International Journal of Molecular Sciences最新文献

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Integrated Transcriptomic and Proteomic Analyses of Antler Growth and Ossification Mechanisms.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313215
Ruijia Liu, Pan Zhang, Jiade Bai, Zhenyu Zhong, Yunfang Shan, Zhibin Cheng, Qingxun Zhang, Qingyun Guo, Hao Zhang, Bo Zhang
{"title":"Integrated Transcriptomic and Proteomic Analyses of Antler Growth and Ossification Mechanisms.","authors":"Ruijia Liu, Pan Zhang, Jiade Bai, Zhenyu Zhong, Yunfang Shan, Zhibin Cheng, Qingxun Zhang, Qingyun Guo, Hao Zhang, Bo Zhang","doi":"10.3390/ijms252313215","DOIUrl":"https://doi.org/10.3390/ijms252313215","url":null,"abstract":"<p><p>Antlers are the sole mammalian organs capable of continuous regeneration. This distinctive feature has evolved into various biomedical models. Research on mechanisms of antler growth, development, and ossification provides valuable insights for limb regeneration, cartilage-related diseases, and cancer mechanisms. Here, ribonucleic acid sequencing (RNA-seq) and four-dimensional data-independent acquisition (4D DIA) technologies were employed to examine gene and protein expression differences among four tissue layers of the Chinese milu deer antler: reserve mesenchyme (RM), precartilage (PC), transition zone (TZ), cartilage (CA). Overall, 4611 differentially expressed genes (DEGs) and 2388 differentially expressed proteins (DEPs) were identified in the transcriptome and proteome, respectively. Among the 828 DEGs common to both omics approaches, genes from the collagen, integrin, and solute carrier families, and signaling molecules were emphasized for their roles in the regulation of antler growth, development, and ossification. Bioinformatics analysis revealed that in addition to being regulated by vascular and nerve regeneration pathways, antler growth and development are significantly influenced by numerous cancer-related signaling pathways. This indicates that antler growth mechanisms may be similar to those of cancer cell proliferation and development. This study lays a foundation for future research on the mechanisms underlying the rapid growth and ossification of antlers.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835836","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
Impact of the COL1A1 Gene Polymorphisms on Pain Perception in Tennis Elbow Patients: A Two-Year Prospective Cohort Study.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313221
Paweł Niemiec, Alicja Jarosz, Tomasz Nowak, Anna Balcerzyk-Matić, Tomasz Iwanicki, Joanna Iwanicka, Katarzyna Gawron, Marcin Kalita, Sylwia Górczyńska-Kosiorz, Wojciech Kania, Karol Szyluk
{"title":"Impact of the <i>COL1A1</i> Gene Polymorphisms on Pain Perception in Tennis Elbow Patients: A Two-Year Prospective Cohort Study.","authors":"Paweł Niemiec, Alicja Jarosz, Tomasz Nowak, Anna Balcerzyk-Matić, Tomasz Iwanicki, Joanna Iwanicka, Katarzyna Gawron, Marcin Kalita, Sylwia Górczyńska-Kosiorz, Wojciech Kania, Karol Szyluk","doi":"10.3390/ijms252313221","DOIUrl":"https://doi.org/10.3390/ijms252313221","url":null,"abstract":"<p><p>The <i>COL1A1</i> gene encodes the α1 chain of type I collagen, and the data reported so far demonstrate that its polymorphic variants may affect biomechanical properties of bones, muscles, and tendons, and contribute to musculoskeletal disorders. Given, however, limited research on these variants in tendon pathology, we analyzed the impact of <i>COL1A1</i> polymorphisms on the tendinopathy phenotype and the effectiveness of platelet-rich plasma (PRP) treatment for tennis elbow. Pain perception and therapy outcomes were analyzed from baseline, i.e., before PRP injection to two years post-PRP injection in a cohort of 107 patients. The study focused on seven <i>COL1A1</i> variants: rs2249492 (C/T), rs2586488 (A/G), rs2075558 (A/C), rs2253369 (C/T), rs35231764 (A/G), rs1800012 (C/A), and rs9898186 (C/T). We demonstrated that carriers of the TT/CT (rs2249492), AA/AC (rs1800012), and TT/CT (rs9898186) genotypes reported pain related to injury more frequently than subjects with other <i>COL1A1</i> variants, also in the context of performing specific activities and other pain characteristics. These polymorphisms did not significantly influence therapy effectiveness, although rs35231764 showed a moderate effect. In conclusion, the T (rs2249492), A (rs1800012), and T (rs9898186) alleles of <i>COL1A1</i> gene are risk factors for pain perception in tennis elbow patients, but do not appear to substantially impact PRP treatment outcomes.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836104","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
Long-Term Yo-Yo Dieting Exaggerates Liver Steatosis and Lesions but Preserves Muscle Performance in Male Zebrafish.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313225
Tzu-Chieh Hsu, Chun-Hsien Chiang, I-Hsuan Liu, Chih-Yun Wang, Ching-Yi Chen
{"title":"Long-Term Yo-Yo Dieting Exaggerates Liver Steatosis and Lesions but Preserves Muscle Performance in Male Zebrafish.","authors":"Tzu-Chieh Hsu, Chun-Hsien Chiang, I-Hsuan Liu, Chih-Yun Wang, Ching-Yi Chen","doi":"10.3390/ijms252313225","DOIUrl":"https://doi.org/10.3390/ijms252313225","url":null,"abstract":"<p><p>Weight regain within one year after weight loss is frequently observed and is referred to as yo-yo dieting or weight cycling. In this study, we explore the effects of yo-yo dieting on the liver, adipose tissue, and muscle characteristics of male zebrafish. Four-month-old AB wild-type male zebrafish were randomly assigned to three groups: high-calorie intake (H, seven meals per day), low-calorie intake (L, two meals per day), and yo-yo diet (the low- and high-calorie alternation switched every two weeks) groups. Feeding the fish the H diet for over 8 weeks led to steatosis and damage to the liver. The yo-yo diet reduced liver lipid accumulation at week eight but caused a similar degree of lipid accumulation as the H diet thereafter. It was found that twenty weeks of yo-yo dieting actually exacerbated hepatic damage. Compared to the L diet, feeding the fish on the yo-yo and H diets for a period of 20 weeks significantly increased the size of muscle fibers, resulting in higher speed during burst swimming and a significant increase in the size and number of adipocytes in the abdominal tissue. To summarize, short-term yo-yo dieting was found to attenuate hepatosteatosis and maintain fast-twitch muscle function. Long-term yo-yo dieting preserved fast-twitch muscle function and muscle fiber size; however, it exacerbated the pathological changes in the liver.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836239","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
The Role of the Vaginal and Endometrial Microbiomes in Infertility and Their Impact on Pregnancy Outcomes in Light of Recent Literature. 从最新文献看阴道和子宫内膜微生物组在不孕症中的作用及其对妊娠结果的影响》(The Role of Vaginal and Endometrial Microbiomes in Infertility and Their Impact on Pregnancy Outcomes in Light of Recent Literature)。
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313227
Bernadett Balla, Anett Illés, Bálint Tobiás, Henriett Pikó, Artúr Beke, Miklós Sipos, Péter Lakatos, János P Kósa
{"title":"The Role of the Vaginal and Endometrial Microbiomes in Infertility and Their Impact on Pregnancy Outcomes in Light of Recent Literature.","authors":"Bernadett Balla, Anett Illés, Bálint Tobiás, Henriett Pikó, Artúr Beke, Miklós Sipos, Péter Lakatos, János P Kósa","doi":"10.3390/ijms252313227","DOIUrl":"10.3390/ijms252313227","url":null,"abstract":"<p><p>The Human Microbiome Project (HMP), initiated in 2007, aimed to gather comprehensive knowledge to create a genetic and metabolic map of human-associated microorganisms and their contribution to physiological states and predisposition to certain diseases. Research has revealed that the human microbiome is highly diverse and exhibits significant interpersonal variability; consequently, its exact impact on health remains unclear. With the development of next-generation sequencing (NGS) technologies, the broad spectrum of microbial communities has been better characterized. The lower female genital tract, particularly the vagina, is colonized by various bacterial species, with <i>Lactobacillus</i> spp. predominating. The upper female genital tract, especially the uterus, was long considered sterile. However, recent studies have identified a distinct endometrial microbiome. A <i>Lactobacillus</i>-dominated microbiome of the female genital tract is associated with favorable reproductive outcomes, including higher success rates in natural conception and assisted reproductive technologies (ART). Conversely, microbial imbalances, or dysbiosis, marked by reduced <i>Lactobacilli</i> as well as an increased diversity and abundance of pathogenic species (e.g., <i>Gardnerella vaginalis</i> or <i>Prevotella</i> spp.), are linked to infertility, implantation failure, and pregnancy complications such as miscarriage and preterm birth. Dysbiosis can impair the vaginal or endometrial mucosal barrier and also trigger pro-inflammatory responses, disrupting essential reproductive processes like implantation. Despite growing evidence supporting the associations between the microbiome of the female genital tract and certain gynecological and obstetric conditions, clear microbial biomarkers have yet to be identified, and there is no consensus on the precise composition of a normal or healthy microbiome. The lack of standardized protocols and biomarkers limits the routine use of microbiome screening tests. Therefore, larger patient cohorts are needed to facilitate comparative studies and improve our understanding of the physiological microbiome profiles of the uterus and vagina, as well as how dysbiosis may influence clinical outcomes. Further research is required to refine diagnostic tools and develop personalized therapeutic strategies to improve fertility and pregnancy outcomes.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835739","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
Mitigation of Atherosclerotic Vascular Damage and Cognitive Improvement Through Mesenchymal Stem Cells in an Alzheimer's Disease Mouse Model. 通过间充质干细胞缓解动脉粥样硬化性血管损伤并改善阿尔茨海默病小鼠模型的认知能力
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313210
Woong Jin Lee, Kyoung Joo Cho, Gyung Whan Kim
{"title":"Mitigation of Atherosclerotic Vascular Damage and Cognitive Improvement Through Mesenchymal Stem Cells in an Alzheimer's Disease Mouse Model.","authors":"Woong Jin Lee, Kyoung Joo Cho, Gyung Whan Kim","doi":"10.3390/ijms252313210","DOIUrl":"https://doi.org/10.3390/ijms252313210","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive memory loss and other cognitive disturbances. Patients with AD can be vulnerable to vascular damage, and damaged vessels can lead to cognitive impairment. Mesenchymal stem cell (MSC) treatment has shown potential in ameliorating AD pathogenesis, but its effect on vascular function remains unclear. This study aimed to improve cognitive function by alleviating atherosclerosis-induced vessel damage using MSCs in mice with a genetic AD background. In this study, a 5xFAD mouse model of AD was used, and atherosclerotic vessel damage was induced by high-fat diets (HFDs). MSCs were injected into the tail vein along with mannitol in 5xFAD mice on an HFD. MSCs were detected in the brain, and vascular damage was improved following MSC treatment. Behavioral tests showed that MSCs enhanced cognitive function, as measured by the Y-maze and passive avoidance tests. Additionally, muscle strength measured by the rotarod test was also increased by MSCs in AD mice with vessel damage induced by HFDs. Overall, our results suggest that stem cells can alleviate vascular damage caused by metabolic diseases, including HFDs, and vascular disease in individuals carrying the AD gene. Consequently, this alleviates cognitive decline related to vascular dementia symptoms.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836172","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 Analysis of TAAR1 Expression in the Intestine Wall and the Effect of Its Gene Knockout on the Gut Microbiota in Mice.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313216
Anastasia N Vaganova, Ilya S Zhukov, Taisiia S Shemiakova, Konstantin A Rozhkov, Lyubov S Alferova, Alena B Karaseva, Elena I Ermolenko, Raul R Gainetdinov
{"title":"Functional Analysis of TAAR1 Expression in the Intestine Wall and the Effect of Its Gene Knockout on the Gut Microbiota in Mice.","authors":"Anastasia N Vaganova, Ilya S Zhukov, Taisiia S Shemiakova, Konstantin A Rozhkov, Lyubov S Alferova, Alena B Karaseva, Elena I Ermolenko, Raul R Gainetdinov","doi":"10.3390/ijms252313216","DOIUrl":"https://doi.org/10.3390/ijms252313216","url":null,"abstract":"<p><p>Currently, the TAAR1 receptor has been identified in various cell groups in the intestinal wall. It recognizes biogenic amine compounds like phenylethylamine or tyramine, which are products of decarboxylation of phenylalanine and tyrosine by endogenous or bacterial decarboxylases. Since several gut bacteria produce these amines, TAAR1 is suggested to be involved in the interaction between the host and gut microbiota. The purpose of this present study was to clarify the TAAR1 function in the intestinal wall and estimate the TAAR1 gene knockout effect on gut microbiota composition. By analyzing public transcriptomic data of the GEO repository, we identified TAAR1 expression in enterocytes, enteroendocrine cells, tuft cells, and myenteric neurons in mice. The analysis of genes co-expressed with TAAR1 in enteroendocrine cells allows us to suggest the TAAR1 involvement in enteroendocrine cell maturation. Also, in myenteric neurons, we identified the co-expression of TAAR1 with calbindin, which is specific for sensory neurons. The 16S rRNA gene-based analysis of fecal microbiota revealed a slight but significant impact of TAAR1 gene knockout in mice on the gut microbial community, which manifests in the higher diversity, accompanied by low between-sample variability and reorganization of the microbial co-occurrence network.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836086","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
Discovery of a Small Molecule with an Inhibitory Role for RAB11.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313224
Camille Lempicki, Julian Milosavljevic, Christian Laggner, Simone Tealdi, Charlotte Meyer, Gerd Walz, Konrad Lang, Carlo Cosimo Campa, Tobias Hermle
{"title":"Discovery of a Small Molecule with an Inhibitory Role for RAB11.","authors":"Camille Lempicki, Julian Milosavljevic, Christian Laggner, Simone Tealdi, Charlotte Meyer, Gerd Walz, Konrad Lang, Carlo Cosimo Campa, Tobias Hermle","doi":"10.3390/ijms252313224","DOIUrl":"https://doi.org/10.3390/ijms252313224","url":null,"abstract":"<p><p>RAB11, a pivotal RabGTPase, regulates essential cellular processes such as endocytic recycling, exocytosis, and autophagy. The protein was implicated in various human diseases, including cancer, neurodegenerative disorders, viral infections, and podocytopathies. However, a small-molecular inhibitor is lacking. The complexity and workload associated with potential assays make conducting large-scale screening for RAB11 challenging. We employed a tiered approach for drug discovery, utilizing deep learning-based computational screening to preselect compounds targeting a specific pocket of RAB11 protein with experimental validation by an in vitro platform reflecting RAB11 activity through the exocytosis of GFP. Further validation included the exposure of <i>Drosophila</i> by drug feeding. In silico pre-screening identified 94 candidates, of which 9 were confirmed using our in vitro platform for Rab11 activity. Focusing on compounds with high potency, we assessed autophagy, which independently requires RAB11, and validated three of these compounds. We further analyzed the dose-response relationship, observing a biphasic, potentially hormetic effect. Two candidate compounds specifically caused a shift in Rab11 vesicles to the cell periphery, without significant impact on Rab5 or Rab7. <i>Drosophila</i> larvae exposed to another candidate compound with predicted oral bioavailability exhibited minimal toxicity, subcellular dispersal of endogenous Rab11, and a decrease in RAB11-dependent nephrocyte function, further supporting an inhibitory role. Taken together, the combination of computational screening and experimental validation allowed the identification of small molecules that modify the function of Rab11. This discovery may further open avenues for treating RAB11-associated disorders.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835725","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
Semisynthesis and Antitumour Evaluation of Natural Derivatives from ent-Kaurene ent-15α-Angeloyloxykaur-l6-en-3β-ol Isolated from Distichoselinum tenuifolium.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313222
Yass K Yasser, Daniel Gil, Houda Zentar, María Jesús Durán-Peña, Belen Prados-Lopez, Jorge Juárez-Moreno, José Manuel Botubol-Ares, Ali Haidour, Juan Sainz, Antonio Fernández, Ramón Alvarez-Manzaneda, Rachid Chahboun, Fernando J Reyes-Zurita
{"title":"Semisynthesis and Antitumour Evaluation of Natural Derivatives from <i>ent</i>-Kaurene <i>ent</i>-15α-Angeloyloxykaur-l6-en-3β-ol Isolated from <i>Distichoselinum tenuifolium</i>.","authors":"Yass K Yasser, Daniel Gil, Houda Zentar, María Jesús Durán-Peña, Belen Prados-Lopez, Jorge Juárez-Moreno, José Manuel Botubol-Ares, Ali Haidour, Juan Sainz, Antonio Fernández, Ramón Alvarez-Manzaneda, Rachid Chahboun, Fernando J Reyes-Zurita","doi":"10.3390/ijms252313222","DOIUrl":"https://doi.org/10.3390/ijms252313222","url":null,"abstract":"<p><p>Two natural <i>ent</i>-kaurene diterpenoids, <i>ent</i>-15α-angeloyloxykaur-16-en-3β-ol (<b>7</b>) and <i>ent</i>-15α-angeloyloxykaur-16-en-3β,9-diol (<b>8</b>), were extracted from the aerial parts of <i>Distichoselinum tenuifolium</i>, and six new derivatives were synthesised from compound (<b>7</b>). The antitumour properties of these natural and derivative <i>ent</i>-kaurenes (<b>2, 7</b>, <b>9</b>-<b>13</b>) were evaluated in three cancer cell lines: HT29 (colon cancer), HepG2 (hepatocellular carcinoma), and B16-F10 (murine melanoma). Among them, the synthesised <i>ent</i>-kaurene (<b>13</b>) containing an exomethylene-cyclopentanone moiety showed the strongest antiproliferative effects in all cell lines tested, with significantly lower IC<sub>50</sub> values around 2.5 μM. Compounds <b>13</b> and <b>12</b>, together with their precursor (<b>7</b>), were selected for further comparative cytometric and microscopic analyses. Cell cycle studies revealed that derivatives <b>12</b> and <b>13</b> exhibited promising cytostatic activity by inducing selective G2/M phase arrest, particularly effective in HT29 and HepG2 cells. Conversely, precursor (<b>7</b>) showed no significant effect on B16-F10 cell cycle distribution. The Annexin V-FITC/PI double staining assay confirmed the robust apoptotic effects of compounds (<b>7</b>), <b>12</b> and <b>13</b>, with compound 13 inducing up to 99% total apoptosis and exhibiting significant apoptotic activity in all cell lines tested. These apoptotic effects were closely linked to mitochondrial dysfunction, as evidenced by a marked loss of mitochondrial membrane potential and reduced Rh123 fluorescence in treated cells, thereby activating the intrinsic apoptotic pathway. These findings highlight the critical role of mitochondrial disruption in the cytotoxic mechanisms of these <i>ent</i>-kaurenes and underscore their potential as promising anticancer agents.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836249","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
OCTN1 (SLC22A4) as a Target of Heavy Metals: Its Possible Role in Microplastic Threats.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313218
Luana S Brunetti, Mariafrancesca Scalise, Raffaella Scanga, Lara Console, Michele Galluccio, Mauro F La Russa, Lorena Pochini, Cesare Indiveri
{"title":"OCTN1 (SLC22A4) as a Target of Heavy Metals: Its Possible Role in Microplastic Threats.","authors":"Luana S Brunetti, Mariafrancesca Scalise, Raffaella Scanga, Lara Console, Michele Galluccio, Mauro F La Russa, Lorena Pochini, Cesare Indiveri","doi":"10.3390/ijms252313218","DOIUrl":"https://doi.org/10.3390/ijms252313218","url":null,"abstract":"<p><p>Microplastics represent a threat due to their ability to enter the food chain, with harmful consequences for living organisms. The riskiness of these particles is also linked to the release of other contaminants, such as heavy metals. Solute Carriers (SLCs) represent eminent examples of first-level targets of heavy metals due to their localization on the cell surface. Putative targets of heavy metals are the organic cation transporters that form a sub-clade of the SLC22 family. Besides the physiological role in the absorption/release of endogenous organic cations, these transporters are crucial in drug disposition and their interaction with xenobiotics. In this work, the human SLC22A4, commonly known as OCTN1, was used as a benchmark to test interactions with heavy metals released by microplastics, exploiting the proteoliposome tool. The potency of metals to interfere with the OCTN1 function has been evaluated by measuring IC50 values calculated in the micromolar range. The molecular mechanism of interaction has been defined using site-directed mutagenesis and computational analyses. Finally, some chemical and physiological thiol-reacting compounds show the capacity to rescue the metal-inhibited OCTN1 function. The conclusions drawn on OCTN1 can be extended to other members of the SLC22 family and orthologous transporters in fish.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836209","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
A Diagnostic Approach in Large B-Cell Lymphomas According to the Fifth World Health Organization and International Consensus Classifications and a Practical Algorithm in Routine Practice.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313213
Magda Zanelli, Francesca Sanguedolce, Maurizio Zizzo, Stefano Ricci, Alessandra Bisagni, Andrea Palicelli, Valentina Fragliasso, Benedetta Donati, Giuseppe Broggi, Ioannis Boutas, Nektarios Koufopoulos, Moira Foroni, Francesca Coppa, Andrea Morini, Paola Parente, Valeria Zuccalà, Rosario Caltabiano, Massimiliano Fabozzi, Luca Cimino, Antonino Neri, Stefano Ascani
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