Pub Date : 2025-06-01DOI: 10.1016/j.jhip.2025.06.004
Haoqiang Hu , Yunjun Chen , Hongtao Xu , Wei Hou
Multidrug resistance (MDR) is a significant challenge in the cancer therapy, with mechanisms primarily involving increased drug efflux mediated by ABC transporters, leading to reduced intracellular drug concentrations. In recent years, various selenium-containing compounds have demonstrated extensive biological activities, including chemoprevention, antioxidant or pro-oxidant effects, and regulation of the nervous and immune system activities. One of the most prominent physiological characteristics of selenium is its antioxidant capacity, which can regulate the levels of reactive oxygen species (ROS) in the body, making it a promising group for reversing MDR activity. Furthermore, research has shown that natural selenium compounds, including selenate, selenite, selenomethionine, and selenocystein, can inhibit the activity of drug resistance proteins and increase the intracellular accumulation of chemotherapeutic drugs by regulating intracellular ROS levels. For instance, sodium selenite has been shown to markedly increase the sensitivity of drug-resistant cell lines to doxorubicin, exhibiting significant antitumor efficacy and potential for reversing MDR. These findings suggest that selenium compounds hold considerable promise in addressing multidrug resistance. Consequently, this review focuses on elucidating the mechanisms of MDR and the chemical properties of selenium compounds, with particular emphasis on their activities in reversing MDR, thereby providing novel strategies for overcoming MDR in tumor cells.
{"title":"Research advances in the role of selenium in reversing tumor multidrug resistance","authors":"Haoqiang Hu , Yunjun Chen , Hongtao Xu , Wei Hou","doi":"10.1016/j.jhip.2025.06.004","DOIUrl":"10.1016/j.jhip.2025.06.004","url":null,"abstract":"<div><div>Multidrug resistance (MDR) is a significant challenge in the cancer therapy, with mechanisms primarily involving increased drug efflux mediated by ABC transporters, leading to reduced intracellular drug concentrations. In recent years, various selenium-containing compounds have demonstrated extensive biological activities, including chemoprevention, antioxidant or pro-oxidant effects, and regulation of the nervous and immune system activities. One of the most prominent physiological characteristics of selenium is its antioxidant capacity, which can regulate the levels of reactive oxygen species (ROS) in the body, making it a promising group for reversing MDR activity. Furthermore, research has shown that natural selenium compounds, including selenate, selenite, selenomethionine, and selenocystein, can inhibit the activity of drug resistance proteins and increase the intracellular accumulation of chemotherapeutic drugs by regulating intracellular ROS levels. For instance, sodium selenite has been shown to markedly increase the sensitivity of drug-resistant cell lines to doxorubicin, exhibiting significant antitumor efficacy and potential for reversing MDR. These findings suggest that selenium compounds hold considerable promise in addressing multidrug resistance. Consequently, this review focuses on elucidating the mechanisms of MDR and the chemical properties of selenium compounds, with particular emphasis on their activities in reversing MDR, thereby providing novel strategies for overcoming MDR in tumor cells.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 184-194"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Skin diseases and chronic wounds are health problems that require solutions for health systems due to their high costs and difficulties in effective and rapid treatment. Hydroxycinnamic acid and its derivatives are powerful antioxidant molecules with widespread applications in medicine, cosmetics, and food industry. In this study, p-hydroxycinnamic acid was used as a potent agent for the management of skin diseases and other disorders.
Method
Herein, sodium alginate and hydroxypropylmethylcellulose-based films loaded with p-hydroxycinnamic acid at various concentrations were prepared by solvent-casting method and characterized in terms of mechanical, physicochemical, bioadhesive properties, and in vitro release kinetic modelling.
Results
The masses of the films were found to be between 16.933 ± 1.108 mg and 15.200 ± 0.432 mg and thicknesses between 135 ± 4 μm and 163 ± 6 μm. F1 formulation with higher sodium alginate concentration exhibited higher moisture absorption and moisture loss percentages (18.373% ± 2.610% and 8.281% ± 1.834%). In terms of water absorption, it was observed that F3 had up to 100% and F1 had the lowest absorption capacity. However, F1 degraded in a shorter time compared to other films. In terms of mechanical properties, F1 has shown that it has higher tensile strength, reaches 100% by providing continuous release with in vitro release studies, and has the highest bioadhesion. In addition, as a result of FTIR analysis and ex vivo permeation and penetration studies, the formulation F1 proved that it is suitable for dermal applications.
Conclusion
The developed formulations exhibited desired dermal film properties, making it a promising treatment option for dermal applications.
{"title":"Development and ex vivo / in vitro evaluation of sodium alginate/ hydroxypropyl methylcellulose films for dermal and/or transdermal delivery of p-hydroxycinnamic acid","authors":"Ayşe Pınar Yağcılar , Gökçe Karaotmarlı Güven , Emre Şefik Çağlar , Neslihan Üstündağ Okur , Panoraia I. Siafaka","doi":"10.1016/j.jhip.2025.06.002","DOIUrl":"10.1016/j.jhip.2025.06.002","url":null,"abstract":"<div><h3>Objective</h3><div>Skin diseases and chronic wounds are health problems that require solutions for health systems due to their high costs and difficulties in effective and rapid treatment. Hydroxycinnamic acid and its derivatives are powerful antioxidant molecules with widespread applications in medicine, cosmetics, and food industry. In this study, <em>p</em>-hydroxycinnamic acid was used as a potent agent for the management of skin diseases and other disorders.</div></div><div><h3>Method</h3><div>Herein, sodium alginate and hydroxypropylmethylcellulose-based films loaded with <em>p</em>-hydroxycinnamic acid at various concentrations were prepared by solvent-casting method and characterized in terms of mechanical, physicochemical, bioadhesive properties, and <em>in vitro</em> release kinetic modelling.</div></div><div><h3>Results</h3><div>The masses of the films were found to be between 16.933 ± 1.108 mg and 15.200 ± 0.432 mg and thicknesses between 135 ± 4 μm and 163 ± 6 μm. F1 formulation with higher sodium alginate concentration exhibited higher moisture absorption and moisture loss percentages (18.373% ± 2.610% and 8.281% ± 1.834%). In terms of water absorption, it was observed that F3 had up to 100% and F1 had the lowest absorption capacity. However, F1 degraded in a shorter time compared to other films. In terms of mechanical properties, F1 has shown that it has higher tensile strength, reaches 100% by providing continuous release with <em>in vitro</em> release studies, and has the highest bioadhesion. In addition, as a result of FTIR analysis and <em>ex vivo</em> permeation and penetration studies, the formulation F1 proved that it is suitable for dermal applications.</div></div><div><h3>Conclusion</h3><div>The developed formulations exhibited desired dermal film properties, making it a promising treatment option for dermal applications.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 175-183"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01DOI: 10.1016/j.jhip.2025.05.001
Fei Li , Zilin Lan , Weiwei Jiang , Jianheng Zhou , Jiumao Lin , Jinyan Zhao
Objective
Multidrug resistance (MDR) is one main cause of chemotherapy failure. Baicalin is an important active ingredient with anticancer potential in many Chinese herbal medicines. In order to understand the function of baicalin reversing MDR in hepatocellular carcinoma (HCC) and the molecular mechanisms that underlie it, the current study was designed.
Methods
Bel-7402 and Bel-7402/5-FU cells were cultured, and MTT assay was applied to detect cell viability and the cross-resistance of Bel-7402/5-FU cells. The pump function, apoptosis, and autophagy were detected by flow cytometry. The related proteins were detected by Western blot assay. The PI3K agonist (740Y-P) was used to verify whether baicalin overcomes the drug resistance of HCC cells by blocking the PI3K/AKT pathway.
Results
The findings showed that Bel-7402/5-FU cells were cross-resistant to different chemotherapeutic drugs. Baicalin inhibited cell viability in both Bel-7402/5-FU and Bel-7402 cells, and baicalin increased sensitivity of Bel-7402/5-FU cells to 5-FU in time- and dose-dependent manners. Baicalin increased the accumulation of doxorubicin and rhodamine-123 in Bel-7402/5-FU cells and inhibited the protein expression of ABCG2, ABCB1, and ABCC1, associated with pump function. In addition, baicalin induced apoptosis of Bel-7402/5-FU cells via up-regulating Bax expression. Furthermore, baicalin increased autophagy through regulating LC3-Ⅱ, p62, and Beclin-1. Baicalin reversed drug resistance in Bel-7402/5-FU cells by inhibiting the PI3K/AKT pathway, which promoted autophagy and apoptosis to restore chemosensitivity.
Conclusion
Baicalin increased accumulation of chemotherapy drugs and induced apoptosis and autophagy in Bel-7402/5-FU cells by inhibiting the PI3K/AKT signaling pathway, that may be the important mechanism by which baicalin reverses the MDR of HCC.
{"title":"Baicalin induces apoptosis and autophagy in resistant human hepatocellular carcinoma cell line Bel-7402/5-FU cells via PI3K/AKT pathway","authors":"Fei Li , Zilin Lan , Weiwei Jiang , Jianheng Zhou , Jiumao Lin , Jinyan Zhao","doi":"10.1016/j.jhip.2025.05.001","DOIUrl":"10.1016/j.jhip.2025.05.001","url":null,"abstract":"<div><h3>Objective</h3><div>Multidrug resistance (MDR) is one main cause of chemotherapy failure. Baicalin is an important active ingredient with anticancer potential in many Chinese herbal medicines. In order to understand the function of baicalin reversing MDR in hepatocellular carcinoma (HCC) and the molecular mechanisms that underlie it, the current study was designed.</div></div><div><h3>Methods</h3><div>Bel-7402 and Bel-7402/5-FU cells were cultured, and MTT assay was applied to detect cell viability and the cross-resistance of Bel-7402/5-FU cells. The pump function, apoptosis, and autophagy were detected by flow cytometry. The related proteins were detected by Western blot assay. The PI3K agonist (740Y-P) was used to verify whether baicalin overcomes the drug resistance of HCC cells by blocking the PI3K/AKT pathway.</div></div><div><h3>Results</h3><div>The findings showed that Bel-7402/5-FU cells were cross-resistant to different chemotherapeutic drugs. Baicalin inhibited cell viability in both Bel-7402/5-FU and Bel-7402 cells, and baicalin increased sensitivity of Bel-7402/5-FU cells to 5-FU in time- and dose-dependent manners. Baicalin increased the accumulation of doxorubicin and rhodamine-123 in Bel-7402/5-FU cells and inhibited the protein expression of ABCG2, ABCB1, and ABCC1, associated with pump function. In addition, baicalin induced apoptosis of Bel-7402/5-FU cells via up-regulating Bax expression. Furthermore, baicalin increased autophagy through regulating LC3-Ⅱ, p62, and Beclin-1. Baicalin reversed drug resistance in Bel-7402/5-FU cells by inhibiting the PI3K/AKT pathway, which promoted autophagy and apoptosis to restore chemosensitivity.</div></div><div><h3>Conclusion</h3><div>Baicalin increased accumulation of chemotherapy drugs and induced apoptosis and autophagy in Bel-7402/5-FU cells by inhibiting the PI3K/AKT signaling pathway, that may be the important mechanism by which baicalin reverses the MDR of HCC.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 150-158"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144239602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01DOI: 10.1016/j.jhip.2025.06.007
Qi Zhang, Shenglan Gou, Jia Lin, Yinglan Zhang, Qiang Li
Objective
To evaluate the effects of honeysuckle extract and its active component, luteolin, on the autistic-like behaviors and neuroinflammatory responses in NDE1-deficient autism spectrum disorder (ASD) zebrafish models. Also, to assess whether differences exist in their behavioral improvement effects and impacts on brain inflammatory factor expression levels.
Methods
Behavioral phenotyping (hyperactivity, stereotypic back-and-forth swimming, and 1VS6 social preference/grouping tests) and molecular analyses (quantification of NF-κB, IL6, TNFα, and IL1β) were performed on NDE1-deficient zebrafish treated with honeysuckle extract or luteolin.
Results
Honeysuckle extract improved two core symptoms of ASD, small circling repetitive stereotyped behavior and 1VS6 social preference behavior. While luteolin enhanced one core symptom, shoaling behavior, and one comorbid symptom, hyperactive locomotor activity. Molecularly, honeysuckle extract normalized IL6 levels, and luteolin reduced IL1β overexpression; their effects on brain inflammation in the NDE1-deficient autism model differed.
Conclusion
Both honeysuckle extract and luteolin demonstrated behavioral rescue and anti-neuroinflammatory effects in NDE1-deficient ASD zebrafish models. The ameliorating effects of luteolin on ASD-related behaviors and neuroinflammation are supported by literature, while the beneficial effects of honeysuckle on ASD-related behaviors represent a novel finding of this study, highlighting medicinal plants and plant-derived compounds as potential ASD therapeutics. Given honeysuckle's traditional Chinese medicinal and food uses, established safety, and superior improvement of core ASD symptoms compared to luteolin, it may offer a safer autism treatment option than luteolin-based small-molecule medication.
{"title":"The ameliorative effects of honeysuckle extract and its major component luteolin on autism-like behaviors in the NDE1 deficiency model","authors":"Qi Zhang, Shenglan Gou, Jia Lin, Yinglan Zhang, Qiang Li","doi":"10.1016/j.jhip.2025.06.007","DOIUrl":"10.1016/j.jhip.2025.06.007","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the effects of honeysuckle extract and its active component, luteolin, on the autistic-like behaviors and neuroinflammatory responses in NDE1-deficient autism spectrum disorder (ASD) zebrafish models. Also, to assess whether differences exist in their behavioral improvement effects and impacts on brain inflammatory factor expression levels.</div></div><div><h3>Methods</h3><div>Behavioral phenotyping (hyperactivity, stereotypic back-and-forth swimming, and 1VS6 social preference/grouping tests) and molecular analyses (quantification of NF-κB, IL6, TNFα, and IL1β) were performed on NDE1-deficient zebrafish treated with honeysuckle extract or luteolin.</div></div><div><h3>Results</h3><div>Honeysuckle extract improved two core symptoms of ASD, small circling repetitive stereotyped behavior and 1VS6 social preference behavior. While luteolin enhanced one core symptom, shoaling behavior, and one comorbid symptom, hyperactive locomotor activity. Molecularly, honeysuckle extract normalized IL6 levels, and luteolin reduced IL1β overexpression; their effects on brain inflammation in the NDE1-deficient autism model differed.</div></div><div><h3>Conclusion</h3><div>Both honeysuckle extract and luteolin demonstrated behavioral rescue and anti-neuroinflammatory effects in NDE1-deficient ASD zebrafish models. The ameliorating effects of luteolin on ASD-related behaviors and neuroinflammation are supported by literature, while the beneficial effects of honeysuckle on ASD-related behaviors represent a novel finding of this study, highlighting medicinal plants and plant-derived compounds as potential ASD therapeutics. Given honeysuckle's traditional Chinese medicinal and food uses, established safety, and superior improvement of core ASD symptoms compared to luteolin, it may offer a safer autism treatment option than luteolin-based small-molecule medication.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 195-203"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01DOI: 10.1016/j.jhip.2025.06.003
Wei liang , Minni Huang , Yue Sun , Shuyu Guan
Objective
This study aimed to use bioinformatics techniques to screen biomarkers related to vitiligo.
Methods
Firstly, the gene expression profiles of vitiligo were obtained from the GEO database, and differentially expressed genes (DEGs) were identified. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on these differentially expressed genes. Through weighted gene co-expression network analysis (WGCNA), the core genes in the module most closely related to vitiligo were identified, and an intersection analysis was conducted with the DEGs. Next, a protein-protein interaction (PPI) network analysis was carried out on the intersection genes. Key genes were further screened using Cytohubba and least absolute shrinkage and selection operator (LASSO) regression analysis, and the roles of these key genes in immune cell infiltration were explored through single-sample gene set enrichment analysis (ssGSEA). In addition, the diagnostic effectiveness of the key genes was verified by the receiver operating characteristic (ROC) curve, and drugs related to the key genes were predicted using databases. Finally, the expression levels of these key genes were verified through reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot experiments.
Results
A total of 667 DEGs were identified, and the enrichment analysis mainly involved cell adhesion molecules, T cell receptor signaling pathway, etc. Nineteen core genes were screened out from the five algorithms of Cytohubba, and LASSO regression analysis further determined four key genes (IL7R, GZMH, CD3G, and UBD). Immune cell infiltration analysis showed that these four key genes had high expression in immune cells. The prediction results of traditional Chinese medicine showed that 15 traditional Chinese medicines were related to the key genes. The results of RT-qPCR showed that the expressions of IL7R, GZMH, and CD3G were significantly upregulated (∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001), and Western blot showed obvious expressions of IL7R, GZMH, CD3G, and UBD.
Conclusion
This study used bioinformatics methods to explore the biomarkers of vitiligo, and verified the potential of IL7R, GZMH, and CD3G as novel candidate genes through in vitro experiments. These genes may become new targets for the diagnosis, prognosis, and treatment of vitiligo.
目的利用生物信息学技术筛选与白癜风相关的生物标志物。方法首先从GEO数据库中获取白癜风基因表达谱，鉴定差异表达基因（DEGs）；随后，对这些差异表达基因进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。通过加权基因共表达网络分析（weighted gene co-expression network analysis， WGCNA），鉴定出模块中与白癜风关系最密切的核心基因，并与deg进行交叉分析。然后，对交叉基因进行蛋白-蛋白相互作用（PPI）网络分析。通过Cytohubba和least absolute shrinkage and selection operator （LASSO）回归分析进一步筛选关键基因，并通过单样本基因集富集分析（ssGSEA）探讨这些关键基因在免疫细胞浸润中的作用。此外，通过受试者工作特征（ROC）曲线验证关键基因的诊断有效性，并利用数据库预测关键基因相关的药物。最后通过逆转录定量聚合酶链反应（RT-qPCR）和Western blot实验验证这些关键基因的表达水平。结果共鉴定出667个deg，富集分析主要涉及细胞粘附分子、T细胞受体信号通路等。从Cytohubba的5种算法中筛选出19个核心基因，LASSO回归分析进一步确定了4个关键基因（IL7R、GZMH、CD3G和UBD）。免疫细胞浸润分析表明，这四个关键基因在免疫细胞中均有高表达。中药预测结果显示，有15种中药与关键基因相关。RT-qPCR结果显示，IL7R、GZMH和CD3G的表达显著上调(∗P <；0.05, * * P <；0.01, * * * P <；0.001)， Western blot显示IL7R、GZMH、CD3G、UBD明显表达。结论本研究采用生物信息学方法探索白癜风的生物标志物，并通过体外实验验证了IL7R、GZMH和CD3G作为新的候选基因的潜力。这些基因可能成为白癜风诊断、预后和治疗的新靶点。
{"title":"Screening of potential markers for vitiligo based on bioinformatics and LASSO regression and prediction of Chinese medicine","authors":"Wei liang , Minni Huang , Yue Sun , Shuyu Guan","doi":"10.1016/j.jhip.2025.06.003","DOIUrl":"10.1016/j.jhip.2025.06.003","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to use bioinformatics techniques to screen biomarkers related to vitiligo.</div></div><div><h3>Methods</h3><div>Firstly, the gene expression profiles of vitiligo were obtained from the GEO database, and differentially expressed genes (DEGs) were identified. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on these differentially expressed genes. Through weighted gene co-expression network analysis (WGCNA), the core genes in the module most closely related to vitiligo were identified, and an intersection analysis was conducted with the DEGs. Next, a protein-protein interaction (PPI) network analysis was carried out on the intersection genes. Key genes were further screened using Cytohubba and least absolute shrinkage and selection operator (LASSO) regression analysis, and the roles of these key genes in immune cell infiltration were explored through single-sample gene set enrichment analysis (ssGSEA). In addition, the diagnostic effectiveness of the key genes was verified by the receiver operating characteristic (ROC) curve, and drugs related to the key genes were predicted using databases. Finally, the expression levels of these key genes were verified through reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot experiments.</div></div><div><h3>Results</h3><div>A total of 667 DEGs were identified, and the enrichment analysis mainly involved cell adhesion molecules, T cell receptor signaling pathway, etc. Nineteen core genes were screened out from the five algorithms of Cytohubba, and LASSO regression analysis further determined four key genes <em>(IL7R, GZMH, CD3G,</em> and <em>UBD</em>). Immune cell infiltration analysis showed that these four key genes had high expression in immune cells. The prediction results of traditional Chinese medicine showed that 15 traditional Chinese medicines were related to the key genes. The results of RT-qPCR showed that the expressions of <em>IL7R</em>, <em>GZMH</em>, and <em>CD3G</em> were significantly upregulated (<sup>∗</sup><em>P</em> < 0.05, <sup>∗∗</sup><em>P</em> < 0.01, <sup>∗∗∗</sup><em>P</em> < 0.001), and Western blot showed obvious expressions of <em>IL7R</em>, <em>GZMH</em>, <em>CD3G</em>, and <em>UBD</em>.</div></div><div><h3>Conclusion</h3><div>This study used bioinformatics methods to explore the biomarkers of vitiligo, and verified the potential of <em>IL7R</em>, <em>GZMH</em>, and <em>CD3G</em> as novel candidate genes through <em>in vitro</em> experiments. These genes may become new targets for the diagnosis, prognosis, and treatment of vitiligo.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 224-234"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01DOI: 10.1016/j.jhip.2025.06.006
Meina Lian , Xiaoxia Wang , Zixian Huang , Yudong Wang , Zhiquan Huang
Objective
To investigate the relationship between tumor metabolism and immune cell infiltration in Head and Neck Squamous Cell Carcinoma (HNSCC), aiming to identify novel biomarkers and potential therapeutic targets.
Methods
Seven major metabolic pathways were analyzed using Gene Set Variation Analysis (GSVA) in HNSCC cohorts to assess their correlation with overall survival (OS) and immune microenvironment characteristics. Unsupervised clustering was applied to identify metabolic subtypes, and differentially expressed metabolism-related genes (MRGs) were screened for prognostic relevance. A risk model was constructed based on 16 core MRGs. TNFAIP6 was further evaluated for its functional role through in vitro assays, including proliferation, migration, and invasion analyses.
Results
The activity of key metabolic pathways, such as glycolysis, oxidative phosphorylation, and fatty acid metabolism, significantly correlated with OS and immune infiltration patterns. Two distinct metabolic clusters (C1 and C2) were identified, with C1 associated with a more immune-enriched microenvironment. A total of 698 MRGs were linked to immune modulation and tumor progression. The risk model based on 16 MRGs effectively stratified patients by prognosis and immune infiltration status. TNFAIP6 was highly expressed in malignant cells and associated with immunosuppression, poor survival, and tumor progression. Functional experiments confirmed that TNFAIP6 knockdown inhibited tumor cell proliferation, migration, and invasion.
Conclusion
Metabolic reprogramming plays a critical role in shaping the immune landscape of HNSCC. TNFAIP6 represents a promising prognostic biomarker and potential therapeutic target for improving personalized treatment in HNSCC patients.
{"title":"Integrating metabolism gene clusters and tumor immune microenvironment in head and neck squamous cell carcinoma","authors":"Meina Lian , Xiaoxia Wang , Zixian Huang , Yudong Wang , Zhiquan Huang","doi":"10.1016/j.jhip.2025.06.006","DOIUrl":"10.1016/j.jhip.2025.06.006","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the relationship between tumor metabolism and immune cell infiltration in Head and Neck Squamous Cell Carcinoma (HNSCC), aiming to identify novel biomarkers and potential therapeutic targets.</div></div><div><h3>Methods</h3><div>Seven major metabolic pathways were analyzed using Gene Set Variation Analysis (GSVA) in HNSCC cohorts to assess their correlation with overall survival (OS) and immune microenvironment characteristics. Unsupervised clustering was applied to identify metabolic subtypes, and differentially expressed metabolism-related genes (MRGs) were screened for prognostic relevance. A risk model was constructed based on 16 core MRGs. TNFAIP6 was further evaluated for its functional role through <em>in vitro</em> assays, including proliferation, migration, and invasion analyses.</div></div><div><h3>Results</h3><div>The activity of key metabolic pathways, such as glycolysis, oxidative phosphorylation, and fatty acid metabolism, significantly correlated with OS and immune infiltration patterns. Two distinct metabolic clusters (C1 and C2) were identified, with C1 associated with a more immune-enriched microenvironment. A total of 698 MRGs were linked to immune modulation and tumor progression. The risk model based on 16 MRGs effectively stratified patients by prognosis and immune infiltration status. TNFAIP6 was highly expressed in malignant cells and associated with immunosuppression, poor survival, and tumor progression. Functional experiments confirmed that TNFAIP6 knockdown inhibited tumor cell proliferation, migration, and invasion.</div></div><div><h3>Conclusion</h3><div>Metabolic reprogramming plays a critical role in shaping the immune landscape of HNSCC. TNFAIP6 represents a promising prognostic biomarker and potential therapeutic target for improving personalized treatment in HNSCC patients.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 235-248"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01DOI: 10.1016/j.jhip.2025.06.001
Jiao Guo
Glycolipid metabolic disorders, linked to cardiovascular diseases and cancer, are a major global health challenge. Current single-disease treatments remain unsatisfied in reducing long-term risks. In 2024, Professor Jiao Guo along with global experts launched the "Global Initiative for Glycolipid Metabolic Health" to enhance prevention through scientific research, public education, and integrated management systems.
{"title":"Global Initiative for Glycolipid Metabolic Health","authors":"Jiao Guo","doi":"10.1016/j.jhip.2025.06.001","DOIUrl":"10.1016/j.jhip.2025.06.001","url":null,"abstract":"<div><div>Glycolipid metabolic disorders, linked to cardiovascular diseases and cancer, are a major global health challenge. Current single-disease treatments remain unsatisfied in reducing long-term risks. In 2024, Professor Jiao Guo along with global experts launched the \"Global Initiative for Glycolipid Metabolic Health\" to enhance prevention through scientific research, public education, and integrated management systems.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 249-250"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01DOI: 10.1016/j.jhip.2025.06.008
Xiao Chen , Xian Lin
Lung cancer, the leading cause of cancer-related deaths, demands innovative models for therapy development. Bioactive natural compounds, with their structural diversity and historical therapeutic significance, remain pivotal in drug discovery for combating lung malignancies. Patient-derived organoids (PDOs) surpass conventional models by preserving tumor heterogeneity, molecular profiles, and tumor microenvironment (TME) dynamics, enabling accurate drug response prediction and personalized therapy design. Recent studies leveraging lung cancer PDOs have validated several plant-derived agents for their tumor-suppressive effects, potential for chemosensitivity enhancement, and subtype-specific efficacy. Advanced co-culture systems incorporating TME components have improved preclinical-to-clinical translatability. The technological integration of bioengineered platforms (e.g., microfluidic systems, 3D bioprinting) and artificial intelligence has further enhanced high-throughput screening and clinical correlation of drug responses. Although lung cancer PDOs exhibit inherent limitations, these advancements establish PDOs as important tools for evaluating the efficacy-toxicity profiles of bioactive natural compounds and advancing precision oncology in lung cancer.
{"title":"Patient-derived organoids: Advancing research on bioactive natural compounds in lung cancer","authors":"Xiao Chen , Xian Lin","doi":"10.1016/j.jhip.2025.06.008","DOIUrl":"10.1016/j.jhip.2025.06.008","url":null,"abstract":"<div><div>Lung cancer, the leading cause of cancer-related deaths, demands innovative models for therapy development. Bioactive natural compounds, with their structural diversity and historical therapeutic significance, remain pivotal in drug discovery for combating lung malignancies. Patient-derived organoids (PDOs) surpass conventional models by preserving tumor heterogeneity, molecular profiles, and tumor microenvironment (TME) dynamics, enabling accurate drug response prediction and personalized therapy design. Recent studies leveraging lung cancer PDOs have validated several plant-derived agents for their tumor-suppressive effects, potential for chemosensitivity enhancement, and subtype-specific efficacy. Advanced co-culture systems incorporating TME components have improved preclinical-to-clinical translatability. The technological integration of bioengineered platforms (e.g., microfluidic systems, 3D bioprinting) and artificial intelligence has further enhanced high-throughput screening and clinical correlation of drug responses. Although lung cancer PDOs exhibit inherent limitations, these advancements establish PDOs as important tools for evaluating the efficacy-toxicity profiles of bioactive natural compounds and advancing precision oncology in lung cancer.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 204-208"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-08DOI: 10.1016/j.jhip.2025.03.007
Mukesh Vijayarangam Rajesh, Karthikeyan Elumalai
The pharmaceutical manufacturing industry transforms through artificial intelligence (AI) by implementing process improvements along with productivity enhancements and product quality improvements. The combination of big data and AI applications through machine learning algorithms analyzes manufacturing inefficiencies and recommends improvements for both medicine formulation and packaging as well as quality control measures. The combination of temperature adjustment, pressure adjustment, and ingredient proportion control enables AI to enhance the production efficiency of tablets, capsules, and injections, and decrease both time requirements and cost expenses. AI also enhances blister pack and vial packing methods and automates quality control inspections to ensure consistency of products by detecting defects. Consistent, reliable, and effective production processes rely on real-time monitoring and AI-driven adjustments, which directly contribute to manufacturing pharmaceutical products of improved quality. The continuous observation of the production process by AI helps to detect safety-related risks, including equipment failures and contamination risks, while addressing them promptly to preserve production security. The utilization of AI helps businesses identify necessary equipment maintenance demands which enables companies to organize maintenance before equipment breakdowns occur. AI-driven data insights enable companies to make strategic choices based on real-time data, automate operational processes for efficiency, and respond to emerging industry patterns positively. Through enhanced operational efficiency, waste minimization, and improvement of profit margins, AI integration in pharmaceutical production can transform the sector.
{"title":"The transformative power of artificial intelligence in pharmaceutical manufacturing: Enhancing efficiency, product quality, and safety","authors":"Mukesh Vijayarangam Rajesh, Karthikeyan Elumalai","doi":"10.1016/j.jhip.2025.03.007","DOIUrl":"10.1016/j.jhip.2025.03.007","url":null,"abstract":"<div><div>The pharmaceutical manufacturing industry transforms through artificial intelligence (AI) by implementing process improvements along with productivity enhancements and product quality improvements. The combination of big data and AI applications through machine learning algorithms analyzes manufacturing inefficiencies and recommends improvements for both medicine formulation and packaging as well as quality control measures. The combination of temperature adjustment, pressure adjustment, and ingredient proportion control enables AI to enhance the production efficiency of tablets, capsules, and injections, and decrease both time requirements and cost expenses. AI also enhances blister pack and vial packing methods and automates quality control inspections to ensure consistency of products by detecting defects. Consistent, reliable, and effective production processes rely on real-time monitoring and AI-driven adjustments, which directly contribute to manufacturing pharmaceutical products of improved quality. The continuous observation of the production process by AI helps to detect safety-related risks, including equipment failures and contamination risks, while addressing them promptly to preserve production security. The utilization of AI helps businesses identify necessary equipment maintenance demands which enables companies to organize maintenance before equipment breakdowns occur. AI-driven data insights enable companies to make strategic choices based on real-time data, automate operational processes for efficiency, and respond to emerging industry patterns positively. Through enhanced operational efficiency, waste minimization, and improvement of profit margins, AI integration in pharmaceutical production can transform the sector.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 2","pages":"Pages 125-135"},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jhip.2025.02.003
Liyan Li, Han Shen, Li Lu
Objective
Mesenchymal stem cell (MSC) therapy represents a promising treatment strategy for osteoarthritis (OA). Nevertheless, the therapeutic efficacy of MSCs may be attenuated under conditions of cellular senescence or when the available clinical quantity is insufficient. α-Ketoglutarate (AKG) exerts beneficial effects on skeletal tissues and the activity of stem cells. Consequently, the present study was designed to explore the potential of AKG in augmenting the viability of MSCs and the potential of their combined utilization in the treatment of OA.
Methods
MSCs with senescence induced by in vitro passaging served as the experimental subjects. The effects of AKG on the activity of senescent MSCs were investigated via morphological observation, scratch assay, and DAPI staining. Bioinformatics methods were employed to explore the action targets and pathways of AKG in the treatment of OA, providing a theoretical basis and experimental evidence for further experiments. The feasibility of this pathway was verified at the animal level. A rat model of OA was induced by intra-articular injection of sodium monoiodoacetate (MIA). Platelet-rich plasma (PRP), a representative drug for clinical OA treatment, was used as a positive control. The efficacy of combined high-dose and low-dose medications was evaluated through morphological observation and pathological section staining.
Results
The outcomes of the in vitro cellular experiments indicate that AKG is capable of decreasing the quantity of MSCs exhibiting senescent morphological features, enhancing the migratory capacity of MSCs, and suppressing the apoptotic process of MSCs. Consequently, AKG exerts a reparative influence on senescent MSCs. Bioinformatics analysis indicated that AKG exerts its repairing effect on OA by inhibiting the Hedgehog (HH) signaling pathway. Additionally, at the animal experiment level, we found that the synergistic effect of high-dose AKG combined with MSCs could more significantly alleviate the severity of OA. It enhances matrix synthesis, reduces endochondral ossification, and promotes cartilage repair through the HH pathway.
Conclusion
Our research indicates that AKG has a significant effect on enhancing the activity of MSCs. The combined treatment can promote the repair of articular cartilage in OA rats through the HH pathway, and it provides a novel approach for the treatment of OA.
{"title":"The repair effect of α-ketoglutarate combined with mesenchymal stem cells on osteoarthritis via the hedgehog protein pathway","authors":"Liyan Li, Han Shen, Li Lu","doi":"10.1016/j.jhip.2025.02.003","DOIUrl":"10.1016/j.jhip.2025.02.003","url":null,"abstract":"<div><h3>Objective</h3><div>Mesenchymal stem cell (MSC) therapy represents a promising treatment strategy for osteoarthritis (OA). Nevertheless, the therapeutic efficacy of MSCs may be attenuated under conditions of cellular senescence or when the available clinical quantity is insufficient. α-Ketoglutarate (AKG) exerts beneficial effects on skeletal tissues and the activity of stem cells. Consequently, the present study was designed to explore the potential of AKG in augmenting the viability of MSCs and the potential of their combined utilization in the treatment of OA.</div></div><div><h3>Method<em>s</em></h3><div>MSCs with senescence induced by <em>in vitro</em> passaging served as the experimental subjects. The effects of AKG on the activity of senescent MSCs were investigated via morphological observation, scratch assay, and DAPI staining. Bioinformatics methods were employed to explore the action targets and pathways of AKG in the treatment of OA, providing a theoretical basis and experimental evidence for further experiments. The feasibility of this pathway was verified at the animal level. A rat model of OA was induced by intra-articular injection of sodium monoiodoacetate (MIA). Platelet-rich plasma (PRP), a representative drug for clinical OA treatment, was used as a positive control. The efficacy of combined high-dose and low-dose medications was evaluated through morphological observation and pathological section staining.</div></div><div><h3>Results</h3><div>The outcomes of the <em>in vitro</em> cellular experiments indicate that AKG is capable of decreasing the quantity of MSCs exhibiting senescent morphological features, enhancing the migratory capacity of MSCs, and suppressing the apoptotic process of MSCs. Consequently, AKG exerts a reparative influence on senescent MSCs. Bioinformatics analysis indicated that AKG exerts its repairing effect on OA by inhibiting the Hedgehog (HH) signaling pathway. Additionally, at the animal experiment level, we found that the synergistic effect of high-dose AKG combined with MSCs could more significantly alleviate the severity of OA. It enhances matrix synthesis, reduces endochondral ossification, and promotes cartilage repair through the HH pathway.</div></div><div><h3>Conclusion</h3><div>Our research indicates that AKG has a significant effect on enhancing the activity of MSCs. The combined treatment can promote the repair of articular cartilage in OA rats through the HH pathway, and it provides a novel approach for the treatment of OA.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 1","pages":"Pages 11-22"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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