Hsp90 Promotes Gastric Cancer Cell Metastasis and Stemness by Regulating the Regional Distribution of Glycolysis-Related Metabolic Enzymes in the Cytoplasm.

Heat-shock protein 90 (Hsp90) plays a crucial role in tumorigenesis and tumor progression; however, its mechanism of action in gastric cancer (GC) remains unclear. Here, the role of Hsp90 in GC metabolism is the focus of this research. High expression of Hsp90 in GC tissues can interact with glycolysis, collectively affecting prognosis in clinical samples. Both in vitro and in vivo experiments demonstrate that Hsp90 is able to regulate the migration and stemness properties of GC cells. Metabolic phenotype analyses indicate that Hsp90 influences glycolytic metabolism. Mechanistically, Hsp90 interacts with glycolysis-related enzymes, forming multienzyme complexes to enhance glycolysis efficiency and yield. Additionally, Hsp90 binds to cytoskeleton-related proteins, regulating the regional distribution of glycolytic enzymes at the cell margin and lamellar pseudopods. This effect could lead to a local increase in efficient energy supply from glycolysis, further promoting epithelial-mesenchymal transition (EMT) and metastasis. In summary, Hsp90, through its interaction with metabolic enzymes related to glycolysis, forms multi-enzyme complexes and regulates regional distribution of glycolysis by dynamic cytoskeletal adjustments, thereby promoting the migration and stemness of GC cells. These conclusions also support the potential for a combined targeted approach involving Hsp90, glycolysis, and the cytoskeleton in clinical therapy.

When and how does the practice environment most benefit the job outcomes of newly graduated nurses?

BACKGROUND: Providing a favourable practice environment has been regarded as an essential to improve the job outcomes of newly graduated nurses (NGNs). However, little is known about how and when NGNs can best utilize their practice environment to produce optimal job outcomes. AIM: The aim of this study, which is based on the Conservation of Resources Theory and the Social Cognitive Model of Career Self-Management, is to investigate whether NGNs who have a higher level of personal growth initiative are more likely to benefit from their practice environment and achieve better job outcomes by increasing their occupational self-efficacy. DESIGN: A cross-sectional study. METHODS: From 1 September 2022, to 30 September 2022, 279 NGNs from five Chinese state-owned hospitals were recruited for this study. The participants completed measures of practice environment, personal growth initiative, occupational self-efficacy, job stress, job satisfaction, turnover intention and quality of care. A descriptive analysis and a moderated mediation model were computed. Reporting adhered to the STROBE statement. RESULTS: The influence of the practice environment on job outcomes was significantly mediated by occupational self-efficacy, with personal growth initiative acting as a moderator of this mediation effect. CONCLUSIONS: NGNs who exhibited a higher degree of personal growth initiative were more likely to derive benefits from their practice environment and attain positive job outcomes by enhancing their occupational self-efficacy. To boost NGNs' occupational self-efficacy and achieve optimal job outcomes, hospital administrators may not only provide a supportive practice environment for them but also conduct interventions that promote their personal growth initiative. NO PATIENT OR PUBLIC CONTRIBUTION: This study was designed to examine the psychosocial factors associated with NGNs' job outcomes. The study was not conducted using suggestions from the patient groups or the public. IMPACTS: Our findings indicate that favourable practise contexts may not always benefit the nursing job outcome if NGNs do not exhibit a high level of personal growth initiative and produce increased occupational self-efficacy. Therefore, hospital administrators should consider implementing an intervention to improve the personal growth initiative of NGNs so that they can take full advantage of the practice environment and gain resources at work to create optimal job outcomes.

Partial Substitution of Whey Protein Concentrate with Spray-Dried Porcine Plasma or Soy Protein Isolate in Milk Replacer Differentially Modulates Ileal Morphology, Nutrient Digestion, Immunity and Intestinal Microbiota of Neonatal Piglets.

Appropriate protein sources are vital for the growth, development and health of neonates. Twenty-four 2-day-old piglets were randomly divided into three groups and fed isoenergetic and isonitrogenous diets. The experimental diets included a milk replacer with 17.70% whey protein concentrate (WPC group), a milk replacer with 6% spray-dried porcine plasma isonitrogenously substituting WPC (SDPP group), and a milk replacer with 5.13% soy protein isolate isonitrogenously substituting WPC (SPI group). Neonatal piglets were fed milk replacer from postnatal day 2 (PND 2) to day 20 (PND 20). The growth performance, intestinal morphology, activities of digestive enzymes, plasma biochemical parameters, immunity-related genes, short-chain fatty acids (SCFA) and intestinal microbiota in the colonic chyme were determined. The results showed that SDPP-fed piglets had higher final BW (p = 0.05), ADG (p = 0.05) and F/G (p = 0.07) compared with WPC- and SPI-fed piglets, and SDPP-fed piglets had a lower diarrhea index (p < 0.01) from PND 2 to PND 8. SDPP-fed piglets had an increased ileal villus height (p = 0.04) and ratio of villus height to crypt depth (VCR) (p = 0.02), and increased activities of sucrase (p < 0.01), lactase (p = 0.02) and trypsin (p = 0.08) in the jejunum, compared with WPC- and SPI-fed piglets. Furthermore, SPI-fed piglets had an increased mRNA expression of IL-6 (p < 0.01) and concentration of plasma urea (p = 0.08). The results from LEfSe analysis showed that SDPP-fed piglets had a higher abundance of beneficial Butyricicoccus compared with WPC- and SPI-fed piglets, in which higher abundances of pathogenic bacteria such as Marinifilaceae, Fusobacterium and Enterococcus were observed. Moreover, SDPP-fed piglets had an increased concentration of butyric acid (p = 0.08) in the colonic chyme compared with WPC- and SPI-fed piglets. These results suggest that neonatal piglets fed milk replacer with SDPP partially substituting WPC had improved growth performance and intestinal morphology and function, associated with higher digestive enzyme activity and fewer pathogenic bacteria.

Palladin promotes cancer stem cell-like properties in lung cancer by activating Wnt/Β-Catenin signaling.

BACKGROUND: Cancer stem cells (CSCs) are responsible for drug resistance, cancer relapse, and metastasis. Here, we report the first analysis of Palladin expression and its impacts on stem cell-like properties in lung cancer. METHODS: Tissue microarrays were used to investigate Palladin expression and its association with prognosis. Immunofluorescence (IF), flow fluorescence assay, and Western blot were performed to detect Palladin expression in 6 NSCLC cell lines. Cell phenotypes and drug resistance were evaluated. Xenograft models were constructed to confirm the role of Palladin in vivo. RESULTS: By using the tissue microarrays, Palladin was identified to be highly expressed in the cytoplasm, specifically in the cytomembrane of NSCLC, and its high expression is associated with poor prognosis. Palladin is widely expressed and enriched in the sphere cells. The in vitro and in vivo studies showed that Palladin promoted stem cell-like properties, including cell viability, invasion, migration, self-renewal abilities, taxol resistance, and tumorigenicity. Western blot revealed that Palladin promoted the accumulation of ß-catenin and activated Wnt/ß-catenin signaling. Tissue microarrays analysis further confirmed the positive correlation between Palladin and ß-catenin. Wnt/ß-catenin pathway inhibitor blocked the Palladin-induced enhancement of sphere-forming. CONCLUSIONS: Palladin might act as an oncogene by promoting CSCs-like properties and tumorigenicity of NSCLC cells via the Wnt/ß-catenin signaling pathway. Besides, Palladin was identified to have the potential as a cell surface marker for LCSCs identification. These findings provide a possible target for developing putative agents targeted to LCSCs.

Long-term maternal intake of inulin exacerbated the intestinal damage and inflammation of offspring rats in a DSS-induced colitis model.

This study aimed to investigate the effects of long-term maternal intake of inulin on intestinal morphology, permeability, inflammation and microbiota of offspring rats treated with dextran sulfate sodium (DSS). Sixteen female adult Sprague-Dawley rats were assigned to two groups receiving the fiber-free diet (FFD) or inulin diet (INU, 5% inulin) for three parities. The offspring weaned rats (third-parity) were fed with the same diet for four weeks until receiving 6% DSS for 7 days; the four groups were as follows: FFD, FFD + DSS, INU and INU + DSS. The results showed that maternal intake of inulin increased the histopathology score and activity of diamine oxidase (DAO) in serum, and the highest histopathology scores and activity of DAO were observed in INU + DSS rats. Maternal intake of inulin increased the activity of myeloperoxidase (MPO), mRNA expressions of inflammatory factors and protein expression of IL-1ß in colonic tissues. Likewise, INU + DSS rats had the highest activity of MPO and mRNA expressions of inflammatory factors in colonic tissues. Maternal intake of inulin increased the abundances of Bacteroidetes, Bacteroides and Parasutterella, which were the highest enriched in INU + DSS rats. The level of acetate in the colonic digesta of INU + DSS rats was lower than that in FFD and INU rats. These results indicated that long-term maternal intake of inulin exacerbated the intestinal damage and inflammation of DSS-induced offspring rats, associated with the decreased level of acetate and altered intestinal microbiota.

Transcriptomic Profiling in Mice With CB1 receptor Deletion in Primary Sensory Neurons Suggests New Analgesic Targets for Neuropathic Pain.

Type 1 and type 2 cannabinoid receptors (CB1 and CB2, respectively) mediate cannabinoid-induced analgesia. Loss of endogenous CB1 is associated with hyperalgesia. However, the downstream targets affected by ablation of CB1 in primary sensory neurons remain unknown. In the present study, we hypothesized that conditional knockout of CB1 in primary sensory neurons (CB1cKO) alters downstream gene expression in the dorsal root ganglion (DRG) and that targeting these pathways alleviates neuropathic pain. We found that CB1cKO in primary sensory neurons induced by tamoxifen in adult Advillin-Cre:CB1-floxed mice showed persistent hyperalgesia. Transcriptome/RNA sequencing analysis of the DRG indicated that differentially expressed genes were enriched in energy regulation and complement and coagulation cascades at the early phase of CB1cKO, whereas pain regulation and nerve conduction pathways were affected at the late phase of CB1cKO. Chronic constriction injury in mice induced neuropathic pain and changed transcriptome expression in the DRG of CB1cKO mice, and differentially expressed genes were mainly associated with inflammatory and immune-related pathways. Nerve injury caused a much larger increase in CB2 expression in the DRG in CB1cKO than in wildtype mice. Interfering with downstream target genes of CB1, such as antagonizing CB2, inhibited activation of astrocytes, reduced neuroinflammation, and alleviated neuropathic pain. Our results demonstrate that CB1 in primary sensory neurons functions as an endogenous analgesic mediator. CB2 expression is regulated by CB1 and may be targeted for the treatment of neuropathic pain.

Effect of Shengmai Yin on the DNA methylation status of nasopharyngeal carcinoma cell and its radioresistant strains.

Shengmai Yin (SMY) is a Chinese herbal decoction that effectively alleviates the side effects of radiotherapy in various cancers and helps achieve radiotherapy's clinical efficacy. In this study, we explored the interaction mechanism among SMY, DNA methylation, and nasopharyngeal carcinoma (NPC). We identified differences in DNA methylation levels in NPC CNE-2 cells and its radioresistant cells (CNE-2R) using the methylated DNA immunoprecipitation array and found that CNE-2R cells showed genome-wide changes in methylation status towards a state of hypomethylation. SMY may restore its original DNA methylation status, and thus, enhance radiosensitivity. Furthermore, we confirmed that the differential gene Tenascin-C (TNC) was overexpressed in CNE-2R cells and that SMY downregulated TNC expression. This downregulation of TNC inhibited NPC cell radiation resistance, migration, and invasion. Furthermore, we found that TNC was hypomethylated in CNE-2R cells and partially restored to a hypermethylated state after SMY intervention. DNA methyltransferases 3a may be the key protein in DNA methylation of TNC.

Curcumin Enhances Radiosensitization of Nasopharyngeal Carcinoma via Mediating Regulation of Tumor Stem-like Cells by a CircRNA Network.

Circular RNAs (circRNAs) are involved in cancer development via inhibition of miRNAs, which are associated with differentiation, proliferation, migration, and carcinogenicity. Curcumin has antioxidant and anti-cancer properties, and it has also been used as a radiosensitizer. In this study, we explored the potential relationships among curcumin, circRNAs, and nasopharyngeal carcinoma (NPC). We compared the differences in circRNA levels in NPC cell lines after radiotherapy and after treatment with curcumin, using a high-throughput microarray. Further, a circRNA-miRNA-mRNA interaction network between radiation resistance NPC cell lines and tumor stem cells was constructed by applying bioinformatics. Finally, it was demonstrated by reverse transcription-quantitative polymerase chain reaction assay and wound healing assay that curcumin could enhance radiosensitization of NPC cell lines via mediating regulation of tumor stem-like cells by the "hsa_circRNA_102115"-"hsa-miR-335-3p"-"MAPK1" interaction network.

Curcumin enhances radiosensitization of nasopharyngeal carcinoma by regulating circRNA network.

Circular RNAs (circRNAs) are involved in the regulation of gene expression in different physiological and pathological processes. These macromolecules can act as microRNA (miRNA) sponges and play an important role as gene regulators throughout the circRNA-miRNA pathway. In this study, we established a radioresistance model with the nasopharyngeal carcinoma cell line CNE-2, and then analyzed the differences in the circRNAs between radioresistant and normal nasopharyngeal carcinoma cell lines using a high-throughput microarray. Tested circRNAs included 1042 upregulated and 1558 downregulated circRNAs. Relevant signaling pathways associated with the circRNAs and their target miRNAs were analyzed using bioinformatics analysis to determine the radioresistance of the differentially expressed circRNAs. Curcumin was used to treat irradiated cell lines, and changes in the circRNA before and after curcumin treatment were analyzed to investigate the radiosensitization effects of curcumin. The results showed that curcumin could regulate the circRNA-miRNA-messenger RNA network and inhibit the epidermal growth factor receptor (EGFR), signal transducers and activators of transcription 3 (STAT3), and growth factor receptor-bound protein 2 (GRB2) to achieve radiosensitization. Thus, circRNA acted as a miRNA sponge and regulated the expression of miRNA, thereby affecting EGFR, STAT3, and GRB2 expression and radiosensitization.

[Detection of chromosomal abnormalities in abortic tissues derived from patients with recurrent abortions using BoBs technique].

OBJECTIVE: To assess the value of BACs-on-Beads (BoBs) technique for the detection of chromosomal abnormalities in abortus tissues from recurrent pregnancy loss. METHODS: A total of 109 abortus samples were collected and analyzed with the BoBs technique. The incidence and types of chromosomal abnormalities for different age groups and gestational weeks were compared. RESULTS: The BoBs assay has succeeded in all cases, with an incidence for chromosomal abnormalities reaching 62.39% (68/109). The major findings included trisomy 16 (12/68), trisomy 22 (9/68), trisomy 13 (9/68) and trisomy 21 (8/68). The abnormal rate was significantly higher in those above 35-year-old compared with that of the <35-year-old group (P<0.05). More aberrations were found among abortus tissues derived from 42-70 days of pregnancy albeit with no statistical significance (P>0.05). The aberration rates were similar for samples derived from second, third and fourth time abortions (P>0.05). CONCLUSION: BoBs technique can detect chromosomal aberrations in miscarriages and may be routinely used for the analysis of early spontaneous abortions.

[Effects of Shengmai Jianghuang San on intestinal flora in nude mice with radio resistant cells of nasopharyngeal carcinoma].

Modern pharmacological studies have shown that Shengmai San has the effects of enhancing immunity and improving blood circulation, and Curcumae Longae Rhizoma(Jianghuang) has anti-inflammatory, anti-cancer, anti-oxidation and other functions. Shengmai San combined with Jianghuang is a new research direction in the study of anti-tumor of traditional Chinese medicines. The main treatment for nasopharyngeal carcinoma is radiation therapy, but radiation therapy can cause a variety of side effects, and it also changes the composition of the intestinal flora. In this study, the 16 s rDNA sequencing platform was used to perform macro-sequence sequencing of the intestinal flora samples of nude mice bearing the veins of Shengmai Jianghuang San, and then the results of intestinal flora data were analyzed to investigate the effect of Shengmai Jianghuang San on tumors. The results showed that Shengmai Jianghuang San combined with irradiation could enhance the therapeutic effect of tumor treatment. Radiation therapy would reduce the total number and diversity of intestinal flora in nude mice, and also change the structure of the flora. Shengmai Jianghuang San could protect the diversity of colonies, and also partially restore the colony imbalance caused by irradiation. This study provides a research idea for Shengmai Jianghuang San as a sensitizing adjuvant for radiotherapy of nasopharyngeal carcinoma.