Publications by authors named "Bo Xiao"

682 Publications

Encephalopathy at admission predicts adverse outcomes in patients with SARS-CoV-2 infection.

CNS Neurosci Ther 2021 Jun 16. Epub 2021 Jun 16.

Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.

Aims: To determine if neurologic symptoms at admission can predict adverse outcomes in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: Electronic medical records of 1053 consecutively hospitalized patients with laboratory-confirmed infection of SARS-CoV-2 from one large medical center in the USA were retrospectively analyzed. Univariable and multivariable Cox regression analyses were performed with the calculation of areas under the curve (AUC) and concordance index (C-index). Patients were stratified into subgroups based on the presence of encephalopathy and its severity using survival statistics. In sensitivity analyses, patients with mild/moderate and severe encephalopathy (defined as coma) were separately considered.

Results: Of 1053 patients (mean age 52.4 years, 48.0% men [n = 505]), 35.1% (n = 370) had neurologic manifestations at admission, including 10.3% (n = 108) with encephalopathy. Encephalopathy was an independent predictor for death (hazard ratio [HR] 2.617, 95% confidence interval [CI] 1.481-4.625) in multivariable Cox regression. The addition of encephalopathy to multivariable models comprising other predictors for adverse outcomes increased AUCs (mortality: 0.84-0.86, ventilation/ intensive care unit [ICU]: 0.76-0.78) and C-index (mortality: 0.78 to 0.81, ventilation/ICU: 0.85-0.86). In sensitivity analyses, risk stratification survival curves for mortality and ventilation/ICU based on severe encephalopathy (n = 15) versus mild/moderate encephalopathy (n = 93) versus no encephalopathy (n = 945) at admission were discriminative (p < 0.001).

Conclusions: Encephalopathy at admission predicts later progression to death in SARS-CoV-2 infection, which may have important implications for risk stratification in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cns.13687DOI Listing
June 2021

RNA methylation and neurovascular unit remodeling.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 May;46(5):536-544

Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.

RNA methylation is of great significance in the regulation of gene expression, among which the more important methylation modifiers are N6-methyladenosine (m6A) and 5-methylcytosine (m5C). The methylation process is mainly regulated by 3 kinds of proteins: methyltransferase, demethylase, and reader. m6A, m5C, and their related proteins have high abundance in the brain, and they have important roles in the development of the nervous system and the repair and remodeling of the vascular system. The neurovascular unit (NVU) is a unit of brain structure and function composed of neurons, capillaries, astrocytes, supporting cells, and extracellular matrix. The local microenvironment for NVU has an important role in nerve cell function repair, and the remodeling of NVU is of great significance in the prognosis of various neurological diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11817/j.issn.1672-7347.2021.200246DOI Listing
May 2021

Identification of Epithelial-Mesenchymal Transition-Related Prognostic lncRNAs Biomarkers Associated With Melanoma Microenvironment.

Front Cell Dev Biol 2021 31;9:679133. Epub 2021 May 31.

Department of Orthopedics, Second Xiangya Hospital, Central South University, Changsha, China.

Melanoma is the most common cancer of the skin, associated with a worse prognosis and distant metastasis. Epithelial-mesenchymal transition (EMT) is a reversible cellular biological process that plays significant roles in diverse tumor functions, and it is modulated by specific genes and transcription factors. The relevance of EMT-related lncRNAs in melanoma has not been determined. Therefore, RNA expression data and clinical features were collected from the TCGA database ( = 447). Melanoma samples were randomly assigned into the training (315) and testing sets (132). An EMT-related lncRNA signature was constructed via comprehensive analyses of lncRNA expression level and corresponding clinical data. The Kaplan-Meier analysis showed significant differences in overall survival in patients with melanoma in the low and high-risk groups in two sets. Receiver operating characteristic (ROC) curves were used to measure the performance of the model. Cox regression analysis indicated that the risk score was an independent prognostic factor in two sets. Besides, a nomogram was constructed based on the independent variables. Gene Set Enrichment Analysis (GSEA) was applied to evaluate the potential biological functions in the two risk groups. Furthermore, the melanoma microenvironment was evaluated using ESTIMATE and CIBERSORT algorithms in the risk groups. This study indicates that EMT-related lncRNAs can function as potential independent prognostic biomarkers for melanoma survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.679133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201078PMC
May 2021

Identification and validation of immune-related lncRNA prognostic signatures for melanoma.

Immun Inflamm Dis 2021 Jun 2. Epub 2021 Jun 2.

Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

Introduction: Melanoma is a highly aggressive malignant skin tumor as well as the primary reason for skin cancer-specific deaths. We first identified immune-related long noncoding RNA (lncRNA) prognostic signature and found potential immunotherapeutic targets for melanoma cancer.

Methods: RNA-seq data and clinical features of melanoma samples were obtained from The Cancer Genome Atlas. Samples of melanoma were randomly assigned to the training and testing cohort. The immune-related lncRNA signature was then obtained via using univariate, LASSO, and multivariate Cox analysis of patients in the training cohort. Eight significant immune-related lncRNA signature was then subsequently obtained through correlation analysis between immune-related genes and lncRNAs. The association between risk score and immune cell infiltration was finally assessed using TIMER and CIBERSORT.

Results: Three hundred and fifty-six immune-related lncRNAs were obtained. Among them, eight immune-related lncRNAs were identified to build a prognostic risk signature model. The model's performance was then confirmed using the Kaplan-Meier curves, risk plots, and time-dependent receiver-operating characteristic curves in the training cohort. The risk score was identified and confirmed as an independent prognostic factor through univariate and multivariate Cox regression analyses. These results were further verified in the testing and whole cohorts. CIBERSORT algorithm showed that the infiltration levels of T cells CD8, M1 macrophages, plasma cells, T cells CD4 memory activated, T cells gamma delta, and mast cells activated were significantly lower in the high-risk group while the infiltration level of macrophages M0 was significantly lower in the low-risk group.

Conclusion: The immune-related lncRNA signature offers prognostic markers and potential immunotherapeutic targets for melanoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/iid3.468DOI Listing
June 2021

Case Report: Aicardi-Goutières Syndrome and Singleton-Merten Syndrome Caused by a Gain-of-Function Mutation in IFIH1.

Front Genet 2021 13;12:660953. Epub 2021 May 13.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.

The gene encodes melanoma differentiation-associated gene 5 (MDA5) and has been associated with Aicardi-Goutières syndrome (AGS), Singleton-Merten syndrome (SMS), and other autoimmune diseases. The mechanisms responsible for how a functional change in a single gene can cause so many different phenotypes remain unknown. Moreover, there is significant controversy as to whether these distinct phenotypes represent the same disease continuum or mutation-specific disorders. Here, we describe the case of a patient with a novel c.1465G > T (p.Ala489Ser) mutation in the gene. The patient presented with spastic paraplegia, dystonia, psychomotor retardation, joint deformities, intracranial calcification, abnormal dentition, characteristic facial features, lymphadenopathy, and autoimmunity. His phenotype appeared to represent an overlap of the phenotypes for AGS and SMS. The patient also experienced unexplained pancytopenia, suggesting that the hemic system may have been affected by a gain-of-function mutation in the gene. In summary, we provide further evidence that SMS and AGS exhibit the same disease spectrum following a gain-of-function mutation in the gene. Our data highlight the genetic heterogeneity of these conditions and expand our knowledge of differential phenotypes created by gain-of-function mutation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2021.660953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155672PMC
May 2021

Knockdown of GBAS regulates esophageal cancer cell viability and apoptosis.

Mol Med Rep 2021 Jul 26;24(1). Epub 2021 May 26.

Department of Thoracic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, P.R. China.

Esophageal cancer (EC) is the sixth leading cause of cancer‑related mortality worldwide, with the incidence gradually increasing each year. Therefore, further clarifying the mechanism underlying the development of EC may be beneficial for identifying novel biomarkers and targets for its treatment. The present study aimed to determine the functional roles of glioblastoma‑amplified sequence (GBAS), a newly identified gene that has been reported to play crucial roles in multiple types of cancer, including in the malignant behavior of EC cells, such as cell viability, colony formation, cell apoptosis and cell cycle progression. The results of the present study revealed that, , the knockdown of GBAS significantly suppressed cell viability and colony formation in TE‑1 and KYSE‑150 cell lines, using a Celigo cell count analysis and colony formation assay respectively, whereas the apoptotic rate of EC cells was significantly increased by the knockdown of GBAS using Annexin V APC staining. Furthermore, following GBAS knockdown, the cell cycle progression of TE‑1 and KYSE‑150 cells was arrested in the G1 phase using PI staining. In conclusion, the findings of the present study suggested that GBAS may serve a role in EC by regulating cell viability, apoptosis and cell cycle progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2021.12162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160481PMC
July 2021

High-efficiency broadband tunable green laser operation of direct diode-pumped holmium-doped fiber.

Opt Express 2021 May;29(10):15564-15575

Green laser sources have become increasingly important for the application in scientific research and industry. Although several laser approaches have been investigated, the development of green lasers with the necessary efficiency and spectral characteristics required for practical deployment continues to attract immense interest. In this study, the efficient green laser operation of a Ho-doped fluoride fiber directly pumped by a commercial blue laser diode (LD) is experimentally investigated at various active fiber lengths. In the free-running laser, the slope efficiency was optimized up to 59.3% with 543.9 nm lasing, with respect to the launched pump power, using a 20-cm long active fiber. This is the maximum slope efficiency reported to date for a green fiber laser. A maximum output power of 376 mW at 543.5 nm was achieved by using a 17-cm long active fiber pumped at a maximum available launched pump power of 996 mW. Moreover, broadband tuning operation was demonstrated by employing a range of active fiber lengths, together with an intracavity bandpass filter. The operating wavelength was tunable from 536.3 nm to 549.3 nm. A maximum tuning power achieved was 118 mW at 543.4 nm for a 17-cm long active fiber. Moderate Ho-doped fiber length is shown to be effective in producing a high performance of a green fiber laser. The short-length of the active fiber considerably extends the green short wavelength operation due to limited reabsorption of the signal below 540 nm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.426482DOI Listing
May 2021

High-powered optical superlattice with robust phase stability for quantum gas microscopy.

Opt Express 2021 Apr;29(9):13876-13886

Optical superlattice has a wide range of applications in the study of ultracold atom physics. Especially, it can be used to trap and manipulate thousands of atom pairs in parallel which constitutes a promising system for quantum simulation and quantum computation. In the present work, we report on a high-power optical superlattice formed by a 532-nm and 1064-nm dual-wavelength interferometer with a short lattice spacing of 630 nm. The short-term fluctuation (in 10 seconds) of the relative phase between the short lattice and the long lattice is measured to be 0.003π, which satisfies the needs for performing two-qubit gates among neighboring lattice sites. We further implement this superlattice in a Rb experiment with a quantum gas microscope of single-site resolution, where the high-power 532-nm laser is necessary for pinning atoms in the short lattice during imaging, providing a unique platform for engineering quantum states.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.423776DOI Listing
April 2021

Early-phase vascular involvement is associated with acute pancreatitis severity: a magnetic resonance imaging study.

Quant Imaging Med Surg 2021 May;11(5):1909-1920

Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.

Background: Although a number of studies have reported on the vascular abnormalities detected by magnetic resonance imaging (MRI) in patients with late-phase acute pancreatitis (AP), few have studied those occurring in the early phase of the disease. The aim of this research was to investigate the MRI findings of early vascular abnormalities in AP and to analyze the correlation of the prevalence of vascular involvement with the severity of AP based on the MR severity index (MRSI) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores.

Methods: A retrospective analysis was conducted of 301 consecutive AP patients who were admitted to our institution between March 2013 and June 2019. All patients underwent initial MRI during the early phase of pancreatitis and one or more repeat MRI scans in the late phase. Peripancreatic vascular conditions and pancreatitis were assessed using T1-/T2-weighted imaging and dynamic-enhanced MRI. The association between the prevalence of vascular involvement and AP severity graded according to the MRSI or APACHE II score was analyzed using Spearman's rank correlation.

Results: Among 301 AP patients, 75 (24.9%) had at least one MRI-detected vascular abnormality. Overall, vascular involvement on MRI was higher in necrotizing pancreatitis than in edematous pancreatitis [43.2% (54/125) 11.9% (21/176), χ=38.2, P<0.001]. In the early phase of AP, the prevalence of splenic vein phlebitis, portal vein phlebitis, and splenic arterial arteritis was 24.9% (75/301), 22.3% (67/301), and 19.9% (60/301), respectively. Splenic vein phlebitis was seen on initial MRI in 55.6% (15/27) of patients who had splenic vein thrombosis on repeat MRI. The MRSI scores showed that the prevalence of splenic vein phlebitis, portal vein phlebitis, and splenic arterial arteritis, respectively, was correlated with the severity of pancreatitis (r=0.532, 0.487, and 0.456; all P<0.01). The APACHE II scores showed that the prevalence of MRI-detected vascular involvement was significantly correlated with AP severity (r=0.335, P<0.05).

Conclusions: Vascular abnormalities, including splenic vein phlebitis and splenic arterial arteritis, are commonly seen on MRI in patients with early-phase AP, and they may be supplementary indicators that can reflect the severity of pancreatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/qims-20-280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047341PMC
May 2021

LRRC4 functions as a neuron-protective role in experimental autoimmune encephalomyelitis.

Mol Med 2021 05 1;27(1):44. Epub 2021 May 1.

Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, 410013, Hunan, China.

Background: Leucine rich repeat containing 4 (LRRC4), also known as netrin-G ligand-2 (NGL-2), belongs to the superfamily of LRR proteins and serves as a receptor for netrin-G2. LRRC4 regulates the formation of excitatory synapses and promotes axon differentiation. Mutations in LRRC4 occur in Autism Spectrum Disorder (ASD) and intellectual disability. Multiple sclerosis (MS) is a chronic neuroinflammatory disease with spinal cords demyelination and neurodegeneration. Here, we sought to investigate whether LRRC4 is involved in spinal cords neuron-associated diseases.

Methods: LRRC4 was detected in the CNS of experimental autoimmune encephalomyelitis (EAE) mice by the use of real-time PCR and western blotting. LRRC4 mice were created and immunized with myelin oligodendrocyte glycoprotein peptide (MOG). Pathological changes in spinal cords of LRRC4 and WT mice 15 days after immunization were examined by using hematoxylin and eosin (H&E), Luxol Fast Blue (LFB) staining and immunohistochemistry. The number of Th1/Th2/Th17/Treg cells in spleens and blood were measured with flow cytometry. Differential gene expression in the spinal cords from WT and LRRC4 mice was analyzed by using RNA sequencing (RNA-seq). Adeno-associated virus (AAV) vectors were used to overexpress LRRC4 (AAV-LRRC4) and were injected into EAE mice to assess the therapeutic effect of AAV-LRRC4 ectopic expression on EAE.

Results: We report that LRRC4 is mainly expressed in neuron of spinal cords, and is decreased in the spinal cords of the EAE mice. Knockout of LRRC4 have a disease progression quickened and exacerbated with more severe myelin degeneration and infiltration of leukocytes into the spinal cords. We also first found that Rab7b is high expressed in EAE mice, and the deficiency of LRRC4 induces the elevated NF-κB p65 by up-regulating Rab7b, and up-regulation of IL-6, IFN-γ and down-regulation of TNF-α, results in more severe Th1 immune response in LRRC4 mice. Ectopic expression of LRRC4 alleviates the clinical symptoms of EAE mice and protects the neurons from immune damages.

Conclusions: We identified a neuroprotective role of LRRC4 in the progression of EAE, which may be used as a potential target for auxiliary support therapeutic treatment of MS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10020-021-00304-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088686PMC
May 2021

Feature of cognitive dysfunction in patients with temporal lobe epilepsy and its clinical influencing factors.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Mar;46(3):240-248

Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.

Objectives: To comprehensively analyze the characteristics of cognitive impairment of temporal lobe epilepsy (TLE), and to explore the effects of different lateral patients' cognitive impairment and different clinical factors on cognitive impairment of TLE.

Methods: A total of 84 patients, who met the diagnostic criteria for TLE in the Department of Neurology, Xiangya Hospital, were collected as a patient group, with 36 cases of left TLE and 48 cases of right TLE. A total of 79 healthy volunteers with matching gender, age and education level were selected as a control group. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the scores of Arithmetic Test, Information Test, Digit Symbol Substitution Test (DSST), Block Design Test (BDT), Hayling Test and Verbal Fluency Test (VFT) of the revised Chinese Adult Wechsler Intelligence scale were retrospectively analyzed in the 2 groups.Multiple regression analysis was used to analyze the relationship between the clinical factors and the cognitive impairment score.

Results: Compared with the control group, the TLE patient group had low scores in all neuropsychological tests, with significant difference (all <0.05). Compared with the control group, there was significant difference in different neuropsychological tests in the patients with TLE on different sides (all <0.05). In the left TLE, there were low scores in Information Test, arithmetic, VFT, the completion time of Hayling Test part A, the completion time of Hayling Test part B, the correct number of Hayling Test part A, the correct number of Hayling Test part B, BDT, Forward Digit Span Test (FDST) and Backward Digit Span Test (BDST). While in the right TLE, there were low scores in Information Test, arithmetic, DSST, VFT, the completion time of Hayling Test part A, the correct number of Hayling Test part A, the completion time of Hayling Test part B, the correct number of Hayling Test part B, BDT, FDST and BDST.

Conclusions: There are multiple cognitive domain dysfunctions in TLE, including language, short-term memory, long-term memory, attention, working memory, executive function and visual space function. Left TLE has greater impairment of executive function and right TLE has greater damage in working memory. Long pathography of disease, hippocampal sclerosis and a history of febrile convulsions may lead to more severe cognitive impairment. Earlier identification and earlier intervention are needed to improve prognosis of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11817/j.issn.1672-7347.2021.200770DOI Listing
March 2021

Improving the Photovoltaic Performance of Flexible Solar Cells with Semitransparent Inorganic Perovskite Active Layers by Interface Engineering.

ACS Appl Mater Interfaces 2021 May 13;13(17):20034-20042. Epub 2021 Apr 13.

State Key Laboratory of Material Processing and Die & Mould Technology, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.

Inorganic perovskite CsPbBr has broad application prospects in photovoltaic windows, tandem cells, and other fields due to its intrinsic semitransparency, excellent photoelectric properties, and stability. In this work, a high-quality semitransparent CsPbBr film was prepared by a sequential vacuum evaporation deposition method without high-temperature annealing and successfully used as the active layer of flexible perovskite solar cells (F-PSCs) for the first time, achieving a power conversion efficiency (PCE) of 5.00%. By introducing an energy-level buffer layer of CuO between CsPbBr and Spiro-OMeTAD, the champion PCE has been further improved to 5.67% owing to the reduction of electron-hole recombination and enhanced charge extraction. The optimized devices present higher stability, which can maintain more than 95% of the initial efficiency even after continuous heating at 85 °C for 240 h. Moreover, the F-PSCs also exhibit excellent mechanical durability, and 90% of the original PCE can be retained after 1000 bending cycles at a curvature radius of 3 mm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c01674DOI Listing
May 2021

Correlation of Seizure Increase and COVID-19 Outbreak in Adult Patients with Epilepsy: Findings and Suggestions from a Nationwide Multi-centre Survey in China.

Seizure 2021 May 31;88:102-108. Epub 2021 Mar 31.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, China. Electronic address:

Objectives: To investigate the impact of the COVID-19 outbreak on the behaviours, mental health and seizure control of adult patients with epilepsy (PWE) and to identify the correlation of seizure increase and the COVID-19 outbreak to guide the medical care of individuals with epilepsy during a public health crisis.

Methods: This study was conducted at 28 centres from February 2020 to April 2020. Participants filled out a 62-item online survey including sociodemographic, COVID-19-related, epilepsy-related and psychological variables and were divided into two groups based on whether their seizure frequency increased during the COVID-19 pandemic. Chi-square tests and t-tests were used to test differences in significant characteristics. Multiple logistic regression analyses were used to identify risk factors for seizure worsening.

Results: A total of 1,237 adult PWE were enrolled for analysis. Of this sample, 31 (8.33%) patients experienced an increase in seizures during the pandemic. Multivariate logistic regression suggested that feeling nervous about the pandemic (P < 0.05), poor quality of life (P = 0.001), drug reduction/withdrawal (P = 0.032), moderate anxiety during the COVID-19 outbreak (P = 0.046) and non-seizure free before the COVID-19 outbreak (P < 0.05) were independently related to seizure increase during the pandemic.

Conclusions: During the COVID-19 pandemic, PWE with poor quality of life and mental status, as well as AED reduction/withdrawal, were more likely to experience seizure increase. This observation highlights the importance of early identification of the population at high risk of seizure worsening and implementation of preventive strategies during the pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2021.03.029DOI Listing
May 2021

Osthole Attenuates Macrophage Activation in Experimental Asthma by Inhibitingthe NF-ĸB/MIF Signaling Pathway.

Front Pharmacol 2021 22;12:572463. Epub 2021 Mar 22.

Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guilin Medical University, Guilin, China.

Inhibition of activated macrophages is an alternative therapeutic strategy for asthma. We investigated whether a coumarin compound, osthole, isolated from (L.) Cuss, alleviated macrophage activation and . Osthole could reduce expression of a marker of activated macrophages, cluster of differentiation (CD)206, in an ovalbumin-challenge model of asthma in mice. Osthole could also inhibit infiltration of inflammatory cells, collagen deposition and production of proinflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor-ɑ, macrophage migration inhibitory factor (MIF)] in asthmatic mice. , expression of phosphorylated-IĸBɑ, MIF and M2 cytokines (Ym-1, Fizz-1, arginase-1) in IL-4-induced macrophages decreased upon exposure to the NF-ĸB inhibitor MG-132. In our short hairpin (sh)RNA-MIF-knockdown model, reduced expression of M2 cytokines was detected in the IL-4 + shRNA-MIF group. Osthole could attenuate the proliferation and migration of an IL-4-induced rat alveolar macrophages line (NR8383). Osthole could reduce IL-4-induced translocation of nuclear factor-kappa B (NF-ĸB) in NR8383 cells. Collectively, our results suggest that osthole ameliorates macrophage activation in asthma by suppressing the NF-ĸB/MIF signaling pathway, and might be a potential agent for treating asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.572463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020258PMC
March 2021

Characteristics of fixation patterns and their relationship with visual function of patients with idiopathic macular holes after vitrectomy.

Sci Rep 2021 Apr 7;11(1):7658. Epub 2021 Apr 7.

Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Nankai University affiliated Eye Hospital, Clinical College of Ophthalmology, Tianjin Medical University, Gansu Road 4, Heping District, Tianjin, 300020, China.

To analyze the relationships between the fixation location and the visual function of idiopathic macular hole (IMH) patients with macular integrity assessment (MAIA) examination preoperatively and 3 months postoperatively. This was a retrospective case analysis. Forty-three eyes of 43 patients diagnosed with IMH were included in this study. The best corrected visual acuity (BCVA) assessments, optical coherence tomography (OCT) and MAIA examinations were performed before surgery and 1 week, 1 month and 3 months after surgery. The relationships between MAIA parameters and visual acuity were assessed by correlation analysis. Grouping by fixation location with the foveola (2°) as the centre, the locations could be divided into five groups, including foveolar, temporal, nasal, inferior and superior fixation. The mean macular sensitivity (MMS) of the macular area was correlated with the BCVA in the IMH patients before and 3 months after surgery (before surgery P = 0.00, after surgery P = 0.00). The MMS could be used as a good indicator for evaluating visual function in IMH patients. There was a significant difference in fixation location before and after the operation (P = 0.01). The preoperative fixation location of IMH patients was mainly in the superior area, while postoperatively moved to the foveola and nasal areas. Paying attention to the changes of fixation locations in IMH patients may provide new clues for further improving postoperative visual function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-87286-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027455PMC
April 2021

Novel PRRT2 gene variants identified in paroxysmal kinesigenic dyskinesia and benign familial infantile epilepsy in Chinese families.

Exp Ther Med 2021 May 18;21(5):504. Epub 2021 Mar 18.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

The present study was performed to investigate the clinical manifestations and pathogenic variants in three large families with autosomal dominant paroxysmal kinesigenic dyskinesia (PKD) and/or benign familial infantile epilepsy (BFIE) in China. Detailed clinical data and family history were collected. Genomic DNA was isolated from the peripheral blood samples of all available members. The genetic diagnosis was made by whole-exome sequencing on the three probands and the candidate variants were verified by PCR-Sanger sequencing. The pathogenicity of variants was predicted by bioinformatics analyses and classified according to the American College of Medical Genetics criteria. A total of three causative heterozygous variants were identified in the proline-rich transmembrane protein 2 (PRRT2) gene by DNA sequencing: A novel c.324_334del(p.Val109Argfs*21) deletion variant in Family A, as well as the previously known c.510_513del(p.Ser172Argfs*3) deletion variant in Family B and c.649dupC(p.Arg217Profs*8) duplication variant in Family C. The three variants of PRRT2 co-segregated with the phenotype and genotype in the family members. The present results deepen the current understanding of PKD/BFIE and extend the genotypic-phenotypic spectrum of PKD/BFIE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2021.9935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005681PMC
May 2021

Rheb mediates neuronal-activity-induced mitochondrial energetics through mTORC1-independent PDH activation.

Dev Cell 2021 Mar 15;56(6):811-825.e6. Epub 2021 Mar 15.

Department of Biology, School of Life Sciences, Brain Research Center, Southern University of Science and Technology, Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Shenzhen 518055, People's Republic of China. Electronic address:

Neuronal activity increases energy consumption and requires balanced production to maintain neuronal function. How activity is coupled to energy production remains incompletely understood. Here, we report that Rheb regulates mitochondrial tricarboxylic acid cycle flux of acetyl-CoA by activating pyruvate dehydrogenase (PDH) to increase ATP production. Rheb is induced by synaptic activity and lactate and dynamically trafficked to the mitochondrial matrix through its interaction with Tom20. Mitochondria-localized Rheb protein is required for activity-induced PDH activation and ATP production. Cell-type-specific gain- and loss-of-function genetic models for Rheb reveal reciprocal changes in PDH phosphorylation/activity, acetyl-CoA, and ATP that are not evident with genetic or pharmacological manipulations of mTORC1. Mechanistically, Rheb physically associates with PDH phosphatase (PDP), enhancing its activity and association with the catalytic E1α-subunit of PDH to reduce PDH phosphorylation and increase its activity. Findings identify Rheb as a nodal point that balances neuronal activity and neuroenergetics via Rheb-PDH axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.devcel.2021.02.022DOI Listing
March 2021

Empowering physicians with health information technology: An empirical investigation in Chinese hospitals.

J Am Med Inform Assoc 2021 Apr;28(5):915-922

Department of Business Information Technology, Pamplin College of Business, Virginia Tech, Blacksburg, Virginia, USA.

Objective: Few studies examine physicians' use of different features of health information technology (HIT) in relation to their psychological empowerment and stress, especially in China, where many hospitals are being pushed to share digitized medical information. Further, there are mixed findings about the impact of HIT on stress, with some studies suggesting that HIT increases stress and others suggesting no effect. Hence, there is a need for a nuanced view of HITs to incorporate different features, regions, and outcomes. This work seeks to extend the existing body of knowledge on HIT by assessing the effects of basic (data-related) and advanced (clinical) HIT features on physician empowerment, stress, and ultimately, job satisfaction in Chinese hospitals.

Materials And Methods: We surveyed 367 physicians at 5 class 3 hospitals (ie, regional hospitals that provide specialist medical and healthcare services and carry out high levels of teaching and scientific research tasks) in 5 provinces in China. We specified and estimated a structural equation model using partial least squares.

Results: Physicians who used advanced features experienced improvement in all dimensions of physician empowerment and significant reduction in stress. Physicians who used basic technology, however, experienced improvement in fewer dimensions of physician empowerment and no significant change in stress. Except for efficacy, all dimensions of physician empowerment and stress predicted job satisfaction.

Conclusions: Healthcare professionals should assess the purpose of HIT features and expect different effects on intermediate and ultimate outcomes. The nuanced view of HIT features and processes leading to outcomes sheds light on their differential effects and resolves inconsistencies in prior findings on HIT effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jamia/ocab034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068424PMC
April 2021

Quadruple-responsive nanoparticle-mediated targeted combination chemotherapy for metastatic breast cancer.

Nanoscale 2021 Mar 11;13(11):5765-5779. Epub 2021 Mar 11.

State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Beibei, Chongqing 400715, P. R. China.

The synergism of combination chemotherapy can only be achieved under specific drug ratios. Herein, hyaluronic acid (HA)-functionalized regenerated silk fibroin-based nanoparticles (NPs) were used to concurrently deliver curcumin (CUR) and 5-fluorouracil (5-FU) at various weight ratios (3.3 : 1, 1.6 : 1, 1.1 : 1, 1 : 1, and 1 : 1.2) to breast tumor cells. The generated HA-CUR/5-FU-NPs were found to have desirable particle sizes (around 200 nm), narrow size distributions, and negative zeta potentials (about -26.0 mV). Interestingly, these NPs showed accelerated drug release rates when they were exposed to buffers that mimicked the multi-hallmarks in the tumor microenvironment (pH/hydrogen peroxide/glutathione/hyaluronidase). The surface functionalization of NPs with HA endowed them with in vitro and in vivo breast tumor-targeting properties. Furthermore, we found that the co-loading of CUR and 5-FU in HA-functionalized NPs exhibited obvious synergistic anti-cancer, pro-apoptotic, and anti-migration effects, and the strongest synergism was found at the CUR/5-FU weight ratio of 1 : 1.2. Most importantly, mice experiments revealed that HA-CUR/5-FU-NPs (1 : 1.2) showed a superior anti-cancer activity against metastatic breast cancer compared to the single drug-loaded NPs and non-functionalized CUR/5-FU-NPs (1 : 1.2). Collectively, these results demonstrate that HA-CUR/5-FU-NPs (1 : 1.2) can be exploited as a robust nanococktail for the treatment of breast cancer and its lung metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0nr08579kDOI Listing
March 2021

Pluronic F127-Modified Electrospun Fibrous Meshes for Synergistic Combination Chemotherapy of Colon Cancer.

Front Bioeng Biotechnol 2020 16;8:618516. Epub 2021 Feb 16.

State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing, China.

Colon cancer ranks as the third most common malignancy in the world. Combination chemotherapy, resorting to electrospun fibrous technology, has been considered as a promising strategy to exert synergistic effects in colon cancer treatment. Herein, we manufactured various pluronic F127 (PF127)-modified electrospun fibrous meshes with different weight ratios of camptothecin (CPT) and curcumin (CUR). The fluorescence characterization of the obtained PF127-CPT-meshes, PF127-CUR-meshes, and PF127-CPT/CUR-meshes (2:1) showed that CPT and CUR were evenly distributed within individual fibers of these meshes. Drug release experiments revealed that both types of drugs could be released from fibrous meshes simultaneously and sustainably. Importantly, these meshes exhibited strong anti-colon cancer activities, compared with the control meshes without drugs. Moreover, the combination index values of the PF127-CPT/CUR-meshes (CPT/CUR weight ratio = 5:1, 3:1, or 2:1) were <0.5 after incubation for respective 24 and 36 h, indicating the synergistic anti-colon cancer effects of CPT and CUR in fibrous meshes. Collectively, these results demonstrate that PF127-CPT/CUR-meshes can be developed as an efficient implantable system for effective synergistic treatment of colon cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fbioe.2020.618516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921460PMC
February 2021

Co-exposure to inorganic arsenic and fluoride prominently disrupts gut microbiota equilibrium and induces adverse cardiovascular effects in offspring rats.

Sci Total Environ 2021 May 29;767:144924. Epub 2021 Jan 29.

Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA; Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.

Co-exposure to inorganic arsenic (iAs) and fluoride (F) and their collective actions on cardiovascular systems have been recognized as a global public health concern. Emerging studies suggest an association between the perturbation of gut bacterial microbiota and adverse cardiovascular effects (CVEs), both of which are the consequence of iAs and F exposure in human and experimental animals. The aim of this study was to fill the gap of understanding the relationship among co-exposure to iAs and F, gut microbiota perturbation, and adverse CVEs. We systematically assessed cardiac morphology and functions (blood pressure, echocardiogram, and electrocardiogram), and generated gut microbiota profiles using 16S rRNA gene sequencing on rats exposed to iAs (50 mg/L NaAsO), F (100 mg/L NaF) or combined iAs and F (50 mg/L NaAsO + 100 mg/L NaF), in utero and during early postnatal periods (postnatal day 90). Correlation analysis was then performed to examine relationship between significantly altered microbiota and cardiac performance indices. Our results showed that co-exposure to iAs and F resulted in more prominent effects in CVEs and perturbation of gut microbiota profiles, compared to iAs or F treatment alone. Furthermore, nine bacterial genera (Adlercreutzia, Clostridium sensu stricto 1, Coprococcus 3, Romboutsia, [Bacteroides] Pectinophilus group, Lachnospiraceae NC2004 group, Desulfovibrio, and two unidentified genera in Muribaculaceae and Ruminococcaceae family), which differed significantly in relative abundance between control and iAs and F co-exposure group, were strongly correlated with the higher risk of CVEs (correlation coefficient = 0.70-0.88, p < 0.05). Collectively, these results suggest that co-exposure to iAs and F poses a higher risk of CVEs, and the part of the mode of action is potentially through inducing gut microbiota disruption, and the strong correlations between them indicate a high potential for the development of novel microbiome-based biomarkers of iAs and/or F associated CVEs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.144924DOI Listing
May 2021

Attitudes Toward Epilepsy Among Parents of Children With Epilepsy in Southern China.

Front Neurol 2020 5;11:602000. Epub 2021 Feb 5.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.

To evaluate the attitudes toward epilepsy among parents of children with epilepsy (CWE) in China and identify some related factors for future interventions for parents to offer more social support for CWE. The Chinese Public Attitudes Toward Epilepsy (CPATE) scale was administered to 234 parents of CWE and 203 parents of normal children in Xiangya hospital during 2019-2020. The cumulative score of the parents of CWE (26.427 ± 6.688) was significantly lower than that of the normal children group (32.330 ± 7.234, < 0.001). Subanalysis showed more positive attitudes among parents of CWE than the control group ( < 0.001) toward education (4.765 ± 1.985 vs. 6.621 ± 2.419), social life (6.556 ± 2.456 vs. 8.010 ± 2.683), marriage (9.586 ± 2.675 vs. 11.025 ± 2.900), and employment (3.876 ± 1.364 vs. 4.5123 ± 1.283). The attitudes toward epilepsy among parents of CWE with seizures in public (27.16 ± 6.66) or during sleep (27.10 ± 6.38) were more negative than those without (25.35 ± 6.62 and 25.08 ± 7.10, respectively) ( < 0.05). In addition, female and low income were negatively related to parents' attitudes toward epilepsy. More active policy guidance and adequate social support should be given to parents of children with seizures in public or during sleep to instruct their children to form a positive perception about epilepsy, which is expected to have a positive impact on their social abilities in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.602000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901895PMC
February 2021

Association of SHANK Family with Neuropsychiatric Disorders: An Update on Genetic and Animal Model Discoveries.

Cell Mol Neurobiol 2021 Feb 17. Epub 2021 Feb 17.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

The Shank family proteins are enriched at the postsynaptic density (PSD) of excitatory glutamatergic synapses. They serve as synaptic scaffolding proteins and appear to play a critical role in the formation, maintenance and functioning of synapse. Increasing evidence from genetic association and animal model studies indicates a connection of SHANK genes defects with the development of neuropsychiatric disorders. In this review, we first update the current understanding of the SHANK family genes and their encoded protein products. We then denote the literature relating their alterations to the risk of neuropsychiatric diseases. We further review evidence from animal models that provided molecular insights into the biological as well as pathogenic roles of Shank proteins in synapses, and the potential relationship to the development of abnormal neurobehavioral phenotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10571-021-01054-xDOI Listing
February 2021

iTRAQ-Based Proteomic Analysis of Dentate Gyrus in Temporal Lobe Epilepsy With Hippocampal Sclerosis.

Front Neurol 2020 25;11:626013. Epub 2021 Jan 25.

Department of Geriatrics, Second Xiangya Hospital, Central South University, Changsha, China.

Temporal lobe epilepsy (TLE) is the most frequent type of focal epilepsy in adults, typically resistant to pharmacological treatment, and mostly presents with cognitive impairment and psychiatric comorbidities. The most common neuropathological hallmark in TLE patients is hippocampal sclerosis (HS). However, the underlying molecular mechanisms involved remain poorly characterized. The dentate gyrus (DG), one specific hippocampal subarea, structural and functional changes imply a key involvement of the DG in the development of TLE. In this study, a isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic technique was performed for the analysis of hippocampal DG obtained from patients with TLE-HS compared to control samples obtained from autopsy. Our proteomic data identified 5,583 proteins, of which 82 proteins were upregulated and 90 proteins were downregulated. Bioinformatics analysis indicated that differentially expressed proteins were enriched in "synaptic vesicle," "mitochondrion," "cell-cell adhesion," "regulation of synaptic plasticity," "ATP binding," and "oxidative phosphorylation." Protein-protein interaction network analysis found a pivotal module of 10 proteins that were related to "oxidative phosphorylation." This study has investigated proteomic alterations in the DG region of TLE-HS patients, and paved the way for the better understanding of epileptogenesis mechanisms and future therapeutic intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.626013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868380PMC
January 2021

Ancient mitochondrial genomes from Chinese cave hyenas provide insights into the evolutionary history of the genus .

Proc Biol Sci 2021 01 27;288(1943):20202934. Epub 2021 Jan 27.

School of Environmental Studies, China University of Geosciences, Wuhan 430078, People's Republic of China.

Cave hyenas (genus ) are extinct bone-cracking carnivores from the family Hyaenidae and are generally split into two taxa that correspond to a European/Eurasian and an (East) Asian lineage. They are close relatives of the extant African spotted hyenas, the only extant member of the genus . Cave hyenas inhabited a wide range across Eurasia during the Pleistocene, but became extinct at the end of the Late Pleistocene. Using genetic and genomic datasets, previous studies have proposed different scenarios about the evolutionary history of However, causes of the extinction of cave hyenas are widely speculative and samples from China are severely understudied. In this study, we assembled near-complete mitochondrial genomes from two cave hyenas from northeastern China dating to 20 240 and 20 253 calBP, representing the youngest directly dated fossils of in Asia. Phylogenetic analyses suggest a monophyletic clade of these two samples within a deeply diverging mitochondrial haplogroup of . Bayesian analyses suggest that the split of this Asian cave hyena mitochondrial lineage from their European and African relatives occurred approximately 1.85 Ma (95% CI 1.62-2.09 Ma), which is broadly concordant with the earliest Eurasian fossil dating to approximately 2 Ma. Comparisons of mean genetic distance indicate that cave hyenas harboured higher genetic diversity than extant spotted hyenas, brown hyenas and aardwolves, but this is probably at least partially due to the fact that their mitochondrial lineages do not represent a monophyletic group, although this is also true for extant spotted hyenas. Moreover, the joint female effective population size of (both cave hyenas and extant spotted hyenas) has sustained two declines during the Late Pleistocene. Combining this mitochondrial phylogeny, previous nuclear findings and fossil records, we discuss the possible relationship of fossil in China and the extinction of cave hyenas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1098/rspb.2020.2934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893252PMC
January 2021

Fluorometric determination of the breast cancer 1 gene based on the target-induced conformational change of a DNA template for copper nanoclusters.

Anal Methods 2021 02 22;13(5):712-718. Epub 2021 Jan 22.

School of Materials Science and Engineering, Xiangtan University, Xiangtan 411105, PR China.

The breast cancer 1 (BRCA1) gene is a tumor suppressor gene, whose mutation is closely related to breast cancer. Therefore, the sensitive detection of the BRCA1 gene is extremely important for human health, particularly for women. In this study, a label-free fluorescent method based on hairpin DNA-templated copper nanoclusters (CuNCs) was for the first time developed for the detection of the BRCA1 gene. In the absence of target DNA, the detection system showed a strong red emission and produced a high emission peak. However, in the presence of the BRCA1 gene, the DNA probe hybridized with the BRCA1 gene and conformation of the DNA probe changed. As a result, the amount of produced CuNCs decreased and a low emission peak was obtained. The fluorescence intensity of the detection system was linearly correlated with the concentration of the BRCA1 gene ranging from 2 nM to 600 nM. The detectable limit was 2 nM for the BRCA1 gene assay, which was comparable with those reported by other non-amplifying sensors. Moreover, the developed method showed satisfactory recoveries for the BRCA1 gene assay in the bovine serum. The DNA-templated CuNC-based fluorescent assay thus offered a promising platform for the diagnosis of a breast cancer biomarker.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0ay01712dDOI Listing
February 2021

Knowledge, attitudes and anxiety toward COVID-19 among domestic and overseas Chinese college students.

J Public Health (Oxf) 2021 Jan 22. Epub 2021 Jan 22.

Department of Neurology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.

Background: To investigate the knowledge, attitudes and anxiety toward COVID-19 among Chinese college students studying in China and abroad.

Method: A structured questionnaire, comprised of demographic characteristics, knowledge and attitudes toward COVID-19 and the State-Trait Anxiety Inventory (STAI), was used to collect data for 566 domestic students and 126 students studying abroad.

Results: Domestic students were better than students abroad in knowledge of epidemiology and manifestations. Domestic students showed a significant higher enthusiasm for voluntary services than students abroad, including medical science popularization, community services, traffic dispersion, logistics transportation and being volunteers for vaccine trials. The scores (Mean ± SD) of S-AI and T-AI among students abroad were 59.48 ± 8.63 and 54.10 ± 7.20, respectively, which were significantly higher than those of domestic students (39.46 ± 8.16 and 39.25 ± 7.72).

Conclusions: Our study showed a better understanding of knowledge, more positive attitudes and less anxiety toward COVID-19 among domestic students, compared with students studying abroad. In light of this information, more attention and appropriate psychological and social intervention should be paid to college students with anxiety, especially those studying abroad.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/pubmed/fdaa268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928746PMC
January 2021

Tumor Microenvironment-Responsive Nanococktails for Synergistic Enhancement of Cancer Treatment via Cascade Reactions.

ACS Appl Mater Interfaces 2021 Feb 20;13(4):4861-4873. Epub 2021 Jan 20.

Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, School of Materials and Energy, Southwest University, 2 Tiansheng Road, Beibei, Chongqing 400715, P. R. China.

A combination treatment strategy that relies on the synergetic effects of different therapeutic approaches has been considered to be an effective method for cancer therapy. Herein, a chemotherapeutic drug (doxorubicin, Dox) and a manganese ion (Mn) were co-loaded into regenerated silk fibroin-based nanoparticles (NPs), followed by the surface conjugation of phycocyanin (PC) to construct tumor microenvironment-activated nanococktails. The resultant [email protected] showed increased drug release rates by responding to various stimulating factors (acidic pH, hydrogen peroxide (HO), and glutathione), revealing that they could efficiently release the payloads (Dox and Mn) in tumor cells. The released Dox could not only inhibit the growth of tumor cells but also generated a large amount of HO. The elevated HO was decomposed into the highly harmful hydroxyl radicals and oxygen through an Mn-mediated Fenton-like reaction. Furthermore, the generated oxygen participated in photodynamic therapy (PDT) and produced abundant singlet oxygen. Our investigations demonstrate that these [email protected] exhibit multiple bioresponsibilities and favorable biosafety. By integrating Dox-induced chemotherapy, Mn-mediated chemodynamic therapy, and PC-based PDT via cascade reactions, [email protected] achieved enhanced and anticancer efficacies compared to all the mono- or dual-therapeutic approaches. These findings reveal that [email protected] can be exploited as a promising nanococktail for cascade reaction-mediated synergistic cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c20268DOI Listing
February 2021

Oral nanotherapeutics with enhanced mucus penetration and ROS-responsive drug release capacities for delivery of curcumin to colitis tissues.

J Mater Chem B 2021 02 20;9(6):1604-1615. Epub 2021 Jan 20.

Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, School of Materials and Energy, Southwest University, Beibei, Chongqing 400715, P. R. China.

The therapeutic efficacies of oral nanotherapeutics for ulcerative colitis (UC) are seriously hindered by the lack of mucus-penetrating capacity and uncontrolled drug release. To overcome these limitations, the surface of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) was functionalized with pluronic F127 (PF127), and catalase (CAT)/curcumin (CUR) was co-encapsulated into these NPs. The obtained P-CUR/CAT-NPs had a hydrodynamic particle size of approximately 274.1 nm, narrow size distribution, negative zeta potential (-14.0 mV), and smooth surface morphology. Moreover, the introduction of PF127 to the surface of NPs not only facilitated their mucus penetration, but also improved their cellular uptake efficiency by the target cells (macrophages). We further found that the encapsulation of CAT could remarkably increase the release rate of CUR from NPs in the presence of an HO-rich environment. Additionally, P-CUR/CAT-NPs showed the strongest capacity to suppress the secretion of the main pro-inflammatory cytokines, in comparison with their counterparts (CUR-NPs and P-CUR-NPs). Importantly, oral administration of P-CAT/CUR-NPs showed the best therapeutic outcomes than the other NPs. Collectively, these results clearly demonstrate that these mucus-penetrating NPs loaded with CAT and CUR can be exploited as an efficient nanotherapeutic for UC therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0tb02092cDOI Listing
February 2021

Injectable, Thixotropic, and Multiresponsive Silk Fibroin Hydrogel for Localized and Synergistic Tumor Therapy.

ACS Biomater Sci Eng 2020 02 13;6(2):1052-1063. Epub 2020 Jan 13.

State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University, No. 2 Tiansheng Road, Chongqing 400715, P. R. China.

Combinational cancer therapy offers a promising strategy to overcome the limitations of single-drug treatment, including limited therapeutic efficacy, serious side effects, and low survival rate. Injectable silk fibroin (SF) hydrogel has emerged as an effective platform for localized treatment. Herein, hydrophilic SF (HSF) was extracted from regenerated SF and self-assembled into hydrogel within 2-6 h. The obtained HSF hydrogel showed obvious viscoelasticity, thixotropic behavior, and self-healing performance. Interestingly, this hydrogel also exhibited excellent stimuli-responsive drug release profiles when triggered by multiple factors (acidity, reactive oxygen species, glutathione, hyperthermia, and near-infrared (NIR)), suggesting that it could achieve spatially and temporally on-demand drug release in response to tumor microenvironment and extra-tumor NIR irradiation. Importantly, intratumoral injection of doxorubicin (DOX)/Cy7-loaded HSF-based hydrogel (DOX/Cy7-hydrogel) plus NIR irradiation exerted the best antitumor effect among all the treatment groups, revealing the strong synergistic effects of chemo/photothermal/photodynamic therapy. It is worth noting that this DOX/Cy7-hydrogel could almost eliminate the entire tumor masses, significantly prolonging the survival time of tumor-bearing mice over 60 days without detectable adverse effects. Collectively, our findings suggest that this injectable DOX/Cy7-hydrogel with thixotropic and multistimuli responsive properties could be developed as a promising platform for localized and synergistic treatment of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsbiomaterials.9b01676DOI Listing
February 2020