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1.
Proc Natl Acad Sci U S A ; 121(17): e2314353121, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38635634

RESUMO

Auxin regulates plant growth and development through downstream signaling pathways, including the best-known SCFTIR1/AFB-Aux/IAA-ARF pathway and several other less characterized "noncanonical" pathways. Recently, one SCFTIR1/AFB-independent noncanonical pathway, mediated by Transmembrane Kinase 1 (TMK1), was discovered through the analyses of its functions in Arabidopsis apical hook development. Asymmetric accumulation of auxin on the concave side of the apical hook triggers DAR1-catalyzed release of the C-terminal of TMK1, which migrates into the nucleus, where it phosphorylates and stabilizes IAA32/34 to inhibit cell elongation, which is essential for full apical hook formation. However, the molecular factors mediating IAA32/34 degradation have not been identified. Here, we show that proteins in the CYTOKININ INDUCED ROOT WAVING 1 (CKRW1)/WAVY GROWTH 3 (WAV3) subfamily act as E3 ubiquitin ligases to target IAA32/34 for ubiquitination and degradation, which is inhibited by TMK1c-mediated phosphorylation. This antagonistic interaction between TMK1c and CKRW1/WAV3 subfamily E3 ubiquitin ligases regulates IAA32/34 levels to control differential cell elongation along opposite sides of the apical hook.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas F-Box , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Transdução de Sinais , Ubiquitinas/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas F-Box/genética , Proteínas F-Box/metabolismo
2.
PLoS Genet ; 18(10): e1010431, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36227834

RESUMO

It is widely stated in the literature that closed mature autophagosomes (APs) fuse with lysosomes/vacuoles during macroautophagy/autophagy. Previously, we showed that unclosed APs accumulated as clusters outside vacuoles in Vps21/Rab5 and ESCRT mutants after a short period of nitrogen starvation. However, the fate of such unclosed APs remains unclear. In this study, we used a combination of cellular and biochemical approaches to show that unclosed double-membrane APs entered vacuoles and formed unclosed single-membrane autophagic bodies after prolonged nitrogen starvation or rapamycin treatment. Vacuolar hydrolases, vacuolar transport chaperon (VTC) proteins, Ypt7, and Vam3 were all involved in the entry of unclosed double-membrane APs into vacuoles in Vps21-mutant cells. Overexpression of the vacuolar hydrolases, Pep4 or Prb1, or depletion of most VTC proteins promoted the entry of unclosed APs into vacuoles in Vps21-mutant cells, whereas depletion of Pep4 and/or Prb1 delayed the entry into vacuoles. In contrast to the complete infertility of diploid cells of typical autophagy mutants, diploid cells of Vps21 mutant progressed through meiosis to sporulation, benefiting from the entry of unclosed APs into vacuoles after prolonged nitrogen starvation. Overall, these data represent a new observation that unclosed double-membrane APs can enter vacuoles after prolonged autophagy induction, most likely as a survival strategy.


Assuntos
Proteínas de Saccharomyces cerevisiae , Vacúolos , Autofagossomos/metabolismo , Autofagia/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Hidrolases/metabolismo , Chaperonas Moleculares/metabolismo , Nitrogênio/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Sirolimo/metabolismo , Sirolimo/farmacologia , Vacúolos/genética , Vacúolos/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo
3.
Oncologist ; 29(6): 543-545, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38204337

RESUMO

Sequential regimens in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) can overcome tyrosine kinase inhibitor (TKI) resistance and maximize clinical benefit. Patients with advanced NSCLC can achieve excellent tumor control after a period of EGFR-TKI treatment. Patients may benefit from additional local treatment, such as surgery or radiation therapy, once the tumor is under control. Here, we present a case of a patient with advanced oligometastatic NSCLC with EGFR mutations who achieved downstaging through sequential EGFR-TKI-based precision medicine allowing resection of residual disease.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Inibidores de Proteínas Quinases/uso terapêutico , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Feminino , Idoso
4.
Invest New Drugs ; 42(1): 24-34, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37975978

RESUMO

Cholangiocarcinoma (CCA) is a primary malignancy which is often diagnosed when it is advanced and inoperable due to the lack of effective biomarkers and poor sensitivity of clinical diagnosis. Molecular profiling may provide information for improved clinical management, particularly targeted therapy. The study aimed to improve the understanding of molecular characteristics and its association with prognosis in Chinese CCA. We enrolled 41 Chinese patients with CCA, including 6 intrahepatic CCA (iCCA), 14 perihilar CCA (pCCA), and 21 distal CCA (dCCA) cases, all patients underwent radical operations and tumor samples underwent next-generation sequencing (NGS) by Foundation One Dx, which analyzed 324 genes. The patients' genetic characteristics, clinical management, and prognosis were analyzed. The most mutated genes were TP53 (68%, 28/41), CDKN2A (37%, 15/41), and SMAD4 (29%, 12/41). The genetic mutations in dCCA, pCCA, and iCCA were significantly different. For example, NOTCH3 mutations were not found in dCCA. The gene mutations of AXL were specifically associated with lymph node metastasis in patients with CCA, whereas gene mutations of SMAD4 were specifically associated with lymphovascular invasion. Furthermore, mutations in APC, DAXX, FANCA, LTK, MAP2K4, and NOTCH1 were associated with a poor prognosis (P < 0.05). This study provides an overview of genetic alterations in Chinese patients with CCA, which will provide novel potential biomarkers for the diagnosis of CCA and may guide targeted therapeutic strategies for Chinese patients with CCA.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias dos Ductos Biliares/genética , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Biomarcadores , Ductos Biliares Intra-Hepáticos/patologia , China
5.
Clin Exp Pharmacol Physiol ; 51(1): 17-29, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37749921

RESUMO

Liver fibrosis is a chronic liver lesion caused by excessive deposition of the extracellular matrix after liver damage, resulting in fibrous scarring of liver tissue. The progression of liver fibrosis is partially influenced by the gut microbiota. Chitosan can play a therapeutic role in liver fibrosis by regulating the gut microbiota based on the 'gut-liver axis' theory. Salvianolic acid B can inhibit the development of liver fibrosis by inhibiting the activation of hepatic stellate cells and reducing the production of extracellular matrix. In this study, the therapeutic effect of chitosan in combination with salvianolic acid B on liver fibrosis was investigated in a mouse liver fibrosis model. The results showed that the combination of chitosan and salvianolic acid B was better than the drug alone, improving AST/ALT levels and reducing the expression of α-SAM, COL I, IL-6 and other related genes. It improved the structure of gut microbiota and increased the abundance of beneficial bacteria such as Lactobacillus. The above results could provide new ideas for the clinical treatment of liver fibrosis.


Assuntos
Benzofuranos , Quitosana , Camundongos , Animais , Quitosana/farmacologia , Quitosana/metabolismo , Quitosana/uso terapêutico , Cirrose Hepática/patologia , Fígado/metabolismo , Benzofuranos/farmacologia , Benzofuranos/uso terapêutico , Benzofuranos/metabolismo , Modelos Animais de Doenças
6.
Yeast ; 39(6-7): 401-411, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35711110

RESUMO

Autophagy-related gene (Atg) proteins are key players in autophagy. Some proteins that function in vesicle trafficking and lipid metabolism are also involved in autophagy. The SPO14 in yeast, which encodes phospholipase D (PLD), is involved in membrane trafficking and plays a vital role in sporulation during meiosis. Crosstalk has been identified between autophagy and sporulation. Although the PLD is required for macroautophagy in mammals, its role in yeast macroautophagy remains unclear. We observed that Spo14 is not required for macroautophagy in yeast and that it is dispensable for Atg8 lipidation, which plays an important role in phagophore extension. Our results also revealed that green fluorescent protein (GFP)-Atg8 degradation is not completely blocked in atg1Δ/atg1Δ cells under sporulation condition. Therefore, Spo14 is not required for macroautophagy in yeast.


Assuntos
Autofagia , Fosfolipase D , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Animais , Autofagia/genética , Autofagia/fisiologia , Família da Proteína 8 Relacionada à Autofagia/genética , Família da Proteína 8 Relacionada à Autofagia/metabolismo , Macroautofagia , Mamíferos , Meiose , Fosfolipase D/genética , Fosfolipase D/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
7.
Gynecol Endocrinol ; 38(4): 324-328, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35188053

RESUMO

OBJECTIVE: To explore the influence of the one-day diabetes mellitus (DM) clinic management model on blood glucose control and prognosis in patients with gestational diabetes mellitus (GDM). METHODS: A total of 930 patients diagnosed with GDM by oral glucose tolerance test screening at 24-28 weeks of gestation were selected from those who underwent outpatient prenatal checkups at our hospital and were randomly divided into one-day DM clinic group (n = 509) and control group (n = 421). A one-day DM clinic intervention was conducted in the one-day DM clinic group, and individualized dietary interventions and exercise instruction were given in the control group. RESULTS: The compliance rates of fasting blood glucose and two-hour postprandial blood glucose (2-h PPBG) were higher in the one-day DM clinic group than in the control group (p < .05). The compliance rates of the oral glucose tolerance test and insulin release test were higher in the one-day DM clinic group than in the control group (p < .05). There existed statistically significant differences in fasting blood glucose before delivery, together with the difference between fasting blood glucose at enrollment and before delivery and the difference between glycated hemoglobin at enrollment and before delivery (p < .05). CONCLUSION: The one-day diabetes mellitus clinic management model is more conducive to blood glucose control in patients with GDM and more conducive to the recovery of blood glucose and islet function in patients with GDM after delivery and to reduce the occurrence of adverse pregnancy outcomes.


Assuntos
Diabetes Gestacional , Glicemia , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/terapia , Feminino , Teste de Tolerância a Glucose , Controle Glicêmico , Humanos , Gravidez , Prognóstico
8.
Int J Mol Sci ; 23(17)2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36076954

RESUMO

Phosphatidylinositol 3-phosphate (PI(3)P) serves important functions in endocytosis, phagocytosis, and autophagy. PI(3)P is generated by Vps34 of the class III phosphatidylinositol 3-kinase (PI3K) complex. The Vps34-PI3K complex can be divided into Vps34-PI3K class II (containing Vps38, endosomal) and Vps34-PI3K class I (containing Atg14, autophagosomal). Most PI(3)Ps are associated with endosomal membranes. In yeast, the endosomal localization of Vps34 and PI(3)P is tightly regulated by Vps21-module proteins. At yeast phagophore assembly site (PAS) or mammalian omegasomes, PI(3)P binds to WD-repeat protein interacting with phosphoinositide (WIPI) proteins to further recruit two conjugation systems, Atg5-Atg12·Atg16 and Atg8-PE (LC3-II), to initiate autophagy. However, the spatiotemporal regulation of PI(3)P during autophagy remains obscure. Therefore, in this study, we determined the effect of Vps21 on localization and interactions of Vps8, Vps34, Atg21, Atg8, and Atg16 upon autophagy induction. The results showed that Vps21 was required for successive colocalizations and interactions of Vps8-Vps34 and Vps34-Atg21 on endosomes, and Atg21-Atg8/Atg16 on the PAS. In addition to disrupted localization of the PI3K complex II subunits Vps34 and Vps38 on endosomes, the localization of the PI3K complex I subunits Vps34 and Atg14, as well as Atg21, was partly disrupted from the PAS in vps21∆ cells. The impaired PI3K-PI(3)P-Atg21-Atg16 axis in vps21∆ cells might delay autophagy, which is consistent with the delay of early autophagy when Atg21 was absent. This study provides the first insight into the upstream sequential regulation of the PI3K-PI(3)P-Atg21-Atg16 module by Vps21 in autophagy.


Assuntos
Autofagossomos , Proteínas de Saccharomyces cerevisiae , Animais , Autofagossomos/metabolismo , Autofagia , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Endopeptidases/metabolismo , Mamíferos/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatos de Fosfatidilinositol , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo
9.
BMC Musculoskelet Disord ; 22(1): 383, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33894744

RESUMO

BACKGROUND: Symptomatic pulmonary embolism (PE) after knee arthroscopy is extremely rare. If the embolism is not treated promptly, the patient may die. Bilateral pulmonary embolism with associated pulmonary infarct without concomitant deep vein thrombosis has never been reported following routine knee arthroscopy. CASE PRESENTATION: A 50-year-old female patient with no other risk factors other than hypertension, obesity, varicose veins in the ipsilateral lower extremities and elevated triglyceride (TG) presented to our ward. She had experienced sudden chest tightness, polypnea and fainting after going to the bathroom the morning of the second postoperative day and received emergency medical attention. Colour ultrasonography of the extremities showed no deep vein thrombosis. Lung computed tomography angiography (CTA) showed multiple embolisms scattered in both pulmonary artery branches. Thus, emergency interventional thrombolysis therapy was performed, followed by postoperative symptomatic treatment with drugs with thrombolytic, anticoagulant and protective activities. One week later, lung CTA showed a significant improvement in the PEs compared with those in the previous examination. Since the aetiology of PE and no obvious symptoms were discerned, the patient was discharged. CONCLUSION: Although knee arthroscopy is a minimally invasive and quick procedure, the risk factors for PE in the perioperative period should be considered and fully evaluated to enhance PE detection. Moreover, a timely diagnosis and effective treatment are important measures to prevent and cure PE after knee arthroscopy. Finally, clear guidelines regarding VTE thromboprophylaxis following knee arthroscopy in patients with a low risk of VTE development are needed.


Assuntos
Embolia Pulmonar , Tromboembolia Venosa , Trombose Venosa , Anticoagulantes , Artroscopia/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/etiologia , Fatores de Risco , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia
10.
Biochem Biophys Res Commun ; 521(3): 584-589, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31677790

RESUMO

A failure of bone marrow mesenchymal stem cells (BM-MSCs) to adhere to hematopoietic cells is an essential cause of the progression of chronic myelogenous leukemia and is also a cause of failure of bone marrow (BM) transplantation, but the exact mechanisms of this have not been fully elucidated. Recent studies have indicated that microRNAs (miRNAs) are contained in leukemia-derived exosomes and are involved in modulating the BM microenvironment. In this study, we found that K562 cell-derived exosomes transfer miR-711 to BM-MSCs and suppress the adhesive function of BM-MSCs. Using qRT-PCR, we also confirmed a significantly higher level of miR-711 in exosomes derived from K562 cells than in exosomes derived from parental cells. The BM-MSCs co-cultured with exosomes derived from K562 cells showed a lower adhesion rate than did controls. We further demonstrated that exosomal transfer of miR-711 induced decreased adhesive abilities by inhibiting expression of adhesion molecule CD44 in BM-MSCs. In conclusion, our study reveals that K562 cell-derived exosomal miR-711 can be transferred to BM-MSCs and weaken adhesive abilities by silencing the expression of the adhesion molecule CD44.


Assuntos
Adesão Celular , Exossomos/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Células Cultivadas , Regulação para Baixo , Exossomos/genética , Exossomos/patologia , Humanos , Receptores de Hialuronatos/genética , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/patologia , MicroRNAs/genética
11.
Chemistry ; 23(49): 11757-11760, 2017 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-28726297

RESUMO

An atom- and step-economic access to an array of unprotected meta-substituted primary anilines was disclosed using the Semmler-Wolff reaction, promoted by molecular iodine. Therein, noble metal catalysts and inert atmosphere are unnecessary while the forcing reaction conditions and the lengthy synthesis can be avoided. The synthetic utility of this approach is evident in the de novo syntheses of three bioactive molecules with good total yields.

12.
Org Biomol Chem ; 15(15): 3165-3169, 2017 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-28345712

RESUMO

A new protocol is described for the conversion of heteroarene N-oxides to heteroarylphosphonates through in situ activation with bromotrichloromethane. The N-oxides of isoquinoline, quinoline, quinoxaline and 1,10-phenanthroline were fast transformed into the corresponding heteroarylphosphonates in up to 92% yield under mild conditions in the absence of solvent and metal catalysts. The good functional group tolerance, low cost, feasibility of scale up, and wide availability of reagents make this method a prominent complement to the Hirao coupling.

13.
Water Sci Technol ; 75(12): 2800-2810, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28659520

RESUMO

MIL-68(Al), a powdered aluminum-based metal organic framework (MOF), was synthesized and used to explore its adsorption behavior toward methyl orange (MO). The adsorption isotherm, thermodynamics, kinetics, and some key operating factors as well as changes in the material's structure were investigated. The adsorption isotherm conformed to the Langmuir isotherm model and the maximum equilibrium adsorption capacity was 341.30 mg g-1. Thermodynamic data demonstrated that the adsorption process was spontaneous, endothermic and showed positive entropy. For kinetics, the process of MO adsorption onto MIL-68(Al) was more suitably described by a pseudo-second-order model. Electrostatic and hydrogen-bonding interactions contributed to dye adsorption, with electrostatic interactions considered to be the principal binding force between adsorbent and adsorbate. Furthermore, MIL-68(Al) maintained a stable structure after adsorption. From these results, MIL-68(Al) was suggested here to be a stable MOF adsorbent for removing MO from aqueous solution.


Assuntos
Alumínio , Compostos Azo , Estruturas Metalorgânicas , Modelos Químicos , Poluentes Químicos da Água , Adsorção , Alumínio/química , Compostos Azo/química , Concentração de Íons de Hidrogênio , Cinética , Termodinâmica , Poluentes Químicos da Água/química
14.
Kidney Blood Press Res ; 41(5): 570-581, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27554668

RESUMO

BACKGROUND/AIMS: Dietary patterns, which represent whole-diet and a complex integration of food and nutrient, have been reported to play an important role in the development of hypertension. However, the results have yielded conflicting findings. Herein, we performed this meta-analysis to evaluate the associations between different dietary patterns and the likelihood of hypertension. METHODS: MEDLINE and EBSCO were searched to identify relevant articles published until the end of March 2016. A random-effects model was used to account for possible heterogeneity between studies.A total of twenty-seven studies met the inclusion criteria and were included in this meta-analysis. RESULTS: There was evidence of a decreased likelihood for hypertension in the highest compared with the lowest categories of healthy pattern (odds ratio (OR)=0.81; 95% confidence interval(CI): 0.67-0.97; P=0.02). An increased likelihood of hypertension was shown for the highest compared with the lowest category of heavy drinking pattern (OR=1.62; 95% CI: 1.16-2.26; P=0.004), whereas no statistically significant association with western-style and light-moderate drinking pattern were observed(OR=1.04, 95% CI: 0.83-1.31; OR=1.20, 95% CI:0.94- 1.53; P>0.05). CONCLUSIONS: Our results of this systematic review and meta-analysis suggest that dietary pattern may be associated with the likelihood of hypertension.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Dieta/efeitos adversos , Hipertensão/etiologia , Humanos
15.
Clin Cosmet Investig Dermatol ; 17: 103-110, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38234694

RESUMO

Necrotizing fasciitis is a rare, severe, rapidly progressing disease with a high mortality rate. We report a case of a 72-year female with erythematous pemphigus who developed erythema, swelling and ulceration on right vulva, groin, and thigh. The early clinical manifestations of the patient were nonspecific and easily misdiagnosed as cellulitis. However, upon the occurrence of ulceration and necrosis, deep fungal infection, pyoderma gangrenosum or lymphoproliferative disorders were considered. The pathology suggested IgG4-related diseases, plasmacytoma et al. But at last, surgical exploration and postoperative pathology confirmed the diagnosis of necrotizing fasciitis. The patient recovered after multiple aggressive surgical debridement procedures and antibiotic therapy and the patient has been followed up for 2 years without recurrence. Clinicians should be vigilant about the possibility of necrotizing fasciitis in patients with erythema, pain, rapid ulceration of skin and soft tissue, particularly in immunocompromised individuals with long-term use of immunosuppressive agents. It is crucial for saving life by early multi-disciplinary consultation, prompt diagnosis, and aggressive treatment.

16.
Zhong Yao Cai ; 36(8): 1297-300, 2013 Aug.
Artigo em Zh | MEDLINE | ID: mdl-24558830

RESUMO

OBJECTIVE: To observe the pro-angiogenic effect of four Chinese medicines and three herbal prescriptions, screen the effective components from them. METHODS: Chicken chorioallantoic membrane (CAM) model was employed to observe the pro-angiogenic activities of Angelicae Sinensis Radix, Salviae Miltiorrhizae Radix, Notoginseng Radix, Astragali Radix, Xuefuzhuyu decoction, Dangguibuxue decoction and Taohongsiwu decoction, all of them were claimed to promote angiogenesis. The effective components were screened from the extracts. RESULTS: Compared with negative control group, the blood vessel densities in Angelicae Sinensis Radix and Notoginseng Radix groups were not increased significantly (P > 0.05). However, blood vessel densities in Astragali Radix group, Salviae Miltiorrhizae Radix group, Xuefuzhuyu decoction group, Dangguibuxue decoction group and Taohongsiwu decoction group were notably enhanced (P < 0.05). Dangguibuxue decoction showed a more than 90% of increase in blood vessel densities as compared with the negative control group (P < 0.01), and components contained ferulic acid and astragaloside from Dangguibuxue decoction displayed significantly pro-angiogenic effect (P < 0.05). CONCLUSION: Dangguibuxue decoction and its extract, components contained ferulic acid and astragaloside, can improve angiogenesis in CAM model significantly.


Assuntos
Membrana Corioalantoide/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicina Herbária , Indutores da Angiogênese , Animais , Astrágalo , Galinhas , Membrana Corioalantoide/irrigação sanguínea , Ácidos Cumáricos , Humanos
17.
Front Oncol ; 13: 1173275, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37546405

RESUMO

Introduction: Sarcomas are classified into two types, bone sarcoma and soft tissue sarcoma (STS), which account for approximately 1% of adult solid malignancies and 20% of pediatric solid malignancies. There exist more than 50 subtypes within the two types of sarcoma. Each subtype is highly diverse and characterized by significant variations in morphology and phenotypes. Understanding tumor molecular genetics is helpful in improving the diagnostic accuracy of tumors that have been difficult to classify based on morphology alone or that have overlapping morphological features. The different molecular characteristics of bone sarcoma and STS in China remain poorly understood. Therefore, this study aimed to analyze genomic landscapes and actionable genomic alterations (GAs) as well as tumor mutational burden (TMB), microsatellite instability (MSI), and programmed death ligand-1 (PD-L1) expression among Chinese individuals diagnosed with primary bone sarcomas and STS. Methods: This retrospective study included 145 patients with primary bone sarcomas (n = 75) and STS (n = 70), who were categorized based on the 2020 World Health Organization classification system. Results: Patients diagnosed with bone sarcomas were significantly younger than those diagnosed with STS (p < 0.01). The top 10 frequently altered genes in bone sarcoma and STS were TP53, CDKN2A, CDKN2B, MAP3K1, LRP1B, MDM2, RB1, PTEN, MYC, and CDK4.The EWSR1 fusions exhibited statistically significant differences (p < 0.01) between primary bone sarcoma and STS in terms of their altered genes. Based on the actionable genes defined by OncoKB, actionable GAs was found in 30.7% (23/75) of the patients with bone sarcomas and 35.7% (25/70) of those with STS. There were 4.0% (3/75) patients with bone sarcoma and 4.3% (3/70) patients with STS exhibited high tumor mutational burden (TMB-H) (TMB ≥ 10). There was only one patient with STS exhibited MSI-L, while the remaining cases were microsatellite stable. The positive rate of PD-L1 expression was slightly higher in STS (35.2%) than in bone sarcoma (33.3%), however, this difference did not reach statistical significance. The expression of PD-L1 in STS patients was associated with a poorer prognosis (p = 0.007). Patients with STS had a better prognosis than those with bone sarcoma, but the observed difference did not attain statistical significance (p = 0.21). Amplification of MET and MYC genes were negatively correlated with clinical prognosis in bone tumors (p<0.01). Discussion: In conclusion, bone sarcoma and STS have significantly different clinical and molecular characteristics, suggesting that it is vital to diagnose accurately for clinical treatment. Additionally, comprehensive genetic landscape can provide novel treatment perspectives for primary bone sarcoma and STS. Taking TMB, MSI, PD-L1 expression, and OncoKB definition together into consideration, there are still many patients who have the potential to respond to targeted therapy or immunotherapy.

18.
Front Oncol ; 12: 966020, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36033485

RESUMO

Dermatofibrosarcoma protuberans (DFSP) is a kind of soft tissue sarcoma, mostly occurs in the trunk, followed by proximal extremities and head and neck. Surgical resection is the most important treatment for DFSP, but the local recurrence rate of DFSP is high. Except reported specific chromosomal tran7slocations occurred in DFSP, the association between DNA repair gene mutations and DFSP still unknown. In this report we found a 19-year-old boy with DFSP carries a novel heterozygous germline ERCC2 mutation, which belongs to the nucleotide excision repair (NER) pathway and genetic defects in ERCC2 may contribute to the cancer susceptibility xeroderma pigmentosum (XP), Cocaine syndrome (CS), and trichothiodystrophy (TTD). Different mutations of the ERCC2 gene can lead to diverse diseases, but there are no targeted therapies. In summary, our results enlarged the mutation spectrum of the DFSP patients. It also provides new insights into genetic counseling and targeted therapeutic strategies for patients with DFSP.

19.
Front Oncol ; 12: 826938, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251994

RESUMO

We presented a 67-year-old nonsmoking female lung adenocarcinoma patient with novel epidermal growth factor receptor (EGFR) A289G/F287_G288insHA cis mutations who responded positively to sintilimab combined with regorafenib and albumin paclitaxel, and sequential treatment of icotinib. Gene mutations in patients were detected by next-generation sequencing (NGS) technology, and changes in gene mutations before and after treatments were observed by ctDNA monitoring. We observed the efficacy of the patient through chest computed tomography (CT) imaging and carcinoembryonic antigen (CEA) level and found that the patient benefited from immunotherapy in combination with antiangiogenesis and chemotherapy for more than 1 year, CEA levels initially fell sharply and then rebounded during the treatment period. After changing to EGFR-TKI therapy, the CEA level of the patient does not only decreased sharply at the initial stage of treatment but also rebounded and increased at the later stage of treatment. The patient was tested for genetic mutations after 4 months of sequential EGFR-TKI therapy and was found to have lost all previous EGFR mutations, which may be the cause of resistance to targeted drug icotinib. We believe that our findings have enriched the EGFR mutation spectrum in NSCLC and highlighted the possible choice for patients harboring this mutation by immunotherapy combined with chemotherapy and antivascular therapy, and EGFR-TKI-targeted therapy.

20.
Front Oncol ; 12: 764923, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35356200

RESUMO

More than half of new cases of hepatocellular carcinoma (HCC) and associated deaths occurring annually worldwide are recorded in China. Chinese patients with HCC exhibit special characteristics in terms of etiology, leading to differences in prognosis versus Western patients. In recent years, several angiogenesis inhibitors were approved, and immune checkpoint blockers (ICBs) were recommended as second-line therapy for advanced HCC. In addition, the recent success of a combination of atezolizumab with bevacizumab signals resulted in an essential change in the first-line treatment of HCC. We investigated the characteristics of patients with HCC in China and summarized the rapidly emerging relevant clinical data, which relate to the prospects and challenges associated with the use of ICBs in this setting. We further evaluated the efficacy of ICBs in Chinese patients with HCC based on data obtained from global trials, and discussed possible factors influencing the effectiveness of ICBs in patients with HCC in China. Immunotherapy offers new options for the treatment of advanced HCC, though responses varied between patients. Currently, there is a need to discover specific biomarkers for the accurate identification of patients who would more likely benefit from immunotherapy. Furthermore, investigation of patient characteristics in different countries is necessary to provide a clinical practice basis and reference value for the diagnosis and treatment of HCC.

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