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1.
J Exp Med ; 218(1)2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33045063

RESUMO

KRAS is the most frequently mutated human oncogene, and KRAS inhibition has been a longtime goal. Recently, inhibitors were developed that bind KRASG12C-GDP and react with Cys-12 (G12C-Is). Using new affinity reagents to monitor KRASG12C activation and inhibitor engagement, we found that an SHP2 inhibitor (SHP2-I) increases KRAS-GDP occupancy, enhancing G12C-I efficacy. The SHP2-I abrogated RTK feedback signaling and adaptive resistance to G12C-Is in vitro, in xenografts, and in syngeneic KRASG12C-mutant pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). SHP2-I/G12C-I combination evoked favorable but tumor site-specific changes in the immune microenvironment, decreasing myeloid suppressor cells, increasing CD8+ T cells, and sensitizing tumors to PD-1 blockade. Experiments using cells expressing inhibitor-resistant SHP2 showed that SHP2 inhibition in PDAC cells is required for PDAC regression and remodeling of the immune microenvironment but revealed direct inhibitory effects on tumor angiogenesis and vascularity. Our results demonstrate that SHP2-I/G12C-I combinations confer a substantial survival benefit in PDAC and NSCLC and identify additional potential combination strategies.

2.
Talanta ; 221: 121660, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076170

RESUMO

As a common plasma protein, alpha-fetoprotein (AFP) is widely applied as the tumor biomarker for the diagnosis of many cancers. To develop a low cost, high sensitive and high-throughput method for the determination of AFP is significant for the disease diagnosis. In this work, an immunoassay with sandwich-type structures was performed on a paper-based chip for the analysis of AFP. AFP could be captured by the primary antibodies which were immobilized on the paper by chitosan. On the secondary antibodies, the modified initiator DNAs could trigger the hybridization chain reaction to amplify the fluorescence signals for AFP. A laser-induced fluorescence detector coupled with an interface was applied to detect the targets on the paper-based chip. Under the optimized conditions, the detection limit for AFP was 1.0 pg/mL. For every test, the sample solution consumption only was 10 µL. Finally, the method was applied to determine the AFP in serum of normal person and hepatopaths with hepatic malignant tumor, chronic hepatitis B and other suspected liver diseases. The AFP could be found from all of the samples and the results were similar to that obtained by chemiluminescence immunoassay. The recoveries for AFP ranged from 93.8% to 106%, which indicated the method was reliable. The method based on paper chip had great potential in the application of AFP determination.

3.
Int J Mol Sci ; 21(19)2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32998359

RESUMO

Mitogen-activated protein kinase phosphatase-5 (MKP-5) is a regulator of extracellular signaling that is known to regulate lipid metabolism. In this study, we found that obesity caused by a high-fat diet (HFD) decreased the expression of MKP-5 in the pancreas and primary islet cells derived from mice. Then, we further investigated the role of MKP-5 in the protection of islet cells from lipotoxicity by modulating MKP-5 expression. As a critical inducer of lipotoxicity, palmitic acid (PA) was used to treat islet ß-cells. We found that MKP-5 overexpression restored PA-mediated autophagy inhibition in Rin-m5f cells and protected these cells from PA-induced apoptosis and dysfunction. Consistently, a lack of MKP-5 aggravated the adverse effects of lipotoxicity. Islet cells from HFD-fed mice were infected using recombinant adenovirus expressing MKP-5 (Ad-MKP-5), and we found that Ad-MKP-5 was able to alleviate HFD-induced apoptotic protein activation and relieve the HFD-mediated inhibition of functional proteins. Notably, HFD-mediated impairments in autophagic flux were restored by Ad-MKP-5 transduction. Furthermore, the autophagy inhibitor 3-methyladenine (3-MA) was used to treat Rin-m5f cells, confirming that the MKP-5 overexpression suppressed apoptosis, dysfunction, inflammatory response, and oxidative stress induced by PA via improving autophagic signaling. Lastly, employing c-Jun amino-terminal kinas (JNK), P38, or extracellular-regulated kinase (ERK) inhibitors, we established that the JNK and P38 MAPK pathways were involved in the MKP-5-mediated apoptosis, dysfunction, and autophagic inhibition observed in islet ß cells in response to lipotoxicity.

4.
Oncol Res ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998794

RESUMO

Wnt molecules play crucial roles in development and adult homeostasis through their receptors Frizzled proteins (Fzds). Fzds mediate canonical ß-catenin pathway and various non-canonical ß-catenin-independent pathways. Aberrant Fzd signaling is involved in many diseases including cancer. Wnt/ß-catenin is a well-established oncogenic pathway involved in almost every aspects of tumor development. However, Fzd-mediated non-canonical Wnt pathways function as both tumor promoters and tumor suppressors depending on cellular context. Fzd-targeted therapies have proven to be effective on cultured tumor cells, tumor cell xenografts, mouse tumor models and patient-derived xenografts (PDX). Moreover, Fzd-targeted therapies synergize with chemotherapy in preclinical models. However, the occurrence of fragility fractures in patients treated with Fzd-targeted agents such as OMP-54F28 and OMP-18R5 limits the development of this combination. Along with new insights on signaling, roles, and modulation mechanisms of Fzds in human tumors, more Fzd-related therapeutic targets will be developed.

5.
Mol Med Rep ; 22(5): 4116-4124, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000255

RESUMO

Hepatitis C virus (HCV) infection is a global public health problem. Cirrhosis and hepatocellular carcinoma are the main causes of death in patients with chronic hepatitis C (CHC) infection. Liver fibrosis is an important cause of cirrhosis and end­stage liver disease after CHC infection. Along with the course of infection, liver fibrosis exhibits a progressive exacerbation. Hepatic stellate cells (HSCs) are involved in both physiological and pathological processes of the liver. During the chronic liver injury process, the activated HSCs transform into myofibroblasts, which are important cells in the development of liver fibrosis. At present, HCV infection still lacks specific markers for the accurate detection of the disease condition and progression. Therefore, the present review focused on HSCs, which are closely related to HCV­infected liver fibrosis, and analyzed the changes in the HSCs, including their surface­specific markers, cytokine production, activation, cell function and morphological structure. The present review aimed to propose novel diagnostic markers, at both the cellular and molecular level, which would be of great significance for the timely diagnosis of the disease. According to this aim, the characteristic changes of HSCs during HCV infection were reviewed in the present article.

6.
Environ Microbiol ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33000483

RESUMO

Ascospores are the primary inoculum in Fusarium graminearum, a causal agent of wheat head blight. In a previous study, FgPAL1 was found to be up-regulated in the Fgama1 mutant and important for ascosporogenesis. However, the biological function of this well-conserved gene in filamentous ascomycetes is not clear. In this study, we characterized its functions in growth, differentiation, and pathogenesis. The Fgpal1 mutant had severe growth defects and often displayed abnormal hyphal tips. It was defective in infectious growth in rachis tissues and spreading in wheat heads. The Fgpal1 mutant produced conidia with fewer septa and more nuclei per compartment than the wild type. In actively growing hyphal tips, FgPal1-GFP mainly localized to the subapical collar and septa. The FgPal1 and LifeAct partially co-localized at the subapical region in the interdependent manner. The Fgpal1 mutant was normal in meiosis with eight nuclei in developing asci but most asci were aborted. Taken together, our results showed that FgPal1 plays a role in maintaining polarized tip growth and coordination between nuclear division and cytokinesis, and it is also important for infectious growth and developments of ascospores by the free cell formation process. This article is protected by copyright. All rights reserved.

7.
Bull Menninger Clin ; 84(3): 278-294, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33000963

RESUMO

Nightmares are prevalent in psychiatric disorders, and personality disorder features might be associated with nightmare experience, especially in nightmare disorder patients. The authors invited 219 healthy volunteers and 118 nightmare disorder patients to undergo tests of the Nightmare Experience Questionnaire (NEQ), the Parker Personality Measure (PERM), and the Plutchik-van Praag Depression Inventory. Compared to healthy volunteers, nightmare disorder patients scored significantly higher on annual nightmare frequency and NEQ Physical Effect, Negative Emotion, Meaning Interpretation, and Horrible Stimulation, and higher on PERM Paranoid, Schizotypal, Borderline, Histrionic, Narcissistic, Avoidant, and Dependent styles. Borderline, Schizotypal, and Passive-Aggressive styles in healthy volunteers and Dependent, Avoidant, Histrionic, and Paranoid in patients were significant predictors of some NEQ scales. Higher annual nightmare frequency, higher scale scores of nightmare experience and personality disorder styles, and more associations between the two were found in nightmare disorder patients, implying the need for personality-adjustment therapy for nightmare disorder.

8.
J Cancer Res Ther ; 16(5): 1082-1087, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33004751

RESUMO

Aims: We aimed to investigate the feasibility, safety, and efficacy of radiofrequency ablation (RFA) combined with percutaneous vertebroplasty (PVP) for treating VX2 vertebral metastases with posterior margin destruction in a rabbit model. Materials and Methods: Sixty rabbit models of VX2 vertebral metastases with posterior margin destruction were constructed through computed tomography (CT)-guided percutaneous puncture and randomly divided into four groups of 15 rabbits each: Groups A, RFA+PVP; B, PVP; C, RFA; and D, control. Five rabbits in each group were sacrificed within 24 h of the procedure. Pathological examination and immunohistochemical staining revealed the presence of a biomembrane barrier at the tumor edge; furthermore, bone cement leakage into the spinal canal was observed. The survival time of the remaining rabbits per group was observed, and the differences were analyzed. Results: CT scans of Group A and C rabbits revealed a low-density band around the tumor ablation region. Bone cement leakage rate significantly differed between Groups A and B (20% vs. 100%; P < 0.05). The average postoperative survival times of Group A, B, C, and D rabbits were 16.72 ± 0.93, 7.26 ± 0.75, 7.80 ± 1.30, and 3.84 ± 1.24 days, respectively, showing a significant difference between Group A and the remaining groups (P < 0.05). Conclusions: The biomembrane barrier formed at the tumor edge after RFA can prevent bone cement leakage into the spinal canal, reducing spinal cord injury and prolonging the survival time.

9.
Int Urol Nephrol ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33006090

RESUMO

OBJECTIVES: Surgical removal of completely endophytic renal tumors has presented great technical difficulties for surgeons. In this study, we aim to introduce the role and use of intraoperative ultrasound (IOUS) performed in robotic-assisted renal partial nephrectomy (RAPN) for endophytic renal tumors. METHODS: We retrospectively assessed the demographics data and surgical outcomes of 58 consecutive endophytic renal tumor patients who were all attributed 3 points for the 'E' domain of the RENAL nephrometry score or 3 points for the exophytic rate of the PADUA score between October 2016 and September 2018. 38 patients who had undergone RAPN with IOUS were grouped. RAPN was carried out in another 20 patients without IOUS and these 20 patients were also grouped. RESULTS: Patients in IOUS-guided group had significantly lower estimated blood loss (P < 0.001), shorter warm ischemia time (P = 0.010) and improved MIC (Margin, ischemia, and complications) rate (P = 0.026) and Pentafecta achievement (P = 0.016) compared to non IOUS-guided group. In multivariate logistic regression analysis, RAPN with IOUS was an independent predictor of MIC achievement (odds ratio 3.595; confidence interval 1.023-12.633; P = 0.046). Surface-intermediate-base (SIB) margin score was lower for IOUS-guided group vs non IOUS-guided group (P = 0.029). CONCLUSION: RAPN for completely endophytic renal tumors is a feasible procedure in terms of complication rates, oncologic and functional outcomes. A robotic ultrasound probe operated by console surgeon generates a favorable perioperative outcomes and surgical margin rates after RAPN.

10.
Curr Biol ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-33007241

RESUMO

Dopamine (DA)-producing neurons are critically involved in the production of motor behaviors in multiple circuits that are conserved from basal vertebrates to mammals. Although there is increasing evidence that DA neurons in the hypothalamus play a locomotor role, their precise contributions to behavior and the circuit mechanisms by which they are achieved remain unclear. Here, we demonstrate that tyrosine-hydroxylase-2-expressing (th2+) DA neurons in the zebrafish hypothalamus fire phasic bursts of activity to acutely promote swimming and modulate audiomotor behaviors on fast timescales. Their anatomy and physiology reveal two distinct functional DA modules within the hypothalamus. The first comprises an interconnected set of cerebrospinal-fluid-contacting DA nuclei surrounding the 3rd ventricle, which lack distal projections outside of the hypothalamus and influence locomotion through unknown means. The second includes neurons in the preoptic nucleus, which send long-range projections to targets throughout the brain, including the mid- and hindbrain, where they activate premotor circuits involved in swimming and sensorimotor integration. These data suggest a broad regulation of motor behavior by DA neurons within multiple hypothalamic nuclei and elucidate a novel functional mechanism for the preoptic DA neurons in the initiation of movement.

11.
Mod Pathol ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009490

RESUMO

Solitary fibrous tumors are a type of translocation-associated sarcoma with up to 30% rates of metastasis and poor response to conventional chemotherapy. Other translocation-associated sarcomas have been shown to display elevated expression of various cancer-testis antigens which may render them susceptible to immunotherapy strategies such as cancer vaccines and adoptive T-cell therapy. After an RNA sequencing assay brought the cancer-testis antigen Preferentially Expressed Antigen In Melanoma (PRAME) to our attention as possibly being upregulated in aggressive TERT promoter-mutated solitary fibrous tumors, we used tissue microarrays to asses PRAME expression in a large series of previously characterized solitary fibrous tumors, with correlation to various clinicopathologic features, as well as with tumor-infiltrating macrophages and the associated signal regulatory protein α (SIRPα)-CD47 regulatory checkpoint. We found that PRAME was expressed in 165/180 solitary fibrous tumors, with high expression seen in 58%, irrespective of TERT promoter status. Elevated PRAME expression was more frequent in primary intrathoracic solitary fibrous tumors and correlated with older age at primary diagnosis. Elevated PRAME was also associated with features suggestive of immune evasion, including lower numbers of antigen-presenting CD163+ and CD68+ macrophages, and expression of the "don't eat me" receptor CD47 on tumor cells. Taken together, these features suggest that strategies targeting PRAME with or without concomitant SIRPα-CD47 axis inhibition may represent a potential future therapeutic option in aggressive solitary fibrous tumor.

12.
Sci Rep ; 10(1): 16325, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004934

RESUMO

The diagnosis of tuberculous pericarditis (TBP) remains challenging. This prospective study evaluated the diagnostic value of Xpert MTB/RIF (Xpert) and T-SPOT.TB and adenosine deaminase (ADA) for TBP in a high burden setting. A total of 123 HIV-negative patients with suspected TBP were enrolled at a tertiary referral hospital in China. Pericardial fluids were collected and subjected to the three rapid tests, and the results were compared with the final confirmed diagnosis. Of 105 patients in the final analysis, 39 (37.1%) were microbiologically, histopathologically or clinically diagnosed with TBP. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio (DOR) for Xpert were 66.7%, 98.5%, 96.3%, 83.3%, 44.0, 0.338, and 130.0, respectively, compared to 92.3%, 87.9%, 81.8%, 95.1%, 7.6, 0.088, and 87.0, respectively, for T-SPOT.TB, and 82.1%, 92.4%, 86.5%, 89.7%, 10.8, 0.194, and 55.8, respectively, for ADA (≥ 40 U/L). ROC curve analysis revealed a cut-off point of 48.5 spot-forming cells per million pericardial effusion mononuclear cells for T-SPOT.TB, which had a DOR value of 183.8, while a cut-off point of 41.5 U/L for ADA had a DOR value of 70.9. Xpert (Step 1: rule-in) followed by T-SPOT.TB [cut-off point] (Step 2: rule-out) showed the highest DOR value of 252.0, with only 5.7% (6/105) of patients misdiagnosed. The two-step algorithm consisting of Xpert and T-SPOT.TB could offer rapid and accurate diagnosis of TBP.

13.
Microb Pathog ; : 104526, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33010364

RESUMO

Cryptosporidium spp. and Enterocytozoon bieneusi are two important zoonotic pathogens that can cause diarrhea and other gastrointestinal illnesses in humans and animals. However, the prevalence and genotype of the parasites in Longjiang Wagyu cattle in Heilongjiang Province, Northeast China have not been reported. In the present study, a total of 423 fecal samples of Longjiang Wagyu cattle collected from different farms in Heilongjiang Province, Northeast China, were examined for Cryptosporidium spp. and E. bieneusi using nested PCR. The overall infection rates for Cryptosporidium spp. and E. bieneusi were 6.38% (n = 27) and 7.09% (n = 30), respectively. The prevalence in different age groups ranged from 3.80% (95% confidence interval (CI) 1.01-6.59) to 8.36% (95% CI 4.83-11.90) for Cryptosporidium spp. and 5.97% (95% CI 2.52-9.43) to 7.94% (95% CI 4.49-11.40) for E. bieneusi. By analyzing the DNA sequences of the small subunit (SSU) rRNA gene, two Cryptosporidium species were detected in this study, namely C. parvum (n = 25) and C. ryanae (n = 2). The IIdA20G1 subtype was further identified by using the 60-kDa glycoprotein (gp60) gene of C. parvum. E. bieneusi was identified using three known sequences through the analysis of internal transcribed spacer (ITS) sequences: J (n = 23), I (n = 5), and BEB4 (n = 2), and all belonged to group 2. The results indicated that some of the Cryptosporidium species and E. bieneusi genotypes identified in Longjiang Wagyu cattle in the study areas might have zoonotic potential.

14.
J Int Med Res ; 48(10): 300060520954722, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33021861

RESUMO

OBJECTIVE: Osteoporosis and osteoarthritis are metabolic skeletal disorders. This study aimed to identify specific networks of competitive endogenous RNA (ceRNA) in osteoporosis that differ from those in osteoarthritis. METHODS: The dataset GSE74209 was downloaded from the Gene Expression Omnibus, and differentially expressed microRNAs (DEmiRNAs) in osteoporotic samples and osteoarthritic samples were identified. After predicting target genes and linked long noncoding (lnc)RNAs, ceRNA networks of DEmiRNAs were constructed. The nodes that overlapped between ceRNA networks and the Comparative Toxicogenomics Database were selected as key candidates. RESULTS: Fifteen DEmiRNAs (including 2 downregulated and 13 upregulated miRNAs) were identified in osteoporotic samples versus osteoarthritic samples; these targeted 161 genes and linked to 60 lncRNAs. The ceRNA network consisted of 6 DEmiRNAs, 63 target genes, and 53 lncRNAs. After searching the Comparative Toxicogenomics Database and mining the literature, 2 lncRNAs (MALAT1 and NEAT1), 2 DEmiRNAs (hsa-miR-32-3p, downregulated; and hsa-miR-22-3p, upregulated) and 6 genes (SP1, PTEN, ESR1, ERBB3, CSF1R, and CDK6) that relate to cell death, growth, and differentiation were identified as key candidates separating osteoporosis from osteoarthritis. CONCLUSIONS: Two miRNA-ceRNA networks (including NEAT1/MALAT1-hsa-miR-32-3p-SP1/FZD6 and NEAT1/MALAT1-hsa-miR-22-3p-PTEN/ESR1/ERBB3/CSF1R/CDK6) might have crucial and specific roles in osteoporosis.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33025078

RESUMO

PURPOSE: Laparoscopy-assisted gastrectomy (LAG) is proven by considerable studies as a safe procedure for early gastric cancer (EGC), but its long-term oncologic outcomes in advanced gastric cancer (AGC) have not been well-described. This study aimed at verifying the non-inferiority of LAG in the treatment of EGC and comparing the oncological feasibility of LAG and open gastrectomy (OG) for AGC. METHODS: A total of 209 consecutive patients who underwent LAG or OG with D2 lymph node dissection between December 2008 and November 2012 were included. The survival rate was estimated with the Kaplan-Meier method and the risk factors affecting the survival and recurrence were evaluated with Cox regression models. Subgroup analysis was performed in AGC patients receiving both distal and total gastrectomy. RESULTS: Of 209 patients, 194 (92.8%; mean age, 62.7 years; 56 [28.9%] women) eligible patients were finally enrolled in this study. No significant differences in the number of lymph nodes retrieved and postoperative complications were observed between patients receiving LAG and OG. During a mean follow-up of 58.3 ± 38.1 months (range 0-121 months), the 5-year overall survival and disease-free survival rates were 56.1% and 53.0% for LAG, and 57.7% and 50.9% for OG. In the subgroup analysis for AGC, laparoscopy-assisted distal gastrectomy and total gastrectomy did not result in inferior long-term outcomes, and recurrence was found in 49 patients (31.2%). Age more than 65 years and the advanced tumor stage were independent risk factors of survival. CONCLUSION: LAG is a feasible and safe treatment for gastric cancer, with good oncologic results.

16.
J Ultrasound Med ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026685

RESUMO

OBJECTIVES: To evaluate the feasibility of a new simple ultrasound-guided transforaminal injection in patients with cervical radiculopathy. METHODS: Ultrasound scans of the neck in a plastic model and in 5 unaffected participants were first performed to identify the intervertebral foramen. Then ultrasound-guided transforaminal injections were performed in 20 patients with radiculopathy in the lower cervical spine, and computed tomography was used to verify the accuracy. Complications, the visual analog score, and the neck disability index were assessed at 1 and 3 months after the injection. RESULTS: Computed tomography confirmed that the needle tip was correctly placed in the intervertebral foramen in 88.5% (23 of 26) of injections. No immediate or short-term complications were observed in all patients. The visual analog score and neck disability index at 1 and 3 months were significantly lower than those before the injection (both P < .0001). CONCLUSIONS: Ultrasound may be a feasible and accurate method to guide cervical transforaminal injection.

17.
Biomed Res Int ; 2020: 2474235, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33015156

RESUMO

The aim of this study was to observe the expression of miR-9, miR-21, miR-27b, and miR-34a related with E6/E7 in HPV16-, HPV52-, and HPV58-infected cervical cancer patients and explore their possible role in cervical cancer with HPV infection. The expression levels of 4 miRNAs were detected in cervical exfoliated cells using qRT-PCR. In the current study, miR-34a expression was significantly upregulated in HPV-positive cervical cancer compared with the HPV-negative healthy population and HPV-positive CIN, but just the expression of miR-34a in HPV16 cervical cancer was statistically significant, and the expression of HPV52 and HPV58 was not statistically significant. The expression of miR-21 increased in HPV-positive cervical cancer compared with HPV-positive CIN, but only HPV16-infected cervical cancer had statistical significance compared with HPV16-infected CIN. By observing the change trend of each subtype group, we can show that the expression of miR-9 in HPV16 CIN was opposite to the other subtypes, and it was upregulated, compared with HPV58 CIN, and significantly increased. The level change of miR-27b in HPV58 cervical cancer and HPV58 CIN was opposite to the other subtypes; unlike the expression of miR-27b which was upregulated in HPV16 and HPV52 infected, it was downregulated compared with Normal. We also found that the expression of miR-34a and miR-9 was contrary to other studies. These findings indicate that the upregulated miR-21 expression may be a biomarker to distinguish between CC and CIN. miR-34a in HPV infection, especially in HPV16 infection, might be related to the occurrence and development of cervical cancer. The infection of different subtypes may play different roles in disease by activating different mechanisms; miRNAs play a very complex role in tumorigenesis and development, and there may be multiple targets in which multiple mechanisms play a role.

18.
Acta Otolaryngol ; : 1-5, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33019832

RESUMO

BACKGROUND: Microscopic type-1 tympanoplasty (T1T) is a classical method for the treatment of chronic otitis media. However, it has its limitations. The development of otoendoscopy provided a new method for T1T. OBJECTIVE: To investigate the difference between endoscopic T1T and microscopic T1T. MATERIAL AND METHODS: Seventy-four patients who underwent T1T were evaluated retrospectively. About 52 cases underwent endoscopic T1T, and 22 cases accepted microscopic T1T. Parameters including operative duration, incision size, graft site, duration of postoperative hospitalization, visual analog scale (VAS) score, complications, hearing improvement, and expenses were compared. RESULTS: Operative duration of endoscopic T1T (47.0 ± 8.2 min) was shorter than microscopic T1T (58.0 ± 9.3 min) (p < .05). The VAS score under endoscopic T1T (1.5 ± 0.2) was lower than microscopic T1T (5.6 ± 0.4) (p < .05). There was no complication during endoscopic T1T, but damage to the chorda tympani nerve (one case) was noted for microscopic T1T. There was no difference in hearing improvement between endoscopic (15.0 ± 1.5 dB) and microscopic T1T (16.0 ± 1.1 dB). Duration of postoperative hospitalization and expenses were lower for endoscopic T1T. CONCLUSIONS AND SIGNIFICANCE: Endoscopic T1T is a minimally invasive surgery with similar graft success rate, comparable hearing improvement, fast recovery, low cost, and high patient satisfaction compared to microscopic T1T.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33019975

RESUMO

Macrophages contribute to abdominal aortic aneurysm (AAA), but the effect of macrophage on AAA formation is not totally understood. Recent research proved that macrophage pyroptosis plays an important role in many cardiovascular disease. However, whether macrophage pyroptosis is involved in AAA and its mechanism remains unknown. In this study, we found that the pyroptosis significantly increased in AAA tissues. ß5i inhibitor PR-957 treatment or ß5i deficiency markedly ameliorated AAA formation and decreased the pyroptosis. Pyroptosis were also significantly attenuated in bone marrow derived macrophages (BMDM) from ß5i-/- mice compared with the control group when they were subjected to OXLDL. Mechanistically, ß5i may promote activation of NFκB which augment NLRP3 expression. In conclusion, this study suggested macrophages pyroptosis are involved in AAA and inhibition or knockout of ß5i decreased macrophage pyroptosis via IκB/NFκB pathway.

20.
J Cell Mol Med ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33021072

RESUMO

DEP domain containing 1(DEPDC1) is involved in the tumorigenesis of a variety of cancers. But its role in tumorigenesis of lung adenocarcinoma (LUAD) is not fully understood. Here, we investigated the role and the underlying mechanisms of DEPDC1 in the development of LUAD. The expression and prognostic values of DEPDC1 in LUAD were analysed by using the data from public databases. Gene enrichment in TCGA LUAD was analysed using GSEA software with the pre-defined gene sets. Cell proliferation, migration and invasion of A549 cells were examined with colony formation, Transwell and wound healing assays. The function of DEPDC1 in autophagy and RAS-ERK1/2 signalling was determined with Western blot assay upon DEPDC1 knockdown and/or overexpression in A549, HCC827 and H1993 cells. The results demonstrated that DEPDC1 expression was up-regulated in LUAD tissues, and its high expression was correlated with unfavourable prognosis. The data also showed that DEPDC1 knockdown impaired proliferation, migration and invasion of A549 cells. Most notably, the results showed that DEPDC1 up-regulated RAS expression and thus enhanced ERK1/2 activity, through which DEPDC1 could inhibit autophagy. In conclusion, our study revealed that DEPDC1 is up-regulated in LUAD tissues and plays an oncogenic role in LUAD, and that DEPDC1 inhibits autophagy through the RAS-ERK1/2 signalling in A549, HCC827 and H1993 cells.

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