Emerging microfluidics for the modeling and treatment of arthritis

Microfluidic is a technology that allows the precise control of fluid in a micro-channel.With its advantages of high throughput and low cost,microfluidic technology has achieved good performance in various fields in recent years.Arthritis is a general term for a variety of joint diseases,which can be clinically manifested as joint pain and swelling,seriously affecting people’s physical and mental health.At present,the causes of arthritis disease are still unknown,and existing disease models and treatment methods are still limited,so more treatments need to be developed.Microfluidic organ chip is a cutting-edge technology to build a bionic human organ model,which can reflect the structure and function characteristics of human organs by simulating the physiological environment of tissues and cells in vitro.This paper reviews the application of microfluidic technology in the modeling and treatment of arthritis,hoping to open up a new vision for the study of arthritis.

CD4^(+)CD25^(+)but not CD4^(+)Foxp3^(+) T cells as a regulatory subset in primary biliary cirrhosis

Increasing evidence indicates a role for regulatory T cells(Tregs)in the immune response and in autoimmune diseases,but the role of Tregs and cytokines in autoimmune hepatic diseases remains largely unclear and controversial,especially in patients with primary biliary cirrhosis(PBC).This study was undertaken to investigate Tregs and different cytokines in the liver and peripheral blood of PBC patients.We found that these patients demonstrated a reduction of CD4^(+)CD25^(+) T cells but elevated CD4^(+)Foxp3^(+) T cells in peripheral blood mononuclear cells(PBMCs)and CD41 T cells.The percentage of CD4^(+)CD25^(+) T cells in PBMCs was negatively correlated with elevated plasma interferon(IFN)-c levels.A liver-specific analysis showed that the frequency of Foxp31 Tregs,transforming growth factor(TGF)-b1 and IFN-c were increased in PBC patients.Our findings suggest that an imbalance between CD4^(+)CD25^(+) Tregs and cytotoxic cytokines plays a crucial role in the pathogenesis of PBC while the role of Foxp3 needs further investigation.

A Pilot Study of the Therapeutic Efficacy and Mechanism of Artesunate in the MRL/lpr Murine Model of Systemic Lupus Erythematosus

Recent evidence indicates that artesunate has immunomodulatory properties that might be useful for treating autoimmune disease.In this study,we conducted a pilot study and explored the effect and mechanism of artesunate on the treatment of systemic lupus erythematosus using an MRL/lpr murine model.MRL/lpr mice were divided into control,cyclophosphamide(CTX)and artesunate treatment groups.Blood was collected to measure serum levels of creatinine,antinuclear antibody(ANA)and anti-double-stranded DNA(anti-dsDNA)antibody.Twenty-four-hour urine was collected to measure levels of proteinuria.The concentration of monocyte chemotactic protein-1(MCP-1)in serum and urine was measured.The expression of MCP-1 in kidney was detected by Western blot and immunohistochemistry assay,respectively.The expression of B cell activating factor(BAFF)in spleen was determined by real time-PCR and immunoblotting.We found that artesunate significantly increased the survival rate,body weight and blood leukocyte counts,and reduced the serum levels of ANA and anti-dsDNA antibody titer,24 h urinary protein,and serum creatinine.Our results indicated that artesunate could decrease MCP-1,major pro-inflammation cytokine,in serum,urine and kidney.We also found that the level of BAFF,the major B cell activation factor,was decreased in artesunate treated MRL/lpr mice.Its efficacy was comparable with that of CTX in this study.Taken together,we have demonstrated that artesunate can inhibit the progression of disease and reverse the pathologic lesion of lupus nephritis.

Hyaluronic acid-based dual-responsive nanomicelles mediated mutually synergistic photothermal and molecular targeting therapies

Precise clinical treatment of triple-negative breast cancer(TNBC)is an obstacle in clinic.Nanotechnology-assisted photothermal therapy(PTT)is a superior treatment modality for TNBC in terms of precision.However,thermoresistance arising from PTT and insufficient drug release from nanocarriers decrease the efficacy of PTT.AT13387 is a novel HSP90 inhibitor that can weaken thermoresistance and undergoing clinic II phase study,showing satisfactory antitumour activity through molecularly targeted therapy(MTT).Whereas,it has poor solubility.Hence hyaluronic acid and stearic acid were connected by hydrazone bonds and disulfide bonds,forming an amphipathic copolymer that could self-assembled into nanomicelles,followed by encapsulating Cypate and AT13387.These nanomicelles exhibited great features,including achieving mutually synergistic PTT/MTT for overcoming thermoresistance and promoting translocation of drugs,increasing the solubility of Cypate and AT13387,showing a pH/redox dual response that contributes to drug release,and having the ability of active targeting.Thus,the nanomicelles developed in this study may be a promising strategy for the precise treatment of TNBC.

Polydopamine functionalized mesoporous silica as ROS-sensitive drug delivery vehicles for periodontitis treatment by modulating macrophage polarization

Periodontitis is recognized as the major cause of tooth loss in adults, posing an adverse impact on systemic health. In periodontitis, excessive production of reactive oxygen species (ROS) at the inflamed site culminates in periodontal destruction. In this study, a novel ROS-responsive drug delivery system based on polydopamine (PDA) functionalized mesoporous silica nanoparticles was developed for delivering minocycline hydrochloride (MH) to treat periodontitis. The outer PDA layer and the inner MH of the nanoparticles acted as ROS scavengers and anti-inflammatory agents, respectively. Under the synergistic action of PDA and MH, macrophages were polarized from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. The in vitro experiments provided convincing evidence that PDA could scavenge ROS effectively, and the expression of pro-inflammatory cytokines was attenuated and the secretion of anti-inflammatory cytokines was enhanced through M1 to M2 polarization of macrophages with the cooperation of MH. In addition, the results obtained from the periodontitis rat models demonstrated that the synergetic effect of PDA and MH prevented alveolar bone loss without causing any adverse effect. Taken together, the results from the present investigation provide a new strategy to remodel the inflammatory microenvironment by inducing the polarization of macrophages from M1 toward M2 state for the treatment of periodontitis.