Differential molecular profiles and associated functionalities characterize connective tissue grafts obtained at different locations and depths in the human palate

The present study aimed to assess the molecular profiles of subepithelial connective tissue grafts(CTGs)obtained at different locations and depths in the human palate.Sixty-four CTGs belonging to anterior deep(AD),anterior superficial(AS),posterior deep(PD),and posterior superficial(PS)groups were subjected to RNA-Sequencing and their transcriptomes were analyzed computationally.Functional correlations characterizing the CTG groups were validated by cell biological experiments using primary human palatal fibroblasts(HPFs)extracted from the CTGs.A clearly more pronounced location-dependent than depth-dependent difference between the grafts,with a minimal number of genes(4)showing no dependence on the location,was revealed.Epithelial,endothelial,and monocytic cell migration was strongly(P<0.001)potentiated by AD-and PS-HPFs.Moreover,significantly increased expression of genes encoding C-C and C-X-C motif chemokine ligands as well as significantly(P<0.01)activated p38 signaling suggested immunomodulatory phenotype for AD-and PS-HPFs.Increased growth factor gene expression and significantly activated(P<0.001)Erk and Akt signaling in HPFs originating from A-CTGs implied their involvement in cell survival,proliferation,and motility.Prominent collagen-rich expression profile contributing to high mechanical stability,increased osteogenesis-related gene expression,and strongly activated(P<0.001)Smad1/5/8 signaling characterized HPFs originating from P-CTGs.The present data indicate that in humans,differences between palatal CTGs harvested from different locations and depths appear to be location-rather than depth-dependent.Our findings provide the basis for future personalization of the therapeutic strategy by selecting an optimal graft type depending on the clinical indications.

Protective effect of Cistanche deserticola on gentamicin-induced nephrotoxicity in rats

Objective: Gentamicin(GM) is a commonly used aminoglycoside antibiotic, however, renal toxicity has limited its usage. The present study was designed to evaluate the ameliorative effect of Cistanche deserticola on GM-induced nephrotoxicity in rats.Methods: The nephrotoxicity in rats was induced by intraperitoneal administration of GM(100 mg/kg)for 10 consecutive days. Glomerular filtration rate, blood urea nitrogen, creatinine and kidney histopathology were detected to assess the GM-induced nephrotoxicity. The oxidative stress(catalase,superoxide dismutase, glutathione and malondialdehyde) was assessed. The inflammatory response(tumor necrosis factor-a, interleukin-6, myeloperoxidase and nuclear factor-kappa B) and apoptotic marker(Bax and Bcl-2) were also evaluated.Results: The results showed that water and 75% ethanol extracts of C. deserticola(named CDW and CDE,respectively)(100, 200 and 400 mg/kg) in combination with GM could recover the reduction of glomerular filtration rate and enhance the renal endogenous antioxidant capability induced by GM. The increase in the expression of renal inflammatory cytokines(tumor necrosis factor-a and interleukin-6), nuclear protein of nuclear factor-kappa B(p65) and the activity of myeloperoxidase induced by GM was significantly decreased upon CDW or CDE treatment. In addition, CDW or CDE treatment could decrease the Bax protein expression and increase the Bcl-2 protein expression in GM-induced nephrotoxicity in rats significantly.Conclusion: The study demonstrated that C. deserticola treatment could attenuate kidney dysfunction and structural damage in rats induced by GM through the reduction of inflammation, oxidative stress and apoptosis.

Metal-free nucleophilic 7,8-dearomatization of quinolines:Spiroannulation of aminoquinoline protected amino acids

Atom-and step-economy in IBX assisted diversity-oriented synthesis is achieved with a versatile AQ auxiliary α-amino acid analogs offering rapid access to polycyclic spiro-quinolines featuring a quaternary stereocenter in 20%–91% yields under mild conditions via 7,8-dearomatization of quinolines. Free of a preinstalled activation group is highlight of this intramolecular oxidation spiroannulation tandem reaction. This type of N-heterospirocycles, traditionally difficult to access, may open the door to a potentially interest scaffold for synthetic and medicinal chemistry.

Protective effect of hydroxysafflor yellow A on MSCs against senescence induced by D-galactose

Objective: To examine the protective effects of hydroxysafflor yellow A(HSYA) against the senescence of mesenchymal stem cells(MSCs) induced by D-galactose(D-gal) in vitro, and investigate the potential mechanism involved.Methods: Grouping experiment, Normal control(NC) group: conventional culture with complete medium;Senescence group: MSCs were cultured for 48 h with complete medium containing 10 g/L D-gal;HSYA group: on the basis of senescence induction, HSYA with the suitable concentration was used to protect MSCs. The key experimental indices associated with oxidative stress, inflammatory response, cell senescence, proliferation and apoptosis were measured through chemical colorimetry, β-galactosidase staining, Ed U incorporation and flow cytometry, respectively. The relative quantity(RQ) of proteins related closely to cell proliferation, apoptosis, and NF-κB signaling were measured by Western blotting.Results: As compared with Senescence group, treatment with HSYA(120 mg/L) effectively ameliorated the adverse situation of MSCs. Oxidation stress and inflammation along with D-Gal induction was dramatically alleviated in MSCs;The β-Gal-positive staining indicated that MSC senescence was significantly mitigated;The proliferative capability of MSCs was significantly increased by up-regulating PCNA and inhibiting p16 expression;The anti-apoptotic effect on MSCs was exerted by down-regulating the RQ of cleaved Caspase-3 and Bax;The activity of NF-κB signaling in MSCs was notably suppressed through inhibiting phosphorylation of IKKβ and p65.Conclusion: HSYA(120 mg/L) significantly delayed the D-Gal-induced senescence process in MSCs through attenuating inflammatory reaction and oxidative stress, and suppressing the activity of NF-κB signaling.

Investigation of the 12 orientations variants of nanoscale Al precipitates in eutectic Si of Al-7Si-0.6Mg alloy

Various orientations and diffraction patterns from nanoscale Al precipitates in eutectic Si were investigated by high-resolution transmission electron microscopy combined with transition matrix and stereographic projection.It was found that the Al precipitates had 12 variants,all orientation relationships can be expressed as:(001)Al//{111}Si,[110]Al//<110>Si.Further,a new diffraction pattern model from Al precipitates was established under[111]Si zone axis,which was in good agreement with the experiment data.The microstructure,adhesion strength and electronic structure of the interface between Al precipitate and Si matrix were studied by first-principles calculation and experimental observation.The results show that the covalent bonds are formed between interfacial Al and Si atoms,which play a key role in interfacial bind strength.Based on the Griffith fracture theory,the cracks tend to form and expand in the interior of Al precipitates firstly,and the interfaces can act as a protective layer to prevent crack propagation.Therefore,the nanoscale Al precipitates will improve the toughness of eutectic Si particles by releasing part of stress through lattice distortion.In addition,the stretched nanoscale Al precipitates can act as effective heterogeneous nucleation sites for high density deformation nanotwins in eutectic Si during deformation,which significantly improved the deformability of eutectic Si.

Synthesis of polycyclic spiro-fused indolines via IBX-mediated cascade cyclization

We report a 2-iodoxybenzoic acid(IBX)-mediated intarmolecular oxidative spiro-fused tandem cyclization reaction of tryptophan analogs bearing an N-arylamides side-chain to rapidly afford polycyclic spiroindolines featuring multiple stereocenters including a quaternary stereocenters under mild reaction conditions.Among them,a novelty azaphosphol idine-containing spiroindoline compound is synthesized for the first time.It may open the door to azaphos pholidine-containing spiroindoline compound of potential interest in synthetic and medicinal chemistry.A plausible mechanism is proposed.