Gut microbial metabolite targets HDAC3-FOXK1-interferon axis in fibroblast-like synoviocytes to ameliorate rheumatoid arthritis

Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that genetics also shape the gut microbiota.It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to CIA.Here,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched B.fragilis than DBA/1J mice and RA patients.Transplantation of B.fragilis prevents CIA in DBA/1J mice.We identify that B.fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate.Fibroblast-like synoviocytes(FLSs)in RA are activated to undergo tumor-like transformation.Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of RA-FLSs.We treat CIA mice with propionate and show that propionate attenuates CIA.Moreover,a combination of propionate with anti-TNF etanercept synergistically relieves CIA.These results suggest that B.fragilis or propionate could be an alternative or complementary approach to the current therapies.

Diagnosis and Management of Knee Osteoarthritis：Chinese Medicine Expert Consensus(2015)

Literature review shows that Chinese medicine and other related treatment are still the main stream treatment of knee osteoarthritis.Currently,there is short of handbook guiding Chinese medicine from evidence-based medical evidence,so it is a top priority to develop a clinical guideline from the expert consensus.After several rounds of discussion during the conference and examination by letter,which has collected opinions from nearly one hundred experts,consensus was reached.Nonpharmacologic interventions include health education,medical exercise,acupuncture,massage,acupotomology,and physiotherapy.Pharmacological interventions are as follows.Topical application includes fumigation,application,hot compressed,ironing and iontophoresis with Chinese herbs,etc.Chinese patent medicine for external use includes plaster,ointment,etc.Western medicine for external use mainly includes emulsion,ointment,plaster and embrocation containing nonsteroidal anti-inflammatory drugs（NSAIDs）.Intraarticular injection mainly includes sodium hyaluronic acid,chitosan（for injection） with prudent use of glucocorticoid.Chinese herbal medicine and Chinese patent medicine can be taken referring to syndrome differentiation which mainly includes syndromes of qi stagnation and blood stasis,cold dampness,deficiency of Gan（Liver） and Shen（Kidney）,deficiency of qi and blood.Western medicine mainly includes analgesic,NSAIDs,diseases modifying drugs.Surgery procedures mainly include joint irrigation,arthroscopic surgery,osteotomy,arthroplasty,etc.

An oxygen reservoir-irrigated photoimmunotherapy of malignant melanoma

Tumor hypoxia is the pivotal factor limiting the therapeutic efficacy of photodynamic therapy(PDT),and can be partly improved by either the oxygen economizing or the oxygen supplementation strategies.Nevertheless,the current studies scarcely integrated the merits of both strategies and neglected the bottleneck of poor oxygen infiltration in deep tumors,resulting in PDT resistance.Herein,we developed an oxygen reservoir-irrigated PDT which integrates oxygen supply,oxygen economizing,and oxygen infiltration altogether.Specifically,mitochondria-targeted mesoporous prussian blue nanoparticles(Ce6@TPB)were fabricated to bridge the gap between oxygen economizing and oxygen supplementation by reducing oxygen output while increasing oxygen input.Hyaluronidase-loaded microneedles were further developed to pave the way for deep PDT with increased infusion of oxygen and photosensitizer by degrading dense extracellular matrix.The modulation of tumor oxygenation and permeability during PDT leads to the complete eradication of primary melanoma and strong immunogenic cell death.Its further combination with checkpoint-blockade inhibitor greatly suppressed the proliferation of distal tumors by reprogramming immune microenvironments,as evidenced by the depletion of M2 macrophage,increased infiltration of anti-tumor immune cells,and elevated excretion of immune cytokines.Therefore,such an oxygen reservoir-irrigated PDT potentiates powerful photoimmunotherapy and provides a favorable prospect for tumor treatment.

Effect of houttuynia cordata aetherolea on adiponectin and connective tissue growth factor in a rat model of diabetes mellitus

OBJECTIVE:To determine the effect of Houttuynia cordata Aetherolea on connective tissue growth factor and adiponectin in a rat model of diabetes mellitus(DM).METHODS:DM was induced in rats using streptozotocin(STZ) and high glucose-lipid animal feed.Animals were then treated with Houttuynia cordata Aetherolea for 8 weeks.Changes in connective tissue growth factor and adiponectin levels in rats were observed.RESULTS:Connective tissue growth factor and adiponectin levels in rats with DM improved after Houttuynia cordata Aetherolea treatment.CONCLUSION:Houttuynia cordata Aetherolea had a positive effect on rats with DM by reducing levels of connective tissue growth factor and increasing adiponectin levels.