Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway.

BACKGROUND: Constipation, a highly prevalent functional gastrointestinal disorder, induces a significant burden on the quality of patients' life and is associated with substantial healthcare expenditures. Therefore, identifying efficient therapeutic modalities for constipation is of paramount importance. Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms. Consequently, we postulate that hydrogen therapy, an emerging and promising intervention, can serve as a safe and efficacious treatment for constipation. AIM: To determine whether hydrogen-rich water (HRW) alleviates constipation and its potential mechanism. METHODS: Constipation models were established by orally loperamide to Sprague-Dawley rats. Rats freely consumed HRW, and were recorded their 24 h total stool weight, fecal water content, and charcoal propulsion rate. Fecal samples were subjected to 16S rDNA gene sequencing. Serum non-targeted metabolomic analysis, malondialdehyde, and superoxide dismutase levels were determined. Colonic tissues were stained with hematoxylin and eosin, Alcian blue-periodic acid-Schiff, reactive oxygen species (ROS) immunofluorescence, and immunohistochemistry for cell growth factor receptor kit (c-kit), PGP 9.5, sirtuin1 (SIRT1), nuclear factor-erythroid-2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1, Nrf2 and HO-1. A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor, EX527, into constipated rats. NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression. RESULTS: HRW alleviated constipation symptoms by improving the total amount of stool over 24 h, fecal water content, charcoal propulsion rate, thickness of the intestinal mucus layer, c-kit expression, and the number of intestinal neurons. HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism. HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway. This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats. The serum metabolites, ß-leucine (ß-Leu) and traumatic acid, were also found to attenuate H2O2-induced oxidative stress in NCM460 cells by up-regulating SIRT1. CONCLUSION: HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway, modulating gut microbiota and serum metabolites. ß-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.

Efficacy of a single Nd:YAG laser dose in reducing pain after mandibular third molar extraction: a prospective randomized controlled clinical trial.

The purpose is to explore the analgesic effect of a single Nd:YAG laser dose after mandibular third molar extraction. This was a prospective randomized controlled clinical trial. Subjects were enrolled according to the inclusion and exclusion criteria and randomly divided into the experimental and control groups. In the experimental group, the wound was irradiated with the Nd:YAG laser (wavelength, 1064 nm; output power, 1.5 W; energy density, 45 J/cm2; and power density, 1.5/cm2, pulsed mode) immediately after mandibular third molar extraction for 120 s (30 s at each site). In the control group, the laser working tip was placed near the extraction site but not activated. The primary outcome was the visual analog scale (VAS) pain scores in both groups at 2, 4, 12, 24, 48, and 72 h and 7 days after surgery. Secondary outcomes included wound healing scores and adverse reactions. The VAS score was significantly lower in the experimental group than in the control group at 2 and 4 h after surgery, while there was no significant difference in the VAS score between the two groups at 12, 24, or 48 h or 7 days after surgery. There were no significant differences in the wound healing scores between the two groups on postoperative day 7. No adverse reactions were observed in any of the laser-irradiated areas. A single Nd:YAG laser dose was effective in reducing pain at 2 and 4 h after mandibular third molar extraction. China Clinical Trial Registry: ChiCTR2000033870 (Registration Date: 2020-6-15).

Advances in the study of antisense long­stranded non­coding RNAs in tumors (Review).

Long­stranded non­coding RNAs (lncRNAs) are RNAs that consist of >200 nucleotides. The majority of lncRNAs do not encode proteins but have been revealed to mediate a variety of important physiological functions. Antisense­lncRNAs (AS­lncRNAs) are transcribed from the opposite strand of a protein or non­protein coding gene as part of the antisense strand of the coding gene. AS­lncRNAs can serve an important role in the tumorigenesis, prognosis, metastasis and drug resistance of a number of malignancies. This has been reported to be exerted through various mechanisms, such as endogenous competition, promoter interactions, direct interactions with mRNAs, acting as 'scaffolds' to regulate mRNA half­life, interactions with 5­untranslated regions and regulation of sense mRNAs. AS­lncRNAs have been found to either inhibit or promote tumor aggressiveness by regulating cell proliferation, energy metabolism, inflammation, inflammatory­carcinoma transformation, invasion, migration and angiogenesis. In addition, accumulating evidence has documented that AS­lncRNAs can regulate tumor therapy resistance. Therefore, targeting aberrantly expressed AS­lncRNAs for cancer treatment may prove to be a promising approach to reverse therapy resistance. In the present review, research advances on the role of AS­lncRNAs in tumor occurrence and development were summarized, with the aim of providing novel ideas for further research in this field.

Rationalizing kinetic behaviors of isolated boron sites catalyzed oxidative dehydrogenation of propane.

Boron-based catalysts exhibit high alkene selectivity in oxidative dehydrogenation of propane (ODHP) but the mechanistic understanding remains incomplete. In this work, we show that the hydroxylation of framework boron species via steaming not only enhances the ODHP rate on both B-MFI and B-BEA, but also impacts the kinetics of the reaction. The altered activity, propane reaction order and the activation energy could be attributed to the hydrolysis of framework [B(OSi≡)3] unit to [B(OSi≡)3-x(OH···O(H)Si≡)x] (x = 1, 2, "···" represents hydrogen bonding). DFT calculations confirm that hydroxylated framework boron sites could stabilize radical species, e.g., hydroperoxyl radical, further facilitating the gas-phase radical mechanism. Variations in the contributions from gas-phase radical mechanisms in ODHP lead to the linear correlation between activation enthalpy and entropy on borosilicate zeolites. Insights gained in this work offer a general mechanistic framework to rationalize the kinetic behavior of the ODHP on boron-based catalysts.

Nd:YAG-photobiomodulation enhanced ADSCs multilineage differentiation and immunomodulation potentials.

To investigate the effects of Nd: YAG (1064 nm) photobiomodulation on multilineage differentiation and immunomodulation potentials of adipose tissue-derived stem cells (ADSCs) in vitro and in vivo. For in vitro experiments, cells were divided into the control group (non-irradiated control ADSCs) and photobiomodulation groups. 0.5 J/cm2, 1 J/cm2, 2 J/cm2, and 4 J/cm2 were used for proliferation assays; for ADSCs adipogenic differentiation assays, 0.5 J/cm2, 1 J/cm2 were applied; 1 J/cm2 was used for migration and immunomodulation assays. The differentiation abilities were assessed by qPCR, Oil Red O staining, and Alizarin Red staining. The immunomodulation potential was assessed by qPCR and human cytokine array. DSS-induced colitis model. was used to test the effect of photobiomodulation on ADSCs immunomodulation potentials in vivo. Nd:YAG-based photobiomodulation dose-dependently promoted ADSCs proliferation and migration; 1 J/cm2 showed the best promotion effect on proliferation. Moreover, Nd:YAG photobiomodulation promoted ADSCs osteogenic differentiation and brown adipose adipogenic differentiation. The potential immunomodulation assays showed Nd:YAG photobiomodulation improved Anti-inflammation capacity of ADSCs and photobiomodulation irradiated ADSCs effectively alleviated DSS-induced colitis severity in vivo. Our study suggests Nd:YAG photobiomodulation might enhance the ADSCs multilineage differentiation and immunomodulation potentials. These results might help to enhance ADSCs therapeutic effects for clinical application. However, further studies are needed to explore the mechanisms of Nd:YAG photobiomodulation promoting multilineage differentiation and immunomodulation potentials of ADSCs.

Increased apoptosis of gingival epithelium is associated with impaired autophagic flux in medication-related osteonecrosis of the jaw.

Macroautophagy/autophagy has both negative and positive aspects in the development of many diseases. Yet, its exact role and specific mechanism in the onset of medication-related osteonecrosis of the jaw (MRONJ) is still not fully understood. Retarded gingiva healing is the primary clinical manifestation in patients with MRONJ. In this study, we aimed to explore the relationship between autophagy and apoptosis in MRONJ gingival epithelium and search for a method to prevent this disease. First, we examined clinical samples from patients diagnosed with MRONJ and healthy controls, finding that autophagy-related markers MAP1LC3/LC3 and SQSTM1/p62 synchronously increased, thus suggesting that autophagic flux was suppressed in MRONJ. Moreover, mRNA sequencing analysis and TUNEL assay showed that the process of apoptosis was upregulated in patients and animals with MRONJ, indicating autophagy and apoptosis participate in the development of MRONJ. Furthermore, the level of autophagy and apoptosis in zoledronic acid (ZA)-treated human keratinocytes cell lines (HaCaT cells) was concentration dependent in vitro. In addition, we also found that RAB7 (RAB7, member RAS oncogene family) activator ML098 could rescue MRONJ gingival lesions in mice by activating the autophagic flux and downregulating apoptosis. To sum up, this study demonstrated that autophagic flux is impaired in the gingival epithelium during MRONJ, and the rescued autophagic flux could prevent the occurrence of MRONJ.Abbreviations: ACTB: actin beta; Baf-A1: bafilomycin A1; CASP3: caspase 3; CASP8: caspase 8; CT: computed tomography; DMSO: dimethyl sulfoxide; GFP: green fluorescent protein; HaCaT cells: human keratinocytes cell lines; H&E: hematoxylin and eosin; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MRONJ: medication-related osteonecrosis of the jaw; PARP: poly(ADP-ribose) polymerase; RAB7: RAB7, member RAS oncogene family; RFP: red fluorescent protein; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; ZA: zoledronic acid.

Clinical effect of wumei bolus on ulcerative colitis: A meta-analysis.

Wumei Bolus is a traditional Chinese medicine prescription, first appeared in Shennong Bencao Jing. Modern pharmacology believes that Wumei Bolus has antibacterial, antitussive, sedative, antiviral and anti-tumor effects, and plays a therapeutic role by acting on multi-target/multi-pathway. Moreover, it has great advantages in digestive system diseases, such as repairing the damaged gastrointestinal mucosa and improving the inflammatory environment. Aim of the study: This review aimed to evaluate the efficacy and safety of prescriptions based on the Wumei Bolus treating ulcerative colitis (UC). Materials and methods: In this meta-analysis, we searched CNKI, Wanfang Database, VIP, Pubmed, Web of Science (WOS) with language restrictions of Chinese and English for articles published from the establishment of the database to Dec 2022. This meta-analysis controlled randomized controlled trials (RCTs) assessing the efficacy and safety of Wumei Bolus against ulcerative colitis and using RevMan 5.4 and Stata 15.0to analyze information from the compliant studies. Results: The search incorporated 3145 results (1617 cases assigned into Wumei Bolus group and 1528 cases assigned into control group), from which 37 studies fulfilled our inclusion criteria and were included. The outcomes of this meta-analysis showed that compared to the control group, the Experiment group was significantly more effective (RR = 1.24，95%CI [1.20，1.28])and lower adverse reactions (RR = 0.32, 95%CI [0.20, 0.53]). According to the subgroup analysis, The results showed that the RR = 1.23 and 95%CI [1.16, 1.30] in the group treated with Wumei Bolus alone and the group treated with Western medicine with RR = 1.25 and 95%CI [1.20, 1.30], indicating that the efficacy of Wumei Bolus in the treatment of UC was better and the difference was statistically significant (P < 0.00001). The results showed that compared with the control group, the experimental group had more advantages in reducing inflammatory factors whether TNF-α or IL-8 (TNF-α:SMD = -4.44, 95%CI [-5.75, -3.14]; IL-8: SMD = -3.02, 95%CI [-4.06, -1.97]) and improving TCM symptoms and reduced TCM syndrome points (SMD = -3.82, 95%CI [-4.30, -3.34]). There was significant association of the basic treatment of Wumei Bolus improving clinical efficacy, reducing serum pro-inflammatory factors, improving symptoms, and reducing adverse reactions in UC patients. These results were statistically significant (P < 0.00001). Conclusions: The prescriptions based on the Wumei Bolus is greatly related to reducing serum pro-inflammatory factors, improving symptoms, improving clinical efficacy and reducing adverse reactions in the treatment of UC compared to conventional western medicine and improve the total clinical effective rate.

Exosomes Derived from Adipose Tissue-Derived Mesenchymal Stromal Cells Prevent Medication-Related Osteonecrosis of the Jaw through IL-1RA.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe disease with unclear pathogenesis. Adipose tissue-derived mesenchymal stromal cells (MSC(AT)s) serve as a special source for cell therapy. Herein, we explored whether exosomes (Exo) derived from MSC(AT)s promote primary gingival wound healing and prevent MRONJ. An MRONJ mice model was constructed using zoledronate (Zol) administration and tooth extraction. Exosomes were collected from the conditioned medium (CM) of MSC(AT)s (MSC(AT)s-Exo) and locally administered into the tooth sockets. Interleukin-1 receptor antagonist (IL-1RA)-siRNA was used to knock down the expression of IL-1RA in MSC(AT)s-Exo. Clinical observations, micro-computed tomography (microCT), and histological analysis were used to evaluate the therapeutic effects in vivo. In addition, the effect of exosomes on the biological behavior of human gingival fibroblasts (HGFs) was evaluated in vitro. MSC(AT)s-Exo accelerated primary gingival wound healing and bone regeneration in tooth sockets and prevented MRONJ. Moreover, MSC(AT)s-Exo increased IL-1RA expression and decreased interleukin-1 beta (IL-1ß) and tumor necrosis factor-α (TNF-α) expression in the gingival tissue. The sequent rescue assay showed that the effects of preventing MRONJ in vivo and improving the migration and collagen synthesis abilities of zoledronate-affected HGFs in vitro were partially impaired in the IL-1RA-deficient exosome group. Our results indicated that MSC(AT)s-Exo might prevent the onset of MRONJ via an IL-1RA-mediated anti-inflammatory effect in the gingiva wound and improve the migration and collagen synthesis abilities of HGFs.

PTHrP Modulates the Proliferation and Osteogenic Differentiation of Craniofacial Fibrous Dysplasia-Derived BMSCs.

Fibrous dysplasia (FD) is a skeletal stem cell disease caused by mutations in the guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (GNAS) gene, which results in the abnormal accumulation of cyclic adenosine monophosphate (cAMP) and hyperactivation of downstream signaling pathways. Parathyroid hormone-related protein (PTHrP) is secreted by the osteoblast lineage and is involved in various physiological and pathological activities of bone. However, the association between the abnormal expression of PTHrP and FD, as well as its underlying mechanism, remains unclear. In this study, we discovered that FD patient-derived bone marrow stromal cells (FD BMSCs) expressed significantly higher levels of PTHrP during osteogenic differentiation and exhibited greater proliferation capacity but impaired osteogenic ability compared to normal control patient-derived BMSCs (NC BMSCs). Continuous exogenous PTHrP exposure on the NC BMSCs promoted the FD phenotype in both in vitro and in vivo experiments. Through the PTHrP/cAMP/PKA axis, PTHrP could partially influence the proliferation and osteogenesis capacity of FD BMSCs via the overactivation of the Wnt/ß-Catenin signaling pathway. Furthermore, PTHrP not only directly modulated cAMP/PKA/CREB transduction but was also demonstrated as a transcriptional target of CREB. This study provides novel insight into the possible pathogenesis involved in the FD phenotype and enhances the understanding of its molecular signaling pathways, offering theoretical evidence for the feasibility of potential therapeutic targets for FD.

Histological analysis for pulp mineralisation after severe intrusive luxation of immature molars in rats.

BACKGROUND/AIM: Pulp mineralisation is a survival process that may occur in the pulp of immature teeth following trauma. However, the mechanism of this process remains unclear. The aim of this study was to evaluate the histological manifestations of pulp mineralisation after intrusion in immature molars of rats. MATERIALS AND METHODS: Three-week-old male Sprague-Dawley rats were subjected to intrusive luxation of the right maxillary second molar by an impact force from a striking instrument through a metal force transfer rod. The left maxillary second molar of each rat was used as a control. The control and injured maxillae were collected at 3, 7, 10, 14, and 30 days after trauma (n = 15 per time group) and evaluated using haematoxylin and eosin staining and immunohistochemistry. Independent two-tailed Student's t-test was used for statistical comparison of the immunoreactive area. RESULTS: Pulp atrophy and mineralisation were observed in 30%-40% of the animals, and no pulp necrosis occurred. Ten days after trauma, pulp mineralisation, with osteoid tissue rather than reparative dentin, formed around the newly vascularised areas in the coronal pulp. CD90-immunoreactive cells were observed in the sub-odontoblastic multicellular layer in control molars, whereas the number of these cells was decreased in the traumatised teeth. CD105 localised in cells around the pulp osteoid tissue of the traumatised teeth, whereas in control teeth, it was only expressed in the vascular endothelial cells of capillaries in the odontoblastic or sub-odontoblastic layers. In specimens with pulp atrophy at 3-10 days after trauma, hypoxia inducible factor expression and CD11b-immunoreactive inflammatory cells increased. CONCLUSIONS: Following intrusive luxation of immature teeth without crown fractures in rats, no pulp necrosis occurred. Instead, pulp atrophy and osteogenesis around neovascularisation with activated CD105-immunoreactive cells were observed in the coronal pulp microenvironment characterised by hypoxia and inflammation.

Low-level laser therapy prevents medication-related osteonecrosis of the jaw-like lesions via IL-1RA-mediated primary gingival wound healing.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a serious debilitating disease caused by anti-resorption and anti-angiogenesis drugs, significantly affecting patients' quality of life. Recent studies suggested that primary gingival wound healing may effectively prevent the development of MRONJ. This study aimed to evaluate the effects of low-level light therapy (LLLT) on promoting gingival wound healing in extraction sockets of MRONJ-like mice and preventing the occurrence of MRONJ. Furthermore, we explored underlying mechanisms. METHODS: Mice were randomly divided into the Ctrl, Zol, and Zol + LLLT groups. Administration of zoledronate and tooth extraction of bilateral maxillary second molars were used to build the MRONJ model, and LLLT was locally administered into the tooth sockets to examine the effect of LLLT. Next, to explore the function of IL-1RA, we performed LLLT with interleukin-1 receptor antagonist (IL-1RA) neutralizing antibody (named Zol + LLLT + IL-1RA NAb group) or negative control antibodies for tooth extraction in subsequent rescue animal experiments. Stereoscope observations, micro-computed tomography, and histological examination were conducted to evaluate gingival wound healing and bone regeneration in tooth sockets. The effects of LLLT on the migration capacities of zoledronate-treated epithelial cells were assessed in vitro. RESULTS: LLLT promoted primary gingival wound healing without exposed necrotic bone. Micro-computed tomography results showed higher bone volume and mineral density of the tooth sockets after LLLT. Histology analysis showed complete gingival coverage, obvious bone regeneration, and reduced soft tissue inflammation, with down-regulated pro-inflammation cytokines, like interleukin-1 beta (IL-1ß) and tumor necrosis factor-α (TNF-α), and up-regulated IL-1RA expression in the gingival tissue in the LLLT group. The rescue assay further showed that the effects of LLLT promoting gingival wound healing and preventing MRONJ might be partially abolished by IL-1RA neutralizing antibodies. In vitro studies demonstrated that LLLT accelerated zoledronate-treated epithelial cell migration. CONCLUSIONS: LLLT might promote primary gingival wound healing and contribute to subsequent bone regeneration of the tooth extractions in MRONJ-like lesions via IL-1RA-mediated pro-inflammation signaling suppression.

Gallbladder Cancer Cell-Derived Exosome-Mediated Transfer of Leptin Promotes Cell Invasion and Migration by Modulating STAT3-Mediated M2 Macrophage Polarization.

Tumor-associated macrophage (TAM) is a major component of tumor microenvironment (TME) and plays critical role in the progression of cancer metastasis. However, TAM-mediated regulation in gallbladder cancer (GBC) has not been fully characterized. Here, we found that exosomes derived from GBC cell polarized macrophage to M2 phenotype, which then facilitated the invasion and migration of GBC cells. We discovered that leptin was enriched in GBC cell-derived exosomes. Exosomal leptin levels promoted invasion and migration of GBC-SD cells. The inhibition of leptin not only attenuated M2 macrophage of polarization but also inhibited the invasive and migratory ability of GBC cell. In addition, GBC-SD cell-derived exosomal leptin induced M2 polarization of macrophage via activation of STAT3 signal pathway. Taken together, our results suggested that GBC cells secrete exosome-enclosed leptin facilitated cell invasion and migration via polarizing TAM.

Application of Hyperspectral Imaging for Maturity and Soluble Solids Content Determination of Strawberry With Deep Learning Approaches.

Maturity degree and quality evaluation are important for strawberry harvest, trade, and consumption. Deep learning has been an efficient artificial intelligence tool for food and agro-products. Hyperspectral imaging coupled with deep learning was applied to determine the maturity degree and soluble solids content (SSC) of strawberries with four maturity degrees. Hyperspectral image of each strawberry was obtained and preprocessed, and the spectra were extracted from the images. One-dimension residual neural network (1D ResNet) and three-dimension (3D) ResNet were built using 1D spectra and 3D hyperspectral image as inputs for maturity degree evaluation. Good performances were obtained for maturity identification, with the classification accuracy over 84% for both 1D ResNet and 3D ResNet. The corresponding saliency maps showed that the pigments related wavelengths and image regions contributed more to the maturity identification. For SSC determination, 1D ResNet model was also built, with the determination of coefficient (R 2) over 0.55 of the training, validation, and testing sets. The saliency maps of 1D ResNet for the SSC determination were also explored. The overall results showed that deep learning could be used to identify strawberry maturity degree and determine SSC. More efforts were needed to explore the use of 3D deep learning methods for the SSC determination. The close results of 1D ResNet and 3D ResNet for classification indicated that more samples might be used to improve the performances of 3D ResNet. The results in this study would help to develop 1D and 3D deep learning models for fruit quality inspection and other researches using hyperspectral imaging, providing efficient analysis approaches of fruit quality inspection using hyperspectral imaging.

Adipose-Derived Stem Cells Promote Bone Coupling in Bisphosphonate-Related Osteonecrosis of the Jaw by TGF-ß1.

This study aimed to investigate molecularly targeted therapy to revive bone remodeling and prevent BRONJ by local adipose-derived stem cells (ADSCs) transplantation. Clinical samples of BRONJ and healthy jawbones were used to examine the bone coupling-related cells and TGF-ß1 expression. Bone coupling-related cells and TGF-ß1 expression were also assessed in BRONJ-like animal model to confirm the results in clinical samples. ADSCs were locally administered in vivo and the therapeutic effects were evaluated by gross observation, radiological imaging, and histological examination. Furthermore, ADSCs-conditioned medium (ADSCs-CM) and neutralizing antibody were applied to assess the effects of ADSCs-derived TGF-ß1 on restoring bone coupling in vivo. Osteoclast formation and resorption assays were performed to evaluate the effects of ADSCs-derived TGF-ß1 on ZA-treated pre-osteoclasts. Cell migration was performed to assess the effects of ADSCs-derived TGF-ß1 on patients' bone marrow stem cells (BMSCs). The number of osteoclasts, Runx2-positive bone-lining cells (BLCs) and TGF-ß1 expression were decreased in BRONJ and animal model jaw bone samples. These reductions were significantly rescued and necrotic jawbone healing was effectively promoted by local ADSCs administration in BRONJ-like animal models. Mechanistically, ADSCs-CM mainly contributed to promoting bone coupling, while TGF-ß1 neutralizing antibody in the conditioned medium inhibited these effects. Besides, osteoclastogenesis and patients' BMSCs migration were also rescued by ADSCs-derived TGF-ß1. Furthermore, bone resorption-released bone matrix TGF-ß1, together with ADSCs-derived TGF-ß1, synergistically contributed to rescuing BMSCs migration. Collectively, ADSCs promoted bone healing of BRONJ by TGF-ß1-activated osteoclastogenesis and BMSCs migration capacities.

Exosomes from Adipose-Derived Stem Cells Can Prevent Medication-Related Osteonecrosis of the Jaw.

The treatment measures of medication-related osteonecrosis of the jaw (MRONJ) is a worldwide challenge in oral and maxillofacial surgery because of its unclear pathogenesis. Previous studies suggested that mesenchymal stem cells played important roles in promoting MRONJ lesion healing, but the detailed mechanisms were unknown. Increasing numbers of studies have demonstrated that exosomes derived from mesenchymal stem cells, especially adipose-derived stem cells, have key roles in stem cell-based therapies by accelerating bone remodeling, facilitating angiogenesis, and promoting wound healing. We hypothesized that exosomes derived from adipose-derived stem cells can prevent MRONJ by accelerating gingival healing and enhancing bone remodeling processes. Our results may provide a promising therapeutic option for MRONJ clinical therapy.

Pathogenesis of traumatic temporomandibular joint ankylosis: a narrative review.

OBJECTIVE: To comprehensively review the literature and summarize the results from human and animal studies related to the possible causes and pathogenesis of traumatic temporomandibular joint ankylosis (TMJA). MATERIALS AND METHODS: The Google Scholar, Embase, and Web of Science databases were used to search for articles related to traumatic TMJA from 2011 to 2020. All articles were screened according to the inclusion and exclusion criteria, collected, and analyzed. RESULTS: Nineteen relevant articles were collected. These articles were classified into three groups: predisposing and etiological factors, cellular studies, and molecular studies. CONCLUSION: The pathological mechanisms are similar between TMJA and nonunion hypertrophy. Aberrant structural and etiological factors as well as disordered cellular and molecular mechanisms might contribute to TMJA formation. Although preclinical and clinical data have provided new evidence on the pathogenesis of traumatic TMJA, the molecular mechanisms and biological events require further exploration.

Corrigendum to "A Chemically Defined Serum-Free Culture System for Spontaneous Human Mesenchymal Stem Cell Spheroid Formation".

[This corrects the article DOI: 10.1155/2020/1031985.].

Depletion of the diabetic gut microbiota resistance enhances stem cells therapy in type 1 diabetes mellitus.

Microbiome, considered as the "second genome" of the host, is altered in type 1 diabetes mellitus (T1DM) patients to a state of dysbiosis. Mesenchymal stem cell (MSC) transplantation is a promising treatment for T1DM but is limited by several factors in the diabetic host. In this study, we tested the hypothesis that dysbiotic gut microbiota may limit MSC therapy, and modulating gut microbiota may help to improve the effects of MSC transplantation. Methods: NOD/Ltj mice, treated with adipose-derived stem cells (ADSCs), were fed with an antibiotics cocktails (Abx) for 1 week. The blood glucose levels, insulitis, intestinal permeability and gut bacteria translocation to the pancreas were evaluated. 16s rRNA and colon tissue transcription sequencing were performed to analyze beneficial bacteria and reactive host biomolecules in the ADSCs+Abx group. Based on the sequencing results, specific bacteria were gavaged orally to diabetic mice to confirm their effect on ADSCs transplantation in T1DM was determined. Results: We found that the recolonized the diabetic gut microbiota abolished the therapeutic effect of ADSCs. On the contrary, depletion of the diabetic gut microbiota by antibiotics treatment in diabetic mice significantly enhanced the therapeutic effects of ADSCs as measured by reversal of hyperglycemia, insulitis, and increased insulin output. Mechanistically, treatment with antibiotics increased the abundance of Bifidobacterium in the gut and reduced bacterial translocation to the pancreas by promoting Mucin2 expression and thickening the mucus layer through TRPM7. The mechanism was confirmed the re-colonization of the gut by B.breve through oral gavage that produced similar results. Conclusions: These results provide the rationale for a new approach to improve MSC therapy for T1DM by altering the gut microbiota.

A Chemically Defined Serum-Free Culture System for Spontaneous Human Mesenchymal Stem Cell Spheroid Formation.

Mesenchymal stem cells (MSCs) possess promising potential in tissue engineering and regenerative medicine. Previous studies demonstrated that spheroid formation of MSCs exhibited improved stemness maintenance and therapeutic potential compared with monolayer culture. To date, various spheroid culture systems have been developed but most of them required low adhesion conditions or special equipment. In this study, we demonstrated that inoculation of dissociated MSCs in TeSR-E8 medium could induce self-assemble spheroid formation in conventional tissue culture polystyrene dishes. Compared with monolayer culture, adipose-derived stem cell (ADSC) spheroids enhanced the proliferation and osteogenic capability of ADSCs compared with monolayer culture. When reseeded in normal serum-containing medium, the expression level of stemness biomarkers was even higher in spheroid-derived ADSCs than monolayer culture. Importantly, spheroid ADSCs could effectively promote the M2 polarization of macrophages both in vitro and in vivo. After transplantation into mouse, spheroid ADSCs improved the survival rate and significantly decreased serum levels of proinflammatory factors IL-1ß and TNF-α following LPS challenge. In summary, we developed a 3D spheroid culture system through TeSR-E8 medium without the involvement of low adhesion conditions and special equipment, which provided a practical and convenient method for spheroid formation of MSCs with great potential for stem cell clinical therapy.

Reducing macrophage numbers alleviates temporomandibular joint ankylosis.

Temporomandibular joint (TMJ) ankylosis is a severe joint disease mainly caused by trauma that leads to a series of oral and maxillofacial function disorders and psychological problems. Our series of studies indicate that TMJ ankylosis development is similar to fracture healing and that severe trauma results in bony ankylosis instead of fibrous ankylosis. Macrophages are early infiltrating inflammatory cells in fracture and play a critical role in initiating fracture repair. We hypothesize that the large numbers of macrophages in the early phase of TMJ ankylosis trigger ankylosed bone mass formation and that the depletion of these macrophages in the early phase could inhibit the development of TMJ ankylosis. By analysing human TMJ ankylosis specimens, we found large numbers of infiltrated macrophages in the less-than-1-year ankylosis samples. A rabbit model of TMJ bony ankylosis was established and large numbers of infiltrated macrophages were found at 4 days post-operation. Local clodronate liposome (CLD-lip) injection, which depleted macrophages, alleviated the severity of ankylosis compared with local phosphate-buffered saline (PBS)-loaded liposome (PBS-lip) injection (macrophage number, PBS-lips vs. CLD-lips: 626.03 ± 164.53 vs. 341.4 ± 108.88 n/mm2; ankylosis calcification score, PBS-lips vs. CLD-lips: 2.11 ± 0.78 vs. 0.78 ± 0.66). Histological results showed that the cartilage area was reduced in the CLD-lip-treated side (PBS-lips vs. CLD-lips: 6.82 ± 4.42% vs. 2.71 ± 2.78%) and that the Wnt signalling regulating cartilage formation was disrupted (Wnt5a expression decreased 60% and Wnt4 expression decreased 73%). Thus, our study showed that large numbers of macrophages infiltrated during the early phase of ankylosis and that reducing macrophage numbers alleviated ankylosis development by reducing cartilage formation.