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1.
BMC Surg ; 22(1): 159, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538511

RESUMO

BACKGROUND: This study aimed to investigate the clinical features, diagnostic criteria, treatment options, and prognosis of patients with gastric schwannoma (GS). METHODS: We collected the clinical data of all patients pathologically diagnosed with GS in Zhejiang Provincial People's Hospital from May 2012 to October 2021. RESULTS: A total of 26 cases of GS were analyzed clinicopathologically, where the sizes of the tumor were found to be in the range of 1-6 cm (mean: 3.16 cm, median: 3.05 cm). A computed tomography (CT) scan analysis revealed that most masses were either moderately progressive or uniformly enhanced. According to ultrasound gastroscopy results, most of them were hypoechoic masses. There were 23 cases of surgery and three cases of endoscopic submucosal tumor dissection. Immunohistochemistry demonstrated that S100 was positive in 26 patients, immunomarker SOX10 was positive in five, whereas CD34, CD117, and SMA were negative in most patients. CK (Pan), Dog-1, and Desmin were also found negative. All 26 cases were followed up after the conclusion of the study where no evidence of recurrence or metastasis was observed. CONCLUSIONS: GS is a unique form of peripheral schwannoma. The diagnosis of this type of tumor depends on the pathology and immunohistochemistry of the individual. The key to treating this type of tumor is endoscopy and surgery. Follow up and related literature review showed that GS was a benign tumor with little possibility of malignant transformation.


Assuntos
Neoplasias do Sistema Digestório , Ressecção Endoscópica de Mucosa , Neurilemoma , Neoplasias Gástricas , Gastroscopia/métodos , Humanos , Imuno-Histoquímica , Neurilemoma/diagnóstico , Neurilemoma/cirurgia , Neoplasias Gástricas/cirurgia
2.
Front Neurol ; 13: 868652, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547381

RESUMO

Objective: This study aimed to determine the ruptured rate and hemodynamic difference between wide-neck aneurysms (WNAs) and narrow-neck aneurysms (NNAs), as well as the hemodynamic parameters of risk factors for aneurysm rupture. Methods: A total of 121 cases of intracranial aneurysms (IAs) were studied retrospectively between January 2019 and April 2021 at Renmin Hospital of Wuhan University. Intracranial aneurysms were classified into four types: ruptured wide-neck aneurysms (RWNAs), unruptured wide-neck aneurysms (UWNAs), ruptured narrow-neck aneurysms (RNNAs), and unruptured narrow-neck aneurysms (UNNAs). The Chi-square test was used to compare differences in rupture ratios. The clinical characteristics and hemodynamics were analyzed statistically to reveal the rupture risk factors. Moreover, significant parameters were subjected to binary logistic regression analysis to identify the independent predictive factors. The receiver operating characteristic (ROC) curve was performed to obtain cutoff values. Results: WNAs ruptured more frequently than NNAs (P = 0.033). Ruptured intracranial aneurysms (RIAs) were characterized by significantly higher intra-aneurysmal pressure (IAP), wall shear stress (WSS), wall shear stress gradient (WSSG), and lower normalized wall shear stress (NWSS) than unruptured intracranial aneurysms (UIAs). RWNAs had higher IAP, WSS, and lower NWSS than UWNAs (P < 0.05). RNNAs had higher IAP, Streamwise WSSG and lower NWSS compared to UNNAs (P < 0.05). Binary logistic regression revealed that IAP and WSS were independent predictive risk factors for WNAs rupture, with cut-off values of 405.5 and 6.66 Pa, respectively. Also, IAP was an independent predictive risk factor for NNA rupture, with a cut-off value of 255.3 Pa. Conclusions: Wide-neck aneurysms and narrow-neck aneurysms have diverse hemodynamics, which prompts a higher rupture ratio for WNAs. IAP could characterize the rupture risk in both WNAs and NNAs independently, but WSS could only predict the rupture risk in WNAs. This research might assist neurosurgeons with fostering a more sensible strategy for the treatment of IAs.

3.
ACS Omega ; 7(16): 14317-14331, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35573216

RESUMO

The mechanical and creep properties of shale strongly influence artificial hydraulic fracturing, wellbore stability, and the evaluation of reservoir performance in shale gas exploration. This study characterized these mechanical and creep properties at the microscale through nanoindentation tests and evaluated their dependence on the indentation test parameters, specifically, the indentation load and the loading strain rate. The mechanical parameters (the Young's modulus and hardness) of shale were strongly influenced by the magnitude of an indentation load (2-400 mN). Both parameters decreased sharply as the load increased from 2 to 200 mN; they then remained relatively stable at loads of 200-400 mN, suggesting that large indentation loads (200-400 mN) can be used to detect the mechanical responses of bulk shale. In contrast, both parameters increased slightly as the loading strain rate increased from 0.005 to 0.1 s-1. The indentation creep (C IT), related to creep behavior, and the creep strain rate sensitivity (m), related to the creep mechanism of shale, both increased with increasing the indentation load, whereas they decreased with increasing the loading strain rate. This demonstrates that increasing the load or decreasing the loading strain rate can increase creep deformation in shale during nanoindentation creep testing. The values of m varied from 0.040 to 0.124 under different loading conditions, suggesting that dislocation power-law creep may be the main mechanism controlling creep in shale. This study standardizes the testing parameters for the characterization of the mechanical properties of shale by nanoindentation testing and also advances our understanding of the deformation mechanisms of shale at the microscale.

4.
Proc Natl Acad Sci U S A ; 119(20): e2122952119, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35561215

RESUMO

SignificanceQuantum anomalous Hall effect (QAHE) and magnetic skyrmion (SK), as two typical topological states in momentum (K) and real (R) spaces, attract much interest in condensed matter physics. However, the interplay between these two states remains to be explored. We propose that the interplay between QAHE and SK may generate an RK joint topological skyrmion (RK-SK), characterized by the SK surrounded by nontrivial chiral boundary states (CBSs). Furthermore, the emerging external field-tunable CBS in RK-SK could create additional degrees of freedom for SK manipulations, beyond the traditional SK. Meanwhile, external field can realize a rare topological phase transition between K and R spaces. Our work opens avenues for exploring unconventional quantum states and topological phase transitions in different spaces.

5.
BMC Cardiovasc Disord ; 22(1): 134, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361126

RESUMO

INTRODUCTION: Fibrosing mediastinitis (FM) complicated with pulmonary hypertension (PH) has been considered as an important cause of morbidity and mortality. This study was designed to observe the possible effects of abnormal hemodynamics on patients by conducting a between-group comparison according to the presence of markedly increased systolic pulmonary arterial pressure (SPAP), so as to provide more information for clinical management. MATERIALS AND METHODS: Fifty-one patients with clinically diagnosed FM were divided in two groups (SPAP < 50 mmHg group; SPAP ≥ 50 mmHg group) and retrospectively included in the study. Data mainly including demographic factors, echocardiographic data, results of right heart catheter and computed tomography (CT) examination were retrieved from the medical database. Echocardiographic parameters pre- and post- balloon pulmonary angioplasty (BPA) treatment were also collected in 8 patients. RESULTS: Significant changes in cardiac structure, hemodynamics and cardiac function were detected in patients complicated with markedly increased SPAP. Patients in the SPAP ≥ 50 mmHg group had increased right heart diameter, right heart ratio and velocity of tricuspid regurgitation (VTR) (p < 0.05). Deteriorated right heart function was also observed. There was no significant difference in CT findings between the two groups, except that more patients in the SPAP ≥ 50 mmHg group had pleural effusion (p < 0.05). After primary BPA in 8 patients, improvement in the right atrium proportion was observed. CONCLUSIONS: Changes due to significantly increased SPAP in patients with FM include adverse structure and function of the right heart, but differences in CT findings were not significant. Echocardiography has advantages as a noninvasive tool for the evaluation of cardiac structure, function and hemodynamics in patients with FM.


Assuntos
Pressão Arterial , Mediastinite , Humanos , Mediastinite/diagnóstico por imagem , Mediastinite/terapia , Estudos Retrospectivos , Esclerose , Sístole
6.
Se Pu ; 40(5): 409-422, 2022 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-35478000

RESUMO

To ensure the success of large-scale sporting events, prevent the contamination of food by prohibited substances, and evaluate the risk of foodborne stimulants and other hormones in food, it is necessary to establish a high-throughput, rapid, and accurate detection method for foodborne stimulants and other hormones. In this study, a QuEChERS method is proposed for the simultaneous determination of 44 foodborne stimulants and 6 progestogens using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The analyzed foodborne stimulants include 19 ß2-agonists, 3 ß-blockers, 11 anabolic agents, 8 glucocorticoids, and 3 diuretics. A meat sample was crushed and homogenized, following which the internal standard was added. Subsequently, the sample was shaken and extracted with water and an acetonitrile solution containing 0.5% acetic acid, then dehydrated and centrifuged with sodium chloride and anhydrous magnesium sulfate. The supernatant was purified by PSA, C18, neutral alumina, and anhydrous magnesium sulfate. It was then dried with nitrogen and concentrated. The concentrated extracts were separated using an ACQUITY BEH C18 column (100 mm×2.1 mm, 1.7 µm) with gradient elution using 0.1% formic acid-5 mmol/L ammonium acetate solution and methanol as mobile phases. The target compounds were detected by ultra-performance liquid chromatography-tandem mass spectrometry with electrospray ionization and positive ion scanning (ESI+) in the multiple reaction monitoring (MRM) mode, and quantified by the internal standard method. The linear ranges of ß2-agonists and ß-blockers were 0.1-20 µg/L, the linear ranges of glucocorticoids were 0.5-200 µg/L, and those of the others were approximately 0.2-50 µg/L. The linear relationships of 50 compounds were good, with correlation coefficients >0.99 in the linear ranges, and limits of quantification (LOQs) in the range of 0.1-0.4 µg/kg. The recoveries of the 50 target compounds spiked in chicken, pork, beef, lamb samples at three levels ranged from 50.3% to 119.9%, while the relative standard deviations (RSDs, n=6) ranged from 0.42% to 15.1%. Nine meat samples (including 3 beef, 3 pork, 2 chicken, and duck samples) were tested by this method and the national standard method (GB/T 21981-2008). The t test was used for statistical analysis of the hydrocortisone and cortisone contents, and no significant difference was found between the results obtained by the two methods. The developed method was used to analyze 12 beef samples from a farm. In all, 4 compounds were detected, while the other 46 were not detected. The content ranges and detection rates of the compounds were as follows: hydrocortisone: 3.3-22.6 µg/kg, 100%; cortisone: 1.5-2.1 µg/kg, 67%; androstenedione: 0.7-1.2 µg/kg, 17%; and testosterone: 0.6-1.5 µg/kg, 42%. In conclusion, the proposed method is simple, accurate, and sensitive, and hence, is suitable for the detection of foodborne stimulants and progestogens in different kinds of raw meat.


Assuntos
Cortisona , Carne Vermelha , Animais , Bovinos , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Glucocorticoides , Hidrocortisona , Sulfato de Magnésio , Progestinas , Carne Vermelha/análise , Ovinos , Espectrometria de Massas em Tandem
7.
Artigo em Inglês | MEDLINE | ID: mdl-35451120

RESUMO

An optimal diet is an important factor for the proper growth and health of crustaceans. However, the regulation of antioxidant activity and non-specific immunity related to the consumption of feed additives has not been studied in RC-crayfish. Triplicate groups of 20 crayfish/tank (36.72 ± 0.70 g) fed with a basal diet and sixteen experimental diets that contained five feed additives with four grade levels (40, 160, 240 and 320 mg/kg vitamin E, 2, 4, 6 and 8 g/kg nucleotides, 2, 4, 6 and 8 g/kg Haematococcus pluvialis, 5, 10, 15 and 20 g/kg arachidonic acid and 2.5, 5, 10 and 15 g/kg yeast extract) on physiological parameters, fatty acids profile and growth of Cherax quadricarinatus for a period of 70 days by using orthogonal array method (L16 45 ). The results showed that the antioxidants activity in the haemolymph and hepatopancreas were both higher in crayfish fed with diets NO. 9 to 12 than others. Also, all the diets except diets NO. 13 to 16 showed lower free radicals contents than the control group. Similarly, significantly higher non-specific immune parameters were observed in the hepatopancreas of crayfish supplementations than those fed a control diet. Biochemical parameters related to protein profile in haemolymph increased in diets NO. 9 to 12 and then decreased in control and diets NO. 13 to 16, while the highest biochemical parameters related to lipid profile except HDL-c contents in haemolymph were observed in crayfish fed the control diet. Fatty acid composition in the hepatopancreas, muscle and ovary of RC-crayfish was significantly influenced by using the combination of Vit E, NT, H. pluvialis and YP compared to the control group. Compared to all treatments, RC-crayfish fed with diets NO. 2 and 12 had significantly stimulated higher growth performance and feed utilisation. Overall, our results suggest that diets supplemented with Vit E level of 240 mg/kg, in combination with 8 g/kg NT, 4 g/kg, H. pluvialis, 5 g/kg ARA and 10 g/kg YP are the promising treatments to increase antioxidants activity, non-specific immune response, fatty acids composition and growth of RC-crayfish. However, high dietary supplementations level can reduce antioxidants activity, immunity and inhibit growth.

8.
Plant Foods Hum Nutr ; 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35441311

RESUMO

Recently, there has been renewed interest in biorefining of agricultural onion into functional products. In this study, onion vinegar (OV) are prepared by a two-stage semi-continuous fermentation method, and its content of total flavonoids (3.01 mg/mL) and polyphenols (976.76 µg/mL) is superior to other commercial vinegars. OV possesses a high radical scavenging activity and enhances the antioxidant enzyme activities in vivo, alleviating intracellular oxidative stress in Caenorhabditis elegans. Treated by OV, the 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH·), diammonium 2,2'-azino-bis (3-ethylbenzo thiazoline-6-sulfonic acid) (ABTS+·) and 2-phenyl-4,4,5,5- tetramethylimidazoline-1-oxyl 3-Oxide (PTIO·) free radicals clearance rates are 88.76, 98.76 and 90.54%, respectively in vitro. Whereas the glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) enzyme activities in C. elegans reach 271.57, 129.26, and 314.68%, respectively. Using RNAi and RT-PCR, it has been further confirmed that OV modulates transcription factor SKN-1, the nuclear factor erythroid 2-related factor 2 (Nrf2) homologous, in C. elegans, enhancing the resistance of C. elegans against sodium arsenite stress. Lifespan analysis reveals that 1 mL OV extends the maximum lifespan of the nematode to 26 days. Evidence is presented which shows that OV increases the lifespan of C. elegans by activating the SKN-1 signaling pathway. Overall, the OV is a well functional condiment, enhancing the value-added of onion.

9.
Molecules ; 27(7)2022 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-35408717

RESUMO

Listeria monocytogenes (L. monocytogenes) is an important Gram-positive food-borne pathogen that severely threatens public health. A checkerboard microdilution method was performed to evaluate the synergistic effect of lithocholic acid (LCA) with Gentamicin (Genta) against L. monocytogenes. BacLight LIVE/DEAD staining, scanning electron microscopy and biofilm inhibition assays were further used to explore the bactericidal effect and antibiofilm effect of this combination on L. monocytogenes. Additionally, the synergistic effects of LCA derivatives with Genta were also evaluated against L. monocytogenes, S.aureus and S. suis. The results indicated that a synergistic bactericidal effect was observed for the combined therapy of LCA at the concentration without affecting bacteria viability, with Genta. Additionally, LCA in combination with Genta had a synergistic effect against Gram-positive bacteria (L. monocytogenes, S. aureus and S. suis) but not against Gram-negative bacteria (E. coli, A. baumannii and Salmonella). BacLight LIVE/DEAD staining and scanning electron microscopy analysis revealed that the combination of LCA with Genta caused L. monocytogenes membrane injury, leading to bacteria death. We found that 8 µg/mL LCA treatment effectively improved the ability of Genta to eradicate L. monocytogenes biofilms. In addition, we found that chenodeoxycholic acid, as a cholic acid derivative, also improved the bactericidal effect of Genta against Gram-positive bacteria. Our results indicate that LCA represents a broad-spectrum adjuvant with Genta for infection caused by L. monocytogenes and other Gram-positive pathogens.


Assuntos
Gentamicinas , Listeria monocytogenes , Antibacterianos/farmacologia , Biofilmes , Escherichia coli , Gentamicinas/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Ácido Litocólico/farmacologia , Testes de Sensibilidade Microbiana , Staphylococcus aureus
10.
Front Genet ; 13: 836256, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432472

RESUMO

MicroRNAs (miRNAs) as small non-coding RNA transcripts bind their complementary sequences in the 3'-untranslated region (3'-UTR) of target messenger RNAs (mRNAs) to regulate their expression. It is known that miR-372 belongs to the miR-371-373 gene cluster and has been found to be abnormally expressed in a variety of cancers, but its precise mechanism in cancer remains to be discovered. In this study, miR-372-3p expression was assessed in 153 frozen tissue samples, including primary diagnosed colon cancer and matched normal and adjacent tissues, using real time quantitative polymerase chain reaction (qPCR). An analysis of qPCR data revealed a significant reduction in miR-372-3p expression (by >2-fold) in colon cancer tissues in 51.5% (34/66) of patients. Consistent with this, mimicking the increased miR-372-3p levels in SW480 colon cancer cells significantly suppressed cell growth and proliferation. Although no direct correlation was found between the low level of miR-372-3p and certain tumor-related factors, such as p53, HRE-2, PMS2, MLH1, MSH2, MSH6, HDAC4, p21, and Wee1, in colon cancer tissues, an inverse relationship between miR-372-3p and Ki67 (a marker of proliferation) or miR-372-3p and MAP3K2(MEKK2), which plays a critical role in the MAPK signaling pathways, was confirmed using tissue samples. The target relationship between miR-372-3p and MAP3K2 was verified using luciferase assays in SW480 colon cancer cells. As expected, miR-372-3p mimics significantly suppressed the luciferase activity of pMIR-luc/MAP3K2 3'-UTR in cells, suggesting that miR-372-3p modulates the expression of MAP3K2 by directly targeting its 3'-UTR. Overall, the results obtained herein suggest that miR-372-3p may function as a tumor-suppressor miRNA in colon cancer by targeting MAP3K2.

11.
Toxicol In Vitro ; 82: 105356, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35427736

RESUMO

Cigarette smoking causes skeletal muscle dysfunction and worse prognosis for patients with diverse systemic diseases. Benzo[a]pyrene (BaP), one major constituent that is inhaled during smoking, is particularly known for its ability to impair neurodevelopment, impede reproductivity, or reduce birth weight. Here, we found that BaP exposure led to the inhibition of C2C12 myoblasts differentiation in a dose-dependent manner and reduced the expression of both early and late myogenic differentiation markers. BaP exposure significantly decreased the expression of p38 mitogen-activated protein kinase (p38MAPK), but not AKT, which are both critical during myogenic differentiation. Mechanistically, BaP downregulated the expression levels of MAPK-activated protein kinase 2 (MK2) and heat shock protein 70 (Hsp70), both of which stabilize p38MAPK. Interestingly, treatment of proteasome inhibitor MG132 was able to reverse BaP-induced degradation of Hsp70/ MK2 and p38MAPK in myoblasts, implying BaP-mediated p38MAPK degradation is proteasome-dependent. Overexpression of p38MAPK also rescued the defective differentiation phenotype of C2C12 induced by BaP. Taken together, we suggest that BaP exposure induces MK2/Hsp70/p38MAPK complex degradation in C2C12 myoblasts and impairs myogenic differentiation by proteasomal-dependent mechanisms. As application of the proteasome inhibitor MG132 or overexpression of p38MAPK could reverse impaired differentiation of myoblasts induced by BaP, this may suggest potential related strategies for preventing tobacco-related skeletal muscle diseases or for respiratory rehabilitation.

12.
Acta Biomater ; 144: 109-120, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35314366

RESUMO

Programmed cell death protein 1 (PD-1)/Programmed Cell Death Ligand 1 (PD-L1) blockade immunotherapy has emerged as a promising strategy to treat both solid and hematological malignancies. Despite the considerable therapeutic effects obtained in pre-clinical and clinical studies, PD-1/PD-L1 blockade therapy is still limited by the low benefit rates and a large number of patients still do not respond to this treatment. In this study, we developed a highly efficient and cancer-specific immunogenic cell death nanoinducer for effective tumor immunotherapy. A leukocyte membrane coated poly (lactic-co-glycolic acid) encapsulating glycyrrhetinic acid (GCMNPs) was developed to enhance targeting, tumor-homing capacity, and reduce toxicity in vivo. GCMNPs could induce ferroptosis in acute myeloid leukemia and colorectal cancer cells by downregulating glutathione-dependent peroxidases 4, leading to increased lipid peroxidation levels. Moreover, GCMNPs and ferumoxytol could synergistically enhance Fe-dependent cytotoxicity through the Fenton reaction. Finally, in vivo studies showed that GCMNPs synergized with ferumoxytol and anti-PD-L1 synergistically improve T-cell immune response against leukemia and colorectal tumor. This study anticipated that the combination of glycyrrhetinic acid-based nanomaterials and ferrotherapy would provide further insights into anti-cancer immune response to PD-1/PD-L1 blockade for both solid and hematological malignancies. STATEMENT OF SIGNIFICANCE: Despite the considerable therapeutic effects obtained in pre-clinical and clinical studies, PD-1/PD-L1 blockade therapy is still limited by the low benefit rates and a large number of patients still do not respond to this treatment. We designed a glycyrrhetinic acid-based nanoplatform as a new ICD inducer (GCMNPs), with high cancer cell specificity and reduced toxicity to AML and CRC. GCMNPs cooperates with ferumoxytol to promote a Fenton reaction and induce ferroptosis. Moreover, the combination of GCMNPs and ferumoxytol enhanced the blockage of PD-1/PD-L1 to activate T cells, subsequently generating a systemic immune response in CRC and AML mouse models. This pre-clinical findings provide the proof-of-concept of combination of glycyrrhetinic acid-based nanomaterials and ferrotherapy as an "ICD nano-inducer" and immunotherapeutic agent for treating cancer.


Assuntos
Ácido Glicirretínico , Neoplasias Hematológicas , Leucemia Mieloide Aguda , Nanopartículas , Animais , Antígeno B7-H1 , Linhagem Celular Tumoral , Óxido Ferroso-Férrico , Ácido Glicirretínico/farmacologia , Humanos , Imunoterapia , Leucemia Mieloide Aguda/terapia , Camundongos , Nanopartículas/uso terapêutico , Receptor de Morte Celular Programada 1/metabolismo
13.
EBioMedicine ; 78: 103943, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35306337

RESUMO

BACKGROUND: Tigecycline is one of the few last-resort antibiotics for the treatment of carbapenem-resistant Enterobacteriaceae infection, the incidence of which has been rapidly increasing. However, the emergence and spread of tigecycline resistance genes tet(X) (including tet(X3) and tet(X4)) has largely compromised the efficient usage of tetracyclines in the clinical settings. METHODS: The synergistic effect was determined by a checkerboard minimum inhibitory concentration (MIC) assay, a time-killing assay and scanning electron microscopy (SEM) analysis. In-depth mechanisms were defined using an enzyme inhibition assay, western blotting, RT-PCR analysis, molecular dynamics (MD) simulations, biolayer interferometry (BLI) assay and metabolomics analysis. FINDINGS: Herein, our work identified a natural compound, plumbagin, as an effective broad-spectrum inhibitor of Tet(X) (also known as monooxygenase) by simultaneously inhibiting the activity and the production of Tet(X3)/Tet(X4). Plumbagin in combination with tetracyclines showed a synergistic bactericidal effect against Tet(X3)/Tet(X4)-producing bacteria. Mechanistic studies revealed that direct engagement of plumbagin with the catalytic pocket of Tet(X3)/Tet(X4) induced an alternation in its secondary structure to inhibit the activity of these monooxygenases. As a consequence, monotherapy or combination therapy with plumbagin increases the oxidative stress and metabolism in bacteria. Moreover, in a mouse systemic infection model of tet(X4)-positive E. coli, the combination of plumbagin and methacycline exhibited remarkable treatment benefits, as shown by a reduced bacterial load and the alleviation of pathological injury. INTERPRETATION: Plumbagin, as an inhibitor of Tet(X3)/Tet(X4), represents a promising lead drug, as well as an adjunct with tetracyclines to treat bacterial infections, especially for extensively drug-resistant bacteria harbouring Tet(X3)/Tet(X4). FUNDING: The National Natural Science Foundation of China.


Assuntos
Escherichia coli , Tetraciclinas , Animais , Antibacterianos/farmacologia , Bactérias/metabolismo , Escherichia coli/genética , Camundongos , Testes de Sensibilidade Microbiana , Oxigenases de Função Mista/genética , Plasmídeos , Tetraciclinas/metabolismo , Tetraciclinas/farmacologia , Tigeciclina/metabolismo , Tigeciclina/farmacologia
14.
Neurotox Res ; 40(2): 508-519, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35305248

RESUMO

Andrographolide (Andro), a diterpene of the labdane family extracted from the Asian plant Andrographis paniculata, is neuroprotective against stroke and Alzheimer's disease. However, whether Andro protected the brain against subarachnoid hemorrhage (SAH) was still unknown. Thus, we explored whether Andro attenuated blood-brain barrier (BBB) disruption and neuronal apoptosis and inhibited oxidative stress to protect the brain against SAH both in vitro and in vivo and detected underlying mechanisms of Andro's neuroprotective effects in the present study. Oxyhemoglobin (OxyHb)-treated neuronal PC12 cells were used as an in vitro model. An in vivo model was established using Sprague-Dawley rats. Moreover, we used an inhibitor of heme oxygenase-1 (HO-1) (ZnPPIX) in vitro and in vivo experiments to evaluate whether the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) cascade acted as one protective molecular mechanism of Andro against SAH. Our results revealed that, in vitro, Andro increased cell viability, inhibited apoptosis, and activated Nrf2/HO-1 cascade of neuronal PC12 cells treated with OxyHb. In vivo, Andro attenuated the neurological dysfunction, neuronal apoptosis, BBB disruption, brain edema, and oxidative stress and activated the Nrf2/HO-1 pathway. ZnPPIX reversed the effects of Andro in vitro and in vivo. Our research suggested that Andro alleviated BBB disruption, neuronal apoptosis, and oxidative stress in SAH, possibly via the Nrf2/HO-1 signaling pathway.


Assuntos
Diterpenos , Fármacos Neuroprotetores , Hemorragia Subaracnóidea , Animais , Apoptose , Barreira Hematoencefálica , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Hemorragia Subaracnóidea/tratamento farmacológico
15.
Artigo em Inglês | MEDLINE | ID: mdl-35270817

RESUMO

The current research was aimed to study the effects of different land use types (LUT) and soil depth (SD) on soil enzyme activity, metal content, and soil fungi in the karst area. Soil samples with depths of 0-20 cm and 20-40 cm were collected from different land types, including grassland, forest, Zanthoxylum planispinum land, Hylocereus spp. land and Zea mays land. The metal content and enzyme activity of the samples were determined, and the soil fungi were sequenced. The results showed that LUT had a significant effect on the contents of soil K, Mg, Fe, Cu and Cr; LUT and SD significantly affected the activities of invertase, urease, alkaline phosphatase and catalase. In addition, Shannon and Chao1 index of soil fungal community was affected by different land use types and soil depths. Ascomycota, Basidiomycota and Mortierellomycota were the dominant phyla at 0-20 cm and 20-40 cm soil depths in five different land types. Land use led to significant changes in soil fungal structure, while soil depth had no significant effect on soil fungal structure, probably because the small-scale environmental changes in karst areas were not the dominant factor in changing the structure of fungal communities. Additionally, metal element content and enzyme activity were related to different soil fungal communities. In conclusion, soil mineral elements content, enzyme activity, and soil fungal community in the karst area were strongly affected by land use types and soil depths. This study provides a theoretical basis for rational land use and ecological restoration in karst areas.


Assuntos
Micobioma , Solo , China , Ecossistema , Fungos , Minerais , Solo/química , Microbiologia do Solo
16.
J Oral Rehabil ; 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35352383

RESUMO

BACKGROUND: Dysphagia is a common complication in patients with laryngeal cancer after surgery and radiotherapy. OBJECTIVES: To explore the effect of swallowing training administered in combination with nutritional intervention on the nutritional status and quality of life of laryngeal cancer patients with dysphagia after surgery and radiotherapy. METHODS: Sixty-six patients with laryngeal cancer who developed dysphagia were randomly divided into control group and intervention group (n = 33 in each group). Patients in both groups received total laryngectomy and prophylactic radiotherapy and were provided routine health counseling and swallowing training. Patients in the intervention group were additionally provided with nutritional intervention. All patients were evaluated using video fluoroscopic swallowing examination (VFSE), Patient-Generated Subjective Global Assessment on nutritional status (PG-SGA) score, and Quality of Life Questionnaire-core 30 (QLQ-c30) score immediately after radiotherapy and 3 months later. RESULTS: Prior to swallowing training, there was no significant between-group difference with respect to VFSE evaluation, PG-SGA score, or QLQ-c30 score. Both groups showed improvement in these measures at 3 months after radiotherapy; however, the improvement in the intervention group was significantly better than that in the control group. CONCLUSIONS: Swallowing training combined with nutritional intervention can improve swallowing function, nutritional status and the quality of life of laryngeal cancer patients with dysphagia after operation and radiotherapy.

17.
Asian J Surg ; 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35346585

RESUMO

OBJECTIVE: To analyze the characteristics of ureteral stricture after ureteroscopic holmium laser lithotripsy and summarize our experience with the reconstructive strategies. METHODS: This study retrospectively reviewed 42 patients with ureteral stricture after ureteroscopic holmium laser lithotripsy between December 2009 and December 2019. Patient demographics, laboratory data, imaging studies, perioperative variables, complications, and follow-up data were recorded. Surgical success was defined as relief of symptoms, improved/stabilized hydronephrosis, and stable renal function. RESULTS: The upper, middle, and lower thirds of the ureter were affected in 27, 6, and 7 cases, respectively. Multiple ureteral strictures were found in 2 patients. The median length of the stricture was 3.5 cm (range 1-30 cm). In the upper ureteral strictures, lingual mucosal ureteroplasty (8/27, 29.6%) is the most commonly used treatment method for stricture longer than 3 cm but shorter than 6 cm, followed by appendiceal onlay ureteroplasty (5/27, 18.5%). Four lower ureteral strictures ranging from 3 to 8 cm were repaired with Boari flap. Reconstructive strategies of the middle ureteral strictures included Boari flap, appendiceal onlay ureteroplasty and ureteroureterostomy. Patients with the length of the stricture longer than 8 cm or multiple strictures underwent ileal ureter replacement. The median follow-up was 27.3 ± 17.2 months. The overall success rate was 97.6%. CONCLUSION: Upper ureter is more vulnerable in ureteroscopic holmium laser lithotripsy. Sufficient follow-up and appropriate examination are necessary for diagnosis. Different treatment strategies need to be flexibly selected according to the location and length of the injury.

18.
Materials (Basel) ; 15(6)2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35329695

RESUMO

A large amount of waste slurry is produced during the construction of pipe jacking projects. To avoid the waste slurry occupying too much urban land, it needs to be rapidly reduced. Due to the complex composition of waste slurry, the existing dewatering methods face the problem of low efficiency, and the soil after dewatering is difficult to recycle as soil materials due to high water content and low strength. There is currently a lack of research on dewatering and resource utilization of waste slurry from pipe jacking projects. In response to this problem, this paper studies the flocculation-settling characteristics of waste slurry and the mechanical properties of solidified sediment. It was found that the anionic polyacrylamide (APAM) 7126 obtained the best separation effect if the waste slurry contains bentonite, which increases the zeta potential, resulting in poor separation. Thus, FeCl3·6H2O and APAM 7126 can be used as compound conditioners. The sediment after settling was further added with 20-30% sulphate aluminum cement (SAC), and the unconfined compressive strength of the solidified sediment for 3 days could exceed 30 kPa. After flocculation-settling and solidification treatment, the waste pipe jacking slurry can be quickly dewatered into a soil material with a certain strength, which provides a reference for engineering applications.

20.
Plant Biotechnol J ; 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35247281

RESUMO

Alternative splicing (AS) is a crucial post-transcriptional regulatory mechanism in plant resistance. However, whether and how plant pathogens target splicing in their host remains mostly unknown. For example, although infection by Puccinia striiformis f. sp. tritici (Pst), a pathogenic fungus that severely affects the yield of wheat worldwide, has been shown to significantly influence the levels of alternatively spliced transcripts in the host, the mechanisms that govern this process, and its functional consequence have not been examined. Here, we identified Pst_A23 as a new Pst arginine-rich effector that localizes to host nuclear speckles, nuclear regions enriched in splicing factors. We demonstrated that transient expression of Pst_A23 suppresses plant basal defence dependent on the Pst_A23 nuclear speckle localization and that this protein plays an important role in virulence, stable silencing of which improves wheat stripe rust resistance. Remarkably, RNA-Seq data revealed that AS patterns of 588 wheat genes are altered in Pst_A23-overexpressing lines compared to control plants. To further examine the direct relationship between Pst_A23 and AS, we confirmed direct binding between two RNA motifs predicted from these altered splicing sites and Pst_A23 in vitro. The two RNA motifs we chose occur in the cis-element of TaXa21-H and TaWRKY53, and we validated that Pst_A23 overexpression results in decreased functional transcripts of TaXa21-H and TaWRKY53 while silencing of TaXa21-H and TaWRKY53 impairs wheat resistance to Pst. Overall, this represents formal evidence that plant pathogens produce 'splicing' effectors, which regulate host pre-mRNA splicing by direct engagement of the splicing sites, thereby interfering with host immunity.

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