The effects of Spinosad on zebrafish larvae and THP-1 cells: Associated with immune cell damage and NF-kappa B signaling pathway activation.

Spinosad is a highly effective macrolide insecticide with a wide range of applications. However, few studies have been reported on the effects of Spinosad on immune cells. The immune system is an important line of defense in the human body and plays an important role in maintaining the normal functioning of the organism. Meanwhile, macrophages, neutrophils and Thymic T cells are an important component of the immune system. We studied the immunotoxicity of Spinosad using zebrafish and THP-1 cells. In vivo, Spinosad (0-20 µM) did not cause developmental toxicity in zebrafish, but induced damage to immune cells. In vitro, Spinosad (0-20 µM) inhibited THP-1 cells viability and induced mitochondrial damage and oxidative stress production. In further studies, it impaired phagocytosis of THP-1 cells and interfered with lipid metabolism. In addition, we found that Spinosad can promote the formation of the inflammatory body NLRP3 (NLR family, pyrin domain-containing 3) and activate the NF-kappa B (NF-κB) signaling pathway. These results suggest that Spinosad has a potential risk for inducing immunotoxicity. This study has drawn attention to Spinosad-induced immunotoxicity.

Dihydroartemisinin Alleviates Imiquimod-Induced Psoriasis-like Skin Lesion in Mice Involving Modulation of IL-23/Th17 Axis.

Background: Psoriasis is a T help 17 (Th17) cell-mediated chronic inflammatory skin disease. Recent studies have shown that dihydroartemisinin (DHA) can significantly reduce experimental autoimmune encephalomyelitis and rheumatoid arthritis by regulating Th17 cells. Objective: To verify whether DHA can improve the symptoms of psoriasis and to further explore the possible mechanism. Methods: The efficiency of DHA was preliminary detected on human keratinocytes (HaCaT) cells in psoriatic condition. Then, imiquimod-induced psoriasis-like model in BALB/c mice was established to evaluate the effects of DHA in vivo. Results: Under the stimulation of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), DHA inhibited the proliferation of HaCaT cells and significantly affected the mRNA expression levels of IFN-γ, interleukin (IL), IL-17A and IL-23. DHA treatment reduced the severity of psoriasis-like skin and resulted in less infiltration of immune cells in skin lesions. DHA restored the expression of IFN-γ, IL-17A, and IL-23 in skins, as well as a decrease of cytokines and chemokines in skin supernatant. DHA also altered the cellular composition in the spleen, which is the makeup of the T cells, dendritic cells (DCs), and macrophages. DHA recovered Th17-related profile with decreased frequency of IL-17+CD4+T cells from splenocyte of mice. Furthermore, DHA also inhibited the concentration of IL-17 from Th17 cells and the expression of Th17 cell-related transcription factors retinoid-related orphan receptor-gamma t (ROR-γt) in vitro. In addition, phosphorylation of signal transducer and activator of transcription-3 (STAT3) was significantly reduced in DHA treatment mice, suggesting that the IL-23/Th17 axis plays a pivotal role. Conclusion: DHA inhibits the progression of psoriasis by regulating IL-23/Th17 axis and is expected to be an effective drug for the treatment of psoriasis.

[Value of Contrast-enhanced Ultrasound in Differential Diagnosis between Cholesterol Polyp and Gallbladder Adenoma].

Objective To compare the performance of contrast-enhanced ultrasound(CEUS)and ultrasound(US)in the differential diagnosis between cholesterol polyps and gallbladder adenomas. Methods A total of 136 patients with gallbladder polyp lesions(GPLs)and undergoing cholecystectomy in the First Medical Center of Chinese PLA General Hospital from January 2019 to October 2020 were retrospectively analyzed.All the patients underwent US and CEUS examinations before cholecystectomy.US and CEUS images of cholesterol polyps and gallbladder adenomas were compared for the evaluation of the performance of CEUS in the diagnosis of gallbladder adenomas. Results The 136 cases of GPLs included 95 cases of cholesterol polyps and 41 cases of gallbladder adenomas.Cholesterol polyps and gallbladder adenomas showed significant differences in the maximum size of GPLs( Z=-5.189, P<0.001), polyp blood flow signal(χ 2=33.630, P<0.001), vascular stalk width(Z=-7.366, P<0.001), polyp enhancement time(χ 2=22.487, P<0.001), enhancement intensity in arterial phase(χ 2=44.371, P<0.001), polyp vascular morphology(χ 2=53.814, P<0.001)and gallbladder wall integrity(χ 2=13.277, P=0.001).The sensitivity, specificity and accuracy of CEUS in distinguishing gallbladder adenomas from cholesterol polyps were 85.37%, 89.47% and 88.24%, respectively, and the area under the curve was 0.874. Conclusion CEUS can effectively distinguish gallbladder adenomas from cholesterol polyps and help patients with GPLs to select the appropriate treatment.

Prognostic value of T cell immunoglobulin mucin-3 in prostate cancer.

BACKGROUND: Optimal treatment for prostate cancer remains a challenge worldwide. Recently, T cell immunoglobulin mucin-3 (TIM-3) has been implicated in tumor biology but its contribution prostate cancer remains unclear. The aim of this study was to investigate the role of TIM-3 as a prognostic marker in patients with prostate cancer. METHODS: TIM-3 protein expression was determined by immunohistochemistry and Western blotting in 137 prostate cancer tumor samples and paired adjacent benign tissue. We also performed cell proliferation assays using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl- 2H tetrazolium bromide (MTT) and cell invasion assays. The effects of small interfering RNA (siRNA)-mediated knockdown of TIM-3 (TIM-3 siRNA) in two human prostate cancer cell lines were also evaluated. RESULTS: TIM-3 expression was higher in prostate cancer tissue than in the adjacent benign tissue (P<0.001). High TIM-3 expression was an independent predictor of both recurrence-free survival and progression-free survival. TIM-3 protein was expressed in both prostate cancer cell lines and knockdown suppressed their proliferation and invasion capacity. CONCLUSIONS: TIM-3 expression is associated with a poor prognosis in prostate cancer. Taken together, our results indicate that TIM-3 is a potential prognostic marker in prostate cancer.