Publications by authors named "Hua Yu"

644 Publications

LIN28 coordinately promotes nucleolar/ribosomal functions and represses the 2C-like transcriptional program in pluripotent stem cells.

Protein Cell 2021 Jul 31. Epub 2021 Jul 31.

Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences and the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
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http://dx.doi.org/10.1007/s13238-021-00864-5DOI Listing
July 2021

Effects of UCMSCs Delivered through Different Transplantation Approaches on Acute Radiation Enteritis in Rats.

Cell Transplant 2021 Jan-Dec;30:9636897211025230

Medical School of Kunming University, Kunming, China.

Radiation enteritis is the most common and serious complication of abdominal or pelvic radiation therapy. Mesenchymal stem cells (MSCs), as well as cell protection agents, inhibit apoptosis and promote the proliferation of injured tissues. 3 human umbilical cords MSCs (UCMSCs) were injected into the tail vein or peritoneal cavity of a rat model of radiation enteritis. The temporary protective effect was assessed by identification of donor cells, detection of cellular immune parameters and inflammatory cytokine levels, quantitation of jejunum mucosal preservation and examination of the rat remaining life. Only the rats in the intraperitoneal injection group exhibited a few positive donor cells 7 days after transplantation. CD /CD T cells, a cellular immune parameter, decreased in the abdominal exudate of intraperitoneal injection group, compared with the model-only control and tail vein groups (both < .05). Both serum and abdominal exudate TNF-α and IL-6 levels in the intraperitoneally injected rats rapidly decreased and were significantly different from those in the model-only control and tail vein injection groups (all < .05). Mucosal surface area and survival time increased in the intraperitoneal injection group compared with the vehicle and tail vein injection groups (all = .000). Therefore, the administration of UCMSCs with intraperitoneal injection approach postponed death in a rat model of radiation enteritis, which was associated with reduced serum levels of proinflammatory cytokines (TNF-α, IL-6). However, UCMSCs injected via the tail vein triggered an intense cellular immune response in the serum that adversely affects their survival. This treatment failed to suppress circulating serum and abdominal exudate levels of TNF-α and IL-6 and could not provide a therapeutic benefit for prolonging life against acute radiation enteritis.
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http://dx.doi.org/10.1177/09636897211025230DOI Listing
July 2021

Treatment of leiomyomatosis peritonealis disseminata with goserelin acetate: A case report and review of the literature.

World J Clin Cases 2021 Jul;9(19):5217-5225

Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Discipline Construction Research Center of China Hospital Development Institute, Shanghai Jiao Tong University, Shanghai 200011, China.

Background: Leiomyomatosis peritonealis disseminata (LPD) is a rare condition characterized by multiple pelvic and abdominal nodules, which are composed of smooth-muscle cells. To date, no more than 200 cases have been reported. The diagnosis of LPD is difficult and there are no guidelines on the treatment of LPD. Currently, surgical excision is the mainstay. However, hormone blockade therapy can be an alternative choice.

Case Summary: A 33-year-old female patient with abdominal discomfort and palpable abdominal masses was admitted to our hospital. She had undergone four surgeries related to uterine leiomyoma in the past 8 years. Computed tomography revealed multiple nodules scattered within the abdominal wall and peritoneal cavity. Her symptoms and the result of the core-needle biopsy were consistent with LPD. The patient refused surgery and was then treated with tamoxifen, ulipristal acetate (a selective progesterone receptor modulator), and goserelin acetate (a gonadotropin-releasing hormone agonist). Both tamoxifen and ulipristal acetate were not effective in controlling the disease progression. However, the patient achieved an excellent response when goserelin acetate was attempted with relieved syndromes and obvious shrinkage of nodules. The largest nodule showed a 25% decrease in the sum of the longest diameters from pretreatment to posttreatment. Up to now, 2 years have elapsed and the patient remains asymptomatic and there is no development of further nodules.

Conclusion: Goserelin acetate is effective for the management of LPD. The long-term use of goserelin acetate is thought to be safe and effective. Hormone blockade therapy can replace repeated surgical excision in recurrent patients.
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http://dx.doi.org/10.12998/wjcc.v9.i19.5217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283592PMC
July 2021

The interactions between childhood adversities and recent stress were associated with early-adulthood depression among Chinese undergraduate students.

Depress Anxiety 2021 Jul 22. Epub 2021 Jul 22.

Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China.

Background: It is widely acknowledged that childhood adversities (CAs) and recent stress are potential risk factors for adult depression. However, the mechanism(s) by which interactions of CAs with recent stress affect adult depression remain unclear.

Aims: To investigate the predictive association of the interaction among CAs and recent stress with early-adult depression.

Method: We conducted an annual survey of all freshmen for the period of 2016-2018 in a Chinese comprehensive university, with a sample size of 23,206. An online questionnaire including standardized self-report instruments was used to assess sociodemographic factors, childhood experiences of left-behind (CELB), and maltreatments (CEMTs) including beating (CEB), neglect (CEN), sexual abuse (CESA), recent stress, and current depression (measured by the 9-item Patient Health Questionnaire).

Results: The correlation of Individual CAs and recent stress was significant. In addition to their significant independent/direct incremental effects, all surveyed CAs were associated with increased severity of early-adult depression, and increased frequency of clinically significant depression (CSD), through significant associations with recent stress (mediation effect). History of CEMTs including CEB, CEN, and CESA significantly increased the effects of recent stress on depression (moderation effect).

Conclusions: Chinese undergraduate students reported frequent history of exposure to CAs, which increased the likelihood of depression in early adulthood, not only directly but also through the increasing the likelihood (mediation effect) and impact (moderation effect) of recent stress on depression. These novel findings may help to extend our understanding of environmental determinants of depression, and to guide further research, clinical practice, and policy in this context.
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http://dx.doi.org/10.1002/da.23201DOI Listing
July 2021

Circ_0000317/microRNA-520g/HOXD10 axis affects the biological characteristics of colorectal cancer.

Kaohsiung J Med Sci 2021 Jul 22. Epub 2021 Jul 22.

Ningbo Institute of Life and Health Industry, Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China.

Circular RNAs (circRNAs) are a class of noncoding RNAs that are widely expressed in cancer tissues and play a pro- or anticancer role in modulating cancer progression. This work is aimed to probe the biological role of circ_0000317 in colorectal cancer (CRC) and its underlying mechanism. Circ_0000317 was selected from the circRNA microarray datasets (GSE121895). Quantitative real-time polymerase chain reaction was utilized to examine circ_0000317, microRNA (miR)-520g, and homeobox D10 (HOXD10) mRNA expression in CRC. Cell Counting Kit-8 and Transwell experiments were conducted to examine the effects of circ_0000317 on proliferation, migration, and invasion of CRC cells. Bioinformatic analysis and dual-luciferase reporter gene experiments were implemented to predict and validate the targeting relationship between circ_0000317 and miR-520g, miR-520g, and HOXD10. Western blot was employed to examine HOXD10 expression at protein level in CRC cells. Circ_0000317 and HOXD10 mRNA expression were unveiled to be down-modulated and miR-520g expression was up-modulated in CRC. Functionally, circ_0000317 overexpression repressed CRC cell proliferation, migration, and invasion. Mechanistically, miR-520g was a direct target of circ_0000317 and miR-520g specifically modulated HOXD10 expression. Furthermore, miR-520g mimics partially counteracted the suppressing effect of circ_0000317 on malignant phenotype of CRC cells. Circ_0000317 represses CRC progression by targeting miR-520g and modulating HOXD10 expression. Hence, circ_0000317 may be a promising diagnostic biomarker and a therapeutic target for CRC.
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http://dx.doi.org/10.1002/kjm2.12422DOI Listing
July 2021

Co-delivery of paclitaxel and STAT3 siRNA by a multifunctional nanocomplex for targeted treatment of metastatic breast cancer.

Acta Biomater 2021 Jul 18. Epub 2021 Jul 18.

Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Metastasis is one of the major causes of mortality in patients suffering from breast cancer. The signal transducer and activator of transcription 3 (STAT3) is closely related to cancer metastasis. Herein, a multifunctional nanocomplex was developed to simultaneously deliver paclitaxel (PTX) and STAT3 siRNA (siSTAT3) to inhibit tumor growth and prevent metastasis of breast cancer cells. PTX was encapsulated into the synthesized polyethyleneimine-polylactic acid-lipoic acid (PPL) micelle through hydrophobic interaction, while siSTAT3 was condensed onto polyethyleneimine through electrostatic interaction. The surface charge of the drug-loaded nanocomplex (PPL) was then converted to negative by coating with hyaluronic acid (HA). The multifunctional nanocomplex (HA/PPL) effectively entered CD44-overexpressed 4T1 cells via an active targeting mechanism. HA shell was degraded by the concentrated hyaluronidase in the endo/lysosome and the rapid drug release was triggered by the redox micro-environment of cytoplasm. Moreover, HA/PPL showed enhanced cytotoxicity against tumor cells due to a synergistic effect of PTX and siSTAT3. The effective inhibition of tumor metastasis was confirmed by in vitro cell migration and invasion in 4T1 cells. More importantly, a superior antitumor efficacy was observed in orthotopic 4T1 tumor-bearing mice, with no side effects in major organs, and the lung metastasis was strongly inhibited in 4T1 metastasis model. In conclusion, the multifunctional nanocomplex provides a versatile platform for efficient treatment of metastatic cancer through tumor-targeted chemo-gene combined therapy. STATEMENT OF SIGNIFICANCE: Metastasis is one of the major causes of mortality in patients suffering from breast cancer. The signal transducer and activator of transcription 3 (STAT3) is closely related to cancer metastasis. In this study, a multifunctional nanocomplex co-loaded with paclitaxel (PTX) and STAT3 siRNA was constructed and characterized. The co-delivery system exhibited active tumor targeting, effective endo/lysosomal escape, and rapid intracellular drug release. Both in vitro and in vivo studies indicated that the nanocomplex could lead to superior tumor growth inhibition, as well as metastasis suppression by silencing expression of STAT3 and p-STAT3. This present study implies that the nanocomplex could be a potential platform for targeted treatment of metastatic cancer through chemo-gene combined therapy.
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http://dx.doi.org/10.1016/j.actbio.2021.07.029DOI Listing
July 2021

Cytosolic GDH1 degradation restricts protein synthesis to sustain tumor cell survival following amino acid deprivation.

EMBO J 2021 Jul 16:e107480. Epub 2021 Jul 16.

CAS Key Laboratory of Tissue Microenvironment and Tumor, Institute of Nutrition and Health Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

The mTORC1 pathway plays key roles in regulating various biological processes, including sensing amino acid deprivation and driving expression of ribosomal protein (RP)-coding genes. In this study, we observed that depletion of glutamate dehydrogenase 1 (GDH1), an enzyme that converts glutamate to α-ketoglutarate (αKG), confers resistance to amino acid deprivation on kidney renal clear cell carcinoma (KIRC) cells. Mechanistically, under conditions of adequate nutrition, GDH1 maintains RP gene expression in a manner dependent on its enzymatic activity. Following amino acid deprivation or mTORC1 inhibition, GDH1 translocates from mitochondria to the cytoplasm, where it becomes ubiquitinated and degraded via the E3 ligase RNF213. GDH1 degradation reduces intracellular αKG levels by more than half and decreases the activity of αKG-dependent lysine demethylases (KDMs). Reduced KDM activity in turn leads to increased histone H3 lysine 9 and 27 methylation, further suppressing RP gene expression and preserving nutrition to support cell survival. In summary, our study exemplifies an economical and efficient strategy of solid tumor cells for coping with amino acid deficiency, which might in the future be targeted to block renal carcinoma progression.
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http://dx.doi.org/10.15252/embj.2020107480DOI Listing
July 2021

Targeted genomic profiling revealed a unique clinical phenotype in intrahepatic cholangiocarcinoma with fibroblast growth factor receptor rearrangement.

Transl Oncol 2021 Jul 9;14(10):101168. Epub 2021 Jul 9.

Department of Oncology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Middle Yanchang Road, Shanghai 200072, P.R. China. Electronic address:

Genomic aberrations (GAs) in fibroblast growth factor receptors (FGFRs) are involved in the pathogenesis of intrahepatic cholangiocarcinoma (ICC), and clinical trials have shown efficacy of FGFR inhibitors in treating ICC patients with FGFR GAs such as FGFR2 rearrangement. To clarify the FGFRs GA profile and corresponding clinicopathological features in Chinese patients with ICC, a total of 257 cases were identified. Fourteen cases (5.45%) were positive for FGFR2 rearrangement. Further analysis on the 110 FGFR2 rearrangement negative cases showed that 13 patients present additional FGFRs GAs, including FGFR3 rearrangement (2.73%), and FGFRs mutations. When compared with patients without FGFRs GAs, those with FGFR2 or FGFR3 rearrangement presented more under the age of 58 years, female sex, HBsAb positivity, CD10 expression, and PD-L1 expression. The clinical characteristics between patients with FGFRs mutation and those without FGFRs GAs were similar, with the exception that cases with FGFRs mutation have more hepatolithiasis. We concluded that FGFR rearrangement is associated with unique clinical phenotypes in ICC.
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http://dx.doi.org/10.1016/j.tranon.2021.101168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283138PMC
July 2021

Diverse Banana Pseudostems and Rachis Are Distinctive for Edible Carbohydrates and Lignocellulose Saccharification towards High Bioethanol Production under Chemical and Liquid Hot Water Pretreatments.

Molecules 2021 Jun 24;26(13). Epub 2021 Jun 24.

Biomass & Bioenergy Research Centre, College of Plant Science & Technology, Huazhong Agricultural University, Wuhan 430070, China.

Banana is a major fruit crop throughout the world with abundant lignocellulose in the pseudostem and rachis residues for biofuel production. In this study, we collected a total of 11 pseudostems and rachis samples that were originally derived from different genetic types and ecological locations of banana crops and then examined largely varied edible carbohydrates (soluble sugars, starch) and lignocellulose compositions. By performing chemical (HSO, NaOH) and liquid hot water (LHW) pretreatments, we also found a remarkable variation in biomass enzymatic saccharification and bioethanol production among all banana samples examined. Consequently, this study identified a desirable banana (Refen1, subgroup Pisang Awak) crop containing large amounts of edible carbohydrates and completely digestible lignocellulose, which could be combined to achieve the highest bioethanol yields of 31-38% (% dry matter), compared with previously reported ones in other bioenergy crops. Chemical analysis further indicated that the cellulose CrI and lignin G-monomer should be two major recalcitrant factors affecting biomass enzymatic saccharification in banana pseudostems and rachis. Therefore, this study not only examined rich edible carbohydrates for food in the banana pseudostems but also detected digestible lignocellulose for bioethanol production in rachis tissue, providing a strategy applicable for genetic breeding and biomass processing in banana crops.
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http://dx.doi.org/10.3390/molecules26133870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270323PMC
June 2021

Application of Ultra Narrow Band Modulation in Enhanced Loran System.

Sensors (Basel) 2021 Jun 25;21(13). Epub 2021 Jun 25.

National Time Service Center, Chinese Academy of Sciences, Xi'an 710600, China.

The Enhanced Loran (eLoran) system is valued for its important role in the positioning, navigation, and timing fields; however, with its current modulation methods, low data rate restricts its development. Ultra narrow band (UNB) modulation is a modulation method with extremely high spectrum utilization. If UNB modulation can be applied to the eLoran system, it will be very helpful. The extended binary phase shift keying modulation in UNB modulation is selected for a detailed study, parameters and application model are designed according to its unique characteristics of signal time and frequency domains, and it is verified through simulation that the application of this modulation not only meets the design constraints of the eLoran system but also does not affect the reception of the respective signals of both parties. Several feasible schemes are compared, analyzed, and selected. Studies have revealed that application of UNB modulation in the eLoran system is feasible, and it will increase the data rate of the system by dozens of times.
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http://dx.doi.org/10.3390/s21134347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271942PMC
June 2021

Genome-wide discovery of hidden genes mediating known drug-disease association using KDDANet.

NPJ Genom Med 2021 Jun 15;6(1):50. Epub 2021 Jun 15.

Department of Basic Medical Sciences, Department of Human Genetics and Women's Hospital, Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Many of genes mediating Known Drug-Disease Association (KDDA) are escaped from experimental detection. Identifying of these genes (hidden genes) is of great significance for understanding disease pathogenesis and guiding drug repurposing. Here, we presented a novel computational tool, called KDDANet, for systematic and accurate uncovering the hidden genes mediating KDDA from the perspective of genome-wide functional gene interaction network. KDDANet demonstrated the competitive performances in both sensitivity and specificity of identifying genes in mediating KDDA in comparison to the existing state-of-the-art methods. Case studies on Alzheimer's disease (AD) and obesity uncovered the mechanistic relevance of KDDANet predictions. Furthermore, when applied with multiple types of cancer-omics datasets, KDDANet not only recapitulated known genes mediating KDDAs related to cancer, but also revealed novel candidates that offer new biological insights. Importantly, KDDANet can be used to discover the shared genes mediating multiple KDDAs. KDDANet can be accessed at http://www.kddanet.cn and the code can be freely downloaded at https://github.com/huayu1111/KDDANet .
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http://dx.doi.org/10.1038/s41525-021-00216-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206141PMC
June 2021

A novel thermal pretreatment method called air frying improves the enzymatic saccharification effect of straw.

Sci Total Environ 2021 Jun 1;790:148191. Epub 2021 Jun 1.

State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China. Electronic address:

Thermal pretreatment is a shared method to improve the efficiency of straw biochemical conversion. However, the process is often accompanied by problems such as the loss of carbon source. The objective of this study was to develop a novel thermal pretreatment method, called air frying, with less loss of biodegradable organic matter and favorable surface hydrophilicity. After pretreatment of two straws, the sugar yields were improved, and the improvement effect of corn stover was more significant. The total saccharification rate of corn stover increased from 31.31 ± 1.06% to 44.77 ± 1.23%, and the cellulose conversion rate increased from 44.10 ± 1.85% to 67.44 ± 2.37%. Functional groups with lower polarity on the surface were oxidized into the one with stronger polarity, so the hydrophilicity was enhanced. The surface roughness decreased, the surface tended to be flat, the original pores collapsed, and the average pore size increased, which was more conducive to the binding of enzyme and active site. The matching relationship between the optimal conditions and substrate, and the possibility of scaling up need further study.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148191DOI Listing
June 2021

Exosomal MicroRNA: Diagnostic Marker and Therapeutic Tool for Lung Diseases.

Curr Pharm Des 2021 Jun 8. Epub 2021 Jun 8.

Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang, China.

Lung diseases are common clinical illnesses with high morbidity and mortality, which seriously threaten human health. In recent years, increasing evidence suggests that exosomes play a pivotal role in intercellular communication by delivering their cargo to pulmonary target cells,such as microRNAs. Physiologically, exosomes have been shown to be a critical mediator in maintaining homeostasis function in the complex thin-walled lung tissue and airway structure. Apart from being a diagnostic and prognostic biomarker, exosomes also participate in the progression of some lung diseases, such as chronic obstructive pulmonary disease, asthma, pulmonary fibrosis, acute lung injury, lung cancer, interstitial lung disease, and tuberculosis. Here, we summarize the recent findings on the involvement of exosomes and exosomal microRNAs in the pathogenesis, diagnosis, and therapy of lung diseases, aiming to provide more information to discover novel diagnostic methods and treatment strategies for these disorders.
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http://dx.doi.org/10.2174/1381612827666210608150640DOI Listing
June 2021

[Study on Adverse Events of Infant Incubator Products].

Zhongguo Yi Liao Qi Xie Za Zhi 2021 Jun;45(3):335-339

Center for Medical Device Adverse Events Monitoring of Zhejiang, Hangzhou, 311121.

Objective: To investigate the risk of adverse events in the clinical use of infant incubators of three kinds of national medical devices in Zhejiang Province.

Methods: Semi-quantitative matrix analysis was used to analyze the risk of adverse events related to incubator products in Zhejiang province from August 2018 to August 2019.

Results: Through the risk analysis of 213 cases of adverse events of infant incubator product, the risk point and degree of the product in practical clinical application were evaluated.

Conclusions: Through the evaluation results of the production enterprises, medical institutions put forward relevant recommendations to reduce the risk of product use to prevent the recurrence of serious adverse events in the use of the product and spread.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2021.03.022DOI Listing
June 2021

A Contemporary Issue of Micro-Foundation of CSR, Employee Pro-Environmental Behavior, and Environmental Performance toward Energy Saving, Carbon Emission Reduction, and Recycling.

Int J Environ Res Public Health 2021 05 18;18(10). Epub 2021 May 18.

Department of Management Sciences, COMSATS University, Islamabad 44000, Pakistan.

The contemporary literature has largely addressed corporate social responsibility (CSR) at the macro or institutional level, whereas its effect at the micro-level is largely ignored. In addition, contemporary researchers have also ignored the importance of employee pro-environmental behavior to reduce the environmental footprint of small and medium enterprises (SMEs). With this background, the present study attempts to decrease the environmental footprint of the SME sector of China by implementing CSR at the micro-level through the involvement of employees because employees spend a significant amount of their time at workplaces, and hence their environment-related behavior may significantly contribute to improve the natural environment. In this regard, here we examined the impact of the micro-foundation of CSR on SMEs' environmental performance with mediating effect of employees' pro-environmental behavior. The data were collected from the different organizations in China. Our sample constitutes a supervisor-subordinate dyad from which we collected 562 filled questionnaires (281 from each). We used the structural equation modeling technique using AMOS software for data analysis, the results show that CSR, directly and indirectly, through employee's pro-environmental behavior affects the environmental performance of SMEs, and employee pro-environmental behavior partially mediates this relationship. The findings of the present study are helpful for policymakers of the SME sector of China to address widespread environmental issues caused by their business operations.
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http://dx.doi.org/10.3390/ijerph18105380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158375PMC
May 2021

Brij-functionalized chitosan nanocarrier system enhances the intestinal permeability of P-glycoprotein substrate-like drugs.

Carbohydr Polym 2021 Aug 24;266:118112. Epub 2021 Apr 24.

Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao; HKBU Shenzhen Research Center, Shenzhen, Guangdong, China. Electronic address:

The highly expressed P-glycoprotein (Pgp) in the intestine plays a key role in preventing drugs across the intestinal epithelium, which linked by tight junctions (TJs). Thus increasing the oral bioavailability of Pgp substrate-like drugs (PSLDs) remains a great challenge. Herein, we construct a nanocarrier system derived from Brij-grafted-chitosan (BC) to enhance the oral bioavailability and therapeutic effect of berberine (BBR, a typical PLSD) against diabetic kidney disease. The developed BC nanoparticles (BC-NPs) are demonstrated to improve the intestinal permeability of BBR via transiently and reversibly modulating the intercellular TJs (paracellular pathway) and Pgp-mediated drug efflux (transcellular pathway). As compared to free BBR and chitosan nanoparticles, the BC-NPs enhanced the relative oral bioavailability of BBR in rats (4.4- and 2.7-fold, respectively), and the therapeutic potency of BBR in renal function and histopathology. In summary, such strategy may provide an effective nanocarrier system for oral delivery of BBR and PSLDs.
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http://dx.doi.org/10.1016/j.carbpol.2021.118112DOI Listing
August 2021

Microvascular Changes in Macular Area After Phacoemulsification and Its Influencing Factors Assessed by Optical Coherence Tomography Angiography.

Ther Clin Risk Manag 2021 14;17:405-414. Epub 2021 May 14.

Department of Ophthalmology, Chaohu Hospital of Anhui Medical University, Hefei, 238000, Anhui, People's Republic of China.

Objective: To investigate macular vascular changes and underlying influencing factors using optical coherence tomography angiography (OCTA) after phacoemulsification in patients with cataracts.

Methods: Patients diagnosed with cataracts at the First Affiliated Hospital of Anhui Medical University from March to September 2019 were included. The macular retinal thickness, the microvascular density in the foveal, parafoveal, and perifoveal area, and the area of the foveal avascular zone (FAZ) were measured using OCTA at baseline, 1-week, 1-month, and 3-month post-operation.

Results: Forty-seven cataract patients (58 eyes) were eligible for this study. Compared with baseline thickness, the foveal, parafoveal, and perifoveal thicknesses, particularly in the inner retina, significantly increased at 1- and 3-month post-operation (P<0.05). There was a nonsignificant difference in the microvascular density of the foveal and perifoveal areas at 1-week, 1-month, and 3-month post-operation (P>0.05). At 1-month post-operation, the deep vessel density at the perifovea significantly increased (P<0.05). The FAZ area significantly diminished at 1- and 3-month post-operation compared with the baseline data (P<0.05).

Conclusion: Phacoemulsification offers a satisfactory efficacy response, with an increased macular thickness, reduced FAZ area, and nonsignificant changes in the microvascular density at the perifovea after surgery.
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http://dx.doi.org/10.2147/TCRM.S309679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131067PMC
May 2021

TPGS and chondroitin sulfate dual-modified lipid-albumin nanosystem for targeted delivery of chemotherapeutic agent against multidrug-resistant cancer.

Int J Biol Macromol 2021 Jul 15;183:1270-1282. Epub 2021 May 15.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Multidrug resistance (MDR) remains the primary issue leading to the failure of chemotherapy. In this study, a d-α-tocopherol polyethylene 1000 glycol succinate (TPGS) and chondroitin sulfate (CS) dual-modified lipid-albumin nanosystem was constructed for targeted delivery of paclitaxel (PTX) in treating MDR cancer. The obtained nanosystem (TLA/[email protected]) had an average size of around 176 nm and a negative zeta potential of around -18 mV. TPGS was confirmed to improve the intracellular accumulation of PTX and facilitate the mitochondrial-targeting of lipid-albumin nanosystem. Functionalized with the outer CS shell, TLA/[email protected] entered MDR breast cancer (MCF-7/MDR) cells via CD44 receptor-mediated endocytosis. CS shell was degraded by concentrated hyaluronidase in the lysosomes, thereby releasing PTX into cytoplasm and inhibiting cell proliferation. In vivo studies revealed that TLA/[email protected] possessed prolonged blood circulation, resulting in elevated tumor accumulation, excellent antitumor efficacy with a tumor inhibition ratio of 75.3%, and significant survival benefit in MCF-7/MDR tumor-bearing mice. Hence, this TPGS and CS dual-modified lipid-albumin nanosystem provides a promising strategy for targeted delivery of chemotherapeutic drug and reversal of MDR in cancer treatment.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.070DOI Listing
July 2021

PHC1 maintains pluripotency by organizing genome-wide chromatin interactions of the Nanog locus.

Nat Commun 2021 05 14;12(1):2829. Epub 2021 May 14.

Center of Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.

Polycomb group (PcG) proteins maintain cell identity by repressing gene expression during development. Surprisingly, emerging studies have recently reported that a number of PcG proteins directly activate gene expression during cell fate determination process. However, the mechanisms by which they direct gene activation in pluripotency remain poorly understood. Here, we show that Phc1, a subunit of canonical polycomb repressive complex 1 (cPRC1), can exert its function in pluripotency maintenance via a PRC1-independent activation of Nanog. Ablation of Phc1 reduces the expression of Nanog and overexpression of Nanog partially rescues impaired pluripotency caused by Phc1 depletion. We find that Phc1 interacts with Nanog and activates Nanog transcription by stabilizing the genome-wide chromatin interactions of the Nanog locus. This adds to the already known canonical function of PRC1 in pluripotency maintenance via a PRC1-dependent repression of differentiation genes. Overall, our study reveals a function of Phc1 to activate Nanog transcription through regulating chromatin architecture and proposes a paradigm for PcG proteins to maintain pluripotency.
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http://dx.doi.org/10.1038/s41467-021-22871-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121881PMC
May 2021

Lower regional grey matter in alcohol use disorders: evidence from a voxel-based meta-analysis.

BMC Psychiatry 2021 05 11;21(1):247. Epub 2021 May 11.

Mental Health Center, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China.

Background: Previous research using whole-brain neuroimaging techniques has revealed structural differences of grey matter (GM) in alcohol use disorder (AUD) patients. However, some of the findings diverge from other neuroimaging studies and require further replication. The quantity of relevant research has, thus far, been limited and the association between GM and abstinence duration of AUD patients has not yet been systematically reviewed.

Methods: The present research conducted a meta-analysis of voxel-based GM studies in AUD patients published before Jan 2021. The study utilised a whole brain-based d-mapping approach to explore GM changes in AUD patients, and further analysed the relationship between GM deficits, abstinence duration and individual differences.

Results: The current research included 23 studies with a sample size of 846 AUD patients and 878 controls. The d-mapping approach identified lower GM in brain regions including the right cingulate gyrus, right insula and left middle frontal gyrus in AUD patients compared to controls. Meta-regression analyses found increasing GM atrophy in the right insula associated with the longer mean abstinence duration of the samples in the studies in our analysis. GM atrophy was also found positively correlated with the mean age of the samples in the right insula, and positively correlated with male ratio in the left middle frontal gyrus.

Conclusions: GM atrophy was found in the cingulate gyrus and insula in AUD patients. These findings align with published meta-analyses, suggesting they are potential deficits for AUD patients. Abstinence duration, age and gender also affect GM atrophy in AUD patients. This research provides some evidence of the underlying neuroanatomical nature of AUD.
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http://dx.doi.org/10.1186/s12888-021-03244-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111920PMC
May 2021

Diabetes increases the risk of meningioma: A systematic review and meta-analysis of observational studies.

Cancer Epidemiol 2021 Aug 6;73:101946. Epub 2021 May 6.

Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. Electronic address:

Background: Increasing epidemiological evidence suggests that diabetes may be associated with meningioma risk, but the evidence supporting this association is still inconclusive. Therefore, we performed a meta-analysis of all eligible observational studies to evaluate the potential association of diabetes with meningioma risk.

Methods: A comprehensive literature search was performed in the PubMed, Web of Science and Cochrane Library databases up to November 30, 2020. A random-effects model was applied to calculate the pooled effect size (ES) and its 95 % confidence interval (CI).

Results: Eight studies were included in this study. In a random-effects pooled analysis, the results showed that DM (diabetes mellitus) increased the risk of meningioma (ES 1.17, 95 % CI: 1.02-1.35, P = 0.027). In subgroup analyses, DM increased the risk of meningioma in women (ES: 1.19, 95 % CI: 1.02-1.40, P = 0.027) and men (ES: 1.53, 95 % CI: 1.25-1.88, P = 0.000). This effect was not observed in the postmenopausal group (ES: 1.18, 95 % CI: 0.64-2.18, P = 0.597).

Conclusion: Our meta-analysis showed that DM increases the risk of meningioma, but the association was only present in some subgroups. This conclusion should be further confirmed.
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http://dx.doi.org/10.1016/j.canep.2021.101946DOI Listing
August 2021

Catalytic Synthesis of Atropisomeric -Terphenyls with 1,2-Diaxes via Axial-to-Axial Diastereoinduction.

J Am Chem Soc 2021 May 7;143(19):7253-7260. Epub 2021 May 7.

Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, and The Institute for Advanced Studies, Wuhan University, 430072 Wuhan, PR China.

Herein, we report a modular and convergent strategy for the assembly of atropisomeric -terphenyls with 1,2-diaxes via palladium/chiral norbornene cooperative catalysis and axial-to-axial diastereoinduction. Readily available aryl iodides, 2,6-substituted aryl bromides, and potassium aryl trifluoroborates are used as the building blocks, laying the foundation for diversity-oriented synthesis of these scaffolds (46 examples). Other features include the unique axial-to-axial diastereoinduction mode, construction of two axes in a single operation, and step economy. DFT calculations are performed to rationalize the axial-to-axial diastereoinduction process. Synthetic utilities of this method in preparation of atropisomeric oligophenyls, chiral catalysts, and ligands are demonstrated.
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http://dx.doi.org/10.1021/jacs.1c02405DOI Listing
May 2021

Correction to: Immunomodulatory effects of a new whole ingredients extract from Astragalus: a combined evaluation on chemistry and pharmacology.

Chin Med 2021 May 6;16(1):38. Epub 2021 May 6.

Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao, China.

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http://dx.doi.org/10.1186/s13020-021-00440-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101214PMC
May 2021

The transcriptional coactivator AF9 simultaneously sustains hypoxia tolerance and metabolic advantages in liver cancer.

Hepatology 2021 Apr 30. Epub 2021 Apr 30.

Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, 510006, China.

Proteins that recognize the epigenetic modifications function as mediators to interpret the epigenetic codes. Hypoxia response and metabolic rewiring are two major events during cancer progression. However, it's still unclear whether and how epigenetic regulator integrates hypoxia response and metabolism together. We data mined the clinical association of 33 histone Kac reader proteins with liver cancer and that AF9 is upregulated in cancer and correlates with tumor stage and poor prognosis. Conditional deletion of Af9 in mouse liver resulted in decreased tumor formation induced by c-Met/β-catenin. Loss of AF9 heavily impaired cell proliferation and completely blocked solid tumor formation. We further discovered AF9 formed a positive feedback circuit with HIF1α and also stabilized cMyc. Mechanically, AF9 interacted with HIF1α and targeted HIF1A promoter while AF9 recognized cMyc acetylation at K148, protected cMyc phosphorylation at S62 and then stabilized the cMyc which in turn upregulates PFKP expression. Otherwise, knockout of Af9 in mouse hepatocyte increased the infiltration of CD8+ T cells which is linked to the downregulation of LDHA. In conclusions, AF9 is upregulated to promote gene expression of hypoxia tolerance and glycolysis by simultaneously forming a complex with HIF1α and recognizing acetylated cMyc. Our results establish the oncogenic role of AF9 in human liver cancer, which could be a potential target for designing novel drugs against liver cancer.
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http://dx.doi.org/10.1002/hep.31870DOI Listing
April 2021

Saponins Modulate the Inflammatory Response and Improve IBD-Like Symptoms via TLR/NF-[Formula: see text]B and MAPK Signaling Pathways.

Am J Chin Med 2021 7;49(4):925-939. Epub 2021 Apr 7.

Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao 999078, P. R. China.

saponins (PNS) are the main active ingredients of (Burk) F. H. Chen, which are used as traditional Chinese medicine for thousands of years and have various clinical effects, including anti-inflammation, anti-oxidation, and cardiovascular protection. Inflammatory bowel disease (IBD) is a complex gastrointestinal inflammatory disease that cannot be cured completely nowadays. The anti-inflammatory and protective effects of PNS were analyzed and in dextran sulfate sodium (DSS)-induced colitis mouse model. PNS inhibited the release of nitric oxide (NO), tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text], interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) in Pam3CSK4-induced RAW 264.7 macrophages. In the animal study, compared with DSS-induced mice, PNS reduced the expression of pro-inflammatory cytokines (TNF-[Formula: see text], IL-6, and MCP-1) in the colon tissues. Furthermore, PNS treatment led to a remarkable reduction in the activation of the inhibitor of nuclear factor kappa-B kinase [Formula: see text]/[Formula: see text] (IKK[Formula: see text]/[Formula: see text], I[Formula: see text]B[Formula: see text] and p65 induced by DSS. On the other hand, PNS inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular regulated protein kinase 1/2 (ERK1/2). Taken together, our results suggested that PNS conferred profound protection for colitis mice through the downregulation of mitogen-activated protein kinase (MAPK) and NF-[Formula: see text]B signaling pathways, which were associated with reducing inflammatory responses, alleviating tissue damage, and maintaining of intestinal integrity and functionality.
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http://dx.doi.org/10.1142/S0192415X21500440DOI Listing
April 2021

Kinetic Resolution of Tertiary Benzyl Alcohols via Palladium/Chiral Norbornene Cooperative Catalysis.

Angew Chem Int Ed Engl 2021 06 6;60(23):12824-12828. Epub 2021 May 6.

Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, The Institute for Advanced Studies, Wuhan University, Wuhan, 430072, China.

Herein we report a highly enantioselective kinetic resolution of tertiary benzyl alcohols via palladium/chiral norbornene cooperative catalysis. With simple aryl iodides as the resolution reagent, a wide range of readily available racemic tertiary benzyl alcohols are applicable to this method. Both chiral tertiary benzyl alcohols and benzo[c]chromene products are obtained in good to excellent enantioselectivities (selectivity factor up to 544). The appealing synthetic utility of the obtained enantioenriched tertiary alcohols is demonstrated by the facile preparation of several valuable chiral heterocycles. Preliminary mechanism studies include DFT calculations to explain the origin of enantiodiscrimination and control experiments to uncover the formation of a transient axial chirality during the kinetic resolution step.
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http://dx.doi.org/10.1002/anie.202103428DOI Listing
June 2021

Cell-Free DNA: Hope and Potential Application in Cancer.

Front Cell Dev Biol 2021 22;9:639233. Epub 2021 Feb 22.

School of Medicine, Shanxi Datong University, Datong, China.

Cell-free DNA (cfDNA) is easily accessible in peripheral blood and can be used as biomarkers for cancer diagnostics, prognostics, and therapeutics. The applications of cfDNA in various areas of cancer management are attracting attention. In this review article, we discuss the potential relevance of using cfDNA analysis in clinical oncology, particularly in cancer screening, early diagnosis, therapeutic evaluation, monitoring disease progression; and determining disease prognosis.
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http://dx.doi.org/10.3389/fcell.2021.639233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938321PMC
February 2021

Association Analysis Between Catechol-O-Methyltransferase Expression and Cognitive Function in Patients with Schizophrenia, Bipolar Disorder, or Major Depression.

Neuropsychiatr Dis Treat 2021 22;17:567-574. Epub 2021 Feb 22.

The Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.

Introduction: Schizophrenia, bipolar disorder (BD), and major depressive disorder are three common mental disorders. Although their diagnosis and treatment differ, they partially overlap.

Methods: To explore the similarities and characteristics of these three psychiatric diseases, an intelligence quotient (IQ) assessment was performed to evaluate cognitive deficits. Relative catechol-O-methyltransferase () expression in peripheral blood mononuclear cells was examined in all three groups compared with healthy controls (HCs).

Results: The results indicated that patients with any of the three psychiatric diseases presented IQ deficits, and that the first-episode schizophrenia (FES) group had even lower cognitive function than the other two groups. The relative expression decreased in the FES group and increased in the BD group compared with the HC group. The correlation analysis of expression level and IQ scores showed a positive correlation between relative expression and full-scale IQ in the HC group. However, this correlation disappeared in all three psychiatric diseases studied.

Conclusion: In conclusion, this cross-disease strategy provided important clues to explain lower IQ scores and dysregulated expression among three common mental illnesses.
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http://dx.doi.org/10.2147/NDT.S286102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910219PMC
February 2021

Prognostic Nomogram for Sorafenib Benefit in Hepatitis B Virus-Related Hepatocellular Carcinoma After Partial Hepatectomy.

Front Oncol 2020 11;10:605057. Epub 2021 Feb 11.

Department of Pathology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China.

Background: Predicting the long-term prognosis of individuals who experienced sorafenib treatment following partial hepatectomy due to hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) is difficult. This work aims to create an effective prognostic nomogram for HBV related HCC patients who are receiving sorafenib treatment as adjuvant therapy after surgery.

Methods: A total of 233 HBV-related HCC patients treated with or without sorafenib following partial hepatectomy at the Eastern Hepatobiliary Surgery Hospital from 2008 to 2013 were matched with propensity score matching analysis. The optimal cut-off point of the overall survival (OS) factor level was determined by x-tile. The selection of indicators was based on clinical findings. The Cox regression model with an interaction term was employed for evaluating the predictive value. Using a multivariate Cox proportional hazards model, a nomogram was subsequently formulated to analyze 111 patients treated with sorafenib. The nomogram's discriminative ability and predictive accuracy were determined using the concordance index (C-index), calibration, and ROC curve.

Results: The matched sorafenib cohort of 111 patients and control cohort of 118 patients were analyzed. Subgroup analysis revealed that low GPC3, pERK, pAKT, serum AFP levels, without MVI, under 50 years old, male, TNM stage I/II and BCLC stage 0/A were significantly associated with a better OS in patients subjected to sorafenib treatment compared to those without sorafenib treatment after surgery. Multivariate analysis of the sorafenib cohort revealed GPC3, pERK, pAKT, serum AST, and BCLC stage as independent factors for OS, and all were included in the nomogram. The survival probability based on the calibration curve showed that the prediction of the nomogram was in good agreement with the actual observation. The C-index of the nomogram for predicting survival was 0.73(95% CI, 0.67-0.78). The area under the ROC curve (AUC) for the nomogram to predict the survival for 1, 3, and 5-year was 0.726, 0.816, and 0.823, respectively.

Conclusion: This proposed nomogram shows the potential to make a precise prediction regarding the prognosis of HBV-related HCC patients and may help to stratify patients for personalized therapy following partial hepatectomy.
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http://dx.doi.org/10.3389/fonc.2020.605057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906076PMC
February 2021

Specific NLRP3 inflammasome inhibitors: promising therapeutic agents for inflammatory diseases.

Drug Discov Today 2021 Jun 23;26(6):1394-1408. Epub 2021 Feb 23.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. Electronic address:

Innate immunity serves as a first line of defence against danger signals, invading pathogens and microbes. The inflammasomes, as pattern recognition receptors, sense these danger signals to initiate pro-inflammatory cascades. The nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3) inflammasome is the most well characterised inflammasome, and its aberrant activation is implicated in many inflammatory diseases. In the past decade, targeting the NLRP3 inflammasome has become an emerging strategy for inflammatory diseases. To avoid off-target immunosuppressive effects, specific NLRP3 inhibitors have been developed and show promising therapeutic effects. This review discusses the therapeutic effects and clinical perspectives of specific NLRP3 inhibitors, as well as recent progress in the development of these inhibitors for the treatment of inflammatory diseases.
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http://dx.doi.org/10.1016/j.drudis.2021.02.018DOI Listing
June 2021
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