IF 5.1 2区生物学

Cells Pub Date : 2025-05-02 DOI: 10.3390/cells14090666

Yuto Shibata, Yuki Matsumoto, Keita Kohno, Yasuharu Nakashima, Makoto Tsuda

{"title":"Microgliosis in the Spinal Dorsal Horn Early After Peripheral Nerve Injury Is Associated with Damage to Primary Afferent Aβ-Fibers.","authors":"Yuto Shibata, Yuki Matsumoto, Keita Kohno, Yasuharu Nakashima, Makoto Tsuda","doi":"10.3390/cells14090666","DOIUrl":"10.3390/cells14090666","url":null,"abstract":"Neuropathic pain results from a lesion or disease affecting the somatosensory nervous system. Injury to primary afferent nerves leads to microgliosis in the spinal dorsal horn (SDH), which plays a crucial role in developing neuropathic pain. Within the SDH, primary afferent fibers broadly project, and microglia are nearly ubiquitously distributed under normal conditions. However, not all microglia react to injuries affecting primary afferent fibers, resulting in spatially heterogeneous microgliosis within the SDH. The mechanisms underlying this phenomenon remain elusive. In this study, the spatial relationship between microgliosis and the projections of injured nerves was investigated by generating mice that had expressed tdTomato in the fourth lumbar dorsal root ganglion (L4-DRG) neurons via intra-L4-spinal nerve (SpN) injection of adeno-associated viral vectors. After transection of the L4-SpN, we found that microgliosis in the SDH selectively occurred in the innervation territories of the injured primary afferent fibers. However, denervating transient receptor potential vanilloid 1 (TRPV1)-expressing primary afferent fibers in the SDH through intrathecal injection of capsaicin did not trigger microgliosis, nor did it influence the microgliosis induced by L4-SpN injury. Conversely, pharmacological damage to myelinated DRG neurons, including Aβ-fibers, was sufficient to induce microgliosis. Furthermore, L4-SpN injury also induced microgliosis in the gracile nucleus, which primarily receives innervation from Aβ-fibers. These findings suggest that microgliosis in the SDH shortly after peripheral nerve injury is predominantly associated with damage to primary afferent Aβ-fibers.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 9","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12071663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RBFOX1 Regulates Calcium Signaling and Enhances SERCA2 Translation. RBFOX1调控钙信号传导并增强SERCA2翻译

IF 5.1 2区生物学

Cells Pub Date : 2025-05-01 DOI: 10.3390/cells14090664

Sadiq Umar, Wuqiang Zhu, Fernando Souza-Neto, Ingrid Bender, Steven C Wu, Chastity L Healy, Timothy D O'Connell, Jop H van Berlo

{"title":"RBFOX1 Regulates Calcium Signaling and Enhances SERCA2 Translation.","authors":"Sadiq Umar, Wuqiang Zhu, Fernando Souza-Neto, Ingrid Bender, Steven C Wu, Chastity L Healy, Timothy D O'Connell, Jop H van Berlo","doi":"10.3390/cells14090664","DOIUrl":"10.3390/cells14090664","url":null,"abstract":"RBFOX1 is an RNA-binding protein that regulates alternative splicing and RNA processing in the neurons, skeletal muscle, and heart. We intended to define the role of RBFOX1 in regulating calcium homeostasis to maintain normal cardiac function. We generated cardiomyocyte-specific Rbfox1 gene-deletion mice (cKO). The cardiomyocyte-specific deletion of RBFOX1 was confirmed by Western blotting and immunohistochemistry. The cKO mice showed mild hypertrophy and depressed cardiac function under homeostatic conditions, which did not deteriorate with age. Pressure overload by trans-aortic constriction (TAC) caused exaggerated cardiac hypertrophy and accelerated heart failure in cKO compared with wild-type mice. We performed Western blotting to assess the expression of important Ca2+-handling proteins, which showed alterations in the phosphorylation of PLN and CAMKII and decreased expression of SERCA2. We measured the Ca2+ dynamics and noted significantly delayed Ca2+ reuptake into the sarcoplasmic reticulum. Importantly, the decrease in SERCA2 expression was not due to reduced mRNA expression or altered splicing. To assess the possibility of the post-transcriptional regulation of SERCA2 expression by RBFOX1, we performed RNA immunoprecipitation (RIP), which showed the binding of RBFOX1 protein to Serca2 mRNA, which was confirmed in luciferase assays with the Serca2a 3'-untranslated region fused to luciferase. Finally, we performed a puromycin incorporation experiment, which showed that RBFOX1 enhances SERCA2 protein translation. Our results show that RBFOX1 plays a crucial role in regulating the expression of Ca2+-handling genes to maintain normal cardiac function. We show an important post-transcriptional role of RBFOX1 in regulating SERCA2 expression.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 9","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12072054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Getting Blood out of a Stone: Vascularization via Spheroids and Organoids in 3D Bioprinting. 从石头中获得血液：在3D生物打印中通过球体和类器官的血管化。

IF 5.1 2区生物学

Cells Pub Date : 2025-05-01 DOI: 10.3390/cells14090665

Daria Revokatova, Polina Bikmulina, Zahra Heydari, Anna Solovieva, Massoud Vosough, Anastasia Shpichka, Peter Timashev

{"title":"Getting Blood out of a Stone: Vascularization via Spheroids and Organoids in 3D Bioprinting.","authors":"Daria Revokatova, Polina Bikmulina, Zahra Heydari, Anna Solovieva, Massoud Vosough, Anastasia Shpichka, Peter Timashev","doi":"10.3390/cells14090665","DOIUrl":"10.3390/cells14090665","url":null,"abstract":"Current developments in bioequivalent technology have led to the creation of excellent models that mimic the structure and function of human organs. These models are based on the original tissues and organs of the human body, but they lack the complex interaction with the extensive network of vasculature, and this is a major challenge for these models. A functional vasculature is essential for oxygen, nutrient, and waste exchange. It is also responsible for inductive biochemical exchange, and provides a structural pattern for organ growth. In vitro systems, containing no perfusable vessels, suffer from the quick formation of a necrotic core of organoids, and further development does not occur due to increased metabolic demands. Another key limitation of 3D-based techniques is the absence of accurate architectural structures and large-scale tissue sizes. Recently, new 3D bioprinting methods have been developed for organoids and spheroids as living building blocks. These methods aim to address some of the challenges associated with 3D technologies. In this review, we discuss recent strategies for vascularization via organoids and spheroids, which are used as structural units in bioprinting to recreate natural organs and tissues with ever-increasing accuracy in structure and function.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 9","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12071597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bilateral Germ Cell Tumor of the Testis: Biological and Clinical Implications for a Stem Versus Genetic Origin of Cancers. 睾丸双侧生殖细胞瘤：肿瘤干细胞与基因起源的生物学和临床意义。

IF 5.1 2区生物学

Cells Pub Date : 2025-04-30 DOI: 10.3390/cells14090658

Jamaal C Jackson, Darren Sanchez, Aron Y Joon, Marcos R Estecio, Andrew C Johns, Amishi Y Shah, Matthew Campbell, John F Ward, Louis L Pisters, Charles C Guo, Miao Zhang, Niki M Zacharias, Shi-Ming Tu

引用次数: 0

Advancing Obstructive Airway Disease Treatment: Dual PDE3/4 Inhibition as a Therapeutic Strategy. 推进阻塞性气道疾病治疗：双重PDE3/4抑制作为治疗策略

IF 5.1 2区生物学

Cells Pub Date : 2025-04-30 DOI: 10.3390/cells14090659

Rinzhin T Sherpa, Cynthia J Koziol-White, Reynold A Panettieri

{"title":"Advancing Obstructive Airway Disease Treatment: Dual PDE3/4 Inhibition as a Therapeutic Strategy.","authors":"Rinzhin T Sherpa, Cynthia J Koziol-White, Reynold A Panettieri","doi":"10.3390/cells14090659","DOIUrl":"10.3390/cells14090659","url":null,"abstract":"Obstructive airway diseases, including asthma and chronic obstructive pulmonary disease (COPD), evoke significant global health concerns manifested by airway inflammation and obstruction. Despite their differing origins, shared pathophysiological features and responses to therapeutic interventions highlight common molecular mechanisms. Standard treatments include inhaled bronchodilators, with combination therapies offering enhanced symptom control. Cyclic AMP (cAMP) plays a crucial role in airway relaxation. Phosphodiesterase (PDE) decreases cAMP levels, thereby attenuating the relaxation of airway smooth muscle, making it a promising therapeutic target. The balance between cAMP production and degradation is essential for regulating airway tone and function. PDE inhibitors for the treatment of obstructive airway diseases have suffered challenges, with adverse side effects of prospective inhibitors causing clinical failures. Efforts to develop PDE inhibitors with an improved safety profile could prove to be beneficial as an add-on treatment for severe asthma and COPD. The recent FDA approval of Ensifentrine, a dual PDE3/4 inhibitor, can significantly advance COPD management by improving bronchodilation, reducing inflammation, and lowering exacerbation rates with favorable safety outcomes.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 9","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12071989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expanded Phenotype of the Cln6^nclf Mouse Model. Cln6nclf小鼠模型的扩展表型。

IF 5.1 2区生物学

Cells Pub Date : 2025-04-30 DOI: 10.3390/cells14090661

Victoria Chaoul, Sara Saab, Omar Shmoury, Ramy Alam, Lynn Al Aridi, Nadine J Makhoul, Jihane Soueid, Rose-Mary Boustany

{"title":"Expanded Phenotype of the Cln6nclf Mouse Model.","authors":"Victoria Chaoul, Sara Saab, Omar Shmoury, Ramy Alam, Lynn Al Aridi, Nadine J Makhoul, Jihane Soueid, Rose-Mary Boustany","doi":"10.3390/cells14090661","DOIUrl":"10.3390/cells14090661","url":null,"abstract":"Neuronal ceroid lipofuscinoses (NCLs) are a group of autosomal recessive neurogenetic disorders caused by mutations in 14 different genes. CLN6 disease manifests as variant late-infantile NCL (vLINCL) or as an adult variant. In childhood, symptoms include speech delay, vision loss, cognitive and motor decline, seizures, and early death. An in-depth characterization of a naturally occurring Cln6 mutant mouse (Cln6nclf) is presented, with implications for translational research. The expanded phenotype provides data showing early death, vision loss, and motor deficits in male and female Cln6nclf mice. Diminished visual acuity in Cln6nclf mice was noted at 28 weeks of age, but the pathological loss of retinal layers began as early as 2 weeks or postnatal day 14 (P14). Apoptosis was confirmed by TUNEL staining in the Cln6nclf mouse brain at P8 and in the retina at P12. A peak in glial fibrillary acidic protein (GFAP) expression was established as a normal developmental phenomenon in the wild-type and Cln6nclf mouse brain cerebellum and the CA2-CA3 regions of the hippocampus at P8. In Cln6nclf mice, GFAP levels were elevated at P12 in the cerebellum and hippocampus. In the retina, a developmental peak in gliosis was absent, with increased astrogliosis noted at P6 and P8 in female and male Cln6nclf mice, respectively. This highlights the lack of a sex-dependent response in wild-type mice. These novel data position the Cln6nclf mouse model as a useful tool for screening potential therapeutics for human CLN6 disease.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 9","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12071971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunosuppression of Tumor-Derived Factors Modulated Neutrophils in Upper Tract Urothelial Carcinoma Through Upregulation of Arginase-1 via ApoA1-STAT3 Axis. 通过ApoA1-STAT3轴上调精氨酸酶-1对上尿路上皮癌中肿瘤源性因子调节的中性粒细胞的免疫抑制

IF 5.1 2区生物学

Cells Pub Date : 2025-04-30 DOI: 10.3390/cells14090660

Chih-Chia Chang, Chia-Bin Chang, Cheng-Huang Shen, Ming-Yang Lee, Yeong-Chin Jou, Chun-Liang Tung, Wei-Hong Lai, Chi-Feng Hung, Meilin Wang, Ya-Yan Lai, Pi-Che Chen, Shu-Fen Wu

{"title":"Immunosuppression of Tumor-Derived Factors Modulated Neutrophils in Upper Tract Urothelial Carcinoma Through Upregulation of Arginase-1 via ApoA1-STAT3 Axis.","authors":"Chih-Chia Chang, Chia-Bin Chang, Cheng-Huang Shen, Ming-Yang Lee, Yeong-Chin Jou, Chun-Liang Tung, Wei-Hong Lai, Chi-Feng Hung, Meilin Wang, Ya-Yan Lai, Pi-Che Chen, Shu-Fen Wu","doi":"10.3390/cells14090660","DOIUrl":"10.3390/cells14090660","url":null,"abstract":"Upper tract urothelial carcinoma (UTUC) presents aggressive features and a tumor microenvironment with T cell depletion. However, the role of tumor-associated neutrophils in UTUC remains unclear. This study aimed to investigate how UTUC tumor-derived factors modulate neutrophils and their impact on T cell immune responses. Our findings demonstrate that UTUC secreted tumor-derived factors, with apolipoprotein A1 (Apo-A1) being the predominant factor, which upregulated arginase-1 expression in neutrophils. STAT3 activation was responsible for the upregulation of arginase-1 in neutrophils. Blocking the interactions between Apo-A1 and its receptors reduced arginase-1 expression in neutrophils treated with tumor tissue culture supernatant (TTCS). Moreover, both CD4+ T and CD8+ T cell proliferation were inhibited by neutrophils treated with Apo-A1 or TTCS. Importantly, blocking Apo-A1 signaling in neutrophils reversed the inhibitory effects on T cells. In UTUC patients, the neutrophil-to-lymphocyte ratio was higher than that in healthy subjects. The expression of arginase-1 in neutrophils and the level of Apo-A1 within UTUC tumors were negatively correlated with tumor-infiltrating CD4+ T cells. Additionally, neutrophils from UTUC patients showed increased expression of arginase-1 and exhibited inhibitory effects of T cell functions. These findings suggest that UTUC orchestrates an immune-suppressive microenvironment through Apo-A1-mediated upregulation of arginase-1 in neutrophils, ultimately leading to the inhibition of T cell proliferation.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 9","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12072159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of Recombinant Human Amelogenin on the Osteogenic Differentiation Potential of SHED. 重组人淀粉原蛋白对SHED成骨分化潜能的影响。

IF 5.1 2区生物学

Cells Pub Date : 2025-04-30 DOI: 10.3390/cells14090657

Akira Hirabae, Ryo Kunimatsu, Yuki Yoshimi, Kodai Rikitake, Shintaro Ogashira, Ayaka Nakatani, Shuzo Sakata, Kotaro Tanimoto

{"title":"Effect of Recombinant Human Amelogenin on the Osteogenic Differentiation Potential of SHED.","authors":"Akira Hirabae, Ryo Kunimatsu, Yuki Yoshimi, Kodai Rikitake, Shintaro Ogashira, Ayaka Nakatani, Shuzo Sakata, Kotaro Tanimoto","doi":"10.3390/cells14090657","DOIUrl":"10.3390/cells14090657","url":null,"abstract":"This study aimed to explore how amelogenin can improve stem cells from human exfoliated deciduous teeth (SHED)-based bone regeneration and promote tissue healing as a treatment for critical-sized bone defects. SHED was induced into bone differentiation by using osteogenic differentiation medium. Real-time polymerase chain reaction, alkaline phosphatase (ALP) staining and quantification, and Alizarin Red S staining, as well as calcium and osteocalcin quantification were performed to assess differentiation. On day 18, a significant increase was observed in the expression of RUNX2, CBFB, BGLAP, COL1, BMP2, BMP4, NOTCH1, NOTCH2, and NES. Osteocalcin gene expression continued to increase significantly. ALP activity was significantly higher in the amelogenin-treated group than in the control group on days 7, 10, and 14. On day 14, enhanced ALP staining was observed in the amelogenin-treated group. Calcium and osteocalcin levels were significantly higher in the amelogenin-treated group than in the control group on day 21. This study suggests that combining SHED and amelogenin may be effective for bone regeneration, offering a potential new approach in regenerative medicine.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 9","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12071429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

mTORopathies in Epilepsy and Neurodevelopmental Disorders: The Future of Therapeutics and the Role of Gene Editing. 癫痫和神经发育障碍中的肌病：治疗学的未来和基因编辑的作用。

IF 5.1 2区生物学

Cells Pub Date : 2025-04-30 DOI: 10.3390/cells14090662

Marina Ottmann Boff, Fernando Antônio Costa Xavier, Fernando Mendonça Diz, Júlia Budelon Gonçalves, Laura Meireles Ferreira, Jean Zambeli, Douglas Bottega Pazzin, Thales Thor Ramos Previato, Helena Scartassini Erwig, João Ismael Budelon Gonçalves, Fernanda Thays Konat Bruzzo, Daniel Marinowic, Jaderson Costa da Costa, Gabriele Zanirati

{"title":"mTORopathies in Epilepsy and Neurodevelopmental Disorders: The Future of Therapeutics and the Role of Gene Editing.","authors":"Marina Ottmann Boff, Fernando Antônio Costa Xavier, Fernando Mendonça Diz, Júlia Budelon Gonçalves, Laura Meireles Ferreira, Jean Zambeli, Douglas Bottega Pazzin, Thales Thor Ramos Previato, Helena Scartassini Erwig, João Ismael Budelon Gonçalves, Fernanda Thays Konat Bruzzo, Daniel Marinowic, Jaderson Costa da Costa, Gabriele Zanirati","doi":"10.3390/cells14090662","DOIUrl":"10.3390/cells14090662","url":null,"abstract":"mTORopathies represent a group of neurodevelopmental disorders linked to dysregulated mTOR signaling, resulting in conditions such as tuberous sclerosis complex, focal cortical dysplasia, hemimegalencephaly, and Smith-Kingsmore Syndrome. These disorders often manifest with epilepsy, cognitive impairments, and, in some cases, structural brain anomalies. The mTOR pathway, a central regulator of cell growth and metabolism, plays a crucial role in brain development, where its hyperactivation leads to abnormal neuroplasticity, tumor formation, and heightened neuronal excitability. Current treatments primarily rely on mTOR inhibitors, such as rapamycin, which reduce seizure frequency and tumor size but fail to address underlying genetic causes. Advances in gene editing, particularly via CRISPR/Cas9, offer promising avenues for precision therapies targeting the genetic mutations driving mTORopathies. New delivery systems, including viral and non-viral vectors, aim to enhance the specificity and efficacy of these therapies, potentially transforming the management of these disorders. While gene editing holds curative potential, challenges remain concerning delivery, long-term safety, and ethical considerations. Continued research into mTOR mechanisms and innovative gene therapies may pave the way for transformative, personalized treatments for patients affected by these complex neurodevelopmental conditions.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 9","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12071303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibitors of Cyclic Dinucleotide Phosphodiesterases and Cyclic Oligonucleotide Ring Nucleases as Potential Drugs for Various Diseases. 环二核苷酸磷酸二酯酶和环寡核苷酸环核酸酶抑制剂作为多种疾病的潜在药物。

IF 5.1 2区生物学

Cells Pub Date : 2025-04-30 DOI: 10.3390/cells14090663

Christopher S Vennard, Samson Marvellous Oladeji, Herman O Sintim

{"title":"Inhibitors of Cyclic Dinucleotide Phosphodiesterases and Cyclic Oligonucleotide Ring Nucleases as Potential Drugs for Various Diseases.","authors":"Christopher S Vennard, Samson Marvellous Oladeji, Herman O Sintim","doi":"10.3390/cells14090663","DOIUrl":"10.3390/cells14090663","url":null,"abstract":"The phosphodiester linkage is found in DNA, RNA and many signaling molecules, such as cyclic mononucleotide, cyclic dinucleotides (CDNs) and cyclic oligonucleotides (cONs). Enzymes that cleave the phosphodiester linkage (nucleases and phosphodiesterases) play important roles in cell persistence and fitness and have therefore become targets for various diseased states. While various inhibitors have been developed for nucleases and cyclic mononucleotide phosphodiesterases, and some have become clinical successes, there is a paucity of inhibitors of the recently discovered phosphodiesterases or ring nucleases that cleave CDNs and cONs. Inhibitors of bacterial c-di-GMP or c-di-AMP phosphodiesterases have the potential to be used as anti-virulence compounds, while compounds that inhibit the degradation of 3',3'-cGAMP, cA3, cA4, cA6 could serve as antibiotic adjuvants as the accumulation of these second messengers leads to bacterial abortive infection. In humans, 2'3'-cGAMP plays critical roles in antiviral and antitumor responses. ENPP1 (the 2'3'-cGAMP phosphodiesterase) or virally encoded cyclic dinucleotide phosphodiesterases, such as poxin, however, blunt this response. Inhibitors of ENPP1 or poxin-like enzymes have the potential to be used as anticancer and antiviral agents, respectively. This review summarizes efforts made towards the discovery and development of compounds that inhibit CDN phosphodiesterases and cON ring nucleases.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 9","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12072042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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