Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 390
Filtrar
1.
BMJ Open ; 12(1): e054011, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35017251

RESUMO

INTRODUCTION: Hereditary spastic paraplegias (HSPs) are uncommon but not rare neurodegenerative diseases. More than 100 pathogenic genes and loci related to spastic paraplegia symptoms have been reported. HSPs have the same core clinical features, including progressive spasticity in the lower limbs, though HSPs are heterogeneous (eg, clinical signs, MRI features, gene mutation). The age of onset varies greatly, from infant to adulthood. In addition, the slow and variable rates of disease progression in patients with HSP represent a substantial challenge for informative assessment of therapeutic efficacy. To address this, we are undertaking a prospective cohort study to investigate genetic-clinical characteristics, find surrogates for monitoring disease progress and identify clinical readouts for treatment. METHODS AND ANALYSIS: In this case-control cohort study, we will enrol 200 patients with HSP and 200 healthy individuals in parallel. Participants will be continuously assessed for 3 years at 12-month intervals. Six aspects, including clinical signs, genetic spectrum, cognitive competence, MRI features, potential biochemical indicators and nerve electrophysiological factors, will be assessed in detail. This study will observe clinical manifestations and disease severity based on different molecular mechanisms, including oxidative stress, cholesterol metabolism and microtubule dynamics, all of which have been proposed as potential treatment targets or modalities. The analysis will also assess disease progression in different types of HSPs and cellular pathways with a longitudinal study using t tests and χ2 tests. ETHICS AND DISSEMINATION: The study was granted ethics committee approval by the first affiliated hospital of Fujian Medical University (MRCTA, ECFAH of FMU (2019)194) in 2019. Findings will be disseminated via presentations and peer-reviewed publications. Dissemination will target different audiences, including national stakeholders, researchers from different disciplines and the general public. TRIAL REGISTRATION NUMBER: NCT04006418.

2.
J Mol Graph Model ; 110: 108069, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34773872

RESUMO

Chiral organophosphorus agents are distributed ubiquitously in the environment, but the neuroactivity of these asymmetric chemicals to humans remains uncertain. This scenario was to explore the stereoselective neurobiological response of human acetylcholinesterase (AChE) to chiral pyraclofos at the enantiomeric scale, and then decipher the microscopic basis of enantioselective neurotoxicity of pyraclofos enantiomers. The results indicated that (R)-/(S)-pyraclofos can form the bioconjugates with AChE with a stoichiometric ratio of 1:1, but the neuronal affinity of (R)-pyraclofos (K = 6.31 × 104 M-1) with AChE was larger than that of (S)-pyraclofos (K = 1.86 × 104 M-1), and significant enantioselectivity was existed in the biochemical reaction. The modes of neurobiological action revealed that pyraclofos enantiomers were situated at the substrate binding domain, and the strength of the overall noncovalent bonds between (S)-pyraclofos and the residues was weaker than that of (R)-pyraclofos, resulting in the high inhibitory effect of (R)-pyraclofos toward the activity of AChE. Dynamic enantioselective biointeractions illustrated that the intervention of inherent conformational flexibility in the AChE-(R)-pyraclofos was greater than that of the AChE-(S)-pyraclofos, which arises from the big spatial displacement and the conformational flip of the binding domain composed of the residues Thr-64~Asn-89, Gly-122~Asp-134, and Thr-436~Tyr-449. Energy decomposition exhibited that the Gibbs free energies of the AChE-(R)-/(S)-pyraclofos were ΔG° = ï¼37.4/-30.2 kJ mol-1, respectively, and the disparity comes from the electrostatic energy during the stereoselective neurochemical reactions. Quantitative conformational analysis further confirmed the atomic-scale computational chemistry conclusions, and the perturbation of (S)-pyraclofos on the AChE's ordered conformation was lower than that of (R)-pyraclofos, which is germane to the interaction energies of the crucial residues, e.g. Tyr-124, Tyr-337, Asp-74, Trp-86, and Tyr-119. Evidently, this attempt will contribute mechanistic information to uncovering the neurobiological effects of chiral organophosphates on the body.


Assuntos
Acetilcolinesterase , Simulação de Dinâmica Molecular , Acetilcolinesterase/metabolismo , Inibidores da Colinesterase , Humanos , Simulação de Acoplamento Molecular , Organotiofosfatos , Análise Espectral , Estereoisomerismo
3.
Neural Regen Res ; 17(3): 643-648, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34380905

RESUMO

It remains unclear whether limitations in activities of daily living (ADL) increase the risk of stroke in older Chinese adults. This longitudinal study used data from the Chinese Longitudinal Healthy Longevity Survey to investigate the effects of limitations in ADL on the incidence of stroke in older adults. Between 2002 and 2011, 46,728 participants from 22 provinces in China were included in this study. Of participants, 11,241 developed limitations in ADL at baseline. A 3-year follow-up was performed to determine the incidence of stroke. During the 3-year follow-up, 929 participants (8.26%) and 2434 participants (6.86%) experienced stroke in the ADL limitations group and non-ADL limitations group, respectively. Logistic regression was used to analyze the effect of ADL limitations on the risk of stroke. The results showed that after adjusting for the confounding factors gender, age, weight, hypertension, diabetes, heart disease, natural teeth, hearing impairment, visual impairment, smoking, alcohol abuse, exercise, ethnicity, literacy, residential area, and poverty, the ADL limitations group had a 77% higher risk of developing stroke than the non-ADL limitations group. After propensity score matching, the ADL limitations group still had a 33% higher risk of developing stroke than the non-ADL limitations group (OR = 1.326, 95% CI: 1.174-1.497). These findings suggest that limitations in ADL are a stroke risk factor.

4.
J Hazard Mater ; 423(Pt B): 127132, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-34537652

RESUMO

The abuse of antibiotics has triggered the rise of drug-resistance bacteria, which has seriously threatened public health globally. As a result, carrying out efficient and accurate antibiotic and bacteria identification are quite significant but challenge. Herein, an unprecedented Cd-MOF-based sensor, [CdL]n [1, H2L = 4-(2-methyl-1H-benzo[d]imidazol-1-yl) isophthalic acid] with multiple fluorescence response behaviours towards antibiotics and bacteria was developed. Single-crystal X-ray diffraction revealed that 1 is a mesomeric 2D bilayer, which is comprised of two opposite chiral mono-layers, each assembled by left-handed or right-handed helixes. More interestingly, 1 represented multiplex detection capability towards antibiotics and bacteria through two detection behaviors: toward nitro-antibiotics and chlortetracycline (CTC) via fluorescent quenching, while toward Staphylococcus albus (S. albus) via fluorescent enhancement. Remarkably, 1 showed a low limit of detection (LOD, 47 CFU/mL) accompanied with specificity in the detection of S. albus compared to other bacteria, such as Staphylococcus aureus, Acinetobacter baumannii, Klebsiella pneumonia, Pseudomonas aeruginosa and Escherichia coli. In addition, the LOD could reach to ppm level for nitro-antibiotics and CTC. Moreover, the practical application of 1 was further reinforced through the detection of nitro-antibiotics and CTC, as well as S. albus in fetal calf serum and river water.


Assuntos
Antibacterianos , Cádmio , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Staphylococcus epidermidis
5.
New Phytol ; 233(1): 390-408, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34643281

RESUMO

Since the roots are the very organ where plants first sense and respond drought stress, it is of great importance to better understand root responses to drought. Yet the underlying molecular mechanisms governing root responses to drought stress have been poorly understood. Here, we identified and functionally characterized a CCCH type transcription factor, PuC3H35, and its targets, anthocyanin reductase (PuANR) and early Arabidopsis aluminum induced1 (PuEARLI1), which are involved in mediating proanthocyanidin (PA) and lignin biosynthesis in response to drought stress in Populus ussuriensis root. PuC3H35 was root-specifically induced upon drought stress. Overexpressing PuC3H35 promoted PA and lignin biosynthesis and vascular tissue development, resulting in enhanced tolerance to drought stress by the means of anti-oxidation and mechanical supporting. We further demonstrated that PuC3H35 directly bound to the promoters of PuANR and PuEARLI1 and overexpressing PuANR or PuEARLI1 increased root PA or lignin levels, respectively, under drought stress. Taken together, these results revealed a novel regulatory pathway for drought tolerance, in which PuC3H35 mediated PA and lignin biosynthesis by collaboratively regulating 'PuC3H35-PuANR-PA' and 'PuC3H35-PuEARLI1-PuCCRs-lignin' modules in poplar roots.


Assuntos
Populus , Proantocianidinas , Secas , Regulação da Expressão Gênica de Plantas , Lignina , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Populus/genética , Populus/metabolismo , Estresse Fisiológico/genética
6.
J Craniofac Surg ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34855629

RESUMO

ABSTRACT: Reconstruction of complete bilateral maxillary defects (CBMDs) can be challenging due to the extensive loss of bone and soft tissues. This is a retrospective case series of 46 consecutive patients with CBMDs that were reconstructed with different microvascular free flaps. The authors aimed to evaluate the surgical outcomes and discuss the different reconstruction options in this case series. Thirty-six patients underwent reconstruction following ablation surgery for malignant tumors, 6 for benign tumors, 3 patients were treated for osteomyelitis, and 1 patient underwent free flap reconstruction for posttraumatic defects. Free fibula flap (n = 26) is the most commonly used reconstruction method in this case series, which was used in all defect types. This is followed by anterolateral thigh flap (n = 10), 5 rectus abdominis myocutaneous free flap, 3 radial forearm free flaps, and 2 composite free flaps. In this series, 44 free flaps survived, whereas only 2 flaps were lost. All patients could resume a soft diet postoperatively. Reconstruction of CBMDs with vascularized free flaps is a safe and reliable procedure.

7.
Aging (Albany NY) ; 13(undefined)2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34890366

RESUMO

Currently, 5-Fluorouracil (5-FU) based chemotherapy is the primary option for colorectal cancer after surgery, whereas chemotherapy resistance related mortality is observed in a large proportion of patients. Anemoside B4 (AB4) is a triterpene saponin, which exhibits a considerable activity in oncotherapy. In this study, we explored the efficacy of AB4 in FU-based chemotherapy in colorectal cancer cells and the underlying molecular mechanisms. Our results indicated a significant synergistic activity of AB4 in 5-FU treated colorectal cancer cells. Furthermore, AB4 treatment eliminated colorectal cancer stem cells by promoting apoptotic cell death in 5-FU resistant colorectal cancer cells. Mechanically, AB4 activated caspase-9 pathway in 5-FU resistant colorectal cancer cells. Elevated Src activity induced cell apoptosis and cancer stem cells elimination effects in AB4 treated colorectal cancer cells. In conclusion, AB4 showed promising sensitization effect in the FU-based chemotherapy of colorectal cancer. Our study may pave a way to ameliorate FU-based chemotherapeutic efficiency in colorectal cancer.

8.
Digestion ; : 1-8, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34781299

RESUMO

BACKGROUND: Epidemiology data of gastroesophageal junction (GEJ) cancers in Asia are extremely scarce. It is hardly registered by any cancer registry in the region, and only a few reports are available. Based on existing literature works, the overall trend indicates similar or gradually increasing GEJ cancers in Asia but comparably less than the West. The increasing trend in Asia is likely a result of rising risk factors, especially of gastroesophageal reflux disease and obesity. SUMMARY: However, epidemiology data may be misleading due to several contentious diagnostic issues. The diagnostic conundrums are due to inherent complexity of the GEJ as a functional and pathological unit. Challenging diagnostic issues in Asia include the following: nonstandardized landmark of the GEJ, misclassification of Barrett esophagus, targeted versus nontargeted tissue sampling, histopathology disagreement and challenges in screening or surveillance of dysplastic BE and early GEJ cancer. The recent Asian-Pacific survey led by the Asian Barrett Consortium (ABC) has provided useful insights into these contentious issues. A key learning point from these diagnostic limitations is that the awareness of the disease and adherence to existing recommendations or guidelines are poor in the region. Key Messages: Standardization in diagnostic methodology is vital for accurate epidemiology data, and this can only come from better awareness and adherence through educational and international efforts. Last, surveillance strategy may need a paradigm shift from a purely diagnostic approach to a combined targeted surveillance and treatment approach using novel endoscopic techniques.

9.
Int J Biol Sci ; 17(14): 3898-3910, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671207

RESUMO

Hypoxia and angiogenesis play key roles in the pathogenesis of esophageal squamous cell carcinoma (ESCC), but regulators linking these two pathways to drive tumor progression remain elusive. Here we provide evidence of ADAM9's novel function in ESCC progression. Increasing expression of ADAM9 was correlated with poor clinical outcomes in ESCC patients. Suppression of ADAM9 function diminished ESCC cell migration and in vivo metastasis in ESCC xenograft mouse models. Using cellular fractionation and imaging, we found a fraction of ADAM9 was present in the nucleus and was uniquely associated with gene loci known to be linked to the angiogenesis pathway demonstrated by genome-wide ChIP-seq. Mechanistically, nuclear ADAM9, triggered by hypoxia-induced translocation, functions as a transcriptional repressor by binding to promoters of genes involved in the negative regulation of angiogenesis, and thereby promotes tumor angiogenesis in plasminogen/plasmin pathway. Moreover, ADAM9 suppresses plasminogen activator inhibitor-1 gene transcription by interacting with its transcription factors at the promoter. Our findings uncover a novel regulatory mechanism of ADAM9 as a transcriptional regulator in angiogenesis and highlight ADAM9 as a promising therapeutic target for ESCC treatment.

10.
Plants (Basel) ; 10(10)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34685919

RESUMO

High-temperature stress is a major risk to fresh-market Salvia production, and heat intolerance is a major constraint in sage cultivation, particularly during the hot summer season. Previously, we investigated heat tolerance in five common-market cultivars of sage plants using leaf relative injury (RI) values and found that S. elegans Vahl (SE) and S. officinalis L. (SO) were the most and least heat-tolerant species, respectively. The exogenous applications of salicylic acid (SA) and calcium chloride (CaCl2) to alleviate heat stress in various species have been extensively studied, but reports of the effects of SA and CaCl2 treatments on the heat tolerance of sage plants are scarce. The objective of this study was to investigate how SA and CaCl2 affect the physiology and morphology of SE and SO plants under high-temperature conditions. Potted plants were pretreated with SA (0, 100, 200, 400, and 800 µM) and CaCl2 (0, 5, 10, and 15 mM), alone and combined, exposed to 55 °C and 80% humidity for 30 min, then placed in an environment-controlled chamber at 30 °C for three days and evaluated for changes in phenotypic appearance, RI, spectral reflectance, and chlorophyll fluorescence indices at different time intervals. Plants watered without chemical solutions were used as controls. Our results show that the growth of SO plants pretreated with SA and CaCl2 was more robust, compared with control plants, which were considerably affected by heat stress, resulting in brown, withered leaves and defoliation. The effects of the combined applications of SA (100 µM) and CaCl2 (5 mM) to SO plants were superior to control plants in increasing values of soil-plant analysis development (SPAD), normalized difference vegetation index (NDVI), and the maximal quantum yield of photosystemII photochemistry (Fv/Fm), while reducing RI%. Furthermore, SO plants exhibited higher SPAD and Fv/Fm values and lower RI% than SE plants in combined treatments at all time intervals after heat stress, implying that different genotypes displayed variations in their SPAD, Fv/Fm, and RI%. Thus, a combined treatment of 100 µM of SA and 5 mM of CaCl2 is effective and beneficial to plant appearance and ability to ameliorate heat stress. These indices can be used as indicators to characterize the physiology of these plants and applied on a commercial scale for informing the development of rapid and precise management practices on bedded sage plants grown in plant factories to achieve maximum market benefit.

11.
Ann Acad Med Singap ; 50(8): 629-637, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34472558

RESUMO

INTRODUCTION: We aimed to provide a practical and evidence-based guide on the indications, performance and reporting of high-resolution oesophageal manometry (HRM) and ambulatory pH monitoring (PHM) in adult patients in Singapore. METHODS: The guideline committee comprised local gastroenterologists from public and private sectors with particular expertise in aspects of HRM and PHM, and it was tasked to produce evidence-based statements on the indications, performance and reporting of these tests. Each committee member performed literature searches to retrieve relevant articles within the context of domains to which they were assigned. RESULTS: Twelve recommendation statements were created and summarised. CONCLUSION: Standardising key aspects of HRM and PHM is imperative to ensure the delivery of high-quality care. We reported the development of recommendations for the performance and interpretation of HRM and ambulatory reflux monitoring in Singapore.


Assuntos
Monitoramento do pH Esofágico , Esôfago , Adulto , Humanos , Concentração de Íons de Hidrogênio , Manometria , Singapura
12.
Life Sci ; 285: 119991, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34592230

RESUMO

AIM: Elevated Treg is relevant to persistent HBV infection, and the regulatory mechanism of Treg levels remains unclear. E proteins are important transcriptional regulators and could be antagonized by inhibitors of DNA-binding (Id) 1-4. We aim to clarify the role of Ids during HBV infection. MAIN METHODS: Changes of Ids and their relationship with Treg were investigated in both HBV transfection model and hepatitis B patients. Significance of Ids was studied by in vitro Treg differentiation induction with Id inhibited or over-expressed. The role of inflammatory cytokines for Id was studied by co-culture. RNA-Seq was conducted to explore the differentially expressed genes in Id-overexpressed CD4 T cells upon Treg differentiation induction conditions. KEY FINDINGS: Id-overexpressed mice attenuated virus clearance in HBV transfection model. In the HBV transfection mouse model, Tregs were up-regulated, with Id3 increased in Treg as well. Clinically, circulating Tregs in chronic hepatitis B (CHB) patients were elevated, and elevated Id3 transcriptional levels were positively correlated with Tregs. IL-1ß could up-regulate Id3 in Treg cells induced in vitro. RNA-Seq revealed that increased Id could cause a series of signaling pathway changes during Treg differentiation. SIGNIFICANCE: Id3 is elevated during HBV infection to ease Treg differentiation, and the antiviral immunity is influenced that make the infection to develop into chronic state.


Assuntos
Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Proteínas Inibidoras de Diferenciação/metabolismo , Proteínas de Neoplasias/metabolismo , Linfócitos T Reguladores/imunologia , Adulto , Animais , Diferenciação Celular , Feminino , Regulação da Expressão Gênica , Humanos , Proteínas Inibidoras de Diferenciação/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , RNA-Seq , Regulação para Cima
13.
Antonie Van Leeuwenhoek ; 114(11): 1771-1789, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34510303

RESUMO

Understanding the role of chemotaxis in ecological interactions between plants and microbes in the rhizosphere is necessary to optimize biocontrol strategies targeting plant soil-borne diseases. Therefore, we examined and profiled the antagonistic endophytic bacteria (AEB) population with chemotaxis potential in the medicinal plant Panax notoginseng using a cheA gene-based approach coupled with 16S rRNA sequencing. Phylogenetic analysis of the chemotactic AEB (CAEB) community in P. notoginseng enabled the identification of 56 CAEB strains affiliated with 30 species of Actinobacteria, Firmicutes, and Proteobacteria; Firmicutes, especially Bacillus, were predominant. We then systematically quantified the chemotactic response profiles of CAEB toward five organic acid (OA) attractants: citric acid, fumaric acid (FA), malic acid, oxalic acid, and succinic acid. Further hierarchical cluster analysis revealed that the chemotaxis of CAEB to the same attractant exhibited different patterns among not only genera but also species and even strains of the same species. Following chemotaxis and hierarchical analysis, we selected the strongest chemoattractant, fumaric acid (FA), as the target for evaluating the effects of OAs on the representative CAEB strain Bacillus amyloliquefaciens subsp. plantarum YP1. Application of FA significantly stimulated the chemotaxis ability and growth of YP1, and increased the transcript levels of cheA and biocontrol-related genes in YP1. This is the first study to characterise the diversity of chemotaxis profiles toward OAs in natural bacterial assemblages of P. notoginseng and to highlight how FA promotes the biocontrol-related traits of P. notoginseng-associated CAEB.


Assuntos
Endófitos , Panax notoginseng , Bacillus , Bactérias/genética , Quimiotaxia , Endófitos/genética , Filogenia , Raízes de Plantas , RNA Ribossômico 16S/genética
14.
Strahlenther Onkol ; 197(12): 1131-1142, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34476531

RESUMO

PURPOSE: Development of a safe and effective systemic chemotherapeutic agent for concurrent administration with definitive thoracic radiotherapy remains a major goal of lung cancer management. The synergistic effect of PEGylated liposomal doxorubicin and irradiation was evaluated in lung cancer cell lines both in vitro and in vivo. METHODS: In vitro radiosensitization of A549 and LLC cell lines was evaluated by colony formation assay, γH2AX fluorescent staining and western blot assay, and annexin V staining. A radiosensitization study with healthy human lung-derived cell line BEAS-2B was performed for comparative purposes. In vivo radiosensitization was evaluated by tumor ectopic growth, cell survival, pharmacokinetics, and biodistribution analyses. Cleaved caspase­3, the marker for apoptosis, was assessed immunohistochemically in A549 xenograft tumors. RESULTS: Treatment with PEGylated liposomal doxorubicin decreased A549 and LLC cell proliferation in a dose-dependent manner. In vitro studies revealed comparable radiosensitizer advantages of PEGylated liposomal doxorubicin and free doxorubicin, showing equivalent DNA double-strand breaks according to γH2AX fluorescent staining and western blot assays, similar numbers of apoptotic cells in the annexin­V staining assay, and moderately decreased clonogenic survival. In vivo studies demonstrated markedly slow ectopic tumor growth with prolonged survival following treatment with PEGylated liposomal doxorubicin plus irradiation in both A549 and LLC mouse models, suggesting that PEGylated liposomal doxorubicin is more effective as a radiosensitizer than free doxorubicin in vivo. Pharmacokinetics evaluation showed a longer half-life of approximately 40 h for PEGylated liposomal doxorubicin, confirming that the liposomal carrier achieved controlled release. Biodistribution evaluation of PEGylated liposomal doxorubicin confirmed high accumulation of doxorubicin in tumors, indicating the promising drug delivery attributes of PEGylated liposomal doxorubicin. Although free doxorubicin caused histopathologic myocarditis with the cardiac muscle fibers showing varying degrees of damage, PEGylated liposomal doxorubicin caused no such effects. The immunohistochemical expression of cleaved caspase-3-positive cells was greatest expressed in the irradiation and PEGylated liposomal doxorubicin combined treatment group, indicating prolonged tumoricidal effects. CONCLUSIONS: Our study provides preclinical in vitro and in vivo evidence of the effectiveness of PEGylated liposomal doxorubicin as a radiosensitizer, supporting its potential clinical development as a component of chemoradiotherapy.

15.
Odontology ; 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398317

RESUMO

Oral squamous cell carcinoma (OSCC) is a malignancy all over the world. WD repeat domain 5 (WDR5) is involved in cancer progression. In addition, it was reported that WDR5 is upregulated in head and neck cancer, while its role in OSCC is unknown. First, the expression of WDR5 in oral cancer tissues and cells was examined by qRT-PCR, IHF and western blot. CCK-8 assay was performed to test the cell viability. Cell migration was assessed by transwell assay. Knocking down WDR5 or CARM1 in oral cancer cells to detect its function on cancer growth, WDR5 and CARM1 were significantly upregulated in OSCC. Silencing WDR5 suppressed OSCC cell viability and migration. CARM1 level in OSCC cells was significantly inhibited by WDR5 downregulation, and CARM1 elevation could rescue the effect of WDR5 knockdown on tumorigenesis of OSCC. Moreover, silencing of WDR5 notably inactivated ß-catenin signaling pathway, while this phenomenon was restored by CARM1 overexpression. Silencing of WDR5 attenuated the tumorigenesis of OSCC via CARM1/ß-catenin axis. Thus, WDR5 might be a target for OSCC treatment.

16.
Pestic Biochem Physiol ; 178: 104946, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34446184

RESUMO

Spodoptera litura (Fabricius) is a widely distributed, highly polyphagous pest that can cause severe damage to a variety of economically important crops. Various populations have developed resistance to different classes of insecticides. In this study, we report on two indoxacarb-resistant S. litura populations, namely Ind-R (resistance ratio = 18.37-fold) derived from an indoxacarb-susceptible (Ind-S) population and a population caught from a field (resistance ratio = 46.72-fold). A synergist experiment showed that piperonyl butoxide (PBO) combined with indoxacarb produced higher synergistic effects (synergist ratio = 5.29) in the Ind-R population as compared to Ind-S (synergist ratio = 3.08). Elevated enzyme activity of cytochrome P450 monooxygenases (P450s) was observed for Ind-R (2.15-fold) and the Field-caught population (4.03-fold) as compared to Ind-S, while only minor differences were noticed in the activities of esterases and glutathione S-transferases. Furthermore, expression levels of P450 genes of S. litura were determined by quantitative reverse transcription PCR to explore differences among the three populations. The results showed that the mRNA levels of CYP6AE68, a novel P450 gene belonging to the CYP6 family, were constitutively overexpressed in Ind-R (32.79-fold) and in the Field-caught population (68.11-fold). CYP6AE68 expression in S. litura was further analyzed for different developmental stages and in different tissues. Finally, we report that RNA interference-mediated silencing of CYP6AE68 increased the mortality of fourth-instar larvae exposed to indoxacarb at the LC50 dose level (increase by 33.89%, 29.44% and 22.78% for Ind-S, Ind-R and the Field-caught population, respectively). In conclusion, the findings of this study indicate that expression levels of CYP6AE68 in S. litura larvae are associated with indoxacarb resistance and that CYP6AE68 may play a significant role in detoxification of indoxacarb.


Assuntos
Inseticidas , Mariposas , Animais , Sistema Enzimático do Citocromo P-450/genética , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Larva/genética , Oxazinas/farmacologia , Spodoptera/genética
17.
Biomed Res Int ; 2021: 5511290, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195262

RESUMO

Background: This study is aimed at determining the predictive value of the gray-matter-white-matter ratio (GWR) on brain computed tomography for delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP). Methods: This retrospective cohort study reviewed 352 patients with acute CO poisoning and who underwent the brain computed tomography test. These patients were admitted to Cangzhou Central Hospital from May 2010 to May 2020. The patients were divided into the DEACMP (n = 16) and non-DEACMP (n = 336) groups. Pearson's correlation coefficients were computed for correlation analysis. The predictive value of GWR for DEACMP was evaluated by using logistic regression analysis and receiver operator characteristic curves. Results: The morbidity of DEACMP was 4.5% (16/352). The GWR-basal ganglia, GWR-cerebrum, and GWR-average in the DEACMP group were lower than those in the non-DEACMP group. Correlation analysis indicated that GWR-basal ganglia (r = 0.276; P < 0.001), GWR-cerebrum (r = 0.163; P = 0.002), and GWR-average (r = 0.200; P < 0.001) were correlated with DEACMP. Multivariate logistic regression analysis revealed that reduced GWR-basal ganglia, GWR-cerebrum, and GWR-average were independent risk factors (P < 0.001; P = 0.008; P = 0.001; respectively). Compared with GWR-cerebrum and GWR-average, GWR-basal ganglia had a higher area under the curve of 0.881 (95% confidence interval: 0.783-0.983) with sensitivity and specificity of 93.8% and 68.7%, respectively. The cut-off value of GWR-basal ganglia was 1.055. Conclusion: GWR, especially GWR-basal ganglia, is an early useful predictor for DEACMP.


Assuntos
Encefalopatias/terapia , Intoxicação por Monóxido de Carbono/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Substância Branca/diagnóstico por imagem , Adulto , Idoso , Área Sob a Curva , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neuroimagem/métodos , Valor Preditivo dos Testes , Curva ROC , Análise de Regressão , Estudos Retrospectivos , Sensibilidade e Especificidade
18.
Surg Endosc ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34327547

RESUMO

BACKGROUND: Peroral endoscopic myotomy (POEM) is gaining traction as a minimally invasive treatment of achalasia. Increased reflux is reported after POEM but the incidence, type and severity of reflux are not fully understood. We aimed to study the prevalence and nature of reflux after POEM and correlate reflux with endoscopy and pH-impedance findings. METHODS: This is a prospective cohort study of achalasia patients undergoing POEM since 2014. Data from Eckardt and GERD symptom scores, high-resolution oesophageal manometry (HRM) and gastroscopy were performed pre-procedure and repeated at 1-year follow-up. Data from 24-h pH-impedance, if performed, were also recorded. A standardized questionnaire was used to determine the severity and frequency of heartburn symptoms and the composite score for each patient was calculated. RESULTS: 58 patients underwent POEM between January 2014 and October 2018. The efficacy of POEM at 1 year was 93.0%. We observed reduction of median Integrated Relaxation Pressure (IRP) from 23.5 ± 33.1 mmHg to 13.4 ± 7.71 mmHg (p = 0.005) and mean Eckardt score improved from 6.09 ± 2.43 points to 1.16 ± 1.70 points (p < 0.001). At 1 year, 43.1% (n = 25) had symptomatic reflux. Of the 40 patients who underwent repeated gastroscopy, 60.0% (n = 24) had endoscopic evidence of oesophagitis with seven patients (18%) diagnosed with Grade C or D oesophagitis. 43.1% (n = 25) of patients had pH-impedance done post-POEM off PPIs. 14 patients (56%) had increased acid exposure. Sixteen percent of reflux episodes were acidic and 77.3% were weakly acidic. CONCLUSION: POEM was an effective treatment for achalasia. However, GERD was common after POEM with incidence of 43% on symptom score, 60% on endoscopy and 56% on pH-impedance test. Post-POEM reflux appeared to be predominantly acidic in nature. Routine surveillance for GERD after POEM is recommended.

19.
Front Neurol ; 12: 627531, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093392

RESUMO

Background: Hereditary spastic paraplegia (HSP) caused by mutations in ALDH18A1 have been reported as spastic paraplegia 9 (SPG9), with autosomal dominant and autosomal recessive transmission (SPG9A and SPG9B). SPG9 is rare and has shown phenotypic and genotypic heterogeneity in previous reports. Methods: This study screened ALDH18A1 mutations in autosomal recessive HSP patients using combined whole exome sequencing and RNA splicing analysis. We conducted in silico investigations, co-segregation analysis, and ELISA-based analysis of P5CS (Δ1-pyrroline-5-carboxylate synthetase; encoded by ALDH18A1) concentration to validate the pathogenicity of the detected ALDH18A1 variants. All previously reported bi-allelic ALDH18A1 mutations and cases were reviewed to summarize the genetic and clinical features of ALDH18A1-related HSP. Results: A novel missense mutation c.880T>C, p.S294P and an intronic splicing mutation c.-28-13A>G were both detected in ALDH18A1 in an autosomal recessive family presenting with a complicated form HSP. ELISA assays revealed significantly decreased P5CS concentration in the proband's plasma compared with that in the healthy controls. Moreover, review of previously reported recessive cases showed that SPG9B patients in our cohort presented with milder symptoms, i.e., later age at onset and without cognitive impairment. Conclusion: The present study expands the genetic and clinical spectrum of SPG9B caused by ALDH18A1 mutation. Our work defines new genetic variants to facilitate future diagnoses, in addition to demonstrating the highly informative value of splicing mutation prediction in the characterization of disease-related intronic variants.

20.
Hemodial Int ; 25(4): 541-547, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34132032

RESUMO

INTRODUCTION: Little is known about the effects of boiling on nutrient levels in fishes that have a relatively high phosphorus-to-protein ratio (PPR), which are important sources of omega-3 polyunsaturated fatty acids. We hypothesized that the beneficial effects of boiling for a shorter duration (15 min) on nutrient contents in fishes were similar to those of boiling for a longer duration (30 min), which has been shown to decrease the PPR in meat. METHODS: The protein, fat, and phosphorus contents and the PPR of three cooked fish species and their corresponding fish broths were chemically analyzed. The effects of boiling on changes in protein, fat, phosphorus, and the PPR was examined by comparing fish that were prepared with usual cooking methods (no boiling), boiled for 15 min, and boiled for 30 min. The nutrients in fish broths that were boiled for 15 min were also compared with those boiled for 30 min. FINDINGS: There were no significant differences in the changes in phosphorus, PPR, protein, and fat content in fish and fish broths prepared with the two boiling methods. In the fish boiled for 15 min, the phosphorus content was 24% lower (p = 0.001), and the PPR was 20% lower (p = 0.04) than those in nonboiled fish. Additionally, boiling for 30 min reduced the phosphorus content by 31% (p = 0.001), and the PPR by 27% (p = 0.04) compared to nonboiled fish, but the protein and fat contents were unchanged after both 15 and 30 min of boiling. DISCUSSION: The 15- and 30-min boiling methods resulted in a similar reduction in phosphorus and the PPR in fish, with minimal effects on protein and fat. A shorter duration of boiling is recommended to achieve better nutrient profiles in fishes consumed by dialysis patients.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...