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Objectives: This review aimed at investigating the impact of bioactive agents on alveolar ridge augmentation at peri-implant sites and edentulous ridges. Material and Methods: Electronic and manual literature searches were conducted for articles up to April 2021. Human randomized clinical trials, clinical trials, or retrospective studies reporting outcomes of alveolar ridge augmentation procedures with or without bioactive agents were included. Sinus lifting or extraction socket preservation articles were excluded in this study. A random-effect meta-analysis was conducted to investigate ridge dimensional changes and complication rate. Results: Overall, ten articles were included in the quantitative analysis. In bone width and height augmentation, the weighted mean difference (WMD) of the horizontal bone gain at edentulous ridges was 0.38 mm (95% CI = 0.07 to 0.69 mm, p = 0.02) when comparing sites with and without PRP/PRF. The WMD of the vertical bone gain at edentulous ridges was 0.46 mm (95% CI = 0.06 to 0.86 mm, p = 0.02) when comparing sites with and without platelet- rich plasma (PRP) or platelet-rich fibrin (PRF). When evaluating the effect of adjunctive use of bone morphogenetic proteins (BMPs) at alveolar ridge augmentation sites compared to alveolar ridge augmentation sites without BMP application, the WMD of the horizontal bone gain at edentulous ridges was 0.90 mm (95% CI = 0.30 to 1.49 mm, p = 0.003). In addition, the odds ratio of the titanium mesh exposure was 0.13 (95% CI of 0.02 to 0.71, p = 0.02). All analyses showed favorable outcomes at the sites with bioactive agent. Conclusion: Within the limits of this review, application of bioactive agents during alveolar ridge augmentation procedures presents increased horizontal and vertical bone augmentative changes. The complication rate can also be reduced with usage of PRP/PRF in titanium mesh-guided alveolar ridge augmentation. &nbsp

Head and neck squamous cell carcinoma (HNSCC) is a major contributor to cancer incidence globally and is currently managed by surgical resection followed by adjuvant chemoradiotherapy. However, local recurrence is the major cause of mortality, indicating the emergence of drug-tolerant persister cells. A specific histone demethylase, namely lysine-specific demethylase 5D (KDM5D), is overexpressed in diverse types of cancers and involved in cancer cell cycle regulation. However, the role of KDM5D in the development of cisplatin-tolerant persister cells remains unexplored. Here, we demonstrated that KDM5D contributes to the development of persister cells. Aurora Kinase B (AURKB) disruption affected the vulnerability of persister cells in a mitotic catastrophe–dependent manner. Comprehensive in silico, in vitro, and in vivo experiments were performed. KDM5D expression was upregulated in HNSCC tumor cells, cancer stem cells, and cisplatin-resistant cells with biologically distinct signaling alterations. In an HNSCC cohort, high KDM5D expression was associated with a poor response to platinum treatment and early disease recurrence. KDM5D knockdown reduced the tolerance of persister cells to platinum agents and caused marked cell cycle deregulation, including the loss of DNA damage prevention, and abnormal mitosis-enhanced cell cycle arrest. By modulating mRNA levels of AURKB, KDM5D promoted the generation of platinum-tolerant persister cells in vitro, leading to the identification of the KDM5D/AURKB axis, which regulates cancer stemness and drug tolerance of HNSCC. Treatment with an AURKB inhibitor, namely barasertib, resulted in a lethal consequence of mitotic catastrophe in HNSCC persister cells. The cotreatment of cisplatin and barasertib suppressed tumor growth in the tumor mouse model. Thus, KDM5D might be involved in the development of persister cells, and AURKB disruption can overcome tolerance to platinum treatment in HNSCC.

Translocation of bacteria and endotoxtin has long been documented in obstructive jaundice, and altered intestinal barrier function is considered to be one of the important mechanisms for this phenomenon. The regulation of gastrointestinal mucosal response to injury is thus of important clinical as well as biological relevance. Integrins play a critical role in enterocyte migration, which is essential to mucosal healing. This study is designed to evaluate the integrins status in obstructive jaundice. Male Sprague-Dawley rats (N = 37) were randomized to three groups. Group 1 (N = 12) underwent common bile duct ligation (CBDL), group 2 (N = 12) underwent common bile duct ligation with oral glutamine administration (CBDL + G), and group 3 (N = 13) underwent a sham operation (sham control). After seven days, segments of proximal jejunum and distal ileum were harvested, and cell surface immunohistochemical expression of LFA-1alpha and VLA-6 were evaluated and recorded. The staining intensities were graded on a scale of 0-4. Comparisons among the three groups were performed. There was no significant difference in VLA-6 staining on small intestine among the three groups (P > 0.05). There was also no significant difference in LFA-1alpha staining the on jejunum between group 1 (CBDL) and group 3 (sham control) (P > 0.05). However, the LFA-1alpha staining on the ileum in group 1 (CBDL) significantly decreased when compared with group 3 (sham control) (P = 0.008). With oral glutamine administration (0.2 g/kg body weight, once daily), LFA-1alpha staining on the ileum was significantly restored in group 2 (CBDL + G). In conclusion, obstructive jaundice for one week down-regulates LFA-1alpha expression on rat ileum. With oral glutamine administration, such down-regulation of LFA-1alpha expression on rat ileum can be restored. Such a phenomenon is intriguing and deserves further evaluation and elucidation.

The outcome of breast carcinoma is usually determined by multiple factors. Aberrant expression of the cell adhesion molecule CD 44 has been claimed to be associated with poor prognosis in various human malignancies. This study was designed to investigate any correlation between the soluble adhesion molecule CD 44 and the clinicopathologic variables and to evaluate the possible prognostic significance of soluble CD 44. Venous blood samples were preoperatively collected from 100 patients with invasive breast carcinoma. The serum levels of different soluble CD 44 molecules (CD 44 standard form and CD 44 splice variant V6) were measured with an enzyme immunoassay method. The data of primary tumor status, age, estrogen receptor status, lymph node status, histologic grading, distant metastases status, TNM staging, S-phase fraction, and ploidy pattern were collected and evaluated simultaneously with the serum levels of soluble CD 44 st and CD 44 V6. Twenty healthy subjects were used as the control group. The serum levels of soluble CD 44 st showed no significant elevation in patient group. The mean value of soluble CD 44 V6 in patient group was 269.2 +/- 94.3 ng/ml and that of the control group was 179.5 +/- 50.7 ng/ml; the difference was significant (p0.01). In multivariate analysis, distant metastasis (p0.05) and TNM staging (p0.01) appeared as independent factors regarding the significant higher serum levels of soluble CD 44 V6. Based on our preliminary results, preoperative serum soluble CD 44 V6 is closely related to distant metastases and TNM staging. The possible role of soluble CD 44 V6 in the prognostic value of breast carcinoma deserves further elucidation and evaluation with long-term patient follow-up.

There is a high incidence of perioperative morbidity and mortality in patients with obstructive jaundice due to sepsis. Tumor necrosis factor-a (TNF-alpha) is considered a crucial mediator in inducing and processing the inflammatory cascade. We hypothesize that obstructive jaundice leads to an increased endotoxin-induced TNF-alpha production and that intestinal bile acid replacement can prevent this phenomenon. Sprague-Dawley rats were randomized to three groups of 12 animals each. Group 1 underwent common bile duct ligation (CBDL) with oral intestinal bile acid (deoxycholic acid 5 mg/100 g body weight/3 times daily) replacement (CBDL + bile acid); group 2 underwent common bile duct ligation with the same amount of normal saline replacement orally (CBDL + saline); and group 3 underwent a sham operation (sham control). After 2 days, endotoxin was given to the animals, and after 90 minutes, tissues (liver and lung) and blood were collected for checking the TNF-alpha levels and biochemical analyses. Comparisons among these three groups were performed and recorded. While serum and tissue (liver and lung) TNF-alpha levels of group 2 (CBDL + saline) were significantly increased after endotoxin challenge, these elevations were reduced to control levels (sham control) following oral replacement of intestinal bile acid (CBDL + bile acid). Obstructive jaundice leads to an increased endotoxin-induced TNF-alpha production and intestinal bile acid replacement can inhibit this phenomenon.

Translocation of bacteria and endotoxtin has long been documented in obstructive jaundice, and altered intestinal barrier function is considered to be one of the important mechanisms for this phenomenon. The regulation of gastrointestinal mucosal response to injury is thus of important clinical as well as biological relevance. Integrins play a critical role in enterocyte migration, which is essential to mucosal healing. This study is designed to evaluate the integrins status in obstructive jaundice. Male Sprague-Dawley rats (N = 37) were randomized to three groups. Group 1 (N = 12) underwent common bile duct ligation (CBDL), group 2 (N = 12) underwent common bile duct ligation with oral glutamine administration (CBDL + G), and group 3 (N = 13) underwent a sham operation (sham control). After seven days, segments of proximal jejunum and distal ileum were harvested, and cell surface immunohistochemical expression of LFA-1alpha and VLA-6 were evaluated and recorded. The staining intensities were graded on a scale of 0-4. Comparisons among the three groups were performed. There was no significant difference in VLA-6 staining on small intestine among the three groups (P0.05). There was also no significant difference in LFA-1alpha staining the on jejunum between group 1 (CBDL) and group 3 (sham control) (P0.05). However, the LFA-1alpha staining on the ileum in group 1 (CBDL) significantly decreased when compared with group 3 (sham control) (P = 0.008). With oral glutamine administration (0.2 g/kg body weight, once daily), LFA-1alpha staining on the ileum was significantly restored in group 2 (CBDL + G). In conclusion, obstructive jaundice for one week down-regulates LFA-1alpha expression on rat ileum. With oral glutamine administration, such down-regulation of LFA-1alpha expression on rat ileum can be restored. Such a phenomenon is intriguing and deserves further evaluation and elucidation.

Matrix metalloproteinases (MMPs) have been reported to be associated with invasive and metastatic behaviors of human malignant tumors. However, there is still limited knowledge about the role of matrix metalloproteinases-2 (MMP-2) in breast cancer. This study was designed with the aim to elucidate the possible relationship between the preoperative circulating MMP-2 and breast cancer. Fifty-seven consecutive patients with invasive breast cancer undergoing surgery were prospectively included and evaluated. Venous blood samples were collected before the surgery. Sera were obtained by centrifugation, and stored at -70 degrees C until assayed. The control group consisted of 12 patients with benign breast tumor (six with fibrocystic disease and six with fibroadenoma). Serum concentrations of MMP-2 were measured by the quantitative sandwich enzyme immunoassay technique. The data on primary tumor stage, age, estrogen receptor, lymph node status, and TNM staging were reviewed and recorded. The mean value of serum MMP-2 in patients with invasive breast cancer was 694.3+/-140.5 ng/ml and those of control group were 593.3+/-134.0 ng/ml and the difference was significant (P=0.026). Furthermore, there were significantly higher serum levels of MMP-2 in the patients with more advanced primary tumor staging (P=0.005), in the patients with more advanced lymph node status(P=0.011) and in the patients with more advanced TNM staging (P0.001). In multivariate analysis, TNM staging (P0.001) appeared as independent factor regarding the significant higher serum levels of MMP-2. Patients with more advanced TNM staging were shown to have higher serum MMP-2 levels. Thus preoperative serum MMP-2 levels might reflect the severity of invasive breast cancer and deserve further evaluation.