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1.
Curr Drug Metab ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38571358

RESUMO

AIM: The aim of this study was to investigate the metabolism of Gelsemium elegans in human, pig, goat and rat liver microsomes and to elucidate the metabolic pathways and cleavage patterns of the Gelsemium alkaloids among different species. METHODS: A human, goat, pig and rat liver microparticles were incubated in vitro. After incubating at 37°C for 1 hour and centrifuging, the processed samples were detected by HPLC/Qq-TOFMS was used to detect alcohol extract of Gelsemium elegans and its metabolites. RESULTS: Forty-six natural products were characterized from alcohol extract of Gelsemium elegans and 13 metabolites were identified. These 13 metabolites belong to the gelsemine, koumine, gelsedine, humantenine, yohimbane, and sarpagine classes of alkaloids. The metabolic pathways included oxidation, demethylation and dehydrogenation. After preliminary identification, the metabolites detected in the four species were different. All 13 metabolites were detected in pig and rat microsomes, but no oxidative metabolites of Gelsedine-type alkaloids were detected in goat and human microsomes. CONCLUSION: In this study, Gelsemium elegans metabolic patterns in different species are clarified and the in vitro metabolism of Gelsemium elegans is investigated. It is of great significance for its clinical development and rational application.

2.
Org Lett ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38636450

RESUMO

We introduce switchable chemoselectivity strategies based on the hydrazone phosphaketene intermediate to synthesize three classes of 1,2,4-diazaphosphol derivatives. First, the five-membered heterocyclic P and O anion intermediates acted as nucleophilic agents in the selective construction of C-P and C-O bonds. Second, the phosphinidene served as a phosphorus synthon, allowing for the formation of C-P and C-N bonds. Finally, a stepwise mechanism, supported by DFT calculations, was invoked to explain the reaction selectivity.

3.
Ear Nose Throat J ; : 1455613241244667, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605528

RESUMO

Hairy polyps, considered a highly unusual congenital anomaly of the pharynx, are believed by many scholars to arise from the ectoderm and mesoderm during the embryonic stage. These growths often have a pear or sausage shape, are pedunculated, and their size ranges between 0.5 and 6 cm. They are typically grayish white or pink in color. This article discusses a 12-year-old female who had a growth at the Eustachian tube's entrance on the left side of the nasopharyngeal wall, as identified by a computed tomography scan of the neck soft tissue; it was suspected to be a hairy polyp originating from the left Eustachian tube. The diagnosis of a hairy polyp was confirmed through pathology. The hairy polyp at the Eustachian tube, in this case, showed an irregular form with a wide base, making it look similar to an adenoid; thus, increasing the risk of it being misdiagnosed as residual adenoid tissue.

4.
Med Chem ; 20(1): 40-51, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37767798

RESUMO

BACKGROUND: Drug-resistant infections kill hundreds of thousands of people globally every year. In previous work, we found that tri-methoxy- and pyridine-substituted imidazoles show strong antibacterial activities. OBJECTIVE: The aim of this work was to investigate the antibacterial activities and bacterial resistances of imidazoles bearing an aromatic heterocyclic, alkoxy, or polycyclic moiety on the central ring. METHODS: Three series of 2-cyclopropyl-5-(5-(6-methylpyridin-2-yl)-2-substituted-1H-imidazol-4- yl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazoles (13a-e, 14a-d, and 15a-f) were synthesized and their antibacterial activity was evaluated. The structures were confirmed by their 1H NMR, 13C NMR, and HRMS spectra. All the synthesized compounds were screened against Gram-positive, Gramnegative, and multidrug-resistant bacterial strains. RESULTS: More than half of the compounds showed moderate or strong antibacterial activity. Among them, compound 13e (MICs = 1-4 µg/mL) showed the strongest activity against Gram-positive and drug-resistant bacteria as well as high selectivity against Gram-negative bacteria. Furthermore, it showed no cytotoxicity against HepG2 cells, even at 100 µM, and no hemolysis at 20 µM. CONCLUSION: These results indicate that compound 13e is excellent candicate for further study as a potential antibacterial agent.


Assuntos
Nitroimidazóis , Tiadiazóis , Humanos , Antibacterianos , Imidazóis/química , Antifúngicos/farmacologia , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade
5.
Tree Physiol ; 44(1)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-37741055

RESUMO

Ginkgo biloba L., an ancient relict plant known as a 'living fossil', has a high medicinal and nutritional value in its kernels and leaves. Ginkgolides are unique diterpene lactone compounds in G. biloba, with favorable therapeutic effects on cardiovascular and cerebrovascular diseases. Thus, it is essential to study the biosynthesis and regulatory mechanism of ginkgolide, which will contribute to quality improvement and medication requirements. In this study, the regulatory roles of the JAZ gene family and GbCOI1/GbJAZs/GbMYC2 module in ginkgolide biosynthesis were explored based on genome and methyl jasmonate-induced transcriptome. Firstly, 18 JAZ proteins were identified from G. biloba, and the gene characteristics and expansion patterns along with evolutionary relationships of these GbJAZs were analyzed systematically. Expression patterns analysis indicated that most GbJAZs expressed highly in the fibrous root and were induced significantly by methyl jasmonate. Mechanistically, yeast two-hybrid assays suggested that GbJAZ3/11 interacted with both GbMYC2 and GbCOI1, and several GbJAZ proteins could form homodimers or heterodimers between the GbJAZ family. Moreover, GbMYC2 is directly bound to the G-box element in the promoter of GbLPS, to regulate the biosynthesis of ginkgolide. Collectively, these results systematically characterized the JAZ gene family in G. biloba and demonstrated that the GbCOI1/GbJAZs/GbMYC2 module could regulate ginkgolides biosynthesis, which provides a novel insight for studying the mechanism of JA regulating ginkgolide biosynthesis.


Assuntos
Acetatos , Ginkgo biloba , Ginkgolídeos , Oxilipinas , Ginkgo biloba/genética , Ginkgo biloba/metabolismo , Ginkgolídeos/metabolismo , Extratos Vegetais/farmacologia , Ciclopentanos/farmacologia , Ciclopentanos/metabolismo
6.
Zhongguo Gu Shang ; 36(11): 1021-5, 2023 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-38012868

RESUMO

OBJECTIVE: To compare and analyze the early clinical effect of direct superior approach(DSA) and posterior lateral approach (PLA) in hemiarthroplasty for elderly patients with femoral neck fracture. METHODS: The clinical data of 72 elderly patients with femoral neck fracture who underwent hemiarthroplasty from January 2020 to December 2021 were retrospectively analyzed. Among them, 36 patients were operated through minimally invasive DSA including 10 males and 26 females with an average age of (82.82±4.05) years old; the other 36 patients underwent traditional PLA including 14 males and 22 females with an average age of (82.79±3.21) years old. The perioperative related indexes and Harris scores during follow-up between two groups were compared. RESULTS: Comparison of operation time between two groups, (79.41±17.39) min of DSA group was shorter than(98.45±26.58) min of PLA group;incision length (8.33±2.69) cm was shorter than (11.18±1.33) cm of PLA group;intraoperative blood loss (138.46±71.58) ml was less than (173.51±87.17) ml of PLA group, initial landing time (3.04±0.95) d was earlier than (4.52±1.10) d of PLA group, hospitalization time (8.70±1.89) d was shorter than (10.67±2.35) d of PLA group(P<0.05). There was no statistical difference in Harris score between two groups before operation(P>0.05), but Harris score in DSA group was higher than that of PLA group at 1 month after operation(P<0.05), but at 12 months after operation, the difference was not statistically significant between two groups(P>0.05). CONCLUSION: Compared with PLA, DSA is superior in clinical indexes such as operation time, intraoperative blood loss, incision length, first landing time, length of hospitalization and Harris score in the first month after operation in hemi hip replacement, and has comparative advantages in promoting early postoperative rehabilitation of elderly patients with femoral neck.


Assuntos
Artroplastia de Quadril , Fraturas do Colo Femoral , Hemiartroplastia , Masculino , Feminino , Humanos , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Estudos Retrospectivos , Fraturas do Colo Femoral/cirurgia , Resultado do Tratamento
7.
Technol Health Care ; 2023 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-37840505

RESUMO

BACKGROUND: With the ageing population in China and an increasing number of the elderly developing chronic illnesses, health services for the elderly have become a major concern. They have significant needs for health information (HI) such as online medical consultation, disease prevention, and medical insurance. OBJECTIVE: To explore the influencing factors and their relative significance in proxy online health information (OHI) seeking among the elderly with chronic illnesses so as to provide a reference for enriching theoretical research and optimizing care for the elderly with chronic illness. METHODS: Twenty-three elderly people with chronic illnesses participated in semi-structured in-depth interviews in this study. The interview transcripts were subject to three levels of coding (open, axial, and selective coding) based on grounded theory to determine the factors influencing proxy OHI seeking among the elderly and to understand how the main categories are interconnected. We used the interpretive structural modeling (ISM) process to analyze the hierarchy and associated pathways among the factors influencing proxy OHI seeking. RESULTS: From our analysis, we identified four main categories affecting proxy HI seeking: the health status, emotional needs, electronic HI literacy, and self-efficacy of the elderly. There were six subcategories that could be further subclassified into direct factors, key factors, and root factors, which constituted the hierarchical model of influencing factors. CONCLUSION: We found that proxy HI seeking among the elderly was directly triggered by self-efficacy and emotional needs following changes in their evaluation of health information and emotional needs, which originates from their perceptions of their health, concerns about their health, and information retrieval capability.

8.
Biochem Biophys Res Commun ; 681: 55-61, 2023 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-37757667

RESUMO

Gelsemium elegans (G.elegans) is a plant of the Loganiaceae family, known for its indole alkaloids, including gelsemine, koumine, and gelsenicine. Gelsemine and koumine are well-studied active alkaloids with low toxicity, valued for their anti-anxiety and analgesic properties. However, gelsenicine, another important alkaloid, remains underexplored due to its high toxicity. This study focuses on evaluating the analgesic properties of gelsenicine and comparing them with gelsemine and koumine. The results indicate that all three alkaloids exhibit robust analgesic properties, with gelsemine, koumine, and gelsenicine showing ED50 values of 0.82 mg/kg, 0.60 mg/kg, and 8.43 µg/kg, respectively, as assessed by the hot plate method. Notably, the therapeutic dose of gelsenicine was significantly lower than its toxic dose (LD50 = 0.185 mg/kg). The study also investigated the mechanism of action by analyzing the expression levels of GlyRα3 and Gephyrin. The PGE2 model group showed decreased expression levels of GlyRα3 and Gephyrin, while groups treated with gelsemine, koumine, and gelsenicine were able to reverse this decrease. These results suggest that gelsenicine effectively alleviates PGE2-induced hyperalgesia by upregulating the expression of GlyRα3 and Gephyrin, which are key targets of the Gly receptor pathway.

9.
Diabetol Metab Syndr ; 15(1): 95, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37158980

RESUMO

OBJECTIVE: For patients with diabetes, high-frequency and -amplitude glycemic variability may be more harmful than continuous hyperglycemia; however, there is still a lack of screening indicators that can quickly and easily assess the level of glycemic variability. The aim of this study was to investigate whether the glycemic dispersion index is effective for screening high glycemic variability. METHODS: A total of 170 diabetes patients hospitalized in the Sixth Affiliated Hospital of Kunming Medical University were included in this study. After admission, the fasting plasma glucose, 2-hour postprandial plasma glucose, and glycosylated hemoglobin A1c were measured. The peripheral capillary blood glucose was measured seven times in 24 h, before and after each of three meals and before bedtime. The standard deviation of the seven peripheral blood glucose values was calculated, and a standard deviation of > 2.0 was used as the threshold of high glycemic variability. The glycemic dispersion index was calculated and its diagnostic efficacy for high glycemic variability was determined by the Mann-Whitney U test, receiver operating characteristic (ROC) curve and, Pearson correlation analysis. RESULTS: The glycemic dispersion index of patients with high glycemic variability was significantly higher than that of those with low glycemic variability (p < 0.01). The best cutoff value of the glycemic dispersion index for screening high glycemic variability was 4.21. The area under the curve (AUC) was 0.901 (95% CI: 0.856-0.945) and had a sensitivity of 0.781 and specificity of 0.905. It was correlated with the standard deviation of blood glucose values (r = 0.813, p < 0.01). CONCLUSIONS: The glycemic dispersion index had good sensitivity and specificity for screening high glycemic variability. It was significantly associated with the standard deviation of blood glucose concentration and is simple and easy to calculate. It was an effective screening indicator of high glycemic variability.

10.
Chem Biodivers ; 20(5): e202300105, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36945745

RESUMO

A series of 2-cyclopropyl-5-(5-(6-methylpyridin-2-yl)-2-substituted-1H-imidazol-4-yl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazoles (15a-t and 16a-f) were synthesized and their antibacterial activities were evaluated. More than half of the compounds showed moderate or strong antibacterial activity. Among them, compounds 15t (MIC=1-2 µg/mL) and 16d (MIC=0.5 µg/mL) showed the strongest antibacterial activities. Notably, compound 16d did not exhibit cytotoxicity in HepG2 cells and did not show hemolysis like the positive control compound Gatifloxacin. The results suggest that compound 16d should be further investigated as a candidate antibacterial agent.


Assuntos
Antibacterianos , Nitroimidazóis , Antibacterianos/farmacologia , Imidazóis/farmacologia , Antifúngicos/farmacologia , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade
11.
Front Surg ; 10: 1087338, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36998599

RESUMO

Hemiarthroplasty is a surgical choice for super-aged patients with a high surgical risk and a sedentary lifestyle. The direct superior approach (DSA), a minimally invasive modification of the posterior approach, is rarely studied in hemiarthroplasty. The aim of the present study was to compare the clinical outcomes in elderly patients with displaced femoral neck fractures undergoing hemiarthroplasty via DSA with the conventional posterolateral approach (PLA). A total of 48 elderly patients with displaced femoral neck fractures who underwent hemiarthroplasty between February 2020 and March 2021 were retrospectively included in the study. Of them, 24 patients (mean age 84.54 ± 2.11 years) were treated with hemiarthroplasty via DSA (DSA group), while the other 24 patients (mean age 84.92 ± 2.15 years) were treated with hemiarthroplasty via PLA (PLA group). Clinical outcomes, perioperative data, and complications were recorded. There were no obvious differences in the baseline characteristics between the DSA and PLA groups, including age, gender, body mass index, Garden type, American Society of Anesthesiologists score, and hematocrit. Perioperative data showed that the length of the incision in the DSA group was smaller than that in the PLA group (p < 0.001). However, the duration of the operation and blood loss in the DSA group were longer and higher than those in the PLA group, respectively (p < 0.001). In addition, the DSA group had a shorter hospitalization time than the PLA group (p < 0.001). The visual analog scale score and Harris score 1 month postoperatively in the DSA group were better than those in the PLA group (p < 0.001). Moreover, there were no significant differences between the two groups in Harris score (for assessment dysfunction) 6 months postoperatively (p > 0.05). DSA is less invasive and has better clinical outcomes, which can allow an early return to daily living activities in elderly patients with displaced femoral neck fractures undergoing hemiarthroplasty.

12.
Biomed Environ Sci ; 35(6): 494-503, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35882409

RESUMO

Objectives: Hand, foot and mouth disease (HFMD) is a widespread infectious disease that causes a significant disease burden on society. To achieve early intervention and to prevent outbreaks of disease, we propose a novel warning model that can accurately predict the incidence of HFMD. Methods: We propose a spatial-temporal graph convolutional network (STGCN) that combines spatial factors for surrounding cities with historical incidence over a certain time period to predict the future occurrence of HFMD in Guangdong and Shandong between 2011 and 2019. The 2011-2018 data served as the training and verification set, while data from 2019 served as the prediction set. Six important parameters were selected and verified in this model and the deviation was displayed by the root mean square error and the mean absolute error. Results: As the first application using a STGCN for disease forecasting, we succeeded in accurately predicting the incidence of HFMD over a 12-week period at the prefecture level, especially for cities of significant concern. Conclusions: This model provides a novel approach for infectious disease prediction and may help health administrative departments implement effective control measures up to 3 months in advance, which may significantly reduce the morbidity associated with HFMD in the future.


Assuntos
Visualização de Dados , Surtos de Doenças , Previsões , Doença de Mão, Pé e Boca , Redes Neurais de Computação , Análise Espaço-Temporal , China/epidemiologia , Cidades/epidemiologia , Surtos de Doenças/prevenção & controle , Surtos de Doenças/estatística & dados numéricos , Previsões/métodos , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/prevenção & controle , Humanos , Incidência , Reprodutibilidade dos Testes , Fatores de Tempo
14.
World J Pediatr ; 18(8): 533-537, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35716276

RESUMO

BACKGROUND: Outbreaks of severe, acute hepatitis among children have recently attracted global attention. The pathogen causing the outbreak remains unknown, but there is growing evidence that it may be associated with human adenovirus (HAdV). DATA SOURCES: A review of adenovirus-related clinical studies, epidemiological studies, etiological studies, and case reports was conducted by reviewers independently. RESULTS: HAdV can cause a wide variety of clinical symptoms. In the Mainland of China, HAdV infection accounts for 5.8%-13% of patients with acute respiratory infections, and these infections are mainly caused by species B, C, and E of HAdV. For acute conjunctivitis, 39.8%-74.9% of sporadic cases were infected by B and D species of HAdV. Outbreaks of keratoconjunctivitis and pharyngoconjunctival fever related to HAdV infection could be found throughout the country. In pediatric patients with acute gastroenteritis, HAdV-41 was the predominant HAdV type, followed by HAdV species B and C. Several types of HAdV, including HAdV-5, HAdV-7, HAdV-1, and HAdV-2, have previously been reported as potential pathogens associated with HAdV hepatitis in immunocompromised patients. However, few HAdV-related hepatitis cases have been reported in China to date. CONCLUSIONS: There are no systematic surveillance and clinical studies on HAdV hepatitis in China. Therefore, it is imperative to establish a nationwide HAdV virological surveillance system to collect relevant clinical, epidemiological and virological surveillance data and risk factor information as soon as possible to assess the potential risk of HAdV hepatitis among children.


Assuntos
Infecções por Adenoviridae , Infecções por Adenovirus Humanos , Infecções Respiratórias , Doença Aguda , Infecções por Adenoviridae/epidemiologia , Infecções por Adenovirus Humanos/diagnóstico , Infecções por Adenovirus Humanos/epidemiologia , Criança , China/epidemiologia , Humanos , Filogenia , Infecções Respiratórias/diagnóstico
15.
Front Chem ; 10: 814880, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35186882

RESUMO

Mucin 1 (MUC1), a well-known tumor-associated antigen and attractive target for tumor immunotherapy, is overexpressed in most human epithelial adenomas with aberrant glycosylation. However, its low immunogenicity impedes the development of MUC1-targeted antitumor vaccines. In this study, we investigated three liposomal adjuvant systems containing toll-like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) and auxiliary lipids of different charges: cationic lipid dimethyldioctadecylammonium (DDA), neutral lipid distearoylglycerophosphocholine (DSPC) or anionic lipid dioleoylphosphatidylglycerol (DOPG), respectively. ELISA assay evidenced that the positively charged DDA/MPLA liposomes are potent immune activators, which induced remarkable levels of anti-MUC1 antibodies and exhibited robust Th1-biased immune responses. Importantly, the antibodies induced by DDA/MPLA liposomes efficiently recognized and killed MUC1-positive tumor cells through complement-mediated cytotoxicity. In addition, antibody titers in mice immunized with P2-MUC1 vaccine were significantly higher than those from mice immunized with P1-MUC1 or MUC1 vaccine, which indicated that the lipid conjugated on MUC1 antigen also played important role for immunomodulation. This study suggested that the liposomal DDA/MPLA with lipid-MUC1 is a promising antitumor vaccine, which can be used for the immunotherapy of various epithelial carcinomas represented by breast cancer.

16.
Lancet Reg Health West Pac ; 20: 100361, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35036977

RESUMO

BACKGROUND: Acute meningitis or encephalitis (AME) results from a neurological infection causing high case fatality and severe sequelae. AME lacked comprehensive surveillance in China. METHODS: Nation-wide surveillance of all-age patients with AME syndromes was conducted in 144 sentinel hospitals of 29 provinces in China. Eleven AME-causative viral and bacterial pathogens were tested with multiple diagnostic methods. FINDINGS: Between 2009 and 2018, 20,454 AME patients were recruited for tests. Based on 9,079 patients with all-four-virus tested, 28.43% (95% CI: 27.50%‒29.36%) of them had at least one virus-positive detection. Enterovirus was the most frequently determined virus in children <18 years, herpes simplex virus and Japanese encephalitis virus were the most frequently determined in 18-59 and ≥60 years age groups, respectively. Based on 6,802 patients with all-seven-bacteria tested, 4.43% (95% CI: 3.94%‒4.91%) had at least one bacteria-positive detection, Streptococcus pneumoniae and Neisseria meningitidis were the leading bacterium in children aged <5 years and 5-17 years, respectively. Staphylococcus aureus was the most frequently detected in adults aged 18-59 and ≥60 years. The pathogen spectrum also differed statistically significantly between northern and southern China. Joinpoint analysis revealed age-specific positive rates, with enterovirus, herpes simplex virus and mumps virus peaking at 3-6 years old, while Japanese encephalitis virus peaked in the ≥60 years old. As age increased, the positive rate for Streptococcus pneumoniae and Escherichia coli statistically significantly decreased, while for Staphylococcus aureus and Streptococcus suis it increased. INTERPRETATION: The current findings allow enhanced identification of the predominant AME-related pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures in China, and a possible reassessment of vaccination strategy. FUNDING: China Mega-Project on Infectious Disease Prevention and the National Natural Science Funds.

17.
Metabolites ; 13(1)2022 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-36676958

RESUMO

Asian Gelsemium elegans (G. elegans) has a wide range of pharmacological activities. However, its strong toxicity limits its potential development and application. Interestingly, there are significant gender differences in G. elegans toxicity in rats. This work aimed to elucidate the overall absorption, distribution, metabolism, and excretion (ADME) of whole G. elegans crude extract in female and male rats using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS), which facilitates determining the reasons for the gender differences in toxicity. A total of 25 absorbed bioactive components and 3 related produced metabolites were tentatively identified in female rats, while only 17 absorbed bioactive components and 3 related produced metabolites were identified in male rats. By comparison of peak intensities, most compounds were found to be more active in absorption, distribution and excretion in female rats than in male rats, which showed that female rats were more sensitive to G. elegans. This study was the first to investigate the multicomponent in vivo process of G. elegans in rats and compare the differences between sexes. It was hypothesized that differences in the absorption of gelsedine-type alkaloids were one of the main reasons for the sex differences in G. elegans toxicity.

18.
Med Chem ; 18(4): 509-520, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34182915

RESUMO

BACKGROUND: TGF-ß signaling pathway inhibition is considered an effective way to prevent the development of several diseases. In the design and synthesis of TGF-ß inhibitors, a rhodanine compound containing a quinoxalinyl imidazole moiety was found to have strong antimicrobial activity. OBJECTIVE: The purpose of this work was to investigate the antimicrobial activity of other chiral rhodanine TGF-ß inhibitors synthesized. METHODS: Two series of 3-substituted-5-(5-(6-methylpyridin-2-yl)-4-(quinoxalinyl-6-yl)- 1Himidazol- 2-yl)methylene)-2-thioxothiazolin-4-ones (12a-h and 13a-e) were synthesized and evaluated for their ALK5 inhibitory and antimicrobial activity. The structures were confirmed by their 1H NMR, 13C NMR and HRMS spectra. All the synthesized compounds were screened against Grampositive strains, Gram-negative strains, and fungi. RESULTS: Among the synthesized compounds, compound 12h showed the highest activity (IC50 = 0.416 µM) against ALK5 kinase. Compound 12h exhibited a good selectivity index of >24 against p38α MAP kinase and was 6.0-fold more selective than the clinical candidate, compound 2 (LY- 2157299). Nearly all the compounds displayed high selectivity toward both Gram-positive and Gram-negative bacteria. They also showed similar or 2.0-fold greater antifungal activity (minimum inhibitory concentration [MIC] = 0.5 µg/mL) compared with the positive control compounds Gatifloxacin (MIC = 0.5 µg/mL) and fluconazole (MIC = 1 µg/mL). CONCLUSION: The findings suggest that the synthesized rhodanine compounds have good ALK5 inhibitory activity, and merit further research and development as potential antifungal drugs.


Assuntos
Rodanina , Antibacterianos , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Imidazóis/farmacologia , Testes de Sensibilidade Microbiana , Rodanina/farmacologia , Relação Estrutura-Atividade
19.
Nat Commun ; 12(1): 5026, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408158

RESUMO

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients' demography, geographic locations and season of illness in China.


Assuntos
Bactérias/isolamento & purificação , Infecções Bacterianas/microbiologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Viroses/virologia , Vírus/isolamento & purificação , Adolescente , Adulto , Bactérias/classificação , Bactérias/genética , Infecções Bacterianas/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Estações do Ano , Viroses/epidemiologia , Vírus/classificação , Vírus/genética , Adulto Jovem
20.
J Xray Sci Technol ; 29(4): 663-674, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34024807

RESUMO

OBJECTIVES: This study aims to evaluate diagnostic performance of radiomic analysis using computed tomography (CT) to identify lymphovascular invasion (LVI) in patients diagnosed with rectal cancer and assess diagnostic performance of different lesion segmentations. METHODS: The study is applied to 169 pre-treatment CT images and the clinical features of patients with rectal cancer. Radiomic features are extracted from two different volumes of interest (VOIs) namely, gross tumor volume and peri-tumor tissue volume. The maximum relevance and the minimum redundancy, and the least absolute shrinkage selection operator based logistic regression analyses are performed to select the optimal feature subset on the training cohort. Then, Rad and Rad-clinical combined models for LVI prediction are built and compared. Finally, the models are externally validated. RESULTS: Eighty-three patients had positive LVI on pathology, while 86 had negative LVI. An optimal multi-mode radiology nomogram for LVI estimation is established. The area under the receiver operating characteristic curves of the Rad and Rad-clinical combined model in the peri-tumor VOI group are significantly higher than those in the tumor VOI group (Rad: peri-tumor vs. tumor: 0.85 vs. 0.68; Rad-clinical: peri-tumor vs. tumor: 0.90 vs 0.82) in the validation cohort. Decision curve analysis shows that the peri-tumor-based Rad-clinical combined model has the best performance in identifying LVI than other models. CONCLUSIONS: CT radiomics model based on peri-tumor volumes improves prediction performance of LVI in rectal cancer compared with the model based on tumor volumes.


Assuntos
Neoplasias Retais , Humanos , Nomogramas , Prognóstico , Neoplasias Retais/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
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