Publications by authors named "Qingmei Liu"

74 Publications

Hair Growth Promoting Effects of 650 nm Red Light Stimulation on Human Hair Follicles and Study of Its Mechanisms via RNA Sequencing Transcriptome Analysis.

Ann Dermatol 2021 Dec 4;33(6):553-561. Epub 2021 Nov 4.

Department of Dermatology, Jing'an District Central Hospital, Shanghai, China.

Background: Androgenetic alopecia (AGA) leads to thinning of scalp hair and affects 60%~70% of the adult population worldwide. Developing more effective treatments and studying its mechanism are of great significance. Previous clinical studies have revealed that hair growth is stimulated by 650-nm red light.

Objective: This study aimed to explore the effect and mechanism of 650-nm red light on the treatment of AGA by using hair follicle culture.

Methods: Human hair follicles were obtained from hair transplant patients with AGA. Hair follicles were cultured in Williams E medium and treated with or without 650-nm red light. Real-time RT-PCR and immunofluorescence staining were used to detect the expression level of genes and proteins in hair follicles, respectively. RNA-sequencing analysis was carried out to reveal the distinct gene signatures upon 650 nm treatment.

Results: Low-level 650 nm red light promoted the proliferation of human hair follicles in the experimental cultured-tissue model. Consistently, 650 nm red light significantly delayed the transition of hair cycle from anagen to catagen . RNA-seq analysis and gene clustering for the differentially expressed genes suggests that leukocyte transendothelial migration, metabolism, adherens junction and other biological process maybe involved in stimulation of hair follicles by 650-nm red light treatment.

Conclusion: The effect of 650-nm red light on hair follicles and the transcriptome set which implicates the role of red light in promoting hair growth and reversing of miniaturization process of AGA were identified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5021/ad.2021.33.6.553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577899PMC
December 2021

Two hypo-allergenic derivatives lacking the dominant linear epitope of Scy p 1 and Scy p 3.

Food Chem 2021 Nov 11:131588. Epub 2021 Nov 11.

College of Food and Biological Engineering, Xiamen Key Laboratory of Marine Functional Food, Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological Resources, Jimei University, Xiamen, Fujian 361021, China. Electronic address:

Scylla paramamosain frequently elicits IgE-mediated type-I hypersensitivity reactions. Molecular candidates for crab allergen-specific immunotherapy have not been studied previously. In this study, reduced and alkylated (red/alk) derivatives with destroyed conformational epitopes and mutant derivatives (mtALLERGEN) with deleted heat/digestion-stable linear epitopes were produced of tropomyosin and myosin light chain. Structural changes and the allergenicity of derivatives was analyzed. Compared with wild-type allergens, red/alk derivatives had dramatically altered protein structures, whereas mtALLERGEN showed slightly structural effects. Enzyme linked immunosorbent assay revealed the heterogeneous epitope-recognition patterns with derivatives among 29 crab-sensitised patients, of whom 13% and 62% recognised conformational and linear epitopes, respectively, whereas 25% recognised both epitope types to the same extent. Furthermore, mtALLERGEN could not bind to IgE or induce basophil activation in some patients. These results imply that hypo-allergenic derivatives of crab myofibril allergens that specifically lacked linear epitopes may serve as viable candidates for immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2021.131588DOI Listing
November 2021

Targeted Bisulfite Sequencing Reveals DNA Methylation Changes in Zinc Finger Family Genes Associated With KRAS Mutated Colorectal Cancer.

Front Cell Dev Biol 2021 28;9:759813. Epub 2021 Oct 28.

Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China.

Colorectal cancer (CRC) is a leading cause of cancer death, and early diagnosis of CRC could significantly reduce its mortality rate. Previous studies suggest that the DNA methylation status of zinc finger genes (ZFGs) could be of potential in CRC early diagnosis. However, the comprehensive evaluation of ZFGs in CRC is still lacking. We first collected 1,426 public samples on genome-wide DNA methylation, including 1,104 cases of CRC tumors, 54 adenomas, and 268 para-tumors. Next, the most differentially methylated ZFGs were identified and validated in two replication cohorts comprising 218 CRC patients. Finally, we compared the prediction capabilities between the ZFGs and the SEPT9 in all CRC patients and the KRAS + and KRAS- subgroup. Five candidate ZFGs were selected: , , , , and . In particular, [area under the curve (AUC) = 0.91] and (AUC = 0.93) showed equivalent or better diagnostic capability for CRC than (AUC = 0.91) in the validation dataset, suggesting that these two ZFGs might be of potential for CRC diagnosis in the future. Furthermore, we performed subgroup analysis and found a significantly higher diagnostic capability in KRAS + (AUC ranged from 0.97 to 1) than that in KRAS- patients (AUC ranged from 0.74 to 0.86) for all these five ZFGs, suggesting that these ZFGs could be ideal diagnostic markers for KRAS mutated CRC patients. The methylation profiles of the candidate ZFGs could be potential biomarkers for the early diagnosis of CRC, especially for patients carrying KRAS mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.759813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581662PMC
October 2021

Activity of KBP-7072 (a novel aminomethylcycline) and comparators against 1,057 geographically diverse recent clinical isolates from the SENTRY Surveillace Program (2019).

Antimicrob Agents Chemother 2021 Oct 11:AAC0139721. Epub 2021 Oct 11.

JMI Laboratories, North Liberty, Iowa, USA.

KBP-7072 is a novel third generation tetracycline (aminomethylcycline) antibacterial in clinical development (oral and intravenous formulations) for the treatment of acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, and complicated intra-abdominal infections. KBP-7072 is active against many of the World Health Organization-priority pathogens. In this study, KBP-7072 and tetracycline class comparators were susceptibility tested against 1,057 geographically diverse surveillance isolates from 2019 according to Clinical and Laboratory Standards Institute (CLSI) guidelines. KBP-7072 demonstrated potent activity against gram-positive and gram-negative bacterial pathogens. KBP-7072 was active against (MIC, 0.06/0.12 mg/L), methicillin-resistant (MIC, 0.06/0.12 mg/L), (MIC, 0.03/0.03 mg/L), and other coagulase-negative staphylococci (MIC, 0.06/0.25 mg/L). KBP-7072 was active against (MIC, 0.03/0.06 mg/L) and vancomycin-susceptible and -nonsusceptible (MIC, 0.03/0.03 mg/L); (MIC, ≤0.015/0.03 mg/L), including penicillin- and tetracycline-resistant strains; (MIC, 0.03/0.06 mg/L), including macrolide-resistant strains; (MIC, 0.03/0.03 mg/L); and viridans group streptococci, including group (MIC, ≤0.015/0.03 mg/L) isolates. KBP-7072 inhibited 90.2% (MIC, 0.25/2 mg/L) of all isolates, including ESBL-phenotype strains, at ≤2 mg/L. KBP-7072 demonstrated potent activity against species complex and isolates (MIC values, 0.5/1 mg/L), (MIC, 0.12/0.25 mg/L; 100.0% inhibited at ≤0.25 mg/L), and (MIC, 0.06/0.06 mg/L). Based on MIC values, KBP-7072 activity was generally superior to the other tetracycline class comparators tested. The potent activity of KBP-7072, including resistant organism groups, merits further clinical investigation in infections where these organisms are likely to occur.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.01397-21DOI Listing
October 2021

Degraded Porphyra haitanensis sulfated polysaccharide relieves ovalbumin-induced food allergic response by restoring the balance of T helper cell differentiation.

Food Funct 2021 May 30;12(10):4707-4719. Epub 2021 Apr 30.

Allergy Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

We previously described that Porphyra haitanensis sulfated polysaccharide (PHSP) maintains the balance of pro-inflammation and immunosuppression. However, it is unclear whether degraded PHSP (DPHSP) still shows the immunomodulatory activity. Here, we degraded PHSP by four different methods alone or combined in pairs, and the results showed that the molecular weight and viscosity of DPHSP were significantly decreased, while the main chemical bonds and functional structure were consistent with those of PHSP. We then investigated the immunomodulatory function of DPHSP in vitro and in vivo. Actually, DPHSP enhances the inhibitory effects on mast cell activation and improves the suppression activity of PHSP on the food anaphylactic response. In an ovalbumin-induced food allergy mouse model, the production of allergic mediators and cytokines (interleukin-4 and 13, and interferon-γ) was inhibited by DPHSP. Meanwhile, DPHSP had a stronger ability to up-regulate the differentiation of regulatory T (Treg) cells and its related cytokines. These results suggested that DPHSP showed a better anti-food allergic ability than PHSP by regulating T helper cell balance and promoting Treg cell differentiation, which indicates that DPHSP is a novel potential nutrient component against food allergy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1fo00335fDOI Listing
May 2021

Anti-Food Allergic Compounds from MCCC 3A00225, a Deep-Sea-Derived Fungus.

Mar Drugs 2021 Apr 16;19(4). Epub 2021 Apr 16.

Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, Ministry of Natural Resources,184 Daxue Road, Xiamen 361005, China.

Ten new (-) and 26 known (-) compounds were isolated from MCCC 3A00225, a deep sea-derived fungus. The structures of the new compounds were determined by detailed analysis of the NMR and HRESIMS spectroscopic data. The absolute configurations were established by X-ray crystallography, Marfey's method, and the ICD method. All isolates were tested for in vitro anti-food allergic bioactivities in immunoglobulin (Ig) E-mediated rat basophilic leukemia (RBL)-2H3 cells. Compound significantly decreased the degranulation release with an IC value of 60.3 μM, compared to that of 91.6 μM of the positive control, loratadine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/md19040224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073018PMC
April 2021

Single-cell analysis reveals innate immunity dynamics in ankylosing spondylitis.

Clin Transl Med 2021 03;11(3):e369

State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, and Human Phenome Institute, Fudan University, Shanghai, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ctm2.369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982614PMC
March 2021

Discovery of andrastones from the deep-sea-derived Penicillium allii-sativi MCCC 3A00580 by OSMAC strategy.

Bioorg Chem 2021 03 27;108:104671. Epub 2021 Jan 27.

Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, Ministry of Natural Sources, 184 Daxue Road, Xiamen, Fujian 361005, China. Electronic address:

Andrastones are unusual 6,6,6,5-tetracyclic meroterpenoids that are rarely found in nature. Previously, three andrastones were obtained from the rice static fermentation extract of the deep-sea-derived fungus Penicillium allii-sativi MCCC 3A00580. Inspired by one strain many compounds (OSMAC) approach, the oat static fermentation on P. allii-sativi was conducted. As a result, 14 andrastones were isolated by UV-guided isolation. The chemical structures of the nine new compounds (1-9) was established by comprehensive analysis of the NMR, MS, ECD, and X-ray crystallography and the five known ones (10-14) were assigned by comparing their NMR, MS, and OR data with those reported in literature. Compound 1 bears a novel hemiketal moiety while 2 is the first example to possess a novel tetrahydrofuran moiety via C-7 and C-15. All isolates were tested for anti-allergic bioactivity. Compound 10, 3-deacetylcitreohybridonol, significantly decreased degranulation with the IC value of 14.8 μM, compared to that of 92.5 μM for the positive control, loratadine. Mechanism study indicated 10 could decrease the generation of histamine and TNF-α by reducing the accumulation of Ca in RBL-2H3 cells. These findings indicate andrastones could be potential to discover new anti-allergic candidate drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2021.104671DOI Listing
March 2021

Increased Expression of Zyxin and Its Potential Function in Androgenetic Alopecia.

Front Cell Dev Biol 2020 11;8:582282. Epub 2021 Jan 11.

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.

Androgenetic alopecia (AGA) is the most common progressive form of hair loss, occurring in more than half of men aged > 50 years. Hair follicle (HF) miniaturization is a feature of AGA, and dermal papillae (DP) play key roles in hair growth and regeneration by regulating follicular cell activity. Previous studies have revealed that adhesion signals are important factors in AGA development. Zyxin (ZYX) is an actin-interacting protein that is essential for cell adhesion and migration. The aim of this research was to investigate the expression and potential role of ZYX in AGA. Real-time polymerase chain reaction (RT-PCR) analysis revealed that ZYX expression was elevated in the affected frontal HF of individuals with AGA compared to unaffected occipital HF. Moreover, increased ZYX expression was also observed within DP using immunofluorescence staining. Our results revealed that ZYX knockout mice showed enhanced hair growth and anagen entry compared to wild-type mice. Reducing ZYX expression in cultured HFs by siRNA resulted in the enhanced hair shaft production, delayed hair follicle catagen entry, increased the proliferation of dermal papilla cells (DPCs), and upregulated expression of stem cell-related proteins. These results were further validated in cultured DPCs . To further reveal the mechanism by which ZYX contributes to AGA, RNA-seq analysis was conducted to identify gene signatures upon ZYX siRNA treatment in cultured hair follicles. Multiple pathways, including focal adhesion and HIF-1 signaling pathways, were found to be involved. Collectively, we discovered the elevated expression of ZYX in the affected frontal hair follicles of AGA patients and revealed the effects of ZYX downregulation on mice, hair follicles, and DPC. These findings suggest that ZYX plays important roles in the pathogenesis of AGA and stem cell properties of DPC and may potentially be used as a therapeutic target in AGA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2020.582282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829366PMC
January 2021

Mapping and IgE-binding capacity analysis of heat/digested stable epitopes of mud crab allergens.

Food Chem 2021 May 28;344:128735. Epub 2020 Nov 28.

College of Food and Biological Engineering, Xiamen Key Laboratory of Marine Functional Food, Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Jimei University, Xiamen, Fujian 361021, China. Electronic address:

Mud crab (Scylla paramamosain) is widely consumed after thermal processing. It is necessary to comprehensively evaluate of the allergenic potential and epitopes of allergens in high temperature-pressure (HTP) treated S. paramamosain. Tropomyosin and arginine kinase presented higher prevalence (30.77% and 42.13%) than the other three important crab allergens by component-resolved diagnosis. The surface expression of basophils CD63 and CD203c were decreased in HTP treated crab, an effect that was even more evident after digestion and absorption by the intestinal Caco-2 cell model. Of the 35 stable epitope, six were for the first time identified in shellfish. Seven heat/digested stable peptides of tropomyosin retained IgE-binding capacity and were shown to interact with MHC-II. Five epitopes (amino acids 19-29, 99-109, 153-162, 170-188 and 211-221) were the first identified in crab. The study provides insight into prevention and therapy of crab allergy, as well as helps to reduce crab allergenicity during thermal processing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2020.128735DOI Listing
May 2021

[Expression of pituitary tumor-transforming gene-1 and its pathogenic role in systemic sclerosis].

Nan Fang Yi Ke Da Xue Xue Bao 2020 Nov;40(11):1564-1570

Department of Dermatology, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China.

Objective: To investigate the expression of tumor-transforming gene-1 (PTTG1) in systemic sclerosis (SSc) and its role in fibrosis.

Methods: Skin biopsy samples were collected from 21 patients with SSc and 22 patients with healthy skin for detecting the mRNA and protein expressions of PTTG1 using real-time PCR (RT-PCR) and immunohistochemistry, respectively. In cultured primary human dermal fibroblasts, PTTG1 expression was knocked down via RNA interference (siRNA), and the mRNA expression levels of PTTG1 and the fibrosis-related genes -SMA, COL1A1, COL1A2, and COL3A1 were detected using RT-PCR; the proliferation of the cells was assessed using a real-time cell proliferation detection system.

Results: Compared with those in normal skin samples, the mRNA and protein expressions of PTTG1 increased significantly in the skin tissue of patients with SSc ( < 0.05). In cultured primary skin fibroblasts, the expression of PTTG1 mRNA was positively correlated with those of -SMA (R=0.8192, < 0.05), COL1A1 (R=0.6398, < 0.05), COL1A2 (R=0.316, < 0.05) and COL3A1 mRNAs (R=0.3727, < 0.05). Interference of PTTG1 expression significantly inhibited the cell proliferation, obviously lowered the expressions of fibrosis-related genes, and down-regulated the expression of collagen in the fibroblasts.

Conclusions: PTTG1 is highly expressed in skin tissues of patients with SSc, and PTTG1 knockdown can reduce the activity of the dermal fibroblasts, suggesting a close correlation of PTTG1 with fibrosis in SSc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12122/j.issn.1673-4254.2020.11.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704385PMC
November 2020

Icaritin Inhibits Skin Fibrosis through Regulating AMPK and Wnt/β-catenin Signaling.

Cell Biochem Biophys 2021 Jun 30;79(2):231-238. Epub 2020 Oct 30.

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, China.

Skin fibrosis is one of the major features of scleroderma. WNT/β-catenin signaling is associated with the progression of skin fibrosis. In this study, we aimed to determine the effect of icaritin (IT), a natural compound, on scleroderma-related skin fibrosis and its mechanisms. We found that IT could reduce the expression of COL1A1, COL1A2, COL3A1, CTGF, and α-SMA in human foreskin fibroblasts (HFF-1 cells), scleroderma skin fibroblasts (SSF cells), and TGF-β-induced HFF-1 cells. Wnt/β-catenin signaling was shown to be suppressed by IT. Additionally, IT activated AMPK signaling in HFF-1 cells. In conclusion, IT has an anti-skin fibrotic effect through activation of AMPK signaling and inhibition of WNT/β-catenin signaling. Our findings indicate the potential role of IT in the treatment of scleroderma and provide novel insight for the selection of drug therapy for scleroderma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12013-020-00952-zDOI Listing
June 2021

Viridicatol Isolated from Deep-Sea Alleviates Anaphylaxis and Repairs the Intestinal Barrier in Mice by Suppressing Mast Cell Activation.

Mar Drugs 2020 Oct 16;18(10). Epub 2020 Oct 16.

College of Food and Biological Engineering, Xiamen Key Laboratory of Marine Functional Food, Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological Resources, Jimei University, 43 Yindou Road, Xiamen 361021, China.

Viridicatol is a quinoline alkaloid isolated from the deep-sea-derived fungus The structure of viridicatol was unambiguously established by X-ray diffraction analysis. In this study, a mouse model of ovalbumin-induced food allergy and the rat basophil leukemia (RBL)-2H3 cell model were established to explore the anti-allergic properties of viridicatol. On the basis of the mouse model, we found viridicatol to alleviate the allergy symptoms; decrease the levels of specific immunoglobulin E, mast cell protease-1, histamine, and tumor necrosis factor-α; and promote the production of interleukin-10 in the serum. The treatment of viridicatol also downregulated the population of B cells and mast cells (MCs), as well as upregulated the population of regulatory T cells in the spleen. Moreover, viridicatol alleviated intestinal villi injury and inhibited the degranulation of intestinal MCs to promote intestinal barrier repair in mice. Furthermore, the accumulation of Ca in RBL-2H3 cells was significantly suppressed by viridicatol, which could block the activation of MCs. Taken together, these data indicated that deep-sea viridicatol may represent a novel therapeutic for allergic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/md18100517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590054PMC
October 2020

Exome-Wide Association Analysis Suggests LRP2BP as a Susceptibility Gene for Endothelial Injury in Systemic Sclerosis in the Han Chinese Population.

J Invest Dermatol 2021 05 15;141(5):1254-1263.e6. Epub 2020 Oct 15.

State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.

Genetic factors play a key role in the pathogenesis of autoimmune diseases, whereas the disease-causing variants remain largely unknown. Herein, we performed an exome-wide association study of systemic sclerosis in a Han Chinese population. In the discovery stage, 527 patients with systemic sclerosis and 5,024 controls were recruited and genotyped. In the validation study, an independent sample set of 479 patients and 1,096 controls were examined. In total, we found that four independent signals reached genome-wide significance. Among them, rs7574865 (P = 3.87 × 10) located within signal transducer and activator of transcription 4 gene was identified previously using samples of European ancestry. Additionally, another signal including three SNPs in linkage disequilibrium might be unreported susceptibility loci located in the epidermis differentiation complex region. Furthermore, two SNPs located within exon 3 of IGHM (rs45471499, P = 1.15 × 10) and upstream of LRP2BP (rs4317244, P = 4.17 × 10) were found. Moreover, rs4317244 was identified as an expression quantitative trait locus for LRP2BP that regulates tight junctions, cell cycle, and apoptosis in endothelial cell lines. Collectively, our results revealed three signals associated with systemic sclerosis in Han Chinese and suggested the importance of LRP2BP in systemic sclerosis pathogenesis. Given the limited sample size and discrepancies between previous results and our study, further studies in multiethnic populations are required for verification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2020.07.039DOI Listing
May 2021

Autologous activated platelet-rich plasma in hair growth: A pilot study in male androgenetic alopecia with in vitro bioactivity investigation.

J Cosmet Dermatol 2021 Apr 2;20(4):1221-1230. Epub 2020 Dec 2.

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.

Background: Platelet-rich plasma (PRP) is effective in the treatment of androgenetic alopecia (AGA).

Aims: The purpose of this study is to assess the effect of PRP on the proliferation of human follicle dermal papilla cells (HFDPCs), to observe the effect of PRP on the growth of hair follicles and hair shaft in vitro, to measure growth factors, and to evaluate the efficacy and safety of PRP injection.

Patients/methods: The effect of PRP on the proliferation of HFDPCs was observed. The length of hair follicle and hair shaft in vitro was measured. Then, the concentration of growth factors (EGF, FGF-2, FGF-7, IGF-1, HGF, PDGF-BB, and VEGF-A) was evaluated. Half-head injection of PRP was conducted to 10 males. Three treatments were conducted at 30-day intervals. Digital photographs were taken; hair diameter, hair density, unit density of hair follicles, and terminal hair/ vellus hair were analyzed.

Results: Platelet-rich plasma significantly promoted the proliferation of HFDPCs. Under the PRP culture, the hair follicle and hair shaft were grown, and the hair growth length on the 3rd and 6th days was greater than that of the control. PRP contained growth factors such as EGF, FGF-2, FGF-7, IGF-1, HGF, PDGF-B, and VEGF-A. Hair diameter, hair density, and unit hair follicle density on the PRP injection side peaked in the 6th month. The terminal hair/ vellus hair of the PRP injection side reached a peak in the 4th month. The average patient satisfaction during the entire treatment was 5.4 points (0-10 points).

Conclusion: Platelet-rich plasma can promote hair growth. PRP injection is safe and effective for the treatment of AGA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocd.13709DOI Listing
April 2021

In vitro evaluation of the effectiveness of bleaching agents activated by KTP and Nd:YAG laser.

Photodiagnosis Photodyn Ther 2020 Sep 24;31:101900. Epub 2020 Jun 24.

Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China; School and Hospital of Stomatology, Shanxi Medical University, Taiyuan, China. Electronic address:

Aim: To compare two different laser sources, a KTP laser with a wavelength of 532 nm and a Nd:YAG laser with a wavelength of 1064 nm, to investigate the relation between laser source and bleaching gel during laser irradiation.

Methods: Extracted human teeth were stained and randomly divided into six groups. Two in-office bleaching gels, Beyond and Opalescence Boost, were applied to stained teeth and then irradiated at either 532 nm or 1064 nm. The temperature change of pulp chamber was measured. The color change (ΔE*) was evaluated at the following time points: immediately after bleaching, 7, 14 and 30 days after the end of bleaching.

Results: Boost irradiated by KTP laser showed the higher temperature increase when compared with Beyond irradiated KTP and Nd:YAG. Boost irradiated by Nd:YAG presented lower temperature increase than by KTP. All groups showed a certain color change. After bleaching, Nd:YAG laser irradiation did not increase the ΔE* value significantly compared with gels without laser (p >  0.05). At each time point, Boost activated by KTP laser showed higher ΔE* value compared with other groups (p < 0.05), but decreased significantly 15 days after the end of bleaching. The other groups showed a relatively small change in ΔE* value after 30 days (p > 0.05).

Conclusions: KTP laser achieved better results than the Nd:YAG laser regarding tooth color change when associated with the Opalescence Boost bleaching gels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pdpdt.2020.101900DOI Listing
September 2020

Involvement of Disabled-2 on skin fibrosis in systemic sclerosis.

J Dermatol Sci 2020 Jul 2;99(1):44-52. Epub 2020 Jun 2.

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China. Electronic address:

Background: Systemic sclerosis (SSc) is a connective tissue disease characterized by inflammation and fibrosis. Our previous research found Disabled-2 (DAB2) expression was significantly downregulated by salvianolic acid B, a small molecular medicine which attenuated experimental skin fibrosis of SSc. These suggest that DAB2 plays an important role in SSc skin fibrosis, but the role of DAB2 in SSc remains unclear.

Objectives: To investigate the role of DAB2 in SSc.

Methods: DAB2 expression level was detected in the skin and peripheral blood mononuclear cells of SSc patients. Bleomycin (BLM)-induced SSc mice and primary SSc skin fibroblasts were used to investigate the effect of DAB2 downregulation on fibrosis. RNA-seq transcriptome analysis was performed to underlie the mechanism of DAB2 in fibroblasts.

Results: DAB2 expression was enhanced in SSc lesion skin and was positively correlated with fibrotic genes, such as α-SMA and PAI-1. The in vivo study revealed that DAB2 downregulation alleviated skin fibrosis, alleviating skin thickness and reducing collagen deposition, and DAB2 knockdown ameliorated the inflammatory cell infiltration. The in vitro study showed that DAB2 knockdown reduced extracellular matrix genes and proteins expression. Moreover, Transcriptome analysis revealed TGF-β and focal adhesion signaling pathways were the main downregulated pathways involved in DAB2 siRNA treated fibroblasts.

Conclusions: Taken together, our results revealed that DAB2 was increased in SSc skin, and DAB2 downregulation inhibited BLM-induced mouse skin fibrosis and SSc skin fibroblasts activation. DAB2 played an important role in the pathogenesis of SSc and DAB2 modulation may represent a potential therapeutic method for SSc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jdermsci.2020.05.009DOI Listing
July 2020

Relative Quantitation of Subclass-Specific Murine IgG Fc -Glycoforms by Multiple Reaction Monitoring.

ACS Omega 2020 Apr 7;5(15):8564-8571. Epub 2020 Apr 7.

NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.

N-Linked glycosylation of the fragment crystallizable (Fc) domain of immunoglobulin G (IgG) is considered a significant modulator of antibody functions, which is known to be subclass-specific. As mice are the most widely used model organisms in immunological research, determining the variation in Fc glycosylation among each murine IgG subclass in different physiological or pathological statuses is beneficial for studying how the IgG subclass effector function is affected by Fc glycosylation. In this study, we established a method to quantify murine IgG Fc glycoforms normalized to the protein abundance at a subclass-specific level for various mouse strains using multiple reaction monitoring. The glycoform level was normalized to the subclass protein abundance (subclass-specific peptide intensity) in each IgG subclass to eliminate the contribution from the subclass protein abundance. Both good linearity and high repeatability of the method were validated by investigating a mixed mouse serum sample. The method was applied to quantify the differences in subclass-specific IgG Fc -glycoforms between systemic sclerosis (SSc) mice and healthy control mice. The results demonstrated that each IgG subclass had its own characteristic-altered glycosylation, implying the close association of subclass-specific IgG Fc glycosylation with SSc in mice. This report demonstrates a method with great reliability and practicality that has promising potential for the relative quantitation of subclass-specific IgG Fc -glycoforms in multiple mouse models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.9b04412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178347PMC
April 2020

Nonclinical Pharmacokinetics, Protein Binding, and Elimination of KBP-7072, an Aminomethylcycline Antibiotic, in Animal Models.

Antimicrob Agents Chemother 2020 05 21;64(6). Epub 2020 May 21.

KBP Biosciences USA, Inc., Princeton, New Jersey, USA.

KBP-7072 is a semisynthetic aminomethylcycline with broad-spectrum activity against Gram-positive and Gram-negative pathogens, including multidrug-resistant bacterial strains. The pharmacokinetics (PK) of KBP-7072 after oral and intravenous (i.v.) administrations of single and multiple doses were investigated in animal models, including during fed and fasted states, and the protein binding and excretion characteristics were also evaluated. In Sprague-Dawley (SD) rats, beagle dogs, and CD-1 mice, KBP-7072 demonstrated a linear PK profile after the administration of single oral and i.v. and multiple oral doses. The oral bioavailability ranged from 12% to 32%. The mean time to maximum concentration ( ) ranged from 0.5 to 4 h, and the mean half-life ranged from approximately 6 to 11 h. The administration of oral doses in the fed state resulted in marked reductions in the maximum plasma concentration ( ) and the area under the concentration-time curve (AUC) compared with dosing in fasted animals. The mean bound fractions of KBP-7072 were 77.5%, 69.8%, 64.5%, 69.3%, and 69.2% in mouse, rat, dog, monkey, and human plasma, respectively. Following a single 22.5-mg/kg oral dose of KBP-7072 in SD rats, the cumulative excretion in feces was 64% and that in urine was 2.5% of the administered dose. The PK results in animal models are consistent with single- and multiple-ascending-dose studies in healthy volunteers and confirm the suitability of KBP-7072 for once-daily oral and i.v. administration in clinical studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.00488-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269484PMC
May 2020

Activity of KBP-7072, a Novel Third-Generation Tetracycline, against 531 Recent Geographically Diverse and Molecularly Characterized Acinetobacter baumannii Species Complex Isolates.

Antimicrob Agents Chemother 2020 04 21;64(5). Epub 2020 Apr 21.

JMI Laboratories, North Liberty, Iowa, USA.

KBP-7072 is a novel third-generation tetracycline (aminomethylcycline) antibacterial that overcomes common efflux and ribosomal protection resistance mechanisms that cause resistance in older-generation tetracyclines. KBP-7072 completed phase 1 clinical development studies for safety, tolerability, and pharmacokinetics (ClinicalTrials.gov identifier NCT02454361) and multiple ascending doses in healthy subjects (ClinicalTrials.gov identifier NCT02654626) in December 2015. Both oral and intravenous formulations of KBP-7072 are being developed. In this study, we evaluated the activities of KBP-7072 and comparator agents by CLSI document M07 (2018) broth microdilution against 531 recent geographically diverse and/or molecularly characterized - species complex () isolates from the United States, Europe, Asia-Pacific (excluding China), and Latin America. isolates included carbapenem-resistant, colistin-resistant, tetracycline-resistant, and extended-spectrum-β-lactamase (ESBL)- and metallo-β-lactamase (MBL)-producing isolates. Overall, KBP-7072 (MIC, 0.25/1 mg/liter) was comparable in activity to colistin (92.8%/92.8% susceptible [S] [CLSI/EUCAST]) against isolates, inhibiting 99.2% of isolates at ≤2 mg/liter and 97.6% of isolates at ≤1 mg/liter. KBP-7072 was equally active against isolates, including carbapenem-resistant, colistin-resistant, and tetracycline-resistant isolates, regardless of geographic location, and maintained activity against ESBL- and MBL-producing isolates. KBP-7072 outperformed comparator agents, including ceftazidime (40.3% S [CLSI]), gentamicin (48.2%/48.2% S [CLSI/EUCAST]), levofloxacin (39.5%/37.9% S [CLSI/EUCAST]), meropenem (42.0%/42.0% S [CLSI/EUCAST]), piperacillin-tazobactam (33.3% S [CLSI]), and all tetracycline-class comparator agents, which include doxycycline (67.3% S [CLSI]), minocycline (73.8% S [CLSI]), tetracycline (37.2% S [CLSI]), and tigecycline (79.5% inhibited by ≤2 mg/liter). The potent activity of KBP-7072 against recent geographically diverse, molecularly characterized, and drug-resistant isolates supports continued clinical development for the treatment of serious infections, including those caused by .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02375-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179608PMC
April 2020

Sulfated oligosaccharide of Gracilaria lemaneiformis protect against food allergic response in mice by up-regulating immunosuppression.

Carbohydr Polym 2020 Feb 6;230:115567. Epub 2019 Nov 6.

College of Food and Biological Engineering, Xiamen Key Laboratory of Marine Functional Food, Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological Resources, Jimei University, 43 Yindou Road, Xiamen, 361021, Fujian, PR China. Electronic address:

Sulfated oligosaccharide of Gracilaria lemaneiformis (GLSO) was prepared from sulfated polysaccharides which possessed antiallergic activity by degradation with high temperature and pressure combined with vitamin C treatment. The present study demonstrated that GLSO could attenuate food anaphylaxis, and inhibit the production of immunoglobulin E, histamine, and related cytokines in both prevention and therapy ovalbumin-induced mice model. Additionally, the gut microbiota analysis revealed that GLSO markedly rescued OVA-induced changes in the Firmicutes to Bacteroidetes ratio. Following flow cytometry, GLSO was found to suppress the subpopulation of T helper 2 and B cells, and significantly up-regulate regulatory T cells (Tregs) differentiation. Furthermore, GLSO-mediated immunosuppression could be verified by co-culturing Tregs sorted from GLSO-treated mice and CD4 T cells or mast cells. In a word, GLSO attenuated food anaphylaxis through the regulation of gut microbiota and induction of immunosuppression. GLSO had the potential to be used as a nutrient component against food allergy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carbpol.2019.115567DOI Listing
February 2020

A rare variant of RNF123 in familial ankylosing spondylitis causes dysfunction of osteoclast formation.

Rheumatology (Oxford) 2020 05;59(5):1174-1177

State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/kez537DOI Listing
May 2020

Increased expression of GAB1 promotes inflammation and fibrosis in systemic sclerosis.

Exp Dermatol 2019 11;28(11):1313-1320

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.

Systemic sclerosis (SSc) is an autoimmune disease mainly characterized by persistent inflammation and fibrosis. The receptor tyrosine kinase (RTK) signal pathway plays an important role in the process of SSc, and Grb2-associated binding protein (GAB) is crucial in activating RTK signalling. A previous study found elevated levels of GAB1 in bleomycin (BLM)-induced fibrotic lungs, but the effects of GAB1 in SSc remain unclear. Our aim was to investigate whether GAB1 was dysregulated and its potential role in SSc. Compared with healthy donors, we found GAB1 expression was 1.6-fold higher in peripheral blood mononuclear cells (PBMC), 2.5-fold higher in CD4 + T cells, and 2-fold higher in skin from of SSc patients (P < .01). At the same time, the levels of type one collagen (COLI) were also significantly increased (1.8-fold higher) in SSc skin. Additionally, BLM-induced SSc mice showed mRNA levels of Gab1 2-fold higher than saline-treated controls, and Gab1 expression correlated positively with collagen content. A further in vitro study showed silencing of GAB1 suppressed inflammatory gene expression in TNF-α induced fibroblasts. Additionally, GAB1 deficiency prominently inhibited cell proliferation and reduced COLI protein levels in TGF-β induced fibroblasts. Taken together, these data suggest that GAB1 has a relatively high expression rate in SSc, and knockdown of GAB1 may attenuate SSc by stimulating inflammatory and fibrotic processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/exd.14033DOI Listing
November 2019

[Expression of calponin-1 and its pathogenic role in systemic sclerosis].

Nan Fang Yi Ke Da Xue Xue Bao 2019 Mar;39(3):279-285

School of Life Sciences, Fudan University, Shanghai 200433, China.

Objective: To investigate the expression of calponin-1 (CNN1) in systemic sclerosis (SSc) and its pathogenic role in fibrosis.

Methods: Skin biopsy samples were collected from 19 patients with SSc and 21 healthy subjects. Real-time PCR was used to detect the expression of and mRNAs in the samples, and the protein expression of CNN1 was detected using immunohistochemistry. In cultured primary human dermal fibroblasts, expression was knocked down RNA interference, and the mRNA expression levels of and the fibrosis-related genes , , , , and were detected using real-time PCR; the proliferation of the cells was assessed using a real-time cell proliferation detection system.

Results: Compared with that in samples from normal subjects, the expression of mRNA was significantly increased in the skin tissue of patients with SSc ( < 0.05) with a positive correlation with α-SMA (=0.7219, < 0.0001); the protein expression of CNN1 was also significantly increased in the skin tissue of patients with SSc. In cultured primary skin fibroblasts, the expression of CNN1 mRNA was positively correlated with and mRNA expressions (=0.6547, < 0.05; =0.6438, < 0.05). knockdown in the fibroblasts significantly inhibited the cell proliferation, obviously lowered the expressions of fibrosis-related genes, and reduced the protein expression of collagen.

Conclusions: The expression of is increased in the skin tissues of patients with SSc, and knockdown can reduce the activity of dermal fibroblasts, suggesting the close correlation of CNN1 with fibrosis in SSc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12122/j.issn.1673-4254.2019.03.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765677PMC
March 2019

Pharmacokinetic/Pharmacodynamic Evaluation of a Novel Aminomethylcycline Antibiotic, KBP-7072, in the Neutropenic Murine Pneumonia Model against Staphylococcus aureus and Streptococcus pneumoniae.

Antimicrob Agents Chemother 2019 03 26;63(3). Epub 2019 Feb 26.

Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA

KBP-7072 is a novel aminomethylcycline antibiotic in clinical development for community-acquired pneumonia. The goal of present studies was to determine which pharmacokinetic/pharmacodynamic (PK/PD) parameter magnitude correlated with efficacy in the murine pneumonia infection model against and KBP-7072 pharmacokinetic measurements were performed in plasma and epithelial lining fluid (ELF) at 4-fold-increasing doses from 1 to 256 mg/kg of body weight subcutaneously. Pharmacokinetic parameters were calculated using a noncompartmental model and were linear over the dose range. Penetration into ELF ranged from 82% to 238% comparing ELF drug concentrations to plasma free drug concentrations. Twenty-four-hour dose-ranging efficacy studies were then performed in the neutropenic murine pneumonia model against 5 (3 methicillin-resistant and 2 methicillin-susceptible) and 6 (2 Tet and 2 Pen) strains. KBP-7072 demonstrated potent activity resulting in a 3- to 5-log kill in CFU burden compared to the start of therapy for all strains. The PK/PD index area under the concentration-time curve (AUC)/MIC corelated well with efficacy ( , 0.80 to 0.89). Net stasis was achieved at plasma 24-h free drug AUC/MIC values of 1.13 and 1.41 (24-h ELF AUC/MIC values of 2.01 and 2.50) for and , respectively. A 1-log kill was achieved at 24-h plasma AUC/MIC values of 2.59 and 5.67 (24-h ELF AUC/MIC values of 4.22 and 10.08) for and , respectively. A 2-log kill was achieved at 24-h plasma AUC/MIC values of 7.16 and 31.14 (24-h ELF AUC/MIC values of 8.37 and 42.92) for and , respectively. The results of these experiments will aid in the rational design of dose-finding studies for KBP-7072 in patients with community-acquired bacterial pneumonia (CAP).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02404-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395904PMC
March 2019

Salvianolic acid B attenuates experimental skin fibrosis of systemic sclerosis.

Biomed Pharmacother 2019 Feb 7;110:546-553. Epub 2018 Dec 7.

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China; Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China; Department of dermatology, Jing'an District Central Hospital, Shanghai, China. Electronic address:

Systemic sclerosis (SSc) is a connective tissue disease characterized mainly by fibrosis of skin and internal organs. Our previous study has shown that salvianolic acid B (SAB), a bioactive component extracted from Salvia miltiorrhiza (SM), was one of the essential ingredients in the traditional Chinese medicine Yiqihuoxue formula, which has been used to treat SSc-related dermal and pulmonary fibrosis. The aim of the present study was to evaluate the effect of SAB on skin fibrosis and explore its underlying anti-fibrotic mechanism. We found that SAB was capable of alleviating skin fibrosis in a bleomycin-induced SSc mouse model, alleviating skin thickness and reducing collagen deposition. in vitro studies indicated that SAB reduced SSc skin fibroblast proliferation and downregulated extracellular matrix gene transcription and collagen protein expression. TGF-β/SMAD and MAPK/ERK pathway activation were also shown to be suppressed in SAB treated fibroblasts. Moreover, RNA-seq revealed that the anti-fibrotic effect of SAB might be related to antioxidant activity, the cell cycle, and the p53 signaling pathway. Taken together, our results suggest that SAB has the ability to alleviate SSc-related skin fibrosis both in vivo and in vitro.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2018.12.016DOI Listing
February 2019

Evaluation of the antifibrotic potency by knocking down SPARC, CCR2 and SMAD3.

EBioMedicine 2018 Dec 20;38:238-247. Epub 2018 Nov 20.

University of Texas-McGovern Medical School, Houston, TX, USA. Electronic address:

Background: The genes of SPARC, CCR2, and SMAD3 are implicated in orchestrating inflammatory response that leads to fibrosis in scleroderma and other fibrotic disorders. The aim of the studies is to evaluate synergistic anti-fibrotic potency of the siRNAs of these genes.

Methods: The efficacy of the siRNA-combination was evaluated in bleomycin-induced mouse fibrosis. The pathological changes of skin and lungs of the mice were assessed by hematoxylin and eosin and Masson's trichrome stains. The expression of inflammation and fibrosis associated genes and proteins in the tissues were assessed by real-time RT-PCR, RNA sequencing, Western blots and ELISA. Non-crosslinked fibrillar collagen was measured by the Sircol colorimetric assay.

Findings: The applications of the combined siRNAs in bleomycin-induced mice achieved favorable anti-inflammatory and anti-fibrotic effects. Activation of fibroblasts was suppressed in parallel with inhibition of inflammation evidenced by reduced inflammatory cells and proinflammatory cytokines in the BALF and/or the tissues by the treatment. Aberrant expression of the genes normally expressed in fibroblasts, monocytes/ macrophage, endothelial and epithelial cells were significantly restrained after the treatment. In addition, transcriptome profiles indicated that some bleomycin-induced alterations of multiple biological pathways were recovered to varying degrees by the treatment.

Interpretation: The application of the combined siRNAs of SPARC, CCR2, and SMAD3 genes ameliorated inflammation and fibrosis in bleomycin-induced mice. It systemically reinstated multiple biopathways, probably through controlling on different cell types including fibroblasts, monocytes/macrophages, endothelial cells and others. The multi-target-combined therapeutic approach examined herein may represent a novel and effective therapy for fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2018.11.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306344PMC
December 2018

Salvianolic acid B attenuates experimental pulmonary inflammation by protecting endothelial cells against oxidative stress injury.

Eur J Pharmacol 2018 Dec 28;840:9-19. Epub 2018 Sep 28.

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China; Department of Dermatology, Jing'an District Central Hospital, Shanghai, China. Electronic address:

Endothelial cell injury and subsequent inflammation play pivotal roles in the pathogenesis of pulmonary fibrosis, a progressive and fatal disorder. We found previously that salvianolic acid B (SAB) attenuated experimental pulmonary fibrosis. Pulmonary fibrosis is driven by inflammation, but the anti-inflammatory role and mechanism of SAB on the treatment of pulmonary fibrosis is still unknown. Here, our in vivo studies showed that SAB had a strong anti-inflammatory effect on bleomycin-instilled mice by inhibiting inflammatory cell infiltration and inflammatory cytokine production. Moreover, SAB protected endothelial cells against oxidative stress injury and inhibited endothelial cell apoptosis in bleomycin-treated mice. The in vitro studies also showed that SAB decreased the HO-induced overproduction of reactive oxygen species to protect EA.hy926 endothelial cells from oxidative damage, and further inhibited HO-induced permeability and overexpression of pro-inflammatory molecules. The next studies revealed that SAB inhibited the HO-induced cell apoptosis and attenuated the decrease of tight junction-related gene expression, resulting in a decrease of the endothelial permeability in injured endothelial cells. Furthermore, Western blot analysis suggested that SAB decreased endothelial cell permeability and expression of pro-inflammatory cytokines by inhibiting MAPK and NF-κB signaling pathways. Taken together, these data indicate that SAB exerted anti-inflammatory roles in pulmonary fibrosis by protection of the endothelial cells against oxidative stress injury, mediated by inhibition of endothelial permeability and expression of pro-inflammatory cytokine via the MAPK and NF-κB signaling pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejphar.2018.09.030DOI Listing
December 2018

Enhanced production of tanshinone IIA in endophytic fungi Emericella foeniculicola by genome shuffling.

Pharm Biol 2018 Dec;56(1):357-362

a College of Life Sciences , Shaanxi Normal University, Chang'an Campus , Xi'an , Shaanxi , China.

Context: Tanshinone IIA, commercially produced from Salvia miltiorrhiza Bunge (C.Y.Wu) (Labiatae), has various biological benefits. Currently, this compound is mainly extracted from plants. However, because of the long growth cycle and the unstable quality of plants, the market demands can barely be satisfied.

Objective: The genomic shuffling technology is applied to screen the high-yield tanshinone IIA strain, which could be used to replace the plant S. miltiorrhiza for the production of tanshinone IIA. The change in the production of tanshinone IIA is clarified by comparing it with the original strain.

Materials And Methods: Tanshinone IIA was extracted from Strains cells, which was prepared through 0.5 mL protoplast samples by using hypertonic solution I from two different strains. Then, it was analyzed by high-performance liquid chromatography at 30 °C and UV 270 nm. Total DNA from the strains was extracted for RAPD amplification and electrophoresis to isolate the product.

Results: In this study, a high-yield tanshinone IIA strain F-3.4 was screened and the yield of tanshinone IIA was increased by 387.56 ± 0.02 mg/g, 11.07 times higher than that of the original strain TR21.

Discussion: This study shows that the genetic basis of high-yield strains is achieved through genome shuffling, which proves that genome shuffling can shorten the breeding cycle and improve the mutagenesis efficiency in obtaining the strains with good traits and it is a useful method for the molecular breeding of industrial strains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13880209.2018.1481108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171462PMC
December 2018

MiR-3606-3p inhibits systemic sclerosis through targeting TGF-β type II receptor.

Cell Cycle 2018 17;17(16):1967-1978. Epub 2018 Sep 17.

a State Key Laboratory of Genetic Engineering, Department of Anthropology and Human Genetics , School of Life Sciences, Fudan University , Shanghai , P. R. China.

Systemic sclerosis (SSc) is a multisystemic fibrotic disease characterized by excessive collagen deposition and extracellular matrix synthesis. Though transforming growth factor-β (TGF-β) plays a fundamental role in the pathogenesis of SSc, the mechanism by which TGF-β signaling acts in SSc remains largely unclear. Here, we showed that TGF-β type II receptor (TGFBR2) was significantly upregulated in both human SSc dermal tissues and primary fibroblasts. In fibroblasts, siRNA-induced knockdown of TGFBR2 resulted in a reduction of p-SMAD2/3 levels and reduced production of type I collagen. Additionally, functional experiments revealed that downregulation of TGFBR2 yielded an anti-growth effect on fibroblasts through inhibiting cell cycle progression. Further studies showed that miR-3606-3p could directly target the 3'-UTR of TGFBR2 and significantly decrease the levels of both TGFBR2 mRNA and protein. Furthermore, SSc dermal tissues and primary fibroblasts contain significantly reduced amounts of miR-3606-3p, and the overexpression of miR-3606-3p in fibroblasts replicates the phenotype of TGFBR2 downregulation. Collectively, our findings demonstrated that increased TGFBR2 could be responsible for the hyperactive TGF-β signaling observed in SSc. Moreover, we identified a pivotal role for miR-3606-3p in SSc, which acts, at least partly, through the attenuation of TGF-β signaling via TGFBR2 repression, suggesting that the regulation of miR-3606-3p/TGFBR2 could be a promising therapeutic target that could improve the treatment strategy for fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15384101.2018.1509621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224271PMC
December 2019
-->