Publications by authors named "Jun Gu"

608 Publications

The negative impact of increasing age and underlying cirrhosis on sensitivity of adenosine deaminase in the diagnosis of tuberculous peritonitis: a cross-sectional study in eastern China.

Int J Infect Dis 2021 Jul 28. Epub 2021 Jul 28.

Department of Infectious Diseases, the First Affiliated Hospital of Wannan Medical College,Wuhu, 241000, China. Electronic address:

Background: This study aims to evaluate the correlation between adenosine deaminase (ADA) test for the diagnosis of tuberculous peritonitis (TBP) and patient age or cirrhosis status.

Methods: Clinical data of patients clinically diagnosed with TPB (n=132) or not (n=147) were assessed. ADA activity was compared among three age groups (< 45 yr, 45-60 yr, and ≥ 60 yr) and cirrhotic-related subgroups. Cut-off values of ADA test were analyzed among three patient populations (young non-cirrhotic, n=97; older non-cirrhotic, n=115; cirrhotic n=67), and validated in a cohort of 259 participants.

Results: By the multivariate regression analyses, age <45 yr is highly predictive of TBP risk. The young non-cirrhotic TBP patients had higher ADA than the middle-aged or old control (P < 0.01). Significantly decreased activity and efficacy of ADA were observed in the cirrhotic subgroup/population, regardless of age or cohort. For the above-mentioned two non-cirrhotic populations in the validation cohort, ADA test showed excellent performance using thresholds of 30.5 IU/L and 20.5 IU/L, with respective sensitivities of 91.1% and 92.6%.

Conclusions: ADA activity is negatively associated with increasing age and underlying cirrhosis. Optimizing cut-off values of ADA test can increase its sensitivity in the non-cirrhotic individuals older than 45 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.07.061DOI Listing
July 2021

Collision Carcinoma Involving Small Cell Neuroendocrine Carcinoma and Squamous Cell Carcinoma of the Ureter: A Case Report and Review of the Literature.

Front Oncol 2021 5;11:663119. Epub 2021 Jul 5.

Department of Urology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China.

Background: Small cell neuroendocrine carcinoma (SCNEC) of the ureter is a rare tumour, accounting for less than 0.5% of all ureteral tumours. SCNEC tumours are highly aggressive and patients have a poor prognosis. Ureteral SCNEC colliding with other pathological types of tumours is extremely rare. In this paper, we present the case of a patient with ureteral small cell carcinoma colliding with squamous cell carcinoma and review the literature regarding the clinicopathological features, treatment and prognosis of thus tumour. To the best of our knowledge, this is the second identified case of ureteral SCNEC colliding with SCC.

Case Presentation: A 64-year-old male patient presented with a history of 1 month of gross haematuria and 3 months of left flank pain. CT urography revealed a soft tissue mass in the upper ureter, which was slightly enhanced on contrast-enhanced CT. Nephroureterectomy was performed after the patient was diagnosed with a tumour in the left ureter. Microscopy and immunohistochemical examination confirmed the mass to be a SCNEC collision with SCC. Two months after the surgery, the patient received adjuvant chemotherapy (cisplatin/etoposide). After 14 months of follow-up, no local recurrence or distant metastasis was found.

Conclusion: Ureteral collision carcinoma with SCNEC predominantly occurs in Asian individuals, is difficult to diagnose preoperatively and is highly invasive. The current management of ureteral collision carcinoma is a comprehensive treatment based on surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.663119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287249PMC
July 2021

Clinical outcomes of reresection in patients with high-risk nonmuscle-invasive bladder cancer treated with en bloc transurethral resection: a retrospective study with a 1-year follow-up.

J Endourol 2021 Jul 8. Epub 2021 Jul 8.

The Second Affiliated Hospital of Hainan Medical University, Department of Urology, The Second Affiliated Hospital of Hainan Medical University, No. 368, Yehai Road, Longhua District, Haikou 570311, China., Haikou, China, 570311;

Purpose To evaluate the impact of reresection on the clinical outcome in patients with primary high-risk nonmuscle-invasive bladder cancer (NMIBC) who initially received en bloc transurethral resection. Methods A retrospective analysis of data on eligible high-risk NMIBC with en bloc resection from June 2015 to June 2019 was performed. Patients were divided into two groups based on the presence or absence of reresection after the initial en bloc resection. The primary study endpoint was recurrence-free survival. The secondary outcomes were the residual rate of the tumor after initial en bloc resection, tumor upstaging rate and progression-free survival. Results We identified 115 eligible patients, including 51 (44.3%) who underwent reresection within 6 weeks of the initial en bloc resection and 64 (55.7%) who did not undergo en bloc reresection after the initial en bloc resection. The clinicopathological features were similar in patients with or without reresection. On finding tumor residues after the first en bloc resection, there were 3 cases (5.9%) in the reresection group compared to 2 cases (3.1%) in the non-reresection group (P=0.473). Two patients (3.9%) in the reresection group had tumor progression to muscle-invasive bladder cancer, whereas one patient (1.6%) in the non-reresection group exhibited tumor progression (P=0.430). The 1-year recurrence-free survival rate was 94.1% in the reresection group and 90.6% in the non-reresection group (P=0.269). In multivariate analysis, multifocality and T1 staging were independent prognostic factors for recurrence in patients with high-risk NMIBC who underwent en bloc resection. Conclusion In patients with high-risk NMIBC not exceeding 4 cm in diameter with no more than 4 lesions and not in the anterior bladder wall, reresection after en bloc resection seems to have failed to improve the patient's prognosis. However, a randomized controlled clinical study is required to confirm this hypothesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/end.2021.0008DOI Listing
July 2021

Predicting the survival benefit of local surgery in patients aged 70 years or older with stage IV breast cancer: A population-based analysis.

Breast 2021 Jun 30;59:124-134. Epub 2021 Jun 30.

Research Institute of General Surgery, Affiliated Jingling Hospital, Medical School of Nanjing University /General Hospital of Eastern Theater Command, PLA, Nanjing, 210002, Jiangsu, China. Electronic address:

Purpose: The aim of this study was to establish individualized nomograms to predict survival outcomes in older female patients with stage IV breast cancer who did or did not undergo local surgery, and to determine which patients could benefit from surgery.

Methods: A total of 3,129 female patients with stage IV breast cancer aged ≥70 years between 2010 and 2015 were included in the Surveillance, Epidemiology, and End Results program. Multivariate Cox regression analysis was used to identify risk factors for overall survival (OS) and breast cancer-specific survival (BCSS). Survival analysis was performed using the Kaplan-Meier plot and log-rank test. Nomograms and risk stratification models were constructed.

Results: Patients who underwent surgery had better OS (HR = 0.751, 95% CI [0.668-0.843], P < 0.001) and BCSS (HR = 0.713, 95% CI [0.627-0.810], P < 0.001) than patients who did not undergo surgery. Patients with human epidermal growth factor receptor 2-positive, lung or liver metastases may not benefit from surgery. In the stratification model, low-risk patients benefited from surgery (OS, HR = 0.688, 95% CI [0.568-0.833], P < 0.001; BCSS, HR = 0.632, 95% CI [0.509-0.784], P < 0.001), while patients in the high-risk group had similar outcomes (OS, HR = 0.920, 95% CI [0.709-1.193], P = 0.509; BCSS, HR = 0.953, 95% CI [0.713-1.275], P = 0.737).

Conclusion: Older female patients with stage IV breast cancer who underwent surgery had better OS and BCSS than those who did not in each specific subgroup. Patients in low- or intermediate-risk group benefit from surgery while those in the high-risk group do not.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.breast.2021.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261080PMC
June 2021

Association study of genetic polymorphisms in with treatment response and dose in methadone maintenance treatment.

Per Med 2021 Jun 23. Epub 2021 Jun 23.

Key Laboratory of Addiction Research of Zhejiang Province, Ningbo Kangning Hospital, Ningbo, Zhejiang, China.

This study determined if gene variants in the GABA receptor delta subunit () are associated with treatment response and dose in methadone maintenance treatment (MMT) for heroin addiction.  A total of 286 MMT patients were recruited and divided into response and nonresponse groups based on retention time in therapy. A total of 177 responders were classified into low dose and high dose subgroups according to the stabilized methadone dose. Four (single nucleotide polymorphisms) SNPs (rs13303344, rs4481796, rs2376805 and rs2229110) in were genotyped using the TaqMan SNP assay. Logistic regression was used to assess the genetic effects of the SNPs in MMT. No significant associations were observed between the SNPs and treatment response or dose, except the frequency of haplotype ACGC at the four SNPs significantly differed between responders and nonresponders. The results indicated that variants may play a small role in modulating methadone treatment response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/pme-2021-0063DOI Listing
June 2021

Identification and Prediction of Novel Clinical Phenotypes for Intensive Care Patients With SARS-CoV-2 Pneumonia: An Observational Cohort Study.

Front Med (Lausanne) 2021 4;8:681336. Epub 2021 Jun 4.

Department of Intensive Care Medicine, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

Phenotypes have been identified within heterogeneous disease, such as acute respiratory distress syndrome and sepsis, which are associated with important prognostic and therapeutic implications. The present study sought to assess whether phenotypes can be derived from intensive care patients with coronavirus disease 2019 (COVID-19), to assess the correlation with prognosis, and to develop a parsimonious model for phenotype identification. Adult patients with COVID-19 from Tongji hospital between January 2020 and March 2020 were included. The consensus k means clustering and latent class analysis (LCA) were applied to identify phenotypes using 26 clinical variables. We then employed machine learning algorithms to select a maximum of five important classifier variables, which were further used to establish a nested logistic regression model for phenotype identification. Both consensus k means clustering and LCA showed that a two-phenotype model was the best fit for the present cohort ( = 504). A total of 182 patients (36.1%) were classified as hyperactive phenotype, who exhibited a higher 28-day mortality and higher rates of organ dysfunction than did those in hypoactive phenotype. The top five variables used to assign phenotypes were neutrophil-to-lymphocyte ratio (NLR), ratio of pulse oxygen saturation to the fractional concentration of oxygen in inspired air (Spo/Fio) ratio, lactate dehydrogenase (LDH), tumor necrosis factor α (TNF-α), and urea nitrogen. From the nested logistic models, three-variable (NLR, Spo/Fio ratio, and LDH) and four-variable (three-variable plus TNF-α) models were adjudicated to be the best performing, with the area under the curve of 0.95 [95% confidence interval (CI) = 0.94-0.97] and 0.97 (95% CI = 0.96-0.98), respectively. We identified two phenotypes within COVID-19, with different host responses and outcomes. The phenotypes can be accurately identified with parsimonious classifier models using three or four variables.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2021.681336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211883PMC
June 2021

In-Situ Visualization of the Cell Formation Process of Foamed Polypropylene under Different Foaming Environments.

Polymers (Basel) 2021 May 1;13(9). Epub 2021 May 1.

College of Materials Science and Metallurgy Engineering, Guizhou University, Guiyang 550025, China.

In this paper, the dynamic foaming process of micro-foaming polypropylene (PP) in different foaming environments in real time was obtained via a visualization device. The relationship curve between cell number () and foaming time () was plotted, and then the nucleation kinetics of foam cells was analyzed. Results showed that the formation rate of cells changed obviously with the variation of melt temperature and the content of the foaming agent. The - curves presented a typical "S" shape, which indicated that the appearance of the cell number increased slowly in the initial foaming period, then increased rapidly in a short time, and finally maintained a certain value. When a certain pressure was applied to the PP melt, the external force had a great influence on the - curve. With the increasing external force, the rate of cell formation increased rapidly, and the shape of the - curve changed from "S" to "semi-S" without an obvious slow increase. The investigation of the - relationship in the PP dynamic foaming process under different foaming environments could provide effective bases for improving the foaming quality of injection molding foaming materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/polym13091468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125430PMC
May 2021

A nerve growth factor persistent delivery scaffold seeded with neurally differentiated bone marrow mesenchymal stem cells promoted the functional recovery of spinal cord injury in rats.

Am J Transl Res 2021 15;13(4):2127-2142. Epub 2021 Apr 15.

School of Medicine, Southeast University Nanjing, China.

The objective was to design a scaffold that could continuously deliver nerve growth factor (NGF) combined with neurally differentiated bone marrow mesenchymal stem cells (BMSCs) to promote better recovery of spinal cord injury (SCI) in rats. BMSCs were induced to differentiate into neurons for 6 days , and then seeded on a NGF persistent delivery scaffold, both were transplanted to SCI rats in combination. Relevant extensive tests were conducted 1, 4 and 8 weeks after transplantation. The results showed that the scaffold had a stable ability to continuously release NGF and that the BMSCs on the scaffold could successfully differentiate into nerve cells. The results of Bacco, Beattie and Bresnahan (BBB) scores, inclined plane tests and electrophysiological investigations revealed that the rats in the combined regimen had better locomotor functional recovery. The results of H&E/Nissl staining, Golgi staining and immunofluorescence showed that the rats in the combined regimen retained the most neurons and had the least cavities and more formations of dendritic spines. Similarly, the positive rate was high for MAP2, NeuN and MBP, and low for GFAP. The graft of the NGF persistent delivery scaffold seeded with neurally differentiated BMSCs significantly reduced the formation of cavities and glial scars at the SCI sites and promoted neuronal survival, axonal regeneration and locomotor function recovery. Compared with the single graft of NGF persistent delivery scaffold or the single graft of neurally differentiated BMSCs, this combined scheme had a better effect in promoting the recovery of SCI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129249PMC
April 2021

Metabolic Reprogramming of GMP Grade Cord Tissue Derived Mesenchymal Stem Cells Enhances Their Suppressive Potential in GVHD.

Front Immunol 2021 4;12:631353. Epub 2021 May 4.

Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.

Acute graft-vs.-host (GVHD) disease remains a common complication of allogeneic stem cell transplantation with very poor outcomes once the disease becomes steroid refractory. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for the treatment of GVHD, but so far this strategy has had equivocal clinical efficacy. Therapies using MSCs require optimization taking advantage of the plasticity of these cells in response to different microenvironments. In this study, we aimed to optimize cord blood tissue derived MSCs (CBti MSCs) by priming them using a regimen of inflammatory cytokines. This approach led to their metabolic reprogramming with enhancement of their glycolytic capacity. Metabolically reprogrammed CBti MSCs displayed a boosted immunosuppressive potential, with superior immunomodulatory and homing properties, even after cryopreservation and thawing. Mechanistically, primed CBti MSCs significantly interfered with glycolytic switching and mTOR signaling in T cells, suppressing T cell proliferation and ensuing polarizing toward T regulatory cells. Based on these data, we generated a Good Manufacturing Process (GMP) Laboratory protocol for the production and cryopreservation of primed CBti MSCs for clinical use. Following thawing, these cryopreserved GMP-compliant primed CBti MSCs significantly improved outcomes in a xenogenic mouse model of GVHD. Our data support the concept that metabolic profiling of MSCs can be used as a surrogate for their suppressive potential in conjunction with conventional functional methods to support their therapeutic use in GVHD or other autoimmune disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.631353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130860PMC
May 2021

Microarray analysis of the time-dependent expression profiles of long non-coding RNAs in the progression of vein graft stenotic disease.

Exp Ther Med 2021 Jun 15;21(6):635. Epub 2021 Apr 15.

Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

Long non-coding RNAs (lncRNAs) have been reported to be involved in various biological processes, including cell proliferation and apoptosis. However, the expression profiles of lncRNAs in patients with vein graft restenosis remain unknown. In the present study, the time-dependent expression profiles of genes in vein bypass grafting models were examined by microarray analysis. A total of 2,572 lncRNAs and 1,652 mRNAs were identified to be persistently significantly differentially expressed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed to investigate the functions of these lncRNAs. A total of 360 lncRNAs and 135 protein-coding genes were predicted to be involved in the vascular remodeling process. Co-expression network analysis revealed the association between 194 lncRNAs and seven associated protein-coding genes, including transforming growth factor-β1, Fes, Yes1 associated transcriptional regulator, sphingosine-1-phosphate receptor 1, Src, insulin receptor and melanoma cell adhesion molecule. Moreover, reverse transcription-quantitative PCR results supported those of the microarray data, and overexpression of AF062402, which regulates the transcription of Src, stimulated the proliferation of primary vascular smooth muscle cells. The findings of the present study may facilitate the development of novel therapeutic targets for vein graft restenosis and may help to improve the prognosis of patients following coronary artery bypass grafting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2021.10067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097238PMC
June 2021

Xiao-Yin-Fang Therapy Alleviates Psoriasis-like Skin Inflammation Through Suppressing γδT17 Cell Polarization.

Front Pharmacol 2021 16;12:629513. Epub 2021 Apr 16.

Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.

Psoriasis is an immune-mediated chronic inflammatory skin disease primarily mediated by the activation of interleukin (IL)-17-producing T cells. Traditional Chinese Medicine (TCM) represents one of the most effective complementary and alternative medicine (CAM) agents for psoriasis, which provides treasured sources for the development of anti-psoriasis medications. Xiao-Yin-Fang (XYF) is an empirically developed TCM formula that has been used to treat psoriasis patients in Shanghai Changhai Hospital for over three decades. Imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model was utilized to investigate the therapeutic effects of XYF by the assessment of disease severity and skin thickness. Flow cytometric assay was performed to explore the influence of XYF on skin-related immunocytes, primarily T cells. And, RNA sequencing analysis was employed to determine the alternation in gene expression upon XYF therapy. We discovered that XYF alleviated psoriasis-like skin inflammation mainly through suppressing dermal and draining lymph-node IL-17-producing γδT (γδT17) cell polarization. Moreover, XYF therapy ameliorated the relapse of psoriasis-like dermatitis and prohibited dermal γδT cell reactivation. Transcriptional analysis suggested that XYF might regulate various inflammatory signaling pathways and metabolic processes. In conclusion, our results clarified the therapeutic efficacy and inner mechanism of XYF therapy in psoriasis, which might promote its clinical application in psoriasis patients and facilitate the development of novel anti-psoriasis drugs based on the bioactive components of XYF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.629513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087247PMC
April 2021

Left ventricular geometry transition in hypertensive patients with heart failure with preserved ejection fraction.

ESC Heart Fail 2021 Aug 1;8(4):2784-2790. Epub 2021 May 1.

Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, China.

Aims: Heart failure with preserved ejection fraction (HFpEF) develops in response to hypertensive left ventricular (LV) hypertrophy and is associated with increased cardiovascular events. Although the progression to systolic heart failure is a known consequence of LV hypertrophy and HFpEF, few data are available on the LV geometry change and frequency of deterioration to systolic dysfunction in this population.

Methods And Results: We evaluated the baseline and follow-up characteristics in 680 patients with LV hypertrophy and HFpEF in this prospective cohort study. The primary endpoint was 5 year all-cause mortality. The changes of LV geometry and heart failure transition were analysed. Systolic dysfunction [left ventricular ejection fraction (LVEF) < 50%] occurred in 182 patients (26.8%) during a 5 year follow-up. Patients with LVEF deterioration were associated with a lower survival rate. Beta-blocker prescription was a protective factor for preserved LVEF. And concentric LV geometry shifted to eccentric hypertrophy was uncommon (10.6%) during a 5 year follow-up.

Conclusions: A quarter of patients with hypertensive LV hypertrophy and HFpEF progresses to systolic dysfunction during a 5 year follow-up, which was accompanied by poor clinical outcomes. And beta-blocker therapy might play a protective role for preserved LVEF in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ehf2.13349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318401PMC
August 2021

Plasmids Expressing shRNAs Specific to the Nucleocapsid Gene Inhibit the Replication of Porcine Deltacoronavirus In Vivo.

Animals (Basel) 2021 Apr 23;11(5). Epub 2021 Apr 23.

Department of Preventive Veterinary Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China.

Porcine deltacoronavirus (PDCoV) is a novel enteric coronavirus and is becoming one of the major causative agents of diarrhea in pig herds in recent years. To date, there are no commercial vaccines or antiviral pharmaceutical agents available to control PDCoV infection. Therefore, developing a reliable strategy against PDCoV is urgently needed. In this study, to observe the antiviral activity of RNA interference (RNAi), four short hairpin RNAs (shRNAs) specific to the nucleocapsid (N) gene of PDCoV were designed and tested in vitro. Of these, a double-shRNA-expression vector, designated as pSil-double-shRNA-N1, was the most effectively expressed, and the inhibition of PDCoV replication was then further evaluated in neonatal piglets. Our preliminary results reveal that plasmid-based double-shRNA-expression targeting the N gene of PDCoV can significantly protect LLC-PK1 cells and piglets from pathological lesions induced by PDCoV. Our study could benefit the investigation of the specific functions of viral genes related to PDCoV infection and offer a possible methodology of RNAi-based therapeutics for PDCoV infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ani11051216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145914PMC
April 2021

Preparation of bioactive glass nanoparticles with highly and evenly doped calcium ions by reactive flash nanoprecipitation.

J Mater Sci Mater Med 2021 Apr 23;32(5):48. Epub 2021 Apr 23.

School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, 225002, China.

Nanoscale bioactive glass particles have greater bioactivity than microscale bioactive glass particles, due to their high-specific surface area and fast ion release rate in body fluid. However, preparation of bioactive glass nanoparticles (BGNPs) is difficult since calcium is not easy to be highly doped into the forming silica atom network, leading to an uneven distribution and a low content of calcium. In addition, BGNPs are usually prepared in a dilute solution to avoid agglomeration of the nanoparticles, which decreases the production efficiency and increases the cost. In this work, BGNPs are prepared by a method of the reactive flash nanoprecipitation (RFNP) as well as a traditional sol-gel method. The results indicate that the BGNPs by the RFNP present a smaller size, narrower size distribution, more uniform composition, and better bioactivity than those by the traditional sol-gel method. The obtained BGNPs have uniform compositions close to the feed values. The high and even doping of calcium in the BGNPs is achieved. This successful doping of calcium into nanoparticles by the RFNP demonstrates a promising way to effectively generate high-quality BGNPs for bone repairs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10856-021-06521-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064980PMC
April 2021

Association between GABA receptor delta subunit gene polymorphisms and heroin addiction.

Neurosci Lett 2021 06 19;755:135905. Epub 2021 Apr 19.

Key Laboratory of Addiction Research of Zhejiang Province, Ningbo Kangning Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang, China. Electronic address:

Evidence suggests that γ-aminobutyric acid (GABA) receptors are involved in the development of drug dependence. Considering its exclusively extrasynaptic localization, GABA receptor delta subunit (GABRD) is likely involved in heroin addiction. The purpose of this study was to explore the association between the single nucleotide polymorphisms (SNPs) of GABRD and heroin addiction. Genotyping of five SNPs (rs13303344, rs4481796, rs2376805, rs2229110, and rs41307846) in GABRD gene was performed by using TaqMan SNP assay. The association between heroin addiction and these SNPs was assessed in 446 heroin dependent patients and 400 normal control subjects of male Han Chinese origin. Only the genotype and allele frequencies at rs13303344 differed significantly between the cases and controls (nominal P values were 0.028 and 0.019, respectively). The C allele of rs13303344 was associated with an increased risk of heroin addiction (OR = 1.281, 95 % CI: 1.042-1.575). After Bonferroni correction, the association lost significance. The frequencies of the haplotype C-C-A and A-C-A at GARBD (rs13303344-rs4481796- rs2376805) differed significantly between the cases and controls. The heroin craving score was significantly higher in patients with CC/AC genotypes at rs13303344 than in those with the AA genotype (nominal P = 0.017). The results suggest that GABRD rs13303344 may contribute to the susceptibility to heroin addiction and is associated with the drug cravings of heroin dependent patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neulet.2021.135905DOI Listing
June 2021

Bioinformatic Analysis of Key Genes and Pathways Related to Keloids.

Biomed Res Int 2021 23;2021:5897907. Epub 2021 Mar 23.

Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

Background: The pathophysiology of keloids is complex, and the treatment for keloids is still an unmet medical need. Our study is aimed at identifying the hub genes among the differentially expressed genes (DEGs) between normal skin tissue and keloids and key pathways in the development of keloids.

Materials And Methods: We downloaded the GSE92566 and GSE90051 microarray data, which contain normal skin tissue and keloid gene expression data. GSE92566 was treated as a discovery dataset for summarizing the significantly DEGs, and GSE90051 served as a validation dataset. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, Reactome enrichment analysis, gene set enrichment analysis, and gene set variation analysis were performed for the key functions and pathways enriched in DEGs. Moreover, we also validated the hub genes identified from the protein-protein interaction network and predicted miRNA-hub gene interactions.

Results: 117 downregulated DEGs and 204 upregulated DEGs in GSE92566 were identified. Extracellular and collagen-related pathways were prominent in upregulated DEGs, while the keratinization-related pathway was associated with downregulated DEGs. The hub genes included COL5A1, COL5A2, and SERPINH1, which were also validated in GSE90051.

Conclusion: This study identified several hub genes and provided insights for the underlying pathways and miRNA-hub gene interactions for keloid development through bioinformatic analysis of two microarray datasets. Additionally, our results would support the development of future therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5897907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009712PMC
May 2021

Iodinated BSA Nanoparticles for Macrophage-Mediated CT Imaging and Repair of Gastritis.

Anal Chem 2021 04 12;93(16):6414-6420. Epub 2021 Apr 12.

State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.

The development of a specific and noninvasive technology for understanding gastritic response together with efficient therapy is an urgent clinical issue. Herein, we fabricated a novel iodinated bovine serum albumin (BSA) nanoparticle based on gastritic microenvironment for computed tomography (CT) imaging and repair of acute gastritis. Derived from the characteristic mucosa defect and inflammatory cell (e.g., macrophage and neutrophil) infiltration in acute gastritis, the pH-sensitive nanoparticles can sedimentate under acidic conditions and be uniformly distributed in the defected mucosal via the phagocytosis of inflammatory cells. Hence, enhanced CT images can clearly reveal the mucosal morphology in the nanoparticle-treated gastritic rat over a long time window comparison with nanoparticle-treated healthy rats and clinical small-molecule-treated gastritic rat. In addition, we have discovered that nanoparticles can repair the atrophic gastric mucosa to a normal state. This repair process mainly stems from inflammatory immune response caused by phagocytized nanoparticles, such as the polarization of proinflammatory macrophages (M1) to anti-inflammatory macrophages (M2). The biocompatible nanoparticles that avoid the inherent defects of the clinical small molecules have great potential for accurate diagnosis and treatment of gastritis in the early stage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.0c05407DOI Listing
April 2021

Long noncoding RNA GAS8-AS1: A novel biomarker in human diseases.

Biomed Pharmacother 2021 Jul 7;139:111572. Epub 2021 Apr 7.

Department of Neurosurgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China. Electronic address:

Long non-coding RNAs (lncRNAs) represent a group of ncRNAs with more than 200 nucleotides. These RNAs can specifically regulate gene expression at both the transcriptional and the post-transcriptional levels, and increasing evidence indicates that they play vital roles in a variety of disease-related cellular processes. The lncRNA GAS8 antisense RNA 1 (GAS8-AS1, also known as C16orf3) is located in the second intron of GAS8 and has been reported to be both abnormally expressed in several diseases and closely correlated with many clinical characteristics. GAS8-AS1 has been shown to affect many biological functions, including cell proliferation, migration, invasiveness, and autophagy using several signaling pathways. In this review, we have summarized current studies on GAS8-AS1 roles in disease and discuss its potential clinical utility. GAS8-AS1 may be a promising biomarker for both diagnoses and prognoses, and a novel target for many disease therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2021.111572DOI Listing
July 2021

Tetracycline-induced decoupling of symbiosis in microalgal-bacterial granular sludge.

Environ Res 2021 06 1;197:111095. Epub 2021 Apr 1.

Advanced Environmental Biotechnology Centre, Nanyang Environment & Water Research Institute, Nanyang Technological University, 1 Cleantech Loop, Singapore, 637141, Singapore; School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore. Electronic address:

Tetracycline has been frequently detected in municipal wastewater due to its extended use for various purposes. This study investigated the influence of tetracycline on non-aerated microalgal-bacterial granular sludge cultivated for municipal wastewater treatment. It was found that ammonia-N removal rate decreased at the tetracycline concentrations of 1 and 10 mg/L. A mass balance on nitrogen further revealed that the observed ammonia-N removal could be mainly attributed to microalgal assimilation which was inhibited by tetracycline at the concentrations studied. In fact, reduced production of chlorophyll in microalgae was observed in the presence of tetracycline, leading to decreased ammonia-N removal rate. Meanwhile, decreased dissolved oxygen (DO) concentration at high tetracycline concentration also indicated inhibition of microalgae. Furthermore, the relative abundances of microalgae containing green algae and cyanobacteria were inhibited by tetracycline. The results gathered in this study indicated the tetracycline-induced decoupling of symbiosis in microalgal-bacterial granular sludge. It is expected that this study can shed lights on the behaviors of non-aerated microalgal-bacterial granules in response to the presence of tetracycline during municipal wastewater treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2021.111095DOI Listing
June 2021

Viral vector-mediated gene therapy for opioid use disorders.

Exp Neurol 2021 Jul 26;341:113710. Epub 2021 Mar 26.

Department of Anesthesiology, Perioperative Medicine & Pain Management, University of Miami Miller School of Medicine, Miami, FL, United States of America. Electronic address:

Chronic exposure to opioids typically results in adverse consequences. Opioid use disorder (OUD) is a disease of the CNS with behavioral, psychological, neurobiological, and medical manifestations. OUD induces a variety of changes of neurotransmitters/neuropeptides in the nervous system. Existing pharmacotherapy, such as opioid maintenance therapy (OMT) is the mainstay for the treatment of OUD, however, current opioid replacement therapy is far from effective for the majority of patients. Pharmacological therapy for OUD has been challenging for many reasons including debilitating side-effects. Therefore, developing an effective, non-pharmacological approach would be a critical advancement in improving and expanding treatment for OUD. Viral vector mediated gene therapy provides a potential new approach for treating opioid abused patients. Gene therapy can supply targeting gene products directly linked to the mechanisms of OUD to restore neurotransmitter and/or neuropeptides imbalance, and avoid the off-target effects of systemic administration of drugs. The most commonly used viral vectors in rodent studies of treatment of opioid-used disorder are based on recombinant adenovirus (AV), adeno-associated virus (AAV), lentiviral (LV) vectors, and herpes simplex virus (HSV) vectors. In this review, we will focus on the recent progress of viral vector mediated gene therapy in OUD, especially morphine tolerance and withdrawal.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.expneurol.2021.113710DOI Listing
July 2021

Polycyclic aromatic hydrocarbons residues and the carcinogenic risk assessment to pregnant women in Nantong, China using QuEChERS method and HPLC-A pilot case study.

Biomed Chromatogr 2021 Aug 18;35(8):e5117. Epub 2021 Apr 18.

Chemical Laboratory, Nantong Center for Disease Control and Prevention, Nantong, China.

A high-performance liquid chromatographic method with a modified QuEChERS extraction for the determination of polycyclic aromatic hydrocarbons (PAHs) in blood serum was developed to investigate the internal exposure level and the carcinogentic toxicity contribution rate of PAHs for pregnant women in Nantong, China. Venous blood (n = 48) was collected in the local hospital and the internal exposure level of 16 PAHs and the contribution rate of carcinogenicity to pregnant women were analyzed. Among all of the detected PAHs, the detection rate of pyrene (77.08%) was the highest, followed by naphthalene (64.58%) and benzo[a]anthracene (BaA, 45.83%). The carcinogenicity contribution rate of BaA (37.37%) was the highest, followed by fluorene (32.96%) and acenaphthylene (22.01%). The results showed that many kinds of carcinogenic PAHs can be detected in the serum of pregnant women in Nantong city, among which BaA should be paid most attention because of its high internal exposure level and carcinogenic risk. Meanwhile, the origins of general PAHs in serum samples were analyzed using the characteristic ratio analysis method. The PAH pollution level of air samples (n = 42) during the collection time of blood samples was also analyzed to compare the possible correlations between the two different results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bmc.5117DOI Listing
August 2021

Over 200 million students being taught online in China during COVID-19: Will online teaching become the routine model in medical education?

Asian J Surg 2021 04 22;44(4):672. Epub 2021 Feb 22.

Department of Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.asjsur.2021.01.034DOI Listing
April 2021

The effectiveness of problem-based learning in gynecology and obstetrics education in China: A meta-analysis of randomized controlled trials.

Medicine (Baltimore) 2021 Mar;100(9):e24660

Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Background: A meta-analysis was conducted to assess the effectiveness of problem-based learning (PBL) in gynecology and obstetrics education in China.

Methods: English and Chinese databases were systematically searched for eligible studies that compared the effects of PBL and traditional teaching methods measuring theoretical knowledge, student satisfaction, clinical operations, and clinical practice scores in gynecology and obstetrics education in China. The authors restricted included studies to randomized controlled trials and performed a meta-analysis. Standardized mean difference (SMD) and risk ratio with 95% confidence interval (CI) were estimated.

Results: A total of 38 randomized controlled trials with 3005 participants were included. Compared with traditional teaching group, the PBL group significantly increased theoretical knowledge scores (SMD: 3.17, 95% CI: 2.28, 4.07), student satisfaction (risk ratio: 1.29, 95% CI: 1.16, 1.43), clinical operations (SMD: 1.15, 95% CI: 0.93, 1.37) and clinical practice (SMD: 2.17, 95% CI: 3.63, 2.71).

Conclusion: The current research shows that PBL in gynecology and obstetrics education in China is more effective than the traditional teaching in enhancing theoretical knowledge, student satisfaction, clinical operations, and clinical practice scores. However, more delicate-designed studies on this topic are needed in the future to validate these results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000024660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939176PMC
March 2021

Association of Circulating Irisin Levels and the Characteristics and Prognosis of Coronary Artery Disease.

Am J Med Sci 2021 07 26;362(1):63-71. Epub 2021 Feb 26.

Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China. Electronic address:

Background: Irisin is a new muscle factor discovered in recent years that shows a strong association with metabolic diseases. However, its role in coronary artery disease (CAD) is still controversial. We performed this study to determine the relationship of serum irisin with the characteristics and prognosis of CAD.

Materials And Methods: Patients with acute coronary syndrome (ACS) (n = 355), stable coronary artery disease (SCAD) (n = 162), nonobstructive coronary artery disease (NO-CAD) (n = 126) and normal coronary arteries (n = 109) were enrolled. An enzyme-linked immunosorbent assay kit was used to measure serum irisin concentrations. Major adverse cardiovascular events (MACEs) of patients with SCAD (n = 132) and ACS (n = 331) after percutaneous coronary intervention (PCI) were recorded during a 12-month follow-up. Receiver-operator characteristic (ROC) curve analysis was used to explore predictors of CAD. Kaplan-Meier survival analysis and the Cox proportional hazards regression model were used to explore the association between serum irisin levels and MACEs.

Results: Serum irisin levels in patients with ACS, SCAD, NO-CAD and normal coronary arteries were 196.62±72.05 ng/ml, 216.81±79.69 ng/ml, 245.26±77.92 ng/ml and 300.17±76.74 ng/ml, respectively (p<0.001). ROC curve analysis indicated that serum irisin concentrations were a valuable biomarker of coronary lesions (AUC=0.799), CAD (AUC=0.734) and ACS (AUC=0.681). Survival analysis demonstrated that patients with high irisin levels exhibited a higher event-free survival rate in both the SCAD and ACS groups after successful PCI.

Conclusions: Serum irisin levels were significantly decreased in patients with CAD. Patients with ACS exhibited the lowest serum irisin levels. Furthermore, serum irisin levels were interrelated with prognosis in patients with CAD after PCI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjms.2021.02.020DOI Listing
July 2021

GIT1 protects traumatically injured spinal cord by prompting microvascular endothelial cells to clear myelin debris.

Aging (Albany NY) 2021 02 17;13(5):7067-7083. Epub 2021 Feb 17.

Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

The clearance of myelin debris is a critical step in the functional recovery following spinal cord injury (SCI). As phagocytes do, microvascular endothelial cells (MECs) participate in myelin debris clearance at the injury site within one week. Our group has verified that G protein-coupled receptor kinase 2 interacting protein-1 (GIT1) is essential in autophagy and angiogenesis, both of which are tightly related to the uptake and degradation of myelin debris by MECs. Here, we analyzed the performance and mechanism of GIT1 in myelin debris clearance after SCI. The SCI contusion model was established and MECs were treated with myelin debris. Better recovery from traumatic SCI was observed in the GIT1 WT mice than in the GIT1 KO mice. More importantly, we found that GIT1 prompted MECs to clear myelin debris and further enhanced MECs angiogenesis and . Mechanistically, GIT1-mediated autophagy contributed to the clearance of myelin debris by MECs. In this study, we demonstrated that GIT1 may prompt MECs to clear myelin debris via autophagy and further stimulate MECs angiogenesis via upregulating VEGF. Our results indicate that GITI may serve as a promising target for accelerating myelin debris clearance and improving SCI recovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993661PMC
February 2021

KIF11 promotes cell proliferation via ERBB2/PI3K/AKT signaling pathway in gallbladder cancer.

Int J Biol Sci 2021 1;17(2):514-526. Epub 2021 Jan 1.

Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.

Proliferation is one of the significant hallmarks of gallbladder cancer, which is a relatively rare but fatal malignance. Aim of this study was to examine the biological impact and molecular mechanism of the candidate hub-gene on the proliferation and tumorigenesis of gallbladder cancer. We analyzed the differentially expressed genes and the correlation between these genes with MKI67, and showed that KIF11 is one of the major upregulated regulators of proliferation in gallbladder cancer (GBC). The Gene Ontology, Gene Sets Enrichment Analysis and KEGG Pathway analysis indicated that KIF11 may promote GBC cell proliferation through the ERBB2/PI3K/AKT signaling pathway. Gain-of-function and loss-of-function assay demonstrated that KIF11 regulated GBC cell cycle and cancer cell proliferation in vitro. GBC cells exhibited G2M phase cell cycle arrest, cell proliferation and clone formation ability reduction after treatment with Monastrol, a specific inhibitor of KIF11. Xenograft model showed that KIF11 promotes GBC growth in vivo. Rescue experiments showed that KIF11-induced GBC cell proliferation dependented on ERBB2/PI3K/AKT pathway. Moreover, we found that H3K27ac signals are enriched among the promoter region of KIF11 in the UCSC Genome Browser Database. Differentially expressed analysis showed that EP300, a major histone acetyltransferase modifying H3K27ac signal, is highly expressed in gallbladder cancer and correlation analysis illustrated that EP300 is positively related with KIF11 in almost all the cancer types. We further found that KIF11 was significantly downregulated in a dose-dependent and time-dependent manner after histone acetylation inhibitor treatment. The present results highlight that high KIF11 expression promotes GBC cell proliferation through the ERBB2/PI3K/AKT signaling pathway. The findings may help deepen our understanding of mechanism underlying GBC cancer development and development of novel diagnostic and therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijbs.54074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893577PMC
January 2021

Utility of serum NOX4 as a potential prognostic biomarker for aneurysmal subarachnoid hemorrhage.

Clin Chim Acta 2021 Jun 16;517:9-14. Epub 2021 Feb 16.

Department of Neurosurgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, PR China.

Background: Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) plays an important role in the formation of oxidative stress in brain tissues. We intended to investigate relationship between serum NOX4 concentrations and severity, delayed cerebral ischemia (DCI) plus prognosis after aneurysmal subarachnoid hemorrhage (aSAH).

Methods: Serum NOX4 concentrations were gauged in a total of 165 aSAH patients. The World Federation of Neurological Surgeons (WFNS) scale and modified Fisher grading scale were recorded for assessing hemorrhagic severity. Relations of serum NOX4 concentrations to DCI and 90-day poor outcome (Glasgow outcome scale score of 1-3) were determined using multivariate analysis.

Results: Serum NOX4 concentrations were substantially higher in patients with 90-day poor outcome or DCI than in other remainders. Serum NOX4 concentrations of patients were intimately correlated with WFNS scores and modified Fisher scores. Serum NOX4 appeared as an independent predictor for DCI and 90-day poor outcome after aSAH. Under ROC curve analysis, serum NOX4 concentrations possessed significantly high predictive capability for DCI and 90-day poor outcome following hemorrhagic stroke.

Conclusions: Serum NOX4 concentrations, in close correlation with hemorrhagic severity, were independently associated with DCI and poor clinical outcome after hemorrhagic stroke, substantializing serum NOX4 as a promising prognostic biomarker for aSAH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2021.02.007DOI Listing
June 2021

Is immunohistochemical expression of GATA3 helpful in the differential diagnosis of transformed mycosis fungoides and primary cutaneous CD30-positive T cell lymphoproliferative disorders?

Virchows Arch 2021 Feb 18. Epub 2021 Feb 18.

Department of Pathology, Dermatopathology Section, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Mycosis fungoides with large cell transformation (MFLCT) can be difficult to distinguish from primary cutaneous CD30+ T cell lymphoproliferative disorders (PC CD30+ LPD), especially primary cutaneous anaplastic large cell lymphoma (PC-ALCL). This diagnostic distinction is critical for appropriate patient management. GATA3 has been proposed to be useful in the discrimination between these two entities. We identified 25 cases of MFLCT and 24 cases of PC CD30+ LPDs (including lymphomatoid papulosis (n=14), PC-ALCL (n=6), and CD30+ LPD, not otherwise specified (n=4)) diagnosed at our institution from 2002 to 2019. Sections from archived specimens were stained to evaluate for GATA3 expression by immunohistochemistry and compared among cutaneous CD30+ T cell LPDs. The majority of the MFLCT cohort had strong, diffuse expression of GATA3 ranging from 0 to 100% of dermal T cells (mean 53.20%) with 15/25 cases (60%) showing GATA3 expression greater than 50%, while the PC CD30+ LPD group showed variable, moderate GATA3 labeling ranging from 0 to 60% of dermal T cells (mean 23.26%), with 5/6 cases (83%) showing GATA3 expression less than 40% (p =0.003). The calculated sensitivity and specificity were 56% and 74%, while positive and negative predictive values were 70% and 61%, respectively. Based on the percent staining of positive cells, using 50% as a cutoff value for expression, GATA3 might be a useful immunohistochemical marker to discriminate MFLCT from PC CD30+ LPDs, including PC-ALCL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00428-021-03056-yDOI Listing
February 2021

MicroRNA-146a Deficiency Delays Wound Healing in Normal and Diabetic Mice.

Adv Wound Care (New Rochelle) 2021 Jul 2. Epub 2021 Jul 2.

Department of Dermatology, Henry Ford Health System, Detroit, Michigan, USA.

MiRNAs are important regulators of inflammation and wound healing. However, the mechanisms through which miRNAs regulate wound healing under normal and diabetic conditions are poorly understood. We aimed to determine the effects of miR-146a on the pathogenesis of wound healing in normal and streptozotocin (STZ)-induced diabetic mice. Wild-type (WT) and miR-146a knockout (KO) mice were induced to develop diabetes with STZ. Next, skin and corneal wounds were produced and measured. Percent wound closure and histology were evaluated. Inflammation at wound sites was analyzed using flow cytometry, reverse-transcription PCR, and western blot. Healing of wounded skin was significantly delayed in miR-146a KO compared with WT mice. However, corneal epithelial wound healing did not differ significantly in the mice with normal blood glucose, whereas corneal and skin wound healing was significantly delayed in KO mice with diabetes. Neutrophil infiltration increased in skin wounds of KO compared with normal mice. The potential mechanisms were associated with dysregulated interleukin 1β, tumor necrosis factor alpha (TNF-α), IRAK1 (interleukin-1 receptor-associated kinase 1), TRAF6 (TNF receptor-associated factor 6), and nuclear factor kappa B (NF-κB) signaling induced by miR-146a KO. Skin wound healing was delayed in miR-146a KO mice and enhanced inflammatory responses were mediated by the NF-κB signaling pathway. Deficiency in miR-146a delayed skin wound healing by enhancing inflammatory responses in normal and diabetic mice. Therefore, miR-146a may be a potential target for modulation to accelerate skin wound healing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/wound.2020.1165DOI Listing
July 2021

Mitochondrial biogenesis factor PGC-1α suppresses spinal morphine tolerance by reducing mitochondrial superoxide.

Exp Neurol 2021 May 29;339:113622. Epub 2021 Jan 29.

Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136, United States. Electronic address:

Opioid use disorders (OUDs) have reached an epidemic level in the United States. The opioid epidemic involves illicit opioid use, prescription opioids for analgesia, counterfeit opioids, new psychoactive substances, and diverted opioids. Opioids remain the last option for the treatment of intractable clinical pain, but chronic use of opioids are limited in part due to antinociceptive/analgesic tolerance. Peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1alpha (PGC-1α), a mitochondrial biogenesis factor can reduce toxic reactive oxygen species (ROS) that play a role in morphine tolerance (MT). Decreased PGC-1α expression has been shown to contribute to various metabolic disorders or neurodegeneration diseases through increasing ROS. We examined the relationship of PGC-1α and ROS in MT. To induce MT, adult Sprague-Dawley rats received intrathecal morphine for 7 days. Mechanical threshold was measured using the von Frey test and thermal latency was examined using the heat plate test. Expression of PGC-1α in the spinal cord dorsal horn (SCDH) was examined using RT-PCR and western blots. Mitochondrial superoxide was detected using MitoSox Red, a mitochondrial superoxide indicator. The antinociceptive effect of recombinant PGC-1α (rPGC-1α) or Mito-Tempol (a mitochondria-targeted superoxide scavenger) was determined using the von Frey test and hot plate test. Furthermore, we examined the effect of rPGC-1α on mitochondrial superoxide using cultured neurons. Our findings include that: (i) spinal MT decreased the expression of spinal PGC-1α in the SCDH neurons; (ii) rPGC-1α increased mechanical threshold and thermal latency in MT animals; (iii) Mito-Tempol reduced MT behavioral response; (iv) rPGC-1α reduced MT-induced mitochondria-targeted superoxide; and (v) cultured neuronal cells treated with TNFα increased mitochondria-targeted superoxide that can be inhibited by rPGC-1α. The present findings suggest that spinal PGC-1α reduce MT through decreasing mitochondria-targeted superoxide in the SCDH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.expneurol.2021.113622DOI Listing
May 2021
-->