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1.
Int J Mol Sci ; 25(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731817

RESUMO

MCPH1 has been identified as the causal gene for primary microcephaly type 1, a neurodevelopmental disorder characterized by reduced brain size and delayed growth. As a multifunction protein, MCPH1 has been reported to repress the expression of TERT and interact with transcriptional regulator E2F1. However, it remains unclear whether MCPH1 regulates brain development through its transcriptional regulation function. This study showed that the knockout of Mcph1 in mice leads to delayed growth as early as the embryo stage E11.5. Transcriptome analysis (RNA-seq) revealed that the deletion of Mcph1 resulted in changes in the expression levels of a limited number of genes. Although the expression of some of E2F1 targets, such as Satb2 and Cdkn1c, was affected, the differentially expressed genes (DEGs) were not significantly enriched as E2F1 target genes. Further investigations showed that primary and immortalized Mcph1 knockout mouse embryonic fibroblasts (MEFs) exhibited cell cycle arrest and cellular senescence phenotype. Interestingly, the upregulation of p19ARF was detected in Mcph1 knockout MEFs, and silencing p19Arf restored the cell cycle and growth arrest to wild-type levels. Our findings suggested it is unlikely that MCPH1 regulates neurodevelopment through E2F1-mediated transcriptional regulation, and p19ARF-dependent cell cycle arrest and cellular senescence may contribute to the developmental abnormalities observed in primary microcephaly.


Assuntos
Pontos de Checagem do Ciclo Celular , Senescência Celular , Inibidor p16 de Quinase Dependente de Ciclina , Camundongos Knockout , Microcefalia , Animais , Camundongos , Senescência Celular/genética , Microcefalia/genética , Microcefalia/metabolismo , Microcefalia/patologia , Pontos de Checagem do Ciclo Celular/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/deficiência , Fator de Transcrição E2F1/genética , Fator de Transcrição E2F1/metabolismo , Fibroblastos/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo
2.
J Org Chem ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787532

RESUMO

Activation and cleavage of C-C double bonds are long-standing challenges in synthetic chemistry. Herein, we report an unprecedented azide-mediated C-C double bond fragmentation of gem-difluoroalkenes under mild and metal-free conditions, enabling the efficient synthesis of structurally diverse aromatic nitriles in moderate to good yields. This protocol is also amenable to the cyanation of gem-dichloro and dibromo alkenes. This reaction features simple operation and good functional group compatibility and can be implemented at a gram scale.

3.
Eur J Med Chem ; 271: 116401, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38640870

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) cause more than 100,000 deaths each year, which need efficient and non-resistant antibacterial agents. SAR analysis of 162 flavonoids from the plant in this paper suggested that lipophilic group at C-3 was crucial, and then 63 novel flavonoid derivatives were designed and total synthesized. Among them, the most promising K15 displayed potent bactericidal activity against clinically isolated MRSA and VRE (MICs = 0.25-1.00 µg/mL) with low toxicity and high membrane selectivity. Moreover, mechanism insights revealed that K15 avoided resistance by disrupting biofilm and targeting the membrane, while vancomycin caused 256 times resistance against MRSA, and ampicillin caused 16 times resistance against VRE by the same 20 generations inducing. K15 eliminated residual bacteria in mice skin MRSA-infected model (>99 %) and abdominal VRE-infected model (>92 %), which was superior to vancomycin and ampicillin.


Assuntos
Antibacterianos , Flavonoides , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Enterococos Resistentes à Vancomicina , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Flavonoides/farmacologia , Flavonoides/química , Flavonoides/síntese química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Animais , Camundongos , Relação Estrutura-Atividade , Estrutura Molecular , Relação Dose-Resposta a Droga , Infecções Estafilocócicas/tratamento farmacológico , Humanos
4.
J Dig Dis ; 25(1): 27-35, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38342693

RESUMO

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.


Assuntos
Medicamentos de Ervas Chinesas , Gastrite Atrófica , Infecções por Helicobacter , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Gastrite Atrófica/tratamento farmacológico , Gastrite Atrófica/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/patologia , Metaplasia , Ácido Fólico/uso terapêutico , Mucosa Gástrica/patologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-38358871

RESUMO

Open-set object detection (OSOD) aims to detect the known categories and reject unknown objects in a dynamic world, which has achieved significant attention. However, previous approaches only consider this problem in data-abundant conditions, while neglecting the few-shot scenes. In this paper, we seek a solution for the generalized few-shot open-set object detection (G-FOOD), which aims to avoid detecting unknown classes as known classes with a high confidence score while maintaining the performance of few-shot detection. The main challenge for this task is that few training samples induce the model to overfit on the known classes, resulting in a poor open-set performance. We propose a new G-FOOD algorithm to tackle this issue, named Few-shOt Open-set Detector (FOOD), which contains a novel class weight sparsification classifier (CWSC) and a novel unknown decoupling learner (UDL). To prevent over-fitting, CWSC randomly sparses parts of the normalized weights for the logit prediction of all classes, and then decreases the co-adaptability between the class and its neighbors. Alongside, UDL decouples training the unknown class and enables the model to form a compact unknown decision boundary. Thus, the unknown objects can be identified with a confidence probability without any threshold, prototype, or generation. We compare our method with several state-of-the-art OSOD methods in few-shot scenes and observe that our method improves the F-score of unknown classes by 4.80%-9.08% across all shots in VOC-COCO dataset settings.

6.
J Chem Ecol ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372833

RESUMO

The melon fly, Zeugodacus cucurbitae (Coquillett), is a major invasive pest, widely distributed in the Asia-Pacific region and some parts of Africa. Melon fly attractants could improve the effectiveness of current pest management measures. Previous studies have shown that some host fruits are attractive to melon flies but few have investigated the chemical compounds responsible for their attraction. In this study, we aimed to identify the volatile compounds from Luffa acutangula L that attract Z. cucurbitae. In headspace trapping, chemical profiling identified 19 compounds from ridge gourds, with 1-pentadecene being the major component. EAG results revealed that seven compounds elicited antennal responses in Z. cucurbitae, and significant differences in antennal responses between male and female Z. cucurbitae adults were recorded to p-xylene, alpha-pinene, and 1-octadecene. Behavioral experiments demonstrated that the EAG-active compounds methyl isovalerate and methyl myristate had either attractive or repellent effects on Z. cucurbitae at different concentrations, and 1-octadecene attracted Z. cucurbitae. Our findings provide a theoretical basis producing repellents or attractants for effective Integrated Pest Management of Z. cucurbitae.

8.
J Orthop Surg Res ; 19(1): 60, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38216968

RESUMO

BACKGROUND: With potential of deep learning in musculoskeletal image interpretation being explored, this paper focuses on the common site of rotator cuff tears, the supraspinatus. It aims to propose and validate a deep learning model to automatically extract the supraspinatus, verifying its superiority through comparison with several classical image segmentation models. METHOD: Imaging data were retrospectively collected from 60 patients who underwent inpatient treatment for rotator cuff tears at a hospital between March 2021 and May 2023. A dataset of the supraspinatus from MRI was constructed after collecting, filtering, and manually annotating at the pixel level. This paper proposes a novel A-DAsppUnet network that can automatically extract the supraspinatus after training and optimization. The analysis of model performance is based on three evaluation metrics: precision, intersection over union, and Dice coefficient. RESULTS: The experimental results demonstrate that the precision, intersection over union, and Dice coefficients of the proposed model are 99.20%, 83.38%, and 90.94%, respectively. Furthermore, the proposed model exhibited significant advantages over the compared models. CONCLUSION: The designed model in this paper accurately extracts the supraspinatus from MRI, and the extraction results are complete and continuous with clear boundaries. The feasibility of using deep learning methods for musculoskeletal extraction and assisting in clinical decision-making was verified. This research holds practical significance and application value in the field of utilizing artificial intelligence for assisting medical decision-making.


Assuntos
Lesões do Manguito Rotador , Manguito Rotador , Humanos , Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/diagnóstico por imagem , Estudos Retrospectivos , Inteligência Artificial , Imageamento por Ressonância Magnética/métodos
9.
Drug Des Devel Ther ; 18: 133-159, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38283137

RESUMO

Purpose: Alzheimer's disease (AD) is the most common neurodegenerative disease, and its multifactorial nature increases the difficulty of medical research. To explore an effective treatment for AD, a series of novel tacrine-selegiline hybrids with ChEs and MAOs inhibitory activities were designed and synthesized as multifunctional drugs. Methods: All designed compounds were evaluated in vitro for their inhibition of cholinesterases (AChE/BuChE) and monoamine oxidases (MAO-A/B) along with their blood-brain barrier permeability. Then, further biological activities of the optimizing compound 7d were determined, including molecular model analysis, in vitro cytotoxicity, acute toxicity studies in vivo, and pharmacokinetic and pharmacodynamic property studies in vivo. Results: Most synthesized compounds demonstrated potent inhibitory activity against ChEs/MAOs. Particularly, compound 7d exhibited good and well-balanced activity against ChEs (hAChE: IC50 = 1.57 µM, hBuChE: IC50 = 0.43 µM) and MAOs (hMAO-A: IC50 = 2.30 µM, hMAO-B: IC50 = 4.75 µM). Molecular modeling analysis demonstrated that 7d could interact simultaneously with both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE in a mixed-type manner and also exhibits binding affinity towards BuChE and MAO-B. Additionally, 7d displayed excellent permeability of the blood-brain barrier, and under the experimental conditions, it elicited low or no toxicity toward PC12 and BV-2 cells. Furthermore, 7d was not acutely toxic in mice at doses up to 2500 mg/kg and could improve the cognitive function of mice with scopolamine-induced memory impairment. Lastly, 7d possessed well pharmacokinetic characteristics. Conclusion: In light of these results, it is clear that 7d could potentially serve as a promising multi-functional drug for the treatment of AD.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Taurina/análogos & derivados , Camundongos , Animais , Tacrina/farmacologia , Tacrina/química , Tacrina/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Colinesterases/metabolismo , Selegilina/farmacologia , Selegilina/uso terapêutico , Monoaminoxidase/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Doenças Neurodegenerativas/tratamento farmacológico , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/química , Acetilcolinesterase/metabolismo , Desenho de Fármacos , Relação Estrutura-Atividade , Peptídeos beta-Amiloides
10.
Heliyon ; 10(1): e22963, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38163185

RESUMO

Zanthoxylum motuoense (Tibetan prickly ash, MTHJ), different from the Chinese prickly ash species, is distributed only in the Tibet. Now the chemical characterization and antibacterial activity of MTHJ extracts were analyzed for the first time. As a result, Schinifoline (12), γ-Fagarine (8), (2E,7E,9E)-6 S-Hydroxy-N-(2-methylpropyl)-11-oxo-2, 7, 9-Dodecatrienamide (6), and Neoechinulin A (17) were found to be the major different factors by untarget LC-MS metabolomics together with quantitative analysis on target. These four compounds were also the major antibacterial constituents. Then, the antimicrobial activity of MTHJ fractions was evaluated with colony forming units (CFU), fluorescence microscopy imaging, SEM and investigating the potential food preservation. Nutritional composition, colour and sensory evaluation of extract-treated samples were evaluated along storage time. The results suggested the MTHJ may be used for meat products preservation, and the scores were significantly higher for its unique flavor, which offered a promising choice for food safety, preservation and reducing foodborne illness.

11.
Bioorg Med Chem ; 97: 117544, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-38071943

RESUMO

It's urgent to discover new antibiotics along with the increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens. In the present investigation, morusin exhibited rapid bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) by targeting the phospholipid of bacterial inner membrane, increasing membrane rigidity and disrupting bacterial homeostasis together with the membrane permeability, which caused fundamental metabolic disorders. Furthermore, morusin can also accumulate ROS, suppress H2S production, and aggravate oxidative damage in bacteria. Importantly, morusin also inhibited the spread of wounds and reduced the bacterial burden in the mouse model of skin infection caused by MRSA. It's a chance to meet the challenge of existing antibiotic resistance and avoid the development of bacterial resistance, given the multiple targets of morusin.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Morus , Animais , Camundongos , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana
12.
J Magn Reson Imaging ; 59(3): 825-834, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37338016

RESUMO

BACKGROUND: Few studies assessed myocardial inflammation using Cardiovascular Magnetic Resonance Imaging in Kawasaki disease (KD) patients. PURPOSE: To quantify myocardial edema in KD patients using T2 mapping and explore the independent predictors of T2 values. STUDY TYPE: Prospective. SUBJECTS: Ninety KD patients including 40 in acute phase (26 males, 65.0%) and 50 in chronic phase (34 males, 68.0%). Thirty-one healthy volunteers (21 males, 70.0%). FIELD STRENGTH/SEQUENCE: 3.0 T T2-weighted Turbo Spin Echo-Short Time of Inversion Recovery sequence, True fast imaging with steady precession flash sequence and fast low-angle shot 3D spoiled gradient echo sequence. ASSESSMENT: T2 values were compared among KD groups and controls. STATISTICAL TEST: Student's t test and Fisher's exact test; One-way analysis of variance; Pearson correlation analysis; Receiver operating curve analysis; Multivariable linear regression. RESULTS: Global T2 value of KD patients in acute phase was the highest, followed by those of chronic-phase patients and controls (38.83 ± 2.41 msec vs. 37.55 ± 2.28 msec vs. 36.05 ± 1.64 msec). Regional T2 values showed a same trend. There were no significant differences in global and regional T2 values between KD patients with and without coronary artery (CA) dilation, no matter in acute or chronic phase (all KD patients: P = 0.51, 0.51, 0.53, 0.72; acute KD: P = 0.61, 0.37, 0.33, 0.83; chronic KD: P = 0.65, 0.79, 0.62, 0.79). No significant difference was observed in global T2 values between KD patients with Z score > 5.0 and 2.0 < Z score ≤ 5.0 (P = 0.65). Multivariate analysis demonstrated that stage of disease (ß = -0.123) and heart rate (ß = 0.280) were independently associated with global T2 values. DATA CONCLUSION: The degree of myocardial edema was more severe in acute-phase than in chronic-phase KD patients. Myocardial edema persists in patients regardless of the existence or degree of CA dilation. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.


Assuntos
Síndrome de Linfonodos Mucocutâneos , Masculino , Criança , Humanos , Estudos Prospectivos , Miocárdio/patologia , Imageamento por Ressonância Magnética/métodos , Edema
13.
J Genet Genomics ; 51(4): 419-432, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37923173

RESUMO

The cerebral cortex is a pivotal structure integral to advanced brain functions within the mammalian central nervous system. DNA methylation and hydroxymethylation play important roles in regulating cerebral cortex development. However, it remains unclear whether abnormal cerebral cortex development, such as microcephaly, could rescale the epigenetic landscape, potentially contributing to dysregulated gene expression during brain development. In this study, we characterize and compare the DNA methylome/hydroxymethylome and transcriptome profiles of the cerebral cortex across several developmental stages in wild-type (WT) mice and Mcph1 knockout (Mcph1-del) mice with severe microcephaly. Intriguingly, we discover a global reduction of 5'-hydroxymethylcytosine (5hmC) level, primarily in TET1-binding regions, in Mcph1-del mice compared to WT mice during juvenile and adult stages. Notably, genes exhibiting diminished 5hmC levels and concurrently decreased expression are essential for neurodevelopment and brain functions. Additionally, genes displaying a delayed accumulation of 5hmC in Mcph1-del mice are significantly associated with the establishment and maintenance of the nervous system during the adult stage. These findings reveal that aberrant cerebral cortex development in the early stages profoundly alters the epigenetic regulation program, which provides unique insights into the molecular mechanisms underpinning diseases related to cerebral cortex development.

14.
J Med Chem ; 67(1): 728-753, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38156615

RESUMO

Alcohol use disorder (AUD) results in numerous disabilities and approximately 3 million deaths annually, caused mainly by alcoholic liver disease (ALD). Phosphodiesterase IV (PDE4) has emerged as an attractive molecular target for a new treatment for AUD and ALD. In this study, we describe the identification of 5-azaindazole analogues as PDE4 inhibitors against AUD and ALD. System optimization studies led to the discovery of ZL40 (IC50 = 37.4 nM) with a remarkable oral bioavailability (F = 94%), satisfactory safety, and a lower emetogenic potency than the approved PDE4 inhibitors roflumilast and apremilast. Encouragingly, ZL40 exhibited AUD therapeutic effects by decreasing alcohol intake and improving acute alcohol-induced sedation and motor impairment. Meanwhile, ZL40 displayed the potential to alleviate alcoholic liver injury and attenuate inflammation in the NIAAA mice model. These results showed that ZL40 is a promising compound for future drug development to treat alcohol-related diseases.


Assuntos
Alcoolismo , Hepatopatias Alcoólicas , Inibidores da Fosfodiesterase 4 , Camundongos , Animais , Inibidores da Fosfodiesterase 4/farmacologia , Inibidores da Fosfodiesterase 4/uso terapêutico , Alcoolismo/tratamento farmacológico , Hepatopatias Alcoólicas/tratamento farmacológico , Etanol/uso terapêutico , Consumo de Bebidas Alcoólicas
15.
Int J Mol Sci ; 24(23)2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38069395

RESUMO

Zn2+-dependent histone deacetylases (HDACs) are enzymes that regulate gene expression by removing acetyl groups from histone proteins. These enzymes are essential in all living systems, playing key roles in cancer treatment and as potential pesticide targets. Previous phylogenetic analyses of HDAC in certain species have been published. However, their classification and evolutionary origins across biological kingdoms remain unclear, which limits our understanding of them. In this study, we collected the HDAC sequences from 1451 organisms and performed analyses. The HDACs are found to diverge into three classes and seven subclasses under divergent selection pressure. Most subclasses show species specificity, indicating that HDACs have evolved with high plasticity and diversification to adapt to different environmental conditions in different species. In contrast, HDAC1 and HDAC3, belonging to the oldest class, are conserved and crucial in major kingdoms of life, especially HDAC1. These findings lay the groundwork for the future application of HDACs.


Assuntos
Histonas , Zinco , Filogenia , Zinco/metabolismo , Histona Desacetilase 1/genética , Histona Desacetilase 1/metabolismo
16.
Sci Data ; 10(1): 848, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-38040744

RESUMO

The fruit fly Zeugodacus tau (Diptera: Tephritidae) is a major pest of melons and other cucurbits in Southeast Asia. In this study, we used Illumina, Nanopore, and Hi-C sequencing technologies to assemble a reference genome of Z. tau at the chromosomal level. The assembled genome was 421.79 Mb and consisted of six chromosomes (one X-chromosome + five autosomes). The contig N50 was 4.23 Mb. We identified 20,922 protein-coding genes, of which 17,251 (82.45%) were functionally annotated. Additionally, we found 247 rRNAs, 435 tRNAs, 67 small nuclear RNAs, and 829 small RNAs in the genome. Repetitive elements accounted for 55.30 Mb (13.15%) of the genome. This high-quality genome assembly is valuable for evolutionary and genetic studies of Z. tau and its relative species.


Assuntos
Genoma de Inseto , Tephritidae , Animais , Cromossomos , Anotação de Sequência Molecular , Filogenia , Sequências Repetitivas de Ácido Nucleico , Tephritidae/genética
17.
World J Gastroenterol ; 29(43): 5834-5847, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38074913

RESUMO

BACKGROUND: 14C urea breath test (14C UBT) and immunohistochemical staining (IHC) are widely used for detection Helicobacter pylori (H. pylori) infection with different sensitivity, and there is a difference in H. pylori infection rate in Uyghur and Han ethnic groups. Both need large cohort studies to evaluate the differences more accurately. AIM: To analyze the difference between 14C UBT and IHC for H. pylori detection in Xinjiang Uyghur Autonomous Region and the difference between Uyghur and Han populations. METHODS: There were 3944 cases of H. pylori infection detected by both IHC and 14C UBT at the same time (interval < 1 wk, with sampling site including gastric antrum, selected from 5747 patients). We compared the sensitivity of 14C UBT and IHC. We also compared 555 pairs of Han/Uyghur cases (completely matched for gender and age) for their H. pylori infection rates. The overall H. pylori infection rate of all 5747 cases and the correlation with other clinicopathological data were also further analyzed. SPSS V23.0 software was used for statistical analysis. RESULTS: The sensitivity was 94.9% for 14C UBT and 65.1% for IHC, which was a significant difference (n = 3944, P < 0.001). However, among those cases negative for H. pylori by 14C UBT (detection value ≤ 100), 4.8% were positive by IHC. Combining both methods, the overall H. pylori infection rate was 48.6% (n = 5747), and differences in gender, age group, ethnicity and region of residence significantly affected the H. pylori positive rates. According to age group (Han/Uyghur), the positive rates were ≤ 30 years (62.2%/100.0%), 31-40 years (45.2%/85.7%), 41-50 years (47.2%/79.2%), 51-60 years (44.6%/76.1%), 61-70 years (40.9%/68.2%), 71-80 years (41.7%/54.1%) and ≥ 81 years (42.9%/NA). The H. pylori infection rates of Han/Uyghur paired cases were 41.4% and 73.3%, which was a significant difference (P < 0.001) (555 pairs). H. pylori positivity was significantly related to moderate-severe grade 2-3 chronic/active gastritis and intestinal metaplasia (all P < 0.05). CONCLUSION: The sensitivity of 14C UBT was significantly higher, but combined application can still increase the accuracy. The prevention H. pylori should be emphasized for Uygur and young people.


Assuntos
Gastrite Atrófica , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Humanos , Adolescente , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/patologia , Prevalência , Testes Respiratórios/métodos , Ureia/análise , Sensibilidade e Especificidade
18.
Front Pharmacol ; 14: 1275041, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37908974

RESUMO

Triterpenoid saponins from Stauntonia chinensis have been proven to be a potential candidate for inflammatory pain relief. Our pharmacological studies confirmed that the analgesic role of triterpenoid saponins from S. chinensis occurred via a particular increase in the inhibitory synaptic response in the cortex at resting state and the modulation of the capsaicin receptor. However, its analgesic active components and whether its analgesic mechanism are limited to this are not clear. In order to further determine its active components and analgesic mechanism, we used the patch clamp technique to screen the chemical components that can increase inhibitory synaptic response and antagonize transient receptor potential vanilloid 1, and then used in vivo animal experiments to evaluate the analgesic effect of the selected chemical components. Finally, we used the patch clamp technique and molecular biology technology to study the analgesic mechanism of the selected chemical components. The results showed that triterpenoid saponins from S. chinensis could enhance the inhibitory synaptic effect and antagonize the transient receptor potential vanilloid 1 through different chemical components, and produce central and peripheral analgesic effects. The above results fully reflect that "traditional Chinese medicine has multi-component, multi-target, and multi-channel synergistic regulation".

19.
Zhongguo Gu Shang ; 36(11): 1065-9, 2023 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-38012876

RESUMO

OBJECTIVE: To explore 3.0T MRI accurate measurement of knee cartilage thickness in healthy youth provides reliable anatomical parameters for quantitative diagnosis of osteoarthritis and accurate osteotomy of joint replacement. METHODS: From January 2013 to December 2013, 30 healthy young volunteers including 14 males and 16 females with an average age of (25.8±2.4) years old ranging from 22 to 33 years were recruited in Changchun, Jilin Province, and a 3.0T MRI scan was performed on the bilateral knee joints of each volunteer. The cartilage thickness was measured on the lateral femoral condyle (LFC), medial femoral condyle (MFC), lateral tibial plateau (LTP) and medial tibial plateau (MTP). RESULTS: In four regions of the knee joint:LFC, MFC, LTP and MTP, whether young men or women, there was no significant difference in cartilage thickness between the left and right knee joints (P>0.05). There were significant differences in knee cartilage thickness between healthy young men and women (P<0.05). In the same sex group, LFC cartilage thickness was thinner in the middle, thicker in front and rear;MFC cartilage thickness was the thinnest in front and gradually thickening from the front to the rear; LTP cartilage thickness was thickest in the middle, second in the rear and thinnest in the front;MTP cartilage thickness was the thinnest in the front, was relatively uniform in the middle and rear and thicker than that in the front. CONCLUSION: In Northeast China, among healthy adults aged 22 to 33, gender difference may be an important factor in the difference of cartilage thickness in various regions of the knee joint. Regardless of whether male or female healthy young people, the cartilage thickness of the entire knee joint is unevenly distributed, but there is no significant difference in cartilage thickness in the same area between the left and right knee joints.


Assuntos
Cartilagem Articular , Osteoartrite , Adulto , Adolescente , Humanos , Masculino , Feminino , Adulto Jovem , Cartilagem Articular/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Imageamento por Ressonância Magnética , Fêmur
20.
Drug Des Devel Ther ; 17: 3151-3167, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37876500

RESUMO

Objective: Traditional Chinese medicine Polygonum cuspidatum (PC) has significant effects on reducing pain. In this study, we investigated the analgesic effects of the alcohol extract of PC on three types of inflammatory pain and explored its mechanism. Methods: Potential targets for the analgesic effects of the main active components of PC alcohol extract were screened by network pharmacology and molecular docking. Three different inflammatory pain mouse models (acetic acid twisting, formalin foot swelling, and xylene ear swelling) were used to study the analgesic effects of PC. The expression of latent signaling pathways in L4-6 spinal cord tissues in formalin foot swelling mice was evaluated using real-time qPCR (RT-qPCR), Western blot (WB), and immunohistochemistry (IHC) analyses. Results: Network pharmacology analysis shows that PC analgesic mechanism is related to the MAPK/ERK signaling pathway. The five main active components of PC have good docking ability with JNK and p38. PC alcohol extract significantly reduced the pain behavior and alleviated inflammatory reactions in three mouse models, inhibited the mRNA and protein phosphorylation levels of JNK, ERK, p38, and CREB in spinal cord tissues. Conclusion: PC alcohol extract can inhibit inflammation and alleviate pain, which is related to its inhibition of the MAPK/ERK signaling pathway in spinal cord. Thus, PC alcohol extract is a promising candidate for pain treatment.


Assuntos
Fallopia japonica , Ratos , Camundongos , Animais , Fallopia japonica/química , Ratos Sprague-Dawley , Simulação de Acoplamento Molecular , Dor/tratamento farmacológico , Transdução de Sinais , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Etanol , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Modelos Animais de Doenças , Formaldeído/farmacologia
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