ABSTRACT
OBJECTIVE@#To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule (, TXL) on the Parkin-mediated mitophagy and the ubiquitin-proteasome system in a rat model of myocardial ischemia-reperfusion injury (MIRI).@*METHODS@#Seventy adult male Sprague-Dawley rats were randomly divided into 7 groups: sham group, MIRI group, low- and high-dose TXL (0.5 and 1 g·kg@*RESULTS@#Compared with the sham group, the MIRI group exhibited a larger infarcted area (27.13%±0.01%, P<0.01), a higher apoptotic index (34.33%±2.03% vs.1.81%±0.03%, P<0.01), and higher cTnI expression (14.18±1.01 vs. 7.96±0.32, P<0.01). The mitochondrial integrity was damaged in the MIRI group, while TXL and ATV alleviated the damage of MIRI. More autophagosomes were observed in the high-dose TXL group than in the MIRI group (7.00±0.58 vs. 4.33±1.15, P<0.05). More amounts of PTEN-induced putative kinase protein 1 (PINK1) and Parkin translocated onto the mitochondria were detected in the high-dose TXL group than in the MIRI group (P<0.05). The ubiquitin response was signifificantly downregulated in the high-dose TXL group relative to the MIRI group (P<0.05). CQ administration abolished the activation of autophagy flux and the PINK1/ Parkin pathway induced by high-dose of TXL.@*CONCLUSIONS@#TXL ameliorates MIRI via activating Parkin-mediated mitophagy in rats. The downregulation of the ubiquitin-proteasome system is also involved.
ABSTRACT
BACKGROUND@#Geriatric hip fracture patients receiving clopidogrel are a surgical challenge. In China, most of these patients undergo delayed surgical treatment after clopidogrel withdrawal for at least 5 to 7 days. However, delayed surgery is associated with increased complications and mortality in the older adults. This retrospective paralleled comparison study investigated the safety of early surgery for geriatric hip fracture patients within 5 days of clopidogrel withdrawal.@*METHODS@#Acute hip fracture patients (≥65 years) who were hospitalized in the orthogeriatric co-management ward of Beijing Jishuitan Hospital between November 2016 and April 2018 were retrospectively reviewed. Sixty patients taking clopidogrel before injury and discontinued 0.050). The percentages of patients with coronary heart disease (61.7% vs. 18.3%; P 0.050). There was no significant difference in perioperative complications, and 30-day and 1-year mortality rates between the groups.@*CONCLUSIONS@#Early hip fracture surgery is safe for elderly patients within 5 days of clopidogrel withdrawal, without increased perioperative blood loss, transfusion requirement, complications, and mortality compared with patients not taking antiplatelet drugs.
Subject(s)
Aged , Humans , Case-Control Studies , Clopidogrel/therapeutic use , Hip Fractures/surgery , Platelet Aggregation Inhibitors/adverse effects , Retrospective Studies , Ticlopidine/adverse effectsABSTRACT
Aim To analyze the molecular mechanism of Bushen Huoxue granules in the treatment of Parkinson's disease by using network pharmacology as the main research method combined with molecular docking technology. Methods TCMSP was used to find the active ingredients of Bushen Huoxue granules, and ADME screening was performed. The obtained active ingredients and targets were combined with PD targets to obtain disease-drug co-action targets; STRING 11.0 was used to construct PPI protein interaction network for the obtained disease-drugs. The Metascape platform was used to analyze the enrichment of disease-drug target functions and pathways, and then Cytoscape 3.7. 1 was used to construct a network diagram of Bushen Huoxue granules-PD targets-action pathways; AUTODOCK and PYMOL software were used for molecular docking and visualization operations. Results The core active ingredients of Bushen Huoxue granules in treating PD were quercetin, luteolin, kaempferol, tanshinone, etc.; the main targets were PTGS2, PTGS1, SCN5A, ADRB2 and CHRM1, etc.; the main signaling pathways are PI3K/AKT, Toll, whose function was mainly to regulate cell apoptosis and neuroinflammatory response. Conclusion This study has initially revealed the mechanism of Bushen Huoxue granules in the multi-level and multi-step treatment of PD, laying a foundation for future animal experiments.
ABSTRACT
OBJECTIVE@#To investigate the effect of early intervention of Tongxinluo (, TXL) on right ventricular function (RVF) of rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT).@*METHODS@#A total of 30 adult male Sprague-Dawley rats were assigned to 5 groups with complete random experiment design: Sham group (Sham), MCT group, TXL group, sildenafil (SIL) group and combination group (TXL+SIL), 6 rats in each group. Rats were injected with 50 mg/kg MCT solution for inducing PAH model except for those in the sham group. From the day of modeling, rats of TXL, SIL and TXL+SIL groups were given TXL (1.2 g/kg), SIL (10 mg/kg) and combination solution (TXL:1.2 g/kg, SIL: 10 mg/kg) respectively, and rats in Sham and MCT groups were given normal saline (5 mL/kg). The samples were collected and tested after 21 consecutive days of intragastric administration. Echocardiography was used to measure the related indices of RVF, including pulmonary arterial flow spectrum, pulmonary artery diameter (PAD), right ventricular wall thickness (RVWT), right ventricular diameter (RVD), tricuspidannular plane systolic excursion (TAPSE), right atrium transverse diameter (RAT), and inferior vena cava diameter (IVCD). Elastic Verhoeff-Van Gieson staining was adopted to measure the percentage of wall thickness (WT%) of pulmonary arteriols. Hematoxylin-eosin staining was used to measure the cross-sectional area (CSA) of right ventricular cardiomyocytes.@*RESULTS@#MCT-induced PAH rat model was successfully established. In MCT group the wall of pulmonary arterioles exhibited a prominent-increase thickness, PAD, RVWT, RVD, RAT, IVCD, WT%, right ventricular hypertrophy index (RVHI) as well as CSA of RV cardiomyocyte significantly increased (all P<0.01), and TAPSE markedly decreased (P<0.01). At the same time, TXL prominently improved all of the above indices (all P<0.01). In comparison with SIL, TXL significantly reduced RVD (P<0.05) and decreased CAS of RV cardiomyocytes (P<0.01), but TAPSE in SIL group was much larger than in TXL group (P<0.01). Moreover, TAPSE in TXL+SIL group was larger than that in TXL group (P<0.01), while the two groups performed equally well in terms of the other indices.@*CONCLUSION@#Early intervention of TXL could inhibit pulmonary arterioles remodeling, and improve RVF by attenuating right ventricular hypertrophy, and TXL has a stronger effect on inhibiting right ventricular remodeling than SIL.
ABSTRACT
Objective: To investigate the mechanism of cytoskeletal recombination and migration inhibition induced by wangzaozin A, ent-kaurane diterpenoid, in A549 cells. Methods: The effects of wangzaozin A on cytotoxicity, cell morphology, cytoskeleton and protein expression as well as cell migration were detected in A549 cells by using MTT, microscope observation, Western blotting, immunofluorescence assay and scratch assay. Results: Wangzaozin A induced significant changes in cell morphology at 24, 48 and 72 h, including increased pseudopods, stretched pseudopods and flattened nucleus in A549 cells. Moreover, microtubules and keratin fibers networks in A549 cells also showed obvious rearrangement, which indicated the cytoskeleton had gone through a continuous recombination process. Further, wangzaozin A significantly increased the phosphorylation of extracellular regulated protein kinase (ERK), microtubule-associated protein 4 (MAP4), keratin 8 (K8) (P < 0.05, 0.01), while wangzaozin A-induced phosphorylation of MAP4 and K8 were suppressed in A549 cells treated with ERK inhibitors U0126 (P < 0.05, 0.01); Wangzaozin A inhibited the migration of A549 cells with a correlation between concentration and time. Conclusion: Wangzaozin A can upregulate the phosphorylation of MAP4 and K8 by activating ERK signaling pathway, which can significantly increase the dynamics of MTs and KFs, disturb the dynamic balance of the cytoskeleton, and inhibit the migration of A549 cells.
ABSTRACT
<p><b>Background</b>Imbalance of interferon-gamma (IFN-γ), interleukin (IL)-4, and IL-17 producing by T cells is confirmed to contribute to the pathogenesis of systemic lupus erythematosus (SLE). Autophagy is now emerging as a core player in the development and the function of the immune system. Therefore, we investigated the autophagic behavior in IFN-γ-, IL-4-, and IL-17-producing T cells from patients with SLE.</p><p><b>Methods</b>Thirty patients with SLE and 25 healthy controls matched for gender and age were recruited between September 2016 and May 2017. The autophagic levels in IFN-γ T cells, IL-4 T cells, and IL-17 T cells from patients with newly diagnosed SLE and healthy controls were measured using flow cytometry. The plasma levels of IFN-γ were determined by enzyme-linked immunosorbent assay in SLE patients and healthy controls. Unpaired t-tests and the nonparametric Mann-Whitney U-test were used to compare data from patients with SLE and controls. Spearman's rank correlation coefficient was applied for calculation of the correlation between parallel variables in single samples.</p><p><b>Results</b>Our results showed increased percentage of autophagy in IFN-γ T cells from patients with SLE and healthy controls ([8.07 ± 2.72]% vs. [3.76 ± 1.67]%, t = 5.184, P < 0.001), but not in IL-4 T cells or IL-17 T cells (P > 0.05) as compared to healthy donors. Moreover, the plasma levels of IFN-γ in SLE patients were significantly higher than those in healthy controls ([68.9 ± 29.1] pg/ml vs. [24.7 ± 17.6] pg/ml, t = 5.430, P < 0.001). Moreover, in SLE patients, the percentage of autophagy in IFN-γ T cells was positively correlated with the plasma levels of IFN-γ (r = 0.344, P = 0.046), as well as the disease activity of patients with SLE (r = 0.379, P = 0.039).</p><p><b>Conclusion</b>The results indicate that autophagy in IFN-γ T cells from SLE patients is activated, which might contribute to the persistence of T cells producing IFN-γ, such as Th1 cells, and consequently result in the high plasma levels of IFN-γ, and then enhance the disease activity of SLE.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Autophagy , China , Interferon-gamma , Metabolism , Interleukin-17 , Metabolism , Interleukin-4 , Metabolism , Lupus Erythematosus, Systemic , Allergy and Immunology , Th1 Cells , PhysiologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of Salvia miltiorrhiza and Ligustrazine Injection (SML) on proliferation and apoptosis of human hepatic stellate cell LX-2 and the expression of N-myc downstreamregulated gene 2 (NDRG2, a tumor suppressor gene).</p><p><b>METHODS</b>HSCs from the LX-2 cell line were cultured in vitro. The proliferative state of different initial LX-2 cell numbers was measured using a 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. LX-2 cells were plated in 96-well plates at an approximate density of 2.50×10cells/mL and cultured for 24 h followed by the application of different concentrations of SML (1, 2, 4 and 8 μL/mL). Cell proliferation was measured using the MTT assay at 24 and 48 h. Apoptosis was detected by flow cytometry at 24 h. LX-2 cells were treated with different concentrations of SML and extracted with protein lysis buffer. The levels of NDRG2 and β-catenin were measured by Western blot.</p><p><b>RESULTS</b>With the exception of the 1 and 2 μL/mL concentrations, 4 and 8 μL/mL SML inhibited cell proliferation in a concentration-dependent manner at 24 and 48 h (P<0.05). With the exception of the 1 and 2 μL/mL concentrations, the NDRG2 expression level was greatly increased in a concentration-dependent manner. However, the level of β-catenin was unaffected.</p><p><b>CONCLUSION</b>SML inhibit LX-2 cell proliferation in a concentration-dependent manner, and the mechanism may be associated with NDRG2 over-expression.</p>
ABSTRACT
<p><b>OBJECTIVE</b>To analyze the clinical evaluation of Parkinson's disease (PD) patients receiving integrated Chinese and Western medicine therapy.</p><p><b>METHODS</b>One hundred and twenty patients were enrolled and randomly allocated to a control group or treatment group. Patients in the two groups received placebo and Bushen Huoxue Granule (, BHG), respectively. Both groups received baseline levodopa and benserazide (Madopar). The effects of treatment were assessed monthly during the 9-month treatment. Means of evaluation included Unified PD Rating Scale (UPDRS) scores (II and III), sleep scale score, 10 m turn back test (getting up time, 10 m×2 times, and turning time), timing motor test (TMT)-left and TMT-right, which were treated as the dependent variables; and age, sex, duration of PD, Hoehn and Yahr (H-Y) stage and Madopar dosage of admitted PD patients were as the independent variables. Multiple linear regression was used to analyze these factors.</p><p><b>RESULTS</b>H-Y stage significantly affected UPDRS II score, UPDRS III score, and getting up time (P<0.01). Madopar dosage and H-Y stage significantly affected the 10 m×2 times (P<0.05 or <0.01). Madopar dosage significantly affected the sleep scale score (P<0.05). There were also significant correlations between age and TMT-left or TMT-right (P<0.01), and duration of PD and TMT-right (P<0.05).</p><p><b>CONCLUSIONS</b>The six assessed means of clinical evaluation (including UPDRS II and UPDRS III scores, sleep scale score, getting up time, 10 m×2 times, and turning time) are sensitive indexes in all PD patients. H-Y stage and Madopar dosage are the major factors influencing means of clinical assessment of PD treatment.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Integrative Medicine , Medicine, Chinese Traditional , Parkinson Disease , Therapeutics , Sleep , Time Factors , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of Modified Zhuye Shigao Decoction (MZSD) and its components on preventing radiation esophagitis of rats.</p><p><b>METHODS</b>One hundred Wistar rats were randomly divided into 5 groups, including the control group, radiation model group, MZSD group, Zhuye Shigao Decoction (ZSD) group, and added ingredients group, 20 rats in each group. The model of radiation esophagitis of rat was established by once local radiation of 40 Gy (330 Mu/min) with a high energy linear accelerator. The administration of Chinese medicine was continued for 14 days from 7 days before radiation application in the three treatment groups. On the 7th and 14th day, the serum was isolated and the levels of inflammatory cytokines tumor necrosis factor (TNF-α), interleukin 1β (IL-1β) and IL-8 were tested. The pathological slices of esophagus were obtained, and the pathological changes were observed. During the whole process, weight and food intake were recorded each day.</p><p><b>RESULTS</b>On the 7th day after radiation, the esophagus of rats in the MZSD group was almost intact, and the pathological injury score was significantly lower than that of the radiation model group, ZSD group and added ingredients group (P<0.01). Compared with the control group, the body weight and food intake of rats in the radiation model group were significantly decreased, and the levels of TNF-α, IL-1β and IL-8 were significantly increased (P<0.05 or P<0.01), while the MZSD group showed a significant increase in body weight and food intake, and a significant decrease in the levels of TNF-α, IL-1β and IL-8 compared with the radiation model group, ZSD group and added ingredients group (P <0.05 or P<0.01).</p><p><b>CONCLUSION</b>MZSD prevents the development of radiation esophagitis probably by inhibiting the generation and release of the inflammatory cytokines TNF-α, IL-1β and IL-8.</p>
Subject(s)
Animals , Male , Body Weight , Cytokines , Metabolism , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Esophagitis , Drug Therapy , Pathology , Esophagus , Pathology , Feeding Behavior , Inflammation Mediators , Metabolism , Neutrophil Infiltration , Radiation Injuries , Drug Therapy , Pathology , Rats, Wistar , Time FactorsABSTRACT
<p><b>OBJECTIVE</b>To observe the clinical curative effect of Chinese medicine Bushen Huoxue Granule(补肾活血颗粒, BHG) on Parkinson's disease (PD) patients with depressive state.</p><p><b>METHODS</b>Sixty-two PD patients with depressive state were randomly assigned to two groups by using a random number table, 31 in each group. Madopar was given to all as the conventional treatment. The fluoxetine hydrochloride dispersible tablet was given to the patients in the control group and BHG was given to those in the treatment group. The therapeutic course for all was 12 weeks. Before and after treatment, Hamilton depression rating scale (HAMD) was applied to judge the curative effect, and the changes of cerebral neurotransmitters levels in the brain of patients were detected by encephalofluctuograph technique.</p><p><b>RESULTS</b>The scores of HAMD in the two groups were decreased markedly after 12-week treatment. It was lower in the treatment group than that in the control group with significant difference (P<0.01). The contents of norepinephrine (NE) and 5-serotonin (5-HT) in the PD patients were obviously lower than normal value. There was no significant difference between the two groups before treatment (P>0.05). The contents of NE and 5-HT were all increased in the two groups after treatment (P<0.05), with significant differences between the two groups (P<0.01).</p><p><b>CONCLUSION</b>BHG could increase the contents of NE and 5-HT in PD patients' brain to improve the depressive state of PD patients.</p>
Subject(s)
Aged , Female , Humans , Male , Brain , Metabolism , Depression , Drug Therapy , Drugs, Chinese Herbal , Therapeutic Uses , Norepinephrine , Metabolism , Parkinson Disease , Drug Therapy , Serotonin , Metabolism , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of Danshen Injection (DSI) on the proliferation of rheumatoid arthritis fibroblast-like synoviocytes (RA FLSs) cultured in RA patients' serum.</p><p><b>METHODS</b>The RA FLSs harvested from RA patients' synovial fluid were primarily cultured by routines. The cells were cultured with 10% inactivated human serum (the healthy human serum and the RA patients' serum) for 24 h. Then DSI at the final concentration of 0. 4 mg/mL was added in the cells for further 24 h culture. By taking 10% fetal calf serum as the control, the morphological changes were observed under optical microscope. The proliferation was analyzed by MTT. The apoptosis was detected by flow cytometry. The total RNA was extracted and reverse transcription was performed. The Bax mRNA expression was detected by fluorescent quantitative PCR.</p><p><b>RESULTS</b>(1) After human serum was added in the healthy human serum and RA patients' serum, cells could grow adhering to the wall. Compared with the fetal calf serum group (FCS), the cell density was higher in the healthy human serum group than in the fetal calf serum group, with no obvious morphological changes. (2) MTT results showed that, compared with the fetal calf serum group, the absorbance value (OD) obviously increased in the healthy human serum group and the RA patients' serum group, showing statistical difference (P <0.01). After adding DSI at the final concentration of 0.4 mg/mL, cells from different serums were inhibited to various degrees (with OD significantly decreased, P <0.05). The OD value significantly increased more in the healthy human serum group and the RA patients' serum group than in the fetal calf serum group, showing statistical difference (P <0.01). There was statistical difference between the healthy human serum group and the RA patients' serum group (P <0.01). (3) The apoptosis rate in the RA patients' serum group obviously decreased with statistical difference, when compared with the Salvia miltiorrhiza free fetal calf serum group (P >0. 01). The apoptosis rate in the fetal calf serum group and the RA patients' serum group significantly increased after adding 0.4 mg/mL Salvia miltiorrhiza, showing statistical difference when compared with the Salvia miltiorrhiza free fetal calf serum group and the Salvia miltiorrhiza free RA patients' serum group (P <0.05). The FLSs were effected by 0.4 mg/mL Salvia miltiorrhiza, the apoptosis rate significantly decreased in the healthy human serum group and the RA patients' serum group, showing statistical difference when compared with the fetal calf serum group (P <0. 05, P <0.01). (4) The expression of Bax gene significantly increased in the RA patients' serum group and the fetal calf serum group after action of 0.4 mg/mL Salvia miltiorrhiza, showing statistical difference (P <0. 01). When 0.4 mg/mL Salvia miltiorrhiza was added, the expression of Bax mRNA obviously increased in the healthy human serum group and the RA patients' serum group, showing statistical difference when compared with the fetal calf serum group (P <0.01).</p><p><b>CONCLUSIONS</b>(1) Although healthy human serum can be favorable to the growth of RA FLSs, the fetal calf serum could reflect the actual results better in the cyto biological research on specific diseases (if there is no serum from patients with corresponding disease). (2) DSI could inhibit the proliferation of RA FLSs through promoting their apoptosis.</p>
Subject(s)
Humans , Apoptosis , Arthritis, Rheumatoid , Pathology , Cell Proliferation , Cells, Cultured , Culture Media , Chemistry , Drugs, Chinese Herbal , Pharmacology , Fibroblasts , Cell Biology , Phenanthrolines , Pharmacology , Salvia miltiorrhiza , Synovial Membrane , Cell BiologyABSTRACT
<p><b>BACKGROUND</b>Surgical treatment of acetabular fracture has long been a challenging area in the field of orthopedic trauma. The aim of this research was to investigate the operative methods for delayed acetabular fractures and to assess the operation results.</p><p><b>METHODS</b>The operative approaches, procedures, results, and complications of the delayed acetabular fractures between 1995 and 2005 were retrospectively evaluated at Beijing Jishuitan Hospital. Quality of life was assessed for each patient with the Merle d'Aubingne and Postel fracture function rating scale and the radiological result was assessed using the Matta radiological score.</p><p><b>RESULTS</b>Sixty-eight cases (70 hips) were followed up with a minimal duration of five years (average of 5.8 years). Excellent functional results were observed in 10 hip joints, good results in 40, fair results in 11, and poor results in nine. The risks of poor prognosis include impact fracture or osteochondral fracture of femoral head, a time beyond 42 days from injury to operative management, and dislocation of femoral head during the injury. Some of the problems, which were observed included postoperative infection in two hips, iatrogenic sciatic nerve injury in eight hips, traumatic arthritis in 15 hips, heterotopic ossification in 17 hips, and necrosis of the femoral head in six hips.</p><p><b>CONCLUSION</b>A careful selection of operative indications for delayed acetabular fractures in combination with a proper operative approach and appropriate reduction and fixation could guarantee relatively good results.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Acetabulum , Wounds and Injuries , General Surgery , Fractures, Bone , General Surgery , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
To explore advantages of Chinese medicine (CM) by analyzing differences in the origin of philosophy for human health between CM and Western medicine (WM). Methodologically, a distinctive feature of CM is its systems theory, which is also the difference between CM and WM. Since the birth of CM, it has taken the human body as a whole from the key concepts of "qi, blood, yin-yang, viscera (Zang-Fu), and meridian and channel", rather than a single cell or a particular organ. WM evolves from the Western philosophic way of thinking and merely uses natural sciences as the foundation. The development of WM is based on human structures, or anatomy, and therefore, research of WM is also based on the way of thinking of decomposing the whole human body into several independent parts, which is the impetus of promoting the development of WM. The core of CM includes the holistic view and the dialectical view. Chinese herbal medicines contain various components and treat a disease from multiple targets and links. Therefore, Chinese herbal medicines treat a diseased state by regulating and mobilizing the whole body rather than just regulating a single factor, since the diseased state is not only a problem in a local part of the body but a local reflection of imbalance of the whole body.
Subject(s)
Humans , Holistic Health , Integrative Medicine , Medicine , Medicine, Chinese Traditional , Philosophy , Systems Biology , Western WorldABSTRACT
<p><b>OBJECTIVE</b>To extract tumor interstitial fluid (TIF) from MKN-45 gastric cancer which is similar to "muddy phlegm" in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid (MKN-45 TIF) intervention on metastasis of gastric cancer and on the expressions of vascular endothelial growth factor (VEGF), kinase insert domain containing receptor (KDR), epithelial-cadherin (E-cad), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1) and telomerase genes and proteins in primary tumor tissue.</p><p><b>METHODS</b>An MKN-45 tumor-bearing model was established in 50 nude mice. The modeled animals were equally randomized to 5 groups: the simple tumor-bearing group (model group), the normal saline (NS) via tail vein injection (i.v.) group (NS i.v. group), MKN-45 TIF i.v. group (TIF i.v. group), NS intraperitoneal injection (i.p.) group (NS i.p. group), and MKN-45 TIF i.p. group (TIF i.p. group). The TIF and NS intervention groups received injection (i.p. or i.v.) of MKN-45 TIF or NS twice a week, 0.2 mL at a time. After 8 weeks, the primary tumors were removed, weighed and HE stained to observe tumor metastasis. The primary tumor tissues were analyzed by immunohistochemistry and real-time quantitative PCR to detect expressions of VEGF, KDR, E-cad, COX-2, ICAM-1, and telomerase genes and proteins in different groups.</p><p><b>RESULTS</b>There were significant differences in tumor weight between TIF intervention groups and the model and NS intervention groups. Tumor metastasis was observed in all 5 groups, but the tumor metastasis rate in TIF intervention groups was significantly higher than those in the model and NS intervention groups. The gene and protein expressions of gastric cancer-related factors VEGF, KDR, COX-2, ICAM-1 and telomerase were unregulated while the gene and protein expressions of E-cad were downregulated in TIF intervention groups.</p><p><b>CONCLUSIONS</b>TIF promotes tumor growth, invasion and metastasis of gastric cancer. These findings provide preliminary experimental clues for verifying the hypothesis of "tumor-phlegm microenvironment".</p>
Subject(s)
Animals , Humans , Male , Mice , Cadherins , Genetics , Metabolism , Cell Line, Tumor , Cyclooxygenase 2 , Genetics , Metabolism , Extracellular Fluid , Metabolism , Gene Expression Regulation, Neoplastic , Intercellular Adhesion Molecule-1 , Genetics , Metabolism , Mice, Nude , Neoplasm Transplantation , Stomach Neoplasms , Metabolism , Telomerase , Genetics , Metabolism , Tumor Microenvironment , Physiology , Vascular Endothelial Growth Factor A , Genetics , Metabolism , Vascular Endothelial Growth Factor Receptor-2 , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the molecular mechanism of sex reversal in a 46,XY female patient.</p><p><b>METHODS</b>Clinical data was collected. Peripheral blood lymphocytes were cultured for G-banding chromosomal analysis and DNA extraction. Sex-determining region of Y-chromosome (SRY) gene was analyzed with polymerase chain reaction (PCR) and DNA sequencing .</p><p><b>RESULTS</b>Although the patient has a female appearance, he has a karyotype of 46,XY. The SRY gene can be detected in all samples. The 6th base of SRY gene coding region was deleted, resulting in a frameshifting mutation and premature termination of protein translation.</p><p><b>CONCLUSION</b>The sex reversal of the patient is probably due to abnormal embryonic development caused by the SRY gene mutation.</p>
Subject(s)
Adolescent , Female , Humans , Amino Acid Sequence , Disorders of Sex Development , Genetics , Genes, sry , Molecular Sequence DataABSTRACT
<p><b>OBJECTIVE</b>To explore the mechanism underlying the therapeutic effect of Bushen Huoxue Decoction (BHD), a traditional Chinese medicinal preparation, on dopamine D2 receptor (DRD2) in the brain of rat models of Parkinson's disease (PD).</p><p><b>METHODS</b>A total of 120 SD rats were randomized into normal control group, saline model group and BHD-treated group. In the latter two groups, PD rat models were established by direct injection of 6-OHDA to destruct the substantia nigra compact part (SNC) with corresponding treatments. The behavioral changes of the rats were observed. Radioimmunoassay was employed to determine the changes in the equilibrium dissociation constant (Kd) and maximal binding capacity (B(max)) of DRD2, and immunohistochemistry was used to observe the number of the DRD2-positive cells in the brain of the rats.</p><p><b>RESULTS</b>BHD can markedly improve the behavioral abnormalities of PD model rats. Compared with those in the saline model group, the B(max) of DRD2 in the damaged hemisphere increased while the Kd of BHD decreased significantly after BHD treatment (P<0.01). The number of DRD2-positive cells in BHD-treated group was significantly higher than that in the model group (80.9∓13.59 vs 11.15∓6.78, P<0.01), but showed no significant difference from that in the normal control group (P>0.05).</p><p><b>CONCLUSION</b>BHD can improve the behavioral abnormalities and increase the cerebral expression and affinity of DRD2 in PD rat models.</p>
Subject(s)
Animals , Female , Rats , Brain , Metabolism , Drugs, Chinese Herbal , Therapeutic Uses , Parkinson Disease , Drug Therapy , Metabolism , Phytotherapy , Receptors, Dopamine D2 , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of Bushen Huoxue Granule (BHG) on dopamine (DA) neurotransmitter and dopamine transporter (DAT) in the brain of patients with Parkinson's disease (PD) as an adjunctive therapy.</p><p><b>METHODS</b>Ninety-four PD patients were randomly assigned to two groups, 47 in each group. Madopar was given to all as the basic treatment group. The placebo was given to those in the control group while BHG was given to those in the treatment. The therapeutic course for all was three months. Before and after treatment DA levels in the brain of patients were detected by encephalofluctuograph (EFG) technique. Changes of DAT in the striatum of patients in the treatment group were detected by positron emission tomography (PET) and region of interest (ROI) analysis.</p><p><b>RESULTS</b>(1) Before treatment the DA level was lower in the two groups than the normal value, showing significant difference (P < 0.01), but with no significant difference between the two groups (P > 0.05). After treatment the DA level obviously increased in the two groups, showing significant difference from that before treatment (P < 0.01). No significant difference existed in the DA level in the two groups when compared with the normal value (P > 0.05), but with significant difference between the two groups (P < 0.05). Better results were obtained in the treatment group than in the control group. (2) The DAT radioactive accumulation inside the striatum increased obviously in the treatment group after treatment. ROI analysis showed the total ratio of striatum/cerebellum before and after treatment was 1.86 +/- 0.32 and 2.61 +/- 0.53 respectively, showing statistical difference (P < 0.05).</p><p><b>CONCLUSION</b>BHG could improve the DA level of PD patients, and increasing DAT contents in the striatum, thus playing a role in effectively treating PD.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Brain , Metabolism , Dopamine , Metabolism , Dopamine Plasma Membrane Transport Proteins , Metabolism , Drugs, Chinese Herbal , Therapeutic Uses , Parkinson Disease , Drug Therapy , Metabolism , PhytotherapyABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of Liangxuehuoxue Recipe (LXHXF), a compound traditional Chinese medicinal preparation, on the expressions of tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) in the lung tissue of rats exposed to X-ray radiation.</p><p><b>METHODS</b>Seventy-two Wistar rats were randomized into exposure group (group A, without treatment) and small-, middle- and high-dose LXHXF groups (groups B, C, and D treated with LXHXF at the daily doses of 9, 18, and 36 g/kg, respectively). After X-ray exposure of the right lung at 3 Gy twice a week for 5 consecutive weeks, the rats were sacrificed at the end of the 5th, 12th and 26th weeks, and the lung tissues were taken for immunohistochemistry of the expressions of TNF-α and TGF-β.</p><p><b>RESULTS</b>In group A, the expression of TNF-α reached the peak level at 5 weeks and TGF-β expression was the highest at 12 and 26 weeks. LXHXF, especially at the middle and high doses, obviously inhibited the expression of TNF-α at 5 weeks; the treatments also resulted in significantly lowered expressions of TGF-β at all the time points of observation as compared with those in group A (P<0.01). The high- and middle-dose groups exhibited no significant difference in the expression levels of TNF-α and TGF-β in the experiment (P>0.05).</p><p><b>CONCLUSION</b>Treatment with LXHXF can effectively inhibit TNF-α expression in the lung tissue in the early stage following radiation exposure, causing even more obvious inhibitory effect on TGF-β in the later stages. A higher dose of LXHXF produces more significant inhibitory effects on TNF-α and TGF-β expressions.</p>
Subject(s)
Animals , Male , Rats , Drugs, Chinese Herbal , Pharmacology , Lung , Metabolism , Radiation Effects , Radiation Injuries , Metabolism , Radiation-Protective Agents , Pharmacology , Random Allocation , Rats, Wistar , Transforming Growth Factor beta , Genetics , Metabolism , Tumor Necrosis Factor-alpha , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To explore the effect of Bushen Huoxue Decoction (BHD) on the orphan receptor (Nurr1) and tyrosine hydroxylase (TH) in the brain of rats with Parkinson's disease (PD).</p><p><b>METHODS</b>One hundred and twenty SD rats were divided into 100 in the model group and 20 in the normal control group, fifty-eight SD rats from the model group, established into PD model successfully by injuring their substantia nigra (SSN) with 6-hydroxydopamine, were divided equally into the model group and the test group, and they were treated with saline and BHD, respectively, for eight successive weeks. The change in the rats' behavior before and after treatment was observed by counting the cycles of rotation induced by apomorphine injection; the pathology of neurons, level of Nurr1 mRNA expression, and amount of TH positive cells in SSN were observed after treatment.</p><p><b>RESULTS</b>The rats' behavior was improved in the tested group significantly, the rotation cycle after treatment being 84.0 ± 20.0 cycles/40 min, which was significantly lower than that in the model group (377.0 ± 62.3 cycles/40 min, P<0.01). Besides, the Nurr1 mRNA expression and TH positive cell in the test group were 0.97 ± 0.15 and 49.40 ± 14.72, respectively, which were significantly higher than those in the model group, 0.22 ± 0.03 and 5.45 ± 2.58, respectively (all P<0.01).</p><p><b>CONCLUSION</b>BHD could treat PD by enhancing the Nurr1 mRNA expression, increasing the TH content in brain, and promoting the repairing of injured neuron in cerebral SSN.</p>
Subject(s)
Animals , Female , Rats , Behavior, Animal , Brain , Pathology , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Gene Expression Regulation , Neurons , Pathology , Nuclear Receptor Subfamily 4, Group A, Member 2 , Genetics , Metabolism , Parkinson Disease , Drug Therapy , Pathology , RNA, Messenger , Genetics , Metabolism , Rats, Sprague-Dawley , Substantia Nigra , Metabolism , Pathology , Tyrosine 3-Monooxygenase , MetabolismABSTRACT
This study was purposed to investigate the mechanism of thrombocytopenia in patients with systemic lupus erythematosus (SLE) through detecting anti-megakaryocyte antibodies in SLE patients. The serum anti-megakaryocyte antibodies in 36 SLE cases with thrombocytopenia were detected by using indirect immunofluorescence, the detected results were compared with detected results of 30 SLE cases without thrombocytopenia and 30 healthy persons. The results showed that the positive incidences of anti-megakaryocyte antibody in serum of 36 SLE cases with thrombocytopenia, 30 SLE cases without thrombocytopenia and 30 healthy persons were 19.4% (7/36), 6.7% (2/30) and 3.3% (1/30) respectively. As compared with SLE patients without thrombocytopenia and healthy persons, SLE patients with thrombocytopenia had higher incidence of anti-megakaryocyte antibodies, moreover there was significant difference between SLE patients with thrombocytopenia and healthy persons (p < 0.05), while there was no significant difference between SLE patients with or without thrombocytopenia (p > 0.05). It is concluded that autoantibodies against megakaryocytes exist in SLE patients and may partially contribute to the incidence of thrombocytopenia in SLE patients. The detection of anti-megakaryocyte antibodies with a enough case number is needed to make a final conclusion on thrombocytopenia pathogenesis in SLE.