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1.
J Colloid Interface Sci ; 606(Pt 2): 913-919, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34487938

RESUMO

With the development of mobile terminals, tunable capacitors for signal processing and memristors for calculation have received a lot of attention. Combining a tunable capacitor and a memristor can improve the performance of mobile terminals and reduce space requirements. In this article, we report on Bi2NiMnO6 (BNMO) films with high dielectric tuning and nonvolatile resistive switching (RS) effects. The BNMO films are fabricated by the sol-gel method and annealed at different temperatures. It exhibits a dielectric tunability of up to 92%. This high dielectric tunability may be attributed to the modulation of the interface dipole by the electric field. When an electric field is applied, the interface dipole of the BNMO film is far away from the interface of the BNMO, and then forms a conductive channel where anions and cations are mixed. The BNMO films are found to have a double-set type effect due to its dielectric tunability properties. This work introduces an ultra-high dielectric tuning material and a new type of RS effect on BNMO thin film, which can achieve tuning and memory behavior on a device.

2.
Redox Biol ; 48: 102201, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34864630

RESUMO

Reactive oxygen species (ROS) which are continuously generated mainly by mitochondria, have been proved to play an important role in the stress signaling of cancer cells. Moreover, pentatricopeptide repeat (PPR) proteins have been suggested to take part in mitochondrial metabolism. However, the mechanisms integrating the actions of these distinct networks in urothelial carcinoma of the bladder (UCB) pathogenesis are elusive. In this study, we found that leucine rich pentatricopeptide repeat containing (LRPPRC) was frequently upregulated in UCB and that it was an independent prognostic factor in UCB. We further revealed that LRPPRC promoted UCB tumorigenesis by regulating the intracellular ROS homeostasis. Mechanistically, LRPPRC modulates ROS balance and protects UCB cells from oxidative stress via mt-mRNA metabolism and the circANKHD1/FOXM1 axis. In addition, the SRA stem-loop interacting RNA binding protein (SLIRP) directly interacted with LRPPRC to protect it from ubiquitination and proteasomal degradation. Notably, we showed that LRPPRC modulated the tumorigenesis of UCB cells in a circANKHD1-FOXM1-dependent manner. In conclusion, LRPPRC exerts critical roles in regulating UCB redox homeostasis and tumorigenesis, and is a prognostic factor for UCB; suggesting that LRPPRC may serve as an exploitable therapeutic target in UCB.

3.
Front Oncol ; 11: 736975, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868926

RESUMO

Objective: Enzalutamide is the most frequently prescribed compound for treating metastatic castration-resistant prostate cancer (mCRPC). Common adverse drug events of enzalutamide are febrile neutropenia, hot flashes, hypertension, and fatigue. Methods: We present a case of a patient with mCRPC who received enzalutamide and developed Stevens-Johnson syndrome (SJS). The culprit drug was confirmed using the Naranjo Adverse Drug Reaction Probability Scale. Clinical characteristics and management principles were analyzed in combination with literature reports. Results: SJS occurred within two weeks of enzalutamide therapy. Supportive care such as steroid treatment led to a complete resolution of skin lesions and improved clinical symptoms after three weeks. Conclusion: Most cutaneous adverse events occur early during enzalutamide therapy, and close observation should be given within two weeks of starting treatment.

4.
Sci Rep ; 11(1): 23272, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34857849

RESUMO

The electromagnetic vortex carrying orbital angular momentum (OAM), which is first studied at optical frequency, has begun to attract widespread attention in the field of radio-frequency/microwave. However, for the OAM mode generated by traditional single antennas, there are problems such as low order and narrow bandwidth, and complex structures such as dual-fed networks may be required. In this paper, based on spoof surface plasmon polariton (SSPP) mode leaky-wave antenna, a single-port traveling-wave ring is proposed to radiate high-order OAM modes working near the cut-off frequency of SSPP state. The achieved 12-order OAM mode within 9.1-10.1 GHz (relative bandwidth of 10.4%) has the main radiation direction close to the antenna surface, forming a plane spiral OAM (PSOAM) wave, which reduces the requirements for mode purity in practical applications. This SSPP ring using periodic units as radiating elements can be an effective radiator for broadband and large-capacity OAM multiplexing communications. The structural characteristics of single feed contribute to the integration of microwave circuits.

5.
BMC Pediatr ; 21(1): 560, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34893057

RESUMO

OBJECTIVE: To explore the efficacy and safety of high-frequency oscillatory ventilation (HFOV) in the treatment of severe meconium aspiration syndrome (MAS) complicated with severe acute respiratory distress syndrome (ARDS). METHODS: A total of 65 infants with severe MAS complicated with severe ARDS were included in the study. The clinical efficacy of treatment for the HFOV group (n = 31) and the conventional mechanical ventilation (CMV) group (n = 34) was retrospectively analysed. The partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2), PaO2/fraction of inspired oxygen (FiO2), and oxygen index values before and at 6, 12, 24, 48, and 72 h after mechanical ventilation, the mechanical ventilation time, oxygen inhalation time, incidence of complications, and outcomes of the two groups were compared. RESULTS: At 6, 12, 24, and 48 h after mechanical ventilation, the PaO2 in the HFOV group was significantly higher than in the CMV group, while the PaCO2 in the HFOV group was significantly lower than in the CMV group (P < 0.05). At 6, 12, 24, 48, and 72 h after mechanical ventilation, PaO2/FiO2 in the HFOV group was significantly higher than in the CMV group, and the OI in the HFOV group was significantly lower than in the CMV group (P < 0.05). Mechanical ventilation time, oxygen inhalation time, and the incidence of air leakage were significantly lower in the HFOV than in the CMV group (P < 0.05). CONCLUSIONS: Overall, HFOV can effectively improve lung ventilation and oxygenation function, shorten ventilator treatment time, and reduce the incidence rate of air leakage for neonatal MAS, making it a safe and effective treatment option.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34886579

RESUMO

The COVID-19 epidemic has caused giant influences on people's life, and China's communities play an important role in dealing with these major public health events (MPHEs). Community as the grassroots autonomous organization has various significant functions in intervening in MPHEs. The community intervention follows a system which directly influences the anti-epidemic effectiveness. To explore the mechanism, we devise a theoretical system for community intervention, mainly consisting of "organizational structure", "functional performance" and "internal and external connections". Questionnaire surveys, the chi-square test, the independent sample T-test, and principal component analysis are used to identify the characteristics of Inner Mongolia Autonomous Region's (Inner Mongolia) community intervention. Through the empirical research, it is verified that the community intervention in MPHEs is the combination of "the structural response of the organization", "the performance of the community's own function", and "the establishment of internal and external connections". The central Inner Mongolia delivers the best performance in community intervention compared to eastern Inner Mongolia and western Inner Mongolia. The urban communities commonly perform better than that in the agricultural and pastoral areas. The built system and findings could provide a guidance for future community to improve its intervention capability.

7.
BMC Cancer ; 21(1): 1347, 2021 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-34923955

RESUMO

BACKGROUND: The accuracy of existing biomarkers for predicting the prognosis of hepatocellular carcinoma (HCC) is not satisfactory. It is necessary to explore biomarkers that can accurately predict the prognosis of HCC. METHODS: In this study, original transcriptome data were downloaded from The Cancer Genome Atlas (TCGA) database. Immune-related long noncoding ribonucleic acids (irlncRNAs) were identified by coexpression analysis, and differentially expressed irlncRNA (DEirlncRNA) pairs were distinguished by univariate analysis. In addition, the least absolute shrinkage and selection operator (LASSO) penalized regression was modified. Next, the cutoff point was determined based on the area under the curve (AUC) and Akaike information criterion (AIC) values of the 5-year receiver operating characteristic (ROC) curve to establish an optimal model for identifying high-risk and low-risk groups of HCC patients. The model was then reassessed in terms of clinicopathological features, survival rate, tumor-infiltrating immune cells, immunosuppressive markers, and chemotherapy efficacy. RESULTS: A total of 1009 pairs of DEirlncRNAs were recognized in this study, 30 of these pairs were included in the Cox regression model for subsequent analysis. After regrouping according to the cutoff point, we could more effectively identify factors such as aggressive clinicopathological features, poor survival outcomes, specific immune cell infiltration status of tumors, high expression level of immunosuppressive biomarkers, and low sensitivity to chemotherapy drugs in HCC patients. CONCLUSIONS: The nonspecific expression level signature involved with irlncRNAs shows promising clinical value in predicting the prognosis of HCC patients.

8.
J Dermatol ; 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34931339

RESUMO

Psoriasis is a chronic inflammatory skin disease with multiple genetic backgrounds, whose etiology and pathogenesis are still unclear. Complex T-cell immune imbalance has been demonstrated to play an important role in pathogenesis of psoriasis. This study reported that microRNA-126 (miR-126) expression was decreased in CD4+ T cells of both psoriasis patients and psoriasis-like mouse models and its expression was negatively correlated with the Psoriasis Area and Severity Index (PASI) score of psoriasis patients. Conditional Mir126 knockout in mouse CD4+ T cells can obviously aggravate the psoriasis-like dermatitis and promote T-helper (Th)1 and Th17 cells' infiltration in spleen of imiquimod (IMQ)-induced psoriasis-like mouse model. In addition, the mRNA expression of Il17a and Il17f were significantly increased in mouse naïve CD4+ T cells with Mir126 knockout after stimulating with CD3 and CD28. Compared with naïve CD4+ T cells, the expression of Mir126 was decreased in Th17 cells, and Mir126 knockout notably promoted the differentiation of naïve CD4+ T cells to Th17 cells as well as the mRNA expression of Il17a, Il17f, Rorc, and Il23R. Our results revealed that decreased miR-126 in psoriatic CD4+ T cells might accelerate the formation of skin lesions through promoting the differentiation of Th17 cells, thus suggesting a potential intervention target for psoriasis.

9.
Am Surg ; : 31348211054532, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34743609

RESUMO

Image-guided local thermal ablation (LTA) plays an important role in the treatment of hepatocellular carcinoma (HCC), especially in patients with HCC who are not suitable for hepatectomy. Radiofrequency ablation (RFA) and microwave ablation (MWA) are the most widely used LTA clinically. Radiofrequency ablation can achieve the best result; that is, a similar therapeutic effect as hepatectomy if the tumor ≤3 cm, while MWA can effectively ablate tumors ≤5 cm. Local thermal ablation has an advantage over liver resection in terms of minimally invasive surgery and can achieve a comparable prognosis and efficacy to liver resection. For borderline liver function, selecting LTA as the first-line therapy may bring more benefits to patients with cirrhosis background. In addition, a combination of multiple therapies for HCC is a good choice, such as LTA combined with transcatheter arterial chemoembolization (TACE), which can achieve a better prognosis than single therapy for larger tumors. For patients who are awaiting liver transplantation, LTA is a good choice. The main problem of LTA needed to be solved is to prevent the local tumor recurrence after ablation in patients with HCC.

10.
Front Cell Dev Biol ; 9: 709923, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722501

RESUMO

Vertebrate erythropoiesis involves nuclear and chromatin condensation at the early stages of terminal differentiation, which is a unique process to distinguish mature erythrocytes from erythroblasts. However, the underlying mechanisms of chromatin condensation during erythrocyte maturation remain elusive. Here, we reported a novel zebrafish mutant cas7 with erythroid maturation deficiency. Positional cloning showed that a single base mutation in tprb gene, which encodes nucleoporin translocated promoter region (Tpr), is responsible for the disrupted erythroid maturation and upregulation of erythroid genes, including ae1-globin and be1-globin. Further investigation revealed that deficient erythropoiesis in tprb cas7 mutant was independent on HIF signaling pathway. The proportion of euchromatin was significantly increased, whereas the percentage of heterochromatin was markedly decreased in tprb cas7 mutant. In addition, TPR knockdown in human K562 cells also disrupted erythroid differentiation and dramatically elevated the expression of globin genes, which suggests that the functions of TPR in erythropoiesis are highly conserved in vertebrates. Taken together, this study revealed that Tpr played vital roles in chromatin condensation and gene regulation during erythroid maturation in vertebrates.

11.
Infect Drug Resist ; 14: 4701-4715, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795487

RESUMO

Purpose: In clinical practice, the clinicopathological profiles and outcomes of patients infected with hepatitis B virus (HBV) are different between genotypes B and C. However, little is known about the potential mechanism and differences in specific biological pathways associated with the different genotype. This study aimed to compare the serum protein profile between patients infected with HBV genotype B and those infected with HBV genotype C. Patients and Methods: A total of 54 serum samples from patients with chronic HBV genotype B infection and those with chronic HBV genotype C infection, and healthy controls were used for the proteomic analysis (n = 18 samples in per group). Serum proteomic profiles were analyzed using data-independent acquisition (DIA)-based liquid chromatography-mass spectrometry to identify differentially expressed proteins (up- or downregulation of at least 1.5-fold) between serum samples from HBV patients infected with HBV genotype B and those infected with genotype C. Results: We identified 1010 proteins, 53 of which were differentially expressed between the serum samples of the healthy controls and those of HBV genotype B infected patients, and 59 that were differentially expressed between the samples of the healthy controls and those of HBV genotype C infected patients. Furthermore, our results indicated that two proteins identified as being differentially expressed (VWF and C8B) have potential as biomarkers for distinguishing genotype B infected HBV patients from those infected with genotype C. Conclusion: The results of our DIA-based quantitative proteomic analysis revealed that HBV genotypes B and C are associated with different molecular profiles and may provide fundamental information for further detailed investigations of the molecular mechanism underlying these differences.

12.
Zhongguo Gu Shang ; 34(11): 1077-82, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34812028

RESUMO

OBJECTIVE: To investigate the value of lumbar quantitative CT (QCT) in vertebroplasty for osteoporotic fracture combined with scoliosis. METHODS: The clinical data of 60 patients with osteoporotic fractures combined with different degrees of scoliosis treated by vertebroplasty from December 2017 to December 2019 were retrospectively analyzed. There were 18 males and 42 females, aged from 65 to 81 (72.63±3.34)years old. All patients were received QCT examination before surgery. According to the QCT value, the patients were divided into osteopenia group(QCT>80 g/L, 10 cases, 12 vertebrae), osteoporosis group(QCT 40-80 g/L, 35 cases, 48 vertebrae) and severe osteoporosis group(QCT<40 g/L, 15 cases, 22 vertebrae). The dispersion and leakage of bone cement in the injured vertebrae of patients with different degrees of QCT value were observed, and the QCT value in the selection of puncture point, correction of Cobb angle and recovery of vertebral height were analyzed in the patients. RESULTS: Among 60 cases of 82 vertebrae, 41 cases of 55 vertebrae were punctured by concave unilateral puncture, according for 67.07%. Among them, there were 2 cases with 2 vertebrae in osteopenia group, 26 cases with 35 vertebrae in osteoporosis group, and 13 cases with 18 vertebrae in severe osteoporosis group. There was significant difference in the number of cases with unilateral or bilateral puncture among the three groups (χ2=13.699, P=0.001); there was no significant difference in the number of cases with bone cement leakage among the three groups (χ2=1.403, P=0.496). The Cobb angle of scoliosis was significantly differentbetween preoperative and postoperative follow-up(P<0.05);the height of injured vertebral body was significantly different between preoperative and postoperative follow-up (P<0.05). CONCLUSION: For patients with osteoporotic fracture combined with scoliosis undergoing vertebroplasty, the severity of osteoporosis should be determined according to lumbar QCT detection, and the concave side of scoliosis should be selected for puncture, which is conducive to improving scoliosis, restoring spinal stability and improving surgical safety.


Assuntos
Fraturas por Compressão , Fraturas por Osteoporose , Escoliose , Fraturas da Coluna Vertebral , Vertebroplastia , Idoso , Cimentos Ósseos , Feminino , Humanos , Masculino , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
Mater Horiz ; 8(2): 589-596, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34821275

RESUMO

Severe corrosion of Mg and Mg alloys is a major issue hindering their wider application in transportation industry, medical implants and aqueous batteries. Previously, no Mg-based material has been found with a significantly lower corrosion rate than that of ultra-high-purity Mg, i.e. 0.25 mm y-1 in concentrated NaCl solution. In this work for the first time, highly corrosion-resistant Mg is found to be accomplishable by Ca micro-alloying, bringing "stainless Mg" closer. The designed Mg-Ca lean alloys possess incredibly low corrosion rates, less than 0.1 mm y-1 in 3.5 wt% NaCl solution, which are significantly lower than that of ultra-high-purity Mg and all Mg alloys reported thus far. The outstanding corrosion resistance is attributed to inhibition of cathodic water reduction kinetics, impurities stabilizing and a protective surface film induced by Ca micro-alloying. Combined with the environmental benignity and economic viability, Ca micro-alloying renders huge feasibility on developing advanced Mg-based materials for diverse applications.

14.
Nanomaterials (Basel) ; 11(11)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34835792

RESUMO

Formic acid (FA) is found to be a potential candidate for the storage of hydrogen. For dehydrogenation of FA, the supports of our catalysts were acquired by conducting ZnCl2 treatment and carbonation for biomass waste. The texture and surface properties significantly affected the size and dispersion of Pd and its interaction with the support so as to cause the superior catalytic performance of catalysts. Microporous carbon obtained by carbonization of ZnCl2 activated peanut shells (CPS-ZnCl2) possessing surface areas of 629 m2·g-1 and a micropore rate of 73.5%. For ZnCl2 activated melon seed (CMS-ZnCl2), the surface area and micropore rate increased to 1081 m2·g-1 and 80.0%, respectively. In addition, the introduction of ZnCl2 also caused the increase in surface O content and reduced the acidity of the catalyst. The results represented that CMS-ZnCl2 with uniform honeycomb morphology displayed the best properties, and the as-prepared Pd/CMS-ZnCl2 catalyst afforded 100% hydrogen selectivity as well as excellent catalytic activity with an initial high turnover number (TON) value of 28.3 at 30 °C and 100.1 at 60 °C.

15.
Environ Sci Technol ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34846873

RESUMO

In aquaculture, it is important to raise the nitrogen recovery efficiency (NRE) to improve sustainability. To achieve this, recovery of microbial protein (RMP), instead of nitrification/denitrification in conventional wastewater treatment, is a promising approach whose microbiological mechanisms must be characterized. Here, periodic RMP was conducted in an in situ biofloc-based aquaculture system (IBAS) and a separating assimilation reactor-based recirculating aquaculture system (SRAS). Kinetic analysis indicated that a microbial biomass level of 3 g L-1 was optimal for inorganic N removal, and excess biomass was harvested to improve the NRE. Unlike the IBAS, the SRAS eliminated the fluctuation in water quality caused by the RMP. Periodic RMP significantly increased the NRE to 44-57% by promoting the filamentous bacterium Herpetosiphon and suppressing anaerobic denitrifiers. Aerobic chemoheterotrophy was the main microbial metabolic process for energy. After RMP, nitrate reductase-encoded functional genes (napA and narG) significantly decreased, while nitrite reductase-encoded functional genes, especially nirK, significantly increased. Co-occurrence networks analysis indicated that the cooperation and competition among organic matter degraders, filamentous bacteria, nitrifiers, and denitrifiers determined the microbial protein yield. These results provide fundamental insights into the influence of the RMP on microbial communities and functions, which is important for realizing sustainable aquaculture.

16.
Dermatol Online J ; 27(8)2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34755965

RESUMO

Adenodermatofibroma is a newly recognized variant of fibrous histiocytoma (dermatofibroma), a benign lesion frequently encountered in dermatologic practice. There are many established variants of fibrous histiocytoma but there are only eight reported cases of this specific variant in the literature. This report reviews a case of an adenodermatofibroma presenting as a large, firm, atrophic plaque on the thigh. Histopathologic findings showed dilated glandular structures with apocrine features within a fibrohistiocytic cellular infiltrate, consistent with the diagnosis. We review the characteristic findings of adenodermatofibroma, discuss the differential diagnosis, and examine current theories speculating the origin of apocrine glands present within these lesions.

17.
Front Med (Lausanne) ; 8: 720401, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778286

RESUMO

Background: Laparoscopy is considered to be the gold standard in the evaluation of causes leading to infertility. Hysterosalpingography (HSG) permits indirect visualization of the cervical canal, uterine cavity, and tube patency, which is helpful for evaluating the causes of infertility. Objective: This study aimed to detect tubal abnormalities in infertile women by HSG or laparoscopy and determine the value of HSG in diagnosing fallopian tube status. Methods: The study group consisted of 1,276 patients. HSG was performed as a preliminary test for the evaluation of fallopian tube status. Women were subjected to laparoscopic examination on evidence of HSG abnormalities. Results: The negative predictive value of HSG for detecting patency or occlusion for the right/left tube was 92.08 and 95.44%, respectively. The kappa values for the consistent diagnosis in the right/left tube were 0.470 and 0.574, respectively. In cases of low patency of the right/left tube, there was a greater than a 40% chance for the tube to be patent, and the remaining high probability was pelvic adhesion. The positive predictive value of HSG for detecting patency or occlusion for both tubes was 87.2%. The kappa value was 0.898 [95% CI (0.838, 0.937), p < 0.001], which meant that the diagnostic accuracy of HSG for both tube patency/occlusion was explicit. The kappa value for the diagnosis of hydrosalpinx (especially for bilateral tube hydrosalpinx) was 0.838 [95% CI (0.754, 0.922), p < 0.001], and the diagnostic accuracy for HSG was 79.8, 67.9, and 72.4%, respectively. Conclusion: The current study concluded that HSG is a good diagnostic modality to detect tube abnormalities in infertile patients. HSG and laparoscopy are complementary to each other and whenever the patient is undertaken for diagnosis of infertility. Cost-effective HSG had good predictive value in identifying tubal factor infertility.

18.
Theranostics ; 11(20): 9967-9987, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815798

RESUMO

Background: BRCA1 plays critical roles in mammary gland development and mammary tumorigenesis. And loss of BRCA1 induces mammary tumors in a stochastic manner. These tumors present great heterogeneity at both intertumor and intratumor levels. Methods: To comprehensively elucidate the heterogeneity of BRCA1 deficient mammary tumors and the underlying mechanisms for tumor initiation and progression, we conducted bulk and single cell RNA sequencing (scRNA-seq) on both mammary gland cells and mammary tumor cells isolated from Brca1 knockout mice. Results: We found the BRCA1 deficient tumors could be classified into four subtypes with distinct molecular features and different sensitivities to anti-cancer drugs at the intertumor level. Whereas within the tumors, heterogeneous subgroups were classified mainly due to the different activities of cell proliferation, DNA damage response/repair and epithelial-to-mesenchymal transition (EMT). Besides, we reconstructed the BRCA1 related mammary tumorigenesis to uncover the transcriptomes alterations during this process via pseudo-temporal analysis of the scRNA-seq data. Furthermore, from candidate markers for BRCA1 mutant tumors, we discovered and validated one oncogene Mrc2, whose loss could reduce mammary tumor growth in vitro and in vivo. Conclusion: Our study provides a useful resource for better understanding of mammary tumorigenesis induced by BRCA1 deficiency.

19.
Nat Commun ; 12(1): 6653, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34789768

RESUMO

BRCA1-BARD1 heterodimers act in multiple steps during homologous recombination (HR) to ensure the prompt repair of DNA double strand breaks. Dysfunction of the BRCA1 pathway enhances the therapeutic efficiency of poly-(ADP-ribose) polymerase inhibitors (PARPi) in cancers, but the molecular mechanisms underlying this sensitization to PARPi are not fully understood. Here, we show that cancer cell sensitivity to PARPi is promoted by the ring between ring fingers (RBR) protein RNF19A. We demonstrate that RNF19A suppresses HR by ubiquitinating BARD1, which leads to dissociation of BRCA1-BARD1 complex and exposure of a nuclear export sequence in BARD1 that is otherwise masked by BRCA1, resulting in the export of BARD1 to the cytoplasm. We provide evidence that high RNF19A expression in breast cancer compromises HR and increases sensitivity to PARPi. We propose that RNF19A modulates the cancer cell response to PARPi by negatively regulating the BRCA1-BARD1 complex and inhibiting HR-mediated DNA repair.

20.
Cancers (Basel) ; 13(22)2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34830921

RESUMO

Systemic inflammation is thought to underlie many of the metabolic manifestations of cachexia in cancer patients. The complement system is an important component of innate immunity that has been shown to contribute to metabolic inflammation. We hypothesized that systemic inflammation in patients with cancer cachexia was associated with complement activation. Systemic C3a levels were higher in cachectic patients with inflammation (n = 23, C-reactive protein (CRP) ≥ 10 mg/L) as compared to patients without inflammation (n = 26, CRP < 10 mg/L) or without cachexia (n = 13) (medians 102.4 (IQR 89.4-158.0) vs. 81.4 (IQR 47.9-124.0) vs. 61.6 (IQR 46.8-86.8) ng/mL, respectively, p = 0.0186). Accordingly, terminal complement complex (TCC) concentrations gradually increased in these patient groups (medians 2298 (IQR 2022-3058) vs. 1939 (IQR 1725-2311) vs. 1805 (IQR 1552-2569) mAU/mL, respectively, p = 0.0511). C3a and TCC concentrations were strongly correlated (rs = 0.468, p = 0.0005). Although concentrations of C1q and mannose-binding lectin did not differ between groups, C1q levels were correlated with both C3a and TCC concentrations (rs = 0.394, p = 0.0042 and rs = 0.300, p = 0.0188, respectively). In conclusion, systemic inflammation in patients with cancer cachexia is associated with the activation of key effector complement factors. The correlations between C1q and C3a/TCC suggest that the classical complement pathway could play a role in complement activation in patients with pancreatic cancer.

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