Increased apoptosis in human knee osteoarthritis cartilage related to the expression of protein kinase B and protein kinase Cα in chondrocytes

Protein kinase B (Akt) and protein kinase Cα (PKCα) play important roles in the regulation of cell apoptosis. The aim of this study was to investigate the expression of Akt and PKCa in chondrocytes of human knee osteoarthritic (OA) cartilage, further evaluating their role in chondrocyte apoptosis during OA progression. Human knee OA cartilages were obtained from 38 patients undergoing knee arthroplasty, which is the medium-late stage of OA. Healthy knee cartilages were obtained from 11 amputees. The samples taken from the condyle of femur were collected routinely for morphological, immunohistochemical and Western blot detection, respectively. Light microscopy and laser-scanning confocal microscopy were used for morphological observation. The optical density with computer image analysis evaluated the intensity of immunohistochemical reaction of Akt and PKCα in OA cartilage. Western blot detected the protein expression levels. The results indicated that Akt and PKCa were involved in OA progression, along with the increase of cell apoptosis. In OA cartilage, Akt decreased (p < 0.05) and PKCα increased (p < 0.05). There was a negative correlation and interaction between Akt and PKCα (r = –0.8). These results demonstrated that both Akt and PKCα are related to increased chondrocyte apoptosis in human OA cartilage. The correlation between human OA progression, the role of Akt and PKCα, and chondrocyte apoptosis allows for new therapeutic strategies to be considered

3′-O-β-Glucosyl-4′,5′-didehydro-5′-deoxyadenosine Is a Natural Product of the Nucleocidin Producers Streptomyces virens and Streptomyces calvus

Leverhulme Trust - RPG-2021-0283′-O-β-Glucosyl-4′,5′-didehydro-5′-deoxyadenosine 13 is identified as a natural product of Streptomyces calvus and Streptomyces virens. It is also generated in vitro by direct β-glucosylation of 4′,5′-didehydro-5′-deoxyadenosine 12 with the enzyme NucGT. The intact incorporation of oxygen-18 and deuterium isotopes from (±)[1-18O,1-2H2]-glycerol 14 into C-5′ of nucleocidin 1 and its related metabolites precludes 3′-O-β-glucosyl-4′,5′-didehydro-5′-deoxyadenosine 13 as a biosynthetic precursor to nucleocidin 1.Publisher PDFPeer reviewe

SIRT6 protects against palmitate-induced pancreatic β-cell dysfunction and apoptosis

Chronic exposure of pancreatic β-cells to abnormally elevated levels of free fatty acids can lead to β-cell dysfunction and even apoptosis, contributing to type 2 diabetes pathogenesis. In pancreatic β-cells, SIRT6 has been shown to regulate insulin secretion in response to glucose stimulation. However, what roles SIRT6 play in β-cells in response to lipotoxicity remain poorly understood. Our data indicated that SIRT6 protein and mRNA levels were reduced in islets from diabetic and aged mice. High concentrations of palmitate also led to a decrease in SIRT6 expression in MIN6 β-cells and resulted in cell dysfunction and apoptosis. Knockdown of Sirt6 caused an increase in cell apoptosis and impairment in insulin secretion in response to glucose in MIN6 cells even in the absence of high palmitate. Furthermore, overexpression of SIRT6 alleviated the palmitate-induced lipotoxicity with improved cell viability and increased glucose-stimulated insulin secretion. In summary, our data suggest that SIRT6 can protect against palmitate-induced β-cell dysfunction and apoptosis

Lateral dipole moments induced by all-cis-pentafluorocyclohexyl groups cause unanticipated effects in self-assembled monolayers

C. F. and A. T. thank the Fonds der Chemischen Industrie (FCI) for providing a PhD stipend. S. D., Y. B. L. and M. Z. thank the Helmholtz Zentrum Berlin for the allocation of synchrotron radiation beamtime at BESSY II and financial support. Y. L. thanks the China Scholarship Council (CSC) for financial support.All-cis-hexafluoro- and all-cis-pentafluoro-cyclohexane (PFCH) derivatives are new kinds of materials, the structures and properties of which are dominated by the highly dipolar Janus-face motif. Here, we report on the effects of integrating the PFCH groups into self-assembled monolayers (SAMs) of alkanethiolates on Au(111). Monolayers with an odd (eleven) and even (twelve) number of methylene groups were characterized in detail by several complementary experimental tools, supported by theoretical calculations. Surprisingly, all the data show a high similarity of both kinds of monolayers, nearly lacking the typically observed odd-even effects. These new monolayers have a packing density about 1/3 lower than that of non-substituted alkanethiolate monolayers, caused by the bulkiness of the PFCH moieties. The orientations of the PFCH groups and the alkyl chains could be determined independently, suggesting a conformation similar to the one found in the solid state structure of an analogous compound. Although in the SAMs the PFCH groups are slightly tilted away from the surface normal with the axial fluorine atoms pointing downwards, most of the dipole moments of the group remain oriented parallel to the surface, which is a unique feature for a SAM system. The consequences are much lower water contact angles compared to other partly fluorinated SAMs as well as rather moderate work function values. The interaction between the terminal PFCH moieties results in an enhanced stability of the PFCH-decorated SAMs toward exchange reaction with potential molecular substituents in spite of the lower packing density of these films.Publisher PDFPeer reviewe

Rehabilitation recognition skeleton data depth learning based on RNN

With the extensive application of deep learning in the field of human rehabilitation, skeleton based rehabilitation recognition is becoming more and more concerned with large-scale bone data sets. The key factor of this task is the two intra frame representations of the combined co-and the inter-frame. In this paper, an inter frame representation method based on RNN is proposed. Pointtion of each joint is joint-coded they are assembled into semantic both spatial and temporal domains.we introduce a global spatial aggregation which is able to learn superior joint co features over local aggregation

1-(5-Chloro-2,4-dihydroxy­phen­yl)-2-(4-ethoxy­phen­yl)ethanone

The structure of the title compound, C16H15ClO4, contains aryl rings which are inclined by 75.6 (1)° to each other. It displays intra­molecular O—H⋯O hydrogen bonding between the 2-hydr­oxy and carbonyl groups, forming a six-membered ring. Furthermore, the 4-hydr­oxy group, acting as a hydrogen-bond donor, is bound to the O atom of the 2-hydr­oxy group of another mol­ecule

Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a 13C-tracer study

BACKGROUND: Evidence suggests that the consumption of anthocyanin-rich foods beneficially affects cardiovascular health; however, the absorption, distribution, metabolism, and elimination (ADME) of anthocyanin-rich foods are relatively unknown. OBJECTIVE: We investigated the ADME of a (13)C5-labeled anthocyanin in humans. DESIGN: Eight male participants consumed 500 mg isotopically labeled cyanidin-3-glucoside (6,8,10,3',5'-(13)C5-C3G). Biological samples were collected over 48 h, and (13)C and (13)C-labeled metabolite concentrations were measured by using isotope-ratio mass spectrometry and liquid chromatography-tandem mass spectrometry. RESULTS: The mean +/- SE percentage of (13)C recovered in urine, breath, and feces was 43.9 +/- 25.9% (range: 15.1-99.3% across participants). The relative bioavailability was 12.38 +/- 1.38% (5.37 +/- 0.67% excreted in urine and 6.91 +/- 1.59% in breath). Maximum rates of (13)C elimination were achieved 30 min after ingestion (32.53 +/- 14.24 mug(13)C/h), whereas (13)C-labeled metabolites peaked (maximum serum concentration: 5.97 +/- 2.14 mumol/L) at 10.25 +/- 4.14 h. The half-life for (13)C-labeled metabolites ranged between 12.44 +/- 4.22 and 51.62 +/- 22.55 h. (13)C elimination was greatest between 0 and 1 h for urine (90.30 +/- 15.28 mug/h), at 6 h for breath (132.87 +/- 32.23 mug/h), and between 6 and 24 h for feces (557.28 +/- 247.88 mug/h), whereas the highest concentrations of (13)C-labeled metabolites were identified in urine (10.77 +/- 4.52 mumol/L) and fecal samples (43.16 +/- 18.00 mumol/L) collected between 6 and 24 h. Metabolites were identified as degradation products, phenolic, hippuric, phenylacetic, and phenylpropenoic acids. CONCLUSION: Anthocyanins are more bioavailable than previously perceived, and their metabolites are present in the circulation fo

Mesenchymal Stem Cell Transplantation for Liver Cell Failure: A New Direction and Option

Background and Aims. Mesenchymal stem cell transplantation (MSCT) became available with liver failure (LF), while the advantages of MSCs remain controversial. We aimed to assess clinical advantages of MSCT in patients with LF. Methods. Clinical researches reporting MSCT in LF patients were searched and included. Results. Nine articles (n=476) related with LF patients were enrolled. After MSCT, alanine aminotransferase (ALT) baseline decreased largely at half a month (P<0.05); total bilirubin (TBIL) baseline declined to a certain stable level of 78.57 μmol/L at 2 and 3 months (P<0.05). Notably, the decreased value (D value) of Model for End-Stage Liver Disease score (MELD) of acute-on-chronic liver failure (ACLF) group was higher than that of chronic liver failure (CLF) group (14.93 ± 1.24 versus 4.6 ± 5.66, P<0.05). Moreover, MELD baseline of ≥20 group was a higher D value of MELD than MELD baseline of <20 group with a significant statistical difference after MSCT (P=0.003). Conclusion. The early assessment of the efficacy of MSCT could be based on variations of ALT at half a month and TBIL at 2 and 3 months. And it had beneficial effects for patients with LF, especially in ACLF based on the D value of MELD

Aryl (β, β', β''-trifluoro)-tert-butyl : a candidate motif for the discovery of bioactives

Funding: UK Engineering and Physical Sciences Research Council - EP/S030506/1; Commonwealth Scholarship Commission.The (β,β′,β″-trifluoro)-tert-butyl (TFTB) group has received very little attention in the literature. This work presents a direct synthesis of this group and explores its properties. The TFTB group arises when the methyl groups of a tert-butyl moiety are exchanged for fluoromethyl groups. Sequential fluoromethylations result in a decrease of Log P (increasing hydrophilicity), ultimately by 1.7 Log P units in the TFTB group relative to that of tert-butyl benzene itself. A focus is placed on synthetic transformations, conformational analysis, and metabolism of the TFTB group in the context of presenting a favorable profile as a motif for the discovery of bioactives.Publisher PDFPeer reviewe