Jing Lin, Fenglu Wu, Yanwen Zhu, Qianqian Zhu, Tong Du, Jiaying Lin
Objective: Our objective was to investigate the efficacy of letrozole co-treatment in an antagonist protocol for infertile women with polycystic ovary syndrome (PCOS). Patients and Methods: This retrospective cohort study included infertile women with PCOS undergoing IVF/ICSI with and without letrozole co-treatment in an antagonist protocol from 2007– 2021 at Shanghai Ninth People’s Hospital (Shanghai, China). A total of 1559 participants were enrolled, with 1227 women in the antagonist group and 332 women in the letrozole co-treatment group. Propensity score-based patient-matching model was conducted to balance covariates between the groups. The primary outcome was the number of retrieved oocytes, with secondary outcomes including endocrine parameters, ovarian stimulation outcomes, pregnancy outcomes, and obstetrical and neonatal complications. Results: Letrozole co-treatment induced significant changes in hormonal regulation, increased the percentage of large follicles, and resulted in fewer retrieved oocytes (P < 0.05). However, there was no negative impact on the number of usable embryos or good-quality embryos (P > 0.05). The live birth rates following fresh embryo transfer were comparable between the letrozole and control groups (single embryo transfer: 28.9% vs 29.7%, P > 0.05; double embryo transfer: 37.3% vs 45.6%, P > 0.05). Additionally, there were no significant differences between the two groups in the live birth rate per patient after frozen embryo transfer and the cumulative live birth rate (P > 0.05). No significant differences in obstetrical and neonatal complications were observed between the groups (P > 0.05). Conclusion: The addition of letrozole to the antagonist protocol for women with PCOS undergoing IVF induces a higher percentage of large follicles during oocyte retrieval, while reducing the overall number of retrieved oocytes. Moreover, the use of letrozole demonstrates comparable clinical outcomes following embryo transfers. These findings highlight the potential application of letrozole in an antagonist protocol for women with PCOS.
目的：我们的目的是研究来曲唑联合治疗多囊卵巢综合征（PCOS）不孕妇女的疗效：我们的目的是研究来曲唑联合治疗对多囊卵巢综合征（PCOS）不孕妇女的疗效：这项回顾性队列研究纳入了2007年至2021年期间在上海市第九人民医院（中国上海）接受IVF/ICSI拮抗剂方案来曲唑联合治疗和未接受来曲唑联合治疗的多囊卵巢综合征不孕妇女。共有1559名患者参加了该研究，其中拮抗剂组1227名，来曲唑联合治疗组332名。研究采用基于倾向评分的患者匹配模型来平衡两组间的协变量。主要结果是取卵数量，次要结果包括内分泌参数、卵巢刺激结果、妊娠结果以及产科和新生儿并发症：结果：来曲唑联合治疗引起了激素调节的显著变化，增加了大卵泡的比例，并导致取卵数量减少（P < 0.05）。但是，对可用胚胎或优质胚胎的数量没有负面影响（P > 0.05）。来曲唑组和对照组在新鲜胚胎移植后的活产率相当（单胚胎移植：28.9% vs 29.7%，P > 0.05；双胚胎移植：37.3% vs 45.6%，P > 0.05）：37.3%对45.6%，P> 0.05）。此外，冷冻胚胎移植后每名患者的活产率和累计活产率在两组间无显著差异（P > 0.05）。两组患者的产科和新生儿并发症无明显差异（P> 0.05）：结论：对接受体外受精的多囊卵巢综合征妇女而言，在拮抗剂方案中加入来曲唑可在卵母细胞提取过程中诱导出更高比例的大卵泡，同时减少提取的卵母细胞总数。此外，来曲唑在胚胎移植后的临床效果也相当可观。这些发现凸显了来曲唑在多囊卵巢综合征妇女拮抗剂方案中的潜在应用。关键词：来曲唑；拮抗剂方案；多囊卵巢综合征；卵泡；体外受精
{"title":"The Efficacy of Letrozole Co-Treatment in an Antagonist Protocol for Women with Polycystic Ovary Syndrome Undergoing IVF: A Retrospective Study","authors":"Jing Lin, Fenglu Wu, Yanwen Zhu, Qianqian Zhu, Tong Du, Jiaying Lin","doi":"10.2147/dddt.s458608","DOIUrl":"https://doi.org/10.2147/dddt.s458608","url":null,"abstract":"<strong>Objective:</strong> Our objective was to investigate the efficacy of letrozole co-treatment in an antagonist protocol for infertile women with polycystic ovary syndrome (PCOS).<br/><strong>Patients and Methods:</strong> This retrospective cohort study included infertile women with PCOS undergoing IVF/ICSI with and without letrozole co-treatment in an antagonist protocol from 2007– 2021 at Shanghai Ninth People’s Hospital (Shanghai, China). A total of 1559 participants were enrolled, with 1227 women in the antagonist group and 332 women in the letrozole co-treatment group. Propensity score-based patient-matching model was conducted to balance covariates between the groups. The primary outcome was the number of retrieved oocytes, with secondary outcomes including endocrine parameters, ovarian stimulation outcomes, pregnancy outcomes, and obstetrical and neonatal complications.<br/><strong>Results:</strong> Letrozole co-treatment induced significant changes in hormonal regulation, increased the percentage of large follicles, and resulted in fewer retrieved oocytes (<em>P</em> < 0.05). However, there was no negative impact on the number of usable embryos or good-quality embryos (<em>P</em> > 0.05). The live birth rates following fresh embryo transfer were comparable between the letrozole and control groups (single embryo transfer: 28.9% vs 29.7%, <em>P</em> > 0.05; double embryo transfer: 37.3% vs 45.6%, <em>P</em> > 0.05). Additionally, there were no significant differences between the two groups in the live birth rate per patient after frozen embryo transfer and the cumulative live birth rate (<em>P</em> > 0.05). No significant differences in obstetrical and neonatal complications were observed between the groups (<em>P</em> > 0.05).<br/><strong>Conclusion:</strong> The addition of letrozole to the antagonist protocol for women with PCOS undergoing IVF induces a higher percentage of large follicles during oocyte retrieval, while reducing the overall number of retrieved oocytes. Moreover, the use of letrozole demonstrates comparable clinical outcomes following embryo transfers. These findings highlight the potential application of letrozole in an antagonist protocol for women with PCOS.<br/><br/><strong>Keywords:</strong> letrozole, antagonist protocol, polycystic ovary syndrome, follicle, in vitro fertilization<br/>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141570040","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}
Haijie Tan, Yi Chen, Yan Jiang, Xiaojing Sun, Wei Ye, Xuefang Zhu, Xiangsheng Xiong
Background: Vasopressors remain an important strategy for managing spinal anesthesia-induced hypotension in women with preeclampsia. The aim of this study was to investigate the ED90s and efficacy ratio of phenylephrine and norepinephrine in managing spinal anesthesia-induced hypotension in women with preeclampsia during cesarean delivery. Methods: 60 women with preeclampsia, who underwent cesarean delivery, were randomly assigned to receive either a continuous intravenous infusion of phenylephrine or norepinephrine following spinal anesthesia. The initial dosage of phenylephrine or norepinephrine for the first women was 0.5 or 0.05 μg/kg/min, respectively, and subsequent infusion dosages were adjusted based on their efficacy in preventing spinal anesthesia-induced hypotension (defined as a systolic blood pressure less than 80% of the baseline level). The incremental or decremental doses of phenylephrine or norepinephrine were set at 0.1 or 0.01 μg/kg/min. The primary outcomes were the ED90s and efficacy ratio of phenylephrine and norepinephrine infusions for preventing spinal anesthesia-induced hypotension prior to delivery. Results: The results obtained from isotonic regression analysis revealed that the ED90 values of the phenylephrine and norepinephrine group for preventing spinal anesthesia-induced hypotension were 0.597 (95% CI: 0.582– 0.628) and 0.054 (95% CI: 0.053– 0.056) μg/kg/min, respectively, with an efficacy ratio of 11.1:1. The results of Probit regression analysis revealed that the ED90 values were determined to be 0.665 (95% CI: 0.576– 1.226) and 0.055 (95% CI: 0.047– 0.109) μg/kg/min, respectively, with an efficacy ratio of 12.1:1. Conclusion: The administration of 0.6 μg/kg/min phenylephrine and 0.05 μg/kg/min norepinephrine has been found to effectively manage a 90% incidence of spinal anesthesia-induced hypotension in women with preeclampsia.
{"title":"Determination of ED90s of Phenylephrine and Norepinephrine Infusion for Prevention of Spinal Anesthesia-Induced Hypotension in Patients with Preeclampsia During Cesarean Delivery","authors":"Haijie Tan, Yi Chen, Yan Jiang, Xiaojing Sun, Wei Ye, Xuefang Zhu, Xiangsheng Xiong","doi":"10.2147/dddt.s467072","DOIUrl":"https://doi.org/10.2147/dddt.s467072","url":null,"abstract":"<strong>Background:</strong> Vasopressors remain an important strategy for managing spinal anesthesia-induced hypotension in women with preeclampsia. The aim of this study was to investigate the ED90s and efficacy ratio of phenylephrine and norepinephrine in managing spinal anesthesia-induced hypotension in women with preeclampsia during cesarean delivery.<br/><strong>Methods:</strong> 60 women with preeclampsia, who underwent cesarean delivery, were randomly assigned to receive either a continuous intravenous infusion of phenylephrine or norepinephrine following spinal anesthesia. The initial dosage of phenylephrine or norepinephrine for the first women was 0.5 or 0.05 μg/kg/min, respectively, and subsequent infusion dosages were adjusted based on their efficacy in preventing spinal anesthesia-induced hypotension (defined as a systolic blood pressure less than 80% of the baseline level). The incremental or decremental doses of phenylephrine or norepinephrine were set at 0.1 or 0.01 μg/kg/min. The primary outcomes were the ED90s and efficacy ratio of phenylephrine and norepinephrine infusions for preventing spinal anesthesia-induced hypotension prior to delivery.<br/><strong>Results:</strong> The results obtained from isotonic regression analysis revealed that the ED90 values of the phenylephrine and norepinephrine group for preventing spinal anesthesia-induced hypotension were 0.597 (95% CI: 0.582– 0.628) and 0.054 (95% CI: 0.053– 0.056) μg/kg/min, respectively, with an efficacy ratio of 11.1:1. The results of Probit regression analysis revealed that the ED90 values were determined to be 0.665 (95% CI: 0.576– 1.226) and 0.055 (95% CI: 0.047– 0.109) μg/kg/min, respectively, with an efficacy ratio of 12.1:1.<br/><strong>Conclusion:</strong> The administration of 0.6 μg/kg/min phenylephrine and 0.05 μg/kg/min norepinephrine has been found to effectively manage a 90% incidence of spinal anesthesia-induced hypotension in women with preeclampsia.<br/><br/>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141547049","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}
Siqi Zhu, Yajun Cui, Weidong Zhang, Yu Ji, Lingshuang Li, Shenglei Luo, Jing Cui, Minqi Li
Purpose: Zoledronate (ZA) stands as a highly effective antiresorptive agent known to trigger medication-related osteonecrosis of the jaw (MRONJ). Its clinical dosages primarily encompass those used for oncologic and osteoporosis treatments. While inflammation is recognized as a potential disruptor of mucosal healing processes associated with ZA, prior research has overlooked the influence of varying ZA dosages on tissue adaptability. Therefore, a deeper understanding of the specific mechanisms by which inflammation exacerbates ZA-induced MRONJ, particularly when inflammation acts as a risk factor, remains crucial. Methods: Cell proliferation and migration of human oral keratinocytes (HOK) was analyzed after treatment with different doses of ZA and/or lipopolysaccharide (LPS) to assess their possible effect on mucosal healing of extraction wounds. Mouse periodontitis models were established using LPS, and histological changes in extraction wounds were observed after the administration of oncologic dose ZA. Hematoxylin and eosin (HE) staining and immunofluorescence were used to evaluate mucosal healing. Results: In vitro, LPS did not exacerbate the effects of osteoporosis therapeutic dose of ZA on the proliferation and migration of HOK cells, while aggravated these with the oncologic dose of ZA treatment by inducing mitochondrial dysfunction and oxidative stress via regulating SIRT1 expression. Furthermore, SIRT1 overexpression can alleviate this process. In vivo, local injection of LPS increased the nonunion of mucous membranes in MRONJ and decreased the expression of SIRT1, PGC-1α, and MnSOD. Conclusion: Inflammation aggravates oncologic dose of ZA-induced mitochondrial dysfunction and oxidative stress via a SIRT1-dependent pathway, enhancing the risk of impaired mucosal healing in MRONJ. Our study implies that inflammation becomes a critical risk factor for MRONJ development at higher ZA concentrations. Elucidating the mechanisms of inflammation as a risk factor for mucosal non-healing in MRONJ could inform the development of SIRT1-targeted therapies.
{"title":"Inflammation Can Be a High-Risk Factor for Mucosal Nonunion of MRONJ by Regulating SIRT1 Signaling When Treated with an Oncologic Dose of Zoledronate","authors":"Siqi Zhu, Yajun Cui, Weidong Zhang, Yu Ji, Lingshuang Li, Shenglei Luo, Jing Cui, Minqi Li","doi":"10.2147/dddt.s456811","DOIUrl":"https://doi.org/10.2147/dddt.s456811","url":null,"abstract":"<strong>Purpose:</strong> Zoledronate (ZA) stands as a highly effective antiresorptive agent known to trigger medication-related osteonecrosis of the jaw (MRONJ). Its clinical dosages primarily encompass those used for oncologic and osteoporosis treatments. While inflammation is recognized as a potential disruptor of mucosal healing processes associated with ZA, prior research has overlooked the influence of varying ZA dosages on tissue adaptability. Therefore, a deeper understanding of the specific mechanisms by which inflammation exacerbates ZA-induced MRONJ, particularly when inflammation acts as a risk factor, remains crucial.<br/><strong>Methods:</strong> Cell proliferation and migration of human oral keratinocytes (HOK) was analyzed after treatment with different doses of ZA and/or lipopolysaccharide (LPS) to assess their possible effect on mucosal healing of extraction wounds. Mouse periodontitis models were established using LPS, and histological changes in extraction wounds were observed after the administration of oncologic dose ZA. Hematoxylin and eosin (HE) staining and immunofluorescence were used to evaluate mucosal healing.<br/><strong>Results:</strong> In vitro, LPS did not exacerbate the effects of osteoporosis therapeutic dose of ZA on the proliferation and migration of HOK cells, while aggravated these with the oncologic dose of ZA treatment by inducing mitochondrial dysfunction and oxidative stress via regulating SIRT1 expression. Furthermore, SIRT1 overexpression can alleviate this process. In vivo, local injection of LPS increased the nonunion of mucous membranes in MRONJ and decreased the expression of SIRT1, PGC-1α, and MnSOD.<br/><strong>Conclusion:</strong> Inflammation aggravates oncologic dose of ZA-induced mitochondrial dysfunction and oxidative stress via a SIRT1-dependent pathway, enhancing the risk of impaired mucosal healing in MRONJ. Our study implies that inflammation becomes a critical risk factor for MRONJ development at higher ZA concentrations. Elucidating the mechanisms of inflammation as a risk factor for mucosal non-healing in MRONJ could inform the development of SIRT1-targeted therapies.<br/><br/><strong>Keywords:</strong> MRONJ, mucosal healing, inflammation, oxidative stress, mitochondrial dysfunction, SIRT1<br/>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141547050","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}
Xin Liu, Ruofan Xi, Xinran Du, Yi Wang, Linyan Cheng, Ge Yan, Hanzhi Lu, Te Liu, Fulun Li
Background: Psoriasis is a common chronic inflammatory skin condition. The emergence of psoriasis has been linked to dysbiosis of the microbiota on the skin surface and an imbalance in the immunological microenvironment. In this study, we investigated the therapeutic impact of topical thymopentin (TP5) on imiquimod (IMQ)-induced psoriasis in mice, as well as the modulatory influence of TP5 on the skin immune milieu and the skin surface microbiota. Methods: The IMQ-induced psoriasis-like lesion mouse model was used to identify the targets and molecular mechanisms of TP5. Immunofluorescence was employed to identify differences in T-cell subset expression before and after TP5 therapy. Changes in the expression of NF-κB signaling pathway components were assessed using Western blotting (WB). 16S rRNA sequencing and network pharmacology were used to detect changes in the skin flora before and after TP5 administration. Results: In vivo, TP5 reduced IMQ-induced back inflammation in mice. H&E staining revealed decreased epidermal thickness and inflammatory cell infiltration with TP5. Masson staining revealed decreased epidermal and dermal collagen infiltration after TP5 administration. Immunohistochemistry showed that TP5 treatment dramatically reduced IL-17 expression. Results of the immunoinfiltration analyses showed psoriatic lesions with more T-cell subsets. According to the immunofluorescence results, TP5 dramatically declined the proportions of CD4+, Th17, ROR+, and CD8+ T cells. WB revealed that TP5 reduced NF-κB pathway expression in skin tissues from IMQ-induced psoriasis model mice. 16S rRNA sequencing revealed a significant increase in Burkholderia and Pseudomonadaceae_Pseudomonas and a significant decrease in Staphylococcaceae_Staphylococcus, Aquabacterium, Herbaspirillum, and Balneimonas. Firmicutes dominated the skin microbial diversity after TP5 treatment, while Bacteroidetes, Verrucomicrobia, TM7, Proteobacteria, Actinobacteria, Acidobacteria, Gemmatimonadetes, and other species dominated in the IMQ group. Conclusion: TP5 may treat psoriasis by modulating the epidermal flora, reducing NF-κB pathway expression, and influencing T-cell subsets.
{"title":"Thymopentapeptide Affects T-Cell Subsets by Modulating the Flora of the Skin Surface to Alleviate Psoriasis","authors":"Xin Liu, Ruofan Xi, Xinran Du, Yi Wang, Linyan Cheng, Ge Yan, Hanzhi Lu, Te Liu, Fulun Li","doi":"10.2147/dddt.s448550","DOIUrl":"https://doi.org/10.2147/dddt.s448550","url":null,"abstract":"<strong>Background:</strong> Psoriasis is a common chronic inflammatory skin condition. The emergence of psoriasis has been linked to dysbiosis of the microbiota on the skin surface and an imbalance in the immunological microenvironment. In this study, we investigated the therapeutic impact of topical thymopentin (TP5) on imiquimod (IMQ)-induced psoriasis in mice, as well as the modulatory influence of TP5 on the skin immune milieu and the skin surface microbiota.<br/><strong>Methods:</strong> The IMQ-induced psoriasis-like lesion mouse model was used to identify the targets and molecular mechanisms of TP5. Immunofluorescence was employed to identify differences in T-cell subset expression before and after TP5 therapy. Changes in the expression of NF-κB signaling pathway components were assessed using Western blotting (WB). 16S rRNA sequencing and network pharmacology were used to detect changes in the skin flora before and after TP5 administration.<br/><strong>Results:</strong> In vivo, TP5 reduced IMQ-induced back inflammation in mice. H&E staining revealed decreased epidermal thickness and inflammatory cell infiltration with TP5. Masson staining revealed decreased epidermal and dermal collagen infiltration after TP5 administration. Immunohistochemistry showed that TP5 treatment dramatically reduced IL-17 expression. Results of the immunoinfiltration analyses showed psoriatic lesions with more T-cell subsets. According to the immunofluorescence results, TP5 dramatically declined the proportions of CD4<sup>+</sup>, Th17, ROR<sup>+</sup>, and CD8<sup>+</sup> T cells. WB revealed that TP5 reduced NF-κB pathway expression in skin tissues from IMQ-induced psoriasis model mice. 16S rRNA sequencing revealed a significant increase in <em>Burkholderia</em> and <em>Pseudomonadaceae_Pseudomonas</em> and a significant decrease in <em>Staphylococcaceae_Staphylococcus, Aquabacterium, Herbaspirillum,</em> and <em>Balneimonas</em>. <em>Firmicutes</em> dominated the skin microbial diversity after TP5 treatment, while <em>Bacteroidetes, Verrucomicrobia, TM7, Proteobacteria, Actinobacteria, Acidobacteria, Gemmatimonadetes,</em> and other species dominated in the IMQ group.<br/><strong>Conclusion:</strong> TP5 may treat psoriasis by modulating the epidermal flora, reducing NF-κB pathway expression, and influencing T-cell subsets.<br/><br/>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141547048","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}
Purpose: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line standard treatment for locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). The evidence also demonstrates improved synergistic effects of chemotherapy when combined with delayed administration of ICIs. In this study, we conducted a retrospective investigation into the treatment efficacy of taxol plus platinum (TP) chemotherapy combined with delayed administration of PD-1 inhibitors for ESCC patients. Patients and Methods: Clinical data of ESCC patients who received PD-1 inhibitors 3– 5 days after TP chemotherapy as first-line treatment was retrospectively reviewed between January 2019 and April 2023. Clinical outcomes and treatment safety were analyzed. The potential roles of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) were investigated. Results: A total of 34 locally advanced, recurrent or metastatic ESCC patients received PD-1 inhibitors 3– 5 days following TP chemotherapy were included. The objective response rate (ORR) and disease control rate (DCR) were 85.3% and 97.1% respectively. The median progression-free survival (PFS) and overall survival (OS) were 13.2 and 19.1 month respectively. Seven patients received radical surgery, 1 patient achieved pathologic complete response (pCR) and 3 patients achieved major pathologic response (MPR). Among the 27 patients without surgery, the median PFS and OS were 9.7 and 19.1 month respectively. A more favorable prognosis was correlated with NLR less than 3 at the 3rd and 4th cycle of immunochemotherapy. No significant correlations between other parameters (PLR, MLR and PIV) and prognosis were observed. A total of 22 patients developed grade 3– 4 toxicity events. Conclusion: The optimized sequence of PD-1 inhibitors administered 3– 5 days after TP chemotherapy as the first-line treatment of ESCC demonstrated favorable treatment efficacy. Pretreatment NLR of less than 3 at the 3rd and 4th cycle of immunochemotherapy is associated with a better prognosis.
{"title":"Clinical Efficacy of Taxol Plus Platinum (TP) Chemotherapy Combined with Delayed Administration of PD-1 Inhibitors in Patients with Locally Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma: A Retrospective Study","authors":"Lin Shen, Zixuan Chen, Zhi Zhang, Yunjiang Wu, Yue Ren, Ying Li, Yue Li, Xudong Yin, Fang Han, Yong Chen","doi":"10.2147/dddt.s455248","DOIUrl":"https://doi.org/10.2147/dddt.s455248","url":null,"abstract":"<strong>Purpose:</strong> Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line standard treatment for locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). The evidence also demonstrates improved synergistic effects of chemotherapy when combined with delayed administration of ICIs. In this study, we conducted a retrospective investigation into the treatment efficacy of taxol plus platinum (TP) chemotherapy combined with delayed administration of PD-1 inhibitors for ESCC patients.<br/><strong>Patients and Methods:</strong> Clinical data of ESCC patients who received PD-1 inhibitors 3– 5 days after TP chemotherapy as first-line treatment was retrospectively reviewed between January 2019 and April 2023. Clinical outcomes and treatment safety were analyzed. The potential roles of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) were investigated.<br/><strong>Results:</strong> A total of 34 locally advanced, recurrent or metastatic ESCC patients received PD-1 inhibitors 3– 5 days following TP chemotherapy were included. The objective response rate (ORR) and disease control rate (DCR) were 85.3% and 97.1% respectively. The median progression-free survival (PFS) and overall survival (OS) were 13.2 and 19.1 month respectively. Seven patients received radical surgery, 1 patient achieved pathologic complete response (pCR) and 3 patients achieved major pathologic response (MPR). Among the 27 patients without surgery, the median PFS and OS were 9.7 and 19.1 month respectively. A more favorable prognosis was correlated with NLR less than 3 at the 3rd and 4th cycle of immunochemotherapy. No significant correlations between other parameters (PLR, MLR and PIV) and prognosis were observed. A total of 22 patients developed grade 3– 4 toxicity events.<br/><strong>Conclusion:</strong> The optimized sequence of PD-1 inhibitors administered 3– 5 days after TP chemotherapy as the first-line treatment of ESCC demonstrated favorable treatment efficacy. Pretreatment NLR of less than 3 at the 3rd and 4th cycle of immunochemotherapy is associated with a better prognosis.<br/><br/><strong>Keywords:</strong> immune checkpoint inhibitors, chemotherapy, rational sequence, esophageal squamous cell carcinoma, peripheral blood parameters<br/>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141524375","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}
Retraction for the article 4-Amino-2-trifluoromethyl-phenyl retinate inhibits proliferation, invasion, and migration of breast cancer cells by independently regulating CRABP2 and FABP5
{"title":"4-Amino-2-Trifluoromethyl-Phenyl Retinate Inhibits Proliferation, Invasion, and Migration of Breast Cancer Cells by Independently Regulating CRABP2 and FABP5 [Retraction]","authors":"Jing Ju, Nan Wang, Jiali Wang, Fanrong Wu, Jinfang Ge, Feihu Chen","doi":"10.2147/dddt.s484570","DOIUrl":"https://doi.org/10.2147/dddt.s484570","url":null,"abstract":"Retraction for the article 4-Amino-2-trifluoromethyl-phenyl retinate inhibits proliferation, invasion, and migration of breast cancer cells by independently regulating CRABP2 and FABP5","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141524377","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}
Yuncheng Ni, Ranglang Huang, Shuang Yang, Xiao Yan Yang, Shan Zeng, An Yao, Jie Huang, Guoping Yang
Background: Oliceridine is a novel G protein‐biased ligand μ-opioid receptor agonist. This study aimed to assess the pharmacokinetics and safety profile of single-ascending doses of oliceridine fumarate injection in Chinese patients with chronic non-cancer pain. Methods: Conducted as a single-center, open-label trial, this study administered single doses of 0.75, 1.5, and 3.0 mg to 32 adult participants. The trial was conducted in two parts. First, we conducted a preliminary test comprising the administration of a single dose of 0.75mg to 2 participants. Then, we conducted the main trial involving intravenous administration of escalating doses of oliceridine fumarate (0.75 to 3 mg) to 30 participants. Pharmacokinetic (PK) parameters were derived using non-compartmental analysis. Additionally, the safety evaluation encompassed the monitoring of adverse events (AEs). Results: 32 participants were included in the PK and safety analyses. Following a 2-min intravenous infusion of oliceridine fumarate injection (0.75, 1.5, or 3 mg), Cmax and Tmax ranged from 51.293 to 81.914 ng/mL and 0.034 to 0.083 h, respectively. AUC0-t and half-life (t1/2) increased more than proportionally with dosage (1.85– 2.084 h). Treatment emergent adverse events (TEAEs) were found to be consistent with the commonly reported adverse effects of opioids, both post-administration and as documented in the original trials conducted in the United States. Critically, no serious adverse events were observed. Conclusion: Oliceridine demonstrated comparable PK parameters and a consistent PK profile in the Chinese population, in line with the PK results observed in the original trials conducted in the United States. Oliceridine was safe and well tolerated in Chinese patients with chronic non-cancer pain at doses ranging from 0.75 mg to 3.0 mg. Trial Registration: The trial is registered at chictr.org.cn (ChiCTR2100047180).
{"title":"Pharmacokinetics and Safety of Oliceridine Fumarate Injection in Chinese Patients with Chronic Non-Cancer Pain: A Phase I, Single-Ascending-Dose, Open-Label Clinical Trial","authors":"Yuncheng Ni, Ranglang Huang, Shuang Yang, Xiao Yan Yang, Shan Zeng, An Yao, Jie Huang, Guoping Yang","doi":"10.2147/dddt.s461416","DOIUrl":"https://doi.org/10.2147/dddt.s461416","url":null,"abstract":"<strong>Background:</strong> Oliceridine is a novel G protein‐biased ligand μ-opioid receptor agonist. This study aimed to assess the pharmacokinetics and safety profile of single-ascending doses of oliceridine fumarate injection in Chinese patients with chronic non-cancer pain.<br/><strong>Methods:</strong> Conducted as a single-center, open-label trial, this study administered single doses of 0.75, 1.5, and 3.0 mg to 32 adult participants. The trial was conducted in two parts. First, we conducted a preliminary test comprising the administration of a single dose of 0.75mg to 2 participants. Then, we conducted the main trial involving intravenous administration of escalating doses of oliceridine fumarate (0.75 to 3 mg) to 30 participants. Pharmacokinetic (PK) parameters were derived using non-compartmental analysis. Additionally, the safety evaluation encompassed the monitoring of adverse events (AEs).<br/><strong>Results:</strong> 32 participants were included in the PK and safety analyses. Following a 2-min intravenous infusion of oliceridine fumarate injection (0.75, 1.5, or 3 mg), Cmax and Tmax ranged from 51.293 to 81.914 ng/mL and 0.034 to 0.083 h, respectively. AUC<sub>0-t</sub> and half-life (t<sub>1/2</sub>) increased more than proportionally with dosage (1.85– 2.084 h). Treatment emergent adverse events (TEAEs) were found to be consistent with the commonly reported adverse effects of opioids, both post-administration and as documented in the original trials conducted in the United States. Critically, no serious adverse events were observed.<br/><strong>Conclusion:</strong> Oliceridine demonstrated comparable PK parameters and a consistent PK profile in the Chinese population, in line with the PK results observed in the original trials conducted in the United States. Oliceridine was safe and well tolerated in Chinese patients with chronic non-cancer pain at doses ranging from 0.75 mg to 3.0 mg.<br/><strong>Trial Registration:</strong> The trial is registered at chictr.org.cn (ChiCTR2100047180).<br/><br/>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141524376","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}
Qin Zhang, Rui Zhao, Yaqing Wu, Liming Zhang, Yi Feng
Purpose: Remimazolam is a novel short-acting benzodiazepine used for sedation and general anesthesia. This study aimed to evaluate the efficacy and safety of remimazolam besylate in elderly patients who underwent diagnostic gastrointestinal endoscopy. Patients and Methods: A total of 120 patients aged 60– 75 years were randomly allocated to one of two groups. Remifentanil 0.3μg/kg was used for analgesia. Patients were administered remimazolam besylate 7 mg (R group) or etomidate 0.1 mg/kg combined with 1% propofol 0.5 mg/kg (EP group) for induction, supplemental repeated doses were given as needed. Some time metrics, vital signs, adverse events were evaluated. Patients’ Mini-cog score and recovery questionnaires were compared. Results: Compared to the EP group, the induction time was slightly longer in the R group (1.50 VS 1.15 minutes) (P< 0.05), the time spent in the post-anesthesia care unit (PACU) was shorter (15.17 VS 17.40 minutes) (P< 0.05). Compare with EP group, SBP was lower in R group at T15 and T25 time point, but heart rate was higher in T2, T3, T5 (P< 0.05). The Mini-Cog score was higher after the procedure (2.83 VS 2.58) (P< 0.05). The incidence of respiratory adverse events was higher in the EP group than R group (18.3% VS 5.0%, P < 0.05). The most common adverse event in R group was hiccups. The sedation satisfaction rate and degree of amnesia were higher in the R group (66.7% VS 11.7%) (P < 0.05), and the effect on patient’s life within 24 hours was lower (12.0% VS 30.5%) (P < 0.05). Conclusion: The safety and efficacy of remimazolam besylate are not inferior to those of etomidate combined with propofol, rendering it a safe option for sedation during gastrointestinal endoscopy in ASA I-II elderly patients, but care should be taken to monitor the occurrence of hiccups.
目的：雷米唑仑是一种新型短效苯并二氮杂卓，用于镇静和全身麻醉：雷马唑仑是一种新型短效苯二氮卓类药物，用于镇静和全身麻醉。本研究旨在评估苯磺酸雷马唑仑对接受消化道内窥镜检查的老年患者的疗效和安全性：共有 120 名 60-75 岁的患者被随机分配到两组中的一组。使用瑞芬太尼 0.3μg/kg 进行镇痛。患者在诱导时使用苯磺酸瑞马唑仑 7 毫克（R 组）或依托咪酯 0.1 毫克/千克联合 1%丙泊酚 0.5 毫克/千克（EP 组），并根据需要补充重复剂量。对一些时间指标、生命体征和不良事件进行了评估。比较了患者的Mini-cog评分和恢复情况问卷：与 EP 组相比，R 组的诱导时间稍长（1.50 VS 1.15 分钟）（P< 0.05），在麻醉后护理病房（PACU）的时间较短（15.17 VS 17.40 分钟）（P< 0.05）。与 EP 组相比，R 组在 T15 和 T25 时间点的 SBP 更低，但在 T2、T3 和 T5 心率更高（P< 0.05）。术后 Mini-Cog 评分更高（2.83 VS 2.58）（P< 0.05）。EP 组呼吸系统不良事件的发生率高于 R 组（18.3% VS 5.0%，P< 0.05）。R 组最常见的不良反应是打嗝。R组的镇静满意率和失忆程度较高（66.7% VS 11.7%）（P <0.05），24小时内对患者生活的影响较低（12.0% VS 30.5%）（P <0.05）：结论：苯乙酸瑞马唑仑的安全性和有效性并不亚于依托咪酯联合异丙酚，是ASA I-II老年患者胃肠道内窥镜检查期间镇静的安全选择，但应注意监测打嗝的发生。
{"title":"Etomidate Combined with Propofol versus Remimazolam for Sedation in Elderly Patients During Gastrointestinal Endoscopy: A Randomized Prospective Clinical Trial","authors":"Qin Zhang, Rui Zhao, Yaqing Wu, Liming Zhang, Yi Feng","doi":"10.2147/dddt.s454314","DOIUrl":"https://doi.org/10.2147/dddt.s454314","url":null,"abstract":"<strong>Purpose:</strong> Remimazolam is a novel short-acting benzodiazepine used for sedation and general anesthesia. This study aimed to evaluate the efficacy and safety of remimazolam besylate in elderly patients who underwent diagnostic gastrointestinal endoscopy.<br/><strong>Patients and Methods:</strong> A total of 120 patients aged 60– 75 years were randomly allocated to one of two groups. Remifentanil 0.3μg/kg was used for analgesia. Patients were administered remimazolam besylate 7 mg (R group) or etomidate 0.1 mg/kg combined with 1% propofol 0.5 mg/kg (EP group) for induction, supplemental repeated doses were given as needed. Some time metrics, vital signs, adverse events were evaluated. Patients’ Mini-cog score and recovery questionnaires were compared.<br/><strong>Results:</strong> Compared to the EP group, the induction time was slightly longer in the R group (1.50 VS 1.15 minutes) (P< 0.05), the time spent in the post-anesthesia care unit (PACU) was shorter (15.17 VS 17.40 minutes) (P< 0.05). Compare with EP group, SBP was lower in R group at T15 and T25 time point, but heart rate was higher in T2, T3, T5 (P< 0.05). The Mini-Cog score was higher after the procedure (2.83 VS 2.58) (P< 0.05). The incidence of respiratory adverse events was higher in the EP group than R group (18.3% VS 5.0%, P < 0.05). The most common adverse event in R group was hiccups. The sedation satisfaction rate and degree of amnesia were higher in the R group (66.7% VS 11.7%) (P < 0.05), and the effect on patient’s life within 24 hours was lower (12.0% VS 30.5%) (P < 0.05).<br/><strong>Conclusion:</strong> The safety and efficacy of remimazolam besylate are not inferior to those of etomidate combined with propofol, rendering it a safe option for sedation during gastrointestinal endoscopy in ASA I-II elderly patients, but care should be taken to monitor the occurrence of hiccups.<br/><br/><strong>Keywords:</strong> gastrointestinal endoscopy, anesthesia, remimazolam besylate, etomidate, propofol<br/>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141524379","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}
Abstract: Hepatic fibrosis (HF) is a pathological process of structural and functional impairment of the liver and is a key component in the progression of chronic liver disease. There are no specific anti-hepatic fibrosis (anti-HF) drugs, and HF can only be improved or prevented by alleviating the cause. Autophagy of hepatic stellate cells (HSCs) is closely related to the development of HF. In recent years, traditional Chinese medicine (TCM) has achieved good therapeutic effects in the prevention and treatment of HF. Several active ingredients from TCM (AITCM) can regulate autophagy in HSCs to exert anti-HF effects through different pathways, but relevant reviews are lacking. This paper reviewed the research progress of AITCM regulating HSCs autophagy against HF, and also discussed the relationship between HSCs autophagy and HF, pointing out the problems and limitations of the current study, in order to provide references for the development of anti-HF drugs targeting HSCs autophagy in TCM. By reviewing the literature in PubMed, Web of Science, Embase, CNKI and other databases, we found that the relationship between autophagy of HSCs and HF is currently controversial. HSCs autophagy may promote HF by consuming lipid droplets (LDs) to provide energy for their activation. However, in contrast, inducing autophagy in HSCs can exert the anti-HF effect by stimulating their apoptosis or senescence, reducing type I collagen accumulation, inhibiting the extracellular vesicles release, degrading pro-fibrotic factors and other mechanisms. Some AITCM inhibit HSCs autophagy to resist HF, with the most promising direction being to target LDs. While, others induce HSCs autophagy to resist HF, with the most promising direction being to target HSCs apoptosis. Future research needs to focus on cell targeting research, autophagy targeting research and in vivo verification research, and to explore the reasons for the contradictory effects of HSCs autophagy on HF.
Keywords: hepatic fibrosis, HSCs autophagy, active ingredients of traditional Chinese medicine, HSCs activation
摘要：肝纤维化（HF）是肝脏结构和功能受损的病理过程，是慢性肝病进展的关键组成部分。目前还没有特效的抗肝纤维化（anti-HF）药物，只能通过缓解病因来改善或预防肝纤维化。肝星状细胞（HSCs）的自噬与肝纤维化的发生发展密切相关。近年来，中药在预防和治疗 HF 方面取得了良好的疗效。中药中的多种有效成分可通过不同途径调节造血干细胞的自噬作用，从而发挥抗高血脂的作用，但目前尚缺乏相关综述。本文综述了AITCM调控造血干细胞自噬抗HF的研究进展，并探讨了造血干细胞自噬与HF的关系，指出了目前研究中存在的问题和局限性，以期为开发以造血干细胞自噬为靶点的中药抗HF药物提供参考。通过查阅PubMed、Web of Science、Embase、CNKI等数据库中的文献，我们发现造血干细胞自噬与高血脂的关系目前尚存在争议。造血干细胞自噬可能通过消耗脂滴为其活化提供能量，从而促进高血脂。相反，诱导造血干细胞自噬可通过刺激造血干细胞凋亡或衰老、减少 I 型胶原积累、抑制细胞外囊泡释放、降解促纤维化因子等机制发挥抗 HF 作用。一些 AITCM 可抑制造血干细胞自噬以抵抗高纤维化，其中最有希望的方向是靶向低密度脂蛋白。而另一些药物则能诱导造血干细胞自噬以抵抗高纤维化，其中最有希望的方向是针对造血干细胞凋亡。关键词：肝纤维化；造血干细胞自噬；中药有效成分；造血干细胞活化
{"title":"Advances in Research on the Effectiveness and Mechanism of Active Ingredients from Traditional Chinese Medicine in Regulating Hepatic Stellate Cells Autophagy Against Hepatic Fibrosis","authors":"Xin-Yu Liu, Wei Zhang, Bao-Feng Ma, Mi-Mi Sun, Qing-Hua Shang","doi":"10.2147/dddt.s467480","DOIUrl":"https://doi.org/10.2147/dddt.s467480","url":null,"abstract":"<strong>Abstract:</strong> Hepatic fibrosis (HF) is a pathological process of structural and functional impairment of the liver and is a key component in the progression of chronic liver disease. There are no specific anti-hepatic fibrosis (anti-HF) drugs, and HF can only be improved or prevented by alleviating the cause. Autophagy of hepatic stellate cells (HSCs) is closely related to the development of HF. In recent years, traditional Chinese medicine (TCM) has achieved good therapeutic effects in the prevention and treatment of HF. Several active ingredients from TCM (AITCM) can regulate autophagy in HSCs to exert anti-HF effects through different pathways, but relevant reviews are lacking. This paper reviewed the research progress of AITCM regulating HSCs autophagy against HF, and also discussed the relationship between HSCs autophagy and HF, pointing out the problems and limitations of the current study, in order to provide references for the development of anti-HF drugs targeting HSCs autophagy in TCM. By reviewing the literature in PubMed, Web of Science, Embase, CNKI and other databases, we found that the relationship between autophagy of HSCs and HF is currently controversial. HSCs autophagy may promote HF by consuming lipid droplets (LDs) to provide energy for their activation. However, in contrast, inducing autophagy in HSCs can exert the anti-HF effect by stimulating their apoptosis or senescence, reducing type I collagen accumulation, inhibiting the extracellular vesicles release, degrading pro-fibrotic factors and other mechanisms. Some AITCM inhibit HSCs autophagy to resist HF, with the most promising direction being to target LDs. While, others induce HSCs autophagy to resist HF, with the most promising direction being to target HSCs apoptosis. Future research needs to focus on cell targeting research, autophagy targeting research and in vivo verification research, and to explore the reasons for the contradictory effects of HSCs autophagy on HF.<br/><br/><strong>Keywords:</strong> hepatic fibrosis, HSCs autophagy, active ingredients of traditional Chinese medicine, HSCs activation<br/>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141531940","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}
Zhiliang Li, Jiali Yang, Yang Sun, Shuo Han, Jietao Gong, Yi Zhang, Zhiyuan Feng, Hong Yao, Peiying Shi
Purpose: Bee pollen possesses favorable anticancer activities. As a medicinal plant source, Schisandra chinensis bee pollen (SCBP) possesses potential pharmacological properties, such as reducing cisplatin-induced liver injury, but its anti–liver cancer effect is still rarely reported. This paper aims to investigate the effect and mechanism of SCBP extract (SCBPE) on hepatocellular carcinoma HepG2 cells. Methods: The effect of SCBPE on cell proliferation and migration of HepG2 cells was evaluated based on MTT assay, morphology observation, or scratching assay. Furthermore, tandem mass tag-based quantitative proteomics was used to study the effect mechanisms. The mRNA expression levels of identified proteins were verified by RT-qPCR. Results: Tandem mass tag-based quantitative proteomics showed that 61 differentially expressed proteins were obtained in the SCBPE group compared with the negative-control group: 18 significantly downregulated and 43 significantly upregulated proteins. Bioinformatic analysis showed the significantly enriched KEGG pathways were predominantly ferroptosis-, Wnt-, and hepatocellular carcinoma-signaling ones. Protein–protein interaction network analysis and RT-qPCR validation revealed SCBPE also downregulated the focal adhesion–signaling pathway, which is abrogated by PF-562271, a well-known inhibitor of FAK. Conclusion: This study confirmed SCBPE suppressed the cell proliferation and migration of hepatocellular carcinoma HepG2 cells, mainly through modulation of ferroptosis-, Wnt-, hepatocellular carcinoma-, and focal adhesion–signaling pathways, providing scientific data supporting adjuvant treatment of hepatocellular carcinoma using SCBP.
{"title":"Schisandra chinensis Bee Pollen Extract Inhibits Proliferation and Migration of Hepatocellular Carcinoma HepG2 Cells via Ferroptosis-, Wnt-, and Focal Adhesion–Signaling Pathways","authors":"Zhiliang Li, Jiali Yang, Yang Sun, Shuo Han, Jietao Gong, Yi Zhang, Zhiyuan Feng, Hong Yao, Peiying Shi","doi":"10.2147/dddt.s461581","DOIUrl":"https://doi.org/10.2147/dddt.s461581","url":null,"abstract":"<strong>Purpose:</strong> Bee pollen possesses favorable anticancer activities. As a medicinal plant source, <em>Schisandra chinensis</em> bee pollen (SCBP) possesses potential pharmacological properties, such as reducing cisplatin-induced liver injury, but its anti–liver cancer effect is still rarely reported. This paper aims to investigate the effect and mechanism of SCBP extract (SCBPE) on hepatocellular carcinoma HepG2 cells.<br/><strong>Methods:</strong> The effect of SCBPE on cell proliferation and migration of HepG2 cells was evaluated based on MTT assay, morphology observation, or scratching assay. Furthermore, tandem mass tag-based quantitative proteomics was used to study the effect mechanisms. The mRNA expression levels of identified proteins were verified by RT-qPCR.<br/><strong>Results:</strong> Tandem mass tag-based quantitative proteomics showed that 61 differentially expressed proteins were obtained in the SCBPE group compared with the negative-control group: 18 significantly downregulated and 43 significantly upregulated proteins. Bioinformatic analysis showed the significantly enriched KEGG pathways were predominantly ferroptosis-, Wnt-, and hepatocellular carcinoma-signaling ones. Protein–protein interaction network analysis and RT-qPCR validation revealed SCBPE also downregulated the focal adhesion–signaling pathway, which is abrogated by PF-562271, a well-known inhibitor of FAK.<br/><strong>Conclusion:</strong> This study confirmed SCBPE suppressed the cell proliferation and migration of hepatocellular carcinoma HepG2 cells, mainly through modulation of ferroptosis-, Wnt-, hepatocellular carcinoma-, and focal adhesion–signaling pathways, providing scientific data supporting adjuvant treatment of hepatocellular carcinoma using SCBP. <br/><br/><strong>Keywords:</strong> <em>Schisandra chinensis</em> bee pollen extract, HepG2 cells, proteomics, ferroptosis, Wnt-signaling pathway, focal adhesion–signaling pathway<br/>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141505479","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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