The influence of tag sequence on recombinant humanized collagen (rhCol) and the evaluation of rhCol on Schwann cell behaviors.

Recombinant humanized collagen (rhCol) was an extracellular matrix (ECM)-inspired biomimetic biomaterial prepared by biosynthesis technology, which was considered non-allergenic and could possibly activate tissue regeneration. The influence of tag sequence on both structures and performances of rhCol type III (rhCol III) was investigated, and the effect of rhCol III on cell behaviors was evaluated and discussed using Schwann cells (SCs) as in vitro model that was critical in the repair process after peripheral nerve injury. The results demonstrated that the introduction of tag sequence would influence both advanced structures and properties of rhCol III, while rhCol III regulated SCs adhesion, spreading, migration and proliferation. Also, both nerve growth factor and brain-derived neurotrophic factor increased when exposed to rhCol III. As the downstream proteins of integrin-mediated cell adhesions, phosphorylation of focal adhesion kinase and expression of vinculin was up-regulated along with the promotion of SCs adhesion and migration. The current findings contributed to a better knowledge of the interactions between rhCol III and SCs, and further offered a theoretical and experimental foundation for the development of rhCol III-based medical devices and clinical management of peripheral nerve injury.

Novel Synthesis of C-Methylated Phytocannabinoids Bearing Anti-inflammatory Properties.

There is growing interest in non-psychoactive phytocannabinoids, namely cannabidiol (CBD), cannabigerol (CBG), and cannabichromene, as potential leads for novel therapeutic agents. In this study, we report on the development of new derivatives in which we methylated either position 4 of olivetol or the phenolic positions of olivetol, or both. We introduce a refinement on previously reported chemical procedures for phytocannabinoid derivatization as well as the biological evaluation of all derivatives in anti-inflammatory in vivo models. Compounds such as the CBD derivative, 2 and the CBG derivative, 11, significantly reduced cytokine levels when compared to their parent compounds. Moreover, both of these derivatives proved to be as potent as dexamethasone for the inhibition of IL-1ß. We believe that these new derivatives, as described herein, can be further developed as novel drug candidates for inflammatory conditions.

Recombination humanized type III collagen promotes oral ulcer healing.

OBJECTIVE: Recombinant humanized type III collagen (rhCol III) is a highly adhesive biomaterial composed of 16 adhesion-related tandem repeats refined from human type III collagen. Here, we aimed to investigate the effect of rhCol III on oral ulcers and reveal the underlying mechanism. METHODS: Acid-induced oral ulcers were induced on the murine tongue, and rhCol III or saline drops were administered. The effect of rhCol III on oral ulcers was assessed using gross and histological analyses. The effects on the proliferation, migration, and adhesion of human oral keratinocytes were investigated in vitro. The underlying mechanism was explored using RNA sequencing. RESULTS: Administration of rhCol III accelerated the lesion closure of oral ulcers, reduced the release of inflammatory factors, and alleviated pain. rhCol III promoted the proliferation, migration, and adhesion of human oral keratinocytes in vitro. Mechanistically, the enrichment of genes associated with the Notch signaling pathway was upregulated after rhCol III treatment. CONCLUSION: rhCol III promoted the healing of oral ulcers, showing promising therapeutic potential in oral clinics.

Modified Osteotome Sinus Floor Elevation Technique for Multiple Edentulous Spaces: A Non-Randomized Controlled Trial.

Objectives: We aimed to demonstrate our modified osteotome sinus floor elevation (OSFE) technique for placing two implants in multiple maxillary posterior edentulous spaces with residual bone height (RBH) < 5 mm, to evaluate the clinical effect and explore the prognosis. Methods: We identified 18 appropriate patients with RBH < 5 mm and 12 patients with RBH ≥ 5 mm. After drill preparation, variously shaped curettes were applied to adequately release the tension of the membrane around the cavity and between two implants by blunt dissection. Then, an osteotome was used to elevate the membrane to the desired height. After filling bone graft into the elevated space, dental implants were inserted. Cone-Beam Computed Tomography (CBCT) was performed after surgery and 6 months later. Results: The implant survival rate was 100%, and after the 6-month resorption, the height of the graft apically between the two implants gradually stabilized at 8.92 mm. Compared with 12 patients with RBH ≥ 5 mm, their graft bone resorption demonstrated no significant difference. Conclusions: It can be suggested that the modified OSFE technique could yield predictable clinical results for placing adjacent implants in patients with RBH less than 5 mm after six months of follow-up. Clinical Significance: Our modified OSFE technique could be applied to place adjacent implants in patients with RBH less than 5 mm, especially for elderly patients or patients with bone crests and vessels on the lateral wall, owing to its advantages including less trauma and fewer complications, minimizing the risk of membrane perforation, shortening the treatment period, avoiding another surgery area or second-stage surgery, improving not only the bone around the implant apex but also between implants, etc.

METTL3-mediated m6A RNA methylation regulates dorsal lingual epithelium homeostasis.

The dorsal lingual epithelium, which is composed of taste buds and keratinocytes differentiated from K14+ basal cells, discriminates taste compounds and maintains the epithelial barrier. N6-methyladenosine (m6A) is the most abundant mRNA modification in eukaryotic cells. How METTL3-mediated m6A modification regulates K14+ basal cell fate during dorsal lingual epithelium formation and regeneration remains unclear. Here we show knockout of Mettl3 in K14+ cells reduced the taste buds and enhanced keratinocytes. Deletion of Mettl3 led to increased basal cell proliferation and decreased cell division in taste buds. Conditional Mettl3 knock-in mice showed little impact on taste buds or keratinization, but displayed increased proliferation of cells around taste buds in a protective manner during post-irradiation recovery. Mechanically, we revealed that the most frequent m6A modifications were enriched in Hippo and Wnt signaling, and specific peaks were observed near the stop codons of Lats1 and FZD7. Our study elucidates that METTL3 is essential for taste bud formation and could promote the quantity recovery of taste bud after radiation.

CHD7 regulates bone-fat balance by suppressing PPAR-γ signaling.

Chromodomain helicase DNA-binding protein 7 (CHD7), an ATP-dependent eukaryotic chromatin remodeling enzyme, is essential for the development of organs. The mutation of CHD7 is the main cause of CHARGE syndrome, but its function and mechanism in skeletal system remain unclear. Here, we show conditional knockout of Chd7 in bone marrow mesenchymal stem cells (MSCs) and preosteoblasts leads to a pathological phenotype manifested as low bone mass and severely high marrow adiposity. Mechanistically, we identify enhancement of the peroxisome proliferator-activated receptor (PPAR) signaling in Chd7-deficient MSCs. Loss of Chd7 reduces the restriction of PPAR-γ and then PPAR-γ associates with trimethylated histone H3 at lysine 4 (H3K4me3), which subsequently activates the transcription of downstream adipogenic genes and disrupts the balance between osteogenic and adipogenic differentiation. Our data illustrate the pathological manifestations of Chd7 mutation in MSCs and reveal an epigenetic mechanism in skeletal health and diseases.

Advances in Chromodomain Helicase DNA-Binding (CHD) Proteins Regulating Stem Cell Differentiation and Human Diseases.

Background: Regulation of gene expression is critical for stem cell differentiation, tissue development, and human health maintenance. Recently, epigenetic modifications of histone and chromatin remodeling have been verified as key controllers of gene expression and human diseases. Objective: In this study, we review the role of chromodomain helicase DNA-binding (CHD) proteins in stem cell differentiation, cell fate decision, and several known human developmental disorders and cancers. Conclusion: CHD proteins play a crucial role in stem cell differentiation and human diseases.

Mapping the immune microenvironment for mandibular alveolar bone homeostasis at single-cell resolution.

Alveolar bone is the thickened ridge of jaw bone that supports teeth. It is subject to constant occlusal force and pathogens invasion, and is therefore under active bone remodeling and immunomodulation. Alveolar bone holds a distinct niche from long bone considering their different developmental origin and postnatal remodeling pattern. However, a systematic explanation of alveolar bone at single-cell level is still lacking. Here, we construct a single-cell atlas of mouse mandibular alveolar bone through single-cell RNA sequencing (scRNA-seq). A more active immune microenvironment is identified in alveolar bone, with a higher proportion of mature immune cells than in long bone. Among all immune cell populations, the monocyte/macrophage subpopulation most actively interacts with mesenchymal stem cells (MSCs) subpopulation. Alveolar bone monocytes/macrophages express a higher level of Oncostatin M (Osm) compared to long bone, which promotes osteogenic differentiation and inhibits adipogenic differentiation of MSCs. In summary, our study reveals a unique immune microenvironment of alveolar bone, which may provide a more precise immune-modulatory target for therapeutic treatment of oral diseases.

CHD7 Regulates Osteogenic Differentiation of Human Dental Follicle Cells via PTH1R Signaling.

Chromodomain helicase DNA-binding protein 7 (CHD7) is an ATP-dependent chromatin remodeling enzyme, functioning as chromatin reader to conduct epigenetic modification. Its effect on osteogenic differentiation of human dental follicle cells (hDFCs) remains unclear. Here, we show the CHD7 expression increases with osteogenic differentiation. The knockdown of CHD7 impairs the osteogenic ability of hDFCs, characterized by reduced alkaline phosphatase activity and mineralization, and the decreased expression of osteogenesis-related genes. Conversely, the CHD7 overexpression enhances the osteogenic differentiation of hDFCs. Mechanically, RNA-seq analyses revealed the downregulated enrichment of PTH (parathyroid hormone)/PTH1R (parathyroid hormone receptor-1) signaling pathway after CHD7 knockdown. We found the expression of PTH1R positively correlates with CHD7. Importantly, the overexpression of PTH1R in CHD7-knockdown hDFCs partially rescued the impaired osteogenic differentiation. Our research demonstrates that CHD7 regulates the osteogenic differentiation of hDFCs by regulating the transcription of PTH1R.

Clinical evidence of photobiomodulation therapy (PBMT) on implant stability and success: a systematic review and meta-analysis.

BACKGROUND: Photobiomodulation therapy (PBMT), a type of light therapy that uses the concept of photobiomodulation, is developed to promote bone healing. Clinical studies have been conducted to assess the influence of PBMT on dental implant stability and success rate. This is the first systematic review and meta-analysis to assess the effect of PBMT and methodological quality of these studies on implants in human clinical trials. METHODS: An electronic search was performed in Pubmed, Embase, and the Cochrane Controlled Register of Trials (CENTRAL). RESULTS: Initially, 675 articles were identified, among which only 8 met the inclusion criteria. Four of the 8 studies presented a low risk of bias, whereas the other 4 were of moderate risk. Our review focused on implant success rates and implant stability measured at days 0 and 10, and at 3, 4, 6, and 12 weeks. No significant differences were observed between the PBMT group and the control group regarding implant stability or success rate. CONCLUSIONS: The existing clinical studies did not provide sufficient evidence to observe positive effects of PBMT on implants in patients. An increased number of high-quality clinical randomized controlled trials (RCTs) are required to verify the data and to draw convincing conclusions.

Tumor characteristics and surgical outcome in incidentally discovered pheochromocytomas and paragangliomas.

OBJECTIVE: The proportion of incidentally discovered pheochromocytomas and paragangliomas(PPGL) has increased over time. However, our knowledge of them is quite limited. The purpose of this retrospective study is to generalize the commonalities in incidentally discovered PPGL, offer evidences for clinical diagnosis and management. METHODS: 526 patients were included in our study after filtration from the database of West China Hospital of Sichuan University between May, 2007 and December, 2016.Among the patients, 148 of them were incidental findings and 378 of them were suspected findings. All patients' demography and tumor characteristics were recorded in detail, especially hemodynamic records and hormonal assays. The reasons for taking radiography were also collected. Most patients received preoperative medical preparation . Intraoperative and postoperative courses as well as surgical outcomes were also analyzed to identify differences between incidental findings and suspected findings. RESULTS: Incidentally discovered PPGL took up 28.1% of the study population. Suspected PPGLs had a higher prevalence of hypertension, lower proportion of non-functioning PPGL, higher prevalence of MEN2 and better post-surgical blood pressure recovery than incidental finding group. However, patients in the incidental finding group showed no significant difference in preoperative blood pressure and hormonal assays with suspected findings in metaphrine and normetaphrine in plasma and urine (P>0.05). CONCLUSIONS: Due to the development of technology, more PPGLs are discovered incidentally. Considering the tumor characteristics and surgical outcome, surgical decisions should be made more cautiously.

Preoperative selective vs non-selective α-blockade in PPGL patients undergoing adrenalectomy.

PURPOSE: Preoperative preparation for adrenalectomy for pheochromocytomas and paragangliomas (PPGL) is universally recognized as necessary, while the optimal strategy remains controversial. Our aims were to increase intraoperative hemodynamic stability, expedite postoperative recovery, decrease side effects and reduce costs for patients with PPGL undergoing adrenalectomy. METHODS: We identified 526 patients undergoing open adrenalectomy for PPGL in the West China Hospital of Sichuan University between May, 2007 and December, 2016. 149 patients received preoperative selective α-blockade with phenoxybenzamine, and 377 patients received non-selective α-blockade with prazosin, doxazosin or terazosin. There were no statistical differences between groups regarding preoperative patient and tumor characteristics. Operations were planned once hypertensive patients were well-controlled with blood pressure ≤130/85 mmHg. Intraoperatively, all patients received arterial blood pressure monitoring, and indwelling urinary catheters to record urine output. We recorded intraoperative hemodynamics, status in the postanesthesia or intensive care unit, postoperative recovery and complications. RESULTS: Patients in the non-selective group showed a more significant decline in postoperative systolic blood pressure than the selective group (P = 0.041). Also, patients in the non-selective group appeared to receive a long-term anti-hypertensive effect, especially for diastolic blood pressure (P = 0.037), which was a novel finding, based on the current literature. CONCLUSIONS: Our results confirmed that non-selective α-blockade produced a more significant anti-hypertensive effect than selective α-blockade. However, we found no significant difference in intraoperative hemodynamic instability, postoperative recovery and postoperative complications between groups.