a crucial tool for better understanding complex biological systems. In comparison to genomics or proteomics, metabolomics more directly reflects the phenotype since it encompasses events that occur downstream of gene expression. In the field of poultry or avian diseases, this method is now well established, although it could have more innovative applications in the future. For example, 13C-guided metabolomics and flux analysis could be used to identify biochemical pathways associated with heat or immune stress. It could also help to explore the effects of alternatives to antimicrobials on the intestinal health of poultry and their action on avian pathogens, including the mechanisms of resistance and persistence. In this review, we discuss some basic principles of metabolomics and its current and potential applications in poultry.

Exploring Vitamin D Synthesis and Function in Cardiovascular Health: A Narrative Review

Vitamin D plays a crucial role in the human body, influencing a wide range of physiological processes from bone health to immune function. The complex biochemical pathways involved in the synthesis, metabolism, and action of Vitamin D are explored, emphasizing its importance in nutrition and food technology. This review also investigates the regulatory mechanisms that control Vitamin D metabolism and its systemic effects on calcium homeostasis, cell proliferation, differentiation, and immune modulation. The role of Vitamin D3 in regulating blood pressure and atherosclerosis in the onset of cardiovascular disorders is discussed. Given the importance of Vitamin D in food science and technology, the regulatory mechanisms that control Vitamin D metabolism and its systemic effects on calcium homeostasis are also investigated, integrating innovative approaches and advanced technologies to improve human health through nutrition. Additionally, the review assesses the influence of food processing on Vitamin D levels and discusses cutting-edge technologies as innovative strategies to mitigate Vitamin D loss during food processing. This comprehensive exploration aims to improve our understanding of the biochemical pathways of Vitamin D and its relevance to food science, contributing to the development of new strategies for food fortification and the promotion of optimal health through diet.

Defense Pathways of Wheat Plants Inoculated with Zymoseptoria tritici under NaCl Stress Conditions: An Overview

Due to being sessile, plants develop a broad range of defense pathways when they face abiotic or biotic stress factors. Although plants are subjected to more than one type of stress at a time in nature, the combined effects of either multiple stresses of one kind (abiotic or biotic) or more kinds (abiotic and biotic) have now been realized in agricultural lands due to increases in global warming and environmental pollution, along with population increases. Soil-borne pathogens, or pathogens infecting aerial parts, can have devastating effects on plants when combined with other stressors. Obtaining yields or crops from sensitive or moderately resistant plants could be impossible, and it could be very difficult from resistant plants. The mechanisms of combined stress in many plants have previously been studied and elucidated. Recent studies proposed new defense pathways and mechanisms through signaling cascades. In light of these mechanisms, it is now time to develop appropriate strategies for crop protection under multiple stress conditions. This may involve using disease-resistant or stress-tolerant plant varieties, implementing proper irrigation and drainage practices, and improving soil quality. However, generation of both stress-tolerant and disease-resistant crop plants is of crucial importance. The establishment of a database and understanding of the defense mechanisms under combined stress conditions would be meaningful for the development of resistant and tolerant plants. It is clear that leaf pathogens show great tolerance to salinity stress and result in pathogenicity in crop plants. We noticed that regulation of the stomata through biochemical applications and some effort with the upregulation of the minor gene expressions indirectly involved with the defense mechanisms could be a great way to increase the defense metabolites without interfering with quality parameters. In this review, we selected wheat as a model plant and Zymoseptoria tritici as a model leaf pathogen to evaluate the defense mechanisms under saline conditions through physiological, biochemical, and molecular pathways and suggested various ways to generate tolerant and resistant cereal plants.

Exploring chitin: novel pathways and structures as promising targets for biopesticides.

Chitin, the most prevalent polymer in nature, a significant structural polysaccharide that comes in second only to cellulose. Chitin is a crucial component of fungal cell walls and also present in many other creatures, such as viruses, plants, animals, insect exoskeletons, and crustacean shells. Chitin presents itself as a promising target for the development of biopesticides. It focuses on unraveling the unique structures and biochemical pathways associated with chitin, aiming to identify vulnerabilities that can be strategically leveraged for effective and environmentally sustainable pest control. It involves a comprehensive analysis of chitinase enzymes, chitin biosynthesis, and chitin-related processes across diverse organisms. By elucidating the molecular intricacies involved in chitin metabolism, this review seeks to unveil potential points of intervention that can disrupt essential biological processes in target pests without harming non-target species. This holistic approach to understanding chitin-related pathways aims to inform the design and optimization of biopesticides with enhanced specificity and reduced ecological impact. The outcomes of this study hold great promise for advancing innovative and eco-friendly pest management strategies. By targeting chitin structures and pathways, biopesticides developed based on these findings may offer a sustainable and selective alternative to conventional chemical pesticides, contributing tothe ongoing efforts towards more environmentally conscious and effective pest control solutions.

High-throughput nanopore DNA sequencing of large insert fosmid clones directly from bacterial colonies.

Fosmids and cosmids are vectors frequently used in functional metagenomic studies. With a large insert capacity (around 30 kb) they can encode dozens of cloned genes or in some cases, entire biochemical pathways. Fosmids with cloned inserts can be transferred to heterologous hosts and propagated to enable screening for new enzymes and metabolites. After screening, fosmids from clones with an activity of interest must be de novo sequenced, a critical step toward the identification of the gene(s) of interest. In this work, we present a new approach for rapid and high-throughput fosmid sequencing directly from Escherichia coli colonies without liquid culturing or fosmid purification. Our sample preparation involves fosmid amplification with phi29 polymerase and then direct nanopore sequencing using the Oxford Nanopore Technologies system. We also present a bioinformatics pipeline termed "phiXXer" that facilitates both de novo read assembly and vector trimming to generate a linear sequence of the fosmid insert. Finally, we demonstrate the accurate sequencing of 96 fosmids in a single run and validate the method using two fosmid libraries that contain cloned large insert (~30-40 kb) genomic or metagenomic DNA.IMPORTANCELarge-insert clone (fosmids or cosmids) sequencing is challenging and arguably the most limiting step of functional metagenomic screening workflows. Our study establishes a new method for high-throughput nanopore sequencing of fosmid clones directly from lysed Escherichia coli cells. It also describes a companion bioinformatic pipeline that enables de novo assembly of fosmid DNA insert sequences. The devised method widens the potential of functional metagenomic screening by providing a simple, high-throughput approach to fosmid clone sequencing that dramatically speeds the pace of discovery.

Ferroptosis inducers – erastin and analogues (review)

Introduction. Improving the efficacy of chemotherapy is a non-trivial task of modern oncology. Its successful solution requires knowledge in many fields, including physiology, pathology, clinical oncology, pharmacology and others. The search for small molecules that selectively kill tumor cells led to the accidental discovery of erastin.Text. Erastin is a unique molecule that has a quinazoline fragment in its structure. Not so long ago it became known that the antitumour effect of this compound is due to the induction of ferroptosis – an iron-dependent form of cell death caused by lipid peroxidation. Erastin is able to induce ferroptosis through various biochemical pathways, including blocking of cystine-glutamate transport channel of cell membrane and potential-dependent anion channel of mitochondria, as well as activation of p53 protein.Conclusion. Pharmacological induction of ferroptosis by erastin and its analogues represents a promising direction in cancer chemotherapy. In addition, erastin and its analogues are able to increase sensitivity to chemotherapy and radiation therapy, which allows us to talk about the possibility of their use in the combined treatment of malignant neoplasms.

PDIA3 driven STAT3/PD-1 signaling promotes M2 TAM polarization and aggravates colorectal cancer progression.

This inquiry endeavors to delineate the influence of PDIA3 on tumor-associated macrophages within the realm of colorectal malignancies, whilst elucidating the intrinsic biochemical pathways. Leveraging bioinformatics, we scrutinized the symbiosis between PDIA3, STAT3, and CD274. A xenograft model in immunodeficient murine served to assess PDIA3's impact on colorectal carcinogenesis. Further, Western blot analysis quantified the protein expression of PDIA3, p-STAT3, PD-1, XBP-1, assorted enzymes, and IL-6. Moreover, in vitro assays gauged SW480 cellular dynamics inclusive of migration, invasive potential, and proliferation. Bioinformatics exploration exposed PDIA3's elevated presence in diverse cancers, with a marked expression in colorectal cancer, as per TCGA and GEO repositories. Correlative studies showed PDIA3 positively aligning with STAT3 and CD274, the latter also associated with monocyte-derived macrophages. Comparative analysis of colorectal neoplasms and normal colon samples unveiled heightened levels of PDIA3 markers which, when overexpressed in SW480 cells, escalated tumorigenicity and oncogenic behaviors, with a noted decrease upon PD-1 monoclonal antibody intervention. PDIA3 augments the M2 polarization of tumor-associated macrophages via modulation of the STAT3/PD-1 cascade, thus invigorating the tumorous proliferation and dissemination in colorectal cancer. Such revelations position PDIA3 as an auspicious target for PD-1 blockade therapeutics, offering a promising foundation for rectifying colorectal carcinoma.

Sleeve Gastrectomy is Associated with Longitudinal Improvements in Lung Function and Patient-Reported Respiratory Outcomes.

Obesity exerts negative effects on pulmonary function through proven mechanical and biochemical pathways. Multiple studies have suggested that bariatric surgery can improve lung function. However, the timing of these effects on lung function and its association with patient reported outcomes is not known. A prospective cohort study of patients undergoing laparoscopic sleeve gastrectomy (LSG) at a tertiary care hospital was undertaken. Spirometry tests, laboratory tests, and self-reported questionnaires on asthma symptoms and asthma control (ACQ and ACT) were administered. All data were recorded pre-operatively (T0) and every 3 months post-operatively for 1 year (T3, T6, T9, T12) and were compared using a mixed-models approach for repeated measures. For the 23 participants, mean age was 44.2 ± 12.3 years, mean BMI was 45.2 ± 7.2 kg/m2, 18(78%) were female, 9(39%) self-reported as non-white and 6(26%) reported to have asthma. Following LSG, % total body weight loss was significant at all follow-up points (P < 0.0001). Rapid improvement in forced expiratory volume (FEV)% predicted and forced vital capacity (FVC)% predicted was seen at T3. Although the overall ACQ and ACT score remained within normal range throughout the study, shortness of breath declined significantly at 3 months post-op (P < 0.05) and wheezing resolved for all patients by twelve months. Patients also reported reduced frequency of sleep interruption and inability to exercise by the end of the study (P < 0.05). Improvements in objective lung function assessments and patient-reported respiratory outcomes begin as early as 3 months and continue until 12 months after sleeve gastrectomy.

From fairy rings to fairy chemicals: The story from nature phenomenon to commercial application

AbstractFairy rings are naturally occurring phenomena that are circular or curved clusters of mushrooms that appear in meadows, forests, and other places. In recent decades, significant progress has been made in deciphering fairy chemicals (FCs) involved in the intricate crosstalk between mushrooms and plants. FCs contain three chemical components: 2‐azahypoxanthine (AHX), 2‐aza‐8‐oxohypoxanthine (AOH), and imidazole‐4‐carboxamide (ICA). FCs can enhance the plant's resistance to environmental stresses such as cold, heat, and salt, and can increase crop yields; In addition, it can also have biological activities such as skin barrier improvement, anti‐ageing, and anti‐tumour. This review systematically integrated multiple facets of FCs, encompassing their discovery, the biochemical synthesis pathways giving rise to FCs, the derivatives and compounds originated from FCs, and their emerging applications in agriculture, beauty industry and medical sciences. Moreover, the review also addresses outstanding questions in FCs and future challenges related to plant growth regulators and other compounds, promising a practical and innovative future in agriculture.

КОФЕЙНАЯ КИСЛОТА СТИМУЛИРУЕТ СВЕЧЕНИЕ МИЦЕЛИЯ ВЫСШИХ ГРИБОВ NEONOTHOPANUS NAMBI, ARMILLARIA BOREALIS IN VIVO

In vivo experiments have shown that the addition of caffeic acid to the luminous mycelia of the higher fungi Neonothopanus nambi and Armillaria borealis stimulates a rapid and significant (by an order of magnitude or more) increase in the intensity of their light emission. It has been suggested that the observed effect of fungal luminescence activation may be mediated by the oxidation of caffeic acid by enzymes of the ligninolytic complex of basidiomycetes (in particular, by peroxidases) with the emission of visible light quanta. Comparative in vivo experiments showed that the addition of hispidin (the precursor of luciferin in the light emission reaction of higher fungi) did not affect the intensity of bioluminescence of the mycelia. At the same time, in vitro studies found that caffeic acid significantly suppressed the NADPH-hispidin-activated emission reaction of luminescent systems isolated from the mycelia of N. nambi and A. borealis. The inhibitory effect of caffeic acid is considered and discussed in the work from the standpoint of the classical biochemistry concept on enzyme inhibition by the reaction product according to the negative feedback principle. In general, the results obtained develop and supplement the understanding of the mechanisms of light emission in higher fungi and testify in favor of the fact that the generation of visible light quanta in basidiomycetes can be carried out by different biochemical pathways involving different enzymes (or enzyme systems). Clarifying the mechanism of stimulation of in vivo bioluminescence of higher fungi by caffeic acid is a priority for further research.

Metabolomic profiling of Prader-Willi syndrome compared with essential obesity

IntroductionPrader-Willi syndrome (PWS) is a rare disease, which shows a peculiar clinical phenotype, including obesity, which is different from essential obesity (EOB). Metabolomics might represent a valuable tool to reveal the biochemical mechanisms/pathways underlying clinical differences between PWS and EOB. The aim of the present (case-control, retrospective) study was to determine the metabolomic profile that characterizes PWS compared to EOB.MethodsA validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) targeted metabolomic approach was used to measure a total of 188 endogenous metabolites in plasma samples of 32 patients with PWS (F/M = 23/9; age: 31.6 ± 9.2 years; body mass index [BMI]: 42.1 ± 7.0 kg/m2), compared to a sex-, age- and BMI-matched group of patients with EOB (F/M = 23/9; age: 31.4 ± 6.9 years; BMI: 43.5 ± 3.5 kg/m2).ResultsBody composition in PWS was different when compared to EOB, with increased fat mass and decreased fat-free mass. Glycemia and HDL cholesterol were higher in patients with PWS than in those with EOB, while insulinemia was lower, as well as heart rate. Resting energy expenditure was lower in the group with PWS than in the one with EOB, a difference that was missed after fat-free mass correction. Carrying out a series of Tobit multivariable linear regressions, adjusted for sex, diastolic blood pressure, and C reactive protein, a total of 28 metabolites was found to be associated with PWS (vs. non-PWS, i.e., EOB), including 9 phosphatidylcholines (PCs) ae, 5 PCs aa, all PCs aa, 7 lysoPCs a, all lysoPCs, 4 acetylcarnitines, and 1 sphingomyelin, all of which were higher in PWS than EOB.ConclusionsPWS exhibits a specific metabolomic profile when compared to EOB, suggesting a different regulation of some biochemical pathways, fundamentally related to lipid metabolism.

Requirements for the biogenesis of [2Fe-2S] proteins in the human and yeast cytosol

The biogenesis of iron-sulfur (Fe/S) proteins entails the synthesis and trafficking of Fe/S clusters, followed by their insertion into target apoproteins. In eukaryotes, the multiple steps of biogenesis are accomplished by complex protein machineries in both mitochondria and cytosol. The underlying biochemical pathways have been elucidated over the past decades, yet the mechanisms of cytosolic [2Fe-2S] protein assembly have remained ill-defined. Similarly, the precise site of glutathione (GSH) requirement in cytosolic and nuclear Fe/S protein biogenesis is unclear, as is the molecular role of the GSH-dependent cytosolic monothiol glutaredoxins (cGrxs). Here, we investigated these questions in human and yeast cells by various in vivo approaches. [2Fe-2S] cluster assembly of cytosolic target apoproteins required the mitochondrial ISC machinery, the mitochondrial transporter Atm1/ABCB7 and GSH, yet occurred independently of both the CIA system and cGrxs. This mechanism was strikingly different from the ISC-, Atm1/ABCB7-, GSH-, and CIA-dependent assembly of cytosolic-nuclear [4Fe-4S] proteins. One notable exception to this cytosolic [2Fe-2S] protein maturation pathway defined here was yeast Apd1 which used the CIA system via binding to the CIA targeting complex through its C-terminal tryptophan. cGrxs, although attributed as [2Fe-2S] cluster chaperones or trafficking proteins, were not essential in vivo for delivering [2Fe-2S] clusters to either CIA components or target apoproteins. Finally, the most critical GSH requirement was assigned to Atm1-dependent export, i.e. a step before GSH-dependent cGrxs function. Our findings extend the general model of eukaryotic Fe/S protein biogenesis by adding the molecular requirements for cytosolic [2Fe-2S] protein maturation.

AFB1 Toxicity in Human Food and Animal Feed Consumption: A Review of Experimental Treatments and Preventive Measures.

The current review aims to outline and summarize the latest research on aflatoxin, with research studies describing natural, herbal and chemical compound applications in animal (pig) models and in vitro cellular studies. Aflatoxin, a carcinogenic toxin metabolite, is produced by Aspergillus flavus in humid environments, posing a threat to human health and crop production. The current treatment involves the prevention of exposure to aflatoxin and counteracting its harmful toxic effects, enabling survival and research studies on an antidote for aflatoxin. To summarize current research prospects and to outline the influence of aflatoxin on animal forage in farm production, food and crop processing. The research application of remedies to treat aflatoxin is undergoing development to pinpoint biochemical pathways responsible for aflatoxin effects transmission and actions of treatment. To underline the environmental stress of aflatoxin on meat and dairy products; to describe clinical syndromes associated with aflatoxicosis on human health that are counteracted with proposed treatment and preventive interventions. To understand how to improve the health of farm animals with feed conditions.

Aerobic anoxygenic phototrophs play important roles in nutrient cycling within cyanobacterial Microcystis bloom microbiomes

BackgroundDuring the bloom season, the colonial cyanobacterium Microcystis forms complex aggregates which include a diverse microbiome within an exopolymer matrix. Early research postulated a simple mutualism existing with bacteria benefitting from the rich source of fixed carbon and Microcystis receiving recycled nutrients. Researchers have since hypothesized that Microcystis aggregates represent a community of synergistic and interacting species, an interactome, each with unique metabolic capabilities that are critical to the growth, maintenance, and demise of Microcystis blooms. Research has also shown that aggregate-associated bacteria are taxonomically different from free-living bacteria in the surrounding water. Moreover, research has identified little overlap in functional potential between Microcystis and members of its microbiome, further supporting the interactome concept. However, we still lack verification of general interaction and know little about the taxa and metabolic pathways supporting nutrient and metabolite cycling within Microcystis aggregates.ResultsDuring a 7-month study of bacterial communities comparing free-living and aggregate-associated bacteria in Lake Taihu, China, we found that aerobic anoxygenic phototrophic (AAP) bacteria were significantly more abundant within Microcystis aggregates than in free-living samples, suggesting a possible functional role for AAP bacteria in overall aggregate community function. We then analyzed gene composition in 102 high-quality metagenome-assembled genomes (MAGs) of bloom-microbiome bacteria from 10 lakes spanning four continents, compared with 12 complete Microcystis genomes which revealed that microbiome bacteria and Microcystis possessed complementary biochemical pathways that could serve in C, N, S, and P cycling. Mapping published transcripts from Microcystis blooms onto a comprehensive AAP and non-AAP bacteria MAG database (226 MAGs) indicated that observed high levels of expression of genes involved in nutrient cycling pathways were in AAP bacteria.ConclusionsOur results provide strong corroboration of the hypothesized Microcystis interactome and the first evidence that AAP bacteria may play an important role in nutrient cycling within Microcystis aggregate microbiomes.Bqr2Xubb8cMPqvNydLEaxMVideo

Relationship between Plasma Lipid Profile and Cognitive Status in Early Alzheimer Disease.

Alzheimer disease (AD) is a heterogeneous and complex disease in which different pathophysiological mechanisms are involved. This heterogenicity can be reflected in different atrophy patterns or clinical manifestations. Regarding biochemical pathways involved in early AD, lipid metabolism plays an important role; therefore, lipid levels have been evaluated as potential AD diagnosis biomarkers, and their levels could be related to different AD clinical manifestations. Therefore, the aim of this work is to study AD lipid profiles from early AD patients and evaluate their clinical significance. For this purpose, untargeted plasma lipidomic analysis was carried out in early AD patients (n = 31) diagnosed with cerebrospinal fluid (CSF) biomarkers. Cluster analysis was carried out to define early AD subgroups according to the lipid levels. Then, the clinical significance of each lipid profile subgroup was studied, analyzing differences for other variables (cognitive status, CSF biomarkers, medication, comorbidities, age, and gender). The cluster analysis revealed two different groups of AD patients. Cluster 1 showed higher levels of plasma lipids and better cognitive status than Cluster 2. However, no differences were found for the other variables (age, gender, medication, comorbidities, cholesterol, and triglycerides levels) between both groups. Plasma lipid levels could differentiate two early AD subgroups, which showed different cognitive statuses. However, further research with a large cohort and longitudinal study evaluating the clinical evolution of these patients is required. In general, it would involve a relevant advance in the knowledge of AD pathological mechanisms, potential treatments, and precision medicine.

Metabolic network analysis of pre-ASD newborns and 5-year-old children with autism spectrum disorder

Classical metabolomic and new metabolic network methods were used to study the developmental features of autism spectrum disorder (ASD) in newborns (n = 205) and 5-year-old children (n = 53). Eighty percent of the metabolic impact in ASD was caused by 14 shared biochemical pathways that led to decreased anti-inflammatory and antioxidant defenses, and to increased physiologic stress molecules like lactate, glycerol, cholesterol, and ceramides. CIRCOS plots and a new metabolic network parameter, V°\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\dot{{{\\boldsymbol{V}}}}\\!$$\\end{document}net, revealed differences in both the kind and degree of network connectivity. Of 50 biochemical pathways and 450 polar and lipid metabolites examined, the developmental regulation of the purine network was most changed. Purine network hub analysis revealed a 17-fold reversal in typically developing children. This purine network reversal did not occur in ASD. These results revealed previously unknown metabolic phenotypes, identified new developmental states of the metabolic correlation network, and underscored the role of mitochondrial functional changes, purine metabolism, and purinergic signaling in autism spectrum disorder.

Salivary Metabolites Produced by Oral Microbes in Oral Diseases and Oral Squamous Cell Carcinoma: A Review.

In recent years, salivary metabolome studies have provided new biological information and salivary biomarkers to diagnose different diseases at early stages. The saliva in the oral cavity is influenced by many factors that are reflected in the salivary metabolite profile. Oral microbes can alter the salivary metabolite profile and may express oral inflammation or oral diseases. The released microbial metabolites in the saliva represent the altered biochemical pathways in the oral cavity. This review highlights the oral microbial profile and microbial metabolites released in saliva and its use as a diagnostic biofluid for different oral diseases. The importance of salivary metabolites produced by oral microbes as risk factors for oral diseases and their possible relationship in oral carcinogenesis is discussed.