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OBJECTIVES@#Ziyin Huatan Recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo.@*METHODS@#Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene.@*RESULTS@#The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT.@*CONCLUSION@#ZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.
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Animals , Mice , Cell Line, Tumor , Cell Movement , Cell Proliferation , China , Gene Expression Regulation, Neoplastic , Mice, Nude , Neoplasm Invasiveness , Stomach Neoplasms/geneticsABSTRACT
Abstract Objectives: To investigate the diagnostic performance of single-source dual-energy computed tomography (DECT) based on gemstone spectral imaging technology (including Discovery CT750HD and Revolution CT) in patients with suspected feet/ankles gouty arthritis, and evaluate the urate deposition with a novel semi-quantitative DECT scoring system. Methods: A total of 196 patients were consecutively included. Feet and ankles were evaluated in all patients by single-source DECT scan. The 2015 EULAR/ACR criteria were used as the reference for the diagnosis of gout. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of DECT for the diagnosis of gout in the early (≤1 year), middle (1-3 years), and late (> 3 years) disease durations were calculated. Besides, a novel semi-quantitative DECT scoring system was assessed for the measurement of urate deposition, and the correlation between the scores and the clinical and serological data were also evaluated. Moreover, the influences of artifacts on the diagnostic performance of DECT were also determined. Results: The sensitivity, specificity, and AUC of DECT in 196 patients were 38.10, 96.43%, and 0.673 in the early-stage group; 62.96, 100.00%, and 0.815 in the middle-stage group; and 77.55, 87.50%, and 0.825 in the late-stage group, respectively. The overall diagnostic accuracies in the AUC of DECT (Discovery CT750HD and Revolution CT) in the middle and late stages of gout were higher than that in the early stage of gout. Besides, the monosodium urate crystals were deposited on the first metatarsophalangeal joints and ankles/midfeet. Age, the presence of tophus, bone erosion, and disease duration considerably affected the total urate score. No statistical difference in the positive detection of nail artifact, skin artifact, vascular calcification, and noise artifact was found between the case and control groups. Conclusion: DECT (Discovery CT750HD and Revolution CT) showed promising diagnostic accuracy for the detection of urate crystal deposition in gout but had limited diagnostic sensitivity for short-stage gout. Longer disease duration, the presence of tophus, and bone erosion were associated with the urate crystal score system. The artifacts do not remarkably affect the diagnostic performance of DECT in gout.
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This report describes a three-month-old Korean domestic kitten presented with dehydration and poor body condition.Physical examination revealed abdominal distension. Rectal diagnosis was unachievable due to the small rectum diameter. X-ray radiography and endoscopy confirmed presence of abdominal distension and indicated a stricture located 1.5 cm from the anus. A balloon was gently inserted into the rectum and inflated several times followed by triamcinolone injection. Four months later, same procedures were repeated. This report is the first to describe the use of balloon dilation of a rectal stricture followed by intralesional triamcinolone injection in a small cat with poor condition.
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Systemic inflammatory reaction – due to severe response to toxins of infection associated with immune inhibition – leads to multi-organ dysfunctions and high mortality. Ultraviolet (UV) blood is used for its therapeutic effects when moving across the cells. This study aims to evaluate the impact of UV-C Haematogenous Oxidation Therapy (HOT) in Lipopolysaccharide (LPS)-induced endotoxemia of rabbit model. A total of 40 rabbits randomly divided into four groups, including normal control (NC). LPS and LPS+UV-C HOT groups received 0.1 mg/kg LPS toxin of E. coli, UV-C HOT and LPS+UV-C HOT groups subjected to UV-C HOT treatments once weekly for five times. Blood collected, perfused with oxygen, UV-C directly irradiated into blood, and then auto-transfused. Rabbits were sacrificed after five weeks; blood and serum were collected for analysis. The survival rate, liver, kidney, lipid profile, and blood ions were assessed in treated rabbits. Mortality was 40% in the LPS group, while other groups showed no death. UV-C HOT enhanced critical pH, base deficit, blood gases, hypomagnesemia, hyperlactatemia, and concurrent acidosis. Besides, TNF-α, nitrite, and nitrate were suppressed in response to UV-C HOT. Moreover, UV-C HOT reduced liver and kidney enzymes, improved lipid metabolism, and ameliorated electrolytes homeostasis. Despite that, UV-C HOT performance in ICU for human and animal endotoxemic or septic patients should be evaluated and considered.
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Objective To investigate the effects of the relationship between bone cement polymethyl methacrylate (PMMA) and endplate on the vertebral height loss after percutaneous vertebroplasty (PVP).Methods A retrospective analysis of 84 female patients with single segment osteoportic vertebral compression fracture who had undergone PVP between Jun.,2013 and May,2016 was conducted.According to the X-ray radiographs and CT scans,all subjects were divided into the doPMMA-endplate-contact group (40 cases,average age 76.88 years) and the non-PMMA-endplatecontact group (44 cases,average age 77.96 years).The volume of bone cement,operation time,fractured vertebral height restoration rate,3-month postoperative vertebral height loss rate,changes in local sagitta view Cobb angle and bone cement leakage rate were respectively recorded and compared.Results There were no significant difference in age,body mass index,the levels of serum calcium and phosphorus,bone mineral density and preoperative vertebral body compression rate between the two groups (P＞0.05).Postoperative vertebral height loss rate and changes in local sagitta view Cobb angle in the do-PMMA-endplate-contact group were significantly less than the non-PMMA-endplate-contact group (P＜0.05).However,there was no significant difference in bone cement leakage rate between the two groups (P＞0.05).Conclusions Making bone cement contact with endplate would reduce the height loss of cemented vertebrae without increasing the rate of cement leakage.
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This study investigated the development characteristics of Dermacentor everestianus under laboratory conditions. The time taken for D. everestianus to complete the whole life cycle was 110.2 days on average, and the average developmental durations of larvae and nymphs were 17.1 days and 29.5 days, respectively. The summation of the prefeeding, feeding, and preoviposition periods of females was 17.8 days, and the oviposition and egg incubation lasted for 18.1 days and 27.7 days, respectively. A highly positive correlation was observed between the weight of engorged female and the number of egg mass laid (r=0.947). The reproductive efficiency index and the reproductive fitness index were 7.1 and 6.1, respectively.
Subject(s)
Female , Humans , Dermacentor , Genetic Fitness , Larva , Life Cycle Stages , Nymph , Oviposition , OvumABSTRACT
Objective: To investigate the protective effects of Nigella sativa seed extract (NSSE) against acetaminophen (APAP)-induced hepatotoxicity in TIB-73 cells and rats. Methods: Toxicity in TIB-73 cells was induced with 10 μmol/L APAP and the protective effects of NSSE were evaluated at 25, 50, 75, 100 μg/mL. For in vivo examination, a total of 30 rats were equally divided into five experimental groups; normal control (vehicle), APAP (800 mg/kg body weight single IP injection) as a hepatotoxic control, and three APAP and NS pretreated (2 weeks) groups (APAP + NSSE 100 mg; APAP + NSSE 300 mg and APAP + NSSE 900 mg/kg). Results: TIB-73 cell viability was drastically decreased by (49.0 ± 1.9)% after the 10 μmol/LAPAP treatment, which also increased reactive oxygen species production. Co-treatment with NSSE at 25, 50, 75, and 100 μg/mL significantly improved cell viability and suppressed reactive oxygen species generation. In vivo, the APAP induced alterations in blood lactate levels, pH, anionic gap, and ion levels (HCO
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OBJECTIVE@#To investigate the protective effects of Nigella sativa seed extract (NSSE) against acetaminophen (APAP)-induced hepatotoxicity in TIB-73 cells and rats.@*METHODS@#Toxicity in TIB-73 cells was induced with 10 μmol/L APAP and the protective effects of NSSE were evaluated at 25, 50, 75, 100 μg/mL. For in vivo examination, a total of 30 rats were equally divided into five experimental groups; normal control (vehicle), APAP (800 mg/kg body weight single IP injection) as a hepatotoxic control, and three APAP and NS pretreated (2 weeks) groups (APAP + NSSE 100 mg; APAP + NSSE 300 mg and APAP + NSSE 900 mg/kg).@*RESULTS@#TIB-73 cell viability was drastically decreased by (49.0 ± 1.9)% after the 10 μmol/LAPAP treatment, which also increased reactive oxygen species production. Co-treatment with NSSE at 25, 50, 75, and 100 μg/mL significantly improved cell viability and suppressed reactive oxygen species generation. In vivo, the APAP induced alterations in blood lactate levels, pH, anionic gap, and ion levels (HCO3(-), Mg(2+) and K(+)), which tended to normalize with the NSSE pretreatment. The NSSE also significantly decreased elevated serum levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase induced by APAP, which correlated with decreased levels of hepatic lipid peroxidation (malondialdehyde), increased superoxide dismutase levels, and reduced glutathione concentrations. Improved hepatic histology was also found in the treatment groups other than APAP group.@*CONCLUSIONS@#The in vitro and in vivo findings of this study demonstrated that the NSSE has protective effects against APAP-induced hepatotoxicity and metabolic disturbances by improving antioxidant activities and suppressing both lipid peroxidation and ROS generation.
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Alcohol abuse and its medical and social consequences are a major health problem in many areas of the world. Korean red ginseng (KRG) has been traditionally used for the treatment of liver disease. This study was conducted to evaluate the hepatoprotective effects of KRG against hepatotoxicity in Sprague-Dawley rats treated with ethanol (EtOH). Administration of EtOH for 20 days induced significant changes in serum biochemical parameters (aspartate aminotransferase, alanine transaminase, and glucose) accompanied by histological changes in the liver tissue. Treatment with KRG prior to administration of EtOH inhibited the EtOH-induced biochemical and histological changes of the liver. In perfused rat livers, administration of EtOH caused an increase in lactate dehydrogenase (LDH) release into the perfusate and activated the pro-apoptotic Bax protein but inhibited the anti-apoptotic Bcl-2 protein. Pretreatment with KRG prior to administration of EtOH decreased the EtOH-induced LDH release and inhibition of Bcl-2 protein. These results suggest that KRG exerts anti-apoptotic effects and alleviated EtOH-induced liver injury in rats.
Subject(s)
Animals , Rats , Alanine Transaminase , Alcoholism , bcl-2-Associated X Protein , Ethanol , L-Lactate Dehydrogenase , Liver , Liver Diseases , Panax , Rats, Sprague-DawleyABSTRACT
A change in pH can alter the intracellular concentration of electrolytes such as intracellular Ca2+ and Na+ ([Na+]i) that are important for the cardiac function. For the determination of the role of pH in the cardiac magnesium homeostasis, the intracellular Mg2+ concentration ([Mg2+]i), membrane potential and contraction in the papillary muscle of guinea pigs using ion-selective electrodes changing extracellular pH ([pH]o) or intracellular pH ([pH]i) were measured in this study. A high CO2-induced low [pH]o causes a significant increase in the [Mg2+]i and [Na+]i, which was accompanied by a decrease in the membrane potential and twitch force. The high [pH]o had the opposite effect. These effects were reversible in both the beating and quiescent muscles. The low [pH]o-induced increase in [Mg2+]i occurred in the absence of [Mg2+]o. The [Mg2+]i was increased by the low [pH]i induced by propionate. The [Mg2+]i was increased by the low [pH]i induced by NH4Cl-prepulse and decreased by the recovery of [pH]i induced by the removal of NH4Cl. These results suggest that the pH can modulate [Mg2+]i with a reverse relationship in heart, probably by affecting the intracellular Mg2+ homeostasis, but not by Mg2+ transport across the sarcolemma.
Subject(s)
Animals , Female , Male , Cations, Divalent , Guinea Pigs , Heart Ventricles/metabolism , Hydrogen-Ion Concentration , Ion Transport/physiology , Ion-Selective Electrodes/veterinary , Magnesium/metabolism , Membrane Potentials/physiology , Papillary Muscles/metabolism , Propionates/pharmacology , Sodium/metabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of cilazapril on endothelial cell function and fibrinolysis system in the canine atrial fibrillation (AF) models.</p><p><b>METHODS</b>All canines were divided into three groups: (1) Control group, without atrial pacing; (2) Atrial pacing group, in which atrial fibrillation was established by rapid atrial pacing at 400 bpm for 6 weeks; (3) Atrial pacing together with cilazapril group, in which cilazapril was given before and after atrial pacing. Nitric oxide (NO) of atrial endocardium was measured with NO-specific microelectrode. The expression of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (tPA) protein in atrium was determined by Western Blot analysis and immunohistochemical staining. Plasma levels of von Willebrand Factor (vWF), PAI-1 and tPA were analyzed by enzyme-linked immunoadsorbent assay.</p><p><b>RESULTS</b>NO production from atrial endocardium was significantly increased in atrial pacing together with cilazapril group than atrial pacing group [(42.6 +/- 9.9) nmol/L vs (23.4 +/- 5.8) nmol/L, P < 0.05], whereas the plasma levels of vWF were decreased [(75.4 +/- 12.8)% vs (125.9 +/- 20.6)%, P < 0.05]. Compared to controls, the expression of atrium tPA protein in atrial pacing together with cilazapril group was significantly upregulated (4052 +/- 857 vs 1936 +/- 421, P < 0.05) and PAI-1 protein was downregulated (2487 +/- 542 vs 3164 +/- 827, P < 0.05). Cilazapril also significantly increased tPA antigen and decreased PAI-1 antigen in plasma.</p><p><b>CONCLUSION</b>Cilazapril can favorably improve endothelial function and resume the balance of fibrinolysis system in AF, which might be of beneficial to hypercoagulated state in AF.</p>