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1.
Front Cell Infect Microbiol ; 10: 592864, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33282751

RESUMO

Monocytes are widely involved in the body's defense response, and abnormally regulated monocyte subsets are closely related to the pathogenesis of various diseases. It is unclear whether Treponema pallidum (Tp) dysregulates monocyte subsets and impacts the functions of monocytes. This study aims to analyze the distribution of monocyte subsets in syphilis patients and the effect of Tp on monocyte functions to explore the pathogenesis of syphilis. Flow cytometry was employed to detect monocyte subsets. With or without pre-treatment with rapamycin, THP-1 cell migration stimulated by Tp was investigated by a Transwell migration assay, and THP-1 cell phagocytosis was studied using fluorescent microspheres. IL-1ß and TNF-α expression was quantified by PCR and flow cytometry, while LC3 and mTOR were investigated in Tp-exposed THP-1 cells using western blotting. Tp infection led to an increase in the proportion of CD14++CD16+ monocytes and a decrease in the proportion of CD14++CD16- monocytes. In addition, Tp promoted monocyte (THP-1) CD14 and CD16 expression in vitro, induced the expression of IL-1ß and TNF-α in a dose-dependent manner and promoted the migration and autophagy of monocytes. Furthermore, mTOR phosphorylation on monocytes was stimulated by Tp, and the levels peaked at 30 min. Pre-treatment with rapamycin (mTOR inhibitor) attenuated the expression of IL-1ß and migration in Tp-exposed THP-1 cells. Tp abnormally regulates monocyte subsets and promotes migration, autophagy, and the expression of IL-1ß and TNF-α in THP-1 cells. Meanwhile, the mTOR affected the expression of IL-1ß and migration in Tp-exposed THP-1 cells. This study is important as it sheds light on the mechanism by which monocytes interact with Tp during infection.

2.
World J Clin Cases ; 8(20): 4908-4916, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33195660

RESUMO

BACKGROUND: The global pandemic of coronavirus disease 2019 pneumonia poses a particular challenge to the emergency surgical treatment of elderly patients with high-risk acute abdominal diseases. Elderly patients are a high-risk group for surgical treatment. If the incarceration of gallstones cannot be relieved, emergency surgery is unavoidable. CASE SUMMARY: We report an 89-year-old male patient with acute gangrenous cholecystitis and septic shock induced by incarcerated cholecystolithiasis. He had several coexisting, high-risk underlying diseases, had a history of radical gastrectomy for gastric cancer, and was taking aspirin before the operation. Nevertheless, he underwent emergency laparoscopic cholecystectomy, with maintenance of postoperative heart and lung function, successfully recovered, and was discharged on day 8 after the operation. CONCLUSION: Emergency surgery for elderly patients with acute abdominal disease is safe and feasible during the coronavirus disease 2019 pandemic, the key is to abide strictly by the hospital's epidemic prevention regulations, fully implement the epidemic prevention procedure for emergency surgery, fully prepare before the operation, accurately perform the operation, and carefully manage the patient postoperatively.

3.
Sex Transm Infect ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33214321

RESUMO

OBJECTIVES: A novel tp0548 sequence-type was identified in one clinical isolate (X-4) from a patient diagnosed with primary syphilis in Xiamen, China. To precisely define and characterise a new clinical isolate, we performed further genome-scale molecular analysis. METHODS: The pooled segment genome sequencing method followed by Illumina sequencing was performed. RESULTS: This novel sequence-type contained a unique nucleotide substitution 'T' at position 167 and belonged to the SS14-like clade of TPA strains, as determined by phylogenetic analysis. Multi-locus sequence analysis of nine chromosomal loci demonstrated that the X-4 isolate was clustered within a monophyletic group of TPA strains. Whole-genome phylogenetic analysis subsequently corroborated the TPA strain classification of the X-4 isolate and revealed that the isolate was closely related to the SS14 strain, with 42 single-nucleotide variations and 12 insertions/deletions. In addition, high intrastrain heterogeneity in the length of the poly G/C tracts was found in the TPAChi_0347 locus, which might indicate that this gene of the X-4 isolate is likely involved in phase variation events. The length heterogeneity of the poly A/T tracts was lower than the genetic variability of the poly G/C tracts, and all the observed intrastrain variations fell within coding regions. CONCLUSION: The novel tp0548 sequence-type was determined to belong to a new TPA isolate, X-4. The identification of variable length in homopolymetic tracts (G/C and A/T) could provide a snapshot of the genes that potentially involved in genotype-phenotype variations. These findings provide an unequivocal characterisation for better understanding the molecular variation of this emerging isolate.

4.
Am J Transl Res ; 12(9): 5343-5361, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042424

RESUMO

Gynecologic cancers, including endometrial, ovarian, and cervical cancers, are the leading causes of cancer-related mortality in women worldwide. Mitochondrial transcription factor A (TFAM) has been demonstrated playing critical roles in the development of tumors. However, the clinical relationship of TFAM expression in gynecologic cancers requires further clarification. Our results showed gynecologic cancer cells are highly expressed TFAM in both protein and RNA levels compared to normal cells. The TCGA dataset revealed that TFAM gene expression is higher in most of the solid tumors than the expression of the known oncogenes (e.g., TP53, BRCA1, and BRCA2). The dataset also suggested a high expression of TFAM in primary and recurrent tumor sites in gynecologic cancers compared to the adjacent normal tissues. Besides, the subcellular fractionation results indicated that the main form of TFAM in cells is chromatin-binding proteins. Further immunohistochemistry study showed that the overexpression of TFAM in tumor tissues is associated with the patient's advanced clinicopathological parameters. The Kaplan-Meier analysis demonstrated that high TFAM expression is a potential prognostic prediction marker for the patient's survival. Furthermore, we observed that downregulated TFAM expression with siRNA suppresses cell proliferation, colony formation, migration, and invasion ability. Taken together, our findings demonstrated that TFAM is highly expressed in cancer cell lines and tumor tissues of gynecologic cancers. The majority of TFAM protein is binding to chromatin in cells, and downregulation of TFAM suppresses cell proliferation, colony formation, migration, and invasion. High level of TFAM in tumor tissues is related to an unfavorable overall survival and disease-free survival in patients with endometrial, ovarian, and cervical cancers, which can serve as a promising prognostic predictive biomarker and a potential therapeutic target.

5.
Front Psychol ; 11: 2231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013582

RESUMO

Background: Coronavirus disease 2019 (COVID-19) has considerably psychologically impacted Chinese college students. Several types of online mental health services were widely implemented for college students during the outbreak. This study investigated the relationship between college students' mental health status and psychological help-seeking behavior to test the phases-decision-making model (PDM). Methods: A cross-sectional survey was conducted among college students in Guangdong Province using an online platform. In total, 4,164 students were assigned to the "counseling group" or "non-counseling group" according to whether they had sought psychological help because of the COVID-19 outbreak; the groups were matched based on age, sex, and grade. Demographics, perceived mental health, and experience with seeking psychological help were recorded. Fear, depression, and trauma were assessed by the COVID-19 Fear Screening Scale, Patient Health Questionnaire, and Impact of Event Scale-6. Results: The fear, depression, and trauma scores were significantly higher in the counseling group than in the non-counseling group (P s < 0.001). Fear (OR = 1.27, p < 0.001), depression (OR = 1.02, p = 0.032), trauma (OR = 1.08, p < 0.001), poor perceived mental health status (OR = 3.61, p = 0.001), and experience with seeking psychological help (OR = 7.06, p < 0.001) increased the odds of seeking psychological help. Conclusion: During the COVID-19 epidemic, the rate of psychological help-seeking was still low, and college students in poor psychological condition sought psychological counseling more. Fear, depression, trauma, experience with seeking psychological help, and perceived mental health can effectively predict psychological help-seeking behavior. These findings emphasized the importance of closely monitoring college students' psychological status, providing psychological intervention, and improving the probability of seeking psychological help.

6.
Exp Cell Res ; 396(1): 112289, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32950474

RESUMO

Lesion healing without treatment is a unique clinical characteristic of the early stages of syphilis infection. Angiogenesis, which involves endothelial cell migration, is an important process in wound healing. Tp0136, an outer membrane protein of T. pallidum, has the ability to bind host fibronectin-producing cells, which plays a crucial role in the pathogenesis of syphilis. In this research, we purposed to analyze the role of Tp0136 in the migration of human microvascular endothelial (HMEC-1) cells and to explore the related mechanism. First, Tp0136 significantly promoted HMEC-1 cell migration. Furthermore, the levels of C-C motif ligand 2 (CCL2) mRNA and protein expression rose with the concentration and time increasing of Tp0136. The migration of HMEC-1 cells was significantly suppressed by an anti-CCL2 antibody and a CCR2 (the CCL2 receptor) inhibitor. Further study revealed that, in cells pretreated with anti-fibronectin antibody, anti-integrin ß1 antibody or RGD (Arg-Gly-Asp), the expression levels of CCL2 induced by Tp0136 were notably decreased. Additionally, after pretreatment with an anti-fibronectin antibody, an anti-integrin ß1 antibody or RGD, the migration of HMEC-1 cells treated with Tp0136 was obviously suppressed. These results show that Tp0136 promots the migration of HMEC-1 cells by inducing CCL2 expression via the interaction of the fibronectin RGD domain with integrin ß1 and the CCL2/CCR2 signaling pathway, and these interactions may contribute to the mechanisms that increase the capacity for self-healing syphilis infection.

7.
Pathol Res Pract ; 216(11): 153153, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32891822

RESUMO

BACKGROUND: Liver is a major metabolic organ containing many metabolic enzymes. Disorders of liver-specific enzymes can cause liver dysfunction and tumorigenesis. Previous studies indicated that 4-Hydroxyphenylpyruvate dioxygenase (HPD) plays an essential role in catalyzing the tyrosinolytic metabolism of 4-hydroxyphenylpyruvate to homogeneous acids in liver tissues. However, the clinical significance of HPD in HCC has not been obtained. Here in our study, we aimed to identify the expression and the clinical significance of HPD in hepatocellular carcinoma (HCC). METHODS: Western Blotting and qRT-PCR were employed to evaluate the level of HPD in HCC cell lines and fresh samples. The expression of HPD was further confirmed by immunohistochemistry (IHC) using a tissue microarray (TMA) cohort with a total of 778 HCC patients. Furthermore, the mRNA expression of HPD in HCC was evaluated from TCGA and GEO public databases. Kaplan-Meier analysis and univariate and multivariate Cox regression analyses were used to determine the correlation between HPD expression with clinicopathological variables and survival rate of HCC patients. The cellular behaviors of transfected cells were respectively examined by CCK8 and Migration assay. RESULTS: The expression of HPD is restricted in liver compared with other cancer types. HPD mRNA and protein expression was dramatically reduced in HCC cell lines and fresh tissue samples. IHC staining in HCC TMA further showed that the decreased of HPD in paraffin-imbedded HCC samples was linked to an adverse overall postoperative survival (p < 0.001). Clinicopathologically, low expression of HPD was correlated with larger tumor size, advanced TNM staging and poor differentiaion. In addition, multivariate analyses indicated that HPD was an independent predictive factor of HCC survival. Our study pioneering validates that knockdown of HPD increases HCC cell cell growth and cell motility. CONCLUSION: Our results suggested that HPD may serve as a valuable prognostic marker, a tumor suppressor, and a potential therapeutic target for HCC patients.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32770259

RESUMO

The "macrotrabecular-massive" (MTM) pattern of hepatocellular carcinoma (HCC) has been suggested to represent a distinct HCC subtype and is associated with specific molecular features. Since the immune microenvironment is heterogenous in HCC, it is important to evaluate the immune microenvironment of this novel variant. CMTM6, a key regulator of PD-L1, is an important immunocheckpoint inhibitor. This study aimed to evaluate the prognostic effect of CMTM6/PD-L1 coexpression and its relationship with inflammatory cells in HCC. We analyzed 619 HCC patients and tumors were classified into MTM and non-MTM HCC subtypes. The expression levels of CMTM6 and PD-L1 in tumor and inflammatory cells were evaluated by immunohistochemistry. The density of inflammatory cells in the cancer cell nest was calculated. Tumoral PD-L1 expression and inflammatory cell density were higher in the MTM type than in the non-MTM type. CMTM6-high expression was significantly associated with shorter OS and DFS than CMTM6-low expression in the whole HCC patient population and the MTM HCC patient population. Moreover, MTM HCC patients with CMTM6/PD-L1 coexpression experienced a higher risk of HCC progression and death. In addition, CMTM6/PD-L1 coexpression was shown to be related to a high density of inflammatory cells. Notably, a new immune classification, based on CMTM6/PD-L1 coexpression and inflammatory cells, successfully stratified OS and DFS in MTM HCC. CMTM6/PD-L1 coexpression has an adverse effect on the prognosis of HCC patients, especially MTM HCC patients. Our study provides evidence for the combination of immune status assessment with anti-CMTM6 and anti-PD-L1 therapy in MTM HCC patients.

9.
Front Pharmacol ; 11: 950, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670066

RESUMO

Since December 2019 to May 2020, coronavirus disease 2019 (COVID-19) has infected over 6 million people worldwide. Due to its sudden and rapid outbreak, effective treatment for COVID-19 is scarce. Based on national clinical trials of novel treatments, China, Italy, Germany, and other countries and organizations have published multiple guidelines for COVID-19 and advised many medicines, such as chloroquine and tocilizumab. In this paper, we summarize the pharmacotherapy for COVID-19 according to those guidelines, highlight updates of the pharmacotherapy guidelines, and review the efficacy and safety of the indicated anti-COVID-19 drugs.

10.
Yi Chuan ; 42(6): 548-555, 2020 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-32694113

RESUMO

Ubiquitination signaling is the main pathway of protein degradation in eukaryotic cells. Ubiquitin-proteasome system degrades the ubiquitinated cytoplasmic proteins and lysosome pathway mainly degrades the ubiquitinated membrane proteins. Previous studies have shown that ubiquitination signaling plays a critical role in fatty acids synthesis. In the process of fatty acids import, disruption of ubiquitination could prevent the degradation of fatty acid transport proteins, thereby promoting fatty acids import and milk fat synthesis in bovine primary mammary epithelial cells. In this review, we summarize the signal transduction and regulation mechanism of ubiquitination signaling in milk fat synthesis, which may provide references and new ideas for future research on milk fat traits in dairy cows.


Assuntos
Glândulas Mamárias Animais , Leite , Animais , Bovinos , Células Epiteliais , Ácidos Graxos/metabolismo , Feminino , Leite/metabolismo , Ubiquitinação
11.
Infect Dis Poverty ; 9(1): 80, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600411

RESUMO

BACKGROUND: It is well established that obesity is a disease of sustained low-grade inflammation. However, it is currently unknown if obesity plays a role in the clinical manifestations and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. In this study, we aimed to investigate whether obesity played a role in clinical manifestations and prognosis in patients infected with SARS-CoV-2. METHODS: This is a retrospective multicenter clinical study. A total of 96 patients hospitalized with SARS-CoV-2 infection were enrolled from Dongguan People's Hospital, Nanfang hospital and the First Affiliated Hospital of Xiamen University between 23 January and 14 February 2020. Demographic and clinical data were extracted from medical records. Acute respiratory distress syndrome (ARDS) was defined as oxygenation index (PaO2/FiO2) ≤ 300 mmHg. We grouped patients through the body mass index (BMI). Associations were examined using the t test, χ2 test and multivariate logistic forward regression test. RESULTS: Patients with BMI <  24 were significantly younger (P = 0.025) with lower creatine kinase (P = 0.013), lower diastolic pressure blood (P = 0.035), lower serum creatinine (P = 0.012), lower lactate dehydrogenase (P = 0.001) and higher platelet count (P = 0.002). The BMI level was 20.78 ± 3.15 in patients without pneumonia compared with the patients with pneumonia (23.81 ± 3.49, P = 0.001). For patients without ARDS, an average BMI level of 22.65 ± 3.53 was observed, significantly lower than patients with ARDS (24.57 ± 3.59, P = 0.022). The mean BMI was 22.35 ± 3.56 in patients experienced with relieving the clinical symptoms or stable condition by radiographic tests, lower than patients with disease exacerbation with 24.89 ± 3.17 (P = 0.001). In addition, lymphocyte count (r = - 0.23, P = 0.027) and platelet count (r = - 0.44, P < 0.001) were negatively correlated with BMI. While hemoglobin (r = 0.267, P = 0.008), creatine kinase (r = 0.331, P = 0.001), serum creatinine (r = 0.424, P < 0.001) and lactate dehydrogenase (r = 0.343, P = 0.001) were significantly positive correlated with BMI. Multivariate analysis showed that older age (OR = 1.046, P = 0.009) and BMI ≥ 24 (OR = 1.258, P = 0.005) were independent risk factors associated ICU admission while BMI ≥ 24 (OR = 4.219, P = 0.007) was independent risk factor associated with radiographic disease exacerbation. CONCLUSIONS: Our study found BMI was significantly associated with clinical manifestations and prognosis of patients with SARS-CoV-2 infection. For patients with increased risk, clinicians should intervene promptly to avoid disease progression.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Obesidade , Pandemias , Pneumonia Viral , Adolescente , Adulto , Índice de Massa Corporal , China , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/epidemiologia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
12.
Huan Jing Ke Xue ; 41(5): 2425-2433, 2020 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608862

RESUMO

Soil microbial metabolism is vital for nutrient cycling and stability of an ecosystem. To elucidate the long-term effects of biochar application on nutrient limitations and carbon use efficiency (CUE) of soil microbial metabolisms, biochars pyrolyzed at 450℃ from trunks and branches of fruit trees under an oxygen-limited condition were mixed with the top Lou soils (0-20 cm) with application amounts of 0, 20, 40, 60, and 80 t·hm-2 in 2012. Corn-wheat rotation was carried out afterwards for seven years. The nutrient limitations of soil microbial metabolisms were analyzed quantitatively through ecoenzymatic stoichiometry in 2019. The results indicated that:① With an increase in the biochar application amount, soil moisture, organic carbon, total nitrogen, C:N, C:P, and N:P significantly increased, whereas there were no clear patterns for the active components of carbon, nitrogen, and phosphorus, microbial biomass carbon, nitrogen, phosphorus and total phosphorus. In contrast, the activities of five extracellular enzymes (ß-1,4-glucosidase, cellobiohydrolase, leucine aminopeptidase, ß-1,4-N-acetylglucosaminidase, and phosphatase) were significantly reduced. ② The soil microorganisms suffered from the phosphorus limitation under all treatments in this study. In the treatments of biochar application, the carbon and phosphorus limitations of microbial metabolisms increased significantly with increasing application amount, whereas the microbial CUE decreased significantly. When the application amount was 20 t·hm-2, the carbon limitation (0.625±0.022) and phosphorus limitation (62.153°±0.892°) were lowest, and the microorganism CUE (0.511±0.007) was highest. ③ Partial least-squares path modeling (PLS-PM) showed that soil carbon, nitrogen, phosphorus, and their stoichiometry had a very direct positive effect on phosphorus limitation (P<0.01), and there was a positive correlation between carbon limitation and phosphorus limitation (R2=0.242, P<0.001); in contrast, the carbon and phosphorus limitations had a very significant negative effect on CUE (P<0.001). It was revealed that the excessive application of biochar had caused a soil element stoichiometry imbalance, which deteriorated the phosphorus limitation of the soil microbial metabolism and further led to carbon limitation and reduction of CUE. When the biochar application amount was 20 t·hm-2, C and P limitations were lowest, and microbial CUE was highest. Therefore, 20 t·hm-2 was optimal for regulating soil microbial metabolism, maintaining ecological functions, and reducing carbon dioxide emission produced by microbial metabolism.

13.
Oral Oncol ; 108: 104771, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32485608

RESUMO

OBJECTIVES: It is unknown whether or not the body composition is correlated with the prognosis and inflammatory response in patients with nasopharyngeal cancer (NPC). MATERIALS AND METHODS: This cohort included 1767 patients with NPC. Visceral, subcutaneous and intra muscular adipose tissues (VAT, SAT and IMAT), and skeletal muscle index were quantified with computed tomography. We used the optimal stratification to select cut points for VAT, SAT and IMAT. We defined sarcopenia according to a widely used cut-point. The primary endpoint was overall survival (OS). The association between body composition and inflammatory response was also examined. RESULTS: Low VAT, SAT, IMAT and sarcopenia were observed in 260 (14.7%), 451 (25.5%), 773 (43.7%) and 683 (38.7%) patients, respectively. Low VAT (P < 0.001, hazard ratio [HR], 1.884; 95% confidence interval [CI], 1.436-2.473,) and SAT (P = 0.022, HR, 1.334, 95%CI, 1.043-1.706) were both associated worse survival. IMAT and sarcopenia were not with prognostic value. In multivariate analysis, we found the prognostic value of the VAT (HR: 1.544, 95% CI: 1.128-2.114; P = 0.007) was independent of T stage, N stage, disease stage, lactic dehydrogenase, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), the systemic immune-inflammation index (SII), EBV-DNA and body mass index. We observed higher NLR (P = 0.028) and PLR (P < 0.001) in patients with low SAT. Both low VAT (P = 0.009) and SAT (P = 0.005) were associated with decreased stromal lymphocyte infiltrating intensity. CONCLUSIONS: Among body composition parameters, VAT was an independent prognostic factor, especially in patients with locally advanced NPC.

14.
Am J Transl Res ; 12(3): 773-786, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32269711

RESUMO

BACKGROUND: Cancer metastasis is the major reason for cancer-related deaths, but the mechanism of cancer metastasis still unclear. Adrenomedullin (ADM), a peptide hormone, functions as a local paracrine and autocrine mediator with multiple biological activities, such as angiogenesis, cell proliferation, and anti-inflammation. However, the expression and potential function of ADM in triple-negative breast cancer (TNBC) remain unclear. METHODS: Real-time polymerase chain reaction and western blotting were performed to examine the expression of ADM in TNBC tissues and cell lines. A total of 458 TNBC tissue samples and adjacent nontumor tissue samples were detected by immunochemistry to determine the correlation between ADM expression and clinicopathological characteristics. We determined the role and mechanistic pathways of ADM in tumor metastasis in cell lines. RESULTS: Our data showed that ADM expression was noticeably decreased in TNBC samples and cell lines. Low expression levels correlate with an increased risk of recurrence and metastasis. Furthermore, low ADM expression was associated with poor prognosis and was an independent marker for TNBC. In vitro, ADM may decrease cancer cell invasion, which is likely the result of its effect on the cancer cell epithelial-mesenchymal transition. CONCLUSIONS: Our findings suggest that ADM is a valuable biomarker for TNBC prognosis and an anti-metastasis candidate therapeutic target in triple-negative breast cancer.

15.
Int Immunopharmacol ; 82: 106344, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32151957

RESUMO

It is unclear whether P2X7 receptor (P2X7R) mediates NOD-like receptor family protein 3 (NLRP3)-dependent IL-1ß secretion and spirochete phagocytosis in syphilis. This study was conducted to investigate the role of P2X7R in modifying NLRP3-dependent IL-1ß secretion and regulating phagocytosis by Treponema pallidum (T. pallidum)-induced macrophages. Macrophages derived from a human acute monocytic leukemia cell line were cultured with T. pallidum. The activation of P2X7R in T. pallidum-treated macrophages occurred in a dose- and time-dependent manner. The P2X7R silencing group showed significantly decreased NLRP3 mRNA and protein levels (vs. the Tp group, P < 0.001). Similar results were observed for IL-1ß secretion using ELISA (vs. the Tp group, P < 0.001). Furthermore, P2X7R siRNA transfection significantly decreased the percentage of spirochete-positive macrophages (29.73% vs. 70.83%, P < 0.001) and spirochete internalization (mean fluorescence intensity (MFI), 9.20 vs. 19.39, P < 0.001). This finding revealed that P2X7R played a role in the induction of NLRP3-dependent IL-1ß secretion by T. pallidum-induced macrophages. Furthermore, we found that P2X7R plays an important role in IL-1ß secretion and in the promotion of T. pallidum phagocytosis by macrophages. These results may not only contribute to our understanding of the immune mechanism that is active during T. pallidum infection but may also lay the groundwork for strategies to combat syphilis.

16.
Int Immunopharmacol ; 83: 106428, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32217461

RESUMO

The effect of anti-TP0136 antibodies on the progression of syphilis is poorly understood. This study aimed to investigate the effect of anti-TP0136 antibodies on the progression of lesions in an infected rabbit model. Intramuscular injection of rTP0136 into rabbits in the immunized group (n = 4) elicited high titers of anti-TP0136 antibodies, and rabbits were then challenged with 105T. pallidum per site along their back. Lesion development was observed, and the injection sites were biopsied for tp0574 mRNA and histological analyses every week until the wound healed. The rabbits in the control group were injected with normal saline instead of rTP0136. Viable T. pallidum in the challenged rabbits was assessed with rabbit infectivity tests. The lesions in the immunized group took longer to heal than those in the control group (42 d vs. 28 d, P < 0.001) and had markedly higher levels of total cellular infiltrates. The mRNA level of tp0574 in the immunized group was significantly higher than that in the control group (P < 0.05). Viable T. pallidum was detected in rabbit lymph nodes in both the immunized and control groups. Our study showed that high titers of anti-TP0136 antibodies promoted the infiltration of inflammatory cells into local lesions and intensified tissue damage, thus delaying wound healing, and had no protective effect on the occurrence of syphilis in the rabbit model.

17.
Oncol Rep ; 43(2): 662-670, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894344

RESUMO

Cullin 4A (CUL4A) is a member of the cullin family of proteins and has been demonstrated to be abnormally expressed in various types of malignancies. However, the function of CUL4A in metastasis of lung adenocarcinoma to the bone has rarely been reported. The aim of present of the study was to explore the biological functions and potential underlying molecular mechanisms of CUL4A in lung adenocarcinoma, highlighting a novel therapeutic target for the diagnosis and treatment of patients with lung adenocarcinoma. A549­CUL4A, H1299­CUL4A and H460­shCUL4A cells were created using lentiviral infection. The efficiency of knockdown or overexpression was assessed using reverse transcription­quantitative PCR and western blotting. The effects of CUL4A on proliferation, migration and invasion of lung adenocarcinoma cells in vitro and metastasis to the bone in vivo were determined using an MTT assay, colony formation assay, wound­healing assay, Transwell assay and a mouse model of bone metastasis. The relationship between CUL4A and the EMT­activator zinc finger E­box binding homeobox 1 (ZEB1) were detected by western blotting. The results showed that overexpression of CUL4A in lung adenocarcinoma cells increased proliferation, migration and invasion, and increased metastasis of A549 to the bones in vivo. Silencing of CUL4A expression in lung adenocarcinoma cells reduced proliferation, migration and invasion in vitro. Mechanistically, CUL4A transcriptionally upregulated expression of ZEB1 which resulted in epithelial­mesenchymal transition, which in turn promoted metastasis of lung adenocarcinoma to the bones. Taken together, these results suggest that CUL4A may serve an important regulatory role in the development of metastasis of lung adenocarcinoma to the bone.


Assuntos
Adenocarcinoma de Pulmão/patologia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Proteínas Culina/genética , Proteínas Culina/metabolismo , Neoplasias Pulmonares/patologia , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Células A549 , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Animais , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Camundongos , Transplante de Neoplasias , Regulação para Cima
18.
Mol Oncol ; 14(2): 373-386, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31670863

RESUMO

Hepatocellular carcinoma (HCC), with its ineffective therapeutic options and poor prognosis, represents a global threat. In the present study, we show that RAD52 motif 1 (RDM1), a key regulator of DNA double-strand break repair and recombination, is downregulated in HCC tissues and suppresses tumor growth. In clinical HCC samples, low expression of RDM1 correlates with larger tumor size, poor tumor differentiation, and unfavorable survival. In vitro and in vivo data demonstrate that knockdown of RDM1 increases HCC cell proliferation, colony formation, and cell population at G2/M phase, whereas RDM1 overexpression results in the opposite phenotypes. Mechanistically, RDM1 binds to the tumor suppressor p53 and enhances its protein stability. In the presence of p53, RDM1 suppresses the phosphorylation of Raf and ERK. Overexpression of p53 or treatment with ERK inhibitor significantly abolishes cell proliferation induced by the depletion of RDM1. In addition, overexpression of methyltransferase-like 3 markedly induces N6-methyladenosine modification of RDM1 mRNA and represses its expression. Taken together, our study indicates that RDM1 functions as a tumor suppressor and may be a potential prognostic and therapeutic factor for HCC.

19.
Huan Jing Ke Xue ; 40(12): 5570-5580, 2019 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854630

RESUMO

Preventing the environmental risks linked to contaminated sites and guaranteeing the safety of human settlements are some of the challenges and tasks involved in the construction of world-class city clusters in the Guangdong-Hong Kong-Macao Greater Bay Area. Due to differences in the political systems and land property rights between Guangdong, Hong Kong, and Macao, as well as in the levels of urbanization, industrial structures, and environmental management capabilities of the nine cities in the Pearl River Delta, the risk management and control mode of contaminated sites varies considerably within the Greater Bay Area. In this context, an analysis of the features of risk management and control in the contaminated sites of typical cities can help strengthening technical communication and cooperation, optimizing risk management and control systems. This article briefly describes the risk management and control systems adopted for polluted sites in China; in particular it elaborates on the features of these systems in Guangzhou, Shenzhen, Dongguan, Hong Kong, and Macao, which have been subjected to monitoring, contamination assessments, and renovation procedures. During our study, the risk management and control systems adopted in different cities have been analyzed and compared; moreover, we elaborated thoughts and suggestions for land planning, policy feedback, information disclosure, and alliance mechanisms. We conclude that, overall, Hong Kong and several cities of the Pearl River Delta have established effective risk management and control systems for the polluted sites, which take into account certain local characteristics. However, with the further development and reuse of contaminated sites, the building of a world-class urban agglomeration in the Guangdong-Hong Kong-Macao Greater Bay Area will require safer, more refined, and more efficient risk management and control strategies. We highlight the need to exchange information among researchers in order to promote technical exchange and cooperation. This is particularly important for the risk management and control of polluted sites distributed within the two regions and nine cities of the Guangdong-Hong Kong-Macao Greater Bay Area, sine it would allow their safe reuse and efficient development.


Assuntos
Monitoramento Ambiental , Poluentes Ambientais , Gestão de Riscos , China , Cidades , Hong Kong , Humanos , Macau
20.
Parasit Vectors ; 12(1): 592, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852494

RESUMO

BACKGROUND: Eimeria tenella is a highly pathogenic coccidian that causes avian coccidiosis. Both nitromezuril (NZL) and ethanamizuril (EZL) are novel triazine compounds with high anticoccidial activity, but the mechanisms of their action are still unclear. This study explored the response of E. tenella to NZL and EZL by the study of changes in protein composition of the second-generation merozoites. METHODS: Label-free quantification (LFQ) proteomics of the second-generation merozoites of E. tenella following NZL and EZL treatment were studied by LC-MS/MS to explore the mechanisms of action. The identified proteins were annotated and analyzed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction (PPI) networks analysis. RESULTS: A total of 1430 proteins were identified by LC-MS/MS, of which 375 were considered as differential proteins in response to drug treatment (DPs). There were 26 only found in the NZL treatment group (N-group), 63 exclusive to the EZL treatment group (E-group), and 80 proteins were present in both drug groups. In addition, among the DPs, the abundant proteins with significantly altered expression in response to drug treatment (SDPs) were found compared with the C-group, of which 49 were upregulated and 51 were downregulated in the N-group, and 66 upregulated and 79 downregulated in the E-group. Many upregulated proteins after drug treatment were involved in transcription and protein metabolism, and surface antigen proteins (SAGs) were among the largest proportion of the downregulated SDPs. Results showed the top two enriched GO terms and the top one enriched pathway treated with EZL and NZL were related, which indicated that these two compounds had similar modes of action. CONCLUSIONS: LFQ proteomic analysis is a feasible method for screening drug-related proteins. Drug treatment affected transcription and protein metabolism, and SAGs were also affected significantly. This study provided new insights into the effects of triazine anticoccidials against E. tenella.


Assuntos
Coccidiose/veterinária , Coccidiostáticos/administração & dosagem , Eimeria tenella/crescimento & desenvolvimento , Merozoítos/efeitos dos fármacos , Doenças das Aves Domésticas/tratamento farmacológico , Proteínas de Protozoários/química , Triazinas/administração & dosagem , Animais , Galinhas , Coccidiose/tratamento farmacológico , Coccidiose/parasitologia , Eimeria tenella/efeitos dos fármacos , Eimeria tenella/genética , Eimeria tenella/metabolismo , Merozoítos/genética , Merozoítos/crescimento & desenvolvimento , Merozoítos/metabolismo , Doenças das Aves Domésticas/parasitologia , Proteômica , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Espectrometria de Massas em Tandem
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