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1.
Article in English | MEDLINE | ID: mdl-38821486

ABSTRACT

BACKGROUND: Inferior alveolar nerve (IAN) injury is one of the complications of impacted lower mandibular third molar (LM3) extraction. Given the unknown prognosis of IAN injuries and limited treatment options, it is critical to understand the risk factors of IAN injury before LM3 extraction. PURPOSE: The purpose of the study was to identify risk factors associated with IAN injury after LM3 extraction. STUDY DESIGN, SETTING, SAMPLE: This was a prospective cohort study including patients who underwent LM3 extraction from May to December 2021 at the authors' institution. Patients with systemic diseases, previous maxillofacial surgeries, or sensory abnormalities were excluded. PREDICTOR VARIABLE: The predictor variable is composed of several risk factors. The variables were grouped into four categories: demographic, radiographic, procedure-related, and surgeon experience. MAIN OUTCOME VARIABLE(S): The outcome variable was postoperative neurosensory disturbance coded as present or absent and was measured at 1-month (transient) and 1-year (permanent). COVARIATES: Not applicable. ANALYSES: The measurement data were represented by mean and standard deviation. The association of each variable with the presence of an IAN injury was tested by the χ2 test. Statistical significance was accepted at P < .05. RESULTS: The study sample consisted of 705 patients (37.0% male) with an average age of 28.51 ± 6.51 years. A total of 17/705 (2.4%) and 4/705 (0.57%) patients developed transient and permanent IAN injuries. The results demonstrated that the following factors were associated with higher rates of transient injury: use of chisels during surgeries (6.4%; 95% confidence interval (CI): 2.7 to 12.3; P = .02; relative risk (RR) = 11.4), LM3s located below the IAN canal (8.7%; 95% CI: 4.3 to 15.7; P < .01; RR = 7.3), compressed contact between LM3s and the IAN canal (36.4%; 95% CI: 12.3 to 78.2; P < .001; RR = 25.4), and not using corticosteroids after surgeries (3.8%; 95% CI: 1.9 to 6.5; P = .03; RR = 3.1). The only factor associated with permanent injury was compressed contact between LM3s and the IAN canal (18.2%; 95% CI: 2.2 to 62.3; P < .001; RR = 48.2). CONCLUSION AND RELEVANCE: Close proximity between LM3s and IAN canal and the use of chisels increase the risk of transient IAN injury. Corticosteroid treatment may promote nerve recovery. Compressed contact between LM3s and IAN canal is the only risk factor for permanent injury.

2.
Cell Reprogram ; 26(2): 67-78, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38598278

ABSTRACT

Repair strategies for injured peripheral nerve have achieved great progresses in recent years. However, the clinical outcomes remain unsatisfactory. Recent studies have found that exosomes secreted by dental pulp stem cells (DPSC-exos) have great potential for applications in nerve repair. In this study, we evaluated the effects of human DPSC-exos on improving peripheral nerve regeneration. Initially, we established a coculture system between DPSCs and Schwann cells (SCs) in vitro to assess the effect of DPSC-exos on the activity of embryonic dorsal root ganglion neurons (DRGs) growth in SCs. We extracted and labeled human DPSC-exos, which were subsequently utilized in uptake experiments in DRGs and SCs. Subsequently, we established a rat sciatic nerve injury model to evaluate the therapeutic potential of DPSC-exos in repairing sciatic nerve damage. Our findings revealed that DPSC-exos significantly promoted neurite elongation by enhancing the proliferation, migration, and secretion of neurotrophic factors by SCs. In vivo, DPSC-exos administration significantly improved the walking behavior, axon regeneration, and myelination in rats with sciatic nerve injuries. Our study underscores the vast potential of DPSC-exos as a therapeutic tool for tissue-engineered nerve construction.


Subject(s)
Exosomes , Nerve Regeneration , Rats , Humans , Animals , Nerve Regeneration/physiology , Rats, Sprague-Dawley , Axons , Dental Pulp , Sciatic Nerve/physiology , Stem Cells , Schwann Cells
3.
Adv Drug Deliv Rev ; 209: 115325, 2024 06.
Article in English | MEDLINE | ID: mdl-38670229

ABSTRACT

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by an inflammatory microenvironment and cartilage erosion within the joint cavity. Currently, antirheumatic agents yield significant outcomes in RA treatment. However, their systemic administration is limited by inadequate drug retention in lesion areas and non-specific tissue distribution, reducing efficacy and increasing risks such as infection due to systemic immunosuppression. Development in local drug delivery technologies, such as nanostructure-based and scaffold-assisted delivery platforms, facilitate enhanced drug accumulation at the target site, controlled drug release, extended duration of the drug action, reduced both dosage and administration frequency, and ultimately improve therapeutic outcomes with minimized damage to healthy tissues. In this review, we introduced pathogenesis and clinically used therapeutic agents for RA, comprehensively summarized locally administered nanostructure-based and scaffold-assisted drug delivery systems, aiming at improving the therapeutic efficiency of RA by alleviating the inflammatory response, preventing bone erosion and promoting cartilage regeneration. In addition, the challenges and future prospects of local delivery for clinical translation in RA are discussed.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Drug Delivery Systems , Humans , Arthritis, Rheumatoid/drug therapy , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/therapeutic use , Animals , Nanostructures/administration & dosage , Delayed-Action Preparations
4.
Mol Neurobiol ; 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38285287

ABSTRACT

The prognosis of peripheral nerve injury (PNI) is usually poor, and currently, there is no effective treatment for PNI. Studies have shown that exosomes derived from mesenchymal stem cells could promote nerve regeneration by optimizing the function of endogenous Schwann cells (SCs), while the mechanism is unclear. Autophagy, a highly conserved intracellular catabolic process responsible for maintaining cellular homeostasis, has been proved to be involved in the regulation of nerve repair after injury. We explored the effect of exosomes derived from dental pulp stem cells (DPSC-Exos) on the regeneration of myelin sheath in rats with sciatic nerve injury (SNI). In vitro and in vivo experiments were performed to clarify whether the effect of DPSC-Exos is associated with autophagy of SCs and to reveal the mechanism at the molecular level. Our results showed that the SCs of SNI rats exhibited the obvious autophagic characteristics, and the increase of P53 expression was an internal factor of autophagy. Our mechanism research indicated that DPSC-Exos could deliver miR-122-5p from DPSCs into SCs and suppressed the rapamycin (RAPA)-induced autophagy in SCs by inhibiting P53 expression. Rescue experiments showed that both the use of GW4869 and overexpression of exogenous P53 in SCs could reverse the inhibitory effect of DPSCs on the autophagy in SCs from co-culture system. In short, our study indicated that DPSC-Exos could promote the regeneration of the myelin sheath through suppressing the autophagy in SCs caused by PNI via miR-122-5p/P53 pathway; this provides researchers with another option for precise repair of PNI.

5.
Int J Surg ; 110(3): 1463-1474, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38270619

ABSTRACT

BACKGROUND: Trigeminal neuralgia (TN) is the most common neuropathic disorder in the maxillofacial region. The etiology and pathogenesis of TN have not been clearly determined to date, although there are many hypotheses. OBJECTIVE: The goal of this study was to investigate the interactions between different types of cells in TN, particularly the impact and intrinsic mechanism of demyelination on the trigeminal ganglion, and to identify new important target genes and regulatory pathways in TN. METHODS: TN rat models were prepared by trigeminal root compression, and trigeminal nerve tissues were isolated for spatial transcriptome sequencing. The gene expression matrix was reduced dimensionally by PCA and presented by UMAP. Gene function annotation was analyzed by Metascape. The progression of certain clusters and the developmental pseudotime were analyzed using the Monocle package. Modules of the gene coexpression network between different groups were analyzed based on weighted gene coexpression network analysis and assigned AddModuleScore values. The intercellular communication of genes in these networks via ligand-receptor interactions was analyzed using CellPhoneDB analysis. RESULTS: The results suggested that the trigeminal ganglion could affect Schwann cell demyelination and remyelination responses through many ligand-receptor interactions, while the effect of Schwann cells on the trigeminal ganglion was much weaker. Additionally, ferroptosis may be involved in the demyelination of Schwann cells. CONCLUSIONS: This study provides spatial transcriptomics sequencing data on TN, reveals new markers, and redefines the relationship between the ganglion and myelin sheath, providing a theoretical basis and supporting data for future mechanistic research and drug development.


Subject(s)
Demyelinating Diseases , Trigeminal Neuralgia , Rats , Animals , Trigeminal Neuralgia/genetics , Ligands , Transcriptome , Trigeminal Nerve , Demyelinating Diseases/complications , Demyelinating Diseases/metabolism , Demyelinating Diseases/pathology
6.
Article in English | MEDLINE | ID: mdl-38064609

ABSTRACT

Objective: To investigate the efficacy and safety of low-dose radiotherapy in treating eosinophilic lymphoid granuloma. Method: This study included a total of 20 patients diagnosed with eosinophilic lymphoid granuloma. All patients underwent low-dose three-dimensional conformal intensity-modulated radiotherapy for their lesions. We analyzed the control status of the lesions and any adverse reactions related to radiotherapy. Results: The overall effectiveness of low-dose radiotherapy in treating eosinophilic lymphoid granuloma was 90%. The incidence of grade I and grade II adverse reactions induced by radiotherapy was 70% and 30%, respectively. Over a median follow-up period of 23.6 months, all patients showed controlled lesions within the target delineation of radiotherapy. After radiotherapy, four patients experienced occasional pruritus, and one patient had a recurrence outside the target area three years later. No long-term severe adverse reactions related to radiotherapy were observed during the follow-up period. Conclusions: Low-dose radiotherapy demonstrates an apparent therapeutic effect on eosinophilic lymphoid granuloma with acceptable adverse reactions.

7.
Adv Drug Deliv Rev ; 185: 114308, 2022 06.
Article in English | MEDLINE | ID: mdl-35472398

ABSTRACT

Cancer immunotherapy, which reprograms a patient's own immune system to eradicate cancer cells, has been demonstrated as a promising therapeutic strategy clinically. Immune checkpoint blockade (ICB) therapies, cytokine therapies, cancer vaccines, and chimeric antigen receptor (CAR) T cell therapies utilize immunotherapy techniques to relieve tumor immune suppression and/or activate cellular immune responses to suppress tumor growth, metastasis and recurrence. However, systemic administration is often hampered by limited drug efficacy and adverse side effects due to nonspecific tissue distribution of immunotherapeutic agents. Advancements in local scaffold-based delivery systems facilitate a controlled release of therapeutic agents into specific tissue sites through creating a local drug reservoir, providing a potent strategy to overcome previous immunotherapy limitations by improving site-specific efficacy and minimizing systemic toxicity. In this review, we summarized recent advances in local scaffold-assisted delivery of immunotherapeutic agents to reeducate the immune system, aiming to amplify anticancer efficacy and minimize immune-related adverse events. Additionally, the challenges and future perspectives of local scaffold-assisted cancer immunotherapy for clinical translation and applications are discussed.


Subject(s)
Cancer Vaccines , Neoplasms , Cancer Vaccines/therapeutic use , Humans , Immunologic Factors/therapeutic use , Immunotherapy/methods , Immunotherapy, Adoptive , Neoplasms/drug therapy
8.
BMC Genomics ; 22(1): 738, 2021 Oct 14.
Article in English | MEDLINE | ID: mdl-34649496

ABSTRACT

BACKGROUND: Transcription factors, including trihelix transcription factors, play vital roles in various growth and developmental processes and in abiotic stress responses in plants. The trihelix gene has been systematically studied in some dicots and monocots, including Arabidopsis, tomato, chrysanthemum, soybean, wheat, corn, rice, and buckwheat. However, there are no related studies on sorghum. RESULTS: In this study, a total of 40 sorghum trihelix (SbTH) genes were identified based on the sorghum genome, among which 34 were located in the nucleus, 5 in the chloroplast, 1 (SbTH38) in the cytoplasm, and 1 (SbTH23) in the extracellular membrane. Phylogenetic analysis of the SbTH genes and Arabidopsis and rice trihelix genes indicated that the genes were clustered into seven subfamilies: SIP1, GTγ, GT1, GT2, SH4, GTSb8, and orphan genes. The SbTH genes were located in nine chromosomes and none on chromosome 10. One pair of tandem duplication gene and seven pairs of segmental duplication genes were identified in the SbTH gene family. By qPCR, the expression of 14 SbTH members in different plant tissues and in plants exposed to six abiotic stresses at the seedling stage were quantified. Except for the leaves in which the genes were upregulated after only 2 h exposure to high temperature, the 12 SbTH genes were significantly upregulated in the stems of sorghum seedlings after 24 h under the other abiotic stress conditions. Among the selected genes, SbTH10/37/39 were significantly upregulated, whereas SbTH32 was significantly downregulated under different stress conditions. CONCLUSIONS: In this study, we identified 40 trihelix genes in sorghum and found that gene duplication was the main force driving trihelix gene evolution in sorghum. The findings of our study serve as a basis for further investigation of the functions of SbTH genes and providing candidate genes for stress-resistant sorghum breeding programmes and increasing sorghum yield.


Subject(s)
Sorghum , Gene Expression Regulation, Plant , Phylogeny , Plant Proteins/genetics , Plant Proteins/metabolism , Sorghum/genetics , Sorghum/metabolism , Stress, Physiological/genetics , Transcription Factors/genetics , Transcription Factors/metabolism
9.
PeerJ ; 9: e12683, 2021.
Article in English | MEDLINE | ID: mdl-35036157

ABSTRACT

BACKGROUND: Soil salinity is a major environmental stress that restricts crop growth and yield. METHODS: Here, crucial proteins and biological pathways were investigated under salt-stress and recovery conditions in Tritipyrum 'Y1805' using the data-independent acquisition proteomics techniques to explore its salt-tolerance mechanism. RESULTS: In total, 44 and 102 differentially expressed proteins (DEPs) were identified in 'Y1805' under salt-stress and recovery conditions, respectively. A proteome-transcriptome-associated analysis revealed that the expression patterns of 13 and 25 DEPs were the same under salt-stress and recovery conditions, respectively. 'Response to stimulus', 'antioxidant activity', 'carbohydrate metabolism', 'amino acid metabolism', 'signal transduction', 'transport and catabolism' and 'biosynthesis of other secondary metabolites' were present under both conditions in 'Y1805'. In addition, 'energy metabolism' and 'lipid metabolism' were recovery-specific pathways, while 'antioxidant activity', and 'molecular function regulator' under salt-stress conditions, and 'virion' and 'virion part' during recovery, were 'Y1805'-specific compared with the salt-sensitive wheat 'Chinese Spring'. 'Y1805' contained eight specific DEPs related to salt-stress responses. The strong salt tolerance of 'Y1805' could be attributed to the strengthened cell walls, reactive oxygen species scavenging, osmoregulation, phytohormone regulation, transient growth arrest, enhanced respiration, transcriptional regulation and error information processing. These data will facilitate an understanding of the molecular mechanisms of salt tolerance and aid in the breeding of salt-tolerant wheat.

10.
Braz J Med Biol Res ; 53(11): e10009, 2020.
Article in English | MEDLINE | ID: mdl-32965322

ABSTRACT

The epidermis, the outermost layer of the skin, is the first barrier that comes into contact with the external environment. It plays an important role in resisting the invasion of harmful substances and microbial infections. The skin changes with age and external environmental factors. This study aimed to investigate epidermal stem cells during the process of aging. This study enrolled 9 volunteers with benign pigmented nevus for clinical dermatologic surgery. The phenotypes associated with skin aging changes such as skin wrinkles and elasticity of the unexposed/healthy parts near benign pigmented skin were measured, and epidermal stem cells from this region were isolated for transcriptome sequencing. The results showed that epidermal stem cells could be obtained by magnetic activated cell sorting (MACS) with high purity. Results of the transcriptome sequencing revealed that aquaporin (AQP)5 significantly decreased in the epidermal stem cells with age, and further functional experiments revealed that AQP5 could promote the proliferation and dedifferentiation of HaCaT, but did not influence cell apoptosis. In summary, AQP5 regulated the proliferation and differentiation of epidermal stem cells in skin aging, and it may play an important role in the balance of proliferation and differentiation. However, further studies are needed to determine the mechanism by which AQP5 regulates the proliferation and differentiation of epidermal skin cells in aging.


Subject(s)
Aquaporin 5/metabolism , Skin Aging , Cell Differentiation , Cell Proliferation , Epidermis , Humans , Stem Cells
11.
Braz. j. med. biol. res ; 53(11): e10009, 2020. tab, graf
Article in English | LILACS, Coleciona SUS | ID: biblio-1132495

ABSTRACT

The epidermis, the outermost layer of the skin, is the first barrier that comes into contact with the external environment. It plays an important role in resisting the invasion of harmful substances and microbial infections. The skin changes with age and external environmental factors. This study aimed to investigate epidermal stem cells during the process of aging. This study enrolled 9 volunteers with benign pigmented nevus for clinical dermatologic surgery. The phenotypes associated with skin aging changes such as skin wrinkles and elasticity of the unexposed/healthy parts near benign pigmented skin were measured, and epidermal stem cells from this region were isolated for transcriptome sequencing. The results showed that epidermal stem cells could be obtained by magnetic activated cell sorting (MACS) with high purity. Results of the transcriptome sequencing revealed that aquaporin (AQP)5 significantly decreased in the epidermal stem cells with age, and further functional experiments revealed that AQP5 could promote the proliferation and dedifferentiation of HaCaT, but did not influence cell apoptosis. In summary, AQP5 regulated the proliferation and differentiation of epidermal stem cells in skin aging, and it may play an important role in the balance of proliferation and differentiation. However, further studies are needed to determine the mechanism by which AQP5 regulates the proliferation and differentiation of epidermal skin cells in aging.


Subject(s)
Humans , Skin Aging , Aquaporin 5/metabolism , Stem Cells , Cell Differentiation , Cell Proliferation , Epidermis
12.
Theranostics ; 9(11): 3293-3307, 2019.
Article in English | MEDLINE | ID: mdl-31244955

ABSTRACT

The noninvasive nature of photodynamic therapy (PDT) enables the preservation of organ function in cancer patients. However, PDT is impeded by hypoxia in the tumor microenvironment (TME) caused by high intracellular oxygen (O2) consumption and distorted tumor blood vessels. Therefore, increasing oxygen generation in the TME would be a promising methodology for enhancing PDT. Herein, we proposed a concept of ferroptosis-promoted PDT based on the biochemical characteristics of cellular ferroptosis, which improved the PDT efficacy significantly by producing reactive oxygen species (ROS) and supplying O2 sustainably through the Fenton reaction. In contrast to traditional strategies that increase O2 based on decomposition of limited concentration of hydrogen peroxide (H2O2), our methodology could maintain the concentration of H2O2 and O2 through the Fenton reaction. Methods: For its association with sensitivity to ferroptosis, solute carrier family 7 member 11 (SLC7A11) expression was characterized by bioinformatics analysis and immunohistochemistry of oral tongue squamous cell carcinoma (OTSCC) specimens. Afterwards, the photosensitizer chlorin e6 (Ce6) and the ferroptosis inducer erastin were self-assembled into a novel supramolecular Ce6-erastin nanodrug through hydrogen bonding and π-π stacking. Then, the obtained Ce6-erastin was extensively characterized and its anti-tumor efficacy towards OTSCC was evaluated both in vitro and in vivo. Results: SLC7A11 expression is found to be upregulated in OTSCC, which is a potential target for ferroptosis-mediated OTSCC treatment. Ce6-erastin nanoparticles exhibited low cytotoxicity to normal tissues. More significantly, The over-accumulated intracellular ROS, increased O2 concentration and inhibited SLC7A11 expression lead to enhanced toxicity to CAL-27 cells and satisfactory antitumor effects to xenograft tumour mouse model upon irradiation. Conclusion: Our ferroptosis promoted PDT approach markedly enhances anticancer actions by relieving hypoxia and promoting ROS production, thereby our work provides a new approach for overcoming hypoxia-associated resistance of PDT in cancer treatment.


Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Squamous Cell/drug therapy , Ferroptosis/drug effects , Macromolecular Substances/pharmacology , Nanomedicine/methods , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Amino Acid Transport System y+/analysis , Animals , Antineoplastic Agents/administration & dosage , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Disease Models, Animal , Humans , Macromolecular Substances/administration & dosage , Mice, Inbred BALB C , Models, Theoretical , Nanostructures , Photosensitizing Agents/administration & dosage , Piperazines/administration & dosage , Piperazines/pharmacology , Porphyrins/administration & dosage , Porphyrins/pharmacology , Tongue Neoplasms/drug therapy , Tongue Neoplasms/pathology
13.
ACS Biomater Sci Eng ; 5(5): 2457-2465, 2019 May 13.
Article in English | MEDLINE | ID: mdl-33405753

ABSTRACT

Full-thickness skin regeneration is still a clinical challenge for skin defects. Porcine small intestinal submucosa (SIS) has been exploited as a new scaffold for tissue reconstruction due to its excellent biocompatibility and ease of handling and modification. However, the application of SIS is dramatically impeded by its compact structure. Thus, a strategy for improving this property of SIS is highly desirable. Herein, SIS was recross-linked by a four-arm polyethylene glycol (fa-PEG) with succinimidyl glutarate-terminated branches into a three-dimensional (3D) bioactive sponge (SIS-PEG), which possessed porous 3D frameworks to mimic the structure of skin. The addition of a suitable proportion of fa-PEG endowed SIS with a uniform pore size, outstanding bioactivity, and flexible shape to promote a rapid healing of a mouse skin defect. Compared with SIS, the bioactive SIS-PEG sponge exhibited excellent mechanical stability and was less prone to collagenase degradation. Moreover, SIS-PEG provided a minimally invasive way to deliver stem cells for in situ wound repair. Remarkably, in vivo evaluation demonstrated that dissociated epidermal and dermal cells loaded with SIS-PEG could form reconstituted skin with regenerated hair after 21 days of treatment. The SIS-PEG bioactive sponge exhibited great potential for skin tissue engineering.

14.
Curr Probl Cancer ; 43(1): 77-85, 2019 02.
Article in English | MEDLINE | ID: mdl-29934220

ABSTRACT

PURPOSE: To analyze clinical factors that were associated with inadequate pain control in cancer patients with metastatic malignancy and moderate to severe baseline pain. PATIENTS: We retrospectively analyzed data from 260 advanced cancer patients who admitted to the First Hospital of Jilin University (Jilin, China) from January 2012-May 2013. MEASUREMENTS: Statistical analysis was performed to assess the correlation between pain control and baseline characteristics including, gender, patient age, type of malignancy, presence of bone metastases, pain intensity, pain location, etiology of pain, type of pain, and presence of breakthrough pain. MAIN RESULTS: A total of 75.4% of patients obtained satisfactory pain control (numerical rating scale ≤ 3) in 3 days. Baseline characteristics including gastrointestinal tumors (P = 0.032), severe pain (P < 0.001), and frequent breakthrough pain (P < 0.001) were independent risk factors of poor pain control in the 3-day treatment. These factors were also significantly associated with longer time needed to achieve stable pain control. Of the 185 patients treated with opioids, higher doses of analgesics were used in younger patients (<60 years old; P = 0.018), and in patients with severe pain (P < 0.001), neuropathic pain (P = 0.002), and frequent breakthrough pain (P = 0.015). CONCLUSIONS: Factors associated with more difficult pain control include gastrointestinal tumor, severe baseline pain, presence of breakthrough pain, and neuropathic etiology of pain.


Subject(s)
Analgesics, Opioid/therapeutic use , Bone Neoplasms/complications , Cancer Pain/drug therapy , Neoplasms/complications , Neuralgia/drug therapy , Pain Management/standards , Bone Neoplasms/secondary , Cancer Pain/etiology , Cancer Pain/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasms/pathology , Neuralgia/etiology , Neuralgia/pathology , Pain Management/methods , Prognosis , Retrospective Studies , Survival Rate
15.
Neurosci Lett ; 685: 196-202, 2018 10 15.
Article in English | MEDLINE | ID: mdl-29920298

ABSTRACT

Adipose-derived stem cell (ADSC) transplantation has emerged as a potential tool for the treatment of cardiovascular disease and skin wounds. However, with a limited renewal capacity and the need for mass cells during the engraftment, strategies are needed to enhance ADSC proliferative capacity. In this study, we explored the effects of Exendin-4, a glucagon-like peptide-1 analog, on the growth of ADSCs, focusing in particular on phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) and Wnt signaling pathways. Firstly, ADSCs were isolated and cultured in vitro. Then, flow cytometry demonstrated that ADSCs were positive for CD44, CD90 and CD29 but negative for CD31, CD34, and CD45. Exendin-4 (0-200 nM) treatment increased ADSC proliferation. In order to examine specific signaling pathways, a western blotting assay was performed. Our results demonstrate that after treated with 50 nM Exendin-4 for 48 h, the phosphorylation of PI3K, Akt, and GSK3ß were increased and phosphorylation of ß-catenin was decreased. From these results, we concluded that PI3K-Akt and Wnt-ß-catenin signaling pathways mediate Exendin-4 induced ADSC proliferation, the function of which might contribute to the regulation of ADSC proliferation. Our findings provided new insights into the function of the mechanisms underlying Exendin-4 of ADSCs.


Subject(s)
Adipocytes/drug effects , Cell Proliferation/drug effects , Exenatide/pharmacology , Stem Cells/drug effects , Wnt Signaling Pathway/drug effects , Adipocytes/metabolism , Animals , Cells, Cultured , Phosphatidylinositol 3-Kinases/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Stem Cells/cytology
16.
PLoS One ; 12(8): e0182696, 2017.
Article in English | MEDLINE | ID: mdl-28797110

ABSTRACT

GNB2L1 and its O-GlcNAcylation has been reported to play roles in gastric cancer metastasis. However, the roles of GNB2L1 in chemoresistance of gastric cancer has never been determined. In the present study, we found that GNB2L1 was downregulated in chemoresistant patients of gastric cancer, and observed the decrease of GNB2L1 in protein levels instead of mRNA levels in different chemoresistant gastric cancer cell lines. Further we proved that this downregulation of GNB2L1 was resulted from its elevated O-GlcNAcylation catalyzed by OGT in both cell lines and patients. Next, we investigate the function of GNB2L1 and its O-GlcNAcylation on gastric cancer metastasis during chemoresistance, and confirmed Ser124 as the major O-GlcNAcylation site on GNB2L1 that regulated its function on metastasis. Furthermore, our data demonstrated that GNB2L1 modulated EMT via regulating the translation of EMT-related proteins in the process of chemoresistance. In summary, this study indicated that GNB2L1 and its O-GlcNAcylation regulated metastasis via modulating the translation of EMT-related proteins in the chemoresistance of gastric cancer.


Subject(s)
Drug Resistance, Neoplasm , Epithelial-Mesenchymal Transition , GTP-Binding Proteins/metabolism , Neoplasm Proteins/metabolism , Protein Processing, Post-Translational , Receptors, Cell Surface/metabolism , Stomach Neoplasms/metabolism , Acetylglucosamine/metabolism , Cell Line, Tumor , Cell Movement , Glycosylation , Humans , N-Acetylglucosaminyltransferases/metabolism , Receptors for Activated C Kinase , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology
17.
Oncotarget ; 8(11): 17849-17861, 2017 Mar 14.
Article in English | MEDLINE | ID: mdl-28147322

ABSTRACT

Chronic sleep disturbance (CSD) has been linked to the development of temporomandibular joint osteoarthritis (TMJ-OA). While the pathogenesis of TMJ-OA is unclear, recent studies indicate that osteochondral angiogenesis is important. We developed a rat model of CSD induced TMJ-OA to investigate the changes caused by sleep disturbance and to correlate them with vascular invasion in the TMJ. We found pathological alterations and an increased microvessel density in the rat TMJ following CSD. VEGF, Dll4 and p-ERK1/2, the expression of angiogenic factors, were highly expressed in the rat mandibular condylar cartilage and their expression increased with CSD. Furthermore, we show that VEGF-induce activation of ERK1/2, which in turn, increases Dll4 expression. Together, our results suggest that CSD can cause OA-like pathological alterations in the rat TMJ by increasing angiogenesis.


Subject(s)
Cartilage/blood supply , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/metabolism , Neovascularization, Pathologic/metabolism , Osteoarthritis/pathology , Sleep Wake Disorders/pathology , Temporomandibular Joint/pathology , Vascular Endothelial Growth Factor A/metabolism , Adrenocorticotropic Hormone/blood , Animals , Corticosterone/blood , Disease Models, Animal , Extracellular Signal-Regulated MAP Kinases/metabolism , MAP Kinase Signaling System/physiology , Mandibular Condyle/pathology , Rats , Rats, Wistar
18.
Am J Transl Res ; 8(11): 5108-5117, 2016.
Article in English | MEDLINE | ID: mdl-27904712

ABSTRACT

Objectives: Mandibular condylar chondrocyte apoptosis is mainly responsible for the development and progression of temporomandibular joint osteoarthritis (TMJ-OA). Interleukin-1ß (IL-1ß) generally serves an agent that induces chondrocyte apoptosis. Hyperbaric oxygen (HBO) treatment increases proteoglycan synthesis in vivo. We explore the protective effect of HBO on IL-1ß-induced mandibular condylar chondrocyte apoptosis in rats and the potential molecular mechanisms. Methods: Chondrocytes were isolated from the TMJ of 3-4-week old Sprague-Dawley rats. The Cell Counting Kit-8 (CCK-8) assay was used to determine cell viability. The phosphorylated phosphoinositide-3 kinase (p-PI3K), phosphorylated AKT (p-Akt), type II collagen (COL2), and aggrecan (AGG) content was detected by immunofluorescence, immunocytochemistry and western blotting. The expression of Pi3k, Akt, Col2 and Agg mRNA was measured using real-time quantitative polymerase chain reaction (RT-qPCR). Results: HBO inhibited the cytotoxicity and apoptosis induced by IL-1ß (10 ng/mL) in the mandibular condylar chondrocytes. HBO also decreased the IL-1ß activity that decreased p-PI3K and p-AKT levels, and increased COL2 and AGG expression, with the net effect of suppressing extracellular matrix degradation. Conclusions: These data suggest that HBO may protect mandibular condylar chondrocytes against IL-1ß-induced apoptosis via the PI3K/AKT signaling pathway, and that it may promote the expression of mandibular condylar chondrocyte extracellular matrix through the PI3K/AKT signaling pathway.

19.
Int J Clin Exp Med ; 8(1): 413-21, 2015.
Article in English | MEDLINE | ID: mdl-25785012

ABSTRACT

BACKGROUND: To illustrate whether the steroid-antivirals treatment could acquire a better recovery in patients with Bell's palsy than the steroids alone treatment. MATERIALS AND METHODS: We conducted an exhaustive search over Pub med/Medline, Ovid, Elsevier search engines and the Cochrane library thereby collecting the randomized controlled trials in the treatment of patients with Bell's palsy with steroid-antivirals and steroids. The qualities of relevant articles were assessed by GRADE, which was used to present the overall quality of evidence as recommended by the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Two investigators evaluated these papers independently, and resolved the disagreements by discussion. At last 8 eligible papers (1816 patients included: 896 treated with steroid-antivirals and 920 treated with steroids alone) match the criteria. Owing to the result (chi(2) = 12.57, P = 0.08, I(2) = 44%) presented by the formal test for heterogeneity, the fixed effect meta-analysis model was chosen. The facial muscle recovery between the steroids-antivirals group and the steroids alone group show significant differences (OR = 1.52, 95% CI: 1.20-1.94), while the statistical outcome of adverse effect shows no statistical significance (OR = 1.28, 95% CI: 0.71-2.31). CONCLUSIONS: The present meta-analysis indicates that the steroid-antivirals treatment could improve the recovery rate in patients with Bell's palsy when comparing with the steroid alone treatment. CLINICAL SIGNIFICANCE: This meta-analysis showed that the steroid-antivirals treatment achieved the better outcomes in patients with Bell's palsy. Clinicians should consider that steroid-antivirals therapy is an alternative choice for the patients with Bell's palsy.

20.
Article in English | MEDLINE | ID: mdl-25767068

ABSTRACT

OBJECTIVE: To carry out a standard meta-analysis to determine if aspirin should be stopped before tooth extraction. STUDY DESIGN: The PubMed, ScienceDirect, EBSCOhost, and Science Citation Index databases were searched for studies published up to September 30, 2014. Eligible studies were restricted to randomized controlled trials (RCTs) and controlled, nonrandomized trials. RESULTS: Three RCTs and seven controlled trials met the inclusion criteria (covering 1752 patients: 529 on aspirin therapy and 1223 not on aspirin therapy). The results showed that the risk of postoperative hemorrhage was significantly higher in patients on aspirin therapy (relative risk [RR] = 2.46; 95% confidence interval [CI]: 1.45-4.81) but that bleeding time (BT) was not significantly different between the two groups (standardized mean difference [SMD] = 0.63; 95% CI: -0.04 to 1.31). Sensitivity analyses showed that the results were unstable. CONCLUSIONS: We could reach a conclusion that BT is prolonged or hemorrhage is exacerbated by long-term use of aspirin. We recommend not stopping long-term aspirin use before tooth extraction but enhancing hemostasis methods, if necessary.


Subject(s)
Aspirin/administration & dosage , Oral Hemorrhage/etiology , Oral Hemorrhage/prevention & control , Tooth Extraction , Humans
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