Publications by authors named "Qing Luo"

364 Publications

LncRNA BCAR4 expression and predicts the clinical response to neoadjuvant chemotherapy in patients with locally advanced breast cancer.

Cancer Biomark 2021 Jun 19. Epub 2021 Jun 19.

Department of Oncology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

Background: Neoadjuvant chemotherapy (NAC) is an important treatment for locally advanced breast cancer (LABC). However, there are no effective biomarkers to predict the efficacy. Therefore, there is an urgent need for new biomarkers to predict the response of LABC to NAC. LncRNA BCAR4 has been detected in a variety of malignant tumor tissues and used as a new biomarker for diagnosis and prognosis. However, LncRNA BCAR4 predicts the response of LABC to NAC is unclear.

Objective: Explore the predictive effect of LncRNA BCAR4 on the efficacy of NAC for LABC in three different evaluation systems.

Methods: First, the TCGA database was used to analyze the expression of LncRNA BCAR4 in 33 kinds of malignant tumors, and further explore its expression in breast cancer and its impact on the survival and prognosis of breast cancer. Furthermore, quantitative methods were used to measure the expression level of LncRNA BCAR4 in cancer tissues of 48 LABC patients, and the correlation between LncRNA BCAR4 and clinicopathological status and response to NAC under the evaluation system of 3, RECIST1.1, Miller-Payne (MP) score and whether it reaches pCR,was analyzed.

Results: TCGA data analysis found that LncRNA is highly expressed in a variety of malignant tumor tissues, including breast cancer. And relatively low expression, the shorter the overall survival time of high expression patients. The high expression of LncRNA BCAR4 is related to the size of the tumor, and there are differences in expression between stage I and other stages, but there is no obvious correlation with the positive lymph node and hormone receptor status. Among the three evaluation systems, only in the RECIST 1.1 evaluation system LncRNA BCAR4 has a predictive effect on NAC for LABC. The expression of LncRNA BCAR4 has no significant correlation with clinical stage, Ki-67% and hormone receptor status, and has no significant correlation with whether patients with locally advanced breast cancer obtain pCR during neoadjuvant chemotherapy.

Conclusion: LncRNA BCAR4 is highly expressed in LABC tissues and may be an effective marker for predicting the efficacy of NAC for LABC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/CBM-210048DOI Listing
June 2021

Changes before and after COVID-19 pandemic on the personal hygiene behaviors and incidence of peritonitis in peritoneal-dialysis patients: a multi-center retrospective study.

Int Urol Nephrol 2021 Jun 19. Epub 2021 Jun 19.

Department of Nephrology, Wuhan No. 1 Hospital, Zhongshan Road 215# Qiaokou Area, Wuhan, 430022, Hubei, China.

Background: The impact of Coronavirus disease (COVID-19) pandemic and its influence on personal hygiene behaviors and peritonitis rate in peritoneal-dialysis patients is unknown.

Methods: A multi-center retrospective study was conducted. We reviewed all the cases of peritoneal-dialysis (PD) patients from four major PD centers in Wuhan before and after COVID-19. There were 567 patients enrolled in total. Information was collected on personal hygiene behaviors, basic clinical characteristics, lab results, peritonitis details. We used Chi-square analysis to compare the personal hygiene behaviors, and used Chi-square goodness-of-fit analysis to compare the peritonitis rates before and after COVID-19. Multivariate logistic regression analysis was used to analyze the risk factors for peritonitis rate.

Results: There were no significant differences on peritonitis rates in six-month period before and after COVID-19 (p = 0.0756, Fig. 2 and Table 3). But Gram-positive infections decreased dramatically (p = 0.0041, Table 4). Personal hygiene behaviors such as length of time for washing hands when performing PD treatment, the frequency of washing hands before PD treatment and six general behaviors had significant differences (P < 0.05 Table 2). The multivariate logistic regression analysis showed never washing hands before PD treatment and serum albumin level were the risk factors of peritonitis during COVID-19 (OR 14.408, 95%CI 3.930 -52.821, P = 0.0002; OR 4.681, 95% CI 1.755 -12.485, P = 0.002, Table 5).

Conclusions: The COVID-19 pandemic had a significant positive influence on personal hygiene behaviors. Peritonitis rate did not significantly decrease but Gram-positive infections dramatically decreased. Never hand washing before PD treatment and serum albumin were the risk factors for peritonitis. We should emphasize hand washing before PD treatment in training and re-training program.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11255-021-02924-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214068PMC
June 2021

MiR-142-3p ameliorates high glucose-induced renal tubular epithelial cell injury by targeting BOD1.

Clin Exp Nephrol 2021 Jun 18. Epub 2021 Jun 18.

Department of Pharmacy, Henan Provincial People's Hospital (Zhengzhou University People's Hospital), No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China.

Background: Tubular injury plays a crucial role in the pathogenesis of diabetic nephropathy (DN). It is well known that many microRNAs (miRNAs) exert crucial effects on tubular injury. This study intends to explore the effect of miR-142-3p on the apoptosis and oxidative stress of high glucose (HG)-treated renal tubular epithelial cells (HK-2) and its underlying mechanism.

Materials And Methods: HK-2 cells were exposed to HG to mimic cell injury. MTT assays and flow cytometry analyses were conducted to measure cell viability and cell apoptosis, respectively. RT-qPCR and western blot analyses were carried out to detect RNA and protein levels, respectively. The levels of oxidative stress markers were evaluated by ELISA. The binding between miR-142-3p and biorientation of chromosomes in cell division 1 (BOD1) was validated by a luciferase reporter assay.

Result: MiR-142-3p is low-expressed in HG-stimulated HK-2 cells. Functionally, miR-142-3p overexpression attenuates the apoptosis and oxidative stress of HG-stimulated HK-2 cells. Mechanistically, BOD1 was confirmed to be targeted by miR-142-3p in HK-2 cells. Moreover, BOD1 overexpression reversed the suppressive effect of miR-142-3p overexpression on the apoptosis and oxidative stress of HK-2 cells treated with HG.

Conclusion: MiR-142-3p ameliorates HG-induced renal tubular epithelial cell injury by targeting BOD1. The finding might provide novel insight into the role of miR-142-3p/BOD1 axis in DN treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10157-021-02102-yDOI Listing
June 2021

Human Neutrophil Elastase Mediates MUC5AC Hypersecretion via the Tumour Necrosis Factor-α Converting Enzyme-Epidermal Growth Factor Receptor Signalling Pathway in vivo.

ORL J Otorhinolaryngol Relat Spec 2021 Jun 15:1-9. Epub 2021 Jun 15.

Department of Otolaryngology, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Objectives: The objective of this study is to examine the role of the tumour necrosis factor-α converting enzyme-epidermal growth factor receptor (TACE-EGFR) pathway in human neutrophil elastase (HNE)-induced MUC5AC mucin expression in mice.

Method: Four groups of mice, treated with HNE alone (HNE group), HNE plus TACE inhibitor (HNE + TAPI-2 group), HNE plus EGFR inhibitor (HNE + AG1478 group), and untreated (control group), were used in the experiment. Histopathological changes were monitored by haematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining. TACE, EGFR, and MUC5AC expression in the nasal mucosa were determined using immunohistochemistry. The expression of p-EGFR, EGFR, and TACE protein was analysed on Western blots, and MUC5AC protein levels were assessed via ELISA. TACE, EGFR, and MUC5AC expression in the nasal mucosa were determined using real-time quantitative PCR.

Results: Compared to the control group, HE-stained tissues from the HNE group showed an irregular epithelium as well as goblet cell and submucosal glandular hyperplasia. In the nasal mucosa, strongly positive fuchsia granules were seen in PAS staining and significant increases in TACE, EGFR, MUC5AC mRNA, and protein expression were detected (p < 0.01). The HNE + TAPI-2 and HNE + AG1478 groups had significantly less goblet cell and submucosal gland hyperplasia as well as weaker PAS staining. Compared to mice treated with HNE alone, in HNE + TAPI-2-treated mice, the levels of TACE, EGFR, and MUC5AC mRNA and protein as well as p-EGFR protein were significantly reduced (p < 0.01). In HNE + AG1478-treated mice, EGFR and MUC5AC mRNA and protein levels and p-EGFR protein expression were reduced significantly (p < 0.01), but the difference in TACE mRNA and protein expression between the HNE + AG1478 and HNE groups was not significant (p > 0.05).

Conclusion: Using a newly developed, stable experimental model of nasal hypersecretion in mice, we showed that TAPI-2 or AG1478 inhibited HNE-induced MUC5AC production. This suggests that MUC5AC mucin expression in vivo is mediated by a cascade involving the HNE-TACE-EGFR signalling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000509982DOI Listing
June 2021

Gene Expression Profiles of Circular RNAs and MicroRNAs in Chronic Rhinosinusitis With Nasal Polyps.

Front Mol Biosci 2021 28;8:643504. Epub 2021 May 28.

Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Chronic rhinosinusitis (CRS) is often classified primarily on the basis of the absence or presence of nasal polyps (NPs), that is, as CRS with nasal polyps (CRSwNP) or CRS without nasal polyps (CRSsNP). Additionally, according to the percentage of eosinophils, CRSwNP can be further divided into eosinophilic CRSwNP (ECRSwNP) and non-ECRSwNP. CRSwNP is a significant public health problem with a considerable socioeconomic burden. Previous research reported that the pathophysiology of CRSwNP is a complex, multifactorial disease. There have been many studies on its etiology, but its pathogenesis remains unclear. Dysregulated expression of microRNAs (miRNAs) has been shown in psoriasis, rheumatoid arthritis, pulmonary fibrosis, and allergic asthma. Circular RNAs (circRNAs) are also involved in inflammatory diseases such as rheumatoid arthritis, septic acute kidney injury, myocardial ischemia/reperfusion injury, and sepsis-induced liver damage. The function of miRNAs in various diseases, including CRSwNP, is a research hotspot. In contrast, there have been no studies on circRNAs in CRSwNP. Overall, little is known about the functions of circRNAs and miRNAs in CRSwNP. This study aimed to investigate the expression of circRNAs and miRNAs in a CRSwNP group and a control group to determine whether these molecules are related to the occurrence and development of CRSwNP. Nine nasal mucosa samples were collected, namely, three ECRSwNP samples, three non-ECRSwNP samples, and three control samples, for genomic microarray analysis of circRNA and microRNA expression. All of the tissue samples were from patients who were undergoing functional endoscopic sinus surgery in our department. Then we selected some differentially expressed miRNAs and circRNAs for qPCR verification. Meanwhile, GO enrichment analysis and KEGG pathway analysis were applied to predict the biological functions of aberrantly expressed circRNAs and miRNAs based on the GO and KEGG databases. Receiver operating characteristic (ROC) curve analysis and principal component analysis (PCA) were performed to confirm these molecules are involved in the occurrence and development of CRSwNP. In total, 2,875 circRNAs showed significant differential expression in the CRSwNP group. Specifically, 1794 circRNAs were downregulated and 1,081 circRNAs were upregulated. In the CRSwNP group, the expression of 192 miRNAs was significantly downregulated, and none of the miRNAs were significantly upregulated. GO and KEGG analysis showed differential circRNAs and miRNAs were enriched in "amoebiasis," "salivary secretion," "pathways in cancer," and "endocytosis." Through qRT-PCR verification, the expression profiles of hsa-circ-0031593, hsa-circ-0031594, hsa-miR-132-3p, hsa-miR-145-5p, hsa-miR-146a-5p, and hsa-miR-27b-3p were shown to have statistical differences. In addition, ROC curve analysis showed that the molecules with the two highest AUCs were hsa-circ-0031593 with AUC 0.8353 and hsa-miR-145-5p with AUC 0.8690. Through PCA with the six ncRNAs, the first principal component explained variance ratio was 98.87%. The AUC of the six ncRNAs was 0.8657. In our study, the expression profiles of ECRSwNP and non-ECRSwNP had no statistical differences. The differentially expressed circRNAs and miRNAs between CRSwNP and control may play important roles in the pathogenesis of CRSwNP. Altered expression of hsa-circ-0031593 and hsa-miR-145-5p have the strongest evidence for involvement in the occurrence and development of CRSwNP because their AUCs are higher than the other molecules tested in this study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2021.643504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194396PMC
May 2021

Using the lamina nutrient foramen as the entry point for posterior cervical pedicle screw placement.

Clin Neurol Neurosurg 2021 May 25;207:106711. Epub 2021 May 25.

Medical Innovation Center, the First Affiliated Hospital of Nanchang University, Nanchang 330006, PR China; Institute of Spine and Spinal Cord, Nanchang University, Nanchang 330006, PR China. Electronic address:

Study Design: A prospective study and technique description.

Objective: This study introduced a method for posterior cervical pedicle screw placement by using the bilateral posterior lamina nutrient foramens as the entry point.

Methods: Firstly, 30 dry C3-C7 vertebrae specimens were harvested for measurement. The lamina nutrient foramens were used as the entry points for posterior cervical pedicle screw placement and four linear and two angle parameters were obtained from a computed tomography scan(CT). Then, 60 patients who underwent C3-C7 pedicle screw fixation using this method were included, linear and angle parameters were obtained from a postoperative CT.

Results: The average incidences of lamina nutrient foramen on the C3-C7 specimens were 88.3%, 90.0%, 95.0%, 95.0%, and 96.7%, respectively. The distances from the entry point to the pedicle screw tip (OD), the pedicle transverse angles (α), and the pedicle sagittal angles (β) measure for the entry points from C3-C7 were 28.74 ± 3.45-30.15 ± 2.01 mm, 26.88 ± 6.89° to 32.72 ± 5.91°, and 12.48 ± 9.31° to 19.71 ± 8.45°, respectively, with no significant differences between the left and right sides. In the 60 patients who underwent surgery, the lengths of the pedicle screws (PL) were 28.34 ± 2.25-30.15 ± 2.31 mm, the pedicle transverse angles (α) were 26.89 ± 6.86° to 32.36 ± 5.65°, and the pedicle sagittal angles (β) were 12.49 ± 9.11° to 20.06 ± 8.91°. The new method had a 96.8% (454/469) success rate among these patients, with no screws penetrating the spinal canal or signs of vertebral artery injury.

Conclusion: Entry at the bilateral lamina nutrient foramen represents an alternative posterior cervical pedicle screw placement technique that is feasible and safe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clineuro.2021.106711DOI Listing
May 2021

Increased TIM-3PD-1 NK cells are associated with the disease activity and severity of systemic lupus erythematosus.

Clin Exp Med 2021 Jun 8. Epub 2021 Jun 8.

Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China.

It is well established that natural killer (NK) cells are dysregulated in systemic lupus erythematosus (SLE) patients. However, the functions of NK cells and the mechanisms regulated by them in SLE remain incompletely understood. Patients with SLE were recruited from The First Affiliated Hospital of Nanchang University, and their clinical characteristics and treatments were recorded. The expression levels of T cell immunoglobulin mucin-3 (TIM-3) and programmed cell death protein 1 (PD-1) on NK cells were examined using flow cytometry. The correlations between the increase in TIM-3PD-1 NK cells in the SLE patients and clinical traits, including inflammatory markers, auto-antibodies, disease activity and severity of SLE, were examined. The TIM-3NK cells, PD-1NK cells and TIM-3PD-1 NK cells were significantly increased in the SLE patients. The increase in TIM-3PD-1 NK cells in the patients with SLE was associated with erythrocyte sedimentation rate, C-reactive protein, anti-double stranded DNA, anti-ribosomal P, SLE disease activity index and clinical features. The frequency of TIM-3PD-1NK cells in SLE patients with a cardiovascular disease (CVD) was significantly lower than that in SLE patients without a CVD. Moreover, the increased TIM-3PD-1 NK cells were significantly decreased in SLE patients following treatment. The present study suggested that the increased TIM-3PD-1 NK cells were associated with the disease activity and severity of SLE and may play a role in SLE pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10238-021-00726-8DOI Listing
June 2021

Deep-red fluorescence from isolated dimers: a highly bright excimer and imaging .

Chem Sci 2020 May 25;11(23):6020-6025. Epub 2020 May 25.

School of Engineering, HuZhou University, Huzhou Cent Hosp 759 Erhuan Rd Huzhou Zhejiang P. R. China

Restricted by the energy-gap law, the development of bright near-infrared (near-IR) fluorescent luminophors in the solid state remains a challenge. Herein, we report a new design strategy for realizing high brightness and deep-red/near-IR-emissive organic molecules based on the incorporation of a hybridized local and charge-transfer (HLCT) state and separated dimeric stacks into one aggregate. Experimental and theoretical analyses show that this combination not only contributes to high photoluminescent quantum yields (PLQYs) but also significantly lessens the energy gap. The fluorophore exhibits excellent fluorescence performance, achieving a PLQY of 54.8% for the fluorescence peak at 690 nm, which is among the highest reported for near-IR fluorescent excimers. In addition, because of its bioimaging performance, the designed luminophor has potential for use as a deep-red fluorescent probe for biomedical applications. This research opens the door for developing deep-red/near-IR emissive materials with high PLQYs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0sc01873bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159302PMC
May 2020

C19orf10 promotes malignant behaviors of human bladder carcinoma cells via regulating the PI3K/AKT and Wnt/β-catenin pathways.

J Cancer 2021 19;12(14):4341-4354. Epub 2021 May 19.

Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518000, P.R. China.

Chromosome 19 open reading frame 10 (C19orf10) is a myocardial repair mediator overexpressed in hepatocellular carcinoma. However, its function and clinical value in bladder cancer (BC) have not been reported. This study aimed to investigate the role of C19orf10 in BC progression and explore underlying mechanisms. C19orf10 expression in BC tissues and human BC cell lines was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The correlation between the C19orf10 protein levels determined by immunohistochemical staining and the clinicopathological characteristics of 192 BC patients was evaluated. BC cell lines SW780, J82 and UMUC-3 were transfected with small interfering RNA (siRNA) targeting C19orf10 or plasmids overexpressing C19orf10. Cell proliferation, migration and invasion were measured by Cell Counting Kit-8, Colony formation, EdU incorporation and Transwell assays. The effect of small hairpin RNA (shRNA)-mediated stable C19orf10 knockdown on tumor formation was assessed in a xenograft mouse model. The expressions of epithelial-mesenchymal transition (EMT) markers, PI3K/AKT and Wnt/β-catenin signaling pathways-related molecules were determined by western blot assay. C19orf10 was significantly upregulated in the BC tissues and a panel of human BC cell lines. High expression of C19orf10 was positively associated with malignant behaviors in BC. C19orf10 knockdown inhibited cell proliferation, migration, and invasion in SW780 and J82 cells, while C19orf10 overexpression in UMUC-3 cells resulted in opposite effects. In addition, C19orf10 silence in SW780 cells suppressed tumor growth in xenograft mice. Moreover, C19orf10 promotes the malignant behaviors and EMT of human bladder carcinoma cells via regulating the PI3K/AKT and Wnt/β-catenin pathways. C19orf10 is overexpressed in BC and functions as an oncogenic driver that promotes cell proliferation and metastasis, and induces EMT of BC cells via mechanisms involving activation of the PI3K/AKT and Wnt/β-catenin pathways. This study provides valuable insight on targeting C19orf10 for BC treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.56993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176426PMC
May 2021

Wolfberry genomes and the evolution of Lycium (Solanaceae).

Commun Biol 2021 Jun 3;4(1):671. Epub 2021 Jun 3.

Key Laboratory of National Forestry and Grassland Administration for Orchid Conservation and Utilization at College of Landscape Architecture, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.

Wolfberry Lycium, an economically important genus of the Solanaceae family, contains approximately 80 species and shows a fragmented distribution pattern among the Northern and Southern Hemispheres. Although several herbaceous species of Solanaceae have been subjected to genome sequencing, thus far, no genome sequences of woody representatives have been available. Here, we sequenced the genomes of 13 perennial woody species of Lycium, with a focus on Lycium barbarum. Integration with other genomes provides clear evidence supporting a whole-genome triplication (WGT) event shared by all hitherto sequenced solanaceous plants, which occurred shortly after the divergence of Solanaceae and Convolvulaceae. We identified new gene families and gene family expansions and contractions that first appeared in Solanaceae. Based on the identification of self-incompatibility related-gene families, we inferred that hybridization hotspots are enriched for genes that might be functioning in gametophytic self-incompatibility pathways in wolfberry. Extremely low expression of LOCULE NUBER (LC) and COLORLESS NON-RIPENING (CNR) orthologous genes during Lycium fruit development and ripening processes suggests functional diversification of these two genes between Lycium and tomato. The existence of additional flowering locus C-like MADS-box genes might correlate with the perennial flowering cycle of Lycium. Differential gene expression involved in the lignin biosynthetic pathway between Lycium and tomato likely illustrates woody and herbaceous differentiation. We also provide evidence that Lycium migrated from Africa into Asia, and subsequently from Asia into North America. Our results provide functional insights into Solanaceae origins, evolution and diversification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42003-021-02152-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175696PMC
June 2021

[Status and influential factors of water-borne diseases in bathing beaches in three cities of China from 2019 to 2020].

Wei Sheng Yan Jiu 2021 May;50(3):472-475

National Center for Rural Water Supply, Technical Guidance, Chinese Center for Disease Control and Prevention, Beijing 102200, China.

Objective: To understand the health status and influencing factors of people in bathing beach after bathing.

Methods: A questionnaire survey was conducted among the beach tourists in Hebei, Shandong and Shanghai Provinces from May to September, 2019-2020, including personal basic information, seawater/beach exposure in the last 7 days, beach activities, personal protective measures, physical health, related symptoms or diseases after bathing, etc. The seawater samples and sand of the three bathing beaches were sampled and detected.

Results: A total of 1222 valid questionnaires were collected. Skin infection(26. 19%), nasal congestion(12. 36%) and eye infection(8. 18%) were the most common symptoms of the tourist after seawater bath. Multivariate logistic regression analysis showed that previous physical discomfort(OR=0. 08-140. 73, 95%CI 0. 04-443. 64) was the common factor of all symptoms(P& lt; 0. 05), the risk factors of stomach cramps, eye infection, nasal congestion and sore throat were no wear of turbinate(OR=4. 65, 95% CI 1. 53-14. 08) and goggles(OR=541. 52, 95% CI 121. 58-2411. 85), swallowing seawater(OR=2. 29-79. 78, 95%CI 19. 83-296. 78) respectively(P& lt; 0. 05).

Conclusion: Personal protective measures and physical conditions affect people& apos; s symptoms and diseases after bathing. There is microbial pollution in beach water and sand.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2021.03.021DOI Listing
May 2021

Stretch-Induced Tenomodulin Expression Promotes Tenocyte Migration via F-Actin and Chromatin Remodeling.

Int J Mol Sci 2021 May 6;22(9). Epub 2021 May 6.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.

The mechanosensitive gene tenomodulin (Tnmd) is implicated in tendon maturation and repair. However, the mechanism by which mechanical loading regulates Tnmd's expression and its role in tenocyte migration is yet to be defined. Here, we show that Tnmd and migration were upregulated in uniaxial cyclic stress-stimulated tenocytes. The knockdown of Tnmd reduced cell migration in the presence and absence of mechanical loading, suggesting that Tnmd is involved in tenocyte migration. Moreover, the treatment of stress-stimulated tenocytes with the actin inhibitor latrunculin (Lat A), histone acetyltransferase inhibitor anacardic acid (ANA), or histone demethylases inhibitor GSK-J4 suppressed Tnmd expression and tenocyte migration. These results show that actin stress fiber formation and chromatin decondensation regulates Tnmd expression, which might then regulate tenocyte migration. Thus, this study proposes the involvement of the actin and chromatin mechanotransduction pathway in the regulation of Tnmd and reveals a novel role of Tnmd in tenocyte migration. The identification of Tnmd function in tenocyte migration provides insight into the molecular mechanisms involved in Tnmd-mediated tendon repair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22094928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124537PMC
May 2021

Circular RNAs hsa-circ0000175 and hsa-circ0044235 in plasma are novel biomarkers for new-onset rheumatoid arthritis.

Autoimmunity 2021 Jun 19;54(4):234-242. Epub 2021 May 19.

Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, PR China.

Circular RNAs (circRNAs) are a class of non-coding RNAs that could serve as potential molecular markers for disease diagnosis. However, the role of circRNAs in plasma from new-onset rheumatoid arthritis (RA) has not been extensively investigated. In this study, the expression of hsa-circ0000175 and hsa-circ0044235 in plasma from RA patients, healthy controls (HCs), systemic lupus erythematosus (SLE) patients, osteoarthritis (OA), and undiagnosed arthritis (UA) patients were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Correlation analysis was used to assess the correlation of the two circRNAs and clinical variables of RA. The receiver operating characteristic (ROC) curves were created to evaluate the diagnostic value and multivariate analysis (logistic regression) was performed to analyse the risk factors. We confirmed that hsa-circ0000175 was significantly elevated in plasma from patients with new-onset RA compared with HC and patients with new-onset SLE, but significantly was reduced when compared with OA + UA patients. Hsa-circ0044235 was found to be significantly decreased in plasma from patients with new-onset RA compared with HC and OA + UA patients, but was significantly increased compared with SLE patients. The expression of plasma hsa-circ0000175 in new-onset RA patients was associated with platelet count (PLT), plateletcrit (PCT), and platelet large cell ratio (PLR), the expression of plasma hsa-circ0044235 new-onset RA patients was associated with swollen joint count (SJC), painful joint count (PJC), and disease activity score 28 (DAS28). ROC curve analysis suggested that the combination of hsa-circ0000175 and hsa-circ0044235 has some value in the diagnosis of new-onset RA from HC, patients with SLE and patients with OA + UA. The logistic regression analysis revealed that the expression of hsa-circ0000175 and hsa-circ0044235 in plasma were risk factors for RA. This study suggests that the combination of plasma hsa-circ0000175 and hsa-circ0044235 improves the diagnostic accuracy for new-onset RA. Moreover, the expression levels of plasma hsa-circ0000175 and hsa-circ0044235 were associated with disease activity and severity of RA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08916934.2021.1922891DOI Listing
June 2021

An update on genetic basis of generalized pustular psoriasis (Review).

Int J Mol Med 2021 Jun 6;47(6). Epub 2021 May 6.

Department of Laboratory Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.

Generalized pustular psoriasis (GPP) is a rare and severe auto‑inflammatory skin disease that is characterized by recurrent, acute onset, and generalized pustular eruptions on erythematous, inflamed skin. GPP is traditionally classified as a variant of psoriasis vulgaris, even though recent clinical, histological and genetic evidence suggests that it is a heterogeneous disease and requires a separate diagnosis. In recent years, variants of , , and genes have been identified as causative or contributing to genetic defects in a proportion of patients affected by GPP. These disease‑related genes are involved in common inflammatory pathways, in particular in the IL‑1/IL‑36‑chemokines‑neutrophil pathogenic axis. At present, no standard therapeutic guidelines have been established for GPP management, and there is a profound need for novel efficacious treatments of GPP. Among them, biological agents antagonizing the IL‑36 pathway are promising therapeutics. The aim of the present review is to provide the most recent updates on the genetics, genotype‑phenotype correlation and pathological basis of GPP, as well as on biologic treatments available for GPP and relative clinical courses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ijmm.2021.4951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083806PMC
June 2021

Melt extrusion deposition (MED™) 3D printing technology - A paradigm shift in design and development of modified release drug products.

Int J Pharm 2021 Jun 24;602:120639. Epub 2021 Apr 24.

Triastek, Inc., 12 East Mozhou Road, U Park P402, Nanjing, Jiangsu, China; Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy, University of the Pacific, 3601 Pacific Ave, Stockton, CA, United States. Electronic address:

Three-dimensional printing (3DP) technology offers unique advantages for pharmaceutical applications. However, most of current 3D printing methods and instrumentations are not specifically designed and developed for pharmaceutical applications. To meet the needs in pharmaceutical applications for precision, compatibility with a wide range of pharmaceutical excipients and drug materials without additional processing, high throughput and GMP compliance, an extrusion-based 3D printer based on Melt Extrusion Deposition (MED™) 3D printing technology was developed in this study. This technology can process powder pharmaceutical excipients and drugs directly without the need of preparing filament as required by FDM 3D printing. Six different tablet designs based on compartment models were used to demonstrate the precision and reproducibility of this technology. The designed tablets were fabricated using the GMP-compliant MED™ 3D printer and were evaluated in vitro for drug release and in vivo for selected designs using male beagle dogs. Tablet designs with one or more compartments showed versatile release characteristics in modulating the release onset time, release kinetics, duration of release and mode of release. Multiple drugs or formulations were fabricated into a single tablet to achieve independent release kinetics for each drug or to fine-tune the pharmacokinetic profile of a drug. Building upon the theoretical analysis of models, precision and reproducibility of MED™ 3D printing technology, a novel product development approach, 3D printing formulation by design (3DPFbD®) was developed to provide an efficient tool for fast and efficient pharmaceutical product development. The MED™ 3D printing represents a novel and promising technology platform encompassing design and development of modified drug release products and has potential to impact the drug delivery and pharmaceutical product development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2021.120639DOI Listing
June 2021

Specifically targeting Mtb cell-wall and TMM transporter: the development of MmpL3 inhibitors.

Curr Protein Pept Sci 2021 Apr 20. Epub 2021 Apr 20.

Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, School of Pharmacy, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610106, China.

Tuberculosis (TB) remains a serious threat to whole human health. In particular, the drug resistance of Mycobacterium tuberculosis (Mtb) has become a huge challenge in clinical medicine, and it is extremely urgent to develop effective inhibitors with novel structures and mechanisms. Belonging to the Resistance, Nodulation and Division (RND) superfamily, Mycobacterial membrane proteins Large 3 (MmpL3) is mainly responsible for transporting mycolic acid outside cell membrane to form cell wall, and plays critical roles in iron acquisition which is vital to the survival of Mtb. As a potential Mtb target in recent years, its inhibitor research has attracted wide attention. A series of inhibitors (such as SQ109, AU1235, BM212, etc.) through experimental screening have been reported in succession, especially SQ109 has entered the clinical stage. In this paper, the structural biology information of target MmpL3 was summarized, and the structure-activity relationship (SAR) of inhibitors reported in recent years and their inhibitory mechanism both were reviewed, aiming to provide help for the rational design of MmpL3 inhibitors in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389203722666210421105733DOI Listing
April 2021

Classification and Design of HIV-1 Integrase Inhibitors Based on Machine Learning.

Comput Math Methods Med 2021 1;2021:5559338. Epub 2021 Apr 1.

Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, School of Pharmacy, Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610106, China.

A key enzyme in human immunodeficiency virus type 1 (HIV-1) life cycle, integrase (IN) aids the integration of viral DNA into the host DNA, which has become an ideal target for the development of anti-HIV drugs. A total of 1785 potential HIV-1 IN inhibitors were collected from the databases of ChEMBL, Binding Database, DrugBank, and PubMed, as well as from 40 references. The database was divided into the training set and test set by random sampling. By exploring the correlation between molecular descriptors and inhibitory activity, it is found that the classification and specific activity data of inhibitors can be more accurately predicted by the combination of molecular descriptors and molecular fingerprints. The calculation of molecular fingerprint descriptor provides the additional substructure information to improve the prediction ability. Based on the training set, two machine learning methods, the recursive partition (RP) and naive Bayes (NB) models, were used to build the classifiers of HIV-1 IN inhibitors. Through the test set verification, the RP technique accurately predicted 82.5% inhibitors and 86.3% noninhibitors. The NB model predicted 88.3% inhibitors and 87.2% noninhibitors with correlation coefficient of 85.2%. The results show that the prediction performance of NB model is slightly better than that of RP, and the key molecular segments are also obtained. Additionally, CoMFA and CoMSIA models with good activity prediction ability both were constructed by exploring the structure-activity relationship, which is helpful for the design and optimization of HIV-1 IN inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5559338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035010PMC
April 2021

Human Methylmercury Exposure and Potential Impacts in Central Tibet: Food and Traditional Tibetan Medicine.

Bull Environ Contam Toxicol 2021 Apr 11. Epub 2021 Apr 11.

Ministry of Education Laboratory of Earth Surface Process, College of Urban and Environmental Sciences, Peking University, Beijing, 100871, China.

Methylmercury presents potent neurotoxicity to humans. Fish consumption is the leading source of human exposure to methylmercury worldwide. However, the exposure source in Tibet remains poorly understood because of the scarcity of observational data on most Tibetan foods, although high mercury levels were recently detected in some traditional Tibetan medicines. Here, the results of field investigations show that the joint consumption of traditional Tibetan medicines (TTMs), fish, and rice constitutes a primary exposure pathway to methylmercury in Tibetans and that the probable daily intake of methylmercury is close to that for many coastal regions. People who are young and high-income may have higher methylmercury exposure levels mainly because of economic development and cultural exchanges among regions. Our analysis indicates that a large proportion of the Tibetan population are likely to face a high methylmercury exposure risk and that mercury-susceptible populations in Tibet should be attentive to consuming TTMs with fish.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00128-021-03216-5DOI Listing
April 2021

Phytotoxicity of tris-(1-chloro-2-propyl) phosphate in soil and its uptake and accumulation by pakchoi (Brassica chinensis L. cv. SuZhou).

Chemosphere 2021 Aug 22;277:130347. Epub 2021 Mar 22.

Key Laboratory of Regional Environment and Eco-Remediation of Ministry of Education, College of Environment, Shenyang University, Shenyang, 110044, China.

This study investigated physiological and biochemical changes in pakchoi at different growth stages (25 and 50 d) under different tris-(1-chloro-2-propyl) phosphate (TCIPP) treatments (10, 100, 500, and 1000 μg kg). The uptake and accumulation of TCIPP by pakchoi and variation of TCIPP speciation in soil were also determined. TCIPP decreased the length and fresh weight of pakchoi root compared with those in blank controls, and this effect was significant when the concentration of TCIPP was higher than 100 μg kg. The fresh weight of pakchoi stems and leaves, the chlorophyll content, and the activities of superoxide dismutase, peroxidase, and catalase in the leaves first increased and then decreased with increasing TCIPP concentration. The inflection point of the variation in these indices was 100 μg kg TCIPP in soil. The contents of proline and malondialdehyde increased continuously with increasing TCIPP concentration. The uptake of TCIPP by pakchoi increased linearly with increasing TCIPP concentration, and the highest TCIPP concentrations in the roots, stems, and leaves were 275.9, 80.0, and 2126.3 μg kg, respectively. TCIPP was easily transferred from the roots to leaves of pakchoi, with translocation factor of up to 12.6. The content of bioavailable TCIPP in soil was high, accounting for 46.5%. Planting pakchoi could significantly reduce the content of bioavailable TCIPP, with removal rate of 39.9%-54.1%. After 50 d of planting pakchoi, the removal rate of TCIPP in soil (10.4%-18.6%) was significantly higher than that in the control without plant, but the contribution of phytoextraction was small, accounting for 2.62%-26.6%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2021.130347DOI Listing
August 2021

Bioaccessibility and public health risk of heavy Metal(loid)s in the airborne particulate matter of four cities in northern China.

Chemosphere 2021 Aug 19;277:130312. Epub 2021 Mar 19.

MOE Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China.

Atmospheric coarse particulate matter (PM) enriched with heavy metal(loid)s could pose potentially significant health risk to humans, while accurate health risk assessment calls for characterization of their bioaccessibility, besides the total contents. The health risk of major toxic heavy metal(loid)s in the PM from four large cities in northern China via inhalation was investigated based on their total contents and bioaccessibility. The annual mean concentrations of PM-bound Zn, As, Pb, and Mn in the atmosphere of the four cities were 650, 305, 227, and 177 ng⋅m, respectively. The levels of heavy metal(loid)s in the PM were generally higher in winter but lower in summer in all four cities, which resulted primarily from the emissions associated with coal combustion for district and household heating and the unfavorable meteorological conditions in winter. The bioaccessibility of heavy metal(loid)s in the PM ranged from 0.9 to 48.7%, following the general order of Mn > Co > Ni > Cd > Cu > As > Cr > Zn > Pb. Based on their total contents in the PM, most heavy metal(loid)s posed significant public health risk via inhalation exposure in the four cities. However, after accounting for the bioaccessibility of metal(loid)s, the non-carcinogenic risk of most metal(loid)s was negligible, except for As in the PM of Jinzhong, while only the carcinogenic risk posed by Cr and As in the PM exceeded the acceptable level. These findings demonstrate the importance of characterizing the bioaccessibility of airborne PM-bound heavy metal(loid)s in health risk assessment and could guide the on-going efforts on reducing the public health risk of PM in northern China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2021.130312DOI Listing
August 2021

Biomaterial-based platforms for cancer stem cell enrichment and study.

Cancer Biol Med 2021 Mar 19. Epub 2021 Mar 19.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.

Cancer stem cells (CSCs) are a relatively rare subpopulation of tumor cell with self-renewal and tumorigenesis capabilities. CSCs are associated with cancer recurrence, progression, and chemoradiotherapy resistance. Establishing a reliable platform for CSC enrichment and study is a prerequisite for understanding the characteristics of CSCs and discovering CSC-related therapeutic strategies. Certain strategies for CSC enrichment have been used in laboratory, particularly fluorescence-activated cell sorting (FACS) and mammosphere culture. However, these methods fail to recapitulate the chemical and physical conditions in tumors, thus potentially decreasing the malignancy of CSCs in culture and yielding unreliable research results. Accumulating research suggests the promise of a biomaterial-based three-dimensional (3D) strategy for CSC enrichment and study. This strategy has an advantage over conventional methods in simulating the tumor microenvironment, thus providing a more effective and predictive model for CSC laboratory research. In this review, we first briefly discuss the conventional methods for CSC enrichment and study. We then summarize the latest advances and challenges in biomaterial-based 3D CSC platforms. Design strategies for materials, morphology, and chemical and physical cues are highlighted to provide direction for the future construction of platforms for CSC enrichment and study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185859PMC
March 2021

The distribution of liver cancer stem cells correlates with the mechanical heterogeneity of liver cancer tissue.

Histochem Cell Biol 2021 Jul 12;156(1):47-58. Epub 2021 Mar 12.

Key Laboratory of Biorheological Science and Technology, College of Bioengineering, Chongqing University, Ministry of Education, Chongqing, 400030, People's Republic of China.

The survival of cancer stem cells is usually limited to a specific tumor microenvironment, and this microenvironment plays a vital role in the development of tumors. The mechanical properties of the microenvironment differ in different regions of solid tumors. However, in solid tumors, whether the distribution of cancer stem cells relates to the mechanical microenvironment of different regions is still unclear. In this study, we undertook a biophysical and biochemical assessment of the changes in the mechanical properties of liver tissue during the progression of liver cancer and explored the distribution of liver cancer stem cells in liver cancer tissues. Our analysis confirmed previous observations that the stiffness of liver tissue gradually increased with the progress of fibrosis. In liver cancer tissues, we found obvious mechanical heterogeneity: the core of the tumor was soft, the invasive front tissue was the hardest, and the para-cancer tissue was in an intermediate state. Interestingly, the greatest number of liver cancer stem cells was found in the invasive front part of the tumor. We finally established that stroma stiffness correlated with the number of liver cancer stem cells. These findings indicate that the distribution of liver cancer stem cells correlates with the mechanical heterogeneity of liver cancer tissue. This result provides a theoretical basis for the development of targeted therapies against the mechanical microenvironment of liver cancer stem cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00418-021-01979-wDOI Listing
July 2021

Activating soil microbial community using bacillus and rhamnolipid to remediate TPH contaminated soil.

Chemosphere 2021 Jul 23;275:130062. Epub 2021 Feb 23.

School of Environment, Shenyang University, Shenyang, 110044, China. Electronic address:

Soil petroleum contamination has become a global environmental problem. In order to develop a new soil remediation technology, this study established bacteria isolation, surfactant toxicity matching and petroleum contaminated soil remediation practice. The simulated field remediation showed that inoculating the soil with Bacillus methylotrophicus and adding 500 mg kg rhamnolipid (N + RL) to soil can remove 80.24% of aged total petroleum hydrocarbons (TPHs) within 30 days. In particular, although the remediated soil has inoculated sufficient bacterial suspension, the microbial abundance of Bacillus was not a significantly dominant genus after remediation, especially in N + RL (0.73% of the total), but the colonies of indigenous petroleum-degrading bacteria (such as Massilia and Streptomyces) increased significantly. The interaction among genera has been further proved to drive soil non-specific oxidases (such as polyphenol oxidase, laccase and catalase) to remove TPHs. This indicates that the interaction among microorganisms, rather than the degradability of exogenous degrading bacteria, plays more critical role in the degradation of organic pollutants, which enriches the traditional understanding of micro-remediation of contaminated soil. It can be concluded from the obtained results that the remediation of pollutants can be achieved by adjusting the purification capacity of the microbial community and the natural environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2021.130062DOI Listing
July 2021

Network Pharmacology-Based Approach to Investigate the Molecular Targets of Sinomenine for Treating Breast Cancer.

Cancer Manag Res 2021 9;13:1189-1204. Epub 2021 Feb 9.

Department of Cell Biology, Center for Stem Cell and Medicine, Navy Medical University (Second Military Medical University), Shanghai, 200433, People's Republic of China.

Purpose: Sinomenine has been known to inhibit the proliferation of breast cancer cells. However, its targets have not been found yet. This study aimed to search for molecular targets of sinomenine for treating breast cancer via network pharmacology.

Methods: Potential targets of sinomenine or breast cancer were separately screened from indicated databases. The common targets of both sinomenine and breast cancer were considered as the targets of sinomenine for treating breast cancer. A sinomenine-target-pathway network was constructed based on the obtained results from Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The putative targets of sinomenine were further determined by using protein-protein interaction (PPI) analysis and molecular docking. Finally, the putative targets were verified in vitro and in vivo.

Results: Twenty predicted targets were identified through network pharmacological analysis. Gene Ontology (GO) and KEGG pathway enrichment indicated that these predicted targets enriched in the process of MAP kinase activity, VEGF signaling pathway, Relaxin signaling pathway, Growth hormone synthesis, secretion and action. MAPK1, NOS3, NR3C1, NOS1 and NOS2 were further identified as the putative targets by using PPI and molecular docking analysis. Expression of MAPK1, NR3C1, NOS1, NOS2 and NOS3 genes were significantly regulated by sinomenine in both MCF-7 cells and MDA-MB-231 cells. Furthermore, the expression of NR3C1 in human breast cancer specimens was lower than that in para-tumor normal tissues. Meanwhile, the expression of NR3C1 in xenograft tumors was up-regulated after sinomenine treatment.

Conclusion: MAPK1, NR3C1, NOS1, NOS2 and NOS3 were identified as the putative targets of sinomenine for treating breast cancer. NR3C1 was preliminarily confirmed as a target of sinomenine in two breast cancer cell lines, xenograft tumor models and human breast cancer specimens. These data indicated that the network pharmacology-based prediction of sinomenine targets for treating breast cancer could be reliable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S282684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881794PMC
February 2021

Proliferation and tenogenic differentiation of bone marrow mesenchymal stem cells in a porous collagen sponge scaffold.

World J Stem Cells 2021 Jan;13(1):115-127

Department of College of Bioengineering, Chongqing University, Chongqing 400030, China.

Background: Collagen is one of the most commonly used natural biomaterials for tendon tissue engineering. One of the possible practical ways to further enhance tendon repair is to combine a porous collagen sponge scaffold with a suitable growth factor or cytokine that has an inherent ability to promote the recruitment, proliferation, and tenogenic differentiation of cells. However, there is an incomplete understanding of which growth factors are sufficient and optimal for the tenogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) in a collagen sponge-based 3D culture system.

Aim: To identify one or more ideal growth factors that benefit the proliferation and tenogenic differentiation of rat BMSCs in a porous collagen sponge scaffold.

Methods: We constructed a 3D culture system based on a type I collagen sponge scaffold. The surface topography of the collagen sponge scaffold was observed by scanning electron microscopy. Primary BMSCs were isolated from Sprague-Dawley rats. Cell survival on the surfaces of the scaffolds with different growth factors was assessed by live/dead assay and CCK-8 assay. The mRNA and protein expression levels were confirmed by quantitative real-time polymerase chain reaction and Western blot, respectively. The deposited collagen was assessed by Sirius Red staining.

Results: Transforming growth factor β1 (TGF-β1) showed great promise in the tenogenic differentiation of BMSCs compared to growth differentiation factor 7 (GDF-7) and insulin-like growth factor 1 (IGF-1) in both the 2D and 3D cultures, and the 3D culture enhanced the differentiation of BMSCs into tenocytes well beyond the level of induction in the 2D culture after TGF-β1 treatment. In the 2D culture, the proliferation of the BMSCs showed no significant changes compared to the control group after TGF-β1, IGF-1, or GDF-7 treatment. However, TGF-β1 and GDF-7 could increase the cell proliferation in the 3D culture. Strangely, we also found more dead cells in the BMSC-collagen sponge constructs that were treated with TGF-β1. Moreover, TGF-β1 promoted more collagen deposition in both the 2D and 3D cultures.

Conclusion: Collagen sponge-based 3D culture with TGF-β1 enhances the responsiveness of the proliferation and tenogenic differentiation of rat BMSCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4252/wjsc.v13.i1.115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859984PMC
January 2021

Low-Density Granulocytes Affect T-SPOT.TB Assay by Inhibiting the Production of Interferon-γ in T Cells via PD-L1/PD-1 Pathway.

Front Microbiol 2020 28;11:622389. Epub 2021 Jan 28.

Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Background: T-SPOT TB (T-SPOT) assay is widely used for detection of infection that is based on the detection of -specific interferon-γ-secreting T cells (ISCs) in peripheral blood mononuclear cells (PBMCs). Recently, high frequencies of low-density granulocytes (LDGs) were found in the PBMCs of tuberculosis patients. Whether these LDGs affect the detection of T-SPOT has not been investigated. The impact of LDGs on T-SPOT assay and related mechanism were investigated in this study.

Methods: The correlations between the frequencies of LDGs and the results of T-SPOT were analyzed. T-SPOT with LDG-removed PBMCs and PBMCs with exogenous addition of LDGs were performed. The possible mechanism was explored by detecting the levels of negative immune regulatory molecules on LDGs. The impact of programmed death ligand 1 (PD-L1) on T-SPOT was evaluated and confirmed by function blocking with neutralizing antibody.

Results: The positive rates of T-SPOT and ISCs in tuberculosis patients with low LDGs frequency ( = 22) were significantly higher than those with high LDGs frequency ( = 39). Removal or exogenous addition of LDGs significantly increased or decreased the ISCs and the positive rate of T-SPOT. The frequencies of interferon-γ-producing T cells were negatively correlated with the frequencies of LDGs. The expression of PD-L1 was significantly elevated on LDGs. Pretreatment of LDGs with anti-PD-L1 antibody significantly counteracted the impact of LDGs on T-SPOT. Treatment of PBMCs with anti-PD-L1 antibody resulted in comparable ISCs with that of LDG removal.

Conclusion: LDGs can inhibit the production of interferon-γ in T cells and decrease the positive rated of T-SPOT assay via highly expressed PD-L1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2020.622389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876290PMC
January 2021

Exogenous NAD Postpones the D-Gal-Induced Senescence of Bone Marrow-Derived Mesenchymal Stem Cells via Sirt1 Signaling.

Antioxidants (Basel) 2021 Feb 7;10(2). Epub 2021 Feb 7.

Key Laboratory of Biorheological Science and Technology, College of Bioengineering, Chongqing University, Chongqing 400030, China.

Cell senescence is accompanied by decreased nicotinamide adenine dinucleotide (NAD) levels; however, whether exogenous NAD affects bone marrow-derived mesenchymal stem cells (BMSCs) senescence and the involved mechanisms is still unclear. Here, we find that exogenous NAD replenishment significantly postpones BMSC senescence induced by D-galactose (D-gal). It is also shown that exogenous NAD leads to increased intracellular NAD levels and reduced intracellular reactive oxygen species in senescent BMSCs here. Further investigation showed that exogenous NAD weakened BMSC senescence by increasing Sirtuin 1 (Sirt1) expression. Moreover, exogenous NAD reduced senescence-associated-β-galactosidase activity, and downregulated poly (ADP-ribose) polymerase 1 expression. In addition, the reduced expression of Sirt1 by small interfering RNA abolished the beneficial effects of exogenous NAD in terms of postponing BMSCs senescence induced by D-gal. Taken together, our results indicate that exogenous NAD could postpone D-gal-induced BMSC senescence through Sirt1 signaling, providing a potential method for obtaining high quality BMSCs to support their research and clinical application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox10020254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915830PMC
February 2021

Panorama of intron dynamics and gene rearrangements in the phylum Basidiomycota as revealed by the complete mitochondrial genome of Turbinellus floccosus.

Appl Microbiol Biotechnol 2021 Mar 8;105(5):2017-2032. Epub 2021 Feb 8.

Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, School of Food and Biological Engineering, Chengdu University, 2025 # Chengluo Avenue, Chengdu, 610106, Sichuan, People's Republic of China.

In the present study, the complete mitogenome of Turbinellus floccosus was sequenced, assembled, and compared with other basidiomycete mitogenomes. The mitogenome of T. floccosus consists of a circular DNA molecule, with a size of 62,846 bp. Gene arrangement analysis indicated that large-scale gene rearrangements occurred in the levels of family and genus of basidiomycete species, and the mitogenome of T. floccosus contained a unique gene order. A significant correlation between the number of introns and the mitochondrial genome size of Basidiomycota were detected (P < 0.01). A total of 896 introns were detected in the core protein-coding genes (PCGs) of 74 basidiomycete species, and the cox1 gene was the largest host gene of basidiomycete introns. Intron position class (Pcls) P383 in the cox1 gene was the most common intron in Basidiomycota, which distributed in 40 of 74 basidiomycete species. In addition, frequent intron loss/gain events were detected in basidiomycete species. More than 50% of bases around insertion sites (- 15 bp to 15 bp) of Pcls from different species were conservative, indicating site preferences of intron insertions in Basidiomycota. Further analysis showed that 76.09% of introns tended to insert downstream to a T base in Basidiomycota. Phylogenetic analysis for 74 basidiomycetes indicated mitochondrial genes are effective molecular markers for phylogeny of basidiomycetes. The study served as the first report on the mitogenome from the family Gomphaceae, which will help to understand the intron origin and evolution in Basidiomycota. KEY POINTS: • The mitogenome of Turbinellus floccosus had a unique gene arrangement. • Intron loss/gain events were detected in the 74 basidiomycete species. • Introns tend to insert downstream of a T base in basidiomycete mitogenomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00253-021-11153-wDOI Listing
March 2021

Clonal evolution in liver cancer at single-cell and single-variant resolution.

J Hematol Oncol 2021 Feb 2;14(1):22. Epub 2021 Feb 2.

Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.

Genetic heterogeneity of tumor is closely related to its clonal evolution, phenotypic diversity and treatment resistance, and such heterogeneity has only been characterized at single-cell sub-chromosomal scale in liver cancer. Here we reconstructed the single-variant resolution clonal evolution in human liver cancer based on single-cell mutational profiles. The results indicated that key genetic events occurred early during tumorigenesis, and an early metastasis followed by independent evolution was observed in primary liver tumor and intrahepatic metastatic portal vein tumor thrombus. By parallel single-cell RNA-Seq, the transcriptomic phenotype of HCC was found to be related with genetic heterogeneity. For the first time we reconstructed the single-cell and single-variant clonal evolution in human liver cancer, and dissection of both genetic and phenotypic heterogeneity will facilitate better understanding of their relationship.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13045-021-01036-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852352PMC
February 2021

The main anthocyanin monomer of Lycium ruthenicum Murray induces apoptosis through the ROS/PTEN/PI3K/Akt/caspase 3 signaling pathway in prostate cancer DU-145 cells.

Food Funct 2021 Feb 2;12(4):1818-1828. Epub 2021 Feb 2.

College of Public Health and Management, Ningxia Medical University, Yinchuan 750004, China.

Anthocyanins have been reported to have effective chemopreventive activity. Lycium ruthenicum Murray is rich in anthocyanins and exhibits many biological activities. The purpose of this study was to investigate the effects and possible biological mechanism of the main anthocyanin monomer (Pt3G) of Lycium ruthenicum Murray on prostate cancer DU-145 cells. The cell proliferation was detected by methyl thiazolyl tetrazolium assay. The cell apoptosis rates were assessed by flow cytometric analysis and TUNEL assay. The expressions of apoptosis related proteins were evaluated by western blotting. Our data demonstrated that Pt3G inhibited cell proliferation, induced apoptosis and promoted cell cycle arrest at the S phase in a concentration-dependent manner (0, 100, 200 and 400 μg mL). Furthermore, it was shown that Pt3G decreased the mitochondrial membrane permeability through regulating the expressions of Bax and Bcl-2. Western blot analysis indicated that Pt3G significantly increased the expression of PTEN and then activated the PI3K/Akt-mediated caspase 3 pathway. In addition, our results also suggested that Pt3G activated the PTEN gene to induce the apoptosis of DU-145 cells by stimulating the overproduction of ROS. To sum up, these results indicate that Pt3G inhibits cell proliferation and induces apoptosis through the ROS/PTEN/PI3K/Akt/caspase 3 signaling pathway in prostate cancer DU-145 cells. Therefore, Pt3G of Lycium ruthenicum Murray may be a potential anti-proliferative agent for the prevention or treatment of prostate cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0fo02382eDOI Listing
February 2021
-->