The therapeutic effect of Picroside II in renal ischemia-reperfusion induced acute kidney injury: An experimental study.

The microcirculation hemodynamics change and inflammatory response are the two main pathophysiological mechanisms of renal ischemia-reperfusion injury (IRI) induced acute kidney injury (AKI). The treatment of microcirculation hemodynamics and inflammatory response can effectively alleviate renal injury and correct renal function. Picroside II (P II) has a wide range of pharmacological effects. Still, there are few studies on protecting IRI-AKI, and whether P II can improve renal microcirculation perfusion is still being determined. This study aims to explore the protective effect of P II on IRI-AKI and evaluate its ability to enhance renal microcirculation perfusion. In this study, a bilateral renal IRI-AKI model in mice was established, and the changes in renal microcirculation and inflammatory response were quantitatively evaluated before and after P II intervention by contrast-enhanced ultrasound (CEUS). At the same time, serum and tissue markers were measured to assess the changes in renal function. The results showed that after P II intervention, the levels of serum creatinine (Scr), blood urea nitrogen (BUN), serum cystatin C (Cys-C), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and superoxide dismutase (SOD), as well as the time-to-peak (TTP), peak intensity (PI) and area under the curve (AUC), and the normalized intensity difference (NID) were all alleviated. In conclusion, P II can improve renal microcirculation perfusion changes caused by IRI-AKI, reduce inflammatory reactions during AKI, and enhance renal antioxidant stress capacity. P II may be a new and promising drug for treating IRI-AKI.

Value of high frame rate contrast enhanced ultrasound in gallbladder wall thickening in non-acute setting.

BACKGROUND: Ultrasound (US) has been widely used in screening and differential diagnosis of gallbladder wall thickening (GWT). However, the sensitivity and specificity for diagnosing wall-thickening type gallbladder cancer are limited, leading to delayed treatment or overtreatment. We aim to explore the value of high frame rate contrast enhanced ultrasound (H-CEUS) in distinguishing wall-thickening type gallbladder cancer (malignant) from GWT mimicking malignancy (benign). METHODS: This retrospective study enrolled consecutive patients with non-acute GWT who underwent US and H-CEUS examination before cholecystectomy. Clinical information, US image and H-CEUS image characteristics between malignant and benign GWT were compared. The independent risk factors for malignant GWT on H-CEUS images were selected by multivariate logistic regression analysis. The diagnostic performance of H-CEUS in determining malignant GWT was compared with that of the gallbladder reporting and data system (GB-RADS) score. RESULTS: Forty-six patients included 30 benign GWTs and 16 malignant GWTs. Only mural layering and interface with liver on US images were significantly different between malignant and benign GWT (P < 0.05). Differences in enhancement direction, vascular morphology, serous layer continuity, wash-out time and mural layering in the venous phase of GWT on H-CEUS images were significant between malignant and benign GWT (P < 0.05). The sensitivity, specificity and accuracy of H-CEUS based on enhancement direction, vascular morphology and wash-out time in the diagnosis of malignant GWT were 93.75%, 90.00%, and 91.30%, respectively. However, the sensitivity, specificity and accuracy of the GB-RADS score were only 68.75%, 73.33% and 71.74%, respectively. The area under ROC curve (AUC) of H-CEUS was significantly higher than that of the GB-RADS score (AUC = 0.965 vs. 0.756). CONCLUSIONS: H-CEUS can accurately detect enhancement direction, vascular morphology and wash-out time of GWT, with a higher diagnostic performance than the GB-RADS score in determining wall-thickening type gallbladder cancer. This study provides a novel imaging means with high accuracy for the diagnosis of wall-thickening type gallbladder cancer, thus may be better avoiding delayed treatment or overtreatment.

Contrast-enhanced ultrasound in evaluating the severity of acute kidney injury: An animal experimental study.

PURPOSE: Early assessment of the severity of acute kidney injury (AKI) is critical to the prognosis of patients. Renal microcirculation hemodynamic changes and inflammatory response are the essential links of AKI induced by ischemia-reperfusion injury (IRI). This study aims to explore the value of contrast-enhanced ultrasound (CEUS) based on vascular cell adhesion molecule-1 (VCAM-1) targeted microbubbles (TM) in evaluating the renal microcirculation hemodynamics and inflammatory response of different severity of AKI. METHODS: Eighteen male C57BL/6J mice were randomly divided into three groups (n = 6): sham operation (sham) group, mild IRI-AKI (m-AKI) group, and severe IRI-AKI (s-AKI) group. CEUS based on VCAM-1 TM was used to evaluate renal microcirculation perfusion and inflammatory response. Pearson's correlation was used to analyze the correlation between ultrasonic variables and pro-inflammatory factors. RESULTS: Compared with the sham group, AUC in m-AKI and s-AKI groups was significantly decreased, and s-AKI group was lower than m-AKI group (P < 0.05). NID of m-AKI and s-AKI groups was significantly higher than that of the sham group, and s-AKI group was higher than that of m-AKI group (P < 0.05). There was a linear positive correlation between NID and VCAM-1 protein expression (r = 0.7384, P < 0.05). NID and AUC were correlated with TNF-α and IL-6 levels (P < 0.05). Compared with early AKI biomarkers, CEUS based on VCAM-1 TM has higher sensitivity in evaluating the severity of AKI. CONCLUSIONS: CEUS based on VCAM-1 TM can evaluate renal microcirculation perfusion and inflammatory response in mild and severe AKI, which may provide helpful information for assessing the severity of AKI.

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.

Value of Micro Flow Imaging in the Prediction of Adenomatous Polyps.

OBJECTIVE: The aim of this study was to assess the value of micro flow imaging (MFI) in distinguishing adenomatous polyps from cholesterol polyps. METHODS: A total of 143 patients who underwent cholecystectomy for gallbladder polyps were retrospectively analyzed. B-mode ultrasound (BUS), color Doppler flow imaging (CDFI), MFI and contrast-enhanced ultrasound (CEUS) were performed before cholecystectomy. The weighted kappa consistency test was used to evaluate the agreement of vascular morphology among CDFI, MFI and CEUS. Ultrasound image characteristics, including BUS, CDFI and MFI images, were compared between adenomatous polyps and cholesterol polyps. The independent risk factors for adenomatous polyps were selected. The diagnostic performance of MFI combined with BUS in determining adenomatous polyps was compared with CDFI combined with BUS. RESULTS: Of the 143 patients, 113 cases were cholesterol polyps, and 30 cases were adenomatous polyps. The vascular morphology of gallbladder polyps was more clearly depicted by MFI than CDFI, and it had better agreement with CEUS. Differences in maximum size, height/width ratio, hyperechoic spot and vascular intensity on CDFI and MFI images were significant between adenomatous polyps and cholesterol polyps (p < 0.05). The maximum size, height/width ratio, and vascular intensity on MFI images were independent risk factors for adenomatous polyps. For MFI combined with BUS, sensitivity, specificity and accuracy were 90.00%, 94.69% and 93.70%, respectively. Area under the receiver operating characteristic curve (AUC) of MFI combined with BUS was significantly higher than that of CDFI combined with BUS (AUC = 0.923 vs. 0.784). CONCLUSION: Compared with CDFI combined with BUS, MFI combined with BUS had higher diagnostic performance in determining adenomatous polyps.

RUNX3 mediates keloid fibroblast proliferation through deacetylation of EZH2 by SIRT1.

BACKGROUND: Keloid is a benign proliferative fibrous disease featured by excessive fibroblast proliferation after skin injury. However, the mechanism of abnormal cell proliferation is still unclear. Herein, we investigated the mechanism of abnormal proliferation in keloids involving Sirtuin 1(SIRT1)/ Zeste Homolog 2 (EZH2)/ Runt-related transcription factor 3 (RUNX3).  METHODS: HE staining was used to observe the histopathological changes. Western blot was performed to detect SIRT1/EZH2/RUNX3 and cell cycle related proteins. RT-PCR detected EZH2 mRNA. After knockdown of EZH2 or overexpression of RUNX3, cell proliferation and cell cycle was analyzed. Immunoprecipitation was used to detect acetylated EZH2. RESULTS: The results showed that overexpression of RUNX3 inhibited cell proliferation and arrested cell cycle at G1/S phase, whereas inhibition of SIRT1 promoted cell proliferation and G1/S phase of the cell cycle. Knockdown of EZH2 promoted the expression of RUNX3, inhibited cell proliferation and shortened the progression of G1 to S phase. Simultaneous knockdown of EZH2 and inhibition of SIRT1 reversed these effects. Inhibition of SIRT1 increased its protein stability by increasing EZH2 acetylation, thereby reducing the expression of RUNX3 and promoting cell proliferation. CONCLUSIONS: Conclusively, the SIRT1/EZH2/RUNX3 axis may be an important pathway in the regulation of abnormal proliferation in keloids.

Quantitative Analysis of Renal Perfusion in Rhabdomyolysis-Induced Acute Kidney Injury Using Contrast-Enhanced Ultrasound: An Experimental Study.

The aim of this study was to evaluate renal perfusion changes in rats with acute kidney injury induced by rhabdomyolysis, using quantitative parameters obtained with contrast-enhanced ultrasound (CEUS). Sprague-Dawley (SD) rats were randomly divided into an experimental group (n = 40) and a control group (n = 20). Each group was further divided into four subgroups (0.5-, 6-, 24- and 72-h groups). Time-intensity curves and related quantitative parameters of the renal cortex and medulla were obtained by CEUS, and the contrast characteristics analyzed for different time points. In the experimental group, the CEUS quantitative parameters for the renal medulla of time to peak (TTP), descending time/2 (DT/2) and area under the curve (AUC) increased, whereas ascending slope (AS) and descending slope (DS) decreased. Similarly, renal cortical AS, DS and AUC in the experimental group differed significantly from those in the control group. With respect to the CEUS quantitative parameters for the renal cortex, AUC increased, and AS and DS decreased. These parameters differed significantly between the experimental and control groups. CEUS is sensitive to change in renal perfusion in rhabdomyolysis-induced acute kidney injury and, thus, has diagnostic value.

A New Perspective for Predicting the Therapeutic Success of RFA in Solid BTNs: Quantitative Initial RFA Ratio by Contrast-Enhanced Ultrasound.

Objective: The short-term therapeutic success of radiofrequency ablation (RFA) in solid benign thyroid nodules is of great concern. The aim of this study was to investigate a new method, initial radiofrequency ablative ratio (IRAR) using contrast-enhanced ultrasound (CEUS), for predicting therapeutic success of RFA in solid benign thyroid nodules (BTNs) immediately and effectively after RFA. Methods: A total of 813 nodules in 776 patients with benign thyroid nodules were treated with RFA from January 2014 to August 2018, among which 120 patients (M:F=41:79) with 120 solid BTNs (small: ≤10ml, n=57; medium: 10-30ml, n=42; large: >30ml, n=21) were enrolled in our study according to the inclusion criteria. The IRAR was defined as the ablative volume ratio immediately after RFA displayed by CEUS. The therapeutic success was evaluated at the 6-month follow-up. The relationship between the IRAR and volume reduction ratio (VRR) at 6-month was analyzed. The marginal regrowth of solid BTNs was also examined by CEUS at the 6 and 12 months of follow-up. Results: In medium and large nodules, the IRAR was significantly and positively correlated with VRR (r= 0.69, P < 0.001) at 6 months after RFA. There was a tendency to achieve therapeutic success (50% VRR: 55/63, 87.3%) when the IRAR exceeded 75%, and marginal regrowth was also relatively slow within 12 months after a single session treatment. No significant correlation between IRAR and VRR of small nodules was found. In conclusion, IRAR is significantly and positively correlated with VRR, which may indicate therapeutic success when it exceeds 75%. Conclusions: CEUS can be used to accurately quantify the IRAR, which is positively correlated with the VRR. Moreover, the IRAR may be used as a parameter to predict the short-term therapeutic success of RFA in solid BTNs.

Effects of G-Rh2 on mast cell-mediated anaphylaxis via AKT-Nrf2/NF-κB and MAPK-Nrf2/NF-κB pathways.

Background: The effect of ginsenoside Rh2 (G-Rh2) on mast cell-mediated anaphylaxis remains unclear. Herein, we investigated the effects of G-Rh2 on OVA-induced asthmatic mice and on mast cell-mediated anaphylaxis. Methods: Asthma model was established for evaluating airway changes and ear allergy. RPMCs and RBL-2H3 were used for in vitro experiments. Calcium uptake, histamine release and degranulation were detected. ELISA and Western blot measured cytokine and protein levels, respectively. Results: G-Rh2 inhibited OVA-induced airway remodeling, the production of TNF-α, IL-4, IL-8, IL-1ß and the degranulation of mast cells of asthmatic mice. G-Rh2 inhibited the activation of Syk and Lyn in lung tissue of OVA-induced asthmatic mice. G-Rh2 inhibited serum IgE production in OVA induced asthmatic mice. Furthermore, G-Rh2 reduced the ear allergy in IgE-sensitized mice. G-Rh2 decreased the ear thickness. In vitro experiments G-Rh2 significantly reduced calcium uptake and inhibited histamine release and degranulation in RPMCs. In addition, G-Rh2 reduced the production of IL-1ß, TNF-α, IL-8, and IL-4 in IgE-sensitized RBL-2H3 cells. Interestingly, G-Rh2 was involved in the FcεRI pathway activation of mast cells and the transduction of the Lyn/Syk signaling pathway. G-Rh2 inhibited PI3K activity in a dose-dependent manner. By blocking the antigen-induced phosphorylation of Lyn, Syk, LAT, PLCγ2, PI3K ERK1/2 and Raf-1 expression, G-Rh2 inhibited the NF-κB, AKT-Nrf2, and p38MAPK-Nrf2 pathways. However, G-Rh2 up-regulated Keap-1 expression. Meanwhile, G-Rh2 reduced the levels of p-AKT, p38MAPK and Nrf2 in RBL-2H3 sensitized IgE cells and inhibited NF-κB signaling pathway activation by activating the AKT-Nrf2 and p38MAPK-Nrf2 pathways. Conclusion: G-Rh2 inhibits mast cell-induced allergic inflammation, which might be mediated by the AKT-Nrf2/NF-κB and p38MAPK-Nrf2/NF-κB signaling pathways.

Peripheral nerve defects repaired with autogenous vein grafts filled with platelet-rich plasma and active nerve microtissues and evaluated by novel multimodal ultrasound techniques.

BACKGROUND: Developing biocompatible nerve conduits that accelerate peripheral nerve regeneration, lengthening and functional recovery remains a challenge. The combined application of nerve microtissues and platelet-rich plasma (PRP) provides abundant Schwann cells (SCs) and various natural growth factors and can compensate for the deficiency of SCs in the nerve bridge, as well as the limitations of applying a single type of growth factor. Multimodal ultrasound evaluation can provide additional information on the stiffness and microvascular flow perfusion of the tissue. This study was designed to investigate the effectiveness of a novel tissue-engineered nerve graft composed of an autogenous vein, nerve microtissues and PRP in reconstructing a 12-mm tibial nerve defect and to explore the value of multimodal ultrasound techniques in evaluating the prognosis of nerve repair. METHODS: In vitro, nerve microtissue activity was first investigated, and the effects on SC proliferation, migration, factor secretion, and axonal regeneration of dorsal root ganglia (DRG) were evaluated by coculture with nerve microtissues and PRP. In vivo, seventy-five rabbits were equally and randomly divided into Hollow, PRP, Micro-T (Microtissues), Micro-T + PRP and Autograft groups. By analysing the neurological function, electrophysiological recovery, and the comparative results of multimodal ultrasound and histological evaluation, we investigated the effect of these new nerve grafts in repairing tibial nerve defects. RESULTS: Our results showed that the combined application of nerve microtissues and PRP could significantly promote the proliferation, secretion and migration of SCs and the regeneration of axons in the early stage. The Micro-T + PRP group and Autograft groups exhibited the best nerve repair 12 weeks postoperatively. In addition, the changes in target tissue stiffness and microvascular perfusion on multimodal ultrasound (shear wave elastography; contrast-enhanced ultrasonography; Angio PlaneWave UltrasenSitive, AngioPLUS) were significantly correlated with the histological results, such as collagen area percentage and VEGF expression, respectively. CONCLUSION: Our novel tissue-engineered nerve graft shows excellent efficacy in repairing 12-mm defects of the tibial nerve in rabbits. Moreover, multimodal ultrasound may provide a clinical reference for prognosis by quantitatively evaluating the stiffness and microvescular flow of nerve grafts and targeted muscles.

High Frame Rate Contrast-enhanced Ultrasound Helps Differentiate Malignant and Benign Focal Liver Lesions.

BACKGROUND AND AIMS: This study aimed to evaluate the diagnostic performance of high frame rate contrast-enhanced ultrasound (H-CEUS) of focal liver lesions (FLLs). METHODS: From July 2017 to June 2019, conventional contrast-enhanced ultrasound (C-CEUS) and H-CEUS were performed in 78 patients with 78 nodules. The characteristics of C-CEUS and H-CEUS in malignant and benign groups and the differences between different lesion sizes (1-3 cm, 3-5 cm, or >5 cm) of C-CEUS and H-CEUS were examined. The diagnostic performance of C-CEUS and H-CEUS was analyzed. The chi-square test or Fisher's exact test was used to assess inter-group differences. The receiver operating characteristic curve was plotted to determine the diagnostic performance of C-CEUS and H-CEUS. RESULTS: There were significant differences in the enhancement area, fill-in direction and vascular architecture between C-CEUS and H-CEUS for both benign and malignant lesions (all p=0.000-0.008), but there were no significant differences in washout results (p=0.566 and p=0.684, respectively). For lesions 1-3 cm in size, the enhancement area, fill-in direction, and vascular architecture on C-CEUS and H-CEUS were significantly different (all p=0.000), unlike for lesions 3-5 cm or >5 cm in size. For differentiation of malignant from benign FLLs in the 1-3 cm group, H-CEUS showed sensitivity, specificity, accuracy, and positive and negative predictive values of 92.86%, 95.0%, 96.3%, 90.48% and 93.75%, respectively, which were higher than those for C-CEUS (75.0%, 70.0%, 77.78%, 66.67% and 72.91%, respectively). CONCLUSIONS: H-CEUS provided more vascular information which could help differentiate malignant from benign FLLs, especially for lesions 1-3 cm in size.

Value of Conventional Ultrasound-based Scoring System in Distinguishing Adenomatous Polyps From Cholesterol Polyps.

BACKGROUND AND AIM: Ultrasound has increased the detection of gallbladder polyps, but it has limitations in evaluating the nature of gallbladder polyps, especially the maximum size of 1.0 to 1.5 cm. We assessed the value of ultrasound scoring system based on independent predictive parameters in distinguishing adenomatous polyps from cholesterol polyps with the maximum size of 1.0 to 1.5 cm. MATERIALS AND METHODS: We enrolled 163 patients with gallbladder polyps (1.0 to 1.5 cm) who underwent ultrasonography and cholecystectomy. Ultrasound image characteristics were compared between cholesterol polyps and adenomatous polyps in the training cohort from April 2018 to January 2020. An ultrasound scoring system was constructed in the training cohort, and its diagnostic performance was evaluated in the validation cohort from February 2020 to February 2021. RESULTS: Maximum size, height/width ratio, stone or sludge, vascularity, and hyperechoic spot were significantly different between cholesterol polyps and adenomatous polyps in the training cohort ( P <0.05). The independent predictive parameters for adenomatous polyps were lower height/width ratio, presence of vascularity and absence of hyperechoic spot. The total score was as follows: (height/width ratio, <0.9=4, ≥0.9=0) + (vascularity, present=3, absent=0) + (hyperechoic spot, absent=2, present=0). The sensitivity, specificity and accuracy of ultrasound scoring system ≥5 for diagnosis of adenomatous polyps in the validation cohort were 73.33%, 80.49%, and 78.57%, respectively. CONCLUSIONS: The ultrasound scoring system aids in distinguishing adenomatous polyps from cholesterol polyps, and effectively decreasing unnecessary cholecystectomy.

Exposure to environmental concentrations of natural pyrethrins induces hepatotoxicity: Assessment in HepG2 cell lines and zebrafish models.

Natural pyrethrins are one variety of botanical pesticide, and are commonly used in organic and ecological agriculture. However, the hepatotoxicity of natural pyrethrins is unknown. In this study, the impact of natural pyrethrins on human HepG2 cells, which are prominent cell model for toxic-induced hepatotoxicity evaluations, was investigated in accordance with the ROS production and the mechanism of DNA damage and repair. And we report the liver toxicity of natural pyrethrins in zebrafish. Our result revealed a significant increase in ROS production, suggesting oxidative stress. Besides, the most notable genotoxic effect of oxidation-induced DNA damage was observed for natural pyrethrins, as detected by neutral comet assay and γH2AX/8-oxoG staining. As revealed by the results, oxidative DNA damage is responsible for the cytotoxic exposure of natural pyrethrins to HepG2 cells in humans. The observed damage is chronic toxicity, which may cause irreversible DNA damage and more severe toxic effects on human HepG2 cells. This can account for the complicated response to DNA impairment. Visual observations of zebrafish liver and oil red staining also demonstrated that natural pyrethrins induced liver degeneration, liver size changes and liver steatosis in zebrafish. In conclusion, the health of humans can be endangered by natural pyrethrins as a result of hepatotoxicity.

The Therapeutic Effects of Curcumin in Early Septic Acute Kidney Injury: An Experimental Study.

PURPOSE: Sepsis is the leading condition associated with acute kidney injury (AKI) in the hospital and intensive care unit (ICU), sepsis-induced AKI (S-AKI) is strongly associated with poor clinical outcomes. Curcumin possesses an ability to ameliorate renal injury from ischemia-reperfusion, but it is still unknown whether they have the ability to reduce S-AKI. The aim of this study was to investigate the protective effects of curcumin on S-AKI and to assess its therapeutic potential on renal function, inflammatory response, and microcirculatory perfusion. METHODS: Male Sprague-Dawley (SD) rats underwent cecal ligation and puncture (CLP) to induce S-AKI and immediately received vehicle (CLP group) or curcumin (CLP+Cur group) after surgery. At 12 and 24h after surgery, serum indexes, inflammatory factors, cardiac output (CO), renal blood flow and microcirculatory flow were measured. RESULTS: Serum levels of creatinine (Scr), cystatin C (CysC), IL-6 and TNF-α were significantly lower in the CLP+Cur group than those in the CLP group (P < 0.05). Treatment with curcumin improved renal microcirculation at 24h by measurement of contrast enhanced ultrasound (CEUS) quantitative parameters [peak intensity (PI); half of descending time (DT/2); area under curve (AUC); P < 0.05]. In histopathological analysis, treatment with curcumin reduced damage caused by CLP. CONCLUSION: Curcumin can alleviate S-AKI in rats by improving renal microcirculatory perfusion and reducing inflammatory response. Curcumin may be a potential novel therapeutic agent for the prevention or reduction of S-AKI.

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.

Evaluation of toxicological effects of organophosphorus pesticide metabolites on human HepG2 cells.

Trichloropyridinol (TCP); 3, 5, 6-trichloro-2-pyridinol is the primary metabolites of the organophosphorus pesticide chlorpyrifos. It is more highly persistent than parent compounds in the environment and might represent serious risks to human health. In this study, we investigated the toxicological effects and mechanism of TCP on HepG2 cells. The results revealed that TCP induced DNA damage and apoptosis on HepG2 cells. Besides, up-regulating the expression level of Bax /Bcl-2, a reduction in mitochondrial membrane potential, caspase-9/-3 activation and the release of cytochrome-c are contributed to the toxicological effects of TCP on HepG2 cells. These data indicated that the cytotoxic effects of TCP might be associated with the activity of mitochondrial apoptotic pathways. In conclusion, the results demonstrated that TCP poses a potential threat to human health by inducing toxicological effects in the liver.

Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO-1 pathways.

INTRODUCTION: Pterostilbene (Pts) may be used for allergic asthma treatment. The AMPK/Sirt1 and Nrf2/HO-1 pathways are potential targets for asthma treatement. However, the relationship between Pts and AMPK/Sirt1 and Nrf2/HO-1 pathways in asthma is unclear. Herein, we aim to explore the pharmacological effects of Pts on oxidative stress and allergic inflammatory response as well as the mechanism involving AMPK/Sirt1 and Nrf2/HO-1 pathways. METHODS: Asthma model was established in mice with ovalbumin (OVA). The model mice were treated by different concentrations of Pts. Lung pathological changes were observed through histological staining. In vitro, lipopolysaccharide (LPS)-stimulated 16HBE cells were treated with Pts. The siAMPKα2, siSirt1 and siNrf2 knockdown, and treatment with compound C, EX-527 or ML385 were also performed in 16HBE cells. Enzyme-linked immunosorbent assay was used to detect interleukin-4 (IL-4), IL-13, IL-5, total and OVA specific immunoglobulin E (IgE), and interferon γ (IFN-γ). Pneumonography was used to measure the airway hyperreactivity (AHR). Superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels were also detected. Immunohistochemistry, Western blot and immunofluorescence were used to measure protein levels. RESULTS: Pts significantly attenuated lung inflammatory cell infiltration and goblet cell proliferation. Meanwhile, Pts treatment could reduce IL-4, IL-13, IL-5, and IgE (total and OVA specific) levels in the asthma model mice. However, IFN-γ in bronchoalveolar lavage fluid was elevated. In addition, Pts reduced AHR. We also found that Pts treatment promoted serum SOD and CAT, and reduced MDA. In vitro results showed that Pts treatment promoted iNOS, TNF-α, COX-2, IL-1ß, and IL-6 expressions in 16HBE cells, prolonged G0/G1 phase of the cell cycle, and resulted in a shortened G2M phase. Moreover, we found that Pts promoted the phosphorylation of AMPK in 16HBE, and meanwhile inhibited the increase of ROS induced by LPS. Additionally, Pts treatment inhibited p-AMPK, Sirt1, Nrf2 and HO-1, which in turn leads to the alleviation of AMPK/Sirt1 and Nrf2/HO-1 pathways. CONCLUSION: Pts alleviated oxidative stress and allergic airway inflammation via regulation of AMPK/Sirt1and Nrf2/HO-1 signaling pathways.

[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.