PubMed

BMJ Med. 2023 Oct 12;2(1):e000548. doi: 10.1136/bmjmed-2023-000548. eCollection 2023.ABSTRACTPolycystic ovary syndrome is characterised by excessive levels of androgens and ovulatory dysfunction, and is a common endocrine disorder in women of reproductive age. Polycystic ovary syndrome arises as a result of polygenic susceptibility in combination with environmental influences that might include epigenetic alterations and in utero programming. In addition to the well recognised clinical manifestations of hyperandrogenism and ovulatory dysfunction, women with polycystic ovary syndrome have an increased risk of adverse mental health outcomes, pregnancy complications, and cardiometabolic disease. Unlicensed treatments have limited efficacy, mostly because drug development has been hampered by an incomplete understanding of the underlying pathophysiological processes. Advances in genetics, metabolomics, and adipocyte biology have improved our understanding of key changes in neuroendocrine, enteroendocrine, and steroidogenic pathways, including increased gonadotrophin releasing hormone pulsatility, androgen excess, insulin resistance, and changes in the gut microbiome. Many patients with polycystic ovary syndrome have high levels of 11-oxygenated androgens, with high androgenic potency, that might mediate metabolic risk. These advances have prompted the development of new treatments, including those that target the neurokinin-kisspeptin axis upstream of gonadotrophin releasing hormone, with the potential to lessen adverse clinical sequelae and improve patient outcomes.PMID:37859784 | PMC:PMC10583117 | DOI:10.1136/bmjmed-2023-000548

J Agric Food Chem. 2023 Oct 19. doi: 10.1021/acs.jafc.3c04515. Online ahead of print.ABSTRACTThe gastrointestinal tract (GIT) is the target of assorted pathological conditions, and dietary components are known to affect its functionality and health. In previous in vitro studies, we observed that reducing sugars induced protein glycoxidation and impaired protein digestibility. To gain further insights into the pathophysiological effects of dietary sugars, Wistar rats were provided with a 30% (w/v) fructose water solution for 10 weeks. Upon slaughter, in vivo protein digestibility was assessed, and the entire GIT (digests and tissues) was analyzed for markers of oxidative stress and untargeted metabolomics. Additionally, the impact of sustained fructose intake on colonic microbiota was also evaluated. High fructose intake for 10 weeks decreased protein digestibility and promoted changes in the physiological digestion of proteins, enhancing intestinal digestion rather than stomach digestion. Moreover, at colonic stages, the oxidative stress was harmfully increased, and both the microbiota and the intraluminal colonic metabolome were modified.PMID:37859404 | DOI:10.1021/acs.jafc.3c04515

Comb Chem High Throughput Screen. 2023 Oct 5. doi: 10.2174/0113862073238503230924180432. Online ahead of print.ABSTRACTBACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is not only the top cause of liver diseases but also a hepatic-correlated metabolic syndrome. This study performed untargeted metabolomics analysis of NAFLD hamsters to identify the key metabolites to discriminate different stages of NAFLD.METHODS: Hamsters were fed a high-fat diet (HFD) to establish the NAFLD model with different stages (six weeks named as the NAFLD1 group and twelve weeks as the NAFLD2 group, respectively). Those liver samples were analyzed by untargeted metabolomics (UM) analysis to investigate metabolic changes and metabolites to discriminate different stages of NAFLD.RESULTS: The significant liver weight gain in NAFLD hamsters was observed, accompanied by significantly increased levels of serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Moreover, the levels of TG, LDL-C, ALT, and AST were significantly higher in the NAFLD2 group than in the NAFLD1 group. The UM analysis also revealed the metabolic changes; 27 differently expressed metabolites were detected between the NAFLD2 and NAFLD1 groups. More importantly, the levels of N-methylalanine, allantoin, glucose, and glutamylvaline were found to be significantly different between any two groups (control, NAFLD2 and NAFLD1). Receiver operating characteristic curve (ROC) curve results also showed that these four metabolites are able to distinguish control, NAFLD1 and NAFLD2 groups.CONCLUSION: This study indicated that the process of NAFLD in hamsters is accompanied by different metabolite changes, and these key differently expressed metabolites may be valuable diagnostic biomarkers and responses to therapeutic interventions.PMID:37859316 | DOI:10.2174/0113862073238503230924180432

Biomed Chromatogr. 2023 Oct 19:e5763. doi: 10.1002/bmc.5763. Online ahead of print.ABSTRACTAlisol B 23-acetate (AB23A) has been demonstrated to have beneficial effects on nonalcoholic steatohepatitis (NASH). However, the mechanisms of AB23A on NASH remain unclear. This study aimed to investigate the mechanisms underlying the metabolic regulatory effects of AB23A on NASH. We used AB23A to treat mice with NASH, which was induced by a methionine and choline deficient (MCD) diet. We initially investigated therapeutic effect and resistance to oxidation and inflammation of AB23A on NASH. Subsequently, we performed untargeted metabolomic analyses and relative validation assessments to evaluate the metabolic regulatory effects of AB23A. AB23A reduced lipid accumulation, ameliorated oxidative stress and decreased pro-inflammatory cytokines in the liver. Untargeted metabolomic analysis found that AB23A altered the metabolites of liver. A total of 55 differential metabolites and three common changed pathways were screened among the control, model and AB23A treatment groups. Further tests validated the effects of AB23A on modulating common changed pathway-involved factors. AB23A treatment can ameliorate NASH by inhibiting oxidative stress and inflammation. The mechanism of AB23A on NASH may be related to the regulation of alanine, aspartate and glutamate metabolism, d-glutamine and d-glutamate metabolism, and arginine biosynthesis pathways.PMID:37858975 | DOI:10.1002/bmc.5763

Toxicology. 2023 Oct 17:153652. doi: 10.1016/j.tox.2023.153652. Online ahead of print.ABSTRACTAflatoxin B1 (AFB1) is a fungal metabolite found in animal feeds and human foods. It is one of the most toxic and carcinogenic of aflatoxins and is classified as a Group 1 carcinogen. Dietary exposure to AFB1 and infection with chronic Hepatitis B Virus (HBV) make up two of the major risk factors for hepatocellular carcinoma (HCC). These two major risk factors raise the probability of synergism between the two agents. This review proposes some collaborative molecular mechanisms underlying the interaction between AFB1 and HBV in accelerating or magnifying the effects of HCC. The HBx viral protein of HBV is one of the main viral proteins of HBV and has many carcinogenic qualities that are involved with HCC. AFB1, when metabolized by CYP450, becomes AFB1-exo-8,9-epoxide (AFBO), an extremely toxic compound that can form adducts in DNA sequences and induce mutations. With possible synergisms that exist between HBV and AFB1 in mind, it is best to treat both agents simultaneously to reduce the risk by HCC.PMID:37858775 | DOI:10.1016/j.tox.2023.153652

Brain Behav Immun. 2023 Oct 17:S0889-1591(23)00316-1. doi: 10.1016/j.bbi.2023.10.016. Online ahead of print.ABSTRACTThe mechanism by which SARS-CoV-2 causes neurological post-acute sequelae of SARS-CoV-2 (neuro-PASC) remains unclear. Herein, we conducted proteomic and metabolomic analyses of cerebrospinal fluid (CSF) samples from 21 neuro-PASC patients, 45 healthy volunteers, and 26 inflammatory neurological diseases patients. Our data showed 69 differentially expressed metabolites and six differentially expressed proteins between neuro-PASC patients and healthy individuals. Elevated sphinganine, ST1A1, sphingolipid metabolism disorder, and attenuated inflammatory responses may contribute to the occurrence of neuro-PASC, whereas decreased levels of 7,8-dihydropterin and activation of steroid hormone biosynthesis may play a role in the repair process. Additionally, a biomarker cohort consisting of sphinganine, 7,8-dihydroneopterin, and ST1A1 was preliminarily demonstrated to have high value in diagnosing neuro-PASC. In summary, our study represents the first attempt to integrate the diagnostic benefits of CSF with the methodological advantages of multi-omics, thereby offering valuable insights into the pathogenesis of neuro-PASC and facilitating the work of neuroscientists in disclosing different neurological dimensions associated with COVID-19.PMID:37858739 | DOI:10.1016/j.bbi.2023.10.016

Biochim Biophys Acta Rev Cancer. 2023 Oct 17:188999. doi: 10.1016/j.bbcan.2023.188999. Online ahead of print.ABSTRACTRecent multi-omics studies, including proteomics, transcriptomics, genomics, and metabolomics have revealed the critical role of post-translational modifications (PTMs) in the progression and pathogenesis of Glioblastoma multiforme (GBM). Further, PTMs alter the oncogenic signaling events and offer a novel avenue in GBM therapeutics research through PTM enzymes as potential biomarkers for drug targeting. In addition, PTMs are critical regulators of chromatin architecture, gene expression, and tumor microenvironment (TME), that play a crucial function in tumorigenesis. Moreover, the implementation of artificial intelligence and machine learning algorithms enhances GBM therapeutics research through the identification of novel PTM enzymes and residues. Herein, we briefly explain the mechanism of protein modifications in GBM etiology, and in altering the biologics of GBM cells through chromatin remodeling, modulation of the TME, and signaling pathways. In addition, we highlighted the importance of PTM enzymes as therapeutic biomarkers and the role of artificial intelligence and machine learning in protein PTM prediction.PMID:37858622 | DOI:10.1016/j.bbcan.2023.188999

Mol Cell Endocrinol. 2023 Oct 17:112086. doi: 10.1016/j.mce.2023.112086. Online ahead of print.ABSTRACTThyroid hormones (THs) are crucial in bodily functions, while iron is essential for processes like oxygen transport. Specialized proteins maintain iron balance, including ferritin, transferrin, ferroportin, and hepcidin. Research suggests that THs can influence iron homeostasis by affecting mRNA and protein expression, such as ferritin and transferrin. Our study focused on male rats to assess mRNA expression of iron homeostasis-related proteins and metabolomics in thyroid dysfunction. We found altered gene expression across various tissues (liver, duodenum, spleen, and kidney) and identified disrupted metabolite patterns in thyroid dysfunction. These findings highlight tissue-specific effects of thyroid dysfunction on essential iron homeostasis proteins and provide insights into associated metabolic changes. Our research contributes to understanding the intricate interplay between thyroid hormones and iron balance. By unveiling tissue-specific gene expression alterations and metabolic disruptions caused by thyroid dysfunction, our work lays a foundation for future investigations to explore underlying mechanisms and develop targeted strategies for managing iron-related complications in thyroid disorders.PMID:37858610 | DOI:10.1016/j.mce.2023.112086

Cell Rep. 2023 Oct 12:113248. doi: 10.1016/j.celrep.2023.113248. Online ahead of print.ABSTRACTThe emergence of three highly pathogenic human coronaviruses-severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle Eastern respiratory syndrome (MERS)-CoV in 2012, and SARS-CoV-2 in 2019-underlines the need to develop broadly active vaccines against the Merbecovirus and Sarbecovirus betacoronavirus subgenera. While SARS-CoV-2 vaccines protect against severe COVID-19, they do not protect against other sarbecoviruses or merbecoviruses. Here, we vaccinate mice with a trivalent sortase-conjugate nanoparticle (scNP) vaccine containing the SARS-CoV-2, RsSHC014, and MERS-CoV receptor-binding domains (RBDs), which elicited live-virus neutralizing antibody responses. The trivalent RBD scNP elicited serum neutralizing antibodies against bat zoonotic Wuhan Institute of Virology-1 (WIV-1)-CoV, SARS-CoV, SARS-CoV-2 BA.1, SARS-CoV-2 XBB.1.5, and MERS-CoV live viruses. The monovalent SARS-CoV-2 RBD scNP vaccine only protected against Sarbecovirus challenge, whereas the trivalent RBD scNP vaccine protected against both Merbecovirus and Sarbecovirus challenge in highly pathogenic and lethal mouse models. This study demonstrates proof of concept for a single pan-sarbecovirus/pan-merbecovirus vaccine that protects against three highly pathogenic human coronaviruses spanning two betacoronavirus subgenera.PMID:37858337 | DOI:10.1016/j.celrep.2023.113248

Fluids Barriers CNS. 2023 Oct 19;20(1):74. doi: 10.1186/s12987-023-00473-w.ABSTRACTThe meninges surround the brain and spinal cord, affording physical protection while also serving as a niche of neuroimmune activity. Though possessing stromal qualities, its complex cellular and extracellular makeup has yet to be elaborated, and it remains unclear whether the meninges vary along the neuroaxis. Hence, studies were carried-out to elucidate the protein composition and structural organization of brain and spinal cord meninges in normal, adult Biozzi ABH mice. First, shotgun, bottom-up proteomics was carried-out. Prominent proteins at both brain and spinal levels included Type II collagen and Type II keratins, representing extracellular matrix (ECM) and cytoskeletal categories, respectively. While the vast majority of total proteins detected was shared between both meningeal locales, more were uniquely detected in brain than in spine. This pattern was also seen when total proteins were subdivided by cellular compartment, except in the case of the ECM category where brain and spinal meninges each had near equal number of unique proteins, and Type V and type III collagen registered exclusively in the spine. Quantitative analysis revealed differential expression of several collagens and cytoskeletal proteins between brain and spinal meninges. High-resolution immunofluorescence and immunogold-scanning electronmicroscopy on sections from whole brain and spinal cord - still encased within bone -identified major proteins detected by proteomics, and highlighted their association with cellular and extracellular elements of variously shaped arachnoid trabeculae. Western blotting aligned with the proteomic and immunohistological analyses, reinforcing differential appearance of proteins in brain vs spinal meninges. Results could reflect regional distinctions in meninges that govern protective and/or neuroimmune functions.PMID:37858244 | DOI:10.1186/s12987-023-00473-w

Clin Epigenetics. 2023 Oct 19;15(1):166. doi: 10.1186/s13148-023-01578-7.ABSTRACTBACKGROUND: B vitamins such as folate (B9), B6, and B12 are key in one carbon metabolism, which generates methyl donors for DNA methylation. Several studies have linked differential methylation to self-reported intakes of folate and B12, but these estimates can be imprecise, while metabolomic biomarkers can offer an objective assessment of dietary intakes. We explored blood metabolomic biomarkers of folate and vitamins B6 and B12, to carry out epigenome-wide analyses across up to three European cohorts. Associations between self-reported habitual daily B vitamin intakes and 756 metabolites (Metabolon Inc.) were assessed in serum samples from 1064 UK participants from the TwinsUK cohort. The identified B vitamin metabolomic biomarkers were then used in epigenome-wide association tests with fasting blood DNA methylation levels at 430,768 sites from the Infinium HumanMethylation450 BeadChip in blood samples from 2182 European participants from the TwinsUK and KORA cohorts. Candidate signals were explored for metabolite associations with gene expression levels in a subset of the TwinsUK sample (n = 297). Metabolomic biomarker epigenetic associations were also compared with epigenetic associations of self-reported habitual B vitamin intakes in samples from 2294 European participants.RESULTS: Eighteen metabolites were associated with B vitamin intakes after correction for multiple testing (Bonferroni-adj. p < 0.05), of which 7 metabolites were available in both cohorts and tested for epigenome-wide association. Three metabolites - pipecolate (metabolomic biomarker of B6 and folate intakes), pyridoxate (marker of B6 and folate) and docosahexaenoate (DHA, marker of B6) - were associated with 10, 3 and 1 differentially methylated positions (DMPs), respectively. The strongest association was observed between DHA and DMP cg03440556 in the SCD gene (effect = 0.093 ± 0.016, p = 4.07E-09). Pyridoxate, a catabolic product of vitamin B6, was inversely associated with CpG methylation near the SLC1A5 gene promoter region (cg02711608 and cg22304262) and with SLC7A11 (cg06690548), but not with corresponding changes in gene expression levels. The self-reported intake of folate and vitamin B6 had consistent but non-significant associations with the epigenetic signals.CONCLUSION: Metabolomic biomarkers are a valuable approach to investigate the effects of dietary B vitamin intake on the human epigenome.PMID:37858220 | DOI:10.1186/s13148-023-01578-7

J Transl Med. 2023 Oct 19;21(1):740. doi: 10.1186/s12967-023-04570-0.ABSTRACTBACKGROUND: Changes in the gut microbiota composition is a hallmark of chronic kidney disease (CKD), and interventions targeting the gut microbiota present a potent approach for CKD treatment. This study aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT), a modified faecal microbiota transplantation method, on the renal activity of patients with renal dysfunction.METHODS: A comparative analysis of gut microbiota profiles was conducted in patients with renal dysfunction and healthy controls. Furthermore, the efficacy of WMT on renal parameters in patients with renal dysfunction was evaluated, and the changes in gut microbiota and urinary metabolites after WMT treatment were analysed.RESULTS: Principal coordinate analysis revealed a significant difference in microbial community structure between patients with renal dysfunction and healthy controls (P = 0.01). Patients with renal dysfunction who underwent WMT exhibited significant improvement in serum creatinine, estimated glomerular filtration rate, and blood urea nitrogen (all P < 0.05) compared with those who did not undergo WMT. The incidence of adverse events associated with WMT treatment was low (2.91%). After WMT, the Shannon index of gut microbiota and the abundance of several probiotic bacteria significantly increased in patients with renal dysfunction, aligning their gut microbiome profiles more closely with those of healthy donors (all P < 0.05). Additionally, the urine of patients after WMT demonstrated relatively higher levels of three toxic metabolites, namely hippuric acid, cinnamoylglycine, and indole (all P < 0.05).CONCLUSIONS: WMT is a safe and effective method for improving renal function in patients with renal dysfunction by modulating the gut microbiota and promoting toxic metabolite excretion.PMID:37858192 | DOI:10.1186/s12967-023-04570-0

J Transl Med. 2023 Oct 19;21(1):739. doi: 10.1186/s12967-023-04564-y.ABSTRACTBACKGROUND: Hepatic ischemia-reperfusion (IR) injury is the primary reason for complications following hepatectomy and liver transplantation (LT). Insulin-induced gene 2 (Insig2) is one of several proteins that anchor the reticulum in the cytoplasm and is essential for metabolism and inflammatory responses. However, its function in IR injury remains ambiguous.METHODS: Insig2 global knock-out (KO) mice and mice with adeno-associated-virus8 (AAV8)-delivered Insig2 hepatocyte-specific overexpression were subjected to a 70% hepatic IR model. Liver injury was assessed by monitoring hepatic histology, inflammatory responses, and apoptosis. Hypoxia/reoxygenation stimulation (H/R) of primary hepatocytes and hypoxia model induced by cobalt chloride (CoCl2) were used for in vitro experiments. Multi-omics analysis of transcriptomics, proteomics, and metabolomics was used to investigate the molecular mechanisms underlying Insig2.RESULTS: Hepatic Insig2 expression was significantly reduced in clinical samples undergoing LT and the mouse IR model. Our findings showed that Insig2 depletion significantly aggravated IR-induced hepatic inflammation, cell death and injury, whereas Insig2 overexpression caused the opposite phenotypes. The results of in vitro H/R experiments were consistent with those in vivo. Mechanistically, multi-omics analysis revealed that Insig2 is associated with increased antioxidant pentose phosphate pathway (PPP) activity. The inhibition of glucose-6-phosphate-dehydrogenase (G6PD), a rate-limiting enzyme of PPP, rescued the protective effect of Insig2 overexpression, exacerbating liver injury. Finally, our findings indicated that mouse IR injury could be attenuated by developing a nanoparticle delivery system that enables liver-targeted delivery of substrate of PPP (glucose 6-phosphate).CONCLUSIONS: Insig2 has a protective function in liver IR by upregulating the PPP activity and remodeling glucose metabolism. The supplementary glucose 6-phosphate (G6P) salt may serve as a viable therapeutic target for alleviating hepatic IR.PMID:37858181 | DOI:10.1186/s12967-023-04564-y

Eur Respir J. 2023 Oct 19;62(4):2301547. doi: 10.1183/13993003.01547-2023. Print 2023 Oct.NO ABSTRACTPMID:37857433 | DOI:10.1183/13993003.01547-2023

Environ Sci Technol. 2023 Oct 19. doi: 10.1021/acs.est.3c04561. Online ahead of print.ABSTRACTPrenatal exposure to single chemicals belonging to the per- and polyfluoroalkyl substances (PFAS) family is associated with biological perturbations in the mother, fetus, and placenta, plus adverse health outcomes. Despite our knowledge that humans are exposed to multiple PFAS, the potential joint effects of PFAS on the metabolome remain largely unknown. Here, we leveraged high-resolution metabolomics to identify metabolites and metabolic pathways perturbed by exposure to a PFAS mixture during pregnancy. Targeted assessment of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS), along with untargeted metabolomics profiling, were conducted on nonfasting serum samples collected from pregnant African Americans at 6-17 weeks gestation. We estimated the overall mixture effect and partial effects using quantile g-computation and single-chemical effects using linear regression. All models were adjusted for maternal age, education, parity, early pregnancy body mass index, substance use, and gestational weeks at sample collection. Our analytic sample included 268 participants and was socioeconomically diverse, with the majority receiving public health insurance (78%). We observed 13.3% of the detected metabolic features were associated with the PFAS mixture (n = 1705, p < 0.05), which was more than any of the single PFAS chemicals. There was a consistent association with metabolic pathways indicative of systemic inflammation and oxidative stress (e.g., glutathione, histidine, leukotriene, linoleic acid, prostaglandins, and vitamins A, C, D, and E metabolism) across all metabolome-wide association studies. Twenty-six metabolites were validated against authenticated compounds and associated with the PFAS mixture (p < 0.05). Based on quantile g-computation weights, PFNA contributed the most to the overall mixture effect for γ-aminobutyric acid (GABA), tyrosine, and uracil. In one of the first studies of its kind, we demonstrate the feasibility and utility of using methods designed for exposure mixtures in conjunction with metabolomics to assess the potential joint effects of multiple PFAS chemicals on the human metabolome. We identified more pronounced metabolic perturbations associated with the PFAS mixture than for single PFAS chemicals. Taken together, our findings illustrate the potential for integrating environmental mixture analyses and high-throughput metabolomics to elucidate the molecular mechanisms underlying human health.PMID:37857362 | DOI:10.1021/acs.est.3c04561

Food Chem. 2023 Oct 11;436:137737. doi: 10.1016/j.foodchem.2023.137737. Online ahead of print.ABSTRACTGanoderma lingzhi is an important medicinal fungus, which is widely used as dietary supplement and for pharmaceutical industries. However, the spatial distribution and dynamic accumulation pattern of active components such as ganoderic acids (GAs) among different parts of G. lingzhi fruiting body are still unclear. In this study, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with untargeted metabolomics analysis was applied to investigate the metabolites distribution within G. lingzhi fruiting body at four different maturity stages (squaring, opening, maturation and harvesting stage). A total of 132 metabolites were characterized from G. lingzhi, including 115 triterpenoids, 11 fatty acids and other component. Most of the GAs content in the cap was significantly higher than that in the stipe, with six components such as ganoderic acid B being extremely significant. GAs in the cap was mainly present in the bottom edge of the mediostratum layer, such as ganoderic A-I and ganoderic GS-1, while in the stipe, they were mainly distributed in the shell layer and the context layer, such as ganoderic A-F. Most ganoderic acids content in both the stipe and the cap of G. lingzhi was gradually decreased with the development of G. lingzhi. The GAs in the stipe was gradually transferred from the shell layer to the content layer, while the distribution of GAs among different tissues of the cap was not significantly changed. In addition, linoleic acid, 9-HODE, 9-KODE and other fatty acids were mainly accumulated in the opening and maturing stage of the caps. This study further clarifies the spatial dynamic distribution of GAs in G. lingzhi fruiting body at four different maturity stages (squaring, opening, maturation and harvesting stage), which provides a basis for the rational utilization of the medicinal parts of G. lingzhi. Furthermore, mass spectrometry imaging combined with non-target metabolome analysis provides a powerful tool for the spatial distribution of active substances in the different regions of the medicinal edible fungi.PMID:37857205 | DOI:10.1016/j.foodchem.2023.137737

Food Chem. 2023 Oct 14;436:137759. doi: 10.1016/j.foodchem.2023.137759. Online ahead of print.ABSTRACTAdjunct cultures strongly determined the distinguishing sensorial and nutritional characteristics of cheeses. Metabolites, flavor profiles and ripening characteristics of Monascus-ripened cheese enhanced by the co-fermentation of Ligilactobacillus salivarius AR809 were investigated. The AR809 significantly increased the contents of soluble nitrogen, small peptides (<1200 Da), free amino acids, and casein degradation degree in the resulting cheese. Furthermore, AR809 significantly promoted the formation of methyl ketones during cheese maturation. Based on untargeted metabolomics analysis, metabolites related to fatty acids metabolism and lysine degradation were highly enriched in Monascus-rich region of cheese. AR809 was primarily engaged in amino acid metabolism, promoting the synthesis of amino acids and dipeptide. L. salivarius and Monascus co-fermentation produced more beneficial bioactive metabolites involved in amino acids and lipid metabolisms than Monascus used alone in cheese ripening. Therefore, as adjunct culture, L. salivarius AR809 exhibited tremendous potential in improving nutrition and flavor quality during cheese ripening.PMID:37857204 | DOI:10.1016/j.foodchem.2023.137759

Microbiol Res. 2023 Oct 12;278:127516. doi: 10.1016/j.micres.2023.127516. Online ahead of print.ABSTRACTSignal-mediated cell fusion is vital for colony development in filamentous fungi. Arthrobotrys oligospora is a representative nematode-trapping (NT) fungus that produces adhesive networks (traps) to capture nematodes. Here, we characterized Aoadv-1, Aoso, Aoham-6, and Aoham-5 of A. oligospora, homologs of proteins involved in cellular communication and fusion in the model fungus Neurospora crassa. The deletion of four genes resulted in the complete loss of cell fusion, and traps produced by mutants did not close to form mycelial rings but were still capable of capturing nematodes. The absence of these genes inhibits aerial mycelial extension, slows colony growth, and increases mycelial branching. In addition, the mutants showed reduced sporulation capacity and tolerance to oxidative stress, increased sensitivity to SDS, and disturbed lipid droplet accumulation and autophagy. In addition, transcriptome and metabolomic analyses suggested that Aoadv-1 and Aoso are involved in multiple cellular processes and secondary metabolism. Our results revealed that Aoadv-1, Aoso, Aoham-6, and Aoham-5 regulate mycelial growth and trap morphogenesis through cell fusion, which contributed to elucidating the molecular mechanisms of cellular communication regulating mycelial development and trap morphogenesis in NT fungi.PMID:37857124 | DOI:10.1016/j.micres.2023.127516

BMC Neurol. 2023 Oct 19;23(1):373. doi: 10.1186/s12883-023-03414-0.ABSTRACTBACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder and, according to the Global Burden of Disease estimates in 2015, was the fastest growing neurological disorder globally with respect to associated prevalence, disability, and deaths. Information regarding the awareness, diagnosis, phenotypic characteristics, epidemiology, prevalence, risk factors, treatment, economic impact and lived experiences of people with PD from the African perspective is relatively sparse in contrast to the developed world, and much remains to be learned from, and about, the continent.METHODS: Transforming Parkinson's Care in Africa (TraPCAf) is a multi-faceted, mixed-methods, multi-national research grant. The study design includes multiple sub-studies, combining observational (qualitative and quantitative) approaches for the epidemiological, clinical, risk factor and lived experience components, as appropriate, and interventional methods (clinical trial component). The aim of TraPCAf is to describe and gain a better understanding of the current situation of PD in Africa. The countries included in this National Institute for Health and Care Research (NIHR) Global Health Research Group (Egypt, Ethiopia, Ghana, Kenya, Nigeria, South Africa and Tanzania) represent diverse African geographies and genetic profiles, with differing resources, healthcare systems, health and social protection schemes, and policies. The research team is composed of experts in the field with vast experience in PD, jointly led by a UK-based and Africa-based investigator.DISCUSSION: Despite the increasing prevalence of PD globally, robust data on the disease from Africa are lacking. Existing data point towards the poor awareness of PD and other neurological disorders on the continent and subsequent challenges with stigma, and limited access to affordable services and medication. This multi-site study will be the first of its kind in Africa. The data collected across the proposed sub-studies will provide novel and conclusive insights into the situation of PD. The selected country sites will allow for useful comparisons and make results relevant to other low- and middle-income countries. This grant is timely, as global recognition of PD and the public health challenge it poses builds. The work will contribute to broader initiatives, including the World Health Organization's Intersectoral global action plan on epilepsy and other neurological disorders.TRIAL REGISTRATION: https://doi.org/10.1186/ISRCTN77014546 .PMID:37858118 | DOI:10.1186/s12883-023-03414-0

BMC Plant Biol. 2023 Oct 20;23(1):503. doi: 10.1186/s12870-023-04467-6.ABSTRACTBACKGROUND: Quinoa is an important economic crop, drought is one of the key factors affecting quinoa yield. Clarifying the adaptation strategy of quinoa to drought is conducive to cultivating drought-tolerant varieties. At present, the study of quinoa on drought stress-related metabolism and the identification of related metabolites are still unknown. As a direct feature of biochemical functions, metabolites can reveal the biochemical pathways involved in drought response.RESULT: Here, we studied the physiological and metabolic responses of drought-tolerant genotype L1 and sensitive genotype HZ1. Under drought conditions, L1 had higher osmotic adjustment ability and stronger root activity than HZ1, and the relative water content of L1 was also higher than that of HZ1. In addition, the barrier-to- sea ratio of L1 is significantly higher than that of HZ1. Using untargeted metabolic analysis, a total of 523, 406, 301 and 272 differential metabolites were identified in L1 and HZ1 on day 3 and day 9 of drought stress. The key metabolites (amino acids, nucleotides, peptides, organic acids, lipids and carbohydrates) accumulated differently in quinoa leaves. and HZ1 had the most DEMs in Glycerophospholipid metabolism (ko00564) and ABC transporters (ko02010) pathways.CONCLUSION: These results provide a reference for characterizing the response mechanism of quinoa to drought and improving the drought tolerance of quinoa.PMID:37858063 | DOI:10.1186/s12870-023-04467-6