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1.
Front Immunol ; 12: 723585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489974

RESUMO

Objectives: Our objective was to determine the antibody and cytokine profiles in different COVID-19 patients. Methods: COVID-19 patients with different clinical classifications were enrolled in this study. The level of IgG antibodies, IgA, IgM, IgE, and IgG subclasses targeting N and S proteins were tested using ELISA. Neutralizing antibody titers were determined by using a toxin neutralization assay (TNA) with live SARS-CoV-2. The concentrations of 8 cytokines, including IL-2, IL-4, IL-6, IL-10, CCL2, CXCL10, IFN-γ, and TNF-α, were measured using the Protein Sample Ella-Simple ELISA system. The differences in antibodies and cytokines between severe and moderate patients were compared by t-tests or Mann-Whitney tests. Results: A total of 79 COVID-19 patients, including 49 moderate patients and 30 severe patients, were enrolled. Compared with those in moderate patients, neutralizing antibody and IgG-S antibody titers in severe patients were significantly higher. The concentration of IgG-N antibody was significantly higher than that of IgG-S antibody in COVID-19 patients. There was a significant difference in the distribution of IgG subclass antibodies between moderate patients and severe patients. The positive ratio of anti-S protein IgG3 is significantly more than anti-N protein IgG3, while the anti-S protein IgG4 positive rate is significantly less than the anti-N protein IgG4 positive rate. IL-2 was lower in COVID-19 patients than in healthy individuals, while IL-4, IL-6, CCL2, IFN-γ, and TNF-α were higher in COVID-19 patients than in healthy individuals. IL-6 was significantly higher in severe patients than in moderate patients. The antibody level of anti-S protein was positively correlated with the titer of neutralizing antibody, but there was no relationship between cytokines and neutralizing antibody. Conclusions: Our findings show the severe COVID-19 patients' antibody levels were stronger than those of moderate patients, and a cytokine storm is associated with COVID-19 severity. There was a difference in immunoglobulin type between anti-S protein antibodies and anti-N protein antibodies in COVID-19 patients. And clarified the value of the profile in critical prevention.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/imunologia , Citocinas/sangue , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , COVID-19/classificação , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia
2.
Food Funct ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34494629

RESUMO

Currently, drug-induced liver injury caused by acetaminophen (APAP) is the second leading cause of human liver transplantation. The only clinical antidote treatment for APAP-induced liver injury is N-acetyl-L-cysteine (NAC), which has many side effects. Chitooligosaccharides (COS) are processed from naturally occurring chitin through chemical desalting and deproteinization, biological enzymatic hydrolysis and other processes. In this study, we constructed in vitro and in vivo models of APAP-induced liver injury to study COS of two molecular weights (MWs), which are COST (MW ≤ 1000 Da) and COSM (MW ≤ 3000 Da). The results showed that COST and COSM can significantly reduce the levels of serum ALT and AST and liver MDA, TNF-α, IL-1ß and IL-6, and increase the levels and activity of GSH, SOD, GSH-Px and CAT. A mechanistic study found that COST and COSM can significantly reduce the expression of liver CYP2E1, Keap1, p-ASK1/ASK1, p-MKK4/MKK4, p-JNK/JNK, Caspase-3 and Bax and increase the expression of Nrf2, HO-1, eNOS, SOD and Bcl-XL. COST and COSM can inhibit toxic APAP metabolism, inhibit oxidative damage and the apoptosis pathway, increase activation of the liver antioxidant pathway, and ultimately ameliorate APAP-induced liver oxidative damage.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34465138

RESUMO

URFs are more likely developed among HIV-1 infections through MSM because of multiple subtypes co-circulation. In this study, two novel URFs deriving from two HIV-positive subjects (HB010014, HB010063) were identified in Shijiazhuang, Hebei province, China, and two sequences formed a distinct monophyletic cluster. The further recombination analysis showed that of two new URFs were consisted of CRF01_AE and CRF07_BC. The subregion phylogenetic analysis indicated that CRF01_AE segments were traced back to cluster 4 of CRF01_AE strains, which were prevalent among HIV-1 infections through MSM in China. New URFs being developing gradually and spreading released that more and more novel recombinant strains of HIV-1 could be developed, which means that the past prevention strategies need to be adjusted.

4.
Nat Commun ; 12(1): 5255, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489438

RESUMO

Monocytes are part of the mononuclear phagocytic system. Monocytes play a central role during inflammatory conditions and a better understanding of their dynamics might open therapeutic opportunities. In the present study, we focused on the characterization and impact of monocytes on brown adipose tissue (BAT) functions during tissue remodeling. Single-cell RNA sequencing analysis of BAT immune cells uncovered a large diversity in monocyte and macrophage populations. Fate-mapping experiments demonstrated that the BAT macrophage pool requires constant replenishment from monocytes. Using a genetic model of BAT expansion, we found that brown fat monocyte numbers were selectively increased in this scenario. This observation was confirmed using a CCR2-binding radiotracer and positron emission tomography. Importantly, in line with their tissue recruitment, blood monocyte counts were decreased while bone marrow hematopoiesis was not affected. Monocyte depletion prevented brown adipose tissue expansion and altered its architecture. Podoplanin engagement is strictly required for BAT expansion. Together, these data redefine the diversity of immune cells in the BAT and emphasize the role of monocyte recruitment for tissue remodeling.


Assuntos
Tecido Adiposo Marrom/citologia , Monócitos/fisiologia , Adiponectina/genética , Tecido Adiposo Marrom/fisiologia , Animais , Diferenciação Celular/genética , Contagem de Leucócitos , Macrófagos/citologia , Macrófagos/fisiologia , Glicoproteínas de Membrana/metabolismo , Camundongos Transgênicos , Monócitos/citologia , Tomografia por Emissão de Pósitrons , Receptores CCR2/genética , Receptores CCR2/metabolismo
5.
Steroids ; 175: 108915, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34508735

RESUMO

Sepsis is a life-threatening disease characterized by acute multiple organ dysfunction and immunosuppression that is also called as immunoparalysis. Increasing evidence suggests that immunoparalysis largely contributes to the high mortality of sepsis, but the effective remedies are lacking. As an important antigen presentation molecule, human leukocyte antigen DR (HLA-DR) is remarkably down-regulated in sepsis-induced immunoparalysis, therefore, re-stimulation of HLA-DR expression is expected to be useful in reversing immunoparalysis. We previously described that ouabain, as a Na+, K+-ATPase ligand, is able to counteract immunoparalysis by regulating TH1 cytokines expression. Here, we expanded the finding that ouabain not only prevents LPS-induced down-regulation of HLA-DR on monocytes, but also transcriptionally activates HLA-DR α/ß expression mediated by CIITA4, IRF1, c-Src, and Stat1 phosphorylation. Since ouabain can improve sepsis-induced immunoparalysis by multiple mechanisms, we propose that ouabain may be a promising agent in septic therapy that deserves further investigation.

6.
Immunity ; 54(9): 2072-2088.e7, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34320366

RESUMO

Cardiac macrophages represent a heterogeneous cell population with distinct origins, dynamics, and functions. Recent studies have revealed that C-C Chemokine Receptor 2 positive (CCR2+) macrophages derived from infiltrating monocytes regulate myocardial inflammation and heart failure pathogenesis. Comparatively little is known about the functions of tissue resident (CCR2-) macrophages. Herein, we identified an essential role for CCR2- macrophages in the chronically failing heart. Depletion of CCR2- macrophages in mice with dilated cardiomyopathy accelerated mortality and impaired ventricular remodeling and coronary angiogenesis, adaptive changes necessary to maintain cardiac output in the setting of reduced cardiac contractility. Mechanistically, CCR2- macrophages interacted with neighboring cardiomyocytes via focal adhesion complexes and were activated in response to mechanical stretch through a transient receptor potential vanilloid 4 (TRPV4)-dependent pathway that controlled growth factor expression. These findings establish a role for tissue-resident macrophages in adaptive cardiac remodeling and implicate mechanical sensing in cardiac macrophage activation.

7.
Gut ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261752

RESUMO

OBJECTIVE: Fibrosis is a common feature of Crohn's disease (CD) which can involve the mesenteric fat. However, the molecular signature of this process remains unclear. Our goal was to define the transcriptional signature of mesenteric fibrosis in CD subjects and to model mesenteric fibrosis in mice to improve our understanding of CD pathogenesis. DESIGN: We performed histological and transcriptional analysis of fibrosis in CD samples. We modelled a CD-like fibrosis phenotype by performing repeated colonic biopsies in mice and analysed the model by histology, type I collagen-targeted positron emission tomography (PET) and global gene expression. We generated a gene set list of essential features of mesenteric fibrosis and compared it to mucosal biopsy datasets from inflammatory bowel disease patients to identify a refined gene set that correlated with clinical outcomes. RESULTS: Mesenteric fibrosis in CD was interconnected to areas of fibrosis in all layers of the intestine, defined as penetrating fibrosis. We found a transcriptional signature of differentially expressed genes enriched in areas of the mesenteric fat of CD subjects with high levels of fibrosis. Mice subjected to repeated colonic biopsies showed penetrating fibrosis as shown by histology, PET imaging and transcriptional analysis. Finally, we composed a composite 24-gene set list that was linked to inflammatory fibroblasts and correlated with treatment response. CONCLUSION: We linked histopathological and molecular features of CD penetrating fibrosis to a mouse model of repeated biopsy injuries. This experimental system provides an innovative approach for functional investigations of underlying profibrotic mechanisms and therapeutic concepts in CD.

8.
Nanomedicine ; 36: 102416, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34147662

RESUMO

The development of atherosclerosis therapy is hampered by the lack of molecular imaging tools to identify the relevant biomarkers and determine the dynamic variation in vivo. Here, we show that a chemokine receptor 2 (CCR2) targeted gold nanocluster conjugated with extracellular loop 1 inverso peptide (AuNC-ECL1i) determines the initiation, progression and regression of atherosclerosis in apolipoprotein E knock-out (ApoE-/-) mouse models. The CCR2 targeted 64Cu-AuNC-ECL1i reveals sensitive detection of early atherosclerotic lesions and progression of plaques in ApoE-/- mice. CCR2 targeting specificity was confirmed by the competitive receptor blocking studies. In a mouse model of aortic arch transplantation, 64Cu-AuNC-ECL1i accurately detects the regression of plaques. Human atherosclerotic tissues show high expression of CCR2 related to the status of the disease. This study confirms CCR2 as a useful marker for atherosclerosis and points to the potential of 64Cu-AuNC-ECL1i as a targeted molecular imaging probe for future clinical translation.

9.
J Cardiovasc Pharmacol ; 78(4): 572-580, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34166304

RESUMO

ABSTRACT: This study aimed to explore the correlation between QTc dispersion (QTcd) and soluble growth-stimulating gene 2 protein (sST2) after heart rate correction in patients with acute carbon monoxide poisoning heart disease. Among the 150 patients, 35 cases had severe toxic heart disease. The concentrations of sST2, cardiac troponin I, and creatine kinase-MB in the severe group began to increase from admission, 24 hours, and 2 days, respectively, and their detected values were all higher than those in the nonsevere group and the normal control group. There were statistically significant differences in sST2 and QTcd between the poisoning, nonsevere, and normal control groups before the treatment. There was a statistically significant difference between the indexes of the poisoning groups at different degrees 2 and 3 days after poisoning. Receiver operating characteristic curve analysis confirmed the sensitivity and specificity of sST2 and QTcd. The correlation analysis showed that sST2 and QTcd levels were positively correlated with the incidence of severe heart disease at admission. Generally, the combined observation of sST2 and QTcd improved the prediction sensitivity and were early predictor indexes of toxic heart disease.

10.
J Infect ; 83(1): 76-83, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33932447

RESUMO

OBJECTIVES: Shenzhen is suffering severe HIV epidemic. No systematic surveillance on high risk populations, HIV genetic diversity, transmitted drug resistance (TDR) and molecular transmission clusters (MTCs) have been reported yet. In this study, we described them based on newly diagnosed HIV positive cases from 2011 to 2018 in Shenzhen city, China. METHODS: Plasma samples of newly reported HIV positive cases in Shenzhen, China were collected from 2011 to 2018. The HIV pol gene was amplified and sequenced for subtyping, genetic characterization, TDR and phylogenetic analysis. Demographic and risk characteristics associated with transmitted drug resistance-associated mutations (TDRAMs) and MTCs were explored by using logistic regression analyses. RESULTS: 10,378 HIV pol sequences were successfully obtained from newly diagnosed patients with available background information. The most prevalent HIV-1 subtype was CRF07_BC (40.92%). CRF07_BC, CRF55_01B and URFs increased across years. Total TDR was 6.02% during 2011 to 2018. CRF01_AE, CRF08_BC, CRF55_01B and subtype B were more likely to be associated with TDRAMs than CRF07_BC. 4460 (42.98%) patients were infected with strains included in MTCs. Patients younger than 30 and over 50 years were more likely to cluster. CONCLUSIONS: The prevalence of HIV-1 drug resistance and molecular transmission clusters in Shenzhen should raise a high alert. Interventions targeting on patients with strains locating in MTCs should be considered to improve prevention effect in Shenzhen.


Assuntos
Infecções por HIV , HIV-1 , China/epidemiologia , Farmacorresistência Viral/genética , Genes pol , Genótipo , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Filogenia
11.
Artigo em Inglês | MEDLINE | ID: mdl-33926207

RESUMO

Homosexual contact is one of the main transmission routes of HIV-1 epidemic in Hebei, China. Several subtypes of HIV are prevalent simultaneously in the population, which always lead to the emergency of unique recombinant forms (URFs). In this study, we reported two new URFs from two HIV-1 positive subjects infected through homosexual contact route in Hebei, China. Phylogenetic and recombinant analyses based on the near full-length genome of the two URFs both revealed the two URFs are the second generation of recombinant strains originated from CRF01_AE and CRF07_BC. The CRF01_AE segments of two URFs located in cluster 4 of CRF01_AE strains in the phylogenetic tree. The emergence of the novel CRF01_AE/CRF07_BC recombinant forms with complicated genomic structures indicated the importance of the continuous monitoring of the HIV-1 epidemic and new URFs among the men who have sex with men populations.

12.
J Nucl Med ; 62(10): 1341-1346, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33863824

RESUMO

Inflammation and fibrosis are hallmarks of tissue repair processes and organ failure progression in cardiovascular diseases. Paradigm-shifting research on diverse immune cell populations within the cardiovascular system have enabled discovery of new biomarkers fostering development of diagnostic and therapeutic agents at the molecular level to better manage cardiovascular diseases. To date, a variety of molecular imaging agents have been developed to visualize the biomarkers expressed on immune cells and fibroblasts within their crosstalk network, which drives the pathogenesis of fibrosis triggered by both innate and adaptive immunity. Herein, key biomarkers upregulated in the immune-fibrosis axis are discussed. The promising molecular imaging agents to reveal this critical pathologic process are summarized.

13.
Mol Ecol Resour ; 21(6): 2034-2049, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33738922

RESUMO

The tea geometrid is a destructive insect pest on tea plants, which seriously affects tea production in terms of both yield and quality and causes severe economic losses. The tea geometrid also provides an important study system to address the ecological adaptive mechanisms underlying its unique host plant adaptation and protective resemblance. In this study, we fully sequenced and de novo assembled the reference genome of the tea geometrid, Ectropis grisescens, using long sequencing reads. We presented a highly continuous, near-complete genome reference (787.4 Mb; scaffold N50: 26.9 Mb), along with the annotation of 18,746 protein-coding genes and 53.3% repeat contents. Importantly, we successfully placed 97.8% of the assembly in 31 chromosomes based on Hi-C interactions and characterized the sex chromosome based on sex-biased sequencing coverage. Multiple quality-control assays and chromosome-scale synteny with the model species all supported the high quality of the presented genome reference. We focused biological annotations on gene families related to the host plant adaptation and camouflage in the tea geometrid and performed comparisons with other representative lepidopteran species. Important findings include the E. grisescens-specific expansion of CYP6 P450 genes that might be involved in metabolism of tea defensive chemicals and unexpected massive expansion of gustatory receptor gene families that suggests potential polyphagy for this tea pest. Furthermore, we developed an efficient genome editing system based on CRISPR/Cas9 technology and successfully implement mutagenesis of a Hox gene in the tea geometrid. Our study provides key genomic resources both for exploring unique mechanisms underlying the ecological adaptation of tea geometrids and for developing environment-friendly strategies for tea pest management.


Assuntos
Edição de Genes , Genoma de Inseto , Insetos/genética , Adaptação Fisiológica , Animais , Sistemas CRISPR-Cas , Cromossomos de Insetos
14.
Mech Ageing Dev ; 196: 111475, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33781783

RESUMO

Kidney ageing, which is always accompanied by renal fibrosis, drives the progression of renal fibrosis. Thioredoxin-interacting protein (TXNIP) is an endogenous suppressor of the reactive oxygen species-scavenging protein thioredoxin, which has been implicated in the ageing of some organs and is involved in renal fibrosis. However, the expression of TXNIP in ageing kidneys has not been examined, and the relationship between TXNIP and ageing-related renal fibrosis is unclear. We found that TXNIP expression was upregulated in aged mouse kidneys, and this upregulation was accompanied by ageing-related renal fibrosis phenotypes. We demonstrated that the ageing biomarkers were downregulated in TXNIP-knockout mice, and these effects resulted in the alleviation of renal fibrosis and impairments in kidney function. TXNIP overexpression in tubular cells upregulated senescence markers, promoted a profibrotic response and activated STAT3 signalling, and these parameters were inhibited by the silencing of TXNIP. Similarly, the TXNIP-mediated profibrotic response was significantly suppressed by a STAT3 inhibitor. By coimmunoprecipitation, we verified that TXNIP directly bound to STAT3, which suggested that TXNIP exacerbates renal tubular epithelial fibrosis by activating the STAT3 pathway. In summary, TXNIP plays an important role in age-related renal fibrosis and might be a therapeutic target for preventing ageing-associated renal fibrosis.

15.
Curr Med Res Opin ; 37(4): 685-691, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538197

RESUMO

OBJECTIVE: Thoracic endometriosis syndrome (TES) is a rare disease in which a functioning endometrial tissue is observed in the pleura, lung, parenchyma, airways, and/or diaphragm. The optimal management of this disease remains a matter of debate. We aimed to report TES cases and their effective hormonal treatment and management. METHODS: In this retrospective study, women presented as catamenial hemoptysis (CH) diagnosed with thoracic endometriosis were included. The main outcome of measure was cessation or recurrence of the clinical manifestations of thoracic endometriosis. RESULTS: The mean onset age of the 14 patients was 30.21 ± 5.40 years. CH was characteristic symptom of these patients. All patients underwent chest computed tomography (CT) scan during menstruation and 2 or 3 weeks after menstruation, which showed the obvious shrinking or disappearance of the lesions. All of the patients were given Gonadotropin releasing hormone agonists (GnRHa) for 3 to 6 months, eleven of them were administered with combined oral contraceptives (COC) cyclically after GnRHa. The median follow-up duration was 24 months. Hemoptysis recurrence was observed in one patient. CONCLUSIONS: CH is a rare clinical entity of thoracic endometriosis, the change of CT images during and after menstruation or the response to GnRHa were helpful for accurate diagnosis. Hormonal treatment with GnRHa followed by COCs cyclically could be employed for efficient management of thoracic endometriosis.

16.
Mol Pharm ; 18(3): 1386-1396, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33591187

RESUMO

Chemokines and chemokine receptors play an important role in the initiation and progression of atherosclerosis by mediating the trafficking of inflammatory cells. Chemokine receptor 5 (CCR5) has major implications in promoting the development of plaques to advanced stage and related vulnerability. CCR5 antagonist has demonstrated the effective inhibition of atherosclerotic progression in mice, making it a potential biomarker for atherosclerosis management. To accurately determine CCR5 in vivo, we synthesized CCR5 targeted Comb nanoparticles through a modular design and construction strategy with control over the physiochemical properties and functionalization of CCR5 targeting peptide d-Ala-peptide T-amide (DAPTA-Comb). In vivo pharmacokinetic evaluation through 64Cu radiolabeling showed extended blood circulation of 64Cu-DAPTA-Combs conjugated with 10%, 25%, and 40% DAPTA. The different organ distribution profiles of the three nanoparticles demonstrated the effect of DAPTA on not only physicochemical properties but also targeting efficiency. In vivo positron emission tomography/computed tomography (PET/CT) imaging in an apolipoprotein E knockout mouse atherosclerosis model (ApoE-/-) showed that the three 64Cu-DAPTA-Combs could sensitively and specifically detect CCR5 along the progression of atherosclerotic lesions. In an ApoE-encoding adenoviral vector (AAV) induced plaque regression ApoE-/- mouse model, decreased monocyte recruitment, CD68+ macrophages, CCR5 expression, and plaque size were all associated with reduced PET signals, which not only further confirmed the targeting efficiency of 64Cu-DAPTA-Combs but also highlighted the potential of these targeted nanoparticles for atherosclerosis imaging. Moreover, the up-regulation of CCR5 and colocalization with CD68+ macrophages in the necrotic core of ex vivo human plaque specimens warrant further investigation for atherosclerosis prognosis.

17.
ACS Nano ; 15(1): 1186-1198, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33406361

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy with dire prognosis due to aggressive biology, lack of effective tools for diagnosis at an early stage, and limited treatment options. Detection of PDAC using conventional radiographic imaging is limited by the dense, hypovascular stromal component and relatively scarce neoplastic cells within the tumor microenvironment (TME). The CC motif chemokine 2 (CCL2) and its cognate receptor CCR2 (CCL2/CCR2) axis are critical in fostering and maintaining this kind of TME by recruiting immunosuppressive myeloid cells such as the tumor-associated macrophages, thereby presenting an opportunity to exploit this axis for both diagnostic and therapeutic purposes. We engineered CCR2-targeting ultrasmall copper nanoparticles (Cu@CuOx) as nanovehicles not only for targeted positron emission tomography imaging by intrinsic radiolabeling with 64Cu but also for loading and delivery of the chemotherapy drug gemcitabine to PDAC. This 64Cu-radiolabeled nanovehicle allowed sensitive and accurate detection of PDAC malignancy in autochthonous genetically engineered mouse models. The ultrasmall Cu@CuOx showed efficient renal clearance, favorable pharmacokinetics, and minimal in vivo toxicity. Systemic administration of gemcitabine-loaded Cu@CuOx effectively suppressed the progression of PDAC tumors in a syngeneic xenograft mouse model and prolonged survival. These CCR2-targeted ultrasmall nanoparticles offer a promising image-guided therapeutic agent and show great potential for translation.


Assuntos
Nanopartículas , Neoplasias Pancreáticas , Animais , Linhagem Celular Tumoral , Cobre , Desoxicitidina/análogos & derivados , Camundongos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Receptores CCR2 , Microambiente Tumoral
18.
Adv Healthc Mater ; 10(15): e2002031, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33470560

RESUMO

Gold nanocages (AuNCs) have emerged as a novel class of multifunctional nanomaterials with an array of applications in nanomedicine, including drug delivery, controlled release, as well as disease diagnosis and treatment. Labeling AuNCs with radionuclides not only offers additional therapeutic capabilities but also makes it easy to analyze their biodistribution, monitor their uptake by the tissue or organ of interest, and optimize their performance in both diagnosis and treatment. Here, an introduction to the chemical synthesis and optical properties of AuNCs is provided in the beginning. The methods developed for their radiolabeling are then showcased, followed by the use of radiolabeled AuNCs in tracking and quantifying their pharmacokinetics, including biodistribution, tumor uptake, and intratumoral distribution. Finally, their potential applications in targeted imaging and image-guided therapy are discussed.


Assuntos
Nanopartículas Metálicas , Neoplasias , Sistemas de Liberação de Medicamentos , Ouro , Humanos , Nanomedicina , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Distribuição Tecidual
19.
AIDS Res Hum Retroviruses ; 37(9): 694-705, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33390081

RESUMO

HIV recombination contributes greatly to its diversity and produces many circulating recombinant forms (CRFs) and unique recombinant forms (URFs). In China, 24 CRFs have been reported to date, and CRFs cause more than 80% of HIV infections. However, the prevalence of CRFs might still be underestimated, as a high level of onward transmission of URFs has been reported. In this study, we analyzed all Chinese pol region (2,253-3,252) sequences in the HIV Database to evaluate potential new CRFs in China. HIV-1 genotypes were verified by the Context-based Modeling for Expeditious Typing (COMET) tool. Maximum-likelihood (ML) trees were constructed based on sequences with unassigned genotypes. Cluster Picker 1.2.1 was used to identify transmission clusters. Meanwhile, a jumping-profile hidden Markov model (jpHMM) was used to perform recombination breakpoint analysis. Beast 1.7.5 was used to estimate the time of the most recent common ancestor of new CRFs. In the HIV databases, CRF01_AE was the most prevalent genetic form in China, accounting for 39.69% of all national infections, followed by CRF07_BC (20.47%), subtype B (17.50%), CRF08_BC (6.60%), subtype C (6.28%), CRF55_01B (2.06%), and other CRFs (1.77%). The URFs were responsible for 5.31% of all infections nationwide. Among URFs, genomes comprising BC, 01BC, 01B, and 01C were dominant. Finally, 17 potential CRFs and 1 novel CRF were identified. BEAST analysis indicates that novel CRF originated around in 2009. The data highlight that more CRFs have been spreading in China. HIV-1 pol sequences that are commonly used to explore drug resistance are helpful for the surveillance of epidemics of different HIV-1 genotypes.


Assuntos
Infecções por HIV , HIV-1 , China/epidemiologia , Genótipo , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Filogenia
20.
Clin Cardiol ; 44(3): 401-406, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33496356

RESUMO

BACKGROUND: Indicators of adverse cardiovascular events in patients with acute carbon monoxide (CO) poisoning-induced myocardial injury have not yet been elucidated. HYPOTHESIS: This study aimed at determining the risk factors for adverse cardiovascular events in patients with acute CO poisoning-induced myocardial injury. METHODS: We enrolled patients with moderate-to-severe acute CO poisoning-induced myocardial injury. Based on the occurrence of adverse cardiovascular events, the patients were assigned into event and non-event group. Binary logistic regression analysis was performed to analyze the potential risk factors for cardiovascular adverse events. RESULTS: A total of 413 eligible patients were enrolled. Among them, 61 (14.8%) patients presented adverse cardiovascular events and were assigned to the event group while 352 patients were assigned to the non-event group. Univariate analysis revealed that cTnI, Lac, and NLR levels at admission and sST2 at day 3 in the event group were significantly higher compared to those in the non-event group. Subsequent multivariate analysis revealed that sST2 at day 3 and NLR at admission were independent risk factors for adverse cardiovascular events in patients with acute CO poisoning-induced myocardial injury. Finally, the sensitivity, specificity, and AUC of sST2 at day 3 combined with NLR for event prediction were 79.5%, 82.8%, and 0.858, respectively. CONCLUSION: A combination of sST2 at day 3 and NLR is a potential predictor for the occurrence of adverse cardiovascular events in patients with acute CO poisoning-induced myocardial injury. Therefore, cardiovascular risk stratification should be taken into consideration, especially in patients with acute CO poisoning-induced myocardial injury.

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