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1.
Chin J Integr Med ; 30(2): 99-106, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37943487

RESUMO

OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS: No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.


Assuntos
Ácidos Aristolóquicos , Carcinoma Hepatocelular , Nefropatias , Neoplasias Hepáticas , Humanos , Estudos Retrospectivos , Incidência , Neoplasias Hepáticas/epidemiologia , Nefropatias/induzido quimicamente , Ácidos Aristolóquicos/efeitos adversos
3.
Zhongguo Gu Shang ; 36(11): 1085-90, 2023 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-38012880

RESUMO

OBJECTIVE: To investigate the relationship between serum matrix metalloproteinase-1(MMP-1) and matrix metalloproteinase-2(MMP-2) and the formation of deep venous thrombosis(LDVT) in lower extremity patients after surgery for lower extremity fracture, and to analyze the value of MMP-1 and MMP-2 in predicting the occurrence of LDVT after lower extremity fracture. METHODS: From June 2018 to December 2021, 352 patients who planned to receive surgical treatment of lower limb fracture in our hospital were selected as the research objects. Venous blood was collected at 1, 2 and 3 days after surgery, respectively, and serum MMP-1 and MMP-2 levels were detected. The incidence of LDVT during hospitalization was analyzed, and the risk factors of postoperative LDVT in patients with lower limb fracture surgery and the predictive value of MMP-1 and MMP-2 for LDVT were analyzed. RESULTS: LDVT occurred in 40 patients (LDVT group), the incidence of LDVT was 11.36%, and 312 patients did not occurred(no occurred group). The serum levels of MMP-1 and MMP-2 in LDVT group increased gradually after surgery; the serum levels of MMP-1 and MMP-2 in the no occurred group increased slightly after surgery at 2 days and then decreased at 3 days after surgery (P<0.01);the serum levels of MMP-1 and MMP-2 in LDVT group were higher than those in the no occurred group at 2 days and 3 days after surgery (P<0.05). Serum levels of MMP-1 and MMP-2 were positively correlated with serum levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor -α (TNF-α) in LDVT patients at 2 days and 3 days postoperatively (P<0.05). Operative time, MMP-1 and MMP-2 postoperative 3 days were related to the occurrence of LDVT after lower limb fracture (P<0.01). The area under the curve(AUC) predicted by MMP-1 and MMP-2 postoperative 3 days for LDVT after lower limb fracture was 0.738 and 0.744 respectively, and the AUC predicted by combined MMP-1 and MMP-2 was 0.910, which was higher than that predicted by single indicator(Z=2.819 and 2.025, P<0.05). CONCLUSION: High levels of MMP-1 and MMP-2 after lower extremity fracture are closely related to the occurrence of LDVT, and 3 d mMP-1 and MMP-2 after surgery maybe used as evaluation indexes for LDVT risk prediction.


Assuntos
Fraturas Ósseas , Metaloproteinase 1 da Matriz , Metaloproteinase 2 da Matriz , Trombose Venosa , Humanos , Extremidade Inferior/cirurgia , Metaloproteinase 1 da Matriz/sangue , Metaloproteinase 2 da Matriz/sangue , Fatores de Risco , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Fraturas Ósseas/cirurgia
4.
Front Immunol ; 14: 1143181, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37187741

RESUMO

Background: Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease of immune hyperactivation that arises in the context of infectious, inflammatory, or neoplastic triggers. The aim of this study was to establish a predictive model for the timely differential diagnosis of the original disease resulting in HLH by validating clinical and laboratory findings to further improve the efficacy of therapeutics for HLH. Methods: We retrospectively enrolled 175 secondary HLH patients in this study, including 92 patients with hematologic disease and 83 patients with rheumatic disease. The medical records of all identified patients were retrospectively reviewed and used to generate the predictive model. We also developed an early risk score using multivariate analysis weighted points proportional to the ß regression coefficient values and calculated its sensitivity and specificity for the diagnosis of the original disease resulting in HLH. Results: The multivariate logistic analysis revealed that lower levels of hemoglobin and platelets (PLT), lower levels of ferritin, splenomegaly and Epstein-Barr virus (EBV) positivity were associated with hematologic disease, but young age and female sex were associated with rheumatic disease. The risk factors for HLH secondary to rheumatic diseases were female sex [OR 4.434 (95% CI, 1.889-10.407), P =0.001], younger age [OR 6.773 (95% CI, 2.706-16.952), P<0.001], higher PLT level [OR 6.674 (95% CI, 2.838-15.694), P<0.001], higher ferritin level [OR 5.269 (95% CI, 1.995-13.920), P =0.001], and EBV negativity [OR 27.656 (95% CI, 4.499-169.996), P<0.001]. The risk score included assessments of female sex, age, PLT count, ferritin level and EBV negativity, which can be used to predict HLH secondary to rheumatic diseases with an AUC of 0.844 (95% CI, 0.836~0.932). Conclusion: The established predictive model was designed to help clinicians diagnose the original disease resulting in secondary HLH during routine practice, which might be improve prognosis by enabling the timely treatment of the underlying disease.


Assuntos
Infecções por Vírus Epstein-Barr , Linfo-Histiocitose Hemofagocítica , Doenças Reumáticas , Humanos , Feminino , Masculino , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4 , Estudos Retrospectivos , Doenças Reumáticas/complicações
5.
J Virol ; 97(1): e0146722, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36475768

RESUMO

Assembly of the adenovirus capsid protein hexon depends on the assistance of the molecular chaperone L4-100K. However, the chaperone mechanisms remain unclear. In this study, we found that L4-100K was involved in the hexon translation process and could prevent hexon degradation by the proteasome in cotransfected human cells. Two nonadjacent domains, 84-133 and 656-697, at the N-terminal and C-terminal regions of human adenovirus type 5 L4-100K, respectively, were found to be crucial and cooperatively responsible for hexon trimer expression and assembly. These two chaperone-related domains were conserved in the sequence of L4-100K and in the function of hexon assembly across different adenovirus serotypes. Different degrees of cross-activity of hexon trimerization with different serotypes were detected in subgroups B, C, and D, which were proven to be controlled by the interaction between the C-terminal chaperone-related domain of L4-100K and hypervariable regions (HVR) of hexon. Additionally, HVR-chimeric hexon mutants were successfully assembled with the assistance of the 1-697 mutant. Structural analysis of 656-697 by nuclear magnetic resonance and structural prediction of L4-100K using Robetta showed that the two conserved domains are mainly composed of α-helices and are located on the surface of the highly folded core region. Our research provides a more complete understanding of hexon assembly and guidance for the development of hexon-chimeric adenovirus vectors that will be safer, smarter, and more efficient. IMPORTANCE Adenovirus vectors have been widely used in clinical trials of vaccines and gene therapy, although some deficiencies remain. Chimeric modification of the hexon was expected to improve the potency of preexisting immune evasion and targeting, but in many cases, viral packaging is prevented by the inability of the chimeric hexon to assemble correctly. So far, few studies have examined the mechanisms of hexon trimer assembly. Here, we show how the chaperone protein L4-100K contributes to the assembly of the adenovirus capsid protein hexon, and these data will provide a guide for novel adenovirus vector design and development, as we desired.


Assuntos
Adenovírus Humanos , Chaperonas Moleculares , Proteínas não Estruturais Virais , Humanos , Adenovírus Humanos/genética , Adenovírus Humanos/metabolismo , Capsídeo/metabolismo , Proteínas do Capsídeo/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo
6.
World J Clin Cases ; 11(36): 8519-8526, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38188217

RESUMO

BACKGROUND: Cholecystoenteric fistula (CEF) involves the formation of a spontaneous anomalous tract between the gallbladder and the adjacent gastrointestinal tract. Chronic gallbladder inflammation can lead to tissue necrosis, perforation, and fistulogenesis. The most prevalent cause of CEF is chronic cholelithiasis, which rarely results from malignancy. Because the symptoms and laboratory findings associated with CEF are nonspecific, the condition is often misdiagnosed, presenting a challenge to the surgeon when detected intraoperatively. Therefore, a preoperative diagnosis of CEF is crucial. CASE SUMMARY: We present the case of a 57-year-old male with advanced gallbladder cancer (GBC) who arrived at the emergency room with persistent vomiting, abdominal pain, and diarrhea. An abdominopelvic computed tomography scan revealed a contracted gallbladder with bubbles in the fundus connected to the second portion of the duodenum and transverse colon. We suspected that GBC had invaded the adjacent gastrointestinal tract through a cholecystoduodenal fistula (CDF) or a cholecystocolonic fistula (CCF). He underwent multiple examinations, including esophagogastroduodenoscopy, an upper gastrointestinal series, colonoscopy, and magnetic resonance cholangiopancreatography; the results of these tests confirmed a diagnosis of synchronous CDF and CCF. The patient underwent a Roux-en-Y gastrojejunostomy and loop ileostomy to address the severe adhesions that were previously observed to cover the second portion of the duodenum and hepatic flexure of the colon. His symptoms improved with supportive treatment while hospitalized. He initiated oral targeted therapy with lenvatinib for further anticancer treatment. CONCLUSION: The combination of imaging and surgery can enhance preoperative diagnosis and alleviate symptoms in patients with GBC complicated by CEF.

7.
Ying Yong Sheng Tai Xue Bao ; 34(12): 3373-3384, 2023 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-38511377

RESUMO

Under the background of the carbon peaking and carbon neutrality goals, the evolution of the spatiotemporal pattern of carbon storage has recently emerged as a research hotspot. The change in land use and land cover (LULC) is the primary driver of carbon storage changes. Understanding the spatiotemporal variations of LULC and carbon storage at the small scale of district and county level and proposing strategies to improve carbon sink, will contribute to the ecological conservation, restoration and sustainable development of districts or counties. With Yanqing District in Beijing as an example, we calculated carbon storage from 1990 to 2020 based on the InVEST model and used the PLUS model to predict LULC type changes under three scenarios (natural growth, ecological conservation and economic development) from 2020 to 2050. We further predicted the carbon storage and proposed mea-sures to improve carbon sink. The results showed that the key LULC change in Yanqing between 1990 and 2020 were the conversion of 88.9% of grassland to forest, 50.1% of farmland to forest, and 39.5% of cropland to impervious surface. The total carbon storage showed an upward trend, with an increase of 3.34×106 Mg. The spatial distribution of carbon storage presented "high in the northeast, low in the southwest, and high in the mountainous areas, low in the riverine areas." The increase in forest and the decrease in grassland were the main reasons for the increase and decrease in carbon storage, respectively. Between 2020 and 2050, the ecological restoration efforts under the ecological protection scenario increased, and the probability of other LULCs transforming into forest increased, resulting in a 5.8% increase in carbon storage, which had the highest increase and carbon storage under the three scenarios. High-value carbon storage areas were concentrated in the northeast, northwest, and south of Yanqing District, basically corresponding to the mountainous regions of Yanqing with high forest coverage, and the low-value areas generally corresponded to the plains with high development intensity and low forest coverage. We could implement comprehensive ecological protection and restoration measures, including forest and grassland ecosystem protection, water environment ecological restoration, farmland ecological restoration, to promote sustainable development in Yanqing District and to achieve the "dual carbon" goal.


Assuntos
Sequestro de Carbono , Ecossistema , Pequim , Carbono , Desenvolvimento Econômico , Florestas , Conservação dos Recursos Naturais , China
8.
ACS Nano ; 16(4): 6634-6645, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35352548

RESUMO

Poly(ethylene glycol) (PEG) is the most widely used polymer to decorate inorganic nanoparticles (NPs) by the "grafting-to" method for antifouling properties. PEG also shows diverse supramolecular interactions with nanoparticle surfaces and polar molecules, suggesting that the physisorption between PEG chains and NPs cannot be ignored in the "grafting-to" process. However, the effect of physisorption of PEG to NPs on the process of chemisorption has been rarely studied. Herein, we report that unfunctionalized PEG is physically adsorbed on various NPs by polyvalent supramolecular interactions, adopting "loop-and-train-tail" conformations. We investigated the effect of molecular weight of PEG and ligands of the NPs on the conformation of PEG chains by experimental methods and simulation. It is demonstrated that the physisorption of PEG on NPs can facilitate the chemisorption in the initial stages but delays it in the later stages during the "grafting-to" process. This work provides a deeper understanding of the conformation of physisorbed PEG on NPs and the relationship between physisorption and chemisorption.

9.
J Phys Chem Lett ; 12(22): 5363-5370, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34076431

RESUMO

Antifouling polymer brushes are widely used to inhibit the formation of protein corona on nanoparticles (NPs) and subsequent accumulation in the liver and spleen. Herein, we demonstrate a θ-solvent-mediated method for the preparation of gold nanoparticles with a high polyethylene glycol (PEG) grafting density. Reaching the θ-solvent by adding salt (e.g., Na2SO4) can significantly increase the grafting density of the PEG brush to 2.08 chains/nm2. The PEG polymer brush prepared in the θ-solvent possesses a double-shell structure consisting of a concentrated polymer brush (CPB) and a semidilute polymer brush (SDPB), denoted as NP@CPB@SDPB, while those prepared in a good solvent have only a SDPB shell, i.e., NP@SDPB. Compared to the NP@SDPB structure, the NP@CPB@SDPB structure decreases the liver accumulation from 34.0%ID/g to 23.1%ID/g, leading to an increase in tumor accumulation from 8.5%ID/g to 12.8%ID/g. This work provides new insights from the perspective of polymer physical chemistry into the improved stealth properties and delivery efficiency of NPs, which will accelerate the clinical translation of nanomedicine.

10.
Front Cell Dev Biol ; 9: 630355, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33937231

RESUMO

Bone-related malignancies, such as osteosarcoma, Ewing's sarcoma, multiple myeloma, and cancer bone metastases have similar histological context, but they are distinct in origin and biological behavior. We hypothesize that a distinct immune infiltrative microenvironment exists in these four most common malignant bone-associated tumors and can be used for tumor diagnosis and patient prognosis. After sample cleaning, data integration, and batch effect removal, we used 22 publicly available datasets to draw out the tumor immune microenvironment using the ssGSEA algorithm. The diagnostic model was developed using the random forest. Further statistical analysis of the immune microenvironment and clinical data of patients with osteosarcoma and Ewing's sarcoma was carried out. The results suggested significant differences in the microenvironment of bone-related tumors, and the diagnostic accuracy of the model was higher than 97%. Also, high infiltration of multiple immune cells in Ewing's sarcoma was suggestive of poor patient prognosis. Meanwhile, increased infiltration of macrophages and B cells suggested a better prognosis for patients with osteosarcoma, and effector memory CD8 T cells and type 2 T helper cells correlated with patients' chemotherapy responsiveness and tumor metastasis. Our study revealed that the random forest diagnostic model based on immune infiltration can accurately perform the differential diagnosis of bone-related malignancies. The immune microenvironment of osteosarcoma and Ewing's sarcoma has an important impact on patient prognosis. Suppressing the highly inflammatory environment of Ewing's sarcoma and promoting macrophage and B cell infiltration may have good potential to be a novel adjuvant treatment option for osteosarcoma and Ewing's sarcoma.

11.
Chemistry ; 27(46): 11879-11887, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34043289

RESUMO

An efficient strategy for simultaneously detecting and removing Hg2+ from water is vital to address mercury pollution. Herein a supramolecular assembly G⊂H with photoluminescent properties is facilely constructed through the self-assembly of a functional pillar[5]arene bearing two N,N-dimethyldithiocarbamoyl binding sites (H) and an AIE-active tetraphenylethene derivative (G). Remarkably, the fluorescence of G⊂H can be exclusively quenched by Hg2+ among the 30 cations due to the formation of non-luminous ground state complex and only L-cysteine can restore fluorescence in the common 20 amino acids. Meanwhile, the probe G⊂H has a considerable thermal and pH stability, a good anti-interference property from various cations, and a satisfactory sensitivity. More importantly, G⊂H exhibits a prominent capability of Hg2+ removal with rapid capture rate (within 1 h) and excellent adsorption efficiency (98 %), as well as a highly efficient recyclability without losing any adsorption activity.


Assuntos
Mercúrio , Adsorção , Cisteína , Espectrometria de Fluorescência , Água
12.
Neurol India ; 69(1): 115-118, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33642281

RESUMO

CONTEXT: A host of microRNAs have been reported to suppress tumor growth, invasion, and metastasis and play roles in neurodegeneration disorders. Moreover, microRNA changes are found in the peripheral blood, cerebrospinal fluid (CSF), and brain tissues of central nervous system diseases, including glioma, Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis, and depression. Compared with other body fluids, CSF can reflect the brain pathological processes more accurately. AIMS: To understand whether microRNA expression may be misregulated in patients with PD, and further discover potential diagnostic biomarkers and promising therapeutic targets for PD. MATERIALS AND METHODS: Here, through real-time reverse-transcription polymerase chain reaction (RT-PCR), we compared CSF microRNA from 15 PD patients, 11 AD patients, and 16 controls with other neurologic disorders, such as encephalitis and Guillain-Barre syndrome. RESULTS: Finally, we identified hsa-miR-626 changes in the CSF of PD patients. The mean expression level of hsa-miR-626 was significantly reduced in the CSF of PD patients compared with AD patients and controls. CONCLUSIONS: Our approach provides a preliminary research for identifying biomarkers in the CSF that could be used for the detection, diagnosis, and monitoring of PD.


Assuntos
Doença de Alzheimer , MicroRNAs , Doença de Parkinson , Biomarcadores , Humanos , MicroRNAs/genética , Doença de Parkinson/genética
13.
Brachytherapy ; 19(1): 66-72, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31837988

RESUMO

PURPOSE: The aim of the study was to compare the dose distributions of combined intracavitary and interstitial (IC/IS) brachytherapy with 3-catheter IC brachytherapy in treating locally advanced (stage IIB) cervical cancer. METHODS AND MATERIALS: In total, 46 patients were included, each with stage IIB cervical cancer, local lesion sizes ≥5 cm, and tumors that had not regressed after 45 Gy/25 F external intensity-modulated radiotherapy. To identify the dosimetric advantage of delivering a local boost to high-risk (HR)-cervix in IC/IS, patients were divided into two groups: IC/IS and IC/IS + HR-cervix. The differences in dosimetric parameters were compared between the two groups. Comparisons were then made between the parameters of the four planning methods: IC (Point A), IC (three dimensional [3D]), IC/IS, and IC/IS + HR-cervix. RESULTS: In patients with IC/IS implants, the relative uterine tandem dwell time was significantly extended in the IC/IS + HR-cervix group, and the V150 and V200 volumes of HR-cervix were increased (all p < 0.001), whereas the D90 and D100 values of the IC/IS + HR-cervix group were lower than those in the IC/IS group. In pairwise comparisons, HR-cervix V150 and V200 values were lowest in the IC/IS group, followed by the IC (3D), IC/IS + HR-cervix, and IC (Point A) groups. All differences were statistically significant (p < 0.05), with the exception of IC/IS vs. IC (3D). CONCLUSIONS: When treating locally advanced cervical cancer (stage IIB, local residual volume ≥5 cm after external radiotherapy), the IC/IS + HR-cervix optimization method can meet the HR clinical target volume D90 dose requirement, normal tissue dose limits, and can escalate doses to local areas of the cervix.


Assuntos
Braquiterapia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias do Colo do Útero/radioterapia , Feminino , Humanos , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Carga Tumoral , Neoplasias do Colo do Útero/patologia
14.
Int J Mol Sci ; 20(22)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31717306

RESUMO

Radiation is a widely used therapeutic method for treating breast cancer. N-dihydrogalactochitosan (GC), a biocompatible immunostimulant, is known to enhance the effects of various treatment modalities in different tumor types. However, whether GC can enhance the radiosensitivity of cancer cells remains to be explored. In this study, triple-negative murine 4T1 breast cancer cells transduced with multi-reporter genes were implanted in immunocompetent Balb/C mice to track, dissect, and identify liver-metastatic 4T1 cells. These cells expressed cancer stem cell (CSC) -related characteristics, including the ability to form spheroids, the expression of the CD44 marker, and the increase of protein stability. We then ex vivo investigated the potential effect of GC on the radiosensitivity of the liver-metastatic 4T1 breast cancer cells and compared the results to those of parental 4T1 cells subjected to the same treatment. The cells were irradiated with increased doses of X-rays with or without GC treatment. Colony formation assays were then performed to determine the survival fractions and radiosensitivity of these cells. We found that GC preferably increased the radiosensitivity of liver-metastatic 4T1 breast cancer cells rather than that of the parental cells. Additionally, the single-cell DNA electrophoresis assay (SCDEA) and γ-H2AX foci assay were performed to assess the level of double-stranded DNA breaks (DSBs). Compared to the parental cells, DNA damage was significantly increased in liver-metastatic 4T1 cells after they were treated with GC plus radiation. Further studies on apoptosis showed that this combination treatment increased the sub-G1 population of cells, but not caspase-3 cleavage, in liver-metastatic breast cancer cells. Taken together, the current data suggest that the synergistic effects of GC and irradiation might be used to enhance the efficacy of radiotherapy in treating metastatic tumors.


Assuntos
Quitosana/farmacologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Neoplasias Mamárias Animais/patologia , Tolerância a Radiação/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Separação Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Rastreamento de Células , Dano ao DNA , Feminino , Histonas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos Endogâmicos BALB C , Imagem Molecular , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/efeitos da radiação , Tolerância a Radiação/efeitos da radiação , Radiação Ionizante , Raios X
15.
J Clin Neurosci ; 70: 198-201, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31492481

RESUMO

microRNAs have been reported to suppress tumor growth, invasion, and metastasis and play roles in neurodegeneration disorders. Moreover, changes in microRNAs are found in the peripheral blood, cerebrospinal fluid (CSF), and brain tissues in patients of central nervous system diseases, including glioma, Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis and depression. Compared with other bodily fluids, CSF is the most accurate at representing the pathological processes of the brain. To understand whether microRNA expression may be dysregulated in the patients of PD, and to further discover potential diagnostic biomarkers and promising therapeutic targets for PD, we used real-time polymerase chain reaction (RT-PCR) to compare CSF microRNAs from 20 PD patients, 13 AD patients and 27 controls with other neurologic disorders such as encephalitis and Guillain-Barre syndrome. Finally, we found that the mean expression level of hsa-miR-626 was significantly reduced in the CSF of patients with PD compared with AD and controls. Our approach potentially identified a biomarker in CSF that upon further investigation, could be used for the detection, diagnosis, and monitoring of PD in combination with other PD biomarkers.


Assuntos
Biomarcadores/líquido cefalorraquidiano , MicroRNAs/líquido cefalorraquidiano , Doença de Parkinson/líquido cefalorraquidiano , Doença de Parkinson/diagnóstico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Cell Cycle ; 18(14): 1619-1634, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31177938

RESUMO

Myocardial ischemia-reperfusion (I/R) injury is caused by endothelial dysfunction and enhanced oxidative stress. The overexpression of JAZF1, a zinc finger protein, has been reported to promote cell proliferation and suppress myogenic differentiation in type 2 diabetes. However, the involvement of JAZF1 in myocardial I/R injury remains to be unclear. The current study aims to investigate the role by which JAZF1 influences cardiac microvascular endothelial cells (CMECs) in a rat model of myocardial I/R injury. A total of 50 rats were established as a myocardial I/R model to isolate CMECs, with alterations in JAZF1 expression. After that, the gain- or loss-function of JAZF1 on the proliferation, apoptosis and tube formation ability of CMECs were evaluated by a series of in vitro experiments. Results indicated that JAZF1 was down-regulated in CMECs of rats with myocardial I/R injury. After treatment with JAZF1, the levels of VEGF, Bcl-2, PDGF and p-Akt/Akt were all increased; however, the expression of Bax, caspase-3, caspase-9, p-Bad/Bad, c-caspase-3/caspase-3, c-caspase-9/caspase-9, and p-FKHR/FKHR exhibited decreased levels; CMEC proliferation and angiogenesis were increased, while cell apoptosis was attenuated. CMECs transfected with JAZF1 shRNA exhibited the contrary tendencies. The key findings of this study suggest that the over-expression of JAZF1 alleviates myocardial I/R injury by enhancing proliferation and angiogenesis of CMECs and in turn inhibiting apoptosis of CMECs via the activation of the Akt signaling pathway.


Assuntos
Proteínas Correpressoras/fisiologia , Proteínas de Ligação a DNA/fisiologia , Células Endoteliais/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Dedos de Zinco/genética , Animais , Apoptose/genética , Caspases/metabolismo , Proliferação de Células/genética , Células Cultivadas , Proteínas Correpressoras/genética , Proteínas de Ligação a DNA/genética , Masculino , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Transdução de Sinais/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteína X Associada a bcl-2/metabolismo
17.
Chem Sci ; 10(7): 2067-2074, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30842864

RESUMO

The grafting density of poly(ethylene glycol) (PEG) on nanoparticle (NP) surfaces is the most important parameter determining the interaction of nanoparticles with serum proteins, the subsequent sequestration of the nanoparticle from the bloodstream by the mononuclear phagocyte system, and the eventual delivery efficiency to tumor tissues. However, the majority of in vivo studies do not characterize or report the grafting density of PEG on nanoparticles due to a lack of feasible characterization methods, making it difficult to evaluate the published studies and reconcile apparent conflicting results. Herein, we develop a facile and non-sacrificial 1H NMR analytical approach for the quantitative characterization of grafting density of thiol-terminated PEG (HS-PEG) on gold NPs (GNPs). A multi-Lorentzian-splitting algorithm is used to distinguish the NMR signal of free PEG from those of the grafted ones, therefore allowing in situ monitoring of the grafting process to study the effects of GNP sizes, PEG molecular weights and NP capping ligands on grafting rates and grafting densities. The main advantage of this method is that it is not limited by the types of terminal functional groups on PEG, surface chemistry of the nanoparticles or their composition. It also provides a set of critical and standard guides for characterization of the PEG grafting density on nanoparticles for in vivo biological and biomedical studies.

19.
J Interferon Cytokine Res ; 36(10): 580-588, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27610743

RESUMO

Studies suggest interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) may be beneficial in obesity-related disorders with inconsistent results. This study was designed to investigate and compare their pathophysiological roles in lipid metabolism with gene knockout approach. Male wild-type (WT), IL-6 knockout (IL-6-/-), and TNF-α knockout (TNF-α-/-) mice were maintained on either a chow diet or a high-fat diet (HFD) for 12 weeks. Indices of lipid metabolism in blood, adipose, and liver were determined. Our data showed that IL-6-/- and TNF-α-/- mice were more pronounced in body weight gains, hypercholesterolemia, fasting and post-load hyperglycemia on a chow diet or a HFD compared with WT mice. In WT mice feeding on a HFD, lipolysis and glyceroneogenesis were enhanced, lipogenesis was inhibited in adipose tissue; lipogenesis was increased in liver tissue. IL-6-/- mice on a chow diet or a HFD showed similar metabolic phenotypes as WT mice on a HFD, since those mice had similar expression profiles of lipid-related genes in adipose tissue and liver. However, TNF-α-/- mice were different. Therefore, IL-6-/- and TNF-α-/- mice showed different hepatic triglyceride infiltration in response to different diets. Our study suggests that complete blockage of IL-6 and TNF-α is unbeneficial in obesity and obesity-related metabolic disorders in mice.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Interleucina-6/deficiência , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/deficiência , Fator de Necrose Tumoral alfa/metabolismo , Animais , Interleucina-6/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator de Necrose Tumoral alfa/genética
20.
Chem Commun (Camb) ; 52(13): 2748-51, 2016 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-26758231

RESUMO

A T-shaped Schiff-base triazatruxene derivative (TATNFF) was designed, synthesized, and explored as a sensitive probe to detect HCl gas by the naked eye. The remarkable color change of TATNFF with turn-on behavior in the presence of a trace amount of HCl gas was obviously observed by the naked eye, which opens up a new strategy to explore a novel set of smart responsive materials for sensing applications.

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