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1.
Microbiologyopen ; 13(2): e1401, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38409911

RESUMO

Prevotella intermedia, a Gram-negative bacterium from the Bacteroidota phylum, is associated with periodontitis. Other species within this phylum are known to possess the general O-glycosylation system. The O-glycoproteome has been characterized in several species, including Tannerella forsythia, Porphyromonas gingivalis, and Flavobacterium johnsoniae. In our study, we used electron cryotomography (cryoET) and glycoproteomics to reveal the ultrastructure of P. intermedia and characterize its O-glycoproteome. Our cryoET analysis unveiled the ultrastructural details of the cell envelope and outer membrane vesicles (OMVs) of P. intermedia. We observed an electron-dense surface layer surrounding both cells and OMVs. The OMVs were often large (>200 nm) and presented two types, with lumens being either electron-dense or translucent. LC-MS/MS analyses of P. intermedia fractions led to the identification of 1655 proteins, which included 62 predicted T9SS cargo proteins. Within the glycoproteome, we identified 443 unique O-glycosylation sites within 224 glycoproteins. Interestingly, the O-glycosylation motif exhibited a broader range than reported in other species, with O-glycosylation found at D(S/T)(A/I/L/M/T/V/S/C/G/F/N/E/Q/D/P). We identified a single O-glycan with a delta mass of 1531.48 Da. Its sequence was determined by MS2 and MS3 analyses using both collision-induced dissociation and high-energy collisional dissociation fragmentation modes. After partial deglycosylation with trifluoromethanesulfonic acid, the O-glycan sequence was confirmed to be dHex-dHex-HexNAc (HPO3 -C6 H12 O5 )-dHex-Hex-HexA-Hex(dHex). Bioinformatic analyses predicted the localization of O-glycoproteins, with 73 periplasmic proteins, 53 inner membrane proteins, 52 lipoproteins, 26 outer membrane proteins, and 14 proteins secreted by the T9SS.


Assuntos
Glicoproteínas , Espectrometria de Massas em Tandem , Glicosilação , Prevotella intermedia/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem/métodos , Proteínas de Membrana/metabolismo , Proteoma/metabolismo , Polissacarídeos
2.
Heliyon ; 10(1): e23893, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38234918

RESUMO

Coluria longifolia Maxim (C. longifolia) is a Chinese folk medication commonly used to treat arthritis and joint pain. Literatures have reported that C. longifolia has significant anti-inflammatory, analgesic and antipyretic effects. The aim of this research was to assay the effective fractions of C. longifolia (EFCL) against rheumatoid arthritis (RA) and to elucidate its anti-RA mechanism on a preliminary basis. The rat model of collagen-induced arthritis (CIA) was established. The therapeutic effects of different fractions in vivo were evaluated by body weight changes, a foot swelling score, inflammatory factors and histopathological examination. The mechanism of EFCL was investigated by activity of oxidative stress related enzyme, qPCR and Western blotting tests. In vivo results showed that total extraction (TE) and n-butanol fraction (NF) could significantly alleviate the symptoms of RA, decrease the levels of IL-6 and TNF-α (P < 0.01), and improve histopathological injury. The mechanism study showed that SOD level was significantly increased with MDA level decreased in the NF group. The upregulated proteins and mRNA expression levels of Nrf2, HO1 and NQO1 after TE and NF administration suggested that the anti-arthritic effect may be related to the Nrf2 signaling pathway and downstream HO1 and NQO1. In conclusion, this study confirmed that C. longifolia is capable of treating RA with NF as the main effective fraction. Its anti-RA action may be associated with Nrf2 signaling pathway and downstream HO1 and NQO1.

3.
J Agric Food Chem ; 71(42): 15497-15505, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37843053

RESUMO

Azadirachtin has been used to control agricultural pests for a long time; however, the molecular mechanism of azadirachtin on lepidopterans is still not clear. In this study, the fourth instar larvae of fall armyworm were fed with azadirachtin, and then the ecdysis was blocked in the fourth instar larval stage (L4). The prothoracic glands (PGs) of the treated larvae were dissected for RNA sequencing to determine the effect of azadirachtin on ecdysis inhibition. Interestingly, one of the PG-enriched genes, the nuclear hormone receptor 3 (HR3), was decreased after azadirachtin treatment, which plays a critical role in the 20-hydroxyecdysone action during ecdysis. To deepen the understanding of azadirachtin on ecdysis, the HR3 was knocked out by using the CRISPR/Cas9 system, while the HR3 mutants displayed embryonic lethal phenotype; thus, the stage-specific function of HR3 during larval molting was not enabled to unfold. Hence, the siRNA was injected into the 24 h L4 larvae to knock down HR3. After 96 h, the injected larvae were blocked in the old cuticle during ecdysis which is consistent with the azadirachtin-treated larvae. Taken together, we envisioned that the inhibition of ecdysis in the fall armyworm after the azadirachtin treatment is due to an interference with the expression of HR3 in PG, resulting in larval mortality. The results in this study specified the understanding of azadirachtin on insect ecdysis and the function of HR3 in lepidopteran in vivo.


Assuntos
Muda , Receptores Citoplasmáticos e Nucleares , Animais , Muda/genética , Larva/metabolismo , Spodoptera/genética , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo
4.
Drug Metab Dispos ; 51(12): 1651-1662, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37775330

RESUMO

Reduced enzyme activity in hepatocellular carcinoma (HCC) and poor targeting limit the application of enzyme-activating prodrugs, which is also detrimental to the effective treatment of HCC. Here, we investigated whether accelerated blood clearance (ABC) phenomenon occurs in HCC models following repeated injections of PEGylated liposomes (PEG-L), thus inducing prodrug accumulation and activation in the liver and exerting highly effective and low-toxicity therapeutic effects on HCC. First, PEGylated liposomal cyclophosphamide was prepared by solvent injection and characterized. Importantly, preinjection of PEG-L induced the ABC phenomenon and activation of CYP3A in both HCC rats and HCC mice by studying the effects of repeated injections of PEG-L on pharmacokinetics and tissue distribution. Next, the efficacy and toxicity of repeated injections of PEG-L in HCC mice were examined, and our data indicate that repeated injections are administered in a manner that significantly enhances the antitumor effect compared with controls, with little or no toxicity to other organs. To further reveal the pharmacokinetic mechanism of PEG-L repeated administration for the treatment of HCC, the protein expression of hepatic CYP3A and the concentration of cyclophosphamide in the liver and spleen of HCC mice by inhibiting CYP3A were analyzed. These results revealed that inducing CYP3A to accelerate the rapid conversion of prodrugs that accumulate significantly in the liver is a key mechanism for the treatment of HCC with repeated injections of PEG-L. Collectively, this work taps into the application potential of the ABC phenomenon and provides new insights into the clinical application of PEGylated nanoformulations. SIGNIFICANCE STATEMENT: This study revealed that repeated injections of PEGylated liposomes could induce the accelerated blood clearance (ABC) phenomenon characterized by hepatic accumulation and CYP3A activation based on hepatocellular carcinoma (HCC) rats and HCC mice. Furthermore, it was verified that induction of the ABC phenomenon dependent on hepatic accumulation and CYP3A activation could enhance the antihepatocellular carcinoma effects of PEGylated anticancer prodrugs in HCC mice. This elucidated the relevant pharmacokinetic mechanisms and unearthed new clues for solving the clinical application of PEGylated nanoparticles.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Pró-Fármacos , Ratos , Camundongos , Animais , Lipossomos , Carcinoma Hepatocelular/tratamento farmacológico , Citocromo P-450 CYP3A , Polietilenoglicóis , Ciclofosfamida
5.
Chemosphere ; 341: 139997, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37648173

RESUMO

BACKGROUND: Environmental exposure to dicofol (DCF), one of common organochlorine pesticides (OCPs) widely used for controlling agricultural pests, elicits a potential risk for human health due to its toxicity. However, potential physiological hazards of oral DCF exposure remain largely unknown. METHODS: Mice were exposed to relatively chronic and subacute DCF at different doses (5, 20 and 100 mg/kg) by gavage for 2 weeks. 1H NMR-based metabolomics was used to explore alterations of metabolic profiling induced by DCF exposure. Targeted metabolomics was subsequently employed to investigate the dose-dependent effects of oral DCF exposure on lipid metabolism and the gut microbiota-derived metabolites of mice. 16S rRNA gene sequencing was further employed to evaluate the changes of gut community of mice exposed to DCF. RESULTS: Oral exposure to DCF dose-dependently induced liver injury, manifested by hepatic lipogenesis, inflammation and liver dysfunction of mice. Typically, DCF exposure disrupted host fatty acids metabolism that were confirmed by marked alteration in the levels of related genes. DCF exposure also dose-dependently caused dysbiosis of the gut bacteria and its metabolites including altered microbial composition accompanied by inhibition of bacterial fermentation. CONCLUSION: These results provide metabolic evidence that DCF exposure dose-dependently induces liver lipidosis and disruption of the gut microbiota in mice, which enrich our views of molecular mechanism of DCF hepatoxicity.


Assuntos
Microbioma Gastrointestinal , Humanos , Camundongos , Animais , Dicofol , RNA Ribossômico 16S/genética , Multiômica , Homeostase , Bactérias/genética , Disbiose/induzido quimicamente
6.
Neuroimage Clin ; 39: 103492, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37603949

RESUMO

BACKGROUND: To systematically investigate the topological organisation of morphological networks of the cerebellum using structural MRI and examine their clinical relevance in chronic insomnia (CI). METHODS: One hundred and one patients with CI and 102 healthy controls (HCs) were recruited in this study. Individual morphological networks of the cerebellum were constructed based on regional grey matter volume, and topologically characterised using weighted graph theory-based network approaches. Between-group comparisons were performed using permutation tests, and Spearman's correlation was used to examine the relationships between topological alterations and clinical variables. RESULTS: Compared with HCs, patients with CI exhibited a lower normalised clustering coefficient. Locally, CI patients exhibited lower nodal efficiency in the cerebellar lobule VIIb and vermis regions, but higher nodal efficiency in the right cerebellar lobule VIIIa regions. No correlations were observed between network alterations and clinical variables. CONCLUSIONS: Individual morphological network analysis provides a new strategy for investigating cerebellar morphometric changes in CI, and our findings may have important implications in establishing diagnostic and categorical biomarkers.


Assuntos
Vermis Cerebelar , Conectoma , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Córtex Cerebral
7.
Brain Behav ; 13(7): e3103, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37278141

RESUMO

BACKGROUND: Functional abnormalities of the cerebellum have been found to be closely associated with chronic insomnia (CI). However, whether there are abnormalities in the topology of the functional connectome of the cerebellum in these patients is still unknown. This study aimed to investigate topological abnormalities of the cerebellar functional connectome in individuals with CI. MATERIALS AND METHODS: We used resting-state functional magnetic resonance imaging (rs-fMRI) and graph-theoretic analysis to construct a functional connectivity matrix and extract topological property features of the cerebellar functional connectome in patients with CI. We examined global and nodal topological property changes in the cerebellar functional connectome in 102 patients with CI (CI group) and 101 healthy participants without insomnia symptoms (HC group) to determine the differences between groups. Correlations between the topological properties of the cerebellar functional connectome and clinical assessments were calculated to confirm the differences between groups. RESULTS: The cerebellar functional connectome of both CI and HC patients exhibited small-world properties. The CI group showed higher standardized clustering coefficients at the global properties and higher betweenness centrality in the cerebellar Crus II vermis region at the nodal properties compared with participants in the HC group. However, the topological properties of cerebellar functional connectome abnormalities in the CI group were not significantly different from those in clinical assessments. CONCLUSION: Our findings suggest that the abnormal global and nodal topological properties of the cerebellar functional connectome are associated with CI and could serve as an important biomarker for CI.


Assuntos
Conectoma , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Encéfalo , Conectoma/métodos , Imageamento por Ressonância Magnética/métodos , Cerebelo/diagnóstico por imagem
8.
Aging (Albany NY) ; 15(9): 3678-3689, 2023 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-37155147

RESUMO

Colorectal cancer (CRC) is presently a health challenge in China. Although clinical chemotherapy is prescribed availably, the negative effects and poor prognoses still occur. Genistein has antitumor properties in our previous studies. However, the molecular mechanisms underlying the anti-CRC effects of genistein remain unclear. Increasing evidences have indicated that the induction of autophagy, one of cell death models, is closely associated with the formation and development of human cancer. In the current study, a systematic bioinformatics approach using network pharmacology and molecular docking imitation was aimed at identifying the pharmacological targets and anti-CRC mechanisms of genistein, characterized by autophagy-related processes and pathways. Moreover, experimental validation was conducted by using clinical and cell culture samples. All 48 potential targets of genistein-anti-CRC-associated autophagy were screened accordingly. Further bioinformatics analyses identified 10 core genistein-anti-CRC targets related to autophagy, and enrichment-assayed results revealed that the biological processes of these core targets might regulate multiple molecular pathways, including the estrogen signaling pathway. Additionally, molecular docking data demonstrated that genistein has a high affinity for epidermal growth factor receptor (EGFR) and estrogen receptor 1 (ESR1). Both EGFR and ESR1 proteins were highly expressed in clinical CRC samples. Preliminary in vitro data showed that genistein effectively reduced cellular proliferation, activated apoptosis, and suppressed EGFR and ESR1 protein expressions in CRC cells. Our research findings uncovered the molecular mechanisms of genistein against CRC, and the potential drug targets associated with autophagy in genistein treatment of CRC were identified and validated experimentally, including EGFR and ESR1.


Assuntos
Neoplasias Colorretais , Genisteína , Humanos , Genisteína/farmacologia , Genisteína/uso terapêutico , Simulação de Acoplamento Molecular , Neoplasias Colorretais/patologia , Receptores ErbB/metabolismo , Transdução de Sinais
9.
PLoS One ; 18(3): e0281630, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36996069

RESUMO

In this paper, climate change in the Jinping area is investigated. The climate change trend in the Jinping area is studied by plotting the porosity value of the carbonate rocks as a curve. By comparing the curve established using the climate change data from published articles, it is found that the B value curve obtained using the saddle line is the closest to the curve established using the climate change data from published articles. This shows that the carbonate porosity in the Jinping area obtained using an image analysis technique can be used for climate change research.


Assuntos
Carbonatos , Mudança Climática , Porosidade , China , Processamento de Imagem Assistida por Computador
10.
Drug Metab Dispos ; 51(5): 543-559, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36732076

RESUMO

Cytochrome P450 3A4 (CYP3A4), one of the most important members of the cytochrome P450 subfamily, is a crucial catalyst in the metabolism of numerous drugs. As it catalyzes numerous processes for drug activation or inactivation, the pharmacological activities and clinical outcomes of anticancer drugs metabolized by CYP3A4 are highly dependent on the enzyme's activity and expression. Due to the complexity of tumor microenvironments and various influencing factors observed in human in vitro models and clinical studies, the pharmacokinetics of most anticancer drugs are influenced by the extent of induction or inhibition of CYP3A4-mediated metabolism, and these details are not fully recognized and highlighted. Therefore, this interindividual variability due to genetic and nongenetic factors, together with the narrow therapeutic index of most anticancer drugs, contributes to their unique set of exposures and responses, which have important implications for achieving the expected efficacy and minimizing adverse events of chemotherapy for cancer in individuals. To elucidate the mechanisms of CYP3A4-mediated activation/inactivation of anticancer drugs associated with personalized therapy, this review focuses on the underlying determinants that contribute to differences in CYP3A4 metabolic activity and provides a comprehensive and valuable overview of the significance of these factors, which differs from current considerations for dosing regimens in cancer therapy. We also discuss knowledge gaps, challenges, and opportunities to explore optimal dosing regimens for drug metabolic activation/inactivation in individual patients, with particular emphasis on pooling and analyzing clinical information that affects CYP3A4 activity. SIGNIFICANCE STATEMENT: This review focuses on anticancer drugs that are activated/deactivated by CYP3A4 and highlights outstanding factors affecting the interindividual variability of CYP3A4 activity in order to gain a detailed understanding of CYP3A4-mediated drug metabolism mechanisms. A systematic analysis of available information on the underlying genetic and nongenetic determinants leading to variation in CYP3A4 metabolic activity to predict therapeutic response to drug exposure, maximize efficacy, and avoid unpredictable adverse events has clinical implications for the identification and development of CYP3A4-targeted cancer therapeutics.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Citocromo P-450 CYP3A/metabolismo , Antineoplásicos/uso terapêutico , Sistema Enzimático do Citocromo P-450/metabolismo , Neoplasias/tratamento farmacológico , Microambiente Tumoral
11.
Virulence ; 14(1): 2171691, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36694288

RESUMO

Polydnaviruses (PDVs), obligatory symbionts with parasitoid wasps, function as host immune suppressors and growth and development regulator. PDVs can induce host haemocyte apoptosis, but the underlying mechanism remains largely unknown. Here, we provided evidence that, during the early stages of parasitism, the activated Cotesia vestalis bracovirus (CvBV) reduced the overall number of host haemocytes by inducing apoptosis. We found that one haemocyte-highly expressed CvBV gene, CvBV-26-4, could induce haemocyte apoptosis. Further analyses showed that CvBV-26-4 has four homologs from other Cotesia bracoviruses and BV from wasps in the genus Glyptapanteles, and all four of them possessed a similar structure containing 3 copies of a well-conserved motif (Gly-Tyr-Pro-Tyr, GYPY). Mass spectrometry analysis revealed that CvBV-26-4 was secreted into plasma by haemocytes and then degraded into peptides that induced the apoptosis of haemocytes. Moreover, ectopic expression of CvBV-26-4 caused fly haemocyte apoptosis and increased the susceptibility of flies to bacteria. Based on this research, a new family of bracovirus genes, Bracovirus apoptosis-inducing proteins (BAPs), was proposed. Furthermore, it was discovered that the development of wasp larvae was affected when the function of CvBV BAP was obstructed in the parasitized hosts. The results of our study indicate that the BAP gene family from the bracoviruses group is crucial for immunosuppression during the early stages of parasitism.


Assuntos
Mariposas , Polydnaviridae , Vespas , Animais , Polydnaviridae/genética , Hemócitos , Larva , Apoptose
12.
Brain Imaging Behav ; 17(1): 114-124, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36418677

RESUMO

This study aimed to systematically investigate abnormal morphological connectivity in subregions of the thalamus and examine the clinical relevance of this connectivity in patients with chronic insomnia. One hundred and two patients with chronic insomnia (aged 45.50 [34.75 ~ 58.00] years; 24 men, 78 women) and one hundred and one healthy controls (aged 45.00 [34.00 ~ 55.00] years; 32 men, 69 women) were recruited. Intrathalamic and thalamocortical morphological connectivity in the thalamic subregions defined in the Human Brainnetome Atlas were computed and compared between the two groups. Spearman's correlation was used to estimate the association between thalamic morphological connectivity alterations and clinical variables. Compared with the control group, the insomnia group exhibited higher intrathalamic mean morphological connectivity than the control group, though no alterations in thalamocortical morphological connectivity were observed. However, no correlation was found between altered intrathalamic morphological connectivity and behavioral scales. In addition, alterations in morphological connectivity among thalamic subregions were found mainly in the left medial premotor thalamus, left medial prefrontal thalamus, and left sensory thalamus; however, these results were no longer significant after correction. Our findings suggest increased intrathalamic morphological connectivity in patients with chronic insomnia, thus enriching the understanding of morphological connectivity at the individual level and providing new perspectives for clinical interventions and diagnostic imaging.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Masculino , Humanos , Feminino , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Tálamo/diagnóstico por imagem , Vias Neurais/diagnóstico por imagem
13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-979159

RESUMO

Objective To improve the detection ability of laboratories, and to identify possible technical defects in the detection of dichloroacetic acid and trichloroacetic acid in drinking water. Methods A number of laboratories were organized to conduct interlaboratory determination of dichloroacetic acid and trichloroacetic acid in drinking water. Prefabricated standard series and intermediate samples were distributed. Data of determination were collected and statistically analyzed to evaluate the detection results. Results The slopes of dichloroacetic acid and trichloroacetic acid working curves were analyzed by Grubbs test. The analysis results showed that there were 1 outlier in the dichloroacetic acid data and 3 outliers in the trichloroacetic acid data, respectively. The determination results of the spiked samples of dichloroacetic acid and trichloroacetic acid were 1.5 and 4 times the actual value, respectively. Conclusion This investigation reveals that there exist some technical problems in the direct determination of dichloroacetic acid and trichloroacetic acid by gas chromatography, such as inappropriate selection of chromatographic conditions and injection port flow control, and incorrect way of spiking internal standards.

14.
Front Pharmacol ; 13: 969611, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36324685

RESUMO

The successful treatment of breast cancer is hampered by toxicity to normal cells, impaired drug accumulation at the tumor site, and multidrug resistance. We designed a novel multifunctional liposome, CUR-DTX-L, to co-deliver curcumin (CUR) and the chemotherapeutic drug docetaxel (DTX) for the treatment of breast cancer in order to address multidrug resistance (MDR) and the low efficacy of chemotherapy. The mean particle size, polydispersity index, zeta potential, and encapsulation efficiency of CUR-DTX-L were 208.53 ± 6.82 nm, 0.055 ± 0.001, -23.1 ± 2.1 mV, and 98.32 ± 2.37%, respectively. An in vitro release study and CCK-8 assays showed that CUR-DTX-L has better sustained release effects and antitumor efficacy than free drugs, the antitumor efficacy was verified by MCF-7 tumor-bearing mice, the CUR-DTX-L showed better antitumor efficacy than other groups, and the in vivo pharmacokinetic study indicated that the plasma concentration-time curve, mean residence time, and biological half-life time of CUR-DTX-L were significantly increased compared with free drugs, suggesting that it is a promising drug delivery system for the synergistic treatment of breast cancer.

15.
World J Clin Cases ; 10(31): 11338-11348, 2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36387832

RESUMO

BACKGROUND: There are few nomograms for the prognosis of Chinese patients with triple-negative breast cancer (TNBC). AIM: To construct and validate a nomogram for overall survival (OS) of Chinese TNBC patients after surgery. METHODS: This study used the data of SEER*stat 8.3.5 and selected Chinese patients with TNBC operated on between 2010 and 2015. Univariate and multivariate Cox proportional hazard regression models were used. The identified variables were integrated to form a predictive nomogram and risk stratification model; it was assessed with C-indexes and calibration curves. RESULTS: The median and maximal OS of the 336 patients was 39 and 83 mo, respectively. The multivariate analysis showed that age (P = 0.043), marital status (P = 0.040), tumor localization (P = 0.030), grade (P = 0.035), T classification (P = 0.012), and N classification (P = 0.002) were independent prognostic factors. The six variables were combined to construct a 1-, 3- and 5-year OS nomogram. The C-indexes of the nomogram to predict OS were 0.766 and compared to the seventh edition staging system, which was higher (0.766 vs 0.707, P < 0.001). In order to categorize patients into different prognostic groups, a risk stratification model was created. There was a significant difference between the Kaplan-Meier curves of the entire cohort and each disease stage according to the nomogram. CONCLUSION: The nomogram provided prognostic superiority over the traditional tumor, node and metastasis system. It could help clinicians make individual OS or risk predictions for Chinese TNBC patients after surgery.

16.
J Nat Prod ; 85(12): 2836-2844, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36399709

RESUMO

Protein tyrosine phosphatase 1B (PTP1B) is highly validated as a therapeutic target for type 2 diabetes. However, active site-directed PTP1B inhibitors generally suffer from poor selectivity and bioavailability. Inspired by the identification of a unique anthraquinone-coumarin hybrid from Knoxia valerianoides exhibiting good specificity for PTP1B over the highly homologous T-cell protein tyrosine phosphatase (TCPTP), further chemical investigation of this plant species led to the isolation of nine new anthraquinone glycosides (1-9) and two known ones (10 and 11). Structures were characterized by a combination of spectroscopic analyses and chemical methods. All compounds showed PTP1B inhibitory activities with IC50 values ranging from 1.05 to 13.74 µM. Compounds 4 and 8 exhibited greater than 64-fold selectivity over TCPTP. Enzyme kinetic studies revealed that compounds 4 and 7 behaved as mixed-type inhibitors. Docking studies predicted similar binding modes of these compounds at the allosteric site positioned between helices α3 and α6.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Monoéster Fosfórico Hidrolases/metabolismo , Monoéster Fosfórico Hidrolases/uso terapêutico , Cinética , Inibidores Enzimáticos/farmacologia , Antraquinonas/química , Glicosídeos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Simulação de Acoplamento Molecular
17.
World J Clin Cases ; 10(26): 9493-9501, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36159419

RESUMO

BACKGROUND: The bone is the second most common site of thyroid cancer metastasis, after the lung. Treatment options for bone metastasis of thyroid cancer include surgery, radioiodine therapy (RAIT), external radiation therapy, thyroid-stimulating hormone (TSH) inhibition, bisphosphonates, and small-molecule targeted therapies. In most cases, thyroid carcinoma is found in the thyroid tissue; reports of follicular thyroid carcinoma with a single metastasis to the lumbar spine are rare. CASE SUMMARY: We report a case of bone metastasis as the only clinical manifestation of thyroid cancer. The patient was a 67-year-old woman with lumbar pain for 7 years and aggravation with intermittent claudication who had previously undergone partial thyroidectomy of a benign thyroid lesion. No abnormal nodules were found in the bilateral thyroid glands. However, imaging studies were consistent with a spinal tumor, and the lesion was diagnosed as a metastatic follicular carcinoma of thyroid origin. We adopted a multidisciplinary collaboration and comprehensive treatment approach. The patient underwent lumbar spine surgery, total resection of the thyroid, postoperative TSH suppression therapy, and RAIT. There were no complications associated with the operation, and the patient had good postoperative recovery. She has experienced no recurrence. CONCLUSION: Follicular thyroid carcinoma is associated with early hematogenous metastasis, and the bone is a typical site of metastasis. Single bone metastasis is not a contraindication to medical procedures, and providing the appropriate therapy can result in better outcomes and quality of life for these patients.

18.
Medicine (Baltimore) ; 101(35): e30293, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36107545

RESUMO

BACKGROUND: Cellular angiofibroma (CAF), a rare benign mesenchymal tumor, is histologically characterized by abundant thick-walled vessels with a spindle cell component. As one of the female reproductive system tumors, its clinical and pathological features are not well characterized. METHODS: A 47-year-old woman presented for the removal of intrauterine device on October 28, 2021, as she had achieved menopause one year back. The patient had no discomfort or awareness of any mass in her vagina. She has history of breast cancer and papillary thyroid cancer. Till date, no progression of thyroid cancer or breast cancer has been observed. Her menstrual cycle was regular, and she had one child delivered vaginally. RESULTS: Pelvic examination revealed a mass sized 2.5 × 2.0 cm located near the fornix in the upper segment of the left vaginal wall. Thin prep cytologic test (TCT) revealed negative intraepithelial lesion or malignancy (NILM). HPV test was negative and leucorrhea routine inspection cleanliness II degree. No cervical mass was detected by ultrasound examination. The patients underwent the operation for intrauterine device removal plus vaginal tumor resection on November 1, 2021. Postoperative antibiotics (intravenous cefuroxime sodium 0.75 g bid for 1 day) were administered to prevent infection. The patient showed no signs of recurrence at one-month follow-up. CONCLUSION: In summary, CAF is a rare benign soft tissue tumor. Surgery is the only treatment method, and the definitive diagnosis of CAF is based on histopathological examination of surgical specimen. Long-term follow-up is needed for surveillance of recurrence.


Assuntos
Angiofibroma , Neoplasias da Mama , Angiofibroma/diagnóstico , Angiofibroma/patologia , Angiofibroma/cirurgia , Cefuroxima , Feminino , Humanos , Pessoa de Meia-Idade , Sódio , Vagina/patologia , Vagina/cirurgia
19.
Sci Rep ; 12(1): 15694, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127382

RESUMO

Rocky desertification is a serious ecological and environmental problem in Southwest China. Quickly and scientifically reveal the distribution and changes of ecological environment quality in rocky desertification areas, which is of great significance to rocky desertification restoration, ecological environment governance and sustainable development. Based on the remote sensing ecological index (RSEI), in addition to greenness, humidity, dryness, and heat, combined with the degree of rocky desertification, this study used the principal component analysis (PCA) method to construct a modified remote sensing ecological index (MRSEI). Then, the temporal and spatial variation characteristics and imaging factors of the ecological environment quality in the typical rocky desertification region of southeastern Chongqing from 2001 to 2021 were explored. The results revealed that the greenness and humidity indicators had a positive effect on the ecological quality, while the indicators of dryness, heat and rocky desertification had the opposite impact. From 2001 to 2021, the ecological environment quality in southeastern Chongqing showed a trend of gradual improvement, and the improvement area accounted for about 70% of the total area. The elevation, slope, monthly average precipitation, and land use pattern were the main factors influencing the quality of the ecological environment in the region.


Assuntos
Ecossistema , Tecnologia de Sensoriamento Remoto , China , Meio Ambiente , Monitoramento Ambiental/métodos
20.
Genomics ; 114(5): 110437, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35902070

RESUMO

Neoneuromus ignobilis is an archaic holometabolous aquatic predatory insect. However, a lack of genomic resources hinders the use of whole genome sequencing to explore their genetic basis and molecular mechanisms for adaptive evolution. Here, we provided a high-contiguity, chromosome-level genome assembly of N. ignobilis using high coverage Nanopore and PacBio reads with the Hi-C technique. The final assembly is 480.67 MB in size, containing 12 telomere-ended pseudochromosomes with only 17 gaps. We compared 42 hexapod species genomes including six independent lineages comprising 11 aquatic insects, and found convergent expansions of long wavelength-sensitive and blue-sensitive opsins, thermal stress response TRP channels, and sulfotransferases in aquatic insects, which may be related to their aquatic adaptation. We also detected strong nonrandom signals of convergent amino acid substitutions in aquatic insects. Collectively, our comparative genomic analysis revealed the evidence of molecular convergences in aquatic insects during both gene family evolution and convergent amino acid substitutions.


Assuntos
Genoma , Insetos , Animais , Insetos/genética , Opsinas/genética , Filogenia , Sulfotransferases/genética
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