The inflammatory microenvironment is closely associated with the initiation and progression of osteoarthritis （OA）， specifically manifesting as macrophage activation， dysregulation of inflammatory cytokines， and redox imbalance. Following an overview of the pathological characteristics of the OA inflammatory microenvironment， this paper reviews the research progress on the mechanism of traditional Chinese medicine （TCM） intervening in OA by modulating the inflammatory microenvironment. It has been found that TCM monomers/active ingredients （such as total alkaloids from Strychnos nux-vomica ， quercetin， triptolide， etc.）， herb pairs （e.g. Angelica pubescens - Gentiana macrophylla ， Carthami Flos-Lycopodii Herba）， and TCM formulas （such as Zhuanggu jianxi formula， Duhuo jisheng decoction and Rongjin niantong formula， etc.） can inhibit macrophage activation， reduce the release of proinflammatory cytokines and the generation of reactive oxygen species by inhibiting multiple signaling pathways， including nuclear factor-κB， Wnt/ β -catenin， and mitogen-activated protein kinase， thereby alleviating the articular inflammatory microenvironment， restoring local joint homeostasis， and slowing the progression of OA.

ObjectiveTo explore the protective effect of glucocorticoid-induced transcription factor 1 （GLCCI1） on cognitive dysfunction in diabetic mice and its mechanism. MethodsTwenty-four C57BL/6J mice were randomly divided into 4 groups， namely Control， DM， DM+AAV-Glcci1， and DM+AAV-NC. The Control group was intraperitoneally injected with saline， while the other groups were all injected with streptozotocin （STZ）. Two weeks after successful modeling， the DM+AAV-Glcci1 group was brain stereotactic injected with Glcci1 overexpressing adeno-associated virus， and the DM+AAV-NC group was stereoscopically injected with the control virus. After 12 weeks， the Morris water maze test was used to evaluate the learning and memory abilities of mice in each group. Subsequently， the localized expression of GLCCI1 in the hippocampus were determined by immunofluorescence and immunohistochemistry experiments. The myelin morphology in the hippocampus was observed by LFB staining， the neuronal morphology was observed by Nissl staining， and the myelin-related proteins MBP and CNPase were stained by immunohistochemistry. Molecular docking was used to predict the interaction between GLCCI1 and HSPA5. The expression of endoplasmic reticulum stress-related proteins was detected by Western blot. ResultsThe results of the behavioral experiment showed that compared with the mice in the Control group， DM mice exhibited obvious cognitive dysfunction behaviors （P＜0.000 1）， and the learning and memory abilities of mice improved after overexpression of Glcci1 （P=0.000 7）. The results of immunofluorescence and immunohistochemistry showed that GLCCI1 was expressed in hippocampal neuron cells. Compared with Control mice， the expression level of GLCCI1 in DM mice was significantly downregulated （P＜0.000 1）. The molecular docking results revealed that GLCCI1 interacts with HSPA5. The Western blot results indicated that， compared with the Control group， the expression levels of endoplasmic reticulum stress-related proteins HSPA5 （P＜0.000 1）， ATF4 （P＜0.000 1）， ATF6 （P=0.001 1）， and p-ELF2α/elF2α （P=0.000 1） in the DM group were significantly increased； Compared with the DM group， the expression of the corresponding protein HSPA5 （P＜0.000 1）， ATF4 （P＜0.000 1）， ATF6 （P=0.000 2）， and p-ELF2α/elF2α （P=0.000 1） was significantly down-regulated after overexpression of Glcci1. LFB staining showed that compared with the Control group， the myelin integrity of DM mice decreased significantly （P=0.010 3）， the expressions of myelin-related proteins MBP and CNPase decreased significantly （P=0.000 4， P=0.000 2）， and Nissl staining observed disordered neuronal arrangement. Compared with the mice in the DM group， the myelin integrity in the hippocampal region significantly increased after overexpression of Glcci1 （P=0.000 3）， the expressions of myelin-related proteins MBP and CNPase significantly increased （P=0.001 4， P=0.000 1）， and the ordered arrangement of neurons was observed by Nissl staining. ConclusionThe down-regulation of GLCCI1 expression in hippocampal neurons promotes demyelination of hippocampal neurons and thereby induces diabetic cognitive dysfunction. The specific mechanism may be related to endoplasmic reticulum stress.

Glioma, the most prevalent primary tumor of the central nervous system (CNS), is also the most lethal primary malignant tumor. Currently, there are limited chemotherapeutics available for glioma treatment, necessitating further research to identify and develop new chemotherapeutic agents. A significant approach to discovering anti-glioma drugs involves isolating antitumor active ingredients from natural products (NPs) and optimizing their structures. Additionally, targeted drug delivery systems (TDDSs) are employed to enhance drug solubility and stability and overcome the blood-brain barrier (BBB). TDDSs can penetrate deep into the brain, increase drug concentration and retention time in the CNS, and improve the targeting efficiency of NPs, thereby reducing adverse effects and enhancing anti-glioma efficacy. This paper reviews the research progress of anti-glioma activities of NPs, including alkaloids, polyphenols, flavonoids, terpenoids, saponins, quinones, and their synthetic derivatives over the past decade. The review also summarizes anti-glioma mechanisms, such as suppression of related protein expression, regulation of reactive oxygen species (ROS) levels, control of apoptosis signaling pathways, reduction of matrix metalloproteinases (MMPs) expression, blocking of vascular endothelial growth factor (VEGF), and reversal of immunosuppression. Furthermore, the functions and advantages of NP-based TDDSs in anti-glioma therapy are examined. The key information presented in this review will be valuable for the research and development of NP-based anti-glioma drugs and related TDDSs.
Humans ; Glioma/metabolism* ; Biological Products/therapeutic use* ; Animals ; Brain Neoplasms/genetics* ; Drug Delivery Systems ; Antineoplastic Agents/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Apoptosis/drug effects*

Objective:The envelope protein Domain I(DI) of type II mutated dengue virus from a DHF patient (B-E) was expressed,refolded and purified.Its immunogenicity was also identified.Methods:The 1-476 bp of B-E was cloned into pET28a(+),and it was transformed into E.coli after digestion and sequencing.The inclusion body was denatured and refolded after inducing with IPTG.Polyclone antibody was obtained by immunizing C57BL/6 and BALB/c mice with purified B-E,and identified with Western blot and ELISA.Results:The cDNA of B-E gene was inserted into pET28a(+) vector and transformed into Rosetta(DE3).The protein of B-E was mainly in inclusion body and the molecular weight was 20 kD as predicted.Western blot was used to identify the recommend protein with anti-his antibody.The soluble recombination protein was purified after denaturation and refolding.The polyclonal antibody was obtained by immunizing BALB/c and C57BL/6 mice and could be used in Western blot and ELISA assay.The titer of polyclonal antibody from C57BL/6 was 1:12 800 through ELISA assay,and titer of polyclonal antibody from BALB/c was 1:500 through Western blot.Conclusion:All the results suggests that B-E is immunogenic in BALB/c and C57BL/6 mice.