Publications by authors named "Hua Jin"

509 Publications

Identification of an immune signature to predict poor clinical outcome in cervical cancer.

Epigenomics 2021 May 6. Epub 2021 May 6.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China.

To explore tumor immune microenvironment and identify immune prognostic-related circRNAs in cervical cancer. RNA-seq in combination with bioinformatics were performed to establish a prognostic risk model and a circRNAs-miRNAs- network. High-risk group correlated with poor survival outcome, and had lower immunogenicity. Additionally, could distinguish normal tissue, low- and high-risk tumor tissues, the expression of which showed an increasing trend among the three groups. RNA-seq and bioinformatics indicated that circRNAs like might upregulate through sponging miRNAs including . We constructed an immune risk model related with CD8 T cells to predict the cervical cancer patients' prognosis and explored the abnormal expression mechanism of through the ceRNA mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/epi-2020-0437DOI Listing
May 2021

Oridonin-Loaded Nanoparticles Inhibit Breast Cancer Progression Through Regulation of ROS-Related Nrf2 Signaling Pathway.

Front Bioeng Biotechnol 2021 7;9:600579. Epub 2021 Apr 7.

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The Scientific Research Center of Dongguan, College of Pharmacy, Institute of Clinical Laboratory Medicine, Guangdong Medical University, Dongguan, China.

Oridonin (ORI) has been shown to inhibit tumor cell growth and proliferation , while its optimum anti-tumor activity is limited due to the poor aqueous solubility and bioavailability. In this study, to improve the bioavailability, we developed a nanoparticle-based drug delivery system to facilitate delivery of ORI to breast tumor. ORI was encapsulated in biodegradable nanoparticles (NPs) based on poly-lactic-co-glycolic acid (PLGA) and polyethylene glycol (PEG) to form ORI NPs (ORI-NPs). The resulting ORI-NPs exhibited a mean particle diameter of 100 nm and displayed an efficient cellular uptake by human breast cancer MCF-7 cells. Compared to free ORI that showed no effects on tumor cell proliferation, the ORI-NPs showed significant cytotoxicity and delayed endothelial cell migration, tube formation and angiogenesis. Pharmacokinetics studies showed that ORI-NPs significantly increased the half-life of ORI in the blood circulation. In the nude mouse xenograft model, ORI-NPs markedly inhibited tumor growth and angiogenesis, while ORI did not show any inhibitory effects on the growth of tumor xenografts. The mechanism experiments showed that the antitumor activity of ORI-NPs against breast cancer might be through ROS related Nrf2/HO-1 signaling pathway. Together, these results demonstrated that ORI-loaded PEG-PLGA NPs enhanced bioactivity and bioavailability over ORI, indicating that ORI-NPs may represent a promisingly effective candidate against breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fbioe.2021.600579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058419PMC
April 2021

GE11 Peptide Conjugated Liposomes for EGFR-Targeted and Chemophotothermal Combined Anticancer Therapy.

Bioinorg Chem Appl 2021 31;2021:5534870. Epub 2021 Mar 31.

Department of Clinical Immunology, Institute of Clinical Laboratory Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, Guangdong 523808, China.

How to actively target tumor sites manipulating the controllable release of the encapsulated anticancer drugs and photosensitizers for synergistic anticancer therapy remains a big challenge. In this study, a cancer cell-targeted, near-infrared (NIR) light-triggered and anticancer drug loaded liposome system (LPs) was developed for synergistic cancer therapy. Photosensitizer indocyanine green (ICG) and chemotherapy drug Curcumin (CUR) were coencapsulated into the liposomes, followed by the surface conjugation of GE11 peptide for epidermal growth factor receptor (EGFR) targeting on the cancer cell surface. Strictly controlled by NIR light, GE11 peptide modified and CUR/ICG-loaded LPs (GE11-CUR/ICG-LPs) could introduce hyperthermia in EGFR overexpressed A549 cancer cells for photothermal therapy, which could also trigger the increased release of CUR for enhanced cancer cell inhibition. GE11-CUR/ICG-LPs synergized photochemotherapy could induce reactive oxygen species (ROS) generation and cytoskeleton disruption to activate stronger apoptotic signaling events than the photothermal therapy or chemotherapy alone by regulating Bax/Bcl-2 and PI3K/AKT pathways. This EGFR-targeted drug-delivery nanosystem with NIR sensitivity may potentially serve in more effective anticancer therapeutics with reduced off-target effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5534870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035035PMC
March 2021

An update on the prevalence of eating disorders in the general population: a systematic review and meta-analysis.

Eat Weight Disord 2021 Apr 8. Epub 2021 Apr 8.

Shanghai Yangpu District Central Hospital, Tongji University School of Medicine, Shanghai, China.

Objective: To update the prevalence of eating disorders in the general population before 2021 and to analyze the distribution characteristics at different times and in different regions and sexes, as well as the diagnostic criteria.

Methods: Based on the method from a previous report by the authors, studies were identified from the following databases: PubMed/Medline, PsycINFO, ISI Web of Knowledge, Ovid and the 4 most important Chinese databases. Articles in English and Chinese before 2021 were retrieved. The data retrieved at this time were pooled with the data from a previous report for analyses.

Results: Thirty-three studies were identified, which included 18 studies supplemented in this retrieval. The pooled lifetime and 12-month prevalence of eating disorders were 0.91% (95% CI, 0.48-1.71) and 0.43% (95% CI, 0.18-0.78), respectively. The pooled lifetime and 12-month prevalence of the subgroup EDs (any), which covers all types of eating disorders, were 1.69% and 0.72%, respectively. The lifetime prevalence of AN, BN and BED was 0.16% (95% CI, 0.06-0.31), 0.63% (95% CI, 0.33-1.02) and 1.53% (95% CI, 1.00-2.17), respectively. The lifetime prevalence of EDs in Western countries was 1.89%, and was high at 2.58% in females. Prevalence studies using DSM-5 criteria were scarce.

Conclusions: The prevalence of eating disorders might be underestimated thus far. Not all types of EDs were included in a majority of epidemiological surveys, and the prevalence rates of the new types of EDs were significantly higher. Eating disorders were especially common in Western countries and in females. New diagnostic criteria should be used to comprehensively assess all types of eating disorders.

Level Of Evidence: 1, systematic review and meta-analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40519-021-01162-zDOI Listing
April 2021

Identifying multimorbidity patterns of non-communicable diseases in paediatric inpatients: a cross-sectional study in Shanghai, China.

BMJ Open 2021 Apr 1;11(4):e042679. Epub 2021 Apr 1.

Department of General Practice, Tongji University Affiliated Yangpu Hospital, Shanghai, China

Objectives: To enhance the understanding of non-communicable disease (NCD) multimorbidity in children who are inpatients by delineating the characteristics of and identifying patterns among paediatric inpatients with multimorbidity in China.

Design: Cross-sectional study.

Setting: Paediatric wards (n=17) in Pudong New Area, Shanghai, China.

Participants: A total of 193 432 paediatric inpatients in the electronic health record systems of 17 hospitals from 2011 to 2016 participated in the study, and 91 004 children with NCDs were extracted and classified based on International Classification of Diseases, 10th version codes.

Main Outcome Measures: Number of the NCDs and multimorbidity patterns of the paediatric inpatients.

Results: In total, 47.05% (95% CI 46.83 to 47.27) of the paediatric inpatients had one or more chronic diseases, and 16.30% (95% CI 16.14 to 16.46) had multimorbidity. Congenital anomalies accounted for 19.43% (95% CI 19.25 to 19.61) of the principal diagnoses among the paediatric inpatients. Five common multimorbidity patterns were identified: a neurological-respiratory cluster, a neurological-respiratory-ear cluster, a cardiovascular-circulatory cluster, a genitourinary cluster (boy group) and a musculoskeletal-connective cluster (10-18 years age group).

Conclusions: Multimorbidity in paediatric inpatients suggests that decisions about reasonable allocation of paediatric inpatient resources should be fully considered. Multimorbidity patterns in paediatric inpatients revealed that prevention, including innovative treatments targeting children, should be further studied.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-042679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023737PMC
April 2021

Wnt/β-catenin signaling mediates the abnormal osteogenic and adipogenic capabilities of bone marrow mesenchymal stem cells from chronic graft-versus-host disease patients.

Cell Death Dis 2021 Mar 23;12(4):308. Epub 2021 Mar 23.

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Chronic graft-versus-host disease (cGVHD) is the main cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Mesenchymal stem cells (MSCs) in bone marrow (BM) remain unclear in the pathophysiology of cGVHD. In this study, we analyzed BM-MSCs from 66 patients after allo-HSCT, including 33 with active cGVHD and 33 without cGVHD. BM-MSCs showed similar morphology, frequency, phenotype, and proliferation in patients with or without cGVHD. MSCs from the active cGVHD group showed a decreased apoptosis rate (P < 0.01). Osteogenic capacity was increased while adipogenic capacity was decreased in the active cGVHD MSCs compared with no-cGVHD MSCs. The expressions of osteogenic gene RUNX2 and COL1A1 were higher (P < 0.001) while adipogenic gene PPAR-γ and FABP4 were lower (P < 0.001) in the active cGVHD MSCs than no-cGVHD MSCs. These changes were associated with the severity of cGVHD (P < 0.0001; r = 0.534, r = 0.476, r = -0.796, and r = -0.747, respectively in RUNX2, COL1A1, PPAR-γ, and FABP4). The expression of Wnt/β-catenin pathway ligand Wnt3a was increased in cGVHD-MSCs. The dysfunction of cGVHD-MSCs could be reversed by Dickkopf related protein 1(DKK1) to inhibit the binding of Wnt3a. In summary, the differentiation of BM-MSCs was abnormal in active cGVHD, and its underlying mechanism is the upregulated of Wnt3a through Wnt/β-catenin signaling pathway of MSCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03570-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988169PMC
March 2021

GRP75-mediated upregulation of HMGA1 stimulates stage I lung adenocarcinoma progression by activating JNK/c-JUN signaling.

Thorac Cancer 2021 May 23;12(10):1558-1569. Epub 2021 Mar 23.

Department of Thoracic Surgery, Daping Hospital, Army Medical University, Chongqing, China.

Background: Recurrence is a major challenge in early-stage lung adenocarcinoma (LUAD) treatment. Here, we investigated the role and mechanism of high-mobility group AT-hook 1 (HMGA1) and glucose-regulated protein 75-kDa (GRP75) in stage I LUAD and evaluated their potential as biomarkers for predicting the recurrence and prognosis of stage I LUAD.

Methods: The TCGA dataset was used to investigate the clinical significance of HMGA1 and GRP75 in early-stage LUAD. The biological functions of HMGA1 and GRP75 in LUAD were investigated both in vitro and in vivo through overexpression and knockdown experiments. The interaction and regulation between HMGA1 and GRP75 were evaluated with coimmunoprecipitation and ubiquitination assays. The downstream signaling pathway of the GRP75/HMGA1 axis was investigated by mRNA-sequencing analysis.

Results: Both HMGA1 expression levels and GRP75 expression levels were associated with recurrence in stage I LUAD patients. In particular, HMGA1 had potential as an independent prognostic factor in stage I LUAD patients. Overexpression of GRP75 or HMGA1 significantly stimulated LUAD cell growth and metastasis, while silencing GRP75 or HMGA1 inhibited LUAD cell growth and metastasis in vitro and in vivo. Importantly, GRP75 inhibited ubiquitination-mediated HMGA1 degradation by directly binding to HMGA1, thereby causes HMGA1 upregulation in LUAD. In addition, the GRP75/HMGA1 axis played its role by activating JNK/c-JUN signaling in LUAD.

Conclusions: The activation of GRP75/HMGA1/JNK/c-JUN signaling is an important mechanism that promotes the progression of stage I LUAD, and a high level of HMGA1 is a novel biomarker for predicting recurrence and a poor prognosis in stage I LUAD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.13944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107037PMC
May 2021

Endoscopic resections for superficial esophageal squamous cell epithelial neoplasia: focus on histological discrepancies between biopsy and resected specimens.

BMC Gastroenterol 2021 Mar 9;21(1):114. Epub 2021 Mar 9.

Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, No. 5 Nanmencang, Dongcheng District, Beijing, 100700, China.

Background: Endoscopic resection has been used for high-grade intraepithelial neoplasia (HGIN) and superficial esophageal squamous cell carcinoma (ESCC) with limited risk of lymph node metastasis. However, some of these lesions cannot be accurately diagnosed based on forceps biopsy prior to treatment. In this study we aimed to investigate how to solve this histological discrepancy and avoid over- and under-treatment.

Methods: The medical records of patients with superficial esophageal squamous cell neoplasia who underwent endoscopic resection at our hospital from January 2012 to December 2019 were reviewed retrospectively. The histological discrepancy between the biopsy and resected specimens was calculated and its association with clinicopathological parameters was analyzed.

Results: A total of 137 lesions from 129 patients were included. The discrepancy rate between forceps biopsy and resected specimens was 45.3% (62/137). Histological discrepancy was associated with the histological category of the biopsy (p < 0.001). In addition, 17 of the 30 (56.7%) biopsies that was diagnosed as indefinite/negative for neoplasia or low-grade intraepithelial neoplasia were upgraded to HGIN or ESCC after resection. The upgrade was due to lesion size ≥ 10 mm (p = 0.002) and type B intrapapillary capillary loops (p < 0.001). Moreover, 34 of the 83 biopsies that were diagnosed with HGIN were upgraded to ESCC after resection, which was related to lesion size (p = 0.001), location (p = 0.018), and pink color sign (p = 0.002).

Conclusions: Histological discrepancy between forceps biopsy and resected specimens is common in clinical practice. Recognizing the risk factors for each histological category of biopsy may reduce these discrepancies and improve clinical management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12876-021-01694-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941920PMC
March 2021

A Chinese multicenter retrospective study of isolated increased nuchal translucency associated chromosome anomaly and prenatal diagnostic suggestions.

Sci Rep 2021 Mar 10;11(1):5596. Epub 2021 Mar 10.

School of Computer Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Extensive researches involving fetuses with multiple ultrasound anomalies have been conducted over the years, but only few were focused on the isolated increased nuchal translucency (NT). On top of that, these limited number of researches were all designed as single-arm studies and the control group was missing. In this study, we conducted a multicenter, retrospective study using amniotic fluid samples collected from 1197 pregnant women having fetuses with isolated increased NT (INT group) or normal NT values (NNT group). Copy number variation sequencing (CNV-seq) was performed to determine their chromosome status and pathogenic variations were validated using SNP array. Overall, 59 chromosome aneuploidies, 34 pathogenic CNVs and 23 copy number variants of unknown significance (VOUS CNVs) were discovered. the INT group had a significantly higher proportion of aneuploidy (19.44%) and pathogenic CNV (8.33%) than the control group (3.49% and 2.30% respectively), and 88.89% of the pathogenic CNVs were related to heart defects. Additionally, more male fetuses were presented in the INT group (68.51%), but they did not have a higher risk (Relative Risk = 1.03) of carrying pathogenic chromosome variations than female fetuses. Our results demonstrated that fetuses with isolated increased NT had a distinct pattern of chromosome abnormality and majority of detected pathogenic CNVs could be linked to the congenital heart disease. Furthermore, because a considerable proportion of pathogenic CNVs were detected, we strongly recommend to perform a joint test of karyotyping and CNV analysis in prenatal diagnosis for fetuses with isolated increased NT in order to decrease the incident of missed diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-85108-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947009PMC
March 2021

m6A mRNA methylation regulates the development of gestational diabetes mellitus in Han Chinese women.

Genomics 2021 Mar 2;113(3):1048-1056. Epub 2021 Mar 2.

Prenatal Diagnosis Center, Jinan Maternal and Child Health Care Hospital, Jinan, Shandong Province, PR China. Electronic address:

N6-methyladenosine (m6A) is the most prevalent mRNA modification in mammals. However, m6A modification profiling and its potential role in gestational diabetes mellitus (GDM) have not yet been investigated. In this work, we performed comprehensive m6A analysis in placental tissues from GDM and control patients to elucidate the role of m6A in GDM. An m6A RNA profile identified that m6A levels were strongly decreased in 3'-untranslated regions (UTRs) and coding sequences (CDSs) near stop codons in GDM placenta samples. Among the many methylated mRNAs, MazF-qPCR verified that the m6A levels of the BAMBI 3'-UTR and CDS were significantly decreased in GDM. BAMBI mRNA and protein expression was significantly decreased in GDM, suggesting that m6A plays a key role in regulating gene expression. In addition, it was verified that the m6A levels of GDM related genes (INSR and IRS1) were significantly reduced in GDM. Taken together, our data suggest that down-regulation of m6A both in the 3'-UTR and CDS near stop codons of placental mRNAs is involved in GDM development in Han Chinese women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygeno.2021.02.016DOI Listing
March 2021

[Intervention effect of Youguiwan on rats with knee osteoarthritis and its mechanism].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2020 Sep;36(5):511-516

Centers for Disease Control and Prevention of Lanzhou, Lanzhou 730000, China.

To study the effects of Youguiwan on the osteoglycin (OGN), osteonectin (ON), fibrinogen 2 (FBN2) of articular cartilage tissue in the model of knee osteoarthritis (KOA). Sixty SD rats were randomly divided into six groups: sham control group, model group, glucosamine sulfate group, Youguiwan (high-dose, middle-dose and low-dose )group. The modified Hulth method was used to establish KOA models for 6 weeks. The sham control group and the model group were treated with normal saline. The rats in Youguiwan high-dose, middle-dose, low-dose groups were treated with Youguiwan at the doses of 4.8, 2.4, 1.2 g/kg by gavage respectively, and the glucosamine sulfate group was treated with glucosamine sulfate 0.17 g/kg. The rats were administrated for 8 weeks according to the dose. After intervening, articular cartilage of rats were obtained, the pathological changes were observed by using HE staining method, and Mankin score was evaluated. The expressions of OGN, ON and FBN2 in articular cartilage were detected by immunohistochemistry. The expression of GSK-3β in articular cartilage was detected by Western blot. Compared with the sham control group, the Mankin score was obviously increased in the model group, the protein expression of FBN2 was increased significantly, yet the protein expressions of OGN, ON and GSK-3β were decreased significantly (<0.01), articular cartilage was seriously damaged, and chondrocytes were arranged in disorder. Compared with the model group, the Mankin score was declined obviously in the high-dose Youguiwan group, the protein expression of FBN2 was significantly decreased, but the protein expression of GSK-3β was significantly increased, the protein expressions of OGN and ON were significantly increased in the middle-dose and high-dose Youguiwan group (<0.05 or <0.01), cartilage structure was tended to be normal, the chondrocytes distribution was uneven, and articular cartilage surface was not smooth. Youguiwan can significantly improve the articular cartilage degeneration of KOA rats, its mechanism maybe raise OGN and ON protein expression level to promote the ossification and reconstruction of articular cartilage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12047/j.cjap.5988.2020.109DOI Listing
September 2020

MET inhibitor, capmatinib overcomes osimertinib resistance via suppression of MET/Akt/snail signaling in non-small cell lung cancer and decreased generation of cancer-associated fibroblasts.

Aging (Albany NY) 2021 02 17;13(5):6890-6903. Epub 2021 Feb 17.

Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin 150001, Heilongjiang, China.

Background: Patients with non-small cell lung cancer (NSCLC) initially responding to tyrosine kinase inhibitors (TKIs) eventually develop resistance due to accumulating mutations in the EGFR and additional lesser investigated mechanisms such as the participation of the tumor microenvironment (TME).

Methods: Here, we examined the potential for MET inhibitor capmatinib for the treatment of osimertinib-resistant NSCLCs and normalizing the TME.

Results: We first established that HCC827 and H1975 cells showed increased resistance against osimertinib when co-cultured with CAFs isolated from osimertinib-resistant patients. Additionally, we showed that CAFs promoted epithelial-mesenchymal transition (EMT) and self-renewal ability in both HCC827 and H1975 cells. We subsequently found that both CAF-cultured HCC827 and H1975 showed a significantly higher expression of MET, Akt, Snail and IL-1β, which were associated with survival and inflammatory responses. These cells in turn, promoted the generation of CAFs from normal lung fibroblasts. Subsequently, we observed that the treatment of capmatinib resulted in the re-sensitization of CAF-co-cultured H1975 and HCC827 to osimertinib, in association with reduced EMT and self-renewal ability. MET-silencing experiment using siRNA supported the observations made with capmatinib while with a greater magnitude. MET-silenced cell exhibited a severely hindered expression of inflammatory markers, IL-1β and NF-κB; EMT markers, Snail and Vimentin, while increased E-cadherin. Finally, we demonstrated that the combination of capmatinib and osimertinib led to an increased tumor inhibition and significantly lower number of CAFs within the patient derived xenograft (PDX) model.

Conclusion: Taken together, our findings suggested that an increased MET/Akt/Snail signaling was induced between the NSCLC cells and their TME (CAFs), resulting in osimertinib resistance. Suppression of this pathway by capmatinib may bypass the EGFR activating mutation and overcomes osimertinib resistance by targeting both tumor cells and CAFs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993678PMC
February 2021

Nasal Delivery of Hesperidin/Chitosan Nanoparticles Suppresses Cytokine Storm Syndrome in a Mouse Model of Acute Lung Injury.

Front Pharmacol 2020 27;11:592238. Epub 2021 Jan 27.

College of Pharmacy, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, China.

The cytokine storm or cytokine storm syndrome (CSS) is associated with high mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), for example following sepsis or infectious diseases including COVID-19. However, there are no effective treatments for CSS-associated ALI or ALI/ARDS. Thus, there remains an urgent need to develop effective drugs and therapeutic strategies against CSS and ALI/ARDS. Nasal and inhaled drug delivery methods represent a promising strategy in the treatment of inflammatory lung disease as a result of their ability to improve drug delivery to lungs. Improving the nasal mucosa absorption of poorly water-soluble drugs with poor mucosa bioavailability to a therapeutically effective level is another promising strategy in the fight against ALI/ARDS. Here, chitosan nanoparticles loaded with hesperidin (HPD/NPs) were developed for nasal delivery of the anti-inflammatory HPD compound to inflammatory lungs. and , HPD/NPs exhibited enhanced cellular uptake in the inflammatory microenvironment compared with free HPD. In a mouse model of inflammatory lung disease, the HPD/NPs markedly inhibited lung injury as evidenced by reduced inflammatory cytokine levels and suppressed vascular permeability compared with free HPD. Collectively, our study demonstrates that nasal delivery of HPD/NPs suppresses CSS and ALI/ARDS in a murine model of inflammatory lung disease, and that nanoparticle-based treatment strategies with anti-inflammatory effects could be used to reduce CSS and ALI in patients with inflammatory lung injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.592238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873598PMC
January 2021

Preparation and evaluation of an injectable curcumin loaded chitosan/hydroxyapatite cement.

J Biomater Appl 2021 May 9;35(10):1372-1379. Epub 2021 Feb 9.

School of Biomedical and Pharmaceutical Science, Guangdong University of Technology - University Town Campus, Guangzhou, China.

Curcumin (Cur) is an active ingredient of Curcuma longa. Cur has many pharmacological effects, such as anti-inflammation, anti-oxidation, anticoagulation, hypolipidemic, anti-angiogenesis and anti-cancer. An injectable curcumin loaded chitosan/hydroxyapatite bone cement (Cur-CS/HA) was prepared as a bone scaffold and drug delivery. Tween 20, a nonionic surfactant, was incorporated into the cement to improve the solubility of curcumin. Four types of Cur-CS/HA (Group0, Group1, Group5 and Group10) were prepared with different Tween 20 ratios (0, 1, 5 and 10%, respectively). The samples were characterized by infrared spectroscopy (IR), X-ray diffraction (XRD) and scanning electron microscope (SEM). Compression tests were carried out to evaluate the strength of the scaffolds. In addition, the inhibition assay was carried out on MG63 cells with the extracts of drug loaded materials. The results showed that Cur had an effect on the setting time (p < 0.05). Cur reduced the compressive strength of the CS/HA cement (p < 0.05). The release studies showed that Tween 20 could effectively improve the solubility of curcumin. When the Tween 20 content in cement increased from 0 to 10%, the cumulative release (30 d) of Cur increased from 5.5 to 10.6%. Moreover, the cement had good injectability, good anti-collapsibility and good biocompatibility to meet the clinical requirements. The result of inhibition assay showed that Cur-CS/HA could inhibit the proliferation of MG63 cells. Tween 20 incorporated Cur-CS/HA had great potential to use as a drug-loaded artificial bone material.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0885328221991946DOI Listing
May 2021

Circular RNA circHECTD1 facilitates glioma progression by regulating the miR-296-3p/SLC10A7 axis.

J Cell Physiol 2021 Feb 9. Epub 2021 Feb 9.

Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.

Glioma is the most common type of primary brain tumor. Treatment options for recurrent gliomas include surgery, chemotherapy, and radiation therapy, but the clinical outcome is usually limited. In recent years, circular RNAs have been found to play a vital role in several human cancers. Gene Expression Omnibus database was utilized to verify the differentially expressed circRNAs. Then we detected that the expression of circular RNA circHECTD1 was significantly increased. The expression and function of circHECDT1 has not yet been reported in glioma. Then we confirmed that the level of circHECTD1 was significantly increased both in glioma tissues and cell lines, which is negatively correlated with the overall survival of patients. Knockdown of circHECTD1 inhibited proliferation and invasion in vitro, and also reduced the growth of tumor and prolonged the prognosis in vivo. Knockdown of circHECTD1 significantly elevated the miR-296-3p expression in LN229 and T98G cells. Luciferase reports and RNA immunoprecipitation data indicated that miR-296-3p was a direct target of circHECTD1 and that the miR-296-3p expression negatively regulated SLC10A7. Rescue experiments showed that the overexpression of SLC10A7 could impede the effects of circHECTD1 silencing on the proliferation and invasion of glioma cells. In this study, we identified that circHECTD1 regulates SLC10A7 by interacting with miR-296-3p in glioma cells. In conclusion, this study investigated a novel biomarker panel consisting of the circHECTD1/miR-296-3p/SLC10A7 axis, which is critical for glioma tumorigenesis and invasiveness and may represent a novel therapeutic target for intervening in glioma progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.30277DOI Listing
February 2021

The Interplay between Whey Protein Fibrils with Carbon Nanotubes or Carbon Nano-Onions.

Materials (Basel) 2021 Jan 28;14(3). Epub 2021 Jan 28.

College of Environment and Safety, Taiyuan University of Science and Technology, Taiyuan 030024, China.

Whey protein isolate (WPI) fibrils were prepared using an acid hydrolysis induction process. Carbon nanotubes (CNTs) and carbon nano-onions (CNOs) were made via the catalytic chemical vapor deposition (CVD) of methane. WPI fibril-CNTs and WPI fibril-CNOs were prepared via hydrothermal synthesis at 80 °C. The composites were characterized by SEM, TEM, FTIR, XRD, Raman, and TG analyses. The interplay between WPI fibrils and CNTs and CNOs were studied. The WPI fibrils with CNTs and CNOs formed uniform gels and films. CNTs and CNOs were highly dispersed in the gels. Hydrogels of WPI fibrils with CNTs (or CNOs) could be new materials with applications in medicine or other fields. The CNTs and CNOs shortened the WPI fibrils, which might have important research value for curing fibrosis diseases such as Parkinson's and Alzheimer's diseases. The FTIR revealed that CNTs and CNOs both had interactions with WPI fibrils. The XRD analysis suggested that most of the CNTs were wrapped in WPI fibrils, while CNOs were partially wrapped. This helped to increase the biocompatibility and reduce the cytotoxicity of CNTs and CNOs. HR-TEM and Raman spectroscopy studies showed that the graphitization level of CNTs was higher than for CNOs. After hybridization with WPI fibrils, more defects were created in CNTs, but some original defects were dismissed in CNOs. The TG results indicated that a new phase of WPI fibril-CNTs or CNOs was formed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ma14030608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865974PMC
January 2021

CD4 derived double negative T cells prevent the development and progression of nonalcoholic steatohepatitis.

Nat Commun 2021 01 28;12(1):650. Epub 2021 Jan 28.

General Surgery Department, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Hepatic inflammation is the driving force for the development and progression of NASH. Treatment targeting inflammation is believed to be beneficial. In this study, adoptive transfer of CD4 T cells converted double negative T cells (cDNT) protects mice from diet-induced liver fat accumulation, lobular inflammation and focal necrosis. cDNT selectively suppress liver-infiltrating Th17 cells and proinflammatory M1 macrophages. IL-10 secreted by M2 macrophages decreases the survival and function of cDNT to protect M2 macrophages from cDNT-mediated lysis. NKG2A, a cell inhibitory molecule, contributes to IL-10 induced apoptosis and dampened suppressive function of cDNT. In conclusion, ex vivo-generated cDNT exert potent protection in diet induced obesity, type 2 diabetes and NASH. The improvement of outcome is due to the inhibition on liver inflammatory cells. This study supports the concept and the feasibility of potentially utilizing this autologous immune cell-based therapy for the treatment of NASH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-20941-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844244PMC
January 2021

Multi-Residue Analysis of Fipronil and Its Metabolites in Eggs by SinChERS-Based UHPLC-MS/MS.

Food Sci Anim Resour 2021 Jan 1;41(1):59-70. Epub 2021 Jan 1.

College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China.

A method for simultaneous detection of fipronil (F) and its metabolites fipronil desulfinyl (FD), fipronil sulfide (FS), fipronil sulfone (FSO) in chicken eggs was applied and validated. It includes single-step, cheap, effective, rugged, safe-based method (SinChERS) for sample preparation and ultra high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS) for chemical analysis. Results suggested that formic acid enhanced the recovery of 4 target residues and 1% supplementation to acetonitrile gained higher recoveries than that of 5%. SinChERS integrated extraction and clean-up steps into one, with shorter time (1.5 h) to operate and higher recoveries (97%-100%) than HLB, Envi-Carb-NH and quik-easy-cheap-effective-rugged-safe method (QuEChERS), and it consumed the smallest volume of extracting solvent (10 mL) as QuEChERS. Quantitative analyses using external standard method suggested the linear ranges of 4 target compounds were 1-20 μg/L with R>0.9947. The limit of detection (S/N>3) and quantification (S/N>10) were 0.3 μg/kg and 1 μg/kg. Recoveries ranged from 89.0% to 104.4%, and the relative standard deviations (n=6) at 1, 10, and 20 μg/kg were lower than 6.03%. Thirty batches of domestic eggs (500 g each) were detected by the established SinChERS-based UHPLC-MS/MS and no target residues were detected in all samples. The method developed in this study is a rapid, sensitive, accurate and economic way for multi-residue analysis of fipronil and its metabolites in eggs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5851/kosfa.2020.e76DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810392PMC
January 2021

Comparative transcriptome analysis of genes involved in the drought stress response of two peanut (Arachis hypogaea L.) varieties.

BMC Plant Biol 2021 Jan 27;21(1):64. Epub 2021 Jan 27.

College of Environment and Resources, Dalian Minzu University, Dalian, 116600, China.

Background: The peanut is one of the most important oil crops worldwide. Qualities and yields of peanut can be dramatically diminished by abiotic stresses particularly by drought. Therefore, it would be beneficial to gain a comprehensive understanding on peanut drought-responsive transcriptional regulatory activities, and hopefully to extract critical drought-tolerance-related molecular mechanism from it.

Results: In this study, two peanut Arachis hypogaea L. varieties, NH5 (tolerant) and FH18 (sensitive), which show significantly differential drought tolerance, were screened from 23 main commercial peanut cultivars and used for physiological characterization and transcriptomic analysis. NH5 leaves showed higher water and GSH contents, faster stomatal closure, and lower relative conductivity (REC) than FH18. Under the time-course of drought-treatments 0 h (CK), 4 h (DT1), 8 h (DT2) and 24 h (DT3), the number of down-regulated differential expressed genes (DEGs) increased with the progression of treatments indicating repressive impacts on transcriptomes by drought in both peanut varieties.

Conclusions: Nevertheless, NH5 maintained more stable transcriptomic dynamics than FH18. Furthermore, annotations of identified DEGs implicate signal transduction, the elimination of reactive oxygen species, and the maintenance of cell osmotic potential which are key drought-tolerance-related pathways. Finally, evidences from the examination of ABA and SA components suggested that the fast stomatal closure in NH5 was likely mediated through SA rather than ABA signaling. In all, these results have provided us a comprehensive overview of peanut drought-responsive transcriptomic changes, which could serve as solid foundation for further identification of the molecular drought-tolerance mechanism in peanut and other oil crops.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12870-020-02761-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839228PMC
January 2021

Comparison of Different Protein Emulsifiers on Physicochemical Properties of β-Carotene-Loaded Nanoemulsion: Effect on Formation, Stability, and In Vitro Digestion.

Nanomaterials (Basel) 2021 Jan 11;11(1). Epub 2021 Jan 11.

College of Art and Science, Northeast Agricultural University, Harbin 150030, China.

In this study, β-carotene-loaded nanoemulsions are emulsified using four biomacromolecular proteins-peanut protein isolate (PPI), soy protein isolate (SPI), rice bran protein isolate (RBPI), and whey protein isolate (WPI)-in order to explore their emulsion stability and in vitro digestion characteristics. All four nanoemulsions attained high encapsulation levels (over 90%). During the three-stage in vitro digestion model (including oral, gastric, and small intestine digestion phases), the PPI-emulsified nanoemulsion showed the highest lipolysis rates (117.39%) and bioaccessibility (37.39%) among the four nanoemulsions. Moreover, the PPI-emulsified nanoemulsion (with the smallest droplet size) also demonstrated the highest stability during storage and centrifugation, while those for the RBPI-emulsified nanoemulsion (with the largest droplet size) were the lowest. In addition, all four nanoemulsions showed superior oxidation stability when compared with the blank control of corn oil. The oxidation rates of the PPI- and WPI-stabilized groups were slower than the other two groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nano11010167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826833PMC
January 2021

Early T-Cell Precursor Leukemia Has a Higher Risk of Induction-Related Infection among T-Cell Acute Lymphoblastic Leukemia in Adult.

Mediators Inflamm 2020 23;2020:8867760. Epub 2020 Dec 23.

Department of Hematology, Nanfang Hospital, Southern Medical University, Rd 1838 North Guangzhou Avenue, Guangzhou 510515, China.

Background: Infections are an important cause of morbidity and mortality for acute lymphoblastic leukemia (ALL). However, the reports regarding risk factors of induction-related infection are roughly unknown/limited in adult T-ALL during induction chemotherapy.

Methods: We performed a retrospective cohort study for the prevalence and risk predictors of induction-related infection among consecutive T-ALL patients ( = 97) enrolled in a PDT-ALL-LBL clinical trial. Of 97 patients with T-ALL enrolled in the trial, 46 were early T-cell precursor (ETP) ALL and 51 were non-ETP ALL.

Results: When compared with non-ETP, ETP ALL subtype was characterized with lower neutrophil count (1.35 × 10/L vs. 8.7 × 10/L, < 0.001) and lower myeloid percentage in the bone marrow (13.35% vs. 35.31%, = 0.007). Additionally, ETP ALL had longer neutropenia before diagnosis ( < 0.001), as well as during induction chemotherapy ( < 0.001). Notably, the ETP cohort experienced higher cumulative incidence of clinically documented infections (CDI; 33.33%, = 0.001), microbiologically documented infections (MDI; 45.24%, = 0.006), resistant infection (11.9%, = 0.013), and mixed infection (21.43%, = 0.003), respectively, than those of the non-ETP cohort. Furthermore, multivariable analysis revealed that T-ALL mixed infection was more likely related to chemotherapy response (OR, 0.025; 95% CI 0.127-0.64; = 0.012) and identified myeloid percentage as a predictor associated with ETP-ALL mixed infection (OR, 0.915; 95% CI 0.843-0.993; = 0.033), with ROC-defined cut-off value of 2.24% in ETP cohorts.

Conclusions: Our data for the first time demonstrated that ETP-ALL characterized with impaired myelopoiesis were more susceptible to induction-related infection among T-ALL populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8867760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775137PMC
December 2020

Serum growth differentiation factor 15 is closely associated with metabolic abnormalities in Chinese pregnant women.

J Diabetes Investig 2020 Dec 23. Epub 2020 Dec 23.

The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.

Aims: To explore the relationship between serum growth differentiation factor 15 (GDF15) and metabolic abnormalities in Chinese pregnant women.

Materials And Methods: We recruited 200 patients with gestational diabetes mellitus (GDM) and 211 matched normal control within 24-28 weeks of pregnancy. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum GDF15 levels of all participants. Then we grouped participants according to the number of metabolic abnormalities (including blood glucose, blood lipids and blood pressure), divided them into a normal metabolic group, one metabolic abnormality group, two or more metabolic abnormalities group. Finally, multinomial logistic regression analysis was used to estimate the odds radio (OR) and 95% CIs expressing the association between GDF15 and metabolic abnormalities in pregnant women.

Results: Through bivariate correlation analysis, we found that serum GDF15 is linearly correlated with glucose metabolism indices, such as 1h-PG, 2h-PG, HbA1c (all P < 0.05). In addition, serum GDF15 and triglycerides were linearly correlated (P < 0.05). Grouping by the number of metabolic abnormalities, we found that as GDF15 levels increased, the risk of metabolic abnormalities also increased (OR > 1), and the risk of multiple metabolic abnormalities was higher. As the number of metabolic abnormalities increased, serum GDF15 levels also were elevated (P < 0.001).

Conclusions: The results suggest that serum GDF15 levels are closely associated with metabolic abnormalities in pregnant women and may be used as a predictor of metabolic abnormalities during pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jdi.13488DOI Listing
December 2020

Evaluation of Cobas HPV and SeqHPV Assays in the Chinese Multicenter Screening Trial.

J Low Genit Tract Dis 2021 Jan;25(1):22-26

Preventive Oncology International, Inc, and the Cleveland Clinic, Cleveland, OH.

Objective: The aim of the study was to evaluate the Cobas 4800 Assay and the SeqHPV Assay with self (S) and direct (D) cervical samples in the Chinese Multicenter Screening Trial (CHIMUST).

Materials And Methods: The CHIMUST is a large population-based multicenter clinical trial, and 10,885 women aged 30-59 years from 15 sites in 7 provinces with no cervical cancer screening for 3 years were eligible. All participating women contributed one self-collected sample (S) and 1 physician-collected endocervical sample (DL). The self-collected sample was first applied to the solid media transport card (SS), and then, the brush placed in 6 mL of ThinPrepSolution (SL). All samples were tested with Cobas 4800 and SeqHPV high-risk HPV assays. Patients human papillomavirus positive (self or direct) were recalled for colposcopy and biopsies.

Results: A total of 10,399 women had complete data. The mean age was 43.9 years. A total of 1.4% (142/10,399) had cervical intraepithelial neoplasia (CIN) 2+ and 0.5% (54/10,339) had CIN 3+. In the liquid specimens, the overall HPV infection rates were 10.8% for Cobas and 10.9% for SeqHPV in D sample, and 13.7% for Cobas and 11.6% for SeqHPV in SL sample, respectively. The sensitivity of Cobas-DL, Cobas-SL, SeqHPV-DL, and SeqHPV-SL for CIN 2+ was 95.07%, 95.07%, 94.33%, and 96.48%, respectively. The specificity of Cobas-DL, Cobas-SL, SeqHPV-DL, and SeqHPV-SL for CIN 2+ was 90.38%, 87.35%, 90.21%, and 89.53%, respectively. There were no differences in sensitivity when applying the 2 assays to both self- and directly collected samples in liquid transport media (p > .05).

Conclusions: Both Cobas and SeqHPV screening assays using both self-collected and directly endocervical collected specimens demonstrate similar sensitivity for the detection of CIN 2+ and CIN 3+.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/LGT.0000000000000577DOI Listing
January 2021

Corticotrophin-Releasing Factor Modulates the Facial Stimulation-Evoked Molecular Layer Interneuron-Purkinje Cell Synaptic Transmission in Mice.

Front Cell Neurosci 2020 26;14:563428. Epub 2020 Nov 26.

Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, China.

Corticotropin-releasing factor (CRF) is an important neuromodulator in central nervous system that modulates neuronal activity via its receptors during stress responses. In cerebellar cortex, CRF modulates the simple spike (SS) firing activity of Purkinje cells (PCs) has been previously demonstrated, whereas the effect of CRF on the molecular layer interneuron (MLI)-PC synaptic transmission is still unknown. In this study, we examined the effect of CRF on the facial stimulation-evoked cerebellar cortical MLI-PC synaptic transmission in urethane-anesthetized mice by cell-attached recording, neurobiotin juxtacellular labeling, immunohistochemistry techniques, and pharmacological method. Cell-attached recordings from cerebellar PCs showed that air-puff stimulation of ipsilateral whisker pad evoked a sequence of tiny parallel fiber volley (N1) followed by MLI-PC synaptic transmission (P1). Microapplication of CRF in cerebellar cortical molecular layer induced increases in amplitude of P1 and pause of SS firing. The CRF decreases in amplitude of P1 waveform were in a dose-dependent manner with the EC of 241 nM. The effects of CRF on amplitude of P1 and pause of SS firing were abolished by either a non-selective CRF receptor antagonist, α-helical CRF-(9-14), or a selective CRF-R1 antagonist, BMS-763534 (BMS, 200 nM), but were not prevented by a selective CRF-R2 antagonist, antisauvagine-30 (200 nM). Notably, application CRF not only induced a significant increase in spontaneous spike firing rate, but also produced a significant increase in the number of the facial stimulation-evoked action potential in MLIs. The effect of CRF on the activity of MLIs was blocked by the selective CRF-R1 antagonist, and the MLIs expressed the CRF-R1 imunoreactivity. These results indicate that CRF increases excitability of MLIs via CRF-R1, resulting in an enhancement of the facial stimulation-evoked MLI-PC synaptic transmission in mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fncel.2020.563428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726213PMC
November 2020

Reactive Oxygen Species-Mediated Autophagy by Ursolic Acid Inhibits Growth and Metastasis of Esophageal Cancer Cells.

Int J Mol Sci 2020 Dec 10;21(24). Epub 2020 Dec 10.

Department of Physiology and Institute of Medical Science, Jeonbuk National University Medical School, Jeonju 54907, Korea.

Ursolic acid (UA) possesses various pharmacological activities, such as antitumorigenic and anti-inflammatory effects. In the present study, we investigated the mechanisms underlying the effects of UA against esophageal squamous cell carcinoma (ESCC) (TE-8 cells and TE-12 cells). The cell viability assay showed that UA decreased the viability of ESCC in a dose-dependent manner. In the soft agar colony formation assay, the colony numbers and size were reduced in a dose-dependent manner after UA treatment. UA caused the accumulation of vacuoles and LC3 puncta, a marker of autophagosome, in a dose-dependent manner. Autophagy induction was confirmed by measuring the expression levels of LC3 and p62 protein in ESCC cells. UA increased LC3-II protein levels and decreased p62 levels in ESCC cells. When autophagy was hampered using 3-methyladenine (3-MA), the effect of UA on cell viability was reversed. UA also significantly inhibited protein kinase B (Akt) activation and increased p-Akt expression in a dose-dependent manner in ESCC cells. Accumulated LC3 puncta by UA was reversed after wortmannin treatment. LC3-II protein levels were also decreased after treatment with Akt inhibitor and wortmannin. Moreover, UA treatment increased cellular reactive oxygen species (ROS) levels in ESCC in a time- and dose-dependent manner. Diphenyleneiodonium (an ROS production inhibitor) blocked the ROS and UA induced accumulation of LC3-II levels in ESCC cells, suggesting that UA-induced cell death and autophagy are mediated by ROS. Therefore, our data indicate that UA inhibits the growth of ESCC cells by inducing ROS-dependent autophagy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21249409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764507PMC
December 2020

Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments (SMART-CAT) in first-episode schizophrenia patients: Rationale and trial design.

Schizophr Res 2020 Dec 2. Epub 2020 Dec 2.

First-episode Schizophrenia and Early Psychosis Program, Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Shanghai Clinical Research Center for Mental Health, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Institute of Mental Health, Fudan University, Shanghai 200030, China. Electronic address:

Accumulated studies have investigated pharmacological interventions for first-episode schizophrenia (FES) patients. However, studies on subsequent treatment steps, which are essential to guide clinicians, are largely missing. This Sequential Multiple-Assignment Randomized Trials comparing Antipsychotic Treatments (SMART-CAT) program intends to evaluate the effectiveness of commonly used antipsychotic drugs in FES patients. The major goals of this study are to examine: 1) what would be the optimal subsequent sequential treatment if the first antipsychotic drug failed; 2) whether clozapine could be used in those first-trial failed and have superior efficacy compared to other atypical antipsychotics. In this article we will report the detail protocol of SMART-CAT. The SMART-CAT is a randomized controlled clinical multicenter trial in which 9 institutions in China will participate. A total of 720 FES patients will be enrolled and followed up for 12 months in this study. The trial includes three treatment phases (each phase lasting for 8 weeks) and a naturalistic follow-up phase; participants who do well on an assigned treatment will remain on that treatment for the duration of the 12-month treatment period, while non-responders will move to the next phase of the study to receive a new treatment. Phase 1 is a randomized controlled trial; patients will be randomly assigned to one of the treatments with oral olanzapine, risperidone, amisulpride, aripiprazole or perphenazine. Subjects who fail to respond after 8 weeks will enter the phase 2 randomization. Phase 2 is an equipoise-stratified randomization trial, and patients will be randomly assigned to oral olanzapine, amisulpride or clozapine for 8 weeks. Subjects who fail to respond after phase 2 will enter an open label trial (phase 3); patients who receive clozapine in phase 2 and fail to respond will be assigned to an extended clozapine treatment or modified electroconvulsive therapy add-on therapy (Phase 3A). Patients who were not assigned to clozapine in phase 2 will be assigned to treatment with clozapine or another SGAs not previously used in phase 1 and 2 (Phase 3B). The primary outcome for the treatment phase is the treatment efficacy rate, which is defined as at least 40% reduction in Positive and Negative Syndrome Scale (PANSS) total score. We hypothesize that clozapine is more therapeutically effective than any other SGAs to patients who failed to meet efficacy criteria in Phase 1, and earlier treatment with clozapine can improve the functional outcomes of schizophrenia patients. As for the naturalistic follow-up phase, time to all-cause treatment failure, marked by its discontinuation is selected as the primary outcome, since it reflects both efficacy and side effects. The all-cause discontinuation is defined as discontinuing for any reasons, including poor efficacy, intolerance of adverse reactions, poor compliance and other reasons. The results of the SMART-CAT trial will provide evidence for the selection of antipsychotics in FES patients who fail to respond to the first trial of an antipsychotic drug. It will also provide evidence for the efficacy and safety of using clozapine in the early phase of schizophrenia treatment by comparing with other SGAs. The study is based on the combination of sequential therapy and dynamic therapy, which can be more suitable to assess the effectiveness of treatment options in the real-world clinical setting. As a result, we hope that this study can provide guidance for an optimal treatment algorithm in first-episode schizophrenia patients. Trial registration: ID NCT03510325 in ClinicalTrials.gov.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.schres.2020.11.010DOI Listing
December 2020

Cobalt oxide nanoparticle-synergized protein degradation and phototherapy for enhanced anticancer therapeutics.

Acta Biomater 2021 02 28;121:605-620. Epub 2020 Nov 28.

Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, IL 60612, USA. Electronic address:

How to enable protein degradation pathways including the autophagy-lysosome pathway (ALP) and the ubiquitin-proteasome system (UPS) to enhance the efficacy of anticancer treatments remains a substantial challenge. Cobalt oxide nanoparticles (CoO NPs) have attracted interest in recent years for their potential use as a synergistic anticancer treatment, although their therapeutic mechanisms of action are still poorly understood. Here, we describe the synergistic use of CoO NPs as an autophagy inhibitor, chemosensitizer and photosensitizer, which manipulate protein degradation pathways (ALP and UPS) and photothermal therapy for enhanced anticancer treatments both in vitro and in vivo. We show that CoO NPs can induce autolysosome accumulation and lysosomal functions damage by inhibiting lysosomal proteolytic activity and reducing intracellular ATP levels. Notably, CoO NPs can be combined with the proteasome inhibitor, Carfilzomib (Cfz), to promote the accumulation of autophagic substrates, protein ubiquitination, and endoplasmic reticulum stress, and in doing so, inhibit cancer progression. By taking advantage of their photothermal conversion efficiency, CoO NPs can also serve as photothermal sensitizer, which synergistically enhances the anticancer efficacy of Cfz both in vitro and in vivo. In summary, we provide evidence of a nanomaterial-synergized, photothermal anticancer strategy that synergistically targets cancer cell survival pathways and may eventually serve to enhance the anticancer efficacy of established cancer therapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2020.11.036DOI Listing
February 2021

Quantitative Assessment of the Pupil: An Underrecognized Yet Important Factor Related to Orbital Blowout Fracture Repair.

J Craniofac Surg 2020 Nov 25. Epub 2020 Nov 25.

Department of Ophthalmology, Affiliated Hospital of Yanbian University, Yanji, Jilin, China.

Purpose: To investigate dynamic pupil changes after orbital blowout fracture repair. To compare postoperative changes in under photopic and mesopic pupil size and center position after orbital blowout fracture repair surgery.

Methods: The study evaluated 19 eyes. Pupils were imaged for pupil size and center position before and 3 months after orbital blowout fracture repair surgery. Pupil size changes were measured, and the correlation between preoperative and postoperative pupil centroid shift was evaluated.

Results: After repair, operative eyes exhibited a growth of 9.3% ± 8.6% in pupil size, and contralateral eyes showed a growth of 8.6% ± 8.2% (P = 0.011, P = 0.007). Similar findings were noted in mesopic conditions. Under mesopic conditions, the pupil of operative eyes in medial orbital wall fracture deviated 0.030 ± 0.019 mm towards the nasal side along the X-axis (P = 0.031). The postoperative orbital floor fracture group demonstrated statistical significance at a spatial frequency of 5 (P = 0.041).

Conclusions: Orbital blowout fracture repair surgery affects pupil size and center position.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SCS.0000000000007213DOI Listing
November 2020

Metal-Organic Frameworks Corset with a Thermosetting Polymer for Improved Molecular-Sieving Property of Mixed-Matrix Membranes.

ACS Appl Mater Interfaces 2020 Dec 26;12(49):55308-55315. Epub 2020 Nov 26.

School of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, P. R. China.

Metal-organic frameworks (MOFs) are promising materials for gas separation membranes. However, the framework flexibility affects their molecular-sieving properties. Herein, we restrict the flexibility of zeolitic imidazolate framework-7 (ZIF-7) by controlling its phase transition in mixed-matrix membranes (MMMs), relying on the so-called "space-confinement effect" of a novel thermosetting polymer, poly 2,2'-(-oxydiphenyl)-5,5'-bibenzimidazole (OPBI) polymer. Compared with the pure OPBI membrane, the optimized membranes containing 30 wt % ZIF-7 with a narrow-pore (np) phase (ZIF-7-II) exhibited a significant improvement in H/CO separation, e.g., the H/CO ideal selectivity increased ∼2.8 times, surpassing the state-of-the-art upper bound of polymeric membranes and exhibited excellent stability at increased pressure and temperature (8 bar, 180 °C).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c17426DOI Listing
December 2020

A high-quality reference genome sequence of Salvia miltiorrhiza provides insights into tanshinone synthesis in its red rhizomes.

Plant Genome 2020 11 17;13(3):e20041. Epub 2020 Sep 17.

Agronomy College, Shandong Agricultural University, Tai'an, Shandong, 271028, China.

Salvia miltiorrhiza Bunge, also known as red sage or Danshen, is an important traditional Chinese medicine (TCM) that has been used for thousands of years to treat cardiovascular and other diseases. It is also considered an important model TCM plant. Here, a high-quality reference genome of S. miltiorrhiza was generated by combining PacBio long-read sequencing and chromatin interaction mapping (Hi-C) technologies, resulting in the chromosome-scale assembly of a 594.75-Mb genome sequence with a contig N50 of 2.70 Mb. This assembly shows the highest level of continuity for a Danshen genome generated thus far. The S. miltiorrhiza genome contained 32,483 protein-coding genes, with a repetitive DNA content of approximately 64.84%. The high percentage of young LTRs suggests that multiple TE transposition bursts occurred recently in S. miltiorrhiza. Genes unique to secondary metabolism pathways were expanded in the S. miltiorrhiza genome. A new CYP450 gene cluster was identified in the phloem of red roots where active components were synthesized. This reference genome sequence will facilitate future studies aimed at the elucidation of the secondary metabolism synthesis pathway and the genetic improvement of S. miltiorrhiza.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/tpg2.20041DOI Listing
November 2020