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1.
Brain Struct Funct ; 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33389041

RESUMO

The frequency of brain activity modulates the relationship between the brain and human behavior. Insufficient understanding of frequency-specific features may thus lead to inconsistent explanations of human behavior. However, to date, the frequency-specific features of the human brain functional network at the whole-brain level remain poorly understood. Here, we used resting-state fMRI data and graph-theory analyses to investigate the frequency-specific characteristics of fMRI signals in 12 frequency bands (frequency range 0.01-0.7 Hz) in 75 healthy participants. We found that brain regions with higher level and more complex functions had a more variable functional connectivity pattern but engaged less in higher frequency ranges. Moreover, brain regions that engaged in fewer frequency bands played more integrated roles (i.e., higher network participation coefficient and lower within-module degree) in the functional network, whereas regions that engaged in broader frequency ranges exhibited more segregated functions (i.e., lower network participation coefficient and higher within-module degree). Finally, behavioral analyses revealed that regional frequency variability was associated with a spectrum of behavioral functions from sensorimotor functions to complex cognitive and social functions. Taken together, our results showed that segregated functions are executed in wide frequency ranges, whereas integrated functions are executed mainly in lower frequency ranges. These frequency-specific features of brain networks provided crucial insights into the frequency mechanism of fMRI signals, suggesting that signals in higher frequency ranges should be considered for their relation to cognitive functions.

2.
Clin Oral Investig ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33432420

RESUMO

OBJECTIVES: The aim of this study was to assess whether alveolar ridge preservation (ARP) can reduce the need of ridge augmentation at posterior tooth sites. MATERIAL AND METHODS: This study enrolled patients who received dental implants at posterior tooth sites during 2013-2019. Demographic data and dental treatment histories were collected. Based on healing patterns after tooth extraction, patients were divided into ARP and spontaneous healing (SH) groups. Three surgical treatment plans were devised according to the alveolar bone volume on cone-beam computed tomography (CBCT). The three treatment plans were to perform implant alone, simultaneous guided bone regeneration (GBR) and implantation, and staged GBR before implantation. Statistical analyses were performed to determine relationships. RESULTS: There were 92 implant records in the ARP group and 249 implant records in the SH group. A significant intergroup difference was observed regarding the frequency distribution of the treatment modality of staged GBR before implant (χ 2 = 15.07, p = 0.0005). Based on the implant alone treatment modality and simple logistic regression, the SH pattern was related to staged GBR before implant (SH vs. ARP: crude odds ratio (OR) = 4.65, 95% confidence interval (CI) = 2.15-11.61, p = 0.0003). After adjusting confounding factors, the risk was still significant (adjusted OR = 5.02, 95% CI = 2.26-12.85, p = 0.0002). CONCLUSIONS: The study results suggested that ARP is more likely to lead to the treatment modality of implant alone and reduce the need for staged GBR before implantation. CLINICAL RELEVANCE: This study describes ARP capable of minimizing the need for staged GBR before implantation and shortening the treatment duration.

3.
Sci Rep ; 11(1): 115, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420227

RESUMO

Immediate postoperative intensive care unit (ICU) admission can increase the survival rate in patients undergoing high-risk surgeries. Nevertheless, less than 15% of such patients are immediately admitted to the ICU due to no reliable criteria for admission. The surgical Apgar score (SAS) (0-10) can be used to predict postoperative complications, mortality rates, and ICU admission after high-risk intra-abdominal surgery. Our study was performed to determine the relationship between the SAS and postoperative ICU transfer after all surgeries. All patients undergoing operative anesthesia were retrospectively enrolled. Among 13,139 patients, 68.4% and < 9% of whom had a SASs of 7-10 and 0-4. Patients transferred to the ICU immediately after surgery was 7.8%. Age, sex, American Society of Anesthesiologists (ASA) class, emergency surgery, and the SAS were associated with ICU admission. The odds ratios for ICU admission in patients with SASs of 0-2, 3-4, and 5-6 were 5.2, 2.26, and 1.73, respectively (P < 0.001). In general, a higher ASA classification and a lower SAS were associated with higher rates of postoperative ICU admission after all surgeries. Although the SAS is calculated intraoperatively, it is a powerful tool for clinical decision-making regarding the immediate postoperative ICU transfer.

4.
Clin Exp Allergy ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33471392

RESUMO

BACKGROUND: In asthma, IL-6 is a potential cause of enhanced inflammation, tissue damage and airway dysfunction. IL-6 signaling is regulated by its receptor, which is composed of two proteins, IL-6R and GP130. In addition to their membrane form, these two proteins may be found as extracellular soluble forms. The interaction of IL-6 with soluble IL-6R (sIL-6R) can trigger IL-6 trans-signaling in cells lacking IL-6R. Conversely, the soluble form of GP130 (sGP130) competes with its membrane form to inhibit IL-6 trans-signaling. OBJECTIVES: We aimed to analyze IL-6 trans-signaling proteins in the airways of subjects after an allergen challenge. METHODS: We used a model of segmental bronchoprovocation with an allergen (SBP-Ag) in human subjects with allergy. Before and 48h after SBP-Ag, bronchoalveolar lavages (BAL) allowed for the analysis of proteins in BAL fluids (BALF) by ELISA, and membrane proteins on the surface of BAL cells by flow cytometry. In addition, we performed RNA-sequencing (RNA-seq) and used proteomics data to further inform on the expression of the IL-6R subunits by eosinophils, bronchial epithelial cells and lung fibroblasts. Finally, we measured the effect of IL-6 trans-signaling on bronchial fibroblasts, in vitro. RESULTS: IL-6, sIL-6R, sGP130 and the molar ratio of sIL-6R/sGP130 increased in the airways after SBP-Ag, suggesting the potential for enhanced IL-6 trans-signaling activity. BAL lymphocytes, monocytes and eosinophils displayed IL-6R on their surface and were all possible providers of sIL-6R, whereas GP130 was highly expressed in bronchial epithelial cells and lung fibroblasts. Finally, bronchial fibroblasts activated by IL-6 trans-signaling produced enhanced amounts of the chemokine, MCP-1 (CCL2). CONCLUSION: and Clinical relevance After a bronchial allergen challenge, we found augmentation of the elements of IL-6 trans-signaling. Allergen-induced IL-6 trans-signaling activity can activate fibroblasts to produce chemokines that can further enhance inflammation and lung dysfunction.

5.
Trials ; 22(1): 35, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413569

RESUMO

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia, which is closely related to cardiovascular morbidity and mortality. Although acupuncture is used in the treatment of AF, the evidence is insufficient. The objective of this pilot trial is to evaluate the feasibility, preliminary efficacy, and safety of acupuncture in reducing AF burden for persistent AF after catheter ablation (CA). METHODS AND DESIGN: This will be a multi-center, 3-arm, pilot randomized controlled trial in China. Sixty patients in total will be randomly assigned to the specific acupoints group, the non-specific acupoints group, or the non-acupoints group in a 1:1:1 ratio. The whole study period is 6 months, including a 3-month treatment period and a 3-month follow-up period. All patients will receive 18 sessions of acupuncture over 12 weeks after CA and appropriate post-ablation routine treatment. The primary outcome is AF burden at 6 months after CA measured by electrocardiography patch that can carry out a 7-day continuous ambulatory electrocardiographic monitoring. The secondary outcomes include AF burden at 3 months after CA, recurrence of AF, quality of life, etc. The adverse events will also be recorded. DISCUSSION: This pilot study will contribute to evaluating the feasibility, preliminary efficacy, and safety of acupuncture in reducing AF burden for persistent AF after CA. The results will be used for the sample size calculation of a subsequent large-scale trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000030576 . Registered on 7 March 2020.

6.
J Dent Sci ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33425239

RESUMO

Background/purpose: Dental visits are a high risk activity during the COVID-19 pandemic. This study investigated the utilization of emergency dental services and clinical practical attitudes of dental residents in this period. Materials and methods: Retrospective chart data from 13th November 2019 to 31st March 2020 in Kaohsiung Medical University Hospital, Taiwan were used. We obtained electronic medical records to review data from 515 patients who visited the emergency department with dental complaints and we contacted the 26 residents assigned to act as primary care providers to participate in this study. Results: After the COVID-19 outbreak, 17% fewer patients had dental emergency utilization at a hospital emergency center relative to the previous period. A survey of residents also showed a decline in the number of patients. There were no significant differences of patients' problems and diagnoses between the two periods. After the COVID-19 outbreak, 61.5% of the residents were afraid of being infected by a patient's disease and the proportions of dentists wearing waterproof gowns, face shields, and surgical hair caps were 76.9%, 88.5%, and 76.3%, respectively. These variables increased significantly after the outbreak of COVID-19. Conclusion: Despite the trend of a decreased number of patients, their utilization of dental emergency services seems to be similar before and after the COVID-19 outbreak, possibly related to strict hospital infection control policies and the relatively low number of COVID-19 confirmed patients internationally at that time.

7.
J Formos Med Assoc ; 120(1 Pt 1): 172-179, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32307323

RESUMO

PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease associated with rapid clinical deterioration and the need for intensive care; therefore, it is essential to identify clinical parameters related to mortality and establish prognostic factors correlated with unfavorable outcome in high risk patients whose treatment may fail. METHODS: Between January 2004 and December 2018, a total of 51 pediatric patients (less than 18 years old) who fulfilled the diagnostic criteria of HLH-2004 with documented results of bone marrow investigations at Kaohsiung Chang Gung Memorial Hospital were enrolled. The treatment protocol was based on hemophagocytic lymphohistiocytosis-94 (HLH-94) and HLH-2004. We retrospectively reviewed electronic medical records (EMR) including clinical features, length of intensive care unit (ICU) stay, serological tests, microscopic reports of bone marrow examination, and ultrasound examination reports at diagnosis to identify prognostic factors. The patients were divided into four groups based on etiology; these included infection associated hemophagocytic syndrome (IAHS), macrophage activation syndrome (MAS), malignancy associated hemophagocytic lymphohistiocytosis (MA-HLH), and idiopathic hemophagocytic lymphohistiocytosis (IHLH) to identify differences among the groups. RESULTS: Out of 51 patients enrolled, 27 patients had IAHS, 12 MAS, 8 MA-HLH, and 4 IHLH. The median age at diagnosis was 7 years. The overall mortality rate was 15.7% (there was no mortality in the MA-HLH group); the mean length of ICU stay was 6 ± 20.8 days. Longer activated partial thromboplastin time (aPTT) (p = 0.007), lower sodium concentration (p = 0.0007), and higher creatinine (p = 0.032) and aspartate aminotransferase (AST) (p = 0.017) were significantly related to mortality. Multivariate Cox regression analysis demonstrated that aPTT (p = 0.045, HR = 1.03, 95% CI = 1.0-1.1) was an independent risk factor for mortality. The receiver operating characteristic (ROC) curve showed that aPTT longer than 44.35 s was the cutoff value predicting mortality, with a sensitivity and specificity of 72% and 66.7%, respectively. CONCLUSION: MA-HLH had the lowest mortality rate, as most children died from the underlying malignant disease and not from HLH. Impaired liver and renal functions were related to mortality. Prolonged aPTT > 44.35 s is a strong predictive factor for mortality.

8.
J Ethnopharmacol ; 265: 113228, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32777517

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The uses of medicinal plants have a long history and become one of the important sources of the health cares in Gaomi City, Shandong Province, China. However, limited studies have been done to identify these medicinal plant species and to scientifically document their associated traditional knowledge. Many species used by indigenous people could potentially represent a novel resource of medicine. The study can aid in further investigations of modern pharmacology and planning of the wild species conservation. AIM OF THE STUDY: The study aimed to investigate and record the medicinal plant taxa and their associated traditional knowledge in Gaomi City, China. MATERIALS AND METHODS: Field study was conducted from March 2018 to May 2019 with 184 residents of Gaomi City. Traditional medicinal plant specimens were collected from the field with the help of these residents and were identified and authenticated in the Herbarium of the School of Pharmacy, Binzhou Medical University. Ethnobotanical knowledge was collected by semi-structured face-to-face interviews. The quantitative data were analyzed by using the informant consensus factor (ICF) method and the number of citations. RESULTS: A total of 181 species belonging to 137 genera and 65 families were collected in Gaomi City. Asteraceae was the predominant family and Fabaceae took the second place. River basins and the southern hills in Gaomi were rich in vegetation. However, the cultivated area of medicinal plants only accounted for 10% of agricultural acreage. The main preparation method was decocting (170, 94.48%) and the most frequent mode of administration was oral (177, 97.97%). The highest numerical ICF value was recorded for treating endocrine, metabolic, and nutritional (ICF: 0.85) conditions. Seven of the medicinal plant species used by the people in Gaomi have not been reported previously in China. Verbena officinalis L. was found in Gaomi City, which is a new distribution record for this species. CONCLUSIONS: People in Gaomi hold valuable knowledge about the use of medicinal plants; however, their knowledge has not been comprehensively documented. The therapeutic uses of the documented medicinal plants will provide a basis for further pharmacological and phytochemical investigations. Additionally, the result of this study indicated that the elder people in Gaomi have more traditional knowledge of plant medicines than the younger ones.

9.
J Ethnopharmacol ; 264: 113267, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32822822

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sleep disorders affect an estimated 150 million people worldwide and result in adverse health, safety, and work performance-related outcomes that have important economic consequences. In Taiwan, Chinese herbal medicine (CHM) is a complementary natural medicine and has been widely used as an adjunctive therapy. AIM OF THE STUDY: This study aimed to investigate the effect of CHM on dementia risk in patients with sleep disorders in Taiwan. MATERIALS AND METHODS: We identified 124,605 patients with sleep disorders between the ages of 20 and 60 years. Of these, 5876 CHM users and 5876 non-CHM users were matched according to age and gender. The chi-squared test, Cox proportional hazard model, Kaplan-Meier method, and log-rank test were used for the comparisons. Association rule mining and network analysis were applied to determine a CHM pattern specialized for sleep disorders. RESULTS: More CHM users did not use sleeping pills than non-CHM users. CHM users had a lower risk of dementia than non-CHM users after adjusting for age, gender, and sleeping pill use (hazard ratio (HR): 0.469, 95% CI = 0.289-0.760; p-value = 0.002). The cumulative incidence of dementia was lower among CHM users (long-rank test, p-value < 0.001). Association rule mining and network analysis showed that Ye-Jiao-Teng (YJT; Caulis Polygoni Multiflori; Polygonum multiflorum Thunb), Suan-Zao-Ren-Tang (SZRT), Jia-Wei-Xiao-Yao-San (JWXYS), He-Huan-Pi (HHP; Cortex Albizziae; Albizia julibrissin Durazz.), and Suan-Zao-Ren (SZR; Semen Zizyphi Spinosae; Ziziphus jujuba Mill.) were important CHMs for patients with sleep disorders in Taiwan. CONCLUSIONS: A comprehensive list of herbal medicines may be useful for the clinical treatment of patients with sleep disorders, and for future scientific investigations into the prevention of dementia in these patients.

10.
Sci Total Environ ; 750: 141547, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32858293

RESUMO

High total urinary arsenic concentrations and low estimated glomerular filtration rate (eGFR) increase the risk of renal cell carcinoma (RCC). This study aimed to determine whether other metals or metalloids can affect RCC. A total of 401 patients with RCC and 774 age- and sex-matched controls were recruited between November 2006 and December 2012 in Taiwan. Surgical resection or image-guided biopsy of renal tumors was performed to pathologically verify RCC. High-performance liquid chromatography linked to a hydride generator and atomic absorption spectrometer were used to measure the urinary arsenic species concentrations. Inductively coupled plasma mass spectrometry was used to determine plasma selenium and red blood cell cadmium and lead concentration. Plasma selenium levels were inversely related to RCC, whereas red blood cell cadmium levels were directly related to RCC. The odds ratio (OR) and 95% confidence interval (CI) were 0.14 (95% CI, 0.10-0.20) and 1.33 (95% CI, 1.03-1.72), respectively. A low plasma selenium level tended to interact with high total urinary arsenic levels or with high red blood cell cadmium concentration to increase the OR of RCC. In particular, low eGFR multiplicatively interacted with high red blood cell cadmium concentration to increase the OR of RCC (Pinteraction=0.003). This study was the first to find a significant multiplicative interaction between eGFR and the red blood cell cadmium levels on the increased OR of RCC.


Assuntos
Arsênico , Carcinoma de Células Renais , Neoplasias Renais , Selênio , Cádmio , Estudos de Casos e Controles , Receptores ErbB , Eritrócitos , Taxa de Filtração Glomerular , Humanos , Taiwan/epidemiologia
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 246: 118944, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33007643

RESUMO

To explore the biological properties of rosin derivatives, two dehydroabietic acid derivatives N-(5-dehydroabietyl-1,3,4-thiadiazole)-yl-pyridine-2-carboxamide (DTPC) and di-N-(5-dehydroabietyl-1,3,4-thiadiazole)-yl-pyridine-2,6-carboxamide (DDTPC) with 1,3,4-thiadiazole, pyridine and amide moieties were designed and synthesized according to superposition principle of activity group. They interact with calf thymus DNA (CT DNA) via intercalation based on the results of circular dichroism (CD) and fluorescence spectroscopy, DNA denaturation and viscosity studies. Fluorescence and CD spectral experiments indicate that they might be transported and stored by protein like bovine serum albumin (BSA). MTT assay was further carried out to examine their cytotoxicity, they both showed selective cytotoxicity and DTPC exhibited better cytotoxicity. The antiproliferative effect of DTPC toward A431 cell line was stronger than that of clinically used cisplatin and oxaliplatin. In addition, the cytotoxicity of DTPC and DDTPC was closely related with their DNA binding ability.

12.
J Colloid Interface Sci ; 581(Pt B): 783-793, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32814198

RESUMO

Carbon nanotube-decorated nitrogen-doped carbon-coated nickel (CNT/Ni@N-C) microspheres have been fabricated by pyrolyzing the mixture of nickel-based metal organic framework (Ni-MOF) and melamine. The resultant composite is assembled from CNTs and spherical Ni@N-C composite. Besides, the CNT/Ni@N-C composite contains abundant nitrogen (N) dopants that contribute to defect dipole polarization. The melamine content is important for controlling the amount of N element and N dopant state in the composite. The optimized CNT/Ni@N-C composite with high content of pyridinic N exhibits strong absorption of -55.1 dB at 10.56 GHz with the thickness of 2.5 mm, and the effective absorbing bandwidth (reflection loss < -10 dB) is 11.2 GHz (6.0-17.2 GHz) with the thickness range of 1.5-4.0 mm. These results indicate that the N content and N dopant state have a great influence on electromagnetic wave absorption properties. This strategy will contribute to fabricate the carbon hybrid network consisting of metal organic frameworks derived metal/carbon hybrid and CNTs for electromagnetic wave absorption.

13.
Acta Crystallogr C Struct Chem ; 76(Pt 12): 1068-1075, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33273144

RESUMO

A new caesium sodium samarium borate phosphate, CsNa2Sm2(BO3)(PO4)2, has been obtained successfully by the high-temperature solution growth (HTSG) method and single-crystal X-ray diffraction analysis reveals that it crystallizes in the orthorhombic space group Cmcm. The structure contains BO3, PO4, NaO7 and SmO7 polyhedra which are interconnected via corner- or edge-sharing O atoms to form a three-dimensional [Na2Sm2(BO3)(PO4)2]∞ network. This network delimits large cavities where large Cs+ cations reside to form the total structure. Under 402 nm light excitation, CsNa2Sm2(BO3)(PO4)2 exhibits three emission bands due to the 4f→4f transitions of Sm3+. Furthermore, we introduced Gd3+ into Sm3+ sites to optimize the Sm3+ concentration and improve the luminescence intensity. The optimal concentration is Gd/Sm = 98/2. The luminescent lifetime of a series of CsNa2Gd2(1-x)Sm2x(BO3)(PO4)2 phosphors shows a gradual degradation of lifetime from 2.196 to 0.872 ms for x = 0.01-0.10. The Commission Internationale de l'Eclairage (CIE) 1931 calculation reveals that CsNa2Gd1.96Sm0.04(BO3)(PO4)2 can emit orange light under 402 nm excitation.

14.
J Dermatol Sci ; 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33358580

RESUMO

BACKGROUND: Atopic dermatitis (AD) is characterized by impaired skin barrier function and immune system dysfunction. The expression and role of Yes-associated protein (YAP) in AD are unclear. OBJECTIVE: To characterize the role of the YAP in T cell imbalance and epidermal keratinocyte dysfunction in the pathogenesis of AD. METHODS: We included 35 patients with AD (21 acute and 14 chronic). An AD mouse model was constructed using 2,4-dinitrofluorobenzene, and AD-like inflammatory cell model was constructed using TNF-α/IFN-γ-activated HaCaT cells. The proportion of Th1/Th2/Th17/Treg cells was detected using flow cytometry. After mononuclear cells were obtained from human peripheral blood or mouse spleen and induced to differentiate into different T cell subsets, YAP mRNA and protein expression were analyzed. Up-regulation of YAP was induced by lentivirus and down-regulation of YAP was induced by its specific inhibitor verteporfin (VP). The expression of YAP in skin lesions and infiltrating T cell subsets was detected using immunohistochemistry and double immunofluorescence staining, respectively. RESULTS: We found differing degrees of Th1/Th2/Th17/Treg imbalance in acute and chronic AD. YAP expression was downregulated in Treg cells and upregulated in Th17 cells; YAP expression was downregulated in the AD epidermis. After YAP overexpression, the proportion of both Th17 and the Treg cells differentiated from mouse spleen mononuclear cells increased. There was an opposite trend after YAP inhibition. The proliferation and migration decreased and apoptosis increased after YAP inhibition in HaCaT cells. CONCLUSION: Change of YAP expression may cause T cell imbalance and hamper the healing of the epidermis in AD.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33358676

RESUMO

BACKGROUND: A peroneal flap, the boneless version of fibula flap, is considered as the equivalent of radial forearm flap of the lower leg. Because it is thinner than an anterolateral thigh (ALT) flap, the use of a peroneal flap is a viable option for the repair of soft tissue defects when a thin flap could bring about better functional and cosmetic outcomes. In this article, we describe the details of peroneal flap harvest and present our experience with the use of peroneal flaps for head and neck reconstruction. MATERIALS AND METHODS: Between 1996 and 2017, a total of 265 peroneal flaps were used to reconstruct a variety of head and neck defects. With the same vascular anatomy and slight modifications to the harvesting technique of a fibula flap, a peroneal flap can be harvested within 1-2 h. All medical records were retrospectively reviewed. RESULTS: A peroneal flap can be harvested as different types of chimeric flaps to fit a variety of head and neck defects. The peroneal flap failure rate was 3.4% and the postoperative complication rate was 12.8%. CONCLUSION: A peroneal flap might be an alternative option for the reconstruction of head and neck defects.

16.
Biomater Sci ; 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33367388

RESUMO

Tumor microenvironment responsive and self-monitored multimodal synergistic theranostic strategies can significantly improve therapeutic efficacy by overcoming biological barriers. Herein, we report a type of smart fluorescent hyaluronic acid nanogel that can respond to the reducing microenvironment and activate tumor targeting with light-traceable monitoring in cancer therapy. First, the derivative of hyaluronic acid (HA) with a vinyl group and cystamine bisacrylamide were used to synthesize bioreducible HA based nanogels via copolymerization in aqueous medium. Then, multifunctional mHA-gold cluster (mHA-GC) hybrid nanogels were successfully prepared by the in situ reduction of gold salt in the HA nanogels. The HA matrix turns the nanogels into a capsule for effective drug loading with excellent colloidal stability. Interestingly, the reducing tumor microenvironment dramatically enhanced the fluorescence signal of gold clusters in the hybrid nanogels. The highly selective cancer cell uptake and efficient intratumoral accumulation of the hybrid nanogels were demonstrated by fluorescence tracking of these nanogels. Responsive disassembly of the hybrid nanogels and drug release were triggered by excess glutathione presence in cancer cells. Moreover, in vivo and in vitro tumor suppression assays revealed that the doxorubicin-loaded hybrid nanogels exhibited significantly superior tumor cell inhibition abilities compared to free DOX. Overall, the mHA-GC hybrid nanogels emerge as a promising theranostic nanoplatform for the targeted delivery and controlled release of antitumor drugs with light-traceable monitoring in cancer treatment.

17.
18.
Environ Toxicol ; 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33325633

RESUMO

The overexpression of EGFR and/or ErbB2 occurs frequently in ovarian cancers and is associated with poor prognosis. The purpose of this study was to examine the anticancer effects and molecular mechanisms of berberine on human ovarian cancer cells with different levels of EGFR and/or ErbB2. We found that berberine reduced the motility and invasiveness of ovarian cancer cells. Berberine depleted both EGFR and ErbB2 in ovarian cancer cells. Furthermore, berberine suppressed the activation of the EGFR and ErbB2 downstream targets cyclin D1, MMPs, and VEGF by down-regulating the EGFR-ErbB2/PI3K/Akt signaling pathway. The berberine-mediated inhibition of MMP-2 and MMP-9 activity could be rescued by co-treatment with EGF. Finally, we demonstrated that berberine induced ErbB2 depletion through ubiquitin-mediated proteasome degradation. In conclusion, the suppressive effects of berberine on the ovarian cancer cells that differ in the expression of EGFR and ErbB2 may be mediated by the dual depletion of EGFR and/or ErbB2.

19.
Protein Cell ; 2020 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-33314005

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs. The infected cells were ciliated, club, and alveolar type 2 (AT2) cells, which were sequentially located from the proximal to the distal airway and terminal alveoli, respectively. Additionally, RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes, especially lipid metabolism, in addition to the well-known upregulation of immune response. Further, Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.

20.
Ultrasonics ; 111: 106329, 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33338730

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Quantitative ultrasound facilitates clinical grading of hepatic steatosis (the early stage of NAFLD). However, the utility of quantitative ultrasound as a first-line method for community screening of hepatic steatosis remains unclear. Therefore, this study aimed to investigate the utility of quantitative ultrasound to screen for hepatic steatosis and for metabolic evaluation at the community level. In total, 278 participants enrolled from a community satisfied the study criteria. Each subject underwent anthropometric and biochemical examinations, and abdominal ultrasound imaging was performed to measure the controlled attenuation (CAP), integrated backscatter (IB), and information Shannon entropy (ISE). The assessment outcomes were compared with the fatty liver index (FLI), hepatic steatosis index (HSI), metabolic syndrome (MetS), and insulin resistance to evaluate the screening performance through the area under the receiver operating characteristic curve (AUROC) and Delong's test. Ultrasound ISE, CAP, and IB were effective in screening hepatic steatosis, MetS, and insulin resistance. In screening for hepatic steatosis, the AUROCs of ISE, CAP, and IB were 0.85, 0.83, and 0.80 (the cutoff FLI = 60), respectively, and 0.84, 0.75, 0.77 (the cutoff HSI = 36), respectively, and those for the evaluation of MetS and insulin resistance were 0.79, 0.75, 0.79, respectively, and 0.83, 0.76, 0.78, respectively. Delong's test revealed that ISE outperformed CAP and IB for the detection of hepatic steatosis and insulin resistance (P < .05). Based on the present results, ultrasound ISE is a potential imaging biomarker during first-line community screening of hepatic steatosis and insulin resistance.

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