International Journal of Molecular Sciences最新文献_第4页

Four Unique Genetic Variants in Three Genes Account for 62.7% of Early-Onset Severe Retinal Dystrophy in Chile: Diagnostic and Therapeutic Consequences 三个基因中的四个独特遗传变异占智利早发严重视网膜营养不良症的 62.7%：诊断和治疗后果

International Journal of Molecular Sciences Pub Date : 2024-06-03 DOI: 10.3390/ijms25116151

Rene Moya, Clémentine Angée, S. Hanein, Fabienne Jabot-Hanin, J. Kaplan, I. Perrault, J. Rozet, L. Fares Taie

{"title":"Four Unique Genetic Variants in Three Genes Account for 62.7% of Early-Onset Severe Retinal Dystrophy in Chile: Diagnostic and Therapeutic Consequences","authors":"Rene Moya, Clémentine Angée, S. Hanein, Fabienne Jabot-Hanin, J. Kaplan, I. Perrault, J. Rozet, L. Fares Taie","doi":"10.3390/ijms25116151","DOIUrl":"https://doi.org/10.3390/ijms25116151","url":null,"abstract":"Leber congenital amaurosis (LCA)/early-onset severe retinal dystrophy (EOSRD) stand as primary causes of incurable childhood blindness. This study investigates the clinical and molecular architecture of syndromic and non-syndromic LCA/EOSRD within a Chilean cohort (67 patients/60 families). Leveraging panel sequencing, 95.5% detection was achieved, revealing 17 genes and 126 variants (32 unique). CRB1, LCA5, and RDH12 dominated (71.9%), with CRB1 being the most prevalent (43.8%). Notably, four unique variants (LCA5 p.Glu415*, CRB1 p.Ser1049Aspfs*40 and p.Cys948Tyr, RDH12 p.Leu99Ile) constituted 62.7% of all disease alleles, indicating their importance for targeted analysis in Chilean patients. This study underscores a high degree of inbreeding in Chilean families affected by pediatric retinal blindness, resulting in a limited mutation repertoire. Furthermore, it complements and reinforces earlier reports, indicating the involvement of ADAM9 and RP1 as uncommon causes of LCA/EOSRD. These data hold significant value for patient and family counseling, pharmaceutical industry endeavors in personalized medicine, and future enrolment in gene therapy-based treatments, particularly with ongoing trials (LCA5) or advancing preclinical developments (CRB1 and RDH12).","PeriodicalId":509625,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141269032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of High and Low IFNG-Expressing Subgroups in Atopic Dermatitis 特应性皮炎 IFNG 高表达亚群和低表达亚群的特征

International Journal of Molecular Sciences Pub Date : 2024-06-03 DOI: 10.3390/ijms25116158

S. Wasserer, M. Jargosch, K. E. Mayer, Jessica Eigemann, Theresa Raunegger, Görkem Aydin, S. Eyerich, T. Biedermann, K. Eyerich, Felix Lauffer

{"title":"Characterization of High and Low IFNG-Expressing Subgroups in Atopic Dermatitis","authors":"S. Wasserer, M. Jargosch, K. E. Mayer, Jessica Eigemann, Theresa Raunegger, Görkem Aydin, S. Eyerich, T. Biedermann, K. Eyerich, Felix Lauffer","doi":"10.3390/ijms25116158","DOIUrl":"https://doi.org/10.3390/ijms25116158","url":null,"abstract":"Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, with an increasing number of targeted therapies available. While biologics to treat AD exclusively target the key cytokines of type 2 immunity, Janus kinase inhibitors target a broad variety of cytokines, including IFN-γ. To better stratify patients for optimal treatment outcomes, the identification and characterization of subgroups, especially with regard to their IFNG expression, is of great relevance, as the role of IFNG in AD has not yet been fully clarified. This study aims to define AD subgroups based on their lesional IFNG expression and to characterize them based on their gene expression, T cell secretome and clinical attributes. RNA from the lesional and non-lesional biopsies of 48 AD patients was analyzed by RNA sequencing. Based on IFNG gene expression and the release of IFN-γ by lesional T cells, this cohort was categorized into three IFNG groups (high, medium, and low) using unsupervised clustering. The low IFNG group showed features of extrinsic AD with a higher prevalence of atopic comorbidities and impaired epidermal lipid synthesis. In contrast, patients in the high IFNG group had a higher average age and an activation of additional pro-inflammatory pathways. On the cellular level, higher amounts of M1 macrophages and natural killer cell signaling were detected in the high IFNG group compared to the low IFNG group by a deconvolution algorithm. However, both groups shared a common dupilumab response gene signature, indicating that type 2 immunity is the dominant immune shift in both subgroups. In summary, high and low IFNG subgroups correspond to intrinsic and extrinsic AD classifications and might be considered in the future for evaluating therapeutic efficacy or non-responders.","PeriodicalId":509625,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141270421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anti-Obesity Properties of Blackberries Fermented with L. plantarum JBMI F5 via Suppression of Adipogenesis Signaling Mechanisms 用植物乳杆菌 JBMI F5 发酵的黑莓通过抑制脂肪生成信号机制抗肥胖的特性

International Journal of Molecular Sciences Pub Date : 2024-06-03 DOI: 10.3390/ijms25116164

Jae Young Park, Ha-Rim Kim, Seung-Hyeon Lee, Sang-Wang Lee, H. Sin, T. Lim, Seon-Young Kim, Mi Hee Park

{"title":"Anti-Obesity Properties of Blackberries Fermented with L. plantarum JBMI F5 via Suppression of Adipogenesis Signaling Mechanisms","authors":"Jae Young Park, Ha-Rim Kim, Seung-Hyeon Lee, Sang-Wang Lee, H. Sin, T. Lim, Seon-Young Kim, Mi Hee Park","doi":"10.3390/ijms25116164","DOIUrl":"https://doi.org/10.3390/ijms25116164","url":null,"abstract":"Blackberries (Rubus fruticosus), which are known to include a variety of bioactive substances, have been extensively studied for their antioxidant properties. Blackberries possess multiple health beneficial effects, including anti-inflammation, anti-atherosclerosis, anti-tumor and immunomodulatory activity. However, the potential biological effects and precise molecular mechanisms of the fermented extracts remain largely unexplored. In this research, we demonstrate the effect of blackberries fermented with Lactobacillus for addressing obesity. We investigated the effect of blackberries fermented by Lactobacillus on mice fed a high-fat (60% kcal) diet for 12 weeks. Fermented blackberry administration reduced the body weight and epididymal fat caused by a high-fat diet compared to the obese group. The triglyceride and total cholesterol, which are blood lipid indicators, and the levels of leptin, which is an insulin resistance indicator, were significantly increased in the obese group but were significantly decreased in the fermented blackberries-treated group. Additionally, the expression of adipogenesis marker proteins, such as CEBPα, PPAR-γ and SREBP-1, was significantly increased in the obese group, whereas it was decreased in the fermented blackberries-treated group. These results suggest that fermented blackberries have a protective effect against high-fat-diet-induced obesity by inhibiting adipogenesis and are a potential candidate for the treatment of obesity.","PeriodicalId":509625,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141272030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Latest Advances in Ink-Based Nanogenerators: From Materials to Applications 墨基纳米发电机的最新进展：从材料到应用

International Journal of Molecular Sciences Pub Date : 2024-06-03 DOI: 10.3390/ijms25116152

Bingqian Shao, Zhitao Chen, Hengzhe Su, Shuzhe Peng, Mingxin Song

{"title":"The Latest Advances in Ink-Based Nanogenerators: From Materials to Applications","authors":"Bingqian Shao, Zhitao Chen, Hengzhe Su, Shuzhe Peng, Mingxin Song","doi":"10.3390/ijms25116152","DOIUrl":"https://doi.org/10.3390/ijms25116152","url":null,"abstract":"Nanogenerators possess the capability to harvest faint energy from the environment. Among them, thermoelectric (TE), triboelectric, piezoelectric (PE), and moisture-enabled nanogenerators represent promising approaches to micro–nano energy collection. These nanogenerators have seen considerable progress in material optimization and structural design. Printing technology has facilitated the large-scale manufacturing of nanogenerators. Although inks can be compatible with most traditional functional materials, this inevitably leads to a decrease in the electrical performance of the materials, necessitating control over the rheological properties of the inks. Furthermore, printing technology offers increased structural design flexibility. This review provides a comprehensive framework for ink-based nanogenerators, encompassing ink material optimization and device structural design, including improvements in ink performance, control of rheological properties, and efficient energy harvesting structures. Additionally, it highlights ink-based nanogenerators that incorporate textile technology and hybrid energy technologies, reviewing their latest advancements in energy collection and self-powered sensing. The discussion also addresses the main challenges faced and future directions for development.","PeriodicalId":509625,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141272471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis and Study of Building Blocks with Dibenzo[b,f]oxepine: Potential Microtubule Inhibitors 二苯并[b,f]氧杂卓构件的合成与研究：潜在的微管抑制剂

International Journal of Molecular Sciences Pub Date : 2024-06-03 DOI: 10.3390/ijms25116155

Piotr Tobiasz, Filip Borys, Marta Kucharska, Marcin Poterała, Hanna Krawczyk

引用次数: 0

Sophoridine Counteracts Obesity via Src-Mediated Inhibition of VEGFR Expression and PI3K/AKT Phosphorylation 槐定碱通过 Src 介导的血管内皮生长因子受体表达和 PI3K/AKT 磷酸化抑制作用抵消肥胖症

International Journal of Molecular Sciences Pub Date : 2024-01-19 DOI: 10.3390/ijms25021206

Jingchun Sun, Xiaoting Wang, Yulin He, Xuekai Tian, Tiantian Yuan, Gongshe Yang, Taiyong Yu

引用次数: 0

Traversing through the Mechanistic Event Analysis in IL-6 and IL-17 Signaling for a New Therapeutic Paradigm in NSCLC IL-6和IL-17信号传导过程中的机制事件分析为NSCLC治疗提供新范例

International Journal of Molecular Sciences Pub Date : 2024-01-19 DOI: 10.3390/ijms25021216

Riya Khilwani, Shailza Singh

{"title":"Traversing through the Mechanistic Event Analysis in IL-6 and IL-17 Signaling for a New Therapeutic Paradigm in NSCLC","authors":"Riya Khilwani, Shailza Singh","doi":"10.3390/ijms25021216","DOIUrl":"https://doi.org/10.3390/ijms25021216","url":null,"abstract":"IL-6 and IL-17 are paradoxical cytokines that progress inflammatory states in chronic diseases, including cancer. In lung cancer, their role has been elucidated to favor cancer development by modulating signaling mechanisms critical to cellular growth. The intrinsic ability of these cytokines to influence macroautophagy is yet another reason to facilitate lung cancer. Here, we employed a systems immunology approach to discover the mechanistic role of these cytokines in cancer development. In a biological system, at later stages, the activation of NFkB stimulates immunosuppressive phenotypes to achieve tolerating effects in a transformed cell. We found that the upregulation of cytokines signaled M2 macrophages to modulate tumor responses through the activation of autophagic intermediates and inflammasome mediators. This caused immune perturbations in the tumor microenvironment, which were associated with cancer inflammation. To address these inflammatory states, we performed triggered event analysis to examine whether overexpressing immune effectors or downregulating immune suppressors may have an effect on cancer reversal. Interestingly, the inhibition of immune regulators opposed the model outcome to an increased immune response. Therefore, IL6-IL17-mediated regulation of lung cancer may address tumor malignancy and potentiate the development of newer therapeutics for NSCLC.","PeriodicalId":509625,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139525363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploitation of Autophagy Inducers in the Management of Dementia: A Systematic Review 利用自噬诱导剂治疗痴呆症：系统回顾

International Journal of Molecular Sciences Pub Date : 2024-01-19 DOI: 10.3390/ijms25021264

M. Corasaniti, G. Bagetta, P. Nicotera, S. Maione, P. Tonin, F. Guida, D. Scuteri

{"title":"Exploitation of Autophagy Inducers in the Management of Dementia: A Systematic Review","authors":"M. Corasaniti, G. Bagetta, P. Nicotera, S. Maione, P. Tonin, F. Guida, D. Scuteri","doi":"10.3390/ijms25021264","DOIUrl":"https://doi.org/10.3390/ijms25021264","url":null,"abstract":"The social burden of dementia is remarkable since it affects some 57.4 million people all over the world. Impairment of autophagy in age-related diseases, such as dementia, deserves deep investigation for the detection of novel disease-modifying approaches. Several drugs belonging to different classes were suggested to be effective in managing Alzheimer’s disease (AD) by means of autophagy induction. Useful autophagy inducers in AD should be endowed with a direct, measurable effect on autophagy, have a safe tolerability profile, and have the capability to cross the blood–brain barrier, at least with poor penetration. According to the PRISMA 2020 recommendations, we propose here a systematic review to appraise the measurable effectiveness of autophagy inducers in the improvement of cognitive decline and neuropsychiatric symptoms in clinical trials and retrospective studies. The systematic search retrieved 3067 records, 10 of which met the eligibility criteria. The outcomes most influenced by the treatment were cognition and executive functioning, pointing at a role for metformin, resveratrol, masitinib and TPI-287, with an overall tolerable safety profile. Differences in sample power, intervention, patients enrolled, assessment, and measure of outcomes prevents generalization of results. Moreover, the domain of behavioral symptoms was found to be less investigated, thus prompting new prospective studies with homogeneous design. PROSPERO registration: CRD42023393456.","PeriodicalId":509625,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139524769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The CYP80A and CYP80G Are Involved in the Biosynthesis of Benzylisoquinoline Alkaloids in the Sacred Lotus (Nelumbo nucifera) CYP80A 和 CYP80G 参与圣莲中苄基异喹啉生物碱的生物合成

International Journal of Molecular Sciences Pub Date : 2024-01-05 DOI: 10.3390/ijms25020702

Chenyang Hao, Yuetong Yu, Yan Liu, An Liu, Sha Chen

{"title":"The CYP80A and CYP80G Are Involved in the Biosynthesis of Benzylisoquinoline Alkaloids in the Sacred Lotus (Nelumbo nucifera)","authors":"Chenyang Hao, Yuetong Yu, Yan Liu, An Liu, Sha Chen","doi":"10.3390/ijms25020702","DOIUrl":"https://doi.org/10.3390/ijms25020702","url":null,"abstract":"Bisbenzylisoquinoline and aporphine alkaloids are the two main pharmacological compounds in the ancient sacred lotus (Nelumbo nucifera). The biosynthesis of bisbenzylisoquinoline and aporphine alkaloids has attracted extensive attention because bisbenzylisoquinoline alkaloids have been reported as potential therapeutic agents for COVID-19. Our study showed that NnCYP80A can catalyze C-O coupling in both (R)-N-methylcoclaurine and (S)-N-methylcoclaurine to produce bisbenzylisoquinoline alkaloids with three different linkages. In addition, NnCYP80G catalyzed C-C coupling in aporphine alkaloids with extensive substrate selectivity, specifically using (R)-N-methylcoclaurine, (S)-N-methylcoclaurine, coclaurine and reticuline as substrates, but the synthesis of C-ring alkaloids without hydroxyl groups in the lotus remains to be elucidated. The key residues of NnCYP80G were also studied using the 3D structure of the protein predicted using Alphafold 2, and six key amino acids (G39, G69, A211, P288, R425 and C427) were identified. The R425A mutation significantly decreased the catalysis of (R)-N-methylcoclaurine and coclaurine inactivation, which might play important role in the biosynthesis of alkaloids with new configurations.","PeriodicalId":509625,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139382387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stress Physiology and Molecular Biology of Fruit Crops 果树作物的应激生理学和分子生物学

International Journal of Molecular Sciences Pub Date : 2024-01-05 DOI: 10.3390/ijms25020706

Lintong Yang, Li-Song Chen

引用次数: 0