Parental Knowledge of Appendicitis and Its Management Options Among Children of Makkah Region, Saudi Arabia.

BACKGROUND: Despite decades of studies, appendicitis in children still presents several uncertainties regarding optimal treatment. OBJECTIVES: To assess parental understanding of appendicitis, along with its risks and treatment, and to determine attitudes to operative and non-operative treatment of uncomplicated appendicitis. METHODS: This is a cross-sectional study. The current study has targeted all parents who visited the pediatric outpatient departments or clinics at three different hospitals in Makkah and Jeddah City, including Maternity and Children Hospital (MCH) in Makkah, King Fahad Armed Force Hospital (KFAFH), and Saudi German Private Hospital (SGH) in Jeddah. Data was collected via an online Google form and was analyzed by using SPSS. RESULTS: A total of 408 subjects were involved in this study. The majority of them were females (74.5%); 25.5% were males. Most of the study participants aged between 25 and 34 years. Our results found that the average knowledge score of the study population was 4.1±1.81 out of 11. Only 23.5% of them had good knowledge about appendicitis. More than half of the respondents identified the appendix as a part of the digestive system and most of the study population were aware of the current treatment for appendicitis, which is surgery (80.9%). Female participants and respondents who knew someone that has been treated for appendicitis were significantly associated with a better level of knowledge about appendicitis (P-values: 0.011 and 0.033, respectively). Moreover, we found that educational level significantly influenced preference for treatment with antibiotics and surgery if appendicitis happened again (P-value: 0.049). CONCLUSION: The study population had poor knowledge of appendicitis and its management options. The highlighted criteria of self-reported relevance to parents should be addressed in all appendicitis counseling and consent. We advocate for the establishment of national public awareness campaigns, as well as increased research and clinical trials. Understanding lay views of treatment alternatives and efficacy will influence future approaches to appendicitis therapy by analyzing the community's preference for emerging treatment modalities and identifying future directions for patient-centered clinical trials.

Keratin 19 binds and regulates cytoplasmic HNRNPK mRNA targets in triple-negative breast cancer.

BACKGROUND: Heterogeneous nuclear ribonucleoprotein K (HNRNPK) regulates pre-mRNA processing and long non-coding RNA localization in the nucleus. It was previously shown that shuttling of HNRNPK to the cytoplasm promotes cell proliferation and cancer metastasis. However, the mechanism of HNRNPK cytoplasmic localization, its cytoplasmic RNA ligands, and impact on post-transcriptional gene regulation remain uncharacterized. RESULTS: Here we show that the intermediate filament protein Keratin 19 (K19) directly interacts with HNRNPK and sequesters it in the cytoplasm. Correspondingly, in K19 knockout breast cancer cells, HNRNPK does not localize in the cytoplasm, resulting in reduced cell proliferation. We comprehensively mapped HNRNPK binding sites on mRNAs and showed that, in the cytoplasm, K19-mediated HNRNPK-retention increases the abundance of target mRNAs bound to the 3' untranslated region (3'UTR) at the expected cytidine-rich (C-rich) sequence elements. Furthermore, these mRNAs protected by HNRNPK in the cytoplasm are typically involved in cancer progression and include the p53 signaling pathway that is dysregulated upon HNRNPK knockdown (HNRNPK KD) or K19 knockout (KRT19 KO). CONCLUSIONS: This study identifies how a cytoskeletal protein can directly regulate gene expression by controlling the subcellular localization of RNA-binding proteins to support pathways involved in cancer progression.

Keratin 19 maintains E-cadherin localization at the cell surface and stabilizes cell-cell adhesion of MCF7 cells.

A cytoskeletal protein keratin 19 (K19) is highly expressed in breast cancer but its effects on breast cancer cell mechanics are unclear. In MCF7 cells where K19 expression is ablated,we found that K19 is required to maintain rounded epithelial-like shape and tight cell-cell adhesion. A loss of K19 also lowered cell surface E-cadherin levels. Inhibiting internalization restored cell-cell adhesion of KRT19  knockout cells, suggesting that E-cadherin internalization contributed to defective adhesion. Ultimately, while K19 inhibited cell migration and invasion, it was required for cells to form colonies in suspension. Our results suggest that K19 stabilizes E-cadherin complexes at the cell membrane to maintain cell-cell adhesion which inhibits cell invasiveness but provides growth and survival advantages for circulating tumor cells.

Keratin 19 regulates cell cycle pathway and sensitivity of breast cancer cells to CDK inhibitors.

Keratin 19 (K19) belongs to the keratin family of proteins, which maintains structural integrity of epithelia. In cancer, K19 is highly expressed in several types where it serves as a diagnostic marker. Despite the positive correlation between higher expression of K19 in tumor and worse patient survival, the role of K19 in breast cancer remains unclear. Therefore, we ablated K19 expression in MCF7 breast cancer cells and found that K19 was required for cell proliferation. Transcriptome analyses of KRT19 knockout cells identified defects in cell cycle progression and levels of target genes of E2F1, a key transcriptional factor for the transition into S phase. Furthermore, proper levels of cyclin dependent kinases (CDKs) and cyclins, including D-type cyclins critical for E2F1 activation, were dependent on K19 expression, and K19-cyclin D co-expression was observed in human breast cancer tissues. Importantly, K19 interacts with cyclin D3, and a loss of K19 resulted in decreased protein stability of cyclin D3 and sensitivity of cells towards CDK inhibitor-induced cell death. Overall, these findings reveal a novel function of K19 in the regulation of cell cycle program and suggest that K19 may be used to predict the efficacy of CDK inhibitors for treatments of breast cancer.

Composition and content of phenolic acids and avenanthramides in commercial oat products: Are oats an important polyphenol source for consumers?

Oats contain a range of phenolic acids and avenanthramides which may have health benefits. Analysis of 22 commercial oat products (oat bran concentrate, oat bran, flaked oats, rolled oats and oatcakes) using HPLC-DAD detected eleven bound and thirteen free + conjugated phenolic acids and avenanthramides. The oat products (excluding concentrate) provided between 15.79 and 25.05 mg total phenolic acids (9.9-19.33 mg bound, 4.96-5.72 mg free + conjugated) and between 1.1 and 2 mg of avenanthramides in a 40 g portion while an 11 g portion of oat concentrate provided 16.7 mg of total phenolic acids (15.17 mg bound, 1.53 mg free + conjugated) and 1.2 mg of avenanthramides. The compositions and concentrations of the components in the different products were broadly similar, with the major component being ferulic acid (58-78.1%). The results show that commercial oat products are a source of phenolic acids and avenanthramides for consumers.

Intermediate Filaments as Effectors of Cancer Development and Metastasis: A Focus on Keratins, Vimentin, and Nestin.

Intermediate filament (IF) proteins make up the largest family of cytoskeletal proteins in metazoans, and are traditionally known for their roles in fostering structural integrity in cells and tissues. Remarkably, individual IF genes are tightly regulated in a fashion that reflects the type of tissue, its developmental and differentiation stages, and biological context. In cancer, IF proteins serve as diagnostic markers, as tumor cells partially retain their original signature expression of IF proteins. However, there are also characteristic alterations in IF gene expression and protein regulation. The use of high throughput analytics suggests that tumor-associated alterations in IF gene expression have prognostic value. Parallel research is also showing that IF proteins directly and significantly impact several key cellular properties, including proliferation, death, migration, and invasiveness, with a demonstrated impact on the development, progression, and characteristics of various tumors. In this review, we draw from recent studies focused on three IF proteins most associated with cancer (keratins, vimentin, and nestin) to highlight how several "hallmarks of cancer" described by Hanahan and Weinberg are impacted by IF proteins. The evidence already in hand establishes that IF proteins function beyond their classical roles as markers and serve as effectors of tumorigenesis.

Oat bran, but not its isolated bioactive ß-glucans or polyphenols, have a bifidogenic effect in an in vitro fermentation model of the gut microbiota.

Wholegrain oats are known to modulate the human gut microbiota and have prebiotic properties (increase the growth of some health-promoting bacterial genera within the colon). Research to date mainly attributes these effects to the fibre content; however, oat is also a rich dietary source of polyphenols, which may contribute to the positive modulation of gut microbiota. In vitro anaerobic batch-culture experiments were performed over 24 h to evaluate the impact of two different doses (1 and 3 % (w/v)) of oat bran, matched concentrations of ß-glucan extract or polyphenol mix, on the human faecal microbiota composition using 16S RNA gene sequencing and SCFA analysis. Supplementation with oats increased the abundance of Proteobacteria (P <0·01) at 10 h, Bacteroidetes (P <0·05) at 24 h and concentrations of acetic and propionic acid increased at 10 and 24 h compared with the NC. Fermentation of the 1 % (w/v) oat bran resulted in significant increase in SCFA production at 24 h (86 (sd 27) v. 28 (sd 5) mm; P <0·05) and a bifidogenic effect, increasing the relative abundance of Bifidobacterium unassigned at 10 h and Bifidobacterium adolescentis (P <0·05) at 10 and 24 h compared with NC. Considering the ß-glucan treatment induced an increase in the phylum Bacteroidetes at 24 h, it explains the Bacteriodetes effects of oats as a food matrix. The polyphenol mix induced an increase in Enterobacteriaceae family at 24 h. In conclusion, in this study, we found that oats increased bifidobacteria, acetic acid and propionic acid, and this is mediated by the synergy of all oat compounds within the complex food matrix, rather than its main bioactive ß-glucan or polyphenols. Thus, oats as a whole food led to the greatest impact on the microbiota.