Dongliang Wang, Caiyun Yin, Yihan Bai, Mingxia Zhou, Naidong Wang, Chunyi Tong, Yi Yang, Bin Liu
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has filled a gap in our knowledge regarding the prevention of CoVs. Swine coronavirus (CoV) is a significant pathogen that causes huge economic losses to the global swine industry. Until now, anti-CoV prevention and control have been challenging due to the rapidly generated variants. Silver nanoparticles (AgNPs) with excellent antimicrobial activity have attracted great interest for biosafety prevention and control applications. In this study, we synthesized chitosan-modified AgNPs (Chi-AgNPs) with good biocompatibility to investigate their antiviral effects on swine CoVs. In vitro assays showed that Chi-AgNPs could significantly impaired viral entry. The direct interaction between Chi-AgNPs and CoVs can destroy the viral surface spike (S) protein secondary structure associated with viral membrane fusion, which is caused by the cleavage of disulfide bonds in the S protein. Moreover, the mechanism showed that Chi-AgNPs reduced the virus-induced apoptosis of Vero cells via the ROS/p53 signaling activation pathway. Our data suggest that Chi-AgNPs can serve as a preventive strategy for CoVs infection and provide a molecular basis for the viricidal effect of Chi-AgNPs on CoVs.
{"title":"Chitosan-Modified AgNPs Efficiently Inhibit Swine Coronavirus-Induced Host Cell Infections via Targeting the Spike Protein","authors":"Dongliang Wang, Caiyun Yin, Yihan Bai, Mingxia Zhou, Naidong Wang, Chunyi Tong, Yi Yang, Bin Liu","doi":"10.3390/biom14091152","DOIUrl":"https://doi.org/10.3390/biom14091152","url":null,"abstract":"The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has filled a gap in our knowledge regarding the prevention of CoVs. Swine coronavirus (CoV) is a significant pathogen that causes huge economic losses to the global swine industry. Until now, anti-CoV prevention and control have been challenging due to the rapidly generated variants. Silver nanoparticles (AgNPs) with excellent antimicrobial activity have attracted great interest for biosafety prevention and control applications. In this study, we synthesized chitosan-modified AgNPs (Chi-AgNPs) with good biocompatibility to investigate their antiviral effects on swine CoVs. In vitro assays showed that Chi-AgNPs could significantly impaired viral entry. The direct interaction between Chi-AgNPs and CoVs can destroy the viral surface spike (S) protein secondary structure associated with viral membrane fusion, which is caused by the cleavage of disulfide bonds in the S protein. Moreover, the mechanism showed that Chi-AgNPs reduced the virus-induced apoptosis of Vero cells via the ROS/p53 signaling activation pathway. Our data suggest that Chi-AgNPs can serve as a preventive strategy for CoVs infection and provide a molecular basis for the viricidal effect of Chi-AgNPs on CoVs.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benzhi Dong, Zheng Liu, Dali Xu, Chang Hou, Na Niu, Guohua Wang
Protein secondary structure prediction (PSSP) plays a crucial role in resolving protein functions and properties. Significant progress has been made in this field in recent years, and the use of a variety of protein-related features, including amino acid sequences, position-specific score matrices (PSSM), amino acid properties, and secondary structure trend factors, to improve prediction accuracy is an important technical route for it. However, a comprehensive evaluation of the impact of these factor features in secondary structure prediction is lacking in the current work. This study quantitatively analyzes the impact of several major factors on secondary structure prediction models using a more explanatory four-class machine learning approach. The applicability of each factor in the different types of methods, the extent to which the different methods work on each factor, and the evaluation of the effect of multi-factor combinations are explored in detail. Through experiments and analyses, it was found that PSSM performs best in methods with strong high-dimensional features and complex feature extraction capabilities, while amino acid sequences, although performing poorly overall, perform relatively well in methods with strong linear processing capabilities. Also, the combination of amino acid properties and trend factors significantly improved the prediction performance. This study provides empirical evidence for future researchers to optimize multi-factor feature combinations and apply them to protein secondary structure prediction models, which is beneficial in further optimizing the use of these factors to enhance the performance of protein secondary structure prediction models.
{"title":"Impact of Multi-Factor Features on Protein Secondary Structure Prediction","authors":"Benzhi Dong, Zheng Liu, Dali Xu, Chang Hou, Na Niu, Guohua Wang","doi":"10.3390/biom14091155","DOIUrl":"https://doi.org/10.3390/biom14091155","url":null,"abstract":"Protein secondary structure prediction (PSSP) plays a crucial role in resolving protein functions and properties. Significant progress has been made in this field in recent years, and the use of a variety of protein-related features, including amino acid sequences, position-specific score matrices (PSSM), amino acid properties, and secondary structure trend factors, to improve prediction accuracy is an important technical route for it. However, a comprehensive evaluation of the impact of these factor features in secondary structure prediction is lacking in the current work. This study quantitatively analyzes the impact of several major factors on secondary structure prediction models using a more explanatory four-class machine learning approach. The applicability of each factor in the different types of methods, the extent to which the different methods work on each factor, and the evaluation of the effect of multi-factor combinations are explored in detail. Through experiments and analyses, it was found that PSSM performs best in methods with strong high-dimensional features and complex feature extraction capabilities, while amino acid sequences, although performing poorly overall, perform relatively well in methods with strong linear processing capabilities. Also, the combination of amino acid properties and trend factors significantly improved the prediction performance. This study provides empirical evidence for future researchers to optimize multi-factor feature combinations and apply them to protein secondary structure prediction models, which is beneficial in further optimizing the use of these factors to enhance the performance of protein secondary structure prediction models.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marta Marszalek-Grabska, Monika Turska-Kozlowska, Edyta Kaczorek-Lukowska, Katarzyna Wicha-Komsta, Waldemar A. Turski, Andrzej K. Siwicki, Kinga Gawel
Kynurenic acid (KYNA) is a metabolite of tryptophan formed on the kynurenine pathway. Its pharmacological effects are relatively well characterized in mammals, whereas its role in fish is poorly understood. Therefore, the aim of the study was to expand the knowledge of KYNA’s presence inside a fish’s body and its impact on fish development and function. The study was performed on zebrafish larvae and adult rainbow trout. We provide evidence that KYNA is present in the embryo, larva and mature fish and that its distribution in organs varies considerably. A study of KYNA’s effect on early larval development suggests that it can accelerate larval maturation, especially under conditions that are suboptimal for fish growth. Moreover, KYNA in concentrations over 1 mM caused morphological impairment and death of larvae. However, long-lasting exposure of larvae to subtoxic concentrations of KYNA does not affect the behavior of 5-day-old larvae kept under standard optimal conditions. We also show that ingestion of KYNA-supplemented feed can lead to KYNA accumulation, particularly in the pyloric caeca of mature trout. These results shed new light on the relevance of KYNA and provide new impulse for further research on the importance of the kynurenine pathway in fish.
{"title":"The Effects of Kynurenic Acid in Zebrafish Embryos and Adult Rainbow Trout","authors":"Marta Marszalek-Grabska, Monika Turska-Kozlowska, Edyta Kaczorek-Lukowska, Katarzyna Wicha-Komsta, Waldemar A. Turski, Andrzej K. Siwicki, Kinga Gawel","doi":"10.3390/biom14091148","DOIUrl":"https://doi.org/10.3390/biom14091148","url":null,"abstract":"Kynurenic acid (KYNA) is a metabolite of tryptophan formed on the kynurenine pathway. Its pharmacological effects are relatively well characterized in mammals, whereas its role in fish is poorly understood. Therefore, the aim of the study was to expand the knowledge of KYNA’s presence inside a fish’s body and its impact on fish development and function. The study was performed on zebrafish larvae and adult rainbow trout. We provide evidence that KYNA is present in the embryo, larva and mature fish and that its distribution in organs varies considerably. A study of KYNA’s effect on early larval development suggests that it can accelerate larval maturation, especially under conditions that are suboptimal for fish growth. Moreover, KYNA in concentrations over 1 mM caused morphological impairment and death of larvae. However, long-lasting exposure of larvae to subtoxic concentrations of KYNA does not affect the behavior of 5-day-old larvae kept under standard optimal conditions. We also show that ingestion of KYNA-supplemented feed can lead to KYNA accumulation, particularly in the pyloric caeca of mature trout. These results shed new light on the relevance of KYNA and provide new impulse for further research on the importance of the kynurenine pathway in fish.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The hormonal system plays a decisive role in controlling plant growth and development [...]
激素系统在控制植物生长和发育方面起着决定性作用 [...]
{"title":"Special Issue “Phytohormones 2022–2023”","authors":"Guzel Kudoyarova, Guzel Akhiyarova","doi":"10.3390/biom14091146","DOIUrl":"https://doi.org/10.3390/biom14091146","url":null,"abstract":"The hormonal system plays a decisive role in controlling plant growth and development [...]","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stimulating erythropoiesis is essential in the treatment of various types of anemia. Sheng Xue Ning (SXN) is commonly used in China as an iron supplement to treat iron deficiency anemia, renal anemia, and anemia in pregnancy. This research reports a novel effect of SXN in enhancing the proliferation of hematopoietic stem/progenitor cell (HSPC) to promote erythropoiesis in the bone marrow, which is distinct from conventional iron supplements that primarily aid in the maturation of red blood cells. Employing a model of hematopoietic dysfunction induced by X-ray exposure, we evaluated the efficacy of SXN in restoring hematopoietic function. SXN significantly promoted the recovery of peripheral erythroid cells and enhanced the proliferation and differentiation of Lin−/c-KIT+/Sca-1+ HSPC in mice exposed to X-ray irradiation. Our results showed that SXN elevated the expression of stem cell factor (SCF) and activated the SCF/c-KIT/PI3K/AKT signaling pathway, facilitating the proliferation and differentiation of HSPC. In vitro, SXN markedly enhanced the proliferation of bone marrow nucleated cell (BMNC) and the colony-forming capacity of BFU-E, CFU-E, and CFU-GM, while also elevating the expression of proteins involved in the SCF/c-KIT/PI3K/AKT pathway in BMNC. Additionally, SXN enhanced the proliferation and differentiation of mesenchymal stem cell (MSC) and increased SCF secretion. In conclusion, SXN demonstrates the capacity to enhance erythropoiesis by upregulating SCF expression, thereby promoting HSPC proliferation and differentiation via the SCF/c-KIT/PI3K/AKT pathway. SXN may offer a new strategy for improving the activity of HSPC and promoting erythropoiesis in the treatment of hematopoiesis disorders.
刺激红细胞生成对治疗各种贫血至关重要。在中国，生血宁（SXN）是一种常用的补铁药物，可用于治疗缺铁性贫血、肾性贫血和妊娠贫血。这项研究报告了圣雪宁在增强造血干细胞/祖细胞（HSPC）增殖以促进骨髓红细胞生成方面的新作用，这有别于主要帮助红细胞成熟的传统铁补充剂。我们利用 X 射线照射引起的造血功能障碍模型，评估了 SXN 在恢复造血功能方面的功效。在接受 X 射线照射的小鼠体内，SXN 能明显促进外周红细胞的恢复，并增强 Lin-/c-KIT+/Sca-1+ HSPC 的增殖和分化。我们的研究结果表明，SXN能提高干细胞因子（SCF）的表达，激活SCF/c-KIT/PI3K/AKT信号通路，促进HSPC的增殖和分化。在体外，SXN能明显增强骨髓有核细胞（BMNC）的增殖以及BFU-E、CFU-E和CFU-GM的集落形成能力，同时还能提高BMNC中参与SCF/c-KIT/PI3K/AKT通路的蛋白质的表达。此外，SXN 还能促进间充质干细胞（MSC）的增殖和分化，并增加 SCF 的分泌。总之，SXN能通过上调SCF的表达来增强红细胞生成，从而通过SCF/c-KIT/PI3K/AKT途径促进HSPC的增殖和分化。SXN 可为提高 HSPC 活性和促进红细胞生成提供一种治疗造血疾病的新策略。
{"title":"Sheng Xue Ning as a Novel Agent that Promotes SCF-Driven Hematopoietic Stem/Progenitor Cell Proliferation to Promote Erythropoiesis","authors":"Yueying Zeng, Chunlu Li, Fei Yang, Ling Zhang, Wanqi Xu, Long Wang, Anguo Wu, Wenjun Zou, Jianming Wu, Feihong Huang","doi":"10.3390/biom14091147","DOIUrl":"https://doi.org/10.3390/biom14091147","url":null,"abstract":"Stimulating erythropoiesis is essential in the treatment of various types of anemia. Sheng Xue Ning (SXN) is commonly used in China as an iron supplement to treat iron deficiency anemia, renal anemia, and anemia in pregnancy. This research reports a novel effect of SXN in enhancing the proliferation of hematopoietic stem/progenitor cell (HSPC) to promote erythropoiesis in the bone marrow, which is distinct from conventional iron supplements that primarily aid in the maturation of red blood cells. Employing a model of hematopoietic dysfunction induced by X-ray exposure, we evaluated the efficacy of SXN in restoring hematopoietic function. SXN significantly promoted the recovery of peripheral erythroid cells and enhanced the proliferation and differentiation of Lin−/c-KIT+/Sca-1+ HSPC in mice exposed to X-ray irradiation. Our results showed that SXN elevated the expression of stem cell factor (SCF) and activated the SCF/c-KIT/PI3K/AKT signaling pathway, facilitating the proliferation and differentiation of HSPC. In vitro, SXN markedly enhanced the proliferation of bone marrow nucleated cell (BMNC) and the colony-forming capacity of BFU-E, CFU-E, and CFU-GM, while also elevating the expression of proteins involved in the SCF/c-KIT/PI3K/AKT pathway in BMNC. Additionally, SXN enhanced the proliferation and differentiation of mesenchymal stem cell (MSC) and increased SCF secretion. In conclusion, SXN demonstrates the capacity to enhance erythropoiesis by upregulating SCF expression, thereby promoting HSPC proliferation and differentiation via the SCF/c-KIT/PI3K/AKT pathway. SXN may offer a new strategy for improving the activity of HSPC and promoting erythropoiesis in the treatment of hematopoiesis disorders.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elham Kayvanpour, Farbod Sedaghat-Hamedani, Daniel Tian Li, Tobias Miersch, Tanja Weis, Imo Hoefer, Norbert Frey, Benjamin Meder
Background: Dilated cardiomyopathy (DCM) involves myocardial remodeling, characterized by significant fibrosis and extracellular matrix expansion. These changes impair heart function, increasing the risk of heart failure and sudden cardiac death. This study investigates the prognostic value of circulating fibrosis biomarkers as a less invasive method in DCM patients. Methods: Plasma samples from 185 patients with confirmed DCM were analyzed to measure 13 circulating biomarkers using Luminex bead-based multiplex assays and ELISA. The prognostic value of these biomarkers was evaluated concerning heart failure-associated events and all-cause mortality. Results: Elevated MMP-2 levels (>1519.3 ng/mL) were linked to older age, higher diabetes prevalence, lower HDL, increased NT-proBNP and hs-TnT levels, and severe systolic dysfunction. High TIMP-1 levels (>124.9 ng/mL) correlated with elevated NT-proBNP, more atrial fibrillation, reduced exercise capacity, and larger right ventricles. Increased GDF-15 levels (>1213.9 ng/mL) were associated with older age, systemic inflammation, renal impairment, and poor exercise performance. Elevated OPN levels (>81.7 ng/mL) were linked to higher serum creatinine and NT-proBNP levels. Over a median follow-up of 32.4 months, higher levels of these biomarkers predicted worse outcomes, including increased risks of heart failure-related events and mortality. Conclusions: Circulating fibrosis biomarkers, particularly MMP-2, TIMP-1, GDF-15, and OPN, are valuable prognostic tools in DCM. They reflect the severity of myocardial remodeling and systemic disease burden, aiding in risk stratification and therapeutic intervention. Integrating these biomarkers into clinical practice could improve DCM management and patient prognosis.
{"title":"Prognostic Value of Circulating Fibrosis Biomarkers in Dilated Cardiomyopathy (DCM): Insights into Clinical Outcomes","authors":"Elham Kayvanpour, Farbod Sedaghat-Hamedani, Daniel Tian Li, Tobias Miersch, Tanja Weis, Imo Hoefer, Norbert Frey, Benjamin Meder","doi":"10.3390/biom14091137","DOIUrl":"https://doi.org/10.3390/biom14091137","url":null,"abstract":"Background: Dilated cardiomyopathy (DCM) involves myocardial remodeling, characterized by significant fibrosis and extracellular matrix expansion. These changes impair heart function, increasing the risk of heart failure and sudden cardiac death. This study investigates the prognostic value of circulating fibrosis biomarkers as a less invasive method in DCM patients. Methods: Plasma samples from 185 patients with confirmed DCM were analyzed to measure 13 circulating biomarkers using Luminex bead-based multiplex assays and ELISA. The prognostic value of these biomarkers was evaluated concerning heart failure-associated events and all-cause mortality. Results: Elevated MMP-2 levels (>1519.3 ng/mL) were linked to older age, higher diabetes prevalence, lower HDL, increased NT-proBNP and hs-TnT levels, and severe systolic dysfunction. High TIMP-1 levels (>124.9 ng/mL) correlated with elevated NT-proBNP, more atrial fibrillation, reduced exercise capacity, and larger right ventricles. Increased GDF-15 levels (>1213.9 ng/mL) were associated with older age, systemic inflammation, renal impairment, and poor exercise performance. Elevated OPN levels (>81.7 ng/mL) were linked to higher serum creatinine and NT-proBNP levels. Over a median follow-up of 32.4 months, higher levels of these biomarkers predicted worse outcomes, including increased risks of heart failure-related events and mortality. Conclusions: Circulating fibrosis biomarkers, particularly MMP-2, TIMP-1, GDF-15, and OPN, are valuable prognostic tools in DCM. They reflect the severity of myocardial remodeling and systemic disease burden, aiding in risk stratification and therapeutic intervention. Integrating these biomarkers into clinical practice could improve DCM management and patient prognosis.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kaiping Bai, Yanping Hou, Zhiyuan Zhang, Fei Yuan, Xiaoling Huang, Pengtao Liu, Xiangyu Zou, Jie Sun
Sacral spinal cord injury (SSCI) can disrupt bladder neuromodulation and impair detrusor function. Current studies provide limited information on the histologic and genetic changes associated with SSCI-related neurogenic lower urinary tract dysfunction (NLUTD), resulting in few treatment options. This study aimed to establish a simple animal model of SSCI to better understand the disease progression. Ninety 8-week-old Sprague-Dawley (SD) rats were randomly separated into sham operation and SSCI groups. The SSCI group underwent sacral spinal cord injury, while the sham group did not. Urodynamic and histological assessments were conducted at various intervals (1, 2, 3, 4, and 6 weeks) post-injury to elucidate the disease process. Urodynamic examinations revealed significant bladder dysfunction in the SSCI group compared to the sham group, stabilizing around 3–4 weeks post-injury. Histological examination, including hematoxylin–eosin and Masson’s trichrome staining, correlated these functional changes with bladder microstructural alterations. RNA-seq was performed on bladder tissues from the sham group and SSCI group at 6 weeks to identify differentially expressed genes and pathways. Selected genes were further analyzed using polymerase chain reaction (PCR). The findings indicated a pronounced inflammatory response in the first 2 weeks post-SSCI, progressing to bladder fibrosis at 3–4 weeks. In conclusion, this study presents a reliable, reproducible, and straightforward SSCI model, providing insights into bladder functional and morphological alterations post-SSCI and laying the groundwork for future therapeutic research.
{"title":"A New Rat Model of Sacral Cord Injury Producing a Neurogenic Bladder and Its Functional and Mechanistic Studies","authors":"Kaiping Bai, Yanping Hou, Zhiyuan Zhang, Fei Yuan, Xiaoling Huang, Pengtao Liu, Xiangyu Zou, Jie Sun","doi":"10.3390/biom14091141","DOIUrl":"https://doi.org/10.3390/biom14091141","url":null,"abstract":"Sacral spinal cord injury (SSCI) can disrupt bladder neuromodulation and impair detrusor function. Current studies provide limited information on the histologic and genetic changes associated with SSCI-related neurogenic lower urinary tract dysfunction (NLUTD), resulting in few treatment options. This study aimed to establish a simple animal model of SSCI to better understand the disease progression. Ninety 8-week-old Sprague-Dawley (SD) rats were randomly separated into sham operation and SSCI groups. The SSCI group underwent sacral spinal cord injury, while the sham group did not. Urodynamic and histological assessments were conducted at various intervals (1, 2, 3, 4, and 6 weeks) post-injury to elucidate the disease process. Urodynamic examinations revealed significant bladder dysfunction in the SSCI group compared to the sham group, stabilizing around 3–4 weeks post-injury. Histological examination, including hematoxylin–eosin and Masson’s trichrome staining, correlated these functional changes with bladder microstructural alterations. RNA-seq was performed on bladder tissues from the sham group and SSCI group at 6 weeks to identify differentially expressed genes and pathways. Selected genes were further analyzed using polymerase chain reaction (PCR). The findings indicated a pronounced inflammatory response in the first 2 weeks post-SSCI, progressing to bladder fibrosis at 3–4 weeks. In conclusion, this study presents a reliable, reproducible, and straightforward SSCI model, providing insights into bladder functional and morphological alterations post-SSCI and laying the groundwork for future therapeutic research.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Epithelial ovarian carcinoma poses a significant challenge due to its resistance to chemotherapy and propensity for metastasis, thereby reducing the effectiveness of conventional treatments. Hence, the identification of novel compounds capable of augmenting the anti-cancer efficacy of platinum-based chemotherapy is imperative. Oxyresveratrol (OXY), a derivative of resveratrol, has been demonstrated to possess antiproliferative and apoptosis-inducing effects across various cancer cell lines. Notably, OXY appears to exert its effects by inhibiting the PI3K/AKT/mTOR signaling pathway. However, the synergistic potential of OXY in combination with cisplatin against epithelial ovarian cancer has not yet been elucidated. The current study investigated the synergistic effects of OXY and cisplatin on the ovarian cancer cell lines SKOV3 and TOV21G. We found that OXY significantly enhanced cisplatin’s ability to reduce cell viability, induce apoptosis, induce cell cycle arrest, and increase the proportion of cells in the sub-G1 phase. Furthermore, OXY treatment alone dose-dependently inhibited the production of anti-apoptotic proteins including Mcl-1, Bcl-xL, and XIAP under EGF activation. Mechanistically, OXY suppressed the PI3K/AKT/mTOR signaling pathway by reducing phosphorylated AKT, while having no discernible effect on the MAPK pathway. These findings highlight OXY’s potential to enhance ovarian cancer cell sensitivity to chemotherapy, suggesting its development as a pharmaceutical adjunct for clinical use in combination therapies.
{"title":"Oxyresveratrol Enhances the Anti-Cancer Effect of Cisplatin against Epithelial Ovarian Cancer Cells through Suppressing the Activation of Protein Kinase B (AKT)","authors":"Phatarawat Thaklaewphan, Nitwara Wikan, Saranyapin Potikanond, Wutigri Nimlamool","doi":"10.3390/biom14091140","DOIUrl":"https://doi.org/10.3390/biom14091140","url":null,"abstract":"Epithelial ovarian carcinoma poses a significant challenge due to its resistance to chemotherapy and propensity for metastasis, thereby reducing the effectiveness of conventional treatments. Hence, the identification of novel compounds capable of augmenting the anti-cancer efficacy of platinum-based chemotherapy is imperative. Oxyresveratrol (OXY), a derivative of resveratrol, has been demonstrated to possess antiproliferative and apoptosis-inducing effects across various cancer cell lines. Notably, OXY appears to exert its effects by inhibiting the PI3K/AKT/mTOR signaling pathway. However, the synergistic potential of OXY in combination with cisplatin against epithelial ovarian cancer has not yet been elucidated. The current study investigated the synergistic effects of OXY and cisplatin on the ovarian cancer cell lines SKOV3 and TOV21G. We found that OXY significantly enhanced cisplatin’s ability to reduce cell viability, induce apoptosis, induce cell cycle arrest, and increase the proportion of cells in the sub-G1 phase. Furthermore, OXY treatment alone dose-dependently inhibited the production of anti-apoptotic proteins including Mcl-1, Bcl-xL, and XIAP under EGF activation. Mechanistically, OXY suppressed the PI3K/AKT/mTOR signaling pathway by reducing phosphorylated AKT, while having no discernible effect on the MAPK pathway. These findings highlight OXY’s potential to enhance ovarian cancer cell sensitivity to chemotherapy, suggesting its development as a pharmaceutical adjunct for clinical use in combination therapies.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Shteinfer-Kuzmine, Manikandan Santhanam, Varda Shoshan-Barmatz
This review presents current knowledge related to the voltage-dependent anion channel-1 (VDAC1) as a multi-functional mitochondrial protein that acts in regulating both cell life and death. The location of VDAC1 at the outer mitochondrial membrane (OMM) allows control of metabolic cross-talk between the mitochondria and the rest of the cell, and also enables its interaction with proteins that are involved in metabolic, cell death, and survival pathways. VDAC1′s interactions with over 150 proteins can mediate and regulate the integration of mitochondrial functions with cellular activities. To target these protein–protein interactions, VDAC1-derived peptides have been developed. This review focuses specifically on cell-penetrating VDAC1-based peptides that were developed and used as a “decoy” to compete with VDAC1 for its VDAC1-interacting proteins. These peptides interfere with VDAC1 interactions, for example, with metabolism-associated proteins such as hexokinase (HK), or with anti-apoptotic proteins such as Bcl-2 and Bcl-xL. These and other VDAC1-interacting proteins are highly expressed in many cancers. The VDAC1-based peptides in cells in culture selectively affect cancerous, but not non-cancerous cells, inducing cell death in a variety of cancers, regardless of the cancer origin or genetics. They inhibit cell energy production, eliminate cancer stem cells, and act very rapidly and at low micro-molar concentrations. The activity of these peptides has been validated in several mouse cancer models of glioblastoma, lung, and breast cancers. Their anti-cancer activity involves a multi-pronged attack targeting the hallmarks of cancer. They were also found to be effective in treating non-alcoholic fatty liver disease and diabetes mellitus. Thus, VDAC1-based peptides, by targeting VDAC1-interacting proteins, offer an affordable and innovative new conceptual therapeutic paradigm that can potentially overcome heterogeneity, chemoresistance, and invasive metastatic formation.
{"title":"VDAC1-Based Peptides as Potential Modulators of VDAC1 Interactions with Its Partners and as a Therapeutic for Cancer, NASH, and Diabetes","authors":"Anna Shteinfer-Kuzmine, Manikandan Santhanam, Varda Shoshan-Barmatz","doi":"10.3390/biom14091139","DOIUrl":"https://doi.org/10.3390/biom14091139","url":null,"abstract":"This review presents current knowledge related to the voltage-dependent anion channel-1 (VDAC1) as a multi-functional mitochondrial protein that acts in regulating both cell life and death. The location of VDAC1 at the outer mitochondrial membrane (OMM) allows control of metabolic cross-talk between the mitochondria and the rest of the cell, and also enables its interaction with proteins that are involved in metabolic, cell death, and survival pathways. VDAC1′s interactions with over 150 proteins can mediate and regulate the integration of mitochondrial functions with cellular activities. To target these protein–protein interactions, VDAC1-derived peptides have been developed. This review focuses specifically on cell-penetrating VDAC1-based peptides that were developed and used as a “decoy” to compete with VDAC1 for its VDAC1-interacting proteins. These peptides interfere with VDAC1 interactions, for example, with metabolism-associated proteins such as hexokinase (HK), or with anti-apoptotic proteins such as Bcl-2 and Bcl-xL. These and other VDAC1-interacting proteins are highly expressed in many cancers. The VDAC1-based peptides in cells in culture selectively affect cancerous, but not non-cancerous cells, inducing cell death in a variety of cancers, regardless of the cancer origin or genetics. They inhibit cell energy production, eliminate cancer stem cells, and act very rapidly and at low micro-molar concentrations. The activity of these peptides has been validated in several mouse cancer models of glioblastoma, lung, and breast cancers. Their anti-cancer activity involves a multi-pronged attack targeting the hallmarks of cancer. They were also found to be effective in treating non-alcoholic fatty liver disease and diabetes mellitus. Thus, VDAC1-based peptides, by targeting VDAC1-interacting proteins, offer an affordable and innovative new conceptual therapeutic paradigm that can potentially overcome heterogeneity, chemoresistance, and invasive metastatic formation.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NMR utilization in fragment-based drug discovery requires techniques to detect weakly binding fragments and to subsequently identify cooperatively binding fragments. Such cooperatively binding fragments can then be optimized or linked in order to develop viable drug candidates. Similarly, ligands or substrates that bind macromolecules (including enzymes) in competition with the endogenous ligand or substrate are valuable probes of macromolecular chemistry and function. The lengthy and costly process of identifying competitive or cooperative binding can be streamlined by coupling computational biochemistry and spectroscopy tools. The Clustering of Ligand Diffusion Coefficient Pairs (CoLD-CoP) method, previously developed by Snyder and co-workers, detects weakly binding ligands by analyzing pairs of diffusion spectra, obtained in the absence and the presence of a protein. We extended the CoLD-CoP method to analyze spectra pairs (each in the presence of a protein) with or without a critical ligand, to detect both competitive and cooperative binding.
{"title":"Application of CoLD-CoP to Detecting Competitively and Cooperatively Binding Ligands","authors":"Shiva V. Patnala, Roberto Robles, David A. Snyder","doi":"10.3390/biom14091136","DOIUrl":"https://doi.org/10.3390/biom14091136","url":null,"abstract":"NMR utilization in fragment-based drug discovery requires techniques to detect weakly binding fragments and to subsequently identify cooperatively binding fragments. Such cooperatively binding fragments can then be optimized or linked in order to develop viable drug candidates. Similarly, ligands or substrates that bind macromolecules (including enzymes) in competition with the endogenous ligand or substrate are valuable probes of macromolecular chemistry and function. The lengthy and costly process of identifying competitive or cooperative binding can be streamlined by coupling computational biochemistry and spectroscopy tools. The Clustering of Ligand Diffusion Coefficient Pairs (CoLD-CoP) method, previously developed by Snyder and co-workers, detects weakly binding ligands by analyzing pairs of diffusion spectra, obtained in the absence and the presence of a protein. We extended the CoLD-CoP method to analyze spectra pairs (each in the presence of a protein) with or without a critical ligand, to detect both competitive and cooperative binding.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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