Pub Date : 2024-08-06eCollection Date: 2024-01-01DOI: 10.1515/biol-2022-0928
Xuan Zhang, Fang Li, Botao Yang, Wei Zhang, Yingchun Wang
The incidence rate of gestational diabetes mellitus (GDM) remains high among pregnant women in the second trimester of pregnancy. However, the main clinical approach to alleviate the symptoms of GDM is to control the diet. Our study explored the therapeutic effects of omega-3 fatty acids (ω-3 FAs) on GDM at the cellular and animal levels. We found that ω-3 FAs can promote the transformation of M0 macrophages into anti-inflammatory M2 macrophages. The transformed M2 macrophages promoted β-oxidation and reduced hepatocyte lipid synthesis (P < 0.05), thereby promoting hepatic function and preventing the excessive accumulation of lipid droplets in the hepatocyte cell line HepG2. Supplementation of ω-3 FAs in pregnant GDM mice significantly reduced fasting blood glucose levels, glucose tolerance test, and insulin tolerance test indices, and lipid accumulation in the liver and effectively prevented the occurrence of liver fibrosis (P < 0.05). These therapeutic effects may be mediated through the anti-inflammatory effects of ω-3 FAs (P < 0.05). ω-3 FAs also had positive effects on the offspring of pregnant GDM mice, as demonstrated by reduced birth mortality and improved glycemic stabilization (P < 0.05). In conclusion, this study provides a possible translational medicine strategy for the treatment of GDM.
{"title":"Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism.","authors":"Xuan Zhang, Fang Li, Botao Yang, Wei Zhang, Yingchun Wang","doi":"10.1515/biol-2022-0928","DOIUrl":"10.1515/biol-2022-0928","url":null,"abstract":"<p><p>The incidence rate of gestational diabetes mellitus (GDM) remains high among pregnant women in the second trimester of pregnancy. However, the main clinical approach to alleviate the symptoms of GDM is to control the diet. Our study explored the therapeutic effects of omega-3 fatty acids (ω-3 FAs) on GDM at the cellular and animal levels. We found that ω-3 FAs can promote the transformation of M0 macrophages into anti-inflammatory M2 macrophages. The transformed M2 macrophages promoted β-oxidation and reduced hepatocyte lipid synthesis (<i>P</i> < 0.05), thereby promoting hepatic function and preventing the excessive accumulation of lipid droplets in the hepatocyte cell line HepG2. Supplementation of ω-3 FAs in pregnant GDM mice significantly reduced fasting blood glucose levels, glucose tolerance test, and insulin tolerance test indices, and lipid accumulation in the liver and effectively prevented the occurrence of liver fibrosis (<i>P</i> < 0.05). These therapeutic effects may be mediated through the anti-inflammatory effects of ω-3 FAs (<i>P</i> < 0.05). ω-3 FAs also had positive effects on the offspring of pregnant GDM mice, as demonstrated by reduced birth mortality and improved glycemic stabilization (<i>P</i> < 0.05). In conclusion, this study provides a possible translational medicine strategy for the treatment of GDM.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06eCollection Date: 2024-01-01DOI: 10.1515/biol-2022-0936
Weilin Shao, Yan Feng, Jin Huang, Tingyu Li, Shengguai Gao, Yihao Yang, Dongqi Li, Zuozhang Yang, Zhihong Yao
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, and is characterized by high heterogeneity, high malignancy, easy metastasis, and poor prognosis. Recurrence, metastasis, and multidrug resistance are the main problems that limit the therapeutic effect and prognosis of OS. PI3K/AKT/mTOR signaling pathway is often abnormally activated in OS tissues and cells, which promotes the rapid development, metastasis, and drug sensitivity of OS. Emerging evidence has revealed new insights into tumorigenesis through the interaction between the PI3K/AKT/mTOR pathway and non-coding RNAs (ncRNAs). Therefore, we reviewed the interactions between the PI3K/AKT/mTOR pathway and ncRNAs and their implication in OS. These interactions have the potential to serve as cancer biomarkers and therapeutic targets in clinical applications.
骨肉瘤(Osteosarcoma,OS)是儿童和青少年最常见的原发性恶性骨肿瘤,具有异质性高、恶性程度高、易转移、预后差等特点。复发、转移和多药耐药是制约OS治疗效果和预后的主要问题。PI3K/AKT/mTOR信号通路通常在OS组织和细胞中异常激活,从而促进了OS的快速发展、转移和药物敏感性。新的证据显示,通过 PI3K/AKT/mTOR 通路与非编码 RNA(ncRNA)之间的相互作用,人们对肿瘤发生有了新的认识。因此,我们回顾了 PI3K/AKT/mTOR 通路与 ncRNA 之间的相互作用及其在 OS 中的影响。这些相互作用有可能成为癌症生物标志物和临床应用中的治疗靶点。
{"title":"Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma.","authors":"Weilin Shao, Yan Feng, Jin Huang, Tingyu Li, Shengguai Gao, Yihao Yang, Dongqi Li, Zuozhang Yang, Zhihong Yao","doi":"10.1515/biol-2022-0936","DOIUrl":"10.1515/biol-2022-0936","url":null,"abstract":"<p><p>Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, and is characterized by high heterogeneity, high malignancy, easy metastasis, and poor prognosis. Recurrence, metastasis, and multidrug resistance are the main problems that limit the therapeutic effect and prognosis of OS. PI3K/AKT/mTOR signaling pathway is often abnormally activated in OS tissues and cells, which promotes the rapid development, metastasis, and drug sensitivity of OS. Emerging evidence has revealed new insights into tumorigenesis through the interaction between the PI3K/AKT/mTOR pathway and non-coding RNAs (ncRNAs). Therefore, we reviewed the interactions between the PI3K/AKT/mTOR pathway and ncRNAs and their implication in OS. These interactions have the potential to serve as cancer biomarkers and therapeutic targets in clinical applications.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06eCollection Date: 2024-01-01DOI: 10.1515/biol-2022-0902
Kaixiao Li, Mingzhu Chen, Jingyi Shi, Tian Mao
The widespread utilization of traditional chemical pesticides has given rise to numerous negative impacts, leading to a surge in interest in exploring environmentally friendly alternatives. Bacillus thuringiensis (Bt), a bacterium renowned for its insecticidal properties, produces Cry proteins during its lifecycle. These proteins have distinct advantages over traditional chemical pesticides, including higher environmental safety, broader insecticidal spectra, and lower pesticide residues. Consequently, the discovery and application of Bt hold immense significance in plant disease and pest management, as well as in plant protection. Currently, Bt preparations occupy a prominent position as the world's largest and most widely used biopesticides. This article comprehensively reviews the fundamental aspects, insecticidal mechanisms, practical applications, and fermentation technologies related to Bt.
{"title":"An overview of the production and use of <i>Bacillus thuringiensis</i> toxin.","authors":"Kaixiao Li, Mingzhu Chen, Jingyi Shi, Tian Mao","doi":"10.1515/biol-2022-0902","DOIUrl":"10.1515/biol-2022-0902","url":null,"abstract":"<p><p>The widespread utilization of traditional chemical pesticides has given rise to numerous negative impacts, leading to a surge in interest in exploring environmentally friendly alternatives. <i>Bacillus thuringiensis</i> (Bt), a bacterium renowned for its insecticidal properties, produces <i>Cry</i> proteins during its lifecycle. These proteins have distinct advantages over traditional chemical pesticides, including higher environmental safety, broader insecticidal spectra, and lower pesticide residues. Consequently, the discovery and application of Bt hold immense significance in plant disease and pest management, as well as in plant protection. Currently, Bt preparations occupy a prominent position as the world's largest and most widely used biopesticides. This article comprehensively reviews the fundamental aspects, insecticidal mechanisms, practical applications, and fermentation technologies related to Bt.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06eCollection Date: 2024-01-01DOI: 10.1515/biol-2022-0934
Sisi Hu, Jichun Liu, Haixia Tang, Xiangrong Xie, Youquan Wei
Hypertension is commonly classified into essential hypertension and secondary hypertension, although definitive classification can be challenging in some cases. Here, we discussed a patient who admitted for refractory hypertension, exhibiting various clinical manifestations including inadequate estrogen secretion, underdeveloped secondary sexual characteristics, primary amenorrhea, short stature, multiple moles, and somatic abnormalities. The patient was finally diagnosed with Turner syndrome (TS) based on clinical findings and chromosomal analysis. The genetic karyotype identified was 46,X,i(X)(q10).
{"title":"Refractory hypertension complicated with Turner syndrome: A case report.","authors":"Sisi Hu, Jichun Liu, Haixia Tang, Xiangrong Xie, Youquan Wei","doi":"10.1515/biol-2022-0934","DOIUrl":"10.1515/biol-2022-0934","url":null,"abstract":"<p><p>Hypertension is commonly classified into essential hypertension and secondary hypertension, although definitive classification can be challenging in some cases. Here, we discussed a patient who admitted for refractory hypertension, exhibiting various clinical manifestations including inadequate estrogen secretion, underdeveloped secondary sexual characteristics, primary amenorrhea, short stature, multiple moles, and somatic abnormalities. The patient was finally diagnosed with Turner syndrome (TS) based on clinical findings and chromosomal analysis. The genetic karyotype identified was 46,X,i(X)(q10).</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pia Rude Nielsen, Lone Schejbel, Pär Lars Josefsson, Lone Skov, Signe Ledou Nielsen
Mycosis fungoides is the most frequent subtype of primary cutaneous T-cell lymphomas. The diagnosis is based on a thorough clinic-pathologic correlation, which can, especially in early-stage disease, be challenging due to similarities with several benign skin disorders such as psoriasis and atopic dermatitis. Here, we present a case of an 81-year-old man with a 20-year-long medical history of skin problems treated as psoriasis with limited effect. Since December 2021, the patient experienced worsening of his skin symptoms with rapidly growing tumors and widespread patches and plaques. Positron emission tomography/computed tomography evaluation revealed markedly metabolic activity related to the skin tumors and increased FDG uptake in several retroperitoneal lymph nodes. Histological assessment of skin biopsies demonstrated a highly proliferative T-cell lymphoma with a γ/δ+ and CD8+ cytotoxic phenotype. The morphology of the tumor cells appeared blastic with an abnormal immunephenotype CD3+, CD2−, CD5dim, CD4−, CD8+, CD56−, and CD30−. Next-generation sequencing detected a likely pathogenic SOCS1 mutation with an allele frequency of 72% as well as a STAT3 variant of unknown significance. This case highlights the diagnostic complexity of an indolent skin lymphoma evolving into an aggressive cytotoxic lymphoma.
{"title":"Atypical presentation of γ/δ mycosis fungoides with an unusual phenotype and SOCS1 mutation","authors":"Pia Rude Nielsen, Lone Schejbel, Pär Lars Josefsson, Lone Skov, Signe Ledou Nielsen","doi":"10.1515/biol-2022-0925","DOIUrl":"https://doi.org/10.1515/biol-2022-0925","url":null,"abstract":"Mycosis fungoides is the most frequent subtype of primary cutaneous T-cell lymphomas. The diagnosis is based on a thorough clinic-pathologic correlation, which can, especially in early-stage disease, be challenging due to similarities with several benign skin disorders such as psoriasis and atopic dermatitis. Here, we present a case of an 81-year-old man with a 20-year-long medical history of skin problems treated as psoriasis with limited effect. Since December 2021, the patient experienced worsening of his skin symptoms with rapidly growing tumors and widespread patches and plaques. Positron emission tomography/computed tomography evaluation revealed markedly metabolic activity related to the skin tumors and increased FDG uptake in several retroperitoneal lymph nodes. Histological assessment of skin biopsies demonstrated a highly proliferative T-cell lymphoma with a γ/δ+ and CD8+ cytotoxic phenotype. The morphology of the tumor cells appeared blastic with an abnormal immunephenotype CD3+, CD2−, CD5<jats:sub>dim</jats:sub>, CD4−, CD8+, CD56−, and CD30−. Next-generation sequencing detected a likely pathogenic <jats:italic>SOCS1</jats:italic> mutation with an allele frequency of 72% as well as a <jats:italic>STAT3</jats:italic> variant of unknown significance. This case highlights the diagnostic complexity of an indolent skin lymphoma evolving into an aggressive cytotoxic lymphoma.","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141871534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuning Kang, Ting Zhao, Yuzhu Song, Jinyang Zhang, Tao Yuan, Qinqin Han
New drugs for the treatment of bacterial vaginosis (BV) are yet to be developed due to concerns that they may contribute to the increase in antibiotic resistance in BV. Antimicrobial peptides (AMPs) are one of the most promising options for next-generation antibiotics. In this study, we investigated the bacteriostatic activity of the AMPs Pexiganan, plectasin, melittin, and cathelicidin-DM against Gram-negative and Gram-positive bacteria both in vitro and in a mouse model of BV infection. The results showed that Pexiganan, melittin, and cathelicidin-DM had significant antibacterial activity against both Gram-negative and Gram-positive bacteria. AMPs have great potential for clinical application in the treatment of vaginitis, and this study provides an experimental basis for their use in the active immunoprophylaxis of BV.
{"title":"Evaluation of the activity of antimicrobial peptides against bacterial vaginosis","authors":"Xuning Kang, Ting Zhao, Yuzhu Song, Jinyang Zhang, Tao Yuan, Qinqin Han","doi":"10.1515/biol-2022-0927","DOIUrl":"https://doi.org/10.1515/biol-2022-0927","url":null,"abstract":"New drugs for the treatment of bacterial vaginosis (BV) are yet to be developed due to concerns that they may contribute to the increase in antibiotic resistance in BV. Antimicrobial peptides (AMPs) are one of the most promising options for next-generation antibiotics. In this study, we investigated the bacteriostatic activity of the AMPs Pexiganan, plectasin, melittin, and cathelicidin-DM against Gram-negative and Gram-positive bacteria both <jats:italic>in vitro</jats:italic> and in a mouse model of BV infection. The results showed that Pexiganan, melittin, and cathelicidin-DM had significant antibacterial activity against both Gram-negative and Gram-positive bacteria. AMPs have great potential for clinical application in the treatment of vaginitis, and this study provides an experimental basis for their use in the active immunoprophylaxis of BV.","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141871537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tingting Wei, Jiajie Cheng, Yonggan Ji, Xue Cao, Shuqin Ding, Quanxia Liu, Zhisheng Wang
Hepatocellular carcinoma (HCC) is a highly vascularized carcinoma, and targeting its neovascularization represents an effective therapeutic approach. Our previous study demonstrated that the baculovirus-mediated endostatin and angiostatin fusion protein (BDS-hEA) effectively inhibits the angiogenesis of vascular endothelial cells and the growth of HCC tumors. However, the mechanism underlying its anti-angiogenic effect remains unclear. Increasing evidence suggests that autophagy has a significant impact on the function of vascular endothelial cells and response to cancer therapy. Hence, the objective of this research was to investigate the correlation between BDS-hEA-induced angiogenesis inhibition and autophagy, along with potential regulatory mechanisms. Our results demonstrated that BDS-hEA induced autophagy in EA.hy926 cells, as evidenced by the increasing number of autophagosomes and reactive oxygen species, accompanied by an upregulation of Beclin-1, LC3-II/LC3-I, and p62 protein expression. Suppression of autophagy using 3-methyladenine attenuated the functions of BDS-hEA-induced EA.hy926 cells, including the viability, proliferation, invasion, migration, and angiogenesis. Moreover, BDS-hEA induced autophagy by downregulating the expression of CD31, VEGF, and VEGFR2, as well as phosphorylated protein kinase B (p-AKT) and phosphorylated mammalian target of rapamycin (p-mTOR), while concurrently upregulating phosphorylated AMP-activated protein kinase (p-AMPK). The in vivo results further indicated that inhibition of autophagy by chloroquine significantly impeded the ability of BDS-hEA to suppress HCC tumor growth in mice. Mechanistically, BDS-hEA prominently facilitated autophagic apoptosis in tumor tissues and decreased the levels of ki67, CD31, VEGF, MMP-9, p-AKT, and p-mTOR while simultaneously enhancing the p-AMPK expression. In conclusion, our findings suggest that BDS-hEA induces autophagy as a cytotoxic response by modulating the AMPK/AKT/mTOR signaling pathway, thereby exerting anti-angiogenic effects against HCC.
{"title":"Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma","authors":"Tingting Wei, Jiajie Cheng, Yonggan Ji, Xue Cao, Shuqin Ding, Quanxia Liu, Zhisheng Wang","doi":"10.1515/biol-2022-0914","DOIUrl":"https://doi.org/10.1515/biol-2022-0914","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a highly vascularized carcinoma, and targeting its neovascularization represents an effective therapeutic approach. Our previous study demonstrated that the baculovirus-mediated endostatin and angiostatin fusion protein (BDS-hEA) effectively inhibits the angiogenesis of vascular endothelial cells and the growth of HCC tumors. However, the mechanism underlying its anti-angiogenic effect remains unclear. Increasing evidence suggests that autophagy has a significant impact on the function of vascular endothelial cells and response to cancer therapy. Hence, the objective of this research was to investigate the correlation between BDS-hEA-induced angiogenesis inhibition and autophagy, along with potential regulatory mechanisms. Our results demonstrated that BDS-hEA induced autophagy in EA.hy926 cells, as evidenced by the increasing number of autophagosomes and reactive oxygen species, accompanied by an upregulation of Beclin-1, LC3-II/LC3-I, and p62 protein expression. Suppression of autophagy using 3-methyladenine attenuated the functions of BDS-hEA-induced EA.hy926 cells, including the viability, proliferation, invasion, migration, and angiogenesis. Moreover, BDS-hEA induced autophagy by downregulating the expression of CD31, VEGF, and VEGFR2, as well as phosphorylated protein kinase B (p-AKT) and phosphorylated mammalian target of rapamycin (p-mTOR), while concurrently upregulating phosphorylated AMP-activated protein kinase (p-AMPK). The <jats:italic>in vivo</jats:italic> results further indicated that inhibition of autophagy by chloroquine significantly impeded the ability of BDS-hEA to suppress HCC tumor growth in mice. Mechanistically, BDS-hEA prominently facilitated autophagic apoptosis in tumor tissues and decreased the levels of ki67, CD31, VEGF, MMP-9, p-AKT, and p-mTOR while simultaneously enhancing the p-AMPK expression. In conclusion, our findings suggest that BDS-hEA induces autophagy as a cytotoxic response by modulating the AMPK/AKT/mTOR signaling pathway, thereby exerting anti-angiogenic effects against HCC.","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141871536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Osteoarthritis (OA) is a chronic degenerative disease characterized by overall joint tissue damage. Metformin (Met) has been shown to inhibit inflammatory reactions, though its potential protective mechanism on cartilage remains unclear. This study investigated Met’s potential to protect cartilage in an OA rat model. Various morphological experiments were conducted to assess changes in cartilage tissue morphology before and after Met treatment. Protein and mRNA levels of cartilage-specific genes were measured using western blot, immunohistochemical staining, and RT-qPCR. Additionally, protein levels of autophagy-related and mTOR pathway-related proteins were measured. The results indicate an imbalance in the synthesis and degradation metabolism of chondrocytes, downregulation of cellular autophagy, and activation of the PI3K/Akt/mTOR pathway after surgery. However, treatment with Met could upregulate the expression of synthetic metabolic factors, indicating its contribution to cartilage repair. Furthermore, analysis of autophagy and pathway protein levels indicated that Met effectively attenuated autophagic damage to osteoarthritic cartilage cells and abnormal activation of the PI3K/Akt/mTOR pathway. In conclusion, Met can inhibit the abnormal activation of the PI3K/AKT/mTOR signaling pathway in cartilage tissue, promote the restoration of cartilage cell autophagic function, improve the balance of cartilage cell synthesis and degradation metabolism, and thus exert a protective effect on rat joint cartilage.
骨关节炎(OA)是一种慢性退行性疾病,其特点是关节组织整体受损。二甲双胍(Met)已被证明能抑制炎症反应,但其对软骨的潜在保护机制仍不清楚。本研究调查了二甲双胍在 OA 大鼠模型中保护软骨的潜力。研究人员进行了各种形态学实验,以评估 Met 治疗前后软骨组织形态的变化。使用 Western 印迹、免疫组化染色和 RT-qPCR 测量了软骨特异性基因的蛋白质和 mRNA 水平。此外,还测定了自噬相关蛋白和 mTOR 通路相关蛋白的水平。结果表明,手术后软骨细胞的合成和降解代谢失衡,细胞自噬功能下调,PI3K/Akt/mTOR 通路被激活。然而,用 Met 治疗可上调合成代谢因子的表达,表明它有助于软骨修复。此外,对自噬和通路蛋白水平的分析表明,Met能有效减轻骨关节炎软骨细胞的自噬损伤和PI3K/Akt/mTOR通路的异常激活。综上所述,Met能抑制软骨组织中PI3K/AKT/mTOR信号通路的异常激活,促进软骨细胞自噬功能的恢复,改善软骨细胞合成和降解代谢的平衡,从而对大鼠关节软骨起到保护作用。
{"title":"Metformin mitigates osteoarthritis progression by modulating the PI3K/AKT/mTOR signaling pathway and enhancing chondrocyte autophagy","authors":"Tianjie Xu, Kainan Liu, Jiaxin Fan, Xiang Jia, Xiaoling Guo, Xingwang Zhao, Yanhua Cao, Hui Zhang, Qian Wang","doi":"10.1515/biol-2022-0922","DOIUrl":"https://doi.org/10.1515/biol-2022-0922","url":null,"abstract":"Osteoarthritis (OA) is a chronic degenerative disease characterized by overall joint tissue damage. Metformin (Met) has been shown to inhibit inflammatory reactions, though its potential protective mechanism on cartilage remains unclear. This study investigated Met’s potential to protect cartilage in an OA rat model. Various morphological experiments were conducted to assess changes in cartilage tissue morphology before and after Met treatment. Protein and mRNA levels of cartilage-specific genes were measured using western blot, immunohistochemical staining, and RT-qPCR. Additionally, protein levels of autophagy-related and mTOR pathway-related proteins were measured. The results indicate an imbalance in the synthesis and degradation metabolism of chondrocytes, downregulation of cellular autophagy, and activation of the PI3K/Akt/mTOR pathway after surgery. However, treatment with Met could upregulate the expression of synthetic metabolic factors, indicating its contribution to cartilage repair. Furthermore, analysis of autophagy and pathway protein levels indicated that Met effectively attenuated autophagic damage to osteoarthritic cartilage cells and abnormal activation of the PI3K/Akt/mTOR pathway. In conclusion, Met can inhibit the abnormal activation of the PI3K/AKT/mTOR signaling pathway in cartilage tissue, promote the restoration of cartilage cell autophagic function, improve the balance of cartilage cell synthesis and degradation metabolism, and thus exert a protective effect on rat joint cartilage.","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141871538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IgG4-related tubulointerstitial nephritis (IgG4-related TIN) is the prevalent clinical manifestation of IgG4-related diseases (IgG4-RD). However, there are limited cases of IgG4-RD occurring with membranous nephropathy (MN) in the absence of phospholipase A2 receptor (PLA2R). There have been no indications of treatment using Tripterygium wilfordii. This study reported a rare case of IgG4-RD with PLA2R-associated MN without any of the distinct IgG4-related TIN. The patient was treated effectively with T. wilfordii. A 71-year-old patient was admitted to the medical facility after presenting with a 1 month history of edema and 8 months of albuminuria. The renal biopsy tissue examination confirmed the presence of MN (phase II) in the absence of pathological manifestations of IgG4-related TIN. Immunohistochemistry identified PLA2R++ (granular capillaries). The serum PLA2R antibody titer was 1:180 (1:20). The patient met the diagnosis with IgG4-RD. Over 8 years of follow-up, the patient was effectively treated with low-dose hormones and T. wilfordii, without any adverse effects. This MN is considered a unique form of IgG4-RD, regardless of whether PLA2R antibodies are present or not. Research suggests that T. wilfordii could be a promising option for elderly people with IgG4-related MN, as it has been found to have fewer adverse effects.
{"title":"IgG4-related disease complicated by PLA2R-associated membranous nephropathy: A case report","authors":"Meichun Huang, Jun Liu, Xiuxiu Li","doi":"10.1515/biol-2022-0921","DOIUrl":"https://doi.org/10.1515/biol-2022-0921","url":null,"abstract":"IgG4-related tubulointerstitial nephritis (IgG4-related TIN) is the prevalent clinical manifestation of IgG4-related diseases (IgG4-RD). However, there are limited cases of IgG4-RD occurring with membranous nephropathy (MN) in the absence of phospholipase A2 receptor (PLA2R). There have been no indications of treatment using <jats:italic>Tripterygium wilfordii</jats:italic>. This study reported a rare case of IgG4-RD with PLA2R-associated MN without any of the distinct IgG4-related TIN. The patient was treated effectively with <jats:italic>T. wilfordii</jats:italic>. A 71-year-old patient was admitted to the medical facility after presenting with a 1 month history of edema and 8 months of albuminuria. The renal biopsy tissue examination confirmed the presence of MN (phase II) in the absence of pathological manifestations of IgG4-related TIN. Immunohistochemistry identified PLA2R++ (granular capillaries). The serum PLA2R antibody titer was 1:180 (1:20). The patient met the diagnosis with IgG4-RD. Over 8 years of follow-up, the patient was effectively treated with low-dose hormones and <jats:italic>T. wilfordii</jats:italic>, without any adverse effects. This MN is considered a unique form of IgG4-RD, regardless of whether PLA2R antibodies are present or not. Research suggests that <jats:italic>T. wilfordii</jats:italic> could be a promising option for elderly people with IgG4-related MN, as it has been found to have fewer adverse effects.","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141779737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-24eCollection Date: 2024-01-01DOI: 10.1515/biol-2023-0001
Yinggang Hua, Yanling Liu, Long Li, Guoyan Liu
[This corrects the article DOI: 10.1515/biol-2022-0078.].
[此处更正了文章 DOI:10.1515/biol-2022-0078]。
{"title":"Erratum to \"Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation\".","authors":"Yinggang Hua, Yanling Liu, Long Li, Guoyan Liu","doi":"10.1515/biol-2023-0001","DOIUrl":"https://doi.org/10.1515/biol-2023-0001","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1515/biol-2022-0078.].</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}