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1.
World J Clin Cases ; 12(10): 1830-1836, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38660070

ABSTRACT

BACKGROUND: Moyamoya syndrome (MMS) is a group of diseases that involves more than one underlying disease and is accompanied by moyamoya vascular phenomena. Psoriasis is a chronic immune skin disease closely linked to high blood pressure and heart disease. However, psoriasis-related MMS has not been reported. CASE SUMMARY: We collected data on patients with stroke due to MMS between January 2017 and December 2019 and identified four cases of psoriasis. Case histories, imaging, and hematological data were collected. The average age of the initial stroke onset was 58.25 ± 11.52 years; three cases of hemorrhagic and one case of ischemic stroke were included. The average duration from psoriasis confirmation to the initial MMS-mediated stroke onset was 17 ± 3.56 years. All MMS-related stenoses involved the bilateral cerebral arteries: Suzuki grade III in one case, grade IV in two cases, and grade V in one case. Abnormally elevated plasma interleukin-6 levels were observed in four patients. Two patients had abnormally elevated immunoglobulin E levels, and two had thrombocytosis. All four patients received medication instead of surgery. With an average follow-up time of 2 years, two causing transient ischemic attacks occurred in two patients, and no hemorrhagic events occurred. CONCLUSION: Psoriasis may be a potential risk factor for MMS. Patients with psoriasis should be screened for MMS when they present with neurological symptoms.

2.
Inorg Chem ; 63(3): 1537-1542, 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38181068

ABSTRACT

The cleavage of inert C-H bonds in methane at room temperature and the subsequent conversion into value-added products are quite challenging. Herein, the reactivity of boron-doped cobalt oxide cluster cations CoBO2+ toward methane under thermal collision conditions was studied by mass spectrometry experiments and quantum-chemical calculations. In this reaction, one H atom and the CH3 unit of methane were transformed separately to generate the product metaboric acid (HBO2) and one CoCH3+ ion, respectively. Theoretical calculations strongly suggest that a catalytic cycle can be completed by the recovery of CoBO2+ through the reaction of CoCH3+ with sodium perborate (NaBO3), and this reaction generates sodium methoxide (CH3ONa) as the other value-added product. This study shows that boron-doped cobalt oxide species are highly reactive to facilitate thermal methane transformation and may open a way to develop more effective approaches for methane (CH4) activation and conversion under mild conditions.

3.
J Phys Chem Lett ; 14(34): 7597-7602, 2023 Aug 31.
Article in English | MEDLINE | ID: mdl-37603698

ABSTRACT

Dinitrogen (N2) activation and its chemical transformations are some of the most challenging topics in chemistry. Herein, we report that heteronuclear metal anions AuNbBO- can mediate the direct coupling of N2 and O2 to generate NO molecules. N2 first forms the nondissociative adsorption product AuNbBON2- on AuNbBO-. In the following reactions with two O2 molecules, two NO molecules are gradually released, with the formation of AuNbBO2N- and AuNbBO3-. In the reaction with the first O2, the generated nitrene radical (N••-) originating from the dissociated N2, induces the activation of O2. Subsequently, the second O2 is anchored and forms a superoxide radical (O2•-); this radical attacks the other N atom to form an N-O bond, releasing the second NO. The N••- and O2•- radicals play key roles in the reactions. The mechanism adopted in this direct oxidation of N2 by O2 to NO can be labeled as a Zeldovich-like mechanism.

4.
Neurochem Int ; 170: 105603, 2023 11.
Article in English | MEDLINE | ID: mdl-37633650

ABSTRACT

Intracerebral hemorrhage (ICH), which has high mortality and disability rate is associated with microglial pyroptosis and neuroinflammation, and the effective treatment methods are limited Epigallocatechin-3-gallate (EGCG) has been found to play a cytoprotective role by regulating the anti-inflammatory response to pyroptosis in other systemic diseases. However, the role of EGCG in microglial pyroptosis and neuroinflammation after ICH remains unclear. In this study, we investigated the effects of EGCG pretreatment on neuroinflammation-mediated neuronal pyroptosis and the underlying neuroprotective mechanisms in experimental ICH. EGCG pretreatment was found to remarkably improved neurobehavioral performance, and decreased the hematoma volume and cerebral edema in mice. We found that EGCG pretreatment attenuated the release of hemin-induced inflammatory cytokines (IL-1ß, IL-18, and TNF-α). EGCG significantly upregulated the expression of heme oxygenase-1 (HO-1), and downregulated the levels of pyroptotic molecules and inflammatory cytokines including Caspase-1, GSDMD, NLRP3, mature IL-1ß, and IL-18. EGCG pretreatment also decreased the number of Caspase-1-positive microglia and GSDMD along with NLRP3-positive microglia after ICH. Conversely, an HO-1-specific inhibitor (ZnPP), significantly inhibited the anti-pyroptosis and anti-neuroinflammation effects of EGCG. Therefore, EGCG pretreatment alleviated microglial pyroptosis and neuroinflammation, at least in part through the Caspase-1/GSDMD/NLRP3 pathway by upregulating HO-1 expression after ICH. In addition, EGCG pretreatment promoted the polarization of microglia from the M1 phenotype to M2 phenotype after ICH. The results suggest that EGCG is a potential agent to attenuate neuroinflammation via its anti-pyroptosis effect after ICH.


Subject(s)
Cerebral Hemorrhage , Heme Oxygenase-1 , Microglia , Neuroinflammatory Diseases , Neuroprotective Agents , Animals , Mice , Caspases/metabolism , Caspases/pharmacology , Cerebral Hemorrhage/drug therapy , Cerebral Hemorrhage/genetics , Cerebral Hemorrhage/metabolism , Cytokines/metabolism , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , Interleukin-18/metabolism , Interleukin-18/pharmacology , Microglia/drug effects , Microglia/metabolism , Neuroinflammatory Diseases/drug therapy , Neuroinflammatory Diseases/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis/drug effects , Pyroptosis/genetics , Antioxidants/pharmacology , Antioxidants/therapeutic use , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use
5.
Zootaxa ; 5227(2): 265-278, 2023 Jan 05.
Article in English | MEDLINE | ID: mdl-37044692

ABSTRACT

Paracanthocobitis putaoensis sp. nov. is described based on analysis of morphological and molecular data (cytochrome c oxidase subunit I-COI). The new species was collected from the Mali Hka River, a tributary of the Irrawaddy River near Putao in Kachin State in northern Myanmar. It can be easily distinguished from all other species of the genus Paracanthocobitis by an incomplete lateral line, a suborbital groove in adult males, and a well-developed axillary pelvic lobe. Phylogenetic relationships of the genus Paracanthocobitis based on the mitochondrial COI locus are revealed for the first time. Maximum likelihood and Bayesian inference phylogenetic analyses indicate that the new species forms an independent clade. Both morphological and molecular phylogenetic analyses suggest that P. putaoensis is a new species.


Subject(s)
Cypriniformes , Male , Animals , Phylogeny , Bayes Theorem , Myanmar , Rivers
6.
J Phys Chem A ; 127(14): 3082-3087, 2023 Apr 13.
Article in English | MEDLINE | ID: mdl-37014705

ABSTRACT

Compared with transition metals, nonmetallic elements have always been considered to have low reactivity toward carbon dioxide. However, in recent years, main-group compounds such as boron-based species have gradually attracted increasing attention due to their prospective applications in different kinds of reactions. Herein, we report that metal-free anions B2O2- can promote two CO2 reductions, producing the oxygen-rich product B2O4-. In most of the reported CO2 reduction reactions mediated by transition-metal-containing clusters, transition metals usually provide electrons for the activation of CO2; one oxygen atom in CO2 is transferred to metal atoms, and CO is released from the metal atoms. In sharp contrast, B atoms are electron donors in the current systems and the formed CO is liberated directly from the activated CO2 unit. The synthesis of novel-metal-free gas-phase clusters and investigation of their reactivity toward carbon dioxide as well as reaction mechanisms can provide a fundamental basis in practice for the rational design of active sites on metal-free catalysts.

7.
Adv Sci (Weinh) ; 10(14): e2204654, 2023 05.
Article in English | MEDLINE | ID: mdl-36932888

ABSTRACT

Ovarian cancer is the most lethal gynecological malignancy. Most patients are diagnosed at an advanced stage with widespread peritoneal dissemination and ascites. Bispecific T-cell engagers (BiTEs) have demonstrated impressive antitumor efficacy in hematological malignancies, but the clinical potency is limited by their short half-life, inconvenient continuous intravenous infusion, and severe toxicity at relevant therapeutic levels in solid tumors. To address these critical issues, the design and engineering of alendronate calcium (CaALN) based gene-delivery system is reported to express therapeutic level of BiTE (HER2×CD3) for efficient ovarian cancer immunotherapy. Controllable construction of CaALN nanosphere and nanoneedle is achieved by the simple and green coordination reactions that the distinct nanoneedle-like alendronate calcium (CaALN-N) with a high aspect ratio enabled efficient gene delivery to the peritoneum without system in vivo toxicity. Especially, CaALN-N induced apoptosis of SKOV3-luc cell via down-regulation of HER2 signaling pathway and synergized with HER2×CD3 to generate high antitumor response. In vivo administration of CaALN-N/minicircle DNA encoding HER2×CD3 (MC-HER2×CD3) produces sustained therapeutic levels of BiTE and suppresses tumor growth in a human ovarian cancer xenograft model. Collectively, the engineered alendronate calcium nanoneedle represents a bifunctional gene delivery platform for the efficient and synergistic treatment of ovarian cancer.


Subject(s)
Calcium , Ovarian Neoplasms , Female , Humans , Alendronate/metabolism , Alendronate/therapeutic use , Calcium/metabolism , Cell Line, Tumor , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , T-Lymphocytes/metabolism , Animals
8.
J Phys Chem Lett ; 13(46): 10697-10704, 2022 Nov 24.
Article in English | MEDLINE | ID: mdl-36367460

ABSTRACT

The conversion of dinitrogen to more useful and reactive molecules has been the focus of intense research by chemists. In contrast to reductive N2 fixation, direct oxidation of N2 by O2 to nitric oxide under mild conditions via a thermochemical process is extremely challenging. Herein, we report the first example of N2 and O2 activation and coupling under thermochemical conditions through the remarkable ability of Y2BO+ to react with one N2 and two O2 molecules. Detailed mechanistic studies using mass spectrometry and quantum chemical calculations revealed that the N2 activation by Y2BO+ is facilitated by the double aromatic character of the Y2BON2+ intermediate. Subsequent oxidation with O2 releases NO in a dearomatization process driven by the formation of stronger Y-O bonds over the Y-N bonds. Our findings represent the first example of N2 and O2 activation and coupling under thermochemical conditions at room temperature, providing a novel strategy for small-molecule activation.

9.
Aquat Toxicol ; 252: 106318, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36206702

ABSTRACT

Mitochondria are recognized as an important target organelle for the toxicity of nanomaterials. Although the toxic effects of silver nanoparticles (AgNPs) on mitochondria have been widely reported, the mechanism behind the toxicity remains unclear. In this study, the effects of two forms of silver (AgNPs and AgNO3) on carp gill mitochondria were investigated by analyzing the mitochondrial ultrastructure, physicochemical properties of mitochondrial membrane, and mitochondrial proteomics. After exposure of common carp to AgNPs (0.75 mg/L) and AgNO3 (0.05 mg/L) for 96 h, both forms of silver were shown to cause gill mitochondrial lesions, including irregular shape, loss of mitochondrial cristae, and increased mitochondrial membrane permeability. Proteomics results revealed that AgNPs and AgNO3 induced 362 and 297 differentially expressed proteins (DEPs) in gill mitochondria, respectively. Among the DEPs, 244 were shared between AgNPs and AgNO3 treatments. These shared proteins were mainly distributed in the mitochondrial membrane and matrix, and were significantly enriched in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation pathway. The functional annotation of DEPs induced by both silver forms was mainly involved in energy production and conversion. These results indicated that the toxic mechanism of AgNPs and AgNO3 on gill mitochondria were comparable and the two forms of silver caused mitochondrial dysfunction in fish gills by inhibiting the TCA cycle and disrupting the electron transport chain.


Subject(s)
Carps , Metal Nanoparticles , Water Pollutants, Chemical , Animals , Silver Nitrate/toxicity , Gills , Metal Nanoparticles/chemistry , Proteomics , Water Pollutants, Chemical/toxicity , Silver/toxicity , Silver/metabolism , Coloring Agents/metabolism , Coloring Agents/pharmacology , Tricarboxylic Acids/metabolism , Tricarboxylic Acids/pharmacology
10.
J Hazard Mater ; 439: 129690, 2022 10 05.
Article in English | MEDLINE | ID: mdl-36104924

ABSTRACT

The trophodynamics of toxic trace metals is significant for assessing the threat of toxic trace metals to the aquatic ecosystem and human safety. However, due to the difficulty of accurately calculating the trophic positions of freshwater aquatic organisms in the food web, the comprehensive process of trophodynamics of toxic trace metals in freshwater ecosystems was still rarely known. By integrating the compound-specific nitrogen stable isotopic analysis of amino acids (CSIA-AAs) and the Bayesian stable isotope mixing model (SIMM) as a novel approach, the present study investigated the trophodynamics of five toxic trace metals (Zn, As, Cr, Cu, and Hg) in the food web of the YangZong Lake, a plateau freshwater lake that was once heavily polluted by arsenic in Yunnan Province, China. The results revealed that Hg tended to be efficiently biomagnified in the food web with a trophic magnification factor of 1.75; As, Cr, and Cu were biodiluted significantly, while Zn showed no biomagnification or biodilution trends. The dietary health risk assessment indicated the potential health risk of toxic trace metals for the local residents of long-term fish consumption. The present work highlights the accuracy and reliability of the novel CSIA-AAS+SIMM approach in the calculation of the trophic positions of freshwater organisms.


Subject(s)
Mercury , Trace Elements , Water Pollutants, Chemical , Animals , Aquatic Organisms/metabolism , Bayes Theorem , China , Ecosystem , Environmental Monitoring/methods , Food Chain , Humans , Lakes/chemistry , Mercury/metabolism , Reproducibility of Results , Risk Assessment , Trace Elements/metabolism , Water Pollutants, Chemical/analysis
11.
Article in English | MEDLINE | ID: mdl-35911148

ABSTRACT

Background: Oxaliplatin is an effective chemotherapeutic agent for the treatment of malignant tumors. However, severe oxaliplatin-induced peripheral neurotoxicity (OIPN) has been well documented. Traditional Chinese medicine injections (TCMIs) have shown significant efficacy in preventing OIPN. However, it is difficult for clinicians to determine the differences in the efficacy of various TCMIs in preventing OIPN. The aim of this study was to compare the efficacy of various TCMIs in preventing OIPN through a network meta-analysis (NMA) to further inform clinical decision-making. Methods: The Chinese Journal Full Text Database, Chinese Biomedical Literature Database, Wanfang Data Knowledge Service Platform, Chinese Science and Technology Journal Full Text Database, the Cochrane Library, Web of Science, PubMed, and Embase databases were searched for randomized controlled trials (RCTs) of TCMIs for OIPN prevention. The retrieval time was from the establishment of the database to April 12, 2021. NMA was performed using Stata 14.0 software after 2 evaluators independently screened the literature, extracted information, and evaluated the risk of bias of the included studies. Results: A total of 45 eligible RCTs involving 3598 cancer patients and 13 TCMIs were included. The 13 TCMIs included Xiaoaiping injection (XAPI), compound kushen injection (CKSI), Aidi injection (ADI), Brucea javanica oil emulsion injection (BJOEI), Shenmai injection (SMI), Kangai injection (KAI), Astragalus injection (AI), elemene emulsion injection (EEI), Shenfu injection (SFI), Shenqi Fuzheng injection (SIFZI), Kanglaite injection (KLEI), Huachansu injection (HCSI), and lentinan injection (LI). NMA results showed that AI was superior to AD and SIFZI was superior to ADI in reducing the incidence of grade I neurotoxicity. SIFZI was superior to EEI and ADI, and BJOEI was superior to chemotherapy alone in reducing the incidence of grade II neurotoxicity. SMI was superior to LI and CKSI in reducing the incidence of grade III neurotoxicity. SIFZI was superior to LI, BJOEI, XAPI, EEI, SMI, chemotherapy alone, HCSI, KLEI, and ADI in reducing the total incidence of grade I-IV neurotoxicity. SFI was superior to ADI. Based on the SUCRA values, AI was the most likely intervention to reduce the incidence of grade I neurotoxicity, SIFZI was the most likely intervention to reduce the total incidence of grade II and I-IV neurotoxicity, and SMI was the most likely intervention to reduce the incidence of grade III and IV neurotoxicity. Conclusion: TCMIs can prevent OIPN to some extent, among which SIFZI, SMI, and AI may be the most promising TCMIs. However, given the limitations of current studies, more well-designed, high-quality clinical trials will be needed in the future to validate the benefits of TCMIs.

12.
Chemistry ; 28(64): e202201170, 2022 Nov 16.
Article in English | MEDLINE | ID: mdl-35997766

ABSTRACT

Transition-metal catalyzed coupling to form C-N bonds is significant in chemical science. However, the inert nature of N2 and CO2 renders their coupling quite challenging. Herein, we report the activation of dinitrogen in the mild plasma atmosphere by the gas-phase monometallic YB1-4 - anions and further coupling of CO2 to form C-N bonds by using mass spectrometry and theoretical calculation. The observed product anions are NCNBO- and N(BO)2 - , accompanied by the formation of neutral products YO and YB0-2 NC, respectively. We can tune the reactivity and the type of products by manipulating the number of B atoms. The B atoms in YB1-4 N2 - act as electron donors in CO2 reduction reactions, and the carbon atom originating from CO2 serves as an electron reservoir. This is the first example of gas-phase monometallic anions, which are capable to realize the functionalization of N2 with CO2 through C-N bond formation and N-N and C-O bond cleavage.

13.
Mol Ther Oncolytics ; 24: 788-798, 2022 Mar 17.
Article in English | MEDLINE | ID: mdl-35317514

ABSTRACT

Bispecific antibodies (BsAbs) are a class of promising anticancer immunotherapies. Among them, the US Food and Drug Administration (FDA)-approved blinatumomab (BLI) is very effective in eliminating the minimum residual disease (MRD) of acute lymphoblastic leukemia (ALL), resulting in long-term remission in many individuals. However, the need for months-long intravenous delivery and high cost limit its clinical acceptance. Here we demonstrate that these problems can be solved by a BsAb expressed by one intramuscular (i.m.) dose of a minicircle DNA vector (MC). In a human B lymphoma xenograft mouse model, when microcancers became detectable in bone marrow, the mice received an i.m. dose of the MC encoding the BsAb anti-CD3/CD20 (BsAb.CD20), followed by 8 subsequent intravenous (i.v.) doses, one every other day (q2d), of human T cells to serve as effectors. The treatment resulted in persistent expression of a therapeutic level of serum BsAb.CD20 and complete regression or growth retardation of the cancers in the mice. These results suggest that the i.m. MC technology can eliminate the physical and financial burdens of i.v. delivered BLI without compromising anticancer efficacy and that cancer can be treated as easily as injecting a vaccine. This, together with other superior MC features, such as safety and affordability, suggests that the i.m. MC BsAb technology has great clinical application potential.

14.
J Phys Chem A ; 126(9): 1511-1517, 2022 Mar 10.
Article in English | MEDLINE | ID: mdl-35226501

ABSTRACT

Alkali atoms are usually used as promoters to significantly increase the catalytic activity of transition-metal catalysts in a wide range of reactions such as dinitrogen conversion reactions. However, the role of alkali metal atoms remains controversial. Herein, a series of quaternary cluster anions containing lithium atoms Nb2LiNO1-4- have been synthesized and reacted with N2 at room temperature. The detailed experimental and theoretical investigations indicate that Nb2LiNO- is capable to cleave the N≡N bond and the Li atoms in Nb2LiNO1,2- act as electron donors in the N2 reduction reaction. With the increase in the number of oxygen atoms, the reactivity toward N2 is reduced from adsorption via a side-on end-on mode in Nb2LiNO2- to the inertness of Nb2LiNO4-. In Nb2LiNO3,4- anions, the Li atoms are bonded with oxygen atoms, acting as structural units to stabilize structures. Therefore, the roles of alkali atoms are able to change with different chemical environments of active sites. For the first time, we reveal how the number of ligands (oxygen atoms herein) can be used to finely regulate the reactivity toward N2.

15.
CNS Neurosci Ther ; 27(10): 1214-1223, 2021 10.
Article in English | MEDLINE | ID: mdl-34242498

ABSTRACT

AIMS: To explore the safety and efficacy of normobaric oxygen (NBO) on correcting chronic cerebral ischemia (CCI) and related EEG anomalies. METHODS: This prospective randomized trial (NCT03745092) enrolled 50 cases of CCI patients, which were divided into NBO (8 L/min of oxygen supplement) group and control group (room air) randomly, and also enrolled 21 healthy volunteers. Two times of 30-min EEG recordings with the interval of 45min of NBO or room air were analyzed quantitatively. RESULTS: The CCI-mediated EEG presented with two patterns of electrical activities: high-power oscillations (high-power EEG, n = 26) and paroxysmal slow activities under the normal-power background (normal-power EEG, n = 24). The fronto-central absolute power (AP) of the beta, alpha, theta, and delta in the high-power EEG was higher than that in healthy EEG (p < 0.05). The fronto-central theta/alpha, delta/alpha and (delta + theta)/(alpha + beta) ratios in the normal-power EEG were higher than those in healthy EEG (p < 0.05). The high-power EEG in NBO group had higher fronto-central AP reduction rates than those in control group (p < 0.05). NBO remarkably reduced the fronto-central theta/alpha, delta/alpha, and (delta + theta)/(alpha + beta) ratios in the normal-power EEG (p < 0.05). CONCLUSIONS: NBO rapidly ameliorates CCI-mediated EEG anomalies, including attenuation of the abnormal high-power oscillations and the paroxysmal slow activities associated with CCI.


Subject(s)
Brain Ischemia/physiopathology , Brain Ischemia/therapy , Electroencephalography , Oxygen Inhalation Therapy/methods , Adult , Aged , Chronic Disease , Entropy , Female , Humans , Male , Middle Aged , Prospective Studies , Reference Values , Wavelet Analysis , Young Adult
16.
Ecotoxicol Environ Saf ; 222: 112548, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34325196

ABSTRACT

Studies have shown silver nanoparticles (AgNPs) exposure can result in a series of toxic effects in fish gills. However, it is still unclear how AgNPs affect metabolite expression and their related molecular metabolic pathways in fish gills. In this study, we employed untargeted metabolomics to study the effects of AgNPs and silver supernatant ions on fish gill metabolites. The results showed that AgNPs can induce significant changes in 96 differentially expressed metabolites, which mainly affect amino acid metabolism and energy metabolism in fish gills. Among these metabolites, AgNPs specifically induce significant changes in 72 differentially expressed metabolites, including L-histidine, L-isoleucine, L-phenylalanine, and citric acid. These metabolites were significantly enriched in the pathways of aminoacyl-tRNA biosynthesis, ABC transporters, and the citrate cycle. In contrast, Ag+ supernatant exposure can specifically induce significant changes in 14 differentially expressed metabolites that mainly interfere with sphingolipid metabolism in fish gills. These specifically regulated fish gill metabolites include sphinganine, sphingosine, and phytosphingosine, which were significantly enriched in the sphingolipid metabolism pathway. Our results clearly reveal the effects and potential toxicity mechanisms of AgNPs on fish gill metabolites. Furthermore, our study further determined the unique functions of released silver ions in AgNPs toxicity in fish gills.


Subject(s)
Carps , Metal Nanoparticles , Animals , Gills , Metabolomics , Metal Nanoparticles/toxicity , Silver/toxicity
17.
Biomaterials ; 250: 120072, 2020 08.
Article in English | MEDLINE | ID: mdl-32361307

ABSTRACT

Ovarian cancer has become one of the most common gynecological cancers with a high mortality. However, conventional surgery together with combination chemotherapy is difficult to achieve ideal therapeutic effect. Although genetic immunotherapy is applied to active immune responses against cancer, the absence of efficient in vivo gene delivery technique is still an obstacle in clinical application. To overcome these problems, a minicircle DNA vector encoding humanized anti-EpCAM/CD3 bispecific antibody (BsAbEPH) has been constructed. Moreover, different shapes of calcium phosphate (CaPO) biomaterials were prepared. Specifically, the CaPO-nanoneedle-mediated "cell perforation" transfection technology achieves high levels of gene expression in peritoneal cavity. In an intraperitoneal xenograft model with human ovarian cancer cell line SKOV3, the CaPO-nanoneedle/minicircle DNA system expressed BsAbEPH resulted in significant retardation of cancer growth and extension of mouse life-span with limited toxicity. And this system can be made as off-the-shelf and easy-to-use products. Therefore, CaPO-nanoneedle based non-viral gene delivery technology will have great potential in clinical application.


Subject(s)
Immunotherapy , Ovarian Neoplasms , Animals , Calcium Phosphates , Female , Gene Transfer Techniques , Humans , Mice , Ovarian Neoplasms/genetics , Ovarian Neoplasms/therapy , Transfection
18.
Curr Med Sci ; 39(5): 741-747, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31612391

ABSTRACT

Visit-to-visit variability in systolic blood pressure (SBP) may have an important additional role in increasing the risk of vascular complications, including stroke. We conducted a meta-analysis to assess the relationship between visit-to-visit SBP variability (SBPV) and stroke risk. PubMed, EMBASE, and the Cochrane library databases were searched for cohort studies with data on visit-to-visit SBPV and stroke risk. Studies that reported adjusted relative risks (RRs) with 95% CIs of stroke associated with SBPV were included. Fourteen cohort studies met the inclusion criteria and were included in our meta-analysis. After adjustment for age, sex, and existing vascular risk factors, the analysis showed that the risk of stroke in patients with SBPV was significantly increased compared with patients with a small baseline SBPV [SD (RR=1.20, 95% CI=(1.07-1.35), P=0.0005), CV (RR=1.12, 95% CI=(1.00-1.26), P=0.008)]. In addition, follow-up variations of more than 5 years were associated with a higher risk of stroke than those of less than 5 years [RR=1.08, 95% CI=(1.04-1.11)]. Visit-to-visit SBPV was associated with an increased risk of stroke, especially in terms of the time of variation. Taken together, SBPV data may be useful as a preventative diagnostic method in the management of stroke.


Subject(s)
Blood Pressure , Hypertension/complications , Stroke/complications , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Hypertension/diagnosis , Hypertension/physiopathology , Male , Middle Aged , Office Visits , Risk Factors , Stroke/diagnosis , Stroke/physiopathology
19.
Mol Med Rep ; 19(6): 4890-4896, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31059012

ABSTRACT

The aim of this study was to investigate the protective effect of sulforaphane (SFN) on 1­methyl­4­phenyl pyridine ion (MPP+)­induced cytotoxicity and to investigate its possible mechanisms. METHODS: PC12 cell toxicity induced by MPP+ served as a cell model of Parkinson's diseases. The cell culture + experiments were divided into four groups based on the different treatments, namely, vehicle control, SFN, MPP+ and SFN pretreatment plus MPP+. Cell viability and apoptosis were examined by MTT assay and flow cytometry, respectively. Expressions of nuclear factor erythroid 2­related factor 2 (Nrf2), heme oxygenase 1 (HO­1) and nicotinamide quinone oxidoreductase 1 (NQO1) were detected using western blotting. RESULTS: MPP+ reduced the survival rate of PC12 cells in a dose­ and time­dependent manner. After 24­h treatment with 500 µmol/l MPP+, the survival rate of PC12 cells decreased to 58.2±0.03% of that in the control groups. Under the same conditions MPP+ resulted in significant apoptosis of PC12 cells (apoptosis rate: 30.4±0.6%). However, SFN pretreatment significantly attenuated the cell damage induced by MPP+. Furthermore, it was demonstrated that SFN reversed the reduction of Nrf2, HO­1 and NQO1 expression induced by MPP+. CONCLUSION: SFN may protect PC12 cells from MPP+­induced damage via activating the Nrf2­ARE (antioxidant responsive element) pathway.


Subject(s)
Isothiocyanates/pharmacology , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , PC12 Cells/drug effects , Protective Agents/pharmacology , 1-Methyl-4-phenylpyridinium/toxicity , Animals , Antioxidant Response Elements , Antioxidants/pharmacology , Antiparkinson Agents/pharmacology , Apoptosis/drug effects , Cell Survival/drug effects , Heme Oxygenase-1/metabolism , Isothiocyanates/administration & dosage , NAD(P)H Dehydrogenase (Quinone)/metabolism , Parkinson Disease/drug therapy , Rats , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Sulfoxides , Survival Rate , Time Factors
20.
Biomed Eng Online ; 17(1): 71, 2018 Jun 05.
Article in English | MEDLINE | ID: mdl-29866126

ABSTRACT

BACKGROUND: Intra-body communication (IBC) is one of the highlights in studies of body area networks. The existing IBC studies mainly focus on human channel characteristics of the physical layer, transceiver design for the application, and the protocol design for the networks. However, there are few safety analysis studies of the IBC electrical signals, especially for the galvanic-coupled type. Besides, the human channel model used in most of the studies is just a multi-layer homocentric cylinder model, which cannot accurately approximate the real human tissue layer. METHODS: In this paper, the empirical arm models were established based on the geometrical information of six subjects. The thickness of each tissue layer and the anisotropy of muscle were also taken into account. Considering the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines, the restrictions taken as the evaluation criteria were the electric field intensity lower than 1.35 × 104 f V/m and the specific absorption rate (SAR) lower than 4 W/kg. The physiological electrode LT-1 was adopted in experiments whose size was 4 × 4 cm and the distance between each center of adjoining electrodes was 6 cm. The electric field intensity and localized SAR were all computed by the finite element method (FEM). The electric field intensity was set as average value of all tissues, while SAR was averaged over 10 g contiguous tissue. The computed data were compared with the 2010 ICNIRP guidelines restrictions in order to address the exposure restrictions of galvanic-coupled IBC electrical signals injected into the body with different amplitudes and frequencies. RESULTS: The input alternating signal was 1 mA current or 1 V voltage with the frequency range from 10 kHz to 1 MHz. When the subject was stimulated by a 1 mA alternating current, the average electric field intensity of all subjects exceeded restrictions when the frequency was lower than 20 kHz. The maximum difference among six subjects was 1.06 V/m at 10 kHz, and the minimum difference was 0.025 V/m at 400 kHz. While the excitation signal was a 1 V alternating voltage, the electric field intensity fell within the exposure restrictions gradually as the frequency increased beyond 50 kHz. The maximum difference among the six subjects was 2.55 V/m at 20 kHz, and the minimum difference was 0.54 V/m at 1 MHz. In addition, differences between the maximum and the minimum values at each frequency also decreased gradually with the frequency increased in both situations of alternating current and voltage. When SAR was introduced as the criteria, none of the subjects exceeded the restrictions with current injected. However, subjects 2, 4, and 6 did not satisfy the restrictions with voltage applied when the signal amplitude was ≥ 3, 6, and 10 V, respectively. The SAR differences for subjects with different frequencies were 0.062-1.3 W/kg of current input, and 0.648-6.096 W/kg of voltage input. CONCLUSION: Based on the empirical arm models established in this paper, we came to conclusion that the frequency of 100-300 kHz which belong to LF (30-300 kHz) according to the ICNIRP guidelines can be considered as the frequency restrictions of the galvanic-coupled IBC signal. This provided more choices for both intensities of current and voltage signals as well. On the other hand, it also makes great convenience for the design of transceiver hardware and artificial intelligence application. With the frequency restrictions settled, the intensity restrictions that the current signal of 1-10 mA and the voltage signal of 1-2 V were accessible. Particularly, in practical application we recommended the use of the current signals for its broad application and lower impact on the human tissue. In addition, it is noteworthy that the coupling structure design of the electrode interface should attract attention.


Subject(s)
Electricity , Finite Element Analysis
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