Biofilms are complex microbial communities formed by the attachment of bacteria or fungi to surfaces encased in a self-produced polymeric matrix. These biofilms are highly resistant to conventional antimicrobial therapies. The resistance mechanisms exhibited by biofilms include low antibiotic absorption, sluggish replication, adaptive stress response, and the formation of dormant-like phenotypes. The eradication of biofilms requires alternative strategies and approaches. Nanotechnological drug delivery systems allow excellent control over the drug chemistry, surface area, particle size, particle shape, and composition of nanostructures. Nanoformulations can enhance the efficacy of antimicrobial agents by improving their bioavailability, stability, and targeted delivery to the site of infection that helps biofilm eradication more effectively. In addition to nanoformulations, the route of administration and choice of dosage forms play a crucial role in treating biofilm infections. Systemic administration of antibiotics is effective in controlling systemic infection and sepsis associated with biofilms. Alternative routes of administration, such as inhalation, vaginal, ocular, or dermal, have been explored to target biofilm infections in specific organs. This review primarily examines the utilisation of nanoformulations in various administration routes for biofilm management. It also provides an overview of biofilms, current approaches, and the drawbacks associated with conventional methods.
{"title":"Advancing biofilm management through nanoformulation strategies: a review of dosage forms and administration routes.","authors":"Oyku Simsekli, Irfan Bilinmis, Sumeyye Celik, Gizem Arık, Abdullah Yucel Baba, Alptug Karakucuk","doi":"10.1080/1061186X.2023.2270619","DOIUrl":"10.1080/1061186X.2023.2270619","url":null,"abstract":"<p><p>Biofilms are complex microbial communities formed by the attachment of bacteria or fungi to surfaces encased in a self-produced polymeric matrix. These biofilms are highly resistant to conventional antimicrobial therapies. The resistance mechanisms exhibited by biofilms include low antibiotic absorption, sluggish replication, adaptive stress response, and the formation of dormant-like phenotypes. The eradication of biofilms requires alternative strategies and approaches. Nanotechnological drug delivery systems allow excellent control over the drug chemistry, surface area, particle size, particle shape, and composition of nanostructures. Nanoformulations can enhance the efficacy of antimicrobial agents by improving their bioavailability, stability, and targeted delivery to the site of infection that helps biofilm eradication more effectively. In addition to nanoformulations, the route of administration and choice of dosage forms play a crucial role in treating biofilm infections. Systemic administration of antibiotics is effective in controlling systemic infection and sepsis associated with biofilms. Alternative routes of administration, such as inhalation, vaginal, ocular, or dermal, have been explored to target biofilm infections in specific organs. This review primarily examines the utilisation of nanoformulations in various administration routes for biofilm management. It also provides an overview of biofilms, current approaches, and the drawbacks associated with conventional methods.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41202759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-11-16DOI: 10.1080/1061186X.2023.2261079
Shuqin Wu, Baoshan Zhong, Yuxin Yang, Yurou Wang, Zezheng Pan
Gynecological cancers are the second most common types of cancer in women. Clinical diagnosis of these cancers is often delayed or misdiagnosed due to lack of insight into their tumorigenesis mechanism and specific diagnostic biomarkers. Many studies have demonstrated that competing endogenous RNAs (ceRNAs) modulate the progression and resistance of gynecological cancer through microRNA (miRNA)-mediated mechanisms, which affect gene expression in multiple cancer-related pathways. Here we review studies on the involvement of the ceRNA hypothesis in the progression and resistance of gynaecological cancers to validate some ceRNAs as therapeutic targets and predictive biomarkers.
{"title":"ceRNA networks in gynecological cancers progression and resistance.","authors":"Shuqin Wu, Baoshan Zhong, Yuxin Yang, Yurou Wang, Zezheng Pan","doi":"10.1080/1061186X.2023.2261079","DOIUrl":"10.1080/1061186X.2023.2261079","url":null,"abstract":"<p><p>Gynecological cancers are the second most common types of cancer in women. Clinical diagnosis of these cancers is often delayed or misdiagnosed due to lack of insight into their tumorigenesis mechanism and specific diagnostic biomarkers. Many studies have demonstrated that competing endogenous RNAs (ceRNAs) modulate the progression and resistance of gynecological cancer through microRNA (miRNA)-mediated mechanisms, which affect gene expression in multiple cancer-related pathways. Here we review studies on the involvement of the ceRNA hypothesis in the progression and resistance of gynaecological cancers to validate some ceRNAs as therapeutic targets and predictive biomarkers.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41138398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Osteoarthritis (OA) is a highly prevalent chronic joint disease and the leading cause of disability. Currently, no drugs are available to control joint damage or ease the associated pain. The wingless-type (WNT) signalling pathway is vital in OA progression. Excessive activation of the WNT signalling pathway is pertinent to OA progression and severity. Therefore, agonists and antagonists of the WNT pathway are considered potential drug candidates for OA treatment. For example, SM04690, a novel small molecule inhibitor of WNT signalling, has demonstrated its potential in a recent phase III clinical trial as a disease-modifying osteoarthritis drug (DMOAD). Therefore, targeting the WNT signalling pathway may be a distinctive approach to developing particular agents helpful in treating OA. This review aims to update the most recent progress in OA drug development by targeting the WNT pathway. In this, we introduce WNT pathways and their crosstalk with other signalling pathways in OA development and highlight the role of the WNT signalling pathway as a key regulator in OA development. Several articles have reviewed the Wnt pathway from different aspects. This candid review provides an introduction to WNT pathways and their crosstalk with other signalling pathways in OA development, highlighting the role of the WNT signalling pathway as a key regulator in OA development with the latest research. Particularly, we emphasise the state-of-the-art in targeting the WNT pathway as a promising therapeutic approach for OA and challenges in their development and the nanocarrier-based delivery of WNT modulators for treating OA.
{"title":"Targeting <i>WNT</i> signalling pathways as new therapeutic strategies for osteoarthritis.","authors":"Zoya Iqbal, Jiang Xia, Ghulam Murtaza, Maryam Shabbir, Khurrum Rehman, Liang Yujie, Li Duan","doi":"10.1080/1061186X.2023.2281861","DOIUrl":"10.1080/1061186X.2023.2281861","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a highly prevalent chronic joint disease and the leading cause of disability. Currently, no drugs are available to control joint damage or ease the associated pain. The <i>wingless-type</i> (<i>WNT</i>) signalling pathway is vital in OA progression. Excessive activation of the <i>WNT</i> signalling pathway is pertinent to OA progression and severity. Therefore, agonists and antagonists of the <i>WNT</i> pathway are considered potential drug candidates for OA treatment. For example, SM04690, a novel small molecule inhibitor of <i>WNT</i> signalling, has demonstrated its potential in a recent phase III clinical trial as a disease-modifying osteoarthritis drug (DMOAD). Therefore, targeting the <i>WNT</i> signalling pathway may be a distinctive approach to developing particular agents helpful in treating OA. This review aims to update the most recent progress in OA drug development by targeting the <i>WNT</i> pathway. In this, we introduce <i>WNT</i> pathways and their crosstalk with other signalling pathways in OA development and highlight the role of the <i>WNT</i> signalling pathway as a key regulator in OA development. Several articles have reviewed the Wnt pathway from different aspects. This candid review provides an introduction to <i>WNT</i> pathways and their crosstalk with other signalling pathways in OA development, highlighting the role of the <i>WNT</i> signalling pathway as a key regulator in OA development with the latest research. Particularly, we emphasise the state-of-the-art in targeting the <i>WNT</i> pathway as a promising therapeutic approach for OA and challenges in their development and the nanocarrier-based delivery of WNT modulators for treating OA.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134649119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The eradication of chronic hepatitis B (CHB) caused by hepatitis B virus (HBV) infection is a crucial goal in clinical practice. Enhancing the anti-HBV activity of interferon type I (IFNI) is a key strategy for achieving a functional cure for CHB. In this study, we investigated the effect of combined treatment with IFNα and Desmethoxycurcumin (DMC) on HBV replication in HepG2 cells and explored the underlying mechanism. Our results indicated IFNα alone was ineffective in completely inhibiting HBV replication, which was attributed to the virus-induced down-regulation of IFNI receptor 1 (IFNAR1) protein. However, the addition of a low dose of DMC significantly synergized with IFNα, leading to notable enhancement of IFNα anti-HBV activity. This effect was achieved by stabilising the IFNAR1 protein. Further investigation revealed that low dose DMC effectively blocked the ubiquitination-mediated degradation of IFNAR1, which was accomplished by rescuing the protein levels of alphaB-crystallin (CRYAB) and orchestrating the interaction between CRYAB and the E3 ubiquitin ligase, β-Trcp. Importantly, over-expression of CRYAB was found to favour the antiviral activity of IFNα against HBV replication. In conclusion, our study demonstrates that low-dose DMC enhanced the anti-HBV activity of IFNα by counteracting the reduction of CRYAB and stabilising the IFNAR1 protein.
{"title":"Desmethoxycurcumin aids IFNα's anti-HBV activity by antagonising CRYAB reduction and stabilising IFNAR1 protein.","authors":"Jinlai Wei, Xichuan Deng, Wenying Dai, Lingxin Xie, Guangyuan Zhang, Xinyue Fan, Xinyue Li, Zhixing Jin, Qin Xiao, Tingting Chen","doi":"10.1080/1061186X.2023.2273200","DOIUrl":"10.1080/1061186X.2023.2273200","url":null,"abstract":"<p><p>The eradication of chronic hepatitis B (CHB) caused by hepatitis B virus (HBV) infection is a crucial goal in clinical practice. Enhancing the anti-HBV activity of interferon type I (IFNI) is a key strategy for achieving a functional cure for CHB. In this study, we investigated the effect of combined treatment with IFNα and Desmethoxycurcumin (DMC) on HBV replication in HepG2 cells and explored the underlying mechanism. Our results indicated IFNα alone was ineffective in completely inhibiting HBV replication, which was attributed to the virus-induced down-regulation of IFNI receptor 1 (IFNAR1) protein. However, the addition of a low dose of DMC significantly synergized with IFNα, leading to notable enhancement of IFNα anti-HBV activity. This effect was achieved by stabilising the IFNAR1 protein. Further investigation revealed that low dose DMC effectively blocked the ubiquitination-mediated degradation of IFNAR1, which was accomplished by rescuing the protein levels of alphaB-crystallin (CRYAB) and orchestrating the interaction between CRYAB and the E3 ubiquitin ligase, β-Trcp. Importantly, over-expression of CRYAB was found to favour the antiviral activity of IFNα against HBV replication. In conclusion, our study demonstrates that low-dose DMC enhanced the anti-HBV activity of IFNα by counteracting the reduction of CRYAB and stabilising the IFNAR1 protein.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41235793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Macrophages are the most abundant cell group in atherosclerosis (AS) lesions and play a vital role in all stages of AS progression. Recent research has shown that reactive oxygen species (ROS) generation from photodynamic therapy (PDT) induces macrophage autophagy to improve abnormal lipid metabolism and inflammatory environment. Especially in macrophage-derived foam cells, which has become a potential strategy for the treatment of AS. In this study, we prepared the conjugate (DB) of dextran (DEX) and bovine serum albumin (BSA). The DB was used as the emulsifier to prepare nanoemulsion loaded with upconversion nanoparticles (UCNPs) and chlorin e6 (Ce6) (UCNPs-Ce6@DB). The DEX modified on the surface of the nanoemulsion can recognise and bind to the scavenger receptor class A (SR-A) highly expressed on macrophages and promote the uptake of macrophage-derived foam cells in AS plates through SR-A-mediated endocytosis. In addition, UCNPs-Ce6@DB-mediated PDT enhanced ROS generation and induced autophagy in macrophage-derived foam cells, enhanced the expression of ABCA1, a protein closely related to cholesterol efflux, and inhibited the secretion of pro-inflammatory cytokines. Ultimately, UCNPs-Ce6@DB was shown to inhibit plaque formation in mouse models of AS. In conclusion, UCNPs-Ce6@DB offers a promising treatment for AS.
{"title":"Targeted treatment of atherosclerosis with protein-polysaccharide nanoemulsion co-loaded with photosensitiser and upconversion nanoparticles.","authors":"Jing Huang, Shan Xu, Lina Liu, Jiyuan Zhang, Jinzhuan Xu, Lili Zhang, Xiang Zhou, Lei Huang, Jianqing Peng, Jianing Wang, Zipeng Gong, Yi Chen","doi":"10.1080/1061186X.2023.2284093","DOIUrl":"10.1080/1061186X.2023.2284093","url":null,"abstract":"<p><p>Macrophages are the most abundant cell group in atherosclerosis (AS) lesions and play a vital role in all stages of AS progression. Recent research has shown that reactive oxygen species (ROS) generation from photodynamic therapy (PDT) induces macrophage autophagy to improve abnormal lipid metabolism and inflammatory environment. Especially in macrophage-derived foam cells, which has become a potential strategy for the treatment of AS. In this study, we prepared the conjugate (DB) of dextran (DEX) and bovine serum albumin (BSA). The DB was used as the emulsifier to prepare nanoemulsion loaded with upconversion nanoparticles (UCNPs) and chlorin e6 (Ce6) (UCNPs-Ce6@DB). The DEX modified on the surface of the nanoemulsion can recognise and bind to the scavenger receptor class A (SR-A) highly expressed on macrophages and promote the uptake of macrophage-derived foam cells in AS plates through SR-A-mediated endocytosis. In addition, UCNPs-Ce6@DB-mediated PDT enhanced ROS generation and induced autophagy in macrophage-derived foam cells, enhanced the expression of ABCA1, a protein closely related to cholesterol efflux, and inhibited the secretion of pro-inflammatory cytokines. Ultimately, UCNPs-Ce6@DB was shown to inhibit plaque formation in mouse models of AS. In conclusion, UCNPs-Ce6@DB offers a promising treatment for AS.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92154718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As bioactive molecules, peptides and proteins are essential in living organisms, including animals and humans. Defects in their function lead to various diseases in humans. Therefore, the use of proteins in treating multiple diseases, such as cancers and hepatitis, is increasing. There are different routes to administer proteins, which have limitations due to their large and hydrophilic structure. Another limitation is the presence of biological and lipophilic membranes that do not allow proteins to pass quickly. There are different strategies to increase the absorption of proteins from these biological membranes. One of these strategies is to use compounds as absorption enhancers. Absorption enhancers are compounds such as surfactants, phospholipids and cyclodextrins that increase protein passage through the biological membrane and their absorption by different mechanisms. This review focuses on using other absorption enhancers and their mechanism in protein administration routes.
{"title":"Absorption enhancer approach for protein delivery by various routes of administration: a rapid review.","authors":"Toktam Salehi, Mohammad Amin Raeisi Estabragh, Soodeh Salarpour, Mandana Ohadi, Gholamreza Dehghannoudeh","doi":"10.1080/1061186X.2023.2271680","DOIUrl":"10.1080/1061186X.2023.2271680","url":null,"abstract":"<p><p>As bioactive molecules, peptides and proteins are essential in living organisms, including animals and humans. Defects in their function lead to various diseases in humans. Therefore, the use of proteins in treating multiple diseases, such as cancers and hepatitis, is increasing. There are different routes to administer proteins, which have limitations due to their large and hydrophilic structure. Another limitation is the presence of biological and lipophilic membranes that do not allow proteins to pass quickly. There are different strategies to increase the absorption of proteins from these biological membranes. One of these strategies is to use compounds as absorption enhancers. Absorption enhancers are compounds such as surfactants, phospholipids and cyclodextrins that increase protein passage through the biological membrane and their absorption by different mechanisms. This review focuses on using other absorption enhancers and their mechanism in protein administration routes.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41235792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1080/1061186X.2023.2247584
Mariam Soliman, Nagwan Shanan, Gamal Eissa, Boris Mizaikoff, Nesrine A El Gohary
Abstract A magnetic molecularly imprinted polymer (MMIP) was synthesised and tested for an in vivo rheumatoid arthritis (RA) rat model. Magnetite coated with mesoporous silica (Fe2O3@mSi) was used as core for surface imprinting, dopamine was used as monomer and methotrexate (MTX) was loaded directly during polymerisation. The amount of MTX loaded on MMIPs reached 201.165 ± 0.315 µmol/g. Characterisation of the polymers was done via SEM, TEM, and FTIR. The pharmacological effect of the selected MMIP was evaluated in a Complete Freund’s Adjuvant (CFA) induced arthritis rat model where a 3D magnet bearing construct was designed for targeted delivery of MMIPs. The parameters evaluated were the change in paw edoema, paw diameter, gait score, and animal’s weight. Results revealed a tendency of MMIP to significantly improve the measured parameters which was confirmed with histopathological findings. In conclusion, the improvement in the arthritic signs associated with MMIP treatment compared to free MTX, indicated successful targeting of MMIPs to the site of inflammation. Graphical Abstract
{"title":"<i>In vivo</i> application of magnetic molecularly imprinted polymer in rheumatoid arthritis rat model.","authors":"Mariam Soliman, Nagwan Shanan, Gamal Eissa, Boris Mizaikoff, Nesrine A El Gohary","doi":"10.1080/1061186X.2023.2247584","DOIUrl":"https://doi.org/10.1080/1061186X.2023.2247584","url":null,"abstract":"Abstract A magnetic molecularly imprinted polymer (MMIP) was synthesised and tested for an in vivo rheumatoid arthritis (RA) rat model. Magnetite coated with mesoporous silica (Fe2O3@mSi) was used as core for surface imprinting, dopamine was used as monomer and methotrexate (MTX) was loaded directly during polymerisation. The amount of MTX loaded on MMIPs reached 201.165 ± 0.315 µmol/g. Characterisation of the polymers was done via SEM, TEM, and FTIR. The pharmacological effect of the selected MMIP was evaluated in a Complete Freund’s Adjuvant (CFA) induced arthritis rat model where a 3D magnet bearing construct was designed for targeted delivery of MMIPs. The parameters evaluated were the change in paw edoema, paw diameter, gait score, and animal’s weight. Results revealed a tendency of MMIP to significantly improve the measured parameters which was confirmed with histopathological findings. In conclusion, the improvement in the arthritic signs associated with MMIP treatment compared to free MTX, indicated successful targeting of MMIPs to the site of inflammation. Graphical Abstract","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10647468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Breast cancer (BC) is considered one of the most frequent cancers among woman worldwide. While conventional therapy has been successful in treating many cases of breast cancer, drug resistance, heterogenicity, tumour features and recurrence, invasion, metastasis and the presence of breast cancer stem cells can hinder the effect of treatments, and can reduce the quality of life of patients. MicroRNAs (miRNAs) are short non-coding RNA molecules that play a crucial role in the development and progression of breast cancer. Several studies have reported that aberrant expression of specific miRNAs is associated with the pathogenesis of breast cancer. However, miRNAs are emerging as potential biomarkers and therapeutic targets for breast cancer. Understanding their role in breast cancer biology could help develop more effective treatments for this disease. The present study discusses the biogenesis and function of miRNAs, as well as miRNA therapy approaches for targeting and treating breast cancer cells.
{"title":"Recent advances in novel miRNA mediated approaches for targeting breast cancer.","authors":"Seyedeh Melika Ahmadi, Shervin Amirkhanloo, Rezvan Yazdian-Robati, Hossein Ebrahimi, Faezeh Hosseini Pirhayati, Waleed H Almalki, Pedram Ebrahimnejad, Prashant Kesharwani","doi":"10.1080/1061186X.2023.2240979","DOIUrl":"https://doi.org/10.1080/1061186X.2023.2240979","url":null,"abstract":"<p><p>Breast cancer (BC) is considered one of the most frequent cancers among woman worldwide. While conventional therapy has been successful in treating many cases of breast cancer, drug resistance, heterogenicity, tumour features and recurrence, invasion, metastasis and the presence of breast cancer stem cells can hinder the effect of treatments, and can reduce the quality of life of patients. MicroRNAs (miRNAs) are short non-coding RNA molecules that play a crucial role in the development and progression of breast cancer. Several studies have reported that aberrant expression of specific miRNAs is associated with the pathogenesis of breast cancer. However, miRNAs are emerging as potential biomarkers and therapeutic targets for breast cancer. Understanding their role in breast cancer biology could help develop more effective treatments for this disease. The present study discusses the biogenesis and function of miRNAs, as well as miRNA therapy approaches for targeting and treating breast cancer cells.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10125415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1080/1061186X.2023.2250574
Mingyu Zhang, Ziyuan Tong, Yaqing Wang, Wenjing Fu, Yilin Meng, Jiayi Huang, Li Sun
Renal fibrosis, characterised by glomerulosclerosis and tubulointerstitial fibrosis, is a typical pathological alteration in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). However, the limited and expensive options for treating renal fibrosis place a heavy financial burden on patients and healthcare systems. Therefore, it is significant to find an effective treatment for renal fibrosis. Ferroptosis, a non-traditional form of cell death, has been found to play an important role in acute kidney injury (AKI), tumours, neurodegenerative diseases, and so on. Moreover, a growing body of research suggests that ferroptosis might be a potential target of renal fibrosis. Meanwhile, mitophagy is a type of selective autophagy that can selectively degrade damaged or dysfunctional mitochondria as a form of mitochondrial quality control, reducing the production of reactive oxygen species (ROS), the accumulation of which is the main cause of renal fibrosis. Additionally, as a receptor of mitophagy, NIX can release beclin1 to induce mitophagy, which can also bind to solute carrier family 7 member 11 (SLC7A11) to block the activity of cystine/glutamate antitransporter (system Xc-) and inhibit ferroptosis, thereby suggesting a link between mitophagy and ferroptosis. However, there have been only limited studies on the relationship among mitophagy, ferroptosis and renal fibrosis. In this paper, we review the mechanisms of mitophagy, and describe how ferroptosis and mitophagy are related to renal fibrosis in an effort to identify potential novel targets for the treatment of renal fibrosis.
{"title":"Relationship between ferroptosis and mitophagy in renal fibrosis: a systematic review.","authors":"Mingyu Zhang, Ziyuan Tong, Yaqing Wang, Wenjing Fu, Yilin Meng, Jiayi Huang, Li Sun","doi":"10.1080/1061186X.2023.2250574","DOIUrl":"https://doi.org/10.1080/1061186X.2023.2250574","url":null,"abstract":"<p><p>Renal fibrosis, characterised by glomerulosclerosis and tubulointerstitial fibrosis, is a typical pathological alteration in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). However, the limited and expensive options for treating renal fibrosis place a heavy financial burden on patients and healthcare systems. Therefore, it is significant to find an effective treatment for renal fibrosis. Ferroptosis, a non-traditional form of cell death, has been found to play an important role in acute kidney injury (AKI), tumours, neurodegenerative diseases, and so on. Moreover, a growing body of research suggests that ferroptosis might be a potential target of renal fibrosis. Meanwhile, mitophagy is a type of selective autophagy that can selectively degrade damaged or dysfunctional mitochondria as a form of mitochondrial quality control, reducing the production of reactive oxygen species (ROS), the accumulation of which is the main cause of renal fibrosis. Additionally, as a receptor of mitophagy, NIX can release beclin1 to induce mitophagy, which can also bind to solute carrier family 7 member 11 (SLC7A11) to block the activity of cystine/glutamate antitransporter (system Xc-) and inhibit ferroptosis, thereby suggesting a link between mitophagy and ferroptosis. However, there have been only limited studies on the relationship among mitophagy, ferroptosis and renal fibrosis. In this paper, we review the mechanisms of mitophagy, and describe how ferroptosis and mitophagy are related to renal fibrosis in an effort to identify potential novel targets for the treatment of renal fibrosis.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10335295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1080/1061186X.2023.2247581
Linlin Zhang, Lei Cheng, Zhemeng Chen, Yi Fang, Changjiang Li, Min Chen, Peijie He, Haitao Wu, Jianzhang Wu, Jian Chen
Hypopharyngeal carcinoma is notorious for its poor prognosis among all head and neck cancers, posing a persistent challenge in clinical settings. The continuous hyperactivation of the NFκB signalling pathway has been noted in various cancer types, including hypopharyngeal carcinoma. In our quest to develop a novel drug that targets hypopharyngeal cancer via the NFκB pathway, we employed curcumin, a well-known lead compound, and performed chemical modifications to create a mono-carbonyl analogue called L42H17. This compound exhibited exceptional stability and displayed an enhanced binding affinity to myeloid differentiation protein 2 (MD2). Consistent with expectations, L42H17 demonstrated the ability to inhibit TNF-α-induced phosphorylation of inhibitor of κB (IκB) kinase (IKK), prevent IκB degradation, and subsequently impede NFκB-p65 nuclear translocation in hypopharyngeal cancer cells. Additionally, L42H17 exhibited a remarkable capacity to induce cell cycle arrest at the G2-M phase by inactivating the cdc2-cyclin B1 complex. Moreover, it facilitated cell apoptosis by reducing Bcl-2 levels and augmenting the expression of cle-PARP and cle-caspase3. Importantly, we observed a significant enhancement in the anti-cancer efficacy of L42H17 in a patient-derived tumour xenograft (PDTX) model of hypopharyngeal carcinoma. In conclusion, our findings strongly suggest that L42H17 holds promise as a potential candidate drug for the treatment of hypopharyngeal carcinoma in the future.
下咽癌是臭名昭著的预后不良的所有头颈部癌症,提出了持续的挑战,在临床设置。NFκB信号通路的持续过度激活已在包括下咽癌在内的各种癌症类型中被注意到。在我们寻求开发一种通过NFκB途径靶向下咽癌的新药的过程中,我们使用了姜黄素,一种众所周知的先导化合物,并进行了化学修饰,创造了一种名为L42H17的单羰基类似物。该化合物表现出优异的稳定性,并显示出与髓样分化蛋白2 (MD2)增强的结合亲和力。与预期一致,L42H17能够抑制TNF-α-诱导的κB (i - κB)激酶抑制剂(IKK)的磷酸化,阻止i - κB降解,并随后阻碍nf - κB-p65在下咽癌细胞中的核易位。此外,L42H17通过灭活cdc2-cyclin B1复合物,表现出在G2-M期诱导细胞周期阻滞的显著能力。此外,它通过降低Bcl-2水平,增加cle-PARP和cle-caspase3的表达,促进细胞凋亡。重要的是,我们观察到L42H17在患者源性肿瘤异种移植(PDTX)下咽癌模型中的抗癌功效显著增强。总之,我们的研究结果强烈表明L42H17有望成为未来治疗下咽癌的潜在候选药物。
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