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1.
ACS Nano ; 18(23): 15312-15325, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38809601

ABSTRACT

The exceptional biocompatibility and adaptability of hydrogels have garnered significant interest in the biomedical field for the fabrication of biomedical devices. However, conventional synthetic hydrogels still exhibit relatively weak and fragile properties. Drawing inspiration from the photosynthesis process, we developed a facile approach to achieve a harmonious combination of superior mechanical properties and efficient preparation of silk fibroin hydrogel through photo-cross-linking technology, accomplished within 60 s. The utilization of riboflavin and H2O2 enabled a sustainable cyclic photo-cross-linking reaction, facilitating the transformation from tyrosine to dityrosine and ultimately contributing to the formation of highly cross-linked hydrogels. These photo-cross-linking hydrogels exhibited excellent elasticity and restorability even after undergoing 1000 cycles of compression. Importantly, our findings presented that hydrogel-encapsulated adipose stem cells possess the ability to stimulate cell proliferation along with stem cell stemness. This was evidenced by the continuous high expression levels of OCT4 and SOX2 over 21 days. Additionally, the utilization of photo-cross-linking hydrogels can be extended to various material molding platforms, including microneedles, microcarriers, and bone screws. Consequently, this study offered a significant approach to fabricating biomedical hydrogels capable of facilitating real-time cell delivery, thereby introducing an innovative avenue for designing silk devices with exceptional machinability and adaptability in biomedical applications.


Subject(s)
Cell Proliferation , Hydrogels , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogels/chemical synthesis , Cell Proliferation/drug effects , Fibroins/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biocompatible Materials/chemical synthesis , Animals , Cross-Linking Reagents/chemistry , Silk/chemistry , Photochemical Processes , Stem Cells/cytology , Stem Cells/metabolism , Stem Cells/drug effects , Riboflavin/chemistry , Riboflavin/pharmacology , Bombyx , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/pharmacology , Humans
2.
J Nanobiotechnology ; 22(1): 258, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755644

ABSTRACT

Electrical stimulation (ES) is considered a promising therapy for chronic wounds via conductive dressing. However, the lack of a clinically suitable conductive dressing is a serious challenge. In this study, a suitable conductive biomaterial with favorable biocompatibility and conductivity was screened by means of an inherent structure derived from the body based on electrical conduction in vivo. Ions condensed around the surface of the microtubules (MTs) derived from the cell's cytoskeleton are allowed to flow in the presence of potential differences, effectively forming a network of biological electrical wires, which is essential to the bioelectrical communication of cells. We hypothesized that MT dressing could improve chronic wound healing via the conductivity of MTs applied by ES. We first developed an MT-MAA hydrogel by a double cross-linking method using UV and calcium chloride to improve chronic wound healing by ES. In vitro studies showed good conductivity, mechanical properties, biocompatibility, and biodegradability of the MT-MAA hydrogel, as well as an elevated secretion of growth factors with enhanced cell proliferation and migration ability in response to ES. The in vivo experimental results from a full-thickness diabetic wound model revealed rapid wound closure within 7d in C57BL/6J mice, and the wound bed dressed by the MT-MAA hydrogel was shown to have promoted re-epithelization, enhanced angiogenesis, accelerated nerve growth, limited inflammation phases, and improved antibacterial effect under the ES treatment. These preclinical findings suggest that the MT-MAA hydrogel may be an ideal conductive dressing for chronic wound healing. Furthermore, biomaterials based on MTs may be also promising for treating other diseases.


Subject(s)
Electric Conductivity , Hydrogels , Mice, Inbred C57BL , Microtubules , Wound Healing , Animals , Wound Healing/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Mice , Microtubules/metabolism , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Male , Humans , Electric Stimulation , Cell Proliferation/drug effects , Cell Movement/drug effects , Bandages
3.
Int J Biol Macromol ; 267(Pt 2): 131519, 2024 May.
Article in English | MEDLINE | ID: mdl-38608985

ABSTRACT

Hydrogel has attracted tremendous attentions due to its excellent biocompatibility and adaptability in biomedical field. However, it is challenging by the conflicts between inadequate mechanical properties and service requirements. Herein, a rapid and robust hydrogel was developed by interpenetrating networks between chitosan and silk fibroin macromolecules. Thanks to these unique networks, the chitosan-based hydrogel exhibited superior mechanical performances. The maximum breaking strength, Young's modulus and swelling ratio of the hydrogel were 1187.8 kPa, 383.1 MPa and 4.5 % respectively. The hydrogel also supported the proliferation of human umbilical vein endothelial cells for 7 days. Notably, the hydrogel was easily molded into bone screw, and demonstrated compressive strengths of 45.7 MPa, Young's modulus of 675.6 MPa, respectively. After 49-day biodegradation, the residual rate of the screw in collagenase I solution was up to 89.6 % of the initial weight. In vitro, the screws not only had high resistance to biodegradation, but also had outstanding biocompatibility of osteoblast. This study provided a promising physical-chemical double crosslinking strategy to build orthopedic materials, holding a great potential in biomedical devices.


Subject(s)
Biocompatible Materials , Bone Screws , Chitosan , Fibroins , Human Umbilical Vein Endothelial Cells , Materials Testing , Chitosan/chemistry , Chitosan/pharmacology , Fibroins/chemistry , Humans , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Hydrogels/chemistry , Cell Proliferation/drug effects , Osteoblasts/drug effects , Osteoblasts/cytology , Compressive Strength , Elastic Modulus
4.
Neural Regen Res ; 19(9): 1890-1898, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38227513

ABSTRACT

Previous studies have demonstrated a bidirectional relationship between inflammation and depression. Activation of the nucleotide-binding oligomerization domain, leucine-rich repeat, and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes is closely related to the pathogenesis of various neurological diseases. In patients with major depressive disorder, NLRP3 inflammasome levels are significantly elevated. Understanding the role that NLRP3 inflammasome-mediated neuroinflammation plays in the pathogenesis of depression may be beneficial for future therapeutic strategies. In this review, we aimed to elucidate the mechanisms that lead to the activation of the NLRP3 inflammasome in depression as well as to provide insight into therapeutic strategies that target the NLRP3 inflammasome. Moreover, we outlined various therapeutic strategies that target the NLRP3 inflammasome, including NLRP3 inflammatory pathway inhibitors, natural compounds, and other therapeutic compounds that have been shown to be effective in treating depression. Additionally, we summarized the application of NLRP3 inflammasome inhibitors in clinical trials related to depression. Currently, there is a scarcity of clinical trials dedicated to investigating the applications of NLRP3 inflammasome inhibitors in depression treatment. The modulation of NLRP3 inflammasomes in microglia holds promise for the management of depression. Further investigations are necessary to ascertain the efficacy and safety of these therapeutic approaches as potential novel antidepressant treatments.

5.
J Integr Neurosci ; 23(1): 11, 2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38287859

ABSTRACT

Parkinson's disease (PD) is a chronic neurodegenerative disease whose main pathological features are the degeneration of dopamine neurons and deposition of α-synuclein in neurons. At present, the most important treatment strategy for PD is drugs, and one of the most used drugs is levodopa. However, this therapy shows many problems, such as tolerance and long-term effects, so other treatment strategies need to be explored. As a traditional Chinese medicine treatment method with effective and few side effects, electroacupuncture is considered a non-drug therapy. It serves as a novel, promising therapeutic approach for the treatment of PD. In this review, the application and the effects of electroacupuncture on PD have been described. Besides, the underlying molecular mechanisms of electroacupuncture on PD that contribute to protecting dopaminergic neurons and reducing α-synuclein levels have been illustrated, including ① anti-oxidant stress response, ② anti-neuroinflammatory response, ③ up-regulation of neurotrophic factors and reduction of nerve cell apoptosis, ④ down-regulation of endoplasmic reticulum stress and improvement of mitochondrial function, ⑤ improvement of the function of the ubiquitin-proteasome system, ⑥ anti-excitatory toxicity response, ⑦ activation of autophagy, and ⑧ modulation of gut microbiota. Achieving a better understanding of the neuroprotective effects of electroacupuncture on PD will provide a theoretical basis and facilitate the application of electroacupuncture on PD.


Subject(s)
Electroacupuncture , Neurodegenerative Diseases , Neuroprotective Agents , Parkinson Disease , Humans , alpha-Synuclein , Neuroprotective Agents/pharmacology , Neurodegenerative Diseases/pathology , Dopaminergic Neurons/pathology
6.
BMC Genomics ; 25(1): 125, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38287255

ABSTRACT

BACKGROUND: Diabetic foot ulcer (DFU) is one of the most common and severe complications of diabetes, with vascular changes, neuropathy, and infections being the primary pathological mechanisms. Glutamine (Gln) metabolism has been found to play a crucial role in diabetes complications. This study aims to identify and validate potential Gln metabolism biomarkers associated with DFU through bioinformatics and machine learning analysis. METHODS: We downloaded two microarray datasets related to DFU patients from the Gene Expression Omnibus (GEO) database, namely GSE134431, GSE68183, and GSE80178. From the GSE134431 dataset, we obtained differentially expressed Gln-metabolism related genes (deGlnMRGs) between DFU and normal controls. We analyzed the correlation between deGlnMRGs and immune cell infiltration status. We also explored the relationship between GlnMRGs molecular clusters and immune cell infiltration status. Notably, WGCNA to identify differentially expressed genes (DEGs) within specific clusters. Additionally, we conducted GSVA to annotate enriched genes. Subsequently, we constructed and screened the best machine learning model. Finally, we validated the predictions' accuracy using a nomogram, calibration curves, decision curve analysis (DCA), and the GSE134431, GSE68183, and GSE80178 dataset. RESULTS: In both the DFU and normal control groups, we confirmed the presence of deGlnMRGs and an activated immune response. From the GSE134431 dataset, we obtained 20 deGlnMRGs, including CTPS1, NAGS, SLC7A11, GGT1, GCLM, RIMKLA, ARG2, ASL, ASNS, ASNSD1, PPAT, GLS2, GLUD1, MECP2, ASS1, PRODH, CTPS2, ALDH5A1, DGLUCY, and SLC25A12. Furthermore, two clusters were identified in DFU. Immune infiltration analysis indicated the presence of immune heterogeneity in these two clusters. Additionally, we established a Support Vector Machine (SVM) model based on 5 genes (R3HCC1, ZNF562, MFN1, DRAM1, and PTGDS), which exhibited excellent performance on the external validation datasetGSE134431, GSE68183, and GSE80178 (AUC = 0.929). CONCLUSION: This study has identified five Gln metabolism genes associated with DFU, revealing potential novel biomarkers and therapeutic targets for DFU. Additionally, the infiltration of immune-inflammatory cells plays a crucial role in the progression of DFU.


Subject(s)
Diabetes Mellitus , Diabetic Foot , Humans , Diabetic Foot/genetics , Glutamine , Computational Biology , Databases, Factual , Biomarkers
7.
Polymers (Basel) ; 15(22)2023 Nov 16.
Article in English | MEDLINE | ID: mdl-38006143

ABSTRACT

Silk fibroin (SF) hydrogels have garnered extensive attention in biomedical materials, owing to their superior biological properties. However, the challenges facing the targeted silk fibroin hydrogels involve chemical agents and shortfalls in performance. In this study, the silk fibroin hydrogels were prepared in different ways: sonication induction, chemical crosslinking, photopolymerization, and enzyme-catalyzed crosslinking. The SF hydrogels derived from photopolymerization exhibited higher compressive properties, with 124 Kpa fracture compressive stress and breaks at about 46% compression. The chemical crosslinking and enzyme-catalyzed silk fibroin hydrogels showed superior toughness, yet sonication-induced hydrogels showed brittle performance resulting from an increase in silk II crystals. The chemical-crosslinked hydrogel demonstrated lower thermostability due to the weaker crosslinking degree. In vitro, all silk fibroin hydrogels supported the growth of human umbilical vein endothelial cells, as the cell viability of hydrogels without chemical agents was relatively higher. This study provides insights into the formation process of silk fibroin hydrogels and optimizes their design strategy for biomedical applications.

8.
Int Wound J ; 20(10): 4394-4409, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37438679

ABSTRACT

Diabetic foot ulcer (DFU), a common intractable chronic complication of diabetes mellitus (DM), has a prevalence of up to 25%, with more than 17% of the affected patients at risk of amputation or even death. Vascular risk factors, including vascular stenosis or occlusion, dyslipidemia, impaired neurosensory and motor function, and skin infection caused by trauma, all increase the risk of DFU in patients with diabetes. Therefore, diabetic foot is not a single pathogenesis. Preclinical studies have contributed greatly to the pathogenesis determination and efficacy evaluation of DFU. Many therapeutic tools are currently being investigated using DFU animal models for effective clinical translation. However, preclinical animal models that completely mimic the pathogenesis of DFU remain unexplored. Therefore, in this review, the preparation methods and evaluation criteria of DFU animal models with three major pathological mechanisms: neuropathy, angiopathy and DFU infection were discussed in detail. And the advantages and disadvantages of various DFU animal models for clinical sign simulation. Furthermore, the current status of vitro models of DFU and some preclinical studies have been transformed into clinical treatment programs, such as medical dressings, growth factor therapy, 3D bioprinting and pre-vascularization, Traditional Chinese Medicine treatment. However, because of the complexity of the pathological mechanism of DFU, the clinical transformation of DFU model still faces many challenges. We need to further optimize the existing preclinical studies of DFU to provide an effective animal platform for the future study of pathophysiology and clinical treatment of DFU.


Subject(s)
Diabetes Mellitus , Diabetic Foot , Humans , Diabetic Foot/etiology , Diabetic Foot/therapy , Diabetic Foot/epidemiology , Risk Factors
9.
Open Life Sci ; 18(1): 20220552, 2023.
Article in English | MEDLINE | ID: mdl-36820208

ABSTRACT

Obesity is a main risk factor for diabetes and cardiovascular disorders and is closely linked to preadipocyte differentiation or adipogenesis. Peroxisome proliferator-activated receptor γ (PPARγ) is an indispensable transcription factor in adipogenesis. A newly identified long noncoding RNA, Acart, exerts a protective effect against cardiomyocyte injury by transactivating PPARγ signaling. However, the function of Acart in preadipocyte differentiation is unclear. To investigate the function of Acart in adipogenesis, a well-established preadipocyte, the 3T3-L1 cell line, was induced to differentiate, and Acart level was assessed during differentiation using quantitative real-time PCR. The biological role of Acart in adipogenesis was analyzed by assessing lipid droplet accumulation, PPARγ and CCAAT/enhancer-binding protein α (C/EBPα) expression, and 3T3-L1 cell proliferation and apoptosis after Acart silencing. We found that Acart level was promptly increased during preadipocyte differentiation in vitro. Acart was also significantly upregulated in obese mouse-derived subcutaneous, perirenal, and epididymal fat tissues compared with nonobese mouse-derived adipose tissues. Functionally, Acart depletion inhibited preadipocyte differentiation, as evidenced by a significant decrease in lipid accumulation and PPARγ and C/EBPα expression levels. Acart silencing also inhibited 3T3-L1 cell proliferation, whereas Acart overexpression accelerated 3T3-L1 cell proliferation and decreased cell apoptosis. Taken together, the current results reveal a novel function of Acart in regulating preadipocyte proliferation and differentiation.

10.
Front Pharmacol ; 13: 1027677, 2022.
Article in English | MEDLINE | ID: mdl-36582537

ABSTRACT

Diabetic ulcer (DU) has been recognized as one of the most prevalent and serious complications of diabetes. However, the clinical efficacy of standard treatments for DU remains poor. Traditional Chinese medicine (TCM) shows a positive therapeutic effect on DU. Specifically, Zizhu ointment (ZZO) has been widely used to treat DU in long-term clinical practice, but the exact mechanism by which it promotes DU wound healing remains unknown. In this study, network analysis and high-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) were conducted to identify the active compounds of ZZO. We detected isovalerylshikonin (ISO), mandenol, daidzein, kaempferol, and formononetin in both network analysis and UPLC-HRMS. Moreover, ZZO could ameliorate DU by regulating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) and inflammation signaling pathways, according to the results of KEGG analysis. We established a DU mouse model with a high-fat diet and streptozotocin injection in vivo to evaluate the network analysis result. The experimental results showed that ZZO could inhibit inflammation, remodel fibrous tissue, and promote angiogenesis in the DU area, facilitating wound healing in DU mice. Moreover, the PI3K/AKT signaling pathway was indeed activated by ZZO treatment, promoting macrophage M2 polarization. In addition, we used molecular docking technology to evaluate the binding sites between ZZO and the PI3K/AKT pathway. The results showed that ISO has a good binding interaction with AKT. Moreover, ISO promoted M2 polarization in macrophages in a dose-dependent manner in vitro. Our study found that ZZO could promote DU wound healing by inhibiting inflammation, which was achieved by macrophage M2 polarization through activating the PI3K/AKT pathway. Further studies have demonstrated that ISO plays major role in the above process. These findings provide a theoretical basis for further preclinical evaluation and lay a foundation for nano-gel compound treatment with ZZO.

11.
Sci Data ; 9(1): 254, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35650240

ABSTRACT

The plant microbiota plays crucial roles in sustaining plant health and productivity. Advancing plant microbiome research and designing sustainable practices for agriculture requires in-depth assessments of microorganisms associated with different host plants; however, there is little information on functional aspects of many microorganisms of interest. Therefore, we enriched microorganisms from the phyllosphere of 110 rice genotypes and subjected them to shotgun metagenomic sequencing to reconstruct bacterial genomes from the obtained datasets. The approach yielded a total of 1.34 terabases of shotgun-sequenced metagenomic data. By separately recovering bacterial genomes from each of the 110 rice genotypes, we recovered 569 non-redundant metagenome-assembled genomes (MAGs) with a completeness higher than 50% and contaminations less than 10%. The MAGs were primarily assigned to Alphaproteobacteria, Gammaproteobacteria, and Bacteroidia. The presented data provides an extended basis for microbiome analyses of plant-associated microorganisms. It is complemented by detailed metadata to facilitate implementations in ecological studies, biotechnological mining approaches, and comparative assessments with genomes or MAGs from other studies.


Subject(s)
Genome, Bacterial , Metagenome , Oryza , Bacteria/genetics , Metagenomics , Oryza/genetics , Oryza/microbiology
12.
Comput Intell Neurosci ; 2022: 5173836, 2022.
Article in English | MEDLINE | ID: mdl-35619768

ABSTRACT

Objective: The long-term clinical practice shows that Zizhu ointment (ZZO) is an empirical formula for the treatment of diabetic ulcers (DUs). In this study, we investigated the underlying mechanism of ZZO in the treatment of DU mice. Methods: Through streptozotocin induction and high-fat diet, a DU mouse model was established and ZZO was given for treatment. The activation of Notch4 signaling was examined by immunofluorescence staining, RT-PCR, as well as Western blotting. Flow cytometry was performed to detect the counts of F4/80+ cells, M1 and M2 macrophages, as well as the expression of CD11c, CD206, etc. The role of Notch4 in wound healing in diabetic mice was verified by Notch4 inhibitors and agonists. Results: Accelerated wound healing and decreased expression levels of Notch4 and its target genes and ligands were observed in diabetic mice treated with ZZO. ZZO promoted M2 macrophage polarization, downregulated the expression of proinflammatory factors, and upregulated the levels of anti-inflammatory factors. The same tendency was observed in diabetic mice after treatment with Notch4 inhibitors. Knockout of Notch4 accelerated the wound healing rate as well. Conclusions: ZZO accelerates wound healing of diabetic mice through inhibiting the activation of Notch4 signaling, promoting M2 macrophage polarization, and alleviating inflammation.


Subject(s)
Diabetes Mellitus, Experimental , Animals , Diabetes Mellitus, Experimental/drug therapy , Macrophages/metabolism , Mice , Mice, Knockout , Ointments/metabolism , Ointments/therapeutic use , Signal Transduction , Ulcer/metabolism , Wound Healing/physiology
14.
Plant Cell Environ ; 45(4): 1109-1126, 2022 04.
Article in English | MEDLINE | ID: mdl-35040151

ABSTRACT

Crop diseases threaten food security and sustainable agriculture. Consumption of crops containing nonessential toxic metals leads to health risks for humans. Therefore, cultivation of disease-resistant and toxic metal-safe crops is a double-gain strategy that can contribute to food security. Here, we show that rice heavy-metal transporter OsNRAMP1 plays an important role in plant immunity by modulating metal ion and reactive oxygen species (ROS) homoeostasis. OsNRAMP1 expression was induced after pathogenic bacteria and fungi infections. The osnramp1 mutants had an increased content of H2 O2 and activity of superoxide dismutase, but decreased activity of catalase, showing enhanced broad-spectrum resistance against bacterial and fungal pathogens. RNA-seq analysis identified a number of differentially expressed genes that were involved in metal ion and ROS homoeostasis. Altered expression of metal ion-dependent ROS-scavenging enzymes genes and lower accumulation of cations such as Mn together induced compromised metal ion-dependent enzyme-catalysing activity and modulated ROS homoeostasis, which together contributed towards disease resistance in osnramp1 mutants. Furthermore, the osnramp1 mutants contained lower levels of toxic heavy metals Cd and Pb and micronutrients Ni and Mn in leaves and grains. Taken together, a proof of concept was achieved that broad-spectrum disease-resistant and toxic heavy-metal-safe rice was engineered by removal of the OsNRAMP1 gene.


Subject(s)
Cation Transport Proteins , Metals, Heavy , Oryza , Soil Pollutants , Cadmium/metabolism , Cadmium/toxicity , Cation Transport Proteins/genetics , Cation Transport Proteins/metabolism , Disease Resistance , Homeostasis , Metals, Heavy/metabolism , Metals, Heavy/toxicity , Oryza/genetics , Oryza/metabolism , Reactive Oxygen Species/metabolism , Soil Pollutants/metabolism
15.
BMC Genomics ; 22(1): 865, 2021 Dec 02.
Article in English | MEDLINE | ID: mdl-34856929

ABSTRACT

BACKGROUND: Ramie is an important fiber-producing crop in China, and its fibers are widely used as textile materials. Fibers contain specialized secondary cellular walls that are mainly composed of cellulose, hemicelluloses, and lignin. Understanding the mechanism underlying the secondary wall biosynthesis of fibers will benefit the improvement of fiber yield and quality in ramie. RESULTS: Here, we performed a proteomic analysis of the bark from the top and middle parts of the stem, where fiber growth is at different stages. We identified 6971 non-redundant proteins from bast bark. Proteomic comparison revealed 983 proteins with differential expression between the two bark types. Of these 983 proteins, 46 were identified as the homolog of known secondary wall biosynthetic proteins of Arabidopsis, indicating that they were potentially associated with fiber growth. Then, we proposed a molecular model for the secondary wall biosynthesis of ramie fiber. Furthermore, interaction analysis of 46 candidate proteins revealed two interacting networks that consisted of eight cellulose biosynthetic enzymes and seven lignin biosynthetic proteins, respectively. CONCLUSION: This study sheds light on the proteomic basis underlying bast fiber growth in ramie, and the identification of many candidates associated with fiber growth provides important basis for understanding the fiber growth in this crop.


Subject(s)
Boehmeria , Cellulose , Lignin , Plant Proteins/genetics , Proteomics
16.
BMC Plant Biol ; 21(1): 473, 2021 Oct 16.
Article in English | MEDLINE | ID: mdl-34656094

ABSTRACT

BACKGROUND: Phosphorylation modification, one of the most common post-translational modifications of proteins, widely participates in the regulation of plant growth and development. Fibers extracted from the stem bark of ramie are important natural textile fibers; however, the role of phosphorylation modification in the growth of ramie fibers is largely unknown. RESULTS: Here, we report a phosphoproteome analysis for the barks from the top and middle section of ramie stems, in which the fiber grows at different stages. A total of 10,320 phosphorylation sites from 9,170 unique phosphopeptides that were assigned to 3,506 proteins was identified, and 458 differentially phosphorylated sites from 323 proteins were detected in the fiber developmental barks. Twelve differentially phosphorylated proteins were the homologs of Arabidopsis fiber growth-related proteins. We further focused on the function of the differentially phosphorylated KNOX protein whole_GLEAN_10029667, and found that this protein dramatically repressed the fiber formation in Arabidopsis. Additionally, using a yeast two-hybridization assay, we identified a kinase and a phosphatase that interact with whole_GLEAN_10029667, indicating that they potentially target this KNOX protein to regulate its phosphorylation level. CONCLUSION: The finding of this study provided insights into the involvement of phosphorylation modification in ramie fiber growth, and our functional characterization of whole_GLEAN_10029667 provide the first evidence to indicate the involvement of phosphorylation modification in the regulation of KNOX protein function in plants.


Subject(s)
Boehmeria/metabolism , Phosphoprotein Phosphatases/metabolism , Phosphoproteins/metabolism , Plant Proteins/metabolism , Protein Kinases/metabolism , Proteome , Boehmeria/genetics , Boehmeria/growth & development , Computational Biology , Gene Expression Regulation, Plant , Gene Library , Phosphoprotein Phosphatases/genetics , Phosphoproteins/genetics , Phosphorylation , Plant Bark/growth & development , Plant Bark/metabolism , Plant Proteins/genetics , Plant Stems/growth & development , Plant Stems/metabolism , Protein Kinases/genetics , Textiles , Two-Hybrid System Techniques
18.
Cell Mol Biol Lett ; 26(1): 35, 2021 Jul 31.
Article in English | MEDLINE | ID: mdl-34332546

ABSTRACT

Alkannin-based pharmaceutical formulations for improving wound healing have been on the market for several years. However, detailed molecular mechanisms of their action have yet to be elucidated. Here, we investigated the potential roles of AAN-II in improving the healing of pressure-induced venous ulcers using a rabbit model generated by combining deep vein thrombosis with a local skin defect/local skin defect. The extent of healing was evaluated using hematoxylin and eosin (HE) or vimentin staining. Rabbit skin fibroblasts were cultured for AAN-II treatment or TGFB1-sgRNA lentivirus transfection. ELISA was used to evaluate the levels of various cytokines, including IL-1ß, IL-4, IL-6, TNF-α, VEGF, bFGF, TGF-ß and PDGF. The protein levels of TGF-ß sensors, including TGF-ß, Smad7 and phosphor-Smad3, and total Smad3, were assayed via western blotting after TGF-ß knockout or AAN-II treatment. The results show that, for this model, AAN-II facilitates ulcer healing by suppressing the development of inflammation and promoting fibroblast proliferation and secretion of proangiogenic factors. AAN-II enhances the activation of the TGF-ß1-Smad3 signaling pathway during skin ulcer healing. In addition, the results demonstrate that AAN-II and TGF-ß have synergistic effects on ulcer healing. Our findings indicate that AAN-II can promote healing of pressure-induced venous skin ulcers via activation of TGF-ß-Smad3 signaling in fibroblast cells and provide evidence that could be used in the development of more effective treatments.


Subject(s)
Boraginaceae/chemistry , Naphthoquinones/pharmacology , Smad3 Protein/metabolism , Transforming Growth Factor beta1/metabolism , Varicose Ulcer/drug therapy , Wound Healing/drug effects , Animals , Disease Models, Animal , Female , Pressure , Rabbits , Signal Transduction , Smad3 Protein/genetics , Transforming Growth Factor beta1/genetics , Varicose Ulcer/metabolism , Varicose Ulcer/pathology
19.
Planta ; 254(1): 1, 2021 Jun 03.
Article in English | MEDLINE | ID: mdl-34081200

ABSTRACT

MAIN CONCLUSION: A total of 249 sites from 197 proteins showed a differential ubiquitination level in the fiber development of ramie barks. The function of two differentially ubiquitinated proteins for fiber growth was demonstrated. Ubiquitination is one of the most common post-translational modifications of proteins, and it plays essential roles in plant growth and development. However, the involvement of ubiquitination in the growth of plant fibers remains largely unknown. We compared the ubiquitylome of the top and middle stems of ramie bark, with different fiber growth stages. We identified 249 differentially ubiquitinated sites in 197 proteins in fiber-developing barks in the stems and found that seven were homologs of Arabidopsis proteins associated with fiber growth. Overexpression of the differentially ubiquitinated proteins, RWA3 homolog whole_GLEAN_10024150 and MYB protein whole_GLEAN_10015497, significantly promoted fiber growth in transgenic Arabidopsis, indicating their involvement in this process. We also found that the abundance of these proteins decreased when their ubiquitination levels increased and vice versa in the fiber-developing bark. These results indicated that the abundance of these two proteins was adjusted through ubiquitin-dependent degradation. Collectively, our findings provide important insights into the involvement of ubiquitination in the growth of ramie fibers.


Subject(s)
Boehmeria , Plant Development , Plant Structures , Ubiquitination
20.
Article in English | MEDLINE | ID: mdl-33880123

ABSTRACT

AIMS: In recent years, the incidence of deep venous thrombosis (DVT) presents an increasing trend year by year. The current evidence regarding the efficacy and safety of Xueshuantong injection for DVT is controversial. This systematic review (SR) aimed to assess the efficacy and safety of Xueshuantong injection in the treatment of DVT systematically and provide an evidence-based reference for clinical treatment. METHODS: Nine electronic databases were used to identify the literature consisting of randomized controlled trials (RCTs) with a date of search of 1 November 2020. Clinical effective rate and incidence rate of adverse events were investigated as primary outcomes. Patency rate of femoral vein, patency rate of popliteal vein, patency rate of posterior tibial vein, circumference difference, activated partial thromboplastin time (APTT), and D-dimer (D-D) were investigated as secondary outcomes. Revman 5.4.1 was used to analyze the results. Analysis of the power of evidence was performed with Trial Sequential Analysis (TSA). RESULTS: A total of 12 articles including 1018 patients were included. The results of the meta-analysis showed that the clinical effective rate in the experimental group was higher than that in the control group, the incidence rate of adverse events in the experimental group was higher than that in the control group; after the operation, the patency rate of femoral vein, patency rate of popliteal vein, patency rate of posterior tibial vein, circumference difference, APTT, and D-D in the experimental group were significantly improved compared with those in the control group, and the difference between the groups was statistically significant. TSA suggested that the meta-analysis concerning the clinical effectiveness of Xueshuantong injection in the treatment of DVT was of adequate power to reach firm conclusions. CONCLUSION: Based on the current analysis, Xueshuantong injection as an add-on treatment provided better treatment effect for DVT with adequate power but this benefit should be considered with caution because of the small number of studies included in the meta-analysis and the high or unclear risk of bias of the included trials, suggesting that further studies are needed.

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