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High-altitude de-acclimatization (HADA) significantly impacts physiological functions when individuals acclimatize to high altitudes return to lower altitudes. This study investigates HADA's effects on renal function and structure in rats, focusing on oxidative and endoplasmic reticulum stress as potential mechanisms of renal injury. To elucidate the pathophysiological mechanisms of renal damage in HADA and evaluate the efficacy of antioxidants Vitamin C (Vit C) and tauroursodeoxycholic acid (TUDCA) in mitigating these effects. 88 male Sprague-Dawley rats were randomly divided into a control group, a high-altitude (HA) group, a high-altitude de-acclimatization (HADA) group, and a treatment group. The control group was housed in a sea level environment (500 m), while the HA, HADA, and treatment groups were placed in a simulated high-altitude chamber (5000 m) for 90 days. After this period, the HA group completed the modeling phase; the HADA group was further subdivided into four subgroups, each continuing to be housed in a sea level environment for 3, 7, 14, and 30 days, respectively. The treatment group was split into the Vit C group, the TUDCA group, and two placebo groups, receiving medication for 3 consecutive days, once daily upon return to the sea level. The Vit C group received 100 mg/kg Vit C solution via intravenous injection, the TUDCA group received 250 mg/kg TUDCA solution via intraperitoneal injection, and the placebo groups received an equivalent volume of saline similarly. Serum, urine, and kidney tissues were collected immediately after the modeling phase. Renal function and oxidative stress levels were assessed using biochemical and ELISA methods. Renal histopathology was observed with H&E, Masson's trichrome, PAS, and PASM staining. Transmission electron microscopy was used to examine the ultrastructure of glomeruli and filtration barrier. TUNEL staining assessed cortical apoptosis in the kidneys. Metabolomics was employed for differential metabolite screening and pathway enrichment analysis. Compared to the control and HA groups, the HADA 3-day group (HADA-3D) exhibited elevated renal function indicators, significant pathological damage, observable ultrastructural alterations including endoplasmic reticulum expansion and apoptosis. TUNEL-positive cells significantly increased, indicating heightened oxidative stress levels. Various differential metabolites were enriched in pathways related to oxidative and endoplasmic reticulum stress. Early intervention with Vit C and TUDCA markedly alleviated renal injury in HADA rats, significantly reducing the number of apoptotic cells, mitigating endoplasmic reticulum stress, and substantially lowering oxidative stress levels. This study elucidates the pivotal roles of oxidative and endoplasmic reticulum stress in the early-stage renal injury in rats undergoing HADA. Early intervention with the Vit C and TUDCA significantly mitigates renal damage caused by HADA. These findings provide insights into the pathophysiological mechanisms of HADA and suggest potential therapeutic strategies for its future management. • Study on renal effects of high-altitude de-acclimatization (HADA) in rats. • Vitamin C and TUDCA reduce oxidative stress and kidney damage from HADA. • Identifies key metabolites and pathways in HADA-related kidney damage. • Advances understanding of physiological impacts in high-altitude medicine. [ABSTRACT FROM AUTHOR]

Background: Chelidonium majus is a well-known traditional Chinese medicine, and has been reported of the effect in relieving cough and asthma. However, the mechanism of action is still unknown. Methods: Asthmatic SD rats were first sensitized and established through ovalbumin (OVA) motivation. Subsequently, Hematoxylin and eosin (H&E) staining, Masson's trichrome (Masson) staining, Periodic acid-Schiff (PAS) staining and inflammatory cytokines assay of interleukin (IL)-4, IL-6, IL-17 were implemented to evaluate the protective effects of Chelidonium majus on asthma. Then, the effects of Chelidonium majus and their molecular mechanisms of action on asthma were detected based on the integration of transcriptomics and metabolomics analyses. Results: After administration with Chelidonium majus, the histological injuries of inflammation, collagen deposition and mucus secretion in lungs were attenuated and the serum inflammatory cytokines perturbations were also converted. Furthermore, integrated analysis revealed that after Chelidonium majus treatment, 7 different expression genes (DEGs) (Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9) and 9 metabolic biomarkers (ADP, Xanthosine, Hypoxanthine, Inosine, prostaglandin E2 (PGE2), prostaglandin F2a (PGF2a), phosphatidylserine, Creatine and LysoPC (10:0)) were discovered to be connected with the enrichment metabolic pathways, including Purine metabolism, Arachidonic acid metabolism, Arginine and proline metabolism and Glycerophospholipid metabolism. The obtained metabolic biomarkers and DEGs were mainly related to energy metabolism and inflammation, and may be potential therapeutic targets. Conclusion: Chelidonium majus relieved OVA-induced asthma in rats by regulating the Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9 genes expression to restore the disorders in energy metabolism and inflammation. [ABSTRACT FROM AUTHOR]

Highlights • Morinda officinalis (MO) mitigates the bone loss induced by glucocorticoid in rats. • MO enhances the bone formation of glucocorticoid-injured osteoblasts. • MO reverses the bone loss in GIOP rats by intervening arachidonic acid pathway. Abstract Morinda officinalis (MO) has long been used as a traditional herbal medicine for the treatment of bone fractures and joint diseases in China. Monotropein (Mon) and rubiadin-1-methyl ether (Rub) are major bioactive components in MO. Ample evidence shows that MO and its chemical constituents can prevent osteoporosis induced by estrogen-deficiency and ageing. However, there is no study reporting glucocorticoid-induced osteoporosis (GIOP). The aim of the present study was to explore the protective effect of MO on GIOP modeled rats and osteoblasts, and elucidate the underlying mechanisms via UHPLC-Q-TOF/MS based metabolomics profiling. Eight weeks after dexamethasone (DEX) injection and MO treatment in female SD rats aged 12 weeks, bone mineral density (BMD), the micro-architecture of the trabecular bone, serum level of bone metabolism markers, and urine metabolomics were assayed in vivo. Cultured osteoblasts were injured with DEX, and the effects of MO, Mon and Rub on osteoblastic proliferation, differentiation and mineralization were examined in vitro. The results showed that MO was able to increase BMD, improve the micro-architecture and intervene bone metabolism via regulating alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP) and c-terminal telopeptides of type I collagen (CTX-I) levels in DEX-treated rats. The in vitro experiment showed that MO, Mon and Rub all increased the cell proliferation and ALP activity, and enhanced extracellular matrix mineralization in DEX-injured osteoblasts. Metabolomics profiling identified a total of 37 differential metabolites in DEX group vs. the control group, of which 20 were reversed significantly after MO treatment. Further metabolic pathway enrichment and Western blotting analysis showed that MO prevented bone loss mainly by interfering with arachidonic acid metabolism. These results suggested MO had a notable anti-GIOP effect, and the underlying mechanisms might be related to arachidonic acid metabolism. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) and bipolar disorder (BD) are psychiatric disorders with overlapping symptoms, leading to high rates of misdiagnosis due to the lack of biomarkers for differentiation. This study aimed to identify metabolic biomarkers in urine samples for diagnosing MDD and BD, as well as to establish unbiased differential diagnostic models. We utilized a metabolomics approach employing ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) to analyze the metabolic profiles of urine samples from individuals with MDD (n = 50), BD (n = 12), and healthy controls (n = 50). The identification of urine metabolites was verified using MS data analysis tools and online metabolite databases. Two diagnostic panels consisting of a combination of metabolites and clinical indicators were identified—one for MDD and another for BD. The discriminative capacity of these panels was assessed using the area under the receiver operating characteristic (ROC) curve, yielding an area under the curve (AUC) of 0.9084 for MDD and an AUC value of 0.9017 for BD. High-resolution mass spectrometry-based assays show promise in identifying urinary biomarkers for depressive disorders. The combination of urine metabolites and clinical indicators is effective in differentiating healthy controls from individuals with MDD and BD. The metabolic pathway indicating oxidative stress is seen to significantly contribute to depressive disorders. • Accurate identification of differential metabolites between healthy controls and disease groups using UHPLC-MS and multiple databases. • Models utilizing urinary metabolites combined with clinical indicators are reliable for the diagnosis of MDD and BD. • Diagnostic models emphasize the important role of oxidative stress in the pathogenesis of psychiatric disorders. [ABSTRACT FROM AUTHOR]

Echinops latifolius Tausch (ELT) is traditional Mongolian medicine in China, and often used to against osteoporosis, strengthen tendons and bones, clear bones heat. To study efficacy of ELT on ovariectomized (OVX) rats and underly metabolic pathways related to trabecular micro-architecture changing of OVX. Three-month-old female Wistar rats were randomly divided into 4 groups (n = 6) including normal group (without surgery), sham group (bilateral laparotomy), OVX group (bilateral ovariectomy), and ELT-treated groups (ELT-treated after bilateral ovariectomy). The effects of ELT on trabecular micro-architecture and biochemical markers of OVX rat were investigated by dual-energy X-ray absorptiometry machine and Enzyme-linked immunosorbent assay (ELISA), respectively. Untargeted metabolomics strategy was applied to discover the potential biomarkers and related metabolic pathways involving the progression of OVX-induced osteoporosis. The trabecular micro-architecture and biochemical markers of OVX rats were improved by ELT. We found 36 potential biomarkers and 21 related metabolic pathways were involved in progression of OVX-induced osteoporosis. Amino acids metabolism and glycerophospholipids metabolism were mainly intervened in ELT treatment on ovariectomized rats. The disordered amino acids and glycerophospholipids metabolism closely related to the imbalance between bone resorption and formation were reversed by administration of ELT, indicating that the influences of ELT on OVX rats' trabecular micro-architecture may possible be associated with intervening amino acids and glycerophospholipids metabolism. This approach may provide the metabolomic perspective to link metabolic alterations and anti-osteoporosis action of ELT, to further explain how ELT works in postmenopausal patients with bone loss. Image 1 • Anti-osteoporosis efficacy of Echinops latifolius Tausch on ovariectomized rats was evaluated by trabecular micro-architecture changing for the first time. • Pharmacodynamics and metabolomics were combined to elucidate the mechanism of Echinops latifolius Tausch in the treatment of osteoporosis for the first time. • The influences of Echinops latifolius Tausch on ovariectomized rats' trabecular micro-architecture were uncovered in this paper for the first time. • This work provides the metabolomic perspective to link metabolic alterations and anti-osteoporosis action of Echinops latifolius Tausch. [ABSTRACT FROM AUTHOR]

We have previously reported that Trichoderma atroviride, an endophytic fungus isolated from S. miltiorrhiza, promotes S. miltiorrhiza hairy root growth and significantly stimulates the biosynthesis of tanshinones specifically the polysaccharide fraction (PSF). However, this study only focused exclusively on six metabolites whilst ignoring changes to the whole metabolite composition of the S. miltiorrhiza hairy roots. In the present study, the dynamic metabonomic responses of S. miltiorrhiza hairy roots were investigated using ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMSn). UHPLC-HRMS typical total ions chromatograms (TICs) of PSF-treated hairy root samples were different from the control. Moreover, the results of principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and hierarchical clustering analysis (HCA) indicated that PSF-treated samples were significantly different from the control. Through the analysis of PLS-DA, a total of 114 and 99 differential metabolites were found from the positive and negative models respectively and a total of 33 differential metabolites were identified. Thus, S. miltiorrhiza hairy roots had been induced to regulate the metabolic profiling in response to PSF and the changes of the metabolic profiling contributed to promoting the biosynthesis of tanshinones notably whilst the biosynthesis of phenolic acids were slightly inhibited. [ABSTRACT FROM AUTHOR]

Indiscriminate drug administration may lead to drug therapy results with varying effects on patients, and the proposal of personalized medication can help patients to receive effective drug therapy. Conventional ways of personalized medication, such as pharmacogenomics and therapeutic drug monitoring (TDM), can only be implemented from a single perspective. The development of pharmacometabolomics provides a research method for the realization of precise drug administration, which integrates the environmental and genetic factors, and applies metabolomics technology to study how to predict different drug therapeutic responses of organisms based on baseline metabolic levels. The published research on pharmacometabolomics has achieved satisfactory results in predicting the pharmacokinetics, pharmacodynamics, and the discovery of biomarkers of drugs. Among them, the pharmacokinetics related to pharmacometabolomics are used to explore individual variability in drug metabolism from the level of metabolism of the drugs in vivo and the level of endogenous metabolite changes. By searching for relevant literature with the keyword "pharmacometabolomics" on the two major literature retrieval websites, PubMed and Web of Science, from 2006 to 2023, we reviewed articles in the field of pharmacometabolomics that incorporated pharmacokinetics into their research. This review explains the therapeutic effects of drugs on the body from the perspective of endogenous metabolites and pharmacokinetic principles, and reports the latest advances in pharmacometabolomics related to pharmacokinetics to provide research ideas and methods for advancing the implementation of personalized medication. [ABSTRACT FROM AUTHOR]

Rehmanniae Radix Preparata (RR), the dry rhizome of Rehmannia glutinosa Libosch., is a traditional herbal medicine for improving the liver and kidney function. Ample clinical and pharmacological experiments show that RR can prevent post-menopausal osteoporosis and senile osteoporosis. In the present study, in vivo and in vitro experiments, as well as a UHPLC-Q/TOF-MS-based metabolomics study, were used to explore the preventing effect of RR on glucocorticoid-induced osteoporosis (GIOP) and its underlying mechanisms. As a result, RR significantly enhanced bone mineral density (BMD), improved the micro-architecture of trabecular bone, and intervened in biochemical markers of bone metabolism in dexamethasone (DEX)-treated rats. For the in vitro experiment, RR increased the cell proliferation and alkaline phosphatase (ALP) activity, enhanced the extracellular matrix mineralization level, and improved the expression of runt-related transcription factor 2 (RUNX2) and osteopontin (OPN) in DEX-injured osteoblasts. For the metabolomics study, a total of 27 differential metabolites were detected in the DEX group vs. the control group, of which 10 were significantly reversed after RR treatment. These metabolites were majorly involved in steroid hormone biosynthesis, sex steroids regulation, and amino acid metabolism. By metabolic pathway and Western blotting analysis, it was further ascertained that RR protected against DEX-induced bone loss, mainly via interfering steroid hormone biosynthesis, as evidenced by the up-regulation of cytochrome P450 17A1 (CYP17A1) and aromatase (CYP19A1), and the down-regulation of 11β-hydroxysteroid dehydrogenase (HSD11B1). Collectively, these results indicated that RR had a notable preventing effect on GIOP, and the action mechanism might be related to steroid hormone biosynthesis. [ABSTRACT FROM AUTHOR]

Most osteoporosis (OP) fracture accidents in men are due not only to a low BMD but also because of unhealthy muscle support. However, there has been a limited number of reports about how muscle metabolism is disturbed by OP in males. In this work, a pathway analysis based on metabolomic research was carried out to fill this gap. A classical orchiectomy procedure was adapted to create an OP animal model. A micro-CT and pathological section were applied for a bone and muscle phenotype assessment and a pathology analysis. UPLC-Q-TOF/MS and UPLC-QQQ-MS/MS were applied to measure metabolites in skeletal muscle samples among groups. In total, 31 significantly differential metabolites were detected by comparing healthy models and OP animals, and 7 representative metabolites among the 31 significantly differential metabolites were identified and validated experimentally by UPLC-QQQ-MS/MS (xanthine, L-phenylalanine, choline, hypoxanthine, L-tryptophan, succinic acid, and L-tyrosine). An ingenuity pathway analysis (IPA) analysis revealed significantly enriched pathways involved in inflammation, oxidative stress, and necrosis. To our best knowledge, this is the first study to investigate early muscle disorder processes in Cases of OP at a metabolic level, facilitating early intervention and protection from OP fractures for aged men. [ABSTRACT FROM AUTHOR]

• NAT2 expression was significantly up-regulated in CRC and at increased risk of developing CRC. • XDH is a metabolic gene associated with low risk prognosis of CRC. • The risk of death remarkably decreased by rare allele count for GPX3 in CRC. • AOC3 is down-regulated in human CRC and can predict CRC mortality. • AKR1C4 is a high risk gene and might be an independent prognosis marker and therapeutic target for CRC patients. • SPHK1 is highly expressed in CRC tissues, and high expression of SPHK1 is positively correlated with the poor prognosis of CRC. • ADCY5 may be a novel and independent prognostic biomarker and therapeutic target for CRC patients. Colorectal cancer (CRC) is one of the most commonplace malignant tumors in the world. The occurrence and development of CRC are involved in numerous events. Metabolic reprogramming is one of the hallmarks of cancer and is convoluted and associated with carcinogenesis. Lots of metabolic genes are involved in the occurrence and progression of CRC. Study methods combining tumor genomics and metabolomics are more likely to explore this field in depth. In this mini-review, we make the latest progress and future prospects into the different molecular mechanisms of seven prognosis-related metabolic genes, we screened out in previous research, involved in the occurrence and development of CRC. [ABSTRACT FROM AUTHOR]

Background: Hypothyroidism is a chronic condition of endocrine disorder and its precise molecular mechanism remains obscure. In spite of certain efficacy of thyroid hormone replacement therapy in treating hypothyroidism, it often results in other side effects because of its over-replacement, so it is still urgent to discover new modes of treatment for hypothyroidism. Sini decoction (SND) is a well-known formula of Traditional Chinese Medicine (TCM) and is considered as efficient agents against hypothyroidism. However, its holistic effect assessment and mechanistic understanding are still lacking due to its complex components. Methodology/Principal Findings: A urinary metabonomic method based on ultra performance liquid chromatography coupled to mass spectrometry was employed to explore global metabolic characters of hypothyroidism. Three typical hypothyroidism models (methimazole-, propylthiouracil- and thyroidectomy-induced hypothyroidism) were applied to elucidate the molecular mechanism of hypothyroidism. 17, 21, 19 potential biomarkers were identified with these three hypothyroidism models respectively, primarily involved in energy metabolism, amino acid metabolism, sphingolipid metabolism and purine metabolism. In order to avert the interference of drug interaction between the antithyroid drugs and SND, the thyroidectomy-induced hypothyroidism model was further used to systematically assess the therapeutic efficacy of SND on hypothyroidism. A time-dependent recovery tendency was observed in SND-treated group from the beginning of model to the end of treatment, suggesting that SND exerted a recovery effect on hypothyroidism in a time-dependent manner through partially regulating the perturbed metabolic pathways. Conclusions/Significance: Our results showed that the metabonomic approach is instrumental to understand the pathophysiology of hypothyroidism and offers a valuable tool for systematically studying the therapeutic effects of SND on hypothyroidism. [ABSTRACT FROM AUTHOR]

Highlights • GC–MS, RPLC-MS and HILIC-MS metabolomic assessed the efficacy of SFI on AVMC. • Computational systems analysis identified SFI-targeted metabolic pathways. • RT-PCR analysis validated the key enzymes in the SFI-targeted pathways. Abstract Acute viral myocarditis (AVMC) is typically caused by cardiotropic viral infection. There is a paucity of specific treatment options available with proven efficacy. Chinese patented pharmaceutical product Shenfu injection (SFI) has potent efficacy on treating AVMC in clinical practice. However, the molecular mechanism is still unknown. We employed cross-platform metabolomics combined with computational systems analysis, based on reversed-phase liquid chromatography–mass spectrometry (RPLC-MS), hydrophilic interaction liquid chromatography–mass spectrometry (HILIC-MS) and gas chromatography-mass spectrometry (GC–MS), to deciphering the targeted metabolic pathways of SFI against AVMC induced by coxsackievirus B3 (CVB3). Quantitative real-time PCR (qRT-PCR) technique was further applied to determining the expressions of the key genes associated with the SFI-targeted metabolic pathways. We have identified 48 significantly changed metabolites related to CVB3-induced AVMC, and SFI can significantly regulate the abnormalities of 33 metabolites and 9 relevant enzymes. Combined metabolic pathway enrichment and topology analyses revealed that the mechanisms of SFI against CVB3-induced AVMC may be attributed to modulating the disordered homeostasis of sphingolipid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, tryptophan metabolism, and TCA cycle. It provides new experimental information on the pathogenesis of AVMC, unravels the potential targeted metabolic pathways of SFI against AVMC on the whole metabolic network and highlights the importance of metabolomics combined with computational systems analysis as a potential tool for deciphering drug-targeted metabolic pathways. [ABSTRACT FROM AUTHOR]

Studies have documented the potential antitumor activities of glaucocalyxin A (GLA), an ent-kaurene diterpenoid isolated from Rabdosia japonica. However, the metabolic mechanism underlying the antitumor activity of GLA remains largely unknown. The effects of GLA on the metabolome of human liver cancer cells using GC/MS- and LC/MS-based metabolic profiling have been investigated. An untargeted metabolomics approach in conjunction with orthogonal projection to latent structures-discriminant analysis (OPLS-DA) has been developed to characterize the metabolic modifications induced by GLA treatment in human hepatoma cell line SMMC7721. Results demonstrated that cells cultured in the presence or absence of GLA displayed different metabolic profiles: the treatment induced an increased purine metabolism, pyrimidine metabolism, and sphingolipid metabolism and a decreased amino acid metabolism. At the same time, GLA treatment induced cell apoptosis and cell cycle arrested at G2/M phase in a dose-dependent manner. In addition, two representative apoptosis-inducing cytotoxic agents were selected as positive control drugs to validate the reasonableness and accuracy of our metabolomic investigation on GLA. The study displayed a systemic metabolic alteration induced by GLA treatment, showing the impaired physiological activity of SMMC7721 cells, which also indicated anti-proliferative and apoptotic effects of GLA. In the meantime, GC/MS- and LC/MS-based metabolomics applied to cell culture enhanced our current understanding of the metabolic response to GLA treatment and its mechanism; such an approach could be transferred to study the mechanism of other anticancer drugs.A systemic metabolic alteration induced by glaucocalyxin A (GLA) treatment of SMMC-7721 cells [ABSTRACT FROM AUTHOR]

Veratrum nigrum L. (VN) is a poisonous traditional Chinese medicine herb present since thousands of years in China. Clinical studies have shown that VN has the ability to cause hepatotoxicity, which severely limits its clinical use. The mechanism of its hepatotoxicity has not been fully elucidated. The purpose of this study was to develop and characterize a model of acute and chronic hepatotoxicity induced by Veratrum nigrum L. extract (VNE) to understand the mechanism of liver tissue metabolomics approach using on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOFMS). Mice were administered with VNE in the acute and chronic phases. Histopathologic inspections and biochemistry analysis disclosed severe liver damage after exposure to VNE. A partial least-squares discriminant analysis (PLS-DA) of the metabolomic profiles of rat liver tissues highlighted a number of metabolic disturbances induced by VNE, focusing on purine and pyrimidine metabolism, tryptophan metabolism, phospholipid metabolism, sphingolipid metabolism and fatty acid metabolism. These findings could well explain VNE-induced acute and chronic hepatotoxicity and reveal several potential biomarkers associated with this toxicity. This indicates that UHPLC-Q-TOFMS-based metabolomics approach demonstrated its feasibility and allowed a better understanding of VNE-induced liver toxicity dynamically. [ABSTRACT FROM AUTHOR]

Polygoni Multiflori Radix (PMR) has been widely used as a tonic for centuries. However, hepatotoxicity cases linked to PMR have been frequently reported and appropriate biomarkers for clinical diagnosis are currently lacking. Here, an approach using UPLC-QqQ/MS-based targeted metabolomics of bile acids (BAs) complemented with biochemistry and histopathology was applied to characterize the development and recovery processes of PMR-induced hepatotoxicity in rats and to identify biomarkers. The expression of bile salt export pump (Bsep) and sodium taurocholate cotransporting polypeptide (Ntcp) were evaluated to investigate the underlying mechanism. Steatosis and inflammatory cell infiltration were observed in PMR-treated rats, which were accompanied by the elevation of serum biochemistry. The metabolic profiles of BAs were analyzed by Principal Component Analysis, hyodeoxycholic acid (HDCA) in serum and tauro-β-muricholic acid (TβMCA) in urine were identified as potential biomarkers for PMR-induced hepatotoxicity. The elevated expression of Bsep and decreased expression of Ntcp in the liver of PMRtreated rats indicated that hepatotoxicity was related to the disorders of BAs metabolism. Our study demonstrated that BAs may be used for clinical diagnosis of PMR-induced hepatotoxicity. Urine TβMCA was identified as a promising biomarker to facilitate the clinical monitoring of PMR-induced hepatotoxicity and may serve as potential therapeutic target. [ABSTRACT FROM AUTHOR]

Postmenopausal osteoporosis (PMOP) and sarcopenia are common diseases that predominantly affect postmenopausal women. In the occurrence and development of these two diseases, they are potentially pathologically connected with each other at various molecular levels. However, the application of metabolomics in sarco-osteoporosis and the metabolic rewiring happening throughout the estrogen loss-replenish process have not been reported. To investigate the metabolic alteration of sarco-osteoporosis and the possible therapeutical effects of estradiol, 24 mice were randomly divided into sham surgery, ovariectomy (OVX), and estradiol-treated groups. Three-dimensional reconstructions and histopathology examination showed significant bone loss after ovariectomy. Estrogen can well protect against OVX-induced bone loss deterioration. UHPLC-Q-TOF/MS was preformed to profile semi- polar metabolites of skeletal muscle samples from all groups. Metabolomics analysis revealed metabolic rewiring occurred in OVX group, most of which can be reversed by estrogen supplementation. In total, 65 differential metabolites were identified, and pathway analysis revealed that sarco-osteoporosis was related to the alterations in purine metabolism, glycerophospholipid metabolism, arginine biosynthesis, tryptophan metabolism, histidine metabolism, oxidative phosphorylation, and thermogenesis, which provided possible explanations for the metabolic mechanism of sarco-osteoporosis. This study indicates that an UHPLC-Q-TOF/MS-based metabolomics approach can elucidate the metabolic reprogramming mechanisms of sarco-osteoporosis and provide biological evidence of the therapeutical effects of estrogen on sarco-osteoporosis. [ABSTRACT FROM AUTHOR]

Abstract: The HIV-1 Tat protein is released by infected cells and has numerous biological activities which might contribute either to the impairment of the immune response or to viral dissemination and pathogenesis. To date, the effects of Tat protein on metabolites remain unclear. In this study, a metabolomic study on serum of HIV-1 Tat-induced ICR mice was performed to research the pathologic mechanism of Tat protein by using gas chromatography coupled to mass spectrometry (GC/MS). Clear separations among the HIV-1 Tat-induced mice and the inaTat-induced or control mice were observed by principal component analysis and partial least-squares discriminant analysis based on the GC/MS spectral data. Additionally, 16 significantly changed metabolites in HIV-1 Tat-induced mice were identified that are involved in multiple perturbed metabolic pathways, which contributed to the elucidation of the complex pathogenic mechanism of Tat protein and may shed new lights on future improvement of HIV-1 therapy. [Copyright &y& Elsevier]

Introduction: Alzheimer's disease (AD) is a chronic neurodegenerative disorder with neither definitive pathogenesis nor effective therapy so far. Danshen, the dried root and rhizome of Salvia miltiorrhiza Bunge, is used extensively in Alzheimer's disease treatment to ameliorate the symptoms, but the underlying mechanism remains to be clarified.Objectives: To investigate potential biomarkers for AD and elucidate the protective mechanism of Danshen on AD cell model.Methods: An ultra high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF/MS)-based approach combined with partial least squares discriminant analysis (PLS-DA) has been developed to discriminate the metabolic modifications between human brain microvascular endothelial cell (hBMEC) and AD cell model induced by amyloid-β protein (Aβ1-42). To further elucidate the pathophysiology of AD, related metabolic pathways have been studied.Results: Thirty-three distinct potential biomarkers were screened out and considered as potential biomarkers corresponding to AD, which were mostly improved and partially restored back to normalcy in Danshen pre-protection group. It was found that AD was closely related to disturbed arginine and proline metabolism, glutathione metabolism, alanine aspartate and glutamate metabolism, histidine metabolism, pantothenate and CoA biosynthesis, phenylalanine tyrosine and tryptophan biosynthesis, citrate cycle and glycerophospholipid metabolism, and the protective mechanism of Danshen in AD cell model may be related to partially regulating the perturbed pathways.Conclusions: These outcomes provide valuable evidences for therapeutic mechanism investigation of Danshen in AD treatment, and such an approach could be transferred to unravel the mechanism of other traditional Chinese medicine (TCM) and diseases. [ABSTRACT FROM AUTHOR]