ObjectiveTo observe the changes in the levels of different subtypes of epidermal growth factor receptor （ErbB）， namely ErbB1， ErbB2， ErbB3， and ErbB4， in the spinal dorsal horn of inflammatory pain model rats， and to explore their mechanism of mediating hyperalgesia as well as the intervention mechanism of electroacupuncture at "Zusanli （ST 36）" and "Kunlun （BL 60）". MethodsThe study was divided into five parts. In experiment 1， 14 Sprague Dawley （SD） rats were randomly divided into control and inflammatory pain group （7 rats each group） to observe the pain behavior and the protein expression of different ErbB receptor subtypes in the spinal dorsal horn. In experiment 2， 30 rats were randomly divided into control group 1， inflammatory pain group 1， and low-， medium-， and high-concentration TX1-85-1 groups， with 6 rats in each group， to observe the effect of inhibiting spinal ErbB3 on inflammatory pain. In experiment 3， 12 rats were randomly divided into control virus group and ErbB3 knockdown virus group， with 6 rats in each group， to observe the effect of knocking down ErbB3 in the spinal dorsal horn on inflammatory pain. In experiment 4， 44 rats were randomly divided into control group 2， inflammatory pain group 2， electroacupuncture group， and sham electroacupuncture group， with 11 rats in each group， to observe the effect of electroacupuncture. In experiment 5， 40 rats were randomly divided into control group 3， inflammatory pain group 3， electroacupuncture group 1， and electroacupuncture + NRG1 group， with 10 rats in each group， to observe the effect of activating ErbB3 on electroacupuncture. A rat model of inflammatory pain was established by subcutaneous injection of 100 μl of complete Freund's adjuvant into the sole of the unilateral hind foot of SD rats. Rats in the low-， medium-， and high-concentration TX1-85-1 groups were intrathecally injected with ErbB3 inhibitor TX1-85-1 on day 5 to day 7 after modeling. Rats in the ErbB3 knockdown virus group were injected with ErbB3 knockdown virus packaged with adenovirus vector-based short hairpin RNA （shRNA） into the spinal dorsal horn in situ 3 weeks before modeling. Rats in each electroacupuncture group received electroacupuncture at bilateral "Zusanli （ST 36）" and "Kunlun （BL 60）" from day 1 to day 7 after modeling， with dense-sparse waves at a frequency of 2 Hz/100 Hz and a current of 0.5-1.5 mA for 30 minutes once a day. Rats in the electroacupuncture + NRG1 group were intrathecally injected with ErbB3 ligand recombinant human neuregulin-1 （NRG1） after electroacupuncture intervention from day 5 to day 7 after modeling. The mechanical withdrawal threshold and thermal withdrawal latency of rats were measured on day 1， 3， 5， and 7 after modeling to evaluate behavior， and Western Blot was used to detect the protein and phosphorylation levels of each ErbB subtype in the spinal dorsal horn. ResultsCompared with the control group， rats in the inflammatory pain group showed decreased mechanical withdrawal threshold and thermal withdrawal latency of rats， and increased expression of phosphorylated ErbB3 （p-ErbB3） protein in the spinal dorsal horn on days 1， 3， 5， and 7 after modeling （P＜0.01）. On day 5 and day 7 after modeling， compared with the inflammatory pain group 1， the mecha-nical withdrawal threshold and thermal withdrawal latency of rats in the medium- and high-concentration TX1-85-1 groups increased， and the expression of p-ErbB3 protein decreased （P＜0.05）. On day 1， 3， 5， and 7 after modeling， compared with the control virus group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the ErbB3 knockdown virus group increased （P＜0.05）. On day 5 and day 7 after modeling， compared with the inflammatory pain group 2 and the sham electroacupuncture group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group increased， and the expression of p-ErbB3 protein decreased （P＜0.05）. On day 5 and day 7 after modeling， compared with the electroacupuncture + NRG1 group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group 1 increased （P＜0.05）. ConclusionThe p-ErbB3 in the spinal dorsal horn involved in hyperalgesia in rats with inflammatory pain， and electroacupuncture at "Zusanli （ST 36）" and "Kunlun （BL 60）" can alleviate inflammatory pain by inhibiting the expression of p-ErbB3 protein in the spinal dorsal horn of rats.

Objective To investigate the effect and mechanism of the signal transducer and activator of transcription 3 (STAT3) inhibitor Stattic on the rejection of mouse heart allograft. Methods BALB/c mice (donors) were used to transplant skin onto C57BL/6 mice (recipients). Four weeks later, memory CD4⁺ T cells (CD4⁺Tm) were isolated from the recipient mice's spleens. Mixed lymphocyte reaction experiment was conducted with C57BL/6 mouse splenocytes and CD4⁺Tm, and the EdU method was used to detect the effect of Stattic on CD4⁺Tm cell proliferation. A C57BL/6 mouse heart transplant (HTx) model was constructed, and the experiment was divided into four groups: Non-HTx group, HTx group, Tm/HTx group, and Tm/HTx+Stattic group. The survival of heart allografts in mice was observed daily. Hematoxylin-eosin staining was used to observe the histopathology of the heart allografts. Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression levels of interferon (IFN)-γ, interleukin (IL)-2, IL-10, and transforming growth factor-β1 (TGF-β1) messenger RNA (mRNA) in the heart allografts. Enzyme-linked immunosorbent assay was used to detect the levels of IFN-γ, IL-2, IL-10, and TGF-β1 in the serum. Flow cytometry was used to detect the levels of CD4⁺Tm (CD4⁺CD44⁺CD62L⁺) in splenic lymphocytes. And Western blotting was used to detect the expression levels of STAT3 and p-STAT3 proteins in the heart allografts. Results When the concentration of Stattic exceeded 2.5 μmol/L, it could inhibit the proliferation of CD4⁺Tm cells. Compared with the HTx group, the Tm/HTx group showed shorter survival time of heart grafts, more severe histopathological damage, increased serum IFN-γ and IL-2 levels, decreased IL-10 and TGF-β1 levels, increased relative expression of IFN-γ and IL-2 mRNA, decreased relative expression of IL-10 and TGF-β1 mRNA in the heart allografts, increased proportion of CD4⁺Tm in splenic lymphocytes, and increased p-STAT3/STAT3 ratio in the heart allografts (all P<0.05). Compared with the Tm/HTx group, the Tm/HTx+Stattic group showed longer survival time of heart grafts, less severe histopathological damage, decreased serum IFN-γ and IL-2 levels, increased IL-10 and TGF-β1 levels, decreased relative expression of IFN-γ and IL-2 mRNA, increased relative expression of IL-10 and TGF-β1 mRNA in the heart allografts, decreased proportion of CD4⁺Tm in splenic lymphocytes, and decreased p-STAT3/STAT3 ratio in the heart allografts (all P<0.05). Conclusions Stattic may prolong the survival time of mouse heart allografts, and its mechanism may be related to the inhibition of CD4⁺Tm- mediated acute rejection.

ObjectiveTo investigate the mechanism of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis extract （ASH） in treating Parkinson's disease （PD） in mice by Data-Independent Acquisition （DIA） proteomics. MethodsThe α-Synuclein （α-Syn） transgenic PD mice were selected as suitable models for PD， and they were randomly assigned into PD， ASH （61.25 mg·kg^-1）， and Madopar （97.5 mg·kg^-1） groups. Male C57BL/6 mice of the same age were selected as the control group， with eight mice in each group. Mice were administrated with corresponding drugs by gavage once a day for 20 days. The pole climbing time and the number of autonomic activities were recorded to evaluate the exercise ability of mice. Hematoxylin-eosin staining was employed to observe neuronal changes in the substantia nigra of PD mice. Immunohistochemistry （IHC） was employed to measure the tyrosine hydroxylase （TH） activity in the substantia nigra and assess the areal density of α-Syn in the striatum. DIA proteomics was used to compare protein expression in the substantia nigra between groups. IHC was utilized to validate key differentially expressed proteins， including Lactotransferrin， Notch2， Ndrg2， and TMEM 166. The cell counting kit-8 （CCK-8） method was used to investigate the effect of ASH on the viability of PD cells with overexpression of α-Syn. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the protein and mRNA levels of Lactotransferrin， Notch2， Ndrg2， and TMEM 166 in PD cells. ResultsCompared with the control group， the model group showed prolonged pole climbing time， diminished coordination ability， reduced autonomic activities （P<0.01）， and reduced swelling neurons. Compared with the model group， ASH and Madopar reduced the climbing time， increased autonomic activities （P<0.01）， and ameliorated neuronal damage. Compared with the control group， the model group showed a decrease in TH activity in the substantia nigra and an increase in α-Syn accumulation in the striatum （P<0.01）. Compared with the model group， the ASH group showed an increase in TH activity and a reduction in α-Syn accumulation （P<0.05）. DIA proteomics revealed a total of 464 differentially expressed proteins in the model group compared with the control group， with 323 proteins being up-regulated and 141 down-regulated. A total of 262 differentially expressed proteins were screened in the ASH group compared with the model group， including 85 proteins being up-regulated and 177 down-regulated. Kyoto encylopedia of genes and genomes （KEGG） pathway analysis indicated that ASH primarily regulated the Notch signaling pathway. The model group showed up-regulation in protein levels of Notch2， Ndrg2， and TMEM 166 and down-regulation in the protein level of Lactotransferrin compared with the control group （P<0.01）. Compared with the model group， ASH down-regulated the protein levels of Notch2， Ndrg2， and TMEM 166 （P<0.05） while up-regulating the protein level of Lactotransferrin （P<0.01）. The IHC results corroborated the proteomics findings. The cell experiment results showed that compared with the control group， the modeling up-regulated the mRNA and protein levels of Notch2， Ndrg2， and TMEM 166 （P<0.01）， while down-regulating the mRNA and protein levels of Lactotransferrin （P<0.01）. Compared with the model group， ASH reduced the mRNA and protein levels of Notch2， Ndrg2， and TMEM 166 （P<0.01）， while increasing the mRNA and protein levels of Lactotransferrin （P<0.05， P<0.01）. ConclusionASH may Synergistically inhibit the Notch signaling pathway and mitigate neuronal damage by down-regulating the expression of Notch2 and Ndrg2. Additionally， by up-regulating the expression of Lactotransferrin and down-regulating the expression of TMEM166， ASH can address brain iron accumulation， intervene in ferroptosis， inhibit mitophagy， and mitigate reactive oxygen species damage， thereby protecting nerve cells and contributing to the treatment of PD.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

Purpose: Interviews play a crucial role in the medical school selection process, although little is known about interviewers’ non-verbal observable communications (NoVOC) during the interviews. This study investigates how interviewers perceive NoVOC exhibited by interviewees in two medical schools, one in Taiwan and the other in Australia. The study also explores potential cross-cultural differences in these perceptions. Methods: A 26-item questionnaire was developed using a Delphi-like method to identify NoVOC. Interviewers from the University of New South Wales, Australia, and National Yang Ming Chiao Tung University, Taiwan (n=47 and N=78, respectively) rated these NoVOC between 2018 and 2021. Factor analyses identified and validated underlying factors. Measurement invariance across countries and genders was examined. Results: A total of 125 interviewers completed the questionnaire, including 78 from Taiwan and 47 from Australia. Using exploratory factor analysis, 14 items yielded reliable three factors “charming,” “disengaged,” and “anxious” (Cronbach’s α=0.853, 0.714, and 0.628, respectively). The measurement invariance analysis indicated that the factor models were invariant across genders but significantly different between the two countries. Further analysis revealed inconsistencies in interpreting the “anxious” factor between Taiwan and Australia. Conclusion The three distinct factors revealed in this study provide valuable insights into the NoVOC that interviewers perceive and evaluate during the interview process. The findings highlight the importance of considering non-verbal communication in selecting medical students and emphasize the need for training and awareness among interviewers. Understanding the impact of non-verbal behaviors can improve selection processes to mitigate bias and enhance the fairness and reliability of medical student selection.

ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis （EMs） patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase （JNK） signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group， with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer （IVF-ET） due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally， while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis， as well as the serum level of cancer antigen 125 （CA125）， were evaluated at the time of enrollment （before treatment） and on the trigger day （after treatment）. Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day， the duration and dosage of gonadotropin （Gn） administration and the serum levels of hormones on the day of human chorionic gonadotropin （HCG） injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval， and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels， Gn days， Gn dosage， hormone levels on the day of HCG administration， number of oocytes retrieved， number of 2 pronucleus （2PN） fertilizations， number of available embryos， high-quality embryo rate， and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK， c-Jun， and nuclear receptor subfamily 4 group A member 2 （NR4A2） in ovarian granulosa cells （GCs） on the day of oocyte retrieval by Western blot. Results（1） There were no statistically significant differences in the baseline data among three groups， indicating comparability. （2） Compared with the baseline within the same group， the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment， serum CA125 levels decreased in both groups （P<0.05）， with a more substantial reduction in the treatment group， resulting in a difference between the two groups （P<0.05）. （3） There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and progesterone （P）， as well as the duration and dosage of Gn administration and the serum levels of LH， E₂， and P on the day of HCG administration. （4） For embryo outcomes， the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group （P<0.05）， and the treatment group and the blank group had similar 2PN fertilizations. （5） There were differences in clinical pregnancy rate among three groups （P<0.05）， and the treatment group had higher pregnancy rate than the control and blank groups. （6） The protein levels of JNK， c-Jun， and NR4A2 in the GCs of the treatment group were lower than those in the control group （P<0.01） and close to those in the blank group （P<0.01）. （7） No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis， reduce the serum CA125 level， increase the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rate， and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK， c-Jun， and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.

ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis （EMs） patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase （JNK） signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group， with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer （IVF-ET） due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally， while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis， as well as the serum level of cancer antigen 125 （CA125）， were evaluated at the time of enrollment （before treatment） and on the trigger day （after treatment）. Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day， the duration and dosage of gonadotropin （Gn） administration and the serum levels of hormones on the day of human chorionic gonadotropin （HCG） injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval， and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels， Gn days， Gn dosage， hormone levels on the day of HCG administration， number of oocytes retrieved， number of 2 pronucleus （2PN） fertilizations， number of available embryos， high-quality embryo rate， and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK， c-Jun， and nuclear receptor subfamily 4 group A member 2 （NR4A2） in ovarian granulosa cells （GCs） on the day of oocyte retrieval by Western blot. Results（1） There were no statistically significant differences in the baseline data among three groups， indicating comparability. （2） Compared with the baseline within the same group， the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment， serum CA125 levels decreased in both groups （P<0.05）， with a more substantial reduction in the treatment group， resulting in a difference between the two groups （P<0.05）. （3） There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and progesterone （P）， as well as the duration and dosage of Gn administration and the serum levels of LH， E₂， and P on the day of HCG administration. （4） For embryo outcomes， the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group （P<0.05）， and the treatment group and the blank group had similar 2PN fertilizations. （5） There were differences in clinical pregnancy rate among three groups （P<0.05）， and the treatment group had higher pregnancy rate than the control and blank groups. （6） The protein levels of JNK， c-Jun， and NR4A2 in the GCs of the treatment group were lower than those in the control group （P<0.01） and close to those in the blank group （P<0.01）. （7） No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis， reduce the serum CA125 level， increase the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rate， and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK， c-Jun， and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.

Diabetic cardiomyopathy is a distinct form of cardiomyopathy that can lead to heart failure, arrhythmias, cardiogenic shock, and sudden death. It has become a major cause of mortality in diabetic patients. The pathogenesis of diabetic cardiomyopathy is complex, involving increased oxidative stress, activation of inflammatory responses, disturbances in glucose and lipid metabolism, accumulation of advanced glycation end products (AGEs), abnormal autophagy and apoptosis, insulin resistance, and impaired intracellular Ca²⁺ homeostasis. Recent studies have shown that adenosine monophosphate-activated protein kinase (AMPK) plays a crucial protective role by lowering blood glucose levels, promoting lipolysis, inhibiting lipid synthesis, and exerting antioxidant, anti-inflammatory, anti-apoptotic, and anti-ferroptotic effects. It also enhances autophagy, thereby alleviating myocardial injury under hyperglycemic conditions. Consequently, AMPK is considered a key protective factor in diabetic cardiomyopathy. As part of diabetes prevention and treatment strategies, both pharmacological and exercise interventions have been shown to mitigate diabetic cardiomyopathy by modulating the AMPK signaling pathway. However, the precise regulatory mechanisms, optimal intervention strategies, and clinical translation require further investigation. This review summarizes the role of AMPK in the prevention and treatment of diabetic cardiomyopathy through drug and/or exercise interventions, aiming to provide a reference for the development and application of AMPK-targeted therapies. First, several classical AMPK activators (e.g., AICAR, A-769662, O-304, and metformin) have been shown to enhance autophagy and glucose uptake while inhibiting oxidative stress and inflammatory responses by increasing the phosphorylation of AMPK and its downstream target, mammalian target of rapamycin (mTOR), and/or by upregulating the gene expression of glucose transporters GLUT1 and GLUT4. Second, many antidiabetic agents (e.g., teneligliptin, liraglutide, exenatide, semaglutide, canagliflozin, dapagliflozin, and empagliflozin) can promote autophagy, reverse excessive apoptosis and autophagy, and alleviate oxidative stress and inflammation by enhancing AMPK phosphorylation and its downstream targets, such as mTOR, or by increasing the expression of silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor‑α (PPAR‑α). Third, certain anti-anginal (e.g., trimetazidine, nicorandil), anti-asthmatic (e.g., farrerol), antibacterial (e.g., sodium houttuyfonate), and antibiotic (e.g., minocycline) agents have been shown to promote autophagy/mitophagy, mitochondrial biogenesis, and inhibit oxidative stress and lipid accumulation via AMPK phosphorylation and its downstream targets such as protein kinase B (PKB/AKT) and/or PPAR‑α. Fourth, natural compounds (e.g., dihydromyricetin, quercetin, resveratrol, berberine, platycodin D, asiaticoside, cinnamaldehyde, and icariin) can upregulate AMPK phosphorylation and downstream targets such as AKT, mTOR, and/or the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby exerting anti-inflammatory, anti-apoptotic, anti-pyroptotic, antioxidant, and pro-autophagic effects. Fifth, moderate exercise (e.g., continuous or intermittent aerobic exercise, aerobic combined with resistance training, or high-intensity interval training) can activate AMPK and its downstream targets (e.g., acetyl-CoA carboxylase (ACC), GLUT4, PPARγ coactivator-1α (PGC-1α), PPAR-α, and forkhead box protein O3 (FOXO3)) to promote fatty acid oxidation and glucose uptake, and to inhibit oxidative stress and excessive mitochondrial fission. Finally, the combination of liraglutide and aerobic interval training has been shown to activate the AMPK/FOXO1 pathway, thereby reducing excessive myocardial fatty acid uptake and oxidation. This combination therapy offers superior improvement in cardiac dysfunction, myocardial hypertrophy, and fibrosis in diabetic conditions compared to liraglutide or exercise alone.

A wealth of prior studies has confirmed that intratumoral microbiota can survive within tumor tissue, thereby promoting or inhibiting tumor growth. With the development of high-throughput sequencing and metabolomics, increasing attention has been paid to the correlation between intratumoral microbiota and host metabolism, and their effect on tumorigenesis and progression. This review focuses on the interaction between intratumoral microbiota and tumor metabolism. It emphasizes the effects of intratumoral microbiota on tumor sugar, lipid, and amino acid metabolism and explores emerging therapeutic strategies for guiding tumor prevention and treatment by modulating tumor metabolism. Although the specific role of intratumoral microbiota in tumor metabolism remains to be further studied, a deepened understanding of the interaction between tumor-specific microbiota and tumor metabolism may provide new directions and application prospects for tumor prevention and treatment.