Tumor promoter TPA activates Wnt/β-catenin signaling in a casein kinase 1-dependent manner.

The tumor promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA) has been defined by its ability to promote tumorigenesis on carcinogen-initiated mouse skin. Activation of Wnt/β-catenin signaling has a decisive role in mouse skin carcinogenesis, but it remains unclear how TPA activates Wnt/β-catenin signaling in mouse skin carcinogenesis. Here, we found that TPA could enhance Wnt/β-catenin signaling in a casein kinase 1 (CK1) ε/δ-dependent manner. TPA stabilized CK1ε and enhanced its kinase activity. TPA further induced the phosphorylation of LRP6 at Thr1479 and Ser1490 and the formation of a CK1ε-LRP6-axin1 complex, leading to an increase in cytosolic β-catenin. Moreover, TPA increased the association of β-catenin with TCF4E in a CK1ε/δ-dependent way, resulting in the activation of Wnt target genes. Consistently, treatment with a selective CK1ε/δ inhibitor SR3029 suppressed TPA-induced skin tumor formation in vivo, probably through blocking Wnt/β-catenin signaling. Taken together, our study has identified a pathway by which TPA activates Wnt/β-catenin signaling

Efficacy and safety of pharmacotherapy for refractory or unexplained chronic cough: a systematic review and network meta-analysis

Background: Refractory chronic cough (RCC) has a significant impact on patient's health-related quality of life and represents a challenge in clinical management. However, the optimal treatment for RCC remains controversial. This study aimed to investigate and compare the efficacy and safety of the current pharmacological therapeutic options for RCC. Methods: A systematic review was performed by searching PubMed, Web of Science, Embase, and Ovid databases from January 1, 2008 to March 1, 2023. All randomised control trials (RCTs) reporting outcomes of efficacy or/and safety were included in the Bayesian network meta-analysis. Here, we compared the effects on Leicester Cough Questionnaire (LCQ), Visual Analogue Scale (VAS), and objective cough frequency of patients with RCC. Besides, we also compared the incidence of adverse events (AEs) for analysis of safety. PROSPERO registration: CRD42022345940. Findings: 19 eligible RCTs included 3326 patients and 7 medication categories: P2X3 antagonist, GABA modulator, Transient Receptor Potential (TRP) modulator, NK-1 agonist, opioid analgesic, macrolide, and sodium cromoglicate. Compared with placebo, mean difference (MD) of LCQ and 24 h cough frequency for P2X3 antagonist relief were 1.637 (95% CI: 0.887–2.387) and −11.042 (P = 0.035). Compared with placebo, effect sizes (MD for LCQ and cough severity VAS) for GABA modulator were 1.347 (P = 0.003) and −7.843 (P = 0.003). In the network meta-analysis, gefapixant is the most effective treatment for patients with RCC (The Surface Under the Cumulative Ranking Curves (SUCRA) is 0.711 in LCQ, 0.983 in 24 h cough frequency, and 0.786 in cough severity VAS). Lesogaberan had better efficacy than placebo (SUCRA: 0.632 vs. 0.472) in 24 h cough frequency. Eliapixant and lesogaberan had better efficacy than placebo in cough severity VAS. However, TRP modulator had worse efficacy than placebo. In the meta-analysis of AEs, the present study found P2X3 antagonist had a significant correlation to AEs (RR: 1.129, 95% CI: 1.012–1.259), especially taste-related AEs (RR: 6.216, P < 0.05). Interpretation: In this network meta-analysis, P2X3 antagonist showing advantages in terms of efficacy is currently the most promising medication for treatment of RCC. GABA modulator also showed potential efficacy for RCC but with AEs of the central system. Nevertheless, the role of TRP modulator needed to be revisited. Further research is needed to determine the potential beneficiary population for optimizing the pharmacological management of chronic cough. Funding: National Natural Science Foundation of China ( 81870079), Guangdong Science and Technology Project ( 2021A050520012), Incubation Program of National Science Foundation for Distinguished Young Scholars ( GMU2020-207)

Enhanced secretion of hepatocyte growth factor in human umbilical cord mesenchymal stem cells ameliorates pulmonary fibrosis induced by bleomycin in rats

Umbilical cord mesenchymal stem cells (UCMSCs) are a reportedly promising choice in the treatment of irreversible pulmonary fibrosis and lethal interstitial lung disease with limited drug treatment options. In this study, we investigated the therapeutic efficacy of UCMSCs overexpressing hepatocyte growth factor (HGF), which is considered one of the main anti-fibrotic factors secreted by MSCs. Adenovirus vector carrying the HGF gene was transfected into UCMSCs to produce HGF-modified UCMSCs (HGF-UCMSCs). Transfection promoted the proliferation of UCMSCs and did not change the morphology, and differentiation ability, or biomarkers. Rats were injected with HGF-UCMSCs on days 7 and 11 after intratracheal administration of bleomycin (10 mg/kg). We performed an analysis of histopathology and lung function to evaluate the anti-fibrotic effect. The results showed that HGF-UCMSCs decreased the Ashcroft scores in hematoxylin and eosin-stained sections, the percentage positive area in Masson trichrome-stained sections, and the hydroxyproline level in lungs. Forced expiratory volume in the first 300 m/forced vital capacity was also improved by HGF-UCMSCs. To explore the possible therapeutic mechanism of HGF-UCMSCs, we detected inflammatory factors in the lungs and performed mRNA sequencing in UCMSCs and HGF-UCMSCs. The data indicated that inhibition of interleukin-17 in the lung may be related to the anti-fibrosis of HGF-UCMSCs, and overexpressed HGF probably played a primary role in the treatment. Collectively, our study findings suggested that the overexpression of HGF may improve the anti-fibrotic effect of UCMSCs through directly or indirectly interacting with interleukin-17-producing cells in fibrotic lungs

Disarm The Bacteria: What Temperate Phages Can Do

In the field of phage applications and clinical treatment, virulent phages have been in the spotlight whereas temperate phages received, relatively speaking, less attention. The fact that temperate phages often carry virulent or drug-resistant genes is a constant concern and drawback in temperate phage applications. However, temperate phages also play a role in bacterial regulation. This review elucidates the biological properties of temperate phages based on their life cycle and introduces the latest work on temperate phage applications, such as on host virulence reduction, biofilm degradation, genetic engineering and phage display. The versatile use of temperate phages coupled with their inherent properties, such as economy, ready accessibility, wide variety and host specificity, make temperate phages a solid candidate in tackling bacterial infections

Wnt/GSK3β/β-catenin signaling pathway regulates calycosin-mediated anticancer effects in glioblastoma multiforme cells

Calycosin, an O-methylated isoflavone, has been widely reported to induce anticancer activity in different cancer cells in vitro. Nonetheless, the associated mechanism of calycosin in glioblastoma multiforme cells (U87) still remains unknown. To explore the anticancer effects, the apoptotic mechanism of calycosin via Wnt/GSK3β/β-catenin signaling was explored in U87 cells. Different assays including: cytotoxicity, free radical determination, SOD and CAT activity, GSH content, qPCR, mitochondrial membrane potential, caspase activity, and western blotting assays were performed. It was shown that calycosin mitigated cell viability in U87 cells, whereas it showed no apparent effect on BV2 microglial cells. Calycosin triggered apoptosis via upregulating the mitochondria-associated caspase pathway in U87 cells. Calycosin induced the reduction of the mitochondrial membrane potential, overexpression of Bax, downexpression of Bcl-2, and activation of caspase-9 and caspase-3. Calycosin-stimulated apoptosis was associated with the upregulation of free radical scavenging through the modulation of antioxidant enzymes, such as SOD and CAT as well as the level of GSH. The apoptotic activity of calycosin was mediated by suppression of pGSK-3βser9, β-catenin, and c-Myc at protein level. The present study suggested that calycosin triggers U87 cell death through an antioxidant effect mediated by Wnt/GSK3β/β-catenin signaling pathway

Bayer Image Demosaicking Using Eight-Directional Weights Based on the Gradient of Color Difference

In this paper, we propose a new demosaicking algorithm which uses eight-directional weights based on the gradient of color difference (EWGCD) for Bayer image demosaicking. To obtain the interpolation of green (G) pixels, the eight-directional G pixel values are first estimated in red (R)/blue (B) pixels. This estimate is used to calculate the color difference in R/B pixels of the Bayer image in diagonal directions. However, in horizontal and vertical directions, the new estimated G pixels are defined to obtain the color difference. The eight-directional weights of estimated G pixels can be obtained by considering the gradient of the color difference and the gradient of the RGB pixels of the Bayer image. Therefore, the eight-directional weighted values and the first estimated G pixel values are combined to obtain the full G image. Compared with six similar algorithms using the same eighteen McMaster images, the results of the experiment demonstrate that the proposed algorithm has a better performance not only in the subjective visual measurement but also in the assessments of peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) index measurement

Emotional labour strategies and job burnout: A meta-analysis of Chinese employees

Emotional labour strategies have a significant impact on job burnout. However, current research results are controversial and unclear. A meta-analysis was conducted to explore the relationship between emotional labour strategies (surface acting and deep acting) and job burnout. A total of 84 empirical studies that included 28,242 participants were selected. The meta-analysis of the relationships between job burnout and surface acting and deep acting included 84 and 75 independent samples respectively. The results show that surface acting had a positive association (r = 0.25) with job burnout, whereas deep acting (r = -0.27) had a negative association with job burnout. Occupational types and measures of emotional labour strategies moderated the relationship between emotional labour strategies and job burnout, but this relationship was not moderated by measures of job burnout

Aerobic and Anaerobic Biodegradation of 1,2-Dibromoethane by a Microbial Consortium under Simulated Groundwater Conditions

This study was conducted to explore the potential for 1,2-Dibromoethane (EDB) biodegradation by an acclimated microbial consortium under simulated dynamic groundwater conditions. The enriched EDB-degrading consortium consisted of anaerobic bacteria Desulfovibrio, facultative anaerobe Chromobacterium, and other potential EDB degraders. The results showed that the biodegradation efficiency of EDB was more than 61% at 15 &deg;C, and the EDB biodegradation can be best described by the apparent pseudo-first-order kinetics. EDB biodegradation occurred at a relatively broad range of initial dissolved oxygen (DO) from 1.2 to 5.1 mg/L, indicating that the microbial consortium had a strong ability to adapt. The addition of 40 mg/L of rhamnolipid and 0.3 mM of sodium lactate increased the biodegradation. A two-phase biodegradation scheme was proposed for the EDB biodegradation in this study: an aerobic biodegradation to carbon dioxide and an anaerobic biodegradation via a two-electron transfer pathway of dihaloelimination. To our knowledge, this is the first study that reported EDB biodegradation by an acclimated consortium under both aerobic and anaerobic conditions, a dynamic DO condition often encountered during enhanced biodegradation of EDB in the field

Identification and Analysis of <i>Phosphatidylethanolamine-Binding Protein</i> Family Genes in the Hangzhou White Chrysanthemum (<i>Chrysanthemum morifolium</i> Ramat)

The Hangzhou White Chrysanthemum (Chrysanthemum morifolium Ramat) is one of the “Zhejiang eight flavors” in traditional Chinese medicine. The phosphatidylethanolamine-binding protein (PEBP) plays an important role in flowering and floral organ development. Even so, the biological role of PEBPs in the Hangzhou White Chrysanthemum has not been studied, which attracted us. Here, nine CmPEBP genes that contain the PF01161 domain were identified in the Hangzhou White Chrysanthemum for the first time, and their biological role in flowering was preliminarily studied. A phylogenetic analysis classified the CmPEBP genes into three subfamilies: MFT-like, TFL-like, and FT-like genes. The differential expression analysis was performed under different tissues and different stressors using qRT-PCR. It showed that each CmPEBP displayed tissue-specific expression patterns. Expression patterns in response to different temperatures and hormone stressors were investigated. They were finally demonstrated to be differentially expressed. TFL-like gene expression, which delayed reproductive growth, was upregulated under heat stress. Conversely, FT-like gene expression was upregulated under low temperatures. CmFT1 expression could be inhibited by GA (gibberellin), 6-BA (benzylaminopurine), ET (ethylene), and MeSA (methyl salicylate) but could be activated by IAA (indole-3-aceticacid), ABA (abscisic acid), and SA (salicylic acid) in the dark, whereas CmFT2 and CmFT3 expression levels were upregulated by ET, MeJA (methyl jasmonate), and ABA but were downregulated by 6-BA, SA, and MeSA. GA, IAA, SA, and MeSA inhibited CmTFL gene expression under light and dark treatments. Further research on CmPEBP genes in the Hangzhou White Chrysanthemum could better determine their roles in flowering and floral organ development, especially in response to the prolonged spraying of exogenous hormones

Isolation and Characterization of a Bacterial Strain Capable of Efficient Berberine Degradation

Background: Berberine (BBR) is a pharmaceutical chemical with a broad antibacterial spectrum, and its biological treatment has been of research and practical interest. In this study, a pure bacterial strain B16 was isolated from the activated sludge in a pharmaceutical wastewater treatment plant. The aim of the study is to characterize the properties of the strain B16, especially its BBR degradation capability. Methods: The identification of strain B16 was conducted by visual observation, as well as biochemical and phylogenetic analysis. The degradation kinetics of strain B16 was tentatively described by Haldane model. Results: The strain B16 was 100% determined as a Sphingopyxis sp. The kinetic parameters of BBR degradation by strain B16 were as follows: Vmax 54.73 &#177; 5.54 mg (g MLSS &#183; h)&#8722;1, Km 66.68 &#177; 8.95 mg L&#8722;1, and Ki 43.16 &#177; 5.92 mg L&#8722;1, with an R2 of 0.996. Stain B16 exhibited considerable capability of BBR degradation. BBR of initial concentration 40 mg L&#8722;1 could be completely degraded in 48 h under optimal conditions. Conclusions: strain B16 was the first pure culture found with the ability to totally mineralize BBR, indicating the potential of B16 application in real industrial processes