PubMed

Front Mol Biosci. 2023 Jul 13;10:1233586. doi: 10.3389/fmolb.2023.1233586. eCollection 2023.ABSTRACTIntroduction: Anisakis simplex are parasitic nematodes that cause anisakiasis. The possibility of infection with this parasite is through consumption of raw or undercooked fish products. A. simplex infections are often misdiagnosed, especially in subclinical cases that do not present with typical symptoms such as urticaria, angioedema, and gastrointestinal allergy. The resulting allergic reactions range from rapid-onset and potentially fatal anaphylactic reactions to chronic, debilitating conditions. While there have been numerous published studies on the genomes and proteomes of A. simplex, less attention has been paid to the metabolomes. Metabolomics is concerned with the composition of metabolites in biological systems. Dynamic responses to endogenous and exogenous stimuli are particularly well suited for the study of holistic metabolic responses. In addition, metabolomics can be used to determine metabolic activity at different stages of development or during growth. Materials and methods: In this study, we reveal for the first time the metabolomes of infectious stages (L3 and L4) of A. simplex using untargeted metabolomics by ultra-performance liquid chromatography-mass spectrometry. Results: In the negative ionization mode (ESI-), we identified 172 different compounds, whereas in the positive ionization mode (ESI+), 186 metabolites were found. Statistical analysis showed that 60 metabolites were found in the ESI- mode with different concentration in each group, of which 21 were more enriched in the L3 larvae and 39 in the L4 stage of A. simplex. Comparison of the individual developmental stages in the ESI + mode also revealed a total of 60 differential metabolites, but 32 metabolites were more enriched in the L3 stage larvae, and 28 metabolites were more concentrated in the L4 stage. Discussion: The metabolomics study revealed that the developmental stages of A. simplex differed in a number of metabolic pathways, including nicotinate and nicotinamide metabolism. In addition, molecules responsible for successful migration within their host, such as pyridoxine and prostaglandins (E1, E2, F1a) were present in the L4 stage. In contrast, metabolic pathways for amino acids, starch, and sucrose were mainly activated in the L3 stage. Our results provide new insights into the comparative metabolome profiles of two different developmental stages of A. simplex.PMID:37520327 | PMC:PMC10373882 | DOI:10.3389/fmolb.2023.1233586

Plant Phenomics. 2023 Jul 28;5:0071. doi: 10.34133/plantphenomics.0071. eCollection 2023.ABSTRACTCurrently, the presence of genetically modified (GM) organisms in agro-food markets is strictly regulated by enacted legislation worldwide. It is essential to ensure the traceability of these transgenic products for food safety, consumer choice, environmental monitoring, market integrity, and scientific research. However, detecting the existence of GM organisms involves a combination of complex, time-consuming, and labor-intensive techniques requiring high-level professional skills. In this paper, a concise and rapid pipeline method to identify transgenic rice seeds was proposed on the basis of spectral imaging technologies and the deep learning approach. The composition of metabolome across 3 rice seed lines containing the cry1Ab/cry1Ac gene was compared and studied, substantiating the intrinsic variability induced by these GM traits. Results showed that near-infrared and terahertz spectra from different genotypes could reveal the regularity of GM metabolic variation. The established cascade deep learning model divided GM discrimination into 2 phases including variety classification and GM status identification. It could be found that terahertz absorption spectra contained more valuable features and achieved the highest accuracy of 97.04% for variety classification and 99.71% for GM status identification. Moreover, a modified guided backpropagation algorithm was proposed to select the task-specific characteristic wavelengths for further reducing the redundancy of the original spectra. The experimental validation of the cascade discriminant method in conjunction with spectroscopy confirmed its viability, simplicity, and effectiveness as a valuable tool for the detection of GM rice seeds. This approach also demonstrated its great potential in distilling crucial features for expedited transgenic risk assessment.PMID:37519936 | PMC:PMC10380542 | DOI:10.34133/plantphenomics.0071

Front Oncol. 2023 Jul 13;13:1213273. doi: 10.3389/fonc.2023.1213273. eCollection 2023.ABSTRACTThe joint analysis of single-cell transcriptomics, proteomics, lipidomics, metabolomics and spatial metabolomics is continually transforming our understanding of the mechanisms of metabolic reprogramming in tumor cells. Since head and neck tumor is the sixth most common tumor in the world, the study of the metabolic mechanism of its occurrence, development and prognosis is still undeveloped. In the past decade, this field has witnessed tremendous technological revolutions and considerable development that enables major breakthroughs to be made in the study of human tumor metabolism. In this review, a comprehensive comparison of traditional metabolomics and spatial metabolomics has been concluded, and the recent progress and challenges of the application of spatial metabolomics combined multi-omics in the research of metabolic reprogramming in tumors are reviewed. Furthermore, we also highlight the advances of spatial metabolomics in the study of metabolic mechanisms of head and neck tumors, and provide an outlook of its application prospects.PMID:37519782 | PMC:PMC10374363 | DOI:10.3389/fonc.2023.1213273

Heliyon. 2023 Jul 17;9(7):e18360. doi: 10.1016/j.heliyon.2023.e18360. eCollection 2023 Jul.ABSTRACTLentinula edodes, one of the most highly regarded edible mushrooms in China, is susceptible to damage from high temperatures. However, a mutant strain derived from L. edodes, known as Le023M, has shown exceptional thermotolerance. Compared to the original strain Le023, Le023M exhibited accelerated mycelial recovery following heat stress. Through RNA-seq analysis, the majority of differentially expressed genes (DEGs) were found to be associated with functions such as "protein refolding", "protein unfolding", "protein folding", and "response to heat", all of which are closely linked to heat shock proteins. Furthermore, qRT-PCR results revealed significant accumulation of heat shock-related genes in Le023M under heat stress. GC-MS analysis indicated elevated levels of trehalose, aspartate, and glutamate in Le023M when subjected to heat stress. The highly expressed genes involved in these metabolic pathways were predominantly found in Le023M. Collectively, these findings highlight the following: (i) the crucial role of heat shock proteins (HSPs) in the thermo-resistant mechanisms of Le023M; (ii) the potential of trehalose accumulation in Le023M to enhance mycelium resistance to heat stress; and (iii) the induction of aspartate and glutamate accumulation in response to heat stress. These results shed light on the molecular mechanisms underlying the thermotolerance of Le023M, providing valuable insights for further understanding and improving heat stress response in L. edodes. The findings also highlight the potential applications of Le023M in the cultivation and production of L. edodes under high-temperature conditions.PMID:37519752 | PMC:PMC10372740 | DOI:10.1016/j.heliyon.2023.e18360

Heliyon. 2023 Jul 11;9(7):e18046. doi: 10.1016/j.heliyon.2023.e18046. eCollection 2023 Jul.ABSTRACTBreast cancer is one of the most common cancers. Oridonin, a traditional Chinese medicine, is believed to inhibit tumor growth, but its particular effects on breast cancer remain unknown. In this study, we examined oridonin's effects on 4T1, MCF-7, and MDAMB-231 cellular activity using CCK8. Scratch assays were used to detect oridonin's effects on cellular migration. Oridonin's effects on the breast cancer cell cycle were studied using flow cytometry, and expression of cell cycle related proteins p53, CDK2, and p21 was detected using Western blot assays. Metabolomics assays were used to detect changes in small molecule metabolites and metabolic pathways in breast cancer cells after treatment with oridonin. Oridonin's effects on breast cancer growth were also studied using xenograft mice. Metabolomics assays were used to detect changes in metabolites and metabolic pathways in xenograft mouse plasma in a control group, model group, and drug administration group. Experimental results showed that oridonin could significantly inhibit breast cancer growth both in vivo and in vitro. Scratch experiments showed that oridonin could inhibit breast cancer cell migration. Oridonin was also able to arrest cells in S phase by affecting several cell cycle-related proteins, including p53, CDK2, and p21. Metabolomic analysis of 4T1 cells identified a total of 33 differential metabolites, including multiple amino acids (such as l-Glutamic acid, l-Asparagine, l-Histidine, l-Valine, and l-Isoleucine). KEGG pathway enrichment analysis showed significant changes in aminoacyl-tRNA biosynthesis, and in multiple amino acid metabolic pathways. Plasma metabolomic analyses of xenograft mice revealed 28 differentially-expressed metabolites between the different animal model groups, including multiple amino acids. KEGG pathway analysis showed significant alterations in multiple amino acid metabolic pathways in oridonin-treated mice. Additionally, changes in the expression of PI3K, AKT and mTOR proteins, as well as in branched amino acids, suggest that oridonin affects the PI3K/AKT/mTOR signaling pathway by inhibiting the biosynthesis of valine, leucine and isoleucine. Taken together, our results suggest that oridonin has strong anti-tumor activity in vitro and in vivo, and has potential as an adjuvant to breast cancer treatment regimens.PMID:37519735 | PMC:PMC10372243 | DOI:10.1016/j.heliyon.2023.e18046

Plant Genome. 2023 Jul 30:e20372. doi: 10.1002/tpg2.20372. Online ahead of print.ABSTRACTDate palm (Phoenix dactylifera L.) is able to grow and complete its life cycle while being rooted in highly saline soils. Which of the many well-known salt-tolerance strategies are combined to fine-tune this remarkable resilience is unknown. The precise location, whether in the shoot or the root, where these strategies are employed remains uncertain, leaving us unaware of how the various known salt-tolerance mechanisms are integrated to fine-tune this remarkable resilience. To address this shortcoming, we exposed date palm to a salt stress dose equivalent to seawater for up to 4 weeks and applied integrative multi-omics analyses followed by targeted metabolomics, hormone, and ion analyses. Integration of proteomic into transcriptomic data allowed a view beyond simple correlation, revealing a remarkably high degree of convergence between gene expression and protein abundance. This sheds a clear light on the acclimatization mechanisms employed, which depend on reprogramming of protein biosynthesis. For growth in highly saline habitats, date palm effectively combines various salt-tolerance mechanisms found in both halophytes and glycophytes: "avoidance" by efficient sodium and chloride exclusion at the roots, and "acclimation" by osmotic adjustment, reactive oxygen species scavenging in leaves, and remodeling of the ribosome-associated proteome in salt-exposed root cells. Combined efficiently as in P. dactylifera L., these sets of mechanisms seem to explain the palm's excellent salt stress tolerance.PMID:37518859 | DOI:10.1002/tpg2.20372

Phytother Res. 2023 Jul 30. doi: 10.1002/ptr.7947. Online ahead of print.ABSTRACTEleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves (ESL) are widely used to treat ischemic stroke (IS); however, the specific mechanism remains unclear. The microbiota-gut-brain axis plays a critical role in IS and has become a potential therapeutic target. This study aimed to reveal and verify the therapeutic effect of ESL on IS through the microbiota-gut-brain axis. Ultra-high-performance liquid chromatography coupled with mass spectrometry-based untargeted/targeted metabolomics combined with 16S rRNA microbiota sequencing strategy were used to investigate the regulatory effect of ESL on the metabolism and intestinal microenvironment after IS. Lactobacillus reuteri and Clostridium butyricum were used to treat rats with IS to verify that elevated levels of probiotics are key factors in the therapeutic effect of ESL. The results showed that IS significantly altered the accumulation of 41 biomarkers, while ESL restored their concentrations back to normal. Moreover, ESL alleviated the dysbiosis of gut microbiota brought on by IS, by reducing the abundance of pathogens and increasing the abundance of probiotics (e.g., Lactobacillus reuteri and Clostridium butyricum); this could reduce post-stroke injury, thereby having a certain protective effect on IS. This study reveals that ESL plays an important role in treating IS through the microbiota-gut-brain axis, maintaining metabolic homeostasis in vivo.PMID:37518502 | DOI:10.1002/ptr.7947

Int J Cardiol. 2023 Jul 28:131223. doi: 10.1016/j.ijcard.2023.131223. Online ahead of print.ABSTRACTOBJECTIVE: Plaque erosion (PE) and plaque rupture (PR) are the main subtypes of ST-segment elevation myocardial infarction (STEMI), the differences of metabolic patterns between PE and PR remain largely unknown.METHODS: 132 STEMI patients were divided into training set (PR, n = 36; PE, n = 36) and test set (PR, n = 30; PE, n = 30), the plasma from patients were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry.RESULTS: We identified 56 and 28 differences in training and test set, respectively. Among these metabolites, it was found that docosahexaenoic acid (DHA), salicylic acid and proline were recognized in both tests. Receiver Operating Characteristic (ROC) analysis showed that the area under curve of docosahexaenoic acid (DHA) was 0.81 and 0.75 in training and test samples, respectively; proline was 0.67 and 0.74 in training and test samples, respectively; salicylic acid was 0.70 and 0.73 in training and test samples, respectively.CONCLUSIONS: DHA, salicylic acid, and proline could be used as non-invasive biomarkers to differentiate PE and PR.TRIAL REGISTRATION: NCT02041650.PMID:37517782 | DOI:10.1016/j.ijcard.2023.131223

Bioresour Technol. 2023 Jul 28:129575. doi: 10.1016/j.biortech.2023.129575. Online ahead of print.ABSTRACTHyperthermophilic composting (HC) has been widely recognized for the advantage of high treatment efficiency for organic wastes. However, the humification process is still unclear. In this study, the humification process of HC was investigated, compared to conventional composting (CK). The results showed that the highest composting temperature, organic matter degradation rate, and humification index in HC were 92.62 °C, 23.98%, and 1.59, while those in CK were 70.23 °C, 14.49 %, and 1.04, indicating HC accelerated humification process. Moreover, the results of metagenomic and untargeted metabolomic showed that the genes and metabolisms related to carbohydrate, lipid, amino acid, fatty acid, and nucleotide were more abundant in HC. Consequently, the metabolic pathways regarding organic matter degradation and microbial reproduction were enhanced in the high temperature stage of HC, further accelerating the humification reaction in the low temperature stage. This work contributes to the comprehension of the humification mechanism in HC.PMID:37517706 | DOI:10.1016/j.biortech.2023.129575

J Biotechnol. 2023 Jul 28:S0168-1656(23)00137-2. doi: 10.1016/j.jbiotec.2023.07.010. Online ahead of print.ABSTRACTHeat-shock proteins (Hsps) are a family of proteins essential in preserving the vitality and functionality of proteins under stress conditions. Cucumber (Cucumis sativus) is a widely grown plant with high nutritional value and is used as a model organism in many studies. This study employed a genomics, transcriptomics, and metabolomics approach to investigate cucumbers' Hsps against abiotic stress conditions. Bioinformatics methods were used to identify six Hsp families in the cucumber genome and to characterize family members. Transcriptomics data from the Sequence Read Archive (SRA) database was also conducted to select CsHsp genes for further study. Real-time PCR was used to evaluate gene expression levels under different stress conditions, revealing that CssHsp-08 was a vital gene for resistance to stress conditions; including drought, salinity, cold, heat stresses, and ABA application. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of plant extracts revealed that amino acids accumulate in leaves under high temperatures and roots under drought, while sucrose accumulates in both tissues under applied most stress factors. The study provides valuable insights into the structure, organization, evolution, and expression profiles of the Hsp family and contributes to a better understanding of plant stress mechanisms. These findings have important implications for developing crops that can withstand environmental stress conditions better.PMID:37517677 | DOI:10.1016/j.jbiotec.2023.07.010

J Hepatol. 2023 Jul 28:S0168-8278(23)04991-7. doi: 10.1016/j.jhep.2023.07.011. Online ahead of print.ABSTRACTBACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a clinical syndrome of high short-term mortality in patients with chronic liver disease. Chronic hepatitis B is the main cause of ACLF (HBV-ACLF) in China and other Asian countries. To improve disease management and survival for ACLF patients, we aimed to discover novel biomarkers to enhance HBV-ACLF diagnosis and prognosis.METHODS: We performed a metabolomics profiling of 1,024 plasma samples collected from HBV-related chronic liver disease patients with acute exacerbation at hospital admission in a multi-year and multi-center prospective study (367 ACLF and 657 non-ACLF). The samples were randomly separated into equal halves as a discovery set and a validation set. We identified metabolites associated with 90-day mortality in the ACLF group and the progression to ACLF within 28 days in the non-ACLF group (pre-ACLF) using statistical analysis and machine learning. We developed diagnostic algorithms in the discovery set and used these to assess the findings in the validation set.RESULTS: ACLF significantly altered the serum metabolome, particularly in membrane lipid metabolism, steroid hormones, oxidative stress pathways, and energy metabolism. Numerous metabolites were significantly associated with 90-day mortality in the ACLF group and/or pre-ACLF in the non-ACLF group. We developed algorithms for the prediction of ACLF 90-day mortality (area under curve, AUC: 0.87 and 0.83 for the discovery set and validation set, respectively) and the diagnosis of pre-ACLF (AUC: 0.94 and 0.88 for the discovery set and validation set, respectively). To translate our discoveries into practical clinical tests, we developed targeted assays using liquid chromatography mass spectrometry (LCMS).CONCLUSIONS: Based on novel metabolite biomarkers, we established HBV-ACLF tests with higher accuracy than existing methods.IMPACT AND IMPLICATIONS: Acute-on-chronic liver failure (ACLF) is a clinical syndrome of high short-term mortality affecting 25% of hospitalized cirrhosis patients. Chronic hepatitis B (HBV) is the main etiology of ACLF in China and other Asian counties. There is currently no effective therapy. Early diagnosis and accurate prognosis for disease management are critical for improving clinical outcomes for ACLF patients. Based on novel metabolite biomarkers, we developed liquid chromatography mass spectrometry (LCMS) tests with improved accuracy for the early diagnosis and prognosis of HBV-ACLF. The LCMS tests can be implemented in clinical labs and used by physicians to triage HBV-ACLF patients for treatment options and proactive disease management.CLINICAL TRIAL NUMBER: NCT02457637 and NCT03641872.PMID:37517452 | DOI:10.1016/j.jhep.2023.07.011

Curr Opin Microbiol. 2023 Jul 27;75:102359. doi: 10.1016/j.mib.2023.102359. Online ahead of print.ABSTRACTA continued rise of antibiotic resistance and shortages of effective antibiotics necessitate the discovery and development of new antibiotics with novel modes of action (MoAs) against resistant pathogens. While natural products remain the best resource for antibiotic discovery, their exploration faces many challenges, including (i) unknown MoAs, (ii) high rediscovery rates, (iii) tedious isolation and structure elucidation, and (iv) insufficient production for further development. We have identified recent innovations in screening methods, microbiology, bioinformatics, and metabolomics technologies, as well as natural product-inspired synthesis and synthetic biology, that have contributed to new natural product antibiotics in the past two years. We highlight their interplay as the key element for successful applications, driving future opportunities to increase the pool of natural product-based antibacterial antibiotics.PMID:37517368 | DOI:10.1016/j.mib.2023.102359

Biomed Pharmacother. 2023 Jul 28;165:115193. doi: 10.1016/j.biopha.2023.115193. Online ahead of print.ABSTRACTProstate cancer remains one of the leading health issues without a fully effective treatment. Medicinal plants are one of the primary sources of compounds for treating numerous ailments. In this sense, the Oenothera genus contains metabolites with antiproliferative activity on cancer cells. For this, the study aimed to explore the antiproliferative activity of its extracts against prostate cancer and identify its metabolites (under metabolomics analyses) associated with anticancer and/or antiproliferative properties. For this reason, a LC-MS/MS-based metabolomic analysis was performed to demonstrate the possible metabolites present in O. rosea. In addition, the antiproliferative activity of different extracts in the human prostate cancer cell line DU145 was evaluated. All extracts have antiproliferative effects on DU145 cells at 72 h, with moderate activity being the best ethanolic either 48 or 72 h. Finally, by LC-MS/MS-based metabolomics, 307 compounds from aqueous, methanolic, ethanolic, and ethyl acetate extracts from which 40 putative metabolites identified were organized as anti-inflammatory, anticancer, and/or antiproliferative activities according to previously reported. These results provide evidence that O. rosea could be used as an antiproliferative agent due to its chemical contents used as polypharmacy with low concentration levels.PMID:37517287 | DOI:10.1016/j.biopha.2023.115193

Environ Int. 2023 Jul 24;178:108112. doi: 10.1016/j.envint.2023.108112. Online ahead of print.ABSTRACTBreast cancer is now the most common cancer globally, accounting for 12% of all new annual cancer cases worldwide. Despite epidemiologic studies having established a number of risk factors, knowledge of chemical exposure risks is limited to a relatively small number of chemicals. In this exposome research study, we used non-targeted, high-resolution mass spectrometry of pregnancy cohort biospecimens in the Child Health and Development Studies to test for associations with breast cancer identified via the California Cancer Registry. Second and third trimester archival samples were analyzed from 182 women who subsequently developed breast cancer and 384 randomly selected women who did not develop breast cancer. Environmental chemicals were annotated with the Toxin and Toxin-Target Database for chemical signals that were higher in breast cancer cases and used with an exposome epidemiology analytic framework to identify suspect chemicals and associated metabolic networks. Network and pathway enrichment analyses showed consistent linkage in both second and third trimesters to inflammation pathways, including linoleate, arachidonic acid and prostaglandins, and identified new suspect environmental chemicals associated with breast cancer, i.e., an N-substituted piperidine insecticide and a common commercial product, 2,4-dinitrophenol, linked to variations in amino acid and nucleotide pathways in second trimester and benzo[a]carbazole and a benzoate derivative linked to glycan and amino sugar metabolism in third trimester. The results identify new suspect environmental chemical risk factors for breast cancer and provide an exposome epidemiology framework for discovery of suspect environmental chemicals and potential mechanistic associations with breast cancer.PMID:37517180 | DOI:10.1016/j.envint.2023.108112

Environ Int. 2023 Jul 20;178:108105. doi: 10.1016/j.envint.2023.108105. Online ahead of print.ABSTRACTCadmium (Cd) and polycyclic aromatic hydrocarbons (PAHs) are prominent soil contaminants found in industrial sites, and their combined effects on plants are not yet fully understood. To investigate the mechanisms underlying the co-exposure of Cd and PAHs and identify key biomarkers for their co-effects, an integrated analysis of metabolomics, transcriptomics, and proteomics was conducted on ryegrass leaves cultivated in soil. In nontarget metabolomics analysis, nine differentially expressed metabolites that were specifically induced by the compound exposure were identified. When combined with the analysis of differentially expressed genes and proteins, it was determined that the major pathways involved in the response to the co-stress of Cd and PAHs were linoleic acid metabolism and phenylpropanoid biosynthesis. The upregulation of 12,13-dihydroxy-9Z-octadecenoic acid and the downregulation of sinapyl alcohol were identified as typical biomarkers, respectively. Compared to scenarios of single exposures, the compound exposure to Cd and PAHs disrupted the oxidation of linoleic acid, leading to alterations in the profiles of linoleate metabolites. Additionally, it intensified hydroxylation, carboxylation, and methylation processes, and interfered with reactions involving coenzyme A, thus inhibiting lignin production. As a result, oxidative stress was elevated, and the cell wall defense system in ryegrass was weakened. The findings of this study highlight the ecological risks associated with unique biological responses in plants co-exposed to Cd and PAHs in polluted soils.PMID:37517176 | DOI:10.1016/j.envint.2023.108105

Curr Opin Plant Biol. 2023 Jul 28;75:102427. doi: 10.1016/j.pbi.2023.102427. Online ahead of print.ABSTRACTFunctional genomics approaches with comparative omics analyses of wild-accessions and cultivars/wild species, as well as comparative genomic analyses in plant species focusing on gene clusters, have successfully detected key metabolic polymorphisms in plant specialized metabolism. In recent decades, (i) intra-species specific metabolic polymorphisms, (ii) new functionalization of tandem duplicated genes, and (iii) metabolic gene clusters were found as the main factors creating metabolic diversity of specialized metabolites in plants. However, given findings aware us that the identification of genes in plant specialized metabolism requires strategic approaches depending on the target metabolic pathways. The increasing availability of plant genome sequences and transcriptome data has facilitated inter-specific comparative analyses, including genomic analysis and gene co-expression network analysis. Here, we introduce functional genomics approaches with the integration of inter-/intra-species comparative metabolomics, their key roles in providing genomic signatures of metabolic evolution, and discuss future prospects of functional genomics on plant specialized metabolism.PMID:37517136 | DOI:10.1016/j.pbi.2023.102427

J Cell Mol Med. 2023 Jul 30. doi: 10.1111/jcmm.17891. Online ahead of print.ABSTRACTLipid metabolism plays an important role in the repair of skin wounds. Studies have shown that acupuncture is very effective in skin wound repair. However, there is little knowledge about the mechanism of electroacupuncture. Thirty-six SD rats were divided into three groups: sham-operated group, model group and electroacupuncture group, with six rats in each group. After the intervention, orbital venous blood was collected for lipid metabolomics analysis, wound perfusion was detected and finally the effect of electroacupuncture on skin wound repair was comprehensively evaluated by combining wound healing rate and histology. Lipid metabolomics analysis revealed 11 differential metabolites in the model versus sham-operated group. There were 115 differential metabolites in the model versus electro-acupuncture group. 117 differential metabolites in the electro-acupuncture versus sham-operated group. There were two differential metabolites common to all three groups. Mainly cholesteryl esters and sphingolipids were elevated after electroacupuncture and triglycerides were largely decreased after electroacupuncture. The electroacupuncture group recovered faster than the model group in terms of blood perfusion and wound healing (p < 0.05). Electroacupuncture may promote rat skin wound repair by improving lipid metabolism and improving local perfusion.PMID:37517065 | DOI:10.1111/jcmm.17891

Brain. 2023 Jul 30:awad254. doi: 10.1093/brain/awad254. Online ahead of print.ABSTRACTNeuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterised cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data was analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses "solved" or "possibly solved" ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% "solved and ∼13% "possibly solved" outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from underrepresented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice, to reduce genetic data inequality and benefit patients globally.PMID:37516995 | DOI:10.1093/brain/awad254

Nutrients. 2023 Jul 14;15(14):3142. doi: 10.3390/nu15143142.ABSTRACTThe primary control of dysmetabolic patients is extremely challenging worldwide, with inadequate dietary habits and sporadic physical activity among the key risk factors for metabolic syndrome onset. Nowadays, there is no exclusive treatment for this condition, and considering that preventive measures usually fail, new therapeutic approaches need to be proposed and investigated. This present pilot study compared the effects of diet alone and in association with a combination of myo-inositol and d-chiro-inositol in their 40:1 ratio, α-lactalbumin, and Gymnema sylvestre on different metabolic parameters in obese dysmetabolic patients. To this purpose, 37 patients with BMI between 30 and 40 and fasting blood glucose between 100 and 125 mg/dL were divided into two groups: (i) the control group followed a hypocaloric Mediterranean diet, (ii) while the study group was also supplemented with a daily dosage of two sachets, each one containing 1950 mg myo-inositol, 50 mg d-chiro-inositol, 50 mg α-lactalbumin, and 250 mg Gymnema Sylvestre. After a 6-month treatment, all parameters improved in both groups. Nevertheless, the treated group experienced a greater improvement, especially concerning the variation from the baseline of HOMA index, triglycerides, BMI, body weight, and waist circumference. These findings support the supplementation with myo-inositol and d-chiro-inositol in the 40:1 ratio, α-lactalbumin, and Gymnema sylvestre as a therapeutical strategy to potentiate the beneficial effects induced via dietary programs in dysmetabolic patients.PMID:37513560 | PMC:PMC10385591 | DOI:10.3390/nu15143142

Molecules. 2023 Jul 23;28(14):5595. doi: 10.3390/molecules28145595.ABSTRACTChitooligosaccharide (COS) is a natural product from the ocean, and while many studies have reported its important role in metabolic diseases, no study has systematically elaborated the anti-obesity effect and mechanism of COS. Herein, COSM (MW ≤ 3000 Da) was administered to diet-induced obese mice by oral gavage once daily for eight weeks. The results show that COSM administration reduced body weight; slowed weight gain; reduced serum Glu, insulin, NEFA, TC, TG, and LDL-C levels; increased serum HSL and HDL-C levels; improved inflammation; and reduced lipid droplet size in adipose tissue. Further lipidomic analysis of adipose tissue revealed that 31 lipid species are considered to be underlying lipid biomarkers in COS therapy. These lipids are mainly enriched in pathways involving insulin resistance, thermogenesis, cholesterol metabolism, glyceride metabolism and cyclic adenosine monophosphate (cAMP), which sheds light on the weight loss mechanism of COS. The Western blot assay demonstrated that COSM intervention can improve insulin resistance, inhibit de novo synthesis, and promote thermogenesis and β-oxidation in mitochondria by the AMPK pathway, thereby alleviating high-fat diet-induced obesity. In short, our study can provide a more comprehensive direction for the application of COS in obesity based on molecular markers.PMID:37513467 | PMC:PMC10384603 | DOI:10.3390/molecules28145595