International Journal of Molecular Sciences最新文献_第10页

Evaluation of Spliceosome Protein SmD2 as a Potential Target for Cancer Therapy. 评估作为癌症治疗潜在靶点的剪接体蛋白 SmD2

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-06 DOI: 10.3390/ijms252313131

Jing Li, Peiyu Li, Tereza Brachtlova, Ida H van der Meulen-Muileman, Henk Dekker, Vishal S Kumar, Marieke Fransen, Idris Bahce, Emanuela Felley-Bosco, Victor W van Beusechem

{"title":"Evaluation of Spliceosome Protein SmD2 as a Potential Target for Cancer Therapy.","authors":"Jing Li, Peiyu Li, Tereza Brachtlova, Ida H van der Meulen-Muileman, Henk Dekker, Vishal S Kumar, Marieke Fransen, Idris Bahce, Emanuela Felley-Bosco, Victor W van Beusechem","doi":"10.3390/ijms252313131","DOIUrl":"https://doi.org/10.3390/ijms252313131","url":null,"abstract":"The core spliceosome Sm proteins are gaining attention as potential targets for cancer treatment. Here, we evaluate this, with focus on SmD2. A pan-cancer analysis including 26 solid tumor types revealed that the SmD2-encoding SNRPD2 gene was overexpressed in almost all cancers. In several cancers, high SNRPD2 expression was associated with a poor prognosis. To investigate the vulnerability of human cells to the loss of SmD2 expression, we silenced SNRPD2 using a short hairpin-expressing lentiviral vector in established cancer cell lines; in short-term cultured melanoma cells; and in several normal cell cultures, including cancer-associated fibroblasts cultured from non-small cell lung cancer resections. Additionally, we analyzed publicly available cell viability datasets for the dependency of cancer cell lines to SmD2 expression. Together, these studies clearly established SmD2 as a cancer-selective lethal target. Delving into genes with similar essentiality profiles to SNRPD2, we uncovered the intersected lethal stress between the loss of SmD2 and the loss of gene products participating in not only different mRNA processing steps including mRNA splicing, but also processes for coordinated protein production, as well as mitosis. Furthermore, we could correlate SNRPD2 expression to the responses of cancer cells to several FDA-approved anti-tumor drugs, especially to drugs inhibiting the cell cycle. Overall, our study confirms the anticipated role for targeting SmD2 in cancer treatment and reveals non-canonical SmD2 functions beyond mRNA splicing that could contribute to the dependency of cancer cells to high SNRPD2 expression.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835682","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}

引用次数: 0

Circadian Rhythms of Clock Genes After Transplantation of Mesenchymal Stem Cells with Type 2 Diabetes Mellitus. 间充质干细胞移植后 2 型糖尿病患者时钟基因的昼夜节律。

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-06 DOI: 10.3390/ijms252313145

Michiko Horiguchi, Kenichi Yoshihara, Kenji Watanabe, Yuya Tsurudome, Yoichi Mizukami, Kentaro Ushijima

{"title":"Circadian Rhythms of Clock Genes After Transplantation of Mesenchymal Stem Cells with Type 2 Diabetes Mellitus.","authors":"Michiko Horiguchi, Kenichi Yoshihara, Kenji Watanabe, Yuya Tsurudome, Yoichi Mizukami, Kentaro Ushijima","doi":"10.3390/ijms252313145","DOIUrl":"https://doi.org/10.3390/ijms252313145","url":null,"abstract":"Regenerative therapy involving stem cell transplantation has become an option for the radical treatment of diabetes mellitus. Disruption in the clock genes of stem cells affects the homeostasis of transplanted tissues. We examined the circadian rhythm of genes in transplanted adipose-derived mesenchymal stem cells derived from a patient with type 2 diabetes mellitus (T2DM-ADSC). The clock genes (PER2, CLOCK1, CRY1, and ARNTL[BMAL1]) exhibited similar daily fluctuations in phase and amplitude between a group transplanted with adipose-derived mesenchymal stem cells derived from a healthy individual (N-ADSC) and a group transplanted with T2DM-ADSC. The findings demonstrated that clock genes in stem cells are synchronized with those in living organisms. Next-generation sequencing was then employed to categorize genes that exhibited variation in expression between N-ADSC and T2DM-ADSC. MTATP8P1 and NDUFA7_2 gene expression was significantly reduced at two time points (ZT6 and ZT18), and daily fluctuations were lost. The present study reports, for the first time, that the circadian rhythms of MTATP8P1 and NDUFA7_2, genes involved in mitochondrial processes, are altered in T2DM-ADSC.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835357","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}

引用次数: 0

Calcium Ions in the Physiology and Pathology of the Central Nervous System. 中枢神经系统生理学和病理学中的钙离子。

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-06 DOI: 10.3390/ijms252313133

Damian Pikor, Mikołaj Hurła, Bartosz Słowikowski, Oliwia Szymanowicz, Joanna Poszwa, Natalia Banaszek, Alicja Drelichowska, Paweł P Jagodziński, Wojciech Kozubski, Jolanta Dorszewska

{"title":"Calcium Ions in the Physiology and Pathology of the Central Nervous System.","authors":"Damian Pikor, Mikołaj Hurła, Bartosz Słowikowski, Oliwia Szymanowicz, Joanna Poszwa, Natalia Banaszek, Alicja Drelichowska, Paweł P Jagodziński, Wojciech Kozubski, Jolanta Dorszewska","doi":"10.3390/ijms252313133","DOIUrl":"10.3390/ijms252313133","url":null,"abstract":"Calcium ions play a key role in the physiological processes of the central nervous system. The intracellular calcium signal, in nerve cells, is part of the neurotransmission mechanism. They are responsible for stabilizing membrane potential and controlling the excitability of neurons. Calcium ions are a universal second messenger that participates in depolarizing signal transduction and contributes to synaptic activity. These ions take an active part in the mechanisms related to memory and learning. As a result of depolarization of the plasma membrane or stimulation of receptors, there is an extracellular influx of calcium ions into the cytosol or mobilization of these cations inside the cell, which increases the concentration of these ions in neurons. The influx of calcium ions into neurons occurs via plasma membrane receptors and voltage-dependent ion channels. Calcium channels play a key role in the functioning of the nervous system, regulating, among others, neuronal depolarization and neurotransmitter release. Channelopathies are groups of diseases resulting from mutations in genes encoding ion channel subunits, observed including the pathophysiology of neurological diseases such as migraine. A disturbed ability of neurons to maintain an appropriate level of calcium ions is also observed in such neurodegenerative processes as Alzheimer's disease, Parkinson's disease, Huntington's disease, and epilepsy. This review focuses on the involvement of calcium ions in physiological and pathological processes of the central nervous system. We also consider the use of calcium ions as a target for pharmacotherapy in the future.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835789","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}

引用次数: 0

Selection for Resilience in Livestock Production Systems. 畜牧生产系统中的抗逆性选择。

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-06 DOI: 10.3390/ijms252313109

Houda Laghouaouta, Lorenzo J Fraile, Ramona N Pena

{"title":"Selection for Resilience in Livestock Production Systems.","authors":"Houda Laghouaouta, Lorenzo J Fraile, Ramona N Pena","doi":"10.3390/ijms252313109","DOIUrl":"https://doi.org/10.3390/ijms252313109","url":null,"abstract":"Selective breeding for improved animal resilience is becoming critical to increase the sustainability of production systems. Despite the existence of a genetic component for resilience, breeding for improved resilience has been limited by the absence of a consensus on its definition and quantifying method. In this work, we provide a review of (i) the definition of resilience and related concepts such as robustness, resistance, and tolerance; (ii) possible quantifying methods for resilience; (iii) its genetic background; and (iv) insights about its improvement through selective breeding. We suggest that a resilient animal may be defined as an individual that is able to cope with a perturbation(s) and rapidly bounce back to normal functioning if altered. Furthermore, since challenging conditions lead to trade-offs and, consequently, deviations between basic physiological functions, we suggest using these deviations as indicators for resilience. These resilience indicators may also be used as proxies to study the genetic determinism and background of resilience in livestock species. Finally, we discuss possible strategies to improve resilience and review the implementation of associated genetic markers for resilience indicators in selection schemes.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836242","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}

引用次数: 0

Functional Study of PTSMAD4 in the Spermatogenesis of the Swimming Crab Portunus trituberculatus.

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-06 DOI: 10.3390/ijms252313126

Yu Zhang, Qiu-Meng Xiang, Chang-Kao Mu, Chun-Lin Wang, Cong-Cong Hou

{"title":"Functional Study of PTSMAD4 in the Spermatogenesis of the Swimming Crab Portunus trituberculatus.","authors":"Yu Zhang, Qiu-Meng Xiang, Chang-Kao Mu, Chun-Lin Wang, Cong-Cong Hou","doi":"10.3390/ijms252313126","DOIUrl":"https://doi.org/10.3390/ijms252313126","url":null,"abstract":"Portunus trituberculatus holds significant economic value. The spermatogenesis is regulated by numerous signaling pathways. Among them, the TGF-β signaling pathway plays an important role in the development of testes and spermatogenesis. Smad4 is a Co-Smad protein that forms a complex with R-Smad to regulate the expression of target genes. The sperm structure in crustaceans differs greatly from that in mammals, with mature sperm lacking tails. Our previous studies have reported the function of R-Smad in the spermatogenesis of P. trituberculatus. In this study, we cloned the full-length cDNA sequence of PTSMAD4; immunofluorescence technology revealed that PTSMAD4 is expressed throughout all stages of spermatogenesis. We knocked down the expression of PTSMAD4 in P. trituberculatus using RNAi technology, and the immunofluorescence results show abnormal co-localization and weakened signals of PTSMAD4 and PTSMAD2. Additionally, transcriptome sequencing results enriched functional genes and pathways related to spermatogenesis. This study indicates that PTSMAD4 may participate in the spermatogenesis process through its involvement in signal transduction. This research not only lays the foundation for further study of the function of the TGF-β signaling pathway in spermatogenesis but also provides a theoretical basis for further investigation of the spermatogenesis mechanism in crustaceans.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835295","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}

引用次数: 0

Spatially Resolved Molecular Characterization of Noninvasive Follicular Thyroid Neoplasms with Papillary-like Nuclear Features (NIFTPs) Identifies a Distinct Proteomic Signature Associated with RAS-Mutant Lesions.

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-06 DOI: 10.3390/ijms252313115

Vanna Denti, Angela Greco, Antonio Maria Alviano, Giulia Capitoli, Nicole Monza, Andrew Smith, Daniela Pilla, Alice Maggioni, Mariia Ivanova, Konstantinos Venetis, Fausto Maffini, Mattia Garancini, Angela Ida Pincelli, Stefania Galimberti, Fulvio Magni, Nicola Fusco, Vincenzo L'Imperio, Fabio Pagni

{"title":"Spatially Resolved Molecular Characterization of Noninvasive Follicular Thyroid Neoplasms with Papillary-like Nuclear Features (NIFTPs) Identifies a Distinct Proteomic Signature Associated with RAS-Mutant Lesions.","authors":"Vanna Denti, Angela Greco, Antonio Maria Alviano, Giulia Capitoli, Nicole Monza, Andrew Smith, Daniela Pilla, Alice Maggioni, Mariia Ivanova, Konstantinos Venetis, Fausto Maffini, Mattia Garancini, Angela Ida Pincelli, Stefania Galimberti, Fulvio Magni, Nicola Fusco, Vincenzo L'Imperio, Fabio Pagni","doi":"10.3390/ijms252313115","DOIUrl":"https://doi.org/10.3390/ijms252313115","url":null,"abstract":"Follicular-patterned thyroid neoplasms comprise a diverse group of lesions that pose significant challenges in terms of differential diagnosis based solely on morphologic and genetic features. Thus, the identification of easily testable biomarkers complementing microscopic and genetic analyses is a highly anticipated advancement that could improve diagnostic accuracy, particularly for noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs). These tumors exhibit considerable morphological and molecular heterogeneity, which may complicate their distinction from structurally similar neoplasms, especially when genetic analyses reveal shared genomic alterations (e.g., RAS mutations). Here, we integrated next-generation sequencing (NGS) with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to perform a proteogenomic analysis on 85 NIFTPs (n = 30 RAS-mutant [RAS-mut] and n = 55 RAS-wild type [RAS-wt]), with the aim to detect putative biomarkers of RAS-mut lesions. Through this combined approach, we identified four proteins that were significantly underexpressed in RAS-mut as compared to RAS-wt NIFTPs. These proteins could serve as readily accessible markers in morphologically borderline cases showing RAS mutations. Additionally, our findings may provide insights into the distinct pathogenic pathways through which RAS-mut and RAS-wt NIFTPs arise, highlighting the pivotal role of constitutive RAS-mitogen-activated protein kinase (MAPK) pathway activation in the development and progression of RAS-mut tumors.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835875","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}

引用次数: 0

Genome-Wide Identification and Expression Analysis of Carotenoid Cleavage Dioxygenase Genes in Salvia miltiorrhiza.

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-06 DOI: 10.3390/ijms252313138

Minyu Shou, Qinzhe Lin, Lulu Peng, Zijie Wang, Ying Xu, Jiaochen Qi, Degang Zhao, Min Shi, Guoyin Kai

{"title":"Genome-Wide Identification and Expression Analysis of Carotenoid Cleavage Dioxygenase Genes in Salvia miltiorrhiza.","authors":"Minyu Shou, Qinzhe Lin, Lulu Peng, Zijie Wang, Ying Xu, Jiaochen Qi, Degang Zhao, Min Shi, Guoyin Kai","doi":"10.3390/ijms252313138","DOIUrl":"https://doi.org/10.3390/ijms252313138","url":null,"abstract":"In the process of catalyzing carotenoids into various apocarotenoids and other derivatives, carotenoid cleavage dioxygenases (CCDs) play key roles. However, little information on CCDs has been reported in regard to Salvia miltiorrhiza. In this study, a total of 21 CCD genes were identified in the whole genome of S. miltiorrhiza, mainly distributed between five chromosomes. Phylogenetic relationship analysis revealed that 21 SmCCD genes were classified into four subfamilies, including SmCCD4, 7, 8, and NCED; the members of the same subfamily show similar gene structures and tertiary structures. The interspecific collinearity with other plant species, such as Arabidopsis thaliana and Oryza sativa was analyzed. Cis-elements analysis demonstrated that the majority were stress response-, light response-, growth-, and development-related. The expression pattern of the SmCCD genes was expressed in the analyzed tissues. Furthermore, the majority of the SmCCD4 subfamily members varied in their expression levels under the treatment of MeJA, YE, and ABA, indicating the potential function of SmCCD4 in the metabolism process of S. miltiorrhiza. In general, this study provides a systematic analysis of SmCCD genes and lays the foundation for uncovering the regulation and function of SmCCD genes in S. miltiorrhiza.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836072","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}

引用次数: 0

Hypoxia-Inducible Factor-2α Promotes Liver Fibrosis by Inducing Hepatocellular Death.

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-06 DOI: 10.3390/ijms252313114

Raja Gopal Reddy Mooli, Dhanunjay Mukhi, Mikayla Watt, Veerababu Nagati, Sara M Reed, Nikita K Gandhi, Michael Oertel, Sadeesh K Ramakrishnan

{"title":"Hypoxia-Inducible Factor-2α Promotes Liver Fibrosis by Inducing Hepatocellular Death.","authors":"Raja Gopal Reddy Mooli, Dhanunjay Mukhi, Mikayla Watt, Veerababu Nagati, Sara M Reed, Nikita K Gandhi, Michael Oertel, Sadeesh K Ramakrishnan","doi":"10.3390/ijms252313114","DOIUrl":"https://doi.org/10.3390/ijms252313114","url":null,"abstract":"The activation of hypoxia-inducible factors (HIF)-1α and 2α in the liver is closely linked to the progression of fatty liver diseases. Prior studies indicated that disrupting hepatocyte HIF-2α attenuates diet-induced hepatic steatosis, subsequently decreasing fibrosis. However, the direct role of hepatocyte HIF-2α in liver fibrosis has not been addressed. Hepatic HIF-2α expression was examined in mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis. Conditional hepatocyte Hif-2α knockout mice were employed to investigate the role of hepatocyte HIF-2α in fibrosis. Markers of apoptosis, proliferation, inflammation, and fibrosis were assessed through biochemical, molecular, and histological analyses. We found an induction of HIF-2α in CCL4-injected liver injury and fibrosis mouse models. Hepatocyte-specific deletion of HIF-2α attenuated stellate cell activation and fibrosis, with no significant difference in inflammation. Disrupting hepatocyte HIF-2α led to reduced injury-mediated hepatocellular apoptosis. Surviving hepatocytes exhibited hypertrophy, which was strongly associated with the activation of c-JUN signaling. Our study demonstrates a direct role of hepatocyte HIF-2α in liver fibrosis by promoting hepatocyte apoptosis. The reduction in apoptosis and induction of hepatocyte hypertrophy following HIF-2α disruption is closely linked to enhanced c-JUN signaling, a survival mechanism in response to liver injury. These findings highlight HIF-2α as a potential therapeutic target for liver fibrosis.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836089","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}

引用次数: 0

Pararamosis, a Neglected Tropical Disease Induced by Premolis semirufa Caterpillar Toxins: Investigating Their Effects on Synovial Cell Inflammation.

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-06 DOI: 10.3390/ijms252313149

Paula C Pohl, Isadora M Villas-Boas, Giselle Pidde, Denise V Tambourgi

{"title":"Pararamosis, a Neglected Tropical Disease Induced by Premolis semirufa Caterpillar Toxins: Investigating Their Effects on Synovial Cell Inflammation.","authors":"Paula C Pohl, Isadora M Villas-Boas, Giselle Pidde, Denise V Tambourgi","doi":"10.3390/ijms252313149","DOIUrl":"https://doi.org/10.3390/ijms252313149","url":null,"abstract":"Pararamosis, also known as Pararama-associated phalangeal periarthritis, is a neglected tropical disease primarily affecting rubber tappers in the Amazon region. It is caused by contact with the urticating hairs of the Premolis semirufa moth caterpillar, which resides in rubber plantations. The condition is marked by the thickening of the articular synovial membrane and cartilage impairment, features associated with chronic synovitis. Given the significance of synovial inflammation in osteoarticular diseases, in this study, the role of synoviocytes and their interactions with macrophages and chondrocytes are examined when stimulated by Pararama toxins. Synoviocytes and macrophages treated with Pararama hair extract showed an increased production of cytokines IL-6, IL-1β, and TNF-α, indicating a direct effect on these cells. In cocultures, there was a significant rise in inflammation, with levels of IL-1β, IL-6, and chemokines CCL2, CCL5, and CXCL8 increasing up to seven times compared to monocultures. Additionally, matrix-degrading enzymes MMP-1 and MMP-3 were significantly elevated in cocultures. Chondrocytes exposed to the extract also produced IL-6, CCL2, and CCL5, and in cocultures with synoviocytes, there was a notable increase in IL-6, CCL5, and CXCL8, as well as a doubling of MMP-1 and MMP-3 levels. These findings underscore the critical role of cell crosstalk in the inflammatory and catabolic processes associated with pararamosis and demonstrate how Pararama hair extract can influence factors affecting cartilage health, providing valuable insights into this condition.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836330","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}

引用次数: 0

Potent Anti-Cancer Activity of 1-Dehydrodiosgenone from the Product of Microbial Transformation of Steroid Saponins. 微生物转化甾体皂苷产物中的 1-脱氢薯蓣皂苷具有强效抗癌活性

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-06 DOI: 10.3390/ijms252313118

Quanshun Li, Shirong Feng, Yuanyuan Zhang, Fangyuan Mou, Ting Guo, Baofu Qin, Yihan Liu

{"title":"Potent Anti-Cancer Activity of 1-Dehydrodiosgenone from the Product of Microbial Transformation of Steroid Saponins.","authors":"Quanshun Li, Shirong Feng, Yuanyuan Zhang, Fangyuan Mou, Ting Guo, Baofu Qin, Yihan Liu","doi":"10.3390/ijms252313118","DOIUrl":"https://doi.org/10.3390/ijms252313118","url":null,"abstract":"Steroids are extensively used in the pharmaceutical industry as industrial raw materials for the production of anti-inflammatory and anti-tumor drugs. Microbial transformation, an environmentally friendly method, displays the potential for preparing steroids on an industrial scale. In this study, four steroids, including Diosgenin, Smilagenone, Yamogenin, and 1-Dehydrodiosgenone, were isolated and identified from the solid-state fermentation (SSF) product of a novel Fusarium oxysporum strain, and their anti-tumor activities were investigated. The cytotoxicity assay showed that 1-Dehydrodiosgenone had significant inhibitory effects on three tumor cell lines, Hala, A549, and Mad-MB468 cells, with IC50s of 6.59 μM, 5.43 μM, and 4.81 μM, respectively. 1-Dehydrodiosgenone significantly induced apoptosis and necrosis of Hala, A549, and Mad-MB468 cells by upregulating the expressions of cleaved caspase-3, cleaved PARP, Bax, and Bad. Moreover, no significant organ damage was observed in mice based on safety tests. Therefore, 1-Dehydrodiosgenone is expected to be developed as a safe and broad-spectrum anti-cancer agent.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836146","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}

引用次数: 0