Publications by authors named "Jing Zhao"

4,166 Publications

  • Page 1 of 1

Generation and validation of knockout human iPSC-derived cerebral organoids.

STAR Protoc 2021 Jun 5;2(2):100571. Epub 2021 Jun 5.

Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

Apolipoprotein E (apoE) is a major lipid carrier in the brain and closely associated with the pathogenesis of Alzheimer's disease (AD). Here, we describe a protocol for efficient knockout of in human induced pluripotent stem cells (iPSCs) using the CRISPR-Cas9 system. We obtain homozygous knockout ( ) iPSCs and further validate the deficiency of apoE in iPSC-derived cerebral organoids. cerebral organoids can serve as a useful tool to study apoE functions and apoE-related pathogenic mechanisms in AD. For complete details on the use and execution of this protocol, please refer to Zhao et al. (2020).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.xpro.2021.100571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190508PMC
June 2021

The Application of Combined Immune Checkpoint Inhibitor Modalities in Previously Treated Non-Small Cell Lung Cancer Patients and the Associations Thereof With the Lung Immune Prognostic Index.

Front Oncol 2021 4;11:690093. Epub 2021 Jun 4.

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Background: Immune checkpoint inhibitor (ICI) monotherapy remains the standard of care for patients with previously treated non-small cell lung cancer. However, few reports have compared the clinical benefits of second-line ICIs alone with those of ICIs combined with other therapies, including anti-angiogenesis therapy or chemotherapy.

Methods: Patients with previously treated advanced non-small cell lung cancer who received ICIs were retrospectively reviewed. The progression-free survival (PFS), overall survival, objective response rate, disease control rate, and safety were assessed. Complete blood cell counts and serum lactate dehydrogenase (LDH) levels were measured before and after ICI treatment.

Results: Of 120 patients, 75 were treated with ICI monotherapy, 26 with ICIs plus anti-angiogenic therapy (ICI+A), and 19 with ICIs plus chemotherapy (ICI+C). The objective response rate was significantly higher in the ICI+C group (57.9%) than ICI monotherapy (26.3%) and ICI+A (31.8%) groups. The depth of response was significantly greater in the ICI+C (-35.1%) than ICI+A (-2.04%) and ICI monotherapy (3.963%) groups. ICI+C afforded a better PFS compared with the ICI monotherapy and ICI+A groups (8.5 . 4.6 and 4.1 months, respectively). Notably, the pre- and post-treatment peripheral neutrophil/lymphocyte ratios and serum LDH levels were negatively correlated with the PFS of the entire cohort. More importantly, the pretreatment lung immune prognostic index (neutrophil/lymphocyte ratio ≥ 4 and LDH level ≥ upper limit of normal) satisfactorily predicted the responses to ICI-based strategies. Adverse events (AEs) occurred in 65.3%, 92.3%, and 94.7% of patients in the ICI monotherapy, ICI+A, and ICI+C groups, respectively. Grade 3-5 AEs were more common in the combination therapy groups (ICI+A, 19.2%; ICI+C, 21%; ICI monotherapy, 4%).

Conclusion: In second-line settings and beyond, ICIs combined with chemotherapy prolonged survival, with tolerable AEs. Addition of anti-angiogenic agents to ICIs did not afford any additional benefits. Further prospective studies are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.690093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213016PMC
June 2021

Perovskite-Inspired Lead-Free AgBiI for Self-Powered NIR-Blind Visible Light Photodetection.

Nanomicro Lett 2020 Jan 20;12(1):27. Epub 2020 Jan 20.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, People's Republic of China.

In recent years, solution-processible semiconductors with perovskite or perovskite-inspired structures have been extensively investigated for optoelectronic applications. In particular, silver-bismuth-halides have been identified as especially promising because of their bulk properties and lack of heavily toxic elements. This study investigates the potential of AgBiI for near-infrared (NIR)-blind visible light photodetection, which is critical to emerging applications (e.g., wearable optoelectronics and the Internet of Things). Self-powered photodetectors were realized and provided a near-constant ≈ 100 mA W responsivity through the visible, a NIR rejection ratio of > 250, a long-wavelength responsivity onset matching standard colorimetric functions, and a linear photoresponse of > 5 orders of magnitude. The optoelectronic characterization of AgBiI photodetectors additionally revealed consistency with one-center models and the role of the carrier collection distance in self-powered mode. This study provides a positive outlook of AgBiI toward emerging applications on low-cost and low-power NIR-blind visible light photodetector.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40820-020-0371-0DOI Listing
January 2020

Dynamic nanoassemblies for imaging and therapy of neurological disorders.

Adv Drug Deliv Rev 2021 Jun 16:113832. Epub 2021 Jun 16.

Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

The past decades have witnessed an increased incidence of neurological disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, ischemic stroke, and epilepsy, which significantly lower patients' life quality and increase the economic and social burden. Recently, nanomedicines composed of imaging and/or therapeutic agents have been explored to diagnose and/or treat NDs due to their enhanced bioavailability, blood-brain barrier (BBB) permeability, and targeting capacity. Intriguingly, dynamic nanoassemblies self-assembled from functional nanoparticles to simultaneously interfere with multiple pathogenic substances and pathological changes, have been regarded as one of the foremost candidates to improve the diagnostic and therapeutic efficacy of NDs. To help readers better understand this emerging field, in this review, the pathogenic mechanism of different types of NDs is briefly introduced, then the functional nanoparticles used as building blocks in the construction of dynamic nanoassemblies for NDs theranostics are summarized. Furthermore, dynamic nanoassemblies that can actively cross the BBB to target brain lesions, sensitively and efficiently diagnose or treat NDs, and effectively promote neuroregeneration are highlighted. Finally, we conclude with our perspectives on the future development in this field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.addr.2021.113832DOI Listing
June 2021

Cellulose nanocrystals produced using recyclable sulfuric acid as hydrolysis media and their wetting molecular dynamics simulation.

Int J Biol Macromol 2021 Jun 17;184:405-414. Epub 2021 Jun 17.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; National Engineering Research Center for Fruits and Vegetables Processing, Beijing 100193, China; Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Beijing 100193, China. Electronic address:

Cellulose nanocrystals (CNCs) were successfully produced with good nanoscales and dispersibility, using a recycled sulfuric acid (HSO) hydrolysis process. This method, at the cost of an overall 25% increase in the hydrolysis time, could significantly reduce the dosage of HSO by approximately 40% without affecting the per-batch yield and performance of CNCs. The obtained CNCs with an average diameter of 6.0-6.5 nm and an average length of 126-134 nm, were successfully applied in the preparation of oil-in-water (O/W) Pickering emulsions via high-pressure homogenization. The emulsions exhibited good storage stability when the concentration of CNC was 1.0 wt%. Further, understanding the wetting behaviors of surface modified CNCs with solvent is critical for the functional designing of Pickering emulsion. Hence, we gained insights into the wetting of hydrophobic and hydrophilic surfaces of sulfate modified CNCs with water and organic solvent (hexadecane) droplets, using molecular dynamic simulation. The results showed that both surfaces had hydrophilic as well as lipophilic properties. Although the sulfate-grafted surface was more hydrophilic than unmodified CNC, substantial local wetting heterogeneities appeared for both solvents. It provides a deeper understanding of the interfacial interactions between modified CNCs and solvent molecules at the molecular level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2021.06.094DOI Listing
June 2021

Landscape of IDH1/2 mutations in Chinese patients with solid tumors: A pan-cancer analysis.

Mol Genet Genomic Med 2021 Jun 18:e1697. Epub 2021 Jun 18.

Department of Medical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Isocitrate dehydrogenase (IDH) is an enzyme family involved in cell aerobic metabolism of tricarboxylic acid cycle. However, the landscape of IDH mutations in pan-cancer has not been fully characterized.

Methods: Tissue or blood samples were subjected to next-generation sequencing (NGS) for detection the IDH mutation.

Results: A total of 28.868 patients from more than 20 solid tumor species were analyzed. A total of 374 cases (1.30%) with IDH mutations were identified. Among all the IDH mutations cases, 80 (21.4%) were biliary tract cancer (BTC), 80 (21.4%) were lung cancer, 57 (15.2%) were liver cancer, and 42 (11.2%) were colorectal cancer. The most common IDH variant were IDH1 and IDH2 which were discovered in 0.81% cases and 0.47% cases, respectively. However, there were significant differences in IDH1 and IDH2 mutation frequency among different tumor species (p = 0.0003). Of the patients with IDH1 mutations, about 53.0% of these mutations occur in codons 132. Codons 172 (25.4%) was high-frequency mutation subtypes in IDH2 mutation. TP53, PBRM1, and BAP1 were the most significantly mutated genes in BTC which were different from others cancer. Moreover, TMB were significantly higher in lung cancer, colorectal cancer, and gastric cancer than BTC (p = 0.0164, p < 0.0001, p = 0.0067, respectively) and BTC patients with IDH mutation had lower TMB compared with wild-type IDH.

Conclusion: Somatic IDH mutation was found in multiple solid tumors and IDH would be a driver gene in BTC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mgg3.1697DOI Listing
June 2021

[Eukaryotic expression and immunoactivity of protein A/G-horseradish peroxidase(PA/G-HRP) fusion protein as universal secondary antibody for detection of IgG originating from mice and rabbits].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Jul;37(7):590-595

State Key Laboratory of Cancer Biology, Department of Immunology, Air Force Medical University, Xi'an 710032, China. *Corresponding authors, E-mail:

Objective To prepare universal secondary antibodies those can bind to the IgG from mice and rabbits, and use the antibodies in a variety of immunoassays. Methods The fusion genes of staphylococcal protein A (SPA), streptococcal protein G (SPG), and horseradish peroxidase (HRP) were synthesized, and cloned into the vector pcDNA3.1 to generate the eukaryotic expression plasmids. The plasmids were transiently transfected into HEK293F cells for expression. The fusion protein expressed in the plasmid was detected by SDS-PAGE and Western blotting, and its immunoactivity was measured by Western blotting, ELISA, and immunohistochemical staining. Results Restriction enzyme digestion and gene sequencing showed the pPA-HRP, pPG-HRP, and pPA/G-HRP plasmids were successfully created. Coomassie brilliant blue staining and Western blotting indicated that the fusion proteins PA-HRP, PG-HRP, and PA/G-HRP successfully expressed in HEK293F cells. Western blotting, ELISA, and immunohistochemical staining showed that IgGs derived from mice and rabbits could be recognized and bound by the three kinds of fusion protein, of which the fusion protein PA/G-HRP exhibited the highest affinity. Conclusion The fusion protein PA/G-HRP with high and universal IgG affinity is successfully prepared. The PA/G-HRP can replace traditional secondary antibodies against mouse and rabbit IgG in a variety of immunological assays.
View Article and Find Full Text PDF

Download full-text PDF

Source
July 2021

A machine learning framework that integrates multi-omics data predicts cancer-related LncRNAs.

BMC Bioinformatics 2021 Jun 16;22(1):332. Epub 2021 Jun 16.

School of Computer and Software, Nanyang Institute of Technology, Changjiang Road 80, Nanyang, 473004, Henan, China.

Background: LncRNAs (Long non-coding RNAs) are a type of non-coding RNA molecule with transcript length longer than 200 nucleotides. LncRNA has been novel candidate biomarkers in cancer diagnosis and prognosis. However, it is difficult to discover the true association mechanism between lncRNAs and complex diseases. The unprecedented enrichment of multi-omics data and the rapid development of machine learning technology provide us with the opportunity to design a machine learning framework to study the relationship between lncRNAs and complex diseases.

Results: In this article, we proposed a new machine learning approach, namely LGDLDA (LncRNA-Gene-Disease association networks based LncRNA-Disease Association prediction), for disease-related lncRNAs association prediction based multi-omics data, machine learning methods and neural network neighborhood information aggregation. Firstly, LGDLDA calculates the similarity matrix of lncRNA, gene and disease respectively, and it calculates the similarity between lncRNAs through the lncRNA expression profile matrix, lncRNA-miRNA interaction matrix and lncRNA-protein interaction matrix. We obtain gene similarity matrix by calculating the lncRNA-gene association matrix and the gene-disease association matrix, and we obtain disease similarity matrix by calculating the disease ontology, the disease-miRNA association matrix, and Gaussian interaction profile kernel similarity. Secondly, LGDLDA integrates the neighborhood information in similarity matrices by using nonlinear feature learning of neural network. Thirdly, LGDLDA uses embedded node representations to approximate the observed matrices. Finally, LGDLDA ranks candidate lncRNA-disease pairs and then selects potential disease-related lncRNAs.

Conclusions: Compared with lncRNA-disease prediction methods, our proposed method takes into account more critical information and obtains the performance improvement cancer-related lncRNA predictions. Randomly split data experiment results show that the stability of LGDLDA is better than IDHI-MIRW, NCPLDA, LncDisAP and NCPHLDA. The results on different simulation data sets show that LGDLDA can accurately and effectively predict the disease-related lncRNAs. Furthermore, we applied the method to three real cancer data including gastric cancer, colorectal cancer and breast cancer to predict potential cancer-related lncRNAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12859-021-04256-8DOI Listing
June 2021

Calorie restriction conferred improvement effect on long-term rehabilitation of ischemic stroke via gut microbiota.

Pharmacol Res 2021 Jun 11;170:105726. Epub 2021 Jun 11.

Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer (SMHC), Minhang Hospital, Fudan University, 201199 Shanghai, China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, 201199 Shanghai, China. Electronic address:

Calorie restriction can modulate the gut microbiota and protect against many diseases including ischemic stroke. However, the role of calorie-restriction-induced microbiota alteration remained unknown in ischemic stroke rehabilitation. Here we conducted 30% reduction of caloric intake on mice for four weeks, to evaluate its role on ischemic stroke rehabilitation. Significantly, this calorie restriction led to better long-term rehabilitation in comparison of normal control. Notably, the transplantation of gut microbiome from calorie-restriction-treated mice to post-stroke mice was eligible to obtain better long-term rehabilitation of stroke mice. Bifidobacterium identified by 16 S ribosomal RNA sequencing were enriched in those of calorie-restriction mice. Then we administrated Bifidobacterium to stroke mice and found Bifidobacterium treatment could successfully improve the long-term rehabilitation of cerebral ischemia mice. Furthermore, the metabolomics analysis revealed a panel of upshifting metabolites, suggesting that calorie restriction greatly altered the gut microbiota composition and its metabolism. Hence, we discovered the novel effect of CR on long-term rehabilitation of ischemic stroke and the underlying role of gut microbiota, which might provide novel thoughts for the clinical post-stroke rehabilitation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2021.105726DOI Listing
June 2021

Metformin Reverses Hashimoto's Thyroiditis by Regulating Key Immune Events.

Front Cell Dev Biol 2021 28;9:685522. Epub 2021 May 28.

Department of Endocrinology, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China.

Background: Hashimoto's thyroiditis (HT) is a common autoimmune disease characterized by high levels of thyroid peroxidase antibody (TPOAb) and thyroid globulin antibody (TgAb) as well as infiltration of lymphocytes in thyroid. In recent years, metformin has been proven to be effective in a variety of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis.

Methods: This study systematically explored the therapeutic effect of metformin on HT and its underlying mechanism by comprehensively utilizing methods including animal model, cell culture and differentiation, mRNA sequencing and 16S rRNA sequencing.

Findings: We found that metformin indeed had a therapeutic effect on mice with HT mainly by reducing TgAb and lymphocyte infiltration in thyroid tissue. In addition, metformin also significantly suppressed the number and function of Th17 cells and M1 macrophages polarization in HT mice. Furthermore, metformin can inhibit the differentiation and function of Th17 . The results of mRNA sequencing of thyroid tissue illustrated that the therapeutic effect of metformin on HT was mainly achieved by regulating immune pathways. 16S RNA sequencing of the intestinal flora found that the intestinal flora of HT mice differs significantly from that of the normal mice and also were altered by metformin treatment.

Interpretation: These experiments provided a preliminary theoretical basis for the clinical application of metformin in the treatment of HT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.685522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193849PMC
May 2021

Integrated Analyses Reveal the Multi-Omics and Prognostic Characteristics of ATP5B in Breast Cancer.

Front Genet 2021 28;12:652474. Epub 2021 May 28.

Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

The beta subunit of F1Fo-ATP synthase (ATP5B) has been demonstrated to play an essential role in tumor progression and metastasis. However, there has been no comprehensive pan-cancer multi-omics analysis of ATP5B, while the clinical relevance of ATP5B and its potential mechanism in regulating breast cancer are still poorly understood. In this study, we demonstrated that ATP5B has a higher frequency of amplification than deletion in most cancer types, and the copy number variation (CNV) of ATP5B was significantly positively correlated with its mRNA expression level. DNA methylation analysis across pan-cancer also revealed a strong correlation between ATP5B expression and epigenetic changes. We identified 6 significant methylation sites involved in the regulation of ATP5B expression. Tissue microarrays (TMA) from 129 breast cancer samples, integrated with multiple additional breast cancer dataset, were used to evaluate the ATP5B expression and its correlation with prognosis. Higher levels of ATP5B expression were consistently associated with a worse OS in all datasets, and Cox regression analysis suggested that ATP5B expression was an independent prognostic factor. Gene enrichment analysis indicated that the gene signatures of DNA damage recognition, the E-cadherin nascent pathway and the PLK1 pathway were enriched in ATP5B-high patients. Moreover, somatic mutation analysis showed that a significant different mutation frequency of CDH1 and ADAMTSL3 could be observed between the ATP5B-high and ATP5B-low groups. In conclusion, this study reveals novel significance regarding the genetic characteristics and clinical value of ATP5B highlighted in predicting the outcome of breast cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2021.652474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194306PMC
May 2021

Race as a factor in donor selection and survival of children with hematologic malignancies undergoing hematopoietic stem cell transplant in Florida.

Pediatr Blood Cancer 2021 Jun 14:e29180. Epub 2021 Jun 14.

Center for Cell and Gene Therapy for Nonmalignant Conditions, Blood and Marrow Transplant Program, Cancer & Blood Disorders Institute, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, USA.

Background: Previous studies have explored posthematopoietic cell transplant (HCT) outcomes by race in adults; however, pediatric data addressing this topic are scarce.

Procedure: This retrospective registry study included 238 White (W) and 57 Black (B) children with hematologic malignancies (HM) receiving first allogeneic HCT between 2010 and 2019 at one of the five Florida pediatric HCT centers.

Results: We found no differences between W and B children in transplant characteristics, other than donor type. There was a significant difference in use of human leukocyte antigen (HLA)-mismatched donors (HLA-MMD) (53% W, 71% B, p = .01). When comparing HLA-MMD use to fully HLA-matched donors, B had relative risk (RR) of 1.47 (95% CI 0.7-3) of receiving a mismatched unrelated donor (MMUD), RR of 2.34 (95% CI 1.2-4.4) of receiving a mismatched related donor (MMRD), and RR of 1.9 (95% CI 0.99-3.6) of receiving a mismatched cord blood donor (MMCBD) HCT, respectively. There was no significant difference in the incidence of aGVHD (48% W, 35% B), p = .1, or cGVHD (19% W, 28% B, p = .1), or primary cause of death. Overall 24-month survival was 61% (95% CI 55%-68%) for W, and 60% (95% CI 48-75) for B children, log-rank p = .7. While HLA matching improved survival in W children, the number of B children receiving HLA-matched HCT was too small to identify the impact of HLA matching on survival.

Conclusions: In this contemporary cohort of children with HM, we found that B children were more likely to receive HLA-MMD transplants, but this did not adversely affect survival or GVHD rates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.29180DOI Listing
June 2021

PTEN nuclear translocation enhances neuronal injury after hypoxia-ischemia via modulation of the nuclear factor-κB signaling pathway.

Aging (Albany NY) 2021 Jun 10;13. Epub 2021 Jun 10.

Department of Neonatology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan, China.

The occurrence of hypoxia-ischemia (HI) in the developing brain is closely associated with neuronal injury and even death. However, the underlying molecular mechanism is not fully understood. This study was designed to investigate phosphatase and tensin homolog (PTEN) nuclear translocation and its possible role in rat cortical neuronal damage following oxygen-glucose deprivation (OGD) . An OGD model was established using primary cortical neurons dissected from newborn Sprague-Dawley rats to mimic HI conditions. The PTEN mutant plasmid, which contains a lysine-to-arginine mutation at the lysine 13 residue, was constructed. The nuclei and cytoplasm of neurons were separated. Neuronal injury following OGD was evidenced by increased lactate dehydrogenase (LDH) release and apoptotic cell counts. In addition, PTEN expression was increased and the phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK1/2) and activation of nuclear factor kappa B (NF-κB) were decreased following OGD. PTEN transfection prevented PTEN nuclear translocation; attenuated the effect of OGD on nuclear p-ERK1/2 and NF-κB, apoptosis, and LDH release; and increased the expression of several anti-apoptotic proteins. We conclude that PTEN nuclear translocation plays an essential role in neuronal injury following OGD via modulation of the p-ERK1/2 and NF-κB pathways. Prevention of PTEN nuclear translocation might be a candidate strategy for preventing brain injury following HI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.203141DOI Listing
June 2021

Heart Failure With Mid-range Ejection Fraction: A Distinctive Subtype or a Transitional Stage?

Front Cardiovasc Med 2021 25;8:678121. Epub 2021 May 25.

State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Heart failure with mid-range ejection fraction (HFmrEF) was first proposed by Lam and Solomon in 2014, and was listed as a new subtype of heart failure (HF) in 2016 European Society of Cardiology guidelines. Since then, HFmrEF has attracted an increasing amount of attention, and the number of related studies on this topic has grown rapidly. The diagnostic criteria on the basis of left ventricular ejection fraction (LVEF) are straightforward; however, LVEF is not a static parameter, and it changes dynamically during the course of HF. Thus, HFmrEF may not be an independent disease with a uniform pathophysiological process, but rather a collection of patients with different characteristics. HFmrEF is often associated with various cardiovascular and non-cardiovascular diseases. Thus, the pathophysiological mechanisms of HFmrEF are particularly complex, and its clinical phenotypes are diverse. The complexity and heterogeneity of HFmrEF may be one reason for inconsistent results between clinical studies. In fact, whether HFmrEF is a distinctive subtype or a transitional stage between HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) is controversial. In this review, we discuss the clinical characteristics, treatment and prognosis of patients with HFmrEF, as well as the differences among HFmrEF, HFrEF, and HFpEF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.678121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185203PMC
May 2021

[Clinical effects of intermittent oro-esophageal tube feeding combined with Xuanqiaoliyan decotion in stroke patients with dysphagia].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 May;33(5):552-556

Department of Neurology, Yidu Central Hospital Affiliated Hospital of Weifang Medical University, Qingzhou 262500, Shandong, China. Corresponding author: Sun Xibo, Email:

Objective: To investigate the clinical effects of intermittent oro-esophageal tube feeding (IOE) combined with Xuanqiaoliyan decotion in stroke patients with dysphagia.

Methods: A prospective study was conducted. Stroke patients with dysphagia admitted to Yidu Central Hospital Affiliated Hospital of Weifang Medical University from January 2018 to December 2019 were enrolled. According to the simple random sampling method, the patients were divided into control group and observation group, with 50 cases in each group. The control group was given routine swallowing function training, including low-frequency pulse electrical stimulation, swallowing function training and acupuncture treatment. The observation group was given IOE and Xuanqiaoliyan decoction (prescription composition: Rhizoma acori tatarinowii 15 g, Radix polygalae 10 g, Rhizoma gastrodiae 15 g, Arisaema cum bile 6 g, Rhizoma typhonii 6 g, Scorpio 6 g, Bombyx batryticatus 6 g, Perilla frutescens 10 g, Rhizoma pinelliae 10 g, Pericarpium citri reticulatae 10 g, Rhizoma zingiberis recens 3 tablets, decoction 200 mL, twice in the morning and evening by oral or nasal feeding) on the basis of the control group. Both groups were treated for 14 days. The standard swallowing function assessment (SSA) and water swallow test were used to evaluate the swallowing function before and after treatment. The time required for the improvement of swallowing function, total hospitalization time and the therapeutic effects were observed and the safety assessment was conducted.

Results: There were no significant differences in the gender, age, course of disease, and location and frequency of stroke between the two groups. After treatment, both the SSA scores in the two groups were decreased, and the grading of water swallow test was improved. The SSA scores in the observation group were significantly lower than that in the control group (19.8±1.8 vs. 23.2±3.2, P < 0.05), the recovery degree of water swallow test was higher than that in the control group [complete recovery (cases): 18 vs. 13, basic recovery (cases): 23 vs. 18, effective (cases): 9 vs. 19, χ = -2.107, P = 0.008]. The total effective rate of swallowing function in the observation group was higher than that in the control group (94.0% vs. 80.0%, Z = 4.684, P = 0.012), the time for improvement (days: 12.8±2.6 vs. 16.9±4.3, t = 11.628, P = 0.008)and total hospitalization time (days: 20.8±4.2 vs. 33.5±5.6, t = 10.924, P = 0.015) were shorter than those in the control group. In the observation group, there was 1 case of throat discomfort during the operation of IOE, and the symptoms disappeared after the operation; there was 1 case of mild elevation of alanine aminotransferase (ALT) and blood urea nitrogen (BUN) respectively, which returned to normal after the treatment. No adverse symptoms and damage to the liver and kidney were observed in the control group.

Conclusions: IOE combined with Xuanqiaoliyan decotion could significantly improve the swallowing function of stroke patients with dysphagia, shorten the hospitalization time, and improve the curative effects and lifequality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3760/cma.j.cn121430-20200628-00487DOI Listing
May 2021

Lysophosphatidic Acid Regulates Rho Family of GTPases in Lungs.

Cell Biochem Biophys 2021 Jun 10. Epub 2021 Jun 10.

Dorothy M. Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH, USA.

The bio-active lipid, lysophosphatidic acid (LPA) interacts with various lysophosphatidic acid receptors (LPARs) to affect a variety of cellular functions, including proliferation, differentiation, survival, migration, morphogenesis and others. The Rho family of small GTPases, is well-known downstream signaling pathways activated by LPA. Among the Rho GTPases, RhoA, Rac1, and Cdc42 are best characterized and LPA-induced activation of the GTPases RhoA, Rac1, and Cdc42 influences a wide range of cellular processes and functions such as cell differentiation, contractile movements, cellular migration, or infiltration. In this review, we will briefly discuss the interplay between LPA and each of these three Rho family proteins, summarizing the main interactions between them. Our discussion will focus mainly on their interplay within lung endothelial and epithelial cells, drawing attention to how these interactions may contribute to pro-inflammatory processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12013-021-00993-yDOI Listing
June 2021

Resveratrol affects the expression of uric acid transporter by improving inflammation.

Mol Med Rep 2021 Aug 10;24(2). Epub 2021 Jun 10.

Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.

Resveratrol (RSV), a polyphenol, non‑flavonoid plant‑derived antitoxin, ameliorates hyperuricemia and kidney inflammation. The present study aimed to establish a model of high‑fat diet (HFD)‑induced insulin resistance (IR) and to determine the specific mechanism of RSV to improve kidney inflammation and reduce uric acid (UA). C57BL/6J mice were fed a HFD for 12 weeks and their glucose tolerance was evaluated by intraperitoneal glucose tolerance testing. The mice were then administered RSV for 6 weeks, and blood and kidney samples were collected. Serum UA and insulin concentrations were determined using ELISA kits. Hematoxylin and eosin, periodic acid‑Schiff and Masson staining were performed to observe the pathological changes of the kidney, and electron microscopy was used to observe changes in the kidney ultrastructure. The renal concentrations of interleukin (IL)‑6, IL‑18, IL‑1β and tumor necrosis factor‑α (TNF‑α) were measured using ELISA kits, and western blotting evaluated changes in the protein expression levels of various indicators. RSV significantly ameliorated HFD‑induced IR and reduced blood UA levels. Long‑term IR can lead to lipid deposition, glycogen accumulation, inflammatory damage and fibrotic changes in the kidney of mice. This leads to a significant increase in the expression of UA transport‑related proteins, an increase in UA reabsorption and an increase in blood UA levels. Notably, RSV intervention was able to reverse this process. The effect of RSV may be achieved by inhibiting the NOD‑like receptor family, pyrin domain‑containing 3 (NLRP3) inflammasome and Toll‑like receptor 4 (TLR4)/myeloid differentiation factor 88/nuclear factor‑κB signaling pathway. In conclusion, RSV may improve kidney inflammation through TLR4 and NLRP3 signaling pathways, and reduce the expression of UA transporter proteins in the kidney of insulin‑resistant mice, thereby reducing blood UA levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2021.12203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201466PMC
August 2021

How Chinese Herbal Medicine Prevents Epidemics: From Ancient Pestilences to COVID-19 Pandemic.

Am J Chin Med 2021 Jun 5:1-28. Epub 2021 Jun 5.

College of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, P. R. China.

The ongoing coronavirus disease 2019 (COVID-19) pandemic calls for effective control and prevention. Chinese medicine (CM) has developed systematic theories and approaches for infectious disease prevention over 2000 years. Here, we review and analyze Chinese herbal medicines (CHM) used in infectious disease prevention from ancient pestilences to modern epidemics and pandemics to share cumulative preventive medical experience. A total of 829 formulas, including 329 herbs from 189 ancient books, 131 formulas with 152 herbs, and 13 Chinese patent medicines (CPM) from 30 official Chinese prevention programs used in ancient epidemics, SARS, influenza and COVID-19 prevention, were reviewed and analyzed. Preventive CHM mainly has four functions and can be taken orally or applied externally. CHM that kill pathogens ( [Xionghuang], [Guanzhong]) were commonly used externally for disinfection in ancient prevention while CHM tonifying Qi ( [Huangq], [Gancao]) are used for modern prevention. Taking CHM that expel pathogens ( [Xionghuang], [Jinyinhua]) and CHM eliminating dampness ( [Cangzhu], [Guanghuoxiang]) have been commonly used from ancient times to COVID-19. Damp toxins are a common characteristic of infectious diseases such as SARS and COVID-19. Thus, taking CHM expelling damp toxins and tonifying Qi are the main methods for SARS and COVID-19 prevention. CHM with different approaches have been widely used in infectious disease prevention from ancient times to the present. Multiple CM prevention methods may provide new perspectives for future pandemics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1142/S0192415X2150049XDOI Listing
June 2021

[Efficacy and Relapse Prediction Model of Allogeneic Peripheral Blood Stem Cell Transplantation in Adult Acute Leukemia].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):696-702

Department of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China,E-mail:

Objective: To observe the clinical efficacy of allogeneic peripheral blood stem cell transplantation(allo-HSCT) on the treatment of adult acute leukemia patients, moreover, to establish and evaluate a Logistic model to predict the risk of relapse in adult acute leukemia patients after allo-HSCT.

Methods: The clinical data of 145 adult acute leukemia patients treated by peripheral blood stem cell transplantation in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2019 was enrolled and analyzed retrospectively. Complications and survival of patients were observed. The relationship between patients' age, diagnosis, leukocyte count at onset, risk stratification, time of diagnosis to transplantation, HCT-CI, minimal residual disease pre-transplantation, donor-recipient sex relationship, HLA match degree, prophylaxis of graft versus host disease(GVHD), donor age, number of transfused mononuclear cells, CD34 positive cells, engraftment time, acute and chronic GVHD, CMV, EBV infection, and hemorrhagic cystitis and recurrence after transplantation were analyzed by logistic regression. Relapse prediction model was established and evaluated according to the results.

Results: Among 145 acute leukemia patients, 81 with acute myeloid leukemia, 64 with acute lymphocytic leukemia, 18 with EBV infection, 2 with post-transplant lymphoproliferative disorder(PTLD), 85 with CMV, 26 with hemorrhagic cystitis, 65 patients developed acute GVHD, 51 patients developed chronic GVHD and 45 patients relapsed. The overall survival (OS) rates in one and three years were 86.4% and 61.8%, and the progress-free survival (PFS) rates in one and three years were 67.5% and 62.4%, respectively. There were significant differences in OS and PFS between relapsed and non-relapsed patients, as well as AML and ALL patients. Univariate analysis revealed that patient's age, risk stratification, time to transplantation, HCT-CI index, ATG based GVHD prophylaxis, minimal residual disease pre-transplantation, GVHD prophylaxis, and acute and chronic GVHD were associated with the relapse of disease, multivariate logistic regression analysis showed that pre-transplantation minimal residual disease showed positively correlation with relapse of the disease, while chronic GVHD showed negatively correlation.

Conclusion: The relapse rate of adult acute leukemia patients treated with allo-HSCT in our hospital is 31.0%, and OS of AML patients is better than ALL patients'. OS of relapsed patients is significantly lower than non-relapsed patients'. Pre-transplantation minimal residual disease is a risk factor of relapse. The risk of relapse is reduced in patients with chronic GVHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.03.007DOI Listing
June 2021

SOX14 hypermethylation as a tumour biomarker in cervical cancer.

BMC Cancer 2021 Jun 7;21(1):675. Epub 2021 Jun 7.

Department of Laboratory Medicine, Tianjin Medical University, Tianjin, China.

Background: The association between SOX14 and cancer has been reported. The aim of this study was to identify and validate the potential value of SOX14 methylation in the early detection of cervical cancer.

Methods: First, we extracted the data for SOX14 methylation and expression within cervical cancer from The Cancer Genome Atlas (TCGA) database and analysed them via UALCAN, Wanderer, MEXPRESS and LinkedOmics. Subsequently, according to the bioinformatics findings, primers and probes were designed for the most significantly differentiated methylation CpG site and synthesized for methylation-specific PCR (MSP) and quantitative methylation-specific PCR (QMSP) to verify SOX14 methylation in both cervical tissuses and liquid-based cell samples. Eventually, the clinical diagnostic efficacy of SOX14 methylation in the normal, cervical intraepithelial neoplasia, and cancer groups was analysed by ROC.

Results: Pooled analysis demonstrated that SOX14 methylation levels were significantly increased in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) compared to normal tissues (P < 0.001). Both the verification and validation cohorts indicated that the methylation level and the positive rate of SOX14 gradually increased with increasing severity from normal to cancer samples (P < 0.01). When the cut-off value was set as 128.45, the sensitivity and specificity of SOX14 hypermethylation in the diagnosis of cervical cancer were 94.12 and 86.46%, respectively. When taken as a screening biomarker (>CINII), the sensitivity was 74.42% and the specificity was 81.48%, with a cut-off value of 10.37.

Conclusion: SOX14 hypermethylation is associated with cervical cancer and has the potential to be a molecular biomarker for the screening and early diagnosis of cervical cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-021-08406-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185922PMC
June 2021

Facile extraction and characterization of cellulose nanocrystals from agricultural waste sugarcane straw.

J Sci Food Agric 2021 Jun 6. Epub 2021 Jun 6.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.

Background: Sugarcane straw is an available but largely ignored lignocellulosic biomass to obtain cellulose nanocrystals (CNCs) with highly crystalline, tunable surface chemistries and a wide-ranging adaptability. Herein, we utilized sugarcane straw to obtain pure cellulose via purification processes, followed by subsequent preparation of CNCs via sulfuric acid hydrolysis. The properties of the purified fibers and obtained CNCs were assessed by their composition, morphology, chemical structure, crystallinity and thermal stability.

Results: After purification process, alkali-treated fibers (ATFs) contained 886.33±1.25 g kg cellulose, and its morphological analysis revealed a smooth and slender fibrous structure. The CNCs obtained by treatment with 64 wt% sulfuric acid at 45°C for 60 min were isolated in a yield of 21.8%, with a diameter and length of 6 ~ 10 nm and 160 ~ 200 nm, respectively. Moreover, crystallinity index of these CNCs reached 62.66%, and thermal stability underwent a two-step degradation. Short-term ultrasonication after hydrolysis was employed to enhance isolation of the CNC particles and improve the anionic charge with higher value -38.00 mV.

Conclusion: Overall, isolation and characterization results indicated the potential for CNCs preparation using sugarcane straw, in addition to offering a fundamental understanding of this material and indicating potential applications. This article is protected by copyright. All rights reserved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jsfa.11360DOI Listing
June 2021

The Sulfation Code of Tauopathies: Heparan Sulfate Proteoglycans in the Prion Like Spread of Tau Pathology.

Front Mol Biosci 2021 20;8:671458. Epub 2021 May 20.

Department of Biological Sciences, Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, United States.

Tauopathies are a heterogenous family of progressive neurodegenerative diseases defined by the appearance of proteinaceous lesions within the brain composed of abnormally folded species of Microtubule Associated Protein Tau (tau). Alzheimer's Disease (AD), the most common tauopathy, is the leading cause of cognitive decline among the elderly and is responsible for more than half of all cases of senile dementia worldwide. The characteristic pathology of many tauopathies-AD included-presents as Neurofibrillary Tangles (NFTs), insoluble inclusions found within the neurons of the central nervous system composed primarily of tau protein arranged into Paired Helical Fibrils (PHFs). The spatial extent of this pathology evolves in a remarkably consistent pattern over the course of disease progression. Among the leading hypotheses which seek to explain the stereotypical progression of tauopathies is the , which proposes that the spread of tau pathology is mediated by the transmission of self-propagating tau conformers between cells in a fashion analogous to the mechanism of communicable prion diseases. Protein-glycan interactions between tau and Heparan Sulfate Proteoglycans (HSPGs) have been implicated as a key facilitator in each stage of the prion-like propagation of tau pathology, from the initial secretion of intracellular tau protein into the extracellular matrix, to the uptake of pathogenic tau seeds by cells, and the self-assembly of tau into higher order aggregates. In this review we outline the biochemical basis of the tau-HS interaction and discuss our current understanding of the mechanisms by which these interactions contribute to the propagation of tau pathology in tauopathies, with a particular focus on AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2021.671458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173255PMC
May 2021

A sensitive and practical ELISA for analyzing naringenin in pummelo and herb samples.

Food Chem 2021 May 27;362:130223. Epub 2021 May 27.

Laboratory of Quality & Safety Risk Assessment for Citrus Products (Chongqing), Ministry of Agriculture, Citrus Research Institute, Southwest University, Chongqing 400712, China. Electronic address:

Naringenin, a flavonoid compound found in pummelo, is a key biological active compound in some traditional Chinese medicines, including Citri reticulatae pericarpium, Citri reticulatae pericarpium viride, Aurantii fructus immaturus, and Aurantii fructus. These Chinese medicinal preparations are the peels or immature fruits of certain citrus species. Aiming at detecting naringenin in complex matrices such as pummelo and traditional Chinese medicines, we put forward a sensitive and practical indirect competitive enzyme-linked immunosorbent assay (icELISA) based on anti-naringenin monoclonal antibodies (anti-Nar-mAbs). The median inhibitory concentration (IC) was 4.43 ng/mL, and the working range was 1.15-15.81 ng/mL. The findings of the icELISA for the analysis of naringenin in pummelo and herb samples had a good correlation with the ultra performance liquid chromatography (UPLC) methodology and showed good accuracy and reproducibility. These data demonstrated that the developed icELISA is reliable, accurate, and suitable for detecting naringenin in pummelo and traditional Chinese medicines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2021.130223DOI Listing
May 2021

Risk and protective factors for anxiety during COVID-19 pandemic.

BMC Public Health 2021 06 4;21(1):1063. Epub 2021 Jun 4.

State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.

Background: Coronavirus Disease 2019 (COVID-19) is a global pandemic and an anxiety-provoking event. There are few studies to identify potential risk and protective factors related to anxiety during COVID-19 pandemic.

Methods: We collected information on demographic data and lifestyles by a web-based survey of 19,802 participants from 34 provinces in China during COVID-19 pandemic. Level of anxiety was evaluated using the Self-Rating Anxiety Scale. We used ordinal multivariable logistic regression to estimate the associations of anxiety level with potential risk and protective factors. We further developed a new score to simplify the assessment of anxiety during COVID-19 crisis.

Results: Among 19,802 participants, we found that those who were front-line medical personnel, suffered from chronic disease, with present symptoms of SARS-CoV-2 infection or contact history had 112, 93, 40 and 15% increased risk of higher anxiety level; while those with knowledge about personal protective measures or wore masks had 75 and 29% lower risk of higher anxiety level respectively. We developed a risk score by calculating the sum of single score of 17 factors. Each one increase of the risk score was associated with a 297% increase in anxiety index score. In categorical analysis, low risk (the risk score between 1 to 2), the moderate risk group (the risk score of 3) and high risk group (the risk score ≥ 4) had - 0.40 (95% CI: - 1.55, 0.76), 1.44 (95% CI: 0.27, 2.61) and 9.18 (95% CI: 8.04, 10.33) increase in anxiety index score, and 26% (95% CI: - 7, 72%), 172% (95% CI: 100, 270%), and 733% (95% CI: 516, 1026%) higher risk of anxiety respectively, when compared with the very low risk group (the risk score of 0). The AUC was 0.73 (95% CI, 0.72, 0.74) for the model fitted the developed risk score, with the cut-off point of 3.5.

Conclusions: These findings revealed protective and risk factors associated with anxiety, and developed a simple method of identifying people who are at an increased risk of anxiety during COVID-19 pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12889-021-11118-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177261PMC
June 2021

Camellia japonica diminishes acetaminophen-induced acute liver failure by attenuating oxidative stress in mice.

Environ Sci Pollut Res Int 2021 Jun 4. Epub 2021 Jun 4.

College of Veterinary Medicine and Bio-safety Research Institute, Jeonbuk National University, Iksan, 54596, South Korea.

This experiment was to explore the possible defensive properties and potential molecular mechanisms of Camellia japonica (CJ) against APAP-stimulated acute liver failure (ALF) in mice. In this study, we investigated the effects of CJ on APAP-induced hepatotoxicity. Mice were orally treated with CJ before or after challenge with APAP. Both pretreatment and post-treatment with CJ attenuated APAP-induced hepatotoxicity, as confirmed by significantly reduced serum toxicity biomarkers and improved hepatic pathological damage. Pretreatment with CJ drastically decreased the rise of hepatic inflammatory cytokines levels and weakened neutrophil infiltration. Furthermore, pretreatment with CJ dramatically decreased the levels of hepatic oxidative stress markers such as hepatic malondialdehyde (MDA) and 4-Hydroxynonenal (4-HNE) expression and rescued the reduced hepatic level of GSH caused by APAP overdose. Additionally, CJ pretreatment markedly attenuated cyclooxygenase-2 (COX-2) activation, transcription factor nuclear factor-kappa B (NF-κB) phosphorylation, c-Jun-N-terminal kinase (JNK) phosphorylation, and activated AMP-activated protein kinase (AMPK) signaling pathway in the liver. The present study thus reveals that CJ attenuated APAP-induced ALF by inhibiting COX-2 activation, NF-κB, and JNK phosphorylation and activating the AMPK signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-021-14530-0DOI Listing
June 2021

Sigma 1 Receptor Modulates Optic Nerve Head Astrocyte Reactivity.

Invest Ophthalmol Vis Sci 2021 Jun;62(7)

Department of Ophthalmology, Medical College of Georgia at Augusta University, Augusta, Georgia, United States.

Purpose: Stimulation of Sigma 1 Receptor (S1R) is neuroprotective in retina and optic nerve. S1R is expressed in both neurons and glia. The purpose of this work is to evaluate the ability of S1R to modulate reactivity responses of optic nerve head astrocytes (ONHAs) by investigating the extent to which S1R activation alters ONHA reactivity under conditions of ischemic cellular stress.

Methods: Wild type (WT) and S1R knockout (KO) ONHAs were derived and treated with vehicle or S1R agonist, (+)-pentazocine ((+)-PTZ). Cells were subjected to six hours of oxygen glucose deprivation (OGD) followed by 18 hours of re-oxygenation (OGD/R). Astrocyte reactivity responses were measured. Molecules that regulate ONHA reactivity, signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-kB), were evaluated.

Results: Baseline glial fibrillary acidic protein (GFAP) levels were increased in nonstressed KO ONHAs compared with WT cultures. Baseline cellular migration was also increased in nonstressed KO ONHAs compared with WT. Treatment with (+)-PTZ increased cellular migration in nonstressed WT ONHAs but not in KO ONHAs. Exposure of both WT and KO ONHAs to ischemia (OGD/R), increased GFAP levels and cellular proliferation. However, (+)-PTZ treatment of OGD/R-exposed ONHAs enhanced GFAP levels, cellular proliferation, and cellular migration in WT but not KO cultures. The (+)-PTZ treatment of WT ONHAs also enhanced the OGD/R-induced increase in cellular pSTAT3 levels. However, treatment of WT ONHAs with (+)-PTZ abrogated the OGD/R-induced rise in NF-kB(p65) activation.

Conclusions: Under ischemic stress conditions, S1R activation enhanced ONHA reactivity characteristics. Future studies should address effects of these responses on RGC survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.62.7.5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185400PMC
June 2021

Quantitative and Single-Nucleotide Resolution Profiling of RNA 5-Methylcytosine.

Methods Mol Biol 2021 ;2298:135-151

Department of Molecular and Biomedical Sciences, School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia.

RNA has coevolved with numerous posttranscriptional modifications to sculpt interactions with proteins and other molecules. One of these modifications is 5-methylcytosine (mC) and mapping the position and quantifying the level in different types of cellular RNAs and tissues is an important objective in the field of epitranscriptomics. Both in plants and animals bisulfite conversion has long been the gold standard for detection of mC in DNA but it can also be applied to RNA. Here, we detail methods for highly reproducible bisulfite treatment of RNA, efficient locus-specific PCR amplification, detection of candidate sites by sequencing on the Illumina MiSeq platform, and bioinformatic calling of non-converted sites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-0716-1374-0_9DOI Listing
January 2021

An alternative domain-swapped structure of the Pyrococcus horikoshii PolII mini-intein.

Sci Rep 2021 Jun 3;11(1):11680. Epub 2021 Jun 3.

Department of Chemistry, College of the Holy Cross, 1 College Street, Worcester, MA, USA.

Protein splicing is a post-translational process by which an intein catalyzes its own excision from flanking polypeptides, or exteins, concomitant with extein ligation. Many inteins have nested homing endonuclease domains that facilitate their propagation into intein-less alleles, whereas other inteins lack the homing endonuclease (HEN) and are called mini-inteins. The mini-intein that interrupts the DNA PolII of Pyrococcus horikoshii has a linker region in place of the HEN domain that is shorter than the linker in a closely related intein from Pyrococcus abyssi. The P. horikoshii PolII intein requires a higher temperature for catalytic activity and is more stable to digestion by the thermostable protease thermolysin, suggesting that it is more rigid than the P. abyssi intein. We solved a crystal structure of the intein precursor that revealed a domain-swapped dimer. Inteins found as domain swapped dimers have been shown to promote intein-mediated protein alternative splicing, but the solved P. horikoshii PolII intein structure has an active site unlikely to be catalytically competent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-91090-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175363PMC
June 2021

Engineering Cell Membrane-Based Nanovesicles for Melanoma Tumor Treatment.

J Biomed Nanotechnol 2021 May;17(5):838-845

State Key Laboratory of Coordination Chemistry Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences, Nanjing University Nanjing 210093, Jiangsu, PR China.

Malignant melanoma has a poor prognosis because of its strong ability to invade tissues and metastasize. Immune checkpoint blockades significantly improve the clinical response in the development of melanoma. However, there are some obstacles to overcome, such as cost and limited application. Therefore, prospective approaches remain to be exploited. We designed cellular nanovesicles (NVs) expressing PD-1 to reactivate T cells by disrupting the PD-1/PD-L1 immunoinhibitory pathway. Furthermore, siNF90 was wrapped into PD-1 NVs to inhibit the proliferation of tumor cells. Such a dual target effect is helpful for the treatment of melanoma. In addition, our results showed that treatment with PD-1 @siNF90 NVs inhibited the growth of melanoma tumors and extended the survival time of mice, exhibiting a better effect than PD-1 NVs alone. The data also verified that the percentage of CD8 T cells in tumors was highest after PD-1 @siNF90 NVs treatment. To sum up, PD-1 @siNF90 NVs could serve as safe and effective blockers in the treatment of melanoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1166/jbn.2021.3072DOI Listing
May 2021

A metabolomics study of Qianliexin capsule treatment of benign prostatic hyperplasia induced by testosterone propionate in the rat model.

Anal Biochem 2021 Jun 1;628:114258. Epub 2021 Jun 1.

Institute of Life Science and Bio-pharmaceuticals, Pharmaceutical College, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning Province, China. Electronic address:

A metabolomics investigation of the treatment effect of Qianliexin (QLX) capsules was conducted on rats with benign prostatic hyperplasia (BPH) induced by testosterone propionate. Establishment of the BPH model was confirmed using the prostatic index. Hematoxylin and eosin (HE) staining for TGF-β, EGFR, collagen, IL-1 β, TNF-α was performed and changes in urine volume were measured. Urine and serum samples were collected from three groups, including a control group, a BPH model group and a QLX-treated group and subjected to metabolomics profiling based on ultrahigh-performance liquid chromatography-mass spectrometry. Pharmacodynamics analysis showed that the QLX group had significantly lower histopathological damage, fibrosis damage, and inflammation and higher urine output compared with the model group. Twenty-two potential biomarkers were identified in urine samples and 23 metabolites were identified in plasma samples. Alterations in metabolic patterns were evident in all sample types. The treatment effects of QLX appear to involve various metabolic pathways including lipid metabolism, fatty acid metabolism and purine generation and significantly reduced the pathological symptoms and related biochemical indicators of BPH and improved the level of potential marker metabolites. This comprehensive study suggested that differential markers provided insights into the metabolic pathways involved in BPH and the treatment effects of QLX.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ab.2021.114258DOI Listing
June 2021