Chondroitin sulfate-mediated albumin corona nanoparticles for the treatment of breast cancer

Chondroitin sulfate-mediated albumin corona nanoparticles were readily prepared without any chemical reaction,and their active tumor targeting and therapeutic effects were examined.Negatively charged chondroitin sulfate(CS)and positively charged doxorubicin(DOX)self-assembled into nanoparticles(CS-DOX-NPs)via electrostatic interactions.Bovine serum albumin(BSA)was then adsorbed on the surface of CS-DOX-NPs to form albumin corona nanoparticles(BC-DOX-NPs)protected from endogenous proteins.Due to the dual effect of BSA and CS,BC-DOX-NPs interacted with the gp60,SPARC and CD44 receptors on tumor cells,facilitating their rapid and efficient transcytosis and improving their accumulation and uptake within tumor tissues.The simultaneous presence of BSA and CS also allowed BC-DOX-NPs to target CD44 efficiently,leading to greater cellular uptake and cytotoxicity against 4 T1 cells than CS-DOX-NPs or free DOX.Intravenous injection of BCDOX-NPs into orthotopic 4 T1 tumor-bearing mice led to greater drug accumulation at the tumor site than with CS-DOX-NPs or free DOX,resulting in significant inhibition of tumor growth and lower exposure of major organs to the drug.

Effects and mechanisms of acupuncture on women related health

Globally,public health interventions have resulted in a 30-year increase in women’s life expectancy.However,women’s health has not increased when socioeconomic status is ignored.Women’s health has become a major public health concern,for those women from developing countries are still struggling with infectious and labor-related diseases,and their counterparts in developed countries are suffering from physical and psychological disorders.In recent years,complementary and alternative medicine has attracted wide attentions with regards to maintaining women’s health.Acupuncture,a crucial component of traditional Chinese medicine,has been used to treat many obstetric and gynecological diseases for thousands of years due to its analgesic and anti-inflammatory effects and its effects on stimulating the sympathetic/parasympathetic nervous system.To fully understand the mechanism through which acupuncture exerts its effects in these diseases would significantly extend the list of available interventions and would allow for more reasonable advice to be given to general practitioners.Therefore,by searching PubMed and CNKI regarding the use of acupuncture in treating obstetric and gynecological diseases,we aimed to summarize the proven evidence of using acupuncture in maintaining women’s health by considering both its effectiveness and the underlying mechanisms behind its effects.

Targeted delivery of celastrol to glomerular endothelium and podocytes for chronic kidney disease treatment

The etiology of chronic kidney disease(CKD)is complex and diverse,which could be briefly categorized to glomerular-or tubularoriginated.However,the final outcomes of CKD are mainly glomerular sclerosis,endothelial dysfunction and injury,and chronic inflammation.Thus,targeted delivery of drugs to the glomeruli in order to ameliorate glomerular endothelial damage may help alleviate CKD and help enrich our knowledge.The herb tripterygium wilfordii shows therapeutic effect on kidney disease,and celastrol(CLT)is one of its active ingredients but with strong toxicity.Therefore,based on the unique structure and pathological characteristics of the glomerulus,we designed a targeted delivery system named peptides coupled CLT-phospholipid lipid nanoparticles(PC-PLNs)to efficiently deliver CLT to damaged endothelial cells and podocytes in the glomerulus for CKD treatment and research.PC-PLNs could effectively inhibit inflammation,reduce endothelial damage,alleviate CKD severity,and reduce the toxicity of CLT.We also studied the mechanism of CLT in the treatment of nephropathy and found that CLT can increase the level of NO by increasing eNOS while inhibiting the expression of VCAM-1,thus provides an anti-inflammatory effect.Therefore,our study not only offered an efficient CKD drug formulation for further development,but also provided new medical knowledge about CKD.

Albumin-based multidrug delivery system enriched in Golgi apparatus against metastatic breast cancer

Breast cancer and metastasis remain great challenges in clinical therapy.Compared with monotherapy,combination therapy,especially mediated by nanomedicine delivery strategy,significantly improves the therapeutic efficacy and reduces undesired toxicity.Cyclooxygenase-2(COX-2)inhibitors are widely used for adjuvant chemotherapy because COX-2 is overexpressed in virtually all cancer cell lines to regulate tumor progression by catalyzing prostaglandin E2(PGE2)synthesis.This drug combination strategy is still required to be improved due to some unsatisfactory clinical trial results.Intricate processes of tumor growth and metastasis are orchestrated by multiple proteins in addition to COX-2,which are modified and transported by Golgi apparatus.Hence,disrupting the structure and function of Golgi apparatus can inhibit the secretion of tumor-related proteins and further suppress carcinoma progression and metastasis.Since COX-2 is also enriched within Golgi apparatus in tumor cells,COX-2 inhibitors and Golgi disrupting agents can be co-delivered to Golgi apparatus to maximize the synergy.In this work,we developed a human serum albumin(HSA)nanoparticle encapsulating pirarubicin(THP),retinoic acid(RA),and indomethacin(IMC),called TIR-HSA,which was observed to be localized in Golgi complex of 4T1 cells.Owing to the synergistic effect of these three drugs,TIR-HSA inhibited the proliferation,migration,and invasion of tumor cells,enhanced the apoptotic rate,and improved the immunosuppressive tumor microenvironment,which remarkably regressed the tumor growth and metastasis and prolonged the survival period of 4T1-bearing mice.

NudCL2 is required for cytokinesis by stabilizing RCC2 with Hsp90 at the midbody

Cytokinesis is required for faithful division of cytoplasmic components and duplicated nuclei into two daughter cells.Midbody,a protein-dense organelle that forms at the intercellular bridge,is indispensable for success-ful cytokinesis.However,the regulatory mechanism of cytokinesis at the midbody still remains elusive.Here,we unveil a critical role for NudC-like protein 2(NudCL2),a co-chaperone of heat shock protein 90(Hsp90),in cytokinesis regulation by stabilizing regulator of chromosome condensation 2(RCC2)at the midbody in mam-malian cells.NudCL2 localizes at the midbody,and its downregulation results in cytokinesis failure,multinu-cleation,and midbody disorganization.Using iTRAQ-based quantitative proteomic analysis,we find that RCC2 levels are decreased in NudCL2 knockout(KO)cells.Moreover,Hsp90 forms a complex with NudCL2 to stabilize RCC2,which is essential for cytokinesis.RCC2 depletion mirrors phenotypes observed in NudCL2-downregulated cells.Importantly,ectopic expression of RCC2 rescues the cytokinesis defects induced by NudCL2 deletion,but not vice versa.Together,our data reveal the significance of the NudCL2/Hsp90/RCC2 pathway in cytokinesis at the midbody.