Recent advances in the study of sepsis-induced depression.

Progress in medicine such as the use of anti-infective drugs and development of the advanced life support equipment has greatly improved the survival rate of patients with sepsis. However, the incidence of sepsis-related diseases is increasing. These include severe neurologic and psychologic disorders, cognitive decline, anxiety, depression, and post-traumatic stress disorder. Cerebral dysfunction occurs via multiple interacting mechanisms, with different causative pathogens having distinct effects. Because sepsis-related diseases place a substantial burden on patients and their families, it is important to elucidate the underlying pathophysiologic mechanisms to develop effective treatments.

Intra-arterial infusion chemotherapy utilizing cisplatin inhibits bladder cancer by decreasing the fibrocytic myeloid-derived suppressor cells in an m6A-dependent manner.

Intra-arterial infusion chemotherapy (IAIC), using immunomodulatory cisplatin, is a novel treatment for bladder cancer (BC) that allows the delivery of specific drugs to the local malignant lesion. To explore the immunomodulatory effect of cisplatin during IAIC, we detected the proportion of immunosuppressed cells in BC tissue from eight BC patients, with the reduction of myeloid-derived suppressor cells (MDSCs), more specifically fibrocytic-MDSCs (f-MDSCs). Further, we demonstrated that cisplatin inhibits their proliferation and immunosuppressive activity. f-MDSCs promote tumor proliferation and metastasis in the BC immune environment. Then, we analyzed the genetic differences detected in samples before and after chemotherapy and found that granulocyte colony-stimulating factors (G-CSF) decreased after IAIC. Furthermore, G-CSF methylation decreased following treatment with cisplatin. Specifically, treatment with cisplatin decreased the methylase (METTL3) levels in BC cells, which is important for G-CSF production. Collectively, cisplatin decreased the number of f-MDSCs during IAIC, by blocking G-CSF methylation via targeting METTL3.

IL-6 Promotes the Proliferation and Immunosuppressive Function of Myeloid-Derived Suppressor Cells via the MAPK Signaling Pathway in Bladder Cancer.

Muscle-invasive bladder cancer (MIBC) is characterized by a highly complex immune environment, which is not well understood. Interleukin-6 (IL-6) is generated and secreted by multifarious types of cells, including tumor cells. This study was aimed at demonstrating that the levels of IL-6 and the number of myeloid-derived suppressor cells (MDSCs), with a positive correlation between them, increased in MIBC tissues, promoting MIBC cell proliferation, especially in patients with recurrence. In coculture analysis, MDSCs, with the stimulation of IL-6, could significantly lower the proliferation ability of CD4+ or CD8+ T lymphocytes. Further, this study demonstrated that IL-6 could upregulate the mitogen-activated protein kinase (MAPK) signaling pathway in MDSCs. The MAPK signaling inhibitor, aloesin, partially reversed the effects of IL-6 on MDSCs. These data suggested that IL-6 promoted MIBC progression by not only accelerating proliferation but also improving the immune suppression ability of MDSCs through activating the MAPK signaling pathway.

Periodontal disease and risk of benign prostate hyperplasia: a cross-sectional study.

BACKGROUND: Both periodontal disease and benign prostatic hyperplasia are age-related diseases that affect millions of people worldwide. Hence, this study aimed to investigate the association between periodontal disease and the risk of benign prostatic hyperplasia. METHODS: A total of 4930 participants were selected from an available health examination that was carried out in 2017, only males were considered for further analysis. All eligible males were divided into benign prostatic hyperplasia and normal groups, the benign prostatic hyperplasia group was then divided into prostate volume ≤ 60 g and > 60 g subgroups; all their periodontal status was extracted and then into normal (CPI score of 0), periodontal disease (CPI score between 1 and 4), and periodontitis (CPI score between 3 and 4) groups. The correlation between periodontal disease and benign prostatic hyperplasia was investigated using logistic regression analyses and greedy matching case-control analysis. Subgroup analysis based on prostate volume was also performed. All analyses were conducted with SAS 9.4 software. RESULTS: A total of 2171 males were selected for this analysis. The presence of periodontal disease significantly increased the risk of benign prostatic hyperplasia by 1.68 times (OR = 1.68, 95% CI: 1.26-2.24), and individuals with periodontitis showed a higher risk (OR = 4.18, 95% CI: 2.75-6.35). In addition, among matched cases and controls, this association remained robust (periodontal disease: OR = 1.85, 95% CI: 1.30-2.64; periodontitis: OR = 4.83, 95% CI: 2.57-9.07). Subgroup analysis revealed that periodontal disease significantly increased benign prostate hyperplasia risk as well (for prostate volume ≤ 60 g: OR = 1.64, 95% CI: 1.22-2.20; for volume > 60 g: OR = 2.17, 95% CI: 1.04-4.53), and there was a higher risk in the group with a prostate volume greater than 60 g. CONCLUSION: Periodontal disease is significantly and positively associated with an increased risk of benign prostatic hyperplasia. Further validation studies should be performed to explore the relationship between periodontal treatment and benign prostate hyperplasia.

Periodontal Disease and Breast Cancer: A Meta-Analysis of 1,73,162 Participants.

Objective: To investigate the correlation between periodontal disease and breast cancer. Materials and Methods: PubMed and China National Knowledge Infrastructure (CNKI) databases were searched up to February 8, 2018 for observational studies examining the association between periodontal disease and breast cancer. Study selection was conducted according to predesigned eligibility criteria, and two authors independently extracted data from included studies. Meta-analysis was performed using the Comprehensive Meta-Analysis v2 software and risk estimates were calculated as relative risks (RRs) with corresponding 95% confidence intervals (CIs). Results: A total of 11 study were included. Meta-analysis indicated that periodontal disease significantly increased the risk of breast cancer by 1.22-fold (RR = 1.22, 95% CI = 1.06-1.40). Amongst participants with periodontal patients and a history of periodontal therapy, the risk of developing breast cancer was not significant (RR = 1.23; 95% CI = 0.95-1.60). The association results between periodontal diseases and breast cancer were found to be robust, as evident in the leave-one-out sensitivity analysis. Conclusions: Periodontal disease may be a potential risk factor for the development of breast cancer among women, and thus effective periodontal therapy may present as a valuable preventive measure against breast cancer.

Injectable hydrogels embedded with alginate microspheres for controlled delivery of bone morphogenetic protein-2.

Some delivery carriers with injectable characteristics were built using the thermosensitive chitosan/dextran-polylactide/glycerophosphate hydrogel and selected alginate microspheres for the controllable release of bone morphogenetic protein-2 (BMP-2). BMP-2 was first loaded into the microspheres with an average size of around 20 µm and the resulting microspheres were then embedded into the gel in order to achieve well-controlled BMP-2 release. The microsphere-embedded gels show their incipient gelation temperature at around 32 °C and pH at about 7.1. Some gels had their elastic modulus close to 1400 Pa and the ratio of elastic modulus to viscous modulus at around 34, revealing that they behaved like mechanically strong gels. Optimized microsphere-embedded gels were found to be able to administer the BMP-2 release without significant initial burst release in an approximately linear manner over a period of time longer than four weeks. The release rate and the released amount of BMP-2 from these gels could be regulated individually or cooperatively by the initial BMP-2 load and the dextran-polylactide content in the gels. Measurements of the BMP-2 induced alkaline phosphatase activity in C2C12 cells confirmed that C2C12 cells responded to BMP-2 in a dose-dependent way and the released BMP-2 from the microsphere-embedded gels well retained their bioactivity. In vivo assessment of some gels revealed that the released BMP-2 maintained its osteogenesis functions.

A detailed study of homogeneous agarose/hydroxyapatite nanocomposites for load-bearing bone tissue.

Agarose/hydroxyapatite (agar/HA) nanocomposites for load-bearing bone substitutes were successfully fabricated via a novel in situ precipitation method. Observation via SEM and TEM revealed that the spherical inorganic nanoparticles of approximately 50 nm were well dispersed in the organic matrix, and the crystallographic area combined closely with the amorphous area. The uniform dispersion of HA nanoparticles had prominent effect on improving the mechanical properties of the agar/HA nanocomposites (the highest elastic modulus: 1104.42 MPa; the highest compressive strength: 400.039 MPa), which proved to be potential load-bearing bone substitutes. The thermal stability of agarose and nanocomposites was also studied. The MG63 osteoblast-like cells on the composite disks displayed fusiform and polygonal morphology in the presence of HA, suggesting that the cell maturation was promoted. The results of cell proliferation and cell differentiation indicated that the cells cultured on the agar/HA composite disks significantly increased the alkaline phosphatase activity and calcium deposition. The structural role of agarose in the composite system was investigated to better understand the effect of biopolymer on structure and properties of the composites. The optimal properties were the result of a comprehensive synergy of the components.

Designed composites for mimicking compressive mechanical properties of articular cartilage matrix.

Collagen, chitosan-polycaprolactone (CH-PCL) copolymer with PCL content of around 40wt% and chondroitin sulfate (CS) were mixed together at various ratios to prepare collagen/CH-PCL/CS composites and the resulting composites were used to build stratified porous scaffolds that are potentially applicable for articular cartilage repair. The ternary composites were designed in such a way that collagen content in the scaffolds decreased from the top layer to the bottom layer while the content of CH-PCL and CS altered in a reversed trend in order to reach partial similarity to cartilage matrix in the composition of main components. Porous structures inside collagen/CH-PCL/CS scaffolds were constructed using a low-temperature deposition processing technique and graded average pore-size and porosity for the scaffolds were established. Such produced scaffolds were further crosslinked using 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide under optimized conditions, and the obtained scaffolds showed well-defined elastic compressive properties. Compressive modulus (E) and stress at 10% strain (σ10) of full scaffolds in wet state reached about 2.8MPa and 0.3MPa, respectively, and meanwhile, E and σ10 of layers inside hydrated scaffolds changed in a gradient-increased manner from the top layer to the bottom layer with significant differences between contiguous layers, which partially mimics compressive mechanical properties of cartilage matrix. In addition, in vitro culture of cell-scaffold constructs exhibited that scaffolds were able to well support the ingrowth and migration of seeded cells, and cells also showed relatively uniform distribution throughout the scaffolds. These results suggest that the presently developed collagen/CH-PCL/CS scaffolds have promising potential for applications in articular cartilage repair.

Null Glutathione S-transferase T1 and M1 genotypes and oral cancer susceptibility in China and India--a meta-analysis.

OBJECTIVE: Genetic variation is considered to strongly impact on detoxification of carcinogens and therefore is related to cancer risk. However, findings for the null genotypes of GSTT1 and GSTM1 have not always been consistent. Therefore the present meta-analysis was conducted. METHODS: We accessed the reported study at different research areas and used various databases, including PubMed and Wanfang Med Onlion from 1990 to May 1st 2013. We calculated the odds ratio (OR), 95% confidence interval (CI) and P value for oral cancer by using Review Manager 5.1 and STATE 12. RESULTS: We found that there was no increased oral cancer risk among subjects carrying GSTM1 and GSTT1 null genotype (OR=1.35, 95%CI=0.68-2.68, P=0.39) and (OR=1.41, 95%CI=0.72-2.77, P=0.31) in the Chinese population. In contrast, in studies in India a significant correlation between GSTM1 null genotype and oral cancer was observed (OR=1.59, 95%CI=1.20-2.11, P=0.001), but not in GSTT1 (OR=1.21, 95% CI = 0.84-1.74, P=0.31). CONCLUSION: We discovered that GSTM1 deletion polymorphism had a significant effect on the susceptibility of oral cancer in the Indian population.

Manufacture of layered collagen/chitosan-polycaprolactone scaffolds with biomimetic microarchitecture.

Chitosan-polycaprolactone (CH-PCL) copolymers with various PCL percentages less than 45 wt% were synthesized. Different CH-PCLs were respectively blended with Type-II collagen at prescribed ratios to fabricate a type of layered porous scaffolds with some biomimetic features while using sodium tripolyphosphate as a crosslinker. The compositions of different layers inside scaffolds were designed in a way so that from the top layer to the bottom layer collagen content changed in a degressive trend contrary to that of chitosan. A combinatorial processing technique involving adjustable temperature gradients, collimated photothermal heating and freeze-drying was used to construct desired microstructures of scaffolds. The resultant scaffolds had highly interconnected porous layers with a layer thickness of around 1mm and porous interface zones without visual clefts. Results obtained from SEM observations and measurements of pore parameters and swelling properties as well as mechanical examinations confirmed that graded average pore-size and porosity, gradient swelling index and oriented compressive modulus for certain scaffolds were synchronously achieved. In addition, certain evaluations of cell-scaffold constructs indicated that the achieved scaffolds were able to well support the growth of seeded chondrocytes. The optimized collagen/CH-PCL scaffolds are partially similar to articular cartilage extracellular matrix in composition, porous microarchitecture, water content and compressive mechanical properties, suggesting that they have promising potential for applications in articular cartilage repair.

Age-related changes in pulp cavity of incisors as a determinant for forensic age identification.

To find a simple and convenient method for age identification upon age-related pulp cavity narrowing, the mesiodistal diameters of the cervical pulp chamber, the middle and terminal parts of the root canal of the pulp cavity of 620 incisors were measured on radiographs taken in situ in 80 Chinese aged from 15 to 80. It was shown that the three mesiodistal diameters significantly decreased in a negative linear relationship with age (-0.4233 ≤ r ≥ -0.8465) in all incisors, but the narrowing velocity of the cervical pulp chamber and the middle part of the root canal in the maxillary incisors (b = -0.02 mm) was faster than that in the mandibular incisors (b = -0.01 mm). Accordingly, a mathematical model describing the ages as a function of any one of the three mesiodistal diameters of the pulp cavity was deduced, which would be useful for age identification in forensic medicine or archaeology.