[Antidepressant mechanism of Shenling Kaixin Granules based on BDNF/TrkB/CREB pathway].

To investigate the antidepressant mechanism of Shenling Kaixin Granules(SLKX) in treating chronic unpredictable mild stress(CUMS) model rats. Ninety male SD rats were randomly divided into control group, model group, Shugan Jieyu Capsules(110 mg·kg~(-1)) group and SLKX low-(90 mg·kg~(-1)), medium-(180 mg·kg~(-1)), and high-dose(360 mg·kg~(-1)) groups. Depression rat model was replicated by CUMS method. After treatment, the behavioral changes of rats were evaluated by sugar preference, open field, elevated cross maze and forced swimming experiments. The contents of interleukin 1 beta(IL-1ß), tumor necrosis factor α(TNF-α), brain-derived neurotrophic factor(BDNF) and 5-hydroxytryptamine(5-HT) in serum were determined by enzyme linked immunosorbent assay(ELISA), and the activities of superoxide dismutase(SOD) and catalase(CAT) in hippocampal CA1 region were also detected. Pathological changes in hippocampal CA1 region were detected by hematoxylin-eosin(HE) staining, and Western blot was used to determine the expression of nerve growth factor(NGF), BDNF, phospho-tyrosine kinase receptor(p-TrkB)/TrkB, phospho-cAMP-response element binding protein(p-CREB)/CREB, nuclear factor E2 related factor 2(Nrf2), heme oxygenase 1(HO-1), B-cell lymphoma-2(Bcl-2)/Bcl-2 associated X protein(Bax) and caspase-3 in hippocampal CA1 region. RESULTS:: showed that compared with the control group, the model group had decreased sugar preference, reduced number of entries and time spent in the center of open field and shortened total distance of movement, reduced number of entries and proportion of time spent in open arm, and increased number and time of immobility in forced swimming experiment. Additionally, the serum contents of IL-1ß and TNF-α and the expression of caspase-3 were higher, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1 and Bcl-2/Bax, and the Nrf2 nuclear translocation were lower in model group than in control group. Compared with the conditions in model group, the sugar preference, the number of entries and time spent in the center of open, total distance of movement, and the number of entries and proportion of time spent in open arm in treatment groups were increased while the number and time of immobility in forced swimming experiment were decreased; the serum contents of IL-1ß and TNF-α and the expression of caspase-3 were down regulated, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1, Bcl-2/Bax, and Nrf2 nuclear translocation were enhanced. In conclusion, SLKX might regulate the Nrf2 nucleus translocation by activating BDNF/TrkB/CREB pathway, lower oxidative stress damage in hippocampus, inhibit caspase-3 activity, and reduce apoptosis of hippocampal nerve cells, thereby playing an antidepressant role.

[Neuroprotective effect of ginsenoside Re on drosophila model of Parkinson's disease].

This study aims to explore the neuroprotective mechanism of ginsenoside Re(GS-Re) on drosophila model of Parkinson's disease(PD) induced by rotenone(Rot). To be specific, Rot was used to induce PD in drosophilas. Then the drosophilas were grouped and respectively treated(GS-Re: 0.1, 0.4, 1.6 mmol·L~(-1); L-dopa: 80 µmol·L~(-1)). Life span and crawling ability of drosophilas were determined. The brain antioxidant activity [content of catalase(CAT), malondialdehyde(MDA), reactive oxygen species(ROS), superoxide dismutase(SOD)], dopamine(DA) content, and mitochondrial function [content of adenosine triphosphate(ATP), NADH:ubiquinone oxidoreductase subunit B8(NDUFB8) Ⅰ activity, succinate dehydrogenase complex, subunit B(SDHB) Ⅱ activity] were detected by enzyme-linked immunosorbent assay(ELISA). The number of DA neurons in the brains of drosophilas was measured with the immunofluorescence method. The levels of NDUFB8 Ⅰ, SDHB Ⅱ, cytochrome C(Cyt C), nuclear factor-E2-related factor 2(Nrf2), heme oxygenase-1(HO-1), B-cell lymphoma/leukemia 2(Bcl-2)/Bcl-2-assaciated X protein(Bax), and cleaved caspase-3/caspase-3 in the brain were detected by Western blot. The results showed that model group [475 µmol·L~(-1) Rot(IC_(50))] demonstrated significantly low survival rate, obvious dyskinesia, small number of neurons and low DA content in the brain, high ROS level and MDA content, low content of SOD and CAT, significantly low ATP content, NDUFB8 Ⅰ activity, and SDHB Ⅱ activity, significantly low expression of NDUFB8 Ⅰ, SDHB Ⅱ, and Bcl-2/Bax, large amount of Cyt C released from mitochondria to cytoplasm, low nuclear transfer of Nrf2, and significantly high expression of cleaved caspase-3/caspase-3 compared with the control group. GS-Re(0.1, 0.4, and 1.6 mmol·L~(-1)) significantly improved the survival rate of PD drosophilas, alleviated the dyskinesia, increased DA content, reduced the loss of DA neurons, ROS level, and MDA content in brain, improved content of SOD and CAT and antioxidant activity in brain, maintained mitochondrial homeostasis(significantly increased ATP content and activity of NDUFB8 Ⅰ and SDHB Ⅱ, significantly up-regulated expression of NDUFB8 Ⅰ, SDHB Ⅱ, and Bcl-2/Bax), significantly reduced the expression of Cyt C, increased the nuclear transfer of Nrf2, and down-regulated the expression of cleaved caspase-3/caspase-3. In conclusion, GS-Re can significantly relieve the Rot-induced cerebral neurotoxicity in drosophilas. The mechanism may be that GS-Re activates Keap1-Nrf2-ARE signaling pathway by maintaining mitochondrial homeostasis, improves antioxidant capacity of brain neurons, then inhibits mitochondria-mediated caspase-3 signaling pathway, and the apoptosis of neuronal cells, thereby exerting the neuroprotective effect.

Spirocyclopiperazinium salt compound DXL-A-24 improves visceral sensation and gut microbiota in a rat model of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is characterized by visceral pain, impaired intestinal barrier and a disorder of the microbiota. DXL-A-24 has analgesic and anti-inflammatory effects by inhibiting neuropeptides and inflammatory factors. In this study, we used chronic unpredictable mild stress (CUMS) induced IBS model, to assess the action of DXL-A-24 on visceral hypersensitivity, barrier function and microbiota. Visceral sensation was assessed by colorectal distension in a model of IBS. The expressions of substance P (SP) and calcitonin gene-related peptide (CGRP) were detected by immunohistochemistry and western blot, the contents of diamine oxidase (DAO) and D-lactic acid were detected by ELISA, and 16S rRNA to detect the diversity of gut microbiota. CUMS reduced visceral pain threshold and increased colonic permeability of rats. DXL-A-24 for 28 days inhibited these changes. DXL-A-24 also decreased the expression of SP, CGRP in colon and D-LA, DAO in serum. Besides, DXL-A-24 increased the richness and diversity of intestinal microbiota. In conclusions, DXL-A-24 reduced visceral sensitivity, improved intestinal barrier and regulated gut microbiota in rats with IBS.

Comparisons between Direct Anterior Approach and Lateral Approach for Primary Total Hip Arthroplasty in Postoperative Orthopaedic Complications: A Systematic Review and Meta-Analysis.

The direct anterior approach (DAA) are attracting increasing attention from orthopedic arthroplasty surgeons, due to the less blood loss, mild soft tissue invasion, rapid rehabilitation and shorter length of stay. However, the longer learning curve in DAA can give rise to several complications, such as intraoperative femoral fracture, lateral femoral cutaneous nerve injury, wound-healing problem, premature revision and so on. This meta-analysis was performed to compare the rate of postoperative orthopedic complications between the DAA and the lateral approach (LA). All studies involving the comparison of postoperative orthopedic complications after THA between the DAA and LA group were searched in 7 databases prior to October 2020. The odds ratio (OR) with the 95% confidence intervals (CI) for each outcome was calculated by using the RevMan 5.3. The methodological bias of included studies was evaluated and the potential heterogeneity sources were analyzed. Thirteen comparative studies including a total of 24853 hips (9575 hips in the DAA group and 15278 hips in the LA group) were eligible for this meta-analysis. There was no significant difference in the rate of surgical site infection [2.59% vs 2.14% (OR = 0.98; 95% CI: 0.59-1.61, P = 0.93)], heterotopic ossification [12.16% vs 26.47% (OR = 0.46; 95% CI: 0.20-1.07, P = 0.07)] and reoperation [2.70% and 2.11% respectively (OR = 0.93; 95% CI: 0.68-1.26, P = 0.64)] between the DAA and LA groups. Although a lower rate in prosthesis malposition [36.19% vs 54.86% (OR = 0.50; 95% CI: 0.35-0.73, P = 0.0003)], leg length discrepancy [1.87% vs 2.37% (OR = 2.35; 95% CI: 1.30-4.25, P = 0.005)] and Trendelenburg gait [1.68% vs 4.78% (OR = 0.29; 95% CI: 0.13-0.65, P = 0.003)] was observed in the DAA group, a higher rate in dislocation [0.77% vs 0.18% (OR = 3.73; 95% CI: 2.35-5.94, P< 0.00001)], periprosthetic fracture [1.05% vs 0.41% (OR = 2.38; 95% CI: 1.58-3.58, P< 0.0001)], prosthesis loosening [0.61% vs 0.37% (OR = 1.66; 95% CI: 1.05-2.62, P = 0.03)] and nerve injury [0.95% vs 0% (OR = 7.12; 95% CI: 1.66-30.48, P = 0.008)] was found in the DAA group. This meta-analysis demonstrated several evidences indicating that the DAA exhibited the advantages in the accurate prosthesis placement and less damage of surrounding hip musculature. However, a higher rate in dislocation, periprosthetic fracture, prosthesis loosening and nerve injury in the DAA group should be paid more attention, due to the limited exposure and a longer learning curve, compared to the LA.

In vitro and in vivo biocompatibility and bio-tribological properties of the calcium/amorphous-C composite films for bone tissue engineering application.

Carbon-and diamond-like-carbon coated Ti alloys hold great promise for tissue engineering applications. Unfortunately, their strong intrinsic stress leads to the adhesion failure of the films. Herein, a series of a-C films with different Ca content were prepared on Ti6Al4V via co-sputtering deposition technology. Homogeneous spherical Ca nanoclusters, with an inner diameter of 2-6 nm, were formed in an amorphous carbon matrix. The addition of Ca induced indistinctive variation in either phase composition or topography. However, the introduction of Ca not only improved the mechanical properties of a-C film but also significantly strengthened its adhesion to osteoblasts. The bio-tribological properties of Ca/a-C films were also assessed using a tribometer in FBS solution. The Ca/a-C films exhibited a low friction coefficient of 0.083 and a low wear rate of 1.02-1.24×10-6 mm3/Nm. The low coefficient of friction (COF) of the Ca/a-C films indicates their superior mechanical properties, making them the promising target of nanocomposite films used in bio-tribological applications. Well-stretched cells and the developed actin filaments were distinctly observed on the Ca/a-C films in the osteoblast cell adhesion experiments. In addition, the Ca/a-C films promoted cell proliferation and showed high cell viability. After being implanted for 4 weeks, the Ca/a-C implant material still adhered well to the muscle tissue, without inducing hyperergic or inflammatory reactions. Collectively, our results suggest that the Ca/a-C film is an ideal mounting material for bone tissue engineering.

Research on in vitro and in vivo biocompatibility of the low-friction Ti+C/amorphous carbon gradient multilayer films for hard tissue engineering.

Ti+C/amorphous carbon (a-C) gradient multilayer (GM) films are prepared on the Ti-alloy substrates via physical vapor deposition. Transmission electron microscopy revealed that the Ti atoms combine with the a-C film to form a TiC phase in the inner layer and the sputtering current significantly influences the amount of the TiC phase. Further, the mechanical properties of the Ti+C/a-C GM films were obtained using nanoindentation, and the results denoted the significant improvement in the mechanical properties of the a-C film after adding the Ti+C transition layers. The hardness and elastic modulus of the a-C GM films became approximately 31 and 265 GPa, respectively, which were obviously greater than those of the a-C films. The biotribological properties of the a-C GM films in fetal bovine serum (FBS) were verified. The coefficient of friction (COF) and wear rate of the obtained Ti+C/a-C GM film were 0.057 and (1.06-1.24) × 10-6 mm3/(N m), respectively, which were lower than those of pure a-C and the bare Ti alloy. The excellent mechanical properties of the Ti+C gradient transition layer and the lubricating effect of the FBS medium caused the low COF of the a-C GM films, indicating the potential biotribology applications of the a-C films. The cell apoptosis tests suggested that the a-C GM films promoted cell proliferation and viability. Meanwhile, the a-C-GM-coated implants and muscle tissue combined, and hyperergic and inflammatory reactions were not observed six weeks after implantation. These data indicate that the Ti+C/a-C GM film exhibits good biocompatibility and is an ideal mounting material for bone tissue engineering.