Acquired docetaxel-resistance of prostate cancer (PCa) remains a clinical obstacle due to the lack of effective therapies. Acetyl-11-keto-β-boswellic acid (AKBA) is a pentacyclic triterpenic acid ...isolated from the fragrant gum resin of the Boswellia serrata tree, which has shown intriguing antitumor activity against human cell lines established from PCa, colon cancer, malignant glioma, and leukemia. In this study, we examined the effects of AKBA against docetaxel-resistant PCa in vitro and in vivo as well as its anticancer mechanisms. We showed that AKBA dose-dependently inhibited cell proliferation and induced cell apoptosis in docetaxel-resistant PC3/Doc cells; its IC
value in anti-proliferation was ∼17 μM. Furthermore, AKBA dose-dependently suppressed the chemoresistant stem cell-like properties of PC3/Doc cells, evidenced by significant decrease in the ability of mammosphere formation and down-regulated expression of a number of stemness-associated genes. The activation of Akt and Stat3 signaling pathways was remarkably enhanced in PC3/Doc cells, which contributed to their chemoresistant stem-like phenotype. AKBA (10-30 μM) dose-dependently suppressed the activation of Akt and Stat3 signaling pathways in PC3/Doc cells. In contrast, overexpression of Akt and Stat3 significantly attenuated the inhibition of AKBA on PC3/Doc cell proliferation. In docetaxel-resistant PCa homograft mice, treatment with AKBA significantly suppresses the growth of homograft RM-1/Doc, equivalent to its human PC3/Doc, but did not decrease their body weight. In summary, we demonstrate that AKBA inhibits the growth inhibition of docetaxel-resistant PCa cells in vitro and in vivo via blocking Akt and Stat3 signaling, thus suppressing their cancer stem cell-like properties.
A low-cost and green biorefinery will increase the economy and revenue from lignocellulosic biomass. Herein, a biomass-derived deep eutectic solvent (DES) pretreatment was developed to deconstruct ...the recalcitrant structure of Eucalyptus for further cellulose enzymatic hydrolysis and lignin valorization. The DES consisted of biomass-derived chemicals (lactic acid and choline chloride). The results showed that DES pretreatment resulted in notable removal of hemicelluloses and lignin, and drastically reduced “biomass recalcitrance”. Under the optimum conditions (DES ratio: 10 : 1, temperature: 110 °C, time: 6 h), the glucose yield by enzymatic hydrolysis reached 94.3%, which was significantly enhanced 9.8 times compared to that of the original biomass without DES pretreatment. The state-of-the-art analysis indicated that the regenerated lignin exhibited well-preserved structures ( i.e. , β- O -4, β–β linkages) without contaminated carbohydrates, and it had a relatively low and homogeneous molecular weight. All these structural characteristics suggested that lignin has great potential application in its conversion into bio-based chemicals and materials. Besides, it is urgent to develop low-cost recycled DESs as green solvents for sustainable biomass pretreatment. The lifetime and recyclability experiment of the DES solution showed that the recovery yield of the DES was at least 90% and the fundamental structural properties of the recycled DES were almost unchanged throughout the recycling cycles. More importantly, the pretreatment efficiency (delignification and enzymatic saccharification) was still largely maintained after the recycling process. Overall, this work demonstrated that biomass pretreatment with the recycled DES was promising for a low-cost biorefinery to achieve an efficient fractionation of lignocellulosic biomass into fermentable glucose and high-quality lignin with tailored chemical structures.
The traditional approach toward improving the crystallization rate as well as the mechanical and barrier properties of poly(lactic acid) (PLA) is the incorporation of nanocelluloses (NCs). ...Unfortunately, little study has been focused on the influence of the differences in NC morphology and dimensions on the PLA property enhancement. Here, by HCOOH/HCl hydrolysis of lyocell fibers, microcrystalline cellulose (MCC), and ginger fibers, we unveil the preparation of cellulose nanospheres (CNS), rod-like cellulose nanocrystals (CNC), and cellulose nanofibers (CNF) with different aspect ratios, respectively. All the NC surfaces were chemically modified by Fischer esterification with hydrophobic formate groups to improve the NC dispersion in the PLA matrix. This study systematically compared CNS, CNC, and CNF as reinforcing agents to induce different kinds of heterogeneous nucleation and reinforce the effects on the properties of PLA. The incorporation of three NCs can greatly improve the PLA crystallization ability, thermal stability, and mechanical strength of nanocomposites. At the same NC loading level, the PLA/CNS showed the highest crystallinity (19.8 ± 0.4%) with a smaller spherulite size (33 ± 1.5 μm), indicating that CNS, with its high specific surface area, can induce a stronger heterogeneous nucleation effect on the PLA crystallization than CNC or CNF. Instead, compared to PLA, the PLA/CNF nanocomposites gave the largest Young’s modulus increase of 350 %, due to the larger aspect ratio/rigidity of CNF and their interlocking or percolation network caused by filler–matrix interfacial bonds. Furthermore, taking these factors of hydrogen bonding interaction, increased crystallinity, and interfacial tortuosity into account, the PLA/CNC nanocomposite films showed the best barrier property against water vapor and lowest migration levels in two liquid food simulates (well below 60 mg kg–1 for required overall migration in packaging) than CNS- and CNF-based films. This comparative study was very beneficial for selecting reasonable nanocelluloses as nucleation/reinforcing agents in robust-barrier packaging biomaterials with outstanding mechanical and thermal performance.
Despite improvements in prevention and treatment, cervical cancer (CC) still poses a serious threat to women’s health. CHMP4C (chromatin modified protein 4C) is a subunit of the endosomal sorting ...complex required for transport, which is expressed in both nucleus and cytoplasm. Here, we examined the effect of CHMP4C on the biological behavior of CC cells and the underlying mechanisms. We report that CHMP4C expression is higher in CC tissues, and high CHMP4C expression is associated with lower survival. Up‐regulation of CHMP4C in C‐33A cells accelerates cell proliferation, migration and invasion, whereas down‐regulation of CHMP4C in Ca Ski cells had the opposite effect. Moreover, overexpression of CHMP4C induced activation of the epithelial–mesenchymal transition pathway, whereas depletion of CHMP4C inhibited activation. Our results suggest that CHMP4C contributes to the viability and motility of CC cells by modulating epithelial–mesenchymal transition and may facilitate the identification of novel biomarkers for CC therapy.
Chromatin modified protein 4C is highly expressed in cervical cancer (CC) tissues and cell lines, and contributes to the proliferation, invasion and migration of CC cells by modulating the epithelial–mesenchymal transition. Our findings may facilitate the identification of novel biomarkers for CC therapy.
The surge of patients in the pandemic of COVID‐19 caused by the novel coronavirus SARS‐CoV‐2 may overwhelm the medical systems of many countries. Mask‐wearing and handwashing can slow the spread of ...the virus, but currently, masks are in shortage in many countries, and timely handwashing is often impossible. In this study, the efficacy of three types of masks and instant hand wiping was evaluated using the avian influenza virus to mock the coronavirus. Virus quantification was performed using real‐time reverse transcription‐polymerase chain reaction. Previous studies on mask‐wearing were reviewed. The results showed that instant hand wiping using a wet towel soaked in water containing 1.00% soap powder, 0.05% active chlorine, or 0.25% active chlorine from sodium hypochlorite removed 98.36%, 96.62%, and 99.98% of the virus from hands, respectively. N95 masks, medical masks, and homemade masks made of four‐layer kitchen paper and one‐layer cloth could block 99.98%, 97.14%, and 95.15% of the virus in aerosols. Medical mask‐wearing which was supported by many studies was opposed by other studies possibly due to erroneous judgment. With these data, we propose the approach of mask‐wearing plus instant hand hygiene (MIH) to slow the exponential spread of the virus. This MIH approach has been supported by the experiences of seven countries in fighting against COVID‐19. Collectively, a simple approach to slow the exponential spread of SARS‐CoV‐2 was proposed with the support of experiments, literature review, and control experiences.
Objective
This study aimed to assess systematically the overall diagnostic value of urinary monocyte chemoattractant protein-1 (uMCP-1) in systemic lupus erythematosus (SLE) patients with active ...lupus nephritis (LN).
Methods
Articles from PubMed, Web of Science, EMBASE and Cochrane Library were retrieved up to 5 November 2019. Study quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, and statistical analyses were performed.
Results
A total of seven original studies with 521 participants were included in this meta-analysis. The summary estimates were: sensitivity 0.89 (95% confidence interval (CI) 0.86–0.93), specificity 0.63 (95% CI 0.55–0.69), positive likelihood ratio 2.16 (95% CI 1.66–2.80), negative likelihood ratio 0.15 (95% CI 0.08–0.30), diagnostic odds ratio 19.40 (95% CI 7.24–51.96) and area under the curve 0.9042.
Conclusion
As a non-invasive biomarker, uMCP-1 has high diagnostic accuracy for active LN.
Alternative polyadenylation (APA), which induces shortening of the 3′‐UTR, is emerging as an important feature in cancer development and progression. Nevertheless, the effects and mechanisms of ...APA‐induced 3′‐UTR shortening in nasopharyngeal carcinoma (NPC) remain largely unclear. Fibronectin type III domain containing 3B (FNDC3B) tended to use proximal polyadenylation site and produce shorter 3′‐UTR according to our previous sequencing study. Herein, we found that FNDC3B with shorter 3′‐UTR could escape from miRNA‐mediated gene repression, and caused its increased expression in NPC. Knocking down of FNDC3B inhibited NPC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Overexpression of FNDC3B, especially those with shorter 3′‐UTR, promoted NPC progression. Furthermore, the mechanism study revealed that FNDC3B could bind to and stabilize myosin heavy chain 9 (MYH9) to activate the Wnt/β‐catenin signaling pathway. In addition, MYH9 could reverse the inhibitory effects of FNDC3B knockdown in NPC. Altogether, our results suggested that the 3′‐UTR shortening of FNDC3B mRNA mediated its overexpression in NPC and promoted NPC progression by targeting MYH9. This newly identified FNDC3B‐MYH9‐Wnt/β‐catenin axis could represent potential targets for individualized treatment in NPC.
FNDC3B tended to use proximal polyadenylation site and produced shorter 3′‐UTR. FNDC3B with shorter 3′‐UTR could escape from microRNA‐mediated gene repression, and caused its increased expression in nasopharyngeal carcinoma (NPC) and promoted NPC progression by targeting MYH9.
Long noncoding RNAs (lncRNAs) have been indicated to play critical roles in cancer development and progression. LncRNA HOXD cluster antisense RNA1 (HOXD-AS1) has recently been found to be ...dysregulated in several cancers. However, the expression levels, cellular localization, precise function and mechanism of HOXD-AS1 in colorectal carcinoma (CRC) are largely unknown.
Real-time PCR and in situ hybridization were used to detect the expression of HOXD-AS1 in CRC tissue samples and cell lines. Gain- and loss-of-function experiments were performed to investigate the biological roles of HOXD-AS1 in CRC cell line. RNA pull down, RNA immunoprecipitation and chromatin immunoprecipitation assays were conducted to investigate the mechanisms underlying the functions of HOXD-AS1 in CRC.
We observed that HOXD-AS1 was located in the nucleus of CRC cells and that nuclear HOXD-AS1 was downregulated in most CRC specimens and cell lines. Lower levels of nuclear HOXD-AS1 expression were associated with poor outcomes of CRC patients. HOXD-AS1 downregulation enhanced proliferation and migration of CRC cells in vitro and facilitated CRC tumourigenesis and metastasis in vivo. Mechanistic investigations revealed that HOXD-AS1 could suppress HOXD3 transcription by recruiting PRC2 to induce the accumulation of the repressive marker H3K27me3 at the HOXD3 promoter. Subsequently, HOXD3, as a transcriptional activator, promoted Integrin β3 transcription, thereby activating the MAPK/AKT signalling pathways.
Our results reveal a previously unrecognized HOXD-AS1-HOXD3-Integrin β3 regulatory axis involving in epigenetic and transcriptional regulation constitutes to CRC carcinogenesis and progression.
Aims
To explore the association between cognitive emotion regulation strategies and anxiety and depression among nurses during the COVID‐19 outbreak.
Background
Nurses play a vital role in responding ...to the COVID‐19 outbreak, but many of them suffer from psychological problems due to the excessive workload and stress. Understanding the correlation between cognitive emotion regulation strategies and anxiety and depression will promote targeted psychosocial interventions for these affected nurses.
Methods
This cross‐sectional study of 586 nurses was conducted in Eastern China. Participants completed online questionnaires that investigated anxiety, depression and cognitive emotion regulation strategies.
Results
The prevalence of nurses' anxiety and depression was 27.6% and 32.8%, respectively. Lower self‐blame, rumination and catastrophizing, as well as greater acceptance and positive refocusing, were related to fewer symptoms of anxiety or depression.
Conclusion
The cognitive emotion regulation strategies of acceptance and positive refocusing contribute to reducing anxiety or depression. These strategies should be considered when implementing psychotherapeutic interventions to improve nurses' adverse emotional symptoms.
Implications for Nursing Management
This study highlights the need to assess cognitive emotion regulation strategies use in screening for anxiety and depression. Nurse managers should develop psychosocial interventions including appropriate strategies to help nurses with adverse emotions during a pandemic.
Pleural effusion (PE) is a common clinical complication of many pulmonary and systemic diseases, including lung cancer and tuberculosis. Nevertheless, there is no clinical effective biomarker to ...identify the cause of PE. We attempted to investigate differential expressed exosomal miRNAs in PEs of lung adenocarcinoma (APE), tuberculous (TPE), and other benign lesions (NPE) by using deep sequencing and quantitative polymerase chain reaction (qRT-PCR). As a result, 171 differentiated miRNAs were observed in 3 groups of PEs, and 11 significantly differentiated exosomal miRNAs were validated by qRT-PCR. We identified 9 miRNAs, including miR-205-5p, miR-483-5p, miR-375, miR-200c-3p, miR-429, miR-200b-3p, miR-200a-3p, miR-203a-3p, and miR-141-3p which were preferentially represented in exosomes derived from APE when compared with TPE or NPE, while 3 miRNAs, including miR-148a-3p, miR-451a, and miR-150-5p, were differentially expressed between TPE and NPE. These different miRNAs profiles may hold promise as biomarkers for differential diagnosis of PEs with more validation based on larger cohorts.
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