Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 16.241
Filtrar
1.
Food Chem ; 366: 130557, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34284195

RESUMO

Diacylglycerol (DAG) is commonly used as fat substitute in food manufacture due to its functional properties, but DAG has poor emulsification and oxidation stability, which limits its wide application in food industry. In this work, fluorescence quenching data and thermodynamic parameters were analyzed to investigate the interaction mechanism between l-theanine (L-Th) and ß-lactoglobulin (ß-LG). DAG emulsion was prepared by using ß-lactoglobulin-theanine (ß-LG-Th) as surface stabilizer, and its emulsification and oxidation stability were evaluated. The results showed that the hydrophobic interaction played an important role on the conjugate of ß-LG and L-Th due to the negative values for ΔG, positive values for ΔH and ΔS at pH 4.0, pH 6.0 and pH 8.0. The DAG has been better embedded by using ß-LG-Th as surface stabilizer, and the droplet size was about 0.2 µm to 1.5 µm when the pH was 6.0, the ratio of L-Th to ß-LG was 1:1. ß-LG-Th as surface stabilizer for DAG can increase the ζ-potential and emulsion index, make the emulsion droplet size distribution more uniform. The l-theanine was better to be used to improve the emulsification stability and antioxidant capacity of DAG by binding ß-LG as surface stabilizer.

2.
Int J Legal Med ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477924

RESUMO

Several studies have confirmed that microRNAs (miRNAs) are promising markers for body fluid identification since they were introduced to this field. However, there is no consensus on the choice of reference genes and identification strategies. In this study, 13 potential candidate miRNAs were screened from three forensically relevant body fluid datasets, and the expression of 12 markers in five body fluids was determined using a real-time quantitative method. Two probabilistic approaches, Naive Bayes (NB) and partial least squares discriminant analysis (PLS-DA), were then applied to predict the origin of the samples to determine whether probabilistic methods are helpful in body fluid identification using miRNA quantitative data. Furthermore, 14 reference combinations were used to validate the influence of different reference choices on the predicted results simultaneously. Our results showed that in the NB model, leave-one-out cross-validation (LOOCV) achieved 100% accuracy and the prediction accuracy of the test set was 100% in most reference combinations. In the PLS-DA model, the first two components could interpret about 80% expression variance and LOOCV achieved 100% accuracy when miR-92a-3p was used as the reference. This study preliminarily proved that probabilistic approaches hold huge potential in miRNA-based body fluid identification, and the choice of references influences the prediction results to a certain extent.

3.
BMC Genomics ; 22(1): 641, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34481466

RESUMO

BACKGROUND: Stroke can induce cardiac dysfunction in the absence of primary cardiac disease; however, the mechanisms underlying the interaction between the neurological deficits and the heart are poorly understood. The objective of this study was to investigate the effects of stroke on cardiac function and to identify the transcriptome characteristics of the heart. RESULTS: Stroke significantly decreased heart weight/tibia length ratio and cardiomyocyte cross-sectional areas and increased atrogin-1 and the E3 ubiquitin ligase MuRF-1, indicating myocardial atrophy in MCAO-induced mouse hearts. RNA sequencing of mRNA revealed 383 differentially expressed genes (DEGs) in MCAO myocardium, of which 221 were downregulated and 162 upregulated. Grouping of DEGs based on biological function and quantitative PCR validation indicated that suppressed immune response and collagen synthesis and altered activity of oxidoreductase, peptidase, and endopeptidase may be involved in MCAO-induced cardiomyopathy. The DEGs were mainly distributed in the membrane or extracellular region of cardiomyocytes and acted as potential mediators of stroke-induced cardiac dysregulation involved in cardiac atrophy. CONCLUSION: Stroke induced a unique transcriptome response in the myocardium and resulted in immediate cardiac atrophy and dysfunction.


Assuntos
Isquemia Encefálica , Cardiopatias , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Isquemia Encefálica/patologia , Cardiopatias/patologia , Camundongos , Atrofia Muscular , Miócitos Cardíacos , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/patologia , Transcriptoma
4.
J Am Chem Soc ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520194

RESUMO

Proteolysis targeting chimeras (PROTACs) represent a new class of promising therapeutic modalities. PROTACs hijack E3 ligases and the ubiquitin-proteasome system (UPS), leading to selective degradation of the target proteins. However, only a very limited number of E3 ligases have been leveraged to generate effective PROTACs. Herein, we report that the KEAP1 E3 ligase can be harnessed for targeted protein degradation utilizing a highly selective, noncovalent small-molecule KEAP1 binder. We generated a proof-of-concept PROTAC, MS83, by linking the KEAP1 ligand to a BRD4/3/2 binder. MS83 effectively reduces protein levels of BRD4 and BRD3, but not BRD2, in cells in a concentration-, time-, KEAP1- and UPS-dependent manner. Interestingly, MS83 degrades BRD4/3 more durably than the CRBN-recruiting PROTAC dBET1 in MDA-MB-468 cells and selectively degrades BRD4 short isoform over long isoform in MDA-MB-231 cells. It also displays improved antiproliferative activity than dBET1. Overall, our study expands the limited toolbox for targeted protein degradation.

5.
J Plant Physiol ; 266: 153510, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34521019

RESUMO

Source sink balance is one of the major determinants of carbon partitioning in plants. However, its effects on photosynthesis in fruit trees are largely unknown. In this work, the effects of low sink demand on net photosynthetic rate (Pn) and chlorophyll fluorescence after fruit removal (-fruit) in peach (Prunus persica (L.) Batsch cv. 'Zaojiubao') trees were investigated. The stepwise energy flow through photosystem II (PSII) at the reaction center (RC) was analyzed with quantitative analyses of fluorescence transient, also called JIP-test. We found that Pn was significantly lower and closely correlated to the leaf stomatal conductance (Gs) of -fruit trees than that of fruit retained (+fruit) trees. Leaf temperature (Tleaf) of -fruit trees was remarkably higher than that of +fruit trees. Day-time-period assays of chlorophyll (Chl) fluorescence revealed that, in the leaves of -fruit trees, the fluorescence parameters, such as NPQ (non-photochemical quenching coefficient) and ΦD0 (maximum quantum yield of non-photochemical de-excitation), decreased in the morning and recovered to the normal level in the afternoon, whereas other parameters, such as ΦE0 (quantum yield for electron transport at t = 0), Ψ0 (probability that a trapped exciton moves an electron to QA pool), F0 (minimum fluorescence, when all PSII RCs are open) and Wk (relative variable fluorescence at 300 µs of the chlorophyll fluorescence transient), did not. These results suggest that OEC complex and QA pool were irreversibly affected by low sink demand, whereas light harvest antenna and PSII potential efficiency retained a strong ability to recover.

6.
EMBO Rep ; : e52901, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523214

RESUMO

Cardiac regeneration occurs primarily through proliferation of existing cardiomyocytes, but also involves complex interactions between distinct cardiac cell types including non-cardiomyocytes (non-CMs). However, the subpopulations, distinguishing molecular features, cellular functions, and intercellular interactions of non-CMs in heart regeneration remain largely unexplored. Using the LIGER algorithm, we assemble an atlas of cell states from 61,977 individual non-CM scRNA-seq profiles isolated at multiple time points during regeneration. This analysis reveals extensive non-CM cell diversity, including multiple macrophage (MC), fibroblast (FB), and endothelial cell (EC) subpopulations with unique spatiotemporal distributions, and suggests an important role for MC in inducing the activated FB and EC subpopulations. Indeed, pharmacological perturbation of MC function compromises the induction of the unique FB and EC subpopulations. Furthermore, we developed computational algorithm Topologizer to map the topological relationships and dynamic transitions between functional states. We uncover dynamic transitions between MC functional states and identify factors involved in mRNA processing and transcriptional regulation associated with the transition. Together, our single-cell transcriptomic analysis of non-CMs during cardiac regeneration provides a blueprint for interrogating the molecular and cellular basis of this process.

7.
J Cell Mol Med ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523794

RESUMO

Adiponectin is an adipocyte-derived hormone, which is closely associated with the development of Alzheimer's disease (AD) and has potential preventive and therapeutic significance. In the present study, we explored the relationship between adiponectin and circadian rhythm disorder in AD, the effect of adiponectin on the abnormal expression of Bmal1 mRNA/protein induced by amyloid-ß protein 31-35 (Aß31-35), and the underlying mechanism of action. We found that adiponectin-knockout mice exhibited amyloid-ß deposition, circadian rhythm disorders and abnormal expression of Bmal1. Adiponectin ameliorated the abnormal expression of the Bmal1 mRNA/protein caused by Aß31-35 by inhibiting the activity of glycogen synthase kinase 3ß (GSK3ß). These results suggest that adiponectin deficiency could induce circadian rhythm disorders and abnormal expression of the Bmal1 mRNA/protein, whilst exogenous administration of adiponectin may improve Aß31-35-induced abnormal expression of Bmal1 by inhibiting the activity of GSK3ß, thus providing a novel idea for the treatment of AD.

8.
Org Biomol Chem ; 19(35): 7690-7694, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524340

RESUMO

A bifunctional cinchona squaramide catalyzed enantioselective aza-Friedel-Crafts reaction between 2-naphthols and benzothiazolimines has been developed, and a series of chiral 2'-aminobenzothiazolomethyl naphthols with potential antiproliferative and anthelmintic activities have been successfully and effectively prepared in good to excellent yields (up to 98%) with excellent enantioselectivities (up to >99% ee) even in a scale-up preparation under mild conditions.

10.
Analyst ; 146(18): 5474-5495, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515706

RESUMO

Acute myocardial infarction (AMI) is the main cause of death from cardiovascular diseases. Thus, early diagnosis of AMI is essential for the treatment of irreversible damage from myocardial infarction. Traditional electrocardiograms (ECG) cannot meet the specific detection of AMI. Cardiac troponin I (cTnI) is the main biomarker for the diagnosis of myocardial infarction, and the detection of cTnI content has become particularly important. In this review, we introduced and compared the advantages and disadvantages of various cTnI detection methods. We focused on the analysis and comparison of the main indicators and limitations of various cTnI biosensors, including the detection range, detection limit, specificity, repeatability, and stability. In particular, we pay more attention to the application and development of electrochemical biosensors in the diagnosis of cardiovascular diseases based on different biological components. The application of electrochemical microfluidic chips for cTnI was also briefly introduced in this review. Finally, this review also briefly discusses the unresolved challenges of electrochemical detection and the expectations for improvement in the detection of cTnI biosensing in the future.

11.
Respir Physiol Neurobiol ; : 103784, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34517114

RESUMO

The influences of the profiles and cross-sectional areas of glottal aperture on the upper respiratory airway are investigated using an idealized cast-based mouth-throat model and three dimensional computational fluid dynamics (CFD). The open source CFD code OpenFOAM is employed. The transient flows are modeled using the very-large eddy simulation with the Smagorinsky sub-grid scale (SGS) model. Five different shapes of glottis are considered, including circular glottis with 100%, 75% and 50% cross-sectional area and elliptic glottis with 75% and 50% cross-sectional area. Both instantaneous and averaged flow fields are analyzed. It is found that the variations of glottis have great impacts on the properties of downstream flow fields such as the secondary flow, laryngeal jet, recirculation zone, turbulent kinetic energy, and vortex. Evident impacts are observed in the region within 6 tracheal diameters downstream of the glottis. The profile of the glottis has more impacts on the laryngeal shape, while the cross-sectional area has more impacts on velocity of the laryngeal jet and turbulent intensity. It is concluded that both the glottal areas and profiles are critical for an idealized geometrical mouth-throat model.

12.
Mol Pain ; 17: 17448069211045211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34517736

RESUMO

Interferons (IFNs) are cytokines secreted by infected cells that can interfere with viral replication. Besides activating antiviral defenses, type I IFNs also exhibit diverse biological functions. IFN-ß has been shown to have a protective effect against neurotoxic and inflammatory insults on neurons. Therefore, we aimed to investigate the possible role of IFN-ß in reducing mechanical allodynia caused by Complete Freund's Adjuvant (CFA) injection in rats. We assessed the antinociceptive effect of intrathecal IFN-ß in naïve rats and the rats with CFA-induced inflammatory pain. After the behavioral test, the spinal cords of the rats were harvested for western blot and immunohistochemical double staining. We found that intrathecal administration of IFN-ß in naïve rats can significantly increase the paw withdrawal threshold and paw withdrawal latency. Further, the intrathecal injection of a neutralizing IFN-ß antibody can reduce the paw withdrawal threshold and paw withdrawal latency, suggesting that IFN-ß is produced in the spinal cord in normal conditions and serves as a tonic inhibitor of pain. In addition, intrathecal injection of IFN-ß at dosages from 1000 U to 10000 U demonstrates a significant transient dose-dependent inhibition of CFA-induced inflammatory pain. This analgesic effect is reversed by intrathecal naloxone, suggesting that IFN-ß produces an analgesic effect through central opioid receptor-mediated signaling. Increased expression of phospho-µ-opioid receptors after IFN-ß injection was observed on western blot, and immunohistochemical staining showed that µ-opioids co-localized with IFN-α/ßR in the dorsal horn of the spinal cord. The findings of this study demonstrate that the analgesic effect of IFN-ß is through µ-opioid receptors activation in spial cord.

13.
mBio ; : e0131621, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34517762

RESUMO

Coronaviruses (CoVs) are emergent pathogens that may cause life-threatening respiratory diseases in humans. Understanding of CoV-host interactions may help to identify novel therapeutic targets. MOV10 is an RNA helicase involved in different steps of cellular RNA metabolism. Both MOV10 antiviral and proviral activities have been described in a limited number of viruses, but this protein has not been previously associated with CoVs. We found that during Middle East respiratory syndrome coronavirus (MERS-CoV) infection, MOV10 aggregated in cytoplasmic structures colocalizing with viral nucleocapsid (N) protein. MOV10-N interaction was confirmed by endogenous MOV10 coimmunoprecipitation, and the presence of other cellular proteins was also detected in MOV10 complexes. MOV10 silencing significantly increased both N protein accumulation and virus titer, with no changes in the accumulation of viral RNAs. Moreover, MOV10 overexpression caused a 10-fold decrease in viral titers. These data indicated that MOV10 has antiviral activity during MERS-CoV infection. We postulated that this activity could be mediated by viral RNA sequestration, and in fact, RNA immunoprecipitation data showed the presence of viral RNAs in the MOV10 cytoplasmic complexes. Expression of wild-type MOV10 or of a MOV10 mutant without helicase activity in MOV10 knockout cell lines, developed by CRISPR-Cas technology, indicated that the helicase activity of MOV10 was required for its antiviral effect. Interestingly MOV10-N interaction was conserved in other mildly or highly pathogenic human CoVs, including the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although MOV10 antiviral activity was found only in highly pathogenic CoVs, suggesting a potential role of MOV10 in the modulation of human CoVs pathogenesis. IMPORTANCE Coronaviruses (CoVs) are emerging pathogens causing life-threatening diseases in humans. Knowledge of virus-host interactions and viral subversion mechanisms of host pathways is required for the development of effective countermeasures against CoVs. The interaction between cellular RNA helicase MOV10 and nucleocapsid (N) protein from several human CoVs is shown. Using MERS-CoV as a model, we demonstrate that MOV10 has antiviral function, requiring its helicase activity, most likely mediated by viral RNA sequestration in cytoplasmic ribonucleoprotein structures. Furthermore, we found that MOV10 antiviral activity may act only in highly pathogenic human CoVs, suggesting a role for MOV10 in modulating CoVs pathogenesis. The present study uncovers a complex network of viral and cellular RNAs and proteins interaction modulating the antiviral response against CoVs.

14.
Proc Natl Acad Sci U S A ; 118(38)2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34518225

RESUMO

Food security has been a significant issue for the livelihood of smallholder family farms in highly populated regions and countries. Industrialized farming in more developed countries has increased global food supply to meet the demand, but the excessive use of synthetic fertilizers and pesticides has negative environmental impacts. Finding sustainable ways to grow more food with a smaller environmental footprint is critical. We developed an integrated cropping system that incorporates four key components: 1) intensified cropping through relay planting or intercropping, 2) within-field strip rotation, 3) soil mulching with available means, such as crop straw, and 4) no-till or reduced tillage. Sixteen field experiments, conducted with a wide range of crop inputs over 12 consecutive years (2006 to 2017), showed that the integrated system with intercropping generates significant synergies-increasing annual crop yields by 15.6 to 49.9% and farm net returns by 39.2% and decreasing the environmental footprint by 17.3%-when compared with traditional monoculture cropping. We conclude that smallholder farmers can achieve the dual goals of growing more food and lowering the environmental footprint by adopting integrated farming systems.

15.
J Food Sci ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519054

RESUMO

Combinations of phytochemical(s) and engineered nanoparticles have attracted immense research interest due to their superior antimicrobial effects against contaminations. Herein, a Pickering emulsion is developed with capsulized phytochemicals including borneol and citral (BC-Cap) stabilized by hydrophilic amine-functionalized silica nanoparticles (SiO2 ─NH2 NPs). The droplet sizes of Pickering emulsion were 5.2 ± 1.4 µm under the condition that the concentrations of SiO2 ─NH2 NPs ranged from 0.6 to 1.2 wt.%, and the emulsion showed desirable stability during storage at 40°C for 365 days. In addition, the antibacterial and antibiofilm activities of the Pickering emulsion were investigated. The antibacterial effect of BC-Cap increased by two- to fourfold compared with citral or borneol alone. Treatment of BC/BC-Cap for 4 h eliminated the formation of biofilms generated by Listeria monocytogenes (at 5/1.25 mg/ml; 2 × MIC concentration) and Pseudomonas aeruginosa (at 5/2.5 mg/ml; 2 × MIC concentration). Further mechanistic studies revealed that the antibiofilm effects of BC-Cap were attributed to its ability to increase the porosity and lytic effects on the cell membrane of bacteria. Findings from the current study support the antibacterial and antibiofilm effects of BC-Cap Pickering emulsion as a promising food additive. PRACTICAL APPLICATION: The Pickering emulsion has potential applications as bacteriostatic agent in packaging materials and general surface disinfectant. The combination of borneol and citral is stabilized by hydrophilic amine-functionalized silica nanoparticles (SiO2 ─NH2 NPs). With the synergistic effects of borneol and citral, the Pickering emulsion shows a promising elimination effect against the formation of biofilms produced by Listeria monocytogenes and Pseudomonas aeruginosa.

16.
ACS Biomater Sci Eng ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519208

RESUMO

To simplify the preparation process of a glucose-responsive microneedle patch, a cross-linking-density changeable microneedle patch was designed. The microneedle patch was made up of a hydrogel formed by phenylboronic acid-grafted polyallylamine and poly(vinyl alcohol) (PVA). The gel was cross-linked by boronate ester bonds between phenylboronic acid groups and PVA. It still had fluidity and could be filled into a mold to prepare microneedle patches. Moreover, insulin could be directly loaded into the microneedle patch by mixing with the gel. The boronate ester bond would be broken in the presence of glucose, resulting in a decrease in the cross-linking density. Therefore, the gel could achieve a greater swelling degree and insulin could be released faster. In addition, PVA chains were crystallized by repeatedly freezing and thawing to improve the mechanical strength of the microneedle patch. In terms of glucose-dependent insulin release, the gel showed good glucose-responsive insulin-release ability. Through additional ion cross-linking, the microneedle patch could also control the insulin release according to glucose concentration. In the hypoglycemic experiment of diabetic rats, the microneedle patch effectively pierced the skin and slowly released insulin.

17.
J Org Chem ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519212

RESUMO

We herein report an iodine-mediated formal [2 + 2 + 1] cyclization of methyl ketones, p-toluenesulfonyl hydrazines, and 1-aminopyridinium iodide for preparation of 4-aryl-NH-1,2,3-triazoles under metal- and azide-free conditions. Notably, this is achieved using p-toluenesulfonyl hydrazines and 1-aminopyridinium iodide as azide surrogates, providing a novel route toNH-1,2,3-triazoles. Furthermore, this approach provides rapid and practical access to potent inhibitors of indoleamine 2,3-dioxygenase (IDO).

18.
Artigo em Inglês | MEDLINE | ID: mdl-34520115

RESUMO

BACKGROUND: Diagnostic criteria for sarcopenia have not been established in Chinese. This study established criteria based on the L3-skeletal muscle index (L3-SMI) and assessed its value for outcomes predicting in cirrhotic Chinese patients. METHODS: Totally 911 subjects who underwent a CT scan at two centres were enrolled in Cohort 1 (394 male and 417 female subjects, aged 20-80 years). The data of those subjects younger than 60 years (365 male and 296 female subjects) were used to determine the reference intervals of the L3-SMI and its influencing factors. Cohort 2 consisted of 480 patients (286 male and 184 female patients) from three centres, and their data were used to investigate the prevalence of sarcopenia and evaluate the value of L3-SMI for predicting the prognosis and complications of cirrhosis. RESULTS: Age and sex had the greatest effects on the L3-SMI (P < 0.001). The L3-SMI scores were clearly higher in male patients than in female patients (52.94 ± 8.41 vs. 38.91 ± 5.65 cm2 /m2 , P < 0.001) and sharply declined in subjects aged ≥ 60 years. Based on the mean -1.28 × SD among adults aged < 60 years, the L3-SMI cut-off value for sarcopenia was 44.77 cm2 /m2 in male patients and 32.50 cm2 /m2 in female patients. Using these values, 22.5% of the cirrhotic patients (28.7% of male patients and 11.9% of female patients) were diagnosed with sarcopenia. Compared with non-sarcopenia individuals, sarcopenia patients had lower body mass index (21.28 ± 3.01 vs. 24.09 ± 3.39 kg/m2 , P < 0.001) and serum albumin levels (31.54 ± 5.93 vs. 32.93 ± 5.95 g/L, P = 0.032), longer prothrombin times (16.39 ± 3.05 vs. 15.71 ± 3.20 s, P = 0.049), higher total bilirubin concentrations (41.33 ± 57.38 vs. 32.52 ± 31.48 µmol/L, P = 0.039), worse liver function (Child-Pugh score, 8.05 ± 2.11 vs. 7.32 ± 2.05, P = 0.001), higher prevalence of cirrhosis-related complications (81.82% vs. 62.24%, P < 0.001) and mortality (30.68% vs. 11.22%, P < 0.001). Overall survival was significantly lower in the sarcopenia group [risk ratio (RR) = 2.643, 95% confidence interval (CI) 1.646-4.244, P < 0.001], accompanied with an increased cumulative incidence of ascites (RR = 1.827, 95% CI 1.259-2.651, P = 0.002), spontaneous bacterial peritonitis (RR = 3.331, 95% CI 1.404-7.903, P = 0.006), hepatic encephalopathy (RR = 1.962, 95% CI 1.070-3.600, P = 0.029), and upper gastrointestinal varices (RR = 2.138, 95% CI 1.319-3.466, P = 0.002). Subgroup analysis showed sarcopenia shortened the survival of the patients with Model For End-Stage Liver Disease score > 14 (RR = 4.310, 95% CI 2.091-8.882, P < 0.001) or Child-Pugh C (RR = 3.081, 95% CI 1.516-6.260, P = 0.002). CONCLUSIONS: Sarcopenia is a common comorbidity of cirrhosis and can be used to predict cirrhosis-related complications and the prognosis.

19.
CNS Neurosci Ther ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510762

RESUMO

AIMS: Human urinary kallidinogenase (HUK) has shown favorable efficacies in acute ischemic stroke (AIS) treatment. We sought confirmation of the safety and efficacy of HUK for AIS in a large population. METHODS: RESK study enrolled patients with AIS of anterior circulation to receive HUK infusion. The primary endpoint was the incidence of treatment-emergent adverse events (AEs). Secondary endpoints assessed neurological and functional improvements and stroke recurrent rate. RESULTS: Of 1206 eligible patients, 1202 patients received at least one dose of HUK infusion and 983 (81.5%) completed the study. The incidence of treatment-emergent AEs and serious AEs were 55.99% and 2.41%, respectively. Pre-specified AEs of special interest occurred in 21.71% of patients, but the majority were mild and unrelated to therapy. Hypertension, age, treatment time, and drug combination were identified to be associated with drug-related blood pressure reduction. Neurological and functional evaluations revealed favorable outcomes from baseline to post-treatment assessment. The cumulative recurrence rate of stroke was 2.50% during the 90-day assessment. CONCLUSION: HUK had an acceptable safety and tolerability profile in AIS patients. Besides, HUK demonstrated the neurological and functional improvements in AIS, further confirming its clinical efficacy in a real-world large population.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34511012

RESUMO

INTRODUCTION: The treatment evidence for entecavir-treated chronic hepatitis B (CHB) patients without maintaining of virologic response (MVR, defined as persistent HBV DNA <20 IU/mL during therapy) remains uncertain. We aimed to determine the relationship between non-MVR and hepatocellular carcinoma (HCC) risk in entecavir-treated CHB patients. METHODS: A cohort of 1447 entecavir-treated CHB patients were enrolled. Multivariate and propensity score-based inverse probability weighting (IPW) model was performed to estimate the effect of MVR on HCC. RESULTS: During a median follow-up of 5 years, 214 (14.8%) patients occurred non-MVR. Non-MVR patients had a higher risk of HCC [the IPW model: hazard ratio (HR)=3.59, 95% confidence interval (CI): 2.23-5.75] than MVR patients, especially in those with cirrhosis (HR=4.60, 95% CI: 2.81-7.56) and the high HCC score by the Chinese University of Hong Kong (HR=4.35, 95% CI: 2.58-7.32). MVR patients with transient (HR=4.72, 95% CI:1.98-11.24) or persistent (HR=12.16, 95% CI: 3.58-41.31) abnormal ALT after virologic response had higher HCC hazard. CONCLUSIONS: Our study indicated an elevated HCC probability for entecavir-treated CHB patients with Non-MVR, especially for those with cirrhosis or a high predicted score at baseline. For MVR patients, the trajectories in ALT after virologic response suggested different HCC risks.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...