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1.
Integr Med Res ; 11(1): 100748, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34189032

RESUMO

Background: Warm acupuncture, a combination of the mechanical stimulation of acupuncture and thermal stimulation of moxibustion, is commonly used in treating acute low back pain (LBP). This trial aimed to compare the efficacy of stronger (above 43°C) and weaker (above 40°C) heat stimulation in warm acupuncture on the function and pain in patients with acute LBP due to lumbosacral disc degeneration (LDD). Methods: One hundred and fifty-nine adults were randomly assigned to receive warm acupuncture treatment with silver needle (SvN) or with stainless steel needle (SSN) (1:1). Both groups received a 3-week therapy with 3 sessions per week. The primary outcome was the modified Oswestry Disability Index at week 4. The secondary outcomes included average pain, three physical sign tests and adverse events. Participants were followed up at week 16 and week 28 after randomization. Results: The LBP related disability and pain intensity significantly relieved more in the SvN warm acupuncture group than in the SSN group, in both the short and long term (p<0.001). The between-groups difference in physical signs showed statistical significance only in the short term (p = 0.024), but not in long term (p = 0.081; p = 0.069). Conclusion: Compared with warm acupuncture with stainless-steel needle at above 40°C, warm acupuncture with silver needle at above 43°C relieved more disability and pain in patients with acute LBP due to LDD. Study registration: Chinese Clinical Trial Registry (ChiCTR1800019051).

2.
Medicine (Baltimore) ; 100(39): e27289, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596125

RESUMO

RATIONALE: Transformation to small cell lung cancer (SCLC) is one of the mechanisms of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, no standard treatment is available after the transformation. In addition, gastric metastasis of primary lung cancer is rarely observed; thus, little is known about its metastatic characteristics. PATIENT CONCERNS: A 58-year-old male patient was treated with gefitinib (0.25 g /day) as the 1st line treatment due of recurrence after surgical resection for EGFR exon 19 mutation pulmonary adenocarcinoma. However, he experienced recurrence with positive T790 M, and osimertinib (80 mg/day) was administered as the 2nd line therapy. DIAGNOSIS: One year and 6 months after osimertinib initiation, he complained of stomachache, and a diagnostic gastroscopy biopsy confirmed small cell lung cancer in the gastric body, indicating osimertinib-induced phenotypic transformation. INTERVENTIONS AND OUTCOMES: The patient was treated with etoposide and platinum chemotherapy and maintenance therapy with osimertinib. Finally, the patient achieved a partial response after 4 cycles. LESSONS: Timely second biopsies should be considered in the diagnosis of phenotypic transformation. After transformation, chemotherapeutic treatment with etoposide and platinum and maintenance therapy with osimertinib inhibited the progression of the disease.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34647456

RESUMO

The development of new high-density memories that can work in harsh environments such as high temperature and humidity will be significant for some special occasions such as oil and geothermal industries. Herein, a facial strategy for implementing a ternary memory device with high working temperature/humidity was executed. In detail, an asymmetric aggregation-induced-emission active molecule (azobenzol-decorated tetraphenylethylene, i.e., TPE-Azo) was embedded into flexible poly(ethylene-alt-maleic anhydride) (PEM) to prepare a TPE-Azo@PEM composite, which served as an active layer to fabricate the FTO/TPE-Azo@PEM/Ag device. This device can demonstrate excellent ternary memory performances with a current ratio of 1:104.2:101.6 for "OFF", "ON1", and "ON2" states. Specially, it can exhibit good environmental endurance at high working temperature (350 °C) and humidity (RH = 90%). The ternary memory mechanism can be explained as the combination of aggregation-induced current/conductance and conformational change-induced charge transfer in the TPE-Azo molecule, which was verified by Kelvin probe force microscopy, UV-vis spectra, X-ray diffraction, and single-crystal structural analysis. This strategy can be used as a universal method for the construction of high-density multilevel memristors with good environmental tolerance.

4.
Front Neurosci ; 15: 726350, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630014

RESUMO

Microvascular complications can accelerate cognitive impairment in patients with type 2 diabetes mellitus (T2DM) and have a high impact on their quality of life; however, the underlying mechanism is still unclear. The complex network in the human brain is the physiological basis for information processing and cognitive expression. Therefore, this study explored the relationship between the functional network topological properties and cognitive function in T2DM patients with and without microvascular complications (T2DM-C and T2DM-NC, respectively). Sixty-seven T2DM patients and 41 healthy controls (HCs) underwent resting-state functional MRI and neuropsychological assessment. Then, graph theoretical network analysis was performed to explore the global and nodal topological alterations in the functional whole brain networks of T2DM patients. Correlation analyses were performed to investigate the relationship between the altered topological parameters and cognitive/clinical variables. The T2DM-C group exhibited significantly higher local efficiency (Eloc), normalized cluster coefficient (γ), and small-world characteristics (σ) than the HCs. Patients with T2DM at different clinical stages (T2DM-C and T2DM-NC) showed varying degrees of abnormalities in node properties. In addition, compared with T2DM-NC patients, T2DM-C patients showed nodal properties disorders in the occipital visual network, cerebellum and middle temporal gyrus. The Eloc metrics were positively correlated with HbA1c level (P = 0.001, r = 0.515) and the NE values in the right paracentral lobule were negatively related with serum creatinine values (P = 0.001, r = -0.517) in T2DM-C patients. This study found that T2DM-C patients displayed more extensive changes at different network topology scales. The visual network and cerebellar may be the central vulnerable regions of T2DM-C patients.

5.
J Cardiothorac Surg ; 16(1): 289, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627304

RESUMO

BACKGROUND: Pulmonary nodular lymphoid hyperplasia (PNLH) is a rare benign illness. Due to atypical clinical and radiographic presentations, diagnosis largely depends on postoperative pathological examination. Thus, preoperative misdiagnosis is often occurred. CASE PRESENTATION: We present a case of asymptomatic PNLH that was seen as ground-glass opacity (GGO) on computed tomography (CT). After 3-year observation, the diagnosis tends to adenocarcinoma owing to increasing density of the node and vessel convergence sign, which were signs of malignancy. Video-assisted segmentectomy (S10) was carried out. Histopathologic examination of postoperative specimen showed follicular lymphoid hyperplasia with interfollicular lymphoplasmacytosis, consistent with PNLH. The follow-up chest CT images showed no recurrence or metastasis. CONCLUSION: Although it is a benign disease, PNLH can exhibit malignant signs in the imaging examinations, which could lead to misdiagnosis. This reminds us of the uncertainty between imaging findings and diagnosis. The diagnosis depends on postoperative pathological examination. Volume doubling time is a potential parameter to differentiate PNLH from lung cancer.


Assuntos
Adenocarcinoma , Pneumopatias , Neoplasias Pulmonares , Humanos , Hiperplasia/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia
6.
J Chem Inf Model ; 61(10): 4924-4939, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34619030

RESUMO

Accurate modeling of compound bioactivities is essential for the virtual screening of drug leads. In real-world scenarios, pharmacists tend to choose from the top-k hit compounds ranked by predicted bioactivities from a large database with interest to continue wet experiments for drug discovery. Significant improvement of the precision of the top hits in ligand-based virtual screening of drug leads is more valuable than conventional schemes for accurately predicting the bioactivities of all compounds from a large database. Here, we proposed a new method, RealVS, to significantly improve the top hits' precision and learn interpretable key substructures associated with compound bioactivities. The features of RealVS involve the following points. (1) Abundant transferable information from the source domain was introduced for alleviating the insufficiency of inactive ligands associated with drug targets. (2) The adversarial domain alignment was adopted to fit the distribution of generated features of compounds from the training data set and that from the screening database for greater model generalization ability. (3) A novel objective function was proposed to simultaneously optimize the classification loss, regression loss, and adversarial loss, where most inactive ligands tend to be screened out before activity regression prediction. (4) Graph attention networks were adopted for learning key substructures associated with ligand bioactivities for better model interpretability. The results on a large number of benchmark data sets show that our method has significantly improved the precision of top hits under various k values in ligand-based virtual screening of drug leads from large compound databases, which is of great value in real-world scenarios. The web server of RealVS is freely available at noveldelta.com/RealVS for academic purposes, where virtual screening of hits from large compound databases is accessible.

7.
Microb Pathog ; 161(Pt A): 105229, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34624494

RESUMO

A new pleuromutilin derivative, 14-O-[(4,6-Diaminopyrimidine-2-yl) thioacetyl] mutilin (DPTM), has been synthesized and proven to be a potent agent against Gram-positive pathogens, especially for Staphylococcus aureus (S. aureus). However, its pharmacological activities against α-hemolysin (Hla), a major virulence factor produced by S. aureus, and inflammations related to S. aureus are still unknown. In the present study, we investigated the DPTM inhibition activities against methicillin-resistant S. aureus (MRSA) Hla and protective efficacy of Raw264.7 cells from injury induced by MRSA. The results showed that DPTM with sub-inhibitory concentrations significantly inhibited Hla on the hemolysis of rabbit erythrocytes and down-regulated the gene expressions of Hla and agrA with a dose-dependent fashion. In Raw264.7 cells infected with MRSA, DPTM efficiently attenuated the productions of lactate dehydrogenase (LDH), nitric oxide (NO) and pro-inflammatory cytokines, as well as the express levels of nuclear factor-kappaB (NF-κB), nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, DPTM inhibited the translocation of p-65 to nucleus in RAW264.7 cells infected by MRSA.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34682742

RESUMO

As one of the nitrogen (N) limitation ecosystems, alpine meadows have significant effects on their structure and function. However, research on the response and linkage of vegetation-soil to short-term low-level N deposition with rhizosphere processes is scant. We conducted a four level N addition (0, 20, 40, and 80 kg N ha-1 y-1) field experiment in an alpine meadow on the Qinghai-Tibetan Plateau (QTP) from July 2014 to August 2016. We analyzed the community characteristics, vegetation (shoots and roots), total carbon (TC), nutrients, soil (rhizosphere and bulk) properties, and the linkage between vegetation and soil under different N addition rates. Our results showed that (i) N addition significantly increased and decreased the concentration of soil nitrate nitrogen (NO3--N) and ammonium nitrogen, and the soil pH, respectively; (ii) there were significant correlations between soil (rhizosphere and bulk) NO3--N and total nitrogen (TN), and root TN, and there was no strong correlation between plant and soil TC, TN and total phosphorus, and their stoichiometry under different N addition rates. The results suggest that short-term low-N addition affected the plant community, vegetation, and soil TC, TN, TP, and their stoichiometry insignificantly, and that the correlation between plant and soil TC, TN, and TP, and their stoichiometry were insignificant.

9.
Aging (Albany NY) ; 13(undefined)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648463

RESUMO

OBJECTIVE: To study the effect of Yu Linzhu on ovarian function and mitochondria in natural aging mice. METHODS: Female BALB/c mice were selected as normal group at 7-8 weeks and natural aging group at 9 months. The natural aging group was divided into Yu Linzhu intervention group and non-intervention group by intragastric administration once a day for 6 weeks. The morphology and blood flow of ovary were observed by ultrasound. Ovarian morphology and follicle were observed by HE staining. Hormone levels were analyzed by ELISA. Serum oxidative stress were detected by radioimmunoassay. The distribution of mitochondria in oocytes was observed by fluorescence staining. The ultrastructure of oocytes and the morphology of mitochondria were observed under electron microscope. The mitochondrial membrane potential was detected by JC-1. RESULTS: Two groups of aging mice had serious disturbance of estrus cycle. The ovarian area of the mice in the aging non-intervention group was smaller than that in the normal group, and the ovarian area of the mice in the aging intervention group recovered. The ovarian blood flow was weak or even disappear in the aging non-intervention group, and the blood flow in the intervention group was improved. The ovarian volume of mice in the non-intervention group was smaller than that in the normal group. Some ovarian tissues were adhered to the surrounding tissues. While in the intervention group, the ovarian volume increased, the degree of adhesion decreased, the infiltration of ovarian interstitial lymphocytes decreased, and the zona pellucida recovered. Granular cell arrangement returned neatly, egg cell shape recover regular and the number also increased. In the non-intervention group, E2 (Estrogen), AMH (Anti-Mullerian hormone) decreased (P = 0.0092 and P = 0.0334, respectively), FSH (Follicle stimulating hormone) increased (P < 0.0001). In the intervention group, FSH decreased (P = 0.0002), LH (luteinizing hormone) decreased and E2, AMH increased. In the non-intervention group, GSH-Px (Glutathione peroxidase) decreased (P = 0.0129), SOD (Superoxide dismutase) decreased, ROS (reactive oxidative species), MDA (Malondialdehyde) increased. In the aging intervention group, ROS, MDA decreased and GSH-Px increased. In the non-intervention group, mitochondrial expression was scattered at the concentrated distribution point, the length of mitochondria was mostly long and the average volume increased, the density decreased, the number decreased and some mitochondria fused, and lesions such as swelling, vacuolar degeneration and inclusion body formation, membrane potential decreased (P = 0.0002). In the aging intervention group, mitochondria were evenly distributed, the mitochondria were basically round, the distribution density was moderate, the inner ridge was clear, and the membrane potential of the aging intervention group increased. CONCLUSION: Yu Linzhu can improve the ovarian function of natural aging mice by improving the mitochondrial function of oocytes.

10.
Front Med (Lausanne) ; 8: 743998, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692734

RESUMO

Background: Acute acalculous cholecystitis (AAC) is characterized by the development of cholecystitis in the gallbladder without gallstones or with small gallstones unrelated to inflammatory diseases. This disease is not rare in the elderly bedridden patients with co-morbidities and prone to develop life-threatening gangrene or perforation of gallbladder. Early imaging is essential for detecting and effectively treating AAC. This study aimed to evaluate the use of ultrasound diagnostic criteria for the diagnosis and prognosis of elderly long-term bedridden patients with suspected AAC. Methods: We retrospectively studied 374 elderly bedridden patients with clinical manifestations of AC at the acute stage of the disease. Gallbladder anomalies were found in 92 patients by ultrasound examination, which correlated with the duration time of clinical manifestations, complications, as well as therapeutic prognosis. The major and minor ultrasound criteria of AAC were made according to the Tokyo Guidelines 2018. Ultrasound results were thought to be AAC positive when they met two major criteria or one major and two minor criteria. Results: Forty-three (46.7%) of the 92 patients presented with AAC (+) test results based on the ultrasound criteria, with a higher incidence of complications (27.9%) than AAC (-) patients (0%; P < 0.001). The median length of symptoms (8 vs. 4 days, P < 0.001) and duration of antibiotic therapy (13 vs. 5 days, P < 0.001) were longer in the AAC (+) group. Conclusions: The ultrasound-based AAC (+) group often had a worse prognosis than the AAC (-) group. Therefore, patients from the AAC (+) group should receive a follow-up ultrasound examination to detect disease progression early.

11.
Front Oncol ; 11: 744251, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650925

RESUMO

Circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) have been considered as biomarkers or regulators in many diseases. However, the exact role of circRNA- or lncRNA-mediated competing endogenous RNA (ceRNA) networks in the modulation of depression pathogenesis-relevant processes is not clear. In this study, we profiled whole transcriptome in depression patients' blood samples via microarray analysis. As a result, a total of 340 circRNAs, 398 lncRNAs, 206 miRNAs, and 92 mRNAs were differentially expressed between the depression and control groups. Then, we constructed ceRNA networks according to the differentially expressed genes (DEGs). Using bioinformatics analysis, 89 pairs of circRNA-ceRNA and 49 pairs of lncRNA-ceRNA networks were obtained. Since depression is a broad and heterogeneous condition that is known as promoter for many chronic diseases including cancer, so we further dug out 28 circRNAs, 61 lncRNAs, 26 miRNAs, and 29 mRNAs that are associated with cancer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the DEGs were significantly enriched in cancer-related signaling pathways such as MAPK, Wnt, IL-17, Ras, and PI3K-Akt. Genes involved in the above pathways such as S100A9, GATA2, SRFP5, SLC45A3, NTRK1, FRZB, has_circ_0014221, has_circ_0014220, and has_circ_0087100 were dysregulated in various cancer cell lines by stress hormones induced. HDC, GATA2, SLC45A3, and NTRK1 were downregulated in tumor-bearing mice subjected to chronic unpredictable mild stress (CUMS). LncRNA-mediated ceRNA network validation showed that overexpression of miR-4530 declined HDC level. Our findings highlight the potential circRNA- and lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of depression and as potential biomarkers in depression cancer comorbidity through the pathways of IL-17 or histidine metabolism.

12.
Org Lett ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34652926

RESUMO

Diastereoselective syntheses of syn- and anti-vicinal dihalides were achieved via an aza-Bellus-Claisen rearrangement, which involved the reaction of an α-chloro carboxylic acid chloride with halogen-substituted trans-allyl morpholines in the presence of Lewis acids. The developed method was used for the total synthesis of a group of monoterpene natural products bearing vicinal dichloride subunits.

13.
Cancer Manag Res ; 13: 7429-7437, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594135

RESUMO

Objective: To investigate the predictive factors of lymph node metastasis (LNM) and evaluate the usefulness of prediction nomograms. Methods: This study included 300 patients diagnosed with penile squamous cell carcinoma at West China Hospital (WCH) of Sichuan University (Chengdu, China) and 412 cases acquired from the Surveillance, Epidemiology, and End Results (SEER) program. Logistic regression analysis was performed on these cohorts to investigate the predictive factors of LNM. We evaluated a recently developed prediction nomogram for LNM, which was established based on the National Cancer Database (NCDB). Moreover, we developed a novel nomogram using cases from the WCH for the prediction of lymphatic metastasis. Results: Logistic analysis identified that younger age at diagnosis, invasion of the penis body, poorer pT stage, cN stage, nuclear grade and the presence of lymph vascular invasion (LVI) were significantly correlated with LNM in WCH cases; however, only race, poorer T stage and cN stage were significantly associated with LNM among the cases from the SEER. Multivariate analysis demonstrated that younger age, poorer T stage, cN stage and nuclear grade were independent predictors of LNM. Receiver operating characteristic curve analysis of WCH cases showed that the tumor T stage 8th edition has better area under the curve than 7th stage (0.672 vs 0.636, respectively). Moreover, well AUC was seen in external validation of NCDB nomogram in WCH cohorts and SEER series (0.833 vs 0.795). The new nomogram included the aforementioned independent predictors and the bootstrap-corrected concordance was 0.876. Conclusion: Younger diagnose age, poorer pT stage, cN stage, nuclear grade and LVI were the most important predictors of LNM in patients with penile cancer. 8th T stage performed better than 7th version in predicting LNM. NCDB nomogram has some application values in both WCH and SEER cases, and our novel model further improved the predictive accuracy.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34601687

RESUMO

The increased growth of vegetation has the potential to slow global climate warming. Therefore, analyzing and predicting the response assessment of Chinese vegetation to climate change is of great significance to studies of global warming. In this paper, we examine the spatiotemporal dynamics of vegetation leaf area index (LAI) values in China from 1981 to 2017 and their correlations with meteorological (hydrothermal) factors based on trend analysis and correlation analysis. We further construct an LAI prediction model based on hydrothermal conditions. The climate data obtained under different scenarios in the CMIP5 and CMIP6 climate models were used to predict the dynamic change trend of vegetation LAI from 2021 to 2100. The results show that most areas of China (72.82%) showed an improving trend in vegetation LAI from 1981 to 2017, during which the annual average LAI value increased at a rate of 0.0029 year-1. Vegetation LAI in China was significantly correlated with climatic factors (temperature, precipitation, and evapotranspiration), and the LAI prediction model constructed based on hydrothermal conditions had a high accuracy (Pearson's Cor value is 0.9729). From 2021 to 2100, approximately 2/3 of China's vegetation LAI area showed an improvement trend, and the impact of climate change on vegetation LAI predictions under the high emission scenario was greater than that under the low emission scenario. This research can provide a basis for studies on the climatic drivers of vegetation change and the global vegetation dynamic model.

15.
ChemMedChem ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34595834

RESUMO

An albumin-binding CsA analogue 4MCsA was achieved by attachment of a thiol-reactive maleimide group at the side-chain of P4 position of CsA derivative. 4MCsA was semi-synthesized from CsA, and the cell-impermeability of albumin-4MCsA was detected by mass spectrometry and a competitive flow cytometry. 4MCsA exhibits inhibition of chemotaxis activity and inflammation by targeting extracellular CypA without immunosuppressive effect and cellular toxicity. These combined results suggested that 4MCsA can be restricted extracellularly through covalently binding to Cys34 of albumin with its maleimide group, and regulate the functions of cyclophilin A extracellularly.

17.
J Environ Sci (China) ; 109: 181-192, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34607667

RESUMO

Macrophytes are usually chosen for phytoremediation tools to remove P in eutrophic aquatic ecosystems, but the lack of test methods hinders the understanding of removal mechanism and application. In this study, we used the novel technologies combined of Diffusive gradients in thin films (DGT), Planar optode (PO), and Non-invasive micro-test technology (NMT) to explore P dynamics in water-sediment continuum and rhizosphere of Potamogeton crispus over time. Results of the high-resolution in situ measurement showed that labile P(LPDGT) fluxes at the surficial sediment significantly decreased from approximate 120, 140, and 200 pg/ (cm2•sec) via 30 days incubation period to 17, 40, and 56 pg/(cm2•sec) via that of 15 days. Obvious synchronous increase of LPDGT was not detected in overlying water, suggesting the intense assimilation of dissolve reactive P via root over time. PO measurement indicated that O2 concentration around the rhizosphere remarkably increased and radially diffused into deeper sediment until 100% saturation along with the root stretch downwards. NMT detection of roots showed the obvious O2 inflow into root tissue with the uppermost flux of 30 pmol/(cm2•sec) from surroundings via aerenchyma on different treatment conditions. Different from previous reports, gradually saturating O2 concentrations around the rhizosphere was principally driven by O2 penetration through interspace attributing to root stretch downward rather than root O2 leakage. Increased O2 concentrations in deep sediment over time finally induced the oxidization of labile Fe(II) into Fe(III) bound P and local P immobilization.


Assuntos
Potamogetonaceae , Poluentes Químicos da Água , Ecossistema , Compostos Férricos , Sedimentos Geológicos , Fósforo , Rizosfera , Poluentes Químicos da Água/análise
18.
World J Clin Cases ; 9(27): 8120-8126, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34621870

RESUMO

BACKGROUND: Gastrointestinal stromal tumor (GIST) with cutaneous metastasis is very rare. As a result, cutaneous GISTs have not been well characterized. Focal segmental glomerulosclerosis (FSGS) is also a rare symptom among paraneoplastic nephritic syndromes (PNS). CASE SUMMARY: In this case report, we describe a patient with cutaneous metastatic GIST accompanied by nephrotic syndrome occurring as a malignancy-associated PNS, for whom symptomatic treatment was ineffective, but clinical remission was achieved after surgery. Moreover, the patient has a missense mutation in NPHP4, which can explain the occurrences of GIST and FSGS in this patient and indicates that the association is not random. CONCLUSION: This is the first reported case of a GIST with cutaneous metastasis accompanied by nephrotic syndrome manifesting as a PNS.

19.
Front Oncol ; 11: 700649, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660270

RESUMO

Metal-regulatory transcription factor-1 (MTF-1) is of importance in maintaining metal homeostasis. Copper exposure considerably stimulates the proliferation of hepatocellular carcinoma (HCC) cells with enhanced MTF-1 expression. However, the underlying molecular mechanisms have not been completely elucidated. In this study, we utilized different approaches to investigate the potential role of MTF-1 involved in HCC progression. The expression levels of MTF-1 and miR-148a-3p were determined using real-time polymerase chain reaction (PCR), Western blotting, and immunohistochemistry. The interaction of MTF-1 with apurinic apyrimidinic endonuclease/redox effector factor 1 (APE/Ref-1) or miR-148a-3p was determined using immunoprecipitation or dual-luciferase reporter assay, respectively. Cell viability and metastatic ability were evaluated using colony formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound scratch, and Transwell assays, and apoptotic cells were detected by flow cytometry. The biological functions of MTF-1 and miR-148a-3p were also determined using a xenograft mouse model. MTF-1 expression was upregulated in HCC cells and was associated with poor survival and recurrence. MTF-1 overexpression enhanced the proliferation and metastatic potential of HCC cells. Further mechanistic analyses demonstrated that MTF-1 bound to APE/Ref-1 and that MTF-1 is a direct target of miR-148-3p, which inversely regulated MTF-1 transcription activity. MiR-148a-3p overexpression effectively inhibited HCC cell proliferation and metastasis stimulated by MTF-1, with increased apoptosis. There was a decrease in miR-148a-3p expression in exosomes isolated from the plasma of patients with HCC and HCC cell culture supernatants. Co-incubation of HCC cells with exosomes from hepatocyte-conditioned media inhibited cell migration and caused apoptosis. The in vivo study revealed slow growth of MTF-1-knockdown and miR-148a-3p-overexpressing Hep3B-derived xenografts, with reduced tumor volume and weight compared with the control group. Collectively, these findings implicate MTF-1 as a modulator of HCC tumorigenesis and progression. Selective targeting towards exosomal miR-148a-3p, which might contribute to the negative regulation of MTF-1 at least partially in HCC, demonstrates therapeutic benefits for patients with HCC.

20.
Acta Biomater ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34678485

RESUMO

Engineered liver organogenesis is not yet a viable therapeutic option, but ectopic liver histogenesis may be possible. Accumulating evidence has suggested that cell-cell interactions and cell-matrix interactions play an important role in determining the properties of engineered hepatic tissue in vitro and in vivo. In the current study, we utilized heparinized decellularized liver scaffolds and bone marrow mesenchymal stromal cell spheroids to fabricate engineered hepatic tissue, which was subsequently implanted into the omentum of Sprague-Dawley rats with or without liver injury. The survival, liver-specific functions, differentiation level and regenerative potential of the implanted hepatocyte-like cells in this ectopic liver system were evaluated, together with the vascularization status and therapeutic potential of the engineered hepatic tissue. We demonstrated that these hepatic grafts could survive and possess hepatocyte specific function in this ectopic liver system but could also efficiently anastomose with host vascular networks. Furthermore, we found that hepatocyte-like cells within grafts expanded more than 9-fold over the course of 4 weeks in immunocompetent rats with injured livers. Immunostaining revealed that these hepatocyte-like cells could self-organize into cord-like structures in vivo. In addition, these hepatic grafts exhibited therapeutic potential in liver injury induced by CCl4. To our knowledge, this is the first report demonstrating the generation of long-term vascularized hepatic parenchyma at ectopic sites based on decellularized liver scaffolds and stem cells. These results provide an economic and feasible method for engineering hepatic tissue from construction to transplantation. This methodology may be applicable in clinical medicine, especially metabolic liver diseases. STATEMENT OF SIGNIFICANCE: : In this manuscript, we presented an optimized method for the hepatic engineered tissue (HET) from construction to transplantation. The core of this method is utilizing the combination of heparinized decellularized liver scaffolds and stem cell spheroids, which could provide necessary cell-cell and cell-extracellular matrix interactions for HET in vitro and in vivo. We proved that these hepatic grafts could possess hepatocyte specific function and exhibit strong proliferative activity in ectopic liver system, but also able to anastomose with the host vascular networks efficiently and be compatible with the host immune system. This methodology may be possible one day to apply in clinical medicine, especially metabolic liver diseases.

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