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1.
J Cell Mol Med ; 28(8): e18292, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38652116

RESUMO

Foodborne illnesses, particularly those caused by Salmonella enterica with its extensive array of over 2600 serovars, present a significant public health challenge. Therefore, prompt and precise identification of S. enterica serovars is essential for clinical relevance, which facilitates the understanding of S. enterica transmission routes and the determination of outbreak sources. Classical serotyping methods via molecular subtyping and genomic markers currently suffer from various limitations, such as labour intensiveness, time consumption, etc. Therefore, there is a pressing need to develop new diagnostic techniques. Surface-enhanced Raman spectroscopy (SERS) is a non-invasive diagnostic technique that can generate Raman spectra, based on which rapid and accurate discrimination of bacterial pathogens could be achieved. To generate SERS spectra, a Raman spectrometer is needed to detect and collect signals, which are divided into two types: the expensive benchtop spectrometer and the inexpensive handheld spectrometer. In this study, we compared the performance of two Raman spectrometers to discriminate four closely associated S. enterica serovars, that is, S. enterica subsp. enterica serovar dublin, enteritidis, typhi and typhimurium. Six machine learning algorithms were applied to analyse these SERS spectra. The support vector machine (SVM) model showed the highest accuracy for both handheld (99.97%) and benchtop (99.38%) Raman spectrometers. This study demonstrated that handheld Raman spectrometers achieved similar prediction accuracy as benchtop spectrometers when combined with machine learning models, providing an effective solution for rapid, accurate and cost-effective identification of closely associated S. enterica serovars.


Assuntos
Salmonella enterica , Sorogrupo , Análise Espectral Raman , Máquina de Vetores de Suporte , Análise Espectral Raman/métodos , Salmonella enterica/isolamento & purificação , Humanos , Algoritmos
2.
J Cell Physiol ; 239(2): e31159, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38212939

RESUMO

Noncoding RNAs, including miRNAs (microRNAs) and circRNAs (circular RNA), are crucial regulators of myoblast proliferation and differentiation during muscle development. However, the specific roles and molecular mechanisms of circRNAs in muscle development remain poorly understood. Based on the existing circRNA-miRNA-mRNA network, our study focuses on circUBE3C, exploring its differential expression in fetal and adult muscle tissue of the cattle and investigating its impact on myoblast proliferation, apoptosis, and differentiation. The functional analysis of overexpression plasmids and siRNAs (small interfering RNAs) targeting circUBE3C was comprehensively evaluated by employing an array of advanced assays, encompassing CCK-8 (cell counting kit-8), EdU (5-ethynyl-20-deoxyuridine), flow cytometry, western blot analysis, and RT-qPCR. In vivo investigations indicated that overexpression of circUBE3C impedes the process of skeletal muscle regeneration. Mechanistically, we demonstrated that circUBE3C interacts with miR-191 and alleviates the suppression of p27 through cytoplasmic separation, bioinformatics prediction, dual-luciferase reporter assay, and RIP (RNA immunoprecipitation). Our findings indicate that the novel circRNA circUBE3C competitively binds to miR-191, thereby inhibiting proliferation and promoting apoptosis in bovine primary myoblasts and unveiling a regulatory pathway in bovine skeletal muscle development. These findings expand our understanding of circRNA functions in mammals and provide a basis for further exploration of their role in myogenesis and muscle diseases.


Assuntos
MicroRNAs , RNA Circular , Animais , Bovinos , Diferenciação Celular/genética , Proliferação de Células/genética , Mamíferos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Desenvolvimento Muscular/genética , Mioblastos/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , RNA Interferente Pequeno/metabolismo , Células Cultivadas , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
3.
Lab Invest ; 104(2): 100310, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38135155

RESUMO

Diagnostic methods for Helicobacter pylori infection include, but are not limited to, urea breath test, serum antibody test, fecal antigen test, and rapid urease test. However, these methods suffer drawbacks such as low accuracy, high false-positive rate, complex operations, invasiveness, etc. Therefore, there is a need to develop simple, rapid, and noninvasive detection methods for H. pylori diagnosis. In this study, we propose a novel technique for accurately detecting H. pylori infection through machine learning analysis of surface-enhanced Raman scattering (SERS) spectra of gastric fluid samples that were noninvasively collected from human stomachs via the string test. One hundred participants were recruited to collect gastric fluid samples noninvasively. Therefore, 12,000 SERS spectra (n = 120 spectra/participant) were generated for building machine learning models evaluated by standard metrics in model performance assessment. According to the results, the Light Gradient Boosting Machine algorithm exhibited the best prediction capacity and time efficiency (accuracy = 99.54% and time = 2.61 seconds). Moreover, the Light Gradient Boosting Machine model was blindly tested on 2,000 SERS spectra collected from 100 participants with unknown H. pylori infection status, achieving a prediction accuracy of 82.15% compared with qPCR results. This novel technique is simple and rapid in diagnosing H. pylori infection, potentially complementing current H. pylori diagnostic methods.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/diagnóstico , Análise Espectral Raman , Estômago , Urease/análise , Sensibilidade e Especificidade
4.
Hum Mol Genet ; 31(12): 2049-2062, 2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35024855

RESUMO

The SLC25A26 gene encodes a mitochondrial inner membrane carrier that transports S-adenosylmethionine (SAM) into the mitochondrial matrix in exchange for S-adenosylhomocysteine (SAH). SAM is the predominant methyl-group donor for most cellular methylation processes, of which SAH is produced as a by-product. Pathogenic, biallelic SLC25A26 variants are a recognized cause of mitochondrial disease in children, with a severe neonatal onset caused by decreased SAM transport activity. Here, we describe two, unrelated adult cases, one of whom presented with recurrent episodes of severe abdominal pain and metabolic decompensation with lactic acidosis. Both patients had exercise intolerance and mitochondrial myopathy associated with biallelic variants in SLC25A26, which led to marked respiratory chain deficiencies and mitochondrial histopathological abnormalities in skeletal muscle that are comparable to those previously described in early-onset cases. We demonstrate using both mouse and fruit fly models that impairment of SAH, rather than SAM, transport across the mitochondrial membrane is likely the cause of this milder, late-onset phenotype. Our findings associate a novel pathomechanism with a known disease-causing protein and highlight the quests of precision medicine in optimizing diagnosis, therapeutic intervention and prognosis.


Assuntos
Doenças Mitocondriais , S-Adenosil-Homocisteína , Animais , Metilação , Camundongos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Doenças Mitocondriais/metabolismo , S-Adenosil-Homocisteína/metabolismo , S-Adenosilmetionina/metabolismo
5.
Small ; 20(23): e2309206, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38149505

RESUMO

Ferroptosis is an emerging non-apoptotic death process, mainly involving lipid peroxidation (LPO) caused by iron accumulation, which is potentially lethal to the intrinsically apoptotic-resistant malignant tumor. However, it is still restricted by the inherent antioxidant systems of tumor cells and the poor efficacy of traditional iron-based ferroptosis initiators. Herein, the study develops a novel ferroptosis-inducing agent based on PEGylated Cu+/Cu2+-doped black phosphorus@polypyrrole heterojunction (BP@CPP), which is constructed by utilizing the phosphate on the surface of BP to chelate Cu ions and initiating subsequent in situ polymerization of pyrrole. As a novel Z-scheme heterojunction, BP@CPP possesses an excellent photocatalytic activity in which the separated electron-hole pairs under laser irradiation endow it with powerful oxidizing and reducing capacities, which synergy with Cu+/Cu2+ self-cycling catalyzing Fenton-like reaction to further strengthen reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, and glutathione peroxidase 4 (GPX4) inactivation, ultimately leading to efficient ferroptosis. Systematic in vitro and in vivo evaluations demonstrate that BP@CPP effectively inhibit tumor growth by inducing desired ferroptosis while maintaining a favorable biosafety in the body. Therefore, the developed BP@CPP-based ferroptosis initiator provides a promising strategy for ferroptosis-like cancer therapy.


Assuntos
Cobre , Ferroptose , Oxirredução , Espécies Reativas de Oxigênio , Ferroptose/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Cobre/química , Cobre/farmacologia , Animais , Linhagem Celular Tumoral , Polímeros/química , Polímeros/farmacologia , Pirróis/química , Pirróis/farmacologia , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Camundongos , Glutationa/metabolismo , Fósforo/química
6.
Crit Rev Microbiol ; : 1-30, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910506

RESUMO

Helicobacter pylori is a gram-negative bacterium that colonizes the stomach of approximately half of the worldwide population, with higher prevalence in densely populated areas like Asia, the Caribbean, Latin America, and Africa. H. pylori infections range from asymptomatic cases to potentially fatal diseases, including peptic ulcers, chronic gastritis, and stomach adenocarcinoma. The management of these conditions has become more difficult due to the rising prevalence of drug-resistant H. pylori infections, which ultimately lead to gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. In 1994, the International Agency for Research on Cancer (IARC) categorized H. pylori as a Group I carcinogen, contributing to approximately 780,000 cancer cases annually. Antibiotic resistance against drugs used to treat H. pylori infections ranges between 15% and 50% worldwide, with Asian countries having exceptionally high rates. This review systematically examines the impacts of H. pylori infection, the increasing prevalence of antibiotic resistance, and the urgent need for accurate diagnosis and precision treatment. The present status of precision treatment strategies and prospective approaches for eradicating infections caused by antibiotic-resistant H. pylori will also be evaluated.

7.
BMC Cancer ; 24(1): 548, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689248

RESUMO

PURPOSE: For patients with early-stage cervical cancer without high-risk factors, there is no consensus regarding the optimal postoperative treatment regimen and whether postoperative concurrent radiochemotherapy (CCRT) is superior to radiotherapy (RT) alone. PATIENTS AND METHODS: The medical records of patients with stage I-IIA cervical cancer, who underwent radical surgery and postoperative RT or CCRT between June 2012 and December 2017, were retrospectively reviewed. Patients with any high-risk factors, including positive pelvic lymph node(s), positive resection margin(s), and parametrial invasion, were excluded. Patients with large tumors (≥ 4 cm), deep stromal invasion (≥ 1/2), and lymphovascular space involvement were categorized as the intermediate-risk group. Patients without intermediate-risk factors were categorized as the low-risk group. RESULTS: A total of 403 patients were enrolled and divided into 2 groups according to postoperative treatment: RT alone (n = 105); and CCRT (n = 298). For risk stratification, patients were also divided into 2 groups: intermediate-risk (n = 350); and low-risk (n = 53). The median follow-up was 51.7 months. Patients in the intermediate-risk group and those with multiple intermediate-risk factors were more likely to undergo CCRT. For patients who underwent RT alone or CCRT in the intermediate-risk group, 5-year overall survival (OS) rates were 93.4% and 93.8% (p = 0.741), and 5-year disease-free survival (DFS) rates were 90.6% and 91.4%, respectively (p = 0.733). Similarly, for patients who underwent RT alone or CCRT in the low-risk group, the 5-year OS rates were 100.0% and 93.5% (p = 0.241), and 5-year DFS rates were 94.4% and 93.5%, respectively (p = 0.736). Adjuvant CCRT or RT were not independent risk factors for either OS or DFS. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those in the RT group (44.0% versus 11.4%, respectively; p < 0.001). There was no significant difference in grade ≥ 3 chronic toxicities of the urogenital and gastrointestinal systems between the CCRT and RT groups. CONCLUSION: There was no significant difference in 5-year OS and DFS rates between patients with early-stage cervical cancer without high-risk factors undergoing postoperative CCRT versus RT alone. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those who underwent RT alone.


Assuntos
Quimiorradioterapia , Radioterapia Adjuvante , Neoplasias do Colo do Útero , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/terapia , Humanos , Adulto , Estudos Retrospectivos , Estadiamento de Neoplasias , Histerectomia , Excisão de Linfonodo , Doses de Radiação , Resultado do Tratamento , Taxa de Sobrevida , Pessoa de Meia-Idade , Idoso
8.
J Org Chem ; 89(8): 5560-5572, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38564232

RESUMO

A simple, efficient, and practical method for the synthesis of S-quinolyl xanthates was developed via Ts2O-promoted deoxygenative C-H dithiocarbonation of quinoline N-oxides with various potassium O-alkyl xanthates. The reaction performed well under transition-metal-free, base-free, and room-temperature conditions with wide substrate tolerance. Employing potassium O-tert-butyl xanthate (tBuOCS2K) as a nucleophile, some valuable quinoline-2-thiones were unexpectedly obtained in a one-pot reaction without any additional base.

9.
Bioorg Chem ; 143: 107093, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38185012

RESUMO

Fungi are microorganisms with biosynthetic potential that are capable of producing a wide range of chemically diverse and biologically interesting small molecules. Chemical epigenetic manipulation has been increasingly explored as a simple and powerful tool to induce the production of additional microbial secondary metabolites in fungi. This review focuses on chemical epigenetic manipulation in fungi and summarizes 379 epigenetic manipulation products discovered from 2008 to 2022 to promote the discovery of their medicinal value.


Assuntos
Epigênese Genética , Fungos , Fungos/química , Metabolismo Secundário
10.
BMC Geriatr ; 24(1): 466, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38807058

RESUMO

BACKGROUND: With the aging population, the number of individuals with dementia in China is increasing rapidly. This community-based study aimed to investigate the prevalence and risk factors for dementia and mild cognitive impairment (MCI) among older adults in China. METHODS: In this study, 20,070 individuals aged ≥ 65 were recruited between January 1, 2022, and February 1, 2023, from ten communities in Xiamen City, China. We collected data on age, sex, level of education, and medical history, as well as global cognition and functional status. The prevalence of dementia and MCI was examined, and the risk factors for different groups were assessed. RESULTS: The overall prevalence of dementia and MCI was approximately 5.4% (95% confidence interval [CI], 5.1-5.7) and 7.7% (95% CI, 7.4-8.1), respectively. The results also indicated that dementia and MCI share similar risk factors, including older age, female sex, hypertension, and diabetes mellitus. Compared with individuals with no formal education, those with > 6 years of education had an odds ratio for MCI of 1.83 (95% CI, 1.49-2.25). We also found that only 5.5% of the positive participants chose to be referred to the hospital for further diagnosis and treatment during follow-up visits. CONCLUSIONS: This study estimated the prevalence and risk factors for dementia and MCI among individuals aged ≥ 65 years in Southeast China. These findings are crucial for preventing and managing dementia and MCI in China.


Assuntos
Disfunção Cognitiva , Demência , Humanos , Masculino , Feminino , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/diagnóstico , Idoso , China/epidemiologia , Demência/epidemiologia , Demência/diagnóstico , Prevalência , Fatores de Risco , Idoso de 80 Anos ou mais
11.
Proc Natl Acad Sci U S A ; 118(7)2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33574059

RESUMO

Ecological flexibility, extended lifespans, and large brains have long intrigued evolutionary biologists, and comparative genomics offers an efficient and effective tool for generating new insights into the evolution of such traits. Studies of capuchin monkeys are particularly well situated to shed light on the selective pressures and genetic underpinnings of local adaptation to diverse habitats, longevity, and brain development. Distributed widely across Central and South America, they are inventive and extractive foragers, known for their sensorimotor intelligence. Capuchins have among the largest relative brain size of any monkey and a lifespan that exceeds 50 y, despite their small (3 to 5 kg) body size. We assemble and annotate a de novo reference genome for Cebus imitator Through high-depth sequencing of DNA derived from blood, various tissues, and feces via fluorescence-activated cell sorting (fecalFACS) to isolate monkey epithelial cells, we compared genomes of capuchin populations from tropical dry forests and lowland rainforests and identified population divergence in genes involved in water balance, kidney function, and metabolism. Through a comparative genomics approach spanning a wide diversity of mammals, we identified genes under positive selection associated with longevity and brain development. Additionally, we provide a technological advancement in the use of noninvasive genomics for studies of free-ranging mammals. Our intra- and interspecific comparative study of capuchin genomics provides insights into processes underlying local adaptation to diverse and physiologically challenging environments, as well as the molecular basis of brain evolution and longevity.


Assuntos
Adaptação Fisiológica , Encéfalo/crescimento & desenvolvimento , Cebus/genética , Genoma , Longevidade/genética , Animais , Evolução Molecular , Citometria de Fluxo/métodos , Florestas , Genômica/métodos
12.
Biomed Chromatogr ; 38(8): e5923, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38837461

RESUMO

Carboxyamidotriazole (CAI) was previously recognized as a well-tolerated anticancer drug. It has also demonstrated significant anti-inflammatory effects in various cell and animal model experiments, prompting its investigation as a potential treatment for rheumatoid arthritis. In this study, the potential biotransformation metabolites of CAI were identified both in vitro and in vivo. A sensitive, specific, and accurate LC-MS method was developed for the quantitative analysis of CAI and its major metabolite, CAI-OH, in rat plasma. CAI, CAI-OH, and telmisartan (used as an internal standard) were separated using a Zorbax SB C18 column. The mobile phase consisted of water (phase A, containing 0.1% formic acid) and acetonitrile (phase B, containing 0.1% formic acid) at a flow rate of 0.2 mL/min. The analytes were examined using a high-resolution mass spectrometer, with detected mass-to-charge ratios of m/z 424.01293 for CAI, m/z 440.00785 for CAI-OH, and m/z 515.24415 for telmisartan. Good linearity was observed within the range of 10-5000 ng/mL. Both inter- and intra-batch precision (relative standard deviation, %) were below 6%, and the accuracy ranged from 94.9% to 106.1%. The analytes remained stable throughout the entire experimental period. This method was successfully applied in a pharmacokinetic study of CAI following oral administration in rats.


Assuntos
Espectrometria de Massas , Ratos Sprague-Dawley , Triazóis , Animais , Ratos , Triazóis/sangue , Triazóis/farmacocinética , Triazóis/química , Masculino , Reprodutibilidade dos Testes , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Modelos Lineares , Antirreumáticos/sangue , Antirreumáticos/farmacocinética , Limite de Detecção , Sensibilidade e Especificidade , Espectrometria de Massa com Cromatografia Líquida
13.
Artigo em Inglês | MEDLINE | ID: mdl-38769797

RESUMO

OBJECTIVE: To explore the clinical feasibility of different treatment methods for persistent occipitotransverse position and the influence on maternal and infant complications. METHOD: During the trial of vaginal delivery from April 2020 to March 2023 in our hospital, the cervix was fully dilated and the presentation was located at +2 station. Ninety-six pregnant women with fetal presentation at +4 station, occipitotransverse fetal position, maternal complications, abnormalities in the second stage of labor, and or fetal distress were divided into two groups: 65 patients with Kielland forceps vaginal delivery and 31 patients underwent emergency cesarean section. The delivery time, vaginal laceration rate, postpartum blood loss volume, puerperal infection rate, neonatal birth injury rate, and neonatal 1 min Apgar scores were analyzed. RESULTS: The delivery outcomes and maternal and neonatal complications of 96 pregnant women were analyzed: the application of Kielland forceps delivery time was shorter, while the vaginal laceration rate, postpartum hemorrhage, puerperal infection rate were significantly lower than that of patients undergoing emergency cesarean section and the neonatal 1 min Apgar score was higher than that of emergency cesarean section group (p < 0.05). CONCLUSION: It was clinically appropriate to use Kielland forceps in vaginal delivery when the persistent occipitotransverse position was present and delivery needed to be expediated. Use of Kielland forceps can shorten the delivery time, improve the success rate of vaginal delivery and reduce the complications of mothers and infants.

14.
Molecules ; 29(5)2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38474508

RESUMO

The incorporation of amide groups into biologically active molecules has been proven to be an efficient strategy for drug design and discovery. In this study, we present a simple and practical method for the synthesis of amide-containing quinazolin-4(3H)-ones under transition-metal-free conditions. This is achieved through a carbamoyl-radical-triggered cascade cyclization of N3-alkenyl-tethered quinazolinones. Notably, the carbamoyl radical is generated in situ from the oxidative decarboxylative process of oxamic acids in the presence of (NH4)2S2O8.

15.
World J Microbiol Biotechnol ; 40(5): 146, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38538920

RESUMO

Bacterial species within the Acinetobacter baumannii-calcoaceticus (Acb) complex are very similar and are difficult to discriminate. Misidentification of these species in human infection may lead to severe consequences in clinical settings. Therefore, it is important to accurately discriminate these pathogens within the Acb complex. Raman spectroscopy is a simple method that has been widely studied for bacterial identification with high similarities. In this study, we combined surfaced-enhanced Raman spectroscopy (SERS) with a set of machine learning algorithms for identifying species within the Acb complex. According to the results, the support vector machine (SVM) model achieved the best prediction accuracy at 98.33% with a fivefold cross-validation rate of 96.73%. Taken together, this study confirms that the SERS-SVM method provides a convenient way to discriminate between A. baumannii, Acinetobacter pittii, and Acinetobacter nosocomialis in the Acb complex, which shows an application potential for species identification of Acinetobacter baumannii-calcoaceticus complex in clinical settings in near future.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Acinetobacter , Humanos , Análise Espectral Raman , Infecções por Acinetobacter/microbiologia
16.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1397-1405, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621988

RESUMO

This study employed evidence mapping to systematically sort out the clinical studies about the treatment of premature ventricular contractions with Chinese patent medicines and to reveal the distribution of evidence in this field. The articles about the treatment of premature ventricular contractions with Chinese patent medicines were searched against PubMed, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP with the time interval from January 2016 to December 2022. Evidence was analyzed and presented by charts and graphs combined with text. According to the inclusion and exclusion criteria, 164 papers were included, including 147 interventional studies, 4 observational studies, and 13 systematic reviews. A total of 27 Chinese patent medicines were involved, in which Shensong Yangxin Capsules and Wenxin Granules had high frequency. There were off-label uses in clinical practice. In recent years, the number of articles published in this field showed a decreasing trend. Eight types of outcome indicators were used in interventional studies. Ambulatory electrocardiography, clinical response rate, safety, and echocardiography had high frequency, while the rate of ß-blocker decompensation, major cardiovascular events, and pharmaceutical economic indicators were rarely reported. The evaluation was one-sided. The low quality of the included articles reduced the reliability of the findings. In the future, the clinical use of medicines should be standardized, and the quality of clinical studies should be improved. Comprehensive clinical evaluation should be carried out to provide a sound scientific basis for the treatment of premature ventricular contractions with Chinese patent medicines.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional do Leste Asiático , Complexos Ventriculares Prematuros , Humanos , Complexos Ventriculares Prematuros/tratamento farmacológico , Medicamentos sem Prescrição/uso terapêutico , Reprodutibilidade dos Testes , Medicamentos de Ervas Chinesas/uso terapêutico , Cápsulas
17.
Beilstein J Org Chem ; 20: 638-644, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533468

RESUMO

Fungal meroterpenoids are diverse structurally intriguing molecules with various biological properties. One large group within this compound class is derived from the aromatic precursor 3,5-dimethylorsellinic acid (DMOA). In this study, we constructed engineered metabolic pathways in the fungus Aspergillus oryzae to expand the molecular diversity of meroterpenoids. We employed the 5-methylorsellinic acid (5-MOA) synthase FncE and three additional biosynthetic enzymes for the formation of (6R,10'R)-epoxyfarnesyl-5-MOA methyl ester, which served as a non-native substrate for four terpene cyclases from DMOA-derived meroterpenoid pathways. As a result, we successfully generated six unnatural 5-MOA-derived meroterpenoid species, demonstrating the effectiveness of our approach in the generation of structural analogues of meroterpenoids.

18.
BMC Bioinformatics ; 24(1): 465, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066424

RESUMO

Hierarchical classification offers a more specific categorization of data and breaks down large classification problems into subproblems, providing improved prediction accuracy and predictive power for undefined categories, while also mitigating the impact of poor-quality data. Despite these advantages, its application in predicting primary cancer is rare. To leverage the similarity of cancers and the specificity of methylation patterns among them, we developed the Cancer Hierarchy Classification Tool (CHCT) using the idea of hierarchical classification, with methylation data from 30 cancer types and 8239 methylome samples downloaded from publicly available databases (The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO)). We used unsupervised clustering to divide the classification subproblems and screened differentially methylated sites using Analysis of variance (ANOVA) test, Tukey-kramer test, and Boruta algorithms to construct models for each classifier module. After validation, CHCT accurately classified 1568 out of 1660 cases in the test set, with an average accuracy of 94.46%. We further curated an independent validation cohort of 677 cancer samples from GEO and assigned a diagnosis using CHCT, which showed high diagnostic potential with generally high accuracies (an average accuracy of 91.40%). Moreover, CHCT demonstrates predictive capability for additional cancer types beyond its original classifier scope as demonstrated in the medulloblastoma and pituitary tumor datasets. In summary, CHCT can hierarchically classify primary cancer by methylation profile, by splitting a large-scale classification of 30 cancer types into ten smaller classification problems. These results indicate that cancer hierarchical classification has the potential to be an accurate and robust cancer classification method.


Assuntos
Neoplasias , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Algoritmos , Epigenoma , Metilação , Metilação de DNA
19.
J Cell Mol Med ; 27(24): 4080-4092, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37837352

RESUMO

Circular RNAs play an important role in the development of various malignancies, including hepatocellular carcinoma (HCC). Nevertheless, the role of Hsa_circ_0093335 (circ0093335) in HCC has not yet been explored. To investigate the biological effects and molecular mechanisms of circ0093335 on HCC. Circ0093335 expression was detected in HCC cells and clinical specimens using qRT-PCR. The association between circ0093335 expression and HCC patients' clinical characteristics was determined using SPSS. The role of circ0093335 in HCC was estimated by overexpression and knockdown experiments in vitro and in vivo. qRT-PCR, nucleoplasma separation assay, FISH assay, RIP, dual luciferase reporter assay and rescue assay were used to validate the regulatory effect of circ0093335 on miR-338-5p. The study findings showed that circ0093335 was upregulated in HCC. High circ0093335 expression was linked with the tumour-node-metastasis stage and microvascular tumour invasion. circ0093335 is greatly involved in HCC cell proliferation, aggressive ability and mouse tumour growth, according to many in vitro and in vivo tests. Mechanistically, circ0093335 downregulated miR-338-5p expression by sponging, consequently promoting HCC progression. Our research indicated that circ0093335 might be a target for HCC therapy since it promotes tumour progression by acting as a miR-338-5p 'sponge'.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , RNA Circular , Animais , Humanos , Camundongos , Bioensaio , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Circular/genética , RNA Circular/metabolismo
20.
J Gene Med ; 25(2): e3466, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36464925

RESUMO

Human dental pulp cells (hDPCs) contain mesenchymal stem cells and are therefore indispensible for reparative dentin formation. Here, we present a pilot study of transcriptomic profiles of mineralized hDPCs isolated from sound human maxillary third molars. We observed altered gene expression of hDPCs between control (dexamethasone free) and experimental (dexamethasone 1 nm) groups. Differential expression analysis revealed up-regulation of several inflammation and mineralization-related genes in the experimental group. After a Gene Ontology analysis for predicting genes involved in biological process, cellular component and molecular function, we found enrichment of genes related to protein binding. Based on the results of Kyoto Encylopedia of Genes and Genomes pathway analysis, it is suggested up-regulated genes in mineralized hDPCs were mostly enriched in the mitogen-activated protein kinase (MAPK) signaling pathway, fluid shear stress and the atherosclerosis signaling pathway, etc. Importantly, Gene Set Enrichment Analysis revealed dexamethasone was positively related to the Janus kinase/signal transducer and activator of transcription, MAPK and Notch signaling pathway. Moreover, it was suggested that dexamethasone regulates signaling pathway in pluripotency of stem cells. Collectively, our work highlights transcriptome level gene regulation and intercellular interactions in mineralized hDPCs. The database produced in the present study paves the way for further investigations looking to explore genes that are involved in dental pulp cells mineralization.


Assuntos
Polpa Dentária , Odontoblastos , Humanos , Diferenciação Celular/genética , Projetos Piloto , Odontoblastos/fisiologia , Análise de Sequência de RNA , Células Cultivadas
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