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1.
Brain ; 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35040478

RESUMO

Chronic pain is the most common neurological disorder of HIV patients. Multiple neuropathologies were identified in the pain pathway. Among them is the prominent astrocytic reaction (a.k.a. astrogliosis). However, the pathogenic role and mechanism of the astrogliosis are unclear. Here, we show that the astrogliosis is crucial for the pain development induced by a key neurotoxic HIV protein gp120 and that a neuron-to-astrocyte Wnt5a signal controls the astrogliosis. Ablation of astrogliosis blocked the development of gp120-induced mechanical hyperalgesia, and concomitantly the expression of neural circuit polarization (NCP) in the spinal dorsal horn (SDH). We demonstrated that conditional knockout (CKO) of either Wnt5a in neurons or its receptor ROR2 in astrocytes abolished not only gp120-induced astrogliosis but also hyperalgesia and NCP. Furthermore, we found that the astrogliosis promoted expression of hyperalgesia and NCP via IL-1ß regulated by a Wnt5a-ROR2-MMP2 axis. Our results shed light on the role and mechanism of astrogliosis in the pathogenesis of HIV-associated pain.

2.
Signal Transduct Target Ther ; 7(1): 9, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35027529

RESUMO

Lung adenocarcinoma (LUAD) and squamous carcinoma (LUSC) are two major subtypes of non-small cell lung cancer with distinct pathologic features and treatment paradigms. The heterogeneity can be attributed to genetic, transcriptional, and epigenetic parameters. Here, we established a multi-omics atlas, integrating 52 single-cell RNA sequencing and 2342 public bulk RNA sequencing. We investigated their differences in genetic amplification, cellular compositions, and expression modules. We revealed that LUAD and LUSC contained amplifications occurring selectively in subclusters of AT2 and basal cells, and had distinct cellular composition modules associated with poor survival of lung cancer. Malignant and stage-specific gene analyses further uncovered critical transcription factors and genes in tumor progression. Moreover, we identified subclusters with proliferating and differentiating properties in AT2 and basal cells. Overexpression assays of ten genes, including sub-cluster markers AQP5 and KPNA2, further indicated their functional roles, providing potential targets for early diagnosis and treatment in lung cancer.

3.
Quant Imaging Med Surg ; 12(1): 796-809, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34993119

RESUMO

Background: Hyperbilirubinemia (HBN) can cause myocardial injury in neonates. Advancement in myocardial deformation imaging allows the detection of subclinical changes in myocardial contractility. The present study aimed to evaluate the changes in left ventricular contractility in newborns with hyperbilirubinemia by 2D speckle tracking imaging (STI). Methods: A group of 134 neonates who reached the diagnostic level of HBN as the HBN group was selected. The control group included 56 healthy newborns. The interventricular septum, anterior partition, anterior wall, sidewall, posterior wall, and inferior wall were separated into the basal, middle, and apical segments. In each segment, speckle tracking analysis was performed in the subintimal, middle, and subadventitial myocardium. The overall longitudinal strain of the myocardium in different ventricular walls and segments and global longitudinal strain (GLS) were computed. At the same time, the laboratory results of blood gas analysis, blood routine tests, liver function, and myocardial enzyme spectrum in HBN neonates were collected and correlated with the left ventricular stratified strain parameters. Results: The gradient of the left ventricular GLS had the same characteristics in both groups of newborns. There was a decreasing trend of longitudinal strain (LS) from the intima to the adventitia (i.e., GLSendo > GLSmid > GLSepi). This gradient was also present in stratified LS in each myocardial segment (P<0.001). The LS showed an increasing trend from the basal to the apical segment (P<0.001). The LS of the ventricular septum, anterior wall (or anterior septum), inferior wall, lateral wall, and posterior wall showed a decreasing trend (P<0.001). Stratified strain parameters of the ventricular wall (i.e., the 3-layer myocardium: LSendo-SEPT, LSmid-SEPT, and LSepi-SEPT) were all significantly lower in the HBN group than in the control group (P=0.019, P=0.019, and P=0.023, respectively). LSedo-ANT, LSmid-ANT, and LSepi-ANT were also reduced, and the difference between LSendo-ANT and LSepi-ANT was statistically significant. The segmental stratified strain parameters (i.e., the apical 3-layer myocardium: LSepi-a, LSmid-a, and LSepi-a) decreased, and the difference in LSepi-a was statistically significant (P=0.043). Overall strain parameters (i.e., the 3-layer myocardial overall strain: GLSendo, GLSmid, and GLSepi) were reduced, but the difference was not statistically significant (P=0.612, P=0.653, and P=0.585, respectively). The subclinical changes in systolic function in the HBN group, reflected by the parameters of longitudinal myocardial strain, correlate to some extent with multiple results of laboratory tests. Conclusions: 2DSTI stratified strain technology can quantitively evaluate changes in the LS of the left ventricle in different ventricular walls, wall segments, and layers of the myocardium.

4.
Sci Rep ; 12(1): 1023, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35046505

RESUMO

It is unclear as to whether Wilms' tumor 1-associated protein (WTAP) promotes or suppresses breast cancer. This immunohistochemistry analysis explored levels of WTAP expression in 347 cases of breast cancer and analyzed the relationship between WTAP expression and the clinicopathological characteristics and prognosis of breast cancer patients. The rate of high WTAP expression was significantly higher in breast cancer tissue than in adjacent normal breast tissue (37.5% vs 0.0%; P < 0.001). WTAP expression was positively associated with tumor size and grade, and negatively associated with axillary lymph node metastasis, estrogen and progesterone receptor status. Rates of high WTAP expression were 66.1% in triple-negative breast cancer (TNBC) tissue and 31.3% in non-TNBC tissue. In multiple logistic regression analysis, independent predictors of WTAP expression in breast cancer included larger tumor size (odds ratio = 1.907; 95% confidence interval: 1.185-3.067; P = 0.008), lymph node metastasis (0.597; 0.373-0.956; P = 0.032) and TNBC status (3.735; 2.056-6.784; P < 0.001). No clear relationship was observed between patient prognosis and WTAP expression. We suggest that WTAP expression is upregulated in breast cancer and appears to both promote tumor growth and inhibit lymph node metastasis.

5.
Fish Shellfish Immunol ; 120: 547-559, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34923115

RESUMO

Aeromonas hydrophila can pose a great threat to survival of freshwater fish. In this study, A. hydrophila infection could decrease blood cell numbers, promote blood cell damage as well as alter the levels of alkaline phosphatase (ALP), lysozyme (LZM), aspartate aminotransferase (AST), total antioxidant capacity (T-AOC), total superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in immune-related tissues of red crucian carp (RCC, 2 N = 100) and triploid cyprinid fish (3 N fish, 3 N = 150). In addition, the significant alternation of antioxidant status was observed in PBMCs isolated from RCC and 3 N following LPS stimulation. The core differential expression genes (DEGs) involved in apoptosis, immunity, inflammation and cellular signals were co-expressed differentially in RCC and 3 N following A. hydrophila challenge. NOD-like receptor (NLR) signals appeared to play a critical role in A. hydrophila-infected fish. DEGs of NLR signals in RCCah vs RCCctl were enriched in caspase-1-dependent Interleukin-1ß (IL-1ß) secretion, interferon (IFN) signals as well as cytokine activation, while DEGs of NLR signals in 3Nah vs 3Nctl were enriched in caspase-1-dependent IL-1ß secretion and antibacterial autophagy. These results highlighted the differential signal regulation of different ploidy cyprinid fish to cope with bacterial infection.

6.
Biotechnol Bioeng ; 119(1): 268-276, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34698369

RESUMO

Generally, high bioelectroactivity of anodophilic biofilm favors high power generation of microbial fuel cell (MFC); however, it is not clear whether it can promote denitrification of MFC synchronously. In this study, we studied the impact of anodophilic biofilm bioelectroactivity on the denitrification behavior of air-cathode MFC (AC-MFC) in steady state and found that high bioelectroactivity of anodophilic biofilm not only favored high power generation of the AC-MFC, but also promoted the growth of denitrifers at the anodes and strengthened denitrification. Anodophilic biofilms of AC-MFC with various bioelectroactivity were acclimated at conditions of open circuit (OC), Rext of 1000 Ω and 20 Ω (denoted as AC-MFC-OC, AC-MFC-1000Ω, and AC-MFC-20Ω, respectively) and performed for over 100 days. Electrochemical tests and microbial analysis results showed that the anode of the AC-MFC-20Ω delivered higher current response of both oxidation and denitrification and had higher abundance of electroactive bacteria than the AC-MFC-OC, AC-MFC-1000Ω, demonstrating a higher bioelectroactivity of the anodophilic biofilms. Moreover, these electroactive bacteria favored the accumulation of denitrifers, like Thauera and Alicycliphilus, probably by consuming trace oxygen through catalyzing oxygen reduction. The AC-MFC-20Ω not only delivered a 61.7% higher power than the AC-MFC-1000Ω, but also achieved a stable and high denitrification rate constant (kDN ) of 1.9 h-1 , which was 50% and 40% higher than that of the AC-MFC-OC and AC-MFC-1000Ω, respectively. It could be concluded that the high bioelectroactivity of the anodophilic biofilms not only favored high power generation of the AC-MFC, but also promoted the enrichment of denitrifers at the anodes and strengthened denitrification. This study provided an effective method for enhancing power generation and denitrification performance of the AC-MFC synchronously.

7.
Fish Shellfish Immunol ; 120: 620-632, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34968709

RESUMO

FerL, a multifunctional iron-storage polypeptide, not only exhibited a regulatory role in iron metabolism, but also participated in the regulation of fish immunity. In this study, ORF sequence of WR-FerL was 522 bp, encoding 173 amino acid residues. Tissue-specific analysis revealed that the highest expression of WR-FerL was detected in spleen. A. hydrophila challenge and LPS stimulation could sharply enhance WR-FerL mRNA expression in tissues and fish cells, respectively. Purified WR-FerL fusion peptide exhibited in vitro binding activity to A. hydrophila and endotoxin, limited bacterial dissemination to tissues as well as attenuated A. hydrophila-induced production of pro-inflammatory cytokines. Moreover, WR-FerL overexpression could abrogate NF-κB and TNFα promoter activity in fish cells. These results indicated that WR-FerL could play an important role in host defense against A. hydrophila infection.

8.
Front Synaptic Neurosci ; 13: 748929, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867259

RESUMO

Opioids are widely used for pain relief; however, chronic opioid use causes a paradoxical state of enhanced pain sensitivity, termed "Opioid-induced hyperalgesia (OIH)." Despite the clinical importance of OIH, the detailed mechanism by which it enhances pain sensitivity remains unclear. In this study, we tested whether repeated morphine induces a neuronal circuit polarization in the mouse spinal dorsal horn (SDH). Transgenic mice expressing GFP to neurokinin 1 receptor-expressing neurons (sNK1Rn) and GABAergic interneurons (sGABAn) that received morphine [20 mg/kg, once daily for four consecutive days (i.p.)] developed mechanical hypersensitivity. Repeated morphine altered synaptic strengths in the SDH as a specific cell-type but not in a gender-dependent manner. In sNK1Rn and non-tonic firing neurons, repeated morphine treatment significantly increased frequency of spontaneous excitatory postsynaptic current (sEPSC) and evoked EPSC (eEPSC). In addition, repeated morphine treatment significantly decreased evoked inhibitory postsynaptic current (eIPSC) in sNK1Rn. Conversely, in sGABAn and tonic firing neurons, repeated morphine treatment significantly decreased sEPSC frequency and eEPSC, but had no change of eIPSC in sGABAn. Interestingly, repeated morphine treatment significantly decreased neuronal rheobase of sNK1Rn but had no effect on sGABAn. These findings suggest that spinal neuronal circuit polarization maybe the mechanism of OIH and identify a potential therapeutic mechanism to prevent or treat opioid-induced pain.

9.
Front Nutr ; 8: 760985, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869532

RESUMO

Background: Vitamins and carotenoids may be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Previously related publications mainly focused on vitamin D and vitamin E, and studies on other vitamins and carotenoids and NAFLD are scarce. Methods: This study aimed to explore the clinical relevance of vitamin A, B vitamins (vitamin B1, vitamin B2, niacin, vitamin B6, folate, vitamin B12, and choline), vitamin C and carotenoids (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, lutein + zeaxanthin) with liver steatosis and fibrosis in the 2017-2018 NHANES (N = 4,352). Liver steatosis and fibrosis were detected by transient elastography. Logistic regression, linear regression and restricted cubic splines were adopted to explore the non-linear dose-response relationships. Results: Higher intakes of vitamin C [0.68 (0.50-0.93)] and ß-carotene [0.71 (0.54-0.93)] were inversely associated with liver steatosis. Higher levels of serum vitamin C [0.45 (0.32-0.62)] were inversely associated with liver fibrosis, while higher intakes of choline [1.43 (1.04-1.98)] and α-carotene [1.67 (1.01-2.74)] were positively associated with liver fibrosis. In addition, marginally inverse association between lutein + zeaxanthin and liver steatosis and positive association between vitamin B12 and liver fibrosis were found. In linear regression, the above-mentioned associations between vitamin C, ß-carotene, and lutein + zeaxanthin and liver steatosis, and serum vitamin C, choline, α-carotene, and vitamin B12 and liver fibrosis were also found. The above-mentioned associations were mainly linear, while the relationship between ß-carotene and liver steatosis might be non-linear. Conclusion: Vitamin C, α-carotene, ß-carotene, lutein + zeaxanthin, choline and vitamin B12 may be associated with liver steatosis and fibrosis.

10.
Front Cell Dev Biol ; 9: 780023, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34917618

RESUMO

Aberrant alternative splicing of pre-mRNA is an emerging cancer hallmark. Many cancer-associated genes undergo alternative splicing to produce multiple isoforms with diverse or even antagonistic functions. Oncogenic isoforms are often up-regulated, whereas tumor suppressive isoforms are down-regulated during tumorigenesis. Serine/arginine-rich splicing factor 6 (SRSF6) is an important splicing factor that regulates the alternative splicing of hundreds of target genes, including many cancer-associated genes. The potential roles of SRSF6 in cancers have attracted increasing attentions in the past decade. Accumulated pieces of evidence have shown that SRSF6 is a potential oncogenic gene that promotes oncogenic splicing when overexpressed. Targeting SRSF6 may suppress tumorigenesis. In this review, we describe the gene, mRNA, and protein structure of SRSF6; summarize the current understanding of the expression, functions, and regulatory mechanisms of SRSF6 during tumorigenesis; and discuss the potential application of targeting SRSF6 in cancer treatment.

11.
Gastroenterol Rep (Oxf) ; 9(6): 533-542, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34925850

RESUMO

Background: The significance of endoscopic evaluation in the diagnosis and management of ulcerative colitis (UC) has been widely recognized. Over the years, scholars have established several endoscopic scores. Herein, we assessed the clinical application value of the Mayo Endoscopic Subscore (Mayo ES), the Degree of Ulcerative Colitis Burden of Luminal Inflammation (DUBLIN) score, and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score in UC patients, by comparing their correlation with disease activity and their predictive potential for treatment response and clinical outcomes. Methods: UC patients hospitalized from September 2015 to September 2019 were retrospectively analysed. We employed Spearman's rank correlation coefficient to assess the linear association of the assessed endoscopic scores with the clinical parameters. The receiver-operating characteristic curve was applied to evaluate the predictive capabilities of the endoscopic scores for treatment escalation and 1-year readmission. Results: A total of 178 patients were enrolled; most of them (82%) suffered moderate or severe colitis. Among them, 48 (27%) patients received treatment escalation and 59 (33%) were readmitted within 1 year. The DUBLIN and UCEIS scores demonstrated higher correlations with clinical parameters than the Mayo ES. The DUBLIN scores significantly differed between patients with mild, moderate, and severe colitis (all P < 0.001). The UCEIS scores demonstrated the best predictabilities for treatment escalation and 1-year readmission with an area under the curve of 0.88 and 0.75, respectively. Compared to the UCEIS and DUBLIN scores, the predictive capabilities of the Mayo ES for treatment escalation (both P < 0.001) and 1-year readmission (P < 0.001 and P = 0.002, respectively) were lower. The UCEIS scores exhibited a significant difference between the steroid-responsive group and the steroid-dependent or steroid-refractory group (both P < 0.001), while no significant differences in the Mayo ES and DUBLIN scores were found among the three groups (both P > 0.05). Conclusion: This study demonstrates that both the DUBLIN and UCEIS scores outperform the Mayo ES in assessing disease severity and predicting treatment response and clinical outcomes in UC patients.

12.
Ann Transl Med ; 9(21): 1624, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34926668

RESUMO

Background: To investigate the abnormal expression of circ_0008590 and its parent gene, reticuloendotheliosis viral oncogene related B (RELB) in human retinal microvascular endothelial cells (hRECs) in hyperglycemia and the potential mechanism. Methods: The levels of RELB, circ_0008590, and miR-1243 in hRECs or clinical samples were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Dual-luciferase reporter assay was used to test the interaction between RELB/circ_0008590 and miR-1243. Cell Counting Kit-8 (CCK-8), Transwell, flow cytometry (FCM), wound healing, and tube formation assays were used for the physiological investigation. The interaction between human RELB and circ_0008590 was studied in streptozotocin (STZ) induced diabetic retinopathy (DR) C57BL/6 mice. Results: The levels of circ_0008590 and RELB were increased in hRECs in hyperglycemia; during the progression of DR, the levels of circ_0008590 and RELB messenger RNA (mRNA) in aqueous humor were first decreased and then increased, whereas miR-1243 showed an opposite trend. Both RELB 3'-untranslated region (UTR) and circ_0008590 shared a similar binding site for miR-1243. Further, miR-1243 mimic suppressed the proliferation and migration of hRECs, promoting the apoptosis ratio, which could be rescued by the overexpression of circ_0008590. In STZ-induced DR mice, miR-1243 agomir rescued the effects of the overexpression of human RELB. Conclusions: In hyperglycemia, high expression of RELB/circ_0008590 could be suppressed by miR-1243, and the nuclear factor-κB (NF-κB) pathway is subsequently affected.

13.
Am J Transl Res ; 13(11): 13156-13166, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956536

RESUMO

AIM: This research is both a case study and a systematic literature review. Our goal was to learn more about the pathophysiology, clinical features, and therapy options for idiopathic mesenteric phlebosclerosis (IMP). METHODS: A case of IMP was treated by surgery in our department. Combined with the data of 240 cases of IMP retrieved from PubMed and Wanfang Data, we conducted a systematic review of this less well-known disease. RESULTS: These 240 cases of IMP mainly occurred in East Asia. Among the patients, 78.7% of them had a history of herbal medicine consumption; 15.2% had no obvious symptoms and their diagnosis was confirmed through characteristic CT findings and colonoscopic manifestations; 58.4% were cured by conservative treatment; 41.6% had severe symptoms and underwent surgical treatment. Additionally, more patients treated with surgical treatment had lesions involving the cecum (59/82 vs. 53/115, P=0.0003) and sigmoid colon (20/82 vs. 10/115, P=0.0025) compared with those treated conservatively. CONCLUSION: The occurrence of IMP is associated with the long-term consumption of herbal medicines. Early diagnosis of IMP could be determined by CT and colonoscopy and conservative or surgical treatment was chosen based on of the severity of the condition (e.g., the involved bowel segment).

14.
Zhonghua Nan Ke Xue ; 27(7): 645-648, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34914234

RESUMO

Objective: To investigate the trend of change in the sperm concentration of Chinese fertile males from 1984 to 2019. METHODS: We searched CNKI, CQVIP and Wanfang Database for literature relevant to human sperm concentration published from 1984 to 2019, and analyzed the trend of change in the sperm concentration of fertile men in China in the past 35 years. RESULTS: A total of 9 495 publications were identified, of which 73 with 11 606 subjects were included. Based on the results of fitting calculation, the perm concentration of the males declined significantly from 98.8486 ×106/ml in 1984 to 72.5531 ×106/ml in 2019, with a mean decrease of 0.7513 ×106/ml annually (P < 0.01), and the reduction was more significant in North than in South China (-1.2754 vs -0.4587 ×106/ml, P = 0.01). CONCLUSIONS: The sperm concentration of fertile Chinese men was decreasing in the past 35 years, which might be related to unhealthy living habits and environmental pollution.


Assuntos
Fertilidade , Procedimentos Cirúrgicos Reconstrutivos , China , Humanos , Masculino , Contagem de Espermatozoides , Espermatozoides
15.
J Healthc Eng ; 2021: 3433615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900182

RESUMO

Effective drug intervention is the most important method to improve the prognosis, improve the quality of life, and prolong the life of patients with heart failure. This study aimed to explore the protective effect of astragaloside IV on myocardial cell injury induced by oxidized low-density lipoprotein (OxLDL) and its regulatory mechanism on the increase of brain natriuretic peptide (BNP) caused by myocardial cell injury. The model of myocardial cell injury, protection, and histone deacetylase (HDAC) inhibition in HL-1 mice was established by OxLDL treatment, astragaloside IV intervention, and UF010 coincubation. The effects of OxLDL and astragaloside IV on apoptosis were detected by flow cytometry. The expression level of BNP mRNA and protein in cells was investigated by real-time fluorescence quantification, western blot, and enzyme-linked immunosorbent assay. HDAC activity in nucleus was calibrated by fluorescence absorption intensity. Enzyme-linked immunosorbent assay (ELISA) was applied to test eNOS level in myocardial cells. OxLDL significantly promoted apoptosis, upregulated BNP mRNA, increased BNP protein level inside and outside cells, and decreased eNOS level. Compared with OxLDL treatment group, apoptosis decreased, BNP mRNA expression level decreased, BNP protein concentration decreased, and eNOS level increased significantly combined with low and high concentration astragaloside IV treatment group. HDAC activity significantly increased in OxLDL treatment group and significantly decreased after combined incubation with low and high concentrations of astragaloside IV. Inhibition of HDAC significantly increased eNOS level and decreased BNP protein level. In conclusion, astragaloside IV can reverse the low level of eNOS caused by OxLDL by regulating HDAC activity to protect myocardial cells from oxide damage, which is manifested by the decrease of BNP concentration.


Assuntos
Histona Desacetilases , Peptídeo Natriurético Encefálico , Animais , Lipoproteínas LDL , Camundongos , Qualidade de Vida , Saponinas , Triterpenos
16.
Exp Cell Res ; 409(1): 112884, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34743935

RESUMO

The dysregulation of deubiquitinating enzymes (DUBs), which regulate the stability of most cellular proteins, have been implicated in many human diseases, including cancers. Ubiquitin-specific protease 18 (USP18), a member of the DUBs family, functions as a potential tumour promoter in various cancers. However, the biological function and clinical significance of USP18 in esophageal squamous cell carcinomas (ESCC) are still unclear. Here, we found that ESCC tumors had higher USP18 expression compared with that of normal esophageal epithelial tissues, and high USP18 level was significantly correlated with malignant phenotype and shorter survival in patients with ESCC. In functional experiments, USP18 knockdown significantly inhibited ESCC invasion and metastasis in vitro. Consistently, a xenograft assay showed that knockdown of USP18 in ESCC cell suppressed their dissemination to lung tissue in vivo. Furthermore, we showed that USP18 promoted ESCC cell metastasis by inducing ZEB1 mediated epithelial-mesenchymal transition (EMT). Importantly, our results demonstrated that the oncogenic effect of USP18 in ESCC is partially dependent on ZEB1 enhancement. Mechanistic investigations revealed that USP18 directly bound ZEB1 and decreased its ubiquitination to enhance the protein stability of ZEB1 in ESCC cells. Overall, our data highlighted an essential role of USP18 in ESCC metastasis, suggesting that it could be a potential diagnostic and therapeutic target for ESCC.

17.
BMC Cancer ; 21(1): 1170, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724907

RESUMO

BACKGROUND: The prognosis of patients with gastrointestinal stromal tumors (GISTs) is generally evaluated at the time of diagnosis but does not reflect the survival dynamics of patients in the future. Therefore, the purpose of this article was to evaluate the conditional survival (CS) of Chinese patients with GISTs after radical resection. METHODS: This retrospective study included 451 patients who underwent radical surgery for GISTs. A Cox proportional hazard model was used to evaluate the prognostic factors of disease-free survival (DFS). The 3-year conditional DFS (CDFS3) of patients who survived for x years was expressed as CDFS3=DFS(x + 3)/DFS(x). RESULTS: The traditional 3-year DFS rate decreased gradually from 94.0% at 3 years to 77.3% at 7 years, while the CDFS3 rate increased from 94.0 to 95.2% over the survival time of the patients. In addition, classic clinicopathological prognostic factors had different effects on CDFS3, with changes observed in survival time, but these effects were only slight or moderate (|d|<0.5). Although multivariate analysis showed that age, sex, mitotic index and tumor rupture were independent risk factors for DFS at baseline, all adverse prognostic factors, except for the mitotic index, lost their predictive significance at 5 years after operation. When the Modified NIH criteria were included, the risk staging was found to be an independent risk factor for recurrence or death. Time-dependent Cox regression analysis showed that the modified NIH criteria independently affected the recurrence or death of GIST patients within 2 years after operation. CONCLUSION: CS provides detailed dynamic survival information about Chinese patients with primary resected GISTs. The mitotic index is of great clinical significance for the monitoring and follow-up of patient populations with a high risk of tumor recurrence or death until 5 years after surgery.

18.
Cancer Commun (Lond) ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34738326

RESUMO

BACKGROUND: To date, there is no approved blood-based biomarker for breast cancer detection. Herein, we aimed to assess semaphorin 4C (SEMA4C), a pivotal protein involved in breast cancer progression, as a serum diagnostic biomarker. METHODS: We included 6,213 consecutive inpatients from Tongji Hospital, Qilu Hospital, and Hubei Cancer Hospital. Training cohort and two validation cohorts were introduced for diagnostic exploration and validation. A pan-cancer cohort was used to independently explore the diagnostic potential of SEMA4C among solid tumors. Breast cancer patients who underwent mass excision prior to modified radical mastectomy were also analyzed. We hypothesized that increased pre-treatment serum SEMA4C levels, measured using optimized in-house enzyme-linked immunosorbent assay kits, could detect breast cancer. The endpoints were diagnostic performance, including area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Post-surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM classification. There was no restriction on disease stage for eligibilities. RESULTS: We included 2667 inpatients with breast lesions, 2378 patients with other solid tumors, and 1168 healthy participants. Specifically, 118 patients with breast cancer were diagnosed with stage 0 (5.71%), 620 with stage I (30.00%), 966 with stage II (46.73%), 217 with stage III (10.50%), and 8 with stage IV (0.39%). Patients with breast cancer had significantly higher serum SEMA4C levels than benign breast tumor patients and normal controls (P < 0.001). Elevated serum SEMA4C levels had AUC of 0.920 (95% confidence interval [CI]: 0.900-0.941) and 0.932 (95%CI: 0.911-0.953) for breast cancer detection in the two validation cohorts. The AUCs for detecting early-stage breast cancer (n = 366) and ductal carcinoma in situ (n = 85) were 0.931 (95%CI: 0.916-0.946) and 0.879 (95%CI: 0.832-0.925), respectively. Serum SEMA4C levels significantly decreased after surgery, and the reduction was more striking after modified radical mastectomy, compared with mass excision (P < 0.001). The positive rate of enhanced serum SEMA4C levels was 84.77% for breast cancer and below 20.75% for the other 14 solid tumors. CONCLUSIONS: Serum SEMA4C demonstrated promising potential as a candidate biomarker for breast cancer diagnosis. However, validation in prospective settings and by other study groups is warranted.

19.
BMC Cancer ; 21(1): 1274, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34823489

RESUMO

BACKGROUND: The present study compared the effectiveness and toxicity of two treatment modalities, namely radiotherapy combined with nimotuzumab (N) and chemoradiotherapy (CRT) in patients with locally recurrent nasopharyngeal carcinoma (LR-NPC). METHODS: Patients with LR-NPC who were treated with radiotherapy were retrospectively enrolled from January 2015 to December 2018. The treatment included radiotherapy combined with N or platinum-based induction chemotherapy and/or concurrent chemotherapy. The comparison of survival and toxicity between the two treatment modalities was evaluated using the log-rank and chi-squared tests. Overall survival (OS) was the primary endpoint. RESULTS: A total of 87 patients were included, of whom 32 and 55 were divided into the N group and the CRT group, respectively. No significant differences were noted in the survival rate between the N and the CRT groups (4-year OS rates, 37.1% vs. 40.7%, respectively; P = 0.735). Mild to moderate acute complications were common during the radiation period and mainly included mucositis and xerostomia. The majority of the acute toxic reactions were tolerated well. A total of 48 patients (55.2%) demonstrated late radiation injuries of grade ≥ 3, including 12 patients (37.5%) in the N group and 36 patients (66.5%) in the CRT group. The CRT group exhibited significantly higher incidence of severe late radiation injuries compared with that of the N group (P = 0.011). CONCLUSION: Radiotherapy combined with N did not appear to enhance treatment efficacy compared with CRT in patients with LR-NPC. However, radiotherapy combined with N may be superior to CRT due to its lower incidence of acute and late toxicities. Further studies are required to confirm the current findings.

20.
Neuroscience ; 480: 108-116, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34762982

RESUMO

Morphine rewarding properties are the main reasons for drug-craving in behaviors occurring during morphine addiction. It has been suggested that morphine addiction relies on signals to the mesolimbic dopamine system, although the mechanisms outside the dopaminergic system are still unclear. Notably, the role of the dorsal raphe nucleus (DRN) serotoninergic (5-hydroxytryptamine, 5-HT) system remains unexplored. Using in vivo electrophysiological and optogenetic approaches, we found that morphine treatment increased DRN 5-TH neurons firing rate and optogenetic activation of DRN 5-HT neurons induced a rewarding effect, indicating that morphine reward is related to DRN 5-HT neurons. Accordingly, optogenetic inhibition of DRN 5-HT neurons following morphine injection reversed conditioned place preference (CPP) during chronic morphine treatment. These findings aid our understanding of the new functions of the DRN 5-HT neurons for morphine rewarding effect and provide a potential approach for the treatment of morphine addiction.

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