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1.
J Oncol ; 2022: 5735462, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072974

RESUMO

Hepatocellular carcinoma (HCC) is a high-mortality malignant tumor with genetic and phenotypic heterogeneity, making predicting clinical outcomes challenging. The purpose of this investigation was to examine the potential usefulness of lncRNA DDX11 antisense RNA 1 (DDX11-AS1) as a biomarker for diagnosis and prognosis in hepatocellular carcinoma (HCC). The TCGA-LIHC datasets were searched for patients' clinical information and RNA-seq data, which were then collected. Relative expression levels of DDX11-AS1 in HCC tissues were determined by qRT-PCR. In order to test the sensitivity and specificity of the DDX11-AS1 receiver, receiver operating characteristic curves were utilized. The association of DDX11-AS1 expression with clinicopathological factors or prognosis was statistically analyzed. We found that the levels of DDX11-AS1 were higher in HCC specimens than in normal specimens. ROC analysis showed that DDX11-AS1 was a useful marker for discriminating HCC tissues from normal nontumor specimens. According to the results of clinical tests, a high level of DDX11-AS1 expressions was significantly related to the pathologic stage (p=0.015) and the histologic grade (p < 0.001). Survival studies indicated that patients with higher DDX11-AS1 expression had a significantly poorer overall survival (p=0.005) and progression-free interval (p=0.003) than those with lower DDX11-AS1 expression. Multivariate survival analysis verified that DDX11-AS1 expression level was an independent predictor for HCC patients. Overall, DDX11-AS1 may serve as a tumor promotor during HCC progression, and its high level may be a potential marker for HCC patients.

2.
Wei Sheng Yan Jiu ; 51(4): 591-595, 2022 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-36047264

RESUMO

OBJECTIVE: To understand the current situation of irritability in the elderly in Mianyang City, explore the influencing factors of irritability. METHODS: In 2019, 823 elderly people over 60 years old in Mianyang City were selected by multi-stage random sampling, including 351(42.65%) males and 472(57.35%) females, with a median age of 67 years and a interquartile interval of 8 years. The information was collected by self rating scale of irritability, depression and anxiety and questionnaire of influencing factors of negative emotion. Questionnaire surveys were used to investigate their irritability, health status, health-related behaviors, support for the elderly, characteristics of the elderly, and mental health knowledge. Describe the detection rate of irritability, and use two-class logistic regression model to analyze the influencing factors of their depressive symptoms. RESULTS: A total of 823 elderly people in Mianyang City were investigated, 178 were found to be irritable, and the prevalence of irritability was 21.63%. The result of Logistic regression model showed that: female(OR= 1.800, 95% CI 1.223-2.627), ill within two weeks(OR = 1.611, 95% CI 1.101-2.358), hospitalized within one year(OR = 2.045, 95% CI 1.327-3.048), no spouse(OR = 0.349, 95% CI 0.209-0.582), good self-rated health(OR = 0.389, 95% CI 0.243-0.625), emotional support for children(OR = 0.549, 95% CI 0.341-0.882), the old-age care model was self care(OR = 0.649, 95% CI 0.453-0.931), they were related to irritating emotions. CONCLUSION: A certain proportion of the elderly in Mianyang City have irritability. Gender, marital status, health status, pension support and characteristics are the influencing factors of irritability.


Assuntos
Comportamentos Relacionados com a Saúde , Idoso , Criança , China/epidemiologia , Cidades , Feminino , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários
3.
World J Clin Cases ; 10(20): 7105-7115, 2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-36051147

RESUMO

BACKGROUND: Lynch syndrome (LS) is an autosomal dominant hereditary disorder because of germline mutations in DNA mismatch repair genes, such as MutL homolog 1 (MLH1), PMS1 homolog 2, MutS homolog 2, and MutS homolog 6. Gene mutations could make individuals and their families more susceptible to experiencing various malignant tumors. In Chinese, MLH1 germline mutation c.(453+1_454-1)_(545+1_546-1)del-related LS has been infrequently reported. Therefore, we report a rare LS patient with colorectal and endometrioid adenocarcinoma and describe her pedigree characteristics. CASE SUMMARY: A 57-year-old female patient complained of irregular postmenopausal vaginal bleeding for 6 mo. She was diagnosed with LS, colonic malignancy, endometrioid adenocarcinoma, secondary fallopian tube malignancy, and intermyometrial leiomyomas. Then, she was treated by abdominal hysterectomy, bilateral oviduct oophorectomy, and sentinel lymph node resection. Genetic testing was performed using next-generation sequencing technology to detect the causative genetic mutations. Moreover, all her family members were offered a free genetic test, but no one accepted it. CONCLUSION: No tumor relapse or metastasis was found in the patient during the 30-mo follow-up period. The genetic panel sequencing showed a novel pathogenic germline mutation in MLH1, c.(453+1_454-1)_(545+1_546-1)del, for LS. Moreover, cancer genetic counseling and testing are still in the initial development state in China, and maybe face numerous challenges in the further.

5.
Dalton Trans ; 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36062936

RESUMO

In this work, a series of Cr3+-doped A2NaYF6 (denoted as ANYF:Cr; A = K, Rb, and Cs) fluoroyttrate double-perovskites with broad blue excitation and near-infrared (NIR) emission bands were prepared using a high-temperature solid-state reaction method. The physicochemical and spectroscopic properties of the as-prepared products, including crystal structure, bandgap, morphology, luminescence behaviour and optical performance, were studied in detail. The results show that the Cr3+ activators undergo a decreasing crystal field in ANYF in the direction from K to Cs, yielding a red shift of the emission peak position from 758 to 786 nm, whilst the full-width-at-half-maximum (FWHM) expands from 98 to 104 nm. By virtue of the broadband NIR emission, clear structural images of the tangerine section, mini LED flashlight and circuit board were obtained by merging the optimal RNYF:Cr phosphor on a blue InGaN chip, implying its potential use in light-emitting diodes for non-destructive testing.

6.
J Environ Manage ; 322: 116083, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36049310

RESUMO

Currently, efficient and cost-effective recycling of waste capacitors is a pressing issue. In this study, the recovery of electrode powder from waste supercapacitors and enabling the reuse of the prepared samples are reported. The recovered powder is directly activated by mixing it with KOH using chemical activation to regenerate the waste-activated carbon. The regenerated activated carbon's specific surface area could be restored to a level similar to that of the original commercial powder, reaching 1803.15 m2/g. The regenerated activated carbon has a high proportion of microporous, which played a crucial role in its electrochemical performance. The samples' capacity in the organic system reached 125.96 F/g at 0.2 A/g and 111.77 F/g at 20 A/g, with a retention rate of 88.74%. Furthermore, the capacitance was maintained at 91.18% after 10,000 cycles, showing good cycling performance. Additionally, the supercapacitor assembled from the regenerated activated carbon delivered a high energy density of 31.83 Wh/kg and a power density of 269.76 W/kg, indicating great application potential. Overall, this study offers a useful and low-cost approach for recycling activated carbon from waste electrodes, which would be possible for supercapacitors recycling.

7.
Cancer Med ; 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36073671

RESUMO

BACKGROUND: Systemic inflammation and handgrip weakness have been used to predict mortality in many cancers. The purpose of current study was to evaluate the association of co-occurrence of inflammation indicators and handgrip weakness with overall survival (OS) of lung cancer (LC) patients with good performance status. METHODS: The cutoff points for handgrip strength (HGS) and the four inflammation indicators were calculated using Maxstat. The time-dependent receiver operating characteristic curve and C-index were used to select optimal inflammation indicator for predicting OS of LC patients. The Cox proportional hazard regression model was used to calculate the hazard ratio (HR) of mortality. Kaplan-Meier curves were constructed to evaluate the association of indicators and the OS of LC patients. RESULTS: Among the 1951 patients, the mean ± standard deviation (SD) age was 60.6 ± 9.9 years, and 1300 (66.6%) patients were male. In patients with good performance status (PS), handgrip weakness (HR, 1.49; 95% confidence interval [95% CI], 1.30-1.70, p < 0.001) and low advanced lung cancer inflammation index (ALI) (HR, 2.05; 95%CI, 1.79-2.34, p < 0.001), high systemic immune-inflammation index (SII) (HR, 1.91; 95%CI, 1.66-2.19, p < 0.001), high platelet: lymphocyte ratio (PLR) (HR, 1.60; 95%CI, 1.40-1.82, p < 0.001), or high neutrophil: lymphocyte ratio (NLR) (HR, 2.01; 95%CI, 1.76-2.30, p < 0.001) were associated with increased mortality risk of LC patients. ALI had better C-index (0.624) and time-AUC in the prediction of OS in LC patients with good PS than other three combinations. The co-occurrence of handgrip weakness and low ALI more than doubled the risk of death in LC with good PS (HR, 2.44; 95% CI, 2.06-2.89, p < 0.001). CONCLUSION: In LC patients who have good PS, patients with combined handgrip weakness and low ALI have the worst prognosis. THE TRIAL REGISTRATION NUMBER: ChiCTR1800020329.

8.
Am J Cancer Res ; 12(8): 3780-3798, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119844

RESUMO

Metabolic reprogramming is critical for the setup of the tumor microenvironment (TME). Glutamine has slipped into the focus of research of cancer metabolism, but its role in clear cell renal cell carcinoma (ccRCC) remains vague. Our study aimed to investigate the regulatory mechanism of glutamine in ccRCC and its prognostic value. Gene expression profiles and clinical data of ccRCC patients were obtained from The Cancer Genome Atlas database (TCGA) and Gene Expression Omnibus (GEO) database. Kaplan-Meier survival analysis was used for survival analysis. Consensus clustering was used to extract differentially expressed genes (DEGs) related to glutamine metabolism. Functional analyses, including gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA), were conducted to elucidate the functions and pathways involved in these DEGs. The single-sample GSEA and Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) methods were applied to estimate the immune infiltration in the TMEs of two clusters. The univariate regression and the least absolute shrinkage and selection operator (LASSO) Cox regression were used to construct a prognostic signature. R software was utilized to analyze the expression levels and prognostic values of genes in ccRCC. A total of 19 glutamine metabolic genes (GMGs) were screened out for differential expression analysis of normal and ccRCC tissues. Based on survival-related GMGs, two glutamine metabolic clusters with different clinical and transcriptomic characteristics were identified. Patients in cluster B exhibited worse survivals, higher immune infiltration scores, more significant immunosuppressive cell infiltration, higher expression levels of immune checkpoints, and more enriched oncogenic pathways. Glutamine metabolic index (GMI) was constructed according to the GMGs and survival data. In addition, the expression levels of GMGs were associated with immune cell infiltration and immune checkpoints in the TME of ccRCC. Among the GMGs, PYCR1 was the most powerful regulator of immune TME. Our analysis revealed higher-level glutamine metabolism in ccRCC patients with a worse prognosis. The GMI could predict the prognosis of ccRCC patients with a high accuracy. GMGs, such as PYCR1, may be exploited to design novel immunotherapies for ccRCC.

9.
Molecules ; 27(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36080380

RESUMO

Ammonia (NH3) is a common pollutant mostly derived from pig manure composting under humid conditions, and it is absolutely necessary to develop materials for ammonia removal with high stability and efficiency. To this end, metal-organic frameworks (MOFs) have received special attention because of their high selectivity of harmful gases in the air, resulting from their large surface area and high density of active sites, which can be tailored by appropriate modifications. Herein, two synthetic metal-organic frameworks (MOFs), 2-methylimidazole zinc salt (ZIF-8) and zinc-trimesic acid (ZnBTC), were selected for ammonia removal under humid conditions during composting. The two MOFs, with different organic linkers, exhibit fairly distinctive ammonia absorption behaviors under the same conditions. For the ZnBTC framework, the ammonia intake is 11.37 mmol/g at 298 K, nine times higher than that of the ZIF-8 framework (1.26 mmol/g). In combination with theoretical calculations, powder XRD patterns, FTIR, and BET surface area tests were conducted to reveal the absorption mechanisms of ammonia for the two materials. The adsorption of ammonia on the ZnBTC framework can be attributed to both physical and chemical adsorption. A strong coordination interaction exists between the nitrogen atom from the ammonia molecule and the zinc atom in the ZnBTC framework. In contrast, the absorption of ammonia in the ZIF-8 framework is mainly physical. The weak interaction between the ammonia molecule and the ZIF-8 framework mainly results from the inherent severely steric hindrance, which is related to the coordination mode of the imidazole ligands and the zinc atom of this framework. Therefore, this study provides a method for designing promising MOFs with appropriate organic linkers for the selective capture of ammonia during manure composting.


Assuntos
Estruturas Metalorgânicas , Adsorção , Amônia/química , Animais , Imidazóis , Esterco , Suínos , Zinco
10.
Int J Public Health ; 67: 1604979, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090824

RESUMO

Objectives: The study aimed at analyzing the prevalence of five psychological outcomes (depression, anxiety, stress, post-traumatic stress disorder (PTSD), and suicidal ideation) among Chinese healthcare workers (HCWs), and measured the total possible negative psychological impact 1 year after the COVID-19 initial outbreak. Methods: A cross-sectional nationwide multi-center study was performed between November 2020 and March 2021 in China. A self-report questionnaire was applied, and three psychological scales were used. Binary logistic regression was performed to analyze the risk factors associated with each psychological outcome. Results: The findings demonstrated that the COVID-19 pandemic had a negative psychological impact on HCWs, which was still evident 1 year after the initial outbreak. Nurses showed higher depression and anxiety than other HCWs. Female gender, passive coping, long working hours, having a chronic disease, and experiencing violence, among other factors, were all risk factors for psychological impairment. Conclusion: Developing and promoting programs to improve mental health among HCWs, and identifying those who might need psychological support is still relevant 1 year after the initial outbreak.


Assuntos
COVID-19 , COVID-19/epidemiologia , China/epidemiologia , Estudos Transversais , Surtos de Doenças , Feminino , Pessoal de Saúde , Humanos , Pandemias
11.
Nanoscale ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069243

RESUMO

Layered IV-VI diluted magnetic semiconductors (DMSs) have exhibited fascinating ferromagnetism down to atomic layers, but their relatively low Curie temperature (TC, ≤200 K) significantly hinders their practical application. In this work, Mn-doped GeSe (GeMnSe) DMSs with high-TC ferromagnetism (FM) are synthesized by chemical vapor deposition. As the Mn concentration varies, the obtained samples exhibit various structures including single-crystalline nanocombs (SC-NCs), polycrystalline nanoparticles (PC-NPs) and amorphous nanoaggregates (a-NAs). All the samples exhibit FM, and their TC and saturation magnetization (MS) are correlated to their structures. Notably, GeMnSe SC-NCs show a record high TC of 309 K and a record strong magnetic moment of 4.37µB/Mn compared to all the previously-reported IV-VI DMSs. Further analysis shows that the FM originates from the synergetic effect of the Ruderman-Kittel-Kasuya-Yoshida (RKKY) interaction, the crystalline order and the shape anisotropy in the samples. Our results provide a panorama of nanostructure-dependent FM in GeSe-based DMSs and suggest a peculiar playground for investigating fundamental physics and spintronic applications in IV-VI compounds.

12.
Hum Vaccin Immunother ; : 2119043, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069667

RESUMO

It is well documented that COVID-19 vaccines greatly reduce the severity and complications of SARS-CoV-2 infection. However, it has been reported that COVID-19 related vaccines may induce or exacerbate autoimmune hematological disorders, for example, a decrease in platelet numbers characteristic of immune thrombocytopenia (ITP). To investigate this, we retrospectively reported, for the first time, the clinical characteristics of 42 ITP patients after COVID-19 vaccination in southwest China. Of the 42 patients, 28 patients were historically diagnosed ITP, and their platelet counts (PC) decrease mainly occurred after the first-dose vaccinations. The average PC after vaccination was 39.5 × 109/L and recovered to an average of 80.6 × 109/L after treatment. Efficacy of treatment was 90%, and only 10% maintained low PC at the third month of treatment. More interestingly, of the 42 patients, 14 were newly diagnosed ITP following vaccination. Of these 14 patients, 6 patients (43%) were found PC deterioration after the first vaccine dose, and 7 patients (50%) after the second dose. Fortunately, the peripheral PC of all 14 patients recovered significantly after treatment, and the average PC was 139.4 × 109/L, including 8 CRs (complete response) and 6 PRs (partial response). Notably, 9 of the 14 cases were found to have abnormal immune indices when thrombocytopenia diagnosed. No severe organ hemorrhage was found in either subgroup. These results are reassuring the vaccine safety for ITP patients, in that the risks of aggravating thrombocytopenia by COVID-19 vaccination do exist, but it was transient and can be effectively controlled through intensive clinical monitoring and management.

13.
Contrast Media Mol Imaging ; 2022: 6729473, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051932

RESUMO

Objective: To investigate the value of preoperative prediction of breast cancer axillary lymph node metastasis based on intratumoral and peritumoral dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) radiomics nomogram. Material and Methods. In this study, a radiomics model was developed based on a training cohort involving 250 patients with breast cancer (BC) who had undergone axillary lymph node (ALN) dissection between June 2019 and January 2021. The intratumoral and peritumoral radiomics features were extracted from the second postcontrast images of DCE-MRI. Based on filtered radiomics features, the radiomics signature was built by using the least absolute shrinkage and selection operator method. The Support Vector Machines (SVM) learning algorithm was used to construct intratumoral, periatumoral, and intratumoral combined periatumoral models for predicting axillary lymph node metastasis (ALNM) in BC. Nomogram performance was determined by its discrimination, calibration, and clinical value. Multivariable logistic regression was adopted to establish a radiomics nomogram. Results: The intratumoral combined peritumoral radiomics signature, which was composed of fifteen ALN status-related features, showed the best predictive performance and was associated with ALNM in both the training and validation cohorts (P < 0.001). The prediction efficiency of the intratumoral combined peritumoral radiomics model was higher than that of the intratumoral radiomics model and the peritumoral radiomics model. The AUCs of the training and verification cohorts were 0.867 and 0.785, respectively. The radiomics nomogram, which incorporated the radiomics signature, MR-reported ALN status, and MR-reported maximum diameter of the lesion, showed good calibration and discrimination in the training (AUC = 0.872) and validation cohorts (AUC = 0.863). Conclusion: The intratumoral combined peritumoral radiomics model derived from DCE-MRI showed great predictive value for ALNM and may help to improve clinical decision-making for BC.


Assuntos
Neoplasias da Mama , Linfoma , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Metástase Linfática/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Nomogramas , Estudos Retrospectivos
14.
Exp Parasitol ; 242: 108376, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36089006

RESUMO

Aminopeptidases P are metalloproteases belonging to the M24 peptidase family. It specifically hydrolyzes the N-terminus of polypeptides free of acidic amino acids, and plays an important role in the nutrition, metabolism and growth of parasites. The aim of this study was to characterize a novel Trichinella spiralis aminopeptidase P (TsAPP) and to investigate its functions in the invasion of T. spiralis. TsAPP contained two domains of creatinase (a creatinase N and creatinase N2) and a domain of peptidase M24C and APP. The complete TsAPP sequence was cloned and expressed in Escherichia coli BL21 cells. The recombinantly produced TsAPP was used to raise polyclonal antibodies that were subsequently used to detect the expression of the protein in the different life stages of T. spiralis. TsAPP was expressed in various T. spiralis stages. TsAPP was primarily localized in the cuticle, stichosome and intrauterine embryos of this nematode. rTsAPP has an enzymatic activity of a natural aminopeptidase P to hydrolyze the substrate H-Ala-Pro-OH. rTsAPP promoted the larval intrusion of intestinal epithelium cells (IECs). The results showed that TsAPP is involved in the T. spiralis intrusion of IECs and it might be a potential candidate vaccine target against Trichinella infection.

15.
Research (Wash D C) ; 2022: 9839502, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36128178

RESUMO

Rotational Doppler effect has made tremendous development in both theoretical and applied research over the last decade. Different from the inertial thinking of focusing on the scalar field dominated by helical phase light, we have revealed a vectorial Doppler effect in our previous work, which is based on the spatially variant polarized light fields to simultaneously acquire the speed and direction of a target. Here, further, we propose a method to construct a flexible and robust velocimeter based on that novel effect by employing an air-core fiber with kilometer-length scale for remotely measuring the vectorial information of angular velocity in situ. In addition, we experimentally substantiate that the measurement system still has commendable accuracy in determining the direction of movement even when the air-core fiber is interfered by the external environment. The demonstrations prove the potential of vectorial Doppler effect in practical scenarios and remote measurements.

16.
Clin Nutr ; 41(10): 2284-2294, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36096062

RESUMO

BACKGROUND: Inflammation is involved in the progression and prognosis of cancer because it can affect the physical status and prognosis of patients. Among numerous systemic inflammatory markers, the optimal prognostic indicator of older adults with cancer is still unclear. We aimed to identify an ideal inflammatory immune marker in older adults with cancer and assess the survival outcome combined with eastern cooperative oncology group performance status (ECOG PS). METHODS: We included 1767 older adults with cancer (66.2% males, 70.97 ± 5.49 years old) from a prospective cohort study. Fifteen systemic inflammatory biomarkers were compared to identify the optimal biomarker using prognostic area under the curve (AUC) and concordance index (C-index) analysis. The prognostic value of the clinical parameters was elucidated by performing uni- and multivariate analyses. RESULTS: The AUC, C-index, and the subgroup survival analysis of ECOG PS groups showed that the lymphocyte-C reactive protein ratio (LCR) and C-reactive protein/albumin ratio (CAR) were more accurate in reflecting patient prognosis than the other 13 inflammatory markers. Compared with patients in the high LCR group, those in the low LCR group had worse survival (hazard ratio (HR) 1.64, 95% confidence interval (95%CI) 1.42-1.91, p < 0.001). Compared with patients in the low CAR group, those in the high CAR group had worse survival (HR 1.65, 95% CI 1.43-1.91, p < 0.001). Older adults with cancer with an ECOG PS score of 2 or 3-4 and a high inflammation (low LCR, 13.3 months and 9.2 months, respectively; or high CAR, 9.6 months and 9.6 months, respectively) had shorter median survival time compared to those with an ECOG PS score of 0/1 and a low inflammation (high LCR, 77.4 months; or low CAR, 77.0 months). CONCLUSION: LCR and CAR might be the better predictive immune inflammatory factors for OS, which improved the survival prediction of different ECOG PS groups in older adults with cancer. High ECOG PS (≥2) and high inflammation increased the risk of death in older adults with cancer.

17.
Front Mol Neurosci ; 15: 990260, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36117915

RESUMO

The microtubule-stabilizing drug paclitaxel (PTX) is a chemotherapeutic agent widely prescribed for the treatment of various tumor types. The main adverse effect of PTX-mediated therapy is chemotherapy-induced peripheral neuropathy (CIPN) and neuropathic pain, which are similar to the adverse effects associated with other chemotherapeutic agents. Dorsal root ganglia (DRG) contain primary sensory neurons; any damage to these neurons or their axons may lead to neuropathic pain. To gain molecular and neurobiological insights into the peripheral sensory system under conditions of PTX-induced neuropathic pain, we used transcriptomic analysis to profile mRNA and non-coding RNA expression in the DRGs of adult male C57BL/6 mice treated using PTX. RNA sequencing and in-depth gene expression analysis were used to analyze the expression levels of 67,228 genes. We identified 372 differentially expressed genes (DEGs) in the DRGs of vehicle- and PTX-treated mice. Among the 372 DEGs, there were 8 mRNAs, 3 long non-coding RNAs (lncRNAs), 16 circular RNAs (circRNAs), and 345 microRNAs (miRNAs). Moreover, the changes in the expression levels of several miRNAs and circRNAs induced by PTX have been confirmed using the quantitative polymerase chain reaction method. In addition, we compared the expression levels of differentially expressed miRNAs and mRNA in the DRGs of mice with PTX-induced neuropathic pain against those evaluated in other models of neuropathic pain induced by other chemotherapeutic agents, nerve injury, or diabetes. There are dozens of shared differentially expressed miRNAs between PTX and diabetes, but only a few shared miRNAs between PTX and nerve injury. Meanwhile, there is no shared differentially expressed mRNA between PTX and nerve injury. In conclusion, herein, we show that treatment with PTX induced numerous changes in miRNA expression in DRGs. Comparison with other neuropathic pain models indicates that DEGs in DRGs vary greatly among different models of neuropathic pain.

18.
Expert Rev Clin Pharmacol ; : 1-8, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36062413

RESUMO

OBJECTIVES: We performed an up-to-date meta-analysis to quantify the overall incidence and risk of severe adverse events (AEs) associated with T-DM1 in patients with breast cancer. METHODS: Pubmed, Embase, and oncology conference proceedings were searched for relevant studies. Data were extracted to calculate the summary incidence rate and relative risk (RR) of grade ≥3 AEs. RESULTS: A total of 5,045 patients from 7 RCTs were included in the meta-analysis. The use of T-DM1 was associated with an increased risk of severe thrombocytopenia (RR 10.66, 95% CI 3.23-35.18, P < 0.001), anemia (RR 1.68, 95% CI 1.15-2.44, P = 0.007), elevated ALT (RR 2.67, 95% CI 1.60-4.47, P < 0.001), and AST (RR 3.76, 95% CI 1.45-9.78, P = 0.007). In addition, the use of T-DM1 can increase the risk of severe hypertension (RR 1.59, 95% CI 1.03-2.45, P = 0.037) and peripheral sensory neuropathy (RR 8.13, 95% CI 1.89-35.03, P = 0.005). CONCLUSIONS: Treatment with T-DM1 increases the risk of severe hematologic toxicities, hepatotoxicity, hypertension, and peripheral sensory neuropathy in patients with breast cancer, while the overall incidence of these AEs is low.

19.
PLoS One ; 17(9): e0273873, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36084059

RESUMO

FastCloning, a reliable cloning technique for plasmid construction, is a widely used protocol in biomedical research laboratories. Only two-step molecular manipulations are required to add a gene (cDNA) of interest into the desired vector. However, parallel cloning of the gene into multiple vectors is still a labor-intensive operation, which requires a range of primers for different vectors in high-throughput cloning projects. The situation could even be worse if multiple fragments of DNA are required to be added into one plasmid. Here, we describe a high-throughput FastCloning (HTFC) method, a protocol for parallel cloning by adding an adaptor sequence into all vectors. The target gene and vectors were PCR amplified separately to obtain the insert product and linear vectors with 18-base overlapping at each end of the DNAs required for FastCloning. Furthermore, a method for generating polycistronic bacterial constructs based on the same strategy as that used for HTFC was developed. Thus, the HTFC technique is a simple, effective, reliable, and low-cost tool for parallel cloning.


Assuntos
Escherichia coli , Vetores Genéticos , Clonagem Molecular , Escherichia coli/genética , Vetores Genéticos/genética , Plasmídeos/genética , Reação em Cadeia da Polimerase/métodos
20.
ACS Pharmacol Transl Sci ; 5(9): 761-773, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36110371

RESUMO

Trefoil factor 3 (TFF3) is a secreted protein with an established oncogenic function and a highly significant association with clinical progression of various human malignancies. Herein, a novel small molecule that specifically targets TFF3 homodimeric functions was identified. Utilizing the concept of reversible covalent interaction, 2-amino-4-(4-(6-fluoro-5-methylpyridin-3-yl)phenyl)-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile (AMPC) was identified as a molecule that interacted with TFF3. AMPC monomerized the cellular and secreted TFF3 homodimer at the cysteine (Cys)57-Cys57 residue with subsequent more rapid degradation of the generated TFF3 monomers. Hence, AMPC treatment also resulted in cellular depletion of TFF3 with consequent decreased cell viability in various human carcinoma-derived TFF3 expressing cell lines, including estrogen receptor positive (ER+) mammary carcinoma (MC). AMPC treatment of TFF3 expressing ER+ MC cells significantly suppressed total cell number in a dose-dependent manner. Consistently, exposure of TFF3 expressing ER+ MC cells to AMPC decreased soft agar colony formation, foci formation, and growth in suspension culture and inhibited growth of preformed colonies in 3D Matrigel. AMPC increased apoptosis in TFF3 expressing ER+ MC cells associated with decreased activity of EGFR, p38, STAT3, AKT, and ERK, decreased protein levels of CCND1, CCNE1, BCL2, and BCL-XL, and increased protein levels of TP53, CDKN1A, CASP7, and CASP9. siRNA-mediated depletion of TFF3 expression in ER+ MC cells efficiently abrogated AMPC-stimulated loss of cell viability and CASPASE 3/7 activities. Furthermore, in mice bearing ER+ MC cell-generated xenografts, AMPC treatment significantly impeded xenograft growth. Hence, AMPC exemplifies a novel mechanism by which small molecule drugs may inhibit a dimeric oncogenic protein and provides a strategy to impede TFF3-dependent cancer progression.

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