Objective To study the therapeutic effect liangxuehuoxue traditional Chinese medicines on the supression of ECV304 by serum pharmacological method,and to explore the interventional target for treatment of neovessels related eye diseases.Methods ECV304cells were cultured with medicated serum with different concentrations of liangxuehuoxue medicines.The proliferation rate of endothelial cells was assayed with MTT methods,the level of VEGF was tested.Result Medicated serum with liangxuehuoxue medicines at concentration of 20% could inhibit the proliferation of ECV304 cells and the expression of VEGF.Conclusion Liangxuehuoxue traditional Chinese medicines cna inhibit the ECV304 cells proliferation and the expression of VEGF,and this may be related to inhibition of neo vessels.
Age-related macular degeneration (AMD) is a multifactorial disease of unclear etiology. We previously proposed that metabolic adaptations in photoreceptors (PRs) play a role in disease progression. We mimicked these metabolic adaptations in mouse PRs through deletion of the tuberous sclerosis complex (TSC) protein TSC1. Here, we confirm our previous findings by deletion of the other complex protein, namely TSC2, in rod photoreceptors. Similar to deletion of Tsc1, mice with deletion of Tsc2 in rods develop AMD-like pathologies, including accumulation of apolipoproteins, migration of microglia, geographic atrophy, and neovascular pathologies. Subtle differences between the two mouse models, such as a significant increase in microglia activation with loss of Tsc2, were seen as well. To investigate the role of altered glucose metabolism in disease pathogenesis, we generated mice with simulation deletions of Tsc2 and hexokinase-2 (Hk2) in rods. Although retinal lactate levels returned to normal in mice with Tsc2-Hk2 deletion, AMD-like pathologies still developed. The data suggest that the metabolic adaptations in PRs that cause AMD-like pathologies are independent of HK2-mediated aerobic glycolysis.
Objective:To study the antagonistic effect of gypenoside(GP) on diaphragm against adriamycin cytotoxicity in rabbits.Methods:The toxicant effect on diaphragm of doxorubicin and the antagonistic effect of GP were examined by measurements of diaphragm evoked potential(DEP) and the transdiaphragmatical pressure(Pdi) and observation of the ultrastructure of diaphragm.All data were evaluated by q test.Results:(1)The amplitude of DEP and the Pdi were markly decreased in rabbits treated with doxorubicin( P 0.01 and P 0.05) ;(2)The disorder of myofibrills and swelling of mitochondria with broken cristae were observed in doxorubicin group;(3)The above mentioned changes were inhibited by gypenoside.Conclusions:The results showed that the gypenoside could antagonize the toxic effect of doxorubicin and protect the diaphragm myocytes. [
Leber congenital amaurosis (LCA) is one of the most severe forms of inherited retinal degeneration and can be caused by mutations in at least 15 different genes. To clarify the proteomic differences in LCA eyes, a cohort of retinal degeneration 12 (rd12) mice, an LCA2 model caused by a mutation in the RPE65 gene, were injected subretinally with an AAV vector (scAAV5-smCBA-hRPE65) in one eye, while the contralateral eye served as a control. Proteomics were compared between untreated rd12 and normal control retinas on P14 and P21, and among treated and untreated rd12 retinas and control retinas on P42. Gene therapy in rd12 mice restored retinal function in treated eyes, which was demonstrated by electroretinography (ERG). Proteomic analysis successfully identified 39 proteins expressed differently among the 3 groups. The expression of 3 proteins involved in regulation of apoptosis and neuroptotection (alpha A crystallin, heat shock protein 70 and peroxiredoxin 6) were investigated further. Immunofluorescence, Western blot and real-time PCR confirmed the quantitative changes in their expression. Furthermore, cell culture studies suggested that peroxiredoxin 6 could act in an antioxidant role in rd12 mice. Our findings support the feasibility of gene therapy in LCA2 patients and support a role for alpha A crystallin, heat shock protein 70 and peroxiredoxin 6 in the pathogenetic mechanisms involved in LCA2 disease process.
Background: Aggressive behaviors are one of the most important negative behaviors that seriously endangers human health. Also, the central para-inflammation of microglia triggered by stress can affect neurological function, plasticity, and behavior. NLRP3 integrates stress-related signals and is a key driver of this neural para-inflammation. However, it is unclear whether the NLRP3 inflammasome is implicated in the development of aggressive behaviors. Methods: First, aggressive behavior model mice were established using the resident intruder paradigm. Then, aggressive behaviors were determined with open-field tests (OFT), elevated plus-maze (EPM), and aggressive behavior tests (AT). Moreover, the expression of P2X7R and NLRP3 inflammasome complexes were assessed by immunofluorescence and Western blot. The levels of NLRP3 and inflammatory cytokines were evaluated using enzyme-linked immunosorbent assay (ELISA) kits. Finally, nerve plasticity damage was observed by immunofluorescence, transmission electron microscope, and BrdU staining. Results: Overall, the resident intruder paradigm induced aggressive behaviors, activated the hippocampal P2X7R and NLRP3 inflammasome, and promoted the release of proinflammatory cytokines IL-1β in mice. Moreover, NLRP3 knockdown, administration of P2X7R antagonist (A804598), and IL-1β blocker (IL-1Ra) prevented NLRP3 inflammasome-driven inflammatory responses and ameliorated resident intruder paradigm-induced aggressive behaviors. Also, the resident intruder paradigm promoted the activation of mouse microglia, damaging synapses in the hippocampus, and suppressing hippocampal regeneration in mice. Besides, NLRP3 knockdown, administration of A804598, and IL-1Ra inhibited the activation of microglia, improved synaptic damage, and restored hippocampal regeneration. Conclusion: The NLRP3 inflammasome-driven inflammatory response contributed to resident intruder paradigm-induced aggressive behavior, which might be related to neuroplasticity. Therefore, the NLRP3 inflammasome can be a potential target to treat aggressive behavior-related mental illnesses.
Transdermal delivery is very important in pharmaceutics. However, the barrier function of the stratum corneum hinders drugs absorption. How to improve transdermal delivery efficiency is a hot topic. The key advantages of physical technologies are their wide application for the delivery of previously nonappropriate transdermal drugs, such as proteins, peptides, and hydrophilic drugs. Based on the improved permeation of drugs delivered via multiple physical techniques, many more diseases may be treated, and transdermal vaccinations become possible. However, their wider application depends on the related convenient and portable devices. Combined products comprising medicine and devices represent future commercial directions of artificial intelligence and 3D printing.
The treatment of thymoma or thymic carcinoma with pleural dissemination remains controversial due to the unpredictable natural history of this tumor. Our study discusses the combination of cytoreductive surgery with hyperthermic intrapleural chemotherapy to treat thymoma or thymic carcinoma with pleural dissemination.From February 2008 to January 2010, there were four patients with pleural thymoma metastases undergoing cytoreductive surgery and intrathoracic hyperthermic perfusion with chemotherapy at our department. After video-assisted thoracoscopic surgery, the hyperthermic perfusion system was set up for hyperthermic intrapleural chemotherapy. The thoracic cavity was perfused at a speed of approximately 1.8-2.3 L/min with 0.9% normal saline. The intrathoracic temperature remained between 42°C and 43°C. The perfusion process lasted for 2 hours.There were no perioperative deaths. During the hyperthermic perfusion, the patient's core temperature varied from 36.3°C and 39.3°C and pulse varied from 59 beats/min and 126 beats/min. Intraoperative sinus tachycardia occurred in two elderly patients. No hematologic toxicity and nephrotoxicity was observed within 1 week after surgery. Postoperative pneumonia occurred in one elderly patient. Patients were followed up for 1-4 years. One elderly patient died of heart failure 1 year after surgery. There were no patients with local recurrence or metastases to distant sites.Cytoreductive surgery and intrathoracic hyperthermic perfusion with chemotherapy may be effective in treating thymoma or thymic carcinoma with pleural dissemination and has an encouraging impact on the patients' long-term survival.
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