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Antagonistic Effects of Actin-Specific Toxins on Salmonella Typhimurium Invasion into Mammalian Cells. 肌动蛋白特异性毒素对鼠伤寒沙门氏菌侵入哺乳动物细胞的拮抗作用
IF 4.8 2区 生物学
Biomolecules Pub Date : 2024-11-09 DOI: 10.3390/biom14111428
David B Heisler, Elena Kudryashova, Regan Hitt, Blake Williams, Michelle Dziejman, John Gunn, Dmitri S Kudryashov
{"title":"Antagonistic Effects of Actin-Specific Toxins on <i>Salmonella</i> Typhimurium Invasion into Mammalian Cells.","authors":"David B Heisler, Elena Kudryashova, Regan Hitt, Blake Williams, Michelle Dziejman, John Gunn, Dmitri S Kudryashov","doi":"10.3390/biom14111428","DOIUrl":"10.3390/biom14111428","url":null,"abstract":"<p><p>Competition between bacterial species is a major factor shaping microbial communities. It is possible but remains largely unexplored that competition between bacterial pathogens can be mediated through antagonistic effects of bacterial effector proteins on host systems, particularly the actin cytoskeleton. Using <i>Salmonella</i> Typhimurium invasion into cells as a model, we demonstrate that invasion is inhibited if the host actin cytoskeleton is disturbed by actin-specific toxins, namely, <i>Vibrio cholerae</i> MARTX actin crosslinking (ACD) and Rho GTPase inactivation (RID) domains, <i>Photorhabdus luminescens</i> TccC3, and <i>Salmonella</i>'s own SpvB. We noticed that ACD, being an effective inhibitor of tandem G-actin-binding assembly factors, is likely to inhibit the activity of another <i>Vibrio</i> effector, VopF. In reconstituted actin polymerization assays and by live-cell microscopy, we confirmed that ACD potently halted the actin nucleation and pointed-end elongation activities of VopF, revealing competition between these two <i>V. cholerae</i> effectors. These results suggest that bacterial effectors from different species that target the same host machinery or proteins may represent an effective but largely overlooked mechanism of indirect bacterial competition in host-associated microbial communities. Whether the proposed inhibition mechanism involves the actin cytoskeleton or other host cell compartments, such inhibition deserves investigation and may contribute to a documented scarcity of human enteric co-infections by different pathogenic bacteria.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725902","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
Investigating MerR's Selectivity: The Crosstalk Between Cadmium and Copper Under Elevated Stress Conditions. 研究 MerR 的选择性:高应激条件下镉和铜之间的相互影响
IF 4.8 2区 生物学
Biomolecules Pub Date : 2024-11-09 DOI: 10.3390/biom14111429
Anne Soisig Steunou, Anne Durand, Sylviane Liotenberg, Marie-Line Bourbon, Soufian Ouchane
{"title":"Investigating MerR's Selectivity: The Crosstalk Between Cadmium and Copper Under Elevated Stress Conditions.","authors":"Anne Soisig Steunou, Anne Durand, Sylviane Liotenberg, Marie-Line Bourbon, Soufian Ouchane","doi":"10.3390/biom14111429","DOIUrl":"10.3390/biom14111429","url":null,"abstract":"<p><p>Bacteria respond to metal pollution through sensors that control the uptake and the detoxification machineries. Specificity in metal recognition is therefore a prerequisite for triggering the appropriate response, particularly when facing a mixture of metals. In response to Cu<sup>+</sup>, the purple bacterium <i>Rubrivivax gelatinosus</i> induces the efflux Cu<sup>+</sup>-ATPase CopA by the Cu<sup>+</sup> regulator CopR. However, genetic analyses have suggested the presence of additional regulators. Here, we show that CadR, the Cd<sup>2+</sup> sensor, is involved in Cd<sup>2+</sup> and Cu<sup>+</sup> tolerance and demonstrate that CopR and CadR share common target genes. Interestingly, expression of the Cu<sup>+</sup> detoxification and efflux (CopI/CopA) system was induced by Cd<sup>2+</sup> and downregulated in the double mutant <i>copRcadR<sup>-</sup></i>. This double mutant was more sensitive to low Cu<sup>+</sup> concentration than the single <i>copR<sup>-</sup></i> mutant, and accumulation of coproporphyrin III pointed to a significantly decreased expression of CopA. Furthermore, analyses of Cd<sup>2+</sup> toxicity in the <i>cadR<sup>-</sup></i> mutant suggested that although CopR is Cu<sup>+</sup> selective, CopR is involved in Cd<sup>2+</sup> response since the addition of Cu<sup>+</sup> alleviates Cd<sup>2+</sup> toxicity. Based on our current knowledge of metal transport across the inner membrane, Cd<sup>2+</sup> and Cu<sup>+</sup> do not share common efflux routes nor do they share common regulators. Nevertheless, the crosstalk between Cd<sup>2+</sup> and Cu<sup>+</sup> tolerance systems is demonstrated in the present study. The modulation of Cu<sup>+</sup> detoxification by a Cd<sup>2+</sup> regulator in vivo places emphasis on the relaxed selectivity, under elevated metal concentration, in MerR regulators.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725872","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
Driving Forces in the Formation of Biocondensates of Highly Charged Proteins: A Thermodynamic Analysis of the Binary Complex Formation. 高电荷蛋白质形成生物冷凝物的驱动力:二元复合物形成的热力学分析。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2024-11-08 DOI: 10.3390/biom14111421
Matthias Ballauff
{"title":"Driving Forces in the Formation of Biocondensates of Highly Charged Proteins: A Thermodynamic Analysis of the Binary Complex Formation.","authors":"Matthias Ballauff","doi":"10.3390/biom14111421","DOIUrl":"10.3390/biom14111421","url":null,"abstract":"<p><p>A thermodynamic analysis of the binary complex formation of the highly positively charged linker histone H1 and the highly negatively charged chaperone prothymosin α (ProTα) is detailed. ProTα and H1 have large opposite net charges (-44 and +53, respectively) and form complexes at physiological salt concentrations with high affinities. The data obtained for the binary complex formation are analyzed by a thermodynamic model that is based on counterion condensation modulated by hydration effects. The analysis demonstrates that the release of the counterions mainly bound to ProTα is the main driving force, and effects related to water release play no role within the limits of error. A strongly negative Δ<i>c<sub>p</sub></i> (=-0.87 kJ/(K mol)) is found, which is due to the loss of conformational degrees of freedom.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725645","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
Adverse Effects of Aβ1-42 Oligomers: Impaired Contextual Memory and Altered Intrinsic Properties of CA1 Pyramidal Neurons. Aβ1-42 寡聚体的不良影响:CA1锥体神经元的内涵记忆受损和内在特性改变。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2024-11-08 DOI: 10.3390/biom14111425
Min-Kaung-Wint-Mon, Hiroyuki Kida, Itsuki Kanehisa, Masahiko Kurose, Junko Ishikawa, Yuya Sakimoto, Paw-Min-Thein-Oo, Ryoichi Kimura, Dai Mitsushima
{"title":"Adverse Effects of Aβ<sub>1-42</sub> Oligomers: Impaired Contextual Memory and Altered Intrinsic Properties of CA1 Pyramidal Neurons.","authors":"Min-Kaung-Wint-Mon, Hiroyuki Kida, Itsuki Kanehisa, Masahiko Kurose, Junko Ishikawa, Yuya Sakimoto, Paw-Min-Thein-Oo, Ryoichi Kimura, Dai Mitsushima","doi":"10.3390/biom14111425","DOIUrl":"10.3390/biom14111425","url":null,"abstract":"<p><p>Aβ<sub>1-42</sub> (amyloid beta) oligomers, the major neurotoxic culprits in Alzheimer's disease, initiate early pathophysiological events, including neuronal hyperactivity, that underlie aberrant network activity and cognitive impairment. Although several synaptotoxic effects have been extensively studied, neuronal hyperexcitability, which may also contribute to cognitive deficits, is not fully understood. Here, we found several adverse effects of in vivo injection of Aβ<sub>1-42</sub> oligomers on contextual memory and intrinsic properties of CA1 pyramidal neurons. Male rats underwent behavioral and electrophysiological studies 1 week after microinjections into the dorsal CA1 region, followed by histological analysis. After 1 week, Aβ<sub>1-42</sub> oligomers impaired contextual learning without affecting basic physiological functions and triggered training-induced neuronal excitability. Furthermore, riluzole, a persistent sodium current (<i>I</i><sub>NaP</sub>) blocker, dose-dependently reduced Aβ<sub>1-42</sub> oligomer-induced hyperexcitability. Congo red staining, which detects insoluble amyloid deposits, further identified labeling of CA1 pyramidal neurons while immunohistochemistry with lecanemab, which detects soluble Aβ oligomers, revealed immunoreactivity of both pyramidal and non-pyramidal cells in the target area. Therefore, our study suggests that a single injection of Aβ<sub>1-42</sub> oligomers resulted in contextual memory deficits along with concomitant neuronal hyperexcitability and amyloid deposition in the CA1 region after 1 week.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725887","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
Common Genetic Factors May Play a Role in the Relationships Between Body Composition, Adipokines, and Low-Back-Pain-Related Disability. 共同的遗传因素可能在身体成分、脂肪因子和腰背痛相关残疾之间的关系中发挥作用。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2024-11-08 DOI: 10.3390/biom14111426
Nader Tarabeih, Alexander Kalinkovich, Shai Ashkenazi, Adel Shalata, Gregory Livshits
{"title":"Common Genetic Factors May Play a Role in the Relationships Between Body Composition, Adipokines, and Low-Back-Pain-Related Disability.","authors":"Nader Tarabeih, Alexander Kalinkovich, Shai Ashkenazi, Adel Shalata, Gregory Livshits","doi":"10.3390/biom14111426","DOIUrl":"10.3390/biom14111426","url":null,"abstract":"<p><p>In this study, we evaluated the contribution of the putative genetic factors into the established associations between selected circulating adipokine levels, body composition measurements, and low-back-pain-related disability scores (LBP_DS). A total of 1078 individuals from 98 nuclear families (with 1 to 11 siblings per family) were examined. A detailed self-report questionnaire was used to collect LBP disability data; body composition (fat, skeletal muscle mass, and extracellular water (ECW)) was assessed using the bioimpedance method; plasma levels of adipokines were measured by ELISA. Pedigree-based statistical analysis methods were used, including family-based variance component analysis (VCA) and principal phenotype analysis (PPA), to estimate the contribution of potential genetic and environmental factors. The VCA revealed a significant additive genetic component in LBP_DS and for the selected body composition phenotypes and adipokines. The study also revealed that both adipokines (GDF-15, chemerin, and follistatin) and body composition variables (BMI, fat mass/weight, waist circumference, and ECW) were genetically correlated with LBP_DS. Next, PPA generated two synthetic phenotypes: PP<sub>CT</sub> (combining cytokines) and PP<sub>BC</sub> (combining body composition variables). There was no significant correlation between the putative genetic factors underlying the created PPs. However, each of them displayed a significant genetic correlation with LBP_DS. These findings indicate that genetic factors that are assumingly common for several adipokine variations and several body composition measurements, respectively, presumably have a pleotropic genetic influence on the LBP_DS variation, independently from one another. This, in turn, suggests that the alleged genetic factors employing pleiotropic effects on LBP_DS have a complex and probably non-overlapping composition.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725929","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
Plasma Proteome Alterations of Laying Hens Subjected to Heat Stress and Fed a Diet Supplemented with Pequi Oil (Caryocar brasiliense Camb.): New Insights in the Identification of Heat Stress Biomarkers. 遭受热应激并饲喂添加了贝壳油(Caryocar brasiliense Camb.)的蛋鸡血浆蛋白质组的变化:热应激生物标志物鉴定的新见解。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2024-11-08 DOI: 10.3390/biom14111424
Joyce da Silva, Luane Andrade, Paola Rodrigues, Laís Cordeiro, Gabrieli Lima, Júlia Lopes, Elis Castillo, Renata Martins, Andrey Assunção, José Vieira, Marília Busalaf, Jiri Adamec, José Sartori, Pedro Padilha
{"title":"Plasma Proteome Alterations of Laying Hens Subjected to Heat Stress and Fed a Diet Supplemented with Pequi Oil (<i>Caryocar brasiliense Camb.</i>): New Insights in the Identification of Heat Stress Biomarkers.","authors":"Joyce da Silva, Luane Andrade, Paola Rodrigues, Laís Cordeiro, Gabrieli Lima, Júlia Lopes, Elis Castillo, Renata Martins, Andrey Assunção, José Vieira, Marília Busalaf, Jiri Adamec, José Sartori, Pedro Padilha","doi":"10.3390/biom14111424","DOIUrl":"10.3390/biom14111424","url":null,"abstract":"<p><p>Heat stress can disrupt the balance between the heat poultry release into the environment and the heat they generate. Pequi oil has antioxidant properties, which may mitigate the heat stress effects. This study aimed to investigate the response of laying hens to pequi oil supplementation under heat stress using a proteomic approach. A total of 96 Lohmann White laying hens with 26 weeks old were housed in a completely randomized design with a 2 × 2 factorial arrangement. They were housed in two climate chambers, thermal comfort temperature ± 24.04 °C with the relative humidity ± 66.35 and heat stress (HS) ± 31.26 °C with the relative humidity ± 60.62. They were fed two diets: a control diet (CON), basal diet (BD) without additives, and with Pequi oil (PO), BD + 0.6% PO. After 84 days, plasma samples were analyzed using Shotgun and LC-MS/MS. Proteins related to anti-inflammation, transport, and the immune system were differentially expressed in hens fed PO and CON under heat stress compared to those in thermoneutral environments. This helps protect against oxidative stress and may support the body's ability to manage heat-induced damage, stabilizing protein expression under stress conditions. The ovotransferrin proteins, fibrinogen isoforms, apolipoprotein A-I, Proteasome activator subunit 4, Transthyretin, and the enzyme serine Peptidase Inhibitor_Kazal Type 5, which presented Upregulated (Up) equal to 1, present characteristics that may be crucial for enhancing the adaptive responses of hens to thermal stress, thereby increasing their tolerance and minimizing the negative effects of heat on egg production. The data presented in this manuscript provides new insights into the plasma proteome alterations of laying hens fed a diet supplemented with pequi oil during heat stress challenges.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725787","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
Comparison of Different Keratinocyte Cell Line Models for Analysis of NLRP1 Inflammasome Activation. 用于分析 NLRP1 炎症小体激活的不同角质细胞系模型的比较
IF 4.8 2区 生物学
Biomolecules Pub Date : 2024-11-08 DOI: 10.3390/biom14111427
Tian Wang, Amir S Yazdi, Diana Panayotova-Dimitrova
{"title":"Comparison of Different Keratinocyte Cell Line Models for Analysis of NLRP1 Inflammasome Activation.","authors":"Tian Wang, Amir S Yazdi, Diana Panayotova-Dimitrova","doi":"10.3390/biom14111427","DOIUrl":"10.3390/biom14111427","url":null,"abstract":"<p><p>The NLRP1 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-1) inflammasome is the most important inflammasome in human keratinocytes. It plays a crucial role in regulating innate immunity in the skin. This study aimed to evaluate NLRP1 inflammasome activation and the corresponding levels of detection in different keratinocyte cell lines to identify a suitable in vitro model for analyzing inflammasome activation in keratinocytes. We compared NLRP1 inflammasome activation, expression, and cell death among primary keratinocytes and immortalized keratinocyte cell lines HaCaT, HaSKpw, and SVTERT upon stimulation with ultraviolet B (UVB) irradiation or talabostat. The effects of both NLRP1 inducers on cell death and the modification of NLRP1 molecules were examined using fluorescence-activated cell sorting analysis, Western blotting, and an enzyme-linked immunosorbent assay. The key inflammasome components had varied expression levels among the keratinocyte cell models, with the highest expression observed in primary keratinocytes. Moreover, our data showed that both UVB and talabostat triggered cell death, and NLRP1 inflammasome activation was readily detected in primary keratinocytes but not in the analyzed immortalized keratinocyte cell lines. Therefore, we do not recommend the use of the immortalized keratinocyte cell lines HaCaT, HaSKpw, and SVTERT for analyzing inflammasome activation in keratinocytes; we strongly recommend the use of primary keratinocytes for these studies.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725931","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
The Development of a Non-Invasive Screening Method Based on Serum microRNAs to Quantify the Percentage of Liver Steatosis. 基于血清 microRNAs 的非侵入性筛查方法的开发,用于量化肝脏脂肪变性的比例。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2024-11-08 DOI: 10.3390/biom14111423
Polina Soluyanova, Guillermo Quintás, Álvaro Pérez-Rubio, Iván Rienda, Erika Moro, Marcel van Herwijnen, Marcha Verheijen, Florian Caiment, Judith Pérez-Rojas, Ramón Trullenque-Juan, Eugenia Pareja, Ramiro Jover
{"title":"The Development of a Non-Invasive Screening Method Based on Serum microRNAs to Quantify the Percentage of Liver Steatosis.","authors":"Polina Soluyanova, Guillermo Quintás, Álvaro Pérez-Rubio, Iván Rienda, Erika Moro, Marcel van Herwijnen, Marcha Verheijen, Florian Caiment, Judith Pérez-Rojas, Ramón Trullenque-Juan, Eugenia Pareja, Ramiro Jover","doi":"10.3390/biom14111423","DOIUrl":"10.3390/biom14111423","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is often asymptomatic and underdiagnosed; consequently, there is a demand for simple, non-invasive diagnostic tools. In this study, we developed a method to quantify liver steatosis based on miRNAs, present in liver and serum, that correlate with liver fat. The miRNAs were analyzed by miRNAseq in liver samples from two cohorts of patients with a precise quantification of liver steatosis. Common miRNAs showing correlation with liver steatosis were validated by RT-qPCR in paired liver and serum samples. Multivariate models were built using partial least squares (PLS) regression to predict the percentage of liver steatosis from serum miRNA levels. Leave-one-out cross validation and external validation were used for model selection and to estimate predictive performance. The miRNAseq results disclosed (a) 144 miRNAs correlating with triglycerides in a set of liver biobank samples (<i>n</i> = 20); and (b) 124 and 102 miRNAs correlating with steatosis by biopsy digital image and MRI analyses, respectively, in liver samples from morbidly obese patients (<i>n</i> = 24). However, only 35 miRNAs were common in both sets of samples. RT-qPCR allowed to validate the correlation of 10 miRNAs in paired liver and serum samples. The development of PLS models to quantitatively predict steatosis demonstrated that the combination of serum miR-145-3p, 122-5p, 143-3p, 500a-5p, and 182-5p provided the lowest root mean square error of cross validation (RMSECV = 1.1, <i>p</i>-value = 0.005). External validation of this model with a cohort of mixed MASLD patients (<i>n</i> = 25) showed a root mean squared error of prediction (RMSEP) of 5.3. In conclusion, it is possible to predict the percentage of hepatic steatosis with a low error rate by quantifying the serum level of five miRNAs using a cost-effective and easy-to-implement RT-qPCR method.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725947","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
Exploring the Biological Activity of a Humanized Anti-CD99 ScFv and Antibody for Targeting T Cell Malignancies. 探索针对 T 细胞恶性肿瘤的人源化抗 CD99 ScFv 和抗体的生物活性。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2024-11-08 DOI: 10.3390/biom14111422
Nuchjira Takheaw, Thanathat Pamonsupornwichit, Ratthakorn Chaiwut, Kamonporn Kotemul, Kanokporn Sornsuwan, On-Anong Juntit, Umpa Yasamut, Passaworn Cheyasawan, Witida Laopajon, Watchara Kasinrerk, Chatchai Tayapiwatana
{"title":"Exploring the Biological Activity of a Humanized Anti-CD99 ScFv and Antibody for Targeting T Cell Malignancies.","authors":"Nuchjira Takheaw, Thanathat Pamonsupornwichit, Ratthakorn Chaiwut, Kamonporn Kotemul, Kanokporn Sornsuwan, On-Anong Juntit, Umpa Yasamut, Passaworn Cheyasawan, Witida Laopajon, Watchara Kasinrerk, Chatchai Tayapiwatana","doi":"10.3390/biom14111422","DOIUrl":"10.3390/biom14111422","url":null,"abstract":"<p><p>CD99, a type I transmembrane protein, emerges as a promising therapeutic target due to its heightened expression in T cell acute lymphoblastic leukemia (T-ALL). This characteristic renders it a potential marker for minimal residual disease detection and an appealing target for antibody-based treatments. Previous studies have revealed that a mouse monoclonal antibody, mAb MT99/3, selectively binds to CD99, triggering apoptosis in T-ALL/T-LBL cells while preserving the integrity of healthy cells. By targeting CD99, mAb MT99/3 suppresses antigen presentation and disrupts T cell functions, offering promise for addressing hyperresponsive T cell conditions. To facilitate clinical translation, we developed a humanized ScFv variant of mAb MT99/3, termed HuScFvMT99/3 in \"ScFvkh\" design. Structural analysis confirms its resemblance to the original antibody, and the immunoreactivity of HuScFvMT99/3 against CD99 is preserved. The fully humanized version of antibody HuMT99/3 was further engineered, exhibiting similar binding affinity at the 10<sup>-10</sup> M level and specificity to the CD99 epitope without antigenic shift. HuMT99/3 demonstrates remarkable selectivity, recognizing both malignant and normal T cells but inducing apoptosis only in T-ALL/T-LBL cells, highlighting its potential for safe and targeted therapy.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"14 11","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725770","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
A Simple and Efficient One-Step Synthesis System for Flexible Production of Circular RNA in E. coli. 在大肠杆菌中灵活生产环状 RNA 的简单高效的一步合成系统。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2024-11-07 DOI: 10.3390/biom14111416
Xiayang Zhao, Yiqing Liu, Huanhui Huang, Yue Sun, Fangli Wu, Weibo Jin
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