RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

Allyl isothiocyanate ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver disease via the Sirt1/AMPK and NF-κB signaling pathways

BACKGROUND Allyl isothiocyanate(AITC),a classic anti-inflammatory and antitumorigenic agent,was recently identified as a potential treatment for obesity and insulin resistance.However,little is known about its direct impact on the liver.AIM To investigate the effect and underlying mechanism of AITC in nonalcoholic fatty liver disease(commonly referred to as NAFLD).METHODS To establish a mouse and cellular model of NAFLD,C57BL/6 mice were fed a high fat diet(HFD)for 8 wk,and AML-12 cells were treated with 200μM palmitate acid for 24 h.For AITC treatment,mice were administered AITC(100 mg/kg/d)orally and AML-12 cells were treated with AITC(20μmol/L).RESULTS AITC significantly ameliorated HFD-induced weight gain,hepatic lipid accumulation and inflammation in vivo.Furthermore,serum alanine aminotransferase and aspartate aminotransferase levels were markedly reduced in AITC-treated mice.Mechanistically,AITC significantly downregulated the protein levels of sterol regulatory elementbinding protein 1(SREBP1)and its lipogenesis target genes and upregulated the levels of proteins involved in fatty acidβ-oxidation,as well as the upstream mediators Sirtuin 1(Sirt1)and AMPactivated protein kinaseα(AMPKα),in the livers of HFD-fed mice.AITC also attenuated the nuclear factor kappa B(NF-κB)signaling pathway.Consistently,AITC relieved palmitate acid-induced lipid accumulation and inflammation in AML-12 cells in vitro through the Sirt1/AMPK and NF-κB signaling pathways.Importantly,further studies showed that the curative effect of AITC on lipid accumulation was abolished by siRNA-mediated knockdown of either Sirt1 or AMPKαin AML-12 cells.CONCLUSION AITC significantly ameliorates hepatic steatosis and inflammation by activating the Sirt1/AMPK pathway and inhibiting the NF-κB pathway.Therefore,AITC is a potential therapeutic agent for NAFLD.

A double-edged sword: CRISPR-Cas9 is emerging as a revolutionary technique for genome editing

In May 2015, professor Xiao Yang authored a review on the development of CRISPR-Cas9 techniques in the journal of Military Medical Research. This review provided a valuable overview of this major scientific advance. It has been four years since the first publication of the CRISPR-Cas9 breakthrough. The use of this technique has expanded into various scientific areas and is being developed into a systematic technical platform that may contribute to many bioengineering fields involving DNA sequence editing.

Ultrasonographic evaluation of the rete testis thickness:a promising approach to differentiate obstructive from nonobstructive azoospermia

This study aimed to evaluate the ability of rete testis thickness(RTT)and testicular shear wave elastography(SWE)to differentiate obstructive azoospermia(OA)from nonobstructive azoospermia(NOA).We assessed 290 testes of 145 infertile males with azoospermia and 94 testes of 47 healthy volunteers at Shanghai General Hospital(Shanghai,China)between August 2019 and October 2021.The testicular volume(TV),SWE,and RTT were compared among patients with OA and NOA and healthy controls.The diagnostic performances of the three variables were evaluated using the receiver operating characteristic curve.The TV,SWE,and RTT in OA differed significantly from those in NOA(all P≤0.001)but were similar to those in healthy controls.Males with OA and NOA were similar at TVs of 9–11 cm^(3)(P=0.838),with sensitivity,specificity,Youden index,and area under the curve of 50.0%,84.2%,0.34,and 0.662(95%confidence interval[CI]:0.502–0.799),respectively,for SWE cut-off of 3.1 kPa;and 94.1%,79.2%,0.74,and 0.904(95%CI:0.811–0.996),respectively,for RTT cut-off of 1.6 mm.The results showed that RTT performed significantly better than SWE in differentiating OA from NOA in the TV overlap range.In conclusion,ultrasonographic RTT evaluation proved a promising diagnostic approach to differentiate OA from NOA,particularly in the TV overlap range.

Cupping therapy for patients with chronic urticaria: A systematic review and meta-analysis

Background:Chronic urticaria(CU)is a common skin disease,which has a negative effect on quality of life.Current treatments do not fully control the symptoms of urticaria for many CU patients,thus effective and safe treatments for CU are still needed.Objective:This review aims to evaluate the effectiveness and safety of cupping therapy in patients with CU.Search strategy:The search strategy looked for the presence of related keywords,such as‘‘chronic urticaria"and‘‘cupping therapy,"in the title and abstract of research articles indexed in major databases.Randomized controlled trials(RCTs)were selected after querying nine electronic databases from their inception to May 2019 with the above search terms.Inclusion criteria:RCTs were included if they recruited patients with CU who were intervened with dry or wet cupping.Publications could be written in Chinese or English.Data extraction and analysis:Data were extracted,and the studies were assessed for the quality of their methodological design and risk of bias.Meta-analyses of the RCT data were conducted to assess the total effective rate of the treatment as the primary outcome.Skin disease quality of life index score,recurrence rate,and adverse events were assessed as secondary outcomes.Subgroup analyses were conducted based on different interventions.Results:Thirteen comparisons from 12 RCTs involving 842 participants were included.There were no significant differences between wet cupping and medications in total effective rate(n=372;risk ratio[RR]=1.10,95%confidence interval[CI]0.97 to 1.25;P=0.14)or recurrence rate(n=240;RR=0.56,95%CI 0.23 to 1.36;P=0.20).Cupping therapy,in combination with antihistamine treatment was more efficacious than antihistamines alone,with a greater total effective rate(n=342;RR=1.18,95%CI 1.01 to1.39;P=0.03)and lower recurrence rate(n=342;RR=0.52,95%CI 0.32 to 0.84;P=0.007).Cupping therapy combined with acupuncture was more effective than acupuncture alone(n=156;RR=1.25,95%CI 1.07 to 1.46;P=0.006).No serious adverse events were reported.Conclusion:Wet cupping may be as effective as treatment with antihistamines.When cupping therapy is used as an adjuvant therapy to antihistamines or acupuncture,it may enhance the efficacy.Results drawn from these studies should be interpreted with caution and applied with care to clinical practice,because of the poor quality among the studies that were reviewed.Systematic review registration:PROSPERO,CRD42019137451.

Focusing with the decomposition of the time reversal operator method in noisy environments

This paper presents a detailed analysis of the effects of noise (reverberation) on the focusing performance of de-composition of the time reversal operator (DORT) in a noise-limited case and in a reverberation-limited case, respectively. Quantitative results obtained from simulations and experiments are presented. The results show the DORT method can be effi-ciently applied to target detection with enough source level to yield significant backscatter. For a target placed on the bottom, the influence of the reverberation on the focusing performance is slight. However, distinguishing between a target and constant backscattering returning from strong local clutter on the bottom (false alarms) needs further research.