Publications by authors named "Zhou Mei"

388 Publications

Quantitative analysis of urea in serum by synchronous modulation and demodulation fluorescence spectroscopy.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Nov 18:120645. Epub 2021 Nov 18.

State Key Laboratory of Precision Measurement Technology and Instruments, Tianjin University, China. Electronic address:

High-precision spectral data is a necessary prerequisite for quantitative analysis of complex solution components. In order to improve the accuracy of spectral data, this paper proposes a method of synchronous modulation and demodulation. This article also combines the "M + N" theory, cleverly uses the excitation fluorescence of the components in the serum and its self-absorption phenomenon, collects the fluorescence spectrum of the serum sample, and then uses the partial least squares (PLS) method and the cubic optimization model method to establish a model to analyze the urea concentration of serum. At the same time, in order to verify the effectiveness of synchronous modulation and demodulation method, the unmodulated fluorescence spectrum is used to establish the regression model of urea concentration. Compared with the unmodulated fluorescence spectrum modeling results, the fluorescence spectrum modeling results after modulation and demodulation have been significantly improved. In the modeling results of fluorescence spectrum after synchronous modulation and demodulation, the Rc is 0.916753, the RMSEC is 2.05848 mmol/L, the Rp is 0.79663, and the RMSEP is 3.16812 mmol/L, the Rp-all is 0.88879, and the RMSEP-all is 2.32114 mmol/L. The results show that the method of synchronous modulation and demodulation proposed in this paper not only reduces the influence of dark current, ambient light and background noise on the signal-to-noise ratio of the spectral data, but also effectively avoids the error caused by the non-synchronization of the chopper and the spectrometer. Therefore, the method used in this paper not only improves the signal-to-noise ratio and accuracy of spectral data, but also improves the accuracy of spectral quantitative analysis of complex solutions.
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http://dx.doi.org/10.1016/j.saa.2021.120645DOI Listing
November 2021

Effects of aging on the histology and biochemistry of rat tendon healing.

BMC Musculoskelet Disord 2021 Nov 15;22(1):949. Epub 2021 Nov 15.

Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing, 400038, China.

Introduction: Tendon diseases and injuries are a serious problem for the aged population, often leading to pain, disability and a significant decline in quality of life. The purpose of this study was to determine the influence of aging on biochemistry and histology during tendon healing and to provide a new strategy for improving tendon healing.

Method: A total of 24 Sprague-Dawley rats were equally divided into a young and an aged group. A rat patellar tendon defect model was used in this study. Tendon samples were collected at weeks 2 and 4, and hematoxylin-eosin, alcian blue and immunofluorescence staining were performed for histological analysis. Meanwhile, reverse transcription-polymerase chain reaction (RT-PCR) and western blot were performed to evaluate the biochemical changes.

Results: The histological scores in aged rats were significantly lower than those in young rats. At the protein level, collagen synthesis-related markers Col-3, Matrix metalloproteinase-1 and Metallopeptidase Inhibitor 1(TIMP-1) were decreased at week 4 in aged rats compared with those of young rats. Though there was a decrease in the expression of the chondrogenic marker aggrecan at the protein level in aged tendon, the Micro-CT results from weeks 4 samples showed no significant difference(p>0.05) on the ectopic ossification between groups. Moreover, we found more adipocytes accumulated in the aged tendon defect with the Oil Red O staining and at the gene and protein levels the markers related to adipogenic differentiation.

Conclusions: Our findings indicate that tendon healing is impaired in aged rats and is characterized by a significantly lower histological score, decreased collagen synthesis and more adipocyte accumulation in patellar tendon after repair.
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http://dx.doi.org/10.1186/s12891-021-04838-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594129PMC
November 2021

Excessive DNA damage mediates ECM degradation via the RBBP8/NOTCH1 pathway in sporadic aortic dissection.

Biochim Biophys Acta Mol Basis Dis 2021 Nov 12;1868(2):166303. Epub 2021 Nov 12.

Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing 210008, China. Electronic address:

Stanford type A aortic dissection (TA-AD) is a life-threatening disease. Most cases of aortic dissection (AD) are sporadic rather than inherited. Unlike that of inherited AD, the pathogenesis of sporadic AD is still unclear. In the current study, we aimed to explore the pathogenesis of sporadic AD through transcriptome sequencing data analyses. We downloaded sporadic TA-AD transcriptome profiles from Gene Expression Omnibus (GEO) and found response to DNA damage stimulus was activated in AD. Furthermore, by conducting mouse AD tissue single cell RNA sequencing and immunostaining, we found that DNA damage mainly occurred in smooth muscle cells (SMCs) and fibroblasts. Next, we examined the repair patterns in response to DNA damage and found the linker molecules RBBP8/NOTCH1 between DNA damage/repair and extracellular matrix (ECM) organization through protein-protein interaction analysis. Thus, we proposed that DNA damage could contribute to AD by regulating ECM changes. To explore the underlying mechanism, we knocked down the DNA repair-related gene RBBP8 in aortic SMCs, which could exacerbate DNA damage, and observed decreased expression level of NOTCH1. Inhibition of NOTCH1 with crenigacestat in vivo accelerated β-aminopropionitrile-induced formation of AD and increased mortality. Meanwhile, phenotype switching of SMCs was induced by Notch1 knockdown or inhibition; this switching occurred via a pathway involving downregulation of contractile marker gene expression and upregulation of MMP2 expression, which might aggravate ECM degradation. In conclusion, excessive DNA damage is a characteristic pathological change of sporadic aortic dissection, which might contribute to ECM changes and AD development via action on the NOTCH1 pathway.
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http://dx.doi.org/10.1016/j.bbadis.2021.166303DOI Listing
November 2021

Histologic and biomechanical evaluation of the thoracolumbar fascia graft for massive rotator cuff tears in a rat model.

J Shoulder Elbow Surg 2021 Nov 11. Epub 2021 Nov 11.

Department of Orthopedic Surgery, Southwest Hospital, Army Military Medical University, Chongqing, China. Electronic address:

Background: Fascial autografts, which are easily available grafts, have provided a promising option in patients with massive rotator cuff tears. However, no fascial autografts other than the fascia lata have been reported, and the exact healing process of the fascia-to-bone interface is not well understood. The objective of this study is to histologically and biomechanically evaluate the effect of the thoracolumbar fascia (TLF) on fascia-to-bone healing.

Methods: A total of 88 rats were used in this study. Eight rats were sacrificed at the beginning to form an intact control group, and the other rats were divided randomly into 2 groups (40 rats per group): the thoracolumbar fascia augmentation group (TLF group) and the repair group (R group). The right supraspinatus was detached, and a 3*5 mm defect of the supraspinatus was created. The thoracolumbar fascia was used to augment the torn supraspinatus in the TLF group, whereas in the R group, the torn supraspinatus was repaired in only a transosseous manner. Histology and biomechanics were assessed at 1, 2, 4, 8 and 16 weeks postoperatively.

Results: The modified tendon maturation score of the TLF group was higher than that of the R group at 8 weeks (23.00 ± 0.71 vs. 24.40 ± 0.89, P=.025) and 16 weeks (24.60 ± 0.55 vs. 26.40 ± 0.55, P≤.001). The TLF group showed a rapid vascular reaction, and the peak value appeared at 1 week. Later, the capillary density decreased, and almost no angiogenesis was observed at 8 weeks postoperatively. Immunohistochemistry results demonstrated a significantly higher percentage of collagen I in the TLF group at 4, 8 and 16 weeks (24.78% ± 2.76% vs. 20.67% ± 2.11% at 4 weeks, p=.046; 25.46% ± 1.77% vs. 21.49% ± 2.33% at 8 weeks, p=.026; 34.77% ± 2.25% vs. 30.01% ± 3.17% at 16 weeks, p=.040) postoperatively. Biomechanical tests revealed that the ultimate failure force in the TLF group was significantly higher than that in the R group at the final evaluation (29.13 ± 2.49 N vs. 23.10 ± 3.47 N, p=.022).

Conclusions: The TLF autograft can promote a faster biological healing process and a better fixation strength. It could be used as an alternative reinforcement or bridging patch when the fascia lata is not appropriate or available for SCR.

Level Of Evidence: Basic Science Study; Histology and Biomechanics.
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http://dx.doi.org/10.1016/j.jse.2021.10.019DOI Listing
November 2021

MiR-6924-5p-rich exosomes derived from genetically modified Scleraxis-overexpressing PDGFRα(+) BMMSCs as novel nanotherapeutics for treating osteolysis during tendon-bone healing and improving healing strength.

Biomaterials 2021 Nov 5;279:121242. Epub 2021 Nov 5.

Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, 400000, China. Electronic address:

Osteolysis at the tendon-bone interface can impair pullout strength during tendon-bone healing and lead to surgery failure, but the effects of clinical treatments are not satisfactory. Mesenchymal stem cell (MSC)-derived exosomes have been used as potent and feasible natural nanocarriers for drug delivery and have been proven to enhance tendon-bone healing strength, indicating that MSC-derived exosomes could be a promising therapeutic strategy. In this study, we explored Scleraxis (Scx) dynamically expressed in PDGFRα(+) bone marrow-derived mesenchymal stem cells (BMMSCs) during natural tendon-bone healing. Then, we investigated the role of PDGFRα(+) BMMSCs in tendon-bone healing after Scx overexpression as well as the underlying mechanisms. Our data demonstrated that Scx-overexpressing PDGFRα(+) BMMSCs (BMMSC) could efficiently inhibit peritunnel osteolysis and enhance tendon-bone healing strength by preventing osteoclastogenesis in an exosomes-dependent manner. Exosomal RNA-seq revealed that the abundance of a novel miRNA, miR-6924-5p, was highest among miRNAs. miR-6924-5p could directly inhibit osteoclast formation by binding to the 3'-untranslated regions (3'UTRs) of OCSTAMP and CXCL12. Inhibition of miR-6924-5p expression reversed the prevention of osteoclastogenic differentiation by BMMSC derived exosomes (BMMSC-exos). Local injection of BMMSC-exos or miR-6924-5p dramatically reduced osteoclast formation and improved tendon-bone healing strength. Furthermore, delivery of miR-6924-5p efficiently inhibited the osteoclastogenesis of human monocytes. In brief, our study demonstrates that BMMSC-exos or miR-6924-5p could serve as a potential therapy for the treatment of osteolysis during tendon-bone healing and improve the outcome.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121242DOI Listing
November 2021

Institutional Design and Incentives for Migrant Workers to Participate in Social Insurance in China: Evidence From a Policy Experiment in Chengdu City.

Front Public Health 2021 21;9:736340. Epub 2021 Oct 21.

Department of Finance, School of Economics, Sichuan University, Chengdu, China.

Rural-to-urban migration has increased rapidly in China since the early 1980s, with the number of migrants has reached 376 million by 2020. Despite this sharp trend and the significant contributions that migrants have made to urban development, the migrant workers have had very limited access to the social insurance that the majority of urban workers enjoy. Against the background of the social insurance system adjustment in Chengdu in 2011, this study uses a difference-in-differences (DID) model to empirically test the impacts of changes in the social insurance policy contribution rates on the social insurance participation rates of migrant workers, using the China Migrants Dynamic Survey (CMDS) data for 2009-2016. We find that the social insurance participation rate of migrant workers was significantly reduced after they were incorporated into the urban worker insurance system. There was no significant change in the wages of migrant workers, but the working hours were increased and their consumption level decreased. In other words, simply changing the social insurance model of migrant workers from "comprehensive social insurance" to "urban employee insurance" reduces the incentives for migrant workers to participate in insurance and harms the overall welfare of migrant workers. Our study indicates that the design of the social security policy is an important reason for the lower participation rate of migrants. It is necessary to solve the problem of insufficient incentives through the targeted social security policies; primarily, the formulation of a social security policy contribution rate suitable for the migrants, and the establishment of a comprehensive social security policy and the gradual integration of the social security system.
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http://dx.doi.org/10.3389/fpubh.2021.736340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566806PMC
November 2021

Bioevaluation and Targeted Modification of Temporin-FL From the Skin Secretion of Dark-Spotted Frog ().

Front Mol Biosci 2021 19;8:707013. Epub 2021 Oct 19.

Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom.

Bioactive proteins secreted by the granular glands of amphibian skin play a self-defensive role, and exhibit various bioactivities and . In light of the severity of the problem of antibiotic resistance for treating infections, many antimicrobial peptides (AMPs) have been developed and applied in clinical microbial treatments. We identified a naturally derived and potent antimicrobial peptide, temporin-FL, obtained from the skin secretion of via "shotgun" cloning. Two truncated analogues of this peptide were chemically synthesized to explore their structural-functional relationships. The results of a functional evaluation showed that all of the tested AMPs were active against Gram-positive bacteria and fungi and demonstrated antibiofilm activity against methicillin-resistant (MRSA) but did not have an effect on Gram-negative bacteria. Moreover, temporin-FLa demonstrated a higher level of hydrophobicity and enhanced antimicrobial efficiency, as well as hemolytic activity and cell cytotoxicity than the parent peptide. Temporin-FLb, which evidenced significantly less α-helicity, was less potent against various microbes but exhibited lower cytotoxicity relating to mammalian cells. Both of the synthesized analogues possessed a higher therapeutic index than the original peptide. Moreover, the membrane permeability assay and the measuring membrane depolarization assay declared that temporin-FL and its analogues induced membrane fracture and depolarization; the quantitative biofilm formation assay and the observations of MRSA biofilms using scanning electron microscopy revealed that the AMPs caused biofilm disruption and blocked biofilm formation, the former experiments all confirming their antimicrobial and antibiofilm properties. Hence, the optimization of temporin-FL offers insights for the discovery of new drugs for treating MRSA infections.
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http://dx.doi.org/10.3389/fmolb.2021.707013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560897PMC
October 2021

Long-Term Effects of COVID-19 on Health Care Workers 1-Year Post-Discharge in Wuhan.

Infect Dis Ther 2021 Oct 23. Epub 2021 Oct 23.

Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.

Introduction: To assess the long-term consequences of coronavirus disease (COVID-19) among health care workers (HCWs) in China (hereafter surviving HCWs).

Methods: A total of 303 surviving HCWs were included. Lung (pulmonary function test, 6-min walk test [6MWT], chest CT), physical (St. George's Respiratory Questionnaire [SGRQ], Modified Medical Research Council dyspnea scale [mMRC], and Borg scale), and psychiatric functions (Essen Trauma Inventory) were evaluated during the 1-year follow-up.

Results: Surviving HCWs had an abnormal diffusion capacity 1 year post-discharge. Participants with a reduced carbon monoxide diffusing capacity (DLCO) comprised 43.48%. The proportion of HCWs with a median 6MWT distance below the lower limit of the normal was 19.4%. An abnormal CT pattern was observed in 37.5% of the HCWs. The SGRQ, mMRC, and Borg scores of surviving HCWs, especially those with critical/severe disease, were significantly higher than those in the normal population. Probable post-traumatic stress disorder (PTSD) was reported in 21.9% of the surviving HCWs. Diffusion capacity impairment was associated with women. Critical/severe illness and nurses were associated with impaired physical function.

Conclusions: Most surviving HCWs, especially female HCWs, still had an abnormal diffusion capacity at 1 year. The physical and psychiatric functions of surviving HCWs were significantly worse than those of the healthy population. Long-term follow-up of pulmonary, physical, and psychiatric functions for surviving HCWs is required.
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http://dx.doi.org/10.1007/s40121-021-00553-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536919PMC
October 2021

Smart Nanogatekeepers for Tumor Theranostics.

Small 2021 Nov 22;17(47):e2103712. Epub 2021 Oct 22.

College of Pharmacy, Anhui University of Chinese Medicine and Anhui Academy of Chinese Medicine, Hefei, 230012, China.

Nanoparticulate drug delivery systems (nano-DDSs) are required to reliably arrive and persistently reside at the tumor site with minimal off-target side effects for clinical theranostics. However, due to the complicated environment and high interstitial pressure in tumor tissue, they can return to the bloodstream and cause secondary side effects in normal organs. Recently, a number of nanogatekeepers have been engineered via structure-transformable/stable strategies to overcome this undesirable dilemma. The emerging structure-transformable nanogatekeepers for tumor imaging and therapy are first overviewed here, particularly for nanogatekeepers undergoing structural transformation in tumor microenvironments, cell membranes, and organelles. Thereafter, intelligent structure-stable nanogatekeepers through reversible activation and artificial individualization receptors are overviewed. Finally, the ongoing challenges and prospects of nanogatekeepers for clinical translation are briefly discussed.
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http://dx.doi.org/10.1002/smll.202103712DOI Listing
November 2021

Adipogenic differentiation was inhibited by downregulation of PPARγ signaling pathway in aging tendon stem/progenitor cells.

J Orthop Surg Res 2021 Oct 18;16(1):614. Epub 2021 Oct 18.

Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing, 400038, China.

Background: Tendon stem/progenitor cells (TSPCs) play a vital role in tendon repair and regeneration. Previously we found more adipocytes accumulated in the patellar tendon injury sites in aging rats compared with the young ones, of which the mechanism is still unknown. Here, we want to identify whether erroneous differentiation of TSPCs by aging accounts for the adipocyte accumulation.

Methods: TSPCs from young and aging rats were isolated and propagated. Both young and aging TSPCs were induced to differentiate into adipocytes, and Oil red O staining, quantitative real-time polymerase chain reaction (qRT-PCR), western-blot and immunofluorescent staining were used to evaluate the capability of TSPCs. RNA sequencing was utilized to screen out different genes and signaling pathways related to adipogenesis between young and aging TSPCs.

Results: The Oil red O staining showed there were more adipocytes formed in young TSPCs. Besides, adipogenic markers perilipin, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding proteins alpha (C/EBPα) and Fatty acid-binding protein 4 (FABP4) were elevated both at gene and protein level. PPARγ signaling pathway was selected as our target via RNA sequencing. After adding the signaling activators, Rosiglitazone maleate (RM), inhibited adipogenesis of aging TSCs was reversed.

Conclusions: In conclusion, aging inhibited adipogenesis of TSPCs by down-regulating PPARγ signaling. It is not likely that the adipocyte accumulation in aging tendon during repair was due to the aging of TSPCs. This may provide new targets for curing aging tendon injuries or tendinopathies.
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http://dx.doi.org/10.1186/s13018-021-02720-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522149PMC
October 2021

WO/AgCO Mixed Photocatalyst with Enhanced Photocatalytic Activity for Organic Dye Degradation.

ACS Omega 2021 Oct 30;6(40):26439-26453. Epub 2021 Sep 30.

Key Laboratory of Green Chemistry of Sichuan Institutes of Higher Education, College of Chemistry and Environmental Engineering, Sichuan University of Science and Engineering, Zigong 643000, Sichuan, China.

The development of an efficient photocatalyst with superior activity under visible light has been regarded as a significant strategy for pollutant degradation and environmental remediation. Herein, a series of WO/AgCO mixed photocatalysts with different proportions were prepared by a simple mixing method and characterized by XRD, SEM, TEM, XPS, and DRS techniques. The photocatalytic performance of the WO/AgCO mixed photocatalyst was investigated by the degradation of rhodamine B (RhB) under visible light irradiation (λ > 400 nm). The photocatalytic efficiency of the mixed WO/AgCO photocatalyst was rapidly increased with the proportion of AgCO up to 5%. The degradation percentage of RhB by WO/AgCO-5% reached 99.7% within 8 min. The pseudo-first-order reaction rate constant of WO/AgCO-5% (0.9591 min) was 118- and 14-fold higher than those of WO (0.0081 min) and AgCO (0.0663 min). The catalytic activities of the mixed photocatalysts are not only higher than those of the WO and AgCO but also higher than that of the WO/AgCO composite prepared by the precipitation method. The activity enhancement may be because of the easier separation of photogenerated electron-hole pairs. The photocatalytic mechanism was investigated by free radical capture performance and fluorescence measurement. It was found that light-induced holes (h) was the major active species and superoxide radicals (·O ) also played a certain role in photocatalytic degradation of RhB.
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http://dx.doi.org/10.1021/acsomega.1c03694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515572PMC
October 2021

Changes in glomerular filtration rate and metabolomic differences in severely ill coronavirus disease survivors 3 months after discharge.

Biochim Biophys Acta Mol Basis Dis 2022 Jan 14;1868(1):166289. Epub 2021 Oct 14.

Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Rd, Wuhan, Hubei 430022, China. Electronic address:

To explore the recovery of renal function in severely ill coronavirus disease (COVID-19) survivors and determine the plasma metabolomic profile of patients with different renal outcomes 3 months after discharge, we included 89 severe COVID-19 survivors who had been discharged from Wuhan Union Hospital for 3 months. All patients had no underlying kidney disease before admission. At patient recruitment, renal function assessment, laboratory examination, chest computed tomography (CT) were performed. Liquid chromatography-mass spectrometry was used to detect metabolites in the plasma. We analyzed the longitudinally change in the estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin-c levels using the CKD-EPI equation and explored the metabolomic differences in patients with different eGFR change patterns from hospitalization to 3 months after discharge. Lung CT showed good recovery; however, the median eGFR significantly decreased at the 3-month follow-up. Among the 89 severely ill COVID-19 patients, 69 (77.5%) showed abnormal eGFR (<90 mL/min per 1.73 m) at 3 months after discharge. Age (odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.08-1.47, p = 0.003), body mass index (OR = 1.97, 95% CI = 1.20-3.22, p = 0.007), and cystatin-c level (OR = 1.22, 95% CI = 1.07-1.39, p = 0.003) at discharge were independent risk factors for post-discharge abnormal eGFR. Plasma metabolomics at the 3-months follow-up revealed that β-pseudouridine, uridine, and 2-(dimethylamino) guanosine levels gradually increased with an abnormal degree of eGFR. Moreover, the kynurenine pathway in tryptophan metabolism, vitamin B6 metabolism, cysteine and methionine metabolism, and arginine biosynthesis were also perturbed in survivors with abnormal eGFR.
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http://dx.doi.org/10.1016/j.bbadis.2021.166289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516480PMC
January 2022

Generation of truncated derivatives through enzymatic digest of peptide GV30 target MRSA both and .

Comput Struct Biotechnol J 2021 29;19:4984-4996. Epub 2021 Aug 29.

Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK.

Methicillin-resistant (MRSA) causing serious hospital-acquired infections and skin infections has become a "superbug" in clinical treatment. Although the clinical treatment of MRSA is continuously improving, due to its unceasing global spread, MRSA has produced much heated discussion and focused study, therefore suggesting an urgent task to find new antibacterial drugs to combat this issue. Antimicrobial peptides (AMPs) are used as the last-resort drugs for treating multidrug-resistant bacterial infections, but their utilisation is still limited due to their low stability and often strong toxicity. Here, we evaluated the structure and the bioactivity of an AMP, GV30, derived from the frog skin secretions of and designed seven truncated derivatives based on the presence of cleavage sites for trypsin using an online proteomic bioinformatic resource PeptideCutter tool. We investigated the anti-MRSA effect, toxicity and salt- and serum-resistance of these peptides. Interestingly, the structure-activity relationship revealed that removing "Rana box" loop could significantly improve the bactericidal speed on MRSA. Among these derivatives, GV21 (GVIFNALKGVAKTVAAQLLKK-NH), because of its faster antibacterial effect, lower toxicity, and retains the good antibacterial activity and stability of the parent peptide, is considered to become a new potential antibacterial candidate against MRSA.
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http://dx.doi.org/10.1016/j.csbj.2021.08.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441110PMC
August 2021

Modification Strategy of D-leucine Residue Addition on a Novel Peptide from , with Enhanced Bioactivity and In Vivo Efficacy.

Toxins (Basel) 2021 08 31;13(9). Epub 2021 Aug 31.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.

Brevinins are a well-characterised, frog-skin-derived, antimicrobial peptide (AMP) family, but their applications are limited by high cytotoxicity. In this study, a wild-type des-Leu2 brevinin peptide, named brevinin-1OS (B1OS), was identified from . To explore the significant role of the leucine residue at the second position, two variants, B1OS-L and B1OS-D-L, were designed by adding L-leucine and D-leucine residues at this site, respectively. The antibacterial and anticancer activities of B1OS-L and B1OS-D-L were around ten times stronger than the parent peptide. The activity of B1OS against the growth of Gram-positive bacteria was markedly enhanced after modification. Moreover, the leucine-modified products exerted in vivo therapeutic potential in an methicillin-resistant (MRSA)-infected waxworm model. Notably, the single substitution of D-leucine significantly increased the killing speed on lung cancer cells, where no viable H838 cells survived after 2 h of treatment with B1OS-D-L at 10 μM with low cytotoxicity on normal cells. Overall, our study suggested that the conserved leucine residue at the second position from the N-terminus is vital for optimising the dual antibacterial and anticancer activities of B1OS and proposed B1OS-D-L as an appealing therapeutic candidate for development.
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http://dx.doi.org/10.3390/toxins13090611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473181PMC
August 2021

Plasma Metabolomic Profiles in Recovered COVID-19 Patients without Previous Underlying Diseases 3 Months After Discharge.

J Inflamm Res 2021 7;14:4485-4501. Epub 2021 Sep 7.

Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People's Republic of China.

Background: It remains unclear whether discharged COVID-19 patients have fully recovered from severe complications, including the differences in the post-infection metabolomic profiles of patients with different disease severities.

Methods: COVID-19-recovered patients, who had no previous underlying diseases and were discharged from Wuhan Union Hospital for 3 months, and matched healthy controls (HCs) were recruited in this prospective cohort study. We examined the blood biochemical indicators, cytokines, lung computed tomography scans, including 39 HCs, 18 recovered asymptomatic (RAs), 34 recovered moderate (RMs), and 44 recovered severe/ critical patients (RCs). A liquid chromatography-mass spectrometry-based metabolomics approach was employed to profile the global metabolites of fasting plasma of these participants.

Results: Clinical data and metabolomic profiles suggested that RAs recovered well, but some clinical indicators and plasma metabolites in RMs and RCs were still abnormal as compared with HCs, such as decreased taurine, succinic acid, hippuric acid, some indoles, and lipid species. The disturbed metabolic pathway mainly involved the tricarboxylic cycle, purine, and glycerophospholipid metabolism. Moreover, metabolite alterations differ between RMs and RCs when compared with HCs. Correlation analysis revealed that many differential metabolites were closely associated with inflammation and the renal, pulmonary, heart, hepatic, and coagulation system functions.

Conclusion: We uncovered metabolite clusters pathologically relevant to the recovery state in discharged COVID-19 patients which may provide new insights into the pathogenesis of potential organ damage in recovered patients.
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http://dx.doi.org/10.2147/JIR.S325853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434912PMC
September 2021

Evaluation of antimicrobial and anticancer activities of three peptides identified from the skin secretion of Hylarana latouchii.

Acta Biochim Biophys Sin (Shanghai) 2021 Nov;53(11):1469-1483

Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, UK.

The skins of frogs of the family Ranidae are particularly rich sources of biologically active peptides, among which antimicrobial peptides (AMPs) constitute the major portion. Some of these have attracted the interest of researchers because they possess both antimicrobial and anticancer activities. In this study, with 'shotgun' cloning and MS/MS fragmentation, three AMPs, homologues of family brevinin-1 (brevinin-1HL), and temporin (temporin-HLa and temporin-HLb), were discovered from the skin secretion of the broad-folded frog, Hylarana latouchii. They exhibited various degrees of antimicrobial and antibiofilm activities against test microorganisms and hemolysis on horse erythrocytes. It was found that they could induce bacteria death through disrupting cell membranes and binding to bacterial DNA. In addition, they also showed different potencies towards human cancer cell lines. The secondary structure and physicochemical properties of each peptide were investigated to preliminarily reveal their structure-activity relationships. Circular dichroism spectrometry showed that they all adopted a canonical α-helical conformation in membrane-mimetic solvents. Notably, the prepropeptide of brevinin-1HL from H. latouchii was highly identical to that of brevinin-1GHd from Hylarana guentheri, indicating a close relationship between these two species. Accordingly, this study provides candidates for the design of novel anti-infective and antineoplastic agents to fight multidrug-resistant bacteria and malignant tumors and also offers additional clues for the taxonomy of ranid frogs.
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http://dx.doi.org/10.1093/abbs/gmab126DOI Listing
November 2021

Fluorescence discrimination of HSA from BSA: A close look at the albumin-induced restricted intramolecular rotation of flavonoid probe.

Spectrochim Acta A Mol Biomol Spectrosc 2022 Jan 22;264:120306. Epub 2021 Aug 22.

College of Materials Science and Engineering, Shenzhen University, Shenzhen 518060, PR China. Electronic address:

Discrimination of human serum albumin (HSA) from bovine serum albumin (BSA) based on the fluorescence probe technique is still challenging due to similar chemical structures. In this work, a novel flavonoid-based fluorescent probe AF is reported for successful discrimination of HSA from BSA. The sensing performances of probe, including sensing dynamic, sensitivity and selectivity, have been carefully studied. Moreover, sensing mechanism was elucidated by Job's plot, displacement experiment, and molecular docking, suggesting that the specific response to HSA originated from the albumin-induced restricted intramolecular rotation (RIR) of probe. This work may provide a simple way for designing of novel probes for HSA with high selectivity.
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http://dx.doi.org/10.1016/j.saa.2021.120306DOI Listing
January 2022

Dual-mode spectrum of transmission and fluorescence using single ultraviolet LED light source and their application in analyzing total bilirubin in serum.

Spectrochim Acta A Mol Biomol Spectrosc 2022 Jan 21;264:120305. Epub 2021 Aug 21.

Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments, China. Electronic address:

In order to improve the accuracy of spectral analysis of complex solutions, based on the "M + N" theory, this paper proposes to use single (365 nm ± 5 nm) ultraviolet LED as emission light to detect transmission spectrum and excited fluorescence spectrum. Taking the total bilirubin in serum as the measurement object, the dual-mode spectrum of transmission and fluorescence about serum is collected, which increases the amount of information. In order to verify the effectiveness of the method proposed in this paper, the transmission and fluorescence spectra of the samples were also collected. Then three models of total bilirubin concentration are established by transmission spectrum, fluorescence spectrum and dual-mode spectrum of transmission and fluorescence respectively. Through the comparison of the parameters of the three models, the model established by dual-mode spectrum of transmission and fluorescence is good. The Rc of the model is 0.91 and the RMSEC is 3.00 (μmol/L). The Rp is 0.92, the RMSEP is 3.53 (μmol/L). Compared with transmission spectrum modeling and fluorescence spectrum modeling, the RMSEP of dual-mode spectrum modeling was reduced by 34.8% and 22.6% respectively. The experimental results show that the measurement method of dual-mode spectrum of transmission and fluorescence by using a single ultraviolet light source proposed in this paper based on the "M + N" theory increases the information of solution composition, which provides a new method for the analysis of the same characteristic components.
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http://dx.doi.org/10.1016/j.saa.2021.120305DOI Listing
January 2022

Improve the precision of platelet spectrum quantitative analysis based on "M+N" theory.

Spectrochim Acta A Mol Biomol Spectrosc 2022 Jan 19;264:120291. Epub 2021 Aug 19.

Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments, China. Electronic address:

Platelets have the functions of promoting blood coagulation and accelerating hemostasis, playing an important role in human body. It is of great medical significance to realize clinical rapid micro-detection of platelets by spectral analysis, which is the development direction of clinical detection in the future. However, due to the problem of unobvious characteristic of platelet absorption spectrum, the results of modeling and analysis cannot meet the clinical accuracy requirements. In order to improve the analysis accuracy, based on the "M+N" theory, this paper comprehensively considers the influence of the concentrations of measured component platelet and non-measured component hemoglobin on modeling analysis, and uses the method of selecting training set based on the concentration distribution of two components. At the same time, considering the characteristic of the linear model, the samples at both ends of the concentration of two components are selected as the training set, and the cubic term fitting method is combined to model and predict the concentration of platelet. The following experiments were designed: the training sets were selected by four different methods and used for modeling to predict the platelet concentration, and compared the modeling results of different methods. Through the modeling and prediction of 222 samples, the result showed that the method of selecting the training set with the concentration distribution of two components could effectively improve the prediction accuracy of the established model, and got a better model with better performance, the correlation coefficient Rc reached 0.63, which was 24.98% higher than the result of full modeling for all samples, and RMSE decreased by 10.02%. Considering the influence of non-measured components in modeling is of great significance to improve the prediction accuracy of measured components, and selecting samples from both ends of the concentration values of two components as the training set can further improve the performance and accuracy of the model.
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http://dx.doi.org/10.1016/j.saa.2021.120291DOI Listing
January 2022

Recent Advances and Challenges in Nanodelivery Systems for Antimicrobial Peptides (AMPs).

Antibiotics (Basel) 2021 Aug 16;10(8). Epub 2021 Aug 16.

Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.

Antimicrobial peptides (AMPs) can be used as alternative therapeutic agents to traditional antibiotics. These peptides have abundant natural template sources and can be isolated from animals, plants, and microorganisms. They are amphiphilic and mostly net positively charged, and they have a broad-spectrum inhibitory effect on bacteria, fungi, and viruses. AMPs possess significant rapid killing effects and do not interact with specific receptors on bacterial surfaces. As a result, drug resistance is rarely observed with treatments. AMPs, however, have some operational problems, such as a susceptibility to enzymatic (protease) degradation, toxicity in vivo, and unclear pharmacokinetics. However, nanodelivery systems loaded with AMPs provide a safe mechanism of packaging such peptides before they exert their antimicrobial actions, facilitate targeted delivery to the sites of infection, and control the release rate of peptides and reduce their toxic side effects. However, nanodelivery systems using AMPs are at an early stage of development and are still in the laboratory phase of development. There are also some challenges in incorporating AMPs into nanodelivery systems. Herein, an insight into the nanotechnology challenges in delivering AMPs, current advances, and remaining technological challenges are discussed in depth.
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http://dx.doi.org/10.3390/antibiotics10080990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388958PMC
August 2021

Study on the Structure-Activity Relationship of an Antimicrobial Peptide, Brevinin-2GUb, from the Skin Secretion of .

Antibiotics (Basel) 2021 Jul 22;10(8). Epub 2021 Jul 22.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.

Antimicrobial peptides (AMPs) are considered potential alternatives to antibiotics due to their advantages in solving antibiotic resistance. Brevinin-2GUb, which was extracted from the skin secretion of , is a peptide with modest antimicrobial activity. Several analogues were designed to explore the structure-activity relationship and enhance its activity. In general, the Rana box is not an indispensable motif for the bioactivity of Brevinin-2GUb, and the first to the 19th amino acids at the N-terminal end are active fragments, such that shortening the peptide while maintaining its bioactivity is a promising strategy for the optimisation of peptides. Keeping a complete hydrophobic face and increasing the net charges are key factors for antimicrobial activity. With the increase of cationic charges, α-helical proportion, and amphipathicity, the activity of t-Brevinin-2GUb-6K (tB2U-6K), in combatting bacteria, drastically improved, especially against Gram-negative bacteria, and the peptide attained the capacity to kill clinical isolates and fungi as well, which made it possible to address some aspects of antibiotic resistance. Thus, peptide tB2U-6K, with potent antimicrobial activity against antibiotic-resistant bacteria, the capacity to inhibit the growth of biofilm, and low toxicity against normal cells, is of value to be further developed into an antimicrobial agent.
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http://dx.doi.org/10.3390/antibiotics10080895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388802PMC
July 2021

ALKBH5 promotes cadmium-induced transformation of human bronchial epithelial cells by regulating PTEN expression in an m6A-dependent manner.

Ecotoxicol Environ Saf 2021 Aug 23;224:112686. Epub 2021 Aug 23.

Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China. Electronic address:

Cadmium is a carcinogenic heavy metal that poses a severe threat to human beings. The underlying mechanism, however, remains elusive. N6-methyladenosine (m6A) is the most abundant post-transcriptional modification in mRNA that regulates RNA metabolism. Emerging evidence shows that m6A is involved in the pathogenesis of various cancers. In this study, human bronchial epithelial BEAS-2B cells were transformed by exposing to 2 μM of cadmium for 20 weeks to investigate the role of m6A in cadmium carcinogenesis. We found the level of m6A in mRNA was significantly decreased in cadmium-transformed BEAS-2B cells, and this change was regulated by m6A demethylase ALKBH5. ALKBH5 was significantly upregulated in the middle and late stages of cell transformation at week 8, 12, 16 and 20. Knockdown of ALKBH5 in cadmium-transformed cells alleviated cell proliferation, migration, invasion, and anchorage-independent growth, but co-transfection with ALKBH5 siRNA and PTEN siRNA restored the inhibitory effects of ALKBH5 knockdown on those transformation properties. ALKBH5 decreased the m6A level of PTEN mRNA, resulting in its instability and reduction of PTEN protein expression. These results indicate that ALKBH5-mediated demethylation m6A at PTEN mRNA is involved in cadmium-induced cell transformation. Our study provides a new perspective for the involvement of m6A modification in cadmium carcinogenesis.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112686DOI Listing
August 2021

Meigs syndrome with pleural effusion as initial manifestation: A case report.

World J Clin Cases 2021 Jul;9(21):5972-5979

Department of Respiratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.

Background: Meigs syndrome is a rare neoplastic disease characterized by the triad of benign solid ovarian tumor, ascites, and pleural effusion. In postmenopausal women with pleural effusions, ascites, elevated CA-125 level, and pelvic masses, the probability of disseminated disease is high. Nevertheless, the final diagnosis is based on its histopathologic features following surgical removal of a mass lesion. Here we describe a case of Meigs syndrome with pleural effusion as the initial manifestation.

Case Summary: A 52-year-old woman presented with a 2-mo history of dry cough and oppression in the chest and was admitted to our hospital due to recurrent pleural effusion and gradual worsening of dyspnea that had occurred over the previous month. Two months before admission, the patient underwent repeated chest drainage and empirical anti-tuberculosis treatment. However, the pleural fluid accumulation persisted, and the patient began to experience dyspnea on exertion leading to admission. A computed tomography scan of the chest, abdominal ultrasound, and magnetic resonance imaging confirmed the presence of right-sided pleural effusion and ascites with a right ovarian mass. Serum tumor markers showed raised CA-125. With a suspicion of a malignant tumor, the patient underwent laparoscopic excision of the ovarian mass and the final pathology was consistent with an ovarian fibrothecoma. On the seventh day postoperation, the patient had resolution of the right-sided pleural effusion.

Conclusion: Despite the relatively high risk of malignancy when an ovarian mass associated with hydrothorax is found in a patient with elevated serum levels of CA-125, clinicians should be aware about rare benign syndromes, like Meigs, for which surgery remains the preferred treatment.
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http://dx.doi.org/10.12998/wjcc.v9.i21.5972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316948PMC
July 2021

Dynamic changes of functional fitness, antibodies to SARS-CoV-2 and immunological indicators within 1 year after discharge in Chinese health care workers with severe COVID-19: a cohort study.

BMC Med 2021 07 14;19(1):163. Epub 2021 Jul 14.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China.

Background: Few studies had described the health consequences of patients with coronavirus disease 2019 (COVID-19) especially in those with severe infections after discharge from hospital. Moreover, no research had reported the health consequences in health care workers (HCWs) with COVID-19 after discharge. We aimed to investigate the health consequences in HCWs with severe COVID-19 after discharge from hospital in Hubei Province, China.

Methods: We conducted an ambidirectional cohort study in "Rehabilitation Care Project for Medical Staff Infected with COVID-19" in China. The participants were asked to complete three physical examinations (including the tests of functional fitness, antibodies to SARS-CoV-2 and immunological indicators) at 153.4 (143.3, 164.8), 244.3 (232.4, 259.1), and 329.4 (319.4, 339.3) days after discharge, respectively. Mann-Whitney U test, Kruskal-Wallis test, t test, one-way ANOVA, χ, and Fisher's exact test were used to assess the variance between two or more groups where appropriate.

Results: Of 333 HCWs with severe COVID-19, the HCWs' median age was 36.0 (31.0, 43.0) years, 257 (77%) were female, and 191 (57%) were nurses. Our research found that 70.4% (114/162), 48.9% (67/137), and 29.6% (37/125) of the HCWs with severe COVID-19 were considered to have not recovered their functional fitness in the first, second, and third functional fitness tests, respectively. The HCWs showed improvement in muscle strength, flexibility, and agility/dynamic balance after discharge in follow-up visits. The seropositivity of IgM (17.0% vs. 6.6%) and median titres of IgM (3.0 vs. 1.4) and IgG (60.3 vs. 45.3) in the third physical examination was higher than that in the first physical examination. In the third physical examination, there still were 42.1% and 45.9% of the HCWs had elevated levels of IL-6 and TNF-α, and 11.9% and 6.3% of the HCWs had decreased relative numbers of CD3 T cells and CD4 T cells.

Conclusion: The HCWs with severe COVID-19 showed improvement in functional fitness within 1 year after discharge, active intervention should be applied to help their recovery if necessary. It is of vital significance to continue monitoring the functional fitness, antibodies to SARS-CoV-2 and immunological indicators after 1 year of discharge from hospital in HCWs with severe COVID-19.
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http://dx.doi.org/10.1186/s12916-021-02042-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277525PMC
July 2021

Comparison of Residual Pulmonary Abnormalities 3 Months After Discharge in Patients Who Recovered From COVID-19 of Different Severity.

Front Med (Lausanne) 2021 25;8:682087. Epub 2021 Jun 25.

NHC Key Laboratory of Pulmonary Diseases, Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

To investigate whether coronavirus disease 2019 (COVID-19) survivors who had different disease severities have different levels of pulmonary sequelae at 3 months post-discharge. COVID-19 patients discharged from four hospitals 3 months previously, recovered asymptomatic patients from an isolation hotel, and uninfected healthy controls (HCs) from the community were prospectively recruited. Participants were recruited at Wuhan Union Hospital and underwent examinations, including quality-of-life evaluation (St. George Respiratory Questionnaire [SGRQ]), laboratory examination, chest computed tomography (CT) imaging, and pulmonary function tests. A total of 216 participants were recruited, including 95 patients who had recovered from severe/critical COVID-19 (SPs), 51 who had recovered from mild/moderate disease (MPs), 28 who had recovered from asymptomatic disease (APs), and 42 HCs. In total, 154 out of 174 (88.5%) recovered COVID-19 patients tested positive for serum SARS-COV-2 IgG, but only 19 (10.9%) were still positive for IgM. The SGRQ scores were highest in the SPs, while APs had slightly higher SGRQ scores than those of HCs; 85.1% of SPs and 68.0% of MPs still had residual CT abnormalities, mainly ground-glass opacity (GGO) followed by strip-like fibrosis at 3 months after discharge, but the pneumonic lesions were largely absorbed in the recovered SPs or MPs relative to findings in the acute phase. Pulmonary function showed that the frequency of lung diffusion capacity for carbon monoxide abnormalities were comparable in SPs and MPs (47.1 vs. 41.7%), while abnormal total lung capacity (TLC) and residual volume (RV) were more frequent in SPs than in MPs (TLC, 18.8 vs. 8.3%; RV, 11.8 vs. 0%). Pulmonary abnormalities remained after recovery from COVID-19 and were more frequent and conspicuous in SPs at 3 months after discharge.
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http://dx.doi.org/10.3389/fmed.2021.682087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270002PMC
June 2021

A novel circular RNA, circPUS7 promotes cadmium-induced transformation of human bronchial epithelial cells by regulating Kirsten rat sarcoma viral oncogene homolog expression via sponging miR-770.

Metallomics 2021 07;13(7)

Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.

Cadmium is a human carcinogen, which induces cancers by mechanisms that are not fully understood. Induction of oxidative stress, apoptosis resistance, genotoxic effects, and epigenetic modulations have been indicated to regulate cadmium-induced carcinogenesis. Circular RNAs are epigenetic regulators that have been recognized to play essential roles in carcinogenesis. Yet, the involvement of circular RNAs in cadmium carcinogenesis remains unclear. In this study, a novel circular RNA, circPUS7, was identified and described for the first time. CircPUS7 was significantly upregulated at week 12, 16, and 20 during the cadmium-induced transformation of human bronchial epithelial BEAS-2B cells. Knockdown of circPUS7 in cadmium-transformed BEAS-2B (T-BEAS-2B) cells significantly attenuated transformation markers including cell proliferation, migration, invasion, and anchorage-independent growth. Moreover, circPUS7 promoted malignant phenotypes by competitively binding with miR-770. Overexpression of miR-770 significantly inhibited the transformation properties of T-BEAS-2B cells while inhibition of miR-770 potently reversed the inhibitory effects of circPUS7 knockdown in proliferation, migration, invasion, and anchorage-independent growth of the T-BEAS-2B cells. Kirsten rat sarcoma viral oncogene homolog (KRAS), which was increased synchronically with circPUS7 during cadmium-induced cell transformation, was regulated by circPUS7 through sponging miR-770. In summary, our findings demonstrate that circPUS7 promotes cadmium-induced cell transformation through sponging miR-770 to regulate KRAS expression, providing a new perspective with the involvement of circular RNAs to further understand the mechanisms of cadmium carcinogenesis.
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http://dx.doi.org/10.1093/mtomcs/mfab043DOI Listing
July 2021

Structure-Activity Relationship and Molecular Docking of a Kunitz-Like Trypsin Inhibitor, Kunitzin-AH, from the Skin Secretion of .

Pharmaceutics 2021 Jun 26;13(7). Epub 2021 Jun 26.

Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau, China.

Kunitz-like trypsin inhibitors are one of the most noteworthy research objects owing to their significance in pharmacological studies, including anticarcinogenic activity, obesity regulation and anticoagulation. In the current study, a novel Kunitz-like trypsin inhibitor, Kunitzin-AH, was isolated from the skin secretion of . The novel peptide displayed a modest trypsin inhibitory activity with the inhibitor constant () value of 1.18 ± 0.08 µM without inducing damage to healthy horse erythrocytes. Then, a series of shortened variants of Kunitzin-AH were designed by truncating a peptide loop and site mutation inside the loop to illustrate the structure-activity relationship of the trypsin inhibition function. Among the variants, a significant decrease was observed for the Cys-Cys loop domain, while the extension of an Arg at N-terminus (RCKAAFC) retained the inhibitory activity, indicating that the -RCK-motif is essential in forming the reactive domain for exerting the inhibitory activity. Furthermore, substitutions of Ala by hydrophobic or hydrophilic residues decreased the activity, indicating suitable steric hindrance provides convenience for the combination of trypsin. Additionally, the conformational simulation of the analogues processed with Chimera and Gromacs and further combination simulations between the peptides and trypsin conducted with HDOCK offered a potential opportunity for the natural trypsin inhibitory drug design. The truncated sequence, AH-798, may be a good replacement for the full-length peptide, and can be optimized via cyclization for further study.
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http://dx.doi.org/10.3390/pharmaceutics13070966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309051PMC
June 2021

The risk factors of autogenous arteriovenous fistula dysfunction in maintenance hemodialysis patients and the curative effect of personalized nursing.

Am J Transl Res 2021 15;13(5):5107-5116. Epub 2021 May 15.

Department of Nephrology, Chongqing Changshou District People's Hospital Chongqing 401220, China.

Objective: To explore the effect of individualized nursing intervention on autologous arteriovenous fistula (AVF) dysfunction and the risk factors leading to failures in maintenance hemodialysis (MHD) patients.

Methods: A total of 196 patients undergoing MHD in our hospital from March 2017 to May 2019 were recruited as the study cohort and divided into two groups according to the nursing method each patient underwent. The patients who underwent individualized nursing intervention were placed in the research group (RG, n = 107), and the patients who underwent routine nursing intervention were placed in the control group (CG, n = 89). The proportion of patients with primary dysfunction in the use of AVF was recorded, and the patients' psychological states, treatment compliance, and self-nursing abilities in the two groups before and after the nursing intervention were observed. The complications, the life treatment scores, and the patients' nursing satisfaction were recorded after the nursing intervention. A logistic regression analysis was performed for the patients with initial AVF dysfunction.

Results: Compared with the CG, the patients in the RG after the nursing intervention had statistically lower AVF dysfunction rates, notably lower SAS and SDS scores, remarkably higher total compliance rates and ESCA scores, and a dramatically lower total incidence of complications. AVF dysfunction occurred in 26 of 196 patients (13.4%) during the follow-up, with an increased risk of AVF loss in patients over 60 years old, lower blood pressure, higher hemoglobin concentrations, lower treatment compliance, self-care inability, and routine nursing interventions. After the nursing, the WHOQOL-BREF and nursing satisfaction scores in the RG were noticeably higher than they were in the CG.

Conclusion: Autologous AVF dysfunction is the result of multiple risk factors, and personalized nursing can reduce the incidence of complications, improve patients' treatment compliance and self-care abilities, and ameliorate their quality of life.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205782PMC
May 2021

A novel bioengineered fragment peptide of Vasostatin-1 exerts smooth muscle pharmacological activities and anti-angiogenic effects via blocking VEGFR signalling pathway.

Comput Struct Biotechnol J 2021 3;19:2664-2675. Epub 2021 May 3.

Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR, China.

Chromogranin A (CgA) is a hydrophilic glycoprotein released by post-ganglionic sympathetic neurons. CgA consists of a single peptide chain containing numerous paired basic residues, which are typical cleavage sites in prohormones to generate bioactive peptides. It is recognized as a diagnostic and prognostic serum marker for neuroendocrine tumours. Vasostatin-1 is one of the most conserved regions of CgA and has diverse inhibitory biological activities. In this study, a novel peptide fragment that contains three typical functional structures of Vasostatin-1 was synthesized. This unique bioengineered Vasostatin-1 Derived Peptide (named V1DP) includes a highly conserved domain between vertebrate species in its N-terminal region, comprising a disulphide bridge formed by two cysteine residues at amino acid positions 17 and 38, respectively. Besides, V1DP contains two significant tripeptide recognition sequences: the amino acid triplets, RGD and KGD. Our data demonstrated that V1DP could induce a dose-dependent relaxation of rat arterial smooth muscle and also increase the contraction activity of rat uterus smooth muscle. More importantly, we found that V1DP inhibits cancer cell proliferation, modulate the HUVEC cell migration, and exhibit anti-angiogenesis effect both in and in We further investigated the actual mechanism of V1DP, and our results confirmed that V1DP involves inhibiting the vascular endothelial growth factor receptor (VEGFR) signalling. We docked V1DP to the apo structures of VEGFR2 and examined the stability of the peptide in the protein pockets. Our simulation and free energy calculations results indicated that V1DP can bind to the catalytic domain and regulatory domain pockets, depending on whether the conformational state of the protein is JM-in or JM-out. Taken together, our data suggested that V1DP plays a role as the regulator of endothelial cell function and smooth muscle pharmacological homeostasis. V1DP is a water-soluble and biologically stable peptide and could further develop as an anti-angiogenic drug for cancer treatment.
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http://dx.doi.org/10.1016/j.csbj.2021.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131715PMC
May 2021

Circ-SHPRH suppresses cadmium-induced transformation of human bronchial epithelial cells by regulating QKI expression via miR-224-5p.

Ecotoxicol Environ Saf 2021 Sep 31;220:112378. Epub 2021 May 31.

Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430030, PR China. Electronic address:

Circular RNAs (circRNAs) have been demonstrated to play critical roles in the pathogenesis of human cancers and carcinogenesis of several environmental pollutants. Nevertheless, the function of circRNAs in cadmium carcinogenesis is unclear. circ-SHPRH is down-regulated in many cancers including non-small cell lung cancer. In our present study, during cadmium-induced transformation of human bronchial epithelial BEAS-2B cells, epithelial-mesenchymal transition (EMT) was induced. Meanwhile, at the middle and late stages of cell transformation, cadmium down-regulated the expression of circ-SHPRH, as well as QKI, a tumor suppressor protein known to prevent the proliferation and EMT during progression of human cancers, compared with passage-matched control BEAS-2B cells. Overexpression of circ-SHPRH in cadmium-transformed BEAS-2B cells promoted the expression of QKI and significantly inhibited proliferation, EMT, invasion, migration and anchorage-independent growth in soft agar of the cells. Mechanistic studies showed that circ-SHPRH functioned as a sponge of miR-224-5p to regulate QKI expression. Interestingly, QKI and circ-SHPRH could form a positive-feedback loop that perpetuated circ-SHPRH/miR-224-5p/QKI axis. Collectively, our results demonstrated that circ-SHPRH inhibited cadmium-induced transformation of BEAS-2B cells through sponging miR-224-5p to regulate QKI expression under cadmium treatment. Our study uncovered a novel molecular mechanism involved in circRNAs in the development of lung cancer due to cadmium exposure.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112378DOI Listing
September 2021
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