Intraocular pressure fluctuation and the risk of glaucomatous damage deterioration: a Meta-analysis

AIM: To systematically review whether the increased fluctuation of intraocular pressure(IOP) is a risk factor for open angle glaucoma(OAG) progression. METHODS: Scientific studies relevant to IOP fluctuation and glaucoma progression were retrieved from MEDLINE,EMBASE and CENTRAL databases, and were listed as references in this paper. The hazard ratio(HR) was calculated by using fixed or random-effects models according to the heterogeneity of included studies. RESULTS: Individual data for 2211 eyes of 2637 OAG patients in fourteen prospective studies were included in this Meta-analysis. All studies were longitudinal clinical studies with follow-up period ranging from 3 to 8.5 y. The combined HR was 1.23(95%CI 1.04-1.46, P=0.02) for the association between IOP fluctuation and glaucoma onset or progression with the evidence of heterogeneity(P<0.1).Subgroup analyses with different types of IOP fluctuation were also evaluated. Results indicated that the summary HR was 0.98(95%CI 0.78-1.24) in short-term IOP fluctuation group, which showed no statistical significance with heterogeneity, whereas, the combined HR was 1.43(95%CI1.13-1.82, P=0.003) in long-term IOP fluctuation group without homogeneity. Sensitivity analysis further showed that the pooled HR was 1.10(95%CI 1.03-1.18, P=0.004) for long-term IOP fluctuation and visual function progression with homogeneity among studies(P=0.3). CONCLUSION: Long-term IOP fluctuation can be a risk factor for glaucoma progression based on the presentedevidence. Thus, controlling the swing of IOP is crucial for glaucoma or glaucoma suspecting patients.

Input of microenvironmental regulation on colorectal cancer: Role of the CCN family

Colorectal cancer(CRC)is a major health problem causing significant morbidity and mortality.Previous results from various studies indicate that CRC tumorigenicity encompasses tumor microenvironment,emphasizing the complex interacting network between cancer cells and nearby host cells,which triggers diverse signaling pathways to promote the growth and spread ofcancer cells.The CCN family proteins share a uniform modular structure,mediating a variety of physiological functions,including proliferation,apoptosis,migration,adhesion,differentiation,and survival.Furthermore,CCN proteins are also involved in CRC initiation and development.Many studies have shown that CCN members,such as CCN1,CCN2,CCN3,Wnt-induced secreted protein(WISP)-1,WISP-2,and WISP-3,are dysregulated in CRC,which implies potential diagnostic markers or therapeutic targets clinically.In this review,we summarize the research findings on the role of CCN family proteins in CRC initiation,development,and progression,highlighting their potential for diagnosis,prognosis,and therapeutic application.

Tailoring Resorption Rates and Osteogenic Response in Xeno-Hybrid Bone Grafts: The Effect of Added Gelatins

Bone defects resulting from trauma,surgery,congenital malformations,and other factors are among the most common health problems nowadays.Although current strategies such as autografts and allografts are recognized as the most successful treatments for stimulating bone regeneration,limitations such as graft source and complications still exist.SmartBone?is a xeno-hybrid bone graft(made from bovine bone matrix,poly(L-lactic-co-e-caprolactone),and gelatin)with a positive clinical record for bone regen-eration.In this study,the formulation for designing xeno-hybrid bone grafts using gelatins from different sources(bovine-and porcine-derived gelatin,with bone grafts named SBN and SPK,respectively)was investigated,and the biological responses were evaluated in vitro and in vivo.The results demonstrate that gelatins from both bovine and porcine sources can be loaded onto SmartBone?successfully and safely,withstanding the aggressive manufacturing processes.Different bone cell responses were observed in vitro.SBN was found to enhance osteocalcin secretion while SPK was found to upregulate osteopontin from human osteoblasts.In vivo,both bone grafts promoted osteogenesis,but SPK degraded earlier than SBN.Our findings suggest that SBN and SPK provide different yet comparable solutions for optimizing the bone resorption and regeneration balance.These xeno-hybrid bone grafts possess ideal potential for bone defect repairing.

The oral commensal Streptococcus mitis activates the aryl hydrocarbon receptor in human oral epithelial cells

Streptococcus mitis （S. mitis） is a pioneer commensal bacterial species colonizing many of the surfaces of the oral cavity in healthy individuals. Yet, not much information is available regarding its interaction with the host. We used examination of its transcriptional regulation in oral keratinocytes to elucidate some of its potential roles in the oral cavity. Transcription factor analysis of oral keratinocytes predicted S. mitis.mediated activation of aryl hydrocarbon receptor （AhR）, Activation and functionality of AhR was confirmed through nuclear translocation determined by immunofluorescence microscopy and real-time polymerase chain reaction with reverse transcription analysis of CYPIA1, the hallmark gene for AhR activation. Addition of Streptococcus mutans or Streptococcus gordonfi did not induce CYPIA1 transcription in the keratinocyte cultures. Introduction of an AhR-specific inhibitor revealed that S. mitis-mediated transcription of CXCL2 and CXCL8 was regulated by AhR. Elevated levels of pmstaglandin E2 （enzyme-linked immunosorbent assay） in supernatants from S. mitis-treated oral epithelial cells were also attenuated by inhibition of AhR activity. The observed AhR-regulated activities point to a contribution of S. mitis in the regulation of inflammatory responses and thereby to wound healing in the oral cavity. The concept that the oral commensal microbiota can induce AhR activation is important, also in view of the role that AhR has in modulation of T-cell differentiation and as an anti-inflammatory factor in macrophaees.

Primary retinal ganglion cells for neuron replacement therapy

Optic nerve damage as a result of trauma, ischemia, glaucoma or other forms of optic neuropathy disease, leads to disconnection between the eye and brain and death of retinal ganglion cells(RGCs), causing permanent loss of vision. Therapeutic options for treating optic neuropathy are limited and represent a significant unmet medical need. Development of a regenerative strategy for replacement of lost RGCs lies at the core of the future cell-based therapy for these conditions. Successful long-term restoration of visual function depends on the type of cells for transplantation. Primary RGCs of neonatal mice are now reported to have the potential for serving such a purpose.

Dual-functional porous and cisplatin-loaded polymethylmethacrylate cement for reconstruction of load-bearing bone defect kills bone tumor cells

Malignant bone tumors are usually treated by resection of tumor tissue followed by filling of the bone defect with bone graft substitutes.Polymethylmethacrylate(PMMA)cement is the most commonly used bone substitute in clinical orthopedics in view of its reliability.However,the dense nature of PMMA renders this biomaterial unsuitable for local delivery of chemotherapeutic drugs to limit the recurrence of bone tumors.Here,we introduce porosity into PMMA cement by adding carboxymethylcellulose(CMC)to facilitate such local delivery of chemotherapeutic drugs,while retaining sufficient mechanical properties for bone reconstruction in load-bearing sites.Our results show that the mechanical strength of PMMA-based cements gradually decreases with increasing CMC content.Upon incorporation of≥3%CMC,the PMMA-based cements released up to 18%of the loaded cisplatin,in contrast to cements containing lower amounts of CMC which only released less than 2%of the cisplatin over 28 days.This release of cisplatin efficiently killed osteosarcoma cells in vitro and the fraction of dead cells increased to 91.3%at day 7,which confirms the retained chemotherapeutic activity of released cisplatin from these PMMA-based cements.Additionally,tibias filled with PMMA-based cements containing up to 3%of CMC exhibit comparable compressive strengths as compared to intact tibias.In conclusion,we demonstrate that PMMA cements can be rendered therapeutically active by introducing porosity using CMC to allow for release of cisplatin without compromising mechanical properties beyond critical levels.As such,these data suggest that our dual-functional PMMA-based cements represent a viable treatment option for filling bone defects after bone tumor resection in load-bearing sites.

Comparative Study between Bone Tissue Engineering Scaffolds with Bull and Rat Cancellous Microarchitectures on Tissue Differentiations of Bone Marrow Stromal Cells： A Numerical Investigation

Tissue-engineered bone scaffolds provide temporary mechanical support for bone tissue growth. Mechanical stimuli are transferred to seeded cells through the scaffold structure to promote cell proliferation and differentiation. This paper presents a numerical investigation specifically on bone and cartilage tissue differentiation with the aim to provide a theoretical basis for scaffold design and bone defect repair in clinics. In this study, the scaffold structures were established on the basis of cancellous bone microarchitectures. For finite element simulations, inlet velocity and compressive strain were applied under in vitro culture conditions. The influences of this scaffold mor- phology and macro-level culture conditions on micro-mechanical stimuli at scaffold surfaces were investigated. Correlations between the microarchitectural parameters and the mechanical parameters, as well as the cell differentiation parameters were analyzed. Highly het- erogeneous stress distributions were observed on the scaffolds with irregular morphology. Cell differentiation on the scaffold was more sensitive to the inlet velocity than the axial strain. In addition, cartilage differentiation on the scaffolds with structures comprising more plate-like trabeculae was more pronounced than on those with more rod-like trabeculae. This paper is helpful to gain more insight into the mechanical environments under in vitro culture conditions that approximate the in vivo mechanical environments of Bone Marrow Stromal Ceils （BMSCs）.

Coating doxycycline on titanium-based implants: Two in vivo studies

Regardless of the substantial progress in designing titanium-based dental implants and aseptic techniques,infection remains as the most common complication after implantation surgeries.Although,having a weakened immune system or systematic diseases is not seen as contraindicated for dental implants anymore,controlling the immune system is required to avoid surgical site infections after implantation.These patients have to control the surgical site infections by taking a high daily dose of oral antibiotics after dental implantation.The antibiotics oral administration has many side effects such as gastrointestinal symptoms,skin rashes and thrush.Coating antibiotics on the biomaterials surface could be a promising solution to reduce these disadvantages through locally releasing antibiotics in a controlled manner.The aim of this study was to investigate the effects of doxycycline coating layer on titanium-zirconium alloy surfaces in vitro and in vivo.In our previous studies,we demonstrated the chemical presence of doxycycline layer in vitro.In this study,we examined its physical presence using field emission scanning electron microscope and confocal microscope.We also analyzed its controlled released manner using Nano-Drop UV Vis spectrometer.After in vitro characterization of the coating layer,we evaluated its effects on the implant osseointegration in dogs and rabbits.The histological and histomorphometrical results exhibited no significant difference between doxycycline coated and uncoated groups regarding the implants osseointegration and biocompatibility for dental applications.Therefore,coating a doxycycline layer on TiZr implants could be favorable for reducing or removing the antibiotics oral administration after the implantation surgery.