Quoc-Anh Tran, Grant Van Tran, Sanel Velic, Hou-Mai Xiong, Jaspreet Kaur, Zuhurr Moosavi, Phuong Nguyen, Nhi Duong, Vy Tran Luu, Gurjot Singh, Tram Bui, Melanie Rose, Linh Ho
{"title":"Effects of Astragaloside IV and Formononetin on Oxidative Stress and Mitochondrial Biogenesis in Hepatocytes.","authors":"Quoc-Anh Tran, Grant Van Tran, Sanel Velic, Hou-Mai Xiong, Jaspreet Kaur, Zuhurr Moosavi, Phuong Nguyen, Nhi Duong, Vy Tran Luu, Gurjot Singh, Tram Bui, Melanie Rose, Linh Ho","doi":"10.3390/ijms26020774","DOIUrl":"10.3390/ijms26020774","url":null,"abstract":"<p><p>Over-accumulation of reactive oxygen species (ROS) causes hepatocyte dysfunction and apoptosis that might lead to the progression of liver damage. Sirtuin-3 (SIRT3), the main NAD+-dependent deacetylase located in mitochondria, has a critical role in regulation of mitochondrial function and ROS production as well as in the mitochondrial antioxidant mechanism. This study explores the roles of astragaloside IV (AST-IV) and formononetin (FMR) in connection with SIRT3 for potential antioxidative effects. It was shown that the condition of combined pre- and post-treatment with AST-IV or FMR at all concentrations statistically increased and rescued cell proliferation. ROS levels were not affected by pre-or post-treatment individually with AST-IV or pre-treatment with FMR; however, post-treatment with FMR resulted in significant increases in ROS in all groups. Significant decreases in ROS levels were seen when pre- and post-treatment with AST-IV were combined at 5 and 10 μM, or FMR at 5 and 20 μM. In the condition of combined pre- and post-treatment with 10 μM AST-IV, there was a significant increase in SOD activity, and the transcriptional levels of Sod2, Cat, and GPX1 in all treatment groups, which is indicative of reactive oxygen species detoxification. Furthermore, AST-IV and FMR activated PGC-1α and AMPK as well as SIRT3 expression in AML12 hepatocytes exposed to <i>t</i>-BHP-induced oxidative stress, especially at high concentrations of FMR. This study presents a novel mechanism whereby AST-IV and FMR yield an antioxidant effect through induction of SIRT3 protein expression and activation of an antioxidant mechanism as well as mitochondrial biogenesis and mitochondrial content and potential. The findings suggest these agents can be used as SIRT3 modulators in treating oxidative-injury hepatocytes.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038540","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}
Wojciech Tynior, Dorota Hudy, Karolina Gołąbek, Agnieszka Raczkowska-Siostrzonek, Joanna Katarzyna Strzelczyk
{"title":"Expression of <i>AMELX</i>, <i>AMBN</i>, <i>ENAM</i>, <i>TUFT1</i>, <i>FAM83H</i> and <i>MMP20</i> Genes in Buccal Epithelial Cells from Patients with Molar Incisor Hypomineralization (MIH)-A Pilot Study.","authors":"Wojciech Tynior, Dorota Hudy, Karolina Gołąbek, Agnieszka Raczkowska-Siostrzonek, Joanna Katarzyna Strzelczyk","doi":"10.3390/ijms26020766","DOIUrl":"10.3390/ijms26020766","url":null,"abstract":"<p><p>Molar incisor hypomineralization (MIH) is a developmental defect that affects the enamel tissue of permanent teeth. Clinicians may observe a range of opacities in the affected teeth, varying from white to creamy, yellow, and brown. Of particular interest is an etiology of MIH that has not been rigorously elucidated. Researchers believe that there are many potential etiological factors with strong genetic and/or epigenetic influence. The primary factors contributing to the risk of MIH development include specific medical conditions and circumstances. These encompass prematurity, cesarean delivery, perinatal hypoxia, and various health issues such as measles, urinary tract infections, otitis media, gastrointestinal disorders, bronchitis, kidney diseases, pneumonia, and asthma. Although genetic research in this area has received substantial attention, the investigation of epigenetic factors remains comparatively underexplored. Special attention is given to genes and their protein products involved in amelogenesis. Examples of such genes are <i>AMELX</i>, <i>AMBN</i>, <i>ENAM</i>, <i>TUFT1</i>, <i>FAM83H</i>, and <i>MMP20</i>. The median relative <i>FAM83H</i> gene expression in the control group was 0.038 (0.031-0.061) and 0.045 (0.032-0.087) in the study group in buccal swabs. The median relative <i>TUFT1</i> gene expression in the control group was 0.328 (0.247-0.456) and 0.704 (0.334-1.183) in the study group in buccal swabs. Furthermore, children with MIH had significantly higher <i>TUFT1</i> expression levels compared to the control group (<i>p</i>-value = 0.0043). Alterations in the expression of the <i>TUFT1</i> and <i>FAM83H</i> genes could be contributing factors to MIH pathogenesis. Nonetheless, further investigation is essential to comprehensively elucidate the roles of all analyzed genes in the pathogenesis of MIH.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058947","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}
Elisa Di Giorgio, Silvia Benavides-Varela, Annamaria Porru, Sara Caviola, Marco Lunghi, Paola Rigo, Giovanna Mioni, Giulia Calignano, Martina Annunziata, Eloisa Valenza, Valentina Liani, Federica Beghetti, Fabiola Spolaor, Elisa Bettella, Roberta Polli, Zimi Sawacha, Alessandra Murgia
{"title":"Neurobehavioral Outcomes Relate to Activation Ratio in Female Carriers of Fragile X Syndrome Full Mutation: Two Pediatric Case Studies.","authors":"Elisa Di Giorgio, Silvia Benavides-Varela, Annamaria Porru, Sara Caviola, Marco Lunghi, Paola Rigo, Giovanna Mioni, Giulia Calignano, Martina Annunziata, Eloisa Valenza, Valentina Liani, Federica Beghetti, Fabiola Spolaor, Elisa Bettella, Roberta Polli, Zimi Sawacha, Alessandra Murgia","doi":"10.3390/ijms26020771","DOIUrl":"10.3390/ijms26020771","url":null,"abstract":"<p><p>Fragile X syndrome (FXS) is a genetic neurodevelopmental disorder that causes a range of developmental problems including cognitive and behavioral impairment and learning disabilities. FXS is caused by full mutations (FM) of the <i>FMR1</i> gene expansions to over 200 repeats, with hypermethylation of the cytosine-guanine-guanine (CGG) tandem repeated region in its promoter, resulting in transcriptional silencing and loss of gene function. Female carriers of FM are typically less impaired than males. The Activation Ratio (AR), the fraction of the normal allele carried on the active X chromosome, is thought to play a crucial modifying role in defining phenotype severity. Here, we compare the cognitive, neuropsychological, adaptive, and behavioral profile of two FXS girls (10 and 11 years old) with seemingly identical <i>FMR1</i> genotypic profile of FM but distinctive AR levels (70% vs. 30%). A multi-method protocol, combining molecular pathophysiology and phenotypical measures, parent reports, lab-based tasks, gait analyses, and eye-tracking was employed. Results showed that lower AR corresponds to worse performances in most (cognitive, neuropsychological, adaptive, behavioral, social, mathematical skills), but not all the considered areas (i.e., time perception and gait analysis). These observations underscore the importance of AR as a phenotypic modifying parameter in females affected with FXS.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038675","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}
Fabrizia Sepe, Anna Valentino, Loredana Marcolongo, Orsolina Petillo, Raffaele Conte, Sabrina Margarucci, Gianfranco Peluso, Anna Calarco
{"title":"Marine-Derived Polysaccharide Hydrogels as Delivery Platforms for Natural Bioactive Compounds.","authors":"Fabrizia Sepe, Anna Valentino, Loredana Marcolongo, Orsolina Petillo, Raffaele Conte, Sabrina Margarucci, Gianfranco Peluso, Anna Calarco","doi":"10.3390/ijms26020764","DOIUrl":"10.3390/ijms26020764","url":null,"abstract":"<p><p>Marine polysaccharide hydrogels have emerged as an innovative platform for regulating the in vivo release of natural bioactive compounds for medical purposes. These hydrogels, which have exceptional biocompatibility, biodegradability, and high water absorption capacity, create effective matrices for encapsulating different bioactive molecules. In addition, by modifying the physical and chemical properties of marine hydrogels, including cross-linking density, swelling behavior, and response to external stimuli like pH, temperature, or ionic strength, the release profile of encapsulated bioactive compounds is strictly regulated, thus maximizing therapeutic efficacy and minimizing side effects. Finally, by using naturally sourced polysaccharides in hydrogel formulations, sustainability is promoted by reducing dependence on synthetic polymers, meeting the growing demand for eco-friendly materials. This review analyzes the interaction between marine polysaccharide hydrogels and encapsulating compounds and offers examples of how bioactive molecules can be encapsulated, released, and stabilized.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038535","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}
Antonio de Jesús Sanchez-Garcia, Mauricio Soule-Egea, Giovanny Fuentevilla-Alvarez, Gilberto Vargas-Alarcon, Benjamín Iván Hernández-Mejia, Humberto Martínez-Hernández, Sergio Luis Mora-Canela, Felipe Santibanez-Escobar, Valeria Ávila-Martinez, Vicente Castrejón-Tellez, Edith Alvarez-León, Regina de la Mora-Cervantes, Israel Pérez-Torres, María Elena Soto
{"title":"Role of miRNAs in Regulating Ascending Aortic Dilation in Bicuspid Aortic Valve Patients Operated for Aortic Stenosis.","authors":"Antonio de Jesús Sanchez-Garcia, Mauricio Soule-Egea, Giovanny Fuentevilla-Alvarez, Gilberto Vargas-Alarcon, Benjamín Iván Hernández-Mejia, Humberto Martínez-Hernández, Sergio Luis Mora-Canela, Felipe Santibanez-Escobar, Valeria Ávila-Martinez, Vicente Castrejón-Tellez, Edith Alvarez-León, Regina de la Mora-Cervantes, Israel Pérez-Torres, María Elena Soto","doi":"10.3390/ijms26020779","DOIUrl":"10.3390/ijms26020779","url":null,"abstract":"<p><p>Deregulation of micro-RNAs (miRNAs) may contribute to mechanisms of injury in the bicuspid aortic valve (BAV). Our objective was to investigate the expression of miRNAs in aortic tissue from patients who underwent aortic valve replacement for aortic stenosis and its relationship with aortic dilatation. The study included 78 patients, 40 with bicuspid aortic valve (BAV) and 38 with tricuspid aortic valve (TAV). The expression of miRNA-17-5p, hsa-let-7e, and miRNA-196a-5p in human aortic tissue was evaluated by a reverse transcriptase polymerase chain reaction (RT-qPCR). Comparative analysis between patients with BAV and controls with TAV explored the association between the miRNAs and aortic dilatation (AD), calcification, valve dysfunction, and stenosis. The results showed that the expression levels of miRNA-Let-7e-5p and miRNA-196-5p were mostly increased in patients with BAV and aortic dilatation (<i>p</i> = 0.01 and <i>p</i> = 0.01), respectively. In contrast, the levels of miRNA-17a-5p (<i>p</i> < 0.20) were lower but without a statistically significant difference. The downregulation of miRNA-17a-5p and the upregulation of miR-Let-7e-5p and miR-196-5p were related to an increased risk of AD risk. Subjects with BAVs with or without double aortic lesions had higher expression levels of Let-7e-5p and miRNA-17a-5p vs. TAV. In all patients, we found an inverse correlation of MiRNA-196-5p with High-Density Lipoprotein-Cholesterol (HDL-C) and indexed valvular area. In subjects with a higher expression of miRNA196, lower levels of HDL-C correlation (r<sup>2</sup>) [r<sup>2</sup> 0.27 (<i>p</i> = 0.02)] and a lower indexed valvular area [r<sup>2</sup> 0.28 (<i>p</i> = 0.05)] were observed. In the specific analysis for each patient group, it was found that in control subjects with tricuspid aortic valve (TAV), miRNA-196-5p had a positive correlation with valvular calcification (r<sup>2</sup> = 0.60, <i>p</i> = 0.02). Deregulation of miRNAs in the aortic tissue of a BAV may influence valvular stenosis, dysfunction, and concomitant aortic dilation. This information could help to define potential therapeutic target strategies to improve the prognosis and treatment of BAV.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038552","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}
{"title":"Mechanism of Transcription Factor ChbZIP1 Enhanced Alkaline Stress Tolerance in <i>Chlamydomonas reinhardtii</i>.","authors":"Ao Wang, Rui Wang, Xiaoling Miao","doi":"10.3390/ijms26020769","DOIUrl":"10.3390/ijms26020769","url":null,"abstract":"<p><p>Alkaline environments such as alkaline lands, lakes, and industrial wastewater are not conducive to the growth of plants and microorganisms due to high pH and salinity. ChbZIP1 is a bZIP family transcription factor isolated from an alkaliphilic microalgae (<i>Chlorella</i> sp. BLD). Previous studies have demonstrated its ability to enhance alkaline tolerance in <i>Arabidopsis thaliana</i>. However, the potential of ChbZIP1 to confer similar alkaline tolerance in other microalgae remains unclear, and the specific mechanisms are not fully understood. The analysis of cellular physiological and biochemical indicators revealed that the ChbZIP1 transformants exhibited enhanced photosynthetic activity, increased lipid accumulation, and reduced fatty acid unsaturation. Genes associated with cellular reactive oxygen species (ROS) detoxification were found to be upregulated, and a corresponding increase in antioxidant enzyme activity was detected. In addition, the relative abundance of intracellular ROS and malondialdehyde (MDA) was significantly lower in the transformants. In summary, our research indicates that ChbZIP1 enhances the tolerance of <i>Chlamydomonas reinhardtii</i> to alkaline environments through several mechanisms, including the repair of damaged photosynthesis, increased lipid accumulation, improved fatty acid unsaturation, and enhanced antioxidant enzyme activity. This study aims to contribute to a more comprehensive understanding of the mechanisms underlying alkalinity tolerance in microalgae and offers new insights and theoretical foundations for the utilization of microalgae in alkaline environments.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038541","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}
{"title":"Functional and Structural Changes in the Inner Ear and Cochlear Hair Cell Loss Induced by Hypergravity.","authors":"Jin Sil Choi, Kyu-Sung Kim, Hyun Ji Kim","doi":"10.3390/ijms26020758","DOIUrl":"10.3390/ijms26020758","url":null,"abstract":"<p><p>Gravitational changes have been shown to cause significant abnormalities in various body systems, including the cardiovascular, immune, vestibular, and musculoskeletal systems. While numerous studies have examined the response of the vestibular system to gravitational stimulation, research on functional changes in the peripheral inner ear remains limited. The inner ear comprises two closely related structures: the vestibule and cochlea. These components share similar structures and neural functions, highlighting the importance of investigating changes in auditory nerve cells in response to gravitational alterations. To address this gap, we studied the functional and structural changes in the inner ear following exposure to hypergravity stimuli. Our findings demonstrate changes in auditory brainstem responses (ABRs) in the cochlea. ABR recordings were used to analyze click thresholds, as well as the amplitude and latency of tone bursts. The click thresholds at all frequencies increased in the group exposed to hypergravity in the long term. Additionally, tone burst results revealed significantly reduced amplitudes at high frequencies and delayed latencies in the hypergravity models. Notably, greater hair cell loss was observed in the middle and basal turns of the cochlea, indicating that mid and high-frequency regions are more vulnerable to hypergravity stimulation. Furthermore, nerve damage on the cochlear surface was evident in subjects exposed to 4G stimulation for 4 weeks. These findings suggest that the inner ear and its neural activity can be functionally and structurally affected by prolonged exposure to hypergravity.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038674","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}
{"title":"A Review of Immunological Evaluation of Patients with Recurrent Spontaneous Abortion (RSA).","authors":"Mihaela Andreescu, Alina Tanase, Bogdan Andreescu, Cosmin Moldovan","doi":"10.3390/ijms26020785","DOIUrl":"10.3390/ijms26020785","url":null,"abstract":"<p><p>In approximately half of the recurrent spontaneous abortion (RSA) cases, the underlying cause is unknown. However, most unexplained miscarriages are thought to be linked to immune dysfunction. This review summarizes the current evidence regarding the immunological evaluations of patients with RSA, with potential implications for clinical research. The immune system plays a crucial role in the successful outcome of pregnancy, as it tolerates the semi-allogeneic fetus while offering protection to both the mother and fetus from pathogens. The maternal-fetal interface is the place where the crosstalk between various immune cells such as macrophages, dendritic cells, natural killer (NK) cells, and T cells takes place. An adequate balance is required between these immune cells for pregnancy to progress. In RSA, a dysregulation between these immune players is witnessed. For example, in RSA, NK cells are not increased but also undergo a change in their activity, manifested as cytotoxic decidual NK. Similarly, regulatory T cells, which are crucial for fostering a tolerant immune environment, are decreased in RSA women. Similarly, imbalances between T-helper (Th1, Th2, Th17) cell subsets have been implicated in RSA. Furthermore, the imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophage phenotypes has been documented, with studies indicating a predominance of M1 macrophages in RSA patients. Targeting immune imbalances with therapies such as immunoglobulin administration, TNF inhibitors, and anticoagulants may improve pregnancy outcomes in women with RSA.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038366","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}
{"title":"Adjuvant Systemic Immunotherapies for Resected Stage III Melanoma: A Single-Centre Retrospective Clinical Practice Review.","authors":"Alicia Yioli Lefas, Cigdem Cinar, Shruti Sreekumar, Farrokh Pakzad, Panagiotis Koliou","doi":"10.3390/ijms26020750","DOIUrl":"10.3390/ijms26020750","url":null,"abstract":"<p><p>Melanoma poses significant challenges due to its resistance to conventional therapies and increasing incidence rates. Stage III melanoma, characterised by regional lymph node involvement, has a high risk of recurrence despite surgical resection. Adjuvant immunotherapy, particularly using the PD-1 inhibitors pembrolizumab and nivolumab, has shown promising results in improving recurrence-free survival (RFS) and overall survival (OS) in Stage III melanoma patients. This retrospective analysis examined the effects of adjuvant pembrolizumab or nivolumab on patients with Stage III melanoma treated in a tertiary oncology centre. Of the 110 patients, 95 received pembrolizumab and 15 received nivolumab. The pembrolizumab completion rate was 62.1%, with 31.2% discontinuing due to disease progression or adverse effects. The nivolumab completion rate was lower at 40%, with 60% discontinuing due to toxicity or disease progression. Grade 3 or higher toxicities were observed in 17% of pembrolizumab and 53.3% of nivolumab patients. Disease progression occurred in 27.4% of pembrolizumab and 26.7% of nivolumab patients. Pembrolizumab showed a 12-month RFS of 78.9% and 24-month RFS of 77.6%, with an OS of 97.9% at 12 months. Nivolumab exhibited a 12-month RFS of 86.7% and 24-month RFS of 80%. RFS rates varied by disease stage and mutation status. Adjuvant pembrolizumab and nivolumab both demonstrate efficacy in improving RFS and OS in Stage III melanoma patients. Pembrolizumab has higher completion rates and fewer toxicities compared to nivolumab. Further studies are warranted to explore long-term outcomes and optimise treatment strategies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038373","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}
Yunrui Hao, Ying-Jou Lee, Kihan Yap, Miny Samuel, Vincent T Chow
{"title":"Comparison of Respiratory Microbiomes in Influenza Versus Other Respiratory Infections: Systematic Review and Analysis.","authors":"Yunrui Hao, Ying-Jou Lee, Kihan Yap, Miny Samuel, Vincent T Chow","doi":"10.3390/ijms26020778","DOIUrl":"10.3390/ijms26020778","url":null,"abstract":"<p><p>Studies have indicated the potential importance of the human nasal and respiratory microbiomes in health and disease. However, the roles of these microbiomes in the pathogenesis of influenza and its complications are not fully understood. Therefore, the objective of this systematic review and analysis is to identify the patterns of nasal and respiratory microbiome dysbiosis and to define the unique signature bacteria associated with influenza compared with other respiratory tract infections. We compared the respiratory microbiome composition between influenza patients and healthy controls; across different influenza severities; in adult versus pediatric influenza patients; as well as influenza versus other respiratory infections. The desired outcomes include the signature bacteria in each cohort and the Shannon index to reflect the alpha diversity. Of the 2269 articles identified, 31 studies fulfilled the inclusion criteria. These studies investigated the respiratory tract microbiomes of patients with influenza, COVID-19, pneumonia, other respiratory infections, and chronic rhinosinusitis (CRS). Our review revealed that the phylum <i>Firmicutes</i> and <i>Actinobacteria</i>, genus <i>Actinomyces</i>, <i>Streptococcus</i> and <i>Granulicatella</i>, and species <i>Neisseria</i> are more prominent in severe influenza than mild to moderate influenza. Reduced microbiome alpha diversity is noted in influenza patients compared to healthy controls. There are some similarities and differences between the signature bacteria in pediatric and adult influenza patients, e.g., <i>Streptococcus</i> is common in both age groups, whereas <i>Pseudomonas</i> is associated with adults. Intriguingly, there is a common predominance of <i>Streptococcus</i> and <i>Firmicutes</i> among influenza and pneumonia patients. COVID-19 patients exhibit an increased abundance of <i>Firmicutes</i> as well as <i>Pseudomonas</i>. In CRS patients, <i>Proteobacteria</i> and <i>Haemophilus</i> are found in high abundance. This review highlights some similarities and differences in the respiratory microbiomes and their signature organisms in influenza of varying severity and in different age groups compared with other respiratory infections. The dysbiosis of the respiratory microbiomes in these respiratory infections enhances our understanding of their underlying pathogenic mechanisms.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038487","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}