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1.
Brain Imaging Behav ; 2022 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-35080703

RESUMO

Dysfunction of the cingulo-frontal-parietal (CFP) cognitive attention network has been associated with the pathophysiology of chronic low back pain (cLBP). However, the direction of information processing within this network remains largely unknown. We aimed to study the effective connectivity among the CFP regions in 36 cLBP patients and 36 healthy controls by dynamic causal modeling (DCM). Both the resting-state and task-related (Multi-Source Interference Task, MSIT) functional magnetic resonance imaging (fMRI) data were collected and analyzed. The relationship between the effective connectivity of the CFP regions and clinical measures was also examined. Our results suggested that cLBP had significantly altered resting-state effective connectivity of the prefrontal cortex (PFC)-to-mid-cingulate cortex (MCC) (increased) and MCC-to-left superior parietal cortex (LPC) (decreased) pathways as compared with healthy controls. MSIT-related DCM suggested that the interference task could significantly increase the effective connectivity of the right superior parietal cortex (RPC)-to-PFC and RPC-to-MCC pathways in cLBP than that in healthy controls. The control task could significantly decrease the effective connectivity of the MCC-to-LPC and MCC-to-RPC pathways in cLBP than that in healthy controls. The endogenous connectivity of the PFC-to-RPC pathway in cLBP was significantly lower than that in healthy controls. No significant correlations were found between the effective connectivity within CFP networks and pain/depression scores in patients with cLBP. In summary, our findings suggested altered effective connectivity in multiple pathways within the CFP network in both resting-state and performing attention-demanding tasks in patients with cLBP, which extends our understanding of attention dysfunction in patients with cLBP.

2.
eNeuro ; 9(1)2022.
Artigo em Inglês | MEDLINE | ID: mdl-34996774

RESUMO

Spinal cord injury (SCI) is a devastating condition. Splenectomy may play a protective role in the development of SCI. However, little is known about whether the timing of splenectomy affects the outcome after SCI. Investigation into splenectomy after SCI would provide insight into how the timing can be selected following SCI to improve neurologic outcomes. Rats were randomized into a sham group, a nonsplenectomized group (NonSPX), four splenectomized groups with the surgery performed immediately, 6 h, 12 h, and 24 h after SCI (SPX0, SPX6, SPX12, and SPX24, respectively). Rats were subjected to severe contusive SCI at the level of the third thoracic vertebra. At different time points following SCI, Basso, Beattie, and Bresnahan (BBB) score was used to assess the recovery of injury. The animals in each group were randomly selected for tissue collection at days 3, 14, and 28 after surgery. Then, immunohistochemistry of immunologic cells was performed and inflammatory mediators were determined. Our study showed that splenectomy within 6 h after SCI improved BBB scores as compared with splenectomy more than 12 h after SCI, and decrease the immune cell responses to SCI. Protein levels of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were significantly elevated in nonsplenectomized group compared with sham group. No difference was observed in IL-10 at the lesion site between splenectomized and nonsplenectomized groups at 3 d post-SCI. The study demonstrates that splenectomy within 6 h after SCI would lessen the development of SCI and improve outcome.


Assuntos
Traumatismos da Medula Espinal , Medula Espinal , Animais , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/cirurgia , Esplenectomia , Fator de Necrose Tumoral alfa
3.
Aging (Albany NY) ; 14(1): 497-508, 2022 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-35027503

RESUMO

AIM: To explore the function of circular RNA CUL2 (circCUL2) in colorectal cancer progression. METHOD: RT-PCR was carried out to detect the expression of circCUL2 in colorectal cancer tissues and cell lines. Western blot and immunofluorescence were used to determine the level of autophagy. CCK-8, clone formation assay, and EdU staining were used to assess the proliferation ability. Luciferase assay verified the relationship between miR-208a-3p and circCUL2 /PPP6C. The xenograft mouse model was used to confirm the function of circCUL2 in vivo. RESULTS: The expression level of circCUL2 was down-regulated in colorectal cancer tissues and cell lines. Forcing expression of circCUL2 inhibited proliferation ability, induced apoptosis, and autophagy in colorectal cancer cells. Luciferase assay verified that miR-208a-3p could bind with circCUL2/PPP6C. Overexpression of circCUL2 could inhibit cancer progression via targeting the miR-208a-3p/PPP6C signal pathway. CONCLUSION: CircCUL2 participates in progression via the miR-208a-3p/PPP6C axis in colorectal cancer. CircCUL2 would be an underlying target for the diagnosis and therapy of colorectal cancer.


Assuntos
Neoplasias Colorretais/metabolismo , Proteínas Culina/metabolismo , Proteínas do Citoesqueleto/metabolismo , MicroRNAs/metabolismo , Fosfoproteínas Fosfatases/metabolismo , RNA Circular/metabolismo , Fatores de Transcrição/metabolismo , Apoptose/fisiologia , Autofagia/fisiologia , Linhagem Celular Tumoral , Proteínas Culina/genética , Proteínas do Citoesqueleto/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Fosfoproteínas Fosfatases/genética , Fatores de Transcrição/genética
4.
Dalton Trans ; 51(6): 2331-2337, 2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35043136

RESUMO

The direct oxidation of C-H bonds in organic materials into necessary oxygen-containing compounds under mild conditions has attracted increasing attention. A Keggin-type polyoxometalate-based metal-organic complex (MOC), [CuII4CuI(H2trz)4(C2O4)(H2O)4(H3PW11.18CuII0.82O40)]·8H2O (1) (H3trz = 1,2,4-triazole), was designed and synthesized under hydrothermal conditions, and was structurally characterized by single crystal X-ray diffraction, PXRD, IR spectroscopy, TGA, and XPS. Complex 1 is a 3D 4,6,8-connected architecture derived from [Cu5(H2trz)4(C2O4)2(H2O)2]n units and [PW11.18Cu0.82O40]6- anions, which can catalytically oxidize various types of alkylbenzenes. Gas chromatographic analysis showed that complex 1 as a heterogeneous catalyst could effectively catalyze the oxidation of diphenylmethane with 93% conversion and 99% selectivity within 6 h. In addition, the conversion for the catalytic oxidation of ethylbenzene was 96% with 99% selectivity. Compared with some reported catalysts, complex 1 exhibited a better catalytic effect and lower reaction time. Meanwhile, the catalytic oxidation of other benzyl derivatives with complex 1 was also investigated, which indicated that complex 1 possessed excellent catalytic performance.

5.
Inorg Chem ; 61(1): 431-438, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34890197

RESUMO

Novel nonlinear optical (NLO) materials possessing simple chemical compositions and facile syntheses are competitive when considering their practical application. Here, a series of ternary selenides GaxIn2-xSe3 (x = 0.07, 0.38, 0.45, and 0.81) that crystallize in a chiral P65 structure are obtained by melting Ga, In, and Se elements. Their three-dimensional structures are built by (Ga/In)Se4 tetrahedra and InSe5 trigonal bipyramids. The hexagonal modification's phase stability is analyzed by energy calculation, and their optical band gaps are determined to be 1.72-1.99 eV. They exhibit large NLO responses that are 1.41-1.64 times that of the benchmark AgGaS2. The results of density functional theory calculations suggest that introduction of Ga onto the In site in (InSe4)5- units can form a deformed tetrahedron with more distortion in the structure, and the (InSe5)7- units contribute a large amount of birefringence to the structure. This work is the first to investigate the ternary chalcogenides M2Q3 (M = Ga or In; Q = S or Se) as new types of infrared NLO crystals with excellent performances, which will stimulate more interest in those possessing simple compositions and outstanding performances.

6.
Acta Pharmacol Sin ; 43(3): 659-671, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34103688

RESUMO

Tubulointerstitial inflammation plays an important role in the progression of diabetic nephropathy (DN), and tubular epithelial cells (TECs) are crucial promoters of the inflammatory cascade. Exchange protein activated by cAMP (Epac) has been shown to suppress the angiotensin II (Ang-II)-induced release of inflammatory cytokines in tubular cells. However, the role of Epac in TEC-mediated tubulointerstitial inflammation in DN remains unknown. We found that administering the Epac agonist 8-pCPT-2'-O-Me-cAMP (8-O-cAMP) to db/db mice inhibited tubulointerstitial inflammation characterized by macrophage infiltration and increased inflammatory cytokine release and consequently alleviated tubulointerstitial fibrosis in the kidney. Furthermore, 8-O-cAMP administration restored CCAAT/enhancer binding protein ß (C/EBP-ß) expression and further upregulated the expression of Suppressor of cytokine signaling 3 (SOCS3), while inhibiting p-STAT3, MCP-1, IL-6, and TNF-α expression in the kidney cortex in db/db mice. And in vitro study showed that macrophage migration and MCP-1 expression induced by high glucose (HG, 30 mM) were notably reduced by 8-O-cAMP in human renal proximal tubule epithelial (HK-2) cells. In addition, 8-O-cAMP treatment restored C/EBP-ß expression in HK-2 cells and promoted C/EBP-ß translocation to the nucleus, where it transcriptionally upregulated SOCS3 expression, subsequently inhibiting STAT3 phosphorylation. Under HG conditions, siRNA-mediated knockdown of C/EBP-ß or SOCS3 in HK-2 cells partially blocked the inhibitory effect of Epac activation on the release of MCP-1. In contrast, SOCS3 overexpression inhibited HG-induced activation of STAT3 and MCP-1 expression in HK-2 cells. These findings indicate that Epac activation via 8-O-cAMP ameliorates tubulointerstitial inflammation in DN through the C/EBP-ß/SOCS3/STAT3 pathway.


Assuntos
Nefropatias Diabéticas/patologia , Fatores de Troca do Nucleotídeo Guanina/agonistas , Inflamação/patologia , Túbulos Renais/efeitos dos fármacos , Animais , Proteína beta Intensificadora de Ligação a CCAAT/efeitos dos fármacos , AMP Cíclico/análogos & derivados , AMP Cíclico/farmacologia , Citocinas/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Fator de Transcrição STAT3/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteína 3 Supressora da Sinalização de Citocinas/efeitos dos fármacos , Regulação para Cima
7.
Angew Chem Int Ed Engl ; 61(9): e202115871, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-34951094

RESUMO

Infrared nonlinear optical (IR NLO) materials are significant in laser technology for civil and military uses. Here, we report the synthesis, structural chemistry and NLO properties of a halogen-rich chalcohalide Sn7 Br10 S2 . Its noncentrosymmetric (NCS, P63 ) structure can be considered as partially aliovalent anion substitution of SnBr2 (P63 /m) induced centrosymmetric (CS) to NCS structural transformation. The 3D ∞ [Sn(1)6 Sn(2)6 Br6 X6 ]6- (X=Br/S) channel framework consists of Sn(1)BrX2 and Sn(2)X3 trigonal pyramids. It exhibits excellent NLO performance, including a strong phase-matchable NLO response of 1.5 × AgGaS2 and high laser-induced damage threshold of 6.3 × AgGaS2 .Investigation of the structure-NLO performance relationship confirms that the effective arrangement of Sn(1)BrX2 and Sn(2)X3 units predominantly contributes to the large SHG response. These results indicate Sn7 Br10 S2 is a potential IR NLO candidate and provides a new feasible system for promising NLO materials.

8.
JAMA Netw Open ; 4(12): e2138444, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34902036

RESUMO

Importance: The treatment of metastatic nasopharyngeal carcinoma (mNPC) is a major challenge because of drug resistance and the toxic effects of chemotherapy. Objective: To evaluate the survival and toxicity outcomes and safety associated with the use of a modified low-dose fluorouracil protocol compared with standard regimens recommended in current guidelines for treatment of mNPC. Design, Setting, and Participants: This retrospective cohort study was based on data retrieved from electronic medical records from Sun Yat-sen University Cancer Center in China for 1397 patients with mNPC diagnosed from January 1, 2006, to December 31, 2017. Data analyses were conducted from October 1, 2020, to May 1, 2021. Exposures: Patients received chemotherapy, including platinum plus low-dose, long-term fluorouracil (PFLL); cisplatin plus standard dose, short-term fluorouracil (PFSS); cisplatin plus gemcitabine (GP); cisplatin plus taxane (TP); and cisplatin plus taxane plus fluorouracil (TPF). Main Outcomes and Measures: The main outcomes included overall survival (OS); subsequent-line, treatment-free survival (sTFS), defined as the period from metastasis to the date requiring subsequent-line treatment or death; and the survival to toxicity ratio (STR), defined as person-year rate of OS divided by person-year rate of severe hematologic toxic effects. Cox regression models were used to compare the outcomes of patients receiving PFLL vs other regimens, adjusting for baseline characteristics. Results: Of 1397 patients with mNPC included in this study (1152 men; median age, 46 years [range, 18-70 years]) 134 received PFLL, 203 received GP, 330 received PFSS, 366 received TP, and 364 received TPF. A total of 764 patients died (75 in treatment group PFLL; 107 in group GP; 204 in group PFSS; 207 in group TP; and 171 in group TPF), and 979 patients had subsequent-line treatment or died, whichever occurred first (PFLL, 77; GP, 144; PFSS, 262; TP, 269; and TPF, 227). The median follow-up was 46.9 months (IQR, 25.4-82.4 months), and the 5-year OS rate among patients who received PFLL was 25.4% (95% CI, 16.7%-38.8%), which was not significantly different from that among patients who did not receive PFLL (30.2%; 95% CI, 27.1%-33.5%; P = .13) or who received GP (25.1%; 95% CI, 18.1%-35.0%; P = .81), PFSS (23.6%; 95% CI, 18.5%-30.0%; P = .80), or TP (28.1%; 95% CI, 22.8%-34.7%; P = .99) but was lower than that for patients who received TPF (40.4%; 95% CI, 34.7%-47.1%; P = .001). The 5-year sTFS among patients who received PFLL (24.1%; 95% CI, 15.4%-37.6%) was significantly higher than that among patients who did not receive PFLL (18.5%; 95% CI, 16.1%-21.3%; P = .005) or who received GP (14.3%; 95% CI, 9.1%-22.5%; P = .001) but similar to that for patients who received TPF (28.0%; 95% CI, 23.0%-34.0%; P = .74). The STR of PFLL was 0.81, substantially better than that of GP (0.41) and TPF (0.65). Conclusions and Relevance: The results of this cohort study suggest that, compared with the use of standard treatment regimens, administration of PFLL was associated with similar OS but prolonged sTFS. PFLL also had better STR than other regimens, which could indicate less severe toxic effects. Thus, PFLL may be an option for first-line treatment of mNPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Platina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
9.
Nanotechnology ; 33(8)2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34731847

RESUMO

2D van der Waals materials are crystals composed of atomic layers, which have atomic thickness scale layers and rich distinct properties, including ultrafast optical response, surface effects, light-mater interaction, small size effects, quantum effects and macro quantum tunnel effects. With the exploration of saturable absorption characteristic of 2D van der Waals materials, a series of potential applications of 2D van der Waals materials as high threshold, broadband and fast response saturable absorbers (SAs) in ultrafast photonics have been proposed and confirmed. Herein, the photoelectric characteristics, nonlinear characteristic measurement technique of 2D van der Waals materials and the preparation technology of SAs are systematically described. Furthermore, the ultrafast pulsed fiber lasers based on classical 2D van der Waals materials including graphene, transition metal chalcogenides, topological insulators and black phosphorus have been fully summarized and analyzed. On this basis, opportunities and directions in this field, as well as the research results of ultrafast pulsed fiber lasers based on the latest 2D van der Waals materials (such as PbO, FePSe3, graphdiyne, bismuthene, Ag2S and MXene etc), are reviewed and summarized.

11.
BMC Plant Biol ; 21(1): 443, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592922

RESUMO

BACKGROUND: Tiller number is a factor determining panicle number and grain yield in wheat (Triticum aestivum). Auxin plays an important role in the regulation of branch production. PIN-FORMED 1 (PIN1), an auxin efflux carrier, plays a role in the regulation of tiller number in rice (Oryza sativa); however, little is known on the roles of PIN1 in wheat. RESULTS: Nine homologs of TaPIN1 genes were identified in wheat, of which TaPIN1-6 genes showed higher expression in the stem apex and young leaf in wheat, and the TaPIN1-6a protein was localized in the plasma membrane. The down-expression of TaPIN1s increased the tiller number in TaPIN1-RNA interference (TaPIN1-RNAi) transgenic wheat plants, indicating that auxin might mediate the axillary bud production. By contrast, the spikelet number, grain number per panicle, and the 1000-grain weight were decreased in the TaPIN1-RNAi transgenic wheat plants compared with those in the wild type. In summary, a reduction of TaPIN1s expression increased the tiller number and grain yield per plant of wheat. CONCLUSIONS: Phylogenetic analysis and protein structure of nine TaPIN1 proteins were analyzed, and subcellular localization of TaPIN1-6a was located in the plasma membrane. Knock-down expression of TaPIN1 genes increased the tiller number of transgenic wheat lines. Our study suggests that TaPIN1s is required for the regulation of grain yield in wheat.


Assuntos
Regulação para Baixo , Proteínas de Membrana Transportadoras/metabolismo , Caules de Planta/crescimento & desenvolvimento , Sementes/crescimento & desenvolvimento , Triticum/crescimento & desenvolvimento , Triticum/genética , Triticum/metabolismo , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Grão Comestível/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Caules de Planta/genética , Caules de Planta/metabolismo , Sementes/genética , Sementes/metabolismo
12.
Acta Pharmacol Sin ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593973

RESUMO

The multi-generation heredity trait of hypertension in human has been reported, but the molecular mechanisms underlying multi-generational inheritance of hypertension remain obscure. Recent evidence shows that prenatal inflammatory exposure (PIE) results in increased incidence of cardiovascular diseases, including hypertension. In this study we investigated whether and how PIE contributed to multi-generational inheritance of hypertension in rats. PIE was induced in pregnant rats by intraperitoneal injection of LPS or Poly (I:C) either once on gestational day 10.5 (transient stimulation, T) or three times on gestational day 8.5, 10.5, and 12.5 (persistent stimulation, P). Male offspring was chosen to study the paternal inheritance. We showed that PIE, irrespectively induced by LPS or Poly (I:C) stimulation during pregnancy, resulted in multi-generational inheritance of significantly increased blood pressure in rat descendants, and that prenatal LPS exposure led to vascular remodeling and vasoconstrictor dysfunction in both thoracic aorta and superior mesenteric artery of adult F2 offspring. Furthermore, we revealed that PIE resulted in global alteration of DNA methylome in thoracic aorta of F2 offspring. Specifically, PIE led to the DNA hypomethylation of G beta gamma (Gßγ) signaling genes in both the F1 sperm and the F2 thoracic aorta, and activation of PI3K/Akt signaling was implicated in the pathologic changes and dysregulated vascular tone of aortic tissue in F2 LPS-P offspring. Our data demonstrate that PIE reprogrammed DNA methylome of cells from the germline/mature gametes contributes to the development of hypertension in F2 PIE offspring. This study broadens the current knowledge regarding the multi-generation effect of the cumulative early life environmental factors on the development of hypertension.

13.
Orthop Surg ; 13(7): 2145-2152, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34559465

RESUMO

OBJECTIVE: To investigate the effect and mechanism of Glucocorticoids (GCs) induced oxidative stress and apoptosis on necrosis of the femoral head in patients and rats. METHODS: Eight patients with steroid-induced avascular necrosis of the femoral head (SINFH) and eight patients with developmental dysplasia of the hips (DDH) were enrolled in our study. In animal model, twenty male Sprague-Dawley rats were randomly divided into two groups (SINFH group and NS group). The SINFH model group received the methylprednisolone (MPS) injection, while control group was injected with normal saline (NS). MRI was used to confirm SINFH rat model was established successfully. Then, the rats were sacrificed 4 weeks later and femoral head samples were harvested. Histopathological staining was preformed to evaluate osteonecrosis. TUNEL staining was performed with 8-OHdG and DAPI immunofluorescence staining to evaluate oxidative injury and osteocyte apoptosis. Immunohistochemistry staining was used to detect Nox1, Nox2, and Nox4 protein expression. RESULTS: MRI showed signs of typical osteonecrosis of femoral head in SIHFH patients. Histopathological staining showed that the rate of empty lacunae in SINFH patients was significantly higher (56.88% ± 9.72% vs 19.92% ± 4.18%, T = -11.04, P < 0.001) than that in DDH patients. The immunofluorescence staining indicated that the TUNEL-positive cell and 8-OHdG-positve cell in SINFH patients were significantly higher (49.32% ± 12.95% vs 8.00% ± 2.11%, T = -7.04, P = 0.002, 54.6% ± 23.8% vs 9.75% ± 3.31%, T = -4.17, P = 0.003) compared to the DDH patients. The immunohistochemistry staining showed that the protein expression of NOX1, NOX2 and NOX4 in SINFH patients were significantly increased (64.50% ± 7.57% vs 37.58% ± 9.23%, T = -3.88, P = 0.018, 90.84% ± 2.93% vs 49.56% ± 16.47%, T = -5.46, P = 0.001, 85.46% ± 9.3% vs 40.69% ± 6.77%, T = -8.03, P = 0.001) compared to the DDH patients. In animal model, MRI showed signs of edema of femoral head in MPS group, which represents SINFH rat model was established successfully. Histological evaluation showed the rate of empty lacunae in MPS group was significantly higher (25.85% ± 4.68% vs 9.35% ± 1.99%, T = -7.96, P < 0.001) than that in NS group. The immunofluorescence staining indicated that the TUNEL-positive cell and 8-OHdG-positve cell (in MPS group were significantly increased (31.93% ± 1.01% vs 11.73% ± 1.16%, T = -32.26, P < 0.001, 47.59% ± 1.39% vs 22.07% ± 2.45%, T = -22.18, P < 0.001) compared to the NS group. The immunohistochemistry staining showed that the expression of NOX2 in MPS group was significantly increased (76.77% ± 8.34% vs 50.32% ± 10.84%, T = -4.74, P = 0.001) compare with NS group. CONCLUSION: Our findings indicated that GC-induced NOXs expression may be an important source of oxidative stress, which could lead to osteocyte apoptosis in the process of SINFH.


Assuntos
Apoptose/efeitos dos fármacos , Necrose da Cabeça do Fêmur/induzido quimicamente , Glucocorticoides/efeitos adversos , Osteócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Adulto , Animais , Modelos Animais de Doenças , Humanos , Masculino , Ratos , Ratos Sprague-Dawley
14.
J Cancer ; 12(19): 5838-5847, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34475997

RESUMO

Background: We sought to investigate whether the expression of the gene EIF2S2 is related to 18F-FDG PET/CT metabolic parameters in patients with colorectal cancer (CRC). Materials and methods: The expression of EIF2S2 in CRC and its relationship with clinicopathological features were obtained through the ONCOMINE, UALCAN and GEPIA databases. EIF2S2 and GLUT1 expression were examined by immunohistochemistry in 42 CRC patients undergoing preoperative PET-CT examination. Spearman correlation analysis was used to assess the relationship between EIF2S2 and GLUT1 levels and clinical parameters. Correlation analysis between EIF2S2 and Reactome-Glycolysis signatures was performed using GEPIA2. We describe the effect of EIF2S2 knockdown on lactate production and the mRNA levels of glycolysis-related genes in human colon cancer SW480 cells. Results: Immunohistochemistry revealed an upregulation of EIF2S2 protein expression in tumor tissues of colorectal cancer patients, which is consistent with the significant upregulation of EIF2S2 transcript levels in the database. These colorectal cancer patients included 24 cases of colon cancer and 18 cases of rectal cancer, ranging in age from 31 to 78 years. The transcription was significantly related to histological subtypes and TP53 mutations (P <0.05). The value of SUVmax in CRC significantly correlated with the expression of EIF2S2 (rho = 0.462, P <0.01). Although SUVmax and SUVmean was not correlate with the expression of GLUT1 (P <0.05), a significant correlation was observed between the expression of GLUT1 and the volumetric PET parameters, such as MTV and TLG (P < 0.01). GLUT1 expression in CRC was positively correlated with EIF2S2 status (rho = 0.470, P <0.01). In SW480 cells, RNAi-mediated depletion of EIF2S2 inhibited lactic acid production (P <0.05) and SLC2A1, SLC2A3, SLC2A10, HK2, PKM2, LDHA mRNA level (P <0.01). Conclusions: Primary CRC FDG uptake is strongly associated with the overexpression of EIF2S2, and EIF2S2 may promote glycolysis in CRC by mediating GLUT1.

15.
Pediatr Rheumatol Online J ; 19(1): 95, 2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34174887

RESUMO

BACKGROUND: Here, we investigated the predictive efficiency of a newly developed model based on single nucleotide polymorphisms (SNPs) and laboratory data for intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD) in a Chinese population. METHODS: Data relating to children with KD were acquired from a single center between December 2015 and August 2019 and used to screen target SNPs. We then developed a predictive model of IVIG resistance using previous laboratory parameters. We then validated our model using data acquired from children with KD attending a second center between January and December 2019. RESULTS: Analysis showed that rs10056474 GG, rs746994GG, rs76863441GT, rs16944 (CT/TT), and rs1143627 (CT/CC), increased the risk of IVIG-resistance in KD patients (odds ratio, OR > 1). The new predictive model, which combined SNP data with a previous model derived from laboratory data, significantly increased the area under the receiver-operator-characteristic curves (AUC) (0.832, 95% CI: 0.776-0.878 vs 0.793, 95%CI:0.734-0.844, P < 0.05) in the development dataset, and (0.820, 95% CI: 0.730-0.889 vs 0.749, 95% CI: 0.652-0.830, P < 0.05) in the validation dataset. The sensitivity and specificity of the new assay were 65.33% (95% CI: 53.5-76.0%) and 86.67% (95% CI: 80.2-91.7%) in the development dataset and 77.14% (95% CI: 59.9-89.6%) and 86.15% (95% CI: 75.3-93.5%) in the validation dataset. CONCLUSION: Analysis showed that rs10056474 and rs746994 in the SMAD5 gene, rs76863441 in the PLA2G7 gene, and rs16944 or rs1143627 in the interleukin (IL)-1B gene, were associated with IVIG resistant KD in a Chinese population. The new model combined SNPs with laboratory data and improved the predictve efficiency of IVIG-resistant KD.


Assuntos
Resistência a Medicamentos , Imunoglobulinas Intravenosas/uso terapêutico , Modelos Estatísticos , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/genética , Polimorfismo de Nucleotídeo Único , Prognóstico
16.
Zhongguo Zhong Yao Za Zhi ; 46(7): 1696-1700, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33982471

RESUMO

At present, the issues regarding multi-center clinical trials of new drugs of traditional Chinese medicine(TCM) remain: the lack of agreement on the content and scope of the ethical review among the ethics committee members of the center and the participating units results in repeated review, which leads to a time-consuming ethical review process. Moreover, the review capabilities of the ethics committees of various research centers are uneven, which is not necessarily beneficial to the protection of subjects' rights and safety. In view of the existing problems, to improve the efficiency of ethical review of multi-center clinical trials of new drugs of TCM and avoid repeated reviews, the TCM Clinical Evaluation Professional Committee of Chinese Pharmaceutical Association organized experts to formulate the "Consensus on collaborative ethical review of multi-center clinical trials of new drugs of TCM(version 1.0)"(hereinafter referred to as "Consensus"). The "Consensus" is formulated in accordance with the requirements of relevant documents such as but not limited to "the opinions on deepening the reform of the evaluation and approval system to encourage the innovation of pharmaceutical medical devices", "the regulations of ethical review of biomedical research involving human subjects". The "Consensus" covers the scope of application, formulation principles, conditions for the ethics committee of the center, sharing of ethical review resources, scope and procedure of collaborative review, rights and obligations, etc. The aims of the "Consensus" is to preliminarily explore and establish a scientific and operable ethical review procedure. Additionally, on the basis of fully protecting the rights and interests of the subjects, a collaborative ethical review agreement needs to be signed to clarify the ethical review responsibilities of all parties, to avoid repeated review, and to improve the efficiency and quality of ethical review in multi-center clinical trials of new drugs of TCM.


Assuntos
Pesquisa Biomédica , Medicamentos de Ervas Chinesas , Preparações Farmacêuticas , Ensaios Clínicos como Assunto , Consenso , Revisão Ética , Humanos , Medicina Tradicional Chinesa , Estudos Multicêntricos como Assunto
17.
Neuroscience ; 466: 101-108, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34000322

RESUMO

Attractin (ATRN), an autosomal recessive gene that is widely distributed in the brain, is involved in the execution of a variety of brain functions and associated with certain neuropsychiatric disorders. Here, we introduce a novel rat strain harboring a mutation in ATRN that was generated by knocking in ATRN-G505C via the CRISPR/Cas9 system. We assessed the behavioral performance of these mutant ATRN knock-in rats. The G505C mutation was introduced into exon 9, and a synthetic primer was inserted into introns 8-9 for genotyping. The 505th amino acid, a Gly (G) residue, was mutated to a Cys (C) residue, i.e., GGC was mutated to TGC. Behavioral experiments showed that homozygous ATRN rats spent significantly more time searching for the escape platform in the acquisition trial and significantly less time in the target area in the probe trial in the Morris water maze (MWM) test and traveled a significantly shorter distance in the open field test (OFT) than wild-type rats. In addition, Western blot analysis and immunohistochemistry showed that rats with the mutant ATRN gene exhibited significantly reduced expression of brain-derived neurotrophic factor (BDNF). In summary, our results indicate that mutations in the ATRN gene directly lead to learning and memory impairments and slight motor deficits. These findings provide new clues for the mechanism by which mutant ATRN induces neurodegenerative changes.


Assuntos
Encéfalo , Aprendizagem Espacial , Animais , Éxons , Homozigoto , Aprendizagem em Labirinto , Mutação , Ratos
18.
Chem Commun (Camb) ; 57(42): 5175-5178, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-33904563

RESUMO

Obtaining new nonlinear-optical (NLO) materials with strong responses and wide band gaps is a hot topic in the laser field. Here, a series of sulfides AAgGa6S10 (A = K, Rb, Cs) were obtained by a facile solid-state reaction routine. They crystallize in the noncentrosymmetric space group Cc with a new structure-type. Their 3D structures are built by an unprecedented {[AgGa6S10]-}∞ anionic framework, which can be considered as the 1 : 1 intergrowth of the AgGaS2 and Ga2S3 structural slabs. They exhibit moderate responses ∼0.7/0.5/0.6 × AGS and the widest bandgaps among NLO chalcogenides containing independent Ag sites, suggesting that they may have high laser-induced damage thresholds, which is verified by the experimental 1.5/3/4 × AGS. This study not only opens a new system of NLO materials, but also provides a reliable design strategy for future NLO materials.

19.
Inorg Chem ; 60(9): 6641-6648, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33857370

RESUMO

Concurrently achieving suitable second harmonic generation (SHG) effect and high laser-induced damage threshold (LIDT) is challenging for infrared nonlinear optical (NLO) materials. Here, a series of pentanary infrared NLO materials CsMIIIMIVSnSe6 (MIII = Ga, In; MIV = Si, Ge) have been obtained by a three-in-one strategy, viz. three kinds of elements (MIII, MIV, and Sn) in one position, which is first adopted to design NLO materials. Their three-dimensional structures are constructed by the MQ4 (M denotes MIII, MIV, and Sn) tetrahedral units. They exhibit promising hybrid NLO properties, witnessed by their moderate/large SHG effects of 0.52, 0.98, 1.05, and 1.12 × AgGaS2, and high powder LIDT values of 6.9, 4.1, 8.1, and 5.4 × AgGaS2, respectively. These NLO properties are well verified by the DFT calculation results. The three-in-one strategy of designing high-performance infrared NLO materials will stimulate more investigations in this field.

20.
Ann Palliat Med ; 10(7): 8322-8327, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33548988

RESUMO

Left ventricular thrombosis and cerebral infarction caused by recurrent episodes of paroxysmal supraventricular tachycardia (PSVT) are uncommon in infants. We present the case of a 23-month-old girl whose echocardiography revealed a left ventricular thrombus, which resolved after sinus rhythm was restored. The girl had experienced repeated systemic convulsions and high muscular tension of the left limb accompanied by movement disorder. Soon afterward, cranial magnetic resonance imaging (MRI) revealed scattered lacunar cerebral infarctions in the right lateral ventricle. The symptoms, signs, and laboratory examination satisfied the diagnosis of left ventricular thrombosis and cerebral infarction caused by recurrent episodes of PSVT. The girl was given antiarrhythmic drugs, including propranolol, esmolol, and amiodarone, intracranial pressure decreasing treatment (mannitol), heart and brain cell nutritional therapy, anticoagulant therapy, and her condition gradually improved. This case report highlights the importance of pediatric PSVT patients' clinical management and that more emphasis should be placed on early recognition and prevention of severe complications. Pediatricians should be trained early recognition of the nonspecific clinical manifestations of PSVT, make effectively and quickly diagnosis by electrocardiogram, evaluation of cardiac function and thrombosis by echocardiography, and termination PSVT as rapidly as possible. Thromboprophylaxis therapy might be considered for recurrent episodes of PSVT.


Assuntos
Taquicardia Supraventricular , Taquicardia Ventricular , Trombose , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Infarto Cerebral/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Taquicardia Supraventricular/diagnóstico
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