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1.
Oxid Med Cell Longev ; 2020: 8430465, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32377309

RESUMO

In an immunocompetent host, excess infiltration of immune cells in the lung is a key factor in infection-induced severe acute lung injury. Kidney transplant patients are immunocompromised by the use of immunosuppressive drugs. Immune cell infiltration in the lung in a renal transplant recipient suffering from pulmonary infection is significantly less than that in an immunocompetent host; however, the extent of lung injury in renal transplant patients is more serious than that in immunocompetent hosts. Therefore, we explored the role of platelet activation in a Klebsiella pneumoniae-induced lung injury model with P-selectin gene knockout mice or wild-type mice. Our study suggested that the inhibition of platelets reduced severe acute lung injury and increased survival after acute lung infection in mice. In addition, P-selectin expression on the surface of platelets in mice increased after administration of immunosuppressive drugs, and the extent of lung injury induced by infection decreased in P-selectin gene knockout mice. In conclusion, p-selectin plays a key role in severe acute lung injury in immunocompromised mice by reducing platelet activation and inflammatory processes.

2.
J Electrocardiol ; 60: 114-117, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32353803

RESUMO

INTRODUCTION: The benefits of MPP delay optimization on hemodynamics and ventricular contraction synchronicity can be quantified with cardiac index (CI) and QRS width. A delay with the maximum CI and minimum QRS width may be the optimized settings for multipoint pacing (MPP). METHODS: Twelve patients with advanced heart failure who received cardiac resynchronization therapy defibrillation with MPP at the Third People's Hospital of Chengdu from March 2016 to April 2019 were included. Interventricular and intraventricular delays were optimized through noninvasive cardiac output monitoring and a 12 lead ECG. RESULTS: According to CI, the optimized left ventricular- left ventricular - right ventricular delay setting was mainly 25 ms-25 ms and 40 ms-40 ms. And the delay with the minimum QRS width was mainly in 5 ms-5 ms, 25 ms-25 ms, and 40 ms-25 ms. The optimal MPP configuration increased CI compared to the MPP setting that produced the minimum CI (4.5 ± 1.3 vs. 2.8 ± 1.0 L/min/m2, P < 0.001). The QRS width of the optimized MPP was narrower than the MPP setting that produced the maximum QRS width (127 ± 20 vs. 160 ± 29 ms, P < 0.001). CONCLUSION: Delay optimization improves hemodynamic response and ventricular contraction synchronicity. The delay of 25 ms-25 ms may be the optimal setting for most MPP patients.

3.
Am J Transplant ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32400965

RESUMO

The ongoing outbreak of coronavirus disease 2019 (COVID-19) first reported in Wuhan has been declared global public health emergency and a pandemic by the World Health Organization. Faced with this novel coronavirus, scientists have been trying to use drugs that have not been validated by rigorous clinical trials, such as lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ). These drugs may be used tentatively for general population with COVID-19, but for solid organ transplant (SOT) recipients with long-term immunosuppressive therapy and drug-related metabolic diseases, antiviral drugs should be chosen with particular care. Notably, the elderly SOT patients commonly suffer from liver and kidney dysfunction of varying degrees, resulting in worse drug metabolism.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32430732

RESUMO

OBJECTIVE: This study was performed to investigate the effect of hypothermic machine perfusion (HMP) after cold storage (CS) on ovarian transplantation. METHODS: Rats aged 8-10 weeks were used as the donors and recipients for allotransplantation. Eighteen donor rats were divided into three groups: the fresh control (n = 6), cold storage (CS; n = 6), and hypothermic machine perfusion (HMP; n = 6) groups. The preservation solution contained Dulbecco's modified Eagle's medium/Ham's F-12 (1:1, v/v), 10% fetal bovine serum, 10 µg/ml insulin, 10 µg/ml transferrin, and 50 mIU/ml follicle-stimulating hormone (FSH). The donor ovaries in the CS and HMP groups were excised and then respectively subjected to 4 h of CS and 2 h of CS combined with 2 h of HMP at 4 °C, and then transplanted beneath the recipient's left renal capsule. At 7 days after transplantation, the ovaries were removed and blood samples were obtained for histological analysis, immunohistochemistry for CD31 and Ki67, and serum anti-Mullerian hormone (AMH) level estimation. RESULTS: The HMP group showed significant increases in serum AMH and CD31-positive areas when compared to these values in the CS group (P < 0.05). However, no differences were noted in the total number of follicles or the Ki67-positive areas among the three groups. CONCLUSION: Hypothermic machine perfusion after static cold storage is more effective than static CS alone for the short-term preservation of whole ovaries during transport. Whole ovary transplantation with vascular pedicle is our future research direction. Graphical Abstract The black rectangle in the figure shows the place where ligation and disconnection are required, the black dotted line shows the place where vascular forceps are used to clamp, and the black circle shows the place where the cannula is inserted This diagram was made for reviewers to understand more intuitively how my hypothermia mechanical perfusion model was built. Organs obtained in this way can be used for subsequent perfusion and whole ovarian transplantation.

5.
Cancer Med ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32372565

RESUMO

INTRODUCTION: Intravenous leiomyomatosis (IVL) is currently regarded as a special variant of the common uterine leiomyoma (LM). Though IVL shows a similar histological morphology to LM, IVL is characterized by unique intravenous growth patterns and low-grade malignant potential, which are quite different from LM. There are currently few studies underlying the molecular alterations of IVL, though this information is important for understanding the pathogenesis of the disease, and for identifying potential biomarkers. METHOD: We carried out a high-throughput whole transcriptome sequencing of tumor and normal tissue samples from five IVL patients and five LM patients and compared the differentially expressed genes (DEGs) between IVL and leiomyoma. We performed multiple different enrichment and target analyses, and the expression of selected DEGs was validated using RT-qPCR in formalin-fixed samples. RESULTS: Our study identified substantial different genes and pathways between IVL and LM, and functional enrichment analyses found several important pathways, such as angiogenesis and antiapoptosis pathways, as well as important related genes, including SH2D2A, VASH2, ADAM8, GATA2, TNF, and the lncRNA GATA6-AS1, as being significantly different between IVL and LM (P = .0024, P = .0195, P = .0212, P = .0435, P = .0401, and P = .0246, respectively). CXCL8, LIF, CDKN2A, BCL2A1, COL2A1, IGF1, and HMGA2 were also differently expressed between IVL and LM groups, but showed no statistical difference (P = .2409, P = .1773, P = .0596, P = .2737, P = .1553, P = .1045, and P = .1847, respectively) due to the large differences among individuals. Furthermore, RT-qPCR results for five selected DEGs in IVL tissues and adjacent nontumor tissues were mainly consistent with our sequencing results. CONCLUSION: Our results indicated that IVL may be a solid entity that is unique and different from LM, proving consistent with previous studies. Furthermore, we identified DEGs, particularly within angiogenesis and antiapoptosis pathway-related genes that may play crucial roles in the development and pathogenesis of IVL and may be potential specific biomarkers.

6.
J Mater Chem B ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32373904

RESUMO

Specific targeted drug delivery and controllable release of drugs at tumor regions are two of the main challenges for hepatocellular carcinoma (HCC) therapy, particularly post metastasis. Herein, we present a platelet membrane-facilitated local chemo-photothermal therapy strategy, in which polypyrrole (PPy) nanoparticles act as photothermal agents and along with antitumor drug doxorubicin (DOX) are encapsulated into platelet membranes (PLT-PPy-DOX). The particles are endowed with immune evasiveness and tumor targeting abilities from platelet membranes, and are then intravenously injected into an orthotopic mouse model of HCC. As expected, the PLT-PPy-DOX nanoplatforms were abundant in the tumor tissues. Hyperthermia was generated under laser irradiation (808 nm) not only to ablate tumor cells directly but also to increase the triggered release of DOX. This combination of local chemotherapy and photothermal therapy demonstrated excellent antitumor efficiency in suppressing primary tumor growth and inhibiting tumor metastases. This localized therapy which adopts biocompatible natural cell membranes and good biodegradable organic photothermal agents may provide new insights into designing biomimetic nano-vehicles for personalized therapy of HCC.

7.
Nucleic Acid Ther ; 30(3): 153-163, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32286934

RESUMO

A population pharmacokinetic (PK) and pharmacodynamic (PD) model was developed for inotersen to evaluate exposure-response relationships and to optimize therapeutic dosing regimen in patients with hereditary transthyretin (TTR) amyloidosis polyneuropathy (hATTR-PN). Inotersen PK and TTR level (PD) data were composed of one Phase 1 study in healthy subjects, one Phase 2/3 study in hATTR patients, and its one open-label extension study. Effects of intrinsic and extrinsic factors (covariates) on PK and PK/PD of inotersen were evaluated using a full model approach. Inotersen PK was characterized by a two-compartment model with elimination from the central compartment. The population PK analysis identified disease status and lean body mass (LBM) as significant covariates for inotersen PK. Nonetheless, the contribution of disease status and LBM on PK was small, as the difference in clearance (CL/F) was 11.1% between healthy subjects and patients with hATTR-PN and 38% between the lowest and highest LBM quartiles of the patient population. Age, race, sex, baseline renal function estimated glomerular filtration rate, and hepatic function markers (baseline albumin, bilirubin, and alanine aminotransferase values) were not statistically significant covariates affecting inotersen PK. An inhibitory effect indirect-response model (inhibition of TTR production) was used to describe the drug effect on TTR-time profiles, with baseline TTR included as a covariate. The overall population Imax and IC50, together with 95% confidence interval, was estimated to be 0.913 (0.899-0.925) and 9.07 (8.08-10.1) ng/mL, respectively. V30M mutation showed no effect on the estimated IC50 value for hATTR patients. The final population PK and PK/PD model was used to simulate four different treatment regimens. The population PK/PD model developed well described the PK and PD of inotersen in patients with hATTR-PN and has been used for label recommendation and trial simulations.

8.
Life Sci ; 253: 117705, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32334008

RESUMO

AIMS: Ischemia-reperfusion injury (IRI) is harmful to patients following kidney transplantation. Hypothermic machine perfusion (HMP) can be adopted to preserve grafts and reduce consequential injury. We hypothesized that aldehyde dehydrogenase 2 (ALDH2) partly mitigates kidney IRI via regulating excessive autophagy in HMP. MATERIALS AND METHODS: The rabbits were assigned to 5 groups: Normal, HMP, HMP + Alda-1, HMP + CYA and cold storage (CS). After the rabbit autologous kidney transplantation, renal pathology and function were evaluated by histological analysis, glomerular related proteins (desmin, nephrin), tubular injury factors (NGAL, Ki67), serum creatinine (Cr) and blood urea nitrogen (BUN). Oxidative stress molecular Malondialdehyde (MDA) and superoxide dismutase (SOD2) expression, as well as inflammatory cytokines (TNF-α, IL-6, IL-10) were assessed by immunohistochemistry. The expression of LC3, p62, ALDH2, p-Akt, mTOR, PTEN, p-PTEN, and 4-HNE were measured by immunohistochemistry, RT-PCR, Western blot analysis or ELISA. KEY FINDINGS: HMP was more effective than CS for kidney preservation, with p- ALDH2 expressed in greater quantities in HMP. The results of kidney pathology and function in HMP + Alda-1 were the best. The MDA & SOD2 and the Vyacheslav score were improved in HMP + CYA. ALDH2 reduced 4-HNE-induced oxidative stress, inflammatory infiltration, the expression of LC3, p62 and inhibited autophagy accompanied by activation of p-Akt and mTOR via p-PTEN/PTEN. SIGNIFICANCE: Akt-mTOR autophagy pathway is a novel target for ALDH2 to reduce renal IRI partly by inhibition of 4-HNE in HMP, then protecting the donated kidney received after cardiac death (DCD).

9.
Am J Transplant ; 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32282986

RESUMO

Over 1 000 000 cases of coronavirus disease 2019 (COVID-19) have been confirmed since the worldwide outbreak began. Not enough data on infected solid organ transplant (SOT) recipients are available, especially data about the management of immunosuppressants. We report two cases of COVID-19 in two transplant recipients, with different treatments and prognoses. The first patient received liver transplantation due to hepatitis B virus-related hepatocellular carcinoma and was confirmed to have COVID-19 9 days later. Following a treatment regimen consisting of discontinued immunosuppressant use and low-dose methylprednisolone-based therapy, the patient developed acute rejection but eventually recovered. The other patient had undergone a renal transplant from a living-related donor 17 years ago, and was admitted to the hospital because of persistent fever. This patient was also diagnosed with COVID-19. His treatment regimen consisted of reduced immunosuppressant use. No signs of rejection were observed during the regimen. In the end, the patient successfully recovered from COVID-19. These effectively treated cases can provide a basis for immunosuppressant management of COVID-19-positive SOT recipients.

10.
Oxid Med Cell Longev ; 2020: 5849794, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32256954

RESUMO

Hepatic ischemia-reperfusion (IR) injury is a clinical issue that can result in poor outcome and lacks effective therapies at present. Mild hypothermia (32-35°C) is a physiotherapy that has been reported to significantly alleviate IR injury, while its protective effects are attributed to multiple mechanisms, one of which may be the regulation of fatty acid ß-oxidation (FAO). The aim of the present study was to investigate the role and underlying mechanisms of FAO in the protective effects of mild hypothermia. We used male mice to establish the experimental models as previously described. In brief, before exposure to in situ ischemia for 1 h and reperfusion for 6 h, mice received pretreatment with mild hypothermia for 2 h and etomoxir (inhibitor of FAO) or leptin (activator of FAO) for 1 h, respectively. Then, tissue and blood samples were collected to evaluate the liver injury, oxidative stress, and changes in hepatic FAO. We found that mild hypothermia significantly reduced the hepatic enzyme levels and the score of hepatic pathological injury, hepatocyte apoptosis, oxidative stress, and mitochondrial injury. In addition, the expression of the rate-limiting enzyme (CPT1a) of hepatic FAO was downregulated almost twofold by IR, while this inhibition could be significantly reversed by mild hypothermia. Experiments with leptin and etomoxir confirmed that activation of FAO could also reduce the hepatic enzyme levels and the score of hepatic pathological injury, hepatocyte apoptosis, oxidative stress, and mitochondrial injury induced by IR, which had the similar effects to mild hypothermia, while inhibition of FAO had negative effects. Furthermore, mild hypothermia and leptin could promote the phosphorylation of JAK2/STAT3 and upregulate the ratio of BCL-2/BAX to suppress hepatocyte apoptosis. Thus, we concluded that FAO played an important role in hepatic IR injury and mild hypothermia attenuated hepatic IR injury mainly via the regulation of JAK2/STAT3-CPT1a-dependent FAO.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32324559

RESUMO

The synchronization control of two chaotic oscillatory systems is designed based on DNA strand displacement in the present work. Thus, combination synchronization of three 3-variable chaotic oscillatory systems is proposed based on DNA strand displacement. Firstly, five chemical reaction modules of double, displacement, adjustment, catalysis and degradation are designed. Based on these five modules, a 3-variable chaotic oscillatory system is designed. Secondly, based on the design principle of coupling terms and theory of stability, synchronization modules and coupling terms are added to three chaotic oscillatory systems to design combination synchronization of three 3-variable chaotic oscillatory systems based on DNA strand displacement. Modules and systems are implemented and tested using visual DSD and Matlab, and the simulation results are presented to demonstrate the effectiveness and correctness of the chemical reaction modules and systems. The combination synchronization of three 3-variable chaotic oscillatory systems is proposed based on DNA strand displacement, which may be extended to the reaction networks of DNA strand displacement and to the combination synchronization of multivariable chaotic oscillatory systems based on DNA strand displacement.

12.
J Gastrointest Surg ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32128678

RESUMO

BACKGROUND: A high rate of postoperative recurrence, especially early recurrence (ER) occurring within 1 year, seriously impedes patients with hepatocellular carcinoma (HCC) from achieving long-term survival. This study aimed to establish a genomic-clinicopathologic nomogram for precisely predicting ER in HCC patients after R0 resection. METHODS: Two reliable datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were selected as the training and validation cohorts, respectively. The prognostic genes related to ER were screened out by univariate Cox regression analysis and differential expression analysis. The gene-based prognostic index was constructed using LASSO and Cox regression analyses, and its independent prognostic value was assessed by Kaplan-Meier and multivariate Cox analyses. Gene set enrichment analysis (GSEA) was performed to explore the biological pathways related to the prognostic index. Finally, the nomogram integrating all the independent prognostic factors was established and comprehensively evaluated by calibration plots, the C-index, receiver operating characteristic curves, and decision curve analysis. RESULTS: Nine dysregulated and prognostic genes related to ER (ZNF131, TATDN2, TXN, DDX55, KPNA2, ZNF30, TIMELESS, SFRP1, and COLEC11) were identified (all P < 0.05). The prognostic index model based on the 9 genes was successfully constructed using the TCGA cohort and showed a certain capability to discriminate the ER group from the non-ER group (P < 0.05) and good independent prognostic value in terms of predicting poor early recurrence-free survival (P < 0.05). Eight biological pathways significantly related to ER were identified by GSEA, such as "cell cycle", "homologous recombination" and "p53 signaling pathway." The genomic-clinicopathologic nomogram integrating the 9-gene-based prognostic index and TNM stage displayed significantly higher predictive accuracy and clinical application value than that of TNM stage model both in the training and validation cohorts (all P < 0.05). CONCLUSIONS: The novel genomic-clinicopathologic nomogram may be a convenient and powerful tool for accurately predicting ER in HCC patients after R0 resection.

13.
Mol Med Rep ; 21(2): 567-574, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31974600

RESUMO

The present study aimed to investigate whether brain death (BD) induces the activation of endoplasmic reticulum stress (ERS) and protein phosphatase 2A (PP2A), and reveal the possible association with BD­induced liver cell apoptosis. A total of 30 healthy adult male Sprague­Dawley rats were randomized into three groups: Sham­operated group (S), BD group and 4­phenylbutyric acid group (BD + 4­PBA), with 10 rats in each group. All rats were anesthetized. The model of BD was established by inflating a balloon catheter that was placed into the extradural space after anesthesia. 4­PBA was administered via an intraperitoneal injection when the BD model was established. Anesthesia of the S group of rats was maintained for 6 h. Liver tissues were harvested after 6 h of BD. HE staining was used to evaluate the damage of liver. Terminal deoxynucleotidyl transferase­mediated 2'­deoxyuridine 5'­triphosphate nick­end labeling staining was used to observe the apoptosis of liver cells. Activation of ERS and PP2A was examined by western blotting and immunohistochemical staining. We reported that the apoptosis of liver cells after BD was significantly promoted than in the S group. Activation of ERS and PP2A was induced in the BD group when compared with S group. Phosphorylation of PP2A was suppressed in BD group. Application of 4­PBA decreased the activation of ERS and apoptosis rate compared with the BD group. In addition, activation of PP2A in the BD + 4­PBA group was decreased due to the reduction of PP2A phosphorylation compared with the BD group, but the levels were higher than in the S group. (P<0.05). In summary, our results indicated that BD induced ERS, then activated PP2A by suppressing the phosphorylation of PP2A, resulting in the apoptosis of liver cells.

14.
IEEE Trans Cybern ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31751264

RESUMO

Most memristor-based Pavlov associative memory neural networks strictly require that only simultaneous food and ring appear to generate associative memory. In this article, the time delay is considered, in order to form associative memory when the food stimulus lags behind the ring stimulus for a certain period of time. In addition, the rate of learning can be changed with the length of time between the ring stimulus and food stimulus. A memristive neural network circuit that can realize Pavlov associative memory with time delay is designed and verified by the simulation results. The designed circuit consists of a synapse module, a voltage control module, and a time-delay module. The functions, such as learning, forgetting, fast learning, slow forgetting, and time-delay learning, are implemented by the circuit. The Pavlov associative memory neural network with time-delay learning provides a reference for further development of the brain-like systems.

15.
DNA Res ; 26(6): 453-464, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31711192

RESUMO

Black rockfish (Sebastes schlegelii) is an economically important viviparous marine teleost in Japan, Korea, and China. It is characterized by internal fertilization, long-term sperm storage in the female ovary, and a high abortion rate. For better understanding the mechanism of fertilization and gestation, it is essential to establish a reference genome for viviparous teleosts. Herein, we used a combination of Pacific Biosciences sequel, Illumina sequencing platforms, 10× Genomics, and Hi-C technology to obtain a genome assembly size of 848.31 Mb comprising 24 chromosomes, and contig and scaffold N50 lengths of 2.96 and 35.63 Mb, respectively. We predicted 39.98% repetitive elements, and 26,979 protein-coding genes. S. schlegelii diverged from Gasterosteus aculeatus ∼32.1-56.8 million years ago. Furthermore, sperm remained viable within the ovary for up to 6 months. The glucose transporter SLC2 showed significantly positive genomic selection, and carbohydrate metabolism-related KEGG pathways were significantly up-regulated in ovaries after copulation. In vitro suppression of glycolysis with sodium iodoacetate reduced sperm longevity significantly. The results indicated the importance of carbohydrates in maintaining sperm survivability. Decoding the S. schlegelii genome not only provides new insights into sperm storage; additionally, it is highly valuable for marine researchers and reproduction biologists.

16.
Sci Rep ; 9(1): 15856, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676802

RESUMO

In this paper, modulation of reflected wavefront out of the incident plane by a tunable acoustic metasurface is investigated based on the fully generalized Snell's law in the three-dimensional space. The metasurface is constructed by a square lattice of circular holes with gradient annular bumps. The phase shift is tuned by changing the volume of water filled in the holes. The acoustic wave steering out of the incident plane and the out-of-plane acoustic focusing with the oblique incidence at the subwavelength scale are demonstrated numerically by selecting suitable distributions of water depth. The numerical results show that the wavefront of the reflected wave can be manipulated over a wide frequency range; and the gradient design of the unit cells can suppress the parasitic reflection. The present work is relevant to the practical design of novel acoustic devices.

17.
Front Neurosci ; 13: 937, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31607839

RESUMO

Objective: To explore novel related genes and potential biomarkers of pancreatic neuroendocrine tumors (PanNETs). Materials and Methods: Two data sets from ICGC and two from the NCBI GEO database were used to identify the differentially expressed genes (DEGs) in PanNETs. The common DEGs among the four sources were analyzed; furthermore, the relationship of these gene expression patterns with different PanNET grades, their mutation status and corresponding impact on prognosis, the interaction network, and the relationship with three known PanNET genes (ATRX, DAXX, and MEN1) were analyzed by two other GEO data and cBioPortal database. Finally, the expressions of novel DEGs were validated in Chinese PanNET tissues by RT-qPCR. Results: Five new DEGs (ABCC8, PCSK2, IL13RA2, KLKB1, and PART1) and one confirmed DEG-ISL1 were identified. The mutation counts of DEGs increased with the tumor grade increasing from G1 to G3, and PanNET patients present vascular invasion or are deceased. These DEG expression patterns in PanNETs are quite different from that of pancreatic ductal adenocarcinoma and are related to A-D-M (ATRX-DAXX-MEN1) mutation. ABCC8 and KLKB1 are co-occurrence with the A-D-M axis in PanNETs. Importantly, patients with DEG mutations have a lower survival rate. RT-qPCR verification results of KLKB1 (P < 0.01), IL13RA2 (P < 0.01), ABCC8 (P < 0.01), and PART1 (P < 0.0001) expressions in Chinese PanNET tissues are consistent with our database analysis, which were significantly up-regulated. However, the expression of PCSK2 (P < 0.01) was contrary to our bioinformatics analysis, which was significantly down-regulated, suggesting that the expression trend of PCSK2 may be different among different races. These results indicated that these five genes may play an important role in the occurrence and progression of PanNETs. Conclusion: Five novel common DEGs identified are related to the development and prognosis of PanNETs and may serve as specific biomarkers and therapeutic targets.

18.
Transplant Proc ; 51(9): 3124-3130, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31611117

RESUMO

BACKGROUND: Previous dismal clinical studies have stated that colorectal cancer with unresectable liver metastases is an absolute contraindication for liver transplantation (LT). During recent decades, it has been shown that patients with colorectal cancer with liver metastasis benefited from LT, but 100% recurrence was inevitable in progressive colorectal cancer with liver metastasis. CASE PRESENTATION: A 61-year-old man was found at the first visit to be suffering from unresectable liver metastases of colorectal cancer. This patient underwent colorectal radical surgery and palliative treatment after the operation. During a 2-year follow-up, we found that CEA and CA199 rebounded sharply to high levels, and liver metastasis lesions increased significantly, so we made the decision to perform LT 2 years after the first surgery. Chemotherapy and sirolimus were given post-LT. Slow-growing pulmonary metastases after transplantation were found 4 months post-LT. This patient survived the next 4 months tumor-free and by now has survived 34 months free of liver tumors. Here, we review the literature on LT for progressive liver metastasis of colorectal cancer and summarize our experience from this successful case. CONCLUSION: This case provides vital evidence that LT is an option and can provide curative therapy for patients with advanced unresectable liver metastasis. Careful selection of patients, postoperative comprehensive treatments, and rational application of immunosuppressive agents are vital factors for favorable prognosis.


Assuntos
Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
19.
Apoptosis ; 24(11-12): 921-933, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31605257

RESUMO

Multiple research groups have demonstrated that the outcome of patients receiving liver grafts from brain death donors (DBD) is poorer when compared with patients receiving grafts from living donors. This might be due to an increased hepatocyte apoptosis induced after brain death (BD). In this work, we found that the activity of PP2A-Akt pathway is significantly increased in clinical donor ex vivo hepatocytes after BD by iTRAQ protein quantification analysis. The same results were confirmed in animal models. A time-dependent promotion of apoptosis was also found in DBD rabbit liver, as demonstrated by the increased levels of cleaved Caspase 3 and the decreased of Bcl-2. To further investigate the roles of PP2A and Akt in regulating apoptosis of hepatocytes after BD, we cultivated human liver cell line L02 with serum deprivation and hypoxia, to simulate the ischemic and hypoxic conditions of hepatocytes in DBD. Increased apoptosis and decreased viability were observed during the time in this model. Meanwhile PP2A activity and Akt activity were respectively increased and decreased. Notably, the proportion of Akt phosphorylation at Ser473 decreased, while other known targets of PP2A (p38, JNK and ERK) were not affected in terms of protein levels or phosphorylation. These results suggested that PP2A is involved in apoptotic induction of hepatocytes after brain death by specific suppression of Akt. This discovery was further confirmed with pharmaceutical and genetic methods. Our work implied potential targets for reducing liver cell apoptosis and improving organ donor quality after BD.

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