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Background: Arrhythmic mitral valve prolapse syndrome (ARMV) is a recognized but underdiagnosed disease pattern. Risk factors for ARMV are established but not very well known, and the association of the structural abnormality with ventricular arrhythmias is incompletely understood. Case summary: Here, we present the case of a young man who presented at our hospital for radiofrequency catheter ablation and mitral valve surgery after two episodes of survived sudden cardiac arrest. We discuss the diagnostic and therapeutic strategies that were used. We shine light on the risk factors for ARMV and why early identification is crucial. We address the topic of primary prevention and its limitations. Finally, we discuss different treatment modalities for patients with ARMV. Discussion: More awareness for ARMV is crucial. A consensus statement on clinical management exists, but scientific gaps in prospective data for primary prevention need to be filled and there is a need for a better understanding of the pathogenesis of ARMV.
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High-quality primer design is essential for the success of all polymerase chain reaction (PCR)-based experiments. We previously developed a thermodynamics-based gene-specific quantitative PCR (qPCR) primer database for 147 organisms, which has been used extensively in gene expression studies. However, the number of organisms and the imperfection of function in the database limits its potential applications. Here, we improved the functionality of qPrimerDB to create a more comprehensive primer resource. Specifically, we (i) developed an improved primer design tool, qPrimer, building upon the previous qPrimerDB pipeline, to enhance the efficiency and simplicity of genome-scale qPCR primer design; (ii) pre-computed qPCR primer resources from 1 308 genomes of 1172 organisms and (iii) introduced a complete system for identifying, designing, checking, marking, and submitting qPCR primers. qPrimerDB 2.0 is freely available at https://qprimerdb.biodb.org. The qPrimer source code is available at https://github.com/swu1019lab/qPrimer.
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To explore the application efficacy and significance of deep learning in anesthesia management for gastrointestinal tumors (GITs) surgery, 80 elderly patients with GITs who underwent surgical intervention at our institution between January and September 2021 were enrolled. According to the preoperative anesthesia management methodology, patients were rolled into a control (Ctrl) group (using 10 mg dexamethasone 1-2 hours before surgery) and an experimental (Exp) group (using a deep learning-based anesthesia monitoring system on the basis of the Ctrl group), with 40 cases in each group. A comprehensive comparative analysis was performed between the two cohorts, encompassing postoperative cognitive evaluations, Montreal Cognitive Assessment (MoCA) scores, gastrointestinal functionality, serum biomarkers (including interleukin (IL)-6, C-reactive protein (CRP), and cortisol levels), length of hospitalization, incidence of complications, and other pertinent metrics. The findings demonstrated that anesthesia monitoring facilitated by deep learning algorithms effectively assessed the anesthesia state of patients. Compared to the Ctrl group, patients in the Exp group showed significant differences in cognitive assessments (word recall, number connection, number coding) (P<0.05). Additionally, the Exp group exhibited a notably increased MoCA score (25.3±2.4), significantly shorter time to first flatus postoperatively (35.8±13.7 hours), markedly reduced postoperative pain scores, significantly shortened time to tolerate a liquid diet postoperatively (19.6±5.2 hours), accelerated recovery of serum-related indicators, and a significantly decreased mean length of hospital stay (11.4±3.2 days) compared to the Ctrl group. In summary, administering dexamethasone under the anesthesia management of GITs surgery based on gradient boosting decision tree (GBDT) and pharmacokinetics pharmacodynamics (PKPD) models can promote patient recovery, reduce the incidence of postoperative cognitive impairment (POCD), and improve patient prognosis.
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Aprendizado Profundo , Dexametasona , Neoplasias Gastrointestinais , Humanos , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Feminino , Masculino , Idoso , Neoplasias Gastrointestinais/cirurgia , Idoso de 80 Anos ou mais , Anestesia/métodos , Complicações Pós-Operatórias/prevenção & controle , Tempo de Internação , Cognição/efeitos dos fármacosRESUMO
Gut microbiome is a group of microorganisms that plays important roles in contributing to health and diseases. These bacterial compositions have been demonstrated to impact bile acids (BAs) profiles, either by directly metabolizing primary BAs to secondary BAs or indirect ways through host metabolism by influencing BAs synthesis, transportation and conjugation in liver. It has been observed sexually dimorphic gut microbiome and bile acids composition, with variations in expression levels of bile acid metabolizing genes in the liver. However, associations between sex-specific differences in gut microbiome and BAs profiles are not well understood. This study aimed to investigate whether gut microbiome could influence BAs profiles in host in a sexspecific manner. We transplanted cecum feces of male and female C57BL/6 mice to male mice and measured BAs concentrations in feces, serum and liver samples 7 days after fecal transplantation. We found different BAs profiles between mice with male and female gut microbiome, including altering levels and proportions of secondary BAs. We also observed varied expression levels of genes related to bile acid metabolism in the liver and distal ileum. Our results highlight sex-specific effects of gut microbiome on shaping bile acid metabolism through gut bacteria and regulation of host genes.
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Purpose: The retrospective study reviewed the clinical and radiological outcomes of patients treated with radiocapitellar joint plasty. Methods: 10 children with missed Monteggia fracture (MMF) were reviewed. The average time from injury to operation was 20 months. The average age of children who underwent the operation was 10.5 years. 6 flat and 4 domed radial heads were included. 7 type I and 3 type III MMF were identified based on the Bado classification. All children with MMF were treated by open radial head reduction with radiocapitellar joint plasty and ulnar osteotomy (UO). Results: The average union time was 4.9 ± 2.6 months. The average osteotomy angle to reduce the radial head was 15.7 ± 3.5°, and the average lengthening of the ulna was 8.2 ± 3.2â mm. The average preoperative flexion range of motion was 110.5 ± 9.1°, and the postoperative flexion range of motion was 138.8 ± 15.1° (p < 0.05). The average preoperative extension range of motion was 10.1 ± 3.2°, and the postoperative extension range of motion was 5.5 ± 3.3° (p < 0.05). The average preoperative pronation range of motion was 78.8 ± 8.7°, while the postoperative pronation range of motion was 81.1 ± 5.6° (p > 0.05). The average preoperative supination range of motion was 68.3 ± 9.7°, and the postoperative supination range of motion was 80.1 ± 7.8° (p < 0.05). The preoperative Kim score was 66.5 ± 10.9°, and the postoperative Kim score was 88.1 ± 12.6 (p < 0.05). The radial head was completely reduced in 9 patients, and subluxation in 1 patient. Osteoarthritis of the radiocapitellar joint was observed in 2 patients. Conclusions: Radiocapitellar joint plasty is effective surgical intervention for MMF with radial head deformity. It yields favorable functional outcomes while ensuring continued radial head reduction.
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The prevalence of different metabolic syndromes has grown globally, and the farnesoid X receptor (FXR), a metabolic homeostat for glucose, lipid, and bile acid metabolisms, may serve an important role in the progression of metabolic disorders. Glucose intolerance by FXR deficiency was previously reported and observed in our study, but the underlying biology remained unclear. To investigate the ambiguity, we collected the nontargeted profiles of the fecal metaproteome, serum metabolome, and liver proteome in Fxr-null (Fxr-/-) and wild-type (WT) mice with LC-HRMS. FXR deficiency showed a global impact on the different molecular levels we monitored, suggesting its serious disruption in the gut microbiota, hepatic metabolism, and circulating biomolecules. The network and enrichment analyses of the dysregulated metabolites and proteins suggested the perturbation of carbohydrate and lipid metabolism by FXR deficiency. Fxr-/- mice presented lower levels of hepatic proteins involved in glycogenesis. The impairment of glycogenesis by an FXR deficiency may leave glucose to accumulate in the circulation, which may deteriorate glucose tolerance. Lipid metabolism was dysregulated by FXR deficiency in a structural-dependent manner. Fatty acid ß-oxidations were alleviated, but cholesterol metabolism was promoted by an FXR deficiency. Together, we explored the molecular events associated with glucose intolerance by impaired FXR with integrated novel multiomic data.
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Intolerância à Glucose , Metabolismo dos Lipídeos , Fígado , Camundongos Knockout , Multiômica , Receptores Citoplasmáticos e Nucleares , Animais , Masculino , Camundongos , Fezes/química , Microbioma Gastrointestinal , Glucose/metabolismo , Intolerância à Glucose/metabolismo , Intolerância à Glucose/sangue , Intolerância à Glucose/genética , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Metaboloma , Multiômica/métodos , Proteoma/metabolismo , Proteômica/métodos , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/deficiênciaRESUMO
In the modern "omics" era, measurement of the human exposome is a critical missing link between genetic drivers and disease outcomes. High-resolution mass spectrometry (HRMS), routinely used in proteomics and metabolomics, has emerged as a leading technology to broadly profile chemical exposure agents and related biomolecules for accurate mass measurement, high sensitivity, rapid data acquisition, and increased resolution of chemical space. Non-targeted approaches are increasingly accessible, supporting a shift from conventional hypothesis-driven, quantitation-centric targeted analyses toward data-driven, hypothesis-generating chemical exposome-wide profiling. However, HRMS-based exposomics encounters unique challenges. New analytical and computational infrastructures are needed to expand the analysis coverage through streamlined, scalable, and harmonized workflows and data pipelines that permit longitudinal chemical exposome tracking, retrospective validation, and multi-omics integration for meaningful health-oriented inferences. In this article, we survey the literature on state-of-the-art HRMS-based technologies, review current analytical workflows and informatic pipelines, and provide an up-to-date reference on exposomic approaches for chemists, toxicologists, epidemiologists, care providers, and stakeholders in health sciences and medicine. We propose efforts to benchmark fit-for-purpose platforms for expanding coverage of chemical space, including gas/liquid chromatography-HRMS (GC-HRMS and LC-HRMS), and discuss opportunities, challenges, and strategies to advance the burgeoning field of the exposome.
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Espectrometria de Massas , Humanos , Espectrometria de Massas/métodos , Expossoma , Metabolômica , Proteômica/métodos , Exposição AmbientalRESUMO
NMDA receptor-dependent long-term depression (LTD) in the hippocampus is a well-known form of synaptic plasticity that has been linked to different cognitive functions. Although the underlying mechanisms remain unclear, this form of LTD cannot be induced by low-frequency stimulation (LFS) in adult mice. In this study, we found that LFS-induced LTD was not easily induced in adult animals and was age dependent. Interestingly, the level of the 5-HT1A receptor was correspondingly increased and exhibited an inverse correlation with the magnitude of LFS-LTD during development. Knockout or pharmacological inhibition of the 5-HT1A receptor reversed impaired LFS-LTD in adult mice (P60), while activation or inhibition of this receptor disturbed or enhanced LFS-LTD in adolescent mice (P21), respectively. Furthermore, the astrocytic 5-HT1A receptor in the hippocampus predominantly mediated age-dependent LFS-LTD through enhancing GABAergic neurotransmission. Finally, fear memory extinction differed among the above conditions. These observations enrich our knowledge of LTD at the cellular level and suggest a therapeutic approach for LTD-related psychiatric disorders.
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Minimizing energy loss plays a critical role in the quest for high-performance organic solar cells (OSCs). However, the origin of large energy loss in OCSs is complicated, involving the strong exciton binding energy of organic semiconductors, nonradiative charge-transfer state decay, defective molecular stacking network, and so on. The recently developed quinoxaline (Qx)-based acceptors have attracted extensive interest due to their low reorganization energy, high structural modification possibilities, and distinctive molecular packing modes, which contribute to reduced energy loss and superior charge generation/transport, thus improving the photovoltaic performance of OSCs. This perspective summarizes the design strategies of Qx-based acceptors (including small-molecule, giant dimeric and polymeric acceptors) and the resulting optoelectronic properties and device performance. In addition, the ternary strategy of introducing Qx-based acceptors as the third component to reduce energy loss is briefly discussed. Finally, some perspectives for the further exploration of Qx-based acceptors toward efficient, stable, and industry-compatible OSCs are proposed.
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Food proteins are considered an ideal source for the identification of bioactive peptides with the potential to intervene in nutrition-related chronic diseases such as cardiovascular disease, obesity, and diabetes. Egg white-derived peptides (EWPs) have been shown to improve glucose tolerance in insulin-resistant rats. However, underlying mechanisms are to be elucidated. Therefore, we hypothesized that EWP exerts a hypoglycemic effect by regulating hepatic glucose homeostasis. Our results showed that 7 weeks of EWP treatment reduced the fasting blood glucose in T2DM mice and the inhibition of the liver gluconeogenic pathway was involved in the mechanisms of actions. Using the untargeted metabolomics technique, we found that EWP treatment also altered the hepatic metabolic profile in T2DM mice, in which, the role of fatty acid esters of hydroxy fatty acids in mediating the hypoglycemic effect of EWPs might be pivotal.
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Glicemia , Diabetes Mellitus Tipo 2 , Dieta Hiperlipídica , Gluconeogênese , Fígado , Peptídeos , Animais , Gluconeogênese/efeitos dos fármacos , Camundongos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Masculino , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Peptídeos/farmacologia , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Estreptozocina , Diabetes Mellitus Experimental/metabolismo , Clara de Ovo/química , Metaboloma/efeitos dos fármacosRESUMO
Rapeseed (Brassica napus) silique is the major carbohydrate source for seed development, and the final silique length has attracted great attention from breeders. However, no studies had focused on the dynamic character of silique elongation length (SEL). Here, the dynamic SEL investigation in a natural population including 588 lines over two years indicate that dynamic SEL during 0-20 days after flowering was the most essential stage associated with seed number per silique (SPS) and thousand seed weight (TSW). Then, nine loci were identified to be associated with SEL based on GWAS analysis, among which five SNPs (over 50%) distributed on the A02 chromosome within 6.08 to 6.48 Mb. Subsequently, we screened 5078 differentially expressed genes between two extreme materials. An unknown protein, BnaA02.SE, was identified combining with GWAS and RNA-Seq analysis. Subcellular localization and expression profiles analysis demonstrated that BnaA02.SE is a chloroplast- and nucleus-localized protein mainly expressed in pericarps and leaves. Furthermore, transgenic verification and dynamic cytological observation reveal that overexpressed BnaA02.SE can promote silique elongation by regulating JA and IAA contents, affecting cell proliferation and expansion, respectively, and finally enhance seed yield by influencing SPS and TSW. Haplotype analysis reveal that the homologs of BnaA02.SE may also be involved in silique elongation regulation. Our findings provided comprehensive insights into a newly SEL trait, and cloned the first gene (BnaA02.SE) controlling silique elongation in B. napus. The identified BnaA02.SE and its homologs can offer a valuable target for improving B. napus yield.
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INTRODUCTION: Existing evidence suggests that exposure to phthalates is higher among younger age groups. However, limited knowledge exists on how phthalate exposure, as well as exposure to replacement plasticizers, di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) and di-2-ethylhexyl terephthalate (DEHTP), change from infancy through early childhood. METHODS: Urine samples were collected across the first 5 years of life from typically developing infants and young children enrolled between 2017 and 2020 in the longitudinal UNC Baby Connectome Project. From 438 urine samples among 187 participants, we quantified concentrations of monobutyl phthalate (MnBP), mono-3-carboxypropyl phthalate (MCPP), monoisobutyl phthalate (MiBP), monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), and metabolites of di(2-ethylhexyl) phthalate (DEHP), diisonoyl phthalate (DiNP), DINCH and DEHTP. Specific gravity (SG) adjusted metabolite and molar sum concentrations were compared across age groups. Intraclass correlation coefficients (ICCs) were calculated among 122 participants with multiple urine specimens (373 samples). RESULTS: Most phthalate metabolites showed high detection frequencies (>80% of samples). Replacement plasticizers DINCH (58-60%) and DEHTP (>97%) were also commonly found. DiNP metabolites were less frequently detected (<10%). For some metabolites, SG-adjusted concentrations were inversely associated with age, with the highest concentrations found in the first year of life. ICCs revealed low to moderate reliability in metabolite measurements (ρ = 0.10-0.48) suggesting a high degree of within-individual variation in exposure among this age group. The first 6 months (compared to remaining age groups) showed an increased ratio of carboxylated metabolites of DEHP and DEHTP, compared to other common metabolites, but no clear age trends for DINCH metabolite ratios were observed. CONCLUSION: Metabolites of phthalates and replacements plasticizers were widely detected in infancy and early childhood, with the highest concentrations observed in the first year of life for several metabolites. Higher proportions of carboxylated metabolites of DEHP and DEHTP in younger age groups indicate potential differences in metabolism during infancy.
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Protein phosphorylation is one of the most common mechanisms regulating cellular signaling pathways, and many kinases and phosphatases are proven drug targets. Upon phosphorylation, protein functions can be further regulated by the distinct isomerase Pin1 through cis-trans isomerization. Numerous protein targets and many important roles have now been elucidated for Pin1. However, no tools are available to detect or target cis and trans conformation events in cells. The development of Pin1 inhibitors and stereo- and phospho-specific antibodies has revealed that cis and trans conformations have distinct and often opposing cellular functions. Aberrant conformational changes due to the dysregulation of Pin1 can drive pathogenesis but can be effectively targeted in age-related diseases, including cancers and neurodegenerative disorders. Here, we review advances in understanding the roles of Pin1 signaling in health and disease and highlight conformational regulation as a distinct signal transduction checkpoint in disease development and treatment.
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Descoberta de Drogas , Peptidilprolil Isomerase de Interação com NIMA , Conformação Proteica , Transdução de Sinais , Humanos , Peptidilprolil Isomerase de Interação com NIMA/metabolismo , Peptidilprolil Isomerase de Interação com NIMA/genética , Peptidilprolil Isomerase de Interação com NIMA/química , Fosforilação , Animais , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/genéticaRESUMO
The transcription factors Related to ABI3/VP1 (RAV) are crucial for various plant processes and stress responses. Although the U's triangle Brassica species genomes have been released, the knowledge regarding the RAV family is still limited. In this study, we identified 123 putative RAV genes across the six U's triangle Brassica species (Brassica rapa, 14; Brassica oleracea, 14; Brassica nigra, 13; Brassica carinata, 27; Brassica juncea, 28; Brassica napus, 27). Phylogenetic analysis categorized them into three groups. The RAV genes exhibited diversity in both functional and structural aspects, particularly in gene structure and cis-acting elements within their promoters. The expression analysis revealed that BnaRAV genes in Group 1/2 exhibited diverse expression patterns across various tissues, while those in Group 3 did not show expression except for BnaRAV3L-2 and BnaRAV3L-6, which were exclusively expressed in seeds. Furthermore, the seed-specific expression of BnaA06. RAV3L (BnaRAV3L-2) was confirmed through promoter-GUS staining. Subcellular localization studies demonstrated that BnaA06.RAV3L is localized to the nucleus. The overexpression of BnaA06. RAV3L in Arabidopsis led to a remarkable inhibition of seed-specific traits such as seed width, seed length, seed area, and seed weight. This study provides insights into the functional evolution of the RAV gene family in U triangle Brassica species. It establishes a foundation for uncovering the molecular mechanisms underlying the negative role of RAV3L in seed development.
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Brassica , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas , Sementes , Fatores de Transcrição , Brassica/genética , Brassica/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Sementes/genética , Sementes/metabolismo , Sementes/crescimento & desenvolvimento , Genoma de Planta , Arabidopsis/genética , Arabidopsis/metabolismoRESUMO
Drug-resistant bacterial infections pose a serious threat to human health; thus, there is an increasingly growing demand for nonantibiotic strategies to overcome drug resistance in bacterial infections. Mild photothermal therapy (PTT), as an attractive antibacterial strategy, shows great potential application due to its good biocompatibility and ability to circumvent drug resistance. However, its efficiency is limited by the heat resistance of bacteria. Herein, Cu2O@MoS2, a nanocomposite, was constructed by the in situ growth of Cu2O nanoparticles (NPs) on the surface of MoS2 nanosheets, which provided a controllable photothermal therapeutic effect of MoS2 and the intrinsic catalytic properties of Cu2O NPs, achieving a synergistic effect to eradicate multidrug-resistant bacteria. Transcriptome sequencing (RNA-seq) results revealed that the antibacterial process was related to disrupting the membrane transport system, phosphorelay signal transduction system, oxidative stress response system, as well as the heat response system. Animal experiments indicated that Cu2O@MoS2 could effectively treat wounds infected with methicillin-resistant Staphylococcus aureus. In addition, satisfactory biocompatibility made Cu2O@MoS2 a promising antibacterial agent. Overall, our results highlight the Cu2O@MoS2 nanocomposite as a promising solution to combating resistant bacteria without inducing the evolution of antimicrobial resistance.
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Antibacterianos , Cobre , Dissulfetos , Raios Infravermelhos , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Molibdênio , Nanocompostos , Molibdênio/química , Molibdênio/farmacologia , Dissulfetos/química , Dissulfetos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Cobre/química , Cobre/farmacologia , Nanocompostos/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Animais , Camundongos , Terapia Fototérmica , HumanosRESUMO
As one of the most widespread musculoskeletal diseases worldwide, intervertebral disc degeneration (IVDD) remains an intractable clinical problem. Currently, oxidative stress has been widely considered as a significant risk factor in the IVDD pathological changes, and targeting oxidative stress injury to improve the harsh microenvironment may provide a novel and promising strategy for disc repair. It is evident that spermidine (SPD) has the ability to attenuate oxidative stress across several disease models. However, limited research exists regarding its impact on oxidative stress within the intervertebral disc. Moreover, enhancing the local utilization rate of SPD holds great significance in IVDD management. This study aimed to develop an intelligent biodegradable mesoporous polydopamine (PDA) nanoplatform for sustained release of SPD. The obtained PDA nanoparticles with spherical morphology and mesoporous structure released loaded-therapeutic molecules under low pH and H2O2. Combined treatment with SPD loaded into PDA nanoparticles (SPD/PDA) resulted in better therapeutic potential than those with SPD alone on oxidative stress injury. Furthermore, both SPD and SPD/PDA could induce anti-inflammatory M2 macrophage polarization. Upon injection into degenerative IVDs, the SPD/PDA group achieved a good repair efficacy with a long-term therapeutic effect. These findings indicated that the synergized use of SPD with responsive drug delivery nanocarriers may steadily scavenge reactive oxygen species and provide an effective approach toward the treatment of IVDD.
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Indóis , Degeneração do Disco Intervertebral , Nanopartículas , Estresse Oxidativo , Polímeros , Espermidina , Polímeros/química , Estresse Oxidativo/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Animais , Nanopartículas/química , Espermidina/farmacologia , Espermidina/química , Camundongos , Ratos , Portadores de Fármacos/química , MasculinoRESUMO
The Bacteroidota is one of the dominant bacterial phyla in corals. However, the exact taxa of those coral bacteria under the Bacteroidota are still unclear. Two aerobic, Gram-stain-negative, non-motile rods, designated strains BMA10T and BMA12T, were isolated from stony coral Porites lutea collected from Weizhou Island, PR China. Global alignment of 16S rRNA gene sequences indicated that both strains are closest to species of Fulvivirga with the highest identities being lower than 93â%, and the similarity value between these two strains was 92.3â%. Phylogenetic analysis based on 16S rRNA gene and genome sequences indicated that these two strains form an monophylogenetic lineage alongside the families Fulvivirgaceae, Reichenbachiellaceae, Roseivirgaceae, Marivirgaceae, Cyclobacteriaceae, and Cesiribacteraceae in the order Cytophagales, phylum Bacteroidota. The genomic DNA G+C contents of BMA10T and BMA12T were 38.4 and 41.9âmol%, respectively. The major polar lipids of BMA10T were phosphatidylethanolamine, unidentified aminophospholipid, four unidentified aminolipids, and five unidentified lipids. While those of BMA12T were phosphatidylethanolamine, two unidentified aminolipids, and five unidentified lipids. The major cellular fatty acids detected in both isolates were iso-C15â:â0 and C16â:â1 ω5c. Carbohydrate-active enzyme analysis indicated these two strains may utilize coral mucus or chitin. Based on above characteristics, these two strains are suggested to represent two new species in two new genera of a new family in the order Cytophagales, for which the name Splendidivirga corallicola gen. nov., sp. nov., Agaribacillus aureus gen. nov., sp. nov. and Splendidivirgaceae fam. nov. are proposed. The type strain of S. corallicola is BMA10T (=MCCC 1K08300T=KCTC 102045T), and that for A. aureus is BMA12T (=MCCC 1K08309T=KCTC 102046T).
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Antozoários , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Antozoários/microbiologia , Animais , RNA Ribossômico 16S/genética , Ácidos Graxos/análise , DNA Bacteriano/genética , China , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Bacteroidetes/classificação , Fosfolipídeos/análiseRESUMO
This review examines the complex role of Pin1 in the development and treatment of cancer. Pin1 is the only peptidyl-prolyl isomerase (PPIase) that can recognize and isomerize phosphorylated Ser/Thr-Pro peptide bonds. Pin1 catalyzes a structural change in phosphorylated Ser/Thr-Pro motifs that can modulate protein function and thereby impact cell cycle regulation and tumorigenesis. The molecular mechanisms by which Pin1 contributes to oncogenesis are reviewed, including Pin1 overexpression and its correlation with poor cancer prognosis, and the contribution of Pin1 to aggressive tumor phenotypes involved in therapeutic resistance is discussed, with an emphasis on cancer stem cells, the epithelial-to-mesenchymal transition (EMT), and immunosuppression. The therapeutic potential of Pin1 inhibition in cancer is discussed, along with the promise and the difficulties in identifying potent, drug-like, small-molecule Pin1 inhibitors. The available evidence supports the efficacy of targeting Pin1 as a novel cancer therapeutic by analyzing the role of Pin1 in a complex network of cancer-driving pathways and illustrating the potential of synergistic drug combinations with Pin1 inhibitors for treating aggressive and drug-resistant tumors.
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Fanconi anemia (FA) is a disease caused by defective deoxyribonucleic acid (DNA) repair that manifests as bone marrow failure, cancer predisposition, and developmental defects. We previously reported that monotherapy with either metformin (MET) or oxymetholone (OXM) improved peripheral blood (PB) counts and the number and functionality of bone marrow hematopoietic stem progenitor cells (HSPCs) number in Fancd2-/- mice. To evaluate whether the combination treatment of these drugs has a synergistic effect to prevent bone marrow failure in FA, we treated cohorts of Fancd2-/- mice and wildtype controls with either MET alone, OXM alone, MET+OXM, or placebo diet from age 3 weeks to 18 months. The OXM treated animals showed modest improvements in blood parameters including platelet count (p = .01) and hemoglobin levels (p < .05). In addition, the percentage of quiescent hematopoietic stem cell (HSC) (LSK [Lin-Sca+c-Kit+]) was significantly increased (p = .001) by long-term treatment with MET alone. The combination of metformin and oxymetholone did not result in a significant synergistic effect in any hematopoietic parameter. Gene expression analysis of liver tissue from these animals showed that some of the expression changes caused by Fancd2 deletion were partially normalized by metformin treatment. Importantly, no adverse effects of the individual or combination therapies were observed, despite the long-term administration. We conclude that androgen therapy is not a contraindication to concurrent metformin administration in clinical trials. HIGHLIGHTS: Long-term coadministration of metformin in combination with oxymetholone is well tolerated by Fancd2-/- mice. Hematopoietic stem cell quiescence in mutant mice was enhanced by treatment with metformin alone. Metformin treatment caused a partial normalization of gene expression in the livers of mutant mice.