Baimai Ointment relieves chronic pain induced by chronic compression of dorsal root ganglion in rats by regulating neuroactive ligand-receptor interaction and HIF-1 signaling pathway / 中国中药杂志

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.

Hollow-structured nanoparticles as an anticancer drug carrier / 中国药理学与毒理学杂志

Many drug candidates identified from natural products are poorly water-soluble. The surfactants used to disperse the hydrophobic anticancer drugs in water may cause a serious of acute hypersensitivity reactions. Nanotech?nology provides an alternative strategy for delivery of anticancer drugs. Drugs can be encapsulated or attached to the nanomaterials such as lipids, polymers and solid-core nanoparticles. In the present study, porous inorganic nanoparti?cles have been utilized for delivery of water-insoluble anticancer drugs. The synthesized nanoparticles were functional?ized with different organic polymers. The porous nanoparticles were readily internalized by human glioblastoma U-87 MG cells, and didn't display cytotoxicity. The internalized nanoparticles were mainly localized in endosomes/lysosomes in cells. With the hydrophobic curcumin and carfilzomib as model drugs, intracellular delivery of hydrophobic anticancer drugs by the porous inorganic nanoparticles was studied. The porous nanoparticle-based encapsulation of hydrophobic drug provides the aqueous dispersion of the drugs. In endosomes/lysosomes mimicking buffers with a pH of 4.5-5.5, pH-dependent drug release was observed from drug loaded nanoparticles. The intracellular drug content and cytotoxicity were significantly higher for drug loaded nanoparticles than free drug. These results suggested porous inorganic nanoparticles might be a promising intracellular carrier for hydrophobic anticancer drugs.

Discussion on the effect pathways of preventing and treating coronavirus disease 2019 by acupuncture and moxibustion from the regulation of immune inflammatory response / 中国针灸

The effect of acupuncture-moxibustion on respiratory system and systemic immune inflammatory response were reviewed to explore the possible role of neuroimmunomodulation in the control of inflammatory response and the effect mechanism of cholinergic anti-inflammatory pathway on coronavirus disease 2019 (COVID-19). Acupuncture-moxibustion could produce the local and systemic anti-inflammatory effect on COVID-19 through the activation of cholinergic anti-inflammatory pathway. Compared with humoral anti-inflammatory pathway, the neuronal anti-inflammatory pathway has earlier initiation, rapider action, and more localization, which play a more important role in the initial stage of inflammatory response. This may be an important basis for acupuncture-moxibustion intervention in the early stage of COVID-19. In addition to cholinergic anti-inflammatory pathway, acupuncture-moxibustion may also play an anti-inflammatory role in activating sympathetic nerve, hypothalamic-pituitary-adrenal axis and other neural anti-inflammatory pathways. How acupuncture-moxibustion play its role in stimulating the vagus nerve and sympathetic nerve in different periods of inflammatory response, and whether the effect is based on the selection of acupoints and the methods of stimulation, will be the research direction of the transformation from basic research to clinical research for acupuncture-moxibustion.

Brucine inhibits bone metastasis of breast cancer cells by suppressing Jagged1/Notch1 signaling pathways / 中国结合医学杂志

<p><b>OBJECTIVE</b>To examine the effects of brucine on the invasion, migration and bone resorption of receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis.</p><p><b>METHODS</b>The osteoclastogenesis model was builded by co-culturing human breast tumor MDA-MB-231 and mouse RAW264.7 macrophages cells. RANKL (50 ng/mL) and macrophage-colony stimulating factor (50 ng/mL) were added to this system, followed by treatment with brucine (0.02, 0.04 and 0.08 mmol/L), or 10 μmol/L zoledronic acid as positive control. The migration and bone resorption were measured by transwell assay and in vitro bone resorption assay. The protein expressions of Jagged1 and Notch1 were investigated by Western blot. The expressions of transforming growth factor-β1 (TGF-β1), nuclear factor-kappa B (NF-κB) and Hes1 were determined by enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>Compared with the model group, brucine led to a dose-dependent decrease on migration of MDA-MB-231 cells, inhibited RANKL-induced osteoclastogenesis and bone resorption of RAW264.7 cells (P<0.01). Furthermore, brucine decreased the protein levels of Jagged1 and Notch1 in MDA-MB-231 cells and RAW264.7 cells co-cultured system as well as the expressions of TGF-β1, NF-κB and Hes1 (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>Brucine may inhibit osteoclastogenesis by suppressing Jagged1/Notch1 signaling pathways.</p>

Advances in methods and toxic mechanisms of rotenone-induced Parkinson disease models / 中国药理学与毒理学杂志

It is important to establish animal models of Parkinson disease (PD) similar to clinical features of human disease. Rotenone can readily penetrate the blood-brain-barrier and cytomem-branes due to its strong lipophilic ability. Rotenone models of PD can not only simulate behavioral changes in patients with PD, but also bear a strong resemblance to the human disease characteristics and pathological process of PD. Based on to researches at home and abroad in recent years, this paper summarizes and analyzes the modeling methods and toxic mechanisms of rotenone-induced PD. These methods include stereotaxis, intravenous injection, abdominal injection, subcutaneous injection, microdialysis drug, intragastric administration, subcutaneous embedded slow-release microspheres and exposure to drugs. The In vitro model invotves SH-SY5Y cells, PC12 cells and DA neurons. The toxic mechanisms involveα-synuclein abnormal aggregation, mitochondrial dysfunction, the generation of reactive oxygen species, damage to the antioxidant defense system, nerve cell apoptosis, and autophagy.

Evaluation of spatial and temporal relationship between left ventricular volume and longitudinal strain in healthy subjects by 2D speckle-tracking echocardiography / 中华超声影像学杂志

Objective To evaluate the coupling relationship between segmental longitudinal strain and left ventricular volume at different phases of the cardiac cycle by two dimensional speckle tracking imaging. Methods 2D grey scale images of 41 healthy adults were acquired,and time curve of left ventricular volume (LVV),segmental longitudinal strain(LS)and segmental longitudinal strain rate(LSr)were outputed by analysis software.The correlations between LVV and LS or LSr in isovolumic relaxation time(IVRT),the rapid filling time(RFT),the atrial filling time(AFT)and the ejection time(ET)were analyzed respectively. Results ①IVRT:LS in basal segment,middle segment,apical segment of interventricular septum,in apical segment,basal segment of the lateral wall,and in middle segment of inferior wall were low-moderate negatively correlated with LVV;only LSr in middle segment of anterior wall was negatively correlated with LVV(P<0.05).② RFT:LS in middle segment,apical segment of interventricular septum,in apical segment of the lateral wall were negatively correlated with LVV;LSr in basal segment,middle segment, apical segment of interventricular septum,in apical segment,middle segment,basal segment of lateral wall, in middle segment,basal segment of inferior wall were low-moderate negatively correlated with LVV(P <0.05).③AFT:LS in basal segment of inferior wall,in apical segment,basal segment of the anterior wall were low negatively correlated wtih LVV(P <0.05).④ET:LS in basal segment,middle segment,apical segment of interventricular septum,in apical segment,basal segment of the lateral wall were low negatively correlated with LVV(P <0.05);only LSr in apical segment of lateral wall was negatively correlated with LVV(P<0.05).Conclusions LS or LSr in special segments of interventricular septum,lateral wall, anterior wall and posterior wall are actively participate in the volume change of the left ventricle in healthy adults,specific myocardial segments of left ventricular wall are involved in left ventricular volume changes.

Effect of traditional Chinese medicines with different properties on thermoregulation and temperature-sensitive transient receptor potentialion channel protein of rats with yeast-induced fever / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the intervention effects of four traditional Chinese medicines (TCMs) with typical cold or hot property on body temperature and temperature-sensitive transient receptor potential ion channel proteins (TRPs) of rats with yeast-induced fever.</p><p><b>METHOD</b>The pyrexia model was induced by injecting yeast suspension subcutaneously. Totally 108 male SD rats were randomly divided into the normal group, the model group, the Rhei Radix et Rhizoma treated group, the Coptidis Rhizoma treated group, the Euodiae Fructus treated group, and the Alpiniae Officinarum Rhizoma treated group, with 18 rats in each group. At the 4 h, 8 h and 12 h after injection of yeast, the rats were sacrificed to collect their hypothalamus and dorsal root ganglion. The expressions of TRPV1 and TRPM8 were detected by immunohistochemistry and Western blot method.</p><p><b>RESULT</b>Compared with the normal group, after injection of yeast, the temperature of rats in the model group notably increased, and reached the peak at 8 h (P < 0.01). The TRPV1 level in hypothalamus and dorsal root ganglia (DRG) of the model group significantly increased, whereas the TRPM8 level significantly reduced. Compared with the model group, the Rhei Radix et Rhizoma group and the Coptidis Rhizoma group showed significant decrease in the high body temperature of rats caused by yeast, down-regulation in the expression of TRPV1, and up-regulation in the expression of TRPM8 (P < 0.05 or P < 0.01). Euodiae Fructus and Alpiniae Officinarum Rhizoma had no significant effect on either temperature or TRPs of fever rats.</p><p><b>CONCLUSION</b>Rhei Radix et Rhizoma and Coptidis Rhizoma, both are TCMs with cold property, can reduce the temperature of fever rats induced by yeast, which may be related to their effective regulation of TRPV1 and TRPM8 in hypothalamus and DRG, while Euodiae Fructus and Alpiniae Officinarum Rhizoma had no relevant effect.</p>

Veiled Paraquat Poisoning: A Focus on Clinical Characteristics

PURPOSE: Most paraquat poisonings are easily diagnosed by history taking on physical examination, however, some are failed to be diagnosed initially if the poisoning was veiled. The purpose of this study was to explore the clinical characteristics of veiled paraquat poisoning. METHODS: We retrospectively reviewed the medical records of patients whose discharge diagnosis was paraquat poisoning in one university teaching hospital between 1 Jan, 2001 and 31 Dec, 2010. Veiled paraquat poisoning was determined when there was a positive urine paraquat kit in patients who did not mention paraquat poisoning in an initial physical examination or had unknown cause of pulmonary fibrosis, acute renal failure, or multi-organ failure. RESULTS: Of the 117 patients with paraquat poisoning during the study period, 6 patients (5.1%) had veiled paraquat poisoning. The clinical characteristics were 1) proteinuria - 6 (100%), 2) increased creatinine - 4 (66.7%), 3) green skin stains - 2 (33.3%), 4) mucosal ulcer - 3 (50%). Blood chemistry results were variable. CONCLUSION: We should suspect veiled paraquat poisoning for patients who have proteinuria, increased creatinine, green skin stain, mucosal ulcer and vomiting, or if they have rapidly progressing acute renal failure or multi-organ failure with unknown cause, even if patients didn't mention about paraquat poisoning upon the initial physical examination. In cases with the above clinical conditions, a thorough repeated physical examination including history taking and use of urine paraquat kits should be performed.

Digitalis-like Toxic Symptoms Occurring after Accidental Nerium indicum Poisoning

Although Nerium indicum poisoning is a globally rare occurrence, Nerium oleander poisoning is known to occur frequently in the Mediterranean regions. To our knowledge, this is the first reported case of accidental Nerium indicum poisoning in Korea. Its poisoning symptoms and signs are similar to that of digitalis poisoning, because of the presence of cardiac glycosides in Nerium indicum. A 16-year-old boy was admitted to the emergency department four hours prior to the accidental ingestion of Nerium indicum petals. The patient complained of nausea, vomiting, and dizziness. His initial vital signs were stable; laboratory blood test results were within normal levels, except for the blood digoxin level (1.5 ng/dL). An electrocardiogram (ECG) analysis showed normal sinus rhythm, progressive PR prolongation and second-degree Morbiz type I AV block. Conservative treatments including activated charcoal administration were conducted, because toxic symptoms and signs were not severe. The patient was admitted to the intensive care unit for close observation. His ECG was converted to normal rhythm after 1 day and the toxic symptoms and signs were completely resolved after 4 days.