Human pan-cancer analysis of the predictive biomarker for the CDKN3.

BACKGROUND: Cell cycle protein-dependent kinase inhibitor protein 3 (CDKN3), as a member of the protein kinase family, has been demonstrated to exhibit oncogenic properties in several tumors. However, there are no pan-carcinogenic analyses for CDKN3. METHODS: Using bioinformatics tools such as The Cancer Genome Atlas (TCGA) and the UCSC Xena database, a comprehensive pan-cancer analysis of CDKN3 was conducted. The inverstigation encompassed the examination of CDKN3 function actoss 33 different kinds of tumors, as well as the exploration of gene expressions, survival prognosis status, clinical significance, DNA methylation, immune infiltration, and associated signal pathways. RESULTS: CDKN3 was significantly upregulated in most of tumors and correlated with overall survival (OS) of patients. Methylation levels of CDKN3 differed significantly between tumors and normal tissues. In addition, infiltration of CD4 + T cells, cancer-associated fibroblasts, macrophages, and endothelial cells were associated with CDKN3 expression in various tumors. Mechanistically, CDKN3 was associated with P53, PI3K-AKT, cell cycle checkpoints, mitotic spindle checkpoint, and chromosome maintenance. CONCLUSION: Our pan-cancer analysis conducted in the study provides a comprehensive understanding of the involvement of CDKN3 gene in tumorigenesis. The findings suggest that targeting CDKN3 may potentially lead to novel therapeutic strategies for the treatment of tumors.

Dyadic psycho-social interventions for stroke survivors and family caregivers: A systematic review and meta-analysis of randomized controlled trials.

AIMS AND OBJECTIVES: To describe dyadic psycho-social intervention measures and to evaluate their influence on stroke survivors and caregiver's functional independence, quality of life, depression, anxiety, self-efficacy and coping ability. BACKGROUND: Because of the importance of dyadic intervention and the seriousness of the psycho-social problems of stroke survivors and caregivers, understanding the influence of dyadic psycho-social interventions is vital. DESIGN: A systematic review and meta-analysis based on PRISMA guidelines. DATA SOURCES: Nine databases were systematically searched for randomized controlled trials submitted from 1910 to 4 July 2022. METHODS: The included papers were evaluated for quality, and quantitative data were standardly extracted and analysed by meta-analysis, followed by synthesis. The meta-analysis was carried out using Review Manager 5.4 software. RESULTS: Fifteen randomized controlled trials were included (n = 2190 for patients, and n = 1933 for caregivers). Study results showed that dyadic psycho-social interventions significantly alleviated the depressive symptoms of patients, obviously improved the ability to function independently of patients and more quickly alleviated the care burden of caregivers. CONCLUSIONS: This study provided moderate support for the benefits of dyadic psycho-social intervention in improving survivor and caregiver's functional independence, quality of life, depression, anxiety, self-efficacy and care burden. Nevertheless, due to limitations of the study, it was deemed necessary that this topic is studied further. RELEVANCE TO CLINICAL PRACTICE: This review suggests that dyadic psycho-social interventions should be considered as effective strategies for decreasing psycho-social problems of stroke survivors and caregivers, and provides evidence for the formulation of targeted intervention programs. The personalized implementation of such interventions should be the focus of clinical practice. NO PATIENT OR PUBLIC CONTRIBUTION: There was no patient or public contribution.

Irradiation stent insertion for inoperable malignant biliary obstruction: a meta-analysis of randomized controlled trials.

The purpose of the study was to compare the relative clinical efficacies of irradiation stent (IRS) and conventional stent (CVS) insertions for the treatment of patients with malignant biliary obstruction (MBO). Pubmed, Embase, and Cochrane Library databases were searched for relevant randomized controlled trials (RCTs) from the date of inception through to August 2020. Data analysis was performed using RevMan v5.3. This meta-analysis included eight RCTs which included a total of 319 patients who had undergone IRS insertion, and 328 who had undergone CVS insertion. No significant differences in pooled Δ total bilirubin values (MD 0.34; P = 0.92), incident rates of cholangitis (P = 0.47), hemobilia (P = 0.60), or pancreatitis (P = 0.89) were detected between two groups. The rate of stent dysfunction was significantly lower in the IRS group compared to the CVS group (22.2% vs. 37.7%, P = 0.02). The pooled stent patency (P < 0.00001) and survival (P < 0.00001) were significantly longer in the IRS group compared to the CVS group. Significant heterogeneity was detected in the endpoints of rate of stent dysfunction (I2 = 52%; P = 0.08) and survival (I2 = 77%; P = 0.0005). Subgroup analysis was performed based on the different IRS types and showed significantly longer survival in the IRS group based on both types of IRS. Funnel plot analyses did not detect any evidence of publication bias. This meta-analysis included eight RCTs which included a total of 319 patients who had undergone IRS insertion, and 328 who had undergone CVS insertion. No significant differences in pooled Δ total bilirubin values (MD 0.34; P = 0.92), incident rates of cholangitis (P = 0.47), hemobilia (P = 0.60), or pancreatitis (P = 0.89) were detected between 2 groups. The rate of stent dysfunction was significantly lower in the IRS group compared to the CVS group (22.2% vs. 37.7%, P = 0.02). The pooled stent patency (P < 0.00001) and survival (P < 0.00001) were significantly longer in the IRS group compared to the CVS group. Significant heterogeneity was detected in the endpoints of rate of stent dysfunction (I2 = 52%; P = 0.08) and survival (I2 = 77%; P = 0.0005). Subgroup analysis was performed based on the different IRS types and showed significantly longer survival in the IRS group based on both types of IRS. Funnel plot analyses did not detect any evidence of publication bias. Our meta-analysis demonstrates that IRS insertion can prolong stent patency and the survival of patients with MBO compared to CVS insertion.

Professional identity and its influencing factors of first-year post-associate degree baccalaureate nursing students: A cross-sectional study.

BACKGROUND: Professional identity is an important and universal concept in the field of nursing because it not only affects nurses' perceptions of their role in nursing, but it also affects retention rates. However, the influential factors that impact the professional identity of nursing students currently are not well known. PURPOSE: This exploratory study aims to investigate the concept of professional identity and confirm its influencing factors among post-associate degree baccalaureate nursing students in China. METHODS: We conducted a cross-sectional study of 198 first-year post-associate degree baccalaureate nursing students enrolled in full-time study at two provincial medical colleges in China. We used paper and pencil questionnaires to conduct the survey and obtain the results used in this study. RESULTS: The overall mean score for 'professional identity' of the sample was 3.63 ±â€¯0.62 on a scale of 1 through 5, with the means for the five dimensions of professional identity ranging from 3.29 to 4.02. A clinical learning experience that is longer than eight months (ref. = 8 months) (ß = 0.138, p < 0.036) and a positive perception of the clinical learning environment (ß = 0.476, p < 0.001) are the dominant factors that we found to be positively associated with professional identity. CONCLUSIONS: Nurse educators should investigate the factors that influence professional identity among their students to help develop a stable and satisfied nursing workforce.

Yoga's Biophysiological Effects on Lower Urinary Tract Symptoms: A Scoping Review.

BACKGROUND AND OBJECTIVES: Yoga is a mind and body practice that includes relaxation, meditation, breathing exercises, and body postures. It can be effective in enhancing the functioning of several body systems, including the lower urinary tract. Normal lower urinary tract functioning depends in part on the coordination of the bladder, urethra, pelvic floor and other muscles, and the nerves that control them. Lower urinary tract dysfunction can lead to symptoms, that is, stress urinary incontinence (UI), urinary frequency, nocturia, urinary urgency with and without incontinence, and mixed UI. Recent evidence suggests that yoga can improve lower urinary tract symptoms (LUTS). Thus, we performed a scoping review of the literature with regard to the evidence for the effects of yoga on LUTS and factors that may mediate yoga's effects on LUTS with the goal to identify gaps in knowledge regarding the relationship between yoga practice and LUTS. METHODS: The authors employed the PRISMA extension for Scoping Reviews (PRISMA-ScR) methodological approach, proposed by Tricco et al., by searching the electronic databases, PubMed, Embase, and PsycINFO, for articles using the following keywords: yoga, urinary incontinence, urinary tract, bladder, and urethra. We assessed the quality of the studies using the Joanna Briggs Institute Critical Appraisal Checklist. RESULTS: Of the 172 articles we found, 8 articles met the inclusion criteria and were reviewed. We found that, despite the use of different protocols, yoga may reduce certain LUTS by increasing the strength of pelvic floor muscle and/or regulating the autonomic nervous system and activating the central nervous system. CONCLUSIONS: Yoga is a noninvasive practice that may improve some LUTS. Rigorous studies are needed to determine the specific mechanisms through which yoga may affect LUTS.

Protective effects of alpinetin on lipopolysaccharide/d-Galactosamine-induced liver injury through inhibiting inflammatory and oxidative responses.

Alpinetin, a type of novel plant flavonoid derived from Alpinia katsumadai Hayata, has been reported to have anti-inflammatory effects. The aim of this investigation was designed to reveal the protective effects of alpinetin on Lipopolysaccharide (LPS)/d-galactosamine (D-Gal)-induced liver injury in mice. Alpinetin (12.5, 25, 50 mg/kg) were given 1 h before LPS and D-Gal treatment. 12 h after LPS and D-Gal treatment, the liver tissues and serum were collected. Our results showed that alpinetin treatment improved liver histology, indicating a marked decrease of inflammatory cell infiltration and restore hepatic lobular architecture. Alpinetin also inhibited liver myeloperoxidase (MPO) activity and malondialdehyde (MDA) level. Furthermore, LPS/D-Gal-induced tumor necrosis factor-α (TNF-α) and Interleukin-1ß (IL-1ß) production were dose-dependently inhibited by alpinetin. Alpinetin also attenuated LPS/D-Gal-induced expression of phospho-NF-κB p65 and phospho-IκBα. In addition, alpinetin was found to increase the expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). In conclusion, these findings suggested that alpinetin inhibited liver injury through inhibiting NF-κB and activating the Nrf2 signaling pathway.

Nuclear protein HMGN2 attenuates pyocyanin-induced oxidative stress via Nrf2 signaling and inhibits Pseudomonas aeruginosa internalization in A549 cells.

Pyocyanin (PCN, 1-hydroxy-5-methyl-phenazine) is one of the most essential virulence factors of Pseudomonas aeruginosa (PA) to cause various cytotoxic effects in long-term lung infectious diseases, however the early effect of this bacterial toxin during PA infection and subsequent autonomous immune response in host cells have not been fully understood yet. Our results display that early onset of PCN stimulates Pseudomonas aeruginosa PAO1 adhesion and invasion in A549 cells via ROS production. Non-histone nuclear protein HMGN2 is found to be involved in the regulation of PCN-induced oxidative stress by promoting intracellular ROS clearance. Mechanistically, HMGN2 facilitates nuclear translocation of transcription factor Nrf2 upon PCN stimulation and in turn elevates antioxidant gene expression. We also found that actin cytoskeleton dynamics is targeted by ROS, which is to be exploited by PAO1 for host cell internalization. HMGN2 regulates actin skeleton rearrangement in both PCN-dependent and independent manners and specifically attenuates PCN-mediated PAO1 infection via ROS elimination. These results uncover a novel link between nuclear protein HMGN2 and Nrf2-mediated cellular redox circumstance and suggest roles of HMGN2 in autonomous immune response to PA infection.

Correlation of interferon-lambda 4 ss469415590 with the hepatitis C virus treatment response and its comparison with interleukin 28b polymorphisms in predicting a sustained virological response: a meta-analysis.

BACKGROUND: Interferon-lambda 4 (IFNL4) ss469415590 is a newly discovered polymorphism that could predict the treatment response in hepatitis C virus (HCV)-infected patients. This meta-analysis was performed in order to clarify its specific effect on the treatment response and to compare it with interleukin 28b (IL28B). METHOD: The commonly used literature databases were searched. Meta-analyses were performed with fixed/random-effects models using Stata 12.0. The sustained virological response (SVR) rate was summarized using R software. Publication bias was examined through Egger's test. RESULTS: A total of seven studies were finally included in this meta-analysis. IFNL4 ss469415590 was demonstrated to be associated with SVR (odds ratio (OR) 3.83, 95% confidence interval (CI) 3.22-4.56, p<0.001). Asians had a higher likelihood of achieving SVR than Caucasians (OR=7.36 vs. 3.54). When stratifying all the patients according to HCV genotype, a significant association was observed in HCV genotype 1 patients (OR 4.5, 95% CI 2.91-6.95, p<0.001). In HCV genotype 2/3 patients, the favorable TT/TT genotype patients tended to have a statistically higher SVR rate than the non-TT/TT genotype patients (84.4% vs. 78.3%, p=0.058). Compared with IL28B rs12979860 (OR 3.45) and rs8099917 (OR 3.50), ss469415590 TT/TT genotype patients showed a slightly higher probability of achieving a SVR (OR 3.61 calculated from studies investigating both IFNL4 and rs12979860; OR 4.86 for studies investigating both IFNL4 and rs8099917). Furthermore, ss469415590 showed a slightly higher predictive value than rs12979860 using the diagnostic test tool (area under the curve=0.71 vs. 0.70). IFNL4 was also correlated with rapid virological response (RVR) (OR 4.35, 95% CI 1.43-13.20, p=0.01), viral clearance (OR 0.31, 95% CI 0.24-0.39, p<0.001), and HCV susceptibility (OR 0.76, 95% CI 0.65-0.89, p=0.001). CONCLUSIONS: IFNL4 ss469415590 is significantly associated with SVR in HCV genotype 1 patients, irrespective of race; there is a tendency towards an association in HCV genotype 2/3 patients. Comparable to IL28B, IFNL4 is correlated with natural viral clearance and HCV susceptibility, additionally IFNL4 ss469415590 has a slightly higher predictive performance over IL28B polymorphisms in regard to SVR.

Dietary flavonoid luteolin attenuates uropathogenic Escherichia. Coli invasion of the urinary bladder.

Uropathogenic Escherichia coli (UPEC), the primary uropathogen, adhere to and invade bladder epithelial cells (BECs) to establish a successful urinary tract infection (UTI). Emerging antibiotic resistance requires novel nonantibiotic strategies. Our previous study indicated that luteolin attenuated adhesive and invasive abilities as well as cytotoxicity of UPEC on T24 BECs through down-regulating UPEC virulence factors. The aims of this study were to investigate the possible function of the flavonoid luteolin and the mechanisms by which luteolin functions in UPEC-induced bladder infection. Firstly, obvious reduction of UPEC invasion but not adhesion were observed in luteolin-pretreated 5637 and T24 BECs sa well as mice bladder via colony counting. The luteolin-mediated suppression of UPEC invasion was linked to elevated levels of intracellular cAMP induced by inhibiting the activity of cAMP-phosphodiesterases (cAMP-PDEs), which resulting activation of protein kinase A, thereby negatively regulating Rac1-GTPase-mediated actin polymerization. Furthermore, p38 MAPK was primarily and ERK1/2 was partially involved in luteolin-mediated suppression of UPEC invasion and actin polymerization, as confirmed with chemical activators of p38 MAPK and ERK1/2. These data suggest that luteolin can protect bladder epithelial cells against UPEC invasion. Therefore, luteolin or luteolin-rich products as dietary supplement may be beneficial to control the UPEC-related bladder infections, and cAMP-PDEs may be a therapy target for UTIs treatment. © 2016 BioFactors, 42(6):674-685, 2016.

Subinhibitory Concentrations of Allicin Decrease Uropathogenic Escherichia coli (UPEC) Biofilm Formation, Adhesion Ability, and Swimming Motility.

Uropathogenic Escherichia coli (UPEC) biofilm formation enables the organism to avoid the host immune system, resist antibiotics, and provide a reservoir for persistent infection. Once the biofilm is established, eradication of the infection becomes difficult. Therefore, strategies against UPEC biofilm are urgently required. In this study, we investigated the effect of allicin, isolated from garlic essential oil, on UPEC CFT073 and J96 biofilm formation and dispersal, along with its effect on UPEC adhesion ability and swimming motility. Sub-inhibitory concentrations (sub-MICs) of allicin decreased UPEC biofilm formation and affected its architecture. Allicin was also capable of dispersing biofilm. Furthermore, allicin decreased the bacterial adhesion ability and swimming motility, which are important for biofilm formation. Real-time quantitative polymerase chain reaction (RT-qPCR) revealed that allicin decreased the expression of UPEC type 1 fimbriae adhesin gene fimH. Docking studies suggested that allicin was located within the binding pocket of heptyl α-d-mannopyrannoside in FimH and formed hydrogen bonds with Phe1 and Asn135. In addition, allicin decreased the expression of the two-component regulatory systems (TCSs) cognate response regulator gene uvrY and increased the expression of the RNA binding global regulatory protein gene csrA of UPEC CFT073, which is associated with UPEC biofilm. The findings suggest that sub-MICs of allicin are capable of affecting UPEC biofilm formation and dispersal, and decreasing UPEC adhesion ability and swimming motility.

MiR-204 inhibits the proliferation and invasion of renal cell carcinoma by inhibiting RAB22A expression.

While miR-204 expression may be linked to renal cell carcinoma (RCC) progression, the detailed mechanisms remain unclear. In the present study, we demonstrated that miR-204 was differentially expressed in RCC tissues when compared with surrounding normal kidney tissues. Ectopic overexpression of miR-204 in human RCC cells suppressed cell proliferation and invasion in vitro and in vivo. Mechanism dissection revealed that miR-204 may function through RAB22A signals to inhibit RCC proliferation and invasion. Overexpression of RAB22A by oe-RAB22A was able to partially reverse the miR-204-mediated suppression of RCC tumor progression. Together, these results revealed that miR-204 suppressed RCC proliferation and invasion by directly targeting the RAB22A gene. Targeting newly identified RAB22A with miR-204 may aid in the suppression of RCC proliferation and invasion.

Efficacy of poly-unsaturated fatty acid therapy on patients with nonalcoholic steatohepatitis.

AIM: To examine whether poly-unsaturated fatty acid (PUFA) therapy is beneficial for improving nonalcoholic steatohepatitis (NASH). METHODS: In total, 78 patients pathologically diagnosed with NASH were enrolled and were randomly assigned into the control group and the PUFA therapy group (added 50 mL PUFA with 1:1 ratio of EHA and DHA into daily diet). At the initial analysis and after 6 mo of PUFA therapy, parameters of interest including liver enzymes, lipid profiles, markers of inflammation and oxidation, and histological changes were evaluated and compared between these two groups. RESULTS: At the initial analysis, in patients with NASH, serum levels of alanine aminotransferase (ALT) and aspartase aminotransferase (AST) were slightly elevated. Triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol levels, markers of systemic inflammation [C-reactive protein (CRP)] and oxidation [malondialdehyde (MDA)], as well as fibrosis parameters of type IV collagen and pro-collagen type III pro-peptide were also increased beyond the normal range. Six months later, ALT and AST levels were significantly reduced in the PUFA group compared with the control group. In addition, serum levels of TG and TC, CRP and MDA, and type IV collagen and pro-collagen type III pro-peptide were also simultaneously and significantly reduced. Of note, histological evaluation showed that steatosis grade, necro-inflammatory grade, fibrosis stage, and ballooning score were all profoundly improved in comparison to the control group, strongly suggesting that increased PUFA consumption was a potential way to offset NASH progression. CONCLUSION: Increased PUFA consumption is a potential promising approach for NASH prevention and reversal.

miR-709 up-regulated in hepatocellular carcinoma, promotes proliferation and invasion by targeting GPC5.

OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most common cancers and is a significant leading cause of cancer-related deaths worldwide. Emerging evidence has shown that microRNAs (miRNAs) are associated with cancer development and progression. However, up to now little has been known concerning the role of miR-709 in HCC. MATERIALS AND METHODS: Real-time RT-PCR was performed to detect expression of miR-709 in HCC cell lines and tissues. To further understand its role in HCC, we restored its expression in HepG2 cell line through transfection with miR-709 mimics or inhibitors. CCK-8 proliferation assay, migration assay and invasion assay were used to detect functional roles of miR-709. Luciferase assay and western blotting were performed to detect the target gene of miR-709. RESULTS: We found that miR-709 was highly expressed in HCC tissues and in HCC cell lines by qRT-PCR. Re-expression of miR-709 in HCC cells remarkably promoted cell migration and invasiveness in vitro. Subsequent investigation revealed that glypican-5 (GPC5) was a direct and functional target of miR-709 in HCC cells where overexpression of miR-709 impaired GPC5-induced inhibition of proliferation and invasion. Finally, analysis of miR-709 and GPC5 levels in human HCC tissues revealed that miR-709 inversely correlated with GPC5 expression. CONCLUSIONS: These results suggest that miR-709 may positively regulate invasion and metastasis of HCC through targeting GPC5.

Luteolin decreases the attachment, invasion and cytotoxicity of UPEC in bladder epithelial cells and inhibits UPEC biofilm formation.

Urinary tract infection (UTI), primarily caused by uropathogenic Escherichia coli (UPEC), is one of the most common infectious diseases worldwide. Emerging antibiotic resistance requires novel treatment strategies. Luteolin, a dietary polyphenolic flavonoid, has been confirmed as a potential antimicrobial agent. Here, we evaluated the sub-MICs of luteolin for potential properties to modulate the UPEC infection. We found that luteolin significantly decreased the attachment and invasion of UPEC J96 or CFT073 in human bladder epithelial cell lines T24. Meanwhile, obvious decreased expression of type 1 fimbriae adhesin fimH gene, lower bacterial surface hydrophobicity and swimming motility, were observed in luteolin-pretreated UPEC. Furthermore, luteolin could attenuate UPEC-induced cytotoxicity in T24 cells, which manifested as decreased activity of lactate dehydrogenase (LDH). Simultaneously, the inhibition of luteolin on UPEC-induced cytotoxicity was confirmed by ethidium bromide/acridine orange staining. Finally, the luteolin-pretreated UPEC showed a lower ability of biofilm formation. Collectively, these results indicated that luteolin decreased the attachment and invasion of UPEC in bladder epithelial cells, attenuated UPEC-induced cytotoxicity and biofilm formation via down-regulating the expression of adhesin fimH gene, reducing the bacterial surface hydrophobicity and motility.

IL-28B polymorphisms correlated with treatment response in HCV-4 mono-infected patients: a meta-analysis.

BACKGROUND: The role of interleukin 28B (IL-28B) polymorphisms played in hepatitis C virus (HCV) infection has been gradually explicit, especially in HCV genotype 1, 2 and 3. However, no confirmative conclusion was acquired in genotype 4 HCV patients. Thus we conducted this meta-analysis. METHODS: We searched the commonly used databases both in English and Chinese. Meta-analysis was performed in fixed/random effects models using STATA 12.0 or R software. Publication bias was examined through Egger's test and Begg's funnel plot. RESULTS: In total, 11 studies were included in this meta-analysis, encompassing 1284 patients who were mono-infected with HCV-4 and received Peg-interferon (Peg-IFN) plus Ribavirin (Rbv). Around 53.0% patients would achieve sustained virologic response (SVR), 36.6% achieve rapid virologic response (RVR) and 62.4% achieve end of treatment response (ETR). Egyptian patients had a higher rate achieving SVR than non-Egyptian patients (56.3% vs. 47.8%). IL-28B rs12979860 CC genotype not only favored SVR (OR = 3.95, 95%CI = 3.03-5.16), regardless of citizenship, but also favored RVR (OR = 3.82, 95%CI = 2.46-5.95) and ETR (OR = 4.22, 95%CI = 2.81-6.34). IL-28B rs8099917 genotype TT also correlated with SVR (OR = 3.41, 95%CI = 1.92-6.07), but might not with RVR. IL-28B rs12980275 might still correlate with SVR, but warrant more studies to validate. CONCLUSIONS: The favorable IL-28B rs12979860 genotype is a statistically significant predictor of SVR, RVR and ETR in HCV-4 monoinfected patients treated with Peg-IFN plus Rbv. Rs8099917 might predict SVR but not RVR. Egyptian HCV-4 patients would achieve better outcomes than non-Egyptian patients when treated with standard care.