Carbonic anhydrase 2 mediates anti-obesity effects of black tea as thermogenic activator

Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a“disease”.Brown adipose tissue(BAT)thermogenesis and white adipose tissue(WAT)browning emerge as a potential strategy of anti-obesity by dissipating energy as heat.However,drugs based on adipose tissue thermogenesis have not been successfully approved yet.In current study,we found that black tea extract(BTE)obtained by patentauthorized manufacturing process prevented body weight gain as novel thermogenic activator with reduction of adiposity,improvement of adipose distribution,and glucose metabolism improvement in diet-induced obesity mice.Mechanismly,anti-obesity effect of BTE depends on promoting BAT thermogenesis and WAT browning with upregulation of uncoupling protein 1(UCP1),especially visceral adipose tissue(VAT)with browning resistance.Specifically,utilizing in silico approach of network pharmacology and molecular docking,we identified carbonic anhydrase 2(CA2)in nitrogen metabolism as anti-obesity target of BTE and further elucidated that protein kinase B(AKT)signaling pathway linked CA2 and UCP1.Meanwhile gut microbiota regulation may prompt the CA2-dependent thermogenesis activation.Our findings demonstrated anti-obesity effect of BTE as thermogenic activator through CA2-mediated BAT thermogenesis and WAT browning via CA2-AKT-UCP1 signaling pathway,which could be developed as promising anti-obesity agent with good safety and efficacy.

Carbon dioxide laser for treating pediatric facial papillomatosis:a case study

Purpose Carbon dioxide(CO_(2))lasers enable precise vaporization of lesions with minimal bleeding and have been widely used to excise a wide variety of lesions with good results.Papillomatosis is a disorder characterized by a wart-like growth that tends to recur relentlessly after surgical removal or medical treatment.Treatment of pediatric facial papillomatosis by utilizing a CO_(2)laser is a viable alternative strategy.This paper presents a case of an 8-month-old child with facial papilloma,that we treated by ablation using a CO_(2)laser,and discusses the efficacy of this treatment modality.Methods A case of pediatric facial papilloma treated with CO_(2)laser ablation was reported,and the benefits of this treatment modality were reviewed and analyzed in the context of the existing literature.Results Under general anesthesia,the lesional tissue of the left lip was excised,and the pathological diagnosis was confirmed to be maxillofacial papilloma.The lesions were surgically ablated in stages using a CO_(2)laser,and erythromycin ointment was applied to the treated areas after surgery.A total of three rounds of CO_(2)laser treatment were performed.The child had no complications during or after the operations;the child’s facial appearance was significantly improved,and there was no sign of recurrence during the 6-month follow-up.Conclusions The CO_(2)laser was useful for resection of this patient who had pediatric facial papillomatosis,and it can restore an aesthetic facial soft tissue profile without significant residual facial deformity.The CO_(2)laser can achieve precise vaporization resection of diseased tissue with minimal blood loss and a good cosmetic result.

Neuronal NR4A1 deficiency drives complement-coordinated synaptic stripping by microglia in a mouse model of lupus

Neuropsychiatric lupus(NPSLE)is a frequent manifestation of systemic lupus erythematosus(SLE)that occurs in 40-90%of SLE patients;however,the underlying mechanisms remain elusive,causing a severe lack of therapeutic targets for this condition.Here,we show that complement-coordinated elimination of synapses participated in NPSLE in MRL/lpr mice,a lupus-prone murine model.We demonstrated that lupus mice developed increased anxiety-like behaviors and persistent phagocytic microglial reactivation before overt peripheral lupus pathology.

N-terminal residues of an HIV-1 gp41 membrane-proximal external region antigen influence broadly neutralizing 2F5-like antibodies

The Human immunodeficiency virus type 1(HIV-1) gp41 membrane proximal external region(MPER) is targeted by broadly neutralizing antibodies(e.g. 2F5, 4E10, Z13 e and m66.6), which makes this region a promising target for vaccine design. One strategy to elicit neutralizing antibodies against the MPER epitope is to design peptide immunogens mimicking neutralization structures. To probe 2F5-like neutralizing antibodies, two yeast-displayed antibody libraries from peripheral blood mononuclear cells from a HIV-1 patient were screened against the 2F5 epitope peptide SP62. Two 2F5-like antibodies were identified that specifically recognized SP62. However,these antibodies only weakly neutralized HIV-1 primary isolates. The epitopes recognized by these two 2F5-like antibodies include not only the 2F5 epitope(amino acids(aa) 662–667 in the MPER)but also several other residues(aa 652–655) locating at the N-terminus in SP62. Experimental results suggest that residues of SP62 adjacent to the 2F5 epitope influence the response of broadly neutralizing 2F5-like antibodies in vaccination. Our findings may aid the design of vaccine immunogens and development of therapeutics against HIV-1 infection.