Pub Date : 2025-11-18DOI: 10.1016/j.joim.2025.11.007
Yue-Fei Geng, Xiu-Ying Ma, Yan Ge, Bin Liu, Jin-Gen Deng, Shu Liu, Tao-Qing Wu, Shun-Ri Jiang, Fu-Neng Geng
Over the past three decades, a growing body of research has been dedicated to the integration of traditional Chinese medicine (TCM) and modern medicine, highlighting the complementary benefits of both disciplines. However, in the context of skin wound treatment, such integration remains limited and warrants further exploration. During the wound healing process, the inflammatory response is a critical physiological event. A harmonious balance between pro-inflammatory and anti-inflammatory events is essential for the progression of inflammation and the overall wound healing process. This equilibrium reflects the dynamic and reciprocal interaction embodied in the TCM concept of yin and yang. This study analyzes the dynamic changes in wound inflammation from the perspective of TCM's yin-yang theory and pinpoints the key cellular and molecular factors that influence the yin-yang balance in wound inflammation. The findings offer significant theoretical and practical value for future clinical and translational research. These insights will inform more effective strategies for the treatment of skin wounds and to facilitate the development of novel therapeutics. Please cite this article as: Geng YF, Ma XY, Ge Y, Liu B, Deng JG, Liu S, Wu TQ, Jiang SR, Geng FN. Yin-yang dynamics in wound inflammation: yin and yang manifestations of inflammatory substances. J Integr Med. 2025; Epub ahead of print.
{"title":"Yin-yang dynamics in wound inflammation: yin and yang manifestations of inflammatory substances.","authors":"Yue-Fei Geng, Xiu-Ying Ma, Yan Ge, Bin Liu, Jin-Gen Deng, Shu Liu, Tao-Qing Wu, Shun-Ri Jiang, Fu-Neng Geng","doi":"10.1016/j.joim.2025.11.007","DOIUrl":"https://doi.org/10.1016/j.joim.2025.11.007","url":null,"abstract":"<p><p>Over the past three decades, a growing body of research has been dedicated to the integration of traditional Chinese medicine (TCM) and modern medicine, highlighting the complementary benefits of both disciplines. However, in the context of skin wound treatment, such integration remains limited and warrants further exploration. During the wound healing process, the inflammatory response is a critical physiological event. A harmonious balance between pro-inflammatory and anti-inflammatory events is essential for the progression of inflammation and the overall wound healing process. This equilibrium reflects the dynamic and reciprocal interaction embodied in the TCM concept of yin and yang. This study analyzes the dynamic changes in wound inflammation from the perspective of TCM's yin-yang theory and pinpoints the key cellular and molecular factors that influence the yin-yang balance in wound inflammation. The findings offer significant theoretical and practical value for future clinical and translational research. These insights will inform more effective strategies for the treatment of skin wounds and to facilitate the development of novel therapeutics. Please cite this article as: Geng YF, Ma XY, Ge Y, Liu B, Deng JG, Liu S, Wu TQ, Jiang SR, Geng FN. Yin-yang dynamics in wound inflammation: yin and yang manifestations of inflammatory substances. J Integr Med. 2025; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-15DOI: 10.1016/j.joim.2025.11.006
Wei-Kang Luo, Xiao-Hang Guo, Li-Na Cao, Jun Zheng, Ming Luo, Yang Wang
The integration of materials science and Chinese medicine (CM) has emerged as a significant interdisciplinary field, playing a crucial role in enhancing the pharmacodynamics of CM and its derived small molecules. This field introduces novel concepts, like carrier-based CM delivery systems and carrier-free CM-based material systems, and here we present a detailed exposition of their respective merits and drawbacks. In recent years, there has been an exponential increase in research on carrier-based drug delivery systems for CM, which are designed to optimize administration routes, improve targeted delivery precision, and enable controlled drug release. Nonetheless, these systems face critical challenges including suboptimal drug payloads, prohibitive manufacturing costs, and compromised biocompatibility. The introduction of carrier-free CM-based material system addresses these shortcomings through inherent advantages including exceptional drug-loading capacity, full-bioactive components, and superior biocompatibility. Comparative analyses demonstrate that nanonization of the active components of herbal medicines can significantly improve the permeability, solubility, stability, and targeting of the active components themselves. The intrinsic therapeutic components, eco-friendly attributes, and sustainable regenerative capacity of CM, combined with the adjustable physicochemical properties of advanced materials create unique therapeutic advantages. The advancement and optimization of CM and materials science concept have significantly bolstered the clinical application of drugs, increasingly aligning with the personalized treatment model in clinical practice. We provide an overview of the future obstacles and potential development strategies in the realm of CM-materials science with the aspiration to propel sustainable development in both CM and materials science. Please cite this article as: Luo WK, Guo XH, Cao LN, Zheng J, Luo M, Wang Y. Collision of Chinese medicine and materials science: Interdisciplinary biomaterials' perspectives. J Integr Med. 2025; Epub ahead of print.
{"title":"Collision of Chinese medicine and materials science: Interdisciplinary biomaterials' perspectives.","authors":"Wei-Kang Luo, Xiao-Hang Guo, Li-Na Cao, Jun Zheng, Ming Luo, Yang Wang","doi":"10.1016/j.joim.2025.11.006","DOIUrl":"https://doi.org/10.1016/j.joim.2025.11.006","url":null,"abstract":"<p><p>The integration of materials science and Chinese medicine (CM) has emerged as a significant interdisciplinary field, playing a crucial role in enhancing the pharmacodynamics of CM and its derived small molecules. This field introduces novel concepts, like carrier-based CM delivery systems and carrier-free CM-based material systems, and here we present a detailed exposition of their respective merits and drawbacks. In recent years, there has been an exponential increase in research on carrier-based drug delivery systems for CM, which are designed to optimize administration routes, improve targeted delivery precision, and enable controlled drug release. Nonetheless, these systems face critical challenges including suboptimal drug payloads, prohibitive manufacturing costs, and compromised biocompatibility. The introduction of carrier-free CM-based material system addresses these shortcomings through inherent advantages including exceptional drug-loading capacity, full-bioactive components, and superior biocompatibility. Comparative analyses demonstrate that nanonization of the active components of herbal medicines can significantly improve the permeability, solubility, stability, and targeting of the active components themselves. The intrinsic therapeutic components, eco-friendly attributes, and sustainable regenerative capacity of CM, combined with the adjustable physicochemical properties of advanced materials create unique therapeutic advantages. The advancement and optimization of CM and materials science concept have significantly bolstered the clinical application of drugs, increasingly aligning with the personalized treatment model in clinical practice. We provide an overview of the future obstacles and potential development strategies in the realm of CM-materials science with the aspiration to propel sustainable development in both CM and materials science. Please cite this article as: Luo WK, Guo XH, Cao LN, Zheng J, Luo M, Wang Y. Collision of Chinese medicine and materials science: Interdisciplinary biomaterials' perspectives. J Integr Med. 2025; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.joim.2025.09.001
Ying Huang , Chen-ling Chu , Wen-hui Qiu , Jia-yi Chen , Lu-xi Cao , Shui-yu Ji , Bin Zhu , Guo-kun Wang , Quan-quan Shen
Objective
Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF.
Methods
The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial–mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations.
Results
Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2′-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells.
Conclusion
AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF.
Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial–mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694–705.
{"title":"Astragaloside IV delayed the epithelial–mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways","authors":"Ying Huang , Chen-ling Chu , Wen-hui Qiu , Jia-yi Chen , Lu-xi Cao , Shui-yu Ji , Bin Zhu , Guo-kun Wang , Quan-quan Shen","doi":"10.1016/j.joim.2025.09.001","DOIUrl":"10.1016/j.joim.2025.09.001","url":null,"abstract":"<div><h3>Objective</h3><div>Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from <em>Astragalus membranaceus</em> (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF.</div></div><div><h3>Methods</h3><div>The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial–mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations.</div></div><div><h3>Results</h3><div>Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2′-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells.</div></div><div><h3>Conclusion</h3><div>AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF.</div><div><br> Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial–mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. <em>J Integr Med</em>. 2025; 23(6):694–705.</div></div>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 6","pages":"Pages 694-705"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.joim.2025.08.003
Ruo-fan Xi , Xin Liu , Yi Wang , Han-zhi Lu , Shao-jie Yuan , Dong-jie Guo , Jian-yong Zhu , Fu-lun Li , Yan-juan Duan
Objective
Psoriasis, a common chronic inflammatory skin condition with genetic underpinnings, is traditionally managed with cupping therapy. Although used historically, the precise mechanical effects and therapeutic mechanisms of cupping in psoriasis remain largely unexamined. This study aimed to evaluate cupping therapy’s efficacy for psoriasis and investigate its role in modulating inflammatory responses and cellular metabolism.
Methods
Psoriasis was induced in mice using topical imiquimod (IMQ). The effects of cupping on psoriatic lesions were assessed using the Psoriasis Area and Severity Index score, histology, immunohistochemistry, and immunofluorescence staining. polymerase chain reaction sequencing (RNA-seq) and Western blotting were conducted to examine changes in mRNA expression and the AMP-activated protein kinase (AMPK) signaling pathway.
Results
Cupping therapy significantly reduced inflammation, epidermal thickness, and inflammatory cell infiltration in mice with IMQ-induced psoriasis. Immunohistochemistry and immunofluorescence showed lower expression of inflammatory markers and a shift in T-cell populations. RNA-seq and Western blotting indicated that cupping upregulated Piezo1 and activated the AMPK pathway, improving energy metabolism in psoriatic skin.
Conclusion
Cupping therapy reduces epidermal hyperproliferation and inflammation in psoriasis, rebalancing the local immune microenvironment. Mechanistically, cupping promotes calcium influx via Piezo1, activates AMPK signaling, and supports metabolic homeostasis, suggesting therapeutic potential for psoriasis.
Please cite this article as: Xi RF, Liu X, Wang Y, Lu HZ, Yuan SJ, Guo DJ, Zhu JY, Li FL, Duan YJ. Mechanosensory activation of Piezo1 via cupping therapy: Harnessing neural networks to modulate AMPK pathway for metabolic restoration in a mouse model of psoriasis. J Integr Med. 2025; 23(6):721–732.
{"title":"Mechanosensory activation of Piezo1 via cupping therapy: Harnessing neural networks to modulate AMPK pathway for metabolic restoration in a mouse model of psoriasis","authors":"Ruo-fan Xi , Xin Liu , Yi Wang , Han-zhi Lu , Shao-jie Yuan , Dong-jie Guo , Jian-yong Zhu , Fu-lun Li , Yan-juan Duan","doi":"10.1016/j.joim.2025.08.003","DOIUrl":"10.1016/j.joim.2025.08.003","url":null,"abstract":"<div><h3>Objective</h3><div>Psoriasis, a common chronic inflammatory skin condition with genetic underpinnings, is traditionally managed with cupping therapy. Although used historically, the precise mechanical effects and therapeutic mechanisms of cupping in psoriasis remain largely unexamined. This study aimed to evaluate cupping therapy’s efficacy for psoriasis and investigate its role in modulating inflammatory responses and cellular metabolism.</div></div><div><h3>Methods</h3><div>Psoriasis was induced in mice using topical imiquimod (IMQ). The effects of cupping on psoriatic lesions were assessed using the Psoriasis Area and Severity Index score, histology, immunohistochemistry, and immunofluorescence staining. polymerase chain reaction sequencing (RNA-seq) and Western blotting were conducted to examine changes in mRNA expression and the AMP-activated protein kinase (AMPK) signaling pathway.</div></div><div><h3>Results</h3><div>Cupping therapy significantly reduced inflammation, epidermal thickness, and inflammatory cell infiltration in mice with IMQ-induced psoriasis. Immunohistochemistry and immunofluorescence showed lower expression of inflammatory markers and a shift in T-cell populations. RNA-seq and Western blotting indicated that cupping upregulated Piezo1 and activated the AMPK pathway, improving energy metabolism in psoriatic skin.</div></div><div><h3>Conclusion</h3><div>Cupping therapy reduces epidermal hyperproliferation and inflammation in psoriasis, rebalancing the local immune microenvironment. Mechanistically, cupping promotes calcium influx via Piezo1, activates AMPK signaling, and supports metabolic homeostasis, suggesting therapeutic potential for psoriasis.</div><div><br>Please cite this article as: Xi RF, Liu X, Wang Y, Lu HZ, Yuan SJ, Guo DJ, Zhu JY, Li FL, Duan YJ. Mechanosensory activation of Piezo1 via cupping therapy: Harnessing neural networks to modulate AMPK pathway for metabolic restoration in a mouse model of psoriasis. <em>J Integr Med</em>. 2025; 23(6):721–732.</div></div>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 6","pages":"Pages 721-732"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145055960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Type 2 diabetes mellitus (T2DM) is a highly prevalent chronic metabolic disease with an increasing incidence worldwide, that poses a significant risk to public health. In many current clinical practices for diabetes management, conventional Western treatments, including oral or injectable hypoglycemic agents, have serious side effects. Given that traditional Chinese medicine (TCM) is characterized by a multi-component, multi-target and multi-pathway approach, its combination with Western medicine could enhance efficacy and reduce adverse effects. Consequently, the use of TCM as a potential auxiliary or alternative treatment for the prevention and/or management of T2DM has emerged as a research hotspot. This article reviews existing reports on TCM in the treatment of T2DM and provides a detailed discussion of its applications. By integrating relevant clinical evidence, this review summarizes the clinical data on 23 TCM formulas and Chinese patent medicines, comprehensively describing their efficacy and potential pharmacological mechanisms in the treatment of T2DM. This includes an exploration of the impacts of TCM-based therapeutic interventions on T2DM-related microRNAs and their target genes. We hope this review not only offers new insights for future research directions but also enhances the understanding of the scientific value of TCM.
Please cite this article as: Ni HX, Cao LH, Gong XX, Zang ZY, Chang H. Traditional Chinese medicine for treatment of type 2 diabetes mellitus: Clinical evidence and pharmacological mechanisms. J Integr Med. 2025; 23(6):605–622.
{"title":"Traditional Chinese medicine for treatment of type 2 diabetes mellitus: Clinical evidence and pharmacological mechanisms","authors":"Hong-xia Ni, Lin-hai Cao, Xiao-xiao Gong, Zi-yan Zang, Hui Chang","doi":"10.1016/j.joim.2025.08.006","DOIUrl":"10.1016/j.joim.2025.08.006","url":null,"abstract":"<div><div>Type 2 diabetes mellitus (T2DM) is a highly prevalent chronic metabolic disease with an increasing incidence worldwide, that poses a significant risk to public health. In many current clinical practices for diabetes management, conventional Western treatments, including oral or injectable hypoglycemic agents, have serious side effects. Given that traditional Chinese medicine (TCM) is characterized by a multi-component, multi-target and multi-pathway approach, its combination with Western medicine could enhance efficacy and reduce adverse effects. Consequently, the use of TCM as a potential auxiliary or alternative treatment for the prevention and/or management of T2DM has emerged as a research hotspot. This article reviews existing reports on TCM in the treatment of T2DM and provides a detailed discussion of its applications. By integrating relevant clinical evidence, this review summarizes the clinical data on 23 TCM formulas and Chinese patent medicines, comprehensively describing their efficacy and potential pharmacological mechanisms in the treatment of T2DM. This includes an exploration of the impacts of TCM-based therapeutic interventions on T2DM-related microRNAs and their target genes. We hope this review not only offers new insights for future research directions but also enhances the understanding of the scientific value of TCM.</div><div><br>Please cite this article as: Ni HX, Cao LH, Gong XX, Zang ZY, Chang H. Traditional Chinese medicine for treatment of type 2 diabetes mellitus: Clinical evidence and pharmacological mechanisms. <em>J Integr Med</em>. 2025; 23(6):605–622.</div></div>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 6","pages":"Pages 605-622"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145055988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.joim.2025.09.002
Mao-feng Zhong , Yu-jun Luo , Yu-yu Guo , Shuang Xiang , Wan-fu Lin
Objective
Angiogenesis is a critical target for hepatocellular carcinoma (HCC) treatment. The previous studies indicated that Jiedu Fang (JDF) could inhibit hypoxia-induced angiogenesis through interleukin-8 (IL-8). Therefore, the present study further explores the mechanisms behind JDF’s inhibition of HCC angiogenesis.
Methods
Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo. A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform. Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels, respectively. The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells. The orthotopic tumor xenograft model was established, and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression, while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels.
Results
In vitro and in vivo assays showed that IL-8 promoted angiogenesis, and JDF could antagonize this effect. Bioinformatics analysis indicated that aurora kinase A (Aurora A) was an important candidate, which can promote IL-8 expression through activation of signal transducer and activator of transcription 3 (STAT3). The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration, invasion, and angiogenesis, which was partly inhibited by JDF. Such effects were validated by in vivo assays. Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A.
Conclusion
JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis.
Please cite this article as: Zhong MF, Luo YJ, Guo YY, Xiang S, Lin WF. Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway. J Integr Med. 2025; 23(6):683–693.
{"title":"Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway","authors":"Mao-feng Zhong , Yu-jun Luo , Yu-yu Guo , Shuang Xiang , Wan-fu Lin","doi":"10.1016/j.joim.2025.09.002","DOIUrl":"10.1016/j.joim.2025.09.002","url":null,"abstract":"<div><h3>Objective</h3><div>Angiogenesis is a critical target for hepatocellular carcinoma (HCC) treatment. The previous studies indicated that Jiedu Fang (JDF) could inhibit hypoxia-induced angiogenesis through interleukin-8 (IL-8). Therefore, the present study further explores the mechanisms behind JDF’s inhibition of HCC angiogenesis.</div></div><div><h3>Methods</h3><div>Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo. A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform. Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels, respectively. The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells. The orthotopic tumor xenograft model was established, and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression, while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels.</div></div><div><h3>Results</h3><div>In vitro and in vivo assays showed that IL-8 promoted angiogenesis, and JDF could antagonize this effect. Bioinformatics analysis indicated that aurora kinase A (Aurora A) was an important candidate, which can promote IL-8 expression through activation of signal transducer and activator of transcription 3 (STAT3). The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration, invasion, and angiogenesis, which was partly inhibited by JDF. Such effects were validated by in vivo assays. Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A.</div></div><div><h3>Conclusion</h3><div>JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis.</div><div>Please cite this article as: Zhong MF, Luo YJ, Guo YY, Xiang S, Lin WF. Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway. <em>J Integr Med</em>. 2025; 23(6):683–693.</div></div>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 6","pages":"Pages 683-693"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.joim.2025.07.012
Xin-di Wu , Xu-qiang Wei , Tong-yu Chen , Wen-xiong Zhou , Ke Wang , Jia Zhou
The evolution of acupuncture anesthesia (AA) has spanned six decades. Cardiothoracic surgery serves as a representative case study to illustrate this evolution. Reflecting on its historical development, the use of AA in cardiothoracic surgery has advanced from basic AA procedures in the 1960s to combined acupuncture and drug anesthesia techniques in the early 1980s. Since 2005, the innovative use of non-intubation AA combined anesthesia has been implemented extensively in cardiothoracic surgery. As the medical industry continues to evolve, the techniques applied in AA have expanded to encompass the entire perioperative period in cardiothoracic surgery, leading to the introduction of the concept of modern AA. The use of AA in cardiothoracic surgery exemplifies the ongoing advances and integration of traditional Chinese and Western medicine. Moving forward, it is imperative to enhance the theoretical framework of AA through the execution of rigorous multicenter clinical trials, to further strengthen the body of evidence supporting evidence-based medicine, and to finally explore the underlying mechanisms of AA.
Please cite this article as: Wu XD, Wei XQ, Chen TY, Zhou WX, Wang K, Zhou J. From pioneering to innovation: A comprehensive review of acupuncture anesthesia in cardiothoracic surgeries. J Integr Med. 2025; 23(6):623–629.
{"title":"From pioneering to innovation: A comprehensive review of acupuncture anesthesia in cardiothoracic surgeries","authors":"Xin-di Wu , Xu-qiang Wei , Tong-yu Chen , Wen-xiong Zhou , Ke Wang , Jia Zhou","doi":"10.1016/j.joim.2025.07.012","DOIUrl":"10.1016/j.joim.2025.07.012","url":null,"abstract":"<div><div>The evolution of acupuncture anesthesia (AA) has spanned six decades. Cardiothoracic surgery serves as a representative case study to illustrate this evolution. Reflecting on its historical development, the use of AA in cardiothoracic surgery has advanced from basic AA procedures in the 1960s to combined acupuncture and drug anesthesia techniques in the early 1980s. Since 2005, the innovative use of non-intubation AA combined anesthesia has been implemented extensively in cardiothoracic surgery. As the medical industry continues to evolve, the techniques applied in AA have expanded to encompass the entire perioperative period in cardiothoracic surgery, leading to the introduction of the concept of modern AA. The use of AA in cardiothoracic surgery exemplifies the ongoing advances and integration of traditional Chinese and Western medicine. Moving forward, it is imperative to enhance the theoretical framework of AA through the execution of rigorous multicenter clinical trials, to further strengthen the body of evidence supporting evidence-based medicine, and to finally explore the underlying mechanisms of AA.</div><div><br>Please cite this article as: Wu XD, Wei XQ, Chen TY, Zhou WX, Wang K, Zhou J. From pioneering to innovation: A comprehensive review of acupuncture anesthesia in cardiothoracic surgeries. <em>J Integr Med</em>. 2025; 23(6):623–629.</div></div>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 6","pages":"Pages 623-629"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study investigated the antidepression mechanisms of Xiaoyaosan (XYS), a classic Chinese prescription, from the perspective of energy metabolism in the brain and intestinal tissues.
Methods
Chronic unpredictable mild stress model—a classic depression rat model—was established. Effects of XYS on behaviors and gastrointestinal motility of depressed rats were investigated. Effects of XYS on energetic charge (EC), adenosine triphosphate-related enzymes, and key enzymes of energy metabolism in both hippocampus and jejunum tissues of depressed rats were investigated using high-performance liquid chromatography, biochemical analysis, and real-time quantitative polymerase chain reaction, respectively. Spearman correlation analysis was conducted to construct a correlation network of “behavior-brain energy metabolism-intestinal energy metabolism” of depression.
Results
XYS significantly reduced the abnormal behaviors that observed in depressed rats and increased the EC and the activity of Na+-K+-adenosine triphosphatase (ATPase) and Ca2+-Mg2+-ATPase in hippocampus and jejunum tissues of depressed rats. XYS restored the key energetic pathways that had been interrupted by depression, including glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, XYS exhibited antidepressive effects in terms of regulating energy metabolism in tissues of both brain and intestine.
Conclusion
XYS significantly corrected the disturbances in EC and energy metabolism-related enzymes of both brain and intestinal tissues, alleviating both core and concomitant symptoms of depression. The current findings underscore the role of energy metabolism in the antidepressive activity of XYS, providing a fresh perspective on depression, and novel research strategies for revealing the mechanism of actions of traditional Chinese medicines on multi-site and multi-symptom diseases.
Please cite this article as: Xiao MT, Wang SY, Wu XL, Zhao ZY, Wang HM, Liu HM, Qin XM, Liu XJ. Antidepressant mechanism of Xiaoyaosan: A perspective from energy metabolism of the brain and intestine. J Integr Med. 2025; 23(6):706–720.
{"title":"Antidepressant mechanism of Xiaoyaosan: A perspective from energy metabolism of the brain and intestine","authors":"Meng-ting Xiao, Sen-yan Wang, Xiao-ling Wu, Zi-yu Zhao, Hui-min Wang, Hui-min Liu, Xue-mei Qin, Xiao-jie Liu","doi":"10.1016/j.joim.2025.07.009","DOIUrl":"10.1016/j.joim.2025.07.009","url":null,"abstract":"<div><h3>Objective</h3><div>This study investigated the antidepression mechanisms of Xiaoyaosan (XYS), a classic Chinese prescription, from the perspective of energy metabolism in the brain and intestinal tissues.</div></div><div><h3>Methods</h3><div>Chronic unpredictable mild stress model—a classic depression rat model—was established. Effects of XYS on behaviors and gastrointestinal motility of depressed rats were investigated. Effects of XYS on energetic charge (EC), adenosine triphosphate-related enzymes, and key enzymes of energy metabolism in both hippocampus and jejunum tissues of depressed rats were investigated using high-performance liquid chromatography, biochemical analysis, and real-time quantitative polymerase chain reaction, respectively. Spearman correlation analysis was conducted to construct a correlation network of “behavior-brain energy metabolism-intestinal energy metabolism” of depression.</div></div><div><h3>Results</h3><div>XYS significantly reduced the abnormal behaviors that observed in depressed rats and increased the EC and the activity of Na<sup>+</sup>-K<sup>+</sup>-adenosine triphosphatase (ATPase) and Ca<sup>2+</sup>-Mg<sup>2+</sup>-ATPase in hippocampus and jejunum tissues of depressed rats. XYS restored the key energetic pathways that had been interrupted by depression, including glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, XYS exhibited antidepressive effects in terms of regulating energy metabolism in tissues of both brain and intestine.</div></div><div><h3>Conclusion</h3><div>XYS significantly corrected the disturbances in EC and energy metabolism-related enzymes of both brain and intestinal tissues, alleviating both core and concomitant symptoms of depression. The current findings underscore the role of energy metabolism in the antidepressive activity of XYS, providing a fresh perspective on depression, and novel research strategies for revealing the mechanism of actions of traditional Chinese medicines on multi-site and multi-symptom diseases.</div><div><br>Please cite this article as: Xiao MT, Wang SY, Wu XL, Zhao ZY, Wang HM, Liu HM, Qin XM, Liu XJ. Antidepressant mechanism of Xiaoyaosan: A perspective from energy metabolism of the brain and intestine. <em>J Integr Med</em>. 2025; 23(6):706–720.</div></div>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 6","pages":"Pages 706-720"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.joim.2025.08.005
Muhammad Shahzad Aslam, Yun Jin Kim
This perspective review explores the transformative potential of personalized herbal medicine, examines the integration of ancient herbal knowledge with modern personalized medicine, delves into the principles of personalized medicine particularly in the context of herbal treatments, and investigates the principles of personalized medicine and elucidates how they are being applied to herbal medicine. It emphasizes the individualized nature of this approach and how it is facilitated through genetic analysis and health profiling. This review also highlights key advancements in herbal medicine, such as deoxyribonucleic acid (DNA) analysis and bioinformatics, and their role in the development of precise and personalized herbal remedies. The outcomes of personalized herbal medicine reveal how genetic variations are being considered to tailor treatments, create target-specific therapies, and customize dosage regimens. Furthermore, this review illustrates the evolution of herbal medicine with technological advancements, particularly DNA analysis and bioinformatics, to enhance precision and personalization. The challenge associated with implementing personalized herbal medicine more broadly includes issues of accessibility, regulation, education and ethics. It underscores the transformative potential of personalized herbal medicine. It calls for continued exploration, research and collaboration in this burgeoning field. This emerging field encourages researchers, practitioners, and stakeholders to engage in advancing healthcare practices that are increasingly personalized, evidence-based, and centered on patient's needs.
Please cite this article as: Aslam MS, Kim YJ. Herbal medicine in the modern age: The era of personalized precision. J Integr Med. 2025; 23(6):591–604.
这篇观点综述探讨了个性化草药的变革潜力，考察了古代草药知识与现代个性化医学的结合，深入研究了个性化医学的原则，特别是在草药治疗的背景下，并调查了个性化医学的原则，并阐明了它们如何应用于草药。它强调了这种方法的个体化性质，以及如何通过遗传分析和健康概况促进这种方法。这篇综述还强调了草药的关键进展，如脱氧核糖核酸（DNA）分析和生物信息学，以及它们在开发精确和个性化草药中的作用。个性化草药的结果揭示了如何考虑基因变异来定制治疗，创建目标特异性治疗和定制剂量方案。此外，本文还阐述了随着技术的进步，特别是DNA分析和生物信息学，草药的发展，以提高精度和个性化。更广泛地实施个性化草药所面临的挑战包括可及性、监管、教育和道德等问题。它强调了个性化草药的变革潜力。它要求在这一新兴领域继续进行探索、研究和合作。这一新兴领域鼓励研究人员、从业人员和利益相关者参与到日益个性化、循证和以患者需求为中心的医疗保健实践中来。这篇文章请注明出处：Aslam MS， Kim YJ。现代草药：个性化精准的时代。集成医学[J]；打印前Epub。
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Pub Date : 2025-11-01DOI: 10.1016/j.joim.2025.08.002
An-na Xie , Sun-zheng-yuan Zhang , Yu Zhang, Jin-long Cao, Cheng-long Wang, Li-bo Wang, Hong-jin Wu, Jie Zhang, Wei-wei Dai
Objective
Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms.
Methods
The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin–eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2ʹ,7ʹ-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro.
Results
Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein–protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (P < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway.
Conclusion
CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway.
Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. J Integr Med. 2025; 23(6):670–682.
{"title":"Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway","authors":"An-na Xie , Sun-zheng-yuan Zhang , Yu Zhang, Jin-long Cao, Cheng-long Wang, Li-bo Wang, Hong-jin Wu, Jie Zhang, Wei-wei Dai","doi":"10.1016/j.joim.2025.08.002","DOIUrl":"10.1016/j.joim.2025.08.002","url":null,"abstract":"<div><h3>Objective</h3><div>Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin–eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2ʹ,7ʹ-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro.</div></div><div><h3>Results</h3><div>Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein–protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (<em>P</em> < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway.</div></div><div><h3>Conclusion</h3><div>CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway.</div><div><br> Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. <em>J Integr Med</em>. 2025; 23(6):670–682.</div></div>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 6","pages":"Pages 670-682"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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