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1.
Front Endocrinol (Lausanne) ; 12: 620117, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33815280

RESUMEN

Background and Objectives: Defects in the human sodium/iodide symporter (SLC5A5) gene have been reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify SLC5A5 mutations in Chinese patients with CH and to evaluate the function of the mutation. Methods: Two hundred and seventy-three patients with primary CH were screened for mutations in SLC5A5 using next-generation sequencing. We investigated the expression and cellular localization of the novel compound heterozygous mutation in SLC5A5. The functional activity of the mutants was further examined in vitro. Results: In 273 patients with CH, two previously undescribed pathogenic mutations p.Gly51AlafsTer45 (G51fs) and p.Gly421Arg (G421R) in a compound heterozygous state in SLC5A5 were identified in a pediatric patient. G51fs was located in the first intercellular loop connecting transmembrane segment I and II, whereas G421R was in the transmembrane segment (TMS) XI. G51fs and G421R resulted in a truncated NIS and reduced protein expression, respectively. In vitro experiments further showed that the normal function of iodine transport of sodium-iodide symporter (NIS) mutants was markedly impaired. Conclusion: The undescribed compound heterozygous mutation of SLC5A5 was discovered in a Chinese CH patient. The mutation led to significantly reduced NIS expression and impaired iodide transport function accompanied by the impaired location of the NIS on the plasma membrane. Our study thus provides further insights into the roles of SLC5A5 in CH pathogenesis.

2.
Biosci Trends ; 2021 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-33840680

RESUMEN

Severe acute pancreatitis (SAP) is a common critical disease with a high mortality rate that involves a complex, rapid change in condition and multiple organ systems. Therefore, a multidisciplinary team (MDT), including staff from the emergency department, intensive care unit, pancreatic surgery, gastroenterology , and imaging, is necessary for the early diagnosis, evaluation, and treatment of patients with SAP. This involves managing the systemic inflammatory response and maintaining organ function in the early stage and managing systemic infection and treatment of peripancreatic complications in the middle-to-late stages. The MDT should be led by departments corresponding to the clinical characteristics of each stage, and those departments should be responsible for the coordination and implementation of treatment by other relevant departments. In the late stage, pancreatic surgery and gastroenterology are the main departments that should manage peripancreatic complications. In line with the principle of minimally invasive treatment, the timely and reasonable selection of endoscopic or minimally invasive surgical debridement can achieve good therapeutic outcomes. Open surgery is also an effective method for treating an intractable massive hemorrhage in the abdominal cavity or necrotic cavity, intractable abdominal compartment syndrome, visceral perforation, and fistulae.

3.
Global Spine J ; : 21925682211000707, 2021 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-33843321

RESUMEN

STUDY DESIGN: Cross-sectional study. OBJECTIVE: Recently, there has been a rise in children and adolescents developing low back pain and/or sciatica. Degenerative lumbar spine MRI phenotypes can occur in this population but reports have been sporadic and the true incidence of such spine changes remains debatable. As such, the study aimed to address the epidemiology of MRI phenotypes of the lumbar spine in this young population. METHODS: 597 children and adolescents with lumbar MRIs were included in the study. T1- and T2-weighted lumbar images from L1/2 to L5/S1 were analyzed in axial and sagittal planes. Global phenotype assessment was performed of each level and based on established nomenclature protocols. RESULTS: The cohort consisted of 57.3% (342) boys and 42.7% (255) girls, with a mean age of 10.75 ± 5.25 years (range: 0 to 18 years). The prevalence of imaging findings of lumbar disc degeneration (LDD) and lumbar disc herniation (LDH) were 2.2% (95% CI: 0.93-3.43) and 5.8% (95%CI: 2.58-8.99), respectively. There was significant difference between each disc segment from L1/2 to L5/S1 for both LDD and LDH. Schmorl's nodes were noted in 16 cases (2.7%, youngest case as 15 years), with 11 boys (68.8%) and most frequent segment as L3/4. Modic changes and high-intensity zones were absent in this cohort. CONCLUSIONS: LDD can emerge as early as the first decade of life with Schmorl's nodes, without additional specific phenotypes, including Modic changes and high-intensity zones. The study provides valuable information of a unique age group that is often under-represented but equally important as adults.

4.
Autophagy ; : 1-20, 2021 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-33843441

RESUMEN

Zinc oxide nanoparticles (ZnONPs) hold great promise for biomedical applications. Previous studies have revealed that ZnONPs exposure can induce toxicity in endothelial cells, but the underlying mechanisms have not been fully elucidated. In this study, we report that ZnONPs can induce ferroptosis of both HUVECs and EA.hy926 cells, as evidenced by the elevation of intracellular iron levels, lipid peroxidation and cell death in a dose- and time-dependent manner. In addition, both the lipid reactive oxygen species (ROS) scavenger ferrostatin-1 and the iron chelator deferiprone attenuated ZnONPs-induced cell death. Intriguingly, we found that ZnONPs-induced ferroptosis is macroautophagy/autophagy-dependent, because the inhibition of autophagy with a pharmacological inhibitor or by ATG5 gene knockout profoundly mitigated ZnONPs-induced ferroptosis. We further demonstrated that NCOA4 (nuclear receptor coactivator 4)-mediated ferritinophagy (autophagic degradation of the major intracellular iron storage protein ferritin) was required for the ferroptosis induced by ZnONPs, by showing that NCOA4 knockdown can reduce the intracellular iron level and lipid peroxidation, and subsequently alleviate ZnONPs-induced cell death. Furthermore, we showed that ROS originating from mitochondria (mtROS) probably activated the AMPK-ULK1 axis to trigger ferritinophagy. Most importantly, pulmonary ZnONPs exposure caused vascular inflammation and ferritinophagy in mice, and ferrostatin-1 supplementation significantly reversed the vascular injury induced by pulmonary ZnONPs exposure. Overall, our study indicates that ferroptosis is a novel mechanism for ZnONPs-induced endothelial cytotoxicity, and that NCOA4-mediated ferritinophagy is required for ZnONPs-induced ferroptotic cell death.

5.
Molecules ; 26(6)2021 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-33801024

RESUMEN

In the area of gene-directed enzyme prodrug therapy (GDEPT), using herpes simplex virus thymidine kinase (HSV-tk) paired with prodrug ganciclovir (GCV) for cancer treatment has been extensively studied. It is a process involved with two steps whereby the gene (HSV-tk) is first delivered to malignant cells. Afterward, non-toxic GCV is administered to that site and activated to cytotoxic ganciclovir triphosphate by HSV-tk enzyme expressed exogenously. In this study, we presented a one-step approach that both gene and prodrug were delivered at the same time by incorporating them with polymeric micellar nanovectors. GCV was employed as an initiator in the ring-opening polymerization of ε-caprolactone (ε-CL) to synthesize hydrophobic GCV-poly(caprolactone) (GCV-PCL), which was furthered grafted with hydrophilic chitosan to obtain amphiphilic polymer (GCV-PCL-chitosan) for the fabrication of self-assembled micellar nanoparticles. The synthesized amphiphilic polymer was characterized using Fourier transform infrared spectroscopy and proton nuclear magnetic resonance. Micellar prodrug nanoparticles were analyzed by dynamic light scattering, zeta potential, critical micelle concentration, and transmission electron microscopy. Polymeric prodrug micelles with optimal features incorporated with HSV-tk encoding plasmids were cultivated with HT29 colorectal cancer cells and anticancer effectiveness was determined. Our results showed that prodrug GCV and HSV-tk cDNA encoded plasmid incorporated in GCV-PCL-chitosan polymeric nanocarriers could be delivered in a one-step manner to HT-29 cells and triggered high cytotoxicity.

6.
Acta Otolaryngol ; : 1-6, 2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33823755

RESUMEN

BACKGROUND: Long-term use of a unilateral cochlear implant (CI) may lead to abnormal development of contralateral auditory pathway. OBJECTIVES: To investigate the usefulness of measuring the electrically evoked auditory brainstem response (eABR) with the electrical stimulation at the round window membrane and the effect of unilateral CI use on the contralateral auditory pathway functions. MATERIALS AND METHODS: According to duration of unilateral CI use, 45 children with severe or profound sensorineural hearing loss were divided into sCI (≤12 months), lCI (≥24 months) and nCI (no CI use) groups. Intra-operative eABRs evoked by electrical stimulation at the round window membrane were recorded. RESULTS: The latencies of eIII and eV were significantly longer in lCI group than in sCI group and in nCI group, respectively, but not significantly different between sCI group and nCI group. The eABR thresholds and eIII-eV latency intervals were not significantly different among three groups. CONCLUSIONS AND SIGNIFICANCE: The eABR evoked by the electrical stimulation at the round window membrane is a reliable and effective way of evaluating functions of the auditory pathway in deaf children. Long-term use of a unilateral CI may promote the degenerative process of the contralateral auditory pathway to the level of the brainstem.

7.
Nanoscale Res Lett ; 16(1): 54, 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33826006

RESUMEN

Bacterial infection especially caused by multidrug-resistant bacteria still endangers human life. Photodynamic therapy (PDT) can effectively kill bacteria, and nanofiber-based PDT can effectively reduce damage to normal tissues. However, current photosensitizers coated on the surfaces of fibers would release to the wound, causing some side effects. And nanofibers prepared by traditional method exhibit poor adhesion on the wound, which severely reduces the PDT effect due to its short-range effect. Herein, core-shell curcumin composite nanofibers are prepared by in situ electrospinning method via a self-made portable electrospinning device. The obtained composite nanofibers show superior adhesiveness on different biological surface than that of traditional preparation method. Upon 808-nm irradiation, these composite nanofibers effectively produced singlet oxygen (1O2) without curcumin falling off. After these composite nanofibers' exposure to drug-resistant bacteria, they exhibit dual antibacterial behaviors and efficiently kill the drug-resistant bacteria. These dual antibacterial nanofiber membranes with excellent adhesiveness may benefit the application of wound infection as antibacterial dressing.

8.
Neurotox Res ; 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33826131

RESUMEN

Copper oxide nanoparticles (CuONPs) are widely used in pharmaceutical, food, and textile industries. They have been shown to cause lung, liver, and kidney damage. However, whether an intratracheal instillation of CuONPs would affect the brain and its underlying mechanisms remain poorly studied. In this study, healthy C57BL/6J male mice were equally subdivided into control group, low-dose (30 µg/animal), medium-dose (50 µg/animal), and high-dose (100 µg/animal) CuONPs-treated groups. Mice were subjected to acute exposure of CuONPs via intratracheal instillation. Brain histopathology, inflammatory factors, oxidative stress markers, and mitochondrial function-related protein expression were determined. Our results demonstrated that CuONPs caused a dose-dependent brain damage in mice. Histopathological changes in the brain, elevation of inflammatory factors (Tnf, Il-6), and significant alterations in oxidative stress markers were also observed after treatment with CuONPs. Intriguingly, we did not observe infiltration of macrophage cell. Moreover, Tim23, TFAM, and MFN2 protein expression levels showed the decreasing trend after treatment with CuONPs. Taken together, these results indicate that pulmonary exposure to CuONPs induces pathological damage, inflammation, oxidative stress, and mitochondrial dysfunction in the cerebral cortex, suggesting that neurotoxicity caused by pulmonary exposure of CuONPs needs more attention from the public and relevant departments.

9.
Biosens Bioelectron ; 183: 113201, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33812291

RESUMEN

Flexible bioassays based on oxidase-catalyzed and electrocatalytic cascade reactions have been widely reported. However, the fluctuant oxygen level and high anodic potential restricts the detection accuracy. To overcome these challenges, we report here a flexible triphase enzyme electrode by assembling an oxidase enzyme layer and Pt electrocatalysts onto a carbon nanotube film/porous polyvinylidene fluoride hydrophobic substrate. Such a flexible enzyme electrode has an air-liquid-solid triphase reaction zone where oxygen level is air phase dependent (constant and sufficient high), which stabilized the oxidase kinetics and enabled the cathodic measurement of enzymatic product H2O2 with minimum interferents caused from oxygen level fluctuation and many oxidizable species in analyte solution. Furthermore, the flexible triphase enzyme electrode exhibited good mechanical stability even after being bent over 600 times and an excellent air permeability, which are crucial to wearable devices that require long-term skin contact.

10.
Chemosphere ; 278: 130396, 2021 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-33819883

RESUMEN

Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as bisphenol A (BPA) substitutes in consumer products. Little is known about the effects of BPA substitutes on reproductive endocrine function in children and adolescents. Thus, we conducted a cross-sectional study to examine the associations of BPA, BPF, and BPS with sex steroid hormones among 6-19-year old participants. Included were 1317 participants with information on BPA, BPF, BPS, and serum sex hormones [total testosterone (TT), estradiol (E2), and sex hormone binding globulin (SHBG)]. Multiple linear regression accounting for complex survey design was used to assess the association between bisphenols and sex hormones by sex-age groups. Exposure-response (ER) relationships were examined via restricted cubic splines. Significant association with BPF or BPS was sporadic, but BPA presented inverse association with the free androgen index (FAI, calculated as the ratio of TT to SHBG) and E2 and positive association with SHBG and TT/E2 in female adolescents. Further exploration of ER relationships showed that BPA (P for non-linearity = 0.03), BPF (P for non-linearity = 0.005), and BPS (P for non-linearity = 0.08) had a U-shaped relationship with FAI among female adolescents. Additionally, an inverse U-shaped curve was observed for BPA (P for non-linearity = 0.03), BPS (P for non-linearity = 0.01), and BPF (P for non-linearity = 0.01) with SHBG. The associations were virtually nonsignificant among males. Our study demonstrated that BPS and BPF may possess similar endocrine interrupting abilities as BPA.

11.
J Zhejiang Univ Sci B ; 22(4): 318-329, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33835766

RESUMEN

With the number of cases of coronavirus disease-2019 (COVID-19) increasing rapidly, the World Health Organization (WHO) has recommended that patients with mild or moderate symptoms could be released from quarantine without nucleic acid retesting, and self-isolate in the community. This may pose a potential virus transmission risk. We aimed to develop a nomogram to predict the duration of viral shedding for individual COVID-19 patients. This retrospective multicentric study enrolled 135 patients as a training cohort and 102 patients as a validation cohort. Significant factors associated with the duration of viral shedding were identified by multivariate Cox modeling in the training cohort and combined to develop a nomogram to predict the probability of viral shedding at 9, 13, 17, and 21 d after admission. The nomogram was validated in the validation cohort and evaluated by concordance index (C-index), area under the curve (AUC), and calibration curve. A higher absolute lymphocyte count (P=0.001) and lymphocyte-to-monocyte ratio (P=0.013) were correlated with a shorter duration of viral shedding, while a longer activated partial thromboplastin time (P=0.007) prolonged the viral shedding duration. The C-indices of the nomogram were 0.732 (95% confidence interval (CI): 0.685‒0.777) in the training cohort and 0.703 (95% CI: 0.642‒0.764) in the validation cohort. The AUC showed a good discriminative ability (training cohort: 0.879, 0.762, 0.738, and 0.715 for 9, 13, 17, and 21 d; validation cohort: 0.855, 0.758, 0.728, and 0.706 for 9, 13, 17, and 21 d), and calibration curves were consistent between outcomes and predictions in both cohorts. A predictive nomogram for viral shedding duration based on three easily accessible factors was developed to help estimate appropriate self-isolation time for patients with mild or moderate symptoms, and to control virus transmission.

12.
Proc Natl Acad Sci U S A ; 118(11)2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33836585

RESUMEN

The alteration of the enteric nervous system (ENS) and its role in neuroimmune modulation remain obscure in the pathogenesis of inflammatory bowel diseases (IBDs). Here, by using the xCell tool and the latest immunolabeling-enabled three-dimensional (3D) imaging of solvent-cleared organs technique, we found severe pathological damage of the entire ENS and decreased expression of choline acetyltransferase (ChAT) in IBD patients. As a result, acetylcholine (ACh), a major neurotransmitter of the nervous system synthesized by ChAT, was greatly reduced in colon tissues of both IBD patients and colitis mice. Importantly, administration of ACh via enema remarkably ameliorated colitis, which was proved to be directly dependent on monocytic myeloid-derived suppressor cells (M-MDSCs). Furthermore, ACh was demonstrated to promote interleukin-10 secretion of M-MDSCs and suppress the inflammation through activating the nAChR/ERK pathway. The present data reveal that the cholinergic signaling pathway in the ENS is impaired during colitis and uncover an ACh-MDSCs neuroimmune regulatory pathway, which may offer promising therapeutic strategies for IBDs.

13.
Carbohydr Polym ; 262: 117890, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-33838792

RESUMEN

The molecular aggregation of a galactomannan (NSAP-25) from Sophora alopecuroides L. seeds was investigated, where three polydisperse systems were confirmed during particle size analysis, indicating existence of different aggregates composed of random coil chains revealed by circular dichroism. Morphologically, NSAP-25 aggregate of various sizes (200-1200 nm) was possibly multi-stranded and formed by ellipsoid-like particles (20-60 nm) composed of compact coil chain, exhibiting extended amorphous structure with chain-like branches intertwined. Hence, NSAP-25 aggregation was inevitable, which exerted an unignorable effect on augmenting flexibility (ß↓, γ↓, α↓ and Lp/ML↓) and compactness (ρ↓, df↑ and C∞↓) of branched random coil chain based on macromolecular analysis, especially when concentration increased. Moreover, it could be relevant to thermokinetic behavior of random nucleation and subsequent growth (A2 model and negative ΔS*) as well as good thermal stability (IPDT, ITS, t0.05, Tm and Tp), thus conferring potential applications for NSAP-25 in food and pharmaceutical industries.

14.
J Insect Physiol ; : 104238, 2021 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-33839141

RESUMEN

The ability to detect and remove dead adult bees is an essential part of honeybee colony fitness that prevents the spread of pathogens. Fatty acid olfactory cues stimulate undertaking behavior among different social species within Hymenoptera, but the chemicals responsible for the death cue in Apis cerana have not yet been identified. We explored the Nasonov gland as a potential source of these chemicals in A. cerana. Gas chromatography indicated that unlike A. mellifera, the A. cerana Nasonov gland does not contain any volatile terpenes, only fatty acids. As a bioassay, dead honeybees were rinsed free of their individual cuticular hydrocarbons via dichloromethane and two concentrations of oleic acid and a synthetic blend of the Nasonov pheromone in A. cerana were applied to the dummies. Results showed that oleic acid did not stimulate corpse removal in A. cerana. However, the synthetic pheromone blend of A. cerana Nasonov did stimulate removal.

15.
Histopathology ; 2021 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-33840132

RESUMEN

PURPOSE: The nuclear proliferation biomarker Ki67 plays potential prognostic and predictive roles in breast cancer treatment. However, lack of inter-pathologist consistency in Ki67 assessment limits the clinical use of Ki67. This paper reports a solution utilizing an artificial intelligence (AI)-empowered microscope to improve Ki67 scoring concordance. METHODS: We developed an AI empowered microscope where the conventional microscope was equipped with AI algorithms and AI results were provided to pathologists in real time through augmented reality. We recruited 30 pathologists with various experience levels from 5 institutes to assess Ki67 label index on 100 Ki67 stained slides for invasive breast cancer patients. In the first round, pathologists conducted visual assessment on a conventional microscope; in the second round, they were assisted with reference cards; and in the third round, they were assisted with an AI-empowered microscope. RESULTS: Experienced pathologists had better reproducibility and accuracy (ICC = 0.864, mean error = 8.25%) than inexperienced pathologists (ICC = 0.807, mean error = 11.0%) in visual assessment. Moreover, with reference cards, inexperienced (ICC = 0.836, mean error = 10.7%) and experienced pathologists (ICC = 0.875, mean error = 7.56%) improved their reproducibility and accuracy. Finally, both experienced (ICC = 0.937, mean error = 4.36%) and inexperienced pathologists (ICC = 0.923, mean error = 4.71%) improved the reproducibility and accuracy significantly with the AI-empowered microscope. CONCLUSION: AI-empowered microscope allows seamless integration of the AI solution into the clinical workflow and helps pathologists to obtain a higher consistency and accuracy for the Ki67 assessment.

16.
Molecules ; 26(5)2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33807509

RESUMEN

In addition to surgery, chemotherapy, radiotherapy, and targeted therapy, immunotherapy has emerged as a standard pillar of cancer treatment. Immune checkpoint inhibitors (ICIs) such as targeting programmed death-1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) have been integrated into standard-of-care regimens for patients with advanced lung squamous cell carcinoma (LUSC), who were previously limited by the lack of treatment options. Atezolizumab, durvalumab, nivolumab, and pembrolizumab are all currently used as part of standard-of-care treatment for different stages of lung cancer. Recent successes and failures of immune checkpoint blockade-based combination therapies have provided significant insights into implementing combination strategies in LUSC. Therefore, there is an urgent need to correctly select patients who are more likely to respond to immunotherapy and understand the mechanisms of primary or acquired resistance. In this review, we aim at summarizing the emerging clinical data on the promise and challenge of ICIs, discussing the unmet need of potential biomarkers for predicting response or resistance to immunotherapy, and providing an overview of the current immune landscape and future directions in advanced LUSC.

17.
Artículo en Inglés | MEDLINE | ID: mdl-33808628

RESUMEN

The Supplemental Nutrition Assistance Program (SNAP) is designed to improve household diet and food security-a pressing problem confronting low-income families in the United States. Previous studies on the issue often ignored the methodological issue of endogenous program participation. We revisit this important issue by estimating a simultaneous equation system with ordinal household food insecurity. Data are drawn from the 2009-2011 Current Population Survey Food Security Supplement (CPS-FSS), restricted to SNAP-eligible households with children. Our results add to the stocks of empirical findings that SNAP participation ameliorates food insecurity among adults only, but increases the probabilities of low and very low food security among children. These contradictory results indicate that our selection approach with a single cross section is only partially successful, and that additional efforts are needed in further analyses of this complicated issue, perhaps with longitudinal data. Socio-demographic variables are found to affect food-secure households and food-insecure households differently, but affect SNAP nonparticipants and participants in the same direction. The state policy tools, such as broad-based categorical eligibility (BBCE) and simplified reporting, can encourage SNAP participation and thus ameliorate food insecurity. Our findings can inform policy deliberations.

18.
Drug Deliv ; 28(1): 709-718, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33825591

RESUMEN

Lupeol liposomes, modified with Gal-PEG-DSPE, were developed following a thin-film dispersion method. Then, the morphology, physicochemical properties, and in vitro release properties of those liposomes were investigated. The scanning electron microscopic images showed that most of the liposomes were spherical particles; they were similar in size and uniformly dispersed. Both lupeol liposomes and Gal-lupeol liposomes exhibited an average particle size of about 100 nm. The encapsulation efficiency was greater than 85%. The encapsulation efficiency of lupeol liposome and Gal-lupeol liposome, stored with 15% sucrose as glycoprotein for 6 months, was higher than 80%; although the particle size increased, they remained within 200 nm. The cell-uptake study demonstrated that the Gal-lupeol-liposome uptake efficiency was the highest in HepG2 cells. The HepG2 cells treated with the Gal-lupeol liposomes had higher apoptotic efficiency than the lupeol liposome and free lupeol. After HepG2 cells were treated with Gal-lupeol liposome, the expressions of AKT/mTOR-related proteins (p-AKT308 and p-AKT473) were also significantly reduced than the lupeol-liposome and free lupeol group. The in vivo targeting studies showed that Gal-NR-L exhibited liver-targeting effects on FVB mice. The pharmacodynamic study was performed by transfecting AKT and c-MET via the high-pressure tail vein of FVB mice. After Gal-lupeol-L administration, the liver index and liver weight of mice were less than those non-targeted group. The histopathological study showed that the lobular structure in the mice liver was clearer, the vacuoles were more obvious, and the cytoplasm was more abundant after Gal-lupeol-L administration. Also, the qRT-PCR study showed that AFP, GPC3, and EpCAM mRNA expression levels were significantly lower than those non-targeted lupeol-liposomes.

19.
Int J Epidemiol ; 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33826715

RESUMEN

BACKGROUND: Acute respiratory infections have been associated with a transient increase in cardiovascular risk. However, whether such an association persists beyond 1 month and the potential modifying effect of cardiovascular risk factors on such an association are less well established. METHODS: The China Kadoorie Biobank enrolled 512 726 participants aged 30-79 years from 10 areas across China during 2004-2008. By the end of 2017, a total of 5444 participants with new-onset ischaemic heart disease (IHD) and 4846 with ischaemic stroke (IS) who also had at least a record of hospitalization for pneumonia during follow-up were included. We used a self-controlled case-series method and calculated the age- and season-adjusted relative incidences (RIs) and 95% confidence intervals (CIs) for ischaemic cardiovascular disease (CVD) after pneumonia. RESULTS: The risk of ischaemic CVD increased during days 1-3 after pneumonia hospitalization, with an RI (95% CI) of 4.24 (2.92-6.15) for IHD and 1.85 (1.02-3.35) for IS. The risk gradually reduced with longer duration since pneumonia hospitalization but remained elevated until days 92-365 for IHD (1.23, 1.12-1.35) and days 29-91 for IS (1.25, 1.05-1.48). Pre-existing cardiovascular risk factors amplified the associations between pneumonia and ischaemic CVD risks, such as chronic obstructive pulmonary disease for both IHD and IS, and diabetes and smoking for IHD (all Pinteraction < 0.05). Besides, the risk of ischaemic CVD was also higher among the participants aged ≥70 years (Pinteraction < 0.001 for IHD and 0.033 for IS). CONCLUSION: Among middle-aged and older Chinese adults, pneumonia hospitalization was associated with both short- and long-term increases in ischaemic CVD risk for ≤1 year.

20.
Am J Chin Med ; : 1-20, 2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33827385

RESUMEN

Neuraminidase, also known as sialidase, is ubiquitous in animals and microorganisms. It is predominantly distributed in the cell membrane, cytoplasmic vesicles, and lysosomes. Neuraminidase generally recognizes the sialic acid glycosidic bonds at the ends of glycoproteins or glycolipids and enzymatically removes sialic acid. There are four types of neuraminidases, named as Neu1, Neu2, Neu3, and Neu4. Among them, Neu1 is the most abundant in mammals. Recent studies have revealed the involvement of Neu1 in several diseases, including cardiovascular diseases, diabetes, cancers, and neurological disorders. In this review, we center the attention to the role of Neu1 in cardiovascular diseases, including atherosclerosis, ischemic myocardial injury, cerebrovascular disease, congenital heart disease, and pulmonary embolism. We also summarize inhibitors from Chinese herbal medicines (CHMs) in inhibiting virus neuraminidase or human Neu1. Many Chinese herbs and Chinese herb preparations, such as Lonicerae Japonicae Flos, Scutellariae Radix, Yupingfeng San, and Huanglian Jiedu Decoction, have neuraminidase inhibitory activity. We hope to highlight the emerging role of Neu1 in humans and potentially titillate interest for further studies in this area.

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