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1.
Artigo em Inglês | MEDLINE | ID: mdl-35026061

RESUMO

OBJECTIVES: Phenylketonuria (PKU) is an inherited autosomal recessive disorder of phenylalanine metabolism. It is mainly caused by a deficiency in phenylalanine hydroxylase (PAH) and frequently diagnosed with Sanger sequencing. To some extent, allelic dropout can explain the inconsistency in genotype and phenotype. METHODS: Three families were evaluated through DNA sequence analysis, multiplex ligation-dependent probe amplification (MLPA) and prenatal diagnosis technologies. The possibility of inconsistency in phenotype and genotype with c.331C>T variant was analysed. RESULTS: Through pedigree analysis, three mothers carried a homozygous c.331C>T variant, which was a false-positive result. New primers were used, and this error was caused by allelic dropout. In this case, c.158G>A was likely a benign variant. CONCLUSIONS: Sequence variants in primer-binding regions could cause allelic dropout, creating unpredictable errors in genotyping. Our results emphasised the need for careful measures to treat genotype-phenotype inconsistencies.

2.
Sci Total Environ ; 815: 152754, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34995588

RESUMO

Nanomaterials play a crucial role in various areas due to their extraordinary chemical and physical properties. Loading microscopic nanomaterials onto macrostructures is inevitable for their implementation from laboratory experiments to practical applications. Nevertheless, the geometries of conventional supporting structures are usually limited and nanomaterials are easy to be inhomogeneously distributed, aggregated, and lost. Therefore, controllably configuring nanomaterials into sophisticated three-dimensional macroscopic structures without sacrificing their inherent properties remains challenging. Here we utilize the advantages of 3D printing technology to realize this purpose. As a proof-of-concept, the application of 3D stereolithography printed macrostructures containing TiO2 nano particles (TiO2 NPs) for direct adsorption removal of As(III) in water was demonstrated. The morphology and distribution of TiO2 NPs mounted on printed macrostructures were initially characterized. Then batch adsorption experiments were conducted to investigate the effect of the 3D printing process, TiO2 NPs doped concentration and TiO2 NP size as well as adsorption kinetics and isotherms. We also demonstrated that 3D printed adsorption structures could be easily reused over 10 times and were effective for raw arsenic-polluted groundwater samples. Our findings show that 3D printing provides a promising route to design and fabricate customized macrostructures endowed with specific properties of nanomaterials.

3.
Cancer Manag Res ; 14: 25-35, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35018119

RESUMO

Purpose: The present study aimed to develop prognostic prediction models based on machine learning (ML) for non-metastatic colon cancer (CRC), which can provide a precise quantitative risk assessment and serve as an assistive method for treatment strategy development. The possibility of improving prediction accuracy using nonlinear methods compared to linear methods was investigated. Patients and Methods: A cancer-specific survival (CSS) model constructed using logistic regression, extreme gradient boosting (XGBoost), and random forest algorithms was trained on the Surveillance, Epidemiology, and End Results datasets for 15,254 patients with non-metastatic CRC (split into training [70%] and internal validation [30%] datasets) and externally validated with an outpatient cohort of 311 cases from Xiyuan Hospital in China. A Chinese cohort was also used to develop recurrence and metastasis (R&M) models for CRC patients. The experiments for each model were performed 100 times to obtain average scores and 95% confidence intervals. The model performance was evaluated using the area under the receiver operating characteristic curve (AUC) values. Results: The XGBoost approach showed the highest AUC values of 0.86 (0.84-0.88), 0.82 (0.81-0.83), and 0.81 (0.79-0.82) for one-, three-, and five-year CSS cohorts, respectively, along with a relatively high generalization ability. The XGBoost approach also performed best for the R&M model, with the AUC values of 0.71 (0.64-0.79), 0.79 (0.74-0.86), and 0.89 (0.82-0.95) for one-, three-, and five-year R&M cohorts, respectively. The rankings of predictor importance for the CSS and R&M models were different, and the higher model accuracy was associated with more prognostic predictors. Conclusion: Three different ML algorithms for developing prognostic prediction models for non-metastatic CRC were compared. The predictive performance results showed that the nonlinear XGBoost approach performed best, suggesting that it can be used for quantifying the prognostic risk. It was also demonstrated that the model performance can be improved when more prognostic predictors are considered.

4.
Biochem Genet ; 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34988777

RESUMO

Non-small cell lung carcinoma (NSCLC) is an aggressive malignant tumor. Growing evidences have revealed that circular RNA (circRNA) is involved in NSCLC progression. This study aims to investigate the role of circular RNA F-box and WD repeat domain containing 8 (circFBXW8) in NSCLC progression and the underlying mechanism. The expression of circFBXW8, microRNA-370-3p (miR-370-3p) and tripartite motif containing 44 (TRIM44) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was detected by western blot analysis or immunohistochemistry assay. Additionally, cell viability, colony-forming ability, proliferation and apoptosis were investigated by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide, cell colony formation, 5-Ethynyl-29-deoxyuridine and flow cytometry analysis assays, respectively. Cell migratory and invasive abilities were examined by wound-healing and transwell assays. The regulatory relationship between miR-370-3p and circFBXW8 or TRIM44 was identified by dual-luciferase reporter and RNA pull-down assays. Furthermore, xenograft experiment was employed to explain the effect of circFBXW8 silencing on tumor formation. CircFBXW8 and TRIM44 expression were upregulated, while miR-370-3p was downregulated in NSCLC tissues, cells and the exosomes from NSCLC cells compared with respective controls. CircFBXW8 depletion repressed NSCLC cell proliferation, migration and invasion, but promoted cell apoptosis. CircFBXW8 acted as a sponge of miR-370-3p and regulated NSCLC cell malignancy by binding to miR-370-3p. Additionally, miR-370-3p repressed NSCLC cell processes by regulating TRIM44. CircFBXW8 knockdown inhibited tumor formation in vivo. Further, circFBXW8 secretion was mediated by exosomes. CircFBXW8 modulated NSCLC progression by increasing TRIM44 expression through sponging miR-370-3p, which provided a new direction for studying the therapy of NSCLC.

5.
Metallomics ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34982823

RESUMO

The widespread application of silver nanomaterials raises health concerns due to the adverse effects that can be associated with silver nanoparticles (AgNPs) exposure. AgNPs can be introduced into human bodies via inhalation, either intentionally (intranasal administration of AgNPs) or unintentionally (environmental pollution, accidental release, or occupational exposure). Recent studies have shown that intranasal exposure of experimental animals to AgNPs can lead to the accumulation of silver (Ag) in brain tissues. However, there is little information available concerning what forms of Ag (particulate and ionic) exist in brain tissues. This study aimed to investigate whether particulate Ag exists in rat brains following intranasal exposure of AgNPs at 1 mg/kg/day using multiple analytical techniques. The results demonstrated that Ag-containing particles were presented in AgNPs-exposed rat brains, accounting for 20.2%- 68.1% of the total Ag. The mass concentrations of Ag-containing particles in brain tissues increased with exposure time but only decreased by 37.5% after elimination for 4 weeks upon exposure cessation. The size of Ag-containing particles identified in rat brains was larger than the original AgNPs. The Ag-containing particles identified in the rat brain were composed of multiple elements, including Ag, sulfur (S), selenium (Se) with atomic percentages of 45.8%, 37.5%, 16.7% respectively. The finding highlighted the occurrence and accumulation of transformed AgNPs containing S and Se in rat brains after intranasal exposure to AgNPs, implying potential risks for brain health.

6.
J Ethnopharmacol ; 285: 114917, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34919988

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Gynura procumbens (Lour.) Merr, (Family Asteraceae), which serves as both medicine and food in traditional ethnic medicine, has the effects of diminishing inflammation, relieving cough, reducing blood glucose and lipids levels, mitigating hepatotoxicity, and can be used for liver cancer prevention and treatment. AIM OF THE STUDY: To explore how the ethanol extract of Gynura procumbens stems (EEGS) can effectively intervene in the tumor microenvironment, it is necessary to study the mechanism of EEGS on the chemical toxicant nanodiethylnitrosamine (nanoDEN) that induces liver cancer. MATERIALS AND METHODS: EEGS contains large quantities of caffeoylquinic acid (CAC) and non-caffeoylquinic acid (n-CAC), which can be separated by high-performance liquid chromatography. The liver cancer model that was induced by the chemical toxin, nanoDEN, was used to clarify the effective mechanism for tumor intervention of the EEGS and its active ingredients. RESULTS: (1) after interventions with the four drugs on liver cancer, the tumor nodules were obviously reduced and inflammation levels improved. (2) The immunohistochemical staining results showed that both the EEGS and its active ingredients could significantly reverse the abnormal changes in inflammation, proliferation, aging and hypoxia-related proteins in mouse liver tissues that were caused by nanoDEN. (3) Real-time PCR results showed that compared with the nanoDEN group, the expression levels of inflammatory, fatty, and fibrosis-related factors in each group after drug intervention were decreased. (4) The transmission electron microscopy measurements showed that the EEGS significantly reversed the nanostructure changes in hepatocytes that were induced by nanoDEN. CONCLUSION: The EEGS component of Gynura procumbens is effective in preventing and treating liver cancer by interfering with the inflammatory microenvironment during oncogenesis induced by nanoDEN.

7.
J Hazard Mater ; 424(Pt B): 127399, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34638072

RESUMO

Methylmercury (MeHg), derived via inorganic mercury (Hg(II)) methylation by anaerobic microorganisms, is a neurotoxic contaminant causing concern worldwide. Establishing how to reduce Hg(II) methylation and MeHg bioavailability is essential for effective control of Hg pollution. Iron sulfide nanoparticles (FeSNP) is a promising passivator for Hg(II) methylation. However, its effect on the fate of MeHg in aquatic systems remains poorly understood. This study investigated the effect of FeSNP on Hg(II) bioavailability, MeHg production and bioavailability in aquatic environments. Results demonstrated that FeSNP rapidly sorbed Hg(II) and MeHg, with sorption affected by pH, chloride ion and dissolved organic matter. Hg-specific biosensor analysis showed that Hg(II) sorbed onto FeSNP significantly reduced its bioavailability to microorganisms. Double stable isotope (199Hg(II) and Me201Hg) addition revealed that FeSNP significantly inhibited MeHg production in anaerobic sediments. Furthermore, synthetic gut juice extraction suggested that FeSNP decrease concentrations of bioavailable MeHg and Hg(II), reducing their integration into food webs. However, the sorbed MeHg and Hg(II) in sediments can be released after FeSNP oxidation, potentially enhancing the risk of exposure to aquatic organisms. Overall, these findings increase our understanding of Hg transformation and exposure risks in aquatic systems, providing valuable information for the development of in situ Hg remediation systems.

8.
Bioact Mater ; 8: 220-240, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34541398

RESUMO

The considerable development of carrier-free nanodrugs has been achieved due to their high drug-loading capability, simple preparation method, and offering "all-in-one" functional platform features. However, the native defects of carrier-free nanodrugs limit their delivery and release behavior throughout the in vivo journey, which significantly compromise the therapeutic efficacy and hinder their further development in cancer treatment. In this review, we summarized and discussed the recent strategies to enhance drug delivery and release of carrier-free nanodrugs for improved cancer therapy, including optimizing the intrinsic physicochemical properties and external modification. Finally, the corresponding challenges that carrier-free nanodrugs faced are discussed and the future perspectives for its application are presented. We hope this review will provide constructive information for the rational design of more effective carrier-free nanodrugs to advance therapeutic treatment.

9.
Environ Sci Technol ; 56(1): 403-413, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34923819

RESUMO

The use of commercial products containing engineered nanomaterials in realistic scenarios may lead to the accumulation of exogenous particles in brain tissues. In this study, we simulated the use of silver (Ag) nasal spray in humans using Sprague-Dawley rats at 0.04 mg/kg/day. Silver-containing particles were explicitly identified in the rat brain after the administration of nasal sprays containing colloidal Ag or silver ions (Ag+) for 2 weeks using multiple methods. The accumulation of Ag-containing particles showed a delayed effect in different brain regions of the rats, with the mass concentration of particles increasing continuously for 1-2 weeks after the termination of administration. The size of the observed Ag-containing particles extracted from the brain tissues ranged from 18.3 to 120.4 nm. Further characterization by high-resolution transmission electron microscopy with energy-dispersive spectroscopy showed that the nanoparticles comprised both Ag and sulfur (S), with Ag/S atomic ratios of 1.1-7.1, suggesting that Ag-containing particles went through a series of transformations prior to or during their accumulation in the brain. Collectively, these findings provide evidence for the accumulation and transformation of Ag-containing particles in the rat brain, indicating a realistic risk to brain health resulting from the application of Ag-containing commercial products.

10.
Glob Chang Biol ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34854168

RESUMO

Our limited understanding of the impacts of drought on tropical forests significantly impedes our ability in accurately predicting the impacts of climate change on this biome. Here, we investigated the impact of drought on the dynamics of forest canopies with different heights using time-series records of remotely sensed Ku-band vegetation optical depth (Ku-VOD), a proxy of top-canopy foliar mass and water content, and separated the signal of Ku-VOD changes into drought-induced reductions and subsequent non-drought gains. Both drought-induced reductions and non-drought increases in Ku-VOD varied significantly with canopy height. Taller tropical forests experienced greater relative Ku-VOD reductions during drought and larger non-drought increases than shorter forests, but the net effect of drought was more negative in the taller forests. Meta-analysis of in situ hydraulic traits supports the hypothesis that taller tropical forests are more vulnerable to drought stress due to smaller xylem-transport safety margins. Additionally, Ku-VOD of taller forests showed larger reductions due to increased atmospheric dryness, as assessed by vapor pressure deficit, and showed larger gains in response to enhanced water supply than shorter forests. Including the height-dependent variation of hydraulic transport in ecosystem models will improve the simulated response of tropical forests to drought.

11.
J Nanobiotechnology ; 19(1): 412, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876145

RESUMO

Recently, DNA nanostructures with vast application potential in the field of biomedicine, especially in drug delivery. Among these, tetrahedral DNA nanostructures (TDN) have attracted interest worldwide due to their high stability, excellent biocompatibility, and simplicity of modification. TDN could be synthesized easily and reproducibly to serve as carriers for, chemotherapeutic drugs, nucleic acid drugs and imaging probes. Therefore, their applications include, but are not restricted to, drug delivery, molecular diagnostics, and biological imaging. In this review, we summarize the methods of functional modification and application of TDN in cancer treatment. Also, we discuss the pressing questions that should be targeted to increase the applicability of TDN in the future.

12.
Biomed Res Int ; 2021: 5503022, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34873571

RESUMO

Introduction: The effect of surgical timing on vertebral refracture rate and mortality remains elusive after percutaneous kyphoplasty (PKP) or percutaneous vertebroplasty (PVP), and we aim to assess the impact of surgical timing on vertebral refracture rate and mortality in patients undergoing percutaneous vertebroplasty. Methods: We did a retrospective cohort study of patients who underwent PKP or PVP because of osteoporotic vertebral compression fracture (OVCF) between April 1, 2014 and March 31, 2016. The primary outcome measure was the incidence of vertebral refracture. Secondary outcomes included the mortality and chronic back pain. Results: The rate of vertebral refracture was significantly lower in early surgical timing group than that in late surgical timing group (HR 2.415, 95% CI 1.318-4.427; P = 0.004). We found that the bone mineral density (BMD) was only the risk factor to increase the vertebral refracture rate after vertebroplasty (P = 0.001). In addition, there was similar mortality between the two groups (15.7% in early surgical timing group versus 10% in late surgical timing group). Male patients (27.3%, 12/44) had higher mortality compared to female patients (10.6%, 20/189), while the mortality was higher in patients with cerebral infarction (25%, 3/12) than those without cerebral infarction (12.1%, 17/140). Conclusions: Surgical timing significantly affects the vertebral refracture rate after PKP or PVP, which is also influenced by BMD. The mortality after the surgery is not affected by the surgical timing, but gender and cerebral infarction may be the risk factors of mortality.

13.
Eur J Histochem ; 65(4)2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34873899

RESUMO

Osteosarcoma (OS), characterized by high morbidity and mortality, is the most common bone malignancy worldwide. MicroRNAs (miRNAs) play a crucial role in the initiation and development of OS. The purpose of this study was to investigate the roles of miR-1270 in OS. RT-qPCR and Western blot were applied to detect the mRNA and protein level, respectively. CCK-8, colony formation, and TUNEL assays were conducted to determine the cell viability, proliferation, and apoptosis of OS cells. Wound healing and transwell assay were performed to detect the migration and invasion ability of OS cells. Bioinformatics analysis and dual-luciferase reporter assay were used to predict the target genes of miR-1270. Tumor xenograft in vivo assay was carried out to determine miR-1270 effect on the tumor size, volume, and weight. In this study, miR-1270 was overexpressed in OS tissues and cells. However, miR-1270 knockdown inhibited the proliferation, migration and invasion, and promoted the OS cells' apoptosis. Mechanistically, cingulin (CGN) was predicted and proved to be a target of miR-1270 and partially alleviated the effects of miR-1270 on the proliferation, migration and invasion ability of OS cells. Taken together, knockdown of miR-1270 may inhibit the development of OS via targeting CGN. This finding may provide a novel therapeutic strategy for OS.

14.
BMC Anesthesiol ; 21(1): 309, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34879822

RESUMO

BACKGROUND: Hyperlactatemia is associated with a poor prognosis in cardiac surgery patients. This study explored the impact of target blood pressure management during cardiopulmonary bypass (CPB) on blood lactate levels after cardiac surgery. METHODS: Adult patients undergoing cardiac valve surgery between 20/1/2020 and 30/6/2020 at Shanghai Chest Hospital were enrolled. The patients were randomized into a low mean arterial pressure (L-MAP) group (target MAP between 50 and 60 mmHg) or a high mean arterial pressure (H-MAP) group (target MAP between 70 and 80 mmHg), n = 20 for each. Norepinephrine was titrated only during CPB to maintain MAP at the target level. Blood lactate levels in the two groups were detected before the operation (T0), at the end of CPB (T1), at the end of the operation (T2), 1 h after the operation (T3), 6 h after the operation (T4) and 24 h after the operation (T5). The primary outcome was the blood lactate level at the end of the operation (T2). The secondary outcomes included the blood lactate level at T1, T3, T4, and T5 and the dose of epinephrine and dopamine within 24 h after the operation, time to extubation, length of stay in the ICU, incidence of readmission within 30 days, and mortality within 1 year. RESULTS: Forty patents were enrolled and analyzed in the study. The lactate level in the H-MAP group was significantly lower than that in the L-MAP group at the end of the operation (3.1 [IQR 2.1, 5.0] vs. 2.1 [IQR 1.7, 2.9], P = 0.008) and at the end of CPB and 1 hour after surgery. The dose of epinephrine within 24 h after the operation, time to extubation and length of stay in the ICU in the L-MAP group were significantly higher than those in the H-MAP group. CONCLUSIONS: Maintaining a relatively higher MAP during CPB deceased the blood lactate level at the end of surgery, reduced epinephrine consumption, and shortened the time to extubation and length of stay in the ICU after surgery. TRIAL REGISTRATION: This single-center, prospective, RCT has completed the registration of the Chinese Clinical Trial Center at 8/1/2020 with the registration number ChiCTR2000028941 . It was conducted from 20/1/2020 to 30/6/2020 as a single, blinded trial in Shanghai Chest Hospital.

15.
Int J Pharm ; : 121351, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34883206

RESUMO

Disulfiram (DSF) has a copper (II)-potentiated anticancer activity in various cancers. Synchronous delivery of DSF and cupric ions to tumor tissues is challenging but holds great potential in improving antitumor outcomes and promoting clinical translation. Herein, we reported a disulfiram prodrug (DQ)-loaded and glucose oxidase (GOD) conjugated copper (II)-based nanoscale metal-organic framework (MOF), MPDG, for tumor-specific, enhanced chemo-chemodynamic therapy. Copper MOF, MOF-199, played a dual role of drug nanocarrier of DQ and copper ion reservoir for sufficient generation of copper (II) diethylthiocarbamate (Cu(DTC)2), a complex of DSF and Cu2+. GOD improved the stability of Cu(II) nano-depot and enabled catalytic generation of H2O2 in response to high concentration of glucose in cancer cells. The catalytically generating and endogenous H2O2 boosted the activation of encapsulated H2O2-activatable prodrug DQ to generate highly cytotoxic Cu(CDTC)2in situ for tumor-specific chemotherapy. Meanwhile, the elevated H2O2 significantly augmented the production of ∙OH for enhanced chemodynamic therapy. The self-activated amplified chemo-chemodynamic therapy nanosystem led to a significantly enhanced inhibition of 4T1 murine breast cancer cells (half inhibitory concentration reduced from 5 µg/mL to 0.8 µg/mL) in the presence of glucose. The in vivo study verified that MPDG showed the highest tumor inhibition rate of 86.2% and negligible toxicity to blood and main organs. Overall, this study provides a novel disulfiram prodrug/Cu2+ co-delivery strategy for enhanced and selective cancer treatment.

16.
ACS Chem Biol ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34860497

RESUMO

Histone deacetylase 6 (HDAC6) is a potential therapeutic target for treating several diseases. A recent study revealed that HDAC6 is important for NLRP3 inflammasome activation, suggesting that targeting HDAC6 could be useful for treating many inflammatory disorders. Using the proteolysis targeting chimera (PROTAC) strategy, we herein report an HDAC6 degrader with low cytotoxicity by tethering a selective HDAC6 inhibitor derived from a natural product, indirubin, with pomalidomide, a CRBN E3 ligand. Our HDAC6 degrader efficiently and selectively decreased HDAC6 levels in several cell lines, including activated THP-1 cells. Application of this HDAC6 degrader attenuated NLRP3 inflammasome activation in LPS-induced mice, which for the first time demonstrates that HDAC6 PROTAC could be a novel strategy to treat NLRP3 inflammasome-associated diseases.

17.
Chem Commun (Camb) ; 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34889325

RESUMO

A series of new BODIPY-tetrazine derivatives have been developed with a twist intramolecular charge transfer (TICT) state in polar solvents, which is an electron transfer process that occurs upon photoexcitation in a molecule that usually consists of an electron donor and acceptor linked by a single bond. Among them, the BODIPY-tetrazine derivative 6i was stable towards long-term storage and red-emitting with excellent performance, and was further used to image trans-cyclooctene-labeled lipids in mammalian cells and cyclopropene-labeled sugars in cancer cells under no-wash conditions.

18.
Neuroimage Clin ; 33: 102903, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34864288

RESUMO

Non-invasive MEG/EEG source imaging provides valuable information about the epileptogenic brain areas which can be used to aid presurgical planning in focal epilepsy patients suffering from drug-resistant seizures. However, the source extent estimation for electrophysiological source imaging remains to be a challenge and is usually largely dependent on subjective choice. Our recently developed algorithm, fast spatiotemporal iteratively reweighted edge sparsity minimization (FAST-IRES) strategy, has been shown to objectively estimate extended sources from EEG recording, while it has not been applied to MEG recordings. In this work, through extensive numerical experiments and real data analysis in a group of focal drug-resistant epilepsy patients' interictal spikes, we demonstrated the ability of FAST-IRES algorithm to image the location and extent of underlying epilepsy sources from MEG measurements. Our results indicate the merits of FAST-IRES in imaging the location and extent of epilepsy sources for pre-surgical evaluation from MEG measurements.

19.
Syst Biol Reprod Med ; : 1-9, 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34913786

RESUMO

This study describes a successful case of preimplantation genetic testing for the monogenic disease (PGT-M) of methylmalonic acidemia (MMA). To avoid the transmission of pathogenic mutations and unnecessary pregnancy termination we applied next-generation sequencing (NGS)-based haplotyping on a couple with a previously deceased MMA offspring. After embryo preparation, all samples were amplified successfully by whole genome amplification. We performed preimplantation genetic testing for aneuploidy (PGT-A) to determine the copy number of embryos' chromosomes. PGT-A results showed five blastocysts (2, 11, 14, 15 and 16) with balanced chromosomes (46, XN). Two techniques were used for PGT-M. Sanger sequencing was used to detect the mutations of MMUT gene directly, and NGS-based single nucleotide polymorphism (SNP) haplotyping was used to distinguish the chromosomes that carried the mutation. Sanger sequencing and NGS-based SNP haplotyping confirmed that samples 2 and 15 carried c.730insTT, samples 11 and 15 carried c.1105 C > T and samples 14 and 16 did not carry any mutation. Thus, blastocyst 14 was transferred into the mother's uterus. After prenatal diagnosis at 18 weeks of gestation, a healthy infant without MMUT mutation was born at full term. This study highlights the efficiency of NGS-based SNP haplotyping for PGT-M of MMA.Abbreviations: MMA: methylmalonic acidemia; MMUT: methylmalonyl-CoA mutase; PGT-M: preimplantation genetic testing for monogenic disease; PGD: preimplantation genetic diagnosis; IVF: in vitro fertilization; ADO: allele dropout; WGA: whole genome amplification; SNP: single nucleotide polymorphism; NGS: next-generation sequencing; PND: prenatal diagnosis; ICSI: intracytoplasmic sperm injection; TE: trophectoderm; DOP-PCR: degenerate oligonucleotide primed polymerase chain reaction; PGT-A: preimplantation genetic testing for aneuploidy; PCR: polymerase chain reaction.

20.
Vet Med Sci ; 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34914190

RESUMO

Arctigenin (ACT) is a novel anti-inflammatory lignan extracted from Arctium lappa L, a herb commonly used in traditional Chinese herbal medicine. In this study, we investigated the molecular mechanism whereby ACT inhibits PCV2 infection-induced proinflammatory cytokine production in vitro and in vivo. We observed that in PCV2 infection+ACT treated PK-15 cells, proinflammatory cytokine production was significantly reduced, compared to the PCV2-infected cells. The transfection and luciferase reporter assay confirmed that ACT suppressed NF-κB signalling pathway activation following PCV2 infection in PK-15 cells. Furthermore, western blotting demonstrated that ACT suppressed the NF-κB signal pathway in PCV2 infection-stimulated PK-15 cells by inhibiting the translocation of p65 from the cytoplasm to the nucleus and IκBα phosphorylation. BALB/c mice were used as a model to evaluate the anti-inflammatory effect of ACT in vivo. We found that the BALB/c mice inoculated with PCV2 infection + ACT treated showed a significant reduction of proinflammatory cytokine production in serum, lung and spleen tissue, compared to the PCV2-infected mice. Western blotting confirmed that ACT suppressed the NF-κB signal pathway in PCV2-infected mice by inhibiting the translocation of p65 from the cytoplasm to the nucleus and IκBα phosphorylation in lung tissue. Our studies first demonstrate that ACT inhibits PCV2 infection-induced proinflammatory cytokine production by suppressing the phosphorylation and nuclear translocation of NF-κB in vitro and in vivo. These results will help further develop ACT as a Traditional Chinese herbal medicine remedy in the treatment of porcine circovirus-associated diseases.

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