ObjectiveTo investigate the mechanism by which adrenoceptor alpha 2A (Adra2a) regulates lipopolysaccharide (LPS)-induced inflammation in primary hepatocytes from lipopolysaccharide-binding protein (LBP) knockout mice (Lbp^-/-). MethodsPrimary hepatocytes from C57BL/6J and Lbp^-/- mice were isolated using a two-step perfusion method. An in vitro inflammatory model was established by LPS stimulation, and an in vivo inflammatory mouse model was established by intraperitoneal injection of LPS. The in vitro experiments were grouped as follows: Control group, LPS group, BRL+LPS group, OE-NC+LPS group, and OE-Adra2a+LPS group. The Control group served as the blank control. The LPS group involved stimulating primary hepatocytes with LPS. The BRL+LPS group involved pretreating primary hepatocytes with BRL-44408 maleate followed by LPS stimulation. The OE-NC+LPS group involved transfecting primary hepatocytes with an empty vector followed by LPS stimulation. The OE-Adra2a+LPS group involved transfecting primary hepatocytes with a lentivirus overexpressing Adra2a, followed by LPS stimulation. The in vivo experimental groups were divided into Control', LPS', BRL+LPS', OE-NC+LPS', and OE-Adra2a+LPS' groups. The Control' group served as the blank control. The LPS' group received intraperitoneal injection of LPS. The BRL+LPS' group received intraperitoneal injection of BRL-44408 maleate for pretreatment, followed by LPS injection. The OE-NC+LPS' group received intraperitoneal injection of empty vector for pretreatment, followed by LPS injection. The OE-Adra2a+LPS' group received intraperitoneal injection of a lentivirus overexpressing Adra2a for pretreatment, followed by LPS injection. Cell viability after Adra2a inhibition and overexpression was assessed via the Cell Counting Kit-8 (CCK-8) assay. RT-qPCR measured changes in gene expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) after Adra2a inhibition and overexpression. Western blotting was performed to detect Adra2a protein expression and phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase (JNK) following LPS stimulation. ResultsIn vitro experiments revealed that LPS stimulation significantly decreased Adra2a protein expression in primary hepatocytes from C57BL/6J mice compared to the Control group (P<0.05), whereas it increased in primary hepatocytes from Lbp^-/- mice (P<0.001). Compared to the LPS group, the BRL+LPS group exhibited significantly increased cell viability (P<0.01), reduced TNF-α, IL-6, and IL-1β gene transcription levels (P<0.01, P<0.001, P<0.001), and decreased phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.01, P<0.001, P<0.001). Compared with the OE-NC+LPS group, the OE-Adra2a+LPS group showed significantly decreased cell viability (P<0.001), increased gene transcription levels of TNF-α, IL-6, and IL-1β genes (P<0.001, P<0.01, P<0.001), and elevated phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.001, P<0.01, P<0.001). In vivo experiments showed that, compared with the LPS' group, the BRL+LPS' group exhibited significantly reduced phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.001, P<0.01, P<0.01). In the OE-Adra2a+LPS' group, the phosphorylation levels of ERK1/2, p38, and JNK were significantly elevated compared to the OE-NC+LPS' group (P<0.01, P<0.001, P<0.01). ConclusionLPS stimulation can cause a significant increase in Adra2a protein expression in primary hepatocytes of Lbp^-/- mice. Adra2a protein can regulate the level of LPS-induced inflammation in primary hepatocytes of Lbp^-/- mice through the MAPK signaling pathway.

Metabolic diseases have seen a steady increase in incidence in recent years, becoming one of the main causes of sub-health status globally. Neutrophil extracellular traps(NETs) are reticular complexes containing DNA, which trap foreign microorganisms or induce an immune response. Current research indicates that NETs are widely active in various metabolic diseases and can cause severe damage to the body through multiple mechanisms, including promoting blood glucose elevation, damaging vascular endothelial cells, forming vascular embolisms, triggering intense inflammation, and promoting lipid accumulation. Therefore, intervening in NETs is an important approach to treating metabolic diseases. Research has shown a close relationship between the theory of spleen heat-turbid toxin theory and metabolic diseases-NETs mechanism. The basic pathogenesis include the internal accumulation of phlegm-dampness, qi stagnation and blood stasis, internal accumulation of dampness-heat, phlegm and blood stasis, and flourishing toxic heat. Various Chinese herbal medicines with the functions of dispelling dampness, resolving phlegm, promoting blood circulation to remove blood stasis, and clearing heat and toxins, along with their extracts and compound prescriptions, can treat metabolic diseases by regulating NETs and delaying disease progression. This paper systematically outlined the formation mechanisms of NETs, their connection to metabolic diseases, the theoretical basis in TCM, their roles in numerous metabolic diseases, and the current research status of TCM in regulating NETs to prevent and control metabolic diseases, aiming to provide effective reference ideas for developing therapeutic strategies for metabolic diseases.
Humans ; Extracellular Traps/metabolism* ; Metabolic Diseases/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Neutrophils/metabolism* ; Medicine, Chinese Traditional

This study aimed to explore the effects and mechanisms of total extracts from Anthriscus sylvestris on pulmonary hypertension in rats. Sixty male SD rats were divided into normal(NC) group, model(M) group, positive drug sildenafil(Y) group, low-dose A. sylvestris(ES-L) group, medium-dose A. sylvestris(ES-M) group, and high-dose A. sylvestris(ES-H) group. On day 1, rats were intraperitoneally injected with monocrotaline(60 mg·kg~(-1)) to induce pulmonary hypertension, and the rat model was established on day 28. From days 15 to 28, intragastric administration of the respective treatments was performed. After modeling and treatment, small animal echocardiography was used to detect the right heart function of the rats. Arterial blood gas was measured using a blood gas analyzer. Hematoxylin and eosin(HE) staining and Masson staining were performed to observe cardiopulmonary pathological damage. Flow cytometry was used to detect apoptosis in the lung and myocardial tissues and reactive oxygen species(ROS) levels. Western blot was applied to detect the expression levels of transforming growth factor-β1(TGF-β1), phosphorylated mothers against decapentaplegic homolog 3(p-Smad3), Smad3, tissue plasminogen activator(t-PA), and plasminogen activator inhibitor-1(PAI-1) in lung tissue. A blood routine analyzer was used to measure inflammatory immune cell levels in the blood. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of P-selectin and thromboxane A2(TXA2) in plasma. The results showed that, compared with the NC group, right heart hypertrophy index, right ventricular free wall thickness, right heart internal diameter, partial carbon dioxide pressure(PaCO_2), apoptosis in cardiopulmonary tissue, and ROS levels were significantly increased in the M group. In contrast, the ratio of pulmonary blood flow acceleration time(PAT)/ejection time(PET), right cardiac output, change rate of right ventricular systolic area, systolic displacement of the tricuspid ring, oxygen partial pressure(PaO_2), and blood oxygen saturation(SaO_2) were significantly decreased in the M group. After administration of the total extract of A. sylvestris, right heart function and blood gas levels were significantly improved, while apoptosis in cardiopulmonary tissue and ROS levels significantly decreased. Further testing revealed that the total extract of A. sylvestris significantly decreased the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and PAI-1 proteins in lung tissue, while increasing the expression of t-PA. Additionally, the extract reduced the levels of inflammatory cells such as leukocytes, lymphocytes, granulocytes, and monocytes in the blood, as well as the levels of P-selectin and TXA2 in plasma. Metabolomics results showed that the total extract of A. sylvestris significantly affected metabolic pathways, including arginine biosynthesis, tyrosine metabolism, and taurine and hypotaurine metabolism. In conclusion, the total extract of A. sylvestris may exert an anti-pulmonary hypertension effect by inhibiting the TGF-β1/Smad3 signaling pathway, thereby alleviating immune-inflammatory responses and thrombosis.
Animals ; Male ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Hypertension, Pulmonary/genetics* ; Thrombosis/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Apoptosis/drug effects*

Objective:To discuss the inhibitory effects of combined application of chlorogenic acid(CA),procyanidin(PC),and paeoniflorin(PF),the active components of Paeoniae Radix Rubra,on Enterococcus faecalis(E.faecalis)and its biofilm,and to clarify the mechanism.Methods:The minimal inhibitory concentration(MIC)and minimal bactericidal concentration(MBC)of CA,PC,and PF against E.faecalis were detected by microdilution method;the fractional inhibitory concentration index(FICI)and fractional bactericidal concentration index(FBCI)of the three active components of Paeoniae Radix Rubra in combination were detected by checkerboard dilution method.The experiment was divided into control group,high concentration of single-drug groups(PF-10 group,PC-6 group,and CA-10 group),and drug combination groups(CA-2+PC-1 group,CA-2+PC-2 group,PF-4+PC-2 group,PF-6+PC-2 group,PF-4+CA-4 group,and PF-6+CA-4 group).Crystal violet staining was used to detect the biofilm formation of E.faecalis in various groups after treated with three active components in combination;scanning electron microscope(SEM)was used to observe the morphology of E.faecalis biofilm in various groups after treated with three active components in combination;spot assay was used to detect the inhibitory effects of three active components in combination on E.faecalis planktonic bacteria and biofilm in various groups;SEM was used to observe the damage to E.faecalis cell membrane in various groups after treated with three active components in combination;kit was used to detect the adenosine triphosphate(ATP)levels in E.faecalis planktonic bacteria and biofilm in various groups after treated with three active components in combination.Results:Among the three active components of Paeoniae Radix Rubra,the MIC of PC was 4 g·L?1 and the MBC was 6 g·L?1;the MIC of CA was 8 g·L?1 and the MBC was 10 g·L?1;the MIC and MBC of PF were both>10 g·L?1,and the concentration of PF was selected as 10 g·L?1.The combination of PC and CA showed synergistic effects,the combination of PC and PF showed additive effects,and the combination of CA and PF showed additive effects.The crystal violet staining results showed that compared with control group,the biofilm formations of E.faecalis in PF-10 group,PC-6 group,CA-10 group,and drug combination groups were significantly decreased(P<0.05);compared with PF-10 group,the biofilm formations of E.faecalis in PC-6 group,CA-10 group,CA-2+PC-1 group,CA-2+PC-2 group,PF-4+PC-2 group,PF-6+PC-2 group,and PF-6+CA-4 group were significantly decreased(P<0.05 or P<0.01).The SEM results showed that in control group,the E.faecalis biofilm was thick,with tightly connected bacteria,regular morphology,and intact cell membranes;in PF-10 group,PC-6 group,and CA-10 group,the thickness of E.faecalis biofilm was significantly reduced,and the arrangement of bacteria became relatively loose;in all drug combination groups,the E.faecalis biofilm was significantly reduced or even completely disappeared,and under high magnification,the biofilm structure was completely absent,with bacterial fragments adhering and aggregating,losing their original bacterial morphology.The spot assay results showed that compared with control group,the colonies of E.faecalis planktonic bacteria in PF-10 group,PC-6 group,and CA-10 group were significantly reduced after treated for 5,10,and 30 min,indicating gradually enhanced bactericidal effects;among drug combination groups,the combination of CA and PC significantly reduced the colonies of E.faecalis planktonic bacteria within 5 min,showing strong bactericidal effects.Compared with CA group and PC group,the colonies of E.faecalis planktonic bacteria in all drug combination groups showed no significant reduction after treated for 5,10,and 30 min;compared with control group,the colonies of E.faecalis biofilm in PF-10 group,PC-6 group,and CA-10 group were gradually decreased after the treated for 30 and 60 min,suggesting that the high concentration of single-drug groups exhibited gradually enhanced bactericidal effects on E.faecalis in biofilm.Among them,the biofilm-killing effect of PC-6 group was the most significant,with no colony formation observed after treated for 30 min;in drug combination groups,only a few colonies of E.faecalis biofilm were observed in CA-2+PC-2 group after treated for 30 min,indicating effective killing of bacteria in biofilm;compared with PC-6 group and CA-10 group,all drug combination groups achieved the bactericidal effects of high concentration of single-drug groups at low concentrations.The SEM results showed that in control group,E.faecalis exhibited an oval shape with intact cell membranes;in PF group,bacterial morphology was altered,and cell membrane integrity was damaged;in CA group,most bacterial cell membranes remained relatively intact,but the bacterial surface showed shrinkage and depression,with a few bacteria exhibiting disrupted cell membrane integrity;in PC group,the integrity of bacterial cell membranes was most severely damaged,leading to leakage of cellular contents and aggregation of cell fragments into flocculent structures;in all drug combination groups,E.faecalis exhibited ruptured cell membranes,leakage of contents,and aggregation of bacterial debris,especially in the combination of CA and PC,where the most severe disruption of bacterial cell membrane integrity and complete leakage of contents were observed;in the combination of PF and CA,bacterial surface pits and shrinkage were observed,with occasional cell membrane rupture.The kit results showed that compared with control group,the ATP levels in E.faecalis planktonic bacteria and biofilm in various groups were significantly decreased(P<0.01);compared with PF-10 group,the ATP levels in E.faecalis planktonic bacteria in CA-10 group,CA-2+PC-2 group,PF-4+CA-4 group,and PF-6+CA-4 group were significantly decreased(P<0.05 or P<0.01),and the ATP levels in E.faecalis biofilm in CA-10 group and CA-2+PC-2 group were significantly decreased(P<0.05 or P<0.01).Conclusion:The combined application of PF,PC,and CA,the active components of Paeoniae Radix Rubra,exhibits significant inhibitory effects on E.faecalis and its biofilm formation.The pairwise combinations of three active components show synergistic or additive effects,with the combination of CA and PC demonstrating the most significant synergistic effect.The underlying mechanism may be related to the disruption of E.faecalis cell membrane integrity and inhibition of bacterial ATP levels.

BACKGROUND: Recent studies have shown that sodium-glucose cotransporters-2 (SGLT2) inhibitors significantly improve major adverse cardiovascular events in heart failure with preserved ejection fraction (HFpEF) patients, but the exact mechanism is unknown. Ferritinophagy is a special form of selective autophagy that participates in ferroptosis. In this study, we aimed to investigate whether ferritinophagy was activated during the occurrence of HFpEF, and whether canagliflozin (CANA) could inhibite ferritinophagy. METHODS: We reared Dahl salt-sensitive (DSS) rats on a high-salt diet to construct a hypertensive HFpEF model, and simultaneously administered CANA intervention. Then we detected indicators related to ferritinophagy. RESULTS: The expression of nuclear receptor coactivator 4 (NCOA4), as well as microtubule-associated proteins light chain 3 (LC3), Bcl-2 interacting protein 1 (Beclin-1) and p62, were upregulated in HFpEF rats, accompanied by the downregulation of ferritin heavy chain 1 (FTH1), upregulation of mitochondrial iron transporter sideroflexin1 (SFXN1) and increased reactive oxygen species (ROS) production. Above changes were diminished by CANA. CONCLUSION Ferritinophagy is activated in HFpEF rats and then inhibited by CANA, leading to HFpEF benefits. The inhibition of ferritinophagy could provide new prospective targets for the prevention and treatment of HFpEF, and provide new ideas for investigating the mechanism of cardiovascular benefit of SGLT2 inhibitors.

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

Objective:To summarized the clinical characteristics and surgical management of anterior cervical enterogenic in pediatric patients. Methods:Clinical data were retrospectively analyzed for 9 children with pathologically confirmed anterior cervical enterogenic cysts（including bronchogenic and esophagogenic subtypes） treated at the Children's Hospital of Shandong University（Jinan Children's Hospital） between January 1, 2020, and November 30, 2023. Results:Nine patients（6 males and 3 females） were involved in this study, aged 14 days to 10 years old. There were 4 cases on the left side, 4 on the right side, and 1 in the middle of the neck. All patients presented with neck masses. The patients were followed up from 3 months to 35 months after surgery and recovered well, with no recurrence or complications observed. Conclusion:①Anterior intestinal cysts in children are rare and easy to be misdiagnosed. ②Concurrent branchial cleft fistulas or associated anomalies may coexist, necessitating comprehensive evaluation. ③Preoperative diagnosis is not easy and mainly depends on pathological diagnosis. ④The treatment of anterior cervical enterogenic cysts in children is surgical resection of the lesion.
Humans ; Male ; Female ; Child ; Retrospective Studies ; Child, Preschool ; Infant ; Neck ; Cysts/surgery*

Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N ⁶-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.

Objective To investigate the screening results and factors affecting abnormal detection rates among high-risk groups of esophageal cancer and to explore effective intervention measures. Methods We investigated and collected the information on gender, education level, age, marital status, symptoms of reflux esophagitis (heartburn, acid reflux, belching, hiccup, foreign body sensation in the pharynx, and difficulty swallowing), consumption of pickled vegetables, salt use, and esophageal cancer incidence of villagers in a natural village in Wenfeng District, Anyang City, Henan Province. Changes in reflux esophagitis symptoms in the high-incidence area of esophageal cancer before and after 16 years were observed, and the relationship of such changes with esophageal cancer was analyzed. Results In 2008, 711 cases were epidemiologically investigated, including 213 cases with one of the symptoms of reflux esophagitis such as heartburn, acid reflux, belching, hiccups, foreign body sensation in the pharynx, and difficulty swallowing (sorted in accordance with the abovementioned symptoms; if there are multiple symptoms, then the former is taken); 55 cases with at least two related symptoms, among which the most symptom was heartburn in 108 cases (15.1%); followed by acid reflux, belching, etc. In 2024, the same group of people was investigated, and eight people were missing because of relocation. A total of 703 people were successfully investigated, of which 189 cases (26.8%) had one of the symptoms of reflux esophagitis, such as heartburn (sorted in accordance with relevant symptoms, if there are multiple symptoms, then the former will be selected); 167 cases (23.7%) had at least two related symptoms, among which the most symptom was heartburn in 139 cases (19.7%); followed by acid reflux. Over 16 years, among the 703 people investigated, 45 cases had esophageal cancer and they had one or more of the abovementioned symptoms. No significant differences in the reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.26); no significant differences in the composition of reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.299). Conclusion The detection rate of reflux esophagitis-related symptoms in the population in a high-risk area of esophageal cancer has not decreased in the past 16 years, and the high-risk factors still exist. Esophageal cancer is closely related to reflux esophagitis, and clinical practice can provide early diagnosis and treatment for high-risk population.

The molecular mechanisms underlying the health-promoting effects of exercise remain to be fully elucidated. As a bridge between genetics, exercise and phenotype, metabolites can be detected in high throughput through metabolomics, offering valuable insights into mechanism elucidation and disease prediction. Metabolic homeostasis is intricately regulated by various factors, including enzyme activity and transporters. Integration of multiple omics technologies such as genomics, transcriptomics, and proteomics enables the comprehensive elucidation of the metabolic network modulated by exercise interventions and facilitates the identification of key metabolic markers. This review summarizes the current research advancements, biological functions, discovery methods, and applications of exercise-induced multi omics metabolic markers, furnishing a theoretical foundation for understanding the mechanisms of exercise-induced health benefits and enabling precision interventions. Relevant literatures from 2000 to 2025 were systematically retrieved from databases including PubMed, CNKI and other databases with the keywords such as “multi-omics”, “metabolic biomarkers”, “exercise”, “health”. Subsequently, the identified literature was meticulously screened to meet the specified criteria and was subsequently incorporated into the study. (1) Exercise induces profound alterations in metabolite levels within the body, with particular emphasis on markers associated with sugar, lipid, and protein metabolism being extensively investigated. As an intensity marker, lactate is implicated in the regulation of fat browning (UCP-1), angiogenesis (VEGF), mitochondrial function (PGC-1α) and metabolic homeostasis (HIF-1α/CES2). Following resistance training, pyruvate levels increase, and an aberrant pyruvate to lactate ratio (approximately 10) may indicate mitochondrial dysfunction. Supplementation with pyruvate has been shown to reduce weight and lipid levels. Ketone bodies regulate metabolism by inhibiting lipolytic enzyme activity and promoting insulin secretion. Plasma ketone body concentrations rise after high-intensity exercise, with levels positively associated with central fatigue. Carnitine levels elevate post-endurance training, and supplementation with carnitine has been linked to increased lean body mass and enhanced cognitive function in older individuals. Serum alanine levels rise following resistance training and, as a precursor of carnosine, supplementation can elevate carnosine concentration by 80%, exerting antioxidant and neuroprotective effects. Creatine, a pivotal molecule in phosphogen energy supply, exhibits a 93% increase in plasma levels post-marathon, with its metabolism intricately related to AMPK activation. (2) Metabolites play a crucial role in disease prediction, particularly in the context of cardiovascular disease where 18 metabolites including glycoprotein acetyl and ketone bodies have been shown to enhance the performance of prediction models. Similarly, in diabetes research, acylcarnitine and other metabolites can improve prediction model efficacy. The combination of multiple metabolites has been found to substantially enhance predictive capabilities for various conditions such as cancer, aging, and other risks, surpassing the predictive power of traditional indicators. (3) Genomics investigations have unveiled the genetic underpinnings of exercise-related metabolites. VO₂max, a significant exercise phenotype with heritability estimates ranging from 0.59 to 0.66, exhibits a negative correlation with the susceptibility to diabetes and cardiovascular disease. SNPs associated with VO₂max, such as variants in the FSHR gene, are positively linked to serum creatinine levels. Reduced creatinine levels have been associated with an elevated risk of T2DM. These findings suggest that creatinine serves as a potential marker of exercise metabolism. (4) Transcriptomic studies have elucidated the molecular mechanisms by which exercise modulates metabolites. Acute exercise induces rapid alterations in the expression profiles of 9 132 transcripts. Exercise elicits upregulation of genes involved in the fructose/mannose metabolic pathway (such as SORD, PFKFB3), suggesting these metabolites may serve as pivotal mediators in the beneficial effects of exercise on Parkinson’s disease. Altitude training enhances the expression of the PHOSPHO1 gene, which encodes an enzyme facilitating choline synthesis. Choline deficiency has been linked to insulin resistance. Choline supplementation has been shown to augment the effects of resistance training, underscoring the significance of choline as a key marker in exercise-mediated metabolic health promotion. (5) Proteomic analyses have unveiled the key mechanisms through which exercise modulates metabolism. Endurance training induces significant alterations in myofibrillar expression, with 237 slow muscles and 172 fast muscles proteins showing differential regulation, of which 65% are associated with metabolism, including ACSL1 and ECHS1. Various training modalities elicit distinct phosphorylation modifications, exemplified by the negative correlation between LDHA3 phosphorylation and lactate levels. Endurance training upregulates SLC25A15 expression in adipose tissue, enhancing arginine synthesis. The post-exercise elevation of plasma GPLD1 levels mimics the neuroprotective effects of exercise on the brain. These findings present novel targets for investigating exercise-related metabolic markers. The application of multi omics technologies has expedited the identification and mechanistic analysis of both established and novel sports-related metabolic markers like lactate. Integrated multi omics strategies (e.g., genome-metabolome) enable the simultaneous examination of metabolic markers and their regulatory mechanisms, facilitating the discovery of exercise-related genetic markers and pivotal regulatory proteins. However, challenges persist, including inadequate data integration and a lack of standardization. Future endeavors should focus on developing dynamic monitoring tools, integrating state-of-the-art approaches such as single-cell/spatial omics, and leveraging AI algorithms for optimized analysis to construct precise predictive models for maximizing health benefits in exercise.