mtDNA Maintenance and Alterations in the Pathogenesis of Neurodegenerative Diseases.

Considerable evidence indicates that the semiautonomous organelles mitochondria play key roles in the progression of many neurodegenerative disorders. Mitochondrial DNA (mtDNA) encodes components of the OXPHOS complex but mutated mtDNA accumulates in cells with aging, which mirrors the increased prevalence of neurodegenerative diseases. This accumulation stems not only from the misreplication of mtDNA and the highly oxidative environment but also from defective mitophagy after fission. In this review, we focus on several pivotal mitochondrial proteins related to mtDNA maintenance (such as ATAD3A and TFAM), mtDNA alterations including mtDNA mutations, mtDNA elimination, and mtDNA release-activated inflammation to understand the crucial role played by mtDNA in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Our work outlines novel therapeutic strategies for targeting mtDNA.

Mesenchymal Stem Cell Therapy: A Potential Treatment Targeting Pathological Manifestations of Traumatic Brain Injury.

Traumatic brain injury (TBI) makes up a large proportion of acute brain injuries and is a major cause of disability globally. Its complicated etiology and pathogenesis mainly include primary injury and secondary injury over time, which can cause cognitive deficits, physical disabilities, mood changes, and impaired verbal communication. Recently, mesenchymal stromal cell- (MSC-) based therapy has shown significant therapeutic potential to target TBI-induced pathological processes, such as oxidative stress, neuroinflammation, apoptosis, and mitochondrial dysfunction. In this review, we discuss the main pathological processes of TBI and summarize the underlying mechanisms of MSC-based TBI treatment. We also discuss research progress in the field of MSC therapy in TBI as well as major shortcomings and the great potential shown.

Ion Channel Dysfunction in Astrocytes in Neurodegenerative Diseases.

Astrocytes play an important role in the central nervous system (CNS). Ion channels in these cells not only function in ion transport, and maintain water/ion metabolism homeostasis, but also participate in physiological processes of neurons and glial cells by regulating signaling pathways. Increasing evidence indicates the ion channel proteins of astrocytes, such as aquaporins (AQPs), transient receptor potential (TRP) channels, adenosine triphosphate (ATP)-sensitive potassium (K-ATP) channels, and P2X7 receptors (P2X7R), are strongly associated with oxidative stress, neuroinflammation and characteristic proteins in neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). Since ion channel protein dysfunction is a significant pathological feature of astrocytes in neurodegenerative diseases, we discuss these critical proteins and their signaling pathways in order to understand the underlying molecular mechanisms, which may yield new therapeutic targets for neurodegenerative disorders.

Mitochondrial Behavior in Axon Degeneration and Regeneration.

Mitochondria are organelles responsible for bioenergetic metabolism, calcium homeostasis, and signal transmission essential for neurons due to their high energy consumption. Accumulating evidence has demonstrated that mitochondria play a key role in axon degeneration and regeneration under physiological and pathological conditions. Mitochondrial dysfunction occurs at an early stage of axon degeneration and involves oxidative stress, energy deficiency, imbalance of mitochondrial dynamics, defects in mitochondrial transport, and mitophagy dysregulation. The restoration of these defective mitochondria by enhancing mitochondrial transport, clearance of reactive oxidative species (ROS), and improving bioenergetic can greatly contribute to axon regeneration. In this paper, we focus on the biological behavior of axonal mitochondria in aging, injury (e.g., traumatic brain and spinal cord injury), and neurodegenerative diseases (Alzheimer's disease, AD; Parkinson's disease, PD; Amyotrophic lateral sclerosis, ALS) and consider the role of mitochondria in axon regeneration. We also compare the behavior of mitochondria in different diseases and outline novel therapeutic strategies for addressing abnormal mitochondrial biological behavior to promote axonal regeneration in neurological diseases and injuries.

Assessment of implant cumulative survival rates in sites with different bone density and related prognostic factors: an 8-year retrospective study of 2,684 implants.

PURPOSE: This retrospective study was set to explore the influence of local bone density (BD) on implant cumulative survival rates (ICSRs) and to assess prognostic factors associated with implant failure at sites with different BD. MATERIALS AND METHODS: Between January 2005 and December 2011, 2,684 implants were placed in 1,377 patients and included in the study. Implants at sites with different BD were divided into four groups (G1 to G4) according to the Lekholm and Zarb classification, corresponding to bone types 1 to 4. ICSRs and the reasons for failure in each group were evaluated. Factors related to the local distribution of BD were also analyzed. A number of predictive variables were examined by univariate and multivariate analyses to evaluate prognostic factors and their influence on implant failure rates. RESULTS: In total, 45 implants were lost, resulting in ICSRs for G1 to G4 of 100%, 98.18%, 96.83%, and 92.25%, respectively. The main reasons for failure in each group were failed osseointegration and occlusal overloading. Low BD was associated with advanced age (> 50 years) and the posterior maxilla. Based on multivariate analysis, diabetes mellitus and nonthreaded implants were significant factors in the high-BD group (G2), while advanced age, smoking, nonthreaded implants, and immediate loading were risk factors for the low-BD group (G3 and G4). CONCLUSION: BD is one of the most important factors influencing the long-term ICSR, which decreases with decreasing BD values. Accurate risk evaluation for sites with different BD before implantation will be beneficial to implant survival.

Dormancy activation mechanism of oral cavity cancer stem cells.

Radiotherapy and chemotherapy are targeted primarily at rapidly proliferating cancer cells and are unable to eliminate cancer stem cells in the G0 phase. Thus, these treatments cannot prevent the recurrence and metastasis of cancer. Understanding the mechanisms by which cancer stem cells are maintained in the dormant G0 phase, and how they become active is key to developing new cancer therapies. The current study found that the anti-cancer drug 5-fluorouracil, acting on the oral squamous cell carcinoma KB cell line, selectively killed proliferating cells while sparing cells in the G0 phase. Bisulfite sequencing PCR showed that demethylation of the Sox2 promoter led to the expression of Sox2. This then resulted in the transformation of cancer stem cells from the G0 phase to the division stage and suggested that the transformation of cancer stem cells from the G0 phase to the division stage is closely related to an epigenetic modification of the cell.

[A clinical retrospective analysis of dental implants replaced in previously failed sites].

PURPOSE: To evaluate the clinical outcomes as well as related factors of dental implants replaced in previously failed sites. METHODS: A total of 12 patients (15 implants) who received replacement in previously failed sites during January 2005 to December 2011 were included. Outcomes of redo-implants were collected and clinical data was recorded and analyzed regarding risk factors related to redo-implants' survival using SPSS13.0 software package. RESULTS: The survival rate of redo-implants was 100% [(33.5±15.4) months]. The mean redo-implant diameter (4.5±0.6) mm was significantly larger than the previous one (4.1±0.7) mm (P<0.05). The mean survival time of implants placed for the first time was (12.9±15.9) months. Implant replacement occurred (6.8±4.4) months after original implant removal. No significant influence was observed on patient and implant-related factors as well as surgery and prosthesis-dependent factors. CONCLUSIONS: Reimplantation in previously failed site is considered as one of feasible prosthesis plans, and surgeons ought to get enough confidence to achieve satisfactory implant survival rates. Supported by Liaoning Provincial Natural Science Foundation (20092093), Liaoning Provincial Science and Technology Foundation (2012225090), and Shenyang Science and Technology Foundation (F11-264-1-25, F12-277-1-18).

[An assessment of different crown-to-implant ratio for implant teeth in the posterior region over 5 years].

PURPOSE: To evaluate the influence of crown-to-implant ratio (C/I ratio) on the results of restoration in the posterior region. METHODS: From January 2007 to January 2012,119 patients with 208 ITI implants in the posterior region were followed up for 6-66 months. Implant restorations were divided into three groups according to their respective clinical C/I ratios after noble porcelain-fused-to-mental crown restoration: C/I ≤1,11.5. Cumulative survival rate was calculated by life-table analysis. SPSS 13.0 software package was used for statistical analysis. RESULTS: The mean clinical C/I ratio of 208 implants was 1.07±0.24, with maximum C/I of 1.8 and C/I of 0.6, 9.6 percent; of 208 implants had biomechanical complications. Differences among three groups were not statistically significant in annual crestal bone loss and biomechanical complications. In addition,implant cumulative survival rate in C/I ratio>1 was 97.6 percent;,and 98.8 percent; in C/I≤ 1. CONCLUSIONS: Clinical C/I ratio does not significantly influence peri-implant crestal bone loss and biomechanical complications, implant restorations with C/I ratios>1 is successfully used in the posterior areas in this study.

[The antibacterial properties of Ca and Zn-containing coatings prepared with micro-arc oxidation].

PURPOSE: To prepare Ca and Zn-containing coatings using micro-arc oxidation on pure titanium surface and to investigate the coatings effect on S.mutans adhesion and morphology. METHODS: Five groups including low Ca-containing (L-Ca), high Ca-containing (H-Ca), low Zn-containing (L-Zn), medium Zn-containing (M-Zn), high Zn-containing (H-Zn) were prepared with micro-arc oxidation on titanium surface and machined commercial pure titanium (CP) was used as control group. Antibacterial properties of S.mutans on samples surface were appraised by the paster method and the change of bacteria was observed by SEM. SPSS 13.0 software package was used for all statistical analysis. RESULTS: The results showed that L-Ca and H-Ca groups had no significant difference in antibacterial property(P>0.05);Zn-containing groups had distinct antibacterial effect(P<0.01) compared with CP group,and there was significant difference between L-Zn and H-Zn group (P<0.05). Meanwhile,Zn-containing groups could affect adhesion and morphology of S.mutans by SEM. CONCLUSIONS: Zn-containing coating prepared with micro-arc oxidation can effectively influence S.mutans adhesion and morphology, which shows better antibacterial effect with the increase of zinc content.

Free posterior tibial artery perforator flap for floor of mouth reconstruction: a case report.

In this report, we present a case with floor of mouth squamous cell carcinoma who underwent wide excision of tumor, a marginal mandibulectomy and bilateral selective neck dissections. A 7 cm × 4 cm fasciocutaneous flap based on a posterior tibial artery perforator (PTAP) from the left posterior leg was harvested to reconstruct a floor of the mouth defect. The donor-site defect was closed primarily. The flap survived in its entirety. No donor or recipient site complications occurred. The patient tolerated a regular diet at 3-month follow-up with normal speech and leg function. To our knowledge, there has been no previous report on the use of the PTAP flap for floor of mouth reconstruction. Our experience has shown the PTAP flap could be one of options for small defects.

[Preoperative Doppler evaluation of vascular perforators in the anterolateral thigh flap harvest].

OBJECTIVE: To evaluate the accuracy of Hadeco ES-1000spm hand-held doppler during the anterolateral thigh (ALT) flap harvest. METHODS: Twenty-five patients (26 sides) with ALT flaps for head and neck reconstruction between May 2005 and May 2010 received preoperative Doppler examination for the location of the cutaneous perforators of ALT flaps. The Doppler signals and body mass index (BMI) were recorded preoperatively according to ABC system. The locations of Doppler signals and of the actual cutaneous perforators at surgery were plotted and compared. The diameter of perforators was measured. RESULTS: One to three cutaneous perforators of the ALT flap were consistently found at specific locations. They were named perforators A, B, C from proximal to distal. Perforators A, B and C were present in 15 (58%), 24 (92%) and 20 (77%) cases and the diameter (> 0.5 mm) of A, B and C were 11/15, 22 (92%) and 8 (40%) respectively. The Doppler signal was within 0.5 cm of the actual perforator location in 85% flaps. The accuracy of Doppler decreased with increase of BMI. CONCLUSIONS: Preoperative assessment by hand-held Doppler is useful in predicting the perforator vessels' locations and diameter although it's accuracy is limited.

Chemokine receptor 7 promotes cell migration and adhesion in metastatic squamous cell carcinoma of the head and neck by activating integrin αvß3.

The mechanisms leading to squamous cell carcinoma of the head and neck (SCCHN) metastasis are incompletely understood. Although evidence shows that the chemokine receptor 7 (CCR7) and its ligand CCL19 may regulate tumor dissemination, their role in SCCHN is not clearly defined. CCR7 has been shown to regulate integrins, which facilitate adhesion of cancer cells to and/or migration through the extracellular matrix (ECM). To investigate the relationship between CCR7 and integrin αvß3 in metastatic SCCHN, we used adhesion and migration assays, immunofluorescence staining and western blotting to determine whether integrin αvß3 can be activated by CCL19 in the metastatic SCCHN cell line PCI-37B, which was pre-incubated with CCL19 or the integrin αvß3 inhibitor, IS201. Our results demonstrate that CCR7 favors PCI-37B cell adhesion and migration, induces reorganization of the actin cytoskeleton and induces integrin αvß3 phosphorylation. The integrin αvß3 inhibitor, IS201, blocked all of these effects. CCR7 and integrin αvß3 expression significantly and positively correlated with tumor size, clinical stage and nodal metastasis. Taken together, our data indicate that CCR7 regulates cell adhesion and migration via integrin αvß3 in metastatic SCCHN. These results should provide the groundwork for new strategies aimed at preventing SCCHN metastasis.

The chemokine receptor 7 regulates cell adhesion and migration via beta1 integrin in metastatic squamous cell carcinoma of the head and neck.

Migration and adhesion of tumor cells are essential prerequisites for the formation of metastases in malignant diseases. Chemokine receptor 7 (CCR7) has been shown to regulate integrin which can then facilitate adhesion of cancer cells to and/or migration through the extracellular matrix (ECM). In order to identify the connection between CCR7 and beta1 integrin, and the influence on cell adhesion and migration in metastatic squamous cell carcinoma of the head and neck (SCCHN). We use adhesion assays, migration assay, immunofluorescence staining, western blotting, and immunohistochemical analysis to find whether beta1 integrin can be activated by CCL19 (CCR7's ligand) and its role in SCCHN. The experiments were performed in the metastatic SCCHN cell line PCI-37B after pre-incubation of the cells with CCL19 and beta1 integrin inhibitors RGD-peptide. Our results demonstrate that CCR7 favours PCI-37B cell adhesion and migration, and induces reorganization of the actin cytoskeleton and up-expression of beta1 integrin protein. beta1 integrin inhibitor RGD-peptide can block all these effects. Taken together, our data indicate that CCR7 regulate cell adhesion and migration via beta1 integrin in metastatic SCCHN, and these results can provide a basis for new strategies in preventing metastases of SCCHN.

[Functional reconstruction of total lower lip defect with mental neurovascular V-Y advancement island flap.].

OBJECTIVE: To introduce a method of functional reconstruction for total lower lip defects. METHODS: Six patients with lower lip cancer were treated by surgery from November 2007 to February 2009. The full thickness defects with a size from eighty percent to total lower lip were reconstructed with two triangular mental neurovascular island flaps of chin. The musculocutaneous and mucous flaps with neurovascular pedicles were advanced in a V-Y manner to close the defect and reconstruct the orbicularis oris muscle. RESULTS: All flaps survived and no recurrence and complication were observed and showed excellent cosmetic and functional results over 6 months of follow-up. The reconstructed lower lips provided a wide-enough mouth opening, and the sensation of oral mucosa and the muscle function of oral sphincter were preserved. CONCLUSIONS: The technique of mental neurovascular V-Y advancement island flap can get satisfactory results in both functional and the aesthetic perspects.

[The expression of M-phase promoting factor in salivary adenoid cystic carcinoma].

PURPOSE: To study the expression and clinical significance of M-phase promoting factor (MPF) in salivary adenoid cystic carcinoma (SACC). METHODS: The expression of MPF was investigated in 40 salivary adenoid cystic carcinomas and 40 normal salivary tissues by immunohistochemistry. The expression of MPF was detected in SACC-83 and SACC-LM with Western blot. Pearson's Chi-square test, paired t test and linear correlation analysis were used to analyze the data with SPSS 11.5 software package. RESULTS: The expression of MPF was significantly higher in salivary adenoid cystic carcinoma than in normal salivary tissues(P<0.05). There was significant correlation between the level of MPF expression and pathological type(P<0.05). The expression of MPF was significantly higher in SACC-LM than in SACC-83 (P<0.05). CONCLUSIONS: MPF highly expressed in salivary adenoid cystic carcinoma, salivary adenoid cystic carcinoma correlated with the expression of MPF and the abnormal activation of MPF was one of the factors for the proliferation of salivary adenoid cystic carcinoma. Metastasis in salivary adenoid cystic carcinoma correlated with the expression of MPF.

[Expression of Livin mRNA and protein in human oral squamous cell carcinoma].

PURPOSE: To investigate the expression of the newly found inhibitor of apoptosis protein Livinalpha and Livinbeta and their gene expression in human oral squamous cell carcinoma. METHODS: Twenty specimens of human squamous cell carcinoma(SCC), 15 cases of benign cysts, 10 cases of normal oral mucosal tissues adjacent to the cancerous lesions were examined. Polymerase chain reaction with reverse transcription (RT-PCR) and Western blot analysed were used to detect mRNA and protein expression of Livin, respectively.The results were analysed by SPSS10.0 software package. RESULTS: Livin protein and mRNA expression was detected in 19 SCC tissues,14 benign cysts and 10 normal oral mucosal tissues adjacent to the cancerous lesions.But the expressions were significantly higher in oral SCC than in benign cysts and normal oral mucosal tissues (P<0.01). CONCLUSION: Livin may play an important role in the tumorigenesis and development of human oral squamous cell carcinoma.

[The expression and activity of protein kinase A I in oral squamous cell carcinoma].

PURPOSE: To detect the expression and distribution of protein kinase A I (PKA I) in oral squamous cell carcinoma as well as its clinicalpathological significance. METHODS: The expression of PKA I was investigated in 40 oral squamous cell carcinomas and 15 normal tissues by immunohistochemistry. The activity of PKAI was detected in 20 human oral squamous cell carcinomas and adjacent normal tissues with Western blot. The data was analysed with SPSS 11.5 for Student's t test, Chi-between different square test and linear correlation analysis. RESULTS: The expression of PKA I was significantly higher in oral squamous cell carcinomas than in normal tissues (P<0.05). There were no differences degrees of histodifferentiation and clinical phases (P>0.05). The activity of PKA I was significantly higher in oral squamous cell carcinomas than in normal tissues (P<0.01), there were obvious dependability of the expression and activity of PKA I (P<0.01). CONCLUSIONS: Protein kinase A I highly expressed in oral squamous cell carcinomas, but was not related to the degree of histodifferentiation and the clinical phases. Oral squamous cell carcinoma correlated with the expression and activity of PKA I and the activation of PKA I was one of the factors for proliferation of oral squamous cell carcinoma.