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1.
J Colloid Interface Sci ; 607(Pt 2): 1919-1927, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34695740

RESUMO

Schottky-contacted nanosensors have attracted extensive attention due to their high sensitivity and fast response time. In this article, we proved that the construction of Schottky contact by Pt nanoparticles (NPs) decoration can effectively improve the performance of V2O5 nanobelts photodetectors. After modified by Pt NPs, the photocurrent of V2O5 nanobelts is increased by more than two orders of magnitude, and the photoresponse speed is improved by at least three orders of magnitude. Detailed studies have shown that the performance enhancement is attributed to the formation of the Schottky contact at the electrode-semiconductor interface due to the decrease of surface gas adsorption and the increase of V2O5 work function after Pt NPs modification. The strong built-in field in the Schottky barrier region will quickly separate photogenerated carriers, thereby reducing the electron-hole recombination rate, resulting in the fast response time and an increase in the free carrier density. Moreover, it is found that this enhancement effect can be regulated by controlling the pressure to modulating the Schottky barrier height at the interface. Overall, the Pt NPs-modified V2O5 nanobelts photodetector exhibits a broad response spectrum (visible to near infrared), fast rise/fall response time (less than 6.12/6.15 ms), high responsivity (5.6 A/W), and high specific detectivity (6.9 × 108 Jones). This study demonstrates the feasibility of building a Schottky barrier to enhance the photodetection performance, which provides a general and effective strategy towards the construction and its practical application of supersensitive and fast-response nanosensors.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 265: 120375, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536888

RESUMO

Single crystal of tin selenide (SnSe) was studied by micro-Raman spectroscopy under atmosphere conditions. The effect of varying the incident laser power on the sample up to 2 mW was analyzed. The Raman spectra showed that the number of all vibrational modes have not decreased or increased, but all peaks red-shifted and softened obviously as the laser power increased to the threshold value. The temperature-dependent micro-Raman study of the single crystal was carried out for illustrating thermal effect due to the high incident laser power. A new SnSe2 phase appeared at high temperature without vacuum and become the dominant phase at the surface of the crystal gradually because of oxidation. Detecting few amounts of SnSe2 crystals on the surface of single crystal shows the high sensitivity of Raman spectroscopy. High resolution transmission electron microscopy (HRTEM) was also used to confirm that the newly generated SnSe2 phase is precipitated by SnSe under high temperature oxidation conditions. To study the Raman spectra of low thermal conductivity materials under high temperature and non-vacuum conditions, lower incident laser power should be used to avoid the influence of additional thermal effects.

3.
Sci Total Environ ; 806(Pt 3): 151228, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34715218

RESUMO

Environmental hypoxic hazard has increasingly become a global public health issue, with impelling evidences supporting the relation between hypoxia and cognitive disorders. As a potent stressor, hypoxia causes mitochondrial dysfunction with insufficient energy production, thus the formation of brain memory disorder. Yet, the underlying molecular mechanism/s against hypoxia induced injury have yet to be identified. Here, we report that cold inducible RNA binding protein (Cirbp) attenuates hypoxia induced insufficient energy production and oxidative stress. Further analyses show that Cirbp sustains protein levels of respiratory chain complexes II (SDHB) and IV (MT-CO1), and directly binds the 3'UTR of Atp5g3 to control mitochondrial homeostasis and ATP biogenesis upon hypoxic stress. Altogether, our data establish Cirbp as a critical protective factor against hypoxic health hazard and provide novel insights into its latent regulation network.

4.
Food Chem ; 371: 131198, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34600370

RESUMO

A method was developed for the simultaneous determination of four nereistoxin-related pesticides, viz. cartap, thiocyclam, thiosultap-monosodium, and thiosultap-disodium, in 20 plant foods. The samples were extracted using a hydrochloric acid solution containing cysteine hydrochloride, derivatized to nereistoxin under alkaline conditions, and analyzed by gas chromatography with electron capture detector. The average recoveries of the method were 72-108%, with relative standard deviations (RSDs) of 0.3-14.7% (n = 1200, p < 0.05). The intermediate precision and reproducibility experiments using established methods were also carried out. All the results passed the Cochrane and Grubbs tests (n = 2400, p < 0.05). The RSDs of intermediate precision and RSDs of reproducibility among laboratories were in the ranges 1.7-10.9% and 2.4-15.3% (n = 2400, p < 0.05), respectively, indicating that the accuracy and precision of the method are satisfactory. This method can be used to detect nereistoxin-related pesticides in plant foods.


Assuntos
Praguicidas , Tiocarbamatos , Compostos Heterocíclicos com 1 Anel , Reprodutibilidade dos Testes
5.
Gene ; 809: 146038, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34688819

RESUMO

Nitrate transporter 2 (NRT2) proteins play an important role in nitrate uptake and utilization in plants. The NRT2 family has been identified and functionally characterized in many plants. However, no systematic identification of NRT2 family members has been reported in cassava (Manihot esculenta Crantz). In this study, six MeNRT2 genes were identified from cassava genome and named as MeNRT2.1-2.6 according to their chromosomal locations. Phylogenetic tree showed that NRT2 proteins were divided into four main subgroups, which was further supported by their gene structure and conserved motifs. All six MeNRT2 genes are randomly distributed on 4 chromosomes (LG8, LG11, LG13, and LG17), two tandem duplicated genes (MeNRT2.3/MeNRT2.4) and a pair of segmental duplicated gene (MeNRT2.1/MeNRT2.2) was detected. Subsequently, expression profiles of MeNRT2 genes in eight different tissues and in response to nitrate deficient treatment were analyzed. The results showed that the MeNRT2 genes had differential expression patterns. All of MeNRT2 genes induced by nitrate deficiency, of them the MeNRT2.2 had the highest expression level after treatment. Arabidopis transformed with MeNRT2.2 gene showed higher fresh weight than wild type plants in response to N starvation, suggesting that MeNRT2.2 play important role in adapting to low nitrogen. Taken together, our results provide the reference for further analyses of the molecular functions of the MeNRT2 gene family, but also some candidate genes for developing nitrogen efficient crops.

6.
Sci Total Environ ; 806(Pt 2): 150634, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34597565

RESUMO

Numerous epidemiological studies have investigated the lipid interference effects of legacy PFASs, however, no studies on PFAS alternatives and blood lipids have been published. In this study, we explored the association between Cl-PFESAs, a typical PFASs alternative in China, and blood lipid profiles in 1336 Guangzhou community residents using linear and non-linear regression models. The results showed a deleterious effect of Cl-PFESAs and blood lipids: adjusted estimates (ß) for TC, TG, LDL-C and HDL-C per natural log unit increase of 6:2 Cl-PFESA were 0.029 (95% CI: 0.020, 0.038), 0.075 (95% CI: 0.049, 0.101), 0.035 (95% CI: 0.021, 0.049) and -0.071 (95% CI: -0.084, -0.058), respectively. The association between Cl-PFESAs and dyslipidemia was also positively significant (P < 0.05). Furthermore, a non-linear relationship was observed in Cl-PFESAs and serum lipid levels using a restricted cubic splines (RCS) model. In summary, our research suggested a negative impact of Cl-PFESAs on blood lipid patterns and a possible non-linear association.

7.
Mol Med Rep ; 25(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34841440

RESUMO

Numerous studies have demonstrated that long non­coding RNAs (lncRNAs) serve an important regulatory role in ischemic injury of cardiomyocytes. lncRNA small nucleolar RNA host gene 1 (SNHG1) could effectively protect cardiomyocytes against various injuries. However, the role of SNHG1 in ischemic cardiomyocyte injury is unclear. It was hypothesized that SNHG1 may have a protective effect on cardiomyocyte injury induced by hypoxia/reoxygenation (H/R) by sponging microRNA (miRNA/miR). The purpose of the present study was to explore the role and molecular mechanism of SNHG1 in ischemic cardiomyocyte injury. A H9c2 cardiomyocyte H/R model was established. The expression levels of SNHG1 in cardiomyocytes treated with H/R were detected using reverse transcription­quantitative PCR. A luciferase reporter assay was used to analyze the associations among SNHG1, miR­16­5p and GATA binding protein 4 (GATA4). Chromatin immunoprecipitation experiments were performed to analyze the interaction between SNHG1 and GATA4. Cell Counting Kit­8, enzyme­linked immunosorbent assay, terminal deoxynucleotidyl­transferase­mediated dUTP nick end labeling and western blotting experiments were used to detect cell activity, lactate dehydrogenase release, apoptosis and apoptosis­related proteins (Bcl­2, Bax, Cleaved caspase­3 and Cleaved caspase­9), respectively. The expression levels of SNHG1 were downregulated in cardiomyocytes treated with H/R. Overexpression of SNHG1 had a protective effect on cardiomyocyte injury induced by H/R. In addition, SNHG1 could regulate the expression levels of GATA4 via sponging of miR­16­5p. Further experiments revealed that GATA4 could bind to the promoter region of SNHG1 and subsequently regulated the expression levels of SNHG1, indicating the important role of the positive feedback loop of SNHG1/miR­16­5p/GATA4 in cardiomyocyte ischemic injury. To conclude, the present study revealed the protective effect of the SNHG1/miR­16­5p/GATA4 positive feedback loop on cardiomyocyte injury induced by H/R and provided a potential therapeutic target for ischemic cardiomyocyte injury.

8.
Cancer Lett ; 525: 84-96, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-34740608

RESUMO

Wnt/ß-catenin signaling is a highly conserved pathway that regulates cell proliferation, differentiation, apoptosis, stem cell self-renewal, tissue homeostasis, and wound healing. Dysregulation of the Wnt pathway is intricately involved in almost all stages of tumorigenesis in various cancers. Through direct and/or indirect effects on effector T cells, T-regulatory cells, T-helper cells, dendritic cells, and other cytokine-expressing immune cells, abnormal activation of Wnt/ß-catenin signaling benefits immune exclusion and hinders T-cell-mediated antitumor immune responses. Activation of Wnt signaling results in increased resistance to immunotherapies. In this review, we summarize the process by which Wnt signaling affects cancer and immune surveillance, and the potential for targeting the Wnt-signaling pathway via cancer immunotherapy.

9.
Microbiol Spectr ; : e0040921, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851179

RESUMO

We designed this study to determine the trend of moxifloxacin resistance among multidrug-resistant tuberculosis (MDR-TB) patients from 2007 to 2013 in China to inform the composition of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment regimens. We assessed moxifloxacin resistance among MDR-TB isolates collected in national drug resistance surveys in 2007 and 2013 that included 3,634 smear-positive and 7,206 culture-positive pulmonary tuberculosis patients, respectively. Moxifloxacin susceptibility was examined by a Mycobacterium growth indicator tube (MGIT) 960 for the 2007 isolates, and by the minimum inhibitory concentration (MIC) method for the 2013 isolates, at both breakpoints 0.5 and 2.0 µg/mL. Risk factors were explored through multivariable log-binominal regression analysis. Mutations in gyrA and gyrB for part of the isolates were also studied through sequencing. Of 401 MDR strains isolated in 2007, moxifiloxacin resistance could be determined for 319 (79.6%): 41 (12.9%) and 10 (3.1%) were resistant at 0.5 and 2.0 µg/mL, respectively. Of 365 MDR strains isolated in 2013, 338 (92.6%) could be analyzed: 140 (41.4%) and 79 (23.4%) were resistant at 0.5 and 2.0 µg/mL. For patients in 2007, no characteristics were significantly associated with moxifloxacin resistance. For patients in 2013, patients aged ≥60 years (adjusted prevalence ratio [aPR], 1.46; 95% confidence interval [CI], 1.10 to 1.93) were more likely to have resistance at 0.5 µg/mL, whereas those residing in eastern China compared to those in central China had an increased risk of resistance at both 0.5 (aPR, 1.85; 95% CI, 1.38 to 2.48) and 2.0 µg/mL (aPR, 2.14; 95% CI, 1.35 to 3.40). Sequencing results were obtained for 245 and 266 MDR-TB isolates in 2007 and 2013, respectively. In total, 34 of 38 (89.5%) and 89 of 104 (85.6%) of 2007 and 2013 moxifloxacin-resistant (0.5 µg/mL) MDR-TB strains had mutations in the gyrA and gyrB gene, respectively. Asp94Gly was the most common mutation among 2007 (11 of 38, 28.9%) and 2013 isolates (24 of 104, 23.1%) and conferred high-level moxifloxacin resistance. Moxifloxacin resistance among MDR-TB patients in China increased from modest to high from 2007 to 2013. Moxifloxacin should be used carefully as a potentially effective drug for composing MDR/RR-TB regimens especially for elderly patients in China. Individual susceptibility testing especially rapid molecular-based assays should be conducted to confirm the susceptibility to moxifloxacin. IMPORTANCE China is one of the high-burden countries for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). Moxifloxacin is one of the critical antituberculosis drugs for MDR/RR-TB treatment. Susceptibility to moxifloxacin is therefore very important to compose effective regimens and to provide protection against development of resistance of companion drugs such as bedaquiline and linezolid. There are, however, no nationally representative data on moxifloxacin resistance among MDR/RR-TB cases in China. Therefore, we assessed the resistance prevalence for moxifloxacin among MDR-TB strains isolated in national drug resistance surveys in 2007 and 2013 that covered 72 sites around the country. We demonstrate that the prevalence of moxifloxacin resistance in MDR-TB isolates increased from modest to high, which should prompt the national tuberculosis program to use moxifloxacin cautiously in second-line regimens to treat MDR/RR-TB unless susceptibility can be laboratory-confirmed.

10.
Am J Cancer Res ; 11(10): 4844-4865, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765296

RESUMO

Non-small cell lung cancer (NSCLC) is one type of the most common cancers, which results in the major death worldwide. This study focuses on the understanding of the molecular mechanism of lncRNA NR2F2-AS1 and its regulation on epithelial-mesenchymal transition (EMT) in the development of NSCLC. Expressions of lncRNA NR2F2-AS1, miR-545-5p, c-Met, biliverdin reductase (BVR), ATF-2 and EMT-related markers in NSCLC tissues and cells were measured by western blotting and RT-qPCR assays. The impact of lncRNA NR2F2-AS1 and miR-545-5p on the cell proliferation, migration, invasion and EMT were analyzed by CCK-8, colony formation, wound healing and transwell assays. The interactions among lncRNA NR2F2-AS1, miR-545-5p and c-Met predicted by bioinformatic analysis were evaluated through dual luciferase reporter assay and fluorescence in situ hybridization (FISH). After generating tumor xenografts, immunohistochemistry was utilized to measure the expression of Ki-67 and EMT-related proteins in vivo. Our results showed that lncRNA NR2F2-AS1, c-Met, BVR and ATF-2 were overexpressed while miR-545-5p was silenced in NSCLC tissues and cells. Silencing of lncRNA NR2F2-AS1 or upregulating miR-545-5p significantly inhibited the cell proliferation, migration, invasion and EMT process. The EMT process could be inhibited by suppressing c-Met/BVR/ATF-2 axis. The tumor xenograft experiments demonstrated that the tumor growth and EMT process were significantly inhibited by silencing lncRNA NR2F2-AS1 or overexpression of miR-545-5p in vivo. LncRNA NR2F2-AS1 promoted the NSCLC development through suppressing miR-545-5p to activate EMT process through c-Met/BVR/ATF-2 axis. Our study indicated that lncRNA NR2F2-AS1 and miR-545-5p could be used as potential therapeutic targets to improve NSCLC treatment.

11.
Chin Med ; 16(1): 116, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34758851

RESUMO

BACKGROUND: Arsenic (As3+) is a carcinogen with considerable environmental and occupational relevancy. Its mechanism of action and methods of prevention remain to be investigated. Previous studies have demonstrated that ROS is responsible for As3+-induced cell transformation, which is considered as the first stage of As3+ carcinogenesis. The NF-E2 p45-related factor-2 (Nrf2) signaling pathway regulates the cellular antioxidant response, and activation of Nrf2 has recently been shown to limit oxidative damage following exposure to As3+ METHODS AND RESULTS: In this study, molecular docking was used to virtually screen natural antioxidant chemical databases and identify molecules that interact with the ligand-binding site of Keap1 (PDB code 4L7B). The cell-based assays and molecular docking findings revealed that curcumin has the best inhibitory activity against Keap1-4L7B. Co-immunoprecipitation (Co-IP) results indicated that curcumin is a potent Keap1 Kelch domain-dependent Nrf2 activator that stabilizes Nrf2 by hindering its ubiquitination. The increased activation of Nrf2 and its target antioxidant genes by curcumin could significantly decrease As3+-generated ROS. Moreover, curcumin induced autophagy in As3+-treated BEAS-2B via inducing autophagy by the formation of a p62/LC-3 complex and increasing autophagic flux by promoting transcription factor EB (TFEB) and lysosome-associated membrane protein 1 (LAMP1) expression. Knockdown of Nrf2 abolished curcumin-induced autophagy and downregulated ROS. Further studies showed that inhibition of autophagosome and lysosome fusion with bafilomycin a1 (BafA1) could block curcumin and prevented As3+-induced cell transformation. These results demonstrated that curcumin prevents As3+-induced cell transformation by inducing autophagy via the activation of the Nrf2 signaling pathway in BEAS-2B cells. However, overexpression of Keap-1 showed a constitutively high level of Nrf2 in As3+-transformed BEAS-2B cells (AsT) is Keap1-independent regulation. Overexpression of Nrf2 in AsT demonstrated that curcumin increased ROS levels and induced cell apoptosis via the downregulation of Nrf2. Further studies showed that curcumin decreased the Nrf2 level in AsT by activating GSK-3ß to inhibit the activation of PI3K/AKT. Co-IP assay results showed that curcumin promoted the interaction of Nrf2 with the GSK-3ß/ß-TrCP axis and ubiquitin. Moreover, the inhibition of GSK-3ß reversed Nrf2 expression in curcumin-treated AsT, indicating that the decrease in Nrf2 is due to activation of the GSK-3ß/ß-TrCP ubiquitination pathway. Furthermore, in vitro and in vivo results showed that curcumin induced cell apoptosis, and had anti-angiogenesis and anti-tumorigenesis effects as a result of activating the GSK-3ß/ß-TrCP ubiquitination pathway and subsequent decrease in Nrf2. CONCLUSIONS: Taken together, in the first stage, curcumin activated Nrf2, decreased ROS, and induced autophagy in normal cells to prevent As3+-induced cell transformation. In the second stage, curcumin promoted ROS and apoptosis and inhibited angiogenesis via inhibition of constitutive expression of Nrf2 in AsT to prevent tumorigenesis. Our results suggest that antioxidant natural compounds such as curcumin can be evaluated as potential candidates for complementary therapies in the treatment of As3+-induced carcinogenesis.

12.
ACS Omega ; 6(44): 29692-29702, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34778641

RESUMO

Inhibiting the penetration of water molecules and aggressive ions is of considerable significance in improving the durability of reinforced concrete structures. In this work, molecular dynamics(MD) is employed to design a high-efficiency organic fluid transport inhibitor. MD results indicate that there is mutual complementation between the hydrophilic and hydrophobic functional groups in the chemical structure of this polymer. One end with the carboxyl groups can stably adsorb on the surface of the cementitious matrix due to the strong attraction from calcium ions. Simultaneously, the rest of the hydrophobic part of the polymer can stand up to maximize the repelling effect on the penetration of fluids. Furthermore, for high cost-effectiveness performance, the minimum number and the optimum position of the carboxyl groups of one polymer inhibitor have been determined. As the molecular structure contains two hydrophilic groups, only if located at the same end, the polymer chain can display the most preferable adsorption morphology.

13.
JCI Insight ; 6(21)2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34747367

RESUMO

COVID-19 is caused by SARS-CoV-2 (SC2) and is more prevalent and severe in elderly and patients with comorbid diseases (CM). Because chitinase 3-like-1 (CHI3L1) is induced during aging and CM, the relationships between CHI3L1 and SC2 were investigated. Here, we demonstrate that CHI3L1 is a potent stimulator of the SC2 receptor angiotensin converting enzyme 2 (ACE2) and viral spike protein priming proteases (SPP), that ACE2 and SPP are induced during aging, and that anti-CHI3L1, kasugamycin, and inhibitors of phosphorylation abrogate these ACE2- and SPP-inductive events. Human studies also demonstrate that the levels of circulating CHI3L1 are increased in the elderly and patients with CM, where they correlate with COVID-19 severity. These studies demonstrate that CHI3L1 is a potent stimulator of ACE2 and SPP, that this induction is a major mechanism contributing to the effects of aging during SC2 infection, and that CHI3L1 co-opts the CHI3L1 axis to augment SC2 infection. CHI3L1 plays a critical role in the pathogenesis of and is an attractive therapeutic target in COVID-19.


Assuntos
Envelhecimento , COVID-19/metabolismo , Proteína 1 Semelhante à Quitinase-3/metabolismo , Envelhecimento/efeitos dos fármacos , Aminoglicosídeos/farmacologia , Aminoglicosídeos/uso terapêutico , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/tratamento farmacológico , Linhagem Celular Tumoral , Proteína 1 Semelhante à Quitinase-3/antagonistas & inibidores , Células HEK293 , Humanos , SARS-CoV-2/fisiologia
14.
Front Pharmacol ; 12: 724306, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790117

RESUMO

Colorectal cancer (CRC) patients are still lacking viable treatments. Chimeric antigen receptor (CAR) T cells have shown promise in hematologic malignancies, but their efficacy in solid tumors has been limited due to the immunosuppressive tumor microenvironment. We found that cancer antigen- EpCAM expression increased in the metastatic stage compared with the primary stage in cancers and the activation of Wnt and TGFß pathways was positively correlated with EpCAM expression in multiple cancers, including colorectal cancer. We constructed CAR T cells targeting EpCAM that successfully showed selective cytotoxicity in highly EpCAM-expressing cancer cell lines. The combination of EpCAM CAR-T with the Wnt inhibitor-hsBCL9CT-24 displayed synergetic effect against EpCAM-positive colon cells in vitro and also in vivo. A mechanistic study showed that hsBCL9CT-24 treatment could modulate the tumor environment and improve infiltration of T cells, while possibly promoting the effector T cells at the early stages and postponing the exhaustion of CAR T cells at advanced stages. Overall, these results demonstrated that the combination of EpCAM CAR T-cell therapy with the Wnt inhibitor can overcome the limitations of CAR T cells in treating solid tumors.

15.
Front Pharmacol ; 12: 766909, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790130

RESUMO

The inflammatory factor IL6 secreted by bone marrow mesenchymal stem cells (BMSCs) in the tumor microenvironment (TME) facilitates the survival and therapeutic resistance of neuroblastoma (NB). Here, we found that IL6 expression in primary tumor tissues or bone marrow (BM) metastases was closely associated with the disease risk and prognosis of NB patients. IL6 secretion from immortalized BMSC (iBMSC) was directly regulated by NB cells and is involved in promoting the proliferation and metastasis of NB cells. Beta-Lapachone (ARQ-501, LPC), an ortho-naphthoquinone natural product, significantly prevented the iBMSC-induced malignant transformation effect on NB cells through suppressing the expression and secretion of IL6 from iBMSC in vitro and in vivo. Mechanistically, LPC disrupted the crosstalk between NB cells and iBMSC in an NQO1-dependent manner through blocking the Gal-3/Gal-3BP/IL6 axis. Our results reveal the effect of iBMSC-derived IL6 on TME-induced malignant transformation of NB cells, and provide theoretical basis for the clinical application of LPC as a potential IL6 inhibitor in high-risk refractory NB patients.

16.
Ann Transl Med ; 9(20): 1519, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790725

RESUMO

Background: Sepsis is a systemic disease characterized by extensive inflammatory responses and impaired organ function, which are characteristics that make it easily missed and complex to treat. A large number of laboratory and clinical studies on the diagnosis and treatment of sepsis have been continuously carried out, confirming the importance of mitochondrial function during the development of sepsis. STEAP4 is an important metalloreductase in mitochondria, which is involved in the biogenesis and respiratory chain of mitochondria. The role of STEAP4 in inflammation remains controversial. Research in this field may contribute to the development of new diagnostic and treatment options for sepsis. Methods: The expression of STEAP4 was measured in the peripheral blood of patients with severe sepsis and compared with healthy controls. Cell and mouse inflammatory models were established to detect the expression of STEAP4 and other inflammatory cytokines. Results: (I) The expression of STEAP4 in the peripheral blood of patients with severe sepsis is higher than that of healthy volunteers (P<0.01), which is related to the SOFA score and transaminase. (II) STEAP4 has a certain predictive effect on the outcome of patients [area under curve (AUC) =0.696, P<0.05, 95% CI: 0.528 to 0.833]. (III) Inflammation led to increased expression of STEAP4 gene in RAW264.7 cells and mouse liver tissue. Conclusions: The expression of STEAP4 is elevated in the early stage of sepsis and the degree of its elevation can be used to predict the clinical outcome of sepsis patients.

17.
J Vasc Surg ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34793925

RESUMO

OBJECTIVES: We conducted a systemic review and meta-analysis to compare the association of prophylactic cerebrospinal fluid drainage (CSFD) versus non-CSFD in preventing spinal cord ischemia following thoracic endovascular aortic repair (TEVAR) for aneurysm and dissection. METHODS: MEDLINE, Embase, and Cochrane databases were systematically searched to identify all relevant studies published prior to April 1, 2020. A systematic review and meta-analysis were performed. We assessed the association between CSFD strategies including routine CSFD versus selective CSFD or non-CSFD and SCI rates following TEVAR in patients with aortic dissection (AD), solitary thoracic aortic aneurysm (TAA) or thoracoabdominal aortic aneurysm (TAAA). Subgroup analyses were conducted to assess the association between different aortic pathologies including AD and thoracic aneurysms and SCI rates following TEVAR with or without prophylactic CSFD. Data were presented using a pooled event rate (ER) with a 95% confidence interval (CI). RESULTS: Thirty-four studies consisting of 3561 patients (2671 with TAA/TAAA and 890 with type B aortic dissection) were included in this analysis. Data were presented using a pooled event rate (ER) with a 95% CI. The overall SCI rate in patients undergoing TEVAR with prophylactic CSFD for aortic dissection (ER, 1.80%; 95% CI, 0.88%-2.72%) was significantly lower than that for aortic aneurysm (ER, 5.73%; 95% CI, 4.20%-7.27%, P values < 0.0001). The SCI rate following TEVAR with prophylactic CSFD was not significantly different from that without CSFD for aortic dissection (P=0.51). There was no association found between the rates of SCI following TEVAR with routine prophylactic CSFD versus with selective prophylactic CSFD for aortic aneurysm (P values = 0.76) and aortic dissection (P values = 0.70), respectively. The SCI rate following TEVAR without CSFD for aortic aneurysm, including isolated TAA and TAAA, (ER, 3.49%; 95% CI, 0.23%-6.76%) was not significantly different from that for aortic dissection (ER, 3.20%; 95% CI, 0.00%-7.20%, P values = 0.91). In patients with TAAA the rate of SCI following TEVAR with routine prophylactic CSFD was significantly lower than that with selective prophylactic CSFD (P values = 0.04). CONCLUSIONS: Our systematic review and meta-analysis showed that spinal cord ischemia occurs more commonly following TEVAR for aortic aneurysm than for aortic dissection. Routine prophylactic CSFD, compared with selective CSFD, is associated with lower rate of postoperative SCI following TEVAR for TAAA. No significant association between the rates of SCI and routine prophylactic CSFD was observed in patients undergoing TEVAR for isolated TAA or AD.

18.
Biomaterials ; : 121244, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34794826

RESUMO

Functional recovery following peripheral nerve injury is limited by progressive atrophy of denervated muscle and Schwann cells (SCs) that occurs during the long regenerative period prior to end-organ reinnervation. Insulin-like growth factor 1 (IGF-1) is a potent mitogen with well-described trophic and anti-apoptotic effects on neurons, myocytes, and SCs. Achieving sustained, targeted delivery of small protein therapeutics remains a challenge. We hypothesized that a novel nanoparticle (NP) delivery system can provide controlled release of bioactive IGF-1 targeted to denervated muscle and nerve tissue to achieve improved motor recovery through amelioration of denervation-induced muscle atrophy and SC senescence and enhanced axonal regeneration. Biodegradable NPs with encapsulated IGF-1/dextran sulfate polyelectrolyte complexes were formulated using a flash nanoprecipitation method to preserve IGF-1 bioactivity and maximize encapsulation efficiencies. Under optimized conditions, uniform PEG-b-PCL NPs were generated with an encapsulation efficiency of 88.4%, loading level of 14.2%, and a near-zero-order release of bioactive IGF-1 for more than 20 days in vitro. The effects of locally delivered IGF-1 NPs on denervated muscle and SCs were assessed in a rat median nerve transection-without- repair model. The effects of IGF-1 NPs on axonal regeneration, muscle atrophy, reinnervation, and recovery of motor function were assessed in a model in which chronic denervation is induced prior to nerve repair. IGF-1 NP treatment resulted in significantly greater recovery of forepaw grip strength, decreased denervation-induced muscle atrophy, decreased SC senescence, and improved neuromuscular reinnervation.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34791251

RESUMO

Growth differentiation factor 11 (GDF11), also known as bone morphogenetic protein 11 (BMP11), has been shown to have rejuvenation and anti-aging properties, but little information is available regarding the role of GDF11 in reproductive system to date. In this study, we first confirmed the bioavailability of recombinant GDF11 (rGDF11) by oral delivery in mice. We also showed that dietary intake of rGDF11 had little influence on body and gonadal (ovary/testis) weights of recipient mice, indicating their general condition and physiology were not affected. Based on these findings, we started to test the function of rGDF11 in ovary and testis of mice and to explore the underlying mechanisms. It was found that to some extent, rGDF11 could attenuate the senescence of ovarian and testicular cells, and contribute to the recovery of ovarian and testicular endocrine functions. Moreover, rGDF11 could rescue the diminished ovarian reserve in female mice and enhance the activities of marker enzymes of testicular function (SDH and G6PD) in male mice, suggesting a potential improvement of fertility. Notably, rGDF11 markedly promoted the activities of antioxidant enzymes in the ovary and testis, and remarkably reduced the levels of lipid peroxidation, protein oxidation and ROS in the ovary and testis. Collectively, these results suggest that GDF11 can protect ovarian and testicular functions of aged mice via slowing down the generation of ROS through enhancing activities of antioxidant enzymes.

20.
CNS Neurosci Ther ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34792857

RESUMO

OBJECTIVE: Postoperative delirium (POD) is a common postoperative complication that is relevant to poor outcomes. Therefore, it is critical to find effective methods to identify patients with high risk of POD rapidly. Creating a fully automated score based on an automated machine-learning algorithm may be a method to predict the incidence of POD quickly. MATERIALS AND METHODS: This is the secondary analysis of an observational study, including 531 surgical patients who underwent general anesthesia. The least absolute shrinkage and selection operator (LASSO) was used to screen essential features associated with POD. Finally, eight features (age, intraoperative blood loss, anesthesia duration, extubation time, intensive care unit [ICU] admission, mini-mental state examination score [MMSE], Charlson comorbidity index [CCI], postoperative neutrophil-to-lymphocyte ratio [NLR]) were used to established models. Four models, logistic regression, random forest, extreme gradient boosted trees, and support vector machines, were built in a training set (70% of participants) and evaluated in the remaining testing sample (30% of participants). Multivariate logistic regression analysis was used to explore independent risk factors for POD further. RESULTS: Model 1 (logistic regression model) was found to outperform other classifier models in testing data (area under the curve [AUC] of 80.44%, 95% confidence interval [CI] 72.24%-88.64%) and achieve the lowest Brier Score as well. These variables including age (OR = 1.054, 95%CI: 1.017~1.093), extubation time (OR = 1.027, 95%CI: 1.012~1.044), ICU admission (OR = 2.238, 95%CI: 1.313~3.793), MMSE (OR = 0.929, 95%CI: 0.876~0.984), CCI (OR = 1.197, 95%CI: 1.038~1.384), and postoperative NLR (OR = 1.029, 95%CI: 1.002~1.057) were independent risk factors for POD in this study. CONCLUSIONS: We have built and validated a high-performing algorithm to demonstrate the extent to which patient risk changes of POD during the perioperative period, thus leading to a rational therapeutic choice.

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