PubMed

Int J Mol Sci. 2024 Nov 26;25(23):12666. doi: 10.3390/ijms252312666.ABSTRACTHigh-altitude plants face extreme environments such as low temperature, low oxygen, low nutrient levels, and strong ultraviolet radiation, causing them to adopt complex adaptation mechanisms. Phenotypic variation is the core manifestation of ecological adaptation and evolution. Many plants have developed a series of adaptive strategies through long-term natural selection and evolution, enabling them to survive and reproduce under such harsh conditions. This article reviews the techniques and methods used in recent years to study the adaptive evolution of high-altitude plants, including transplantation techniques, genomics, transcriptomics, proteomics, and metabolomics techniques, and their applications in high-altitude plant adaptive evolution. Transplantation technology focuses on phenotypic variation, which refers to natural variations in morphological, physiological, and biochemical characteristics, exploring their key roles in nutrient utilization, photosynthesis optimization, and stress-resistance protection. Multiple omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, have revealed genes, regulatory pathways, and metabolic networks associated with phenotypic variations at the genetic and molecular levels. At the same time, the limitations and deficiencies of current technologies used to study plant adaptation to high-altitude environments were discussed. In addition, we propose future improvements to existing technologies and advocate for the integration of different technologies at multiple levels to study the molecular mechanisms of plant adaptation to high-altitude environments, thus providing insights for future research in this field.PMID:39684378 | DOI:10.3390/ijms252312666

Int J Mol Sci. 2024 Nov 25;25(23):12638. doi: 10.3390/ijms252312638.ABSTRACTMicrogravity may profoundly impact the cardiovascular system, skeletal muscle system, and immune system of astronauts. At the cellular level, microgravity may also affect cell proliferation, differentiation, and growth, as well as lipid metabolism. In this work, we investigated lipid changes in Caco-2 cells cultured in a clinostat for 24 h under simulated microgravity conditions (SMC). Complex lipids were measured using a UHPLC-QTOF/MS platform, and the data were subjected to multivariate analysis. Under SMC, levels of ceramides Cer 18:0;O2/16:0, Cer 18:1;O2/16:0, Cer 18:1; O2/22:0, Cer 18:1;O2/24:0, and Cer 18:2;O2/24:0 were found to be upregulated, while sphingomyelins SM 16:1;O2/16:0, SM 16:1;O2/18:1, SM 18:1;O2/24:0, and SM 18:2;O2/24:0 were found to be downregulated. On the other hand, considering that sphingolipids are involved in the process of inflammation, we also treated Caco-2 cells with dextran sodium sulfate (DSS) to induce cell inflammation and lipopolysaccharide (LPS) to induce cell immune responses. As a result, we observed similar lipid dysregulation, indicating that SMC may exert a condition similar to inflammation. Our lipidomics strategy provides new insights into the altered metabolic pathway of ceramides and sphingomyelins of Caco-2 cells under SMC.PMID:39684348 | DOI:10.3390/ijms252312638

Int J Mol Sci. 2024 Nov 25;25(23):12629. doi: 10.3390/ijms252312629.ABSTRACTThe astringent selection criteria for milk-oriented traits in dairy cattle have rendered these animals prone to various metabolic disorders. Postpartum lactational peak and reduced feed intake lead to negative energy balance in cattle. As a compensatory mechanism, cattle start mobilizing fat reserves to meet the energy demand for vital body functions. Consequently, diminished glucose concentrations and elevated ketone body levels lead to poor ovarian function. The impaired follicular development and subpar oocyte quality diminish the conception rates, which poses significant economic repercussions. Follicular fluid is integral to the processes of follicular growth and oocyte development. Hence, the present study was performed to identify potential alterations in metabolites in the follicular fluid under in vitro culture conditions mimicking negative energy balance. Our results revealed nine distinct metabolites exhibiting differential expression in follicular fluid under negative energy balance. The differentially expressed metabolites were predominantly associated with pathways related to amino acid metabolism, lipid metabolism, signal transduction mechanisms, and membrane transport, alongside other biological processes. The identified signature metabolites may be further validated to determine oocyte fitness subjected to in vitro fertilization or embryo production from slaughterhouse source ovaries.PMID:39684341 | DOI:10.3390/ijms252312629

Int J Mol Sci. 2024 Nov 24;25(23):12610. doi: 10.3390/ijms252312610.ABSTRACTThe problem of marine noise pollution has a long history. Strong noise (>120 dB re 1 µPa) will affects the growth, development, physiological responses, and behaviors of fish, and also can induce the stress response, posing a mortal threat. Although many studies have reported that underwater noise may affect the survival of fish by disturbing their nervous system and endocrine system, the underlying causes of death due to noise stimulation remain unknown. Therefore, in this study, we used the underwater noise stress models to conduct underwater strong noise (50-125 dB re 1 µPa, 10-22,000 Hz) stress experiments on small yellow croaker for 10 min (short-term noise stress) and 6 days (long-term noise stress). A total of 150 fishes (body weight: 40-60 g; body length: 12-14 cm) were used in this study. Omics (metabolomics and transcriptomics) studies and quantitative analyses of important genes (HPA (hypothalamic-pituitary-adrenal)-axis functional genes) were performed to reveal genetic and metabolic changes in the important tissues associated with the HPA axis (brain, heart, and adrenal gland). Finally, we found that the strong noise pollution can significantly interfere with the expression of HPA-axis functional genes (including corticotropin releasing hormone (CRH), corticotropin releasing hormone receptor 2 (CRHR2), and arginine vasotocin (AVT)), and long-term stimulation can further induce metabolic disorders of the functional tissues (brain, heart, and adrenal gland), posing a lethal threat. Meanwhile, we also found that there were two kinds of death processes, direct death and chronic death, and both were closely related to the duration of stimulation and the regulation of the HPA axis.PMID:39684322 | DOI:10.3390/ijms252312610

Int J Mol Sci. 2024 Nov 23;25(23):12592. doi: 10.3390/ijms252312592.ABSTRACTElm (Ulmus) species are important components of forest resources with significant ecological and economic value. As tall hardwood trees that are drought-resistant, poor-soil-tolerant, and highly adaptable, Ulmus species are an excellent choice for ecologically protected forests and urban landscaping. Additionally, the bioactive substances identified in the fruits, leaves, bark, and roots of Ulmus have potential applications in the food and medical fields and as raw materials in industrial and cosmetic applications. However, the survival of Ulmus species in the natural environment has been threatened by recurrent outbreaks of Dutch elm disease, which have led to the death of large numbers of Ulmus trees. In addition, severe damage to the natural habitats of some Ulmus species is driving their populations to extinction. Omics technology has become an important tool for the collection, protection, and biological characteristic analysis of Ulmus species and their resources due to its recent advances. This article summarizes the current research and application status of omics technology in Ulmus. The remaining problems are noted, and future research directions are proposed. Our review is aimed at providing a reference for resource conservation of Ulmus and for scientific research into this genus.PMID:39684304 | DOI:10.3390/ijms252312592

Int J Mol Sci. 2024 Nov 22;25(23):12560. doi: 10.3390/ijms252312560.ABSTRACTAggressiveness is one of the personality traits of crustaceans, playing a crucial role in their growth, life history, and adaptability by influencing resource acquisition. However, the neuroregulatory mechanisms of aggressiveness in crustaceans remain poorly understood. The thoracic ganglion offers valuable insights into complementary aspects of aggression control. This study identified the aggressiveness of swimming crabs Portunus trituberculatus, conducted transcriptomic and metabolomic analyses of the thoracic ganglia, and confirmed the neural regulatory effects on aggressiveness. Behavioral analyses showed that highly aggressive individuals exhibited increased frequency and duration of chela extension, more frequent attacks, approaches and retreats, as well as extended movement distances. Omics analysis revealed 11 key candidate genes and three metabolites associated with aggressiveness, which were primarily enriched in pathways related to energy metabolism and neurodegeneration. Injection of an NMDAR activator significantly decreased aggressiveness in highly aggressive crabs, accompanied by a significant increase in NMDAR protein fluorescence intensity and downregulation of NR2B, CaMKII, and CREB genes. Conversely, when lowly aggressive crabs were injected with an NMDAR inhibitor, they showed increased aggressiveness alongside significantly decreased NMDAR protein fluorescence intensity, upregulated NR2B expression, and downregulated CaMKII and CREB genes. These results suggest that NMDAR within the thoracic ganglia serves as a key receptor in modulating aggressiveness in P. trituberculatus, potentially by influencing neural energy state via the NMDAR-CaMKII pathway, which in turn affects oxidative phosphorylation, cAMP, and FoxO pathways.PMID:39684272 | DOI:10.3390/ijms252312560

Int J Mol Sci. 2024 Nov 21;25(23):12515. doi: 10.3390/ijms252312515.ABSTRACTAutoimmune diseases represent a severe personal and healthcare problem that seeks novel therapeutic solutions. Mesenchymal stem cells (MSCs) are multipotent cells with interesting cell biology and promising therapeutic potential. The immunoregulatory effects of secretory factors produced by umbilical cord mesenchymal stem cells (UC-MSCs) were assessed on B lymphocytes from 17 patients with systemic lupus erythematosus (SLE), as defined by the 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE, and 10 healthy volunteers (HVs). Peripheral blood mononuclear cells (PBMCs) from patients and HVs were cultured in a UC-MSC-conditioned medium (UC-MSCcm) and a control medium. Flow cytometry was used to detect the surface expression of CD80, CD86, BR3, CD40, PD-1, and HLA-DR on CD19+ B cells and assess the percentage of B cells in early and late apoptosis. An enzyme-linked immunosorbent assay (ELISA) quantified the production of BAFF, IDO, and PGE2 in PBMCs and UC-MSCs. Under UC-MSCcm influence, the percentage and mean fluorescence intensity (MFI) of CD19+BR3+ cells were reduced in both SLE patients and HVs. Regarding the effects of the MSC secretome on B cells in lupus patients, we observed a decrease in CD40 MFI and a reduced percentage of CD19+PD-1+ and CD19+HLA-DR+ cells. In contrast, in the B cells of healthy participants, we found an increased percentage of CD19+CD80+ cells and decreased CD80 MFI, along with a decrease in CD40 MFI and the percentage of CD19+PD-1+ cells. The UC-MSCcm had a minimal effect on B-cell apoptosis. The incubation of patients' PBMCs with the UC-MSCcm increased PGE2 levels compared to the control medium. This study provides new insights into the impact of the MSC secretome on the key molecules involved in B-cell activation and antigen presentation and survival, potentially guiding the development of future SLE treatments.PMID:39684227 | DOI:10.3390/ijms252312515

Int J Mol Sci. 2024 Nov 21;25(23):12504. doi: 10.3390/ijms252312504.ABSTRACTCertain molecules found on the surface or within the cargo of extracellular vesicles (EVs) are linked to osteoarthritis (OA) severity and progression. We aimed to identify plasma pathogenic EV subpopulations that can predict knee radiographic OA (rOA) progression. We analyzed the mass spectrometry-based proteomic data of plasma EVs and synovial fluid (SF) EVs from knee OA patients (n = 16, 50% female). The identified surface markers of interest were further evaluated in plasma EVs from an independent cohort of knee OA patients (n = 30, 47% female) using flow cytometry. A total of 199 peptides with significant correlation between plasma and SF EVs were identified. Of these, 41.7% were linked to immune system processes, 15.5% to inflammatory responses, and 16.7% to the complement system. Crucially, five previously identified knee rOA severity-indicating surface markers-FGA, FGB, FGG, TLN1, and AMBP-were confirmed on plasma EV subpopulations in an independent cohort. These markers' baseline frequencies on large plasma EVs predicted rOA progression with an AUC of 0.655-0.711. Notably, TLN1 was expressed in OA joint tissue, whereas FGA, FGB, FGG, and AMBP were predominantly liver derived. These surface markers define specific pathogenic EV subpopulations, offering potential OA prognostic biomarkers and novel therapeutic targets for disease modification.PMID:39684216 | DOI:10.3390/ijms252312504

Int J Mol Sci. 2024 Nov 21;25(23):12500. doi: 10.3390/ijms252312500.ABSTRACTThe effects of starvation and refeeding on the gut condition of juvenile largemouth bass (Micropterus salmoides) remain unclear. Therefore, our research aimed to explore these effects. Amylase and lipase activities were remarkably decreased in the starvation (ST) group, yet prominently increased in the refeeding (RE) group (p < 0.05). In addition to the malondialdehyde (MDA) level, catalase (CAT) and superoxide dismutase (SOD) activities were significantly upregulated in the ST group (p < 0.05) in marked contrast to those in the controls; however, the RE group showed no substantial variations in CAT and SOD activities or the MDA level (p > 0.05). During starvation, the expression of Nrf2-Keap1 pathway-associated genes was significantly upregulated (p < 0.05). The comparative levels of TNF-α, IL-1β, and IL-15 were highly increased, with the levels of TGF-β1 and IL-10 apparently downregulated in the ST group; in contrast, these levels were restored to their original values in the RE group (p < 0.05). In contrast to the controls, the ST group showed significantly lower height and width of the villi, muscle thickness, and crypt depth and a higher goblet cell number; however, these values were recovered to some extent in the RE group (p < 0.05). The dominant bacterial phyla in the intestines of both groups were Proteobacteria, Firmicutes, Bacteroidetes, Acidobacteria, and Actinobacteria, with marked inter-group differences in the genera Serratia and Lactobacillus. Metabolomics analysis showed that amino acid metabolism is disrupted during starvation and is restored after refeeding. In summary, this study expands our comprehension of the interaction between oxidative stress and antioxidant defenses among juvenile largemouth bass subjected to starvation and refeeding.PMID:39684211 | DOI:10.3390/ijms252312500

Int J Mol Sci. 2024 Nov 21;25(23):12487. doi: 10.3390/ijms252312487.ABSTRACTShort-chain fatty acids (SCFAs) are produced by the fermentation of undigested polysaccharides; they are a group of metabolites resulting from the activity of intestinal bacteria. The main SCFAs are acetic, butyric, propionic, valeric, and caproic acid, and their levels and proportions depend on various factors. The aim of this study was to investigate the relationship between the concentration of SCFAs and the occurrence of specific gastrointestinal symptoms in infants. This study was conducted using faecal samples obtained at 1, 3, 6, and 12 months of age. The SCFA content was measured using gas chromatography. At 1 month, an association was found between butyric acid and flatulence. At 3 months, an association was found between butyric acid and flatulence/gas and between 3,4-methylovaleric acid and mucus in the stool. At 6 months, an association was found between butyric and valeric acids and flatulence. By 12 months, the gastrointestinal symptoms had decreased significantly. This study confirms that there is an association between SCFA levels and the presence of bloating, gas, mucus in the stool, and constipation in the gastrointestinal tract. Higher levels of butyric and valeric acids may lead to an increase in troublesome symptoms, such as flatulence and gas, in the first few months of life but are not associated with the occurrence of intestinal colic. The level of 3,4-methylovaleric acid is associated with the presence of allergies, whereas a decrease in acetic acid and an increase in isovaleric acid may exacerbate defecation problems in infants.PMID:39684199 | DOI:10.3390/ijms252312487

Molecules. 2024 Dec 3;29(23):5703. doi: 10.3390/molecules29235703.ABSTRACTSelenium is an essential trace element for the human body. However, its intake is usually low. Therefore, the production and utilization of selenium-enriched food are currently a research hotspot. Despite the remarkable scientific interest in this topic, only a few of the numerous studies focus on commercially available products. This study examined the nutritional quality, physical and chemical properties, cooking characteristics, and eating quality of four commercially available hot-selling rice types, both selenium-enriched and non-selenium-enriched, and discovered that selenium-enriched rice outperforms ordinary rice in terms of both nutritional quality and taste. In addition, we employed the gas chromatography-ion mobility spectrometry (GC-IMS) technique to evaluate the volatile chemicals of rice. Some of the chemicals that made selenium-rich rice taste different from regular rice were pentanal, (E)-2-Hexen-1-ol, ethyl-3-methyl butanoate, 2-furan methanol acetate, ethyl heptanoate, ethyl hexanoate, methyl hexanoate, isopentyl pentanoate, and ethyl butyrate. We looked into the metabolite profiles of rice using LC-MS-based untargeted metabolomics to obtain a better idea of the different metabolites that are found in selenium-enriched rice compared to regular rice. We identified a total of 522 metabolites and screened 182, 227, and 100 differential metabolites in selenium-enriched (A) vs. non-selenium-enriched rice (B/C/D) groups, respectively. This study revealed that selenium primarily influenced the metabolism of D-amino acids, starch, sucrose, and linoleic acid in rice. This study systematically analyzed the quality differences between selenium-enriched and non-selenium-enriched rice available on the market. For consumers, it is essential to understand the quality of selenium-rich rice on the market to guide the purchase of rice.PMID:39683861 | DOI:10.3390/molecules29235703

Molecules. 2024 Nov 28;29(23):5647. doi: 10.3390/molecules29235647.ABSTRACTPost-fermented Pu-erh tea (PFPT) is a microbial fermented tea characterized by unique sensory attributes and multiple health benefits. Aspergillus niger is the dominant fungus involved in the fermentation process and plays a significant role in imparting the distinct characteristics of PFPT. To investigate the role of Aspergillus niger in the fermentation of Pu-erh tea, this study inoculated unsterilized sun-dried green tea with Aspergillus niger isolated from Pu-erh tea to enhance the fermentation process. Metabolites and microbial communities in sun-dried green tea (CK), fortified fermented tea (TF), and naturally fermented tea (NF) were analyzed using non-targeted metabolomics, 16S rDNA, and internal transcribed spacer sequencing. Non-targeted metabolomics revealed that Aspergillus niger significantly altered the metabolite profile of the tea samples, identifying a total of 200 different metabolites, with 95 showing significant increases and 105 significant decreases, predominantly enriched in metabolic pathways associated with amino acid biosynthesis and degradation. High-throughput sequencing revealed that although the relative abundance of the fungal community remained largely unchanged, the inoculation of Aspergillus niger significantly increased the abundance of Bacillales and Pseudomonas within the bacterial community, thereby influencing the dynamic balance of the microbial ecosystem. Collectively, the inoculation of Aspergillus niger altered the composition of the microbial community and metabolic activities, resulting in changes to the content of amino acid-dominated metabolites, thereby enhancing the flavor profile and overall quality of Pu-erh tea. These findings provide important insights for optimizing the production processes of Pu-erh tea and the application of microorganisms in other fermented foods.PMID:39683805 | DOI:10.3390/molecules29235647

Molecules. 2024 Nov 25;29(23):5556. doi: 10.3390/molecules29235556.ABSTRACTKudzu, scientifically known as Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (P. lobata), is a perennial vine belonging to the family Leguminosae. Puerarin, a unique constituent and primary active ingredient of this genus, exhibits a broad spectrum of pharmacological activities. This study started with several practical questions: Why is the root the main medicinal part? Why is it not peeled for medicinal purposes? Why is the harvest period usually from December to February? Although the puerarin biosynthesis pathway has been investigated, the stage at which the 8-C glycosylation reaction occurs remains controversial. In this study, metabolomics and transcriptomics analyses were performed on P. lobata organs and tissues, including leaves, young stems, mature stems, tuberous cortices, and cortex-excised tubers of roots. Two modules containing genes associated with puerarin biosynthesis were identified by WGCNA. The final selection of important candidate UDP-glucosyltransferases (UGTs) that may be involved in the puerarin biosynthesis pathway included two 8-C-GTs, three 7-O-GTs, and key transcription factors. On this basis, the regulatory network of puerarin biosynthesis was constructed and laid the foundation for the cultivation of high-quality medicinal kudzu with high puerarin content.PMID:39683717 | DOI:10.3390/molecules29235556

Nutrients. 2024 Dec 9;16(23):4242. doi: 10.3390/nu16234242.ABSTRACTBackground: Small vulnerable newborns (SVNs), including those born preterm, small for gestational age, or with low birth weight, are at higher risk of neonatal mortality and long-term health complications. Early exposure to maternal vaginal microbiota and breastfeeding plays a critical role in the development of the neonatal microbiota and immune system, especially in low-resource settings like Burkina Faso, where neonatal mortality rates remain high. Objectives: The DenBalo study aims to investigate the role of maternal and neonatal factors, such as vaginal and gut microbiota, immune development, and early nutrition, in shaping health outcomes in SVNs and healthy infants. Methods: This prospective cohort observational study will recruit 141 mother-infant pairs (70 SVNs and 71 healthy controls) from four health centers in Bobo-Dioulasso, Burkina Faso. The mother-infant pairs will be followed for six months with anthropometric measurements and biospecimen collections, including blood, breast milk, saliva, stool, vaginal swabs, and placental biopsies. Multi-omics approaches, encompassing metagenomics, metabolomics, proteomics, and immune profiling, will be used to assess vaginal and gut microbiota composition and functionality, immune cell maturation, and cytokine levels at critical developmental stages. Conclusions: This study will generate comprehensive data on how microbiota, metabolomic, and proteomic profiles, along with immune system development, differ between SVNs and healthy infants. These findings will guide targeted interventions to improve neonatal health outcomes and reduce mortality, particularly in vulnerable populations.PMID:39683635 | DOI:10.3390/nu16234242

Nutrients. 2024 Dec 4;16(23):4195. doi: 10.3390/nu16234195.ABSTRACTIn this review, we provide an evidence-based approach to determine the cellular and systemic actions of two structurally similar flavonoids, apigenin and chrysin. We have clearly evaluated and charted the overlapping and diverging properties of these two sister flavonoids. Based on two separate Omics-based approaches by our group and independent reports from others, the cholesterol-lowering properties have been revealed. In addition, the prevention of uric acid biosynthesis and enhancement of ketogenesis have also been quite evident in these two flavonoids. Along with these overlapping functions, apigenin and chrysin have also demonstrated unique properties that allow them to stand out from each other. Chrysin has demonstrated abilities like downregulating alanine metabolism and pyrimidine synthesis, which could be helpful in metabolic diseases like cancer. In contrast, apigenin has demonstrated anti-oxidant and anti-inflammatory properties by enhancing endogenous anti-inflammatory lipids and upregulating vasoprotective metabolites, which could be beneficial for cardiovascular, renal, and cerebrovascular complications. Further validation studies using in vivo and translational approaches could provide us with better clarity regarding the use of these agents therapeutically and to treat a combination or pool of metabolic diseases.PMID:39683588 | DOI:10.3390/nu16234195

Nutrients. 2024 Nov 30;16(23):4161. doi: 10.3390/nu16234161.ABSTRACTBackground: Fibromyalgia (FM) is a chronic disorder that causes damage to the neuro-muscular system and alterations in the intestinal microbiota and affects the psychological state of the patient. In our previous study, we showed that 22 women patients subjected to a specific very low-carbohydrate ketogenic therapy (VLCKD) showed an improvement in clinical scores as well as neurotransmission-related and psychological dysfunctions and intestinal dysbiosis. Furthermore, NMR metabolomic data showed that changes induced by VLCKD treatment were evident in all metabolic pathways related to fibromyalgia biomarkers. Methods: Based on this evidence, we extend our investigation into dietary interventions for fibromyalgia by evaluating the impact of transitioning from a VLCKD to a low-glycemic insulinemic (LOGI) diet over an additional 45-day period. Therefore, participants initially following a VLCKD were transitioned to the LOGI diet after 45 days to determine whether the improvements in FM symptoms and metabolic dysfunctions achieved through VLCKD could be sustained with LOGI. Results: Our findings suggested that while VLCKD serves as an effective initial intervention for correcting metabolic imbalances and alleviating FM symptoms, transitioning to a LOGI diet offers a practical and sustainable dietary strategy. This transition preserves clinical improvements and supports long-term adherence and quality of life, underscoring the importance of adaptable nutritional therapies in chronic disease management. Control patients who adhered only to the LOGI diet for 90 days showed only modest improvement in clinical and psychological conditions, but not elimination of fibromyalgia symptoms. Conclusions: In conclusion the LOGI diet is an excellent alternative to maintain the results obtained from the regime VLCKD.PMID:39683556 | DOI:10.3390/nu16234161

Nutrients. 2024 Nov 28;16(23):4096. doi: 10.3390/nu16234096.ABSTRACTObjectives: This study investigates the effectiveness of an herbal formulation, STRESSLESS (ST-65), which combines ashwagandha (Withania somnifera) and bacopa (Bacopa monnieri), on SH-SY5Y human neuroblastoma cells. Given the rising interest in natural compounds for neuroprotection and stress alleviation, we aimed to explore the cellular and molecular effects of this formulation. Methods: Utilizing a nuclear magnetic resonance (NMR) metabolomic approach and ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS), we identified key bioactive compounds in ST-65, including withanolides from ashwagandha and bacosides from bacopa. Results: Our findings indicate that ST-65 treatment significantly alters the metabolic profile of SH-SY5Y cells. Key changes included increased levels of metabolites linked to neuroprotection, energy metabolism, and antioxidant defense. Notable enhancements were observed in specific amino acids and neuroprotective compounds, suggesting activation of neuroprotective mechanisms and mitigation of stress-induced damage. Conclusions: The study reveals a complex phyto-chemical profile of ST-65 and underscores its potential as a natural active agent for addressing stress-related neurodegenerative conditions. These insights into neuronal mechanisms provide a foundation for further exploration of herbal formulations in neuroprotection.PMID:39683490 | DOI:10.3390/nu16234096

Commun Med (Lond). 2024 Dec 16;4(1):265. doi: 10.1038/s43856-024-00637-1.ABSTRACTBACKGROUND: Distal sensorimotor polyneuropathy (DSPN) is a common neurological disorder in elderly adults and people with obesity, prediabetes and diabetes and is associated with high morbidity and premature mortality. DSPN is a multifactorial disease and not fully understood yet.METHODS: Here, we developed the Interpretable Multimodal Machine Learning (IMML) framework for predicting DSPN prevalence and incidence based on sparse multimodal data. Exploiting IMMLs interpretability further empowered biomarker identification. We leveraged the population-based KORA F4/FF4 cohort including 1091 participants and their deep multimodal characterisation, i.e. clinical data, genomics, methylomics, transcriptomics, proteomics, inflammatory proteins and metabolomics.RESULTS: Clinical data alone is sufficient to stratify individuals with and without DSPN (AUROC = 0.752), whilst predicting DSPN incidence 6.5 ± 0.2 years later strongly benefits from clinical data complemented with two or more molecular modalities (improved ΔAUROC > 0.1, achieved AUROC of 0.714). Important and interpretable features of incident DSPN prediction include up-regulation of proinflammatory cytokines, down-regulation of SUMOylation pathway and essential fatty acids, thus yielding novel insights in the disease pathophysiology.CONCLUSIONS: These may become biomarkers for incident DSPN, guide prevention strategies and serve as proof of concept for the utility of IMML in studying complex diseases.PMID:39681608 | DOI:10.1038/s43856-024-00637-1

Zhonghua Xin Xue Guan Bing Za Zhi. 2024 Dec 24;52(12):1446-1451. doi: 10.3760/cma.j.cn112148-20240922-00561.ABSTRACT肥厚型心肌病是最常见的遗传性心脏病，是青少年和运动员心脏性猝死的主要病因。梗阻性肥厚型心肌病是肥厚型心肌病的重要类型，多项研究显示，与非梗阻性肥厚型心肌病患者及正常人群相比，梗阻性肥厚型心肌病患者机体及心肌细胞存在代谢改变，且与患者不良临床症状与临床结局密切相关。同时，应用代谢组学研究结果可对梗阻性肥厚型心肌病发病机制与通路进行探究。该文就梗阻性肥厚型心肌病能量代谢改变进行综述，总结与梗阻性肥厚型心肌病有关的发病机制及通路，归纳有效的治疗靶点或评估预后的科学指标。.PMID:39681452 | DOI:10.3760/cma.j.cn112148-20240922-00561

Am J Physiol Endocrinol Metab. 2024 Dec 16. doi: 10.1152/ajpendo.00248.2024. Online ahead of print.ABSTRACTDiabetic kidney disease (DKD) is a severe diabetic microvascular complication featured by chronic low-grade inflammation. Roux-en-Y gastric bypass (RYGB) surgery has gained importance as a safe and effective surgery to treat DKD. Bile acids are significantly changed after RYGB, which brings a series of metabolic benefits, but the relationship with the improvement of DKD is unclear. Therefore, this study performed RYGB surgery on db/db mice to observe the beneficial effects of the surgery on the kidneys, and performed bile acid targeted metabolomics analysis to explore bile acid changes. We found that RYGB significantly reduced albuminuria in db/db mice, improved renal function, reversed renal structural lesions, and attenuated podocyte injury, inflammation. Notably, bile acid metabolomic analysis revealed taurolithocholic acid (TLCA) as the most significantly altered bile acid after RYGB. Further in vitro and in vivo validation experiments revealed that TLCA supplementation improved renal function and reduced renal inflammatory damage in db/db mice. In addition, TLCA inhibited high glucose-induced inflammatory damage in MPC-5 cells, and its mechanism of action may be related to activating Takeda G protein-coupled receptor 5 (TGR5), inhibiting NF-κB phosphorylation, and thus inhibiting inflammatory response. In conclusion, RYGB may play a protective role in the kidneys of diabetic mice by activating the TLCA/TGR5 pathway.PMID:39681344 | DOI:10.1152/ajpendo.00248.2024