Ginsenoside Rg4 Enhances the Inductive Effects of Human Dermal Papilla Spheres on Hair Growth Via the AKT/GSK-3β/β-Catenin Signaling Pathway
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- Journal of Microbiology and Biotechnology
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- v.31 no.7
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- pp.933-941
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- 2021
Ginsenoside Rg4 is a rare ginsenoside that is naturally found in ginseng, and exhibits a wide range of biological activities including antioxidant and anti-inflammatory properties in several cell types. The purpose of this study was to use an in vivo model of hair follicle (HF)-mimic based on a human dermal papilla (DP) spheroid system prepared by three-dimensional (3D) culture and to investigate the effect of Rg4 on the hair-inductive properties of DP cells. Treatment of the DP spheroids with Rg4 (20 to 50 ㎍/ml) significantly increased the viability and size of the DP spheres in a dose-dependent manner. Rg4 also increased the mRNA and protein expression of DP signature genes that are related to hair growth including ALP, BMP2, and VCAN in the DP spheres. Analysis of the signaling molecules and luciferase reporter assays further revealed that Rg4 induces the activation of phosphoinositide 3-kinase (PI3K)/AKT and the inhibitory phosphorylation of GSK3β, which activates the WNT/β-catenin signaling pathway. These results correlated with not only the increased nuclear translocation of β-catenin following the treatment of the DP spheres with Rg4 but also the significant elevation of mRNA expression of the downstream target genes of the WNT/β-catenin pathway including WNT5A, β-catenin, and LEF1. In conclusion, these results demonstrated that ginsenoside Rg4 promotes the hair-inductive properties of DP cells by activating the AKT/GSK3β/β-catenin signaling pathway in DP spheres, suggesting that Rg4 could be a potential natural therapy for hair growth.
Due to its biofilm formation and colonization of the osteocyte-lacuno canalicular network (OLCN), Staphylococcus aureus (S.aureus) implant-associated bone infection (SIABI) is difficult to cure thoroughly, and may occur recurrently subsequently after a long period dormant. It is essential to explore an alternative therapeutic strategy that can eradicate the pathogens in the infected foci. To address this, the polymethylmethacrylate (PMMA) bone cement and Fe3O4 nanoparticles compound cylinder were developed as implants based on their size and mechanical properties for the alternative magnetic field (AMF) induced thermal ablation, The PMMA mixed with optimized 2% Fe3O4 nanoparticles showed an excellent antibacterial efficacy in vitro. It was evaluated by the CFU, CT scan and histopathological staining on a rabbit 1-stage transtibial screw model. The results showed that on week 7, the CFU of infected soft tissue and implants, and the white blood cells (WBCs) of the PMMA+2% Fe3O4+AMF group decreased significantly from their controls (p<0.05). PMMA+2% Fe3O4+AMF group did not observe bone resorption, periosteal reaction, and infectious reactive bone formation by CT images. Further histopathological H&E and Gram Staining confirmed there was no obvious inflammatory cell infiltration, neither pathogens residue nor noticeably burn damage around the infected screw channel in the PMMA+2% Fe3O4+AMF group. Further investigation of nanoparticle distributions in bone marrow medullary and vital organs of heart, liver, spleen, lung, and kidney. There were no significantly extra Fe3O4 nanoparticles were observed in the medullary cavity and all vital organs either. In the current study, PMMA+2% Fe3O4+AMF shows promising therapeutic potential for SIABI by providing excellent mechanical support, and promising efficacy of eradicating the residual pathogenic bacteria in bone infected lesions.
The advent of 5G mobile communications, which is expected in 2020, will provide many services such as Internet of Things (IoT) and vehicle-to-infra/vehicle/nomadic (V2X) communication. There are many requirements to realizing these services: reduced latency, high data rate and reliability, and real-time service. In particular, a high level of reliability and delay sensitivity with an increased data rate are very important for M2M, IoT, and Factory 4.0. Around the world, 5G standardization organizations have considered these services and grouped them to finally derive the technical requirements and service scenarios. The first scenario is broadcast services that use a high data rate for multiple cases of sporting events or emergencies. The second scenario is as support for e-Health, car reliability, etc.; the third scenario is related to VR games with delay sensitivity and real-time techniques. Recently, these groups have been forming agreements on the requirements for such scenarios and the target level. Various techniques are being studied to satisfy such requirements and are being discussed in the context of software-defined networking (SDN) as the next-generation network architecture. SDN is being used to standardize ONF and basically refers to a structure that separates signals for the control plane from the packets for the data plane. One of the best examples for low latency and high reliability is an intelligent traffic system (ITS) using V2X. Because a car passes a small cell of the 5G network very rapidly, the messages to be delivered in the event of an emergency have to be transported in a very short time. This is a typical example requiring high delay sensitivity. 5G has to support a high reliability and delay sensitivity requirements for V2X in the field of traffic control. For these reasons, V2X is a major application of critical delay. V2X (vehicle-to-infra/vehicle/nomadic) represents all types of communication methods applicable to road and vehicles. It refers to a connected or networked vehicle. V2X can be divided into three kinds of communications. First is the communication between a vehicle and infrastructure (vehicle-to-infrastructure; V2I). Second is the communication between a vehicle and another vehicle (vehicle-to-vehicle; V2V). Third is the communication between a vehicle and mobile equipment (vehicle-to-nomadic devices; V2N). This will be added in the future in various fields. Because the SDN structure is under consideration as the next-generation network architecture, the SDN architecture is significant. However, the centralized architecture of SDN can be considered as an unfavorable structure for delay-sensitive services because a centralized architecture is needed to communicate with many nodes and provide processing power. Therefore, in the case of emergency V2X communications, delay-related control functions require a tree supporting structure. For such a scenario, the architecture of the network processing the vehicle information is a major variable affecting delay. Because it is difficult to meet the desired level of delay sensitivity with a typical fully centralized SDN structure, research on the optimal size of an SDN for processing information is needed. This study examined the SDN architecture considering the V2X emergency delay requirements of a 5G network in the worst-case scenario and performed a system-level simulation on the speed of the car, radius, and cell tier to derive a range of cells for information transfer in SDN network. In the simulation, because 5G provides a sufficiently high data rate, the information for neighboring vehicle support to the car was assumed to be without errors. Furthermore, the 5G small cell was assumed to have a cell radius of 50-100 m, and the maximum speed of the vehicle was considered to be 30-200 km/h in order to examine the network architecture to minimize the delay.
This study examined metabolic profiles of 1349 Holstein cows from 91 commercial herds. Thirteen parameters which are consisted of twelve blood components and body condition score were examined and their mean values. standard deviations and standard limits, which are 80% confidential limits, in each lactational stage were reported. The variations of each parameter affected by season, individual milk yield, adjusted corrected milk yield of herd. and lactation number were also reported. A model of metabolic profile test applicable to this country where the average number of cows in a herd is small as to be fifteen is designed. Metabolic profiles as reflected in each parameter were discussed in relation to adequacy of dietary intake for production, milk production, reproductive performance, and diseases, and the possible measure to improve productivity of dairy cows were proposed. Much of the variation in parameters was due to differences between herds, and less to differences between seasons, differences between individual milk yield, and differences between lactational stages. As the average herd size in this country is small, it is believed that all the cows in a herd must be sampled, and the individual result of each parameter was compared with the standard limit for each lactational stage, and the percentage of cows which are outside the standard limits in a herd was calculated to use as a criteria for evaluation of the herd. Data outside the 99% confidential limits were to be deleted at first, but when the trends of the data outside the 99% confidential limits are same as the trends of the data within 99% confidential limits, the deleted data must be reviewed again, otherwise some important informations would be missed. The mean concentration of blood urea nitrogen in this study was much higher than that was reported in England, U.S.A. and Japan, and it was similar to the upper limits reported in England, U.S.A. and Japan. So it was thought that the concentration of blood urea nitrogen is improper as a criteria for protein intake. The increase of serum total protein cocentration beyond standard limits was due to increase of serum globulin concentration in most of the cows. The correlation coefficient between serum and protein and serum globulin concentration was 0.83. Serum globulin concentration was negatively related to adjusted corrected milk of herd. Serum albumin, calcium and magnessium concentrations were negatively related to adjusted corrected milk of herd, which indicate that high-producing individual or high-producing herd have not taken sufficient protein/amino acids, calcium and magnessium. Packed cell volume was negatively related to adjusted corrected milk of the herd, and the trend was same In each lactational stage. The correlation coefficient between serum and packed cell volume was 0.16 and the correlation was very weak. Blood glucose concentration was lowest in early lactational stage, which indicates negative energy balance in early lactational stage. Blood glucose concentration was negatively related to adjusted corrected milk of herd from peak to late lactational stage, which indicates negative energy balance during the period in high-producing individuals or high-producing herds. Correlation coefficient between serum aspartate aminotransferase activity and serum
Filtering rates of two farming ascidians Styela clava and S. plicata, and of a farming mussel Mytilus edulis were experimentally investigated with reference to effects of water temperature and size. Absorptiometric determinations of filtering rates were carried out in a closed system with experimental animals being decreased indicate dyes neutral red. Optical density (OD) of 440 nm in path length 22 mm cell used as the indication of food particles absorption was appeared directly in proportion with the concentration of neutral red dyes. The filtering rate F is calculated by Kim's equation
Liposomes as drug delivery system have proved useful carrier for various disease, including cancer. In addition, perfluorocarbon cored microbubbles are utilized in conjunction with high-intensity focused-ultrasound (HIFU) to enable simultaneous diagnosis and treatment. However, microbubbles generally exhibit lower drug loading efficiency, so the need for the development of a novel liposome-based drug delivery material that can efficiently load and deliver drugs to targeted areas via HIFU. This study aims to develop a liposome-based drug delivery material by introducing a substance that can burst liposomes using ultrasound energy and confirm the ability to target tumors using PET imaging. Liposomes (Lipo-DOX, Lipo-DOX-Au, Lipo-DOX-Au-RGD) were synthesized with gold nanoparticles using an avidin-biotin bond, and doxorubicin was mounted inside by pH gradient method. The size distribution was measured by DLS, and encapsulation efficiency of doxorubicin was analyzed by UV-vis spectrometer. The target specificity and cytotoxicity of liposomes were assessed in vitro by glioblastoma U87mg cells to HIFU treatment and analyzed using CCK-8 assay, and fluorescence microscopy at 6-hour intervals for up to 24 hours. For the in vivo study, U87mg model mouse were injected intravenously with 1.48 MBq of 64Cu-labeled Lipo-DOX-Au and Lipo-DOX-Au-RGD, and PET images were taken at 0, 2, 4, 8, and 24 hours. As a result, the size of liposomes was 108.3 ± 5.0 nm at Lipo-DOX-Au and 94.1 ± 12.2 nm at Lipo-DOX-Au-RGD, and it was observed that doxorubicin was mounted inside the liposome up to 52%. After 6 hours of HIFU treatment, the viability of U87mg cells treated with Lipo-DOX-Au decreased by around 20% compared to Lipo-DOX, and Lipo-DOX-Au-RGD had a higher uptake rate than Lipo-DOX. In vivo study using PET images, it was confirmed that 64Cu-Lipo-DOX-Au-RGD was taken up into the tumor immediately after injection and maintained for up to 4 hours. In this study, drugs released from liposomes-gold nanoparticles via ultrasound and RGD targeting were confirmed by non-invasive imaging. In cell-level experiments, HIFU treatment of gold nanoparticle-coupled liposomes significantly decreased tumor survival, while RGD-liposomes exhibited high tumor targeting and rapid release in vivo imaging. It is expected that the combination of these models with ultrasound is served as an effective drug delivery material with therapeutic outcomes.
Purpose : A ginkgo biloba extract (GBE) has been known as a hypoxic cell radiosensitizer. Its mechanisms of action are increase of the red blood cell deformability, decrease the blood viscosity, and decrease the hypoxic cell fraction in the tumor. The aims of this study were to estimate the effect of GBE on fractionated radiotherapy and to clarify the mechanism of action of the GBE by estimating the blood flow in tumor and normal muscle. Materials and Methods : Fibrosarcoma (FSall) growing in a C3H mouse leg muscle was used as the tumor model. When the tumor size reached 7 mm in diameter, the GBE was given intraperitoneally at 1 and 25 hours prior to irradiation. The tumor growth delay was measured according to the various doses of radiation (3, 6, 9, 12 Gy and 15 Gy) and to the fractionation (single and fractionated irradiation) with and without the GBE injection. The radiation dose to the tumor the response relationships and the enhancement ratio of the GBE were measured. In addition, the blood flow of a normal muscle and a tumor was compared by laser Doppler flowmetry according to the GBE treatment. Results : When the GBE was used with single fraction irradiation with doses ranging from 3 to 12 Gy, GBE increased the tumor growth delay significantly (p<0.05) and the enhancement ratio of the GBE was 1.16. In fractionated irradiation with 3 Gy per day, the relationships between the radiation dose (D) and the tumor growth delay (TGD) were TGD
Background: Ginsenoside compound K (CK), the main active metabolite in Panax ginseng, has shown good safety and bioavailability in clinical trials and exerts neuroprotective effects in cerebral ischemic stroke. However, its potential role in the prevention of cerebral ischemia/reperfusion (I/R) injury remains unclear. Our study aimed to investigate the molecular mechanism of ginsenoside CK against cerebral I/R injury. Methods: We used a combination of in vitro and in vivo models, including oxygen and glucose deprivation/reperfusion induced PC12 cell model and middle cerebral artery occlusion/reperfusion induced rat model, to mimic I/R injury. Intracellular oxygen consumption and extracellular acidification rate were analyzed by Seahorse multifunctional energy metabolism system; ATP production was detected by luciferase method. The number and size of mitochondria were analyzed by transmission electron microscopy and MitoTracker probe combined with confocal laser microscopy. The potential mechanisms of ginsenoside CK on mitochondrial dynamics and bioenergy were evaluated by RNA interference, pharmacological antagonism combined with co-immunoprecipitation analysis and phenotypic analysis. Results: Ginsenoside CK pretreatment could attenuate mitochondrial translocation of DRP1, mitophagy, mitochondrial apoptosis, and neuronal bioenergy imbalance against cerebral I/R injury in both in vitro and in vivo models. Our data also confirmed that ginsenoside CK administration could reduce the binding affinity of Mul1 and Mfn2 to inhibit the ubiquitination and degradation of Mfn2, thereby elevating the protein level of Mfn2 in cerebral I/R injury. Conclusion: These data provide evidence that ginsenoside CK may be a promising therapeutic agent against cerebral I/R injury via Mul1/Mfn2 mediated mitochondrial dynamics and bioenergy.
The wall shear stress in the vicinity of end-to end anastomoses under steady flow conditions was measured using a flush-mounted hot-film anemometer(FMHFA) probe. The experimental measurements were in good agreement with numerical results except in flow with low Reynolds numbers. The wall shear stress increased proximal to the anastomosis in flow from the Penrose tubing (simulating an artery) to the PTFE: graft. In flow from the PTFE graft to the Penrose tubing, low wall shear stress was observed distal to the anastomosis. Abnormal distributions of wall shear stress in the vicinity of the anastomosis, resulting from the compliance mismatch between the graft and the host artery, might be an important factor of ANFH formation and the graft failure. The present study suggests a correlation between regions of the low wall shear stress and the development of anastomotic neointimal fibrous hyperplasia(ANPH) in end-to-end anastomoses. 30523 T00401030523 ^x Air pressure decay(APD) rate and ultrafiltration rate(UFR) tests were performed on new and saline rinsed dialyzers as well as those roused in patients several times. C-DAK 4000 (Cordis Dow) and CF IS-11 (Baxter Travenol) reused dialyzers obtained from the dialysis clinic were used in the present study. The new dialyzers exhibited a relatively flat APD, whereas saline rinsed and reused dialyzers showed considerable amount of decay. C-DAH dialyzers had a larger APD(11.70
The wall shear stress in the vicinity of end-to end anastomoses under steady flow conditions was measured using a flush-mounted hot-film anemometer(FMHFA) probe. The experimental measurements were in good agreement with numerical results except in flow with low Reynolds numbers. The wall shear stress increased proximal to the anastomosis in flow from the Penrose tubing (simulating an artery) to the PTFE: graft. In flow from the PTFE graft to the Penrose tubing, low wall shear stress was observed distal to the anastomosis. Abnormal distributions of wall shear stress in the vicinity of the anastomosis, resulting from the compliance mismatch between the graft and the host artery, might be an important factor of ANFH formation and the graft failure. The present study suggests a correlation between regions of the low wall shear stress and the development of anastomotic neointimal fibrous hyperplasia(ANPH) in end-to-end anastomoses. 30523 T00401030523 ^x Air pressure decay(APD) rate and ultrafiltration rate(UFR) tests were performed on new and saline rinsed dialyzers as well as those roused in patients several times. C-DAK 4000 (Cordis Dow) and CF IS-11 (Baxter Travenol) reused dialyzers obtained from the dialysis clinic were used in the present study. The new dialyzers exhibited a relatively flat APD, whereas saline rinsed and reused dialyzers showed considerable amount of decay. C-DAH dialyzers had a larger APD(11.70