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1.
Front Oncol ; 11: 770565, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804972

RESUMO

Background: It is undeniable that the tumor microenvironment (TME) plays an indispensable role in the progression of kidney renal clear cell carcinoma (KIRC). However, the precise mechanism of activities in TME is still unclear. Methods and Results: Using the CIBERSORT and ESTIMATE calculation methods, the scores of the two main fractions of tumor-infiltrating immune cells (TICs) from The Cancer Genome Atlas (TCGA) database of 537 KIRC patients were calculated. Subsequently, differentially expressed genes (DEGs) were drawn out by performing an overlap between Cox regression analysis and protein-protein interaction (PPI) network. Aquaporin 9 (AQP9) was identified as a latent predictor through the process. Following research revealed that AQP9 expression was positively correlated with the pathological characteristics (TNM stage) and negatively connected with survival time. Then, by performing gene set enrichment analysis (GSEA), it can be inferred that genes with high expression level of AQP9 were mainly enriched in immune-related activities, while low AQP9 group was associated with functions of cellular metabolism. Further studies have shown that regulatory T cells (Tregs), macrophages M2, macrophages M0, CD4+ T cells, and neutrophils were positively correlated with AQP9 expression. While the levels of mast cells, natural killer (NK) cells, and CD8+ T cells are negatively correlated with AQP9. The result of multiple immunohistochemistry (mIHC) suggests a negative relevance between AQP9 and CD8+ T cells and reveals a trend of consistent change on AQP9 and M2 macrophages. Conclusion: The expression level of AQP9 may be helpful in predicting the prognosis of patients with KIRC, especially to the TME state transition, the mechanism of which is possibly through lipid metabolism and P53, Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways that affect M2 polarization. AQP9 was associated with the expression levels of M2, tumor-associated macrophages (TAMs), and the recruitment of CD8+ T cells in tumor environment. The research result indicates that AQP9 may be an obstacle to maintain the immune activity of TME.

2.
World J Clin Cases ; 9(29): 8871-8878, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34734069

RESUMO

BACKGROUND: Synovial sarcoma (SS) is a highly malignant tumor of unknown histological origin. This tumor can occur in various parts of the body, including those without synovial structures, but mainly in and around the joints, mostly in the lower extremities. Primary intracranial SSs are remarkably rare. This paper aims to report a case of primary intracranial SS with hemorrhage. CASE SUMMARY: A 35-year-old male patient suffered a headache and slurred speech during manual labor and was sent to the emergency department. Through imaging examination, the patient was considered to have high-grade glioma complicated with hemorrhage and was treated with craniotomy. Postoperative pathology revealed SS. positron emission tomography/computed tomography was performed, which ruled out the possibility of metastasis to the intracranial from other parts of the body. Postoperative radiotherapy was given to the patient, during which radiation necrosis occurred. Sixteen months after craniotomy, cranial magnetic resonance imaging revealed recurrence of the tumor. CONCLUSION: Primary intracranial SS is a rare malignant tumor. Primary intracranial SS with hemorrhage and radiation necrosis should be carefully monitored during postoperative radiotherapy. Surgical resection of the tumor combined with postoperative radiotherapy and chemotherapy is currently used, but the prognosis is poor.

4.
Br J Cancer ; 125(11): 1570-1581, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34671129

RESUMO

BACKGROUND: Genetic correlations, causalities and pathways between large-scale complex exposures and ovarian and breast cancers need systematic exploration. METHODS: Mendelian randomisation (MR) and genetic correlation (GC) were used to identify causal biomarkers from 95 cancer-related exposures for risk of breast cancer [BC: oestrogen receptor-positive (ER + BC) and oestrogen receptor-negative (ER - BC) subtypes] and ovarian cancer [OC: high-grade serous (HGSOC), low-grade serous, invasive mucinous (IMOC), endometrioid (EOC) and clear cell (CCOC) subtypes]. RESULTS: Of 31 identified robust risk factors, 16 were new causal biomarkers for BC and OC. Body mass index (BMI), body fat mass (BFM), comparative body size at age 10 (CBS-10), waist circumference (WC) and education attainment were shared risk factors for overall BC and OC. Childhood obesity, BMI, CBS-10, WC, schizophrenia and age at menopause were significantly associated with ER + BC and ER - BC. Omega-6:omega-3 fatty acids, body fat-free mass and basal metabolic rate were positively associated with CCOC and EOC; BFM, linoleic acid, omega-6 fatty acids, CBS-10 and birth weight were significantly associated with IMOC; and body fat percentage, BFM and adiponectin were significantly associated with HGSOC. Both GC and MR identified 13 shared factors. Factors were stratified into five priority levels, and visual causal networks were constructed for future interventions. CONCLUSIONS: With analysis of large-scale exposures for breast and ovarian cancers, causalities, genetic correlations, shared or specific factors, risk factor priority and causal pathways and networks were identified.

5.
Biotechnol Adv ; 53: 107856, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34666147

RESUMO

Bacterial cellulose (BC) is an important polysaccharide synthesized by some bacterial species under specific culture conditions, which presents several remarkable features such as microporosity, high water holding capacity, good mechanical properties and good biocompatibility, making it a potential biomaterial for medical applications. Since its discovery, BC has been used for wound dressing, drug delivery, artificial blood vessels, bone tissue engineering, and so forth. Additionally, BC can be simply manipulated to form its derivatives or composites with enhanced physicochemical and functional properties. Several polymers, carbon-based nanomaterials, and metal nanoparticles (NPs) have been introduced into BC by ex situ and in situ methods to design hybrid materials with enhanced functional properties. This review provides comprehensive knowledge and highlights recent advances in BC production strategies, its structural features, various in situ and ex situ modification techniques, and its potential for biomedical applications.

6.
Clin Respir J ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34610651

RESUMO

INTRODUCTION: Chronic eosinophilic pneumonia (CEP) is a rare disease with unknown etiology. Due to lack of specificity of CEP symptoms, clinicians are not experienced in establishing its diagnosis. OBJECTIVES: To summarize the clinical data of CEP patients to improve the understanding of CEP and reduce misdiagnosis. METHODS: Data of patients pathologically diagnosed with CEP in the PLA General Hospital between May 2013 and May 2019 were collected, and clinical manifestations, imaging characteristics, pathological features, and treatment were retrospectively analyzed. RESULTS: Twenty patients, including 6 males and 14 females, were diagnosed with CEP. The average age was 47.0 ± 10.2 years. The main clinical manifestations were cough and dyspnea. The average duration of CEP was 15.5 ± 11.5 months. The average proportion of eosinophils in the peripheral blood was 18.9 ± 17.8%, and the average proportion of eosinophils in the bronchoalveolar lavage fluid was 41.5 ± 19.4%. The main imaging features were patchy shadows and consolidation shadows. The most common manifestations on bronchoscopic examination were congestion and edema of the bronchial mucosa. Two patients had granular protrusions of the endotracheal membrane. Histological examination indicated infiltration of numerous eosinophils. All patients improved after prednisone therapy. CONCLUSION: CEP onset is insidious, and clinical manifestations lack specificity. Typical imaging features are peripheral and subpleural distribution of lung infiltrates. Some patients have a normal proportion of eosinophils in the peripheral blood, but most have an increased number of eosinophils in the BALF, which contributes to CEP diagnosis. A biopsy is necessary when differential diagnosis is difficult. A systemic glucocorticoid is effective.

7.
Ying Yong Sheng Tai Xue Bao ; 32(8): 2818-2828, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34664455

RESUMO

Taking the main production area of yam in North China Plain as the research area, we analyzed the status of soil fertility and fertilizer application in yam production through field investigation and tracking monitoring, examined soil nutrient balance using the input-output model of nutrients in agricultural system, and assessed the environmental risks in the yam planting system. The results showed that: 1) the contents of soil organic matter and total N were extremely low, and the contents of available P and available Zn were both low; both nitrate and available Cu contents were at the middle level, the contents of soil slowly available K, available S, and exchangeable Ca and Mg were all extremely high, the contents of available K, available Fe, and available Mn were all at high level; 2) The nitrogen (N), phosphorus (P2O5), and potassium (K2O) inputs were 575-943 kg·hm-2, 341-981 kg·hm-2, and 655-1219 kg·hm-2 during the whole growth period of yam, with chemical fertilizer accounting for 83.0%, 88.6%, and 91.3%, respectively; The input imbalance between organic and inorganic fertilizer, as well as the excessive nutrients input were prominent; 3) The surplus rate of soil nitrogen, phosphorus and potassium reached 271.14 kg·hm-2, 466.34 kg·hm-2, and 739.97 kg·hm-2, with corresponding surplus ratio of 48.7%, 258.1%, and 324.5%, respectively, which all exceeded the environmental safety threshold and were classified as moderate risk, severe risk, and severe risk, respectively. The overall environmental risk caused by chemical fertilizer application in yam production had reached severe risk level.


Assuntos
Dioscorea , Solo , China , Nutrientes , Medição de Risco
8.
Int J Mol Med ; 48(6)2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34676876

RESUMO

Epilepsy comorbidities and anti­epileptic drugs (AEDs) are currently the main limitations of epilepsy treatment. Semaglutide is a glucagon like peptide­1 analogue that has entered the market as a new once­weekly drug for type II diabetes. The aim of the present study was to investigate the functions of semaglutide in epilepsy and inflammation models, in order to investigate its potential mechanism. In vitro, an inflammation model was established using lipopolysaccharide (LPS) and nigericin stimulation in BV2 cells. In vivo, chronic epilepsy model mice were generated using a pentylenetetrazole (PTZ) kindling method. BV2 cell proliferation was assessed using the Cell Counting Kit­8. The effects of semaglutide on NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and inflammatory cytokine secretion were determined using western blotting (WB) and ELISA. A lactate dehydrogenase (LDH) assay kit was used to detect the effect of semaglutide on LDH release. Electrocorticography and the modified Racine scale were used to assess seizure severity. Cognitive function was evaluated with behavioral assessment. Morphological changes in the hippocampus were observed with Nissl staining. Double immunofluorescence staining for NeuN and Iba­1, WB and immunofluorescence analysis of apoptosis­related proteins were used to evaluate neuronal apoptosis. The NLRP3 inflammasome was assessed by reverse transcription­quantitative PCR, WB and immunofluorescence staining, and inflammatory cytokine release was evaluated by WB analysis in the hippocampus of C57/BL6J model mouse. Semaglutide attenuated the LPS­ and nigericin­induced inflammatory response and LDH release by blocking NLRP3 inflammasome activation in BV2 cells. Moreover, semaglutide decreased seizure severity, alleviated hippocampal neuronal apoptosis, ameliorated cognitive dysfunction, blocked NLRP3 inflammasome activation and decreased inflammatory cytokine secretion in PTZ­kindled mice. These results indicated that semaglutide reduced seizure severity, exerted neuroprotective effects and ameliorated cognitive dysfunction, possibly via inhibition of NLRP3 inflammasome activation and inflammatory cytokine secretion. Semaglutide may therefore be a novel, promising adjuvant therapeutic for epilepsy and its associated comorbidities.

9.
J Biomed Nanotechnol ; 17(10): 2071-2084, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34706807

RESUMO

Uric acid is the final product of purine metabolism, and excessive serum uric acid can cause gouty arthritis and uric acid nephropathy. Therefore, lowering the uric acid level and alleviating inflammation in the body are the key points to treating these diseases. A stable nanosuspension of peptide BmK9 was prepared by the precipitation-ultrasonication method. By combining uricase on the surface of a positively charged carrier, a complex consisting of neutral rod-shaped BmK9 and uricase nanoparticles (Nplex) was formed to achieve the delivery of BmK9 and uricase, respectively. The formulation of Nplex has a diameter of 180 nm and drug loading up to 200%, which releases BmK9 and uricase slowly and steadily in drug release tests in vitro. There was significantly improved pharmacokinetic behavior of the two drugs because Nplex prolonged the half-life and increased tissue accumulation. Histological assessments showed that the dual drug Nplex can reduce the inflammation response in acute gouty arthritis and chronic uric acid nephropathy in vivo. In the macrophage system, there was lower toxicity and increased beneficial effect on inflammation with Nplex than free BmK9 or uricase. Collectively, this novel formulation provides a dual drug delivery system that can treat gouty arthritis and uric acid nephropathy.


Assuntos
Artrite Gotosa , Nefropatias , Nanopartículas , Artrite Gotosa/induzido quimicamente , Artrite Gotosa/tratamento farmacológico , Humanos , Urato Oxidase , Ácido Úrico
10.
Healthcare (Basel) ; 9(9)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34574896

RESUMO

Education, medical services, and living conditions can influence individual health and health literacy. We used the 2015 China Health and Nutrition Survey data to analyze the impact of education, medical services, and living conditions on individual health by extending the Grossman model. As a result, using the instrumental variable (read, write, and draw) two-stage least square method, we found that education, medical services, and living conditions have a positive impact on individual health, both physical health and psychological health. Among them, medical services have the largest influence, followed by living conditions and education. In addition, the results are robust. However, individual characteristics, family income, and working status also affect individual health. Moreover, we observed heterogeneity in age, sex, and residence in the impact of education, medical services, and living conditions on individual health. In particular, the health of the rural elderly and elderly women is more sensitive to education, the medical services of middle-aged women and young men have a greater impact on their health, and the living conditions of the rural elderly and youth have a greater impact on their health. All the findings are helpful for optimizing the path of the Healthy China program.

11.
Environ Res ; 204(Pt B): 112019, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34534524

RESUMO

BACKGROUND: In epidemiology studies, ambient measurements of PM2.5 are often used as surrogates for personal exposures. However, it is unclear the degree to which ambient PM2.5 reflects personal exposures. OBJECTIVE: In order to examine potential sources of bias in epidemiology studies, we conducted a review and meta-analysis of studies to determine the extent to which short-term measurements of ambient PM2.5 levels are related to short-term measurements of personal PM2.5 levels. METHODS: We conducted a literature search of studies reporting both personal and ambient measurements of PM2.5 published in the last 10 years (2009-2019) and incorporated studies published prior to 2009 from reviews. RESULTS: Seventy-one studies were identified. Based on 17 studies reporting slopes, a meta-analysis revealed an overall slope of 0.56 µg/m3 (95% CI: [0.39, 0.73]) personal PM2.5 per µg/m3 increase in ambient PM2.5. Slopes for summer months were higher (slope = 0.73, 95% CI: [0.64, 0.81]) than for winter (slope = 0.46, 95% CI: [0.36, 0.57]). Based on 44 studies reporting correlations, we calculated an overall personal-ambient PM2.5 correlation of 0.63 (95% CI: [0.55, 0.71]). Correlations were stronger in studies conducted in Canada (r = 0.86, 95% CI: [0.67, 0.94]) compared to the USA (r = 0.60, 95% CI: [0.49, 0.70]) and China (r = 0.60, 95% CI: [0.46, 0.71]). Correlations also were stronger in urban areas (r = 0.53, 95% CI: [0.43, 0.62]) vs. suburban areas (r = 0.36, 95% CI: [0.21, 0.49]). SIGNIFICANCE: Our results suggest a large degree of variability in the personal-ambient PM2.5 association and the potential for exposure misclassification and measurement error in PM2.5 epidemiology studies.

12.
J Mech Behav Biomed Mater ; 124: 104811, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34500354

RESUMO

The control of interfacial interaction between polymers and fillers is essential for the fabrication of high-performance polymer composites. In this work, poly(ether-ether-ketone)/silica (PEEK/SiO2) and PEEK/SiO2/graphene oxide (GO) composite were prepared by ball milling-ultrasonic dispersion combined with melt extrusion injection molding. GO nanosheets were introduced as the interfacial enhancer to improve interfacial binding between SiO2 and PEEK. Mechanical tests showed that the incorporation of SiO2 and GO greatly optimized the modulus, strength, and fracture toughness of the composites. The tensile strength and Young's modulus of the PEEK/SiO2 composites increases with the increase of SiO2 content. The maximum tensile strength and Young's modulus of the PEEK/SiO2 composites are approximate 95.9 ± 0.6 MPa and 4.007 ± 0.005 GPa at 30 wt% of SiO2, an increase of 6.4% and 21.2% than that of pure PEEK. The maximum tensile strength and Young's modulus of the PEEK/SiO2/GO composite are further improved to approximate 101.5 ± 0.7 MPa and 4.62 ± 0.08 GPa at a GO content of 1.5% wt, which is 12.6% and 39.4% higher than that of pure PEEK. In addition, SEM images show that numerous HA formed on the surface of the PEEK/SiO2/GO composite after immersion in SBF for 7 days, and the HA layer becomes gradually thicker after 14 days, implying the good osteogenic activity of PEEK/SiO2/GO composites. Therefore, these results suggest that the use of GO as a novel filler surface modifier for the preparation of high-performance composites may become a novel interfacial design strategy for the development of high-performance composites.


Assuntos
Cetonas , Dióxido de Silício , Éter , Éteres , Grafite , Polietilenoglicóis
13.
Appl Microbiol Biotechnol ; 105(20): 7801-7811, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34581846

RESUMO

Quorum sensing is a mechanism that facilitates cell-to-cell communication. Through signal molecular density for signal recognition, which leads to the regulation of some physiological and biochemical functions. Gluconacetobacter xylinus CGMCC 2955, which produces bacterial cellulose (BC), synthesizes the LuxR protein belonging to the LuxI/LuxR type QS system. Here, a luxR overexpression vector was transformed into G. xylinus CGMCC 2955. The overexpression of luxR increased the yield of BC by 15.6% after 16 days static culture and reduced the cell density by 15.5% after 120-h-agitated culture. The glucose was used up by G. xylinus-pMV24-luxR at 72-h-agitated fermentation, which 12 h earlier than the wild-type (WT). The total N-acylhomoserine lactones (AHL) content of the luxR-overexpressing strain and the WT strain attained 1367.9 ± 57.86 mg/L and 842.9 ± 54.22 mg/L, respectively. The C12-HSL and C14-HSL contents of G. xylinus-pMV24-luxR were 202 ± 21.66 mg/L and 409.6 ± 0.91 mg/L, which were significantly lower than that of WT. In contrast, C6-HSL showed opposite results. The difference of AHL content proved that overexpression of luxR improved the binding of AHL and showed preference for some specific AHL. The metabolic results demonstrated that upon glucose exhaustion, the consumption of gluconic acid was promoted by luxR overexpression, and the content of D- ( +)-trehalose, an antiretrograde metabolite, increased significantly. KEY POINTS: • The overexpression of luxR increased the yield of bacterial cellulose • The content of signal molecules was significantly different • Differential metabolites were involved in multiple metabolic pathways.


Assuntos
Gluconacetobacter xylinus , Percepção de Quorum , Acil-Butirolactonas , Proteínas de Bactérias/genética , Celulose , Gluconacetobacter xylinus/genética , Transativadores/genética
14.
Cell Death Dis ; 12(9): 799, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404767

RESUMO

Lactate dehydrogenase A (LDHA), a critical component of the glycolytic pathway, relates to the development of various cancers, including thyroid cancer. However, the regulatory mechanism of LDHA inhibition and the physiological significance of the LDHA inhibitors in papillary thyroid cancer (PTC) are unknown. Long non-coding RNA (lncRNA) plays a vital role in tumor growth and progression. Here, we identified a novel lncRNA LINC00671 negatively correlated with LDHA, downregulating LDHA expression and predicting good clinical outcome in thyroid cancer. Moreover, hypoxia inhibits LINC00671 expression and activates LDHA expression largely through transcriptional factor STAT3. STAT3/LINC00671/LDHA axis regulates thyroid cancer glycolysis, growth, and lung metastasis both in vitro and in vivo. In thyroid cancer patients, LINC00671 expression is negatively correlated with LDHA and STAT3 expression. Our work established STAT3/LINC00671/LDHA as a critical axis to regulate PTC growth and progression. Inhibition of LDHA or STAT3 or supplement of LINC00671 could be potential therapeutic strategies in thyroid cancer.

15.
Parasitol Res ; 120(10): 3519-3527, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34417865

RESUMO

Free-range chickens might mediate the spread of Cryptosporidium oocysts to humans and other animals. Few studies have evaluated the prevalence of Cryptosporidium species in domestic free-range poultry in China. Here, we characterized the prevalence and distribution of species and genotypes of Cryptosporidium in domestic free-range chickens, ducks, and geese in Anhui Province, China. A total of 1910 fresh fecal samples from three poultry species were examined from 18 free-range poultry farms by nested PCR and analysis of the Cryptosporidium SSU rRNA gene. The overall prevalence of Cryptosporidium species was 2.9% (55/1910), with infection rates of 1.3% (11/829) in chickens, 7.3% (36/487) in ducks, and 1.4% (8/594) in geese. C. baileyi (0.6%), C. meleagridis (0.2%), C. galli (0.2%), and C. xiaoi-like genotype (0.2%) were identified in chickens, and only C. baileyi was identified in ducks and geese, with infection rates of 7.4% and 1.3%, respectively. C. baileyi was the most prevalent species. Sequencing of the GP60 gene revealed that the C. meleagridis isolates belonged to the IIIbA26G1R1b subtype. This is the first study to document C. galli and C. xiaoi-like genotype in domestic free-range chickens in China. These findings expand the range of avian hosts known for Cryptosporidium and highlight the need for additional studies to characterize the diversity of Cryptosporidium in avian species.


Assuntos
Criptosporidiose , Cryptosporidium , Doenças das Aves Domésticas , Animais , Galinhas , China/epidemiologia , Criptosporidiose/epidemiologia , Cryptosporidium/genética , Fezes , Genótipo , Humanos , Aves Domésticas , Doenças das Aves Domésticas/epidemiologia , Prevalência
16.
Hepatology ; 74(6): 3213-3234, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34322883

RESUMO

BACKGROUND AND AIMS: Oxaliplatin (OXA) is one of the most common chemotherapeutics in advanced hepatocellular carcinoma (HCC), the resistance of which poses a big challenge. Long noncoding RNAs (lncRNAs) play vital roles in chemoresistance. Therefore, elucidating the underlying mechanisms and identifying predictive lncRNAs for OXA resistance is needed urgently. METHODS: RNA sequencing (RNA-seq) and fluorescence in situ hybridization (FISH) were used to investigate the OXA-resistant (OXA-R) lncRNAs. Survival analysis was performed to determine the clinical significance of homo sapiens long intergenic non-protein-coding RNA 1134 (LINC01134) and p62 expression. Luciferase, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and chromatin isolation by RNA purification (ChIRP) assays were used to explore the mechanisms by which LINC01134 regulates p62 expression. The effects of LINC01134/SP1/p62 axis on OXA resistance were evaluated using cell viability, apoptosis, and mitochondrial function and morphology analysis. Xenografts were used to estimate the in vivo regulation of OXA resistance by LINC01134/SP1/p62 axis. ChIP, cell viability, and xenograft assays were used to identify the demethylase for LINC01134 up-regulation in OXA resistance. RESULTS: LINC01134 was identified as one of the most up-regulated lncRNAs in OXA-R cells. Higher LINC01134 expression predicted poorer OXA therapeutic efficacy. LINC01134 activates anti-oxidative pathway through p62 by recruiting transcription factor SP1 to the p62 promoter. The LINC01134/SP1/p62 axis regulates OXA resistance by altering cell viability, apoptosis, and mitochondrial homeostasis both in vitro and in vivo. Furthermore, the demethylase, lysine specific demethylase 1 (LSD1) was responsible for LINC01134 up-regulation in OXA-R cells. In patients with HCC, LINC01134 expression was positively correlated with p62 and LSD1 expressions, whereas SP1 expression positively correlated with p62 expression. CONCLUSIONS: LSD1/LINC01134/SP1/p62 axis is critical for OXA resistance in HCC. Evaluating LINC01134 expression in HCC will be effective in predicting OXA efficacy. In treatment-naive patients, targeting the LINC01134/SP1/p62 axis may be a promising strategy to overcome OXA chemoresistance.

17.
Ther Adv Urol ; 13: 17562872211018006, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104222

RESUMO

Background: Primary adenocarcinoma of the bladder (ACB) is a rare malignant tumor of the bladder with limited understanding of its incidence and prognosis. Methods: Patients diagnosed with ACB between 2004 and 2015 were obtained from the SEER database. The incidence changes of ACB patients between 1975 and 2016 were detected by Joinpoint software. Nomograms were constructed based on the results of multivariate Cox regression analysis to predict overall survival (OS) and cancer-specific survival (CSS) in patients with ACB, and the constructed nomograms were validated. Results: The incidence of ACB was trending down from 1991 to 2016. A total of 1039 patients were included in the study and randomly assigned to the training cohort (727) and validation cohort (312). In the training cohort, multivariate Cox regression showed that age, marital status, primary site, histology type, grade, AJCC stage, T stage, SEER stage, surgery, radiotherapy, and chemotherapy were independent prognostic factors for OS, whereas these were age, marital status, primary site, histology type, grade, AJCC stage, T/N stage, SEER stage, surgery, and radiotherapy for CSS. Based on the above Cox regression results, we constructed prognostic nomograms for OS and CSS in ACB patients. The C-index of the nomogram OS was 0.773 and the C-index of CSS was 0.785, which was significantly better than the C-index of the TNM staging prediction model. The area under the curve (AUC) and net benefit of the prediction model were higher than those of the TNM staging system. In addition, the calibration curves were very close to the ideal curve, suggesting appreciable reliability of the nomograms. Conclusion: The incidence of ACB patients showed a decreasing trend in the past 25 years. We constructed a clinically useful prognostic nomogram for calculating OS and CSS of ACB patients, which can provide a personalized risk assessment for ACB patient survival.

18.
Chem Commun (Camb) ; 57(51): 6308-6311, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34075974

RESUMO

Here, we describe the identification of PARP1/2 as direct binding proteins of andrographolide (Andro) using protein microarray, surface plasmon resonance (SPR), and enzyme activity assays. We then evaluated the proliferation inhibition, apoptosis, and cell migration effects of Andro on the MDA-MB-436 cell line in vitro. The final biological evaluation confirmed that Andro was a highly effective single agent in the MDA-MB-436 xenograft model and had a low hERG-mediated cardiac toxicity. Therefore, Andro represents the first natural product, non-amide member of a novel nanomolar-potency PARP1/2 inhibitor family.


Assuntos
Diterpenos/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Ensaios Enzimáticos , Humanos , Cinética , Camundongos , Simulação de Dinâmica Molecular , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Ftalazinas/metabolismo , Ftalazinas/farmacologia , Piperazinas/metabolismo , Piperazinas/farmacologia , Poli(ADP-Ribose) Polimerase-1/análise , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Poli(ADP-Ribose) Polimerases/análise , Poli(ADP-Ribose) Polimerases/química , Análise Serial de Proteínas , Razão Sinal-Ruído , Ressonância de Plasmônio de Superfície , Transplante Heterólogo
19.
Aging (Albany NY) ; 13(11): 14590-14603, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083496

RESUMO

CD8+ cytotoxic T-lymphocytes are essential components of the anti-tumor immunity. To better understand the expansion of CD8+ T-cells we used multiplex fluorescence immunohistochemistry to study Ki67+CD8+ cells in normal lymphoid tissues, selected inflammatory diseases and cancers in 41 large sections/ microenvironment tissue microarrays (TMAs) as well as 765 samples in a conventional TMA format. The evaluation of more than 20 different compartments of normal lymphoid tissues revealed that the percentage of proliferating (ki67+) CD8+ cells did commonly not exceed 3%. In inflammations, the percentage of Ki67+CD8+ cells was more variable and higher compared to normal tissues. In cancers, the percentage of Ki67+CD8+ cells was higher in the tumor center than at the invasive margin. In the tumor center of 765 colorectal cancers, the density of Ki67+CD8+ cells and the percentage of proliferating CD8+ cytotoxic T-cells was significantly associated with microsatellite instability (p<0.0001), pT (p<0.0002) and pN category (p<0.0098). In summary, these data show that the percentage of Ki67+CD8+ cells is usually at a baseline proliferation rate below 3% in healthy secondary lymphoid organs. This rate is often markedly higher in inflammatory and neoplastic diseases compared to normal tissues. The striking link with unfavorable tumor features in colorectal cancer suggest a potential clinical utility of assessing the percentage of Ki67+CD8+ cells to predict patients outcome.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Neoplasias Colorretais/imunologia , Inflamação/imunologia , Tecido Linfoide/imunologia , Proliferação de Células , Neoplasias Colorretais/patologia , Humanos , Antígeno Ki-67/metabolismo , Fenótipo
20.
Int J Cardiol ; 339: 179-184, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34181993

RESUMO

BACKGROUND: Although observational studies have shown an association between sex hormone-binding globulin (SHBG), testosterone (T) and cardiovascular diseases (CVD), controversy remains. In this study, we aim to explore the causal effects of SHBG and T on Coronary heart disease (CHD). METHODS: We used univariable, network and multivariable mendelian randomization (MR) analysis to investigate the causal effect of SHBG and T on CHD. We performed inverse variance weighted (IVW) MR as the primary analysis, with the robustness of this approach further tested by other methods in sensitivity analysis. The SHBG and T were collected from the UK Biobank data, about 180,000 men aged 40 to 69 years. CHD was collected from CARDIoGRAMplusC4D 1000 Genomes-based GWAS, which was a meta-analysis including 48 studies and involving 60,801 CHD cases and 123,504 controls. RESULTS: Using univariable MR-IVW, the results suggested that a one standard deviation (SD) increase in SHBG, the risk of CHD decreased by approximately 14% (OR (95% CI): 0.86(0.76,0.97)), and that a SD increase in total testosterone (TT), the risk also decreased, approximately 8% (OR (95% CI): 0.92(0.85,0.99)). Multivariable MR showed that both SHBG and TT had no direct causal effect with CHD (a SD increase in SHBG: OR (95% CI):0.75(0.57,1.00), P = 0.053; a SD increase in TT: OR (95% CI): 1.05(0.90,1.22), P = 0.53). In the network MR analysis, the results suggested that TT might act as mediator in the causal pathway from SHBG to CHD and account for 93% of the total effect of SHBG on CHD, and that SHBG might be a mediator in the causal pathway from TT to CHD and account for 67% of the total effect of TT on CHD. CONCLUSIONS: Genetically predicted SHBG and TT were negatively correlated with CHD in both univariable and network MR, which may provide a causal explanation behind the observed conclusion. In addition, TT and SHBG had a bidirectional causal effect. Further work is required to disentangle the downstream effects of SHBG/TT on CHD and the molecular pathways involved, as the simultaneous regulation of SHBG and TT may make it a viable strategy for the prevention or treatment of CHD.


Assuntos
Doença das Coronárias , Globulina de Ligação a Hormônio Sexual , Doença das Coronárias/epidemiologia , Doença das Coronárias/genética , Humanos , Masculino , Análise da Randomização Mendeliana , Fatores de Risco , Testosterona
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