CaSR modulates proliferation of the superficial zone cells in temporomandibular joint cartilage via the PTHrP nuclear localization sequence.

The superficial zone cells in mandibular condylar cartilage are proliferative. The present purpose was to delineate the relation of calcium-sensing receptor (CaSR) and parathyroid hormone-related peptide nuclear localization sequence (PTHrP87-139 ), and their role in the proliferation behaviors of the superficial zone cells. A gain- and loss-of-function strategy were used in an in vitro fluid flow shear stress (FFSS) model and an in vivo bilateral elevation bite model which showed mandibular condylar cartilage thickening. CaSR and PTHrP87-139 were modulated through treating the isolated superficial zone cells with activator/SiRNA and via deleting CaSR or parathyroid hormone-related peptide (PTHrP) gene in mice with the promoter gene of proteoglycan 4 (Prg4-CreERT2 ) in the tamoxifen-inducible pattern with or without additional injection of Cinacalcet, the CaSR agonist, or PTHrP87-139 peptide. FFSS stimulated CaSR and PTHrP expression, and accelerated proliferation of the Prg4-expressing superficial zone cells, in which process CaSR acted as an up-streamer of PTHrP. Proteoglycan 4 specific knockout of CaSR or PTHrP reduced the cartilage thickness, suppressed the proliferation and early differentiation of the superficial zone cells, and inhibited cartilage thickening and matrix production promoted by bilateral elevation bite. Injections of CaSR agonist Cinacalcet could not improve the phenotype caused by PTHrP mutation. Injections of PTHrP87-139 peptide rescued the cartilage from knockout of CaSR gene. CaSR modulates proliferation of the superficial zone cells in mandibular condylar cartilage through activation of PTHrP nuclear localization sequence. Our data support the therapeutic target of CaSR in promoting PTHrP production in superficial zone cartilage.

Long-term effect of bilateral anterior elevation of occlusion on the temporomandibular joints.

OBJECTIVE: Incisors tubed prosthesis with bilateral anterior elevation (BAE) relation had been reported to stimulate the proliferative response in the mandibular condylar cartilage of mice, thus the prosthetic occlusion elevation had been proposed to treat cartilage degeneration. Currently, we aimed to detect the long-term effect of BAE on temporomandibular joints (TMJs). MATERIALS AND METHODS: Twelve 6-week-old female mice were assigned to age-matched control and BAE groups (n = 6). Micro-CT images and the macro- and micro-morphology of the mandibular condyles were analyzed at 29 weeks. RESULTS: Compared with the age-matched controls, in BAE group, there were loss of subchondral cortical bone and heavy loss of the subchondral trabecular bone at the superior sites of the TMJ condyles, but hyperostosis at the inferior sites as revealed by micro-CT images and histological slices. In BAE group, cartilage thickness and matrix area were increased with upregulated expression of type II, type X collagen, and Ki67, but the expression of cleaved caspase-3 was downregulated (all, p < 0.05). CONCLUSION: In addition to cartilage thickening, long-term BAE induces loss of the subchondral cortical bone and heavy loss of the underneath subchondral trabecular bone, but hyperostosis further underneath. Using BAE as a treatment remains double-edged.

Effects of wogonoside on the inflammatory response and oxidative stress in mice with nonalcoholic fatty liver disease.

CONTEXT: Wogonoside has many pharmacological activities, but whether it has a protective effect against non-alcoholic fatty liver disease (NAFLD) has not been reported. OBJECTIVE: This study investigates the protective effect of wogonoside against NAFLD in mice and its potential mechanism. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into control group, NAFLD group and low-, medium- and high-dose wogonoside groups (5, 10 and 20 mg/kg, respectively) (n= 12). Mice in the control group were fed with the standard diet, and those in NAFLD group and low-, medium- and high-dose wogonoside groups were fed with a high-fat diet. The different doses of wogonoside were administered by gavage once a day for 12 weeks. RESULTS: Compared with those in NAFLD group, the liver mass, liver index and the LDL, TG, TC, IL-2, IL-6, TNF-α, MDA and NF-κB p65 levels were decreased, and the SOD and GSH-Px activities, and HDL, IκBα, Nrf2 and HO-1 contents were increased in wogonoside groups. Compared with those in the NAFLD group, wogonoside (5, 10 and 20 mg/kg) reduced AST (132.21 ± 14.62, 115.70 ± 11.32 and 77.94 ± 8.86 vs. 202.35 ± 19.58 U/L) and ALT (104.37 ± 11.92, 97.53 ± 10.12 and 56.74 ± 6.33 vs. 154.66 ± 14.23 U/L) activities in the serum. DISCUSSION AND CONCLUSIONS: Wogonoside has a protective effect against NAFLD in mice, which may be related to its anti-inflammation and inhibition of oxidative stress, suggesting that wogonoside may be a potential therapeutic agent for the treatment of NAFLD.

Antibacterial properties and biocompatibility in vivo and vitro of composite coating of pure magnesium ultrasonic micro-arc oxidation phytic acid copper loaded.

Bone infection and implant secondary removal remains a clinical challenge. We used ultrasonic micro-arc oxidation (UMAO) and conversion of phytic acid copper plating to prepare a pure magnesium polyhydric biofilm; we evaluated the surface microstructures, phase, element composition, and wettability of the film in vitro. The antibacterial activity of films with different Cu contents was confirmed by coating method, imaging examination, and microbiological cultures in vitro. The biocompatibility of biofilms was confirmed by cell proliferation, vitality, and morphology assays in vitro and histological evaluation in vivo. MC3T3-E1 cells were co-cultured with different films to assess cell viability on the films. The results showed that the mass fraction of Cu increased with increasing time of copper plating, and the surface of the Cu group was more dense and uniform. Additionally, copper coating significantly inhibited the growth of E. coli and Staphylococcus aurous. We also found that the adhesion, proliferation, and differentiation of the cells on the surface of copper plating were enhanced. Copper implantation of animals in vivo showed fine ability to promote bone growth. Antibacterial activity and biocompatibility of pure magnesium UMAO-phytic acid-Cu3min implant film are excellent, so the film has potential application value in the treatment of bone implantation.

Hydrothermal Growth and Electrochemical Performance of Carbon-Coated Porous SnO2 Nanospheres.

The porous SnO2 nanospheres were fabricated by hydrothermal method and then the carbon layer was coated as a buffer cushion through a facile hydrothermal process in aqueous D-glucose followed by a subsequent calcination at 500 °C in a nitrogen (N2) atmosphere. The materials were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), thermogravimetric analysis and Raman spectra. Based on the experimental results, the thickness of carbon layer could be well-controlled by hydrothermal time and D-glucose concentration. The typical as-prepared carbon-coated porous SnO2 nanospheres show an initial discharge capacity of 711.26 mAhg-1 and a stabilized capacity at 414 mAhg-1 after 50 cycles. It was shown that the carbon-coated porous SnO2 nanospheres exhibited better electrochemical properties in terms of high Columbic efficiency and rate performance, which are attributed to the porous structure and the outer carbon layer.

Construction and application of a new cell electrochemical detecting system based on the hyposmotic principle.

A new cell electrochemical detecting system has been constructed based on the hyposmotic principle, in which the electrochemical signals have been strengthened by about 109.75% for the signal at about +0.70 V and 532.94% for the signal at about +1.03 V. The electrochemical detection limits of the cells have been improved by one order of magnitude. The individual concentrations of intracellular purines have been obtained.

Two-signal electrochemical method for evaluation suppression and proliferation of MCF-7 cells based on intracellular purine.

Two electrochemical signals ascribed to xanthine/guanine and hypanthine/adenine in MCF-7 cells were detected at 0.726 and 1.053 V, respectively. Based on the intensity of signals, the genistein-induced proliferation and suppression of MCF-7 cells could be evaluated. The results showed that with the increase of genistein dose at the range of 10(-9) to 10(-6)M, the two electrochemical signals of MCF-7 cell suspension increased due to the proliferation, whereas the tendency at the high dosage range of more than 10(-5)M was decreased. The proliferation and cytotoxicity obtained by the electrochemical method were in agreement with those obtained by cell counting and the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium] method. Thus, the two-signal electrochemical method is an effective way to evaluate the effect of drugs on cell activity based on purine metabolism.

In situ electrochemical assessment of cytotoxicity of chlorophenols in MCF-7 and HeLa cells.

An in situ electrochemical method was used to assess the cytotoxicity of chlorophenols using human breast cancer (MCF-7) and cervical carcinoma (HeLa) cells as models. On treatment with different chlorophenols, the electrochemical responses of the selected cells, resulting from the oxidation of guanine and xanthine in the cytoplasm, indicated the cell viability. In addition, the in situ in vitro electrochemical method was further compared with the traditional MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. Although similar cytotoxicity data were obtained from both methods, the effective concentrations of chlorophenols that inhibited 50% cell growth (EC50 values) from the electrochemical method were only slightly lower than those from the MTT assay. These results indicate that the in situ in vitro electrochemical method paves a simple, rapid, strongly responsive, and label-free way to the cytotoxicity assessment of different chlorophenol pollutants.

Microbial inactivation of pressure spray combined with high-voltage electrospray and its application in honey raspberry juice.

Pressure spray combined with high-voltage electrospray (PS-ES) has garnered considerable interest as a novel, non-thermal approach for microbial inactivation and preservation of liquid food. This study compared PS-ES with heat treatment (HT) to understand its inactivation mechanism against E. coli and S. aureus in a simulated system. Microbial activity, cell permeability, membrane integrity, membrane potential, and cell membrane structure were assessed. Furthermore, the impact of PS-ES treatment on microbial activity and flavor in honey raspberry juice, was examined. The changes in microbial growth and color during storage were also discussed. The experimental findings revealed that PS-ES treatment effectively reduced the number of E. coli and S. aureus by 1.99 and 1.83 log colony-forming units (CFU/mL). Additionally, it disrupted the integrity of bacterial cell membranes increasing their permeability, which led to the release of cellular proteins and nucleic acids. PS-ES treatment lowered the membrane potential and altered the structure of bacterial proteins. Application of PS-ES in honey raspberry juice reduced bacterial counts from 4.48 log CFU/mL to 1.99 log CFU/mL, with less flavor deterioration compared to HT treatment. After 30 days of storage at 4 °C and room temperature, PS-ES effectively controlled the growth of microorganisms in raspberry juice and maintained the color of the juice.

Detection of the cell viability and proliferation using two-signal electrochemical method.

Two electrochemical signals of the MCF-7 cell were simultaneously detected by using multiwall carbon nanotubes and room temperature ionic liquid composite film modified electrode. The signal at +0.726 V due to the oxidation of xanthine and guanine, was obviously improved. And the signal at +1.053 V due to the oxidation of hypoxanthine and adenine was found for the first time. This two-signal electrochemical method is credible to detect cell viability and proliferation.

SIPA1 boosts migration and proliferation, and blocks apoptosis of glioma by activating the phosphorylation of the FAK signaling pathway.

Background: We aimed to analyze the regulatory effects of SIPA1 (signal-induced proliferation-associated protein 1) on glioma progression and the dominant signaling pathway. Methods: Differential level of SIPA1 in glioma and normal tissues and cells was determined. Migratory, proliferative, apoptotic and cell cycle progression changes in A172 cells with overexpression or knockdown of SIPA1 were examined. Finally, protein levels of phosphorylated FAKs in A172 cells intervened by SIPA1, and the FAK inhibitor PF562271 were detected. Results: SIPA1 was upregulated in glioma cases. Knock-down of SIPA1 reduced migratory and proliferative rates of glioma cells, increased apoptotic cell rate, and declined cell ratio in the S phase. The knockdown of SIPA1 also downregulated cell cycle proteins. In addition, SIPA1 upregulated phosphorylated FAKs in A172 cells and thus boosted malignant phenotypes of glioma. Conclusions: SIPA1 is upregulated in glioma that boosts migratory and proliferative potentials of glioma cells by activating the phosphorylation of the FAK signaling pathway.

Protective effect of Monarda didymaL. essential oil and its main component thymol on learning and memory impairment in aging mice.

The aging process of human beings is accompanied by the decline of learning and memory ability and progressive decline of brain function, which induces Alzheimer's Disease (AD) in serious cases and seriously affects the quality of patient's life. In recent years, more and more studies have found that natural plant antioxidants can help to improve the learning and memory impairment, reduce oxidative stress injury and aging lesions in tissues. This study aimed to investigate the effect of Monarda didymaL. essential oil and its main component thymol on learning and memory impairment in D-galactose-induced aging mice and its molecular mechanism. The composition of Monarda didymaL. essential oil was analyzed by Gas Chromatography-Mass Spectrometer (GC-MS). A mouse aging model was established by the subcutaneous injection of D-galactose in mice. The behavior changes of the mice were observed by feeding the model mice with essential oil, thymol and donepezil, and the histopathological changes of the hippocampus were observed by HE staining. And the changes of acetylcholinesterase (AchE), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities, and the content of malondialdehyde (MDA) in hippocampal tissues were detected by corresponding kits. The expression of mitogen activated protein kinase (MAPK) and nuclear factor E2 related factor 2 (Nrf2) pathways related proteins were detected by western blot. Animal experimental results showed that compared with model group, the above indexes in Monarda didymaL. essential oil and thymol groups improved significantly in a dose-dependent manner. Monarda didymaL. essential oil and its main active component thymol can improve the learning and memory impairment of aging mice to some extent, and Nrf2 and MAPK pathways may be involved in its action process.

The improvement of Coreopsis tinctoria essential oil on learning and memory impairment of d-galactose-induced mice through Nrf2/NF-κB pathway.

Essential oil of Coreopsis tinctoria (EOC) is a essential substance extracted from Coreopsis tinctoria with the excellent anti-oxidant effect. However, it is still unclear whether EOC can improve learning and memory impairment and its mechanism. The purpose of this study was to investigate the effect of EOC on learning and memory impairment induced by D-galactose (D-gal) in mice and reveal its mechanism. The composition of EOC was analyzed by GC-MS, and the results showed that the highest content was D-limonene. The follow-up experiments were conducted by comparing EOC with D-limonene. The aging model was established by subcutaneous injection of D-gal, and donepezil, D-limonene and EOC were given by intragastric administration. It was found that EOC and D-limonene significantly improved learning and memory impairment induced by D-gal through the Morris water maze and step-through tests. Pathological and biochemical analysis showed that the hippocampal morphologic of mice was damage and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) induced by D-gal were decreased, while the content of malondialdehyde (MDA) was increased, while EOC and D-limonene could reverse the morphological changes and reduce oxidative damage. In addition, EOC and D-limonene significantly increased body weight and organ coefficients, including liver, spleen and kidney. Moreover, EOC and D-limonene improved the expression of nuclear factor E2 related factor 2 (Nrf2) pathway and inhibited nuclear transcription factors-κB (NF-κB) pathway. In summary, the results showed that EOC and D-limonene could improve learning and memory impairment induced by D-gal through Nrf2/ NF-κB pathway. It was clear that as a mixture, EOC was better than D-limonene on improving learning and memory impairment.

A Conductive Bamboo Fabric with Controllable Resistance for Tailoring Wearable Sensors.

Force-sensitive textile sensors are becoming a research hotspot as a part of wearable devices. The core research topic is the method to obtain the sensing property, which decides the sensitivity and service performance of the sensors. Here, we introduce a new sensing mechanism based on a statistical change of contact resistance that exhibits an exponential decay upon strain or pressure, where a novel conductive bamboo fabric is prepared and the dependence of electric conductivity on the fabric structure is discovered. The fabric surface resistivity (ρs) is anisotropic with respect to the measuring directions and the warp, weft, and linear densities. The surface resistance (Rs) decreases rapidly under pulling force, especially in diagonal directions, making it available in designing strain sensors. The volume resistivity (ρv) decreases with increasing weft and linear densities, too. The vertical resistance (Rv) decays exponentially under pressure, and the rule is retained even if the fabric is coated with a polymer, leading to diverse possible pressure sensors with a good service performance (e.g., waterproof). Finally, the conductive fabric could be facilely tailored to various wearable sensors with a fast response time, e.g., sensing finger sleeves and sensing insole, which could be used to operate the manipulator's fingers or to monitor human walking gestures, respectively.

Effects of ethyl acetate extract from Coreopsis tinctoria on learning and memory impairment in d-galactose-induced aging mice and the underlying molecular mechanism.

The aim of this study was to investigate the effects of ethyl acetate extract from Coreopsis tinctoria (EACC) on learning and memory impairment in d-galactose-induced aging mice and the underlying molecular mechanism. The composition of EACC was analyzed by UPLC-MS, and the targets and pathways of EACC to improve learning and memory impairment were predicted and analyzed by the network pharmacology method. A mouse aging model was established by subcutaneous injection of d-galactose in mice, and EACC and piracetam were given to the model mice by gavage to observe their behavioral changes and changes in their SOD and GSH-Px activities in MDA contents in their peripheral blood serum and in the contents of Glu and GABA in their brain tissues. Then the hippocampus of the three mice selected from each of the MOD group and EACC-H group was separated for RT-qPCR assay. The results of the animal experiments showed that EACC could improve the learning and memory impairment of model mice by affecting the level of oxidative stress enzymes in serum and the content of neurotransmitters in the brain tissue. The results of network pharmacology analysis showed that the EACC components corresponded to 74 learning and memory-related targets, of which 13 were enriched in the long-term potentiation pathway. The results of RT-qPCR showed that 12 of the 13 detected targets were consistent with the predicted targets, and 9 of them were located in the NMDA receptor-related pathway of the long-term potentiation process and the pathway played an important regulatory role. It is believed that EACC could improve the learning and memory impairment of d-galactose-induced aging mice by acting on the nine targets Grin1, Grin2a, Camk2a, Camk2b, Kras, Raf1, Mapk1, Mapk3 and Creb to affect the NMDA receptor-related pathway of long-term potentiation.

Hawthorn pectin: Extraction, function and utilization.

Pectin has been widely used as emulsifiers, gelling agents, glazing agents, stabilizers, and thickeners in food products. Hawthorn pectin has a higher viscosity than other foods-derived pectin such as lemon and apple pectin. It is also reported as a multifunctional fruit substance, which reduces the risk of hyperlipidemia and dyslipidemia. Therefore, hawthorn pectin is a potential resource for the development of new drugs, functional foods, and health-care products. This review symmetrically summarized the extraction methods, physiological characteristics, functional properties, and processing technologies of hawthorn pectin. It laid a foundation for the further research of hawthorn pectin and promoted the diversified utilization of hawthorn.

Strain-Induced Form Transition and Crystallization Behavior of the Transparent Polyamide.

A transparent polyamide, poly(4,4'-aminocyclohexyl methylene dodecanedicarboxylamide) (PAPACM12), was studied and characterized by in situ wide-angle X-ray diffraction (WAXD) to establish the relationship between its crystallization behavior, crystalline form transition under external fields, and macroscopic properties. During the heating process, cold crystallization occurred and increased, and there was no form transition below the melting point. During the isothermal process, PAPACM12 exhibited the same crystalline structure as that during the heating process. The crystalline structure of PAPACM12 was attributed to α-form crystal, which is the stable form, according to the WAXD diffraction peaks of the conventional AABB-type polyamides. During stretching deformation, the crystal transition from α-form to γ-form and strain-induced crystallization were observed to contribute to the PAPACM12 with higher breaking strength and elongation. This study firstly determine the crystalline structure of transparent polyamides, and then the controlled strain-induced crystallization and transformation are demonstrated to be effective preparation methods for polyamides with high properties.

Highly Efficient Photochromic Tungsten Oxide@PNIPAM Composite Spheres with a Fast Response.

Coloration efficiency and a fast response are important in developing materials for optical switching. A novel, highly efficient photochromic tungsten oxide@poly(N-isopropylacrylamide) (PNIPAM) hybrid sphere is reported, whose colors can be rapidly converted between yellow and blue under different lights. The color change can be seen clearly even if the tungsten oxide content in the hybrid sphere is very low, exhibiting outstanding coloration efficiency of tungsten oxide. A photochromic mechanism is proposed in which the amide group in PNIPAM spheres participates in electron injection and the transition of valence states between W5+ and W6+ in the photochromic process. The interaction between tungsten oxide and PNIPAM plays a key role in enhancing the coloration efficiency of tungsten oxide and accelerating the switchable speed of color transformation, which is very useful in developing new photochromic materials. These hybrid spheres can be used in rewritable record displays and have wide potential applications in controlling energy transmittance in smart windows or in detecting UV light in optical sensors.

Enterovirus 71 induces autophagy in mice via mTOR inhibition and ERK pathway activation.

AIMS: Enterovirus 71 (EV71) is one of the main viruses that cause hand-foot-mouth disease; however, its pathogenic mechanism remains unclear. This study characterized the relationship between EV71 infection and autophagy in vivo and explored the molecular mechanism underlying EV71-induced autophagy. MATERIALS AND METHODS: A mouse model of EV71 infection was prepared by intraperitoneally injecting one-day-old BALB/c suckling mice with 30 µL/g of EV71 virus stock solution for 3 days. The behavior, fur condition, weight, and mice mortality were monitored, and disease scores were calculated. The pathological damage to the brain, lung, and muscle tissues after the viral infection was assessed by hematoxylin and eosin staining. Western blot and immunofluorescence analyses were used to detect the expression levels of viral protein 1, Beclin-1, microtubule-associated protein light chain 3B, mammalian target of rapamycin (mTOR), phosphorylated (p)-mTOR, extracellular signal-regulated protein kinase (ERK) 1/2, and p-ERK. KEY FINDINGS: EV71 infection can trigger autophagy in the brains, lungs, and muscles of infected mice. The autophagy response triggered by EV71 is achieved by the simultaneous mTOR inhibition and the ERK pathway activation. Blocking the mTOR pathway may aggravate autophagy, whereas ERK inhibition alleviates autophagy but cannot completely prevent it. SIGNIFICANCE: EV71 infection can induce autophagy in mice, involving mTOR and ERK signaling pathways. These two signaling pathways are independent and do not interfere with each other.

Effectiveness and safety of repetitive transcranial magnetic stimulation for the treatment of morphine dependence: A retrospective study.

ABSTRACT: Morphine dependence (MD) is a very common complication because of the chronic morphine consumption. Studies suggest that repetitive transcranial magnetic stimulation (rTMS) can be used for the treatment of MD. However, there is still lacking evidence to support rTMS for MD. Thus, this retrospective study aimed to investigate the effectiveness and safety of rTMS for patients with MD.In this retrosepctive study, a total of 100 patients with MD were included, and they were divided into a rTMS group (n = 50), and a control group (n = 50). All patients in both groups received occupational therapy. In addition, patients in the rTMS group received rTMS. All patients in both groups received a total of 8 weeks treatment. The outcomes comprised of morphine craving intensity, depression, anxiety, and sleep quality, which were appraised by Visual Analogue Scale (VAS), Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Pittsburgh Sleep Quality Index (PSQI), respectively. In addition, treatment-related adverse events were also considered for assessment.After 8 weeks treatment, patients in the rTMS group exerted better benefits in improving VAS (P < .01), SDS (P < .01), SAS (P < .01), and PSQI (P < .01), than patients in the control group. In addition, this study did not identify treatment-related adverse events in both groups.The findings of this study showed that rTMS treatment showed promising effectiveness on patients with MD. However, future studies should focus on warranting the present findings.