Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.480
Filtrar
1.
Bioact Mater ; 19: 282-291, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35574055

RESUMO

Acute kidney injury (AKI) leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs. Here, a series of polyvinylpyrrolidone (PVP)-curcumin nanoparticles (PCurNP) are designed to meet the renal excretion threshold (∼45 kDa), presenting a controllable delivery nanosystem for kidney targeting. Renal accumulation of the relatively small nanoparticles, 89Zr-PCurNP M10 with the diameter between 5 and 8 nm, is found to be 1.7 times and 1.8 times higher than the accumulation of 89Zr-PCurNP M29 (20-50 nm) and M40 (20-50 nm) as revealed by PET imaging. Furthermore, serum creatinine analysis, kidney tissues histology, and tubular injury scores revealed that PCurNP M10 efficiently treated cisplatin-induced AKI. Herein, PCurNP offers a novel and simple strategy for precise PET image-guided drug delivery of renal protective materials.

2.
Int J Cardiol ; 2022 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-35705168

RESUMO

BACKGROUND: Cholesterol crystals (CCs) are regular microstructures found within the necrotic core of atherosclerotic plaques and have been hypothesized to be related to plaque destabilization. We attempted to investigate the potential association between CCs and non-culprit plaque vulnerability in patients with ST-segment elevated myocardial infarction (STEMI) and study morphological features of CCs in ruptured non-culprit plaques. METHODS: A total of 261 patients with ST-segment elevation myocardial infarction who underwent 3-vessel optical coherence tomography (OCT) imaging were included. Non-culprit plaques were divided into two groups according to the presence or absence of CCs in the plaque to compare the morphological characteristics of the plaques. The differences in parameters of the non-culprit plaque CCs were explored between ruptured plaques and unruptured plaques. RESULTS: Totally, 530 non-culprit plaques (29 ruptured plaques and 501 unruptured plaques) were identified by OCT. The incidence of CCs was 21.1%. Compared with non-culprit plaques without CCs, those with CCs had a larger lipid burden. Macrophages (p < 0.001) and spotty calcification (p = 0.002) were more frequently observed in non-culprit plaques with CCs. The frequency of CCs was significantly higher (p = 0.001) and the CCs were larger (p = 0.046) and more superficial (p = 0.005) in ruptured non-culprit plaques than in unruptured non-culprit plaques. The maximum lipid arc and fibrous cap thickness were independent predictors of plaque rupture, but the presence of CCs was not. CONCLUSIONS: Non-culprit plaques with CCs have more vulnerable features. CCs are more frequently found in ruptured non-culprit plaques and larger and more superficial CCs are associated with plaque rupture.

3.
Front Cardiovasc Med ; 9: 865615, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35647085

RESUMO

Background: The differentiation between hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) is challenging due to similar myocardial hypertrophic phenotype. The purpose of this study is to evaluate the feasibility of cardiovascular magnetic resonance feature tracking (CMR-FT) and late gadolinium enhancement (LGE) to distinguish between HCM and HHD and the potential relationship between myocardial strain and cardiac functional parameters. Methods: One hundred and seventy subjects (57 HCM, 45 HHD, and 68 controls) underwent 3.0 T CMR, including steady-state free precession cines and LGE images. Global and segmental (basal, mid, and apical) analyses of myocardial radial, circumferential, longitudinal strain, and left ventricular (LV) torsion, as well as global and 16 segments of LGE were assessed. The multivariate analysis was used to predict the diagnostic ability by combining comprehensive myocardial strain parameters and LGE. Results: Global radial strain (GRS), global circumferential strain (GCS), and LV torsion were significantly higher in the HCM group than in the HHD group (GRS, 21.18 ± 7.52 vs. 14.56 ± 7.46%; GCS, -13.34 ± 3.52 vs. -10.11 ± 4.13%; torsion, 1.79 ± 0.69 vs. 1.23 ± 0.65 deg/cm, all P < 0.001). A similar trend was also seen in the corresponding strain rate. As for segmental strain analysis, basal radial strain (BRS), basal circumferential strain (BCS), basal longitudinal strain (BLS), mid-radial strain (MRS), and mid-circumferential strain (MCS) were higher in the HCM group than in the HHD group (all P < 0.001). The receiver operating characteristic (ROC) results showed that the area under the curve (AUC) of LGE in the mid-interventricular septum (mIVS) was the highest among global and segmental LGE analyses. On the multivariate regression analysis, a combined model of LGE (mIVS) with GRS obtained the highest AUC value, which was 0.835 with 88.89% sensitivity and 70.18% specificity, respectively. In addition, for patients with HCM, GRS, GCS, and global longitudinal strain had correlations with LV ejection fraction (LVEF), maximum interventricular septum thickness (IVST max), and left ventricular mass index (LVMi). Torsion was mildly associated with LVEF. Conclusion: CMR-FT-derived myocardial strain and torsion provided valuable methods for evaluation of HCM and HHD. In addition, the combination of GRS and LGE (mIVS) achieved the highest diagnostic value.

4.
Ann Med ; 54(1): 1657-1666, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35703920

RESUMO

BACKGROUND: The epidemic of type 2 diabetes mellitus (T2DM) poses a great challenge to pulmonary tuberculosis (PTB) control. However, the incidence and prevalence of PTB among T2DM patients has not been fully determined. This meta-analysis aimed to provide the estimation on the global incidence and prevalence of PTB among T2DM patients (T2DM-PTB). METHODS: Online databases including Web of Science, PubMed, China National Knowledge Infrastructure and Cochrane Library were searched for all relevant studies that reported the incidence or prevalence of T2DM-PTB through 31 January 2022. Pooled incidence and prevalence of T2DM-PTB with 95% confidence interval (CI) was estimated by the random-effect model. All statistical analyses were performed using R software. RESULTS: A total of 24 studies (14 cohort studies, 10 cross-sectional studies) were included. The pooled incidence and prevalence of T2DM-PTB were 129.89 per 100,000 person-years (95% confidence interval (CI): 97.55-172.95) and 511.19 per 100,000 (95% CI: 375.94-695.09), respectively. Subgroup analyses identified that the incidence of T2DM-PTB was significantly higher in Asia (187.20 per 100,000 person-years, 95% CI: 147.76-237.17), in countries with a high TB burden (172.04 per 100,000 person-years, 95% CI: 122.98-240.68) and in studies whose data collection ended before 2011 (219.81 per 100,000 person-years, 95% CI: 176.15-274.28), but lower in studies using International Classification of Diseases-10 codes (73.75 per 100,000 person-years, 95% CI: 40.92-132.91). The prevalence of T2DM-PTB was significantly higher in countries with a high TB burden (692.15 per 100,000, 95% CI: 468.75-1022.04), but lower in Europe (105.01 per 100,000, 95% CI: 72.55-151.98). CONCLUSIONS: This systematic review and meta-analysis suggests high global incidence and prevalence of PTB among T2DM patients, underlining the necessity of more preventive interventions among T2DM patients especially in countries with a high TB-burden. Key messagesA total of 24 studies (14 cohort studies, 10 cross-sectional studies) containing 2,569,451 T2DM patients were included in this meta-analysis.The pooled incidence and prevalence of T2DM-PTB are 129.89 per 100,000 person-years (95% CI: 97.55-172.95) and 511.19 per 100,000 (95% CI: 375.94-695.09) respectively.The incidence of T2DM-PTB was significantly higher in Asia, in countries with a high TB burden and in studies whose data collection ended before 2011, but lower in studies using International Classification of Diseases-10 codes.The prevalence of T2DM-PTB was significantly higher in countries with a high TB-burden, but lower in Europe.


Assuntos
Diabetes Mellitus Tipo 2 , Tuberculose Pulmonar , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Incidência , Prevalência , Tuberculose Pulmonar/epidemiologia
5.
Oxid Med Cell Longev ; 2022: 7043883, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35656023

RESUMO

Methylmalonic acid (MMA) can act as a diagnosis of hereditary methylmalonic acidemia and assess the status of vitamin B12. Moreover, as a new potential biomarker, it has been widely reported to be associated with the progression and prognosis of chronic diseases such as cardiovascular events, renal insufficiency, cognitive impairment, and cancer. MMA accumulation may cause oxidative stress and impair mitochondrial function, disrupt cellular energy metabolism, and trigger cell death. This review primarily focuses on the mechanisms and epidemiology or progression in the clinical study on MMA.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Ácido Metilmalônico , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Humanos , Ácido Metilmalônico/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo , Deficiência de Vitamina B 12
6.
J Hazard Mater ; 437: 129375, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35724616

RESUMO

Shallow lakes and ponds, providing essential ecological and environmental services, are simultaneously disrupted by various pollutants of emerging concern (PECs). As a group of PECs, microplastics (MPs) ubiquitously found in freshwater are toxic to a huge variety of organisms. However, the consequence of secondary factors such as food quantity determining MPs toxicity, and the corresponding water safety risks await assessment is still poorly understood. Accordingly, we investigated how MPs across three particle sizes (10, 1 and 0.07 µm) interacted with food abundance to affect survival, reproduction and population performance in the waterflea Daphnia magna. Across multiple population traits, we found that MPs toxicity on Daphnia population performance was attenuated by higher food quantity, but this attenuation size was strongly dependent on MPs size. Path analysis results showed population growth rate was mainly constrained by reduced survival rather than fecundity. Furthermore, the additive null model revealed that the interactive effects of food abundance and MPs were predominately recognized as synergism and trait dependency. The present findings underscore the importance of considering the complexity of interactions that can occur in the wild, when assessing the effects of plastics pollution on population dynamics of the basic trophic level in lakes and ponds.

7.
World J Clin Cases ; 10(13): 4301-4313, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35665108

RESUMO

BACKGROUND: Primary intracranial extraskeletal myxoid chondrosarcoma (EMC) is an extremely rare low- to intermediate-grade malignant soft tissue sarcoma, and only 15 cases have been reported in the literature. Due to its rarity, clinical data and research on this tumor type are extremely limited, the pathogenesis and histological origin are still unclear, and the diagnostic and standard clinical treatment strategies for intracranial EMC remain controversial and undefined. CASE SUMMARY: We reported a case of a 52-year-old male who was admitted to the hospital with headache and dizziness for 1 mo, and his health status deteriorated during the last week. CT of the head showed a well-defined low-density lesion situated in the left cavernous sinus. Brain magnetic resonance imaging (MRI) showed a 3.4 cm × 3.0 cm sized, well-defined, round-shaped and heterogeneously enhanced lesion located in the left cavernous sinus. The entire lesion was removed via supratentorial craniotomy and microsurgery. Postoperative pathological diagnosis indicated primary intracranial EMC. Subsequently, the patient underwent 45 Gy/15 F stereotactic radiotherapy after discharge. At present, it is 12 mo after surgery, with regular postoperative follow-up and regular MRI examinations, that there are no clinical symptoms and radiographic evidence indicating the recurrence of the tumor, and the patient has returned to normal life. CONCLUSION: Currently, the most beneficial treatment for primary intracranial EMC is gross total resection combined with postoperative radiotherapy. Long-term follow-up is also necessary for patients.

8.
Entropy (Basel) ; 24(6)2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35741565

RESUMO

Activity recognition methods often include some hyper-parameters based on experience, which greatly affects their effectiveness in activity recognition. However, the existing hyper-parameter optimization algorithms are mostly for continuous hyper-parameters, and rarely for the optimization of integer hyper-parameters and mixed hyper-parameters. To solve the problem, this paper improved the traditional cuckoo algorithm. The improved algorithm can optimize not only continuous hyper-parameters, but also integer hyper-parameters and mixed hyper-parameters. This paper validated the proposed method with the hyper-parameters in Least Squares Support Vector Machine (LS-SVM) and Long-Short-Term Memory (LSTM), and compared the activity recognition effects before and after optimization on the smart home activity recognition data set. The results show that the improved cuckoo algorithm can effectively improve the performance of the model in activity recognition.

9.
Life (Basel) ; 12(6)2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35743878

RESUMO

Epoxy resin-based sealers are commonly used for successful endodontic treatment. This study aimed to evaluate the cytotoxicity and genotoxicity of epoxy resin-based sealers under unset and set conditions. Three epoxy resin-based sealers were used: Adseal, AH Plus, and Dia-Proseal. To test cytotoxicity, an agar overlay test and a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay were performed using unset and set sealers on L929 mouse fibroblasts. The genotoxicity test of the comet assay was performed using the same cell line. Extract dilutions in the culture media were used as test materials for the MTT and comet assays. The comet tail produced by the damaged DNA was calculated by image analyses. Statistical analyses were performed using one-way analysis of variance and Tukey's post hoc test. Unset sealers did not show defined decolorized areas. Hardened specimens of resin-based sealers showed circular discolored zones in the agar overlay test. Dia-Proseal was the least cytotoxic after hardening. These results were confirmed in the MTT assay. Cell viability was significantly higher in cells treated with hardened sealers in both groups than that in cells treated with freshly mixed sealers in the MTT assay. Unset AH Plus® and Dia-Proseal™ significantly increased cell viability with decreasing dilution. Adseal™ was the least cytotoxic. Freshly mixed Adseal™ was more genotoxic when freshly mixed than when set. Unset epoxy resin-based sealers were generally more cytotoxic and genotoxic than set materials. Cytotoxicity does not always match the genotoxicity results; therefore, various test tools are required to test toxicity. It is necessary to properly evaluate the toxic effects to establish a biocompatibility test that mimics clinical conditions.

10.
Materials (Basel) ; 15(12)2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35744325

RESUMO

Particle-reinforced composites are widely applied as nuclear radiation shielding materials for their excellent comprehensive properties. The work aimed to calculate the influence of the functional reinforced particles spatial arrangement on the neutron shielding performance of composites and attempted to explain the influence mechanism by investigating the neutron flux distribution in the materials. Firstly, four suitable physical models were established based on the Monte Carlo Particle Transport Program (MCNP) and mathematical software MATLAB, namely the RSA (Random Sequential Adsorption) Model with particles random arrangement and FCC Model, BCC Model and Staggered Arrangement Model (SA Model) with particle periodic arrangements. Later, based on these four physical models, the neutron transmittance of two kinds of typical B4C reinforced composites, 316 stainless steel matrix composite and polyethylene matrix composite, were calculated under different energy neutrons sources (0.0253 eV, 50 eV, 50 keV, fission spectrum, 241Am-Be spectrum and 14.1 MeV) and the neutron flux distribution in the 316 stainless steel composite was also analyzed under 0.0253 eV neutron and fission neutron sources. The results indicated that the spatial arrangement of B4C has an impact on the neutrons shielding performance of the composite and the influence changes with neutron energy and B4C content. It can be concluded that the RSA model and the periodic arrangement models can be used in different calculation cases in the future.

11.
Molecules ; 27(12)2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35744861

RESUMO

Naringenin (NRG) is a natural compound with several biological activities; however, its bioavailability is limited owing to poor aqueous solubility. In this study, NRG nanoparticles (NPs) were prepared using the wet media milling method. To obtain NRG NPs with a small particle size and high drug-loading content, the preparation conditions, including stirring time, temperature, stirring speed, and milling media amount, were optimized. The NRG (30 mg) and D-α-tocopherol polyethylene glycol succinate (10 mg) were wet-milled in deionized water (2 mL) with 10 g of zirconia beads via stirring at 50 °C for 2 h at a stirring speed of 300 rpm. As a result, the NRG NPs, with sheet-like morphology and a diameter of approximately 182.2 nm, were successfully prepared. The NRG NPs were stable in the gastrointestinal system and were released effectively after entering the blood circulation. In vivo experiments indicated that the NRG NPs have good antitussive effects. The cough inhibition rate after the administration of the NRG NPs was 66.7%, cough frequency was three times lower, and the potential period was 1.8 times longer than that in the blank model group. In addition, the enzyme biomarkers and histological analysis results revealed that the NRG NPs can effectively regulate the inflammatory and oxidative stress response. In conclusion, the NRG NPs exhibited good oral bioavailability and promoted antitussive and anti-inflammatory effects.

12.
Polymers (Basel) ; 14(12)2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35745892

RESUMO

The development of direct pulp-capping materials with favorable biological and structural properties is an important goal in restorative dentistry. Fucoidan is a sulfated, fucose-containing polysaccharide obtained from brown seaweed, with a wide range of applications; however, its use as a direct pulp-capping material has not been examined. This study aimed to evaluate the mechanical, physical, and biological effects of fucoidan combined with conventional mineral trioxide aggregate (MTA) for direct pulp capping. The capping materials were created using Portland cement (80 wt%) and zirconium oxide (20 wt%) as base components, compared with base components plus 5 wt% fucoidan (PZF5) and base components plus 10 wt% fucoidan (PZF10). The initial and final setting time, compressive strength, chemical components, cell viability, adhesion, migration, osteogenesis, and gene expression were analyzed. Fucoidan significantly reduced the initial and final setting time, regardless of quantity. However, the compressive strength was lower for PZF5. Sulfur levels increased with fucoidan. The biological activity improved, especially in the PZF5 group. Cell migration, Alizarin Red S staining, and alkaline phosphatase activity were upregulated in the PZF5 group. Fucoidan is a useful regenerative additive for conventional pulp-capping materials because it reduces the setting time and improves cell migration and osteogenic ability.

13.
Phytochemistry ; 201: 113258, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35654136

RESUMO

Six undescribed abietane-type diterpenoids (tripterydinoids A-F) and five undescribed oleanane-type triterpenoids (tripterytrinoids A-E) were obtained and determined from the stem and branch of Tripterygium wilfordii Hook. f. (Celastraceae). Tripterydinoids A-C possessed the abietane-type diterpenoid skeleton with rare 8, 9-epoxy ring. The structures of undescribed compounds were established by extensive spectroscopic studies [HRESIMS, 1D/2D-NMR and electronic circular dichroism (ECD) calculation]. The absolute configurations of tripterydinoids A, B, E and tripterytrinoid A were defined by X-ray crystallographic analyses. Bioactivity screening indicated that tripterydinoids A-C exhibited potent inhibitory effects against NO release in LPS-activated RAW 264.7 macrophages with IC50 values of 6.93, 4.46 and 2.98 µM, respectively. Meanwhile, tripterydinoids A-D and tripterytrinoids B, C showed moderate and selective cytotoxicities against five human tumor cell lines (A375, Huh7, MCF-7, HCT-116 and NCI-H460).

14.
Polymers (Basel) ; 14(11)2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35683914

RESUMO

Poly(amino acids) have advanced characteristics, including unique secondary structure, enzyme degradability, good biocompatibility, and stimuli responsibility, and are suitable as drug delivery nanocarriers for tumor therapy. The isoform structure of poly(amino acids) plays an important role in their antitumor efficacy and should be researched in detail. In this study, two kinds of pH-sensitive isoforms, including α-poly(glutamic acid) (α-PGA) and γ-PGA, were selected and used as nanocarriers to prepare a nanodrug delivery system. According to the preparation results, α-PGA can be used as an ideal drug carrier. Selecting doxorubicin (DOX) as the model drug, an α-PGA/DOX nanoparticle (α-PGA/DOX NPs) with a particle size of 110.4 nm was prepared, and the drug-loading content was 66.2%. α-PGA/DOX NPs presented obvious sustained and pH-dependent release characteristics. The IC50 value of α-PGA/DOX NPs was 1.06 ± 0.77 µg mL-1, decreasing by approximately 8.5 fold in vitro against 4T1 cells after incubation for 48 h. Moreover, α-PGA/DOX NPs enhanced antitumor efficacy in vivo, the tumor inhibition rate was 67.4%, increasing 1.5 fold over DOX injection. α-PGA/DOX NPs also reduced the systemic toxicity and cardiotoxicity of DOX. In sum, α-PGA is a biosafe nanodrug delivery carrier with potential clinical application prospects.

15.
Chin J Cancer Res ; 34(2): 95-108, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35685992

RESUMO

Objective: Emerging studies have demonstrated the promising clinical value of circulating tumor cells (CTCs) for diagnosis, disease assessment, treatment monitoring and prognosis in epithelial ovarian cancer. However, the clinical application of CTC remains restricted due to diverse detection techniques with variable sensitivity and specificity and a lack of common standards. Methods: We enrolled 160 patients with epithelial ovarian cancer as the experimental group, and 90 patients including 50 patients with benign ovarian tumor and 40 healthy females as the control group. We enriched CTCs with immunomagnetic beads targeting two epithelial cell surface antigens (EpCAM and MUC1), and used multiple reverse transcription-polymerase chain reaction (RT-PCR) detecting three markers (EpCAM, MUC1 and WT1) for quantification. And then we used a binary logistic regression analysis and focused on EpCAM, MUC1 and WT1 to establish an optimized CTC detection model. Results: The sensitivity and specificity of the optimized model is 79.4% and 92.2%, respectively. The specificity of the CTC detection model is significantly higher than CA125 (92.2% vs. 82.2%, P=0.044), and the detection rate of CTCs was higher than the positive rate of CA125 (74.5% vs. 58.2%, P=0.069) in early-stage patients (stage I and II). The detection rate of CTCs was significantly higher in patients with ascitic volume ≥500 mL, suboptimal cytoreductive surgery and elevated serum CA125 level after 2 courses of chemotherapy (P<0.05). The detection rate of CTCEpCAM + and CTCMUC1+ was significantly higher in chemo-resistant patients (26.3% vs. 11.9%; 26.4% vs. 13.4%, P<0.05). The median progression-free survival time for CTCMUC1+ patients trended to be longer than CTCMUC1- patients, and overall survival was shorter in CTCMUC1+ patients (P=0.043). Conclusions: Our study presents an optimized detection model for CTCs, which consists of the expression levels of three markers (EpCAM, MUC1 and WT1). In comparison with CA125, our model has high specificity and demonstrates better diagnostic values, especially for early-stage ovarian cancer. Detection of CTCEpCAM+ and CTCMUC1+ had predictive value for chemotherapy resistance, and the detection of CTCMUC1+ suggested poor prognosis.

17.
EJNMMI Res ; 12(1): 35, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35695985

RESUMO

BACKGROUND: Adnectin is a protein family derived from the 10th type III domain of human fibronectin (10Fn3) with high-affinity targeting capabilities. Positron emission tomography (PET) probes derived from anti-programmed death ligand-1 (PD-L1) Adnectins, including 18F- and 68Ga-labeled BMS-986192, are recently developed for the prediction of patient response to immune checkpoint blockade. The 68Ga-labeled BMS-986192, in particular, is an attractive probe for under-developed regions due to the broader availability of 68Ga. However, the pharmacokinetics and biocompatibility of 68Ga-labeled BMS-986192 are still unknown, especially in non-human primates, impeding its further clinical translation. METHODS: We developed a variant of 68Ga-labeled BMS-986192 using 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) as the radionuclide-chelator. The resultant probe, 68Ga-NODAGA-BMS986192, was evaluated in terms of targeting specificity using a bilateral mouse tumor model inoculated with wild-type B16F10 and B16F10 transduced with human PD-L1 (hPD-L1-B16F10). The dynamic biodistribution and radiation dosimetry of this probe were also investigated in non-human primate cynomolgus. RESULTS: 68Ga-NODAGA-BMS986192 was prepared with a radiochemical purity above 99%. PET imaging with 68Ga-NODAGA-BMS986192 efficiently delineated the hPD-L1-B16F10 tumor at 1 h post-injection. The PD-L1-targeting capability of this probe was further confirmed using in vivo blocking assay and ex vivo biodistribution studies. PET dynamic imaging in both mouse and cynomolgus models revealed a rapid clearance of the probe via the renal route, which corresponded to the low background signals of the PET images. The probe also exhibited a favorable radiation dosimetry profile with a total-body effective dose of 6.34E-03 mSv/MBq in male cynomolgus. CONCLUSIONS: 68Ga-NODAGA-BMS986192 was a feasible and safe tool for the visualization of human PD-L1. Our study also provided valuable information on the potential of targeted PET imaging using Adnectin-based probes.

18.
Artigo em Inglês | MEDLINE | ID: mdl-35675665

RESUMO

BACKGROUND: The persistent trigeminal artery (PTA) is the most common remnant of primitive circulation, communicating the developing carotid and vertebrobasilar junction. PURPOSE: This study aimed to evaluate the implementation of magnetic resonance angiography for the detection of PTA and to reclassify the variations based on Weon typing. Moreover, the correlation of various Weon types with the posterior cerebral artery (PCA), Willis ring, basilar artery (BA) dysplasia, and the relationship between PTA and arteriosclerosis were analyzed. METHODS: From November 2017 to October 2019, a total of 48,184 patients underwent magnetic resonance angiography examination in our hospital, and 79 patients were diagnosed with PTA. Of these, 70 patients with complete radiological and clinical information were included in this study. RESULTS: Among the 70 patients with complete data, 27 were classified as Weon type I (38.6%), 7 as type II (10%), 14 as type III (20%), 8 as type IV (11.4%), and 3 as type V (4.3%: type Va, 1 case; type Vb, 2 cases). The remaining 11 cases were PCA with mixed blood supply, so the new type VI was divided into 3 subtypes: type VIa, type VIb, and type VIc, and each subtype of type V was further refined into 4 subtypes. There were 32 cases of PTA with BA dysplasia, including 14 with type I (51.9%), 5 with type II (71.4%), 2 with type III (14.3%), 5 with type IV (62.5%), and 6 with type VI (54.5%). Cerebral infarction was found in 55 cases (78.6%) of PTA, among which 11 had a cerebral infarction in the posterior circulation blood supply area. There were 46 cases (65.7%) accompanied by intracranial arteriosclerosis, and in 6 cases, arteriosclerosis mainly occurred in the posterior circulation. CONCLUSIONS: We redefined the classification of PTA based on Weon typing for a better understanding of clinical symptoms and surgical risks. Moreover, PTA was correlated with the fetal origin of PCA, BA dysplasia, and posterior circulation arteriosclerosis. These factors may increase the incidence of cerebral infarction in the posterior circulation blood supply area.

19.
Front Public Health ; 10: 899077, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646803

RESUMO

Streptococcal toxic shock syndrome (STSS) caused by group A streptococcus is a rare condition that rapidly developed to multiple organ failure even death. Therefore, prompt diagnosis, initiate appropriate antibiotics and other supportive treatments are critical. Here we reported a case of STSS caused by group A streptococcus infection. A healthy 39-year-old man presented a sudden pain in the left lower extremity, followed by a high fever (40.0 °C) with dizziness, nausea, and shortness of breath. Twenty-four hours before the visit, the patient showed anuria. The patient was then admitted to the intensive care unit. Blood examination revealed elevated levels of inflammatory markers and creatinine. He suffered from septic shock, dysfunction of coagulation, acute kidney dysfunction, acute respiratory distress syndrome, and acute liver function injury. The diagnosis was obtained through clinical manifestation and metagenomic next-generation sequencing (mNGS) drawn from the pustule and deep soft tissue (lower limb) samples while all bacterial cultures came back negative. The pustule mNGS report detected a total of 132 unique group A streptococcus sequence reads, representing 96.3% of microbial reads while the soft tissue mNGS report identified a total of 142474 unique group A streptococcus sequence reads, representing 100% of microbial reads. The patient was treated with aggressive fluid resuscitation, antibiotics comprising piperacillin/tazobactam and clindamycin, respiratory support, following the delayed surgical debridement. Intravenous immunoglobulin was also used for 5 days. On the 14th day after admission, he was transferred to the general ward for follow-up treatment. Our case highlighted, for the first time, the key role of mNGS in the early diagnosis of culture-negative invasive group A streptococcal infection. The case also suggested that clindamycin combined with beta-lactam antibiotics and adjunction of intravenous immunoglobulin therapy with delayed debridement performed well in the management of unstable STSS patients.


Assuntos
Choque Séptico , Infecções Estreptocócicas , Adulto , Antibacterianos/uso terapêutico , Clindamicina/uso terapêutico , Desbridamento , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Choque Séptico/diagnóstico , Choque Séptico/microbiologia , Choque Séptico/terapia , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/terapia , Streptococcus pyogenes
20.
STAR Protoc ; 3(2): 101430, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35664260

RESUMO

The adult Drosophila compound eye is an ideal in vivo model for studying biological questions. However, light microscopy of this tissue requires cumbersome embedding and sectioning. Here, we document detailed whole-mount procedures for immunolabeling the adult retina, enabling high-quality studies of fluorescent-tagged targets with straightforward preparations. We describe the steps for visualizing the nuclear lamina, membrane-associated protein, and actin-rich rhabdomere, but this robust protocol can apply to other cellular structures and target proteins. For complete details on the use and execution of this protocol, please refer to Chang et al. (2021).


Assuntos
Drosophila , Técnicas Histológicas , Actinas , Animais , Técnicas Histológicas/métodos , Microscopia , Retina/diagnóstico por imagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...