Oral Microbiota and Porphyromonas gingivalis Kgp Genotypes Altered in Parkinson's Disease with Mild Cognitive Impairment.

Cognitive impairment (CI) is a common complication of the non-motor symptoms in Parkinson's disease (PD), including PD with mild cognitive impairment (PD-MCI) and PD dementia. Recent studies reported the oral dysbiosis in PD and CI, respectively. Porphyromonas gingivalis (P. gingivalis), a pathogen of oral dysbiosis, plays an important role in PD, whose lysine-gingipain (Kgp) could lead to AD-type pathologies. No previous study investigated the composition of oral microbiota and role of P. gingivalis in PD-MCI. This study aimed to investigate the differences of oral microbiota composition, P. gingivalis copy number, and Kgp genotypes among PD-MCI, PD with normal cognition (PD-NC) and periodontal status-matched control (PC) groups. The oral bacteria composition, the copy number of P. gingivalis, and the Kgp genotypes in gingival crevicular fluid from PD-MCI, PD-NC, and PC were analyzed using 16S ribosomal RNA sequencing, quantitative real-time PCR, and MseI restriction. We found that the structures of oral microbiota in PD-MCI group were significantly different compared to that in PD-NC and PC group. The relative abundances of Prevotella, Lactobacillus, Megasphaera, Atopobium, and Howardella were negatively correlated with cognitive score. Moreover, there was a significant difference of Kgp genotypes among the three groups. The predominant Kgp genotypes of P. gingivalis in the PD-MCI group were primarily Kgp II, whereas in the PD-NC group, it was mainly Kgp I. The Kgp II correlated with lower MMSE and MoCA scores, which suggested that Kgp genotypes II is related to cognitive impairment in PD.

Retrospective study of the clinicopathological characteristics and prognosis of elderly patients with oropharyngeal squamous cell carcinoma.

OBJECTIVE: Oropharyngeal squamous cell carcinoma (OPSCC) is a malignant tumor that occurs at the tongue base, soft palate, palatine tonsil, and pharyngeal wall. Few studies of OPSCC have been performed in elderly patients. METHODS: Patients with human papilloma virus (HPV)-related OPSCC were extracted from the Head and Neck with HPV Status Database of the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. We identified 355 patients with HPV-positive status, and we retrospectively evaluated elderly (≥65 years) and younger (30-64 years) patient groups to compare the differences. RESULTS: Of the 355 patients who were diagnosed with HPV-related OPSCC, 113 constituted the elderly group. Comparing the elderly group with the younger group, the 3-year HPV-positive overall survival (OS) rates were 62.4% and 70.2%, respectively, and the 5-year OS rates were 50.4% and 59.2%, respectively. Cox regression analysis demonstrated that tumor (T) stage and chemotherapy were prognostic factors for OS. CONCLUSION: Elderly patients with OPSCC had different clinicopathological characteristics. T stage and chemotherapy should be priorities when evaluating the OS of elderly patients with OPSCC.

Constructing self-adhesive and robust functional films on titanium resistant to mechanical damage during dental implanting.

HYPOTHESIS: Osseointegration can be enhanced by introducing bioactive polyelectrolyte-multilayer films on implant surfaces. To guarantee films to function successfully in use, keeping structural integrity during implanting is necessary, which requires films with strong adhesion and cohesion to resist the mechanical damage. Catechol is considered as the origin of amazing adhesion of mussels. We hypothesize that catechol functionalization of polyelectrolytes enables film construction on implants in a non-aggressive way, and helps films resist mechanical damages during implanting. EXPERIMENTS: With lipopolysaccharide-amine nanopolymersomes (NPs), catechol-functionalized hyaluronic acid and NPs (cHA, cNPs) as a polycation, polyanion and primer, respectively, catechol-functionalized polyelectrolyte-multilayer films (cPEMs) were constructed on substrates via Layer-by-layer self-assembly. Effects of catechol functionalization on construction, surface properties, assembly mechanisms, structural integrity, mechanical properties and cytotoxicity of cPEMs were studied. FINDINGS: Self-adhesive cPEMs can be constructed on substrates, which grow exponentially and are driven by coordination, covalent bonding, electrostatic interactions, hydrogen bonding, etc. cPEMs with suitable catechol concentrations can resist mechanical damage to keep structural integrity in simulated clinical implantation, show stronger adhesion and cohesion than non-catechol-functionalized films in nanoscratch and nanoindentation tests, and are non-cytotoxic to MSCs. With excellent drug-loading and cytosolic-delivery capacity of NPs, cPEM is promising in improving osseointegration of implants.

Panax notoginseng preparations as adjuvant therapy for diabetic kidney disease: a systematic review and meta-analysis.

Context: Panax notoginseng (Burk.) F.H. Chen (Araliaceae) preparations (PNP) are traditional Chinese medicines used as adjuvant therapeutics for diabetic kidney disease (DKD).Objective: To systematically review the efficacy of PNP as adjunct DKD therapy, including their effects on kidney function, serum lipid levels and fasting blood glucose levels.Methods: The databases PubMed, Embase, Medline, Cochrane Library, CINAHL, China Biology Medicine disc, Wanfang, VIP and China National Knowledge Infrastructure were systematically searched from the date of their inception until May 2019. Panax notoginseng, Panax notoginseng saponins, Lulutong, Xueshuantong and Xuesaitong were the key terms searched. Randomized controlled trials (RCTs) comparing the combined use of PNP and conventional medicines (CM) versus CM for DKD were included. Data were pooled using random or fixed effect models depending on heterogeneity.Results: In total, 24 RCTs involving 1918 participants were analysed. Adjunct PNP with CM was associated with reduction of albuminuria (MD -26.89 mg, 95% CI: -33.35 to -20.42), proteinuria (MD -0.32 g/24 h, 95% CI: -0.36 to -0.27), serum creatinine (MD -4.52 µmol/L, 95% CI: -8.71 to -0.32), total cholesterol (MD -1.56 mmol/L, 95% CI: -2.33 to -0.78), triglycerides (TG) (MD -0.56 mmol/L, 95% CI: -0.80 to -0.31) and low-density lipoprotein cholesterol (MD -0.94 mmol/L, 95% CI: -1.49 to -0.40) compared with CM.Conclusions: This is the first meta-analysis investigating adjuvant PNP therapy for DKD. PNP apparently exerted beneficial effects on kidney function and improved the metabolism of serum lipids by CM. Further, well-conducted, high-quality trials on DKD patients are needed to provide high-quality evidence.

Comparison of osteogenic differentiation induced by siNoggin and pBMP-2 delivered by lipopolysaccharide-amine nanopolymersomes and underlying molecular mechanisms.

Purpose: Gene therapies via Noggin small interfering (si)RNA (siNoggin) and bone morphogenetic protein (BMP)-2 plasmid DNA (pBMP-2) may be promising strategies for bone repair/regeneration, but their ideal delivery vectors, efficacy difference, and underlying mechanisms have not been explored, so these issues were probed here. Methods: This study used lipopolysaccharide-amine nanopolymersomes (LNPs), an efficient cytosolic delivery vector developed by the research team, to mediate siNoggin and pBMP-2 to transfect MC3T3-E1 cells, respectively. The cytotoxicity, cell uptake, and gene knockdown efficiency of siNoggin-loaded LNPs (LNPs/siNoggin) were studied, then the osteogenic-differentiation efficacy of MC3T3-E1 cells treated by LNPs/pBMP-2 and LNPs/siNoggin, respectively, were compared by measuring the expression of osteogenesis-related genes and proteins, alkaline phosphatase (ALP) activity, and mineralization of the extracellular matrix at all osteogenic stages. Finally, the possible signaling pathways of the two treatments were explored. Results: LNPs delivered siNoggin into cells efficiently to silence 50% of Noggin expression without obvious cytotoxicity. LNPs/siNoggin and LNPs/pBMP-2 enhanced the osteogenic differentiation of MC3T3 E1 cells, but LNPs/siNoggin was better than LNPs/pBMP-2. BMP/Mothers against decapentaplegic homolog (Smad) and glycogen synthase kinase (GSK)-3ß/ß-catenin signaling pathways appeared to be involved in osteogenic differentiation induced by LNPs/siNoggin, but GSK-3ß/ß-catenin was not stimulated upon LNPs/pBMP-2 treatment. Conclusion: LNPs are safe and efficient delivery vectors for DNA and RNA, which may find wide applications in gene therapy. siNoggin treatment may be a more efficient strategy to enhance osteogenic differentiation than pBMP-2 treatment. LNPs loaded with siNoggin and/or pBMP-2 may provide new opportunities for the repair and regeneration of bone.

Cellular behaviours of bone marrow-derived mesenchymal stem cells towards pristine graphene oxide nanosheets.

OBJECTIVES: Graphene oxide (GO), the derivative of graphene with unique properties, has attracted much attention for applications in dental implants. The aim of this study was, by two biomimetic cell culture methods, to investigate the quantitative relationship between the concentration of pristine GO nanosheets and their cellular behaviours towards bone marrow-derived mesenchymal stem cells (BMSCs). MATERIALS AND METHODS: The cells were firstly characterized according to their morphology, self-renewal capabilities and multipotency. Subsequently, adhesion density, proliferation, alkaline phosphatase activity and mineralization of BMSCs treated with various concentrations of GO were analysed. In addition, osteogenic-related proteins were measured for further verification of the GO-induced osteogenic differentiation. RESULTS: Pristine GO nanosheets inhibited the proliferation of BMSCs at a high concentration of 10 µg/mL during the first 3 days with two seeding methods and facilitated proliferation of BMSCs at a low concentration of 0.1 µg/mL after 5 days with a sequential-seeding method compared to a co-seeding method. Analogously, osteogenic differentiation was promoted when BMSCs were treated with 0.1 µg/mL of GO. Both the proliferation and differentiation showed concentration-dependent behaviour. Interestingly, Wnt/ß-catenin signalling pathway appeared to be involved in osteogenic differentiation induced by pristine GO nanosheets. CONCLUSIONS: Pristine GO nanosheets at a concentration of 0.1 µg/mL provide benefits to promote BMSCs proliferation and osteogenesis under a sequential-seeding method, contributing to the use of GO for dental implantation.