Publications by authors named "Hua Fang"

537 Publications

Leaked Mitochondrial C1QBP Inhibits Activation of the DNA Sensor cGAS.

J Immunol 2021 Sep 15. Epub 2021 Sep 15.

Department of Microbiology and Immunology, Tulane University, New Orleans, LA; and

Cytosolic DNA from pathogens activates the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) that produces the second messenger, cGAMP. cGAMP triggers a signal cascade leading to type I IFN expression. Host DNA is normally restricted in the cellular compartments of the nucleus and mitochondria. Recent studies have shown that DNA virus infection triggers mitochondrial stress, leading to the release of mitochondrial DNA to the cytosol and activation of cGAS; however, the regulatory mechanism of mitochondrial DNA-mediated cGAS activation is not well elucidated. In this study, we analyzed cGAS protein interactome in mouse RAW264.7 macrophages and found that cGAS interacted with C1QBP. C1QBP predominantly localized in the mitochondria and leaked into the cytosol during DNA virus infection. The leaked C1QBP bound the NTase domain of cGAS and inhibited cGAS enzymatic activity in cells and in vitro. Overexpression of the cytosolic form of C1QBP inhibited cytosolic DNA-elicited innate immune responses and promoted HSV-1 infection. By contrast, deficiency of C1QBP led to the elevated innate immune responses and impaired HSV-1 infection. Taken together, our study suggests that C1QBP is a novel cGAS inhibitor hidden in the mitochondria.
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http://dx.doi.org/10.4049/jimmunol.2100392DOI Listing
September 2021

Preliminary Study on Antifungal Mechanism of Aqueous Extract of Against .

Front Microbiol 2021 19;12:707174. Epub 2021 Aug 19.

Department of Emergency and Critical Care Medicine, Pudong New Area People' s Hospital, Shanghai, China.

Trichoderma rubrum (T. rubrum) is one of the important pathogens because it is the cause of most dermatomycosis. The treatment of infection is time-consuming and very expensive; it is easy for the infections to reoccur, leading to therapeutic failures, persistence, and chronic infection. These issues have inspired researchers to study natural alternative therapies instead. (L.), as a kind of traditional Chinese medicine, has a variety of pharmacological activities and a wide range of applications, so it has a high potential for researching and economic value. We detected the effect of aqueous extract of (L.) on the activity of by Cell Count Kit-8 assay (CCK-8), and we found that 128 and 256 μg/ml of aqueous extracts of (L.) co-cultured with for 24 h showed the inhibitory effect on . The results of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed that aqueous extract of (L.) damaged the . At the same time, mass spectrometry screening with before and after the treatment of 256 μg/ml of aqueous extracts of (L.) showed that 966 differentially expressed proteins were detected, including 524 upregulated differentially expressed genes (DEGs) and 442 downregulated DEGs. The most significantly downregulated protein was chitin synthase (CHS); and the results of qRT-PCR and Western blotting demonstrated that the expression level of CHS was downregulated in the 256 μg/ml group compared with the control group. The study showed that the aqueous extract of (L.) could destroy the morphology of mycelia and the internal structure of , and it could inhibit the growth of . The antifungal effect of aqueous extract of (L.) may be related to the downregulation of the expression of CHS in , and CHS may be one of the potential targets of its antifungal mechanism. We concluded that aqueous extract from (L.) may be a potential candidate for antifungal agents.
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http://dx.doi.org/10.3389/fmicb.2021.707174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417377PMC
August 2021

Rapid maxillary expansion may increase the upper airway volume of growing patients with maxillary transverse deficiency.

J Evid Based Dent Pract 2021 09 29;21(3):101579. Epub 2021 Apr 29.

Article Title And Bibliographic Information: Niu X, Di Carlo G, Cornelis MA, Cattaneo PM. Three-dimensional analyses of short- and long-term effects of rapid maxillary expansion on nasal cavity and upper airway: A systematic review and meta-analysis. Orthod Craniofac Res. 2020 Aug;23(3):250-276. doi: 10.1111/ocr.12378. Epub 2020 May 5. PMID: 32248642.

Source Of Funding: China Scholar Council TYPE OF STUDY/DESIGN: Systematic review with meta-analysis.
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http://dx.doi.org/10.1016/j.jebdp.2021.101579DOI Listing
September 2021

Betanin Prevents Experimental Abdominal Aortic Aneurysm Progression by Modulating the TLR4/NF-κB and Nrf2/HO-1 Pathways.

Biol Pharm Bull 2021 ;44(9):1254-1262

Department of Vascular Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University.

Betanin, a bioactive ingredient mostly isolated from beetroots, exhibits a protective effect against cardiovascular diseases. However, its effects on abdominal aortic aneurysm (AAA) have not been elucidated. In this study, an AAA model was constructed by infusion of porcine pancreatic elastase in C57BL/6 mice. Mice were then administered with betanin or saline intragastrically once daily for 14 d. Our results showed that treatment with betanin remarkably limited AAA enlargement and mitigated the infiltration of inflammatory cells in the adventitia. The increased expression of proinflammatory cytokines and matrix metalloproteinases (MMPs) was also significantly alleviated following betanin treatment. Furthermore, betanin suppressed the activation of toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-κB) signaling in the aortic wall, and downregulated the levels of tissue-reactive oxygen species as well as circulating 8-isoprostane by stimulating the nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Taken together, these data suggest that betanin may attenuate AAA progression and may be used as a therapeutic drug against AAA.
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http://dx.doi.org/10.1248/bpb.b21-00042DOI Listing
January 2021

Automated Adenoid Hypertrophy Assessment with Lateral Cephalometry in Children Based on Artificial Intelligence.

Diagnostics (Basel) 2021 Jul 31;11(8). Epub 2021 Jul 31.

Department of Orthodontics, Hubei-MOST KLOS & KLOBM, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.

Adenoid hypertrophy may lead to pediatric obstructive sleep apnea and mouth breathing. The routine screening of adenoid hypertrophy in dental practice is helpful for preventing relevant craniofacial and systemic consequences. The purpose of this study was to develop an automated assessment tool for adenoid hypertrophy based on artificial intelligence. A clinical dataset containing 581 lateral cephalograms was used to train the convolutional neural network (CNN). According to Fujioka's method for adenoid hypertrophy assessment, the regions of interest were defined with four keypoint landmarks. The adenoid ratio based on the four landmarks was used for adenoid hypertrophy assessment. Another dataset consisting of 160 patients' lateral cephalograms were used for evaluating the performance of the network. Diagnostic performance was evaluated with statistical analysis. The developed system exhibited high sensitivity (0.906, 95% confidence interval [CI]: 0.750-0.980), specificity (0.938, 95% CI: 0.881-0.973) and accuracy (0.919, 95% CI: 0.877-0.961) for adenoid hypertrophy assessment. The area under the receiver operating characteristic curve was 0.987 (95% CI: 0.974-1.000). These results indicated the proposed assessment system is able to assess AH accurately. The CNN-incorporated system showed high accuracy and stability in the detection of adenoid hypertrophy from children' lateral cephalograms, implying the feasibility of automated adenoid hypertrophy screening utilizing a deep neural network model.
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http://dx.doi.org/10.3390/diagnostics11081386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394806PMC
July 2021

The chemokine CCL1 triggers an AMFR-SPRY1 pathway that promotes differentiation of lung fibroblasts into myofibroblasts and drives pulmonary fibrosis.

Immunity 2021 Sep 17;54(9):2042-2056.e8. Epub 2021 Aug 17.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address:

Recruitment of immune cells to the site of inflammation by the chemokine CCL1 is important in the pathology of inflammatory diseases. Here, we examined the role of CCL1 in pulmonary fibrosis (PF). Bronchoalveolar lavage fluid from PF mouse models contained high amounts of CCL1, as did lung biopsies from PF patients. Immunofluorescence analyses revealed that alveolar macrophages and CD4 T cells were major producers of CCL1 and targeted deletion of Ccl1 in these cells blunted pathology. Deletion of the CCL1 receptor Ccr8 in fibroblasts limited migration, but not activation, in response to CCL1. Mass spectrometry analyses of CCL1 complexes identified AMFR as a CCL1 receptor, and deletion of Amfr impaired fibroblast activation. Mechanistically, CCL1 binding triggered ubiquitination of the ERK inhibitor Spry1 by AMFR, thus activating Ras-mediated profibrotic protein synthesis. Antibody blockade of CCL1 ameliorated PF pathology, supporting the therapeutic potential of targeting this pathway for treating fibroproliferative lung diseases.
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http://dx.doi.org/10.1016/j.immuni.2021.06.008DOI Listing
September 2021

The presence and characteristics of 'spin' among randomized controlled trial abstracts in orthodontics.

Eur J Orthod 2021 Aug 16. Epub 2021 Aug 16.

Hubei-MOST KLOS & KLOBM, School & Hospital of Stomatology, Wuhan University, China.

Objectives: To identify the presence and characteristics of spin (using reporting strategies to distort study results and mislead readers) within randomized controlled trial (RCT) abstracts published in orthodontic journals, and to explore the association between spin and potentially related factors.

Methods: A manual search was conducted to identify abstracts of RCTs with statistically non-significant primary outcomes published in five leading orthodontic journals between 2015 and 2020. Spin in the Results and Conclusions sections of each included abstract was evaluated and categorized according to pre-determined spin strategies. Logistic regression analyses were employed to explore the association between spin and relevant factors.

Results: A total of 111 RCT abstracts were included, of which 69 (62.2 per cent) were identified with spin. In the Results section, 47 (42.3 per cent) abstracts had spin, and 'focusing on significant within-group comparison for primary outcomes' was the most frequent spin strategy. In the Conclusions section, 57 (51.4 per cent) abstracts presented spin, with the most common strategy being 'claiming equivalence or non-inferiority for statistically nonsignificant results'. According to multivariable logistic regression analysis, a significantly lower presence of spin was found in studies with international collaboration (odds ratio [OR]: 0.331, 95 per cent confidence interval [CI]: 0.120-0.912, P = 0.033) and trial registration (OR: 0.336, 95 per cent CI: 0.117-0.962, P = 0.042).

Conclusion: The prevalence of spin is high among RCT abstracts in orthodontics. Clinicians need to be aware of the definition and presence of spin. Concerted efforts are needed from researchers and other stakeholders to address this issue.
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http://dx.doi.org/10.1093/ejo/cjab044DOI Listing
August 2021

Emissions and light absorption of carbonaceous aerosols from on-road vehicles in an urban tunnel in south China.

Sci Total Environ 2021 Oct 2;790:148220. Epub 2021 Jun 2.

State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Protection and Resources Utilization, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China; CAS Center for Excellence in Deep Earth Science, Guangzhou 510640, China; Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

With changing numbers, compositions, emission standards and fuel quality of on-road vehicles, it is imperative to accordingly characterize and update vehicular emissions of carbonaceous aerosols for better understanding their health and climatic effects. In this study, a 7-day field campaign was conducted in 2019 in a busy urban tunnel (>30,000 vehicles day) in south China with filter-based aerosol samples collected every 2 h at both the inlet and the outlet for measuring carbonaceous aerosols and their light absorbing properties. Observed fleet average emission factor (EF) of total carbon (TC) was 13.4 ± 8.3 mg veh km, and 17.4 ± 11.3 mg veh km if electric and LPG-driven vehicles were excluded; and fleet average EF of organic carbon (OC) and elemental carbon (EC) was 8.5 ± 6.6 and 4.9 ± 2.6 mg veh km (11.0 ± 8.8 and 6.3 ± 3.6 mg veh km if excluding electric and LPG vehicles), respectively. Regression analysis revealed an average TC-EF of 319.8 mg veh km for diesel vehicles and 2.1 mg veh km for gasoline vehicles, and although diesel vehicles only shared ~4% in the fleet compositions, they still dominate on-road vehicular carbonaceous aerosol emissions due to their over 150 times higher average TC-EF than gasoline vehicles. Filter-based light absorption measurement demonstrated that on average brown carbon (BrC) could account for 19.1% of the total carbonaceous light absorption at 405 nm, and the average mass absorption efficiency of EC at 635 nm and that of OC at 405 nm were 5.2 m g C and 1.0 m g C, respectively.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148220DOI Listing
October 2021

Effect of microincisional cataract surgery on inflammatory indicators in tears and corneal endothelial cells in cataract patients.

Authors:
Hangzhu Li Hua Fang

Am J Transl Res 2021 15;13(7):7705-7714. Epub 2021 Jul 15.

Department of Ophthalmology, The First People's Hospital of Fuyang Hangzhou Hangzhou 311400, Zhejiang, China.

Objective: To analyze the effect of microincisional cataract surgery on inflammation in tears and corneal endothelial cells in cataract patients.

Methods: A total of 103 patients with cataracts in our hospital were enrolled and randomly divided into group A (n=52) and group B (n=51) by a random double-blind lottery. Group A received 1.8 mm coaxial microincision cataract surgery (C-MICS) while group B received 3.0 mm C-MICS, and the efficacy was compared between the two groups.

Results: Average ultrasound energy (AVG), accumulative phaco time (APT), and effective phaco time (EPT) did not differ between groups ( > 0.05). Group A exhibited higher interleukin-2 (IL-2) levels at 5 days postoperatively and lower interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and tumor necrosis factor-β1 (TNF-β1) levels than group B ( < 0.05). The density of corneal endothelial cells, coefficient of variation, and percentage of hexagonal cells showed no significant difference in both groups at 5 days postoperatively ( > 0.05). Group A had higher visual acuity and lower visual acuity loss, visual fatigue, foreign body sensation, tingling, and photophobia scores than group B at 7, 14, and 28 days postoperatively ( < 0.05). The tear film break-up time (TBUT) in group A was longer than that in group B at 7, 14, and 28 days postoperatively, and the tear secretion length (in mm) on the strip in group A was longer than that in group B at 14 and 28 days postoperatively ( < 0.05).

Conclusion: Compared with other types of similar surgery, C-MICS can significantly control inflammation levels, with less effect on corneal endothelial cells, improve postoperative visual acuity, delay tear film break-up, increase tear secretion, and improve dry eye syndrome.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340243PMC
July 2021

Extracellular Mitochondrial Components and Effects on Cardiovascular Disease.

DNA Cell Biol 2021 Sep 7;40(9):1131-1143. Epub 2021 Aug 7.

Department of Cardiology, Wuxi Huishan District People's Hospital, Wuxi, China.

Besides being powerhouses of the cell, mitochondria released into extracellular space act as intercellular signaling. Mitochondria and their components mediate cell-to-cell communication in free form or embedded in a carrier. The pathogenesis of cardiovascular disease is complex, which shows close relationship with inflammation and metabolic abnormalities. Since mitochondria sustain optimal function of the heart, extracellular mitochondria are emerging as a key regulator in the development of cardiovascular disease. In this review, we provide recent findings in the presence and forms of mitochondria transfer between cells, as well as the effects of these mitochondria on vascular inflammation and ischemic myocardium. Mitochondrial transplantation is a novel treatment paradigm for patients suffering from acute cardiovascular accident and challenges the traditional methods of mitochondria isolation.
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http://dx.doi.org/10.1089/dna.2021.0087DOI Listing
September 2021

Outcomes used in trials regarding the prevention and treatment of orthodontically induced white spot lesions: A scoping review.

Am J Orthod Dentofacial Orthop 2021 Aug 5. Epub 2021 Aug 5.

Department of Orthodontics, School and Hospital of Stomatology, Hubei-MOST KLOS & KLOBM, Wuhan University, Wuhan, China. Electronic address:

Introduction: The objective was to identify and summarize the outcomes and evaluation methods used in clinical trials regarding the prevention and treatment of orthodontically induced white spot lesions (WSLs).

Methods: Three electronic databases were searched to identify studies that were (1) clinical trials on prevention and/or treatment of orthodontically induced WSLs, (2) reported in English, and (3) published between January 2010 and October 2019. At least 2 authors assessed the eligibility and extracted the characteristics, outcomes, and evaluation methods from included studies. All disagreements were resolved through discussion.

Results: Among 1328 studies identified, 51 were eligible and included. A total of 48 different outcomes and 11 different evaluation methods were used in these studies. The most frequently used outcomes were WSLs clinical visual examination scores (n = 22, 43.1%), DIAGNOdent values (n = 14; 27.5%), fluorescence loss measured with quantitative light-induced fluorescence (QLF) (n = 10; 19.6%), and lesion area measured with QLF (n = 10; 19.6%). The most frequently used evaluation methods were clinical examination (n = 25; 49.0%), visual inspection by photographs (n = 15; 29.4%), DIAGNOdent (n = 14; 27.5%), and QLF (n = 10; 19.6%). None of the included studies reported data on quality of life.

Conclusions: Substantial outcome heterogeneity exists among studies regarding the prevention and treatment of orthodontically induced WSLs. Most of the identified outcomes are aimed to assess morphologic changes of WSLs and may not reflect patient perspectives.

Registration: The Core Outcome Set for trials on the prevention and treatment of enamel White Spot Lesions (COS-WSL) project was registered in the COMET Initiative database (No. 1399).
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http://dx.doi.org/10.1016/j.ajodo.2021.04.018DOI Listing
August 2021

The circular RNA circINPP4B acts as a sponge of miR-30a to regulate Th17 cell differentiation during progression of experimental autoimmune encephalomyelitis.

Cell Mol Immunol 2021 Sep 6;18(9):2177-2187. Epub 2021 Aug 6.

Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.

Circular RNAs (circRNAs) regulate gene expression and participate in various biological and pathological processes. However, little is known about the effects of specific circRNAs on T helper cell 17 (Th17) differentiation and related autoimmune diseases, such as multiple sclerosis (MS). Here, using transcriptome microarray analysis at different stages of experimental autoimmune encephalomyelitis (EAE), we identified the EAE progression-related circINPP4B, which showed upregulated expression in Th17 cells from mice with EAE and during Th17 differentiation in vitro. Silencing of circINPP4B inhibited Th17 differentiation and alleviated EAE, characterized by less demyelination and Th17 infiltration in the spinal cord. Mechanistically, circINPP4B served as a sponge that directly targeted miR-30a to regulate Th17 differentiation. Furthermore, circINPP4B levels were associated with the developing phases of clinical relapsing-remitting MS patients. Our results indicate that circINPP4B plays an important role in promoting Th17 differentiation and progression of EAE by targeting miR-30a, which provides a potential diagnostic and therapeutic target for Th17-mediated MS.
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http://dx.doi.org/10.1038/s41423-021-00748-yDOI Listing
September 2021

Secondary organic aerosols produced from photochemical oxidation of secondarily evaporated biomass burning organic gases: Chemical composition, toxicity, optical properties, and climate effect.

Environ Int 2021 Jul 31;157:106801. Epub 2021 Jul 31.

Department of Earth and Planetary Sciences, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address:

Biomass burning (BB) is an important source of primary organic aerosols (POA). These POA contain a significant fraction of semivolatile organic compounds, and can release them into the gas phase during the dilution process in transport. Such evaporated compounds were termed "secondarily evaporated BB organic gases (SBB-OGs)" to distinguish them from the more studied primary emissions. SBB-OGs contribute to the formation of secondary organic aerosols (SOA) through reactions with atmospheric oxidants, and thus may influence human health and the Earth's radiation budget. In this study, tar materials collected from wood pyrolysis were taken as proxies for POA from smoldering-phase BB and were used to release SBB-OGs constantly in the lab. OH-initiated oxidation of the SBB-OGs in the absence of NO was investigated using an oxidation flow reactor, and the chemical, optical, and toxicological properties of SOA were comprehensively characterized. Carbonyl compounds were the most abundant species in identified SOA species. Human lung epithelial cells exposed to an environmentally relevant dose of the most aged SOA did not exhibit detectable cell mortality. The oxidative potential of SOA was characterized with the dithiothreitol (DTT) assay, and its DTT consumption rate was 15.5 ± 0.5 pmol min μg. The SOA present comparable light scattering to BB-POA, but have lower light absorption with imaginary refractive index less than 0.01 within the wavelength range of 360-600 nm. Calculations based on Mie theory show that pure airborne SOA with atmospherically relevant sizes of 50-400 nm have a cooling effect; when acting as the coating materials, these SOA can counteract the warming effect brought by airborne black carbon aerosol.
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http://dx.doi.org/10.1016/j.envint.2021.106801DOI Listing
July 2021

Protocol for the development of a Core Outcome Set for trials on the prevention and treatment of Orthodontically induced enamel White Spot Lesions (COS-OWSL).

Trials 2021 Jul 31;22(1):507. Epub 2021 Jul 31.

Department of Orthodontics, School & Hospital of Stomatology, Wuhan University, Luoyu Rd. 237, Wuhan, 430079, China.

Background: Enamel white spot lesions (WSLs), characterized by an opaque, matt, and chalky white appearance of enamel, are a sign of incipient caries. WSLs are common in orthodontic practice and can affect both the oral health and dental aesthetics of patients. Extensive studies have been conducted to evaluate the effectiveness of prevention or treatment for orthodontically induced enamel WSLs. However, substantial heterogeneity has been found in the outcomes used for the prevention and treatment of WSLs in literature, which prevents researchers from comparing and combining the results of different studies to draw more decisive conclusions. Therefore, we aim to develop a Core Outcome Set for trials on the prevention and treatment of Orthodontically induced enamel White Spot Lesions (COS-OWSL).

Methods: The development of COS-OWSL comprises four phases: (1) a scoping review to identify and summarize all existing outcomes that have been used in trials on the prevention or treatment of orthodontically induced WSLs; (2) qualitative interviews with orthodontic patients without (for prevention) and with WSL-affected teeth (for treatment) and relevant dental professionals to identify additional outcomes relevant to them; (3) Delphi surveys to collect opinions from key stakeholders including patients, dental professionals, and researchers and to reach a preliminary consensus; and (4) a consensus meeting to develop the final COS-OWSL.

Discussion: The COS-OWSL will be developed to facilitate the synthesis of evidence regarding the prevention and treatment of orthodontically induced WSLs and to promote the consistent use of relevant patient-important outcomes among future studies in this field.

Trial Registration: Core Outcome Measures in Effectiveness Trials (COMET) initiative (the COS-WSL project) 1399.
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http://dx.doi.org/10.1186/s13063-021-05371-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325281PMC
July 2021

FIP200 restricts RNA virus infection by facilitating RIG-I activation.

Commun Biol 2021 07 29;4(1):921. Epub 2021 Jul 29.

Department of Microbiology and Immunology, Tulane University, New Orleans, LA, USA.

Retinoic acid-inducible gene I (RIG-I) senses viral RNA and instigates an innate immune signaling cascade to induce type I interferon expression. Currently, the regulatory mechanisms controlling RIG-I activation remain to be fully elucidated. Here we show that the FAK family kinase-interacting protein of 200 kDa (FIP200) facilitates RIG-I activation. FIP200 deficiency impaired RIG-I signaling and increased host susceptibility to RNA virus infection. In vivo studies further demonstrated FIP200 knockout mice were more susceptible to RNA virus infection due to the reduced innate immune response. Mechanistic studies revealed that FIP200 competed with the helicase domain of RIG-I for interaction with the two tandem caspase activation and recruitment domains (2CARD), thereby facilitating the release of 2CARD from the suppression status. Furthermore, FIP200 formed a dimer and facilitated 2CARD oligomerization, thereby promoting RIG-I activation. Taken together, our study defines FIP200 as an innate immune signaling molecule that positively regulates RIG-I activation.
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http://dx.doi.org/10.1038/s42003-021-02450-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322336PMC
July 2021

Physiological Responses of Cucumber Seedlings to Different Supplemental Light Duration of Red and Blue LED.

Front Plant Sci 2021 12;12:709313. Epub 2021 Jul 12.

College of Horticulture, Gansu Agricultural University, Lanzhou, China.

Normal development of plants is inhibited by inadequate light in winter in greenhouses in Northwest China. Growth lamps, using light-emitting diodes (LEDs) with red blue light (7R2B), were used to supplement daylight for 1, 2, and 3 h. Seedling growth, photosynthesis, and photosynthetic product; the Calvin cycle key and sugar metabolism-related enzymes and their encoding genes; and the light signal sensing regulation of key gene expression were studied in greenhouse cucumbers under three treatments to determine the best supplemental light durations to enhance cucumber cultivation in greenhouses in winter. Treatment with LED red and blue light for 3 h significantly promoted the growth and development of cucumbers, root growth, and dry matter accumulation. It improved the photosynthetic rate, photosynthetic pigment content, and light energy utilization efficiency in cucumbers. Supplementation with red and blue LED light for 3 h upregulated the expression levels of key genes encoding the Calvin cycle and enzymes related to sugar metabolism in cucumber leaves, which promoted the synthesis and accumulation of photosynthates. The expression levels of phytochrome B, cryptochrome 1, and hypocotyl 5 in the cucumber leaves were also significantly upregulated after 3 h of light supplementation. Combined LED red and blue light for 3 h should be used to supplement natural light to enhance the cucumber cultivation in greenhouses in winter.
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http://dx.doi.org/10.3389/fpls.2021.709313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311605PMC
July 2021

Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis.

Mol Med 2021 07 15;27(1):77. Epub 2021 Jul 15.

Department of Anesthesiology, Guizhou Provincial People's Hospital, No. 83, East Zhongshan Road, Guiyang, Guizhou, 550002, People's Republic of China.

Background: Propofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β).

Methods: C57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured.

Results: Our experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression.

Conclusion: Overall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.
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http://dx.doi.org/10.1186/s10020-021-00332-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281462PMC
July 2021

Biting pain reproduced by the Tooth Slooth: aid for early diagnosis of cracked tooth.

Quintessence Int 2021 Jul 8;0(0). Epub 2021 Jul 8.

Objective: The purpose of this study was to find a reliable method to reproduce biting pain to facilitate an early diagnosis of cracked tooth and to verify the feasibility of the Tooth Slooth in diagnosing a cracked tooth.

Method And Materials: In this study, 46 intact teeth diagnosed as cracked teeth were selected. Patients were asked to bite wet cotton rolls and the Tooth Slooth, and clinical findings were recorded. The difference in the relevance ratio between these two bite test methods was determined.

Results: The relevance ratio of biting pain by the Tooth Slooth and wet cotton rolls was 91.3% and 32.6%, respectively. There was a statistically significant difference between these two bite tests (P < .001).

Conclusions: Within the limitations of this study, the relevance ratio of biting pain by the Tooth Slooth was significantly higher than that of the wet cotton rolls. The Tooth Slooth was a reliable method to reproduce biting pain and was useful for early diagnosis of cracked teeth.
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http://dx.doi.org/10.3290/j.qi.a41498DOI Listing
July 2021

Abstracts for reports of randomised trials of COVID-19 interventions had low quality and high spin.

J Clin Epidemiol 2021 Jul 2:107-120. Epub 2021 Jul 2.

Northern Ireland Clinical Trials Unit and Methodology Hub, Centre for Public Health, Queen's University Belfast, Belfast, UK. Electronic address:

Objectives: To assess the reporting quality of abstracts for published randomized controlled trials (RCTs) of interventions for coronavirus disease 2019 (COVID-19), including the use of spin strategies and the level of spin for RCTs with statistically non-significant primary outcomes, and to explore potential predictors for reporting quality and the severity of spin.

Study Design And Setting: PubMed was searched to find RCTs that tested interventions for COVID-19, and the reporting quality and spin in the abstracts were assessed. Linear regression analyses were used to identify potential predictors.

Results: Forty RCT abstracts were included in our assessment of reporting quality, and a higher word count in the abstract was significantly correlated with higher reporting scores (95% CI 0.044 to 0.658, P=0.026). Multiple spin strategies were identified. Our multivariate analyses showed that geographical origin was associated with severity of spin, with research from non-Asian regions containing fewer spin strategies (95% CI -0.760 to -0.099, P=0.013).

Conclusions: The reporting quality of abstracts of RCTs of interventions for COVID-19 is far from satisfactory. A relatively high proportion of the abstracts contained spin, and the findings reported in the results and conclusion sections of these abstracts need to be interpreted with caution.
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http://dx.doi.org/10.1016/j.jclinepi.2021.06.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253697PMC
July 2021

The Effect of Periodontitis on Dementia and Cognitive Impairment: A Meta-Analysis.

Int J Environ Res Public Health 2021 06 25;18(13). Epub 2021 Jun 25.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.

The association between periodontal disease and dementia/cognitive impairment continues to receive increasing attention. However, whether periodontal disease is a risk factor for dementia/cognitive impairment is still uncertain. This meta-analysis was conducted to comprehensively analyze the effect of periodontitis on dementia and cognitive impairment, and to assess the periodontal status of dementia patients at the same time. A literature search was undertaken on 19 October 2020 using PubMed, Web of Science, and Embase with different search terms. Two evaluators screened studies according to inclusion and exclusion criteria, and a third evaluator was involved if there were disagreements; this process was the same as that used for data extraction. Included studies were assessed with the Newcastle-Ottawa Scale (NOS), and results were analyzed using software Review Manager 5.2. Twenty observational studies were included. In the comparison between periodontitis and cognitive impairment, the odds ratio (OR) was 1.77 (95% confidence interval (CI), 1.31-2.38), which indicated that there was a strong relationship between periodontitis and cognitive impairment. There was no statistical significance in the effect of periodontitis on dementia (OR = 1.59; 95%CI, 0.92-2.76). The subgroup analysis revealed that moderate or severe periodontitis was significantly associated with dementia (OR = 2.13; 95%CI, 1.25-3.64). The mean difference (MD) of the community periodontal index (CPI) and clinical attachment level (CAL) was 0.25 (95%CI, 0.09-0.40) and 1.22 (95%CI, 0.61-1.83), respectively. In this meta-analysis, there was an association between periodontitis and cognitive impairment, and moderate or severe periodontitis was a risk factor for dementia. Additionally, the deterioration of periodontal status was observed among dementia patients.
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http://dx.doi.org/10.3390/ijerph18136823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297088PMC
June 2021

Optimization of Model Training Based on Iterative Minimum Covariance Determinant In Motor-Imagery BCI.

Int J Neural Syst 2021 Jul 26;31(7):2150030. Epub 2021 Jun 26.

Skolkowo Institute of Science and Technology (SKOLTECH), 143026 Moscow, Russia.

The common spatial patterns (CSP) algorithm is one of the most frequently used and effective spatial filtering methods for extracting relevant features for use in motor imagery brain-computer interfaces (MI-BCIs). However, the inherent defect of the traditional CSP algorithm is that it is highly sensitive to potential outliers, which adversely affects its performance in practical applications. In this work, we propose a novel feature optimization and outlier detection method for the CSP algorithm. Specifically, we use the minimum covariance determinant (MCD) to detect and remove outliers in the dataset, then we use the Fisher score to evaluate and select features. In addition, in order to prevent the emergence of new outliers, we propose an iterative minimum covariance determinant (IMCD) algorithm. We evaluate our proposed algorithm in terms of iteration times, classification accuracy and feature distribution using two BCI competition datasets. The experimental results show that the average classification performance of our proposed method is 12% and 22.9% higher than that of the traditional CSP method in two datasets ([Formula: see text]), and our proposed method obtains better performance in comparison with other competing methods. The results show that our method improves the performance of MI-BCI systems.
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http://dx.doi.org/10.1142/S0129065721500301DOI Listing
July 2021

No correlation between acetylcholine receptor antibody concentration and individual clinical symptoms of myasthenia gravis: A systematic retrospective study involving 67 patients.

Brain Behav 2021 07 2;11(7):e02203. Epub 2021 Jun 2.

Department of Neuroimmunology, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.

Objective: To investigate the correlation between acetylcholine receptor antibodies (AChR-Ab) concentration levels and individualized clinical symptoms in patients with AChR myasthenia gravis (AChR-MG) in China.

Methods: ELISA was used to determine the concentration of AChR-Ab in patients with MG. The Myasthenia Gravis Foundation of America (MGFA) Clinical Classification, Quantitative Myasthenia Gravis (QMG) score, and MG-specific activities of daily living (MG-ADL) scoring systems were used to evaluate the clinical status of patients. Spearman correlation analysis was used to determine the correlation between the AChR-Ab concentration and clinical score. The changes in the antibody concentration and clinical score are shown in MGFA-antibody concentration-treatment plots.

Results: Autoantibody detection tests were performed in 67 patients, and their clinical scores were recorded. Forty-nine patients received immunosuppressive therapy, 17 patients received pyridostigmine only, and 1 patient under thymectomy without any medication. The AChR-Ab concentration correlated with the MGFA Classification in 5 (29.4%) patients in the pyridostigmine-only group and 15 (30.6%) patients in the immunosuppressive drug group. The changes in the MGFA Classification preceded the changes in the AChR-Ab concentration in 4 (23.5%) patients treated with pyridostigmine and 10 (20.4%) patients on immunosuppressive drugs. In patients on oral non-steroidal immunosuppressants, the AChR-Ab concentration changed by more than 50%, whereas the MGFA Classification did not increase. The AChR-Ab concentration decreased in 17/32 (53.1%) patients after thymectomy, and then increased, whereas the AChR-Ab concentration increased in 15/32 (46.9%) patients and the MGFA Classification decreased in 27/32 (81.8%) patients after thymectomy. The AChR-Ab concentration presented a slight correlation with the corresponding MGFA, QMG, and MG-ADL in patients with thymoma.

Discussion: In the Chinese AChR-MG population, the Changes in the AChR-Ab concentration in individuals with AChR-MG did not consistently correlate with the severity of clinical symptoms.
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http://dx.doi.org/10.1002/brb3.2203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323040PMC
July 2021

Rat plasma protein binding of kaempferol-3-O-rutinoside from Lu'an GuaPian tea and its anti-inflammatory mechanism for cardiovascular protection.

J Food Biochem 2021 07 26;45(7):e13749. Epub 2021 May 26.

Natural Products Laboratory, State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei, China.

Previous study found a high content of kaempferol-3-O-rutinoside (KR) in Lu'an GuaPian tea, however, the rat plasma protein binding and mechanism of KR for cardiovascular protection are unclear. Thus, we studied plasma protein binding using ultrafiltration followed by UPLC, and screened its inhibition against LPS-induced inflammation injury in vitro as well as the underlying mechanism by molecular docking and western blot. KR showed over 74% plasma protein binding ratio. Furthermore, KR may act on the toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). In vitro experiments showed that KR decreases the overexpression of TLR4, MyD88, and nuclear factor-κB (NF-κB), which further validates the molecular docking results, suggesting that KR could block TLR4/MyD88/NF-κB signaling. These results indicate that KR could be a potential active agent in the protection of myocardial injury. PRACTICAL APPLICATIONS: Health benefits of tea are largely dependent on the intake of flavonoids. Flavonoids are a group of compounds beneficial to cardiovascular disease and an important part of "functional foods." Lu'an GuaPian tea is mainly produced in Lu'an City, Anhui Province and is one of the top 10 famous teas in China. Kaempferol-3-O-rutinoside in Lu'an GuaPian has good hypoglycemic effect, mainly manifested in a strong inhibition of α-glucosidase and α-amylase activities. Present study showed that kaempferol-3-O-rutinoside could block TLR4/MyD88/NF-κB signaling, suggesting that it could be a potential active agent in the protection of myocardial injury.
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http://dx.doi.org/10.1111/jfbc.13749DOI Listing
July 2021

Effects of reductive inorganics and NOM on the formation of chlorite in the chlorine dioxide disinfection of drinking water.

J Environ Sci (China) 2021 Jun 22;104:225-232. Epub 2020 Dec 22.

Collaborative Innovation Center of Atmospheric Environment and Equipment Technology, School of Environmental Science & Engineering, Nanjing University of Information Science & Technology, Nanjing 210044, China.

Chlorine dioxide (ClO) disinfection usually does not produce halogenated disinfection by-products, but the formation of the inorganic by-product chlorite (ClO) is a serious consideration. In this study, the ClO formation rule in the ClO disinfection of drinking water was investigated in the presence of three representative reductive inorganics and four natural organic matters (NOMs), respectively. Fe and S mainly reduced ClO to ClO at low concentrations. When ClO was consumed, the ClO would be further reduced by Fe and S, leading to the decrease of ClO. The reaction efficiency of Mn with ClO was lower than that of Fe and S. It might be the case that MnO generated by the reaction between Mn and ClO had adsorption and catalytic oxidation on Mn. However, Mn would not reduce ClO. Among the four NOMs, humic acid and fulvic acid reacted with ClO actively, followed by bovine serum albumin, while sodium alginate had almost no reaction with ClO. The maximum ClO yields of reductive inorganics (70%) was higher than that of NOM (around 60%). The lower the concentration of reductive substances, the more ClO could be produced by per unit concentration of reductive substances. The results of the actual water samples showed that both reductive inorganics and NOM played an important role in the formation of ClO in disinfection.
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http://dx.doi.org/10.1016/j.jes.2020.11.033DOI Listing
June 2021

An evaluation of social media utilization by general surgery programs in the COVID-19 era.

Am J Surg 2021 Apr 22. Epub 2021 Apr 22.

School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.

Background: Our study investigates how general surgery residency programs utilized social media to adapt to the challenges of COVID-19.

Methods: 319 participating general surgery residency programs provided by the Electronic Residency Application Service were analyzed in this study. Associated Twitter, Instagram, and Facebook accounts were assessed to find virtual open houses and externships.

Results: Of the 319 program, 188 (59%) were found to have a social media presence. A total of 348 social media accounts were found, as some of the programs had separate residency and department accounts. Of all the social media accounts, 112 (32%) of the accounts were created after March 1, 2020. Virtual open houses opportunities were found to be advertised across all platforms.

Conclusion: Many general surgery programs responded to the physical limitations of COVID-19 pandemic by increasingly utilizing social media during the COVID-19 pandemic. Virtual opportunities should be considered as a novel approach for future outreach and recruitment.
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http://dx.doi.org/10.1016/j.amjsurg.2021.04.014DOI Listing
April 2021

First-in-Human Phase I Study of ABBV-085, an Antibody-Drug Conjugate Targeting LRRC15, in Sarcomas and Other Advanced Solid Tumors.

Clin Cancer Res 2021 Jul 5;27(13):3556-3566. Epub 2021 Apr 5.

University of Colorado - Anschutz Medical Campus, Aurora, Colorado.

Purpose: Leucine-rich repeat containing 15 (LRRC15) is expressed on stromal fibroblasts in the tumor microenvironment of multiple solid tumor types and may represent an interesting target for therapy, particularly in patients with sarcomas where LRRC15 is also expressed by malignant cells. ABBV-085 is a monomethyl auristatin-E antibody-drug conjugate that targets LRRC15 and showed antineoplastic efficacy in preclinical experiments. Herein, we report findings of ABBV-085 monotherapy or combination therapy in adult patients with sarcomas and other advanced solid tumors.

Patients And Methods: This first-in-human phase I study (NCT02565758) assessed ABBV-085 safety, pharmacokinetics/pharmacodynamics, and preliminary antitumor activity. The study consisted of two parts: dose escalation and dose expansion. ABBV-085 was administered by intravenous infusion at 0.3 to 6.0 mg/kg every 14 days.

Results: In total, 85 patients were enrolled; 45 patients received the recommended expansion dose of 3.6 mg/kg ABBV-085 monotherapy, including 10 with osteosarcoma and 10 with undifferentiated pleomorphic sarcoma (UPS). Most common treatment-related adverse events were fatigue, nausea, and decreased appetite. The overall response rate for patients with osteosarcoma/UPS treated at 3.6 mg/kg was 20%, including four confirmed partial responses. No monotherapy responses were observed for other advanced cancers treated at 3.6 mg/kg. One patient treated with ABBV-085 plus gemcitabine achieved partial response.

Conclusions: ABBV-085 appeared safe and tolerable at a dose of 3.6 mg/kg every 14 days, with preliminary antitumor activity noted in patients with osteosarcoma and UPS. Given the high unmet need in these orphan malignancies, further investigation into targeting LRRC15 in these sarcomas may be warranted.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4513DOI Listing
July 2021

Thoughts on 2021-2022 visiting rotation recommendations from current and recent applicants in surgery.

Am J Surg 2021 Mar 26. Epub 2021 Mar 26.

Hansjörg Wyss Department of Plastic Surgery, NYU Langone, New York, NY, USA. Electronic address:

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http://dx.doi.org/10.1016/j.amjsurg.2021.03.047DOI Listing
March 2021

Theoretical investigations on forward-backward ESIPT processes of three fluorophores deriving from 2-(2'-hydroxyphenyl)thiazole.

Photochem Photobiol Sci 2021 Apr 31;20(4):533-546. Epub 2021 Mar 31.

Department of Chemistry and Material Science, College of Science, Nanjing Forestry University, Nanjing, 210037, People's Republic of China.

The photophysical properties and excited-state intramolecular proton transfer (ESIPT) processes for 2-(2'-hydroxyphenyl)-4-chloromethylthiazole (1), 2-(2'-hydroxyphenyl)-4-phenylthiazole (2), 2-(2'-hydroxyphenyl)-4-hydroxymethyl-thiazole (3) were studied at the TD-B3PW91/6-31 + G(d, p)/IEFPCM level. The structures of 1-3 were fully optimized and the corresponding structural parameters, infrared spectra and electron densities in the ground (S) and the first excited (S) states were analyzed. The calculated absorption and fluorescence wavelengths of 1-3 reproduced the experimental data. The potential energy curves of the S and S states were built and the ESIPT processes were clarified. Our results showed that the intramolecular H-bonds of 3 and 2 in the S state were the strongest and the weakest, respectively, and then the ESIPT potential barriers of 3 and 2 were the lowest and highest, respectively. Among the three phenol-thiazole type probes, the compound 2 with phenyl ring group at the 4 position of the thiazole ring had the larger π-conjugation, and had the higher ESIPT potential barrier at the same time. The corresponding compound 1 and 3 with CHCl and CHOH had the lower ESIPT barrier.
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http://dx.doi.org/10.1007/s43630-021-00036-8DOI Listing
April 2021

The additional benefit of professional fluoride application for children as an adjunct to regular fluoride toothpaste: a systematic review and meta-analysis.

Clin Oral Investig 2021 Jun 29;25(6):3409-3419. Epub 2021 Mar 29.

Centre for Evidence-Based Stomatology, Hubei-MOST KLOS & KLOBM, School & Hospital of Stomatology, Wuhan University, Luoyu Road 237, Wuhan, 430079, China.

Objective: To assess whether professional fluoride application (PFA) used in addition to regular fluoride toothpaste (RFT, ≥ 1,000 ppm) is more effective than RFT alone in children.

Materials And Methods: A systematic search was conducted using the PubMed, Embase, Google Scholar and CENTRAL databases. Randomized controlled trials (RCTs) comparing the effectiveness of RFT + PFA and RFT alone were included. Meta-analyses with random-effects models were performed. The certainty of evidence was assessed using the GRADE approach.

Results: A total of 2,729 records were identified from electronic and manual searches, which were screened by two reviewers independently and in duplicate. Six RCTs (5,034 participants) were included, of which four had high risk of bias and two had unclear risk of bias. The PFA used in all these trials was fluoride varnish (FV). In meta-analyses, no significant difference was observed between participants receiving FV + RFT and RFT alone of d(m/e)fs increment (mean difference (MD) - 0.17, 95% confidence interval (CI) - 0.60 to 0.26, P = 0.43, I = 38%; 6 trials, 5,034 participants, moderate certainty evidence), incidence of caries (risk ratio (RR) 0.91, 95% CI 0.80 to 1.05, P = 0.21, I = 41%; 4 trials, 4,487 participants, moderate certainty evidence) or changes in prevalence of caries (RR 0.89, 95% CI 0.78 to 1.01, P = 0.07, I = 0%, 4 trials, 4,189 participants, low certainty evidence).

Conclusions: Low to moderate certainty evidence suggests that FV does not have significant additional caries-preventive benefit for children (under 8 years old) when provided as an adjunct to daily tooth brushing with RFT (≥ 1,000 ppm). There is insufficient evidence regarding the additional benefit of other PFA interventions.

Clinical Relevance: The decision to apply FV to children needs to be made in light of their actual usage of RFT.

Trial Registration: PROSPERO (CRD42020165270).
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http://dx.doi.org/10.1007/s00784-021-03909-5DOI Listing
June 2021

Faciogenital Dysplasia 5 supports cancer stem cell traits in basal-like breast cancer by enhancing EGFR stability.

Sci Transl Med 2021 03;13(586)

Immunology and Cancer Pharmacology Group, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

Most basal-like breast cancers (BLBCs) are triple-negative breast cancers (TNBCs), which have the worst prognosis and distant metastasis-free survival among breast cancer subtypes. Now, no targeted therapies are available for patients with BLBC due to the lack of reliable and effective molecular targets. Here, we performed the BLBC tissue microarray-based immunohistochemical analysis and showed that Faciogenital Dysplasia 5 (FGD5) abundance is associated with poor prognosis in BLBCs. deletion decreased the proliferation, invasion, and tumorsphere formation capacity of BLBC cells. Furthermore, genetic inhibition of in mouse mammary epithelial cells attenuated BLBC initiation and progression by reducing the self-renewal ability of tumor-initiating cells. In addition, FGD5 abundance was positively correlated with the abundance of epidermal growth factor receptor (EGFR) in BLBCs. ablation decreased EGFR abundance by reducing EGFR stability in TNBC cells in 2D and 3D culture conditions. Mechanistically, FGD5 binds to EGFR and interferes with basal EGFR ubiquitination and degradation induced by the E3 ligase ITCH. Impaired EGFR degradation caused BLBC cell proliferation and promoted invasive properties and self-renewal. To verify the role of the FGD5-EGFR interaction in the regulation of EGFR stability, we screened a cell-penetrating α-helical peptide PER3 binding with FGD5 to disrupt the interaction. Treatment of BLBC patient-derived xenograft-bearing mice with the peptide PER3 disrupting the FGD5-EGFR interaction either with or without chemotherapy reduced BLBC progression. Our study identified FGD5 as a positive modulator of tumor-initiating cells and suggests a potential therapeutic option for the BLBC subtype of breast cancer.
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http://dx.doi.org/10.1126/scitranslmed.abb2914DOI Listing
March 2021
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