Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency ...of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next‐generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non‐BRCA1/2 gene. Major mutant non‐BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non‐BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER‐2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non‐BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non‐BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.
What's new?
The prevalence of mutations in breast cancer predisposition genesare not well investigated in Asia. We assessed germline mutations of 40 cancer susceptibility genes in 937 consecutive selected breast cancer patients from 26 centers of China, and discovered 23.8% of participates carried the pathogenic mutation, including 6.8% with mutations in non‐BRCA1/2 genes, while TP53 and PALB2 had a relatively high mutation rates (1.9% and 1.2%).There was no factors predicted for detrimental mutations in non‐BRCA1/2 genes when treated as a whole.
Aberrant expression of microRNAs (miRs) has been shown to play a critical role in the pathogenesis and progression of tumors. microRNA‐219‐5p (miR‐219‐5p) has been reported to be abnormally expressed ...in some types of human tumors. However, the mechanism between miR‐219‐5p and colorectal cancer (CRC) metastasis remains unclear. In the present study, miR‐219‐5p was found to be downregulated in CRC tissue compared with matched normal tissue. Through luciferase reporter assay, we demonstrated lymphoid enhancer‐binding factor 1 (LEF1) as a direct target of miR‐219‐5p. Overexpression of miR‐219‐5p could inhibit motility, migration and invasion of CRC cells, and inhibit epithelial‐mesenchymal transition (EMT). Furthermore, silencing LEF1 phenocopied this metastasis‐suppressive function. The recovery experiment showed that re‐expression of LEF1 rescued this suppressive effect on tumor metastasis and reversed the expression of EMT markers caused by miR‐219‐5p. Additionally, we demonstrated that miR‐219‐5p exerted this tumor‐suppressive function by blocking activation of the AKT and ERK pathways. Finally, a nude mice experiment showed that miR‐219‐5p reduced the lung metastasis ability of CRC cells. Taken together, our findings indicate that miR‐219‐5p inhibits metastasis and EMT of CRC by targeting LEF1 and suppressing the AKT and ERK pathways, which may provide a new antitumor strategy to delay CRC metastasis.
We determined miR‐219‐5p as a tumor suppressor that can block the expression of LEF1, thereby inhibiting EMT in CRC via inactivating the AKT and MAPK signaling pathways. This presents a promising strategy for treating CRC metastasis. Targets of miR‐219 other than LEF1 need to be identified to fully understand its activity. Our elucidation of the roles of miR‐219‐5p in EMT and metastasis of CRC will enable the discovery of specific therapeutic approaches for CRC patients.
Objectives/Hypothesis
The role of respiratory viral infection in the pathogenesis of chronic rhinosinusitis (CRS) has been rarely studied and remains controversial. The aim of this study was to ...explore the prevalence of respiratory viruses in the chronic status of CRS.
Study Design
A case‐control prospective study.
Methods
Fifty‐three control subjects, and 67 CRS with nasal polyp (CRSwNP) and 61 CRS without nasal polyp (CRSsNP) patients without signs of acute viral infection were enrolled. Epithelial cells scraped from the middle nasal meatus were tested for the nucleic acid of nine common respiratory viruses using polymerase chain reaction assay. The clinical disease severity was compared between subjects with and without viral infection.
Results
The overall detection rate of viral infection was 75.47%, 68.66%, and 73.77% in controls, CRSwNP, and CRSsNP, respectively, and no significant difference among studied groups was observed. There was no significant difference in detection rate of any specific individual virus or multiple viruses among the groups studied either. Visual analog scale scores of symptoms, computed tomography scores, or endoscope scores did not show obvious difference between subjects with and without viral infection.
Conclusions
Although a high frequency of viral infection could be observed in the middle nasal meatus, no increase of frequency of viral infection could be demonstrated in chronic persistent phase of CRSsNP and CRSwNP. The contribution of the interaction between viral infection and host immunity to the pathogenesis of CRS remains to be determined.
Level of Evidence
3b. Laryngoscope, 124:832–837, 2014
Biological remediation including bioremediation and phytoremediation has been used to remediate contaminated sites due to their cost-effectiveness, energy conservation, and environmental ...friendliness. There are 24 articles in Critical Reviews in Environmental Science and Technology (CREST) from 2018 to 2022 focusing on this topic. Bioremediation employs microorganisms to modify and/or degrade contaminants, while phytoremediation uses plants to remove, contain, and/or change contaminants. They cover different contaminants including traditional (nutrients, petroleum hydrocarbons, organo-pesticides, plastics, and heavy metals such as Cd, Cr, Pb and U) and emerging contaminants (pharmaceutical and personal care products, and perfluoroalkyl and polyfluoroalkyl substances). However, these remediation technologies have limitations in applications including lengthy periods, environmental sensitivity, nutrient deficiency and contaminant toxicity. Therefore, improvement strategies including immobilization of microbial/microalgal cells, construction of microbial/microalgal consortia, and use of amendments have been employed to overcome its drawbacks. Further studies should focus on cost-effective strategies to enhance the efficiency of biological remediation and their environmental adaptability, especially under extreme environments and with emerging contaminants. Microbes, microalgae and plants with good contaminant removal capability should be coupled with engineering practices based on their interactive mechanisms among bio-association and contaminants at molecular levels.
Nonalcoholic steatohepatitis (NASH) is among the most common liver diseases in the world. Flavonoids from Scutellaria amoena (SAF) are used in the treatment of hepatopathy in China. However, the ...effect and mechanism against NASH remain unclear. We investigated the alleviating effect of SAF on NASH via regulating mitochondrial dysfunction and oxidative stress.
The effects of SAF on NASH were evaluated using in vitro and in vivo methods. L02 cells were induced by fat emulsion to establish an adipocytes model, followed by treatment with SAF for 24 h. NASH rat models were established by the administration of a high-fat diet for 12 weeks and were administered SAF for six weeks. Changes in body weight, organ indexes, lipid levels, inflammatory cytokines, mitochondrial indicators, and fatty acid metabolism were investigated.
SAF significantly improved body weight, organ indexes, lipid levels, liver injury, and inflammatory infiltration in NASH rats. SAF notably regulated interleukin-6, tumor necrotic factor-alpha, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), kelch-like ECH-associated protein 1 (Keap1), nuclear factor-erythroid factor 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Additionally, SAF improved mitochondrial dysfunction, increased the levels of GSH, SOD, ATP synthase, complex I and II, and decreased the level of MDA in liver mitochondria. SAF regulated the expression of β-oxidation genes, including peroxisome proliferator-activated receptor -gamma coactivator-1alpha (PGC-1α), carnitine palmitoyltransferase-1 (CPT1) A, CPT1B, medium-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, very long-chain acyl-CoA dehydrogenase, and PPARα.
SAF can alleviate NASH by regulating mitochondrial function and oxidative stress via the Keap1/Nrf2/HO-1 axis.
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•SAF has a strong effect on improving NASH.•SAF can alleviate HFD-induced NASH by regulating mitochondrial dysfunction.•SAF improves HFD-induced NASH by regulating oxidative stress Keap1/Nrf2/HO-1 axis.•SAF offers new mitochondrial regulators/nutrients for NASH.
Clavulanic acid (CA) is usually used together with other β‐lactam antibiotics as combination drugs to inhibit bacterial β‐lactamases, which is mainly produced from the fermentation of microorganism ...such as Streptomyces clavuligerus. Recently, it is still a challenge for downstream processing of low concentration and unstable CA from fermentation broth with high solid content, high viscosity, and small cell size. In this study, an integrated process was developed for simultaneous solid–liquid separation and primary purification of CA from real fermentation broth of S. clavuligerus using salting‐out extraction system (SOES). First, different SOESs were investigated, and a suitable SOES composed of ethanol/phosphate was chosen and further optimized using the pretreated fermentation broth. Then, the optimal system composed of 20% ethanol/15% K2HPO4 and 10% KH2PO4 w/w was used to direct separation of CA from untreated fermentation broth. The result showed that the partition coefficient (K) and recovery yield (Y) of CA from untreated fermentation broth were 29.13 and 96.8%, respectively. Simultaneously, the removal rates of the cells and proteins were 99.8% and 63.3%, respectively. Compared with the traditional method of membrane filtration or liquid–liquid extraction system, this developed SOES showed the advantages of simple operation, shorter operation time, lower process cost and higher recovery yield of CA. These results demonstrated that the developed SOES could be used as an attractive alternative for the downstream processing of CA from real fermentation broth.
Summary We explored the relations between PTEN/PI3K/AKT expression and clinicopathological characteristics and prognosis in breast cancer patients with and without axillary lymph node metastasis ...(LNM). Tissues and follow-up data from 142 patients with (LNM group) and 154 without (non-LNM group) metastases were collected. Expression of PTEN/PI3K/AKT was detected using immunohistochemistry staining. With axillary LNM, the positive rate of PTEN was reduced, whereas that of PI3K and AKT was increased. Expression of AKT was negatively correlated with PTEN expression but positively correlated with PI3K expression. Apparent correlations were detected between AKT and axillary LNM with a tumor size of 2 cm or less; between PTEN, PI3K, and AKT and axillary LNM in stage T1 or T2 breast cancer and invasive carcinoma of a nonspecial type; and between PTEN and AKT and axillary LNM of histologic grade I or II tumors and non–triple-negative breast cancer (all P < .05). In the LNM group, the 5-year survival rate of patients with PTEN-positive tumors was higher than that of patients with PTEN-negative lesions; whereas in the non-LNM group, the 5-year survival rate of patients with AKT-positive tumors was lower than that of patients with AKT-negative lesions (both P < .05). Cox regression analysis showed that PTEN expression was an independent prognostic factor for patients with LNM; AKT expression, tumor diameter, pathologic grade, and pathologic type were independent prognostic factors for patients without LNM. In conclusion, TEN/PI3K/AKT proteins are related to the clinicopathological features and prognosis of breast cancer with axillary LNM.
Purpose:
This study aimed to investigate the applicability of plasma extracellular vesicles (EVs) miR-99a-5p as a potential head and neck squamous cell carcinoma (HNSCC) diagnostic biomarker.
...Methods:
The miRNA expression of HNSCC tissue and plasma EVs were profiled by small RNA sequencing. qRT-PCR was performed to detect miR-99a-5p expression in HNSCC (
n
= 93) and benign disease (
n
= 39) plasma EVs and formalin-fixed and paraffin-embedded (FFPE) tissue (
n
= 110). We constructed receiver-operating characteristic curves to investigate the diagnostic efficiency of plasma EVs miR-99a-5p.
Results:
Tumor tissue exhibited lower miR-99a-5p than para-tumor tissue. Patients with high miR-99a-5p expression exhibited significantly more p16 positive status. In contrast, HNSCC plasma EVs harbored more miR-99a-5p than the benign disease group. Plasma EVs miR-99a-5p distinguished HNSCC with area under the curve (AUC) of 0.7494 (95% CI: 0.6692–0.8296;
p
< 0.0001), with 61.54% sensitivity and 75.27% specificity, respectively. Furthermore, plasma EVs miR-99a-5p also distinguished early HNSCC with AUC of 0.7394 (95% CI: 0.6284–0.8504;
p
= 0.0002), with 79.07% sensitivity and 61.54% specificity, respectively.
Conclusion:
Plasma EVs miR-99a-5p is a potential biomarker for predicting early HNSCC.
Semiconductor nanoparticle/graphene composite photocatalysts containing semiconductor CdS or TiO sub(2) nanoparticles are fabricated by one-pot solution methods and their structures are ...characterized. The photocatalytic hydrogen-generating capabilities of the composite photocatalysts are investigated in the presence of sacrificial reagent and compared with those of the same semiconductor materials with platinum as a co-catalyst under the same conditions. The results obtained by the measurements of time-resolved emission spectra, photocurrent generated response and electrochemical impedance spectra revealed that graphene attached to semiconductor surfaces can efficiently accept and transport electrons from the excited semiconductor, suppressing charge recombination and improving interfacial charge transfer processes. The semiconductor nanoparticle/graphene photocatalysts displayed higher activity for photocatalytic hydrogen evolution, which can be compared with the hydrogen-generating efficiency of systems containing the well-known Pt co-catalyst. This work provides an inexpensive means of harnessing solar energy to achieve highly efficient hydrogen evolution without noble metals.
Ageratina adenophora is a noxious plant and it is known to cause acute asthma, diarrhea, depilation, and even death in livestock (Zhu et al., 2007; Wang et al., 2017). A. adenophora grows near ...roadsides and degraded land worldwide (He et al., 2015b). In the areas where it grows, A. adenophora is an invasive species that inhibits the growth of local plants and causes poisoning in animals that come in contact with it (Nie et al., 2012). In China, these plants can be found in Yunnan, Sichuan, Guizhou, Chongqing, and other southwestern areas (He et al., 2015a) and they have become a dominant species in these local regions. It threatens the native biodiversity and ecosystem in the invaded areas and causes serious economic losses (Wang et al., 2017). It has been reported that A. adenophora can grow in the northeast direction at a speed of 20 km per year in China (Guo et al., 2009). Because of the damage caused by A. adenophora, it ranks among the earliest alien invasive plant species in China (Wang et al., 2017).
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