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2.
Mil Med Res ; 8(1): 60, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819142

RESUMO

BACKGROUND: The burden of kidney, bladder, and prostate cancers has changed in recent decades. This study aims to investigate the global and regional burden of, and attributable risk factors for genitourinary cancers during the past 30 years. METHODS: We extracted data of kidney, bladder, and prostate cancers from the Global Burden of Disease 2019 database, including incidence, mortality, disability-adjusted life-years (DALYs), and attributable risk factors from 1990 to 2019. Estimated annual percentage changes (EAPC) were calculated to assess the changes in age-standardized incidence rate, age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR). The associations between cancers burden and socio-demographic index (SDI) were also analyzed. RESULTS: Compared with 1990, the global incident cases in 2019 were higher by 154.78%, 123.34%, and 169.11% for kidney, bladder, and prostate cancers, respectively. During the 30-year study period, there was a downward trend in ASMR and ASDR for bladder cancer (EAPC = - 0.68 and - 0.83, respectively) and prostate cancer (EAPC = - 0.75 and - 0.71, respectively), but an upward trend for kidney cancer (EAPC = 0.35 and 0.12, respectively). Regions and countries with higher SDI had higher incidence, mortality, and DALYs for all three types of cancers. The burden of bladder and prostate cancers was mainly distributed among older men, whereas the burden of kidney cancer increased among middle-aged men. Smoking related mortality and DALYs decreased, but high body mass index (BMI) and high fasting plasma glucose (FPG) related mortality and DALYs increased among kidney, bladder, and prostate cancers during the study period. CONCLUSIONS: Kidney, bladder, and prostate cancers remain major global public health challenges, but with distinct trend for different disease entity across different regions and socioeconomic status. More proactive intervention strategies, at both the administrative and academic levels, based on the dynamic changes, are needed.

3.
Int J Med Robot ; : e2350, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34773438

RESUMO

BACKGROUND: This study aimed to examine the effectiveness of microsurgery practice during an interval in robotic surgical training. METHODS: Two participant groups with 30 trainees each practiced Thread the Rings 1 on a dV-Trainer. There were four 2-h training sessions, with a 72-h interval between each session. Group A received no additional training during the study period. During every interval, Group B practiced a similar 2-h ring penetration exercise using a microscope three times (once every 24 h). RESULTS: The 72-h delay between two sessions for Group A caused the forgetting effect. For Group B, additional microscope-based training aided memory retention. After the training session, Group B presented a significantly higher score than Group A in Thread the Ring 1 learning curves. CONCLUSIONS: Adding microsurgical skill training into the basic robotic-surgery training curriculum could be helpful because additional trainings with a binocular microscope could improve robotic surgical skill levels. This article is protected by copyright. All rights reserved.

4.
Updates Surg ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635985

RESUMO

Enhanced recovery after surgery (ERAS) pathway comprises a set of comprehensive elements which have been reported to enhance patient postoperative prognosis. In the current study, we aimed to evaluate the effectiveness of the ERAS in patients undergoing laparoscopic adrenal resection. A retrospective review was performed to compare the outcomes of patients undergoing adrenalectomy for primary aldosteronism between the pre-ERAS period and the ERAS era. Data was generated from the traditional surgical period (September 1, 2019, to December 31, 2019) and the ERAS period (September 1, 2020, to December 31, 2020), respectively. Forty-seven adrenalectomy patients were enrolled (pre-ERAS, n = 21; ERAS, n = 26) in analysis. The results revealed that both total length of hospital stay and postoperative length of stay decreased in the ERAS period compared with the pre-ERAS period (14.19 ± 4.96 vs 11.27 ± 4.37, p = 0.015; 5.43 ± 1.08 vs 3.31 ± 0.97, p < 0.001). The medical expenses decreased significantly in the ERAS group (p < 0.05). While, the surgery-related complications, including urinary retention, retroperitoneal effusion and gastrointestinal discomfort, possessed no statistical difference. The ERAS pathway was safe and feasible for adrenalectomy in patients with primary aldosteronism. The ERAS could promote patients to quickly recover from the postoperative status to a physiological state, and decrease the length of hospitalization and medical cost after surgery.

5.
Front Cell Dev Biol ; 9: 720349, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604222

RESUMO

NF-κB signaling is very important in cancers. However, the role of BRCC3-associated NF-κB signaling activation in bladder cancer remains to be characterized. Western blotting and IHC of tissue microarray were used to confirm the abnormal expression of BRCC3 in bladder cancer. Growth curve, colony formation, soft agar assay and Xenograft model were performed to identify the role of BRCC3 over-expression or knock-out in bladder cancer. Further, RNA-Seq and luciferase reporter assays were used to identify the down-stream signaling pathway. Finally, co-immunoprecipitation and fluorescence confocal assay were performed to verify the precise target of BRCC3. Here, we found that high expression of BRCC3 promoted tumorigenesis through targeting the TRAF2 protein. BRCC3 expression is up-regulated in bladder cancer patients which indicates a negative prognosis. By in vitro and in vivo assays, we found genetic BRCC3 ablation markedly blocks proliferation, viability and migration of bladder cancer cells. Mechanistically, RNA-Seq analysis shows that NF-κB signaling is down-regulated in BRCC3-deficient cells. BRCC3 binds to and synergizes with TRAF2 to activate NF-κB signaling. Our results indicate that high BRCC3 expression activates NF-κB signaling by targeting TRAF2 for activation, which in turn facilitates tumorigenesis in bladder cancer. This finding points to BRCC3 as a potential target in bladder cancer patients.

6.
Eur J Clin Microbiol Infect Dis ; 40(12): 2669-2676, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34625887

RESUMO

The humoral and cellular immunity of convalescent COVID-19 patients is involved in pathogenesis and vaccine immunity. In this study, through CoV-psV neutralization assay and IFN-γ ELISpot testing in 30 cases of COVID-19 patients after 9 months post-SARS-CoV-2 infection, it found that the ratio of memory/naive CD4+ T lymphocytes cells and levels of anti-SARS-CoV-2-IgM and RBD-IgM were slightly but significantly higher in COVID-19 severe convalescent patients than that in non-severe patients. The specific cellular and humoral immunity against SARS-CoV-2 were detectable, regardless of the severity of the disease in the acute phase. This information may help understanding the immune status after SARS-CoV-2 infection.


Assuntos
Linfócitos T CD4-Positivos/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Anticorpos Antivirais/sangue , COVID-19/sangue , ELISPOT , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/genética , SARS-CoV-2/fisiologia
7.
Pathol Res Pract ; 227: 153610, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34601398

RESUMO

The coronavirus disease 2019(COVID-19) is recognized as systemic inflammatory response syndrome. It was demonstrated that a rapid increase of cytokines in the serum of COVID-19 patients is associated with the severity of disease. However, the mechanisms of the cytokine release are not clear. By using immunofluorescence staining we found that the number of CD11b positive immune cells including macrophages in the spleens of died COVID-19 patients, was significantly higher than that of the control patients. The incidence of apoptosis as measured by two apoptotic markers, TUNEL and cleaved caspase-3, in COVID-19 patients' spleen cells is higher than that in control patients. By double immunostaining CD11b or CD68 and SARS-CoV-2 spike protein, it was found that up to 67% of these immune cells were positive for spike protein, suggesting that viral infection might be associated with apoptosis in these cells. Besides, we also stained the autophagy-related molecules (p-Akt、p62 and BCL-2) in spleen tissues, the results showed that the number of positive cells was significantly higher in COVID-19 group. And compared with non-COVID-19 patients, autophagy may be inhibited in COVID-19 patients. Our research suggest that SARS-CoV-2 may result in a higher rate of apoptosis and a lower rate of autophagy of immune cells in the spleen of COVID-19 patients. These discoveries may increase our understanding of the pathogenesis of COVID-19.


Assuntos
Apoptose , Autofagia , COVID-19/patologia , SARS-CoV-2/patogenicidade , Baço/patologia , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Autopsia , Biomarcadores/análise , Antígeno CD11b/análise , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/virologia , Estudos de Casos e Controles , Caspase 3/análise , Interações Hospedeiro-Patógeno , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Fosforilação , Proteínas Proto-Oncogênicas c-akt/análise , Proteínas Proto-Oncogênicas c-bcl-2/análise , SARS-CoV-2/imunologia , Proteína Sequestossoma-1/análise , Glicoproteína da Espícula de Coronavírus/análise , Baço/imunologia , Baço/virologia
8.
Urol Int ; : 1-5, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34515252

RESUMO

OBJECTIVES: This study aimed to describe a novel double-sheath vacuum suction minimally invasive percutaneous nephrolithotomy (mini-PCNL) to overcome the deficiencies of the conventional procedure. PATIENTS AND METHODS: Between March 2019 and December 2019, 65 patients (37 males and 28 females) with a mean age of 41 years (range 23-69) underwent mini-PCNL with double-sheath vacuum suction. It consisted of an F20 Y-shaped sheath as an outer sheath and an F16 Y-shaped sheath as an inner sheath, in which the inner sheath was longer than the outer sheath. The oblique arm of the outer sheath and the inner sheath was connected to the perfusion inflow and the vacuum suction, respectively. A 550-µm holmium-YAG laser was introduced for stone fragmentation through the working channel of the mini-nephroscope, which was no longer connected to the perfusion fluid. RESULTS: All procedures were successful. Mean operation time was 50.2 min (range 39-83). Mean hemoglobin decrease was 5.2 g/L (range 1.0-15.5), and no patient needed a blood transfusion. One patient (1.5%) with low fever (<38°C) at day 1 had returned to normal at day 2 without administration of antibiotics. There were no Clavien grade 2-4 complications. Mean postoperative hospital stay was 2.4 days (range 2-6). The initial stone-free rate of PCNL was 81.53% (53 of 65 patients). One month after surgery, the final stone-free rate increased to 90.77% (59/65 patients). CONCLUSIONS: The double-sheath vacuum suction mini-PCNL is a safe and effective modality for large renal stones, which might increase the efficiency of stone extraction with low intrapelvic pressure.

10.
Front Pharmacol ; 12: 683296, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539392

RESUMO

Background: In addition to supportive therapy, antiviral therapy is an effective treatment for coronavirus disease 2019 (COVID-19). Objective: To compare the efficacy and safety of favipiravir and umifenovir (Arbidol) to treat COVID-19 patients. Methods: We conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Enrolled patients with initial symptoms within 12 days were randomly assigned in a 1:1 ratio to receive conventional therapy plus Arbidol (200 mg*3/day) or favipiravir (1600 mg*2/first day followed by 600 mg*2/day) for 7 days. The primary outcome was the clinical recovery rate at day 7 of drug administration (relief for pyrexia and cough, respiratory frequency ≤24 times/min; oxygen saturation ≥98%). Latency to relief for pyrexia and cough and the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV)/mechanical ventilation (MV) were the secondary outcomes. Safety data were collected for 17 days. Results: A total of 240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive favipiravir (116 assessed), and 120 patients were assigned to receive Arbidol (120 assessed). The clinical recovery rate at day 7 of drug administration did not significantly differ between the favipiravir group (71/116) and Arbidol group (62/120) (p = 0.1396, difference in recovery rate: 0.0954; 95% CI: -0.0305∼0.2213). Favipiravir contributed to relief for both pyrexia (difference: 1.70 days, p < 0.0001) and cough (difference: 1.75 days, p < 0.0001). No difference was observed in the AOT or NMV/MV rate (both p > 0.05). The most frequently observed favipiravir-associated adverse event was increased serum uric acid (16/116, OR: 5.52, p = 0.0014). Conclusion: Among patients with COVID-19, favipiravir, compared to Arbidol, did not significantly improve the clinical recovery rate at day 7. Favipiravir significantly improved the latency to relieve pyrexia and cough. Adverse effects caused by favipiravir are mild and manageable.

11.
Mil Med Res ; 8(1): 54, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34588004

RESUMO

Periodontitis has been proposed as a novel risk factor of genitourinary cancers: although periodontitis and genitourinary cancers are two totally distinct types of disorders, epidemiological and clinical studies, have established associations between them. Dysbiosis of oral microbiota has already been established as a major factor contributing to periodontitis. Recent emerging epidemiological evidence and the detection of oral microbiota in genitourinary organs indicate the presence of an oral-genitourinary axis and oral microbiota may be involved in the pathogenesis of genitourinary cancers. Therefore, oral microbiota provides the bridge between periodontitis and genitourinary cancers. We have carried out this narrative review which summarizes epidemiological studies exploring the association between periodontitis and genitourinary cancers. We have also highlighted the current evidence demonstrating the capacity of oral microbiota to regulate almost all hallmarks of cancer, and proposed the potential mechanisms of oral microbiota in the development of genitourinary cancers.

12.
Nanoscale ; 13(37): 15743-15754, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34528655

RESUMO

Extensive full-thickness skin defect lacks self-healing ability. Tissue engineering wound dressing is considered as the most promising approach to promote wound healing. In this study, a series of biocompatible and hemostatic nanofiber dressings were fabricated. Soy protein isolate (SPI) and poly(L-lactic acid) (PLLA) solutions were mixed in certain proportions for high-voltage electrospinning. The obtained products were coded as SPNF-n (n = 100, 80, 60 and 40, corresponding to the weight percentage of PLLA solution). We found that SPNF-n (n = 100, 80, 60 and 40) could facilitate the adhesion and spread of L929 cells. In particular, SPNF-80 was capable of promoting fibroblast proliferation and diminishing inflammation. Compared with the neat PLLA film (SPNF-100), the biosafety and hemostatic effect of SPNF-80 got significantly improved. The hemostatic effect of SPNF-80 was comparable with that of a commercial gelatin sponge. In vivo wound healing assay demonstrated that SPNF-80 could accelerate the wound healing process by enhancing vascularization, re-epithelization and collagen formation. In conclusion, our results reveal that SPNF-n has good biocompatibility and hemostatic effect, and exhibits great application potential in wound healing.


Assuntos
Hemostáticos , Nanofibras , Hemostáticos/farmacologia , Pele , Proteínas de Soja , Cicatrização
13.
JCI Insight ; 6(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34499617

RESUMO

Proline rich 11 (PRR11), a novel tumor-related gene, has been identified in different tumors. However, the relevant biological functions of PRR11 in human clear cell renal cell carcinoma (ccRCC) have not been studied. In this study, we first identified PRR11 as a biomarker of ccRCC and predictor of poor prognosis by bioinformatics. Then, we showed that PRR11 silencing substantially reduced ccRCC cell proliferation and migration in vitro and in vivo. Importantly, we found that PRR11 induced the degradation of the E2F1 protein through its interaction with E2F1, and PRR11 reduced the stability of the E2F1 protein in ccRCC cells, thereby affecting cell cycle progression. Further results indicated that the downregulation of E2F1 expression partially reversed the changes in ccRCC cell biology caused by PRR11 deletion. In addition, we showed that PRR11 was a target gene of c-Myc. The transcription factor c-Myc may have promoted the expression of PRR11 in ccRCC cells by binding to the PRR11 promoter region, thereby accelerating the progression of ccRCC. In summary, we found that PRR11 served as an oncogene in ccRCC, and PRR11 reduced the protein stability of E2F1 and could be activated by c-Myc.

14.
Cancer Cell Int ; 21(1): 461, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34461908

RESUMO

BACKGROUND: New effective drugs for prostate cancer (PCa) treatment are urgently needed. Avasimibe was recently identified as a promising drug for anticancer therapies. The main purpose of this study was to explore the effects and the underlying mechanisms of avasimibe in prostate cancer. METHODS: In this study, MTT and clonogenic survival assays were performed to detect cell proliferation after avasimibe treatment. The effect of avasimibe on cell migration was measured by wound healing and transwell migration assays. Cell cycle distribution and apoptosis were detected by flow cytometry. Immunofluorescence staining and western blot analysis were used to detect the expression of cell cycle-related proteins and epithelial-mesenchymal transition (EMT)-related proteins. In vivo, the antitumour effects of avasimibe were evaluated using a xenograft model and pulmonary metastasis model. RESULTS: The study found that avasimibe suppresses tumour growth and triggers G1 phase arrest. Moreover, the expression of the cell cycle-related proteins CDK2/4/6, Cyclin D1 and Cyclin A1 + A2 was significantly increased and p21 expression was decreased after avasimibe treatment. The migration of PCa cells was attenuated after treatment with avasimibe, followed by the downregulation of the expression of the EMT-related proteins N-cadherin, ß-catenin, vimentin, Snail and MMP9 and upregulation of E-cadherin expression. Moreover, E2F-1 was elevated after treatment with avasimibe. After knockdown of E2F-1 expression, the inhibition of cell proliferation and migration caused by avasimibe was significantly recovered. The results of the xenograft model showed that avasimibe suppressed tumour growth in vivo. Immunofluorescence staining revealed lower levels of Ki67 and higher levels of E2F-1 in tumour tissues of the avasimibe group than those of the control group. A pulmonary metastasis model also confirmed the inhibition of PCa metastasis by avasimibe. The number of lung metastatic foci in the avasimibe group was significantly decreased compared with that in the control group. CONCLUSIONS: Our results suggest that avasimibe can suppress tumour proliferation and metastasis via the E2F-1 signalling pathway. These findings demonstrate the potential of avasimibe as a new effective drug for PCa treatment.

15.
Intell Med ; 1(1): 3-9, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34447599

RESUMO

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has put radiologists at a higher risk of infection during the computer tomography (CT) examination for the patients. To help settling these problems, we adopted a remote-enabled and automated contactless imaging workflow for CT examination by the combination of intelligent guided robot and automatic positioning technology to reduce the potential exposure of radiologists to 2019 novel coronavirus (2019-nCoV) infection and to increase the examination efficiency, patient scanning accuracy and better image quality in chest CT imaging . Methods: From February 10 to April 12, 2020, adult COVID-19 patients underwent chest CT examinations on a CT scanner using the same scan protocol except with the conventional imaging workflow (CW group) or an automatic contactless imaging workflow (AW group) in Wuhan Leishenshan Hospital (China) were retrospectively and prospectively enrolled in this study. The total examination time in two groups was recorded and compared. The patient compliance of breath holding, positioning accuracy, image noise and signal-to-noise ratio (SNR) were assessed by three experienced radiologists and compared between the two groups. Results: Compared with the CW group, the total positioning time of the AW group was reduced ((118.0 ± 20.0) s vs. (129.0 ± 29.0) s, P = 0.001), the proportion of scanning accuracy was higher (98% vs. 93%), and the lung length had a significant difference ((0.90±1.24) cm vs. (1.16±1.49) cm, P = 0.009). For the lesions located in the pulmonary centrilobular and subpleural regions, the image noise in the AW group was significantly lower than that in the CW group (centrilobular region: (140.4 ± 78.6) HU vs. (153.8 ± 72.7) HU, P = 0.028; subpleural region: (140.6 ± 80.8) HU vs. (159.4 ± 82.7) HU, P = 0.010). For the lesions located in the peripheral, centrilobular and subpleural regions, SNR was significantly higher in the AW group than in the CW group (centrilobular region: 6.6 ± 4.3 vs. 4.9 ± 3.7, P = 0.006; subpleural region: 6.4 ± 4.4 vs. 4.8 ± 4.0, P < 0.001). Conclusions: The automatic contactless imaging workflow using intelligent guided robot and automatic positioning technology allows for reducing the examination time and improving the patient's compliance of breath holding, positioning accuracy and image quality in chest CT imaging.

16.
Intell Med ; 1(1): 10-15, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34447600

RESUMO

During the highly infectious pandemic of coronavirus disease 2019 (COVID-19), artificial intelligence (AI) has provided support in addressing challenges and accelerating achievements in controlling this public health crisis. It has been applied in fields varying from outbreak forecasting to patient management and drug/vaccine development. In this paper, we specifically review the current status of AI-based approaches for patient management. Limitations and challenges still exist, and further needs are highlighted.

18.
Signal Transduct Target Ther ; 6(1): 256, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234102

RESUMO

We collected blood from coronavirus disease 2019 (COVID-19) convalescent individuals and investigated SARS-CoV-2-specific humoral and cellular immunity in these discharged patients. Follow-up analysis in a cohort of 171 patients at 4-11 months after the onset revealed high levels of IgG antibodies. A total of 78.1% (164/210) of the specimens tested positive for neutralizing antibody (NAb). SARS-CoV-2 antigen peptide pools-stimulated-IL-2 and -IFN-γ response can distinguish COVID-19 convalescent individuals from healthy donors. Interestingly, NAb survival was significantly affected by the antigen peptide pools-stimulated-IL-2 response, -IL-8 response, and -IFN-γ response. The antigen peptide pools-activated CD8+ T cell counts were correlated with NAb. The antigen peptide pools-activated natural killer (NK) cell counts in convalescent individuals were correlated with NAb and disease severity. Our data suggested that the development of NAb is associated with the activation of T cells and NK cells. Our work provides a basis for further analysis of the protective immunity to SARS-CoV-2 and for understanding the pathogenesis of COVID-19. It also has implications for the development of an effective vaccine for SARS-CoV-2 infection.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Convalescença , Citocinas/imunologia , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Imunoglobulina G/imunologia , Subpopulações de Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Clin Sci (Lond) ; 135(13): 1591-1608, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34195782

RESUMO

Benign prostatic hyperplasia (BPH) is a quite common illness but its etiology and mechanism remain unclear. Neural epidermal growth factor-like like 2 (NELL2) plays multifunctional roles in neural cell growth and is strongly linked to the urinary tract disease. Current study aims to determine the expression, functional activities and underlying mechanism of NELL2 in BPH. Human prostate cell lines and tissues from normal human and BPH patients were utilized. Immunohistochemical staining, immunofluorescent staining, RT-polymerase chain reaction (PCR) and Western blotting were performed. We further generated cell models with NELL2 silenced or overexpressed. Subsequently, proliferation, cycle, and apoptosis of prostate cells were determined by cell counting kit-8 (CCK-8) assay and flow cytometry analysis. The epithelial-mesenchymal transition (EMT) and fibrosis process were also analyzed. Our study revealed that NELL2 was up-regulated in BPH samples and localized in the stroma and the epithelium compartments of human prostate tissues. NELL2 deficiency induced a mitochondria-dependent cell apoptosis, and inhibited cell proliferation via phosphorylating extracellular signal-regulated kinase 1/2 (ERK1/2) activation. Additionally, suppression of ERK1/2 with U0126 incubation could significantly reverse NELL2 deficiency triggered cell apoptosis. Consistently, overexpression of NELL2 promoted cell proliferation and inhibited cell apoptosis. However, NELL2 interference was observed no effect on EMT and fibrosis process. Our novel data demonstrated that up-regulation of NELL2 in the enlarged prostate could contribute to the development of BPH through enhancing cell proliferation and inhibited a mitochondria-dependent cell apoptosis via the ERK pathway. The NELL2-ERK system might represent an important target to facilitate the development of future therapeutic approaches in BPH.


Assuntos
Apoptose , Proliferação de Células , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Próstata/enzimologia , Hiperplasia Prostática/enzimologia , Adulto , Idoso , Estudos de Casos e Controles , Linhagem Celular , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/enzimologia , Mitocôndrias/genética , Mitocôndrias/patologia , Proteínas do Tecido Nervoso/genética , Fosforilação , Próstata/patologia , Hiperplasia Prostática/genética , Hiperplasia Prostática/patologia , Transdução de Sinais , Adulto Jovem
20.
Lancet Infect Dis ; 21(12): 1654-1664, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34324836

RESUMO

BACKGROUND: SARS-CoV-2 has caused millions of deaths, and, since Aug 11, 2020, 20 intramuscular COVID-19 vaccines have been approved for use. We aimed to evaluate the safety and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in adults without COVID-19 from China. METHOD: This was a randomised, single-centre, open-label, phase 1 trial done in Zhongnan Hospital (Wuhan, China), to evaluate the safety and immunogenicity of the Ad5-nCoV vaccine by aerosol inhalation in adults (≥18 years) seronegative for SARS-CoV-2. Breastfeeding or pregnant women and people with major chronic illnesses or history of allergies were excluded. Participants were enrolled and randomly assigned (1:1:1:1:1) into five groups to be vaccinated via intramuscular injection, aerosol inhalation, or both. Randomisation was stratified by sex and age (18-55 years or ≥56 years) using computer-generated randomisation sequences (block sizes of five). Only laboratory staff were masked to group assignment. The participants in the two aerosol groups received an initial high dose (2 × 1010 viral particles; HDmu group) or low dose (1 × 1010 viral particles; LDmu group) of Ad5-nCoV vaccine on day 0, followed by a booster on day 28. The mixed vaccination group received an initial intramuscular (5 × 1010 viral particles) vaccine on day 0, followed by an aerosolised booster (2 × 1010 viral particles) vaccine on day 28 (MIX group). The intramuscular groups received one dose (5 × 1010 viral particles; 1Dim group) or two doses (10 × 1010 viral particles; 2Dim group) of Ad5-nCoV on day 0. The primary safety outcome was adverse events 7 days after each vaccination, and the primary immunogenicity outcome was anti-SARS-CoV-2 spike receptor IgG antibody and SARS-CoV-2 neutralising antibody geometric mean titres at day 28 after last vaccination. This trial is registered with ClinicalTrials.gov, number NCT04552366. FINDINGS: Between Sept 28, 2020, and Sept 30, 2020, 230 individuals were screened for inclusion, of whom 130 (56%) participants were enrolled into the trial and randomly assigned into one of the five groups (26 participants per group). Within 7 days after vaccination, adverse events occurred in 18 (69%) in the HDmu group, 19 (73%) in the LDmu group, 19 (73%) in the MIX group, 19 (73%) in the 1Dim group, and 15 (58%) in the 2Dim group. The most common adverse events reported 7 days after the first or booster vaccine were fever (62 [48%] of 130 participants), fatigue (40 [31%] participants), and headache (46 [35%] participants). More adverse events were reported in participants who received intramuscular vaccination, including participants in the MIX group (49 [63%] of 78 participants), than those who received aerosol vaccine (13 [25%] of 52 participants) after the first vaccine vaccination. No serious adverse events were noted within 56 days after the first vaccine. At days 28 after last vaccination, geometric mean titres of SARS-CoV-2 neutralising antibody was 107 (95% CI 47-245) in the HDmu group, 105 (47-232) in the LDmu group, 396 (207-758) in the MIX group, 95 (61-147) in the 1Dim group, and 180 (113-288) in the 2Dim group. The geometric mean concentrations of receptor binding domain-binding IgG was 261 EU/mL (95% CI 121-563) in the HDmu group, 289 EU/mL (138-606) in the LDmu group, 2013 EU/mL (1180-3435) in the MIX group, 915 EU/mL (588-1423) in the 1Dim group, and 1190 EU/mL (776-1824) in the 2Dim group. INTERPRETATION: Aerosolised Ad5-nCoV is well tolerated, and two doses of aerosolised Ad5-nCoV elicited neutralising antibody responses, similar to one dose of intramuscular injection. An aerosolised booster vaccination at 28 days after first intramuscular injection induced strong IgG and neutralising antibody responses. The efficacy and cost-effectiveness of aerosol vaccination should be evaluated in future studies. FUNDING: National Key Research and Development Programme of China and National Science and Technology Major Project. TRANSLATION: For the Chinese translation of the Summary see Supplementary Material.

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