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2.
Artigo em Inglês | MEDLINE | ID: mdl-34613377

RESUMO

OBJECTIVES: In this study, we developed an IS26-based CRISPR/Cas9 system as a proof-of-concept study to explore the potential of a re-engineered bacterial translocatable unit (TU) for curing and immunizing against the replication genes and antimicrobial resistance genes. METHODS: A series of pIS26-CRISPR/Cas9 suicide plasmids were constructed, and specific guide RNAs were designed to target the replication gene of IncX4, IncI2 and IncHI2 plasmids, and the antibiotic resistance genes mcr-1, blaKPC-2 and blaNDM-5. Through conjugation and induction, the transposition efficiency and plasmid-curing efficiency in each recipient were tested. In addition, we examined the efficiency of the IS26-CRISPR/Cas9 system of cell immunity against the acquisition of the exogenous resistant plasmids by introducing this system into antimicrobial-susceptible hosts. RESULTS: This study aimed to eliminate the replication genes and antimicrobial resistance genes using pIS26-CRISPR/Cas9. Three plasmids with different replicon types, including IncX4, IncI2 and IncHI2 in three isolates, two pUC19-derived plasmids, pUC19-mcr-1 and pUC19-IS26mcr-1, in two lab strains, and two plasmids bearing blaKPC-2 and blaNDM-5 in two isolates were all successfully eliminated. Moreover, the IS26-based CRISPR/Cas9 system that remained in the plasmid-cured strains could efficiently serve as an immune system against the acquisition of the exogenous resistant plasmids. CONCLUSIONS: The IS26-based CRISPR/Cas9 system can be used to efficiently sensitize clinical Escherichia coli isolates to antibiotics in vitro. The single-guide RNAs targeted resistance genes or replication genes of specific incompatible plasmids that harboured resistance genes, providing a novel means to naturally select bacteria that cannot uptake and disseminate such genes.

3.
J Chem Inf Model ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606272

RESUMO

Hypochloric acid (HOCl) plays a vital role in the natural defense system, but abnormal levels of it can cause cell damage, accelerated human aging, and various diseases. It is of great significance to develop new probes for detecting HOCl in biosystems nondestructively and noninvasively. The purpose of this work is to explore new chemical modification strategies of two-photon excitation fluorescence (TPEF) probes to improve the poor water solubility and low efficiency in imaging applications. Nil-OH-6 has a two-photon absorption cross-section value as high as 243 GM and attains a good quantum yield of 0.49. In addition, the modification of terminal groups with different azetidine-heterospirocycles or N,N-dialkyl fused amino groups to Nile Red can effectively improve the fluorescence efficiency as well as increase the solubility to some extent. This study provides some strategies to simultaneously improve the fluorescence performance and solubility of these two-photon probes and, hence, reliable guidance and a foundation for the subsequent synthesis of TPEF probes based on Nile Red.

4.
Zhongguo Zhong Yao Za Zhi ; 46(17): 4433-4437, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34581047

RESUMO

The combination of normal-phase silica gel column chromatography, octadecyl silica(ODS) column chromatography, semi-preparative high performance liquid chromatography(HPLC), etc. was employed to isolate and purify the chemical components from Euphorbia resinifera, and 7 triterpenoids were separated from the ethanol extract of the medicinal materials. Their structures were identified by various spectroscopy methods as cycloartan-1,24-diene-3-one(1), cycloartan-1,24-diene-3-ol(2), 3ß-hydroxy-lanosta-8,24-diene-11-one(3), lnonotusane C(4), eupha-8,24-diene-3ß-ol-7,11-dione(5), eupha-24-methylene-8-ene-3ß-ol-7,11-dione(6), and eupha-8,24-diene-3ß,11ß-diol-7-one(7). Compounds 1 and 2 are new compounds, and compound 3 is obtained from nature for the first time.


Assuntos
Medicamentos de Ervas Chinesas , Euphorbia , Triterpenos , Estrutura Molecular
5.
Huan Jing Ke Xue ; 42(10): 4834-4843, 2021 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34581126

RESUMO

To reveal the speciation and pollution status of heavy metal(loid) s (HMs) in the dewatered sewage sludge(SS) of municipal wastewater treatment plants(MWTPs) in China, SS samples were collected from 40 MWTPs located in different regions of China. The total concentrations and geochemical fractions of As, Cd, Cr, Cu, Ni, Pb, and Zn in the SS samples were analyzed. The ecological risks induced by HMs in the SS were assessed based on the toxicity characteristic leaching procedure(TCLP), risk assessment code(RAC), and potential ecological risk index(RI). The median values of HMs in SS followed the order Zn > Cu > Cr > Pb > Ni > As > Cd. The general attainment rates of HMs in SS were satisfactory(>90%). As showed a generally even distribution among all the fractions; Cd and Zn mainly existed in the reducible fraction; Cr mainly occurred in the residual fraction, followed by oxidizable and reducible fractions; Cu mainly occurred in the oxidizable fraction; Ni occurred mainly as exchangeable forms; and Pb mainly occurred in the reducible and residual fractions, with its exchangeable form being the lowest fraction. According to the RAC method, the environmental risks induced by HMs in the SS followed the order Ni > As > Zn > Cd > Cu > Cr > Pb. The ecological risk of Ni was high; Zn, As, and Cd had a medium level of risk; Cr and Cu had a low level of risk; and the risk of Pb was negligible. According to the RI method, Cd and Cu showed the highest potential ecological risk, indicating that these are the primary HM pollutants in the SS. However, if the agricultural application of SS is carried out in accordance with the national standards, the overall level of risk from soil HM pollution is considered relatively low.


Assuntos
Metais Pesados , Poluentes do Solo , Agricultura , China , Monitoramento Ambiental , Metais Pesados/análise , Medição de Risco , Esgotos , Poluentes do Solo/análise
6.
Ultrasound Med Biol ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34538708

RESUMO

This study analyzed which imaging characteristics may contribute to misdiagnosis of benign and malignant thyroid nodules (TNs) through strain imaging (SI). We analyzed SI parameters and conventional ultrasound (CUS) characteristics of 264 nodules with histopathology results and we applied binary logistic regression analysis to select independent variables for incorrect SI results. The elastography imaging (EI) score and the virtual touch tissue imaging (VTI) score of malignant TNs were remarkably higher than that in benign TNs. VTI, of which the false-positive rate (FPR), the false-negative rate (FNR), and the cutoff value were 47.6% (39/82), 17.6% (32/182) and 3.5, presented higher diagnostic performance than EI. Aspect ratio (odd ratio [OR]: 14.208) and intra-nodular calcification (OR: 20.384) were significantly associated with false-positive VTI findings, while posterior acoustic feature (OR: 30.424) was significantly associated with false-negative VTI findings. Sex (OR: 0.221) and aspect ratio (OR: 0.268) were negatively associated with false-negative EI findings. In conclusion, sex and aspect ratio significantly affect the accuracy of EI results, while aspect ratio, intra-nodular calcification and posterior acoustic features notably affect the accuracy of VTI results. These CUS features of TNs should not be ignored before explaining SI examination results.

7.
Enzyme Microb Technol ; 150: 109891, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34489044

RESUMO

ß-Mannanases hydrolyze lignocellulosic biomass with the release of mannan oligosaccharides, which are considered as renewable resource in higher plants. Here, we cloned, expressed and characterized a novel endo-ß-mannanase (ManAC) from Aspergillus calidoustus. Homology alignment analysis indicated that ManAC belonged to glycosyl hydrolase (GH) 5 family members. The analysis of structural homologous model revealed that five residues, Arg116, Asn231, His305, Tyr307, and Trp370, constituted the active site of ManAC. Glu232 and Glu340, proton donor and nucleophile, formed the catalytic residues of ManAC. The recombinant ManAC exhibited maximal activity at pH 2.5 and 70 °C, and it was acid tolerant at a pH range of 2.0-6.0 and thermostable under 60 °C. Meanwhile, the activity of ManAC was not significantly affected by various metal ions, except for Mg2+ and Ag2+. The recombinant ManAC exhibited the highest ß-mannanase activity towards locust bean gum (669.7 U/mg) with the Km and Vmax values of 3.4 mg/mL and 982.4 µmol/min/mg, respectively. These thermophilic and acidophilicc characteristics is better than most extreme ß-mannanase. As the first reported mannanse from Aspergillus calidoustus (ManAC), these excellent properties of ManAC strongly promote the synthesis of mannooligosaccharides which have potential for food and feed industrial applications.


Assuntos
Aspergillus , beta-Manosidase , Aspergillus/genética , Clonagem Molecular , Oligossacarídeos , beta-Manosidase/genética
8.
Nat Biotechnol ; 39(9): 1129-1140, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504351

RESUMO

Assessing the reproducibility, accuracy and utility of massively parallel DNA sequencing platforms remains an ongoing challenge. Here the Association of Biomolecular Resource Facilities (ABRF) Next-Generation Sequencing Study benchmarks the performance of a set of sequencing instruments (HiSeq/NovaSeq/paired-end 2 × 250-bp chemistry, Ion S5/Proton, PacBio circular consensus sequencing (CCS), Oxford Nanopore Technologies PromethION/MinION, BGISEQ-500/MGISEQ-2000 and GS111) on human and bacterial reference DNA samples. Among short-read instruments, HiSeq 4000 and X10 provided the most consistent, highest genome coverage, while BGI/MGISEQ provided the lowest sequencing error rates. The long-read instrument PacBio CCS had the highest reference-based mapping rate and lowest non-mapping rate. The two long-read platforms PacBio CCS and PromethION/MinION showed the best sequence mapping in repeat-rich areas and across homopolymers. NovaSeq 6000 using 2 × 250-bp read chemistry was the most robust instrument for capturing known insertion/deletion events. This study serves as a benchmark for current genomics technologies, as well as a resource to inform experimental design and next-generation sequencing variant calling.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Sequenciamento de Nucleotídeos em Larga Escala/normas , Análise de Sequência de DNA/métodos , Análise de Sequência de DNA/normas , Pareamento Incorreto de Bases , Benchmarking , DNA/genética , DNA Bacteriano/genética , Genoma Bacteriano , Genoma Humano , Humanos
9.
Parkinsonism Relat Disord ; 91: 77-82, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34537494

RESUMO

BACKGROUND: Although single-photon emission computed tomography (SPECT/CT) could help to predetermine dystonic muscles in patients with cervical dystonia (CD), its efficacy in aiding botulinum toxin injection is undetermined. This randomized, double-blinded study aimed to assess the efficacy of SPECT/CT aided botulinum toxin injection in CD. METHODS: Patients were randomized into study group (candidate muscles selected by SPECT/CT and clinical evaluation) or control group (clinical evaluation). Follow-ups were done at two weeks (T1), one (T2), three (T3) and six months (T4). The primary outcomes included symptom improvement assessed using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui score at T2. RESULTS: A total of 122 patients were enrolled and 108 patients accomplished the study. For primary outcomes, the study group had significantly better symptom improvement at T2 (TWSTRS: ß, -4.86 [95%CI -9.40 to -0.32; P = 0.036]; Tsui: ß, -1.65 [95%CI -2.77 to -0.54; P = 0.004]). For secondary outcomes, the study group also showed better outcomes at T1 (TWSTRS: ß, -6.33 [95%CI -10.17 to -2.49; P = 0.001]; Tsui: ß, -1.42 [95%CI -2.48 to -0.37; P = 0.008]) and T3 (TWSTRS: ß, -6.05 [95%CI -11.09 to -1.01; P = 0.019]; Tsui: ß, -1.24 [95%CI -2.40 to -0.08; P = 0.037]). The interval of re-injection was significantly longer in the study group than the control group (159.1 ± 28.6 versus 141.8 ± 51.0 days, P = 0.032). CONCLUSIONS: SPECT/CT could improve the efficacy of botulinum toxin in CD. It could become a useful tool to aid botulinum toxin injection.

10.
Zhongguo Zhong Yao Za Zhi ; 46(12): 2923-2930, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467682

RESUMO

The present study determined the quantitative markers of total proanthocyanidins in the purification of the industrial waste Choerospondias axillaris pericarp based on the comparison results of high-performance liquid chromatography(HPLC) and mass spectrometry(MS) and optimized the purification process with two stable procyanidins as markers. The adsorption and desorption of five different macroporous adsorption resins, the static adsorption kinetics curve of NKA-Ⅱ resin, the maximum sample load, and the gradient elution were investigated. The UPLC-Q-TOF-MS/MS was employed for qualitative analysis of the newly-prepared total proanthocyanidins of C. axillaris pericarp. As revealed by the results, NKA-Ⅱ resin displayed strong adsorption and desorption toward total proanthocyanidins. The sample solution(50 mg·mL~(-1)) was prepared from 70% ethanol crude extract of C. axillaris pericarp dissolved in water and 7-fold BV of the sample solution was loaded, followed by static adsorption for 12 h. After 8-fold BV of distilled water and 6-fold BV of 10% ethanol were employed to remove impurities, the solution was eluted with 8-fold BV of 50% ethanol, concentrated, and dried under reduced pressure, and purified total proanthocyanidin powder was therefore obtained. Measured by vanillin-hydrochloric acid method, the purity and transfer rate of total proanthocyanidins were 47.67% and 59.92%, respectively, indicating the feasibi-lity of the optimized process. UPLC-Q-TOF-MS/MS qualitative analysis identified 16 procyanidins in C. axillaris total proanthocyanidins. The optimized purification process is simple in operation and accurate in component identification, and it can be applied to the process investigation of a class of components that are difficult to be separated and purified. It can also provide technical support and research ideas for the comprehensive utilization of industrial waste.


Assuntos
Anacardiaceae , Proantocianidinas , Adsorção , Cromatografia Líquida de Alta Pressão , Extratos Vegetais , Proantocianidinas/análise , Resinas Sintéticas , Espectrometria de Massas em Tandem
11.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3859-3864, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472260

RESUMO

This study explored the chemical constituents of the aerial part of Hypericum curvisepalum. Sixteen compounds were isolated from the 95% ethanol extract of H. curvisepalum with various chromatographic techniques, including a new prenylated phenyl polyketide, mysorenone D(1). Other compounds were mysorenone-A(2), mysorenone-C(3), mysorenone-B(4), peplidiforone A(5), 4-methoxy-3-(2-methylbut-3-en-2-yl)-6-phenyl-2H-pyran-2-one(6), hyperenone-A(7), 4-(3,3-dimethylallyl)oxy-6-phenyl-α-pyrone(8), peplidiforone B(9), elegaphenone(10), hypercohin A(11), hyperisampsin G(12), spathulenol(13), quercetin(14), ß-sitosterol(15), and ß-amyrin(16).


Assuntos
Hypericum , Benzofenonas , Quercetina
12.
Appl Microbiol Biotechnol ; 105(20): 7801-7811, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34581846

RESUMO

Quorum sensing is a mechanism that facilitates cell-to-cell communication. Through signal molecular density for signal recognition, which leads to the regulation of some physiological and biochemical functions. Gluconacetobacter xylinus CGMCC 2955, which produces bacterial cellulose (BC), synthesizes the LuxR protein belonging to the LuxI/LuxR type QS system. Here, a luxR overexpression vector was transformed into G. xylinus CGMCC 2955. The overexpression of luxR increased the yield of BC by 15.6% after 16 days static culture and reduced the cell density by 15.5% after 120-h-agitated culture. The glucose was used up by G. xylinus-pMV24-luxR at 72-h-agitated fermentation, which 12 h earlier than the wild-type (WT). The total N-acylhomoserine lactones (AHL) content of the luxR-overexpressing strain and the WT strain attained 1367.9 ± 57.86 mg/L and 842.9 ± 54.22 mg/L, respectively. The C12-HSL and C14-HSL contents of G. xylinus-pMV24-luxR were 202 ± 21.66 mg/L and 409.6 ± 0.91 mg/L, which were significantly lower than that of WT. In contrast, C6-HSL showed opposite results. The difference of AHL content proved that overexpression of luxR improved the binding of AHL and showed preference for some specific AHL. The metabolic results demonstrated that upon glucose exhaustion, the consumption of gluconic acid was promoted by luxR overexpression, and the content of D- ( +)-trehalose, an antiretrograde metabolite, increased significantly. KEY POINTS: • The overexpression of luxR increased the yield of bacterial cellulose • The content of signal molecules was significantly different • Differential metabolites were involved in multiple metabolic pathways.


Assuntos
Gluconacetobacter xylinus , Percepção de Quorum , Acil-Butirolactonas , Proteínas de Bactérias/genética , Celulose , Gluconacetobacter xylinus/genética , Transativadores/genética
13.
Cell ; 184(19): 5015-5030.e16, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34407392

RESUMO

Group 3 innate lymphoid cells (ILC3s) regulate immunity and inflammation, yet their role in cancer remains elusive. Here, we identify that colorectal cancer (CRC) manifests with altered ILC3s that are characterized by reduced frequencies, increased plasticity, and an imbalance with T cells. We evaluated the consequences of these changes in mice and determined that a dialog between ILC3s and T cells via major histocompatibility complex class II (MHCII) is necessary to support colonization with microbiota that subsequently induce type-1 immunity in the intestine and tumor microenvironment. As a result, mice lacking ILC3-specific MHCII develop invasive CRC and resistance to anti-PD-1 immunotherapy. Finally, humans with dysregulated intestinal ILC3s harbor microbiota that fail to induce type-1 immunity and immunotherapy responsiveness when transferred to mice. Collectively, these data define a protective role for ILC3s in cancer and indicate that their inherent disruption in CRC drives dysfunctional adaptive immunity, tumor progression, and immunotherapy resistance.

14.
J Food Sci ; 86(10): 4566-4576, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34431100

RESUMO

The structural andphysicochemical properties of okara protein (OP) subjected to different cavitation jet (CJ) treatment times (0-15 min) were analyzed. In this study, the microstructure and apparent morphology of OP were analyzed by Raman spectrum, fluorescence spectrum, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and atomic force microscopy (AFM). Physicochemical properties, such as emulsion ability (EA), emulsion stability index (ESI), foaming characteristics (FC), foaming stability (FS), and solubility analysis of the OPs, were characterized. Raman spectrum analysis showed that CJ treatment caused increases in the ordered structure of OPs (α-helix, ß-sheet, and ß-turn), and the disulfide bond g-g-g and g-g-t modes, while it caused a decrease in the t-g-t mode. However, the tertiary structure of OP unfolded and mostly degraded into small subunits because of higher cavitation, shear and temperature effects. AFM observation indicated that CJ resulted in a more uniform distribution of OP. Moreover, changes in the structure of OP significantly affected its functional properties. The results showed that when CJ treatment time was 10 min, the solubility of OP was up to (28.72 ± 1.26)%, the soluble protein content of okara was up to (10.44 ± 0.03) g/100 g, and interface properties were better. In summary, OP has great potential for application in the food area, especially in emulsifying agent and foam system. PRACTICAL APPLICATION: The cavitation jet technology improves the structure and physical and chemical properties of the protein extracted from soybean residue (okara) and provides new ideas for the further development and utilization of soybean residue protein, which may lead to the production of high-value-added functional ingredients from the processing of soybean byproducts.

15.
Phytomedicine ; 91: 153686, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34333330

RESUMO

BACKGROUND: A crosstalk exists between diabetes and Alzheimer's disease (AD), and diabetic encephalopathy displays AD-like disorders. Sarsasapogenin (Sar) has strong anti-inflammatory efficacy, showing neuroprotection and memory-enhancement effects. PURPOSE: This study aims to verify the ameliorative effects of Sar on diabetic encephalopathy in vivo and in vitro, and to clarify the mechanisms from attenuation of AD-like pathology. METHODS: Streptozotocin-induced type 1 diabetic rats and high glucose-cultured SH-SY5Y cells were used in this study. After Sar treatment (20 and 60 mg/kg) for consecutive 9 weeks, Morris water maze and novel object recognition tasks were performed. Hematoxylin-eosin staining was used for examining loss of neurons in CA1 area and ki67 expression for reflecting neurogenesis in DG area of hippocampus. Aß production pathway and tau phosphorylation kinase cascade were examined in these two models. RESULTS: Sar improved learning and memory ability, loss of neurons and reduction of neurogenesis in the hippocampus of diabetic rats. Moreover, Sar suppressed Aß overproduction due to up-regulation of BACE1 in protein and mRNA and tau hyperphosphorylation from inactivation of AKT/GSK-3ß cascade in the hippocampus and cerebral cortex of diabetic rats and high glucose-cultured SH-SY5Y cells, and PPARγ antagonism abolished the effects of Sar on key molecules in the two pathways. Additionally, it was found that high glucose-stimulated Aß overproduction was prior to tau hyperphosphorylation in neurons. CONCLUSION: Sar alleviated diabetic encephalopathy, which was obtained through inhibitions of Aß overproduction and tau hyperphosphorylation mediated by the activation of PPARγ signaling. Hence, Sar is a good candidate compound for AD-like disorders.


Assuntos
Doença de Alzheimer , Encefalopatias/tratamento farmacológico , Diabetes Mellitus Experimental , Espirostanos/farmacologia , Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide , Peptídeos beta-Amiloides/metabolismo , Animais , Ácido Aspártico Endopeptidases , Linhagem Celular , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Glicogênio Sintase Quinase 3 beta , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , PPAR gama , Fosforilação , Ratos , Proteínas tau/metabolismo
16.
Antimicrob Agents Chemother ; 65(10): e0105421, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34339270

RESUMO

The global spread of antimicrobial-resistant bacteria has been one of the most severe threats to public health. The emergence of the mcr-1 gene has posed a considerable threat to antimicrobial medication since it deactivates one last-resort antibiotic, colistin. There have been reports regarding the mobilization of the mcr-1 gene facilitated by ISApl1-formed transposon Tn6330 and mediated rapid dispersion among Enterobacteriaceae species. Here, we developed a CRISPR/Cas9 system flanked by ISApl1 in a suicide plasmid capable of exerting sequence-specific curing against the mcr-1-bearing plasmid and killing the strain with chromosome-borne mcr-1. The constructed ISApl1-carried CRISPR/Cas9 system either restored sensitivity to colistin in strains with plasmid-borne mcr-1 or directly eradicated the bacteria harboring chromosome-borne mcr-1 by introducing an exogenous CRISPR/Cas9 targeting the mcr-1 gene. This method is highly efficient in removing the mcr-1 gene from Escherichia coli, thereby resensitizing these strains to colistin. The further results demonstrated that it conferred the recipient bacteria with immunity against the acquisition of the exogenous mcr-1 containing the plasmid. The data from the current study highlighted the potential of the transposon-associated CRISPR/Cas9 system to serve as a therapeutic approach to control the dissemination of mcr-1 resistance among clinical pathogens.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Antibacterianos/farmacologia , Sistemas CRISPR-Cas/genética , Cromossomos , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Humanos , Plasmídeos/genética
17.
Cardiovasc Pathol ; 56: 107381, 2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34433104

RESUMO

BACKGROUND: Cardiac fibroma (CF) is a rare tumor that has not been widely reported. This study investigated the clinical findings, histologic features, and differential diagnosis of CF. METHODS: A total of 12 CF cases were studied and reviewed using hematoxylin and eosin (H&E), special staining and immunohistochemical staining. The ALK gene was tested in 4 cases of cardiac fibroma with significant inflammatory cells. Clinicopathological data were retrospectively analyzed and followed up. RESULTS: The cases occurred in six males and six females ranging in age from 0.5 to 55 years (median, 5 years). The tumors were grossly single and solid (1-17 cm; mean 5.6 cm). The clinical signs and symptoms depended largely on the location of the tumor. Microscopically, the CFs observed were composed of monomorphic spindle cells and abundant collagen. The spindle cells demonstrated little or no atypia. The histology of CFs in infants and young children showed some differences from those in adults. Infants and young children with fibromas exhibited cellular types with more inflammatory infiltration. All tumors expressed vimentin markers. Eleven of 12 cases (91.7%) were positive for SMA by immunohistochemistry. ALK immunostaining and ALK-FISH tests showed negative results. Follow-up information was available for all patients. The mean postoperative follow-up was at 3 years (range 2 months-8.8 years). All patients were alive with no evidence of disease. CONCLUSIONS: Our study shows that CFs exhibit a wide morphological spectrum of soft tissue tumors with fibroblastic or myofibroblastic differentiation and/or components. Infants and younger pediatric patients with fibromas have tumors that are more hypercellular and more likely to be misdiagnosed with aggressive or malignant lesions than adults. Finally, the data indicate that CF exhibits benign behavior and that local resection is safe and effective.

18.
Int J Cancer ; 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398969

RESUMO

Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline pathogenic variants (PVs) in mismatch repair (MMR) genes. LS-associated endometrial cancer (LS-EC) is the most common extraintestinal sentinel cancer caused by germline PVs in MMR genes, including MLH1, MSH2, MSH6 and PMS2. The clinicopathologic features of LS-EC include early age of onset, lower body mass index (BMI), endometrioid carcinoma and lower uterine segment involvement. There has been significant progress in screening, diagnosis, surveillance, prevention and treatment of LS-EC. Many studies support universal screening for LS among patients with EC. Screening mainly involves a combination of traditional clinical criteria and molecular techniques, including MMR-immunohistochemistry (MMR-IHC), microsatellite instability (MSI) testing, MLH1 promoter methylation testing and gene sequencing. The effectiveness of endometrial biopsy and transvaginal ultrasound (TVS) for clinical monitoring of asymptomatic women with LS are uncertain yet. Preventive strategies include hysterectomy and bilateral salpingo-oophorectomy (BSO) as well as chemoprophylaxis using exogenous progestin or aspirin. Recent research has revealed the benefits of immunotherapy for LS-EC. The NCCN guidelines recommend pembrolizumab and nivolumab for treating patients with advanced or recurrent microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) EC.

19.
Int J Biol Sci ; 17(11): 2811-2825, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34345209

RESUMO

Chemotherapy plays an irreplaceable role in the treatment of GC, but currently available chemotherapeutic drugs are not ideal. The application of medicinal plants is an important direction for new drug discovery. Through drug screening of GC organoids, we determined that ailanthone has an anticancer effect on GC cells in vitro and in vivo. We also found that AIL can induce DNA damage and apoptosis in GC cells. Further transcriptome sequencing of PDX tissue indicated that AIL inhibited the expression of XRCC1, which plays an important role in DNA damage repair, and the results were also confirmed by western blotting. In addition, we found that AIL inhibited the expression of P23 and that inhibition of P23 decreased the expression of XRCC1, indicating that AIL can regulate XRCC1 via P23. The results of coimmunoprecipitation showed that AIL can inhibit the binding of P23 and XRCC1 to HSP90. These findings indicate that AIL can induce DNA damage and apoptosis in GC cells. Meanwhile, AIL can decrease XRCC1 activity by downregulating P23 expression to inhibit DNA damage repair. The present study sheds light on the potential application of new drugs isolated from natural medicinal plants for GC therapy.

20.
Sci Total Environ ; 799: 149360, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34365265

RESUMO

Tetracycline antibiotics (TCs) are massively produced and consumed in various industries resulting in large quantities of residuals in the environment. In this study, to achieve safe and efficient removal of residual TCs, a Pichia pastoris (P. pastoris) was gained to stably express glycosylated TCs degrading enzyme Tet(X) followed codon and expression parameter optimization of tet(X4). As expected, glycosylated Tet(X) still maintains efficient capacity of degrading TCs. The expressed Tet(X) maintained efficient TCs degrading ability over a pH range of 6.5 - 9.5 and temperature range of 17 - 47 °C. We tested this recombinant protein for its ability to degrade tetracycline in pond water and sewage models of tetracycline removal at starting levels of 10 mg/L substrate. 80.5 ± 3.8% and 26.2 ± 2.6% of tetracycline was degraded within 15 min in the presence of 0.2 µM Tet(X) and 50 µM NADPH, respectively. More importantly, the direct use of a Tet(X) degrading enzymes reduces the risk of gene transmission during degradation. Thus, the Tet(X) degrading enzyme expressed by P. pastoris is an effective and safe method for treating intractable TCs residues.

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