Tumor-derived small extracellular vesicles promote breast cancer progression by upregulating PD-L1 expression in macrophages.

BACKGROUND: The metastasis of breast cancer (BC) is a complex multi-step pathological process, strictly dependent on the intrinsic characteristics of BC cells and promoted by a predisposing microenvironment. Although immunotherapy has made important progress in metastasis BC, the heterogeneity of PD-L1 in tumor associated macrophages (TAMs) in BC and the underlying mechanisms in the metastasis development of BC are still not completely elucidated. Small extracellular vesicles (sEVs) represent essential interaction mediators between BC cells and TAMs. It is worth noting to explore the underlying mechanisms typical of sEVs and their role in the metastasis development of BC. METHODS: The structure of sEVs was identified by TEM, while the particle size and amounts of sEVs were detected by BCA and NTA analysis. The specific PD-L1 + CD163 + TAM subpopulation in metastasis BC was identified by scRNA-seq data of GEO datasets and verified by IHC and IF. The function of TAMs and sEVs in metastasis BC was explored by RT-qPCR, WB, IF, flow cytometry and in vivo experiment. The expression profiles of plasma sEVs-miRNA in relation to BC metastasis was analyzed using next-generation sequencing. Further detailed mechanisms of sEVs in the metastasis development of BC were explored by bioinformatics analysis, RT-qPCR, WB and luciferase reporter assay. RESULTS: In this study, we identified that the immunosuppressive molecule PD-L1 was more abundant in TAMs than in BC cells, and a specific PD-L1 + CD163 + TAM subpopulation was found to be associated with metastasis BC. Additionally, we found that BC cells-derived sEVs can upregulate the PD-L1 expression and induce the M2 polarization, enhancing the metastasis development both in vitro and in vivo. Also, Clinical data showed that sEV-miR-106b-5p and sEV-miR-18a-5p was in relation to BC metastasis development and poor prognosis of BC patients. Further mechanistic experiments revealed that BC-derived sEV-miR-106b-5p and sEV-miR-18a-5p could synergistically promoted the PD-L1 expression in M2 TAMs by modulating the PTEN/AKT and PIAS3/STAT3 pathways, resulting in the enhancement of the BC cells invasion and metastasis. CONCLUSIONS: Our study demonstrated that BC-derived sEVs can induce metastasis in BC through miR-106b-5p/PTEN/AKT/PD-L1 and miR-18a-5p/PIAS3/STAT3/PD-L1 pathways in TAMs. Therefore, the inhibition of these specific interactions of signaling pathways would represent a promising target for future therapeutic strategies for treatment of BC.

A Patient with Adalimumab-Induced Refractory Paradoxical Palmoplantar Pustulosis Was Successfully Treated by Ixekizumab: A Case Report.

Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disorder involving the sacroiliac (SI) joints, the spine and often the hips. Biologic therapy has been shown to be efficacious in patients with AS and could improve patients' quality of life. With the increased use of tumor necrosis factor-ɑ (TNF-ɑ) inhibitors, more paradoxical reactions have been revealed. However, the treatment option for patients with AS is still a challenge when refractory paradoxical palmoplantar pustulosis appeared after the use of TNF-ɑ inhibitors. We reported the case of a 45-year-old male patient with AS treated with adalimumab treatment who developed a refractory paradoxical palmoplantar pustulosis after failure of prior secukinumab treatment. A dramatic improvement was seen in all skin and low back pain after the use of ixekizumab. We conclude that, in TNF-α inhibitors induced refractory paradoxical palmoplantar pustulosis, ixekizumab should be considered as an alternative option to choose from.

Combination treatment with 30% salicylic acid and fractional CO2 laser for acne scars: A 20-week prospective, randomized, split-face study.

Multiple approaches are used to treat acne scars, but some are expensive, ineffective, and cause complications. We aimed to evaluate the efficacy and safety of ultra-pulsed CO2 fractional laser combined with 30% supramolecular salicylic acid in the treatment of acne scars in a prospective split-face control study. Twenty patients with facial symmetrical acne scars were enrolled. One side of face was randomly treated with 30% supramolecular salicylic acid, and two sides were treated with ultra-pulsed CO2 fractional laser. The Echelle d'evaluation clinique des cicatrices d'acne (ECCA) scale was used to evaluate the clinical efficacy before and 3 months after treatment, and a quartile scale was used to self-evaluate the improvement of patients. A visual analog scale was used to record pain scores after each treatment, and side effects and other adverse reactions on the face were recorded. All the patients completed treatment and follow-up. There was statistical difference in ECCA scores of bilateral facial acne scars after three treatments (p < 0.001). ECCA scores on the combined side were lower after three treatments than those on the laser side (p = 0.003). The patient satisfaction quartile scale on the combined side was higher than that on the laser side alone (p = 0.015). Ultra-pulsed CO2 fractional laser combined with 30% supramolecular salicylic acid has better efficacy in the treatment of acne scars than laser alone, and patient self-assessment of combined treatment has a greater degree of improvement in acne scars, and does not increase patient pain scores and related adverse reactions.

A new indole alkaloid from the traditional Chinese medicine Chansu.

A new indole alkaloid N'-formylserotonin (1), along with five known indole alkaloids N'-methylserotonin (2), 5-hydroxy-1H-indole-3-carbaldehyde (3), N-acetylserotonin (4), 6-hydroxy-1-oxo-3,4-dihydro-ß-carboline (5), and bufoserotoin C (6), were isolated from the water extract of traditional Chinese medicine Chansu. Their structures were elucidated on the basis of spectral analyses. The cytotoxicities of 1-6 against human lung adenocarcinoma epithelial cells A549 were tested using the MTT method. Compound 6 exhibited stronger cytotoxic effect than 5-FU, and 1-5 showed no cytotoxic effects. Bufoserotonin C is one of the cytotoxic components in water-soluble extract of Chansu.

[HBVcccDNA of patients with hepatitis B in the serum, PBMC and liver tissue distribution].

OBJECTIVE: Hepatitis B virus covalently closed circular DNA in the serum of patients with hepatitis B, peripheral mononuclear cells (PBMC) and liver tissue distribution. METHODS: Serum HBV DNA > 10(5) copies/ml 50 cases of hepatitis B patients, serum HBV DNA < 10(5) copies/ml 30 cases of hepatitis B patients, patients with fatty liver (hepatitis B) 20 cases, using real-time quantitative polymerase chain reaction for detection of serum, and liver tissue in PBMC HBVcccDNA the existence. RESULTS: Of 50 serum HBV DNA > 10(5) copies/ml cccDNA the serum specimens were 28 cases, 56% detection rate, 29 cases were PBMC HBVcccDNA, 58% detection rate, liver tissue HBVcccDNA were 44 cases, 88% detection rate, serum, the PBMC were detected in liver tissue were significant differences in P < 0.005, compared serum PBMC were no significant differences in P > 0.005. 30 serum HBV DNA < 10(5) copies/ml the serum specimens, PBMC cccDNA detected two cases were 6.67% detection rate, liver tissue cccDNA were six cases 20% detection rate, serum, PBMC, were among the liver tissue was not significantly different P > 0.005. 20 in the serum of patients with fatty liver, liver tissue in PBMCwere not detected HBVcccDNA. CONCLUSION: HBVcccDNA mainly in the liver of patients with hepatitis B, hepatitis B patients and also cccDNA PBMC in the presence of liver tissue but a few of many.