Publications by authors named "Yi-Ping Li"

260 Publications

[Quality value transmitting of volatile components in personalized preparations:a case study of Menthae Haplocalycis Herba].

Zhongguo Zhong Yao Za Zhi 2021 Aug;46(15):3780-3788

Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine, Ministry of Education,Shanghai University of Traditional Chinese Medicine Shanghai 201203, China.

Considering the characteristic chromatograms and quality value transmitting of three volatile components, this study investigated the changes in volatile components of Menthae Haplocalycis Herba in each heating process of personalized preparations and identified the critical control points for the application of volatile components from traditional Chinese medicine in such preparations. The characteristic chromatograms of volatile components in Menthae Haplocalycis Herba were established by gas chromatography, followed by the quantitative determination of three volatile components menthone, menthol, and piperitone and the comparison of retention rates of volatile components during the crushing, extraction, concentration and drying of preparation products and their change rules in characteristic peaks. The results showed that the volatile components of Menthae Haplocalycis Herba were reduced in each process. The loss rate was low in the crushing process when the volatile component peaks were present, but high in the extraction and concentration processes, manifested as the absence of partial component peaks and the presence of new component peaks. The changes in volatile components of Chuanxiong Chatiao Granule in the drying process were compared with those in Chuanxiong Chatiao Pill, both of which were prepared from the raw Menthae Haplocalycis Herba powder, and the findings demonstrated that Chuanxiong Chatiao Pill was superior to Chuanxiong Chatiao Granule. This study confirmed that the retention rates of volatile components in Menthae Haplocalycis Herba were mostly affected by the extraction and concentration processes, and the packing of preparations helped to reduce the loss of volatile components in Menthae Haplocalycis Herba powder, which has provided reference for the application of Chinese medicinal materials containing volatile components in the personalized preparations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19540/j.cnki.cjcmm.20210525.303DOI Listing
August 2021

[Characteristics and development assumptions of personalized traditional Chinese medicine granules].

Zhongguo Zhong Yao Za Zhi 2021 Aug;46(15):3746-3752

Shanghai Traditional Chinese Medicine Health Service Collaborative Innovation Center, Shanghai University of Traditional Chinese Medicine Shanghai 201203, China.

Personalized traditional Chinese medicine(TCM) granules are positioned as a solid dosage form of TCM decoctions, boasting strong applicability and wide application range. The market prospect of personalized TCM granules is promising in that their preparation by mixed decoction makes up for the shortcoming of formula granules like the Chinese patent medicine granules and classical TCM prescription granules whose components cannot be changed flexibly. However, such factors as insufficient basic research, equipment mismatch, and low process commonality have limited their clinical application. After analyzing the characteristics of perso-nalized TCM granules, their production status, and the bottlenecks restricting their development, this paper pointed out the meaning and key points of developing a generalized preparation process for personalized TCM granules and affirmed the vital roles of the preparation and process prediction system and the on-line detection technology in improving the productivity of granulation. Finally, some assumptions on technology development for solving the specific problems of personalized TCM granules were shared to provide some ideas for the application and development of personalized TCM granules in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19540/j.cnki.cjcmm.20210422.302DOI Listing
August 2021

Development of cell culture infectious clones for hepatitis C virus genotype 1b and transcription analysis of 1b-infected hepatoma cells.

Antiviral Res 2021 09 9;193:105136. Epub 2021 Jul 9.

Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, 510080, China; Department of Infectious Disease, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China. Electronic address:

Globally, hepatitis C virus (HCV) genotype 1b is the most prevalent, and its infection has been found to associate with a higher risk of hepatocellular carcinoma (HCC) than other genotype viruses. However, an efficient infectious HCV genotype 1b culture system is unavailable, which has largely hampered the study of this important genotype virus. In this study, by using a systematic approach combining the sequences of infectious 1a TNcc clone and adaptive mutations, we succeeded in culture adaption of two full-length 1b clones for the reference strain Con1 and a clinical isolate A6, and designated as Con1cc and A6cc, respectively. Con1cc and A6cc replicated efficiently in hepatoma Huh7.5.1 cells, released HCV infectivity titers of 10 and 10 focus forming units per milliliter, respectively, and maintained the engineered mutations after passages. Both viruses responded to sofosbuvir and velpatasvir in a dose-dependent manner. With culture infectious 1b clones, we characterized the transcriptomes of 1b Con1cc-infected cells, in comparison with 2a-infected and uninfected cells. In conclusion, we have developed two infectious clones for genotype 1b and shown a novel strategy for culture adaptation of HCV isolates by using a genetically close backbone sequence. Furthermore, this study provides transcriptional landscape of HCV 1b-infected hepatoma cells facilitating the study of genotype 1b infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.antiviral.2021.105136DOI Listing
September 2021

Dengue fever and dengue virus in the People's Republic of China.

Rev Med Virol 2021 May 19:e2245. Epub 2021 May 19.

Institute of Human Virology, Zhongshan School of Medicine, Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yet-sen University, Guangzhou, China.

Infection with dengue virus (DENV) leads to symptoms variable from dengue fever to severe dengue, which has posed a huge socioeconomic and disease burden to the world population, particularly in tropical and subtropical regions. To date, four serotypes of DENV (DENV-1 to DENV-4) have been identified to sustain the transmission cycle in humans. In the past decades, dengue incidences have become more frequent, and four serotypes and various genotypes have been identified in PR China. Several large-scale dengue outbreaks and frequent local endemics occurred in the southern and coastal provinces, and the imported dengue cases accounted primarily for the initiation of the epidemics. No antiviral drug exists for dengue, and no vaccine has been approved to use in PR China, however strategies including public awareness, national reporting system of infectious diseases and public health emergencies, vector mosquito control, personal protection, and improved environmental sanitation have greatly reduced dengue prevalence. Some new technologies in vector mosquito control are emerging and being applied for dengue control. China's territory spans tropical, subtropical, and temperate climates, hence understanding the dengue status in China will be of beneficial for the global prevention and control of dengue. Here, we review the dengue status in PR China for the past decades and the strategies emerging for dengue control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/rmv.2245DOI Listing
May 2021

Plant-derived lignans as potential antiviral agents: a systematic review.

Phytochem Rev 2021 May 31:1-51. Epub 2021 May 31.

School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, P. R. China.

Medicinal plants are one of the most important sources of antiviral agents and lead compounds. Lignans are a large class of natural compounds comprising two phenyl propane units. Many of them have demonstrated biological activities, and some of them have even been developed as therapeutic drugs. In this review, 630 lignans, including those obtained from medicinal plants and their chemical derivatives, were systematically reviewed for their antiviral activity and mechanism of action. The compounds discussed herein were published in articles between 1998 and 2020. The articles were identified using both database searches (e.g., Web of Science, Pub Med and Scifinder) using key words such as: antiviral activity, antiviral effects, lignans, HBV, HCV, HIV, HPV, HSV, JEV, SARS-CoV, RSV and influenza A virus, and directed searches of scholarly publisher's websites including ACS, Elsevier, Springer, Thieme, and Wiley. The compounds were classified on their structural characteristics as 1) arylnaphthalene lignans, 2) aryltetralin lignans, 3) dibenzylbutyrolactone lignans, 4) dibenzylbutane lignans, 5) tetrahydrofuranoid and tetrahydrofurofuranoid lignans, 6) benzofuran lignans, 7) neolignans, 8) dibenzocyclooctadiene lignans and homolignans, and 9) norlignans and other lignoids. Details on isolation and antiviral activities of the most active compounds within each class of lignan are discussed in detail, as are studies of synthetic lignans that provide structure-activity relationship information.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11101-021-09758-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165688PMC
May 2021

[Sensitivity Analysis of Boundary Load Reduction in a Large Shallow Lake Water Quality Model].

Huan Jing Ke Xue 2021 Jun;42(6):2778-2786

State Key Laboratory of Hydrology-Water Resources and Hydraulic Engineering, Hohai University, Nanjing 210098, China.

To explore the spatial and temporal response of water quality to external load reduction in Lake Taihu, Jiangsu Province, China, and clarify the exogenous load reduction under different water inflow and pollution conditions, a water quality model was constructed and the inflow boundaries were divided into seven groups based on the EFDC model. Taking COD and ammonia nitrogen as output targets, the sensitivities of Taihu Lake water quality boundaries were analyzed using a local sensitivity analysis. The results showed that COD and ammonia nitrogen concentrations of each lake area were more sensitive to the boundary load of the lake area than the rest of the lake area, and the sensitivity index was the highest in the Northwest Lake area. Furthermore, the improvement rates of mean COD concentrations in the whole lake decreased by 28.40%-34.71% in the dry season relative to the wet season, and the ranked sensitivity order of the boundaries was as follows:Northwest Lake boundary > Zhushan Lake boundary > Gonghu Lake boundary > Meiliang Bay boundary > Southwest Lake area boundary > Eastern Lake area boundary > East Lake Taihu boundary. The average improvement rates of ammonia nitrogen concentrations in the whole lake were 41.59%-42.34% higher in the dry season relative to the wet season, and the ranked boundary sensitivity order was as follows:Northwest Lake boundary > Meiliang Bay boundary > Zhushan Lake boundary > Gonghu Lake boundary > Southwest Lake boundary > East Lake Taihu boundary > Eastern Lake area boundary. This difference was affected by algal growth and metabolism, and artificial water diversion and drainage. Therefore, it is necessary to consider the reduction period and inflow location according to different water-quality indicators when planning external prevention and control measures in large lakes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13227/j.hjkx.202010049DOI Listing
June 2021

Trio cooperates with Myh9 to regulate neural crest-derived craniofacial development.

Theranostics 2021 25;11(9):4316-4334. Epub 2021 Feb 25.

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.

Trio is a unique member of the Rho-GEF family that has three catalytic domains and is vital for various cellular processes in both physiological and developmental settings. TRIO mutations in humans are involved in craniofacial abnormalities, in which patients present with mandibular retrusion. However, little is known about the molecular mechanisms of Trio in neural crest cell (NCC)-derived craniofacial development, and there is still a lack of direct evidence to assign a functional role to Trio in NCC-induced craniofacial abnormalities. , we used zebrafish and NCC-specific knockout mouse models to investigate the phenotype and dynamics of NCC development in Trio morphants. , iTRAQ, GST pull-down assays, and proximity ligation assay (PLA) were used to explore the role of Trio and its potential downstream mediators in NCC migration and differentiation. In zebrafish and mouse models, disruption of Trio elicited a migration deficit and impaired the differentiation of NCC derivatives, leading to craniofacial growth deficiency and mandibular retrusion. Moreover, Trio positively regulated Myh9 expression and directly interacted with Myh9 to coregulate downstream cellular signaling in NCCs. We further demonstrated that disruption of Trio or Myh9 inhibited Rac1 and Cdc42 activity, specifically affecting the nuclear export of β-catenin and NCC polarization. Remarkably, craniofacial abnormalities caused by deficiency in zebrafish could be partially rescued by the injection of mRNA encoding , ca-Rac1, or ca-Cdc42. Here, we identified that Trio, interacting mostly with Myh9, acts as a key regulator of NCC migration and differentiation during craniofacial development. Our results indicate that morphant zebrafish and mice offer potential model systems to facilitate the study of the pathogenic mechanisms of Trio mutations causing craniofacial abnormalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.51745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977452PMC
July 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Brain-Derived Neurotrophic Factor, a New Predictor of Coronary Artery Calcification.

Clin Appl Thromb Hemost 2021 Jan-Dec;27:1076029621989813

Department of Cardiology, Xishan Hospital, Wuxi, People's Republic of China.

Brain-derived neurotrophic factor (BDNF) plays a functional role in vascular endothelium homeostasis and the alleviation of atherosclerosis. Matrix gla protein (MGP) and Nε-(1-carboxymethyl)-l-lysine (CML) are both confirmed to be VC predictors. This study investigated the association between BDNF, MGP, CML and coronary artery calcification (CAC). Plasma BDNF, MGP, and CML levels were measured in 274 patients who underwent computed tomography to determine the CAC score (Agatston score). It was found that patients with CAC exhibited lower BDNF and MGP and higher CML levels than those without CAC. Plasma BDNF levels in patients with diabetes or hypertension were lower compared with the control groups. In logistic regression analysis, age, hypertension, BDNF, and MGP were independent predictors of CAC. Plasma BDNF and MGP levels were both correlated with the Agatston score even after adjustment for age, total cholesterol level, triglycerides, low-density lipoprotein level, creatinine clearance rate, and the presence of hypertension and diabetes mellitus. In 167 patients with CAC, circulating BDNF level was inversely associated with CML level and positively related to MGP level. In the receiver operating characteristic analysis for CAC, the areas under the curves for BDNF, MGP, and CML were 0.757, 0.777 and 0.653, respectively. In summary, plasma BDNF levels are associated with the Agatston score, and BDNF further predicts the occurrence of CAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1076029621989813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863173PMC
February 2021

Developments in Antibacterial Therapy: Focus on Physical Stimuli Approaches.

Chin J Dent Res 2020 ;23(4):235-255

At present, various antibacterial therapeutic modalities are available in the clinic. However, due to the rampant abuse of antibiotics over the past few decades and the consequent emergence of innumerable drug-resistant strains of bacteria, it is imperative to develop new and effective antibacterial therapeutic strategies. In recent years, the physical stimuli-based approach to antibacterial therapy has aroused much interest as an alternative to antibiotics and has become a major focus of antibacterial research. In this review, the application of different physical stimuli, including electricity, magnetism, light, ultrasound and thermal stimulation, in antibacterial research is critically examined in order to provide new ideas and directions for the further development of antibacterial therapy in clinical dentistry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3290/j.cjdr.b867883DOI Listing
January 2021

Runx1 is a central regulator of osteogenesis for bone homeostasis by orchestrating BMP and WNT signaling pathways.

PLoS Genet 2021 01 21;17(1):e1009233. Epub 2021 Jan 21.

Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States of America.

Runx1 is highly expressed in osteoblasts, however, its function in osteogenesis is unclear. We generated mesenchymal progenitor-specific (Runx1f/fTwist2-Cre) and osteoblast-specific (Runx1f/fCol1α1-Cre) conditional knockout (Runx1 CKO) mice. The mutant CKO mice with normal skeletal development displayed a severe osteoporosis phenotype at postnatal and adult stages. Runx1 CKO resulted in decreased osteogenesis and increased adipogenesis. RNA-sequencing analysis, Western blot, and qPCR validation of Runx1 CKO samples showed that Runx1 regulates BMP signaling pathway and Wnt/β-catenin signaling pathway. ChIP assay revealed direct binding of Runx1 to the promoter regions of Bmp7, Alk3, and Atf4, and promoter mapping demonstrated that Runx1 upregulates their promoter activity through the binding regions. Bmp7 overexpression rescued Alk3, Runx2, and Atf4 expression in Runx1-deficient BMSCs. Runx2 expression was decreased while Runx1 was not changed in Alk3 deficient osteoblasts. Atf4 overexpression in Runx1-deficient BMSCs did not rescue expression of Runx1, Bmp7, and Alk3. Smad1/5/8 activity was vitally reduced in Runx1 CKO cells, indicating Runx1 positively regulates the Bmp7/Alk3/Smad1/5/8/Runx2/ATF4 signaling pathway. Notably, Runx1 overexpression in Runx2-/- osteoblasts rescued expression of Atf4, OCN, and ALP to compensate Runx2 function. Runx1 CKO mice at various osteoblast differentiation stages reduced Wnt signaling and caused high expression of C/ebpα and Pparγ and largely increased adipogenesis. Co-culture of Runx1-deficient and wild-type cells demonstrated that Runx1 regulates osteoblast-adipocyte lineage commitment both cell-autonomously and non-autonomously. Notably, Runx1 overexpression rescued bone loss in OVX-induced osteoporosis. This study focused on the role of Runx1 in different cell populations with regards to BMP and Wnt signaling pathways and in the interacting network underlying bone homeostasis as well as adipogenesis, and has provided new insight and advancement of knowledge in skeletal development. Collectively, Runx1 maintains adult bone homeostasis from bone loss though up-regulating Bmp7/Alk3/Smad1/5/8/Runx2/ATF4 and WNT/β-Catenin signaling pathways, and targeting Runx1 potentially leads to novel therapeutics for osteoporosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1009233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819607PMC
January 2021

Hepatitis C virus genotype and its correlation with viral load in patients from Kathmandu, Nepal.

J Infect Dev Ctries 2020 12 31;14(12):1470-1474. Epub 2020 Dec 31.

Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, China.

Introduction: Knowledge about the distribution of hepatitis C virus (HCV) genotype and its correlation with viral load are important for the decision of treatment and the prediction of disease progression, however such information is very limited in Nepal. Here, we investigated the distribution of HCV genotypes and viral load for HCV-infected patients from Kathmandu, Nepal.

Methodology: Ninety-six patients with HCV infection and not on antiviral therapy were enrolled from three different medical centers in Kathmandu valley, Nepal. Demographics were recorded and blood samples were collected. Plasma was separated and HCV RNA was extracted. Reverse transcriptase PCR (RT-PCR) was performed to measure the viral load, and virus genotype was determined.

Results: Genotype 3a (n = 53, 55.2%) was the most prevalent, followed by 1b (n = 19, 19.8%), 1a (n = 18, 18.8%), 5a (n = 3, 3.1%), and mix types (n = 3, 3.1%). The median viral load for HCV genotype 1a was 770,942 IU/mL (IQR, 215,268-3,720,075), 1b was 700,000 IU/mL (IQR, 431,560-919,000), 3a was 1,060,000 IU/mL (IQR, 641,050-6,063,500), 5a was 673,400 IU/mL, and mixed was 6,428,000 IU/mL. A correlation between genotype and viral load was observed (p = 0.02), of which genotype 3a showed a high viral load.

Conclusions: HCV genotypes 1a, 1b, 3a, and 5a were identified in Kathmandu, Nepal, and mixed genotype patients were observed in the patients studied. HCV genotype showed a correlation with viral load in patient plasma. This finding may contribute to the treatment and prevention of hepatitis C in Kathmandu, Nepal.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3855/jidc.10391DOI Listing
December 2020

Cancer-Induced Muscle Wasting Requires p38β MAPK Activation of p300.

Cancer Res 2021 02 22;81(4):885-897. Epub 2020 Dec 22.

Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, Texas.

Cancer-associated cachexia, characterized by muscle wasting, is a lethal metabolic syndrome without defined etiology or established treatment. We previously found that p300 mediates cancer-induced muscle wasting by activating C/EBPβ, which then upregulates key catabolic genes. However, the signaling mechanism that activates p300 in response to cancer is unknown. Here, we show that upon cancer-induced activation of Toll-like receptor 4 in skeletal muscle, p38β MAPK phosphorylates Ser-12 on p300 to stimulate C/EBPβ acetylation, which is necessary and sufficient to cause muscle wasting. Thus, p38β MAPK is a central mediator and therapeutic target of cancer-induced muscle wasting. In addition, nilotinib, an FDA-approved kinase inhibitor that preferentially binds p38β MAPK, inhibited p300 activation 20-fold more potently than the p38α/β MAPK inhibitor, SB202190, and abrogated cancer cell-induced muscle protein loss in C2C12 myotubes without suppressing p38α MAPK-dependent myogenesis. Systemic administration of nilotinib at a low dose (0.5 mg/kg/day, i.p.) in tumor-bearing mice not only alleviated muscle wasting, but also prolonged survival. Therefore, nilotinib appears to be a promising treatment for human cancer cachexia due to its selective inhibition of p38β MAPK. SIGNIFICANCE: These findings demonstrate that prevention of p38β MAPK-mediated activation of p300 by the FDA-approved kinase inhibitor, nilotinib, ameliorates cancer cachexia, representing a potential therapeutic strategy against this syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-19-3219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456613PMC
February 2021

Enhanced hydrolysis of β-cypermethrin caused by deletions in the glycin-rich region of carboxylesterase 001G from Helicoverpa armigera.

Pest Manag Sci 2021 Apr 12;77(4):2129-2141. Epub 2021 Jan 12.

College of Plant Protection, Northwest A&F University, Yangling, China.

Background: Carboxylesterase (CarE) is a major class of enzyme involved in the detoxification of toxic xenobiotics in various insect species. Previous work has shown that the carboxylesterase gene CarE001G found in Helicoverpa armigera is more active and can metabolize synthesized pyrethroids, such as β-cypermethrin, one of the commonly used commercial insecticides for lepidopteran pest control. In addition, CarE001G is very special as it has a very specific glycine-rich region located adjacent to its C-terminal. But whether mutations in this unique sequence can change the biochemistry and function of CarE001G are unknown.

Results: In this study, four variants of CarE001G with different deletions in the glycine-rich region were obtained and functionally expressed in Escherichia coli. The recombinant proteins were purified and confirmed by Western blot and mass spectrometry analyses. These mutant enzymes showed high catalytic efficiency toward the model substrate α-naphthyl acetate. Inhibition study showed that β-cypermethrin had relatively strong inhibition on CarE activities. In vitro metabolism assay showed that the mutant enzymes significantly enhanced their metabolic activities toward β-cypermethrin with specific activities between 4.0 and 5.6 nmol L min mg protein. Molecular docking analyses consistently demonstrated that deletion mutations in the glycine-rich region may facilitate the anchoring of the β-cypermethrin molecule in the active binding pocket of the mutant enzymes.

Conclusion: The data show that deletion mutations can cause qualitative change in the capacity of CarEs in the detoxification of β-cypermethrin. This indicates that deletion mutations in the glycine-rich region may have the potential to cause synthesized pyrethroid (SP) resistance in H. armigera in the future. © 2020 Society of Chemical Industry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ps.6242DOI Listing
April 2021

BDNF corrects NLRP3 inflammasome-induced pyroptosis and glucose metabolism reprogramming through KLF2/HK1 pathway in vascular endothelial cells.

Cell Signal 2021 02 27;78:109843. Epub 2020 Nov 27.

Department of Cardiology, Xishan Hospital, Wuxi 214000, PR China.

NLRP3 inflammasome-mediated vascular EC pyroptosis is a key event in the pathogenesis of atherosclerosis. Dysregulation of glucose metabolism is involved in EC dysfunction. Although BDNF plays a protective role in vascular endothelium physiological activity, the mechanisms underlying this activity are not yet clear. In this study, we investigated the role of BDNF in NLRP3 inflammasome-mediated EC pyroptosis and its associated reprogramming of glucose metabolism. HUVECs were treated with human rBDNF under ox-LDL stimulation. rBDNF alleviated ox-LDL-induced NLRP3 inflammasome formation and HUVEC pyroptosis, as evaluated by NLRP3, caspase1-p10, interleukin-18, and interleukin-1β protein levels, co-localization of NLRP3 and apoptosis-associated speck-like protein, and lactate dehydrogenase release. These effects were prevented by tropomyosin receptor kinase B inhibition and KLF2 silencing. The hyper-activation of glycolysis induced by ox-LDL-induced was mitigated by rBDNF via KLF2 as assessed by glucose uptake, lactate production, and extracellular acidification rate. In addition, the BDNF/KLF2 pathway preserved the mitochondrial membrane potential, intracellular reactive oxygen species generation, electron transport chain processing, oxygen consumption rate, and adenosine triphosphate production. Furthermore, KLF2 interacted with HK1 and HK1 overexpression evoked NLRP3 inflammasome formation. At the clinical level, plasma BDNF and lactate levels were measured in 274 patients who underwent computed tomography and coronary angiography for CAD diagnosis. Patients with CAD had lower BDNF and increased lactate levels than those without CAD. In 94 patients with CAD, circulating BDNF levels were inversely associated with lactate levels. In the receiver operating characteristic analysis of CAD, the areas under the curves for 1/BDNF, lactate, and 1/BDNF+lactate were 0.707, 0.702, and 0.753 respectively. These results indicate that BDNF and lactate are linked in atherosclerotic patients, and BDNF inhibits ox-LDL induced NLRP3 inflammasome formation and pyroptosis in HUVECs via KLF2/HK1-mediated glucose metabolism modulation and mitochondrial homeostasis preservation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cellsig.2020.109843DOI Listing
February 2021

Spike-specific circulating T follicular helper cell and cross-neutralizing antibody responses in COVID-19-convalescent individuals.

Nat Microbiol 2021 01 16;6(1):51-58. Epub 2020 Nov 16.

The Baoqing Psychiatric Hospital, Shaoyang, China.

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and individuals with COVID-19 have symptoms that can be asymptomatic, mild, moderate or severe. In the early phase of infection, T- and B-cell counts are substantially decreased; however, IgM and IgG are detectable within 14 d after symptom onset. In COVID-19-convalescent individuals, spike-specific neutralizing antibodies are variable. No specific drug or vaccine is available for COVID-19 at the time of writing; however, patients benefit from treatment with serum from COVID-19-convalescent individuals. Nevertheless, antibody responses and cross-reactivity with other coronaviruses in COVID-19-convalescent individuals are largely unknown. Here, we show that the majority of COVID-19-convalescent individuals maintained SARS-CoV-2 spike S1- and S2-specific antibodies with neutralizing activity against the SARS-CoV-2 pseudotyped virus, and that some of the antibodies cross-neutralized SARS-CoV, Middle East respiratory syndrome coronavirus or both pseudotyped viruses. Convalescent individuals who experienced severe COVID-19 showed higher neutralizing antibody titres, a faster increase in lymphocyte counts and a higher frequency of CXCR3 T follicular help (T) cells compared with COVID-19-convalescent individuals who experienced non-severe disease. Circulating T cells were spike specific and functional, and the frequencies of CXCR3 T cells were positively associated with neutralizing antibody titres in COVID-19-convalescent individuals. No individuals had detectable autoantibodies. These findings provide insights into neutralizing antibody responses in COVID-19-convalescent individuals and facilitate the treatment and vaccine development for SARS-CoV-2 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41564-020-00824-5DOI Listing
January 2021

Adaptive mutations promote hepatitis C virus assembly by accelerating core translocation to the endoplasmic reticulum.

J Biol Chem 2021 Jan-Jun;296:100018. Epub 2020 Nov 23.

Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, China; Department of Infectious Disease, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China. Electronic address:

The envelopment of hepatitis C virus (HCV) is believed to occur primarily in the endoplasmic reticulum (ER)-associated membrane, and the translocation of viral Core protein from lipid droplets (LDs) to the ER is essential for the envelopment of viral particles. However, the factors involved are not completely understood. Herein, we identified eight adaptive mutations that enhanced virus spread and infectivity of genotype 1a clone TNcc in hepatoma Huh7 cells through long-term culture adaptation and reverse genetic study. Of eight mutations, I853V in NS2 and C2865F in NS5B were found to be minimal mutation sets that enabled an increase in virus production without apparently affecting RNA replication, thus suggesting its roles in the post-replication stage of the HCV life cycle. Using a protease K protection and confocal microscopy analysis, we demonstrated that C2865F and the combination of I853V/C2865F enhanced virus envelopment by facilitating Core translocation from the LDs to the ER. Buoyant density analysis revealed that I853V/C2865F contributed to the release of virion with a density of ∼1.10 g/ml. Moreover, we demonstrated that NS5B directly interacted with NS2 at the protease domain and that mutations I853V, C2865F, and I853V/C2865F enhanced the interaction. In addition, C2865F also enhanced the interaction between NS5B and Core. In conclusion, this study demonstrated that adaptive mutations in NS2 and NS5B promoted HCV envelopment by accelerating Core translocation from the LDs to the ER and reinforced the interaction between NS2 and NS5B. The findings facilitate our understanding of the assembly of HCV morphogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.RA120.016010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949066PMC
August 2021

Arthroscopic Management of Glenoid and Greater Tuberosity Bipolar Fractures.

Orthop Surg 2020 Oct 20;12(5):1405-1412. Epub 2020 Oct 20.

Department of Upper Limb, Sichuan Provincial Orthpaedics Hospital, Chengdu, China.

Objective: To report the clinical and radiological outcomes of arthroscopically assisted surgery for combination of glenoid and greater tuberosity fractures after traumatic shoulder dislocation.

Methods: From December 2013 to December 2018, patients with concomitant fracture of the greater tuberosity and glenoid who underwent arthroscopically assisted surgery were retrospectively reviewed. Fifteen patients were included. Preoperative computed tomography (CT) scans with 3D reconstruction were performed to evaluate the fracture configuration and associated fractures. All patients underwent arthroscopically assisted surgery under general anesthesia with brachial plexus anesthesia in the lateral position. Under the arthroscopic approach, a comprehensive inspection of the joints was firstly conducted to examine the injury of bones and other tissues. With arthroscopy support, closed reduction and internal fixation of both fractures were performed with suture anchors, with or without additional cannulated screws. At the same time, other injuries were also repaired under the arthroscope. Patients were followed up (6 weeks,8 weeks,3 months,6 months,1 year after surgery) regularly for at least 1 year. At the follow-up, clinical outcomes (Constant score, ASES score, range of motion, and VAS score) and radiological outcomes were analyzed.

Results: Of the 15 patients, there are seven cases of men, eight cases of women; aged 22-66 years, with an average age of 48 years; left shoulder for five cases, 10 cases of the right shoulder. The injury mechanisms were: a simple fall (n = 9), an epileptic seizure (n = 1), a high fall injury (n = 2), and a traffic accident (n = 3). Of the 15 cases of glenoid fracture, 11 cases were type Ia and four cases were type II according to the Ideberg Classification System. The mean size of the glenoid fracture fragment was 28.4% (range, 8.7%-47.2%). According to the Mutch classification system, the fractures of the greater tuberosity were divided into: five cases of avulsion, one case of compression, and nine cases of split. Average time of follow-up was 38.2 months (range, 12-70 months), and one case was lost to follow-up. With fractures healing well, almost all patients had a good joint function. At the final follow-up, mean anterior flexion was 157°; mean external rotation was 40°; mean internal rotation was T level; the mean Constant-Murley score was 94.6 points (range, 70-100 points); the mean ASES score was 94.6 points (range, 79-100 points); and the mean VAS score was 0.4 points (range, 0-2 points). No recurrent instability or re-dislocation occurred. No patient had revision surgery.

Conclusion: Arthroscopic management of glenoid and greater tuberosity bipolar fractures was useful and effective with minimal injury, and it achieved satisfactory clinical and radiological outcomes at a mean follow-up time of more than 3 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/os.12786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670139PMC
October 2020

Silencing of Ac45 Simultaneously Inhibits Osteoclast-Mediated Bone Resorption and Attenuates Dendritic Cell-Mediated Inflammation through Impairing Acidification and Cathepsin K Secretion.

Infect Immun 2020 12 15;89(1). Epub 2020 Dec 15.

Department of Pathology, The School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA

Endodontic disease is characterized by inflammation and destruction of periapical tissues, leading to severe bone resorption and tooth loss. ATP6AP1 (Ac45) has been implicated in human immune diseases, yet the mechanism underlying how Ac45 regulates immune response and reaction in inflammatory diseases remains unknown. We generated endodontic disease mice through bacterial infection as an inflammatory disease model and used adeno-associated virus (AAV)-mediated RNA interference knockdown to study the function of Ac45 in periapical inflammation and bone resorption. We demonstrated that the AAV small hairpin RNA targeting (AAV-sh-) impaired cellular acidification, extracellular acidification, and bone resorption. Our results showed that local delivery of AAV-sh- in periapical tissues in bacterium-induced inflammatory lesions largely reduced bone destruction, inhibited inflammation, and dramatically reduced mononuclear immune cells. T-cell, macrophage, and dendritic cell infiltration in the periapical lesion was dramatically reduced, and the periodontal ligament was protected from inflammation-induced destruction. Furthermore, AAV-sh- significantly reduced osteoclast formation and the expression of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin-10 (IL-10), IL-12, IL-1α, IL-6, and IL-17. Interestingly, AAV-sh- impaired mature cathepsin K secretion more significantly than that by AAV-sh- and AAV-sh- Unbiased genome-wide transcriptome sequencing analysis of dendritic cells stimulated with lipopolysaccharide demonstrated that the ablation of Ctsk dramatically reduced dendritic cell-mediated inflammatory signaling. Taken together, our results indicated that AAV-sh- simultaneously inhibits osteoclast-mediated bone resorption and attenuates dendritic cell-mediated inflammation through impairing acidification and cathepsin K secretion. Thus, Ac45 may be a novel target for therapeutic approaches to attenuate inflammation and bone erosion in endodontic disease and other inflammation-related osteolytic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/IAI.00436-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927931PMC
December 2020

Injury Mechanism of Acute Anterior Shoulder Dislocation Associated with Glenoid and Greater Tuberosity Fractures: A Study Based on Fracture Morphology.

Orthop Surg 2020 Oct 19;12(5):1421-1429. Epub 2020 Aug 19.

Department of Upper Limb, Sichuan Provincial Orthopaedic Hospital, Chengdu, China.

Objective: Based on the morphological characteristics of glenoid and greater tuberosity (GT) fractures and the relationship between them, we explored the injury mechanism of acute anterior shoulder dislocation associated with glenoid and GT fractures.

Methods: From December 2013 to December 2019, we retrospectively reviewed the clinical data of patients who were diagnosed with acute anterior shoulder dislocation associated with glenoid and GT fractures in our hospital. According to the fracture site, a glenoid fracture group and a greater tuberosity fracture (GT) group were established, and the morphological characteristics of both glenoid and GT fractures were measured and statistically analyzed.

Results: A total of 41 patients (43 shoulders) met the inclusion criteria (39 unilateral shoulders and 2 bilateral shoulders). The mean age was 50.21 years (range, 22-71 years). A total of 27 shoulder injuries (62.8%) were split GT fractures and 33 shoulder injuries (76.7%) were combined with rotator cuff tears. The mean size of glenoid fragments was 30.16% and the mean displacement was 8.85 mm. The mean size of GT fragments was 28.43 mm. The mean superoinferior and anteroposterior displacements of the GT fragment were 6.77 mm and 4.96 mm, respectively. There was a negative correlation between the size of glenoid and GT fracture fragments (r = -0.64, P < 0.05). The glenoid fragments in the Ideberg type Ia glenoid fracture group were smaller than those in the Ideberg type II glenoid fracture group (28.41% and 40.95%, respectively), while the size of GT fragments in the type Ia group were larger than those in the type II group (29.77 mm and 20.21 mm, respectively) (P < 0.05). The GT fragments in the split GT fracture group were larger than those in the avulsion or depression GT fracture group (33.69 mm, 19.07 mm and 21.12 mm, respectively), while the size of glenoid fragments in the split GT fracture group were smaller than those in the avulsion or depression GT fracture group (23.57%, 41.37%, and 43.42%, respectively) (P < 0.05). As for the displacement direction of GT fragments, depression fractures were mainly inferior displacements, avulsion fractures were mainly anterosuperior displacements, while split fractures were mainly posteroinferior displacements (P < 0.05). Multiple regression analysis suggested that the type and the fragment size of GT fractures have a significant influence on the size of glenoid fragments.

Conclusion: Acute anterior shoulder dislocations associated with glenoid and GT fractures are often combined with rotator cuff tears. There is a negative correlation between the size of glenoid and GT fragments, and split GT fractures are most common. Such injuries are highly correlated to the relative spatial location between the GT and the glenoid when the shoulder dislocates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/os.12767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670144PMC
October 2020

Dexmedetomidine inhibits pyroptosis by down-regulating miR-29b in myocardial ischemia reperfusion injury in rats.

Int Immunopharmacol 2020 Sep 14;86:106768. Epub 2020 Jul 14.

Department of Anesthesiology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, PR China. Electronic address:

Objective: Dexmedetomidine (DEX) was reported to protect heart against ischemic-reperfusion (IR) but the mechanism herein remains elusive. This study aims to explore the mechanism of DEX on pyroptosis induced by myocardial ischemic reperfusion (MIR).

Methods: MIR rat models were established and injected DEX or miR-29b agomir/antagomir separately. The possible effect of DEX or miR-29b on myocardial cells was assessed according to measurement on creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), interleukin-1β (IL-1β) and interleukin-18 (IL-18), myocardial infarction size, myocardial injury and apoptosis. Western blot determined the expression levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC) and cleaved-caspase-1. Hypoxia/reoxygenation (H/R) cell model was established. The lactate dehydrogenase (LDH) content released by myocardial cells was examined. The relation between miR-29b and FoxO3a was confirmed by dual luciferase reporter gene assay. FoxO3a or ARC level was elevated in H/R myocardial cells to detect its effect on pyroptosis.

Results: MIR rat models were successfully established, in which cell pyroptosis was triggered as evidenced by increased expression levels of NLRP3, ASC and cleaved-caspase-1. Rats with DEX precondition had attenuated cell pyroptosis and ameliorated inflammatory response. FoxO3a was a target of miR-29b. MiR-29b agomir or miR-29b antagomir could inhibit or promote the protective effect of DEX on MIR. Overexpression of FoxO3a/ARC axis could suppress myocardial pyroptosis induced by H/R.

Conclusion: DEX could ameliorate MIR injury (MIRI) and H/R injury in rats and inhibit H/R induced pyroptosis in myocardial cells via down-regulating miR-29b to activate FoxO3a/ARC axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2020.106768DOI Listing
September 2020

Association between neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and diabetic retinopathy among diabetic patients without a related family history.

Diabetol Metab Syndr 2020 2;12:55. Epub 2020 Jul 2.

Department of Endocrinology and Metabolism, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, 650021 China.

Background: Diabetic retinopathy (DR) is a specific neurovascular complication of diabetes mellitus (DM). Clinically, family history is a widely recognized risk factor for DR, assisting diagnosis and risk strata. However, among a great amount of DR patients without hereditary history like hypertension and diabetes, direct and simple risk factors to assist clinical decisions are still required. Herein, we intend to investigate the associated risk factors for these DR patients based on systemic inflammatory response indexes, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR).

Methods: We consecutively enrolled 1030 patients with a definite diagnosis of type 2 diabetes mellitus (T2DM) from the endocrinology department of the Second hospital of People in Yun Nan. Based on funduscopy and family history checking, we excluded patients with a family history of hypertension and diabetes and finally enrolled 264 patients with DR and 206 patients with non-diabetic retinopathy (NDR). Through correlation analysis, univariate and multivariate regression, we further explore the association between NLR, PLR, and DR. On top of that, we investigate the effect of NLR and PLR on risk reclassification of DR.

Results: Compared with NDR patients, NLR and PLR levels are significantly higher among DR patients (NLR: 2.36 ± 1.16 in DR group versus 1.97 ± 1.06 in NDR group, p < 0.001; PLR: 11.62 ± 4.55 in DR group versus10.56 ± 4.45 in NDR group, p = 0.012). According to univariate analysis, NLR and PLR add risks to DR. After fully adjusting co-founders, NLR, as both continuous and categorical variate, remains an independent risk factor for DR (OR (95%CI): 1.37 (1.06, 1.78) P = 0.018). And though PLR was not independently associated with DR as a continuous variable (OR (95%CI) 1.05 (0.99, 1.11) p = 0.135), the highest quantile of PLR add two-fold increased risk (OR (95%CI) 2.20 (1.05, 4.59) p = 0.037) in the fully adjusted model for DR. In addition, addition of PLR and NLR to the established factor hemoglobin (Hb) improved the discriminability of the model and assisted the reclassification of DR. After combining PLR and NLR the Area under curve (AUC) of Hb based model raised from 0.76 to 0.78, with a category-free net reclassification improvement (NRI) of 0.532 (p < 0.001) and integrated discrimination improvement (IDI) of 0.029 (p < 0.001).

Conclusions: Systemic inflammatory response indexes NLR and PLR were associated with the presence of DR among patients without associated family history and contributed to improvements in reclassification of DR in addition to Hb.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13098-020-00562-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331251PMC
July 2020

[Distribution Characteristics and Migration Rules of Pollutants in Sediments of Reservoirs with Plantation, Southern China].

Huan Jing Ke Xue 2020 May;41(5):2247-2256

Nanjing Hohai Technology Corporation, Nanjing 210016, China.

The safety of water quantity and quality caused by large-scale blackwater in reservoirs with plantation is currently a point of great interest. is largely planted in southern China, especially in Nanning, Guangxi, where more than 90% of the drinking water source reservoirs are surrounded by , and different degrees of blackwater often occur in many reservoirs. Recent research has demonstrated that reservoir sediments play an important role in the migration and transformation of Fe, Mn, S, and dissolved organic carbon (DOC) in the overlying water. It is of great significance to explore the distribution characteristics and migration rules of pollutants in the sediment-water interface to reveal the mechanism of blackwater in reservoirs. Experiments were carried out three times in a typical blackwater reservoir (Tianbao Reservoir) in southern China from July to December 2018. The distribution characteristics and seasonal variations of iron, manganese, sulfide, and organic matter in sediments were analyzed, focusing mainly on the profile distribution and migration direction of Fe, Mn S and DOC in pore water during blackwater periods. The results showed that:① The content of iron and manganese in sediments of reservoirs with plantation is high, far exceeding the background value of soil content in China. The content of iron, manganese, and total organic carbon (TOC) in the surface sediments increases simultaneously, mainly caused by the input and settlement of the material (litter, decomposed liquids. and soil particles) in the forest around the reservoir. ② The concentration of Fe(16.99 mg·L) and the content of DOC (36.80%) in pore water during the blackwater period are significantly higher than those in Taihu Lake during the black bloom (12.15 mg·L, 10.78%). The mean concentrations of Fe and Mn are more than 300 times higher than that of S, and the reduction conditions in the sediments are dominated by iron and manganese oxides. ③ The diffusion flux of Fe is 27.4-33.5 mg·(m·d), which is 32.6, 4.9, and 30.8 times higher than those of Taihu Lake, Aha Reservoir, and Hongfeng Lake, respectively. This implies strong Fe release ability from sediments to the overlying water. As a positive correction exists between Fe and DOC, the complex reaction between Fe and organic matter is one of the most important causes of blackwater in reservoirs with plantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13227/j.hjkx.201909255DOI Listing
May 2020

Runt-related transcription factor 1 is required for murine osteoblast differentiation and bone formation.

J Biol Chem 2020 08 22;295(33):11669-11681. Epub 2020 Jun 22.

Department of Pathology, the University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA

Despite years of research investigating osteoblast differentiation, the mechanisms by which transcription factors regulate osteoblast maturation, bone formation, and bone homeostasis is still unclear. It has been reported that runt-related transcription factor 1 () is expressed in osteoblast progenitors, pre-osteoblasts, and mature osteoblasts; yet, surprisingly, the exact function of RUNX1 in osteoblast maturation and bone formation remains unknown. Here, we generated and characterized a pre-osteoblast and differentiating chondrocyte-specific conditional knockout mouse model to study RUNX1's function in bone formation. ablation in osteoblast precursors and differentiating chondrocytes via osterix-Cre (Osx-Cre) resulted in an osteoporotic phenotype and decreased bone density in the long bones and skulls of mice compared with and mice. RUNX1 deficiency reduced the expression of SRY-box transcription factor 9 (SOX9), Indian hedgehog signaling molecule (IHH), Patched (PTC), and cyclin D1 in the growth plate, and also reduced the expression of osteocalcin (OCN), OSX, activating transcription factor 4 (ATF4), and RUNX2 in osteoblasts. ChIP assays and promoter activity mapping revealed that RUNX1 directly associates with the gene promoter and up-regulates expression. Furthermore, the ChIP data also showed that RUNX1 associates with the promoter. In conclusion, RUNX1 up-regulates the expression of and multiple bone-specific genes, and plays an indispensable role in bone formation and homeostasis in both trabecular and cortical bone. We propose that stimulating activity may be useful in therapeutic approaches for managing some bone diseases such as osteoporosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.RA119.007896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450143PMC
August 2020

Selective autophagy controls the stability of transcription factor IRF3 to balance type I interferon production and immune suppression.

Autophagy 2021 06 31;17(6):1379-1392. Epub 2020 May 31.

State Key Laboratory of Oncology in South China, MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou, GD, China.

IRF3 (interferon regulatory factor 3) is one of the most critical transcription factors in antiviral innate immune signaling, which is ubiquitously expressed in a variety of cells. Although it has been demonstrated that IRF3 can provoke multiple cellular processes during viral infection, including type I interferon (IFN) production, the mechanisms underlying the precise regulation of IRF3 activity are still not completely understood. Here, we report that selective macroautophagy/autophagy mediated by cargo receptor CALCOCO2/NDP52 promotes the degradation of IRF3 in a virus load-dependent manner. Deubiquitinase PSMD14/POH1 prevents IRF3 from autophagic degradation by cleaving the K27-linked poly-ubiquitin chains at lysine 313 on IRF3 to maintain its basal level and IRF3-mediated type I IFN activation. The autophagic degradation of IRF3 mediated by PSMD14 or CALCOCO2 ensures the precise control of IRF3 activity and fine-tunes the immune response against viral infection. Our study reveals the regulatory role of PSMD14 in balancing IRF3-centered IFN activation with immune suppression and provides insights into the crosstalk between selective autophagy and type I IFN signaling. ATG5: autophagy related gene 5; Baf A: bafilomycin A; BECN1: beclin 1; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CGAS: cyclic GMP-AMP synthase; DDX58/RIG-I: DExD/H-box helicase 58; DUBs: deubiquitinating enzymes; IFN: interferon; IRF3: interferon regulatory factor 3; MAVS: mitochondrial antiviral signaling protein; MOI: multiplicity of infection; PAMPs: pathogen-associated molecule patterns; PBMC: peripheral blood mononuclear cell; PSMD14/POH1: proteasome 26S subunit, non-ATPase 14; RIPA: RLR-induced IRF3-mediated pathway of apoptosis; SeV: Sendai virus; SQSTM1/p62: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1; Ub: ubiquitin; WT: wild type.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15548627.2020.1761653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205069PMC
June 2021

Runx1 up-regulates chondrocyte to osteoblast lineage commitment and promotes bone formation by enhancing both chondrogenesis and osteogenesis.

Biochem J 2020 07;477(13):2421-2438

Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, U.S.A.

One of the fundamental questions in bone biology is where osteoblasts originate and how osteoblast differentiation is regulated. The mechanism underlying which factors regulate chondrocyte to osteoblast lineage commitment remains unknown. Our data showed that Runt-related transcription factor 1 (Runx1) is expressed at different stages of both chondrocyte and osteoblast differentiation. Runx1 chondrocyte-specific knockout (Runx1f/fCol2α1-cre) mice exhibited impaired cartilage formation, decreased bone density, and an osteoporotic phenotype. The expressions of chondrocyte differentiation regulation genes, including Sox9, Ihh, CyclinD1, PTH1R, and hypertrophic chondrocyte marker genes including Col2α1, Runx2, MMP13, Col10α1 in the growth plate were significantly decreased in Runx1f/fCol2α1-cre mice chondrocytes. Importantly, the expression of osteoblast differentiation regulation genes including Osx, Runx2, ATF4, and osteoblast marker genes including osteocalcin (OCN) and osteopontin (OPN) were significantly decreased in the osteoblasts of Runx1f/fCol2α1-cre mice. Notably, our data showed that osteoblast differentiation regulation genes and marker genes are also expressed in chondrocytes and the expressions of these marker genes were significantly decreased in the chondrocytes of Runx1f/fCol2α1-cre mice. Our data showed that chromatin immunoprecipitation (ChIP) and promoter mapping analysis revealed that Runx1 directly binds to the Indian hedgehog homolog (Ihh) promoter to regulate its expression, indicating that Runx1 directly regulates the transcriptional expression of chondrocyte genes. Collectively, we revealed that Runx1 signals chondrocyte to osteoblast lineage commitment and promotes endochondral bone formation through enhancing both chondrogenesis and osteogenesis genes expressions, indicating Runx1 may be a therapeutic target to enhance endochondral bone formation and prevent osteoporosis fractures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/BCJ20200036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984603PMC
July 2020

Long-chain fatty acyl-coenzyme A suppresses hepatitis C virus infection by targeting virion-bound lipoproteins.

Antiviral Res 2020 05 10;177:104734. Epub 2020 Feb 10.

State Key Laboratory of Respiratory Disease, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou, China. Electronic address:

Hepatitis C virus (HCV) is a leading cause of chronic hepatitis and end-stage liver diseases. Mature HCV virions are bound by host-derived lipoproteins. Lack of an HCV vaccine warrants a major role of antiviral treatment in the global elimination of hepatitis C. Although direct-acting antivirals (DAAs) are replacing the interferon-based treatment and have dramatically improved the cure rate, the presence of viral variants resistant to DAAs, HCV genotype/subtype-specific efficacy, and high cost of DAAs argue novel and affordable regimens. In this study, we identified the antiviral effects of long-chain fatty acyl-coenzyme A (LCFA-CoA) against the infections of HCV genotypes 1-6 through targeting mature HCV-bound lipoproteins, suggesting novel mechanism(s) of antiviral different from those used by host-targeting agents or DAAs. We found that the antiviral activity of LCFA-CoA relied on the long-chain saturated fatty acid and the CoA group, and was enhanced when combined with pegylated-interferon or DAAs. Importantly, we demonstrated that LCFA-CoA efficiently inhibited the infection of HCV variants carrying DAA-resistant mutations. The mechanistic study revealed that LCFA-CoA specifically abolished the attachment and binding steps and also inhibited the cell-to-cell viral transmission. LCFA-CoA targeted mature HCV-bound lipoproteins, but not apolipoproteins B or E. In addition, LCFA-CoA could also inhibit the infection of the dengue virus. Our findings suggest that LCFA-CoA could potentially serve as a supplement HCV therapy, particularly for the DAA-resistant HCV variants. Taken together, LCFA-CoA may be further developed to be a novel class of antivirals with mechanism(s), different from host-targeting agents or DAAs, of targeting the components associated with mature HCV virions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.antiviral.2020.104734DOI Listing
May 2020

Optimizing the Use of the Gamma-Glutamyl Transpeptidase-to-Platelet Ratio and Transient Elastography to Identify Liver Cirrhosis in Patients with Chronic Hepatitis B Concurrent with Nonalcoholic Fatty Liver Disease.

Dis Markers 2019 5;2019:2585409. Epub 2019 Dec 5.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background And Aim: Little information is available about the assessment and optimal use of the gamma-glutamyl transpeptidase-to-platelet ratio (GPR) and transient elastography (TE) in predicting liver cirrhosis in patients with chronic hepatitis B (CHB) and concurrent nonalcoholic fatty liver disease (NAFLD). This study is aimed at comparing their diagnostic performances and developing an optimal approach for predicting liver cirrhosis in CHB patients with NAFLD.

Methods: Consecutive CHB patients with NAFLD were enrolled. The GPR was calculated, and TE was performed using liver biopsy as a reference standard. The accuracy of predicting liver cirrhosis using GPR and TE was assessed and compared, and an optimal approach was developed.

Results: Both TE and GPR correlated significantly with the histological fibrosis stage. TE and GPR had excellent performance in predicting liver cirrhosis, and the comparison of areas under the receiver operating characteristic curves revealed that TE was superior to GPR (0.95 vs. 0.85, = 0.039). Moreover, the dual cutoffs established by the likelihood ratio showed that GPR had a similar misclassification but higher indeterminate rate than TE (54.5% vs. 11.7%, < 0.001). Additionally, a 2-step approach using GPR followed by TE had comparable performance to that of both GPR and TE tests for all patients (misclassification: 8.9% vs. 8.3%, = 0.866; indeterminate rate: 15.2% vs. 17.2%, = 0.750) but could reduce TE scans by approximately one-third.

Conclusions: Both TE and GPR show excellent performance in predicting liver cirrhosis in CHB patients with NAFLD. The 2-step approach using GPR followed by TE may be optimal for the assessment of cirrhosis in CHB patients with NAFLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/2585409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915133PMC
May 2020

[Comparative analysis of clinical effects according to syndrome differentiation of Qili Qiangxin Capsules on ischemic heart failure: Meta-analysis].

Zhongguo Zhong Yao Za Zhi 2019 Nov;44(22):4975-4984

Department of Cardiology,Shuguang Hospital of Shanghai University of Traditional Chinese Medicine Shanghai 201203,China Cardiovascular Research Institute of Traditional Chinese Medicine,Shuguang Hospital of Shanghai University of Traditional Chinese Medicine Shanghai 201203,China.

Databases including CNKI,Wan Fang,CBM,VIP,PubMed and Cochrane Library were searched to collect qualified researches,and the quality of articles was evaluated according to scales. Meta-analysis including subgroup analysis was performed by using Rev Man 5. 3 software and Meta-regression test was performed by using Stata 12. 0 software. All of these methods were used to systematically evaluate the safety and clinical efficacy of Qili Qiangxin Capsules in treatment of ischemic heart failure under two circumstances( with or without syndrome differentiation). A total of 22 randomized controlled trials( RCTs) involving 1 942 patients were included,with generally low quality. RESULTS: of Meta-analysis showed that as compared with the routine Western treatment alone,additional use of Qili Qiangxin Capsules could improve the clinical efficacy( RR = 1. 21,95%CI[1. 16,1. 27],P<0. 000 01) in treatment of ischemic heart failure,with its combined effect of syndrome differentiation group greater than that of non-syndrome differentiation group( P= 0. 03,I~2= 78. 9%),Meta-regression( sig = 0. 9,P = 0. 057); left ventricular ejection fraction( WMD = 7. 28,95% CI[5. 18,9. 38],P<0. 000 01),with combined effect of syndrome differentiation group greater than that of non-syndrome differentiation group( P= 0. 01,I2= 83. 2%),Meta-regression( I~2= 81. 09%,R2= 29. 08%,sig = 0. 47,P = 0. 029); 6-minute walk test( WMD = 33. 20,95%CI[24. 70,41. 70 ],P < 0. 000 01); left ventricular end diastolic diameter( WMD =-4. 61,95% CI[-5. 38,-3. 84 ],P <0. 000 01); left ventricular end diastolic volume( WMD =-34. 43,95%CI[-38. 81,-30. 05],P< 0. 000 01); and left ventricular end systolic volume( WMD =-9. 60,95% CI[-13. 16,-6. 05],P < 0. 000 01). Adverse effects were reported in 11 patients taking Qili Qiangxin Capsules and in 20 patients with routine treatment group,tolerable in both groups. None of the patients had obvious abnormality in liver and kidney function. Qili Qiangxin Capsules were effective and safe in the treatment of ischemic heart failure,which can further improve clinical efficacy as compared with routine treatment alone. Qili Qiangxin Capsules with syndrome differentiation showed more significant effects than those without syndrome differentiation,indicating better efficacy of clinical syndrome differentiation. However,these conclusions still need to be verified with more high-quality and large-sample literature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19540/j.cnki.cjcmm.20190909.501DOI Listing
November 2019

[Uncertainty and Sensitivity Analysis of Phosphorus Model Parameters in Large Shallow Lakes].

Huan Jing Ke Xue 2019 Oct;40(10):4478-4486

College of Environment, Hohai University, Nanjing 210098, China.

Lake Taihu was chosen as a typical large shallow lake, and a diagenesis model of phosphorus was established based on environmental fluid dynamic code (EFDC). The uncertainty of the simulation results and the sensitivity of 16 parameters related to phosphorus migration and transformation in the diagenesis model were analyzed using Latin hypercube sampling (LHS), generalized likelihood uncertainty estimation (GLUE), and regionalized sensitivity analysis (RSA). The results showed that the temporal and spatial distribution of phosphate and total phosphorus in Lake Taihu was extremely uneven. Furthermore, the uncertainty of the diagenesis model had a strong influence on the simulation of phosphate and total phosphorus. For phosphate in the overlying, wind and wave disturbance at the 'sediment-water' interface was stronger in shallower water regions. The circulation of water in the bay area, where the dissolved oxygen content was low, was poor, which was conducive to the release of dissolved phosphorus in the sediment. For total phosphorus in the overlying water, the granular phosphorus and dissolved organic phosphorus contents in the central lake area were greatly affected by parameter uncertainties in the diagenesis model. The sensitive parameters mainly consisted of two kinds related to oxygen and dynamic characteristics, respectively. For large shallow lakes, the importance of parameter sensitivity in diagenesis models is no less than for hydrodynamic and water quality models. For large shallow lakes, the calibration of sensitive parameters should, therefore, be given attention when simulating the phosphorus content of areas with complicated water quality and sediment distributions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13227/j.hjkx.201903110DOI Listing
October 2019
-->