Publications by authors named "Sheng Chen"

1,056 Publications

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Moving nail bands in systemic lupus erythematosus.

J Eur Acad Dermatol Venereol 2021 Sep 23. Epub 2021 Sep 23.

Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

We read with interest the article by SS Ocampo-Garza et al.[1] that discussed nail changes associated to COVID-19 infection. Interestingly, we recently encountered a patient with SLE (systemic lupus erythematosus ) that developed red half-moon-like nail sign in the course of the disease, which has only been reported in COVID-19 cases twice[2,3].
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http://dx.doi.org/10.1111/jdv.17695DOI Listing
September 2021

Expanding the clinical spectrum of anti-IgLON5 disease: A multicenter retrospective study.

Eur J Neurol 2021 Sep 20. Epub 2021 Sep 20.

Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: We conducted this study to describe detailed clinical characteristics, ancillary test results and treatment response of a group of Chinese patients with anti-IgLON5 disease.

Methods: We recruited 13 patients with positive IgLON5 antibodies in serum and/or cerebrospinal fluid from nine tertiary referral centers. Patients were enrolled from February 2017 to July 2021. We retrospectively collected information on the presenting and main symptoms, treatment response and follow-up outcomes.

Results: The median age of onset for symptoms was 60 years (range: 33-73) and six of the 13 patients were females. The predominant clinical presentations included sleep disturbance (eight patients) and cognitive impairment (seven patients), followed by movement disorders (six patients). Parainfectious cause seemed plausible. Notably, we identified the first case of possible EB virus-related anti-IgLON5 disease. Coexisting neural autoantibodies were identified in two patients. Furthermore, two patients had other autoimmune diseases. The IgG subclass was determined in four patients, including two with dominant IgG4 subtype and two with dominant IgG1 subtype. Additionally, 10 patients were treated with immunotherapy and four patients exhibited improvement. Overall, six of 10 patients for whom follow-up results were assessable had favorable clinical outcomes (modified Rankin Scale score ≤2).

Conclusions: The clinical spectrum of anti-IgLON5 disease is variable. Our results highlight a boarder spectrum of anti-IgLON5 disease.
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http://dx.doi.org/10.1111/ene.15117DOI Listing
September 2021

Heat shock treatment maintains the quality attributes of postharvest jujube fruits and delays their senescence process during cold storage.

J Food Biochem 2021 Sep 16:e13937. Epub 2021 Sep 16.

Hunan Provincial Key Laboratory for Fruits and Vegetables Storage Processing and Quality Safety, Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha, China.

The effects of heat shock (HT), 1-methylcyclopropene (1-MCP), or their combination (HT + 1-MCP) on the quality of fresh jujube fruits during cold storage were studied. Among them, HT showed the best preservation effect on jujube fruits, which was more effective than others in inhibiting the increase of red index, decay incidence, and weight loss and delaying the decrease of firmness, soluble solids content (SSC), titratable acidity (TA), and ascorbic acid (AsA) content. Besides, it could delay the degradation rate of the cell wall to maintain the integrity of cell membrane, and keep the high activity of active oxygen scavenging enzymes. During cold storage, malondialdehyde (MDA) content and relative electrolyte leakage (REL) of the HT group were significantly lower than those of the control group, 1-MCP, and HT + 1-MCP group (p < .05), while superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities were significantly higher than those of other groups (p < .05). It was concluded that the postharvest HT treatment could effectively delay the senescence and decay of jujube fruits. PRACTICAL APPLICATIONS: Jujube fruits have high nutritional value used for food and medicine. However, they are not tolerant to storage after harvest, resulting in high economic losses. Therefore, it is of great significance to find a suitable method to maintain the quality of jujube fruits. Our results revealed the effect of HT, 1-MCP, and their combination on the quality maintenance of jujube fruits, and found that HT could effectively maintain the quality of them, which could be used as an effective method for keeping jujube fruits fresh.
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http://dx.doi.org/10.1111/jfbc.13937DOI Listing
September 2021

Intestinal-derived HDL: The portal guardian of the liver.

Authors:
Sheng Chen Di Wang

Immunity 2021 Sep;54(9):1903-1905

Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China. Electronic address:

The trafficking and function of intestine-derived high-density lipoprotein (HDL) have not been identified. In a recent issue of Science, Han et al. (2021) find that intestine-derived HDL neutralizes intestinal-leaked LPS in the portal vein, serving as a host disease tolerance strategy to restrain liver damage of enteric origin under physiological conditions.
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http://dx.doi.org/10.1016/j.immuni.2021.08.010DOI Listing
September 2021

An Adrenocortical Carcinoma Evolving After Nine Years of Latency From a Small Adrenal Incidentaloma.

Cureus 2021 Aug 3;13(8):e16851. Epub 2021 Aug 3.

Department of Critical Care Medicine, Mayo Clinic Health System, Mankato, USA.

Adrenal incidentalomas (AIs) are common incidental findings in medical practice with clinical significance. Although most AIs are nonsecretory and nonmalignant, they require a short course of follow-up over one to two years to rule out malignancy or hormonal secretion according to clinical practice guidelines. However, this can result in some adrenocortical carcinomas (ACCs) being missed if they transform at a later stage or evolve slowly. Here, we report one such case of an AI, which although remained indolent, eventually transformed into an ACC many years after the initial detection.
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http://dx.doi.org/10.7759/cureus.16851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425154PMC
August 2021

Active maintenance of proton motive force mediates starvation-induced bacterial antibiotic tolerance in Escherichia coli.

Commun Biol 2021 09 14;4(1):1068. Epub 2021 Sep 14.

Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong.

Recent evidence suggests that metabolic shutdown alone does not fully explain how bacteria exhibit phenotypic antibiotic tolerance. In an attempt to investigate the range of starvation-induced physiological responses underlying tolerance development, we found that active maintenance of the transmembrane proton motive force (PMF) is essential for prolonged expression of antibiotic tolerance in bacteria. Eradication of tolerant sub-population could be achieved by disruption of PMF using the ionophore CCCP, or through suppression of PMF maintenance mechanisms by simultaneous inhibition of the phage shock protein (Psp) response and electron transport chain (ETC) complex activities. We consider disruption of bacterial PMF a feasible strategy for treatment of chronic and recurrent bacterial infections.
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http://dx.doi.org/10.1038/s42003-021-02612-1DOI Listing
September 2021

A Conjugative IncI1 Plasmid Carrying (B) and That Mediates Resistance to Azithromycin and Cephalosporins.

Microbiol Spectr 2021 Sep 8:e0028621. Epub 2021 Sep 8.

Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Konggrid.35030.35, Kowloon, Hong Kong.

In this study, an IncI1 plasmid encoding resistance to both cefotaxime and azithromycin was recovered from a clinical Klebsiella pneumoniae strain. The azithromycin resistance was confirmed to be mediated by the (B) gene. This plasmid could be readily conjugated to strains of Escherichia coli and Salmonella, promoting rapid dissemination of azithromycin- and ceftriaxone-resistance-encoding elements among Gram-negative bacterial pathogens. Transmission of this plasmid in Salmonella is of particular concern, since it could mediate expression of phenotypic resistance to azithromycin and ceftriaxone, which are the current choices for treatment of Salmonella infections. Our findings suggest a need to monitor the efficiency and pattern of transmission of this plasmid among key Gram-negative bacterial pathogens. Since the approval by the FDA of azithromycin for treatment of Salmonella infections, efforts have been made to monitor the development of resistance to azithromycin in these organisms. In this study, we report an IncI1 plasmid from a clinical K. pneumoniae strain that encodes resistance to both cefotaxime and azithromycin. This plasmid could be readily conjugated to strains of Escherichia coli and Salmonella, promoting rapid dissemination of azithromycin- and ceftriaxone-resistance-encoding elements among Gram-negative bacterial pathogens. Furthermore, data from this study confirmed for the first time the role of the (B) gene in mediating resistance to azithromycin in various bacterial species, particularly Salmonella.
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http://dx.doi.org/10.1128/Spectrum.00286-21DOI Listing
September 2021

Reattachment After Foldable Capsular Vitreous Body Implantation in Severe Retinal Detachment Eyes.

Transl Vis Sci Technol 2021 Sep;10(11)

Affiliated Shenzhen Eye Hospital of Jinan University, Shenzhen Eye Hospital, Shenzhen Key Laboratory of Ophthalmology, Shenzhen University School of Medicine, Shenzhen, Guangdong province, China.

Purpose: To evaluate the clinical effectiveness and safety of foldable capsular vitreous body (FCVB) implantation for severe retinal detachment.

Methods: A retrospective analysis was performed on 26 patients with severe ocular trauma and one with recurrent retinal detachment. Clinical data-including surgery success, complications, retinal reattachment, vision, and intraocular pressure (IOP)-were analyzed for patients who underwent 23G pars plana vitrectomy and FCVB implantation combined with silicone oil tamponade.

Results: The mean follow-up period was 10.44 ± 2.68 months. All surgeries were smooth; the FCVBs were properly positioned and supported the retina well, and the retinal reattachment rate reached 92.59%. At the six-month follow-up, preoperative (1.30 ± 1.20) and postoperative (0.63 ± 0.79) vision was significantly different (t = 3.03, P = 0.005), and the postoperative IOP (7.93 ± 3.57 mm Hg) was lower than the preoperative IOP (13.98 ± 10.72 mm Hg) (t = 2.74, P = 0.01). Among 20 patients followed up for >12 months, preoperative (1.20 ± 0.95) and postoperative (0.75 ± 0.91) visions were significantly different (t = 1.831, P = 0.005), and the postoperative IOP (9.85 ± 6.48 mm Hg) was lower than the preoperative IOP (14.85 ± 12.17 mm Hg) (t = 1.82, P = 0.01). No endophthalmitis, sympathetic ophthalmia, and rejection of FCVB occurred during follow-up.

Conclusions: FCVB combined with silicone oil tamponade showed good efficacy and safety in severe retinal detachment treatment during the follow-up period.

Translational Relevance: Vitreous substitution is deemed a highly challenging and interesting research topic in ophthalmology. Traditional method such as silicone oil tamponade often causes various complications such as silicone oil emulsification, silicone oil migration, and corneal degeneration. The foldable capsular vitreous body as a novel vitreous substitute combined silicone oil injection into it can stay in the eyeball for a long time without obvious complications.
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http://dx.doi.org/10.1167/tvst.10.11.8DOI Listing
September 2021

Exploration of differentially-expressed exosomal mRNAs, lncRNAs and circRNAs from serum samples of gallbladder cancer and xantho-granulomatous cholecystitis patients.

Bioengineered 2021 Dec;12(1):6134-6143

Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.

Gallbladder cancer (GBC) is the most common biliary tract malignancy worldwide. Although a growing number of studies have explored the mechanism of GBC, thus far, few molecules have been discovered that can be utilized as specific biomarkers for the early diagnosis and therapeutic treatment of GBC. Recent studies have shown that exosomes not only participate in the progression of tumors, but also carry specific information that can define multiple cancer types. The present study investigated the expression profiles of coding (or messenger) ribonucleic acids (mRNAs) and non-coding RNAs (ncRNAs, including long non-coding RNAs [lncRNAs] and circular RNAs [circRNAs]) in plasma-derived exosomes from GBC patients. Using high-throughput RNA sequencing and subsequent bioinformatic analysis, a number of differentially expressed (DE) mRNAs, lncRNAs, and circRNAs were identified in GBC exosomes, compared to their expressions in xantho-granulomatous cholecystitis (XGC) exosomes. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analyses were then conducted to investigate the potential functions of these DE RNAs. Furthermore, the interaction networks and competing endogenous RNA networks of these DE RNAs and their target genes were investigated, revealing a complex regulatory network among mRNAs and ncRNAs. In summary, this study demonstrates the diagnostic value of plasma-derived exosomes in GBC and provides a new perspective on the mechanism of GBC.
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http://dx.doi.org/10.1080/21655979.2021.1972780DOI Listing
December 2021

Functional Heterogeneity of Reelin in the Oral Squamous Cell Carcinoma Microenvironment.

Front Oncol 2021 17;11:692390. Epub 2021 Aug 17.

Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.

Background: Reelin, an extracellular glycoprotein, is expressed on neuronal cells and participates in neuronal migration during brain development. Recently, Reelin also has a vital role in carcinogenesis. However, its role in oral squamous cell carcinoma (OSCC) remains to be explored. The purpose of this study was to explore the roles of Reelin in OSCC.

Methods: The expression of Reelin in cancerassociated fibroblasts (Reelin) and tumor cells (Reelin) was analyzed by the Gene Expression Omnibus (GEO) database. Immunohistochemistry (IHC) was used to detect the spatial pattern of Reelin in 75 OSCCs. The diagnostic and prognostic values of Reelin were evaluated and also verified by The Cancer Genome Atlas (TCGA) database. Primary CAFs from 13 OSCC patients were isolated to confirm Reelin expression. Thirty-nine OSCC peripheral blood samples were used to analyze the change of immunocytes based on Reelin levels by flow cytometry. The relationship between Reelin and tumor immune microenvironment in head and neck squamous cell carcinoma (HNSCC) tissues was determined by TISIDB and the Tumor Immune Estimation Resource (TIMER) database.

Results: In breast cancer, pancreatic cancer and rectal cancer, Reelin in CAFs was significantly upregulated compared with Reelin in TCs. The IHC results in OSCC also showed that Reelin levels were higher in CAFs. Upregulated Reelin was related to a decreased pN stage and distant metastasis. Strikingly, patients with enhanced Reelin had a high risk of lymph node metastasis, poor worst pattern of invasion (WPOI), and distant metastasis, but showed comparable Ki-67 level in all OSCC patients, resulting in shorter overall survival (OS) and disease-specific survival (DSS). Unexpectedly, Reelin in tumor-infiltrating lymphocytes (Reelin) was correlated with postoperative relapse. Patients with high Reelin, but not Reelin and Reelin, had poor cytotoxicity of CD8 T cells and higher ratio of CD4/CD8 in peripheral blood. However, Reelin was positively associated with tissue-resident B cells and NK cells in the tumor microenvironment.

Conclusion: Reelin has a versatile function in distinct cell types during the development of OSCC governing tumor cell and stroma microenvironment.
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http://dx.doi.org/10.3389/fonc.2021.692390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416082PMC
August 2021

High incidence and mortality of Pneumocystis jirovecii infection in anti-MDA5-antibody-positive dermatomyositis: experience from a single center.

Arthritis Res Ther 2021 Sep 4;23(1):232. Epub 2021 Sep 4.

Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200001, China.

Background: Idiopathic inflammatory myopathies (IIM) are associated with a significantly higher risk of opportunistic infections including Pneumocystis jirovecii pneumonia (PJP), a potentially fatal opportunistic infection. However, no prior studies have evaluated PJP infection in subtypes of IIM.

Objectives: To investigate the prevalence and mortality rate of PJP infection in subgroups of IIM patients stratified according to myopathy-specific antibodies.

Methods: In the first part of the study, 463 consecutive patients with IIM were prospectively followed for a period of at least 1 year to analyze the incidence of PJP. In the second part of the study, we enrolled 30 consecutive PJP patients with any rheumatic disease in order to identify the mortality rate and risk factors by Cox regression analysis. The Kaplan-Meier method with log-rank testing was used to assess differences in survival.

Results: The prevalence of PJP in IIM patients was found to be 3.0/100 person-years, while in MDA5 DM patients it was 7.5/100 person-years and in MDA5 IIM patients 0.7/100 person-years (P < 0.05). PJP typically occurred in the first 2 months in the case of MDA5 DM patients who had a significant decrease in their CD4 T cell counts and lymphocyte counts (P < 0.05). In PJP patients, 3-month mortality was higher for MDA5 DM patients than in those with other rheumatic diseases (83.3% vs 38.9%, P < 0.05). Alarmingly, MDA5 DM patients seemed not to benefit from prompt anti-PJP treatment, unlike patients with other rheumatic diseases whose survival improved when anti-PJP treatment was started within 6 days (P < 0.05).

Conclusion: PJP has an alarming high incidence and mortality in MDA5 DM patients. Timely treatment for PJP seems not to improve the prognosis of patients with this particular subtype. Hence, there remains a crucial unmet need to develop PJP prophylaxis for MDA5 DM patients.
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http://dx.doi.org/10.1186/s13075-021-02606-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417987PMC
September 2021

Priming of NLRP3 inflammasome activation by Msn kinase MINK1 in macrophages.

Cell Mol Immunol 2021 Sep 3. Epub 2021 Sep 3.

Institute of Immunology and Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, P. R. China.

The nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain-containing 3 (NLRP3) inflammasome is essential in inflammation and inflammatory disorders. Phosphorylation at various sites on NLRP3 differentially regulates inflammasome activation. The Ser725 phosphorylation site on NLRP3 is depicted in multiple inflammasome activation scenarios, but the importance and regulation of this site has not been clarified. The present study revealed that the phosphorylation of Ser725 was an essential step for the priming of the NLRP3 inflammasome in macrophages. We also showed that Ser725 was directly phosphorylated by misshapen (Msn)/NIK-related kinase 1 (MINK1), depending on the direct interaction between MINK1 and the NLRP3 LRR domain. MINK1 deficiency reduced NLRP3 activation and suppressed inflammatory responses in mouse models of acute sepsis and peritonitis. Reactive oxygen species (ROS) upregulated the kinase activity of MINK1 and subsequently promoted inflammasome priming via NLRP3 Ser725 phosphorylation. Eliminating ROS suppressed NLRP3 activation and reduced sepsis and peritonitis symptoms in a MINK1-dependent manner. Altogether, our study reveals a direct regulation of the NLRP3 inflammasome by Msn family kinase MINK1 and suggests that modulation of MINK1 activity is a potential intervention strategy for inflammasome-related diseases.
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http://dx.doi.org/10.1038/s41423-021-00761-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414466PMC
September 2021

Complete Genetic Analysis of Plasmids Carried by Two Nonclonal - and -Bearing Escherichia coli Strains: Insight into Plasmid Transmission among Foodborne Bacteria.

Microbiol Spectr 2021 Sep 1:e0021721. Epub 2021 Sep 1.

Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR.

Our objective was to characterize the genetic features of plasmids harbored by two genetically related, MCR-1 and NDM-5-producing Escherichia coli strains recovered from a chicken meat sample. The genetic profiles of all plasmids harbored by the two test strains, namely, 1106 and 1107, were determined by whole-genome sequencing, S1-pulsed-field gel electrophoresis (PFGE), Southern hybridization, and bioinformatics analysis. The transferability of plasmids harbored by the two strains was assessed by filter mating assay. Strains 1106 and 1107 were resistant to almost all the antibiotics, including colistin and fosfomycin, but remained susceptible to amikacin and tigecycline. The plasmids of p1107-NDM-5 and p1106-NDM-5 both contain a class I integron which lacks the IS element. The backbone of p1106-IncFII exhibited a high degree of similarity with that of p1106-NDM-5 and p1107-NDM-5, implying that events of plasmid fusion and resolution were involved in the formation of the two plasmids. The plasmids p1106-IncHI2MCR and p1107-IncHI2MCR belong to an IncHI2 replicon type, with three copies of IS being observed in p1106-IncHI2MCR, implying that the gene was transferable among bacteria that reside in the same food matrix. In this study, p1106-IncFIB, p1107-99K, p1107-111K, and p1107-118K were all found to be phage-like plasmids, with p1106-IncFIB and p1107-118K containing several virulence genes, including , , , , and . Surprisingly, resistance genes such as , , and could also be found in p1107-118K, but resistance genes were not detected in other phage-like plasmids. In conclusion, enhanced surveillance is required to monitor and control the dissemination of various resistance determinants among foodborne pathogens. Carbapenem and colistin are last-resort antibiotics used to treat serious clinical infections caused by multidrug-resistant (MDR) bacterial pathogens. Plasmids encoding resistance to carbapenems and colistin have been reported in clinical pathogens in recent years, and yet few studies reported cocarriage of and genes in Escherichia coli strains of food origin. How plasmids encoding these two important resistance determinants are being evolved and transmitted in bacterial pathogens is not well understood. In this study, we investigated the genetic features of plasmids harbored by two nonclonal, - and -bearing E. coli strains (1106 and 1107) recovered from a fresh chicken meat sample to understand and provide evidence of the level and dynamics of MDR plasmid transmission. Our data confirmed that active plasmid fusion and resolution events were involved in the formation of plasmids that harbor multiple resistance genes, which provide insights into the further control of plasmid evolution in bacterial pathogens.
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http://dx.doi.org/10.1128/Spectrum.00217-21DOI Listing
September 2021

Genomic signatures of vegetable and oilseed allopolyploid Brassica juncea and genetic loci controlling the accumulation of glucosinolates.

Plant Biotechnol J 2021 Aug 27. Epub 2021 Aug 27.

Laboratory of Germplasm Innovation and Molecular Breeding, Institute of Vegetable Science, Zhejiang University, Hangzhou, China.

Allopolyploid Brassica juncea crops in Brassicaceae are becoming increasingly revitalized as vegetables and oilseeds owing to wide adaptability and significant economic values. However, the genomic differentiation of diversified vegetables and oilseed B. juncea and the genetic basis underlying glucosinolates accumulation have yet to be elucidated. To address this knowledge gap, we report the sequencing of pairwise genomes of vegetable and oilseed B. juncea at chromosome-scale. Comparative genomics analysis unveils panoramic structural variation footprints, particularly the genetic loci of HSP20 and TGA1 associated with abiotic and biotic stresses responses between oilseed and vegetable subgroups. We anchored two major loci of MYB28 (HAG1) orthologues caused by copy number variations on A02 and A09 chromosomes using scored genomic SNPs based GWAS, that are responsible for seed oil quality-determining glucosinolates biosynthesis. These findings will provide valuable repertories of polyploidy genomic information enabling polyploidy genome evolution studies and precise genomic selections for crucial traits like functional components of glucosinolates in B. juncea crops and beyond.
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http://dx.doi.org/10.1111/pbi.13687DOI Listing
August 2021

LOXL2 attenuates osteoarthritis through inactivating Integrin/FAK signaling.

Sci Rep 2021 Aug 23;11(1):17020. Epub 2021 Aug 23.

Department of Orthodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.

Temporomandibular joint OA (TMJOA) is a common degenerative joint disease, leads to structural damage and ultimately loss of function. Matrix degradation is one of the first pathogenesis during the progression of OA, it was effective to inhibit matrix degradation to block the development of OA. In this study, an in vivo model (compressive mechanical force) and an in vitro model (IL-1β) were used to induce OA-like changes in TMJ cartilage and chondrocytes. We revealed lysyl oxidase like-2 (LOXL2) play a critical role in TMJOA. LOXL2 expression decreased in mechanical stress/IL-β induced TMJOA-like lesions in both in vivo models and in vitro models. Furthermore, recombinant LOXL2 (rhLOXL2) treatment ameliorated the degenerative changes induced by mechanical stress in vivo, including the thinning cartilage, down-expression of collagen II and proteoglycan, and over-expression of TNF-a, while LOXL2 antibody (anti-LOXL2) treatment exacerbated these changes. Mechanistically, the protection of LOXL2 in chondrocytes was induced partly through activation of the Integrin/FAK pathway. The inhibition of the Integrin/FAK pathway could neutralized the effects caused by rhLOXL2. Collectively, our study suggests that the LOXL2 plays a protective role in mechanical stress induced TMJOA-like changes, and the Integrin/FAK pathway may be a key downstream pathway in this process.
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http://dx.doi.org/10.1038/s41598-021-96348-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382747PMC
August 2021

Identification of a novel metallo-β-lactamase, VAM-1, in a foodborne isolate from China.

Antimicrob Agents Chemother 2021 Aug 23:AAC0112921. Epub 2021 Aug 23.

Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong.

A multidrug-resistant isolate recovered from a shrimp sample with reduced carbapenem susceptibility produced a novel metallo-β-lactamase, VAM-1. That carbapenemase shared 67% to 70% amino acid identity with several VMB family subclass B1 MBLs which were recently reported among some marine bacteria including , and . The gene was located in a novel conjugative plasmid, namely pC1579 and multiple copies of via an unusual mechanism of gene amplification were detected in pC1579. These findings underline the emergence of marine organisms acting as natural reservoirs for MBL genes and the importance of continuous bacterial antibiotic resistance surveillance.
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http://dx.doi.org/10.1128/AAC.01129-21DOI Listing
August 2021

Sleep Disturbances in Autoimmune Neurologic Diseases: Manifestation and Pathophysiology.

Front Neurosci 2021 6;15:687536. Epub 2021 Aug 6.

Department of Neurology, Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Autoimmune neurologic diseases are a new category of immune-mediated disease demonstrating a widely varied spectrum of clinical manifestations. Recently, sleep disturbances in patients with autoimmune neurologic diseases have been reported to have an immense negative impact on the quality of life. Excessive daytime sleep, rapid eye movement sleep behavior disorder (RBD), and narcolepsy are the most frequent sleep disorders associated with autoimmune neurologic diseases. Sleep disturbances might be the initial symptoms of disease or persist throughout the course of the disease. In this review, we have discussed sleep disturbances in different autoimmune neurologic diseases and their potential pathophysiological mechanisms.
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http://dx.doi.org/10.3389/fnins.2021.687536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377735PMC
August 2021

Defect Regulating of Few-Layer Antimonene from Acid-Assisted Exfoliation for Enhanced Electrocatalytic Nitrogen Fixation.

ACS Appl Mater Interfaces 2021 Sep 20;13(34):40618-40628. Epub 2021 Aug 20.

Key Laboratory of Jiangsu Province for Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu, China.

Nitrogen reduction reaction (NRR), as a green and sustainable technology, is far from a practical application due to the lack of efficient electrocatalysts. In this work, we found that antimonene, a group-VA elemental two-dimensional (2D) material, is attractive as an electrocatalyst for NRR. The antimonene here is acquired through chemical exfoliation of antimony (Sb) using HSO for the first time, which simultaneously achieved efficient large-sized exfoliation and created a high density of active edge sites. Moreover, the concentration of defects shows a gradual increasing tendency as the treatment time extends. The obtained antimonene exhibited favorable average ammonia (NH) yield and Faradaic efficiency as high as 2.08 μg h cm and 14.25% at -0.7 V versus RHE, respectively. Density functional theory calculations prove that the sufficient exposure of edge defects is favorable for reducing the reaction barrier and strengthening the interaction between antimonene and the intermediates of NRR, thus increasing the selectivity and yield rate of NH. The chemical exfoliation of Sb reported here offers an alternative avenue to engineer the surface structures of group-VA elemental-based catalysts. Investigation of NRR using 2D antimonene can further provide deep insight into the mechanism and principle of NRR over group-VA elemental nanosheets.
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http://dx.doi.org/10.1021/acsami.1c10967DOI Listing
September 2021

A Novel Biomimetic Nanoprobe as a Photoacoustic Contrast Agent.

Front Chem 2021 3;9:721799. Epub 2021 Aug 3.

The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Specific detection of tumors is of pivotal importance to cancer prevention and therapy yet a big challenge. Photoacoustic imaging (PAI) as an emerging non-invasive modality has shown great potential in biomedical and clinical applications. The performance of PAI largely depends on the light-absorption coefficient of the imaged tissue and the PAI contrast agent being used, either endogenously or exogenously. The exogenous contrast agents developed so far have greatly helped to improve PAI, but still have some limitations, such as lack of targeting capacity and easy clearance by the host immune system. Herein, we fabricated a biomimetic nanoprobe with cell membrane coating as a novel PAI contrast agent, namely, MPD [membrane-coated poly(lactic-co-glycolic acid) (PLGA)/dye]. In brief, the organic dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) was encapsulated by the Food and Drug Administration-approved polymer, poly(lactic-co-glycolic acid) (PLGA), to form polymer nanoparticles by emulsification. The nanoparticles are further coated with the cancer cell membrane to form MPD. MPD has outstanding biocompatibility, tumor specificity, and stability. Thus, MPD is a versatile NIR-I theranostic nanoplatform for PAI-guided cancer diagnosis and therapy.
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http://dx.doi.org/10.3389/fchem.2021.721799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369425PMC
August 2021

Folic acid-modified ROS-responsive nanoparticles encapsulating luteolin for targeted breast cancer treatment.

Drug Deliv 2021 Dec;28(1):1695-1708

Department of Pharmacy, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Luteolin (Lut) is a natural flavonoid polyphenolic compound with multiple pharmacological activities, such as anti-oxidant, anti-inflammatory, and anti-tumor effects. However, the poor aqueous solubility and low bioactivity of Lut restrict its clinical translation. Herein, we developed a reactive oxygen species (ROS)-responsive nanoplatforms to improve the bioactivity of Lut. Folic acid (FA) was employed to decorate the nanoparticles (NPs) to enhance its targeting ability. The size of Lut-loaded ROS-responsive nanoparticles (Lut/Oxi-αCD NPs) and FA-modified Lut/Oxi-αCD NPs (Lut/FA-Oxi-αCD NPs) is 210.5 ± 6.1 and 196.7 ± 1.8 nm, respectively. Both Lut/Oxi-αCD NPs and Lut/FA-Oxi-αCD NPs have high drug loading (14.83 ± 3.50 and 16.37 ± 1.47%, respectively). cellular assays verified that these NPs could be efficiently internalized by 4T1 cells and the released Lut from NPs could inhibit tumor cells proliferation significantly. Animal experiments demonstrated that Lut/Oxi-αCD NPs, especially Lut/FA-Oxi-αCD NPs obviously accumulated at tumor sites, and inhibited tumor growth ∼3 times compared to the Lut group. In conclusion, the antitumor efficacy of Lut was dramatically improved by targeting delivery with the ROS-responsive nanoplatforms.
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http://dx.doi.org/10.1080/10717544.2021.1963351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428179PMC
December 2021

Pituitary adenylate cyclase-activating polypeptide attenuates mitochondria-mediated oxidative stress and neuronal apoptosis after subarachnoid hemorrhage in rats.

Free Radic Biol Med 2021 10 13;174:236-248. Epub 2021 Aug 13.

Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address:

Mitochondria-mediated oxidative stress and neuronal apoptosis play an important role in early brain injury following subarachnoid hemorrhage (SAH). Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to reduce oxidative stress and cellular apoptosis by maintaining mitochondrial function under stress. The objective of this study is to investigate the effects of PACAP on mitochondria dysfunction - induced oxidative stress and neuronal apoptosis in both vivo and vitro models of SAH. PACAP Knockout CRISPR and exogenous PACAP38 were used to verify the neuroprotective effects of PACAP in rats after endovascular perforation - induced SAH as well as in primary neuron culture after hemoglobin stimulation. The results showed that endogenous PACAP knockout aggravated mitochondria dysfunction - mediated ATP reduction, reactive oxygen species accumulation and neuronal apoptosis in ipsilateral hemisphere at 24 h after SAH in rats. The exogenous PACAP38 treatment provided both short- and long-term neurological benefits by attenuating mitochondria - mediated oxidative stress and neuronal apoptosis after SAH in rats. Consistently, the exogenous PACAP38 treatment presented similar neuroprotection in the primary neuron culture after hemoglobin stimulation. Pharmacological inhibition of adenylyl cyclase (AC) or extracellular signal-regulated kinase (ERK) partly abolished the anti-oxidative stress and anti-apoptotic effects provided by PACAP38 treatment after the experimental SAH both in vivo and in vitro, suggesting the involvement of the AC-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and ERK pathway. Collectively, PACAP38 may serve as a promising treatment strategy for alleviating early brain injury after SAH.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.08.011DOI Listing
October 2021

In situ DESI-MSI lipidomic profiles of mucosal margin of oral squamous cell carcinoma.

EBioMedicine 2021 Aug 12;70:103529. Epub 2021 Aug 12.

Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210000, China. Electronic address:

Background: Although there is consensus that the optimal safe margin is ≥ 5mm, obtaining clear margins (≥5 mm) intraoperatively seems to be the major challenge. We applied a molecular diagnostic method at the lipidomic level to determine the safe surgical resection margin of OSCC by desorption electrospray ionisation mass spectrometry imaging (DESI-MSI).

Methods: By overlaying mass spectrometry images with hematoxylin-eosin staining (H&E) from 18 recruited OSCC participants, the mass spectra of all pixels across the diagnosed tumour and continuous mucosal margin regions were extracted to serve as the training and validation datasets. A Lasso regression model was used to evaluate the test performance.

Findings: By leave-one-out validation, the Lasso model achieved 88.6% accuracy in distinguishing between tumour and normal regions. To determine the safe surgical resection distance and margin status of OSCC, a set of 14 lipid ions that gradually decreased from tumour to normal tissue was assigned higher weight coefficients in the Lasso model. The safe surgical resection distance of OSCC was measured using the developed 14 lipid ion molecular diagnostic model for clinical reference. The overall accuracy of predicting tumours, positive margins, and negative margins was 92.6%.

Interpretation: The spatial segmentation results based on our diagnostic model not only clearly delineated the tumour and normal tissue, but also distinguished the different status of surgical margins. Meanwhile, the safe surgical resection margin of OSCC on frozen sections can also be accurately measured using the developed diagnostic model.

Funding: This study was supported by Nanjing Municipal Key Medical Laboratory Constructional Project Funding (since 2016) and the Centre of Nanjing Clinical Medicine Tumour (since 2014).
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http://dx.doi.org/10.1016/j.ebiom.2021.103529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374374PMC
August 2021

AKT controls NLRP3 inflammasome activation by inducing DDX3X phosphorylation.

FEBS Lett 2021 Aug 13. Epub 2021 Aug 13.

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, China.

The NLRP3 inflammasome, a critical component of the innate immune system, induces caspase-1 activation and interleukin-1β maturation and drives cell fate toward pyroptosis. However, the mechanism of NLRP3 inflammasome activation still remains elusive. Here we provide evidence that AKT regulates NLRP3 inflammasome activation. Upon NLRP3 activation, AKT activity is inhibited by second stimulus-induced reactive oxygen species. In contrast, AKT activation leads to NLRP3 inhibition and improved mitochondrial fitness. Mechanistically, AKT induces the phosphorylation of the DDX3X (DEAD-box helicase 3, X-linked), a recently identified NLRP3 inflammasome component, and impairs the interaction between DDX3X and NLRP3. Furthermore, an AKT agonist reduces NLRP3-dependent inflammation in two in vivo models of LPS-induced sepsis and Alum-induced peritonitis. Altogether, our study highlights an important role of AKT in controlling NLRP3 inflammasome activation.
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http://dx.doi.org/10.1002/1873-3468.14175DOI Listing
August 2021

A perspective on therapies for amyotrophic lateral sclerosis: can disease progression be curbed?

Transl Neurodegener 2021 08 10;10(1):29. Epub 2021 Aug 10.

Department of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200020, China.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons, leading to paralysis and eventually death. Symptomatic treatments such as inhibition of salivation, alleviation of muscle cramps, and relief of spasticity and pain still play an important role in enhancing the quality of life. To date, riluzole and edaravone are the only two drugs approved by the Food and Drug Administration for the treatment of ALS in a few countries. While there is adequate consensus on the modest efficacy of riluzole, there are still open questions concerning the efficacy of edaravone in slowing the disease progression. Therefore, identification of novel therapeutic strategies is urgently needed. Impaired autophagic process plays a critical role in ALS pathogenesis. In this review, we focus on therapies modulating autophagy in the context of ALS. Furthermore, stem cell therapies, gene therapies, and newly-developed biomaterials have great potentials in alleviating neurodegeneration, which might halt the disease progression. In this review, we will summarize the current and prospective therapies for ALS.
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http://dx.doi.org/10.1186/s40035-021-00250-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353789PMC
August 2021

Total Synthesis of Mannopeptimycin β via β-Hydroxyenduracididine Ligation.

J Am Chem Soc 2021 Aug 5;143(32):12784-12790. Epub 2021 Aug 5.

Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China.

Nonribosomal peptide synthesis in bacteria has endowed cyclic peptides with fascinating structural complexity via incorporating nonproteinogenic amino acids. These bioactive cyclic peptides provide interesting structural motifs for exploring total synthesis and medicinal chemistry studies. Cyclic glycopeptide mannopeptimycins exhibit antibacterial activity against antibiotic-resistant Gram-positive pathogens and act as the lipid II binder to stop bacterial cell wall biosynthesis. Here, we report a strategy streamlining solution phase-solid phase synthesis and chemical ligation-mediated peptide cyclization for the total synthesis of mannopeptimycin β.
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http://dx.doi.org/10.1021/jacs.1c05922DOI Listing
August 2021

The hypermucoviscosity of hypervirulent confers the ability to evade neutrophil-mediated phagocytosis.

Virulence 2021 12;12(1):2050-2059

Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong.

Hypervirulent (HvKP), which causes highly fatal infections, is a new threat to human health. In an attempt to investigate the underlying mechanisms of resistance to neutrophil-mediated killing and hence expression of high-level virulence by HvKP, we tested the binding affinity of HvKP strains to various types of human cells. Our data showed that HvKP exhibited weaker binding to both lung epithelial cells, intestinal Caco-2 cells and macrophages when compared to the classic, non-hypervirulent strains (cKP). Consistently, transconjugants that have acquired a or -bearing plasmid were found to exhibit decreased adhesion to various types of human cells, and hence higher survival rate upon exposure to neutrophil cells. We further found that over production of hypermucoviscosity (HMV), but not capsular polysaccharide (CPS), contributed to the reduced binding and phagocytosis. The effect of hypermucoviscosity on enhancing HvKP virulence was further shown in human serum survival assays and animal experiments. Findings in this study therefore confirmed that -mediated hypermucoviscosity in HvKP plays a key role in the pathogenesis of this organism through conferring the ability to evade neutrophil binding and phagocytosis.
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http://dx.doi.org/10.1080/21505594.2021.1960101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8331041PMC
December 2021

Microplastics as carbon-nutrient sources and shaper for microbial communities in stagnant water.

J Hazard Mater 2021 Jul 17;420:126662. Epub 2021 Jul 17.

College of Defense Engineering, The Army Engineering University of PLA, Nanjing 210007, China.

Microplastics (MPs) are emerging pollutants as vectors for microbial colonization, but their role as nutrients sources for microbial communities has rarely been reported. This study explored the impact of six types of MPs on assimilable organic carbon (AOC) and microbial communities over eight weeks. The following were the primary conclusions: (1) MPs contributed to AOC increment and subsequently increased bacterial regrowth potential. The maximum AOC reached 722.03 μg/L. The increase in AOC formation corresponded to AOC NOX, except in PVC samples where AOC P17 primarily increased. (2) The MPs accelerated bacterial growth and changed the bacterial distribution between the biofilm and water phases. A high MP surface-area-to-volume ratio or low MPs density contributed to bacterial accumulation and biofilm formation around the plastisphere, thereby decreasing the relative microbial proportion in the water phase. (3) High-throughput sequencing and scanning electron microscope revealed that different MPs shaped various microbial communities temporally and spatially. (4) Biofilm formatting and formatted models were established and simulated to explain the kinetic interaction between the AOC and bacteria inhabiting the plastisphere. Finally, the challenges that plastic-deprived AOC represent in terms of anti-bacterial measures and chemical safety are discussed.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126662DOI Listing
July 2021

Screening-based identification of xanthone as a novel NLRP3 inflammasome inhibitor via metabolic reprogramming.

Clin Transl Med 2021 Jul;11(7):e496

Eye Center of the 2nd Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.

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http://dx.doi.org/10.1002/ctm2.496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288006PMC
July 2021

Development of a nomogram for predicting clinical outcome in patients with angiogram-negative subarachnoid hemorrhage.

CNS Neurosci Ther 2021 Jul 28. Epub 2021 Jul 28.

Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China.

To the best of our knowledge, this is the largest clinical retrospective study in AN-SAH patients, and is the first time to establish accurate predictive models paired with bleeding pattern.

Background: Angiogram-negative subarachnoid hemorrhage (AN-SAH) has a definite incidence of delayed cerebral ischemia (DCI) and poor clinical outcomes. The purpose is to screen independent factors and establish a nomogram to guide the clinical therapy and assess post-discharge prognosis.

Methods: We identified 273 consecutive patients referred to our institute from 2013 to 2018 for AN-SAH. A nomogram to predict poor outcomes was formulated based on the multivariable models of independent risk factors. The accuracy and discrimination of nomograms were determined in training and internal validation cohorts.

Results: The overall poor outcome rates of AN-SAH were 14.3% and 8.7% at 3 months and 12 months, respectively. In addition, perimesencephalic AN-SAH (PAN-SAH) presented with a more unfavorable prognosis compared with non-perimesencephalic AN-SAH (NPAN-SAH). The clinical prognosis was associated with the World Federation of Neurosurgical Societies scale (WFNS) (odds ratio, 3.82 [95% CI, 1.15-12.67] for 3-month outcome; and odds ratio, 31.69 [95% CI, 3.65-275.43] for 12-month outcome), Subarachnoid hemorrhage Early Brain Edema Score (SEBES) (odds ratio, 10.39 [95% CI, 1.98-54.64] for 3-month outcome; odds ratio, 10.01 [95% CI, 1.87-53.73] for 12-month outcome), and symptomatic vasospasm (odds ratio, 3.16 [95% CI, 1.03-9.70] for 3-month outcome; odds ratio, 5.15 [95% CI, 1.34-19.85] for 12-month outcome). The nomogram was constructed based on the above features, which represented great predictive value in clinical outcomes.

Conclusions: Symptomatic vasospasm, high WFNS, cerebral edema, and NPAN-SAH after hemorrhage were associated with poor outcome of AN-SAH. The nomogram with WFNS (3-5), SEBES (3-4), vasospasm, and NPAN-SAH represented a practical approach to provide individualized risk assessment for AN-SAH patients.
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http://dx.doi.org/10.1111/cns.13712DOI Listing
July 2021

Epigenetic inhibition assisted chemotherapeutic treatment of lung cancer based on artificial exosomes.

Pharmacol Res 2021 Sep 24;171:105787. Epub 2021 Jul 24.

The Fifth Affiliated Hospital, Key Laboratory of Molecular Target & Clinical Pharmacology and The State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, PR China. Electronic address:

We adopted a novel strategy by combining histone deacetylase (HDAC) inhibitors with traditional chemotherapeutics to treat solid tumors. However, chemotherapeutics often have a narrow therapeutic index and need multiple administrations with undesired side effects that lead to the intolerance. To reduce the non-specificity of chemotherapeutics, targeted therapy was introduced to restrict such agents in the tumor with minimum effects on other tissues. We developed bioinspired artificial exosomes (AE), which enabled to deliver chemotherapeutics to the tumors effectively after systemic administration. AE were produced by incorporating membrane proteins from cancer cells into phospholipid liposomes that mimicked the plasma membrane. The synthesized AE were used for the delivery of broad-spectrum chemotherapeutic doxorubicin (DOX) and vorinostat (SAHA), an epigenetic inhibitor. The combination of DOX and SAHA showed synergistic effects on suppressing non-small cell lung cancer cells and xenograft tumors without apparent adverse effects. AE facilitated the delivery of drugs to tumor tissue and extended the retention time of drugs within tumors. Taken together, these studies suggest that the bioengineered artificial exosomes may serve as novel delivery strategy for chemotherapeutics to treat non-small cell lung cancer.
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http://dx.doi.org/10.1016/j.phrs.2021.105787DOI Listing
September 2021
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