Fluvastatin prevents lung metastasis in triple-negative breast cancer by triggering autophagy via the RhoB/PI3K/mTOR pathway.

Triple-negative breast cancer is more common among younger than older women and is associated with the poorest survival outcomes of all breast cancer types. Fluvastatin inhibits tumour progression and induces the autophagy of breast cancer cells; however, the role of autophagy in fluvastatin-induced inhibition of breast cancer metastasis is unknown. Therefore, this study aimed to determine this mechanism. The effect of fluvastatin on human hormone receptor-negative breast cancer cells was evaluated in vitro via migration and wound healing assays, western blotting, and morphological measurements, as well as in vivo using a mouse xenograft model. Chloroquine, a prophylactic medication used to prevent malaria in humans was used as an autophagy inhibitor. We found that fluvastatin administration effectively prevented the migration/invasion of triple-negative breast cancer cells, an effect that was largely dependent on the induction of autophagy. Administration of the autophagy inhibitor chloroquine prevented the fluvastatin-induced suppression of lung metastasis in the nude mouse model. Furthermore, fluvastatin increased Ras homolog family member B (RhoB) expression, and the autophagy and anti-metastatic activity induced by fluvastatin were predominantly dependent on the regulation of RhoB through the protein kinase B-mammalian target of rapamycin (Akt-mTOR) signaling pathway. These results suggest that fluvastatin inhibits the metastasis of triple-negative breast cancer cells by modulating autophagy via the up regulation of RhoB through the AKT-mTOR signaling pathway. Fluvastatin may be a promising therapeutic option for patients with triple-negative breast cancer.

Detection of volatile organic compounds in adulterated tea using Fourier transform infrared spectroscopy and Proton-transfer-reaction mass spectrometry.

Aroma is a key factor used to evaluate tea quality. Illegal traders usually add essence to expired or substandard tea to improve its aroma so as to gain more profit. Traditional physical and chemical testing methods are time-consuming and costly. Furthermore, rapid detection techniques, such as near-infrared spectroscopy and machine vision, can only be used to detect adulterated powdered solid essences in tea. In this study, proton-transfer reaction mass spectrometry (PTR-MS) and Fourier-transform infrared spectroscopy (FTIR) were employed to detect volatile organic compounds (VOCs) in samples, and rapid detection of different tea adulterated liquid essence was achieved. The prediction accuracies of PTR-MS and FTIR reached over 0.941 and 0.957, respectively, and the minimum detection limits were lower than the actual used values in both. In this study, the different application scenarios of the two technologies are discussed based on their performance characteristics.

Non-destructive and in-situ detection of shrimp freshness using mid-infrared fiber-optic evanescent wave spectroscopy.

There is strong interest in non-destructive and rapid determination of food freshness in food research. In this study, mid-infrared (MIR) fiber-optic evanescent wave (FOEW) spectroscopy was applied to monitor shrimp freshness through the evaluation of protein, chitin, and calcite contents in conjunction with a Partial Least Squares Discriminant Analysis (PLS-DA) model. Shrimp shells were wiped with a micro fiber-optic probe to obtain a FOEW spectrum which quickly and nondestructively allowed evaluation of the shrimp freshness. Peaks for proteins, chitin, and calcite, which are closely related to shrimp freshness, were detected and quantified. Compared with the standard indicator for evaluating shrimp freshness (total volatile basic nitrogen), the PLS-DA model gave recognition rates for shrimp freshness using calibration and validation sets of the FOEW data of 87.27%, 90.28%, respectively. Our results show that FOEW spectroscopy is a feasible method for non-destructive and in-site detection of shrimp freshness.

Development of amplified luminescent proximity homogeneous assay for quantitation of gastrin-17.

A highly sensitive and convenient amplified luminescent proximity homogeneous assay (AlphaLISA) method with high throughput and automation potential was developed for quantitation of serum Gastrin-17 (G-17) levels, which can facilitate the early diagnosis of atrophic gastritis in people at high risk of gastric cancer using a non-invasive approach. In this study, donor and acceptor beads with modified carboxyl groups on the surface were directly coupled to anti-G-17 antibodies through activation was proposed for application in the development of the new AlphaLISA, which can effectively simplify the steps and shorten the reaction time to achieve faster detection. Therefore, the G-17-AlphaLISA only needs to react for 15 min to obtain good analysis results. The proposed method has a wider detection range than commercial enzyme-linked immunosorbent assay (ELISA) kits (0.12-112.8 pmol/L > 0.5-40 pmol/L). In addition, results of G-17-AlphaLISA and ELISA had good correlation and agreement (ρ = 0.936). Importantly, the developed method may be more suitable for the large-scale screening of people at high risk for gastric cancer than traditional ELISA and provides a novel solution for other biomarkers that require accurate, highly sensitive, and high throughput detection.

A Real-Time Detection Method of Hg2+ in Drinking Water via Portable Biosensor: Using a Smartphone as a Low-Cost Micro-Spectrometer to Read the Colorimetric Signals.

This paper reported a real-time detection strategy for Hg2+ inspired by the visible spectrophotometer that used a smartphone as a low-cost micro-spectrometer. In combination with the smartphone's camera and optical accessories, the phone's built-in software can process the received light band image and then read out the spectral data in real time. The sensor was also used to detect gold nanoparticles with an LOD of 0.14 µM, which are widely used in colorimetric biosensors. Ultimately, a gold nanoparticles-glutathione (AuNPs-GSH) conjugate was used as a probe to detect Hg2+ in water with an LOD of 1.2 nM and was applied successfully to natural mineral water, pure water, tap water, and river water samples.

In situ detection of fruit spoilage based on volatile compounds using the mid-infrared fiber-optic evanescent wave spectroscopy.

Volatile compounds such as ethanol released from fruit can be rapidly detected using Fourier Transform Infrared spectroscopy based on a long-path gas cell. However, this method relies on a long optical path length and requires pumping fruit volatiles into the gas cell. This can lead to the volatile compounds being contaminated and not detectable in situ. Fiber optic evanescent wave spectroscopy (FOEW) is not influenced by the path length so can detect materials (solid, liquid and gas phase) rapidly in situ, using only a few millimeters of optical fiber. In the present study, a spiral silver halide FOEW sensor with a length of approximately 21 mm was used to replace a long-path gas cell to explore the feasibility of identifying volatile compounds released from grapes in situ. The absorption peaks of ethanol in the volatile compounds were clearly found in the FOEW spectra and their intensity gradually increased as the storage time of the grapes increased. PCA analysis of these spectra showed clear clustering at different storage times (1-3, 4-5 and 6-7 d), revealing that the concentration of the ethanol released from the grapes changed significantly with time. The qualitative model established by PLS-DA algorithm could accurately classify grape samples as "Fresh," "Slight spoilage," or "Severe spoilage". The accuracy of the calibration and validation sets both were 100.00%. These changes can therefore be used for rapidly identifying fruit deterioration. Compared with the method used in a previous study by the authors, this method avoids using a pumping process and can thus identify volatile compounds and hence monitor deterioration in situ and on-line by placing a very short optical fiber near the fruit.

Sanzi Yangqin Decoction Alleviates Allergic Asthma by Modulating Th1/Th2 Balance: Coupling Network Pharmacology with Biochemical Pharmacology.

This study aimed to verify that Sanzi Yangqin Decoction (SYD) can relieve asthma in mice and explore the effect on TH1/Th2 balance. The targets of SYD and asthma were explored from the public database using various methods. The potential targets and signaling pathways were identified by KEGG enrichment analysis from DAVID database. Mice asthma models were established using OVA and aluminum hydroxide. Lung tissues of mice were stained with HE and Masson. The contents of IFN-γ, IL-4, and TNF-α in BALF and IgE in mouse serum were detected using ELISA. In addition, the changes in Th1 and Th2 cells of the spleen were detected by flow cytometry. Fourteen core targets including IL4, IFNG, and MMP9 were identified for the treatment of asthma by SYD. The content of IL-4 in the lung tissue and BALF was gradually decreased with the increase in SYD concentration, while the IFN-γ was gradually increased. The drug significantly reduced IgE levels in serum and TNF-α in BALF. The number of Th1 cells in the spleen increased, while Th2 cells decreased in a concentration-dependent manner. SYD can alleviate pulmonary inflammation, restore Th1/Th2 balance, and relieve asthma.

The relationship between post-diagnostic statin usage and breast cancer prognosis varies by hormone receptor phenotype: a systemic review and meta-analysis.

BACKGROUND: Preclinical studies and epidemiologic data had indicated statins had antineoplastic properties in breast cancer patients. Since breast cancer treatment is based on its phenotype, it is important to explore influence of post-diagnosis statin usage on breast cancer patients with different phenotypes. METHODS: We searched the related studies between inception and August, 2019 from MEDLINE and EMBASE. A total of 7 studies with 24,541 patients were identified. Stata/SE 15.0 and Review Manager 5.3 were used to analyze data. Inconsistency index was used to estimate heterogeneity. Begg's and Egger's regression test was used to examine publication bias. RESULTS: Overall post-diagnostic statin use was associated with improved recurrence free survival (recurrence free survival (RFS); hazard ratio (HR) 0.74; 95% confidential interval (95% CI) 0.57-0.98), overall survival (overall survival (OS); HR 0.53; 95% CI 0.31-0.91) and cancer-specific survival (cancer-specific survival (CSS); and HR 0.61; 95% CI 0.41-0.91). In hormone receptor positive patients, statin use was associated with improved CSS (HR 0.74, 95% CI 0.65-0.84). No protective effect was found in either OS or RFS. In hormone receptor negative patients, statin was associated with reduced OS (HR 2.19, 95% CI 1.34-3.59) and reduced RFS, but without statistical significance. CONCLUSIONS: Post-diagnostic statin use was associated with improved RFS, OS and CSS in breast cancer patients. Subgroup analysis indicted that the benefits of statin usage varied from hormone receptor phenotype type. Prospective randomized trial with patients of different hormone receptor types might be needed to help identify which subtype of breast cancer patients would benefit from post-diagnostic statin usage.

Upregulation of ARHGAP30 attenuates pancreatic cancer progression by inactivating the ß-catenin pathway.

BACKGROUND: Pancreatic cancer is a highly malignant gastrointestinal cancer that can widely metastasize during the early stage of disease, and it is associated with one of the worst prognoses among cancers. In this study, we aimed to investigate the function of Rho GTPase-activating protein 30 (ARHGAP30) in pancreatic cancer cells and thus propose a novel therapy for pancreatic cancer. METHODS: ARHGAP30 expression in tumor tissues from patients with pancreatic cancer as well as cell lines was detected using immunohistochemistry (IHC), real-time polymerase chain reaction, and western blotting. Cell proliferation, transwell, and apoptosis assays were performed and the levels of related proteins were determined after ARHGAP30 knockdown or overexpression. Additionally, in vivo experiments were performed on nude mice. RESULTS: ARHGAP30 expression was found to be significantly increased in tumor tissues from patients with pancreatic cancer as well as in pancreatic cancer cell lines. IHC and prognostic analyses indicated that patients with high ARHGAP30 expression had a good prognosis. ARHGAP30 overexpression significantly decreased pancreatic cancer cell proliferation and metastasis; promoted apoptosis; reduced ß-catenin, B-cell lymphoma 2 (Bcl-2), matrix metalloproteinase-2 (MMP2), and MMP9 expression; and increased Bcl-2-associated X protein (Bax) and cleaved caspase-3 expression. ARHGAP30 knockdown elicited the opposite effects. The effects of ARHGAP30 knockdown were potently attenuated by the ß-catenin inhibitor XAV939. ARHGAP30 knockdown-induced RHOA activity was potently attenuated by the RHOA inhibitor CCG1423. In vivo, ARHGAP30 overexpression significantly inhibited lung metastasis in nude mice and increased the survival of mice with lung metastases. CONCLUSIONS: Our findings indicate that ARHGAP30 may function as a tumor suppressor in pancreatic cancer progression by regulating the expression of related genes and the ß-catenin pathway.

Cullin-1 promotes cell proliferation in human breast cancer and is related to diabetes.

AIM: Breast carcinoma (BCA) and diabetes mellitus (DM) are two major health problems in women and the general population. Cullin-1 is reported to be an important tumor-related protein involved in cell-cycle progression, signal transduction and transcription. The aim of this work is to investigate the role of Cullin-1 in the development of BCA and to find potential relationships between Cullin-1 and diabetes in BCA patients. METHODS: To evaluate the function of Cullin-1, we entered 168 patients with primary invasive BCA in this study. Pairs of BCA tissues and adjacent noncancerous tissues from these patients were collected between 2006 and 2008. We used immunohistochemistry to analyze the correlation between Cullin-1 expression and clinicopathological variables and patient survival. In addition, we investigated the role of Cullin-1 in BCA cell proliferation. RESULTS: Cullin-1 expression was upregulated in BCA tissues. Enhanced immunoreactivity for Cullin-1 in BCA tissues was inversely correlated with overall survival and disease-free survival, which suggested a poor prognosis in BCA patients. Strong expression of Cullin-1 was more frequently observed in patients with estrogen receptor negativity and HER2 positivity. We also found that Cullin-1 expression was increased in BCA patients with a previous diagnosis of diabetes. CONCLUSIONS: Our results demonstrate that increased Cullin-1 expression is significantly correlated with poor prognosis in patients with BCA. Cullin-1 might regulate BCA cell proliferation through the ubiquitin-proteasome system. Thus, Cullin-1 might be an important marker and a therapeutic target in BCA.

Influence of diabetes mellitus on mortality in breast cancer patients.

BACKGROUND: Breast cancer is one of the most common malignant tumours among women worldwide. Besides, diabetes mellitus is also a major health problem in developed countries. This study explores the association between diabetes mellitus and breast cancer patients' survival outcomes. METHODS: A systematic literature search in Embase (http://www.embase.com) and MEDLINE (http://www.ncbi.nlm.nih.gov/pubmed) was conducted from January 1960 to April 2014 and systematically identified clinical studies that evaluated the association between breast cancer mortality and diabetes mellitus. Clinical studies investigating the association between diabetes mellitus and breast cancer patients' survival outcomes were included. RESULTS: Twenty publications were chosen for the meta-analysis, of which 16 studies had all-cause mortality data and 12 studies had breast cancer mortality data. Published from 2001 to 2013, all 20 studies followed a total of 2,645,249 patients including more than 207,832 diabetic patients. Pre-existing diabetes mellitus was associated with a 37% increased risk for all-cause mortality in women with breast cancer (hazard ratio (HR) = 1.37; 95% confidence interval (CI): 1.34-1.41; P = 0.02). Diabetes mellitus was associated with a 17% increased risk for breast cancer mortality in women with breast cancer (HR = 1.17; 95% CI: 1.11-1.22; P < 0.01). CONCLUSIONS: Women with diabetes mellitus are at higher risk of breast cancer-specific and all-cause mortality after initial breast cancer diagnosis.

Current evidence on the relationship between CYP1B1 polymorphisms and lung cancer risk: a meta-analysis.

The association between single-nucleotide polymorphisms (SNPs) of the CYP1B1 gene and lung cancer risk is still ambiguous. In this meta analysis, we assessed 10 case-control studies included 7,067 cases and 9,374 controls of the association between CYP1B1 SNPs of Leu432Val (rs1056836, 432C>G), Asn453Ser (rs1800440, 453A>G), Ala119Ser (rs1056827, 119G>T), Arg48Gly (rs10012, 48C>G) and the risk of lung cancer. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of association between the polymorphism and lung cancer risk under codominant model, dominant model and additive model respectively. Although there were limitations, this meta analysis indicated that individuals with 432GG genotype had a 39.7% higher risk of having lung cancer than those with the 432CC genotype, and individuals with the 432G allele had a 26.3% increased risk as well. An increased risk of lung cancer of 2.13 fold was observed in individuals with 119TT genotype. For Arg48Gly, individuals with 48GG genotype had a significantly increased risk of lung cancer compared with individuals with 48CC (OR 3.859; 95% CI 2.536-5.87). Elevated risk of lung cancer were observed in dominant model (OR 2.115; 95% CI 1.653-2.705) as well. The risk of lung cancer was elevated as the frequency of G allele increased in additive model (P = 0.000). For individuals with the polymorphism at codon 453, no evidence of such association was observed. Furthermore, a possible association between the CYP1B1 polymorphism at codon 432 and the lung cancer could be detected in individuals of Caucasian origin, while a negative association was suggested in Asians and African-Americans. An increased lung cancer risk was also found in women with polymorphism at codon 453. These results are supportive for the hypothesis that the CYP1B1 432GG, 119TT and 48GG genotypes are low-penetrance risk factors for developing lung cancer, and further studies are needed to validate these associations.