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1.
Mol Med ; 27(1): 12, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546582

RESUMO

BACKGROUND: Osteoarthritis (OA) is the most common articular disorder, leading to joint malfunction and disability. Although the incidence of OA is increasing globally, the treatment of OA is very limited. LncRNA CIR has been implicated in OA through unclear mechanisms. Here, we investigated the role of lncRNA CIR in chondrogenic differentiation. METHODS: Human umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) were obtained from human umbilical cords. Flow cytometry was used to analyze the surface markers of hUC-MSCs. Various culture conditions and corresponding staining assays were employed to assess the differentiation abilities of hUC-MSC. qRT-PCR, western blot, and immunostaining were used to measure expression levels of related genes and proteins such as lncRNA CIR, ATOH8, EZH2, and H3K27me3. RNA immunoprecipitation assay, biotin pull-down, and chromatin immunoprecipitaion assay were performed to analyze the interactions of lncRNA CIR, EZH2, H3K27me3 and ATOH8 promoter. RESULTS: hUC-MSCs exhibited MSCs features and could differentiate into chondrocytes under specific conditions. LncRNA CIR was downregulated while ATOH8 was upregulated during the chondrogenic differentiation of hUC-MSCs. Knockdown lncRNA CIR or overexpression of ATOH8 promoted chondrogenic differentiation. Further, lncRNA CIR bound to EZH2 and repressed ATOH8 expression via EZH2-mediated H3K27me3, which promotes the methylation of ATOH8. Inhibition of ATOH8 reversed the effects of knockdown lncRNA CIR on chondrogenic differentiation. CONCLUSION: LncRNA CIR suppresses chondrogenic differentiation of hUC-MSCs. Mechanistically, lncRNA CIR could inhibit ATOH8 expression that functions to promote chondrogenic differentiation through EZH2-mediated epigenetic modifications.

2.
Funct Integr Genomics ; 21(1): 125-138, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33415515

RESUMO

Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) play vital roles in the tumorigenesis of esophageal squamous cell carcinoma (ESCC). Nevertheless, the mechanism and regulatory network associated with this process remain largely unknown. In this study, we performed a comprehensive analysis of the expression of mRNAs, lncRNAs, and circRNAs by RNA-seq. A total of 3265 mRNAs, 1084 lncRNAs, and 38 circRNAs were found to be differentially expressed. Among these, 269 mRNAs were found to encode transcription factors (TFs). Functional enrichment analysis indicated that the dysregulated TFs are associated with the Hedgehog, Jak-STAT, TGF-beta, and MAPK signaling pathways. Furthermore, we constructed co-expression networks to screen the core lncRNAs and circRNAs involved in the regulation of transcription factors in these four pathways. Finally, we constructed a competing endogenous RNA (ceRNA) network of ESCC based on the abovementioned pathways. Our findings provide important insight into the role of lncRNAs and circRNAs in ESCC; the differentially expressed lncRNAs and circRNAs may represent potential targets for ESCC diagnosis and therapy.

3.
Sci Total Environ ; 764: 144275, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33385656

RESUMO

Visceral leishmaniasis (VL) is a neglected disease caused by trypanosomatid protozoa in the genus Leishmania, which is transmitted by phlebotomine sandflies. Although this vector-borne disease has been eliminated in several regions of China during the last century, the reported human VL cases have rebounded in Western and Central China in recent decades. However, understanding of the spatial epidemiology of the disease remains vague, as the spatial risk factors driving the spatial heterogeneity of VL. In this study, we analyzed the spatiotemporal patterns of annual human VL cases in Western and Central China from 2007 to 2017. Based on the related spatial maps, the boosted regression tree (BRT) model was adopted to explore the relationships between VL and spatial correlates as well as predicting both the existing and potential infection risk zones of VL in Western and Central China. The mined links reveal that elevation, minimum temperature, relative humidity, and annual accumulated precipitation make great contributions to the spatial heterogeneity of VL. The maps show that Xinjiang Uygur Autonomous Region, Gansu, western Inner Mongolia Autonomous Region, and Sichuan are predicted to fall in the highest infection risk zones of VL. Approximately 61.60 million resident populations lived in the high-risk regions of VL in Western and Central China. Our results provide a better understanding of how spatial risk factors driving VL spread as well as identifying the potential endemic risk region of VL, thereby enhancing the biosurveillance capacity of public health authorities.


Assuntos
Leishmaniose Visceral , Doenças Negligenciadas , Psychodidae , Animais , China/epidemiologia , Humanos , Leishmaniose Visceral/epidemiologia , Fatores de Risco
4.
J Nanosci Nanotechnol ; 21(3): 1549-1559, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33404418

RESUMO

Cellulose acetate (CA) fibrous membranes blended with poly-(γ-glutamic acid) (γ-PGA) and ZnO were produced via electrospinning. The performance of the obtained composite membrane was investigated by scanning electron microscopy (SEM), Fourier transform IR spectroscopy, tensile test, water contact angle, and thermogravimetric analysis. The corn plant height, leaf area and SPAD (soil and plant analyzer development) were compared with plants covered with CA/γ-PGA and CA/γ-PGA/ZnO fibrous membranes at room temperature. Simultaneously, the water absorption and degradation rate were also studied. The results obtained indicate the potential use of these fibrous membranes for mulching film applications. The fibrous membranes could also find potential use as a material for food packing, facial mask and as antimicrobial films for wound dressing.

5.
Sci Total Environ ; 754: 142229, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254864

RESUMO

Cystic echinococcosis (CE), which is caused by Echinococcus granulosus, is a worldwide helminthozoonosis that is highly endemic in the Tibet Autonomous Region of China and has important public health and economic impacts. However, the spatial epidemiological characteristics of CE in Tibet are still unclear. Based on recorded human CE cases and the use of a geographic information system, the spatial distribution patterns of CE prevalence at three different scales were analyzed. In addition, a spatial agglomeration map of CE prevalence was generated based on cold/hot spot analysis. By combining maps of environmental and biological covariates with information about known human CE cases, the links between CE prevalence and relevant covariates were explored, revealing that the annual average precipitation, elevation, water accessibility and animal population (dog and yak) were associated with the prevalence of CE at the significance level of P < 0.05. Our results provide a novel insight and better understanding of the current situation of and the factors influencing CE in Tibet, which can help public health authorities develop disease prevention and control strategies.


Assuntos
Equinococose , Animais , China/epidemiologia , Cães , Equinococose/epidemiologia , Sistemas de Informação Geográfica , Humanos , Prevalência , Saúde Pública , Tibet/epidemiologia
6.
Toxins (Basel) ; 13(1)2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33374143

RESUMO

Insecticidal proteins from Bacillus thuringiensis (Bt) are used widely in sprays and transgenic crops to control insect pests. However, evolution of resistance by pests can reduce the efficacy of Bt toxins. Here we analyzed resistance to Bt toxins Cry1Ac and Cry1Fa in the diamondback moth (Plutella xylostella), one of the world's most destructive pests of vegetable crops. We used CRISPR/Cas9 gene editing to create strains with knockouts of the ATP-binding cassette (ABC) transporter genes PxABCC2, PxABCC3, or both. Bioassay results show that knocking out either gene alone caused at most 2.9-fold resistance but knocking out both caused >10,320-fold resistance to Cry1Ac and 380-fold resistance to Cry1Fa. Cry1Ac resistance in the double knockout strain was recessive and genetically linked with the PxABCC2/PxABCC3 loci. The results provide insight into the mechanism of cross-resistance to Cry1Fa in diamondback moth. They also confirm previous work with this pest showing that mutations disrupting both genes cause higher resistance to Cry1Ac than mutations affecting either PxABCC2 or PxABCC3 alone. Together with previous work, the results here highlight the value of using single and multiple gene knockouts to better understand the independent and synergistic effects of putative Bt toxin receptors on resistance to Bt toxins.

7.
Zhongguo Zhong Yao Za Zhi ; 45(17): 4140-4148, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33164398

RESUMO

In this study, network pharmacology technology was combined with molecular docking technology and experimental verification to clarify the active ingredients, potential targets and mechanism of Alisma orientale for nonalcoholic fatty liver disease(NAFLD), providing a basis for its clinical application. The active ingredients of A. orientale were screened through traditional Chinese medicine systems pharmacology database(TCMSP), and the potential targets related to both active ingredients and NAFLD were predicted through protein databases by considering the oral bioavailability(OB) and drug-likeness(DL). The "active ingredient-potential target" network was constructed by using Cytoscape software, and the molecular docking was performed between active ingre-dients and potential targets. KEGG pathway analysis and enrichment analysis were performed through DAVID biological information annotation databases. ClueGO software was used to analyze target GO annotation. Western blot and immunocytochemistry were used to detect the protein expression levels, and fluorescent probe was used to detect the reactive oxygen species(ROS) generation level. The results revealed that 7 active ingredients of A. orientale were obtained from TCMSP database and analysis platform, 140 ingredient-related targets were screened, and 59 potential targets were obtained by intersecting disease targets with ingredient-related targets. Molecular docking showed that 7 active ingredients of A. orientale could act on the potential targets including 3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGCR) and tyrosine-protein phosphatase non-receptor type 1(PTPN1). In addition, KEGG enrichment analysis showed that the potential targets were mainly enriched in inflammatory mediator regulation, insulin resistance, neuroactive ligand-receptor interaction, vascular smooth muscle contraction, FcγR-mediated phagocytosis and other related pathways of tryptophan(TRP) channel. GO enrichment analysis showed that potential targets mainly affected the biological processes of G-protein coupled receptor signaling pathway, organic hydroxyl compound transport, positive regulation of lipid biosynthesis process, positive regulation of lipid metabolic process. Western blot, immunocytochemistry and fluorescent probe confirmed that the extract of A. orientale could reduce HMGCR and PTPN1 protein expression levels effectively, and also could reduce ROS production level of HepG2 cells. This study systematically revealed the material basis and mechanism of A. orientale in regulating NAFLD through multi-component, multi-target, and multi-pathway characteristics, which provided a theoretical basis and scientific basis for the clinical application of A. orientale.


Assuntos
Alisma , Medicamentos de Ervas Chinesas , Hepatopatia Gordurosa não Alcoólica , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética
8.
Sensors (Basel) ; 20(21)2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33171748

RESUMO

We present an innovative method for quantum two-party cryptography. Our protocol introduces joint measurement and error estimation to improve the security of two-party cryptographic protocols. Our protocol removes the assumption of the attacker's limited power and catches the attacking actions through highly estimated bit error rate. Our protocol is formally proved to be secure against both eavesdroppers and dishonest communication parties. We also utilize our designed protocol to construct two specific two-party cryptographic applications: Quantum bit commitment and quantum password identification.

9.
BMC Musculoskelet Disord ; 21(1): 730, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172443

RESUMO

PURPOSE: Muscle strength training is a common strategy for treating chronic ankle instability (CAI), but the effectiveness decreases for mechanical ankle instability (MAI) patients with initial severe ligament injuries. The purpose of this study was to investigate the characteristics and the potential predictors of muscle strength deficit in MAI patients, with a view to proposing a more targeted muscle strength training strategy. METHODS: A total of 220 MAI patients with confirmed initial lateral ankle ligament rupture and a postinjury duration of more than 6 months were included. All patients underwent a Biodex isokinetic examination of the ankle joints of both the affected and unaffected sides. Then, the associations between the limb symmetry index (LSI) (mean peak torque of the injury side divided by that of the healthy side) and the patients' sex, body mass index, postinjury duration, presence of intra-articular osteochondral lesions, presence of osteophytes and ligament injury pattern (i.e., isolated anterior talofibular ligament (ATFL) injury or combined with calcaneofibular ligament injury) were analysed. RESULTS: There was significantly weaker muscle strength on the affected side than on the unaffected side in all directions (p < 0.05). The LSI in plantar flexion was significantly lower than that in dorsiflexion at 60°/s (0.87 vs 0.98, p < 0.001). A lower LSI in eversion was significantly correlated with female sex (0.82 vs 0.94, p = 0.016) and isolated ATFL injury (0.86 vs 0.95, p = 0.012). No other factors were found to be associated with muscle strength deficits. CONCLUSION: MAI patients showed significant muscle strength deficits on the affected side, especially in plantar flexion. There were greater strength deficits in eversion in females and individuals with an isolated ATFL injury. Thus, a muscle strength training programme for MAI patients was proposed that focused more on plantar flexion training and eversion training for females and those with an isolated ATFL injury.

10.
Fish Physiol Biochem ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33215297

RESUMO

Gonadotropin-inhibitory hormone (GnIH) plays a critical role in regulating gonadotropin-releasing hormone (GnRH), gonadotropin hormone (GtH), and steroidogenesis. The Lpxrfa (the piscine ortholog of GnIH) system has been found to regulate fish reproduction. To gain insight into the role of Lpxrfa in the regulation of spotted scat (Scatophagus argus) reproduction, spotted scat Lpxrfa (ssLpxrfa), and its receptor (ssLpxrfa-r) were cloned and analyzed. Tissue distribution and expression patterns at the hypothalamo-pituitary-gonadal axis (HPG axis) of sslpxrfa and sslpxrfa-r mRNA were also investigated during gonadal development of spotted scat. The open reading frame (ORF) of the sslpxrfa was 606 bp encoding 201 amino acids and includes a putative signal peptide and two mature ssLpxrfa peptides with LPXRFamide motif at their C-terminus. The sslpxrfa-r ORF was 1449 bp encoding 482 amino acids and contracted a seven-hydrophobic transmembrane (TM) domain structure. The tissue distribution showe d that the sslpxrfa was highly expressed in hypothalami, gill, and the gonads. In addition, sslpxrfa-r was highly expressed in hypothalami, pituitaries, and the gonads. Quantitative real-time polymerase chain reaction (qPCR) revealed that sslpxrfa had the highest expression in the hypothalami and pituitaries, and the lowest expression in the gonads in stage V. During gonadal development, the expression of sslpxrfa-r was gradually increased in the hypothalami but reduced in the gonads. However, no obvious trend was observed in the pituitaries. The expression of sslpxrfa and sslpxrfa-r decreased significantly after injection with 17ß-estradiol (E2). However, the expression of both sslpxrfa and sslpxrfa-r was not changed after injection with 17α-methyltestosterone(17α-MT) in the hypothalami. In addition, no changes were observed in the expression of fshß and lhß in the pituitaries after injecting ssLpxrfa-1. However, ssLpxrfa-2 could downregulate the expression of sbgnrh and fshß in the hypothalami and pituitaries, respectively. Taken together, these findings suggested that ssLpxrfa may participate in E2 feedback in reproduction and regulate the reproductive axis of spotted scat.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33216188

RESUMO

PURPOSE: To compare the long-term clinical outcomes of single-bundle anterior cruciate ligament reconstruction (SBR) and double-bundle anterior cruciate ligament reconstruction (DBR) in patients with isolated anterior cruciate ligament (ACL) rupture, presenting no meniscus injury and no obvious preoperative cartilage degeneration. METHODS: One hundred and three patients (38.6 ± 9.5 years) with a median follow-up of 151.6 months (range, 144-189 months) completed the retrospective study (SBR group: n = 51; DBR group: n = 52). Clinical outcomes were evaluated with physical examinations, KT-2000 anterior and posterior stability measurement with the knee in 30º of flexion, International Knee Documentation Committee (IKDC) subjective score, Tegner score, Lysholm score; magnetic resonance imaging (MRI) (3.0 T) was performed, and International Cartilage Repair Society (ICRS) cartilage degeneration grades were determined. Multivariate analysis was performed to identify factors associated with cartilage degeneration. RESULTS: There were significant differences in the pre- and postoperative IKDC, Lysholm and Tegner scores between the SBR and DBR groups. The SBR group had over double the rate of positive pressure/rub patellar test results (SBR vs DBR, 43.1% vs. 19.2%, p < 0.011). The KT-2000, pivot-shift and Lachman test results were stratified and analyzed, and significant differences between the SBR and DBR groups were found (p < 0.05, respectively). The distribution of ICRS grades differed significantly between the groups at the last follow-up (p = 0.013). A multivariate analysis found that age and operation procedures were significant predictors of 0 and non-0 ICRS grades (odds ratio, 6.077 [95% CI 2.117-17.447] and 0.210 [95% CI 0.068-0.654], respectively) (p < 0.05). CONCLUSION: Both SBR and DBR achieved overall good long-term results. DBR had advantages in objective outcome measures and was superior in preventing the occurrence of cartilage degeneration. Age was identified as a preoperative risk factor for significant postoperative cartilage degeneration. LEVEL OF EVIDENCE: III. ClinicalTrials.gov: NCT03984474.

12.
Plant Biotechnol J ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33236499

RESUMO

Foods high in amylose content and resistant starch (RS) offer great potential to improve human health and lower the risk of serious noninfectious diseases. Common wheat (Triticum aestivum L.) is a major staple food crop globally. However, the RS contents in the grains of modern wheat varieties are low. Here, we report the generation of high-amylose wheat through targeted mutagenesis of TaSBEIIa in a modern winter wheat cv Zhengmai 7698 (ZM) and a spring wheat cv Bobwhite by CRISPR/Cas9, respectively. We generated a series of transgene-free mutant lines either with partial or triple null TasbeIIa alleles in ZM and Bobwhite, respectively. Analyses of starch composition, structure and properties revealed that the effects of partial or triple null alleles were dosage dependent with triple null lines demonstrated more profound impacts on starch composition, fine structures of amylopectin, and physiochemical and nutritional properties. The flours of triple null lines possessed significantly increased amylose, RS, protein and soluble pentosan contents which benefit human health. Baking quality analyses indicated that the high-amylose flours may be used as additives or for making cookies. Collectively, we successfully modified the starch composition, structure and properties through targeted mutagenesis of TaSBEIIa by CRISPR/Cas9 in both winter and spring wheat varieties, and generated transgene-free high-amylose wheat. Our finding provides deep insights on the role of TaSBEIIa in determining starch composition, structure, properties and end-use quality in different genetic backgrounds, and improving RS content with multiple breeding and end-use applications in cereal crop species through genome editing for health benefits.

13.
Gene ; : 145211, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33053422

RESUMO

OBJECTIVE: The purpose of this study was to investigate associations between two single nucleotide polymorphisms (SNPs) rs505922 and rs532436 in ABO gene and the risk of small artery occlusion stroke (SAO) in southern Chinese Han population. METHODS: Our case-control study comprising 121 patients with SAO and 136 controls. All participants were Han population of southern China. IS sub-type was defined on the basis of the TOAST criteria. SAO was strictly diagnosed after a systematic physical examination and neuroimaging via MRI. Genotype analysis was conducted by the snapshot technique. RESULTS: The distribution of rs532436 genotype between these two groups showed a statistically significant difference (P = 0.048) while that of rs505922 genotype showed no significant difference (P = 0.572). SNP rs532436 was significantly associated with SAO in overdominant model (GA vs. GG + AA) after adjusting for age, hypertension history, diabetes history and cigarette smoking (adjusted OR = 2.03, 95% CI: 1.14-3.62, P = 0.016). However, under all genetic models, the rs505922 polymorphism failed to show association with SAO. CONCLUSION: The resultsindicate that rs532436 polymorphism in ABO gene may have association with SAO in southern Chinese Han population.

14.
J Biol Inorg Chem ; 25(8): 1107-1116, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33079244

RESUMO

As the "powerhouse" of a cell, mitochondria maintain energy homeostasis, synthesize ATP via oxidative phosphorylation, generate ROS signaling molecules, and modulate cell apoptosis. Herein, three Re(I) complexes bearing guanidinium derivatives have been synthesized and characterized. All of these complexes exhibit moderate anticancer activity in HepG2, HeLa, MCF-7, and A549 cancer cells. Mechanism studies indicate that complex 3, [Re(CO)3(L)(Im)](PF6)2, can selectively localize in the mitochondria and induce cancer cell death through mitochondria-associated pathways. In addition, complex 3 can effectively depress the ability of cell migration, cell invasion, and colony formation.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32889045

RESUMO

Growth hormone (GH) is the most important endocrine factor to regulate somatic growth. Spotted scat (Scatophagus argus) is a famous marine aquaculture species in China with a typical sexual growth dimorphism in which females grow faster and larger than males. In this study, gh messenger RNA (gh mRNA) and GH protein expression were examined in the pituitary glands of female and male spotted scat. Based on qPCR analysis, gh mRNA was mainly expressed in the pituitary gland, and weakly in the gonads and hypothalamus. Furthermore, gh mRNA expression in the pituitary gland was significantly higher in females at stages II-IV than in males at stages III-V. In addition, gh mRNA was highly expressed in the ovary and testis during mature development stages. In this study, spotted scat GH polyclonal antibody was produced. Western blot analysis showed that the molecular weight of spotted scat GH was about 21 KDa. Immunohistochemistry (IHC) in pituitary glands showed that GH was mainly expressed in the proximal pars distal (PPD) and a few cells were distributed in the rostral pairs distal (RPD). After injecting 17ß-Estradiol (E2) in vivo, gh mRNA expression was significantly up-regulated in the pituitary gland, whereas igf1 and ghr1 mRNA levels were down-regulated in the liver, which might regulate gh mRNA expression in the pituitary gland. These results provide valuable insight into the molecular mechanisms of E2 regulating gh expression in spotted scat.

16.
Sensors (Basel) ; 20(18)2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32957519

RESUMO

Wood is widely used in construction, the home, and art applications all over the world because of its good mechanical properties and aesthetic value. However, because the growth and preservation of wood are greatly affected by the environment, it often contains different types of defects that affect its performance and ornamental value. To solve the issues of high labor costs and low efficiency in the detection of wood defects, we used machine vision and deep learning methods in this work. A color charge-coupled device camera was used to collect the surface images of two types of wood from Akagi and Pinus sylvestris trees. A total of 500 images with a size of 200 × 200 pixels containing wood knots, dead knots, and checking defects were obtained. The transfer learning method was used to apply the single-shot multibox detector (SSD), a target detection algorithm and the DenseNet network was introduced to improve the algorithm. The mean average precision for detecting the three types of defects, live knots, dead knots and checking was 96.1%.

17.
Drug Dev Ind Pharm ; 46(11): 1881-1888, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32951478

RESUMO

OBJECTIVE: To prepare α-(8-quinolinyloxy) monosubstituted phthalocyanine zinc nanosuspension (ZnPc-NS) for photodynamic therapy by intravenous administration. METHODS: The formulation and preparation technology of ZnPc-NS were assessed by particle size using the precipitation-high pressure homogenization method. The efficacy of ZnPc-NS was evaluated based on particle size, zeta potential, sedimentation ratio, TEM imaging, stability assessment, photodynamic activity and safety. RESULTS AND DISCUSSION: The content, average particle size, polydispersity and photodegradation constant of ZnPc-NS were 0.2 mg/ml, 219.7 ± 7.41 nm, 0.19 ± 0.02 and 0.006, respectively. The photosensitization rate of singlet oxygen (1O2) of the ZnPc-NS was three times higher than that of the ZnPc DMF solution. ZnPc-NS exhibited optimal antitumor activity in HepG2 cells under light exposure and low photo- and non-light-associated toxicity in HELFX cells. In addition, low hemolysis and vascular stimulation were evident in the experiments performed. CONCLUSION: The ZnPc-NS exhibited optimal stability, faster photosensitization rate of 1O2, and optimal antitumor activity and safety than the ZnPc DMF solution, which could provide potential support for further research and development.

18.
Int J Pharm ; 591: 119864, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32991961

RESUMO

BACKGROUND: Pediatric pulmonary arterial hypertension (PPAH) is a malignant progressive rare disease characterized by restricted pulmonary artery blood flow and progressively increasing blood pressure, which has shorter survival time of only about 10 months as compared to adults. Previous studies have shown that low-dose vardenafil hydrochloride (Var) could significantly improve the symptoms of PPAH. However, Var is currently available only in tablet form in the market for erectile dysfunction, and no special preparation is available for PPAH. METHODS: In this study, borneol-mediated vardenafil hydrochloride patch (BO-VarP) with sodium polyacrylate as the skeleton material was prepared by coating method, which was characterized by temperature resistance, formability, adhesive force, skin irritation and in vitro permeation. Blood concentration of optimized BO-VarP was measured by LC-MS/MS using intragastric administration (i.g.) as a control, and pharmacodynamic studies were conducted using a rat model of pulmonary arterial hypertension induced by monocrotaline. RESULTS AND DISCUSSION: Optimized BO-VarP showed good appearance, with optimal temperature resistance and formability, appropriate adhesive force and low skin irritation, and its cumulative permeation flux was 14.9 times higher than patch without penetration enhancer. The blood concentration within therapeutic window of BO-VarP lasted longer than i.g., and BO-VarP could improve symptoms of PPAH by reducing pulmonary arterial pressure and right heart hypertrophy index. CONCLUSION: BO-VarP had good therapeutic effect in PPAH rats and suitable compliance in children, which provided a potential industrial transdermal delivery system for the treatment of PPAH.

19.
Medicine (Baltimore) ; 99(34): e21106, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846752

RESUMO

RATIONALE: Colonic telangiectasia, also known as colonic angiodysplasia, refers to arteriovenous malformations that occur in the colon, which are common vascular lesions in the GI tract. PATIENT CONCERNS: We report a patient, who was admitted to our hospital for colonoscopy. DIAGNOSES: Under a microscope, all the segments of the whole colon and the varicose veins showed multiple flaky spider-like telangiectasia changes. The blood vessels were radially distributed and converged in the center. The largest blood vessel was about 10 mm in diameter and had a smooth surface with no ulcers, erosion, or bleeding. INTERVENTIONS: It was recommended that the patient undergo a capsule endoscopy to examine small intestine. OUTCOMES: The patient did not agree to endoscopy for personal reasons. During the follow-up half a year later, the patient had no melena with normal range of hemoglobin and red blood cell counts. The fecal occult blood test came out negative. LESSONS: While the etiology of colonic telangiectasia remains unclear, it is common in the elderly, and is more associated with geriatric conditions and diseases, especially atherosclerotic diseases. Patients who are diagnosed with colonic telangiectasia but are asymptomatic, do not need further treatment. It is usually recommended to monitor the color of stool and check the hemoglobin and fecal occult blood regularly. Colonoscopy is the main method of diagnosis of colonic telangiectasia, and the positive rate is greater than 90%. This procedure should be performed when there is no bleeding or a small amount of bleeding.


Assuntos
Doenças do Colo/diagnóstico , Telangiectasia/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade
20.
Insect Biochem Mol Biol ; 125: 103453, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32798712

RESUMO

The diamondback moth Plutella xylostella is a major destructive pest of Brassica worldwide. P. xylostella has evolved resistance to nearly all commercial insecticides used for its control, including the most recent chemical class, diamide insecticides. Several studies show that the G4946E and I4790M mutations of ryanodine receptor (RyR) are strongly associated with diamide resistance in insects. While the pivotal functional role of G4946E in conferring diamide resistance phenotype has confirmed by several studies in different species, no direct evidence has unambiguously confirmed the functional significance of the single I4790M mutation in diamide resistance. Here, we successfully constructed a knockin homozygous strain (I4790M-KI) of P. xylostella using CRISPR/Cas9 coupled with homology directed repair approach to introduce I4790M into RyR. When compared with the background susceptible IPP-S strain, the manipulated I4790M-KI strain exhibited moderate resistance to the phthalic acid diamide flubendiamide (40.5-fold) and low resistance to anthranilic diamides chlorantraniliprole (6.0-fold) and cyantraniliprole (7.7-fold), with no changes to the toxicities of indoxacarb and ß-cypermethrin. Furthermore, the acquired flubendiamide resistance was inherited in an autosomally recessive mode and significantly linked with the I4790M mutation of RyR in this I4790M-KI strain. Our findings provide in vivo functional evidence for the causality of I4790M mutation of PxRyR with moderate levels of resistance to flubendiamide in P. xylostella, and support the hypothesis that the diamide classes have different interactions with RyRs.

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