ABSTRACT
Sophorae Tonkinensis Radix et Rhizoma （STRER） is a commonly used Chinese medicine in clinical practice， which has the effects of clearing heat， removing the toxin， alleviating edema， and relieving sore throat. In recent years， the clinical reports of STRER-induced poisoning have gradually increased， with neurotoxicity and hepatotoxicity as the main characteristics of the acute attack. Timely treatment will lead to the good prognosis， but long-term or high-dose administration will cause irreversible damage. Therefore， the safety of clinical use of STRER should be highlighted. The chemical components in STRER mainly include alkaloids， flavonoids， triterpenoids， triterpenoid saponins， and polysaccharides， as well as small amounts of proteins， organic acids， and trace elements， where alkaloids both serve as the important material basis for the pharmacodynamic action and the main substances causing toxicity. The adverse events induced by STRER and its alkaloids include nerve injury, Hepatic injury, cardiovascular injury, kidney injury and reproductive injury， and gastrointestinal reaction. Quinolizidine alkaloids are the main toxic components， mainly including matrine， oxymatrine， cytisine， sophocarpine， oxysophocarpine， sophoridine， sophoramine， and lehmannine. Many studies have been carried out on the toxicity of different extracts and alkaloids of STRER in China and abroad， but there are no comprehensive and detailed reports on the toxicity mechanism of alkaloids in STRER. As a Chinese medicine， STRER is widely used. It's an urgent problem to clarify the material basis and mechanism of toxicity caused by STRER and reduce the toxicity for good clinical application. The present study reviewed the components of alkaloids， toxicity， and toxic mechanism of extracts and alkaloids in STRER to provide the basis for further development and clinical safe and effective application of STRER.
ABSTRACT
Stroke is the leading cause of death and major cause of diability in China, but with few effective therapies. As few as 3%-5% of ischemic stroke patients have access to drug treatment with tissue plasminogen activators, and no drug treatment is available to patients of hemorrhagic stroke. Stem cell therapy has been proposed as a potential regenerative strategy for stroke patients. In the future, stroke stem cell research can be combined with genetic editing, 3D and other emerging technologies or drug treatments, to promote the development of stroke stem cell regenerative medicine. Based on the guidelines for stem cell research of stroke, this review elaborates on the action mechanism and clinical reasearch of stem cells for the treatment of stroke, including neural stem cells (human neural precursor cell line NT2/D1 and human immortalized neural stem cell line CTX) and adult stem cells (bone marrow mononuclear cells, mesenchymal stem cells, and multipotent adult progenitor cells), while disclosing the limitations of stem cell therapy. In the future, stem cell research in stroke can be combined with gene editing technology and drug treatment to improve the safety and effectiveness of stem cell therapy in the hope of promoting the research of regenerative medicine for stroke.
ABSTRACT
Objective To investigate the protective effects of intravitreal injection of pigment epithelial-derived factor (PEDF) gene-modified human umbilical cord mesenchymal stem cells (PEDF-MSCs) on the pathological changes in retinal tissue of diabetic rats.Methods hUCMSCs were isolated from human umbilical cord tissue using tissue culture methods,and transfected with lentiviral vectors at a infection multiplicity of 50.Then diabetic model in rats was successfully induced by intraperitoneal injection of streptozotocin.And the rats were divided into normal control (N),PBS treatment (D1),hUCMSCs treatment (D2) and PEDF-MSC treatment (D3) group according to different treatment methods.Three months after modeling,treatment began in D1,D2 and D3 group,but N group left untreated.Two weeks after treatment,the expression of PEDF-MSCs in the eye of rats was detected by fluorescence microscopy,and HE staining was performed to observe the changes in retinal structure and the full-thickness of the retina in each group.Results The expression of CD105,CD73,CD90 was observed,while the expression of CD34,CD45,CD11b,CD19 and HLA-DR did not present.After 2 weeks of treatment,it was in the vitreous cavity not the retina that clusters of red fluorescence appeared in D2 group with fluorescence microscope.There were clusters of green fluorescence in the vitreous cavity not in the retina of D3 group.HE staining showed that the retina had intact structure and clear layers as well as neatly arranged and stained evenly cells in N group.In D1 group,the nerve fibers layer (NFL) showed obvious edema,the blood vessels were dilated,the inner plexiform layer (IPL) were loose and the inner nuclear layer (INL) cells were disordered.In D2 group,the edema of NFL relieved.In D3 group,NFL edema was significantly alleviated,and the cells of INL and outer nuclear layer (ONL) arranged in regular.Full-thickness of retina was (103.82 ±4.15) μm in N group,(138.86 ±4.71) μm in D1 group,(131.17 ±3.89) μm in D2 group,and (112.24 ±4.22) μm in D3 group,respectively,and the differences were statistically significant (all P ＜ 0.05).Conclusion PEDF-MSCs can survive and continue to express in the vitreous cavity of diabetic rats for a long time.Meanwhile,intravitreal injection of PEDF-MSCs can ameliorate retinal edema and the retinal injury in diabetic rats.