Publications by authors named "Xuan Deng"

87 Publications

Single-cell transcriptome analysis of diffuse large B cells in cerebrospinal fluid of central nervous system lymphoma.

iScience 2021 Sep 11;24(9):102972. Epub 2021 Aug 11.

Department of Clinical Laboratory, Huashan Hospital, Fudan University, Shanghai, China.

Diffuse large B cells in the cerebrospinal fluid (CSF-DLBCs) have offered great promise for the diagnostics and therapeutics of central nervous system lymphoma (CNSL) leptomeningeal involvement. To explore the phenotypic states of CSF-DLBCs, we analyzed the transcriptomes of more than one thousand CSF-DLBCs from six patients with CNSL diffuse large B-cell lymphoma (DLBCL) using Smart-seq2 single-cell RNA sequencing. CSF-DLBCs were defined based on abundant expression of B-cell markers, the active cell proliferation and energy metabolism properties, and immunoglobulin light chain restriction. We identified inherent heterogeneity of CSF-DLBCs, which were mainly manifested in cell cycle state, cancer-testis antigen expression, and classification based on single-cell germinal center B-cell signature. In addition, the 16 upregulated genes in CSF-DLBCs compared to various normal B cells showed great possibility in the homing effect of the CNS-DLBCL for the leptomeninges. Our results will provide insight into the mechanism research and diagnostic direction of CNSL-DLBCL leptomeningeal involvement.
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http://dx.doi.org/10.1016/j.isci.2021.102972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387906PMC
September 2021

An Overview of Preferred Retinal Locus and Its Application in Biofeedback Training for Low-Vision Rehabilitation.

Semin Ophthalmol 2021 Aug 26:1-11. Epub 2021 Aug 26.

Aier School of Ophthalmology, Central South University, Changsha, Hunan, China.

Central vision loss (CVL) caused by macular damage generally disables common daily tasks, which cannot be reversed by present treatments. Fortunately, it has been found that biofeedback training by inducing or reinforcing preferred retinal locus (PRL) as an eccentric fixation reference contributes to the improvement of visual performance in patients with CVL. However, the clinical application is still under controversy due to poor knowledge of its fundamental and inconsistent practical standards. This article aims to summarize the possible rationale for the development, location, re-location and evaluating indicators of PRL, and the general apparatus, protocol, and outcome of biofeedback PRL training.
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http://dx.doi.org/10.1080/08820538.2021.1931355DOI Listing
August 2021

[Preparation of hydrophilic Indigo Naturalis based on polyethylene glycol( PEG) surface film-forming method and evaluation].

Zhongguo Zhong Yao Za Zhi 2021 Jul;46(13):3213-3221

State Key Laboratory of Southwestern Chinese Medicine Resources,Chengdu University of Traditional Chinese Medicine Chengdu 611137,China.

Polyethylene glycol (PEG) surface film-forming method was used to prepare hydrophilic Indigo Naturalis decoction pieces with stable effect.The preparation process of modified Indigo Naturalis was optimized and its microscopic properties,hydrophilicity,antipyretic efficacy,and safety were systematically evaluated.With equilibrium contact angle as assessment index,the influence of modifier type,modifier dosage,dispersant dosage,and co-grinding time on water solubility of Indigo Naturalis was investigated by single factor test.The results showed that the optimal preparation process was as follows.The 6%PEG6000 is dissolved in 10%anhydrous ethanol solution by sonification and then the mixture is ground with Indigo Naturalis for 2 min.The resultant product is dried on a square tray in an oven at 60℃to remove ethanol and thereby the PEG-modified hydrophilic Indigo Naturalis decoction pieces are yielded.The morphological observation under scanning electron microscope (SEM) indicated that the modified Indigo Naturalis had smoother surface than Indigo Naturalis,and energy spectrometer measurement showed that the nitrogen (N),calcium(Ca),oxygen (O),and silicon (Si) on the surface of modified Indigo Naturalis powder were less than those of Indigo Naturalis powder.Modified Indigo Naturalis had the equilibrium contact angle 18.96°smaller,polar component 22.222 m J·m~(-2)more,and nonpolar component 7.277 m J·m~(-2)smaller than the Indigo Naturalis powder.Multiple light scattering technique was employed to evaluate the dispersion in water and the result demonstrated that the transmittance of Indigo Naturalis and modified Indigo Naturalis was about85%and 75%,respectively,suggesting the higher dispersity of modified Indigo Naturalis.The suspension rate of modified Indigo Naturalis in water was determined by reflux treatment.The result showed that 57%of Indigo Naturalis was not wetted after refluxing for1 h,while the modified Indigo Naturalis was all wetted and dispersed into water.The dissolution of indigo and indirubin of modified Indigo Naturalis increased and the process was more stable.Then,rats were randomized into the blank group,model group,acetaminophen group,Indigo Naturalis group,and hydrophilic Indigo Naturalis group.The temperature changes of rats were observed after administration and the concentration of IL-1βand TNF-αin serum and IL-1βand PGE_2in hypothalamus was measured.The results indicated that the temperature of Indigo Naturalis group and hydrophilic Indigo Naturalis group dropped and the IL-1βlevel of the hydrophilic Indigo Naturalis group decreased (P<0.05) as compared with those in the model group.Thus,both Indigo Naturalis and hydrophilic Indigo Naturalis had antipyretic effect,particularly the hydrophilic Indigo Naturalis.The acute toxicity test of hydrophilic Indigo Naturalis verified that it had no toxicity to rats.In this study,the hydrophilic Indigo Naturalis decoction pieces were prepared with the PEG surface film-forming method,and the antipyretic efficacy and safety were evaluated,which expanded the technological means of powder modification for Chinese medicine and provided a method for clinical use of Chinese medicine.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210319.306DOI Listing
July 2021

Combination of ultra-low dose rituximab and low dose tacrolimus versus tacrolimus alone in the treatment of non-responsive idiopathic membranous nephropathy: a Chinese retrospective cohort study.

Am J Transl Res 2021 15;13(7):7622-7631. Epub 2021 Jul 15.

Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology 1095 Jiefang Ave, Wuhan 430030, Hubei, China.

Introduction: Some patients with idiopathic membranous nephropathy (iMN) do not respond to cyclophosphamide plus steroids treatment, and we define them as non-responsive iMN. The combined regimen of rituximab (RTX) and tacrolimus (TAC) has an excellent effect on this kind of non-responsive iMN patients; however, the optimal dose is still unclear. In this retrospective study, we comapred the efficacy and safety of ultra-low dose RTX plus low-dose TAC therapy versus standard TAC monotherapy in patients with non-responsive iMN.

Materials And Methods: Sixty-seven Chinese non-responsive iMN patients were included. There were 41 patients received standard tacrolimus monotherapy (TAC) and 26 patients received ultra-low dose rituximab plus low dose tacrolimus (RTX/TAC) combination therapy. All patients were observed for 12 months.

Results: 18 patients (18/26, 69.2%) in the RTX/TAC group and 17 patients (17/41, 41.5%) in the TAC group achieved clinical response after 12-month follow-up (=0.044). The median time for achieving response in the two groups was 3.0 months. As indicated by Kaplan-Meier curve, the response rate in the RTX/TAC group was higher than that in the TAC group (=0.015). 24-hour proteinuria, serum albumin, estimated glomerular filtration rate (eGFR) and serum creatinine in the two groups were comparable at baseline; howerver, after 12-month follow up, they were significantly improved in the RTX/TAC group compared with the TAC group (<0.05). B-cell depletion was achieved in all patients in the RTX/TAC group during the whole follow-up period. Pneumonia, urinary tract infections and glucose intolerance were the major side effects observed in this study. All adverse events were mild, and the cumulative incidence was lower in the RTX/TAC group compared with that in the TAC group (9 (34.6%) vs 27 (65.9%), =0.023).

Conclusion: The combination of ultra-low dose rituximab and low dose tacrolimus is more effective in inducing proteinuria response, improving eGFR and serum albumin in non-responsive iMN patients than standard tacrolimus monotherapy. The combined treatment also has higher safty.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340240PMC
July 2021

Influencing factors and necessity of post-vaccination serologic testing follow-up for HBsAg-positive mothers and their infants: A 5-year prospective study in Zhejiang Province, China (2016-2020).

J Viral Hepat 2021 Oct 8;28(10):1413-1421. Epub 2021 Aug 8.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.

In 2016, China officially proposed for the first time that infants born to HBsAg-positive mothers should be tested for HBsAg and anti-HBs 1-2 months after their third dose of HepB, also known as the post-vaccination serological testing programme. This study aimed to systematically evaluate the implementation and influencing factors of PVST to further reduce HBV infection risk in infants and improve the protective effect of HepB to the greatest extent. A prospective observational study was conducted to investigate the interruption of MTCT of hepatitis B. Univariate and multivariate analyses were applied to explore factors associated with the PVST follow-up rate among HBsAg-positive mothers and their infants. Additionally, bivariate analysis was performed on HBsAg and anti-HBs results in infants born to HBsAg-positive mothers. Here, the participation rate of PVST was 67.08% among 2120 pairs of positive mothers and infants. The HBsAg-positive rate among participants was 0.77%, whereas the anti-HBs positive rate was 96.84%, and both negative rates were 2.39%. Among infants with double negative results (34), only 15 completed three doses of HepB and PVST again, and 14 (93.33%) of which the antibody test results turned positive. Older mothers with high educational levels who reside in the local area were the most likely to PVST follow-up. The PVST programme is necessary to evaluate the HepB response status of newborns after vaccination. Moreover, revaccination for susceptible infants can effectively improve the MTCT-blocking rate of hepatitis B. Therefore, the scope of PVST projects in Zhejiang and China should be expanded.
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http://dx.doi.org/10.1111/jvh.13581DOI Listing
October 2021

The probiotic L. casei Zhang slows the progression of acute and chronic kidney disease.

Cell Metab 2021 Jul 8. Epub 2021 Jul 8.

Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China. Electronic address:

The relationship between gut microbial dysbiosis and acute or chronic kidney disease (CKD) is still unclear. Here, we show that oral administration of the probiotic Lactobacillus casei Zhang (L. casei Zhang) corrected bilateral renal ischemia-reperfusion (I/R)-induced gut microbial dysbiosis, alleviated kidney injury, and delayed its progression to CKD in mice. L. casei Zhang elevated the levels of short-chain fatty acids (SCFAs) and nicotinamide in the serum and kidney, resulting in reduced renal inflammation and damage to renal tubular epithelial cells. We also performed a 1-year phase 1 placebo-controlled study of oral L. casei Zhang use (Chinese clinical trial registry, ChiCTR-INR-17013952), which was well tolerated and slowed the decline of kidney function in individuals with stage 3-5 CKD. These results show that oral administration of L. casei Zhang, by altering SCFAs and nicotinamide metabolism, is a potential therapy to mitigate kidney injury and slow the progression of renal decline.
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http://dx.doi.org/10.1016/j.cmet.2021.06.014DOI Listing
July 2021

Potential Implications of Quercetin in Autoimmune Diseases.

Front Immunol 2021 23;12:689044. Epub 2021 Jun 23.

Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.

Autoimmune diseases are a worldwide health problem with growing rates of morbidity, and are characterized by breakdown and dysregulation of the immune system. Although their etiology and pathogenesis remain unclear, the application of dietary supplements is gradually increasing in patients with autoimmune diseases, mainly due to their positive effects, relatively safety, and low cost. Quercetin is a natural flavonoid that is widely present in fruits, herbs, and vegetables. It has been shown to have a wide range of beneficial effects and biological activities, including anti-inflammation, anti-oxidation, and neuroprotection. In several recent studies quercetin has reportedly attenuated rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and systemic lupus erythematosus in humans or animal models. This review summarizes the evidence for the pharmacological application of quercetin for autoimmune diseases, which supports the view that quercetin may be useful for their prevention and treatment.
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http://dx.doi.org/10.3389/fimmu.2021.689044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260830PMC
June 2021

Economic and disease burden of Japanese encephalitis in Zhejiang Province, 2013-2018.

PLoS Negl Trop Dis 2021 Jun 21;15(6):e0009505. Epub 2021 Jun 21.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, People's Republic of China.

Background: Japanese encephalitis (JE) is a mosquito-borne disease and associated with high mortality and disability rate among symptomatic cases. In the absence of local data, this study estimated the economic burden and the disability-adjusted life years (DALYs) due to JE in Zhejiang Province, China during 2013-2018, to increase disease awareness and provide evidence for effective health policy.

Methodology/principle Findings: We merged multiple data sources, including National Notifiable Disease Registry System (NNDRS), patient interviews and medical records from corresponding hospitals for JE cases which occurred during 2013-2018 in Zhejiang Province. Direct costs were extracted from hospitals' billing systems and patient interviews. Indirect costs and disease burden were calculated based on questionnaire survey from patient interviews and follow-up assessment by general practitioners. Given under-reporting, an expansion factor (EF) was applied to extrapolate the JE burden to the provincial level. The total economic burden of JE during 2013-2018 was estimated at US $12.01 million with an EF = 3. Of this, $8.32 million was due to direct economic cost and $3.69 million to indirect cost. The disease burden of JE was 42.75 DALYs per million population (28.44 YLD, 14.28 YLL) according to the 1990 Global Burden of Disease (GBD 1990) methodology and 80.01 DALYs (53.67YLD, 26.34YLL) according to the GBD 2010 methodology. Sensitivity analysis demonstrated that the overall economic burden varied from US$ 1.73-36.42 million. The greatest variation was due to the prognosis of illness (-85.57%-203.17%), followed by occupation (-34.07%-134.12%) and age (-72.97%-47.69%).

Conclusions/significance: JE imposes a heavy burden for families and society in Zhejiang Province. This study provides comprehensive empirical estimates of JE burden to increase awareness and strengthen knowledge of the public. These data may support provincial level public health decision making for prevention and control of JE. Ongoing surveillance for acute meningitis and encephalitis syndrome (AEMS) in sentinel hospitals, is needed to further refine estimates of JE burden.
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http://dx.doi.org/10.1371/journal.pntd.0009505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248708PMC
June 2021

Separated parabiont reveals the fate and lifespan of peripheral-derived immune cells in normal and ischaemia-induced injured kidneys.

Open Biol 2021 Jun 9;11(6):200340. Epub 2021 Jun 9.

Division of Nephrology, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei 430030, People's Republic of China.

Immune cell infiltration plays a key role in acute kidney injury (AKI) to chronic kidney disease (CKD) progression. T lymphocytes, neutrophils, monocytes/macrophages and other immune cells regulate inflammation, tissue remodelling and repair. To determine the kinetics of accumulation of various immune cell populations, we established an animal model combining parabiosis and separation surgery to explore the fate and lifespan of peripheral leucocytes that migrate to the kidney. We found that peripheral T lymphocytes could survive for a long time (more than 14 days), whereas peripheral neutrophils survived for a short time in both healthy and ischaemia-induced damaged kidneys. Nearly half of the peripheral-derived macrophages disappeared after 14 days in normal kidneys, while their existing time in the inflammatory kidneys was prolonged. A fraction of F4/80 macrophages were renewed from the circulating monocyte pool. In addition, we found that after renal ischaemia reperfusion, neutrophils increased significantly in the early phase, and T lymphocytes mainly accumulated in the late stage, whereas macrophages infiltrated throughout AKI-CKD progression and were sustained longer in injured as opposed to normal kidneys. In conclusion, peripheral-derived macrophages, T lymphocytes and neutrophils exhibit different lifespans in the kidney, which may play different roles during AKI-CKD progression.
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http://dx.doi.org/10.1098/rsob.200340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187026PMC
June 2021

High or low temperature extraction, which is more conducive to Triphala against chronic pharyngitis?

Biomed Pharmacother 2021 Aug 4;140:111787. Epub 2021 Jun 4.

State Key Laboratory of Southwest Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address:

Objective: Explore the effects of high-temperature reflux extraction and low-temperature decompressing inner ebullition on Triphala's chemical composition and anti-chronic pharyngitis activity.

Methods: The network pharmacology was used to analyze the material basis, targets and pathways of Triphala for chronic pharyngitis. HPLC were used to compare the fingerprint profile and content of components between the two extracts. The antioxidant and anti-chronic pharyngitis activities of the two extracts were compared by DPPH assay and ammonia induced chronic pharyngitis model in rats.

Results: The network pharmacology results showed that the active ingredients of Triphala for chronic pharyngitis are epigallocatechin-3-gallate, (+)-catechin, epicatechin, epicatechin gallate, (+)-gallocatechin, quercetin, luteolin, leucodelphinidin and other flavonoids; phenolic acids such as gallic acid and ellagic acid; alkaloids such as ellipticine, cheilanthifoline; hydrolyzed tannins such as corilagin and chebulic acid. The high-temperature reflux extract and the low-temperature decompressing inner ebullition extract have extremely significant differences in the fingerprint profile. Among them, the content of gallic acid, ellagic acid, chebulic acid, catechin, epicatechin, corilagin, quercetin, and epicatechin gallate in the reflux extract is 1.1-5.3 times as much as decompressing inner ebullition extract. The free radical scavenging ability of reflux extract is significantly stronger than that of decompression extract (p < 0.01), and it has a repairing effect on pharyngeal mucosal damage (reducing keratinization or hyperplasia of mucosal epithelium, reducing inflammatory cell infiltration and bleeding), and reducing IL-1β (P<0.05), IL-6 (p<0.05), TNF-α overexpression ability is stronger than the decompressing inner ebullition extract.

Conclusions: gallic acid, ellagic acid, chebulic acid, catechin, epicatechin, corilagin and epicatechin gallate are the basic aglycones or oligomers of tannin. High temperature reflux extraction can significantly promote the occurrence of the hydrolysis of tannins and significantly increases the content of these components.Therefore, its anti-chronic pharyngitis activity is enhanced. It is suggested that high temperature reflux extraction should be used in the treatment of chronic pharyngitis.
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http://dx.doi.org/10.1016/j.biopha.2021.111787DOI Listing
August 2021

A KLF4/PiHL/EZH2/HMGA2 regulatory axis and its function in promoting oxaliplatin-resistance of colorectal cancer.

Cell Death Dis 2021 05 13;12(5):485. Epub 2021 May 13.

Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, China.

Long noncoding RNAs (lncRNAs) have emerged as a new class of regulatory molecules implicated in therapeutic resistance, yet the mechanisms underlying lncRNA-mediated oxaliplatin resistance in colorectal cancer (CRC) are poorly understood. In this study, lncRNA P53 inHibiting LncRNA (PiHL) was shown to be highly induced in oxaliplatin-resistant CRC cells and tumor tissues. In vitro and in vivo models clarified PiHL's role in conferring resistance to oxaliplatin-induced apoptosis. PiHL antagonized chemosensitivity through binding with EZH2, repressing location of EZH2 to HMGA2 promoter, and downregulating methylation of histone H3 lysine 27 (H3K27me3) level in HMGA2 promoter, thus activating HMGA2 expression. Furthermore, HMGA2 upregulation induced by PiHL promotes PI3K/Akt phosphorylation, which resulted in increased oxaliplatin resistance. We also found that transcription factor KLF4 was downregulated in oxaliplatin-resistant cells, and KLF4 negatively regulated PiHL expression by binding to PiHL promoter. In vivo models further demonstrated that treatment of oxaliplatin-resistant CRC with locked nucleic acids targeting PiHL restored oxaliplatin response. Collectively, this study established lncRNA PiHL as a chemoresistance promoter in CRC, and targeting PiHL/EZH2/HMGA2/PI3K/Akt signaling axis represents a novel choice in the investigation of drug resistance.
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http://dx.doi.org/10.1038/s41419-021-03753-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119946PMC
May 2021

Advances in the Application of Natural Products and the Novel Drug Delivery Systems for Psoriasis.

Front Pharmacol 2021 21;12:644952. Epub 2021 Apr 21.

State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Psoriasis, an incurable autoimmune skin disease, is one of the most common immune-mediated disorders. Presently, numerous clinical research studies are underway, and treatment options are available. However, these treatments focus on improving symptoms of the disease and fail to achieve a radical cure; they also have certain toxic side effects. In recent years, natural products have increasingly gained attention because of their high efficiency and low toxicity. Despite their obvious therapeutic effects, natural products' biological activity was limited by their instability, poor solubility, and low bioavailability. Novel drug delivery systems, including liposomes, lipospheres, nanostructured lipid carriers, niosomes, nanoemulsions, nanospheres, microneedles, ethosomes, nanocrystals, and foams could potentially overcome the limitations of poor water solubility and permeability in traditional drug delivery systems. Thus, to achieve a therapeutic effect, the drug can reach the epidermis and dermis in psoriatic lesions to interact with the immune cells and cytokines.
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http://dx.doi.org/10.3389/fphar.2021.644952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097153PMC
April 2021

Characteristics of Preferred Retinal Locus in Eyes with Central Vision Loss Secondary to Different Macular Lesions.

Semin Ophthalmol 2021 Mar 25:1-8. Epub 2021 Mar 25.

Aier School of Ophthalmology, Central South University, Changsha, Hunan, China.

Objective: Preferred retinal locus (PRL) training has been applied to low-vision rehabilitation for patients with central vision loss (CVL). This study aimed to explore the characteristics of a natural PRL in eyes with different macular lesions. The data may be useful in customizing training programs.

Methods: A total of 72 eyes with CVL were included and assigned into two groups. In group A, 29 eyes diagnosed with macular holes featured relatively sharp borders and small areas of lesions. In group B, 44 eyes showed lesions characterized by irregular borders and large areas. The PRL location relative to a scotoma in the retina, fixation stability, and the average threshold surrounding the PRL were determined and compared between the two groups.

Results: In group A, the PRL was located above in 48.28%, below in 27.59%, left in 62.07%, right in 31.03%, and inside in 3.45% of the eyes. In group B, the PRL was located above in 39.53%, below in 4.65%, left in 44.19%, right in 6.98%, and inside in 27.91% of eyes. The amount of retinal displacement occurring within 1° from an initial reference point (< .05) and the 95% bivariate contour ellipse area (< .05) in group A were respectively higher and lower than those in group B. However, the average thresholds around the PRLs in the two groups showed no significant difference ( > .05).

Conclusions: A PRL to the left of or above a scotoma tends to develop to avoid the right and inferior field defect, regardless of the scale and boundary of lesions. Although light sensitivity around a PRL shows no relation to lesion features, fixation stability is worse in irregular and large lesions.
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http://dx.doi.org/10.1080/08820538.2021.1900289DOI Listing
March 2021

Intention to accept pertussis vaccination among Chinese people older than age 5.

Hum Vaccin Immunother 2021 06 15;17(6):1686-1692. Epub 2021 Jan 15.

Department of Immunization Program, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, P.R. China.

: The intention of Chinese people older than age 5 to accept the pertussis vaccination is unknown, which is important for the future design of an effective pertussis vaccination program in China.: We conducted a cross-sectional survey among people older than age 5 in China. A 24-item questionnaire was used to explore the determinants of intention to accept a pertussis vaccination, and for children and adolescents (≦15 years old), their guardian was required to help answer the questionnaire on their behalf. Univariate and multivariate logistic regression was used to analyze the influencing factors of intention.: A total of 3,041 individuals participated in our survey and 3025 completed the questionnaire, among which 1938 (64.07%) reported a positive intention to be vaccinated. A multiple logistic regression analysis revealed that the main positive factors for the intention to accept pertussis vaccination were younger age (Odd ratio [OR] 0.838, < .001), higher educational attainment (OR 1.171, = .002), no hospitalization because of the most recent cough (OR 2.468, < .001), awareness about pertussis (OR 1.958, < .001), and consideration of pertussis vaccination to be safe (OR 1.450, = .026).: There is a relatively high level of intention to receive the pertussis vaccine among people older than age 5 in China. Future pertussis vaccination strategies geared at them should consider focusing on middle-aged and older individuals and those with a low education as well as strengthen the promotion of disease characteristics, vaccine effectiveness, and safety.
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http://dx.doi.org/10.1080/21645515.2020.1849517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115748PMC
June 2021

Selenium(Ⅳ) alleviates chromium(Ⅵ)-induced toxicity in the green alga Chlamydomonas reinhardtii.

Environ Pollut 2021 Mar 31;272:116407. Epub 2020 Dec 31.

Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei, 430072, China. Electronic address:

The wide range of industrial applications of chromium (Cr) has led to an increasing risk of water contamination by Cr(Ⅵ). However, efficient methods to remove or decrease the toxicity of Cr(Ⅵ) in situ are lacking. The main aim of this study was to investigate the mechanisms by which selenite alleviates chromium(Ⅵ)-induced toxicity in Chlamydomonas reinhardtii. Our results showed that KCrO had toxic effects on both the structure and physiology of C. reinhardtii in a dose-dependent manner. Adding selenite significantly alleviated chromium accumulation and toxicity in cells. RNA-seq data showed that the expression level of selenoproteins such as SELENOH was significantly increased. Both SELENOH-amiRNA knockdown mutants and selenoh insertional mutant produced more reactive oxygen species (ROS) and grew slower than the wild type, suggesting that SELENOH can reduce chromium toxicity by decreasing the levels of ROS produced by Cr(Ⅵ). We also demonstrated that selenite can reduce the absorption of Cr(Ⅵ) by cells but does not affect the process of Cr(Ⅵ) adsorption and efflux. This information on the molecular mechanism by which selenite alleviates Cr(Ⅵ) toxicity can be used to increase the bioremediation capacity of algae and reduce the human health risks associated with Cr(Ⅵ) toxicity.
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http://dx.doi.org/10.1016/j.envpol.2020.116407DOI Listing
March 2021

Myopic retinal changes screening: comparison of sensitivity and specificity among 15 combinations of ultrawide field scanning laser ophthalmoscopy images.

Ophthalmic Res 2021 Jan 5. Epub 2021 Jan 5.

Aims: To investigate the evaluation indices (diagnostic test accuracy and agreement) of 15 combinations of ultrawide field scanning laser ophthalmoscopy (UWF SLO) images in myopic retinal changes (MRC) screening to determine the combination of imaging that yields the highest evaluation indices in screening MRC.

Methods: This is a retrospective study of UWF SLO images obtained from myopes and were analyzed by two retinal specialists independently. 5-field UWF SLO images that included the posterior (B), superior (S), inferior (I), nasal (N) and temporal (T) regions were obtained for analysis and its results used as a reference standard. The evaluation indices of different combinations comprising of one to four fields of the retina were compared to determine the abilities of each combinations screen for MRC.

Results: UWF SLO images obtained from 823 myopic patients (1646 eyes) were included for the study. Sensitivities ranged from 50.0% to 98.9% (95% confidence interval (CI), 43.8-99.7%); the combinations of B+S+I (97.3%; 95% CI, 94.4-98.8%), B+T+S+I (98.5%; 95% CI, 95.9-99.5%), and B+S+N+I (98.9%; 95% CI, 96.4-99.7%) ranked highest. Furthermore, the combinations of B+S+I, B+T+S+I and B+S+N+I also revealed the highest accuracy (97.7%; 95% CI, 95.1-100.0%, 98.6%; 95% CI, 96.7-100.0%, 98.8%; 95% CI, 96.9-100.0%) and agreement (Kappa = 0.968, 0.980 and 0.980). For the various combinations, specificities were all higher than 99.5% (95% CI, 99.3-100.0%).

Conclusion: In our study, screening combinations of B+S+I, B+T+S+I and B+S+N+I stand out with high-performing optimal evaluation indices. However, when time is limited, B+S+I may be more applicable in primary screening of MRC.
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http://dx.doi.org/10.1159/000514176DOI Listing
January 2021

Circulating tumor cell characterization of lung cancer brain metastases in the cerebrospinal fluid through single-cell transcriptome analysis.

Clin Transl Med 2020 Dec;10(8):e246

Department of Clinical Laboratory, Huashan Hospital, Fudan University, Shanghai, China.

Background: Brain metastases explain the majority of mortality associated with lung cancer, which is the leading cause of cancer death. Cytology analysis of the cerebrospinal fluid (CSF) remains the diagnostic gold standard, however, the circulating tumor cells (CTCs) in CSF (CSF-CTCs) are not well defined at the molecular and transcriptome levels.

Methods: We established an effective CSF-CTCs collection procedure and isolated individual CSF cells from five lung adenocarcinoma leptomeningeal metastases (LUAD-LM) patients and three controls. Three thousand seven hundred ninety-two single-cell transcriptomes were sequenced, and single-cell RNA sequencing (scRNA-seq) gene expression analysis was used to perform a comprehensive characterization of CSF cells.

Results: Through clustering and expression analysis, we defined CSF-CTCs at the transcriptome level based on epithelial markers, proliferation markers, and genes with lung origin. The metastatic-CTC signature genes are enriched for metabolic pathway and cell adhesion molecule categories, which are crucial for the survival and metastases of tumor cells. We discovered substantial heterogeneity in patient CSF-CTCs. We quantified the degree of heterogeneity and found significantly greater among-patient heterogeneity compared to among-cell heterogeneity within a patient. This observation could be explained by spatial heterogeneity of metastatic sites, cell-cycle gene, and cancer-testis antigen (CTA) expression profiles as well as the proportion of CTCs displaying mesenchymal and cancer stem cell properties. In addition, our CSF-CTCs transcriptome profiling allowed us to determine the biomarkers during the progression of an LM patient with cancer of unknown primary site (CUP).

Conclusions: Our results will provide candidate genes for an RNA-based digital detection of CSF-CTCs from LUAD-LM and CUP-LM cases, and shed light on the therapy and mechanism of LUAD-LM.
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http://dx.doi.org/10.1002/ctm2.246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737787PMC
December 2020

From natural dye to herbal medicine: a systematic review of chemical constituents, pharmacological effects and clinical applications of indigo naturalis.

Chin Med 2020 Dec 14;15(1):127. Epub 2020 Dec 14.

Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shierqiao Road, Chengdu, 610075, People's Republic of China.

Background: Indigo naturalis is a blue dye in ancient, as well as an extensive used traditional Chinese medicine. It has a wide spectrum of pharmacological properties and can be used to treat numerous ailments such as leukemia, psoriasis, and ulcerative colitis. This article aims to expand our understanding of indigo naturalis in terms of its chemical constituents, pharmacological action and clinical applications.

Methods: We searched PubMed, web of science, CNKI, Google academic, Elsevier and other databases with the key words of "Indigo naturalis", and reviewed and sorted out the modern research of indigo naturalis based on our research results.

Results: We outlined the traditional manufacturing process, chemical composition and quality control of indigo naturalis, systematically reviewed traditional applictions, pharmacological activities and mechanism of indigo naturalis, and summarized its clinical trials about treatment of psoriasis, leukemia and ulcerative colitis.

Conclusions: Indigo naturalis has a variety of pharmacological activities, such as anti-inflammatory, antioxidant, antibacterial, antiviral, immunomodulatory and so on. It has very good clinical effect on psoriasis, leukemia and ulcerative colitis. However, it should be noted that long-term use of indigo naturalis may produce some reversible adverse reactions. In summarize, indigo naturalis is an extremely important drug with great value and potential.
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http://dx.doi.org/10.1186/s13020-020-00406-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734464PMC
December 2020

Exogenous bone marrow derived-putative endothelial progenitor cells attenuate ischemia reperfusion-induced vascular injury and renal fibrosis in mice dependent on pericytes.

Theranostics 2020 25;10(26):12144-12157. Epub 2020 Oct 25.

Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei, 430030, China.

Capillaries are composed of endothelial cells and the surrounding mural cells, pericytes. Microvascular repair after injury involves not only the proliferation of endothelial cells but also pericyte-based vessel stabilization. Exogenous bone marrow derived-putative endothelial progenitor cells (b-pEPCs) have the potential for vascular repair; however, their effect on vascular structure stabilization and pericyte-related pathobiological outcomes in the injured kidney has not been fully examined. We applied ischemia-reperfusion (IR) to induce renal vascular injury and renal fibrosis in mice. Platelet-derived growth factor receptor β (PDGFR-β)-DTR-positive mice were generated to deplete pericytes, and exogenous b-pEPCs and the PDGFR-β ligand, PDGF chain B (PDGF-BB), were employed to explore the relationship among b-pEPCs, pericytes, vascular repair, and early renal fibrosis. Administration of b-pEPCs reduced IR-induced pericyte-endothelial detachment, pericyte proliferation, and myofibroblast transition via a paracrine mode, which preserved not only vascular stabilization but also ameliorated IR-initiated renal fibrosis. PDGF-BB upregulated the expression of PDGFR-β, exacerbated vascular abnormality, and pericyte-myofibroblast transition, which were ameliorated by b-pEPCs administration. The exogenous b-pEPCs and their culture medium (CM) induced vascular injury protection, and renal fibrosis was blocked by selective deletion of pericytes. Exogenous b-pEPCs directly protect against IR-induced vascular injury and prevent renal fibrosis by inhibiting the activation of PDGFR-β-positive pericytes.
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http://dx.doi.org/10.7150/thno.48562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667688PMC
June 2021

Target-Induced Core-Satellite Nanostructure Assembly Strategy for Dual-Signal-On Fluorescence Imaging and Raman Quantification of Intracellular MicroRNA Guided Photothermal Therapy.

Small 2020 12 12;16(49):e2005511. Epub 2020 Nov 12.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, P. R. China.

Integrating biological detection and treatment into one system is a smart therapeutic maneuver for efficient cancer treatment. Herein, a target-activated core-satellite nanostructure (CS nanostructure) assembly built on gold nanobipyramids motor (AuNBPs motor)/gold nanoparticle probe (AuNP probe) exhibiting simultaneous dual signal-on imaging, quantification of intracellular microRNA-21 (miR-21), and photothermal therapy (PTT) for cancer is designed. Of note, when the AuNBPs motor/AuNP probe enters into cells, miR-21 triggers the reaction between AuNBPs motor and AuNP probe, resulting in the formation of CS nanostructure assembly. The process of assembling the CS nanostructure is accompanied with strong fluorescent signals from TAMRA and surface-enhanced Raman scattering (SERS) signals from adenine. The fluorescent signal is leveraged to image the intracellular miR-21 level, whereas the SERS signal is utilized for absolute quantification of intracellular miR-21, and the CS nanostructure acts as the photosensitizer for PTT. This strategy can successfully image and quantify miR-21 in a single cell, and also distinguish normal cells from tumor cells. Moreover, under the guidance of fluorescence signal, the assembly kills tumor cells and inhibits tumor growth via PTT. In vitro and in vivo results prove that the proposed strategy possesses enormous potential for application in the diagnosis and treatment of cancer.
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http://dx.doi.org/10.1002/smll.202005511DOI Listing
December 2020

Serological and molecular epidemiology of Japanese Encephalitis in Zhejiang, China, 2015-2018.

PLoS Negl Trop Dis 2020 08 27;14(8):e0008574. Epub 2020 Aug 27.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, People's Republic of China.

Background: Shifts have occurred in the epidemiological characteristics of Japanese encephalitis (JE), extending from the molecular level to the population level. The aim of this study was to investigate the seroprevalence of JE neutralizing antibodies in healthy populations from different age groups in Zhejiang Province, and to conduct mosquito monitoring to evaluate the infection rate of Japanese encephalitis virus (JEV) among vectors, as well as the molecular characteristics of the E gene of isolated JEV strains.

Methodology/principal Findings: A total of 1190 sera samples were screened by a microseroneutralization test, including 429 infants (28d-11m) and 761 participants (2y-82y). For those under 1 year old, the geometric mean titers (GMTs) of the JE neutralizing antibody was 9.49 at birth and significantly declined as the age of month increased (r = -0.225, P<0.001). For those above 1-year old, seropositive proportions were higher in subjects aged 1-3 years old as well as ≥25 years old (65%-75%), and relatively lower in subjects aged between 4-25 years old (22%-55%). Four or more years after the 2nd dose of JEV-L (first dose administered at 8 months and the second at 2 years of age), the seropositive proportion decreased to 32.5%, and GMTs decreased to 8.08. A total of 87,201 mosquitoes were collected from livestock sheds in 6 surveillance sites during 2015-2018, from which 139 E gene sequences were successfully amplified. The annual infection rate according to bias-corrected maximum likelihood estimation of JEV in Culex tritaeniorhynchus was 1.56, 2.36, 5.65 and 1.77 per 1000, respectively. JEV strains isolated during 2015-2018 all belonged to Genotype I. The E gene of amplified 139 samples differed from the JEV-L vaccine strain at fourteen amino acid residues, including the eight key residues related to virulence and virus attenuation. No divergence was observed at the sites related to antigenicity.

Conclusions/significance: Zhejiang Province was at a high risk of JE exposure due to relatively lower neutralizing antibody levels among the younger-aged population and higher infection rates of JEV in mosquitoes. Continuous, timely and full coverage of JE vaccination are essential, as well as the separation of human living areas and livestock shed areas. In addition, annual mosquito surveillance and periodic antibody level monitoring are important for providing evidence for improvement in JE vaccines and immunization schedules.
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http://dx.doi.org/10.1371/journal.pntd.0008574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491720PMC
August 2020

CSF-1R inhibition attenuates ischemia-induced renal injury and fibrosis by reducing Ly6C M2-like macrophage infiltration.

Int Immunopharmacol 2020 Nov 6;88:106854. Epub 2020 Aug 6.

Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Ave, Wuhan, Hubei, 430030, China. Electronic address:

Acute kidney injury (AKI) to chronic kidney disease (CKD) progression has become a life-threatening disease. However, an effective therapeuticstrategyis still needed. The pathophysiology of AKI-to-CKD progression involves chronic inflammation and renal fibrosis driven by macrophage activation, which is physiologically dependent on colony-stimulating factor-1 receptor (CSF-1R) signaling. In this study, we modulated macrophage infiltration through oral administration of the CSF-1R inhibitor GW2580 in an ischemia-reperfusion (I/R)-induced AKI model to evaluate its therapeutic effects on preventing the progression of AKI to CKD. We found that GW2580 induced a significant reduction in the number of macrophages in I/R-injured kidneys and attenuated I/R-induced renal injury and subsequent interstitial fibrosis. By flow cytometry, we observed that the reduced macrophages were primarily Ly6C inflammatory macrophages in the GW2580-treated kidneys, while there was no significant difference in the number and percentage of Ly6CCX3CR1 macrophages. We further found that these reduced macrophages also demonstrated some characteristics of M2-like macrophages, which have been generally regarded as profibrotic subtypes in chronic inflammation. These results indicate the existence of phenotypic and functional crossover between Ly6C and M2-like macrophages in I/R kidneys, which induces AKI worsening to CKD. In conclusion, therapeutic GW2580 treatment alleviates acute renal injury and subsequent fibrosis by reducing Ly6C M2-like macrophage infiltration in ischemia-induced AKI.
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http://dx.doi.org/10.1016/j.intimp.2020.106854DOI Listing
November 2020

A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407.

J Thorac Oncol 2020 10 26;15(10):1657-1669. Epub 2020 Jun 26.

Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York.

Introduction: In the randomized KEYNOTE-407 study (ClinicalTrials.gov, NCT02775435), pembrolizumab plus carboplatin and paclitaxel/nab-paclitaxel (chemotherapy) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus chemotherapy in patients with previously untreated metastatic squamous NSCLC. We report updated efficacy outcomes from the protocol-specified final analysis and, for the first time, progression on next line of treatment.

Methods: Eligible patients were randomized to chemotherapy plus either pembrolizumab (n = 278) or placebo (n = 281). After positive results from the second interim analysis, patients still receiving placebo could cross over to pembrolizumab monotherapy at the time of confirmed progressive disease. The primary end points were OS and PFS. PFS-2 (time from randomization to progression on next-line treatment/death, whichever occurred first) was an exploratory end point.

Results: After median (range) follow-up of 14.3 (0.1-31.3) months, pembrolizumab plus chemotherapy continued to exhibit a clinically meaningful improvement over placebo plus chemotherapy in OS (median, 17.1 mo [95% confidence interval (CI): 14.4‒19.9] versus 11.6 mo [95% CI: 10.1‒13.7]; hazard ratio [HR], 0.71 [95% CI: 0.58‒0.88]) and PFS (median, 8.0 mo [95% CI: 6.3‒8.4] versus 5.1 mo [95% CI: 4.3‒6.0]; HR, 0.57 [95% CI: 0.47‒0.69]). PFS-2 was longer for patients randomized to first-line pembrolizumab plus chemotherapy (HR, 0.59 [95% CI: 0.49‒0.72]). Grade 3 to 5 adverse events occurred in 74.1% and 69.6% of patients receiving pembrolizumab plus chemotherapy and placebo plus chemotherapy, respectively.

Conclusions: Pembrolizumab plus chemotherapy continued to exhibit substantially improved OS and PFS in patients with metastatic squamous NSCLC. The PFS-2 outcomes support pembrolizumab plus chemotherapy as a standard first-line treatment in patients with metastatic squamous NSCLC.
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http://dx.doi.org/10.1016/j.jtho.2020.06.015DOI Listing
October 2020

Immunogenicity of three sequential schedules with Sabin inactivated poliovirus vaccine and bivalent oral poliovirus vaccine in Zhejiang, China: an open-label, randomised, controlled trial.

Lancet Infect Dis 2020 09 19;20(9):1071-1079. Epub 2020 May 19.

National Immunisation Programme, Chinese Center for Disease Control and Prevention, Beijing, China. Electronic address:

Background: The globally synchronised introduction of inactivated poliovirus vaccine (IPV) and replacement of trivalent oral poliovirus vaccine (OPV) with bivalent OPV (bOPV) were successfully implemented in China's routine immunisation programme in May, 2016. In response to the global shortage of Salk-strain IPV, Sabin-strain IPV production was encouraged to develop and use in low-income and middle-income countries. We assessed the immunogenicity of the current routine poliovirus vaccination schedule in China and compared it with alternative schedules that use Sabin-strain IPV (sIPV) and bOPV.

Methods: This open-label, randomised, controlled trial recruited healthy infants aged 60-75 days from two centres in Zhejiang, China. Eligible infants were full-term, due for their first polio vaccination, weighed more than 2·5 kg at birth, were healthy on physical examination with no obvious medical conditions, and had no contraindications to vaccination. Infants were randomly assigned (1:1:1) using permuted block randomisation (block size of 12) to one of three polio vaccination schedules, with the first, second, and third doses given at ages 2 months, 3 months, and 4 months, respectively: sIPV-bOPV-bOPV (1sIPV+2bOPV group; current regimen), sIPV-sIPV-bOPV (2sIPV+1bOPV group), or sIPV-sIPV-sIPV (3sIPV group). The primary endpoint was the proportion of infants with seroconversion to each of the three poliovirus serotypes 1 month after the third dose. Serious and medically important adverse events were monitored for up to 30 days after each vaccination. We assessed immunity in the per-protocol population (all children who completed all three vaccinations and had pre-vaccination and post-vaccination laboratory data) and safety in all children who received at least one dose of study vaccine. This trial is registered with Clinicaltrials.gov, NCT03147560.

Results: Between May 1, 2016, and Dec 1, 2017, we enrolled and randomly assigned 528 eligible infants to one of the three treatment groups (176 in each group); 473 infants (158 in the 1sIPV+2bOPV group, 152 in the 2sIPV+1bOPV group, and 163 in the 3sIPV group) were included in the per-protocol population. 100% seroconversion against poliovirus types 1 and 3 was observed in all three groups. Infants who received an immunisation schedule containing bOPV had significantly higher antibody titres against poliovirus types 1 and 3 than did the sIPV-only group (2048 in all three treatment groups; p<0·0001). Seroconversion against type 2 poliovirus was observed in 98 (62%) infants in the 1sIPV+2bOPV group, 145 (95%) infants in the 2sIPV+1bOPV group, and 161 (99%) infants in the 3sIPV group. No serious adverse events occurred during the study; 14 minor, transient adverse events were observed, with no significant differences across study groups.

Interpretation: All three study schedules were well tolerated and highly immunogenic against poliovirus types 1 and 3. Schedules containing two or three sIPV doses had higher seroconversion rates against poliovirus type 2 than did the schedule with a single dose of sIPV. Our findings support inclusion of two sIPV doses in the routine poliovirus vaccination schedule in China to provide better protection against poliovirus type 2 than provided by the current regimen.

Funding: Chinese Center for Disease Control and Prevention and China National Biotec Group Company.
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http://dx.doi.org/10.1016/S1473-3099(19)30738-8DOI Listing
September 2020

Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.

Mol Psychiatry 2021 Jun 5;26(6):2111-2125. Epub 2020 May 5.

Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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http://dx.doi.org/10.1038/s41380-020-0719-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641978PMC
June 2021

Transcriptomic and Physiological Responses to Oxidative Stress in a Glutathione Peroxidase Mutant.

Genes (Basel) 2020 04 24;11(4). Epub 2020 Apr 24.

Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, Hubei, China.

Aerobic photosynthetic organisms such as algae produce reactive oxygen species (ROS) as by-products of metabolism. ROS damage biomolecules such as proteins and lipids in cells, but also act as signaling molecules. The mechanisms that maintain the metabolic balance in aerobic photosynthetic organisms and how the cells specifically respond to different levels of ROS are unclear. Glutathione peroxidase (GPX) enzymes detoxify hydrogen peroxide or organic hydroperoxides, and thus are important components of the antioxidant system. In this study, we employed a glutathione peroxidase knockout () mutant to identify the genetic response to singlet oxygen (O) generated by the photosensitizer rose bengal (RB). To this end, we compared the transcriptomes of the parental strain CC4348 and the mutant sampled before, and 1 h after, the addition of RB. Functional annotation of differentially expressed genes showed that genes encoding proteins related to ROS detoxification, stress-response-related molecular chaperones, and ubiquitin-proteasome pathway genes were upregulated in CC4338. When GPX5 was mutated, higher oxidative stress specifically induced the TCA cycle and enhanced mitochondrial electron transport. Transcription of selenoproteins and flagellar-associated proteins was depressed in CC4348 and the mutant. In addition, we found iron homeostasis played an important role in maintaining redox homeostasis, and we uncovered the relationship between O stress and iron assimilation, as well as selenoproteins. Based on the observed expression profiles in response to different levels of oxidative stress, we propose a model for dose-dependent responses to different ROS levels in .
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http://dx.doi.org/10.3390/genes11040463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230881PMC
April 2020

Emotion Recognition Positively Correlates with Steady-state Visual Evoked Potential Amplitude and Alpha Entrainment.

Neuroscience 2020 05;434:191-199

School of Computer and Electronics Information, Guangxi University, China. Electronic address:

Emotion recognition reflects the psychological and physiological status of humans. Numerous studies have investigated the neural mechanisms of emotion recognition based on electroencephalography (EEG) features. In the previous study, emotion target was presented under a static or irregular background, which made the response highly time-locked. As an oscillatory component of EEG, steady-state visual evoked potential (SSVEP) has distinctive frequency and phase properties, which provides more stable information than the other components of EEG. This study combined the emotion target with SSVEP to explore neural mechanisms of visual neurons under flickering background. Three basic emotions (delightfulness, sadness and, anger) were presented in 216 frequency-intensity conditions. Participants were asked to recognize the emotions and make judgments. The degree of alpha entrainment (valued as normalized Shannon entropy), SSVEP amplitude and recognition accuracy were calculated as response features. The results indicated that: SSVEP amplitude and recognition accuracy positively correlated with each other in frequency domain (7-15 Hz); alpha entrainment, and recognition accuracy had similar linear variation in intensity domain (level 1-4), and had a threshold around intensity 3; the three basic emotions had no clear relationship with each other in recognition. This study provided a new sight for neuroscience and would be an important reference to clinical psychology.
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http://dx.doi.org/10.1016/j.neuroscience.2020.01.045DOI Listing
May 2020

Fis Contributes to Resistance of Pseudomonas aeruginosa to Ciprofloxacin by Regulating Pyocin Synthesis.

J Bacteriol 2020 05 11;202(11). Epub 2020 May 11.

State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China

Factor for inversion stimulation (Fis) is a versatile DNA binding protein that plays an important role in coordinating bacterial global gene expression in response to growth phases and environmental stresses. Previously, we demonstrated that Fis regulates the type III secretion system (T3SS) in In this study, we explored the role of Fis in the antibiotic resistance of and found that mutation of the gene increases the bacterial susceptibility to ciprofloxacin. We further demonstrated that genes related to pyocin biosynthesis are upregulated in the mutant. The pyocins are produced in response to genotoxic agents, including ciprofloxacin, and the release of pyocins results in lysis of the producer cell. Thus, pyocin biosynthesis genes sensitize to ciprofloxacin. We found that PrtN, the positive regulator of the pyocin biosynthesis genes, is upregulated in the mutant. Genetic experiments and electrophoretic mobility shift assays revealed that Fis directly binds to the promoter region of and represses its expression. Therefore, our results revealed novel Fis-mediated regulation on pyocin production and bacterial resistance to ciprofloxacin in is an important opportunistic pathogenic bacterium that causes various acute and chronic infections in human, especially in patients with compromised immunity, cystic fibrosis (CF), and/or severe burn wounds. About 60% of cystic fibrosis patients have a chronic respiratory infection caused by The bacterium is intrinsically highly resistant to antibiotics, which greatly increases difficulties in clinical treatment. Therefore, it is critical to understand the mechanisms and the regulatory pathways that are involved in antibiotic resistance. In this study, we elucidated a novel regulatory pathway that controls the bacterial resistance to fluoroquinolone antibiotics, which enhances our understanding of how responds to ciprofloxacin.
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http://dx.doi.org/10.1128/JB.00064-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221260PMC
May 2020

Stepwise progressive parametric multiple testing procedure with correlated normal test statistics.

J Biopharm Stat 2020 05 19;30(3):550-563. Epub 2020 Mar 19.

Department of Biostatistics, Boston University, Boston, Massachusetts, USA.

Multiple testing problems are often seen in clinical trials. An appropriate testing procedure should be specified to deal with the potential inflation of type I error rate due to multiplicity. In this article, we propose a stepwise progressive parametric multiple (SPPM) testing procedure, which constructs the testing using the products of all the combinations of local [Formula: see text]-values and the critical values are determined by numerical integrations progressively using the closure principle. We have compared the performance of SPPM to several other procedures, and demonstrate the advantage of SPPM procedure, in terms of power, for the certain situations of multiple testing.
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http://dx.doi.org/10.1080/10543406.2020.1726369DOI Listing
May 2020

MiR-1246 promotes anti-apoptotic effect of mini-αA in oxidative stress-induced apoptosis in retinal pigment epithelial cells.

Clin Exp Ophthalmol 2020 07 31;48(5):682-688. Epub 2020 Mar 31.

Guangzhou Aier Eye Hospital, Aier Eye Hospital Group, Guangzhou, China.

Background: Geographic atrophy (GA) is a late-stage symptom of an age-related macular degeneration (AMD), characterized by the loss of retinal pigment epithelial (RPE) cells and photoreceptor functions. Despite being a major cause of blindness in individuals of 65 years of age and older, some forms of AMD, including GA, still lack targeted treatment. Our previous study demonstrated that mini-αA peptide, which contains the functional site of αA-crystallin, protected RPE cells from NaIO -induced apoptosis.

Methods: To further investigate the underlying mechanism, we applied next-generation sequencing analysis to identify miR-1246 as a putative mediator of mini-αA protective function. To investigate the role of miR-1246 in RPE cell apoptosis, a stable miR-1246-low-expression cell line was established by using miR-1246 inhibitor. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to investigate the proliferation of RPE cells, mRNA and miR-1246 expression were detected by the quantitative reverse transcriptase-polymerase chain reaction.

Results: We have further identified caspase-3 and caspase-14 as molecular targets of miR-1246 involved in regulation of apoptosis in NaIO -incubated cells. Interestingly, disruption of miR-1246 expression enhanced anti-apoptotic effect of mini-αA on RPE cells during oxidative stress.

Conclusions: Our results provide a mechanistic basis for evaluation of miR-1246 as a new candidate target for the clinical treatment of AMD.
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http://dx.doi.org/10.1111/ceo.13751DOI Listing
July 2020
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