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1.
Front Immunol ; 13: 939344, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35844572

RESUMO

Background: DCBLD1 is highly expressed in several kinds of cancer and plays a potential prognostic factor. However, the prognostic value and immune infiltration in head and neck squamous cell carcinoma remain unclear and need further research. Materials and Methods: DCBLD1 expression and clinical information were obtained from the Cancer Genome Atlas (TCGA) database. The mRNA level in cell lines (SCC25 and CAL27) and gingival fibroblasts were detected using quantitative PCR. Cox regression analysis was used to evaluate the prognostic values of DCBLD1 and clinical data in HNSCC. A nomogram was also established to predict the impact of DCBLD1 on prognosis based on Cox multivariate results. The methylation level of DCBLD1 in HNSC and its prognosis were analyzed in UALACN and MethSurv. Finally, the potential biological functions of DCBLD1 were investigated using gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA). Results: The mRNA and protein expression levels of DCBLD1 were highly expressed in HNSCC tissue and cell lines. The Cox analyses demonstrate that highly expressed DCBLD1 is an independent prognosis marker (p < 0.05). ROC curve analysis showed the performance of DCBLD1 (area under the ROC curve: 0.948, sensitivity: 93.2%, specificity: 84.7%). The methylation was increased in HNSCC patients compared with normal subjects (p < 0.05) and was associated with poor prognosis at sites cg27642470 and cg21104965. Additionally, DCBLD1 expression is poorly associated with immune cell infiltration and immunological checkpoints PD-L1 and TIM-3. Conclusion: In head and neck squamous cell carcinoma, DCBLD1 is overexpressed, associated with poor patient prognosis. The detailed underlying mechanism merits further research.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço , Neoplasias de Cabeça e Pescoço/genética , Humanos , Prognóstico , RNA Mensageiro , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
2.
J Phys Condens Matter ; 34(35)2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35709706

RESUMO

Ion implantation has been widely used in biomaterials, alloys, and semiconductors modification. Basing on the studying of trapping states in the equilibrium state, we investigate the ultrafast carrier dynamics of SnSe/TiO2and SnSe/Li/TiO2heterojunctions under Li+implantation by the real-time time-dependent density functional theory. The special type II band alignment and Li+interfacial states in SnSe/TiO2heterojunction effectively facilitate the exciton dissociation in a benign process and suppresses the interfacial nonradiative recombination. By monitoring the instantaneous ion-solid interaction energy, electronic stropping power and the excitation electron evolution, we find that atomic reconstruction introduced by the Li inserting layer changes the charge density and crystal potential field in the injection channel, and thus weakens the violent oscillation force and electron excitation on the Ti and O atoms. There exists a weaker and shorter charge excitation at the interface for SnSe/Li/TiO2implantation system, which suggests that the Li ion layer weakens the e-ph coupling between the interface electrons and the moving ion. Meanwhile, only the hot electrons are produced in the interface region, reducing the probability of carrier recombination. These results provide an understanding for the behavior of carriers in SnSe based heterojunctions and the electron-phonon coupling mechanism at the phase/grain boundary under ion implantation.

3.
J Cancer Res Ther ; 18(2): 587-589, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35645132

RESUMO

In non-small cell lung cancer (NSCLC), about 15% of epidermal growth factor receptor (EGFR) mutations are rare. Herein, we report a 39-year-old male with stage IV NSCLC with a rare EGFR M277E mutation and high PD-L1 expression. The patient first underwent gamma-knife treatment for brain metastasis; then, he was started on 40 mg afatinib daily in combination with two cycles of chemotherapy. The clinical effect was stable disease (SD), so the patient underwent intensity-modulated radiation therapy guided by cone beam computed tomography on the lesion in the lower lobe of the right lung. A combination therapy with afatinib and chemotherapy was employed as the first-line therapy. A palliative radiotherapy to the primary pulmonary tumor was added, resulting in a significant response based on the next computerized tomography (CT) scan. To date, this is the first presented case of NSCLC with EGFR p.M277E mutation and its corresponding clinical outcome to combination therapies.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/radioterapia , Adulto , Afatinib/uso terapêutico , Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Masculino , Mutação
4.
Front Pharmacol ; 13: 714408, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35677433

RESUMO

Lung cancer is the most common solid tumor in the worldwide. Targeted therapy and immunotherapy are important treatment options in advanced non-small cell lung cancer (NSCLC). The association of PTEN mutation and tumor immunotherapy is less established for patients with NSCLC. We present the case of an Asian woman diagnosed with stage IV lung adenocarcinoma harboring an ERBB2 mutation. She received Nivolumab treatment when her disease progresses after previous chemotherapy and Afatinib treatment. However, the patient did not response to Nivolumab. PTEN mutation was detected by next-generation sequencing (NGS) after treatment with Nivolumab. PTEN, a secondary mutation, may be served as a biomarker of resistance to anti-PD-1 immunotherapy in lung adenocarcinoma. The relationship between PTEN mutation and immunotherapy is complex and needs further study.

5.
Exp Cell Res ; 418(1): 113249, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35691378

RESUMO

The well-documented tumor suppressor p53 is also a major stress response factor for its diverse regulation on cellular energetics. However, the effect of p53 on mitochondrial biogenesis, which plays a predominant role in response to the elevated energy demands, appears to be pleiotropic in various conditions and has not reached agreement. Mitochondrial ribosomal protein L12 (MRPL12), reported as a bi-functional protein for its roles in both mitochondrial ribosomes and transcriptional complexes, is a core regulatory component in mitochondrial biogenesis. Here we proved that MRPL12 is transcriptionally regulated by p53. Furthermore, the p53/MRPL12 regulation of mitochondria is part of the signaling pathway that maintains the basal mitochondrial content and positively coordinates the mitochondrial biogenesis and oxidative phosphorylation (OXPHOS) in response to metabolic perturbation. Since p53 serves as the'Guardian of the Genome', our findings may revealed a new mechanism underlying the conditions when more ATP is warranted to maintain the genome integrity and cell survival. Therefore the pharmacological intervention or metabolic modulation (e.g., through fasting or exercise) of the p53/MRPL12 pathway promises to be a therapeutic approach that can safeguard health.


Assuntos
Biogênese de Organelas , Proteína Supressora de Tumor p53 , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
6.
BMC Surg ; 22(1): 235, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35725426

RESUMO

OBJECTIVE: It has been reported that papillary thyroid carcinoma (PTC) patients with lymph node metastasis (LNM) are largely associated with adverse outcomes. The present study aimed to assess the correlation between the number of metastatic lymph nodes (NMLNs) and clinical prognosis in patients with PTC. METHODS: We retrospectively reviewed the medical records of patients with PTC who underwent initial thyroid cancer surgery in Renmin Hospital of Wuhan University between 2017 and 2019. A total of 694 patients with PTC and cervical lymph node dissection as well as a total checked number of lymph nodes ≥ 5 were involved in this study. The clinicopathological characteristics of patients were compared according to NMLNs, the number of central cervical lymph nodes (CLNs) and the number of lateral lymph nodes (LLNs). RESULTS: NMLNs > 5, CLNs > 5 and LLNs > 5 were 222 (32.0%), 159 (24.3%) and 70 (10.1%) seen in the analyzed samples, respectively. Young patients, patients with larger tumor diameter, bilaterality, multifocality and gross extrathyroidal extension (ETE) were more inclined to NMLNs > 5, CLNs > 5 and LLNs > 5 (P < 0.05). It was found that the recurrence-free survival among pN1 patients was significantly discrepant between different groups (NMLNs ≤ 5/5: P = 0.001; LLNs ≤ 5/5: P < 0.001). In multivariate logistic regression analysis, patients aged < 55 years (OR = 1.917), primary tumor size > 10 mm (OR = 2.131), bilaterality (OR = 1.889) and tumor gross ETE (OR = 2.759) were independent predictors for high prevalence of total NMLNs > 5 (P < 0.05). Specially, patients aged < 55 years (OR = 2.864), primary tumor size > 10 mm (OR = 2.006), and tumor gross ETE (OR = 2.520) were independent predictors for high prevalence of CLNs > 5 (P < 0.01); Bilaterality (OR = 2.119), CLNs > 5 (OR = 6.733) and tumor gross ETE (OR = 4.737) were independent predictors for high prevalence of LLNs > 5 (P < 0.05). CONCLUSIONS: In conclusion, it is evident that NMLNs is related to the invasive clinicopathological features and adverse outcome of patients with PTC which should be correctly evaluated to provide an appropriate guidance for reasonable treatment and careful follow-up.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , China , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
7.
Sci Rep ; 12(1): 9486, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35676514

RESUMO

Mud shale, used in drilling engineering, is prone to hydration and expansion, resulting in creep deformation that leads to wellbore shrinkage and pipe sticking incidents. Studying the creep characteristics of mud shale is significant for designing a reasonable well structure and determining the lower limit of drilling fluid density. The influence of moisture content on rock strength and creep mechanical properties were studied using water absorption, uniaxial compression, and creep tests. Test results show that with an increase in the moisture content, the mud shale was damaged and softened; moreover, the elastic modulus decreased with increase in moisture content. Under the same load level, the instantaneous strain increased with increasing moisture content. Under different loading stresses, the creep of the rock had nonlinear characteristics, which could be divided into three different creep stages: attenuation, second, and accelerated creep. A new improved creep model based on the Nishihara model was established to describe the accelerated creep characteristics of mud shale under different moisture contents. The ageing degradation and water-bearing weakening effects were introduced. The Levenberg-Marquardt nonlinear least-squares method was applied to invert the creep parameters. The results show that the simulated creep curves, generated using the new creep model, conform to the experimental ones. The relationship between the drilling fluid density and wellbore shrinkage ratio can be defined using this model; it provides a reference for reasonably determining the drilling fluid density.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35529915

RESUMO

Objective: To examine the clinical efficacy of budesonide/glycopyrronium bromide/formoterol (Breztri Aerosphere) as an adjunct to acute respiratory distress syndrome (ARDS). Methods: A prospective study enrolled 120 patients with pulmonary endogenous ARDS admitted to the Department of Critical Care Medicine at the Fourth Hospital of Baotou from January 2017 to January 2020, and all enrollments were assigned (1 : 1) to receive conventional treatment (control group) or Breztri Aerosphere (study group). Results: Breztri Aerosphere was associated with a significantly higher total efficacy versus conventional treatment. Breztri Aerosphere resulted in significantly lower acute physiology and chronic health evaluation scoring system (APACHE II) scores and Murray lung injury scores versus conventional treatment. Both groups saw an increase in the partial pressure of carbon dioxide (PCO2), partial pressure of oxygen (PO2), and oxygen saturation (SaO2) after treatment, with higher levels seen in patients given Breztri Aerosphere. After treatment, systemic vascular resistance (SVR) in both groups rose markedly, with greater elevation witnessed in the study group. The patients given Breztri Aerosphere showed significantly lower levels of pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (MAPA), pulmonary artery wedge pressure (PAWP), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and procalcitonin (PCT) versus those receiving conventional treatment. The patients experienced shorter mechanical ventilation time and intensive care unit (ICU) time after treatment of Breztri Aerosphere versus conventional treatment. Conclusion: Adjuvant therapy with Breztri Aerosphere in ARDS can significantly lower APACHE II scores and Murray lung injury scores, improve blood gas indexes and pulmonary circulation function indexes, and shorten mechanical ventilation time and ICU time, which may be attributed to its improvement of organism inflammation status and reduction of inflammatory factors.

9.
Front Pharmacol ; 13: 870699, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35592411

RESUMO

Background: Liquiritin (LQ) is one of the main flavonoids extracted from the roots of Glycyrrhiza spp., which are widely used in traditional Chinese medicine. Studies in both cellular and animal disease models have shown that LQ attenuates or prevents oxidative stress, inflammation, and apoptosis. However, the potential therapeutic effects of LQ on pressure overload-induced cardiac hypertrophy have not been so far explored. Therefore, we investigated the cardioprotective role of LQ and its underlying mechanisms in the aortic banding (AB)-induced cardiac hypertrophy mouse model. Methods and Results: Starting 3 days after AB surgery, LQ (80 mg/kg/day) was administered daily over 4 weeks. Echocardiography and pressure-volume loop analysis indicated that LQ treatment markedly improved hypertrophy-related cardiac dysfunction. Moreover, hematoxylin and eosin, picrosirius red, and TUNEL staining showed that LQ significantly inhibited cardiomyocyte hypertrophy, interstitial fibrosis, and apoptosis. Western blot assays further showed that LQ activated LKB1/AMPKα2/ACC signaling and inhibited mTORC1 phosphorylation in cardiomyocytes. Notably, LQ treatment failed to prevent cardiac dysfunction, hypertrophy, and fibrosis in AMPKα2 knockout (AMPKα2-/-) mice. However, LQ still induced LKB1 phosphorylation in AMPKα2-/- mouse hearts. In vitro experiments further demonstrated that LQ inhibited Ang II-induced hypertrophy in neonatal rat cardiomyocytes (NRCMs) by increasing cAMP levels and PKA activity. Supporting the central involvement of the cAMP/PKA/LKB1/AMPKα2 signaling pathway in the cardioprotective effects of LQ, inhibition of Ang II-induced hypertrophy and induction of LKB1 and AMPKα phosphorylation were no longer observed after inhibiting PKA activity. Conclusion: This study revealed that LQ alleviates pressure overload-induced cardiac hypertrophy in vivo and inhibits Ang II-induced cardiomyocyte hypertrophy in vitro via activating cAMP/PKA/LKB1/AMPKα2 signaling. These findings suggest that LQ might be a valuable adjunct to therapeutic approaches for treating pathological cardiac remodeling.

10.
Cell Commun Signal ; 20(1): 43, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361231

RESUMO

As an important mechanism to maintain cellular homeostasis, autophagy exerts critical functions via degrading misfolded proteins and damaged organelles. Recent years, alternative autophagy, a new type of autophagy has been revealed, which shares similar morphology with canonical autophagy but is independent of Atg5/Atg7. Investigations on different diseases showed the pivotal role of alternative autophagy during their physio-pathological processes, including heart diseases, neurodegenerative diseases, oncogenesis, inflammatory bowel disease (IBD), and bacterial infection. However, the studies are limited and the precise roles and mechanisms of alternative autophagy are far from clear. It is necessary to review current research on alternative autophagy and get some hint in order to provide new insight for further study. Video Abstract.


Assuntos
Autofagia , Doenças Neurodegenerativas , Homeostase , Humanos , Proteínas
11.
J Clin Anesth ; 79: 110788, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35429906

RESUMO

STUDY OBJECTIVE: Emergence delirium is a common complication in preschool children after general anesthesia and may result in undesirable complications. This study aimed to determine whether breathing training after watching an informative video during the pre-operative visit could reduce the incidence of emergence delirium in preschool children after otorhinolaryngologic surgery under general anesthesia. DESIGN: A single-center, double-blinded, randomized controlled trial. SETTING: Perioperative care. PATIENTS: A total of 170 children undergoing otorhinolaryngologic surgery, aged 3-7 years, ASA physical status I or II were involved. INTERVENTIONS: Patients were randomized to receive breathing training during the pre-operative visit (Training group) or to receive pre-operative visit only (Control group) the day before surgery. MEASUREMENTS: Emergence delirium was measured by the Pediatric Anesthesia Emergence Delirium score during the anesthesia recovery time. Data regarding extubation time and post-anesthesia care unit stay time were collected. MAIN RESULTS: Children who received breathing training during the pre-operative visit had a significantly lower incidence of emergence delirium than those who only underwent the pre-operative visit (10.4% vs. 35.1%, P < 0.001). The awakening time score and the maximum score in the post-anesthesia care unit were significantly lower in the training group compared with the control group [4.4 ± 3.4 vs. 6.9 ± 4.2, P < 0.001 and 5.0 (5.0) vs 7.0 (7.0), P = 0.001, respectively]. We found no differences in the extubation time and post-anesthesia care unit stay time between groups. CONCLUSIONS: We concluded that breathing training based on video learning during the pre-operative visit in preschool children undergoing otorhinolaryngologic surgery could significantly decrease the incidence of emergence delirium. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Reference number: ChiCTR1900026162); registered on September 24, 2019.


Assuntos
Delírio do Despertar , Período de Recuperação da Anestesia , Anestesia Geral/efeitos adversos , Criança , Pré-Escolar , Delírio do Despertar/epidemiologia , Delírio do Despertar/etiologia , Delírio do Despertar/prevenção & controle , Humanos , Incidência , Estudos Prospectivos
12.
Artigo em Inglês | MEDLINE | ID: mdl-35329024

RESUMO

BACKGROUND: Previous work has indicated that pubertal timing and parenting styles are associated with adolescents' drinking behavior, but studies on the relationship between the above three variables are lacking. METHODS: Participants were 1408 Chinese adolescents aged 11-16 years old (46.52% girls). The data emphasized pubertal timing, parenting styles, drinking behavior, and socioeconomic and demographic characteristics of the adolescent and his or her family. RESULTS: Early pubertal timing was related to drinking behavior; however, parenting styles played a moderating role. For male adolescents, father emotional warmth, mother rejection, and mother emotional warmth moderated the relationship between early pubertal timing and drinking behavior. For female adolescents, mother rejection, mother emotional warmth, and mother over-protection moderated the relationship between pubertal timing and drinking behavior. CONCLUSIONS: Parenting styles that include emotional warmth, rejection, and over-protection appear to influence the negative outcomes associated with early pubertal timing, and may be useful in reducing adolescents' drinking behavior.


Assuntos
Comportamento do Adolescente , Poder Familiar , Adolescente , Comportamento do Adolescente/psicologia , Criança , China , Comportamento de Ingestão de Líquido , Feminino , Humanos , Masculino , Mães/psicologia , Poder Familiar/psicologia
13.
J Appl Toxicol ; 42(8): 1323-1336, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35128688

RESUMO

Farnesoid X receptor (FXR) is a nuclear receptor involved in the metabolism of bile acid. However, the molecular signaling of FXR in bile acid homeostasis in cholestatic drug-induced liver injury remains unclear. Oleanolic acid (OA), a natural triterpenoid, has been reported to produce evident cholestatic liver injury in mice after a long-term use. The present study aimed to investigate the role of FXR in OA-induced cholestatic liver injury in mice using C57BL/6J (WT) mice and FXR knockout (FXR-/- ) mice. The results showed that a significant alleviation in OA-induced cholestatic liver injury was observed in FXR-/- mice as evidenced by decreases in serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase as well as reduced hepatocyte necrosis. UPLC-MS analysis of bile acids revealed that the contents of bile acids decreased significantly in liver and serum, while increased in the bile in FXR-/- mice compared with in WT mice. In addition, the mRNA expressions of hepatic transporter Bsep, bile acid synthesis enzymes Bacs and Baat, and bile acids detoxifying enzymes Cyp3a11, Cyp2b10, Ephx1, Ugt1a1, and Ugt2b5 were increased in liver tissues of FXR-/- mice treated with OA. Furthermore, the expression of membrane protein BSEP was significantly higher in livers of FXR-/- mice compared with WT mice treated with OA. These results demonstrate that knockout of FXR may alleviate OA-induced cholestatic liver injury in mice by decreasing accumulation of bile acids both in the liver and serum, increasing the export of bile acids via the bile, and by upregulation of bile acids detoxification enzymes.


Assuntos
Colestase , Ácido Oleanólico , Animais , Ácidos e Sais Biliares/metabolismo , Colestase/induzido quimicamente , Colestase/metabolismo , Cromatografia Líquida , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ácido Oleanólico/metabolismo , Ácido Oleanólico/toxicidade , Espectrometria de Massas em Tandem
14.
Psychol Med ; 52(3): 433-445, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35199638

RESUMO

BACKGROUND: T long-term effects of cognitive therapy and behavior therapy (CTBT) for menopausal symptoms are unknown, and whether the effects are different between natural menopause and treatment-induced menopause are currently unclear. Therefore, we sought to conduct an accurate estimate of the efficacy of CTBT for menopausal symptoms. METHODS: We conducted searches of Cochrane Library, EMBASE, PsycINFO, PubMed, and Web of Science databases for studies from 1 January 1977 to 1 November 2021. Randomized controlled trials (RCTs) comparing intervention groups to control groups for menopausal symptoms were included. Hedge's g was used as the standardized between-group effect size with a random-effects model. RESULTS: We included 14 RCTs comprising 1618 patients with a mean sample size of 116. CTBT significantly outperformed control groups in terms of reducing hot flushes [g = 0.39, 95% confidence interval (CI) 0.23-0.55, I2 = 45], night sweats, depression (g = 0.50, 95% CI 0.34-0.66, I2 = 51), anxiety (g = 0.38, 95% CI 0.23-0.54, I2 = 49), fatigue, and quality of life. Egger's test indicated no publication bias. CONCLUSIONS: CTBT is an effective psychological treatment for menopausal symptoms, with predominantly small to moderate effects. The efficacy is sustained long-term, although it declines somewhat over time. The efficacy was stronger for natural menopause symptoms, such as vasomotor symptoms, than for treatment-induced menopause symptoms. These findings provide support for treatment guidelines recommending CTBT as a treatment option for menopausal symptoms.


Assuntos
Terapia Cognitivo-Comportamental , Fogachos , Feminino , Fogachos/terapia , Humanos , Menopausa , Qualidade de Vida
15.
J Agric Food Chem ; 70(8): 2673-2683, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35191700

RESUMO

Astaxanthin is a highly value-added keto-carotenoid compound. The astaxanthin 3S,3'S-isomer is more desirable for food additives, cosmetics, and pharmaceuticals due to health concerns about chemically synthesized counterparts with a mixture of three isomers. Biosynthesis of 3S,3'S-astaxanthin suffers from limited content and productivity. We engineered Yarrowia lipolytica to produce high levels of 3S,3'S-astaxanthin. We first assessed various ß-carotene ketolases (CrtW) and ß-carotene hydroxylases (CrtZ) from two algae and a plant. HpCrtW and HpCrtZ from Haematococcus pluvialis exhibited the strongest activity in converting ß-carotene into astaxanthin in Y. lipolytica. We then fine-tuned the HpCrtW and HpCrtZ transcriptional expression by increasing the rounds of gene integration into the genome and applied a modular enzyme assembly of HpCrtW and HpCrtZ simultaneously. Next, we rescued leucine biosynthesis in the engineered Y. lipolytica, leading to a five-fold increase in biomass. The astaxanthin production achieved from these strategies was 3.3 g/L or 41.3 mg/g dry cell weight under fed-batch conditions, which is the highest level reported in microbial chassis to date. This study provides the potential for industrial production of 3S,3'S-astaxanthin, and this strategy empowers us to build a sustainable biorefinery platform for generating other value-added carotenoids in the future.


Assuntos
Engenharia Metabólica , Yarrowia , Xantofilas/química , Yarrowia/genética , Yarrowia/metabolismo , beta Caroteno/metabolismo
16.
Oxid Med Cell Longev ; 2022: 5213573, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35320975

RESUMO

Low-intensity extracorporeal shockwave therapy (Li-ESWT), as a microenergy therapy, has the effects of inhibiting oxidative stress, antiapoptosis, and tissue repair, which is increasingly applied to a variety of diseases. Our research aims to explore the protective effects of Li-ESWT in the aging rat model and its possible molecular mechanism through in vivo and in vitro experiments. In vitro, TM3 Leydig cells incubated with H2O2 were treated with Li-ESWT at 4 energy levels (0.01, 0.05, 0.1, and 0.2 mJ/mm2). In vivo, we employed an androgen-deficient rat model to simulate male aging and treated it with Li-ESWT at three different energy levels (0.01, 0.05, and 0.2 mJ/mm2). Li-ESWT increased the expression of vascular endothelial growth factor (VEGF) in TM3 cells, improved antioxidant capacity, and reduced apoptosis, with the effect being most significant at 0.05 mJ/mm2 energy level. In androgen-deficient rat model, LI-ESWT can improve sperm count, motility, and serum testosterone level, enhancing tissue antioxidant capacity and antiapoptotic ability, and the effect is most significant at 0.05 mJ/mm2 energy level. Therefore, Li-ESWT at an appropriate energy level can improve sperm count, motility, and serum testosterone levels in androgen-deficient rat models, reduce oxidative stress in the testis, and increase antioxidant capacity and antiapoptotic abilities. The mechanism of this condition might be related to the increased VEGF expression in Leydig cells by Li-ESWT.


Assuntos
Tratamento por Ondas de Choque Extracorpóreas , Androgênios/farmacologia , Animais , Peróxido de Hidrogênio , Masculino , Ratos , Testículo , Fator A de Crescimento do Endotélio Vascular
17.
Exp Ther Med ; 23(5): 357, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35493433

RESUMO

Vitamin D3 supplementation has been previously reported to inhibit the occurrence and development of chronic obstructive pulmonary disease (COPD). However, the underlying mechanism remains unclear. Epithelial-mesenchymal transition (EMT) and fibrogenesis have been associated with the development of COPD. The aim of the present study was to investigate the potential effects and mechanism of vitamin D3 in an in vitro model of cigarette smoke (CS)-induced EMT and fibrosis, with specific focus on the role of club cell protein 16 (CC16). CS extract (CSE) at different concentrations (5, 10 and 20%) was used to treat 16-HBE cells to induce EMT and fibrogenesis following which they were treated with vitamin D3. Subsequently, the 20% CSE group was selected for further experiments, where 16-HBE cells were divided into the following five groups: The control group; the CSE group; the low-dose vitamin D3 group (250 nM); the medium-dose vitamin D3 group (500 nM); and the high-dose vitamin D3 group (1,000 nM). Western blot analysis was used to detect the protein expression levels of the EMT-related proteins E-cadherin, N-cadherin, Slug and α-SMA, fibrogenesis-related proteins collagen Ⅳ and fibronectin 1, proteins involved in the TGF-ß1/SMAD3 signaling pathway and CC16. Immunofluorescence was used to measure the protein expression levels of E-cadherin, N-cadherin and collagen Ⅳ. Specific CC16 knockdown was performed using short hairpin RNA transfection to investigate the role of CC16. The results of the present study found that vitamin D3 could increase the protein expression level of CC16 to inhibit the activation of the TGF-ß1/SMAD3 signaling pathway; thereby reducing the 20% increase in CSE-induced EMT- and fibrogenesis-related protein expression levels. Following CC16 knockdown, the inhibitory effects of vitamin D3 on EMT- and fibrogenesis-related protein expression were partially reversed. To conclude, these results suggest that vitamin D3 can inhibit the protein expression levels of EMT- and fibrogenesis-related proteins induced by CSE, at least partially through the function of CC16. These findings are expected to provide novel theoretical foundations and ideas for the pathogenesis and treatment of COPD.

18.
Front Pharmacol ; 12: 716884, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867324

RESUMO

Objectives: Sestrin2 (Sesn2) has been demonstrated to be a cysteine sulfinyl reductase and protects cells from multiple stress insults, including hypoxia, endoplasmic reticulum stress, and oxidative stress. However, the roles and mechanisms of Sesn2 in pressure overload-induced mouse cardiac hypertrophy have not been clearly clarified. This study intended to investigate whether sestrin2 (Sesn2) overexpression could prevent pressure overload-induced cardiac hypertrophy via an AMPKα2 dependent pathway through conditional knockout of AMPKα2. Methods and results: Sesn2 expression was significantly increased in mice hearts at 2 and 4 weeks after aortic banding (AB) surgery, but decreased to 60-70% of the baseline at 8 weeks. Sesn2 overexpression (at 3, 6, and 9 folds) showed little cardiac genetic toxicity in transgenic mice. Cardiac dysfunctions induced by pressure overload were attenuated by cardiomyocyte-specific Sesn2 overexpression when measured by echocardiography and hemodynamic analysis. Results of HE and PSR staining showed that Sesn2 overexpression significantly alleviated cardiac hypertrophy and fibrosis in mice hearts induced by pressure overload. Meanwhile, adenovirus-mediated-Sesn2 overexpression markedly suppressed angiotensin II-induced neonatal rat cardiomyocyte hypertrophy in vitro. Mechanistically, Sesn2 overexpression increased AMPKα2 phosphorylation but inhibited mTORC1 phosphorylation. The cardiac protections of Sesn2 overexpression were also via regulating oxidative stress by enhancing Nrf2/HO-1 signaling, restoring SOD activity, and suppressing NADPH activity. Particularly, we first proved the vital role of AMPKα2 in the regulation of Sesn2 with AMPKα2 knockout (AMPKα2-/-) mice and Sesn2 transgenic mice crossed with AMPKα2-/-, since Sesn2 overexpression failed to improve cardiac function, inhibit cardiac hypertrophy and fibrosis, and attenuate oxidative stress after AMPKα2 knockout. Conclusion: This study uniquely revealed that Sesn2 overexpression showed little genetic toxicity in mice hearts and inhibited mTORC1 activation and oxidative stress to protect against pressure overload-induced cardiac hypertrophy in an AMPKα2 dependent pathway. Thus, interventions through promoting Sesn2 expression might be a potential strategy for treating pathological cardiac hypertrophy and heart failure.

19.
J Exp Clin Cancer Res ; 40(1): 390, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34893086

RESUMO

BACKGROUND: Centromere protein N (CENP-N) has been reported to be highly expressed in malignancies, but its role and mechanism in nasopharyngeal carcinoma (NPC) are unknown. METHODS: Abnormal CENP-N expression from NPC microarrays of GEO database was analyzed. CENP-N expression level was confirmed in NPC tissues and cell lines. Stable CENP-N knockdown and overexpression NPC cell lines were established, and transcriptome sequencing after CENP-N knockdown was performed. In vitro and in vivo experiments were performed to test the impact of CENP-N knockdown in NPC cells. ChIP and dual luciferase reporter assays were used to verify the combination of IRF2 and CENP-N. Western blot analysis, cellular immunofluorescence, immunoprecipitation and GST pulldown assays were used to verify the combination of CENP-N and AKT. RESULTS: CENP-N was confirmed to be aberrantly highly expressed in NPC tissues and cell lines and to be associated with high 18F-FDG uptake in cancer nests and poor patient prognosis. Transcriptome sequencing after CENP-N knockdown revealed that genes with altered expression were enriched in pathways related to glucose metabolism, cell cycle regulation. CENP-N knockdown inhibited glucose metabolism, cell proliferation, cell cycling and promoted apoptosis. IRF2 is a transcription factor for CENP-N and directly promotes CENP-N expression in NPC cells. CENP-N affects the glucose metabolism, proliferation, cell cycling and apoptosis of NPC cells in vitro and in vivo through the AKT pathway. CENP-N formed a complex with AKT in NPC cells. Both an AKT inhibitor (MK-2206) and a LDHA inhibitor (GSK2837808A) blocked the effect of CENP-N overexpression on NPC cells by promoting aerobic glycolysis, proliferation, cell cycling and apoptosis resistance. CONCLUSIONS: The IRF2/CENP-N/AKT axis promotes malignant biological behaviors in NPC cells by increasing aerobic glycolysis, and the IRF2/CENP-N/AKT signaling axis is expected to be a new target for NPC therapy.


Assuntos
Proteínas Cromossômicas não Histona/metabolismo , Fator Regulador 2 de Interferon/metabolismo , Neoplasias Nasofaríngeas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apoptose , Ciclo Celular , Proliferação de Células , Genes Sintéticos , Humanos , Camundongos , Camundongos Nus , Prognóstico , Proteínas Recombinantes , Transdução de Sinais , Efeito Warburg em Oncologia
20.
Zhonghua Nan Ke Xue ; 27(2): 150-154, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-34914332

RESUMO

OBJECTIVE: To study the clinical effect of transurethral columnar balloon dilation of the prostate (TUCBDP) in the treatment of BPH and introduce the experience with the surgical procedure. METHODS: We retrospectively analyzed the clinical data on 265 cases of BPH treated by TUCBDP from August 2016 to August 2019. RESULTS: Operations were successfully completed in all the cases, with the mean operation time of (24.67 ± 7.6) min and the average intraoperative blood loss of (26.5 ± 21.4) ml, and all the patients had urinary patency after removal of the catheter. Follow-up examinations every 3 months after surgery showed significant improvement over the baseline in IPSS, quality of life score (QOL), maximum urinary flow rate (Qmax), postvoid residual urine (PVR) and other indicators (P < 0.05). Forty-five of the patients with sexual life exhibited no significant difference from the baseline in IIEF-5 and erectile hardness scale (EHS) scores (P > 0.05). Postoperative complications were observed in 53 cases (20%), including 28 cases of transient urinary incontinence (10.56%), 3 cases of hemorrhage (1.13%), 11 cases of urinary tract infection (4.15%), 1 case of urethral stricture (0.37%), and 8 cases of acute urinary retention (3.01%), which were all improved after regular treatment, with no occurrence of true urinary incontinence. Retrograde ejaculation occurred in 2 (4.45%) of the 45 patients with sexual life. CONCLUSIONS: Transurethral columnar balloon dilation of the prostate, with the advantages of short operation time and less intraoperative bleeding, has a significant short-term clinical effect in the treatment of BPH, particularly suitable for the elderly and those who want to retain the sexual function. Intraoperative localization of the protrusion may significantly influence the outcome of surgery, which deserves strengthened studies. Special attention should be paid to the incidence of postoperative transient urinary incontinence.


Assuntos
Hiperplasia Prostática , Idoso , Dilatação , Humanos , Masculino , Próstata/cirurgia , Hiperplasia Prostática/cirurgia , Qualidade de Vida , Estudos Retrospectivos
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