Metabolomic characteristics of spontaneously hypertensive rats under chronic stress and the treatment effect of Danzhi Xiaoyao Powder, a traditional Chinese medicine formula / 中西医结合学报

OBJECTIVE@#Numerous studies have demonstrated the close relationship between chronic stress and blood pressure (BP). Hypertensive subjects exhibit exaggerated reactions to stress, especially higher BP. The mechanisms by which stress affects pre-existing hypertension still need to be explored. Danzhi Xiaoyao Powder (DP), a historical traditional Chinese medicine formula, is a promising treatment for BP control in hypertensive patients under stress. The present study investigated the metabolomic disruption caused by chronic stress and the treatment effect and mechanism of DP.@*METHODS@#Spontaneously hypertensive rats (SHRs) were subjected to chronic restraint stress (CRS) for 4 weeks. BP was measured via the tail-cuff method, and anxiety-like behavior was quantified using the elevated-plus-maze test. Meanwhile, DP was administered intragastrically, and its effects were observed. Global metabolomic analysis was performed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by multivariate statistical analysis to detect differential metabolites and pathways.@*RESULTS@#DP alleviated the CRS-induced increase in BP and anxiety-like behavior. Systematic metabolic differences were found among the three study groups. A total of 29 differential plasma metabolites were identified in both positive- and negative-ion modes. These metabolites were involved in triglyceride metabolism, amino acid (phenylalanine, tryptophan, and glycine) metabolism, and steroid hormone pathways.@*CONCLUSION@#These findings expose the metabolomic disturbances induced by chronic stress in SHRs and suggest an innovative treatment for this disorder.

GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus mediates nerve injury-induced neuropathic pain in rats / 生理学报

The present study was aimed to investigate the role of GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus (CSF-CN) in neuropathic pain. Intra-lateral ventricle injection of cholera toxin subunit B conjugated with horseradish peroxidase (CBHRP) was used to label the CSF-CN. Double-labeled immunofluorescent staining and Western blot were used to observe the expression of GluN2B and BDNF in the CSF-CN. Chronic constriction injury of sciatic nerve (CCI) rat model was used to duplicate the neuropathic pain. Pain behavior was scored to determine the analgesic effects of GluN2B antagonist Ro 25-6981 and BDNF neutralizing antibody on CCI rats. GluN2B and BDNF were expressed in the CSF-CN and their expression was up-regulated in CCI rats. Intra-lateral ventricle injection of GluN2B antagonist Ro 25-6981 or BDNF neutralizing antibody notably alleviated thermal hyperalgesia and mechanical allodynia in CCI rats. Moreover, the increased expression of BDNF protein in CCI rats was reversed by intra-lateral ventricle injection of Ro 25-6981. These results suggest that GluN2B and BDNF are expressed in the CSF-CN and alteration of GluN2B-BDNF pathway in the CSF-CN is involved in the modulation of the peripheral neuropathic pain.

Overview of Metabolomics in Research of Hypertension / 中国实验方剂学杂志

Hypertension is one of the most common chronic diseases, also an important risk factor for a series of cardio-and cerebra-vascular diseases. Due to its polygenic, multi-factorial nature and heterogeneity, the underlying cause has not been fully elucidated, satisfied therapeutic effect hasn't been totally achieved either. Metabolomics is used to evaluate metabolic changes of organisms from a holistic perspective, associating with biological processes to reveal the whole situation of the body. In recent years, researchers have used metabolomics to study the pathogenesis of hypertension, potential biomarkers, effects of lifestyle interventions, and mechanisms of antihypertensive drugs. Targeted or untargeted ways are applied to study metabolites form blood, urine, or tissues of human or animals. Metabolic pathways of gut microflora, oxidative stress, fatty acids, and amino acids have drawn more attention, and the discovered metabolites may become potential biomarkers, further the diagnostic biomarkers and treatment targets. In addition, traditional Chinese medicine (TCM) is an integrated complex system in syndrome diagnosis and treatment, and metabolomics coincides well with the concepts of it. TCM researchers also use this method to study the biological basis of syndromes in hypertension and the mechanism of antihypertensive Chinese medicine. There are significant differences in the metabolites between different syndromes. TCM treatments can restore the metabolite disturbance caused by high pressure, which is probably one of the pharmacological pathways of antihypertensive Chinese medicine. Metabolomic studies in hypertension have achieved great progress, but there're still challenges in data analysis, integration with other metabolomic studies and other omic studies and causal relationship in further study.

Comparison of the short-term efficacy of extracorporeal shock wave therapy for middle-aged and elderly knee osteoarthritis: A meta-analysis / 中国组织工程研究

OBJECTIVE: To compare the effectiveness of extracorporeal shock wave therapy with other treatments in relieving knee osteoarthritis pain and improving knee function in the elderly. METHODS: A computer search was performed on PubMed, Embase, CNKI, and SinoMed databases to compare the efficacy of extracorporeal shock wave with the energy density of 0, non-steroidal drugs, and sodium hyaluronate for knee osteoarthritis. The search period was from the inception of the database to March 2020. Simultaneously, the obtained reference index was looked up. According to the incision and exclusion criteria, two researchers independently screened the literature. Visual analogue scale and The Western Ontario and McMaster Universities Osteoarthritis Index were the primary outcomes, and the Lequensne score was the secondary outcome. Cochrane bias risk assessment tool was used to evaluate literature quality. Data analysis was performed by RevMan 5.3 software. RESULTS: (1) Twelve articles were included with a total of 1 040 patients, and all of them were randomized controlled trails. (2) Meta-analysis results showed that compared with the blank control, extracorporeal shock wave therapy could relieve the pain score of patients with knee osteoarthritis (MD=-2.00, 95%CI:-2.25 to-1.75, P < 0.000 01), improve The Western Ontario and McMaster Universities Osteoarthritis Index (MD=-8.45, 95%CI:-14.83 to-2.07, P=0.009) and Lequesne score (MD=-2.39, 95%CI:-4.24 to-0.54, P=0.01), with significant differences. (3) There was no significant difference between the group of extracorporeal shock wave and the group of non-steroidal drugs in terms of pain relief (MD=0.01, 95%CI:-0.48-0.51, P=0.95), but the effect of extracorporeal shock wave on improving knee function was better than that of non-steroidal drugs (MD=-6.56, 95%CI:-8.24 to-4.87, P < 0.000 01). (4) The knee pain (MD=0.22, 95%CI: 0.18, 0.25, P < 0.000 01) and The Western Ontario and McMaster Universities Osteoarthritis Index (MD=-1.29, 95%CI:-3.61 to-0.74, P=0.003) were improved in the group of extracorporeal shock wave compared with the group of sodium hyaluronate. (5) There was no significant difference in the scores of Lequesne (MD=-0.21, 95%CI:-1.09-0.67, P=0.64) between the group of extracorporeal shock wave and the group of sodium hyaluronate in terms of pain relief. CONCLUSION: Compared with oral non-steroidal anti-inflammatory drugs and intra-articular sodium hyaluronate injection, extracorporeal shock wave shows a better clinical effect on relieving knee osteoarthritis pain and improving knee joint function. The above conclusions need to be verified through higher quality and larger sample clinical trial result.

Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn's Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study

BACKGROUND/AIMS: Only moderate to severe Crohn's Disease (CD) patients without a satisfactory conventional therapy effect are eligible to get reimbursement from the National Health Insurance of Taiwan for using adalimumab. These are more stringent criteria than in many Western countries and Japan and Korea. We aim to explore the efficacy of using adalimumab in CD patients under such stringent criteria. METHODS: A retrospective analysis was conducted in nine medical centers in Taiwan and we collected the results of CD patients receiving adalimumab from Sep 2009 to Mar 2014. The clinical characteristics, response measured by CDAI (Crohn's Disease Activity Index), adverse events and survival status were recorded and analyzed. CR-70, CR-100, and CR-150 were defined as attaining a CDAI decrease of 70, 100 or 150 points compared with baseline. RESULTS: A total of 103 CD patient records were used in this study. Sixty percent of these patients received combination therapy of adalimumab together with immunomodulators. CR-70 was 68.7%, 74.5% and 88.4% after week 4, 8 and 12 of treatment, respectively. The steroid-free rate, complications and survival were 47.6%, 9.7% and 99% of patients, respectively. In considering the mucosal healing, only 25% patients achieve mucosal healing after treatment for 6 to12 months. Surgery was still needed in 16.5% of patients. Combination treatment of adalimumab with immunomodulators further decreased the level of CDAI at week 8 when compared with the monotherapy. CONCLUSIONS: Even under the stringent criteria for using adalimumab, the response rate was comparable to those without stringent criteria.

Application of Decellularized Scaffold Combined with Loaded Nanoparticles for Heart Valve Tissue Engineering in vitro / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to fabricate decelluarized valve scaffold modified with polyethylene glycol nanoparticles loaded with transforming growth factor-β1 (TGF-β1),by which to improve the extracellular matrix microenvironment for heart valve tissue engineering in vitro.Polyethylene glycol nanoparticles were obtained by an emulsion-crosslinking method,and their morphology was observed under a scanning electron microscope.Decelluarized valve scaffolds,prepared by using trypsinase and TritonX-100,were modified with nanoparticles by carbodiimide,and then TGF-β1 was loaded into them by adsorption.The TGF-β1 delivery of the fabricated scaffold was measured by asing enzyme-linked immunosorbent assay.Whether unseeded or reseeded with myofibroblast from rats,the morphologic,biochemical and biomechanical characteristics of hybrid scaffolds were tested and compared with decelluarized scaffolds under the same conditions.The enzyme-linked immunosorbent assay revealed a typical delivery of nanoparticles.The morphologic observations and biological data analysis indicated that fabricated scaffolds possessed advantageous biocompatibility and biomechanical property beyond decelluarized scaffolds.Altogether this study proved that it was feasible to fabricate the hybrid scaffold and effective to improve extracellular matrix microenvironment,which is beneficial for an application in heart valve tissue engineering.

Aquaporin-1 and aquaporin-3 expressions in the temporo-mandibular joint condylar cartilage after an experimentally induced osteoarthritis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Over 70% of the total tissue weight in the cartilage matrix consists of water, and the early-stage osteoarthritic cartilage is characterized by swelling. Water transport in the cartilage matrix and across the membranes of chondrocytes may be important in normal and pathological conditions of cartilage. The purpose of this study was to identify aquaporin-1 (AQP1) and aquaporin-3 (AQP3) expressions in the mandibular condylar cartilage after experimentally induced osteoarthritis (OA) in rats.</p><p><b>METHODS</b>An experimental temporomandibular joint OA was induced by partial discectomy in rats. The pathological characteristics of the normal, early-stage, and late-stage osteoarthritic TMJ cartilages were verified by histological techniques. The AQP1 and AQP3 gene expressions in the normal and osteoarthritic cartilages were measured using quantitative real-time reverse-transcription PCR analysis. The cartilage sections were incubated in primary polyclonal antibodies to AQP3; immunofluorescent microscopy was used to examine the AQP3 expression shown by its protein level.</p><p><b>RESULTS</b>The mRNA expression levels of AQP1 and AQP3, analyzed using quantitative PCR, revealed that AQP3 mRNA was highly up-regulated in the OA cartilage, which was considered significant. There was no notable difference in the expression of AQP1 mRNA between OA and normal controls. With the progressing of the OA, the localization of the AQP3 protein was quite different from that of the normal cartilage. Compared to the normal cartilage, the expressions of AQP3 protein were observed mainly in the proliferative zone and the upper mid-zone chondrocytes at the early-stage of OA, and were observed to appear frequently throughout the mid- and deep zone during the late-stage of OA.</p><p><b>CONCLUSIONS</b>The high expression of AQP3 mRNA in the OA cartilage and the different localization of the AQP3 protein suggest that it may play a particular role in OA pathogenesis. Further study of AQP3 function may provide new insight into the understanding of the molecular mechanisms underlying OA.</p>

Study on the characteristics of apoptosis in the condyles of osteoarthritic temporomandibular joints / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To study the characteristics of apoptosis in the condyles of osteoarthritic temporomandibular joints, and investigate its role in the pathogenesis of the disease.</p><p><b>METHODS</b>Temporomandibular joint osteoarthrosis model of rabbits was created by partial resection of joint disc. The animal models were sacrificed in the 15th day, the 1st month, the 2nd month, the 3rd month, the 4th month, the 5th month, and the 6th month chronologically. Then the pathological condyles were sectioned and detected with TUNEL method to investigate the apoptosis within the tissue.</p><p><b>RESULTS</b>In the reactive repairing state of osteoarthrosis, the apoptosis cells mainly located in the superficial fibrous layer of articular cartilage. With the remodeling of articular cartilage and bone, the apoptosis cells gradually appeared in the proliferating layer, especially in the "clusters of chondrocytes". Accompanied with the severe damage and loss of articular cartilage, the phenomena of apoptosis decreased in the lower zone of cartilage and increased in the hypertrophic and calcified zone.</p><p><b>CONCLUSION</b>There were abundant phenomena of apoptosis within the condylar cartilage of osteoarthritic temporomandibular joint. Abnormal proliferation and abundant apoptosis would disturb the regulation mechanism in the cartilage matrix and lead to the osteoarthrosis.</p>

Bone formation in vitro and in vivo by human bone marrow-derived mesenchymal stem cells / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To culture and study the osteogenic characteristics of human bone marrow-derived mesenchymal stem cells (hBMMSCs).</p><p><b>METHODS</b>hBMMSCs were separated and cultured from human iliac crest marrow. Growth kinetics of hBMMSCs was studied by growth curve. Under the osteoinductive culture, osteogenic differentiation of hBMMSCs was tested by alkaline phosphatase (ALP). Osteogenic functions of hBMMSCs in vitro and in vivo were also respectively detected by von Kossa stain and by transplanting hydroxyapatite/tricalcium phosphate ceramics (HA/TCP) with hBMMSCs.</p><p><b>RESULTS</b>hBMMSCs were cultured successfully. The growth curve of the second passage of BMMSCs indicated that the time of population doublings was about 3.5 days. The results of ALP stain were evident by the significant increase in ALP activity after hBMMSCs cultured in osteoinductive medium. Some mineralized nodules were detected by von Kossa stain at nineteenth day of osteoinductive culture. In vivo assay, histological evalution showed bone formation in 3 months after grafts of HA/TCP with hBMMSCs.</p><p><b>CONCLUSIONS</b>Osteoinductive solution can induce hBMMSCs to differentiate osteogenetic cell lines. Mineralized nodules and bone formation were found in vitro and in vivo assay. The results demonstrate that hBMMSCs have the potential for osteogenesis.</p>