Tortoiseshell and deer antler gelatin has been used to treat bone diseases in Chinese society. A pepsin-digested gelatin peptide with osteoblast-proliferation-stimulating properties was identified ...via LC-MS/MS. The resulting pentapeptide, TSKYR, was presumably subjected to further degradation into TSKY, TSK, and YR fragments in the small intestine. The above four peptides were chemically synthesized. Treatment of tripeptide TSK can lead to a significant 30- and 50-fold increase in the mineralized nodule area and density in osteoblast cells and a 47.5% increase in the number of chondrocyte cells. The calcium content in tortoiseshell was relatively higher than in human soft tissue. The synergistic effects of calcium ions and the peptides were observed for changes in osteoblast proliferation and differentiation. Moreover, these peptides can enhance the expression of RUNX2, OCN, FGFR2, and FRFR3 genes in osteoblasts, and aggrecan and collagen type II in chondrocyte (patent pending).
The number of published articles describing associations between mutations and diseases is increasing at a fast pace. There is a pressing need to gather such mutation-disease associations into public ...knowledge bases, but manual curation slows down the growth of such databases. We have addressed this problem by developing a text-mining system (DiMeX) to extract mutation to disease associations from publication abstracts. DiMeX consists of a series of natural language processing modules that preprocess input text and apply syntactic and semantic patterns to extract mutation-disease associations. DiMeX achieves high precision and recall with F-scores of 0.88, 0.91 and 0.89 when evaluated on three different datasets for mutation-disease associations. DiMeX includes a separate component that extracts mutation mentions in text and associates them with genes. This component has been also evaluated on different datasets and shown to achieve state-of-the-art performance. The results indicate that our system outperforms the existing mutation-disease association tools, addressing the low precision problems suffered by most approaches. DiMeX was applied on a large set of abstracts from Medline to extract mutation-disease associations, as well as other relevant information including patient/cohort size and population data. The results are stored in a database that can be queried and downloaded at http://biotm.cis.udel.edu/dimex/. We conclude that this high-throughput text-mining approach has the potential to significantly assist researchers and curators to enrich mutation databases.
Cadmium (Cd), one of well-known highly toxic environmental and industrial pollutants, causes a number of adverse health effects and diseases in humans. The growing epidemiological studies have ...suggested a possible link between Cd exposure and diabetes mellitus (DM). However, the toxicological effects and underlying mechanisms of Cd-induced pancreatic β-cell injury are still unknown. In this study, we found that Cd significantly decreased cell viability, and increased sub-G1 hypodiploid cells and annexin V-Cy3 binding in pancreatic β-cell-derived RIN-m5F cells. Cd also increased intracellular reactive oxygen species (ROS) generation and malondialdehyde (MDA) production and induced mitochondrial dysfunction (the loss of mitochondrial membrane potential (MMP) and the increase of cytosolic cytochrome c release), the decreased Bcl-2 expression, increased p53 expression, poly (ADP-ribose) polymerase (PARP) cleavage, and caspase cascades, which accompanied with intracellular Cd accumulation. Pretreatment with the antioxidant N-acetylcysteine (NAC) effectively reversed these Cd-induced events. Furthermore, exposure to Cd induced the phosphorylations of c-jun N-terminal kinases (JNK), extracellular signal-regulated kinases (ERK)1/2, and p38-mitogen-activated protein kinase (MAPK), which was prevented by NAC. Additionally, the specific JNK inhibitor SP600125 or JNK-specific small interference RNA (si-RNA) transfection suppressed Cd-induced β-cell apoptosis and related signals, but not ERK1/2 and p38-MAPK inhibitors (PD98059 and SB203580) did not. However, the JNK inhibitor or JNK-specific si-RNA did not suppress ROS generation in Cd-treated cells. These results indicate that Cd induces pancreatic β-cell death via an oxidative stress downstream-mediated JNK activation-triggered mitochondria-regulated apoptotic pathway.
Pain is strongly associated with neuro-immune activation. Thus, the emerging role of the endocannabinoid system in neuro-inflammation is important. Acupuncture has been used for over 2500 years and ...is widely accepted for the management of pain. Our study aimed to investigate the effects of electroacupuncture on the regulation of cannabinoid receptor type 1 within the peripheral nervous system. Inflammatory pain was induced by injecting Complete Freund's adjuvant to induce mechanical and thermal hyperalgesia. Electroacupuncture significantly attenuated the mechanical and thermal sensitivities, and AM251, a cannabinoid receptor type 1 antagonist, eliminated these effects. Dual immunofluorescence staining demonstrated that electroacupuncture elevated expression of cannabinoid receptor type 1, co-localized with Nav 1.8. Furthermore, electroacupuncture significantly reduced levels of Nav 1.8 and COX-2 by western blot analysis, but not vice versa as AM251 treatment. Our data indicate that electroacupuncture mediates antinociceptive effects through peripheral endocannabinoid system signaling pathway and provide evidence that electroacupuncture is beneficial for pain treatment.
Older people are subject to an increased risk of falling compared to the young, especially during obstacle negotiation. This study aimed to quantify the effects of long-term Tai-Chi Chuan (TCC) ...practice on the balance control during obstacle-crossing in older people in terms of the inclination angles (IA) of the body's centre of mass (COM) relative to the centre of pressure (COP), and the rate of change of IA (RCIA). Fifteen healthy older adults who had practised TCC for at least 13 years and 15 healthy controls without any experience in TCC performed obstacle-crossing in a gait laboratory. The TCC group showed significantly greater leading and trailing toe-obstacle clearances but smaller trailing stride lengths when compared to controls. In the sagittal plane, the TCC group showed significantly smaller average anterior IA when the COM was anterior to the COP but greater average posterior IA when the COM was posterior to the COP, with significantly smaller average and peak RCIA over the crossing cycle. Long-term TCC practitioners showed an obstacle-crossing technique for less risk of tripping and better balance control, as indicated respectively by significantly increased toe-obstacle clearances and more posterior COM position relative to the COP with smaller anterior IA and RCIA during leading crossing and greater posterior IA and frontal RCIA at trailing-toe crossing. These benefits appeared to be related to the main features of TCC movements that emphasized maintaining balance during single-leg support and keeping the body weight on the trailing limb during the slow weight-shifting of double-limb support.
The mechanism of hepatoprotective compounds is usually related to its antioxidant or anti-inflammatory effects. Black garlic is produced from garlic by heat treatment and its anti-inflammatory ...activity has been previously reported. Therefore, the aim of this study was to investigate the hepatoprotective effect of five different extracts of black garlic against carbon tetrachloride (CCl₄)-induced acute hepatic injury (AHI). In this study, mice in the control, CCl₄, silymarin, and black garlic groups were orally administered distilled water, silymarin, and different fraction extracts of black garlic, respectively, after CCl₄ was injected intraperitoneally to induce AHI. The results revealed that the
-butanol layer extract (BA) and water layer extract (WS) demonstrated a hepatoprotective effect by reducing the levels of alanine aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and hepatic malondialdehyde (MDA). Furthermore, the BA and WS fractions of black garlic extract increased the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd), tumor necrosis factor alpha (TNF-α), and the interleukin-1 (IL-1β) level in liver. It was concluded that black garlic exhibited significant protective effects on CCl₄-induced acute hepatic injury.
Orally administered "tortoiseshell and deer antler gelatin" is a common traditional medicine for patients with osteoporosis or osteoarthritis. From the pepsin-digested gelatin, we previously isolated ...and identified the osteoblast-stimulating pentapeptide, TSKYR. Its trypsin digestion products include the dipeptide YR, enhancing calcium ion uptake, and tripeptide TSK, resulting in remarkable 30- and 50-fold increases in mineralized nodule area and density in human osteoblast cells. These peptides were chemically synthesized in this study. The composition of deer antler preparations comprises not only proteins and peptides but also a significant quantity of metal ion salts. By analyzing osteoblast growth in the presence of peptide YR and various metal ions, we observed a synergistic effect of calcium and strontium on the effects of YR. Those peptides could also stimulate the growth of C2C12 skeletal muscle cells and human chondrocytes, increasing collagen and glycosaminoglycan content in a three-dimensional environment. The maintenance of bone homeostasis relies on a balance between osteoclasts and osteoblasts. Deer antler peptides were observed to inhibit osteoclast differentiation, as evidenced by ROS generation, tartrate-resistant acid phosphatase (TRACP) activity assays, and gene expression in RAW264.7 cells. In summary, our findings provide a deep understanding of the efficacy of this folk medicine.
In this paper, we study the Roadside Unit (RSU) placement problem in vehicular networks. We focus on the highway-like scenario in which there may be multiple lanes with exits or intersections along ...the road. In our model, each vehicle can access RSUs in two ways: 1) direct delivery, which occurs when the vehicle is in the transmission range of the RSUs, and 2) multi-hop relaying, which takes place when the vehicle is out of RSU transmission range. We account for both access patterns in our placement strategy and formulate this placement problem via an integer linear programming model such that the aggregate throughput in the network can be maximized. We also take into account the impact of wireless interference, vehicle population distribution, and vehicle speeds in the formulation. The performance of the proposed placement strategy is evaluated via ns-2 simulations together with VanetMobisim to generate vehicle mobility patterns. The results show that our strategy leads to the best performance as compared with the uniformly distributed placement and the hot spot placement. More importantly, our solution needs the least number of RSUs to achieve the maximal aggregate throughput in the network, indicating that our scheme is indeed a cost effective yet highly efficient placement strategy for vehicular networks.
5-Hydroxymethylfurfural (5-HMF) is a harmful substance generated during the processing of black garlic. Our previous research demonstrated that impregnation of black garlic with epigallocatechin ...gallate (EGCG) could reduce the formation of 5-HMF. However, there is still a lack of relevant research on the mechanism and structural identification of EGCG inhibiting the production of 5-HMF. In this study, an intermediate product of 5-HMF, 3-deoxyglucosone (3-DG), was found to be decreased in black garlic during the aging process, and impregnation with EGCG for 24 h further reduced the formation of 3-DG by approximately 60% in black garlic compared with that in the untreated control. The aging-mimicking reaction system of 3-DG + EGCG was employed to determine whether the reduction of 3-DG was the underlying mechanism of decreased 5-HMF formation in EGCG-treated black garlic. The results showed that EGCG accelerated the decrease of 3-DG and further attenuated 5-HMF formation, which may be caused by an additional reaction with 3-DG, as evidenced by LC-MS/MS analysis. In conclusion, this study provides new insights regarding the role of EGCG in blocking 5-HMF formation.
Catechu is a dried decoction from twigs with the leaves of Uncaria gambir. Its antioxidant, anti-inflammatory, and antimicrobial activities have been previously reported because of its high catechin ...and epicatechin content (>21%). It is also one of the components used in traditional Chinese herbal medicine, “Jinchuang Ointment,” which has excellent efficacy in treating chronic diabetic wounds. An in vivo zebrafish embryo platform and an in vitro cell-based tube formation assay were used to measure the angiogenic activity of catechu extracts. Interestingly, for the first time, catechu extracts stimulated angiogenic activity on both platforms. The expression of the IL-8 gene was induced in HMEC1 cells after treatment with catechu extracts for 1 h only. In contrast, the upregulation of FGFR2, FGFR3, NF-κB, STAT3, and vimentin persisted for 24 h. A summary of the possible mechanisms underlying the angiogenic activity of catechu extracts in HMEC1 cells is shown. Unexpectedly, catechu extracts inhibited the migration of HaCaT cells. These results can account for the intense blood flow flux in porcine excisional wound sites in our previous studies, which provides insights into the therapeutic activity of catechu extract in chronic diabetic wounds.
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