Chondroprotective effect of Alpinia oxyphylla extract in experimentally induced cartilage degradation in rabbit articular cartilage explants.

Alpinia oxyphylla is a widely used medicinal herb for diarrhea, gastralgia, tumors, hypertention, and cerebrovascular disorders. Here, we evaluated the chondroprotective effect of A. oxyphylla dried fruit ethanol extract (AOE) against cartilage degradation in rabbit articular cartilage explants. Treatment of interleukin-1α (IL-1α) and plasminogen increased degraded collagen release in culture supernatants, but pretreatment of AOE (50, 100, 200 µg/ml) inhibited the collagen release in dose-dependent manner. To examine the mechanism of action of AOE on chondroprotection, the level of matrix metalloproteinases-3 (MMP-3), matrix metalloproteinases-13 (MMP-13), tissue inhibitor of metalloprotease-1 (TIMP-1), and inflammatory mediators like prostaglandin E2 (PGE2 ) and nitric oxide (NO) was evaluated. AOE inhibited upregulation of MMP-3 and MMP-13 and downregulation of TIMP-1 and also reduced increase of PGE2 and NO level induced by exposure of IL-1α and plasminogen. These results indicate that AOE show chondroprotective effect through inhibiting collagen degradation via regulating MMPs, TIMP-1, and inflammatory mediators. PRACTICAL APPLICATIONS: Osteoarthritis (OA) is a one of the most common chronic disorders in elderly persons. Because the regenerative power of joint articular cartilage is very low, treatment of OA is difficult to expect complete recovery. Therefore, there is a need to develop a therapeutic agent that can safely and effectively inhibit the cartilage destruction. For the first time, we exhibited the inhibitory effect of AOE on collagen degradation through regulating MMPs and TIMP-1 in articular cartilage explants. These findings support AOE could be used as herbal therapeutic application for protecting articular cartilage to prevent OA.

Purpurin, a anthraquinone induces ROS-mediated A549 lung cancer cell apoptosis via inhibition of PI3K/AKT and proliferation.

OBJECTIVES: In this study, we sought to evaluate purpurin, a natural biomedicine and a potential inhibitor in decreasing the growth rate of lung cancer cells by modulating the role of PI3K/AKT signalling-associated proliferation and apoptosis. METHODS: A549 cells were treated with purpurin (30 µM) for 24 and 48 h incubation, respectively, and it has been analysed for cytotoxicity, ROS-mediated apoptotic staining. Moreover, purpurin-mediated lipid peroxidation and GSH were measured by biochemical estimation. Furthermore, PI3K/AKT signalling-mediated cell proliferation and apoptotic gene expression done were by western blot. KEY FINDINGS: In this study, we observed that purpurin could effectively kill A549 cancer cell lines and leads to cell death, thus conforming increased cytotoxicity, production of ROS-mediated enhancement of lipid peroxidation, nuclear fragmentation and apoptosis. Moreover, the GSH content of A549 cell lines was also diminished after treatment with purpurin. This study demonstrates that purpurin inhibits the phosphorylated PI3K/AKT molecules mediated cyclin-D1 and PCNA, thereby inducing apoptosis by observing increased proapoptotic mediators Bax, cleaved PARP, cytochrome-c, caspase-9 and caspase-3; and decreased Bcl-2 expression in the lung cancer cell lines. CONCLUSION: This result concluded that purpurin eliminates the A549 lung cancer cells by blocking the PI3K/AKT pathway thereby inducing apoptosis.

Improvement of Figure of Merit Pb(Zr,Ti)O3-Pb(Zn,Ni,Nb)O3-Pb(In,Nb)O3 Piezoelectric Ceramics.

Figure of merit the product of piezoelectric charge constant and the piezoelectric voltage constant-d33 × g33 in piezoelectric energy harvesting systems are critical measures in energy harvester applications. It is difficult to achieve high figure of merit because of the interdependence of d33 and the relative dielectric constant, εr. Until now, the prohibitive amount of effort required to solve this problem has led to it being considered an unsolvable issue. Lead zirconate titanate ceramic, Pb(Zr,Ti)O3, has been reported to exhibit high values of d33 and εr. However, to be employed as piezoelectric energy harvester, a candidate material is required to exhibit both high piezoelectric charge coefficient and high piezoelectric electric voltage coefficient simultaneously. To enhance the figure of merit of Pb(Zr,Ti)O3-based materials, dopants have also been considered. Pb(Zn,Ni,Nb)O3- added Pb(Zr,Ti)O3, Pb(Zr,Ti)O3-Pb(Zn,Ni,Nb)O3 ceramic has been reported to exhibit a high d33 value of 561 pC/N. It's dielectric constant has also been reported to be low at 1898. In this study, Pb(Zr,Ti)O3-Pb(Zn,Ni,Nb)O3-Pb(In,Nb)O3 was investigated in the context of enhancing the figure of merit of Pb(Zr,Ti)O3-based materials. During the proposed process, we increased the corresponding figure of merit by adding Pb(In,Nb)O3 material. Besides exhibiting a low dielectric constant, the Pb(In,Nb)O3 material was also observed to exhibit high d33 × g33 as the proposed doping increased the value of d33 greatly, while maintaining the dielectric constant (Yan, J., et al., 2019. Large engancement of trans coefficient in PZT-PZN energy harvesting system through introducing low εrPIN relaxor. Journal of the European Ceramic Society, 39, pp.2666-2672). Further, we conducted an optimization experiment by controlling the doping concentration and the sintering temperature.

Combination of Red Clover and Hops Extract Improved Menopause Symptoms in an Ovariectomized Rat Model.

Red clover and hops are already known for their alternative menopausal therapies; however, their combination has not yet been studied. This study aimed to evaluate the efficacy of the combination of red clover and hops extract (RHEC) for treating menopausal symptoms for the first time. A high-performance liquid chromatography (HPLC) method for RHEC was developed and validated for the analysis of biochanin A in red clover extract and xanthohumol in hops extract. An in vivo study was conducted using an ovariectomized rat model treated with RHEC (125, 250, and 500 mg/kg, p.o.) for a 12-week test period. Changes in body weight, tail skin temperature (TST), serum lipid profile, bone metabolism, antioxidants, and markers of vasorelaxation and uterus endometrium were evaluated. RHEC significantly inhibited body weight gain and decreased fat weight. Changes in TST associated with flashes were significantly inhibited in the RHEC groups. Other markers related to menopausal symptoms, such as blood lipid profile (total cholesterol and low-density-lipoprotein cholesterol), bone metabolism (serum alkaline phosphatase, osteocalcin, and c-terminal telopeptide type 1), antioxidants (superoxide dismutase and malondialdehyde), and vasorelaxants (endothelin-1 and nitric oxide), were significantly improved after the administration of RHEC. We also confirmed the safety of RHEC through histopathological observation of the endometrium. Our findings demonstrate that RHEC appears to have high potential for comprehensively improving various symptoms of menopause.

Anti-inflammatory and anti-nociceptive activities of Alpinia Oxyphylla Miquel extracts in animal models.

ETHNOPHARMACOLOGICAL RELEVANCE: Alpinia Oxyphylla Miquel is a widely used traditional herbal medicine for the treatment of abdominal pain, intestinal disorders, enuresis, and inflammatory conditions. AIM OF THE STUDY: In this study we aimed to demonstrate the anti-inflammatory and anti-nociceptive effects of Alpinia Oxyphylla Miquel extracts with 50% ethanol (AOE) in animal models. MATERIAL AND METHOD: The anti-inflammatory and nociceptive effects of AOE were estimated in vivo using a carrageenan-induced rat paw edema model, an arachidonic acid-induced mice ear edema model, an acetic acid induced mice writhing test model, and an ex vivo sulfated glycosaminoglycan (GAG) inhibition assay. In vitro inhibition assays for cyclooxygenase (COX) and lipoxygenase (LOX) were performed to determine the IC50 of AOE. RESULTS: Compared with the control, AOE caused a significant inhibition of paw edema, ear thickness, and abdominal constriction in animals. Compared with untreated explants exposed to interleukin-l alpha (IL-1α), preoteoglycan degradation by IL-1α was inhibited (18.2%-82.0%) in explants treated with AOE (50-400 µg/ml). In vitro, IC50 values of AOE were 299.87, 199.07, and 170.29 µg/ml for COX-1, COX-2, and 5-LOX respectively. CONCLUSIONS: These data demonstrate the potent anti-inflammatory and analgesic effects of AOE and suggest AOE to be useful for the treatment of osteoarthritis and/or associated symptoms.

28-day repeated oral dose toxicity study of an aqueous extract of Gryllus bimaculatus in sprague-dawley rat.

This study was performed to demonstrate a No Observed Adverse Effect Level (NOAEL) for an aqueous extract of Gryllus bimaculatus. According to other studies, using dried material or extract with ethanol or methanol determined a NOAEL dose of 1000 mg/kg or 5000 mg/kg in rats. Therefore, the Gryllus bimaculatus groups were administered orally at doses of 0, 1000, 2000, and 3000 mg/kg for four weeks. Two-week recovery groups were administered at doses of 0, and 3000 mg/kg. During administration and recovery period, the animals were observed for clinical signs, change of body weight, food consumption, hematology, and clinical chemistry. Rats in each group were periodically sacrificed, and organs were weighed and examined histologically. No difference arose between any of the dosage groups and the control group in clinical signs, histopathological examination, hematology, or clinical chemistry. In conclusion, 3000 mg/kg is a NOAEL dose for Gryllus bimaculatus extracts in Sprague Dawley rats.

Improved Multilayered (Bi,Sc)O3-(Pb,Ti)O3 Piezoelectric Energy Harvesters Based on Impedance Matching Technique.

As a piezoelectric material, (Bi,Sc)O3-(Pb,Ti)O3 ceramics have been tested and analyzed for sensors and energy harvester applications owing to their relatively high Curie temperature and high piezoelectric coefficient. In this work, we prepared optimized (Bi,Sc)O3-(Pb,Ti)O3 piezoelectric materials through the conventional ceramic process. To increase the output energy, a multilayered structure was proposed and designed, and to obtain the maximum output energy, impedance matching techniques were considered and tested. By varying and measuring the energy harvesting system, we confirmed that the output energies were optimized by varying the load resistance. As the load resistance increased, the output voltage became saturated. Then, we calculated the optimized output power using the electric energy formula. Consequently, we identified the highest output energy of 5.93 µW/cm2 at 3 MΩ for the quadruple-layer harvester and load resistor using the impedance matching system. We characterized and improved the electrical properties of the piezoelectric energy harvesters by introducing impedance matching and performing the modeling of the energy harvesting component. Modeling was conducted for the piezoelectric generator component by introducing the mechanical force dependent voltage sources and load resistors and piezoelectric capacitor connected in parallel. Moreover, the generated output voltages were simulated by introducing an impedance matching technique. This work is designed to explain the modeling of piezoelectric energy harvesters. In this model, the relationship between applied mechanical force and output energy was discussed by employing experimental results and simulation.

Hydroxyapatite Nanorod-Modified Sand Blasted Titanium Disk for Endosseous Dental Implant Applications.

BACKGROUND: Sand blasted titanium (Ti) is commonly used in designing endosseous dental implants due to its biocompatibility and ability to form bonds with bone tissues. However, titanium implants do not induce strong interactions with teeth bones. To increase strong interactions between Ti disk implants and teeth bones, the l-glutamic acid grafted hydroxyapatite nanorods (nHA) were immobilized on albumin modified Ti disk implants (Ti-Alb). METHODS: For modification of Ti disk implants by nHA, the l-glutamic acid grafted nHA was synthesized and then immobilized on albumin modified Ti disk implants. Fourier transformed infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscope; energy dispersive spectroscopy and confocal laser scanning microscopy were used to confirm the modification of Ti disk implants. The bioactivity of nHA-modified Ti disk implants was evaluated by seeding MC3T3-E1 cells on Ti-nHA implants. RESULTS: Characterization techniques have confirmed the successful modification of Ti disk implants by l-glutamic acid grafted nHA. The nHA-modified Ti disk implants have shown enhanced adhesion, proliferation and cytotoxicity of MC3T3-E1 cells in comparison to pristine Ti implants. CONCLUSIONS: The modification of Ti implants by l-glutamic acid grafted nHA has produced highly osteogenic Ti disk plants in comparison to pristine Ti disk implants due to the formation of bioactive surfaces by hydroxyapatite nano rods on Ti disk implants. Ti-nHA disk implants showed enhanced adhesion, proliferation, and MC3T3-E1 cells viability in comparison to pristine Ti disk implants. Thus nHA might be to be useful to enhance the osseointegration of Ti implants with teeth bones.

The Effect of Interleukin 38 on Angiogenesis in a Model of Oxygen-induced Retinopathy.

Interleukin 38 (IL-38) is a novel identified cytokine of IL-1 family in which some members are important in inflammation and angiogenesis. However, the role of IL-38 in regulating angiogenesis is unknown. The aim of the present study is to explore the effect of IL-38 on angiogenesis. Oxygen-induced retinopathy (OIR) of C57BL/6 J mice was induced by exposure of hyperoxia (75% oxygen) from postnatal day 7 (P7) to P12 and then returned to room air. The mice were injected with IL-38. At P17, neovascular region (tufts) and avascular area of the retinas were analyzed. The data showed that administration of IL-38 in vivo inhibited retinal angiogenesis significantly. Furthermore, the addition of IL-38 to the cell cultures attenuated the proliferation, scratch wound healing and tube formation of vascular endothelial cells induced by VEGF significantly. Our findings suggest that IL-38 is an antiangiogenic cytokine in pathophysiological settings and may have therapeutic potential for angiogenesis related diseases.

The evolution mechanism of intron length.

Within two years of their discovery in 1977, introns were found to have a positive effect on gene expression. Our result shows that introns can achieve gene expression and regulation through interaction with corresponding mRNA sequences. On the base of Smith-Waterman method, local comparing helps us get the optimal matched segments between intron sequences and mRNA sequences. Studying the distribution regulation of the optimal matching region on intron sequences of ribosomal protein genes about 27 species, we find that the intron length evolution processes beginning from 5' end to 3' end and increasing one by one structural unit, which comes up with a possible mechanism for the intron length evolution. The intron of structure units is conservative with about 60bp length, but the length of linker sequence between structure units changes a lot. Interestingly, distributions of the length and matching rate of optimal matched segments are consistent with sequence features of miRNA and siRNA. These results indicate that the interaction between intron sequences and mRNA sequences is a kind of functional RNA-RNA interaction. Meanwhile, the two kinds of sequences above are co-evolved and interactive to play their functions.

Chk1, but not Chk2, is responsible for G2/M phase arrest induced by diallyl disulfide in human gastric cancer BGC823 cells.

Diallyl disulfide (DADS) has been shown to cause G2/M phase cell cycle arrest in several human cancers. Here we demonstrate a mechanism by which DADS induces G2/M phase arrest in BGC823 human gastric cancer cells via Chk1. From cell cycle gene array results, we next confirmed that cyclin B1 expression was decreased by DADS, while the expression of p21, GADD45α and p53 were increased. Despite the lack of change in Chk1 gene expression in response to DADS according to the array analysis, intriguingly overexpression of Chk1, but not Chk2, exhibited increased accumulation in G2/M phase. Moreover, overexpression of Chk1 promoted the effect of DADS-induced G2/M arrest. Augmented phosphorylation of Chk1 by DADS was observed in Chk1-transfected cells, followed by downregulation of Cdc25C and cyclin B1 proteins. In contrast, phosphorylated Chk2 showed no obvious change in Chk2-transfected cells after DADS treatment. Furthermore, knockdown of Chk1 by siRNA partially abrogated DADS-induced downregulation of Cdc25C and cyclin B1 proteins and G2/M arrest. In contrast, knockdown of Chk2 did not show these effects. Therefore, these data indicate that DADS may specifically modulate Chk1 phosphorylation, and DADS-induced G2/M phase arrest in BGC823 cells could result in part from Chk1-mediated inhibition of the Cdc25C/cyclin B1 pathway.

The effects of endovenous radiofrequency ablation on coagulation and the vein wall in an experimental canine model.

Endovenous radiofrequency ablation (RFA) has been introduced as a less invasive alternative to traditional surgery for varicose veins, but vein thrombosis after RFA remains a concern. This study investigated the influence of endovenous RFA on coagulable states of canine blood, and changes in the vein wall and lumen. Eight canines underwent RFA of the iliac-femoral vein. Levels of plasma granule membrane protein-140, tissue plasminogen activator and plasminogen activator inhibitor-1 increased at different time points after RFA, which were monitored by enzyme-linked immunosorbent assay. Venography after ablation showed that there was left iliac-femoral vein occlusion in three canines and vein stenosis in the remaining five. Histological examination revealed intimal injury and inflammatory cell infiltration of the vessel wall. Our findings suggest that RFA is an effective microinvasive technique, which can result in a hypercoagulable state, with venous thrombosis and stenosis.

[Preparation and luminescence properties of nanomaterials TiO2-SiO2 doped with Eu3+].

In the present paper, the samples of nanomaterials TiO2-SiO2:Eu3+ with different proportion of Ti/Si were prepared with the sol-gel method, and influence of the proportion of Ti/Si on the luminescence properties of samples have was studied. The structure of the samples was examined by FTIR, indicating that the compound TiO2 and SiO2 reacted, forming the new chemical bond of Ti-O-Si. The TEM of samples show that TiO2-SiO2:Eu3+ are sphericity nanoparticles with monodispersion and uniform size of 35 nm. The samples were still anatase phase after annealing at 900 degrees C, which was studied by XRD and SAED, suggesting that the bond of Ti-O-Si was conducive to the stability of anatase phase. There will be isoelectronic trap as Si4+ enters the TiO2 lattice replacing some of the Ti4+ position, and this structure is conducive to transfering energy and improving the transition of Eu3+ (7F0 --> 5D2), which were found by excitation and emission spectra.

[Preparation and luminescent properties of CaMoO4:Tb3+].

The precursor of the sample CaMoO4:Tb3+ was prepared by the coprecipitation method. TG-DTA spectra show that there is, at 850 degrees C, an energy absorption peak, suggesting that the sample reaches the activation spot of its response. The XRD pattern of the roasted sample shows that CaMoO4:Tb3+, in the single phase, is a representative scheelite structure of CaMoO4, but the peaks shift toward right, implying that tiny crystal defect in the crystal is produced. The defect is likely to be formed by the formation of the holes as two Tb3+ replace three Ca2+ in a cell. The excitation and emission spectra of the sample were investigated and revealed that the defect structure of the sample is in favor of the energy transfer of the characteristic peak (488 nm) of the MoO4(2-) effectively to Tb3+, and makes the 4f electrons of the Tb3+ transit, especially the (7)F6-->(5)D4 electronic transition (488 nm) of the Tb3+, to be greatly strengthened. As a result, the emission spectra with lamdaex=488 nm show that the emission intensity of the spontaneously activated fluorescence MoO4(2-) is greatly weakened, while the green light luminescence intensity of the (5)D4-->(7)F5 transition (544 nm) of the Tb3+ is greatly enhanced. This suggests that the sample CaMoO4:Tb3+ will become the luminescence material with potentially great application value.