Current Issues in Molecular Biology最新文献

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A Review of Syndromic Forms of Obesity: Genetic Etiology, Clinical Features, and Molecular Diagnosis. 肥胖症症候群:遗传病因、临床特征和分子诊断综述。
IF 3 3区 生物学
Current Issues in Molecular Biology Pub Date : 2025-09-03 DOI: 10.3390/cimb47090718
Anam Farzand, Mohd Adzim Khalil Rohin, Sana Javaid Awan, Zubair Sharif, Adnan Yaseen, Abdul Momin Rizwan Ahmad
{"title":"A Review of Syndromic Forms of Obesity: Genetic Etiology, Clinical Features, and Molecular Diagnosis.","authors":"Anam Farzand, Mohd Adzim Khalil Rohin, Sana Javaid Awan, Zubair Sharif, Adnan Yaseen, Abdul Momin Rizwan Ahmad","doi":"10.3390/cimb47090718","DOIUrl":"10.3390/cimb47090718","url":null,"abstract":"<p><strong>Background: </strong>Syndromic forms of obesity are uncommon, complicated illnesses that include early-onset obesity along with other clinical characteristics such as organ-specific abnormalities, dysmorphic symptoms, and intellectual incapacity. These syndromes frequently have a strong genetic foundation, involving copy number variations, monogenic mutations, and chromosomal abnormalities.</p><p><strong>Methods: </strong>Using terms like \"syndromic obesity,\" \"genetic diagnosis,\" and \"monogenic obesity,\" a comprehensive literature search was conducted to find articles published between 2000 and 2025 in PubMed, Scopus, and Web of Science. Peer-reviewed research addressing the clinical, molecular, or genetic aspects of syndromic obesity were among the inclusion criteria. Conference abstracts, non-English publications, and research without genetic validation were among the exclusion criteria. The whole genetic, clinical, diagnostic, and therapeutic domains were thematically synthesized to create a thorough, fact-based story. Research using chromosomal microarray analysis (CMA), whole-exome sequencing (WES), next-generation sequencing (NGS), and new long-read sequencing platforms was highlighted.</p><p><strong>Results: </strong>Despite the fact that molecular diagnostics, especially NGS and CMA, have made tremendous progress in identifying pathogenic variants, between 30 and 40 percent of instances of syndromic obesity are still genetically unexplained. One significant issue is the variation in phenotype across people with the same mutation, which suggests the impact of environmental modifiers and epigenetic variables. In addition, differences in access to genetic testing, particularly in areas with limited resources, can make it difficult to diagnose patients in a timely manner. Additionally, recent research emphasizes the possible contribution of gene-environment interactions, gut microbiota, and multi-omic integration to modifying disease expression.</p><p><strong>Conclusions: </strong>Syndromic obesity is still poorly understood in a variety of groups despite significant advancements in technology. Multi-layered genomic investigations, functional genomic integration, and standardized diagnostic frameworks are necessary to close existing gaps. The development of tailored treatment plans, such as gene editing and focused pharmaceutical therapies as well as fair access to cutting-edge diagnostics are essential to improving outcomes for people with syndromic obesity.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Methane, Bacteria, Fungi, and Fermentation: Pathophysiology, Diagnosis and Treatment Strategies for Small Intestinal Bacterial Overgrowth, Intestinal Methanogen Overgrowth and Small Intestinal Fungal Overgrowth. 甲烷、细菌、真菌和发酵:小肠细菌过度生长、肠道产甲烷菌过度生长和小肠真菌过度生长的病理生理、诊断和治疗策略
IF 3 3区 生物学
Current Issues in Molecular Biology Pub Date : 2025-09-02 DOI: 10.3390/cimb47090713
Adam Wawrzeńczyk, Marta Czarnowska, Samira Darwish, Aleksandra Ćwirko-Godycka, Kinga Lis, Maciej Szota, Paweł Treichel, Aleksandra Wojtkiewicz, Katarzyna Napiórkowska-Baran
{"title":"Methane, Bacteria, Fungi, and Fermentation: Pathophysiology, Diagnosis and Treatment Strategies for Small Intestinal Bacterial Overgrowth, Intestinal Methanogen Overgrowth and Small Intestinal Fungal Overgrowth.","authors":"Adam Wawrzeńczyk, Marta Czarnowska, Samira Darwish, Aleksandra Ćwirko-Godycka, Kinga Lis, Maciej Szota, Paweł Treichel, Aleksandra Wojtkiewicz, Katarzyna Napiórkowska-Baran","doi":"10.3390/cimb47090713","DOIUrl":"10.3390/cimb47090713","url":null,"abstract":"<p><p>The human gastrointestinal tract hosts a complex ecosystem known as the gut microbiota, which plays a crucial part in digestion and immune system function. Among the clinically recognized manifestations of dysbiosis in this system are Small Intestinal Bacterial Overgrowth (SIBO), Intestinal Methanogen Overgrowth (IMO), Small Intestinal Fungal Overgrowth (SIFO), and Large Intestinal Bacterial Overgrowth (LIBO). This study aims to investigate the complex pathophysiological mechanisms underlying these syndromes and their diagnostics and therapeutic options, focusing primarily on the roles of methane-producing archaea and fungal overgrowth. The methods employed in this study involve a comprehensive analysis and synthesis of peer-reviewed articles, systematic reviews, clinical trials, and meta-analyses. This review summarizes that methane production by <i>Methanobrevibacter smithii</i> was linked to altered fermentation, reduced microbial diversity, and slowed intestinal transit. Fungal species were associated with increased intestinal permeability, inflammation, and biofilm formation. Targeted interventions addressing microbial imbalances demonstrated potential therapeutic value. This review highlights the complex and multifactorial nature of gut dysbiosis, revealing its impact beyond the gastrointestinal tract. While emerging therapies targeting methanogens, fungi, and biofilms show promise, further research is essential to optimize their clinical application. The findings emphasize the need for interdisciplinary collaboration to refine diagnostic and therapeutic strategies.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
The TOX2 Gene Is Responsible for Conidiation and Full Virulence in Fusarium pseudograminearum. TOX2基因与伪谷物镰刀菌的条件作用和全毒力有关。
IF 3 3区 生物学
Current Issues in Molecular Biology Pub Date : 2025-09-02 DOI: 10.3390/cimb47090714
Sen Han, Shaobo Zhao, Yajiao Wang, Qiusheng Li, Mengwei Sun, Lingxiao Kong, Xianghong Chen, Jianhai Gao, Yuxing Wu
{"title":"The TOX2 Gene Is Responsible for Conidiation and Full Virulence in <i>Fusarium pseudograminearum</i>.","authors":"Sen Han, Shaobo Zhao, Yajiao Wang, Qiusheng Li, Mengwei Sun, Lingxiao Kong, Xianghong Chen, Jianhai Gao, Yuxing Wu","doi":"10.3390/cimb47090714","DOIUrl":"10.3390/cimb47090714","url":null,"abstract":"<p><p>Fusarium crown rot, a widespread and destructive disease affecting cereal crops (particularly wheat and barley), is primarily caused by the soil-borne fungal pathogen <i>Fusarium pseudograminearum</i>. Secondary metabolites (SMs) play a crucial role in colonization and host tissue invasion by pathogenic fungi. In this study, we investigated the functional role of <i>FpTox2</i>, a secondary metabolite-related gene in <i>F. pseudograminearum</i>. An <i>FpTox2</i> deletion mutant exhibited significantly reduced radial growth compared to wild-type <i>F. pseudograminearum</i>. Notably, the mutant strain completely lost conidiation capacity under induced conditions. Furthermore, although it showed decreased sensitivity to the cell membrane inhibitor sodium dodecyl sulfate (SDS), the mutant demonstrated enhanced susceptibility to NaCl, a metal ion stressor. Most importantly, the pathogen's virulence was markedly attenuated in wheat stem base infections following <i>FpTox2</i> deletion, and we demonstrated that <i>FpTox2</i> regulates pathogen virulence by influencing deoxynivalenol production. In conclusion, <i>FpTox2</i> is crucial for vegetative growth, asexual development, abiotic stress responses, and full virulence in <i>F. pseudograminearum</i>.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Homologous Recombination Proficiency in High-Grade Serous Epithelial Ovarian Cancer Tumors: The Dark Side of the Moon. 高级别浆液上皮性卵巢癌的同源重组熟练程度:月球的阴暗面。
IF 3 3区 生物学
Current Issues in Molecular Biology Pub Date : 2025-09-01 DOI: 10.3390/cimb47090702
Marina Pavanello, Carolina Martins Vieira, Martina Parenza Arenhardt, Angelica Nogueira-Rodrigues
{"title":"Homologous Recombination Proficiency in High-Grade Serous Epithelial Ovarian Cancer Tumors: The Dark Side of the Moon.","authors":"Marina Pavanello, Carolina Martins Vieira, Martina Parenza Arenhardt, Angelica Nogueira-Rodrigues","doi":"10.3390/cimb47090702","DOIUrl":"10.3390/cimb47090702","url":null,"abstract":"<p><p>Extensive research on homologous-recombination-deficient (HRD) tumors has led to advancements in targeted therapies, such as PARP inhibitors (PARPis). Around 50% of high-grade serous ovarian cancer (HGSOC) cases exhibit HR deficiency, but understanding the remaining half, referred to as homologous-recombination-proficient (HRP) tumors, is limited. This review explores existing knowledge regarding HGSOC patients with HRP tumors and offers insights into potential targets for innovative treatments. Patients with HRP tumors do not experience the same benefits from PARPi and have poorer survival outcomes compared to those with HRD tumors. <i>CCNE1</i> amplification is a common, well-established molecular feature in HGSOC HRP tumors, occurring in about 20% of cases. Targeting <i>CCNE1</i> amplification and/or overexpression shows promise with emerging therapies like CDK2 or Wee1 inhibitors. Additionally, approaches using immunotherapy and antibody-drug conjugates could represent promising targets for HRP patients. This review also covers lesser-known molecular features in HRP tumors, such as fold-back inversions and <i>CARM1</i> amplification and/or overexpression, as well as HRD tumors that acquire HR proficiency (<i>BRCA1/2</i> reversion mutations, demethylation of <i>BRCA1</i> and <i>RAD51C</i>). We also discuss controversial topics regarding HRP tumors and limitations of HRD detection. Addressing this need is critical to reduce toxicity and improve disease management.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12469131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Synergism of Synthetic Sulfonamides and Natural Antioxidants for the Management of Diabetes Mellitus Associated with Oxidative Stress. 合成磺胺类药物与天然抗氧化剂对氧化应激相关糖尿病的协同作用
IF 3 3区 生物学
Current Issues in Molecular Biology Pub Date : 2025-09-01 DOI: 10.3390/cimb47090709
Ancuța Dinu Iacob, Luminita-Georgeta Confederat, Ionut Dragostin, Ionela Daniela Morariu, Dana Tutunaru, Oana-Maria Dragostin
{"title":"Synergism of Synthetic Sulfonamides and Natural Antioxidants for the Management of Diabetes Mellitus Associated with Oxidative Stress.","authors":"Ancuța Dinu Iacob, Luminita-Georgeta Confederat, Ionut Dragostin, Ionela Daniela Morariu, Dana Tutunaru, Oana-Maria Dragostin","doi":"10.3390/cimb47090709","DOIUrl":"10.3390/cimb47090709","url":null,"abstract":"<p><p>In the context of expanding research on the development of compounds with multiple therapeutic actions, this study aims to consolidate findings from the last decade on new synthetic sulfonamide therapies for managing type 2 diabetes mellitus (T2DM) associated with oxidative stress (OS). The novelty of this synthesis study lies in the synergistic approach of antidiabetic molecular targets with those against oxidative stress, having the sulfonylurea class as a common point. By utilizing international databases, we identified and selected conclusive studies for this review. Promising results have been achieved through dual therapies that combine antioxidants (such as sesame oil, naringin, alpha-lipoic acid, resveratrol, and quercetin) with sulfonylureas (including glipizide, glibenclamide, gliclazide, and glimepiride). Additionally, triple therapies that associated sulfonylureas with other classes of antidiabetic medications have also shown encouraging outcomes. These findings are supported by in vivo tests conducted on experimental laboratory models as well as on human subjects. These recent advancements in synthetic sulfonamide research point to a promising future in diabetes management, especially considering the dual functionalities demonstrated by in vivo studies-specifically, their antidiabetic and antioxidant effects. Moreover, the synergy between sulfonamides and other antioxidant agents represents a beneficial strategy for optimizing future chemical structures, potentially allowing for their integration into personalized treatments aimed at combating T2DM.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 Sperm DNA Fragmentation and Chromatin Decondensation on PLCζ Efficacy in Infertile Patients. 精子DNA断裂和染色质去致密化对不孕症患者PLCζ疗效的影响。
IF 3 3区 生物学
Current Issues in Molecular Biology Pub Date : 2025-09-01 DOI: 10.3390/cimb47090707
Soukaina Azil, Ismail Kaarouch, Debbie Montjean, Marie-Hélène Godin Pagé, Rosalie Cabry, Noureddine Louanjli, Bouchra Ghazi, Moncef Benkhalifa
{"title":"Effect of Sperm DNA Fragmentation and Chromatin Decondensation on PLCζ Efficacy in Infertile Patients.","authors":"Soukaina Azil, Ismail Kaarouch, Debbie Montjean, Marie-Hélène Godin Pagé, Rosalie Cabry, Noureddine Louanjli, Bouchra Ghazi, Moncef Benkhalifa","doi":"10.3390/cimb47090707","DOIUrl":"10.3390/cimb47090707","url":null,"abstract":"<p><p>This study aimed to describe phospholipase C zeta (PLCζ) deficiency from patients who experienced oocyte fertilization failure following intracytoplasmic sperm injection (ICSI) and to investigate the relationship between sperm DNA fragmentation, chromatin decondensation, and PLCζ. A total of 135 patients participated in this study-65 fertile men and 70 infertile patients- and semen samples were obtained to analyze concentration, motility, and morphology. PLCζ protein levels were assessed by immunofluorescence and quantitative techniques, DNA fragmentation by TUNEL essay, and chromatin decondensation by aniline blue staining. The proportion of spermatozoa presenting PLCζ was significantly lower in infertile patients (18.41 ± 18.84%) compared to fertile controls (67.31 ± 13.79%) (<i>p</i> < 0.001). A significant decrease in PLCζ protein levels was observed in infertile patients compared to fertile controls, which was the same for localization patterns for each region (acrosomal, equatorial, and combination of these regions). Significant correlations were also observed between sperm parameters and PLCζ levels, DNA fragmentation, and chromatin decondensation. Furthermore, a statistically significant correlation was detected between the percentage of spermatozoa presenting PLCζ and DNA integrity (<i>p</i> < 0.001). In summary, DNA fragmentation and chromatin decondensation are associated with alterations in the localization patterns and reduced protein levels of PLCζ, which may contribute to total fertilization failure.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
PSMB9 Orchestrates Tumor Immune Landscape and Serves as a Potent Biomarker for Prognosis and T Cell-Based Immunotherapy Response. PSMB9协调肿瘤免疫景观,作为预后和T细胞免疫治疗反应的有效生物标志物。
IF 3 3区 生物学
Current Issues in Molecular Biology Pub Date : 2025-09-01 DOI: 10.3390/cimb47090712
Xinran Ma, Qi Zhu, Zhiqiang Wu, Weidong Han
{"title":"PSMB9 Orchestrates Tumor Immune Landscape and Serves as a Potent Biomarker for Prognosis and T Cell-Based Immunotherapy Response.","authors":"Xinran Ma, Qi Zhu, Zhiqiang Wu, Weidong Han","doi":"10.3390/cimb47090712","DOIUrl":"10.3390/cimb47090712","url":null,"abstract":"<p><p>Proteasome subunit beta type-9 (PSMB9), a member of the proteasome beta subunit family, encodes the pivotal β1i component of the immunoproteasome. PSMB9 plays a crucial role in antigen processing and presentation; however, its comprehensive role in orchestrating a tumor-immune landscape and regulating the anti-tumor immune responses remains unexplored. Here we investigated the context-dependent functions of PSMB9 by integrating multi-omics data from The Cancer Genome Atlas, Genotype-Tissue Expression database, Human Protein Atlas, Tumor Immunotherapy Gene Expression Resource, and multiple other databases. Moreover, we explored the predictive value of PSMB9 in multiple immunotherapy cohorts and investigated its functional relevance in CAR-T therapy using genome-scale CRISPR/Cas9 screening, gene knockout cell line in vitro, and clinical cohort validation. We found widespread dysregulation in PSMB9 across cancers, predominantly upregulated in most malignancies and associated with advanced pathological stages in specific contexts. PSMB9 was also broadly and negatively correlated with tumor stemness indices. Crucially, PSMB9 expression was robustly linked to anti-tumor immunity by being significantly correlated with immune-pathway activation (e.g., IFN response, cytokine signaling), immune regulatory and immune checkpoint gene expression, and enhanced infiltration of T cells across nearly all tumor types. Consequently, elevated PSMB9 predicted superior response to immune checkpoint inhibitors in multiple cohorts, showing comparable predictive power to established predictive signatures. Furthermore, CRISPR/Cas9 screening identified PSMB9 loss as a novel mechanism of resistance to CD19 CAR T cell therapy, with PSMB9-deficient tumor cells exhibiting a survival advantage under CAR-T pressure, supported by trends in clinical CAR-T outcomes. Our study uncovers PSMB9 as a previously unrecognized critical regulator of the tumor immune landscape in a pan-cancer scope, whose expression orchestrates key immune processes within the tumor microenvironment and serves as a potent biomarker for patient prognosis. Critically, we first established PSMB9 as a novel prognostic indicator for both checkpoint blockade and CAR-T cell therapies, highlighting its dual role as a crucial immune modulator and a promising biomarker for guiding T cell-based immunotherapy strategies across diverse human cancers.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
B-Cell Acute Lymphoblastic Leukemia in a Child with Down Syndrome and High-Risk Genomic Lesions. 唐氏综合征儿童b细胞急性淋巴母细胞白血病和高危基因组病变。
IF 3 3区 生物学
Current Issues in Molecular Biology Pub Date : 2025-09-01 DOI: 10.3390/cimb47090704
Cristina-Crenguţa Albu, Florin Bica, Laura Nan, Lucia Bubulac, Claudia Florina Bogdan-Andreescu, Ionuţ Vlad Şerbanică, Cristian-Viorel Poalelungi, Emin Cadar, Andreea-Mariana Bănățeanu, Alexandru Burcea
{"title":"B-Cell Acute Lymphoblastic Leukemia in a Child with Down Syndrome and High-Risk Genomic Lesions.","authors":"Cristina-Crenguţa Albu, Florin Bica, Laura Nan, Lucia Bubulac, Claudia Florina Bogdan-Andreescu, Ionuţ Vlad Şerbanică, Cristian-Viorel Poalelungi, Emin Cadar, Andreea-Mariana Bănățeanu, Alexandru Burcea","doi":"10.3390/cimb47090704","DOIUrl":"10.3390/cimb47090704","url":null,"abstract":"<p><p><b>Background:</b> Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, with cure rates exceeding 80% due to advancements in treatment protocols and supportive care. However, in children with Down syndrome (DS), ALL (DS-ALL) presents distinct genomic and clinical challenges. These include mutations in Janus kinase 2 (<i>JAK2</i>), neuroblastoma RAS viral oncogene homolog (<i>NRAS</i>), and E1A-binding protein p300 (<i>EP300</i>), as well as cytokine receptor-like factor 2 (<i>CRLF2</i>) rearrangements-such as <i>P2RY8-CRLF2</i> fusion-and intrachromosomal amplification of chromosome 21 (<i>iAMP21</i>). These aberrations are associated with poor prognosis and increased risk of relapse. The objective of this study was to present a unique DS-ALL case with five concurrent high-risk genomic lesions and to contextualize its management in light of existing literature, emphasizing minimal residual disease (MRD)-guided therapy and supportive care. <b>Case Report and Results:</b> We present the case of a three-year-old boy with DS and B-cell ALL (B-ALL), in whom multiple high-risk genomic features co-occurred. Despite these adverse prognostic markers, the patient achieved complete remission following an intensive high-dose induction protocol. We also discuss therapeutic strategies that aim at balancing individualized treatment approaches with optimized supportive care to reduce toxicity and minimize relapse risk. <b>Conclusions:</b> This case underlines the importance of comprehensive molecular diagnostics, serial MRD monitoring, and personalized multidisciplinary care in DS-ALL.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
The Central Nervous System Modulatory Activities of N-Acetylcysteine: A Synthesis of Two Decades of Evidence. n -乙酰半胱氨酸对中枢神经系统的调节作用:二十年证据的综合。
IF 3 3区 生物学
Current Issues in Molecular Biology Pub Date : 2025-09-01 DOI: 10.3390/cimb47090710
Desislava Ivanova Cherneva, Gabriela Kehayova, Simeonka Dimitrova, Stela Dragomanova
{"title":"The Central Nervous System Modulatory Activities of N-Acetylcysteine: A Synthesis of Two Decades of Evidence.","authors":"Desislava Ivanova Cherneva, Gabriela Kehayova, Simeonka Dimitrova, Stela Dragomanova","doi":"10.3390/cimb47090710","DOIUrl":"10.3390/cimb47090710","url":null,"abstract":"<p><p>N-acetylcysteine (NAC) has garnered increasing interest for its neurotherapeutic capabilities beyond its recognized functions as a mucolytic agent and an antidote for acetaminophen toxicity. This review consolidates findings from both preclinical and clinical studies to investigate NAC's diverse modulatory effects on the central nervous system (CNS). NAC primarily functions as an antioxidant by replenishing glutathione and mitigating oxidative stress; however, it produces glutathione-independent effects through the modulation of mitochondrial redox systems, ferroptosis, and the Nrf2-ARE signaling pathway. It plays a significant role in neuroinflammatory processes by inhibiting the production of cytokines, the expression of iNOS, and the activation of microglia. Furthermore, NAC affects various neurotransmitter systems-including glutamatergic, dopaminergic, GABAergic, serotonergic, cholinergic, and adrenergic pathways-by modulating synaptic transmission, receptor activity, and transporter functionality. It promotes neuroprotection through the enhancement of neurotrophic factors, the preservation of mitochondrial integrity, and the upregulation of survival signaling pathways. Recent evidence also emphasizes NAC's role in gene expression and the regulation of cortisol levels. The extensive range of NAC's neurobiological effects highlights its therapeutic potential in treating neurodegenerative and neuropsychiatric disorders. Nevertheless, the variability in clinical outcomes indicates a pressing need for more focused, mechanism-based research.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Smart Red Blood Cell Carriers: A Nanotechnological Approach to Cancer Drug Delivery. 智能红细胞载体:一种纳米技术的癌症药物输送方法。
IF 3 3区 生物学
Current Issues in Molecular Biology Pub Date : 2025-09-01 DOI: 10.3390/cimb47090711
Ioannis Tsamesidis, Georgios Dryllis, Sotirios P Fortis, Andreas Sphicas, Vasiliki Konstantinidou, Maria Chatzidimitriou, Stella Mitka, Maria Trapali, Petros Skepastianos, Anastasios G Kriebardis, Ilias Pessach
{"title":"Smart Red Blood Cell Carriers: A Nanotechnological Approach to Cancer Drug Delivery.","authors":"Ioannis Tsamesidis, Georgios Dryllis, Sotirios P Fortis, Andreas Sphicas, Vasiliki Konstantinidou, Maria Chatzidimitriou, Stella Mitka, Maria Trapali, Petros Skepastianos, Anastasios G Kriebardis, Ilias Pessach","doi":"10.3390/cimb47090711","DOIUrl":"10.3390/cimb47090711","url":null,"abstract":"<p><p>The efficient and targeted delivery of pharmaceutical substances remains a major challenge in modern therapeutics. Traditional drug delivery systems often suffer from limited bioavailability, rapid clearance, and off-target effects. Red blood cells (erythrocytes), due to their long circulation time, biocompatibility, and immune-evasive properties, have emerged as promising carriers in the development of novel nanotechnology-based drug delivery platforms.A comprehensive literature review was conducted, analyzing recent studies on erythrocyte membrane-coated nanoparticles, their interactions with loaded therapeutic agents, and their performance in vitro and in vivo. Special focus was given to applications in chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), and immunotherapy. Erythrocyte-based nanocarriers demonstrated improved circulation times, reduced immune clearance, and enhanced targeting capabilities compared to traditional nanoparticles. Encapsulation of nanoparticles within erythrocyte membranes preserved the functional integrity of the carrier while minimizing systemic toxicity. However, challenges such as membrane stability, hemocompatibility, and the potential for nanoparticle-induced hemoglobin dysfunction were identified as areas requiring further research. In conclusion, erythrocyte membrane-coated nanoparticles represent a unique and promising strategy for drug delivery, combining the natural advantages of red blood cells with the versatility of nanotechnology.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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