Comparative Study of the Efficacy of Autologous Tooth Bone Powder and Inorganic Bovine Bone Powder on the Repair of Jaw Defects.

Context: The main pathological features of jaw cysts are bone defects. Obtaining autologous bone for transplantation repair has been associated with postoperative complications, and the amount of bone that dentist can collect is limited. Studies have found that autologous tooth bone powder is safe and has good bone-formation ability and stability. Objective: The study intended to examine the efficacy of implantation of autologous tooth bone powder and inorganic bovine bone powder, after marsupialization and second-stage curettage for large jaw cysts that dentist can't directly remove by surgery in clinical practice. Design: The research team designed a prospective randomized controlled trial. Setting: The study took place in the Head and Neck Surgery Department at Chongqing University Cancer Hospital in Chongqing, China. Participants: Participants were 60 patients at the hospital between 2016 and 2018 who had mandibular cysts that surgical operation couldn't directly remove by surgery in clinical practice. Intervention: At 4 months after curettage, the research team randomly divided participants into three groups: (1) an intervention group who received implants of autologous tooth bone powder into the bone defects, (2) a positive control group who received implants of inorganic bovine bone powder, and (3) a negative control group who received no implants of any material. Outcome Measures: The research team performed: (1) periodontal probing at a fixed anatomical point for the intervention and both control groups postintervention at one day and 4 months after surgery and recorded the changes in probing depth and (2) computed tomography (CT) scans at baseline one day before and postintervention at 4 months after the implantation to determine changes in the bone mineral density and compared them among the three groups. Results: The change in the height of the intervention group's fixed anatomical point postintervention at 4 months after surgery was significantly smaller than that of the positive control group (P < .05). In the CT scan analysis, the differences between the intervention and negative control groups and between the positive and negative control groups were statistically significant (P < .05); however, the difference between the intervention and positive control groups wasn't significant (P > .05). Conclusions: Autologous tooth bone powder and inorganic bovine bone powder can effectively repair bone defects caused by large jaw cysts and that the repaired effect may be better than that of spontaneous osteogenesis. The autologous tooth bone powder was associated with lower levels of bone loss than those seen with use of inorganic bovine bone powder.

Discovery of Mycothiogranaticins from Streptomyces vietnamensis GIMV4.0001 and the Regulatory Effect of Mycothiol on the Granaticin Biosynthesis.

Granaticins are benzoisochromanequinone polyketides with remarkable antibacterial and anticancer activities. Three sulfur-containing granaticin congeners, mycothiogranaticins A (1), B (2) and granaticin MA (3) were discovered from a granaticin-producing strain of Streptomyces vietnamensis GIMV4.0001. Two of them were structurally determined with mycothiol or N-acetylcysteine moieties and found to be bio-actively reluctant. Disruption of the mshA gene (SVTN_RS20640) that encodes the D-inositol-3-phosphate glycosyltransferase crucial for mycothiol biosynthesis, fully abolished the production of mycothiogranaticins. The result substantiated that the newly discovered mycothiogranaticins are consequences of the combination of the granaticin and mycothiol biosynthetic pathways. The overall granaticin production of the ΔmshA mutant strain was unexpectedly decreased by at least more than 50%, while similar production level of granaticins to that of the wild type strain was observed in an mycothiol-S transferase gene (SVTN_RS22215) disruptant Δmst. These results indicated that the mycothiol deficiency was responsible for the decreased production of granaticins. Mycothiol may positively regulate the biosynthesis of granaticin possibly by maintaining the cellular redox balance. To the best of our knowledge, this is the first report that mycothiol can not only be a direct building block of polyketides but also play a regulatory role in the polyketide biosynthesis.

The different role of YKL-40 in glioblastoma is a function of MGMT promoter methylation status.

Inter- and intratumoral heterogeneity is a hallmark of glioblastoma (GBM) that facilitates recurrence, treatment resistance, and worse prognosis. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is a significant prognostic marker for Temozolomide (TMZ) resistance in GBM patients. YKL-40 is a molecular marker for the mesenchymal subtype of GBMs and is responsible for TMZ resistance. However, underlying mechanisms by which MGMT epigenetics impacts patient outcomes and the function of YKL-40 are not fully determined. Herein, we performed in vitro and in vivo experiments, six human IDH1/2 wild-type glioblastoma stem-like cells (GSCs) were established and studied to further determine a potential interaction of YKL-40 and MGMT promoter methylation. We demonstrated that YKL-40 functioned differently in human IDH1/2 wild-type GSCs. In MGMT promoter-methylated (MGMT-m) GSCs, it acted as a tumor suppressor gene. On the other hand, in MGMT promoter-unmethylated (MGMT-um) GSCs, it promoted tumorigenesis. Notably, the reason that YKL-40 played different roles in GSCs could not be interpreted by the molecular classification of each GSCs, but is a function of MGMT promoter methylation status and involves the RAS-MEK-ERK pathway. YKL-40 mediated TMZ sensitivity by activating DNA damage responses (DDRs) in MGMT-m GSCs, and it mediated resistance to TMZ by inhibiting DDRs in MGMT-um GSCs. Our report demonstrated that MGMT promoter methylation status might influence a gene's function in human cancer. Moreover, our data also highlight the point that gene function should be investigated not only according to the molecular tumor classification, but also the epigenetic signature.

The Role of NF-κB in Chronic Rhinosinusitis With Nasal Polyps.

PURPOSE: Whereas the majority of nasal polyps observed in Western populations are eosinophilic, non-eosinophilic nasal polyps are significantly more frequent in Asian countries. Given the importance of nuclear factor-kappa B (NF-κB) in inflammation, this study focused on the role of NF-κB in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNPs) in Asian patients. METHODS: A total of 46 patients were enrolled in this study (22 diagnosed with CRSwNPs, 10 with chronic rhinosinusitis without nasal polyps [CRSsNP], and 14 control subjects). Nasal polyps and uncinate tissues (UTs) were collected and the tissues prepared for hematoxylin-eosin staining and immunohistochemistric (IHC) analysis. Total RNA was isolated for real-time polymerase chain reaction for p65, interleukin (IL)-6, IL-8, intracellular adhesion molecule (ICAM)-1, IL-1ß, tumor necrosis factor (TNF)-α, and eotaxin. RESULTS: In the CRSwNPs group, 50% of nasal polyps were non-eosinophilic. IHC revealed a significantly higher fraction of NF-κB p65-positive cells in nasal polyps of the CRSwNPs group than in the UTs of control and CRSsNP groups. No difference in NF-κB p65-positive cell fraction was observed between eosinophilic and non-eosinophilic nasal polyps. The mRNA expression of p65, IL-6, IL-8, and eotaxin was significantly higher in nasal polyps of the CRSwNPs than in the UTs of control and CRSsNP group. However, no difference in expression was observed between eosinophilic and non-eosinophilic nasal polyps, with the exception of IL-1ß expression. CONCLUSIONS: Elevated expression of NF-κB- and NF-κB-associated inflammatory cytokines suggests NF-κB as the key factor for CRSwNPs pathogenesis in Asian patients. Understanding NF-κB-associated mechanisms will provide a deeper insight into CRSwNPs pathogenesis and ultimately improve therapeutic strategies for CRSwNPs.

Antiallergic Effect of Hizikia fusiformis in an Ovalbumin-Induced Allergic Rhinitis Mouse Model.

OBJECTIVES: The extract of Hizikia fusiformis is known to exhibit anticancer, antiatopic and antioxidant activities. We aimed to investigate the extract of H. fusiformis on allergic rhinitis inflammation in a mouse model. METHODS: The 4-week-old BALB/c mice were randomly assigned into four groups: group A, control group (n=9); group B, allergic rhinitis group (n=10); group C (n=10) received 300 mg/kg of H. fusiformis during nasal challenging period; group D (n=10) received 600 mg/kg of H. fusiformis during general sensitization period and 300 mg/kg of H. fusiformis during nasal challenging period. Allergic inflammation was made with ovalbumin (OVA) and alum then challenged intranasally with OVA. H. fusiformis was intraperitoneally administered 3 hours before the OVA administration. Allergic symptom score and the levels of immunoglobulin G1 (IgG1), IgG2a, OVA-specific IgE antibodies, levels of cytokines in the nasal mucosa and in spleen cell culture supernatant, such as tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4), IL-5, IL-13, and IL-10 were assessed. The percentage of regulatory T cell was analyzed by flow cytometry. Eosinophilic infiltration and goblet cell hyperplasia were also evaluated. RESULTS: H. fusiformis administered groups C and D showed significant inhibitory effects on nasal symptoms, IL-13 mRNA expression and eosinophil infiltration/goblet cell hyperplasia in the nasal tissue; OVA-specific IgE production in serum (P<0.05). In group D, H. fusiformis treatment downregulated IL-4, IL-5, IL-13, TNF-α, and IL-10 cytokine expression in splenocyte culture as well as significantly decreased IgG2a, IgG1 levels in serum compared with group B (P<0.05). However, the expressions of IL-5, interferon-γ and forkhead box P3 mRNA did not change in groups C and D. CONCLUSION: H. fusiformis could induce antiallergic inflammation by suppressing the T-helper type 2 cytokine production (IL-13) locally and systemically, OVA-specific IgE formation, goblet cell hyperplasia, and eosinophilic infiltration in a mouse model of allergic rhinitis. Thus, H. fusiformis could be considered as a potential therapeutic agent in treating allergic rhinitis.

Healing of the nasal septal mucosa in an experimental rabbit model of mucosal injury.

OBJECTIVE: The aim of this study was to investigate the regeneration process of the nasal mucosa after a surgically created mucosal defect in the rabbit nasal septum, and to evaluate the effects of different interventions. METHODS: A 7 mm-diameter circular mucosal defect was made in the septum of forty New Zealand white rabbits. The rabbits were divided into four groups (ten rabbits in each group) according to the type of intervention; no treatment (control), silastic sheet (SS), hyaluronic acid (HA), and silastic sheet and hyaluronic acid (SS + HA) group. The diameter of the defect, mucosal thickness, epithelial thickness, and ciliated cell count were evaluated every week for five weeks. RESULTS: The average diameter of the defect in the control group were 5.1, 3.65, 1.2, 0.75, and 0.05 mm at postoperative 1, 2, 3, 4, and 5 weeks. In the SS group, the diameter decreased to 4.35, 2.1, 0.35, 0.15, and 0 mm at postoperative 1, 2, 3, 4, and 5 weeks, respectively, in which the mean diameter of the postoperative week 2 was significantly smaller compared to control (3.65 mm vs. 2.1 mm, P = 0.039). For the HA group and SS + HA group, the diameter of the defect did not show a significant difference from the control group during the five weeks. The mucosal thickness, epithelial thickness, and ciliated cell count of the regenerated mucosa were not significantly different among the groups. CONCLUSION: The regeneration process of the nasal septal mucosa was identified using a novel rabbit model. Mucosal regeneration can be accelerated by applying silastic sheets.

Role of Interleukin-17A on the Chemotactic Responses to CCL7 in a Murine Allergic Rhinitis Model.

BACKGROUND: The proinflammatory cytokine interleukin (IL)-17A is associated with eosinophil infiltration into the nasal mucosa in a mouse model of ovalbumin-induced allergic rhinitis. Chemotaxis of eosinophils is mediated primarily through C-C chemokine receptor type 3 (CCR3). However, the mechanism underlying the IL-17A-mediated enhancement of eosinophil recruitment via chemoattractants/chemokines remains unknown. OBJECTIVES: In this study, we assessed the contribution of IL-17A to eosinophil-related inflammation via the CCL7/CCR3 pathway in experimental allergic rhinitis. METHODS: IL-17A knockout (KO) and wild-type (WT) BALB/c mice were injected intraperitoneally and challenged intranasally with OVA to induce allergic rhinitis. Various parameters of the allergic response were evaluated, and mRNA and protein levels of CCL7 and CCR3 in nasal tissue and serum were compared between the two groups. The chemotactic response to CCL7 with or without IL-17A in bone marrow-derived eosinophils (bmEos) from BALB/c mice was measured. RESULTS: In the allergic rhinitis model, IL-17A deficiency significantly decreased nasal symptoms, serum IgE levels, and eosinophil recruitment to the nasal mucosa. CCL7 and CCR3 mRNA and protein levels were decreased in the nasal mucosa of IL-17A KO mice compared with the WT mice. BmEos showed a significantly increased chemotactic response to -low concentration of CCL7 in the presence of IL-17A compared with its absence. CONCLUSION: The suppression of nasal inflammation due of IL-17A deficiency in allergic rhinitis is partly responsible for the regulation of CCL7 secretion and eosinophil infiltration, which may be regulated via the CCL7/CCR3 pathway.

Interleukin-17A-induced inflammation does not influence the development of nasal polyps in murine model.

BACKGROUND: Nasal polyposis associated with chronic rhinosinusitis (CRS) is a chronic inflammatory disease that is characterized by infiltration of many inflammatory cells. Meanwhile, interleukin (IL)-17A is a well-known proinflammatory cytokine that induces both eosinophilic and neutrophilic inflammation. We investigated the role of IL-17A in the development of nasal polyps in the CRS murine model. METHODS: Eosinophilic CRS with nasal polyps was induced by using ovalbumin (OVA) and Staphylococcus aureus enterotoxin B (SEB) in wild-type BALB/c and IL-17A knockout (KO) mice. Histopathologic changes of the sinonasal cavity were evaluated using hematoxylin and eosin, Periodic acid-Schiff, Sirius red, Masson's trichrome, and immunohistochemistry. The levels of total and OVA-specific immunoglobulin Es (IgEs) in sera were measured using enzyme-linked immunosorbent assay. The expression levels of IL-4, IL-5, and interferon-γ (IFN-γ) in the nasal mucosa were assessed by quantitative real-time polymerase chain reaction. RESULTS: Under the IL-17A deficiency, total and OVA-specific IgEs in sera were reduced significantly. Infiltration of both eosinophils and neutrophils into the nasal mucosa, subepithelial fibrosis, and goblet cell count also decreased significantly in IL-17A KO mice treated with both OVA and SEB compared with those in the wild-type counterpart. However, there were no significant differences in the number of polypoid lesions among groups. Meanwhile, IL-4 increased and IFN-γ decreased in the nasal mucosa in IL-17A KO mice treated with both OVA and SEB. CONCLUSION: This study suggests that even though IL-17A plays an important role in both nasal inflammation and remodeling, it does not influence the development of nasal polypoid lesions.

Application of self-retaining bidirectional barbed absorbable suture in retroperito- neoscopic partial nephrectomy.

OBJECTIVE: To investigate the safety and feasibility of self-retaining bidirectional barbed absorbable suture application in retroperitoneoscopic partial nephrectomy. MATERIALS AND METHODS: From Sep 2011 and Aug 2012, 76 cases of retroperitoneoscopic partial nephrectomy were performed at our hospital. The patients were divided into two groups: self-retaining barbed suture (SRBS) group (n = 36) and non-SRBS group (n = 40). There was no significant difference in age, sex, tumor size and location between the two groups. Clinical data and outcomes were analyzed retrospectively. RESULTS: All 76 cases of retroperitoneoscopic partial nephrectomy were successfully performed, without conversion to open surgery or serious intraoperative complications. In the SRBS group, the suture time, warm ischemia time and operation blood loss were significantly shorter than that of non-SRBS group (p < 0.01), and operation time and hospital stay were shorter than that of non-SRBS group (p < 0.05). CONCLUSIONS: The application of self-retaining bidirectional barbed absorbable suture in retroperitoneoscopic partial nephrectomy could shorten suture time and warm ischemia time, with good safety and feasibility, worthy of being used in clinic.

Contribution of interleukin 17A to the development and regulation of allergic inflammation in a murine allergic rhinitis model.

BACKGROUND: Interleukin (IL) 17A, a key cytokine of T(H)17 cells, is a well-known proinflammatory cytokine. Despite the important role of T(H)17 cells in acute airway inflammation, the role of IL-17A in allergic rhinitis (AR) remains unclear. OBJECTIVE: To investigate the role of IL-17A in the allergic response in AR. METHODS: Wild-type BALB/c and IL-17A-deficient mice were immunized intraperitoneally and were challenged intranasally with ovalbumin. Allergic symptom scores, eosinophil infiltration, serum IgE level, and the levels of several cytokines in nasal lavage fluid and splenocyte supernatants were analyzed. RESULTS: IL-17A levels increased significantly more in ovalbumin-sensitized wild-type mice than in the negative control group. IL-17A-deficient mice showed a significant decrease in allergic symptoms, serum IgE levels, and eosinophil infiltration into the nasal mucosa compared with wild-type mice. IL-17A-deficient mice also showed decreased histamine and cysteinyl leukotriene release. Bone marrow-derived mast cells from IL-17A-deficient mice showed significantly lower degranulation and secretion of tumor necrosis factor α. Moreover, IL-17A deficiency attenuated the IL-5 level in nasal lavage fluid and its production in response to ovalbumin but did not increase interferon γ production and its level in nasal lavage fluid. In addition, secretion of IL-17A from spleen cells induced the expression of proinflammatory cytokine messenger RNA in macrophages. The mean level of proinflammatory cytokines, including tumor necrosis factor α and IL-17, decreased in IL-17A-deficient mice. CONCLUSION: These results suggest that IL-17A may partly contribute to the development of nasal allergic inflammation in an AR animal model and regulate AR via the activation of proinflammatory cytokines and modulation of T(H)2 cytokine.

[Investigation of health status of workers exposed to low concentration cadmium in a zinc powder factory].

OBJECTIVE: To explore the health status of workers exposed to Cd at low concentration. METHODS: One hundred eighteen workers of zinc powder finishing and 34 staffs were served as the exposure group and control group, respectively. The physical examination, blood cadmium, urinary cadmium, blood lead, urinary 32-microglobin, urine creatine, chest film, pulmonary function , pure tone teat and were detected for all subjects. RESULTS: Twelve air samples from 6 monitoring points in workshop were detected, the air Cd concentrations were 0.002-0.015 mg/m³, which were under the national limit of occupational exposure. In exposure group, the rates of exceeding standards of blood Cd and urinary Cd were 65.25% and 38.16%, respectively, the rate of exceeding standards of urinary Cd for two times was 27.12%, the rate of exceeding standard of urine Cd for two times plus the positive urinary 32-microglobin was 2.54 %. In control group, the rates of exceeding national standard of blood Cd was 26.47 %, but the values of urinary Cd were normal. In exposure group, the rate of exceeding standards of urinary Cd increased with the service length. Smoking could enhance the rates of exceeding standards of blood Cd and urinary Cd. CONCLUSION: In zinc powder finishing, the low-concentration cadmium exposure could cause the occupational cadmium poisoning, the comprehensive protection measures can reduce the occupational cadmium poisoning. It is suggested that the limits of occupational exposure to cadmium should be declined.

[Analysis of urine cadmium and blood cadmium of workers before and after the cadmium dust control].

OBJECTIVE: To analyze the urinary cadmium, blood cadmium and urinary beta2-MG of workers in a zinc powder processing plant before and after the cadmium dust control, and to explore the effects of dust control on the prevention and treatment of cadmium hazards. METHODS: The on-site occupational hazard survey was used to investigate the changes of urine cadmium, blood cadmium and beta3-MG of 84 workers exposed to cadmium before and after the treatment by self-control analysis for evaluating the effects of dust control measures in a zinc powder processing plant. RESULTS: After treatment of the cadmium dust, the geometric mean of zinc dust in the workplace significantly decreased from 3.38 mg/m3 to 2.22 mg/m3 (P < 0.01). The geometric mean concentration of blood cadmium [(2.19 +/- 1.19) microg/L] and urine cadmium [(1.96 +/- 0.74) microg/g Cr] before treatment were significantly higher than those of one year [(1.63 +/- 0.83) microg/L] and [(1.25 +/- 0.83) microg/g Cr] and two years [(1.36 +/- 0.95) microg/L] and [(0.94 +/- 0.72) microg/g Cr] after the cadmium dust control (P < 0.01), respectively. The positive correlations analysis between urine cadmium and blood cadmium concentration of one and two years before and after the cadmium dust treatment implied that there was significant difference (r = 0.466, P < 0.01). CONCLUSION: Dust treatment could reduce the impact of low concentration cadmium on the urine cadmium and blood cadmium concentrations of the workers exposed to cadmium, and effectively prevent the cadmium poisoning.

Biphasic electric current stimulates proliferation and induces VEGF production in osteoblasts.

This study investigated biphasic electric current (BEC) functions as a new type of electrical stimulation to induce rat calvarial osteoblasts to proliferate, differentiate and synthesize cytokines. The culture system was designed so that biphasic current flowed between upper and lower gold plates. BEC helps to minimize the net charge accumulation during cell exposure to the electrical stimulation. Osteoblasts were exposed to electrical stimulation of 1.5 microA/cm2 at 3000 Hz, and the effect of BEC was assessed in the interrupted mode (6 h daily) and in the continuous mode (24 h daily), depending on the interval of stimulation. Whereas proliferation increased by 31% after stimulation in the continuous mode for 2 days, it was unaffected in the interrupted mode. The transcriptional expression of osteogenesis-related genes such as alkaline phosphatase (ALP), osteopontin, and type I collagen was unchanged 4 days after stimulation in both modes, while cbfa1 was decreased under the same conditions. There was no detectable change in mRNA expression of growth factors (BMP-2, -4, IGF-2 and TGF-beta1) that promote osteoblast differentiation. However, real-time RT-PCR and ELISA demonstrated that vascular endothelial growth factor (VEGF) was markedly up-regulated by BEC. Induction of VEGF by BEC was not hypoxia driven. In conclusion, the present in vitro study demonstrates that BEC increases cell proliferation and induces the production of VEGF. The BEC was more effective with continuous stimulation than with interrupted stimulation. To confirm whether BEC can enhance osteogenesis, further in vivo studies are needed.