miR-377-3p drives malignancy characteristics via upregulating GSK-3ß expression and activating NF-κB pathway in hCRC cells.

MicroRNA (miRNA) dysregulation has been associated with carcinogenesis in many cancers, including human colorectal cancer (hCRC). However, the effect and mechanism of miR-377-3p on CRC remains elusive. Herein, we first found that miR-377-3p was upregulated in CRC tissues and promoted tumorigenic activity by accelerating the G1 -S phase transition, promoting cell proliferation and epithelial-mesenchymal transition (EMT) while repressing apoptosis in CRC cells. Glycogen synthase kinase-3ß (GSK-3ß) was a direct target of miR-377-3p, and upregulated by miR-377-3p. Knockdown of GSK-3ß partly rescued miR-377-3p-mediated malignancy characteristics. Most importantly, we showed that miR-377-3p promoted carcinogenesis by activating NF-κB pathway. Taken together, our results first reported that miR-377-3p functions as an oncogene and promotes carcinogenesis via upregulating GSK-3ß expression and activating NF-κB pathway in hCRC cells.

Systemic immune-inflammation index combined with pediatric appendicitis score in assessing the severity and prognosis for paediatric appendicitis.

BACKGROUND: Pediatric appendicitis is a common cause of abdominal pain in children and is recognized as a significant surgical emergency. A prompt and accurate diagnosis is essential to prevent complications such as perforation and peritonitis. AIM: To investigate the predictive value of the systemic immune-inflammation index (SII) combined with the pediatric appendicitis score (PAS) for the assessment of disease severity and surgical outcomes in children aged 5 years and older with appendicitis. METHODS: Clinical data of 104 children diagnosed with acute appendicitis were analyzed. The participants were categorized into the acute appendicitis group and chronic appendicitis group based on disease presentation and further stratified into the good prognosis group and poor prognosis group based on prognosis. The SII and PAS were measured, and a joint model using the combined SII and PAS was constructed to predict disease severity and surgical outcomes. RESULTS: Significant differences were observed in the SII and PAS parameters between the acute appendicitis group and chronic appendicitis group. Correlation analysis showed associations among the SII, PAS, and disease severity, with the combined SII and PAS model demonstrating significant predictive value for assessing disease severity [aera under the curve (AUC) = 0.914] and predicting surgical outcomes (AUC = 0.857) in children aged 5 years and older with appendicitis. CONCLUSION: The study findings support the potential of integrating the SII with the PAS for assessing disease severity and predicting surgical outcomes in pediatric appendicitis, indicating the clinical utility of the combined SII and PAS model in guiding clinical decision-making and optimizing surgical management strategies for pediatric patients with appendicitis.

Diagnostic significance of serum levels of serum amyloid A, procalcitonin, and high-mobility group box 1 in identifying necrotising enterocolitis in newborns.

BACKGROUND: Necrotising enterocolitis (NEC) is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates. Serum amyloid A (SAA), procalcitonin (PCT), and high-mobility group box 1 (HMGB1) have emerged as potential biomarkers for NEC due to their roles in inflammatory response, tissue damage, and immune regulation. AIM: To evaluate the diagnostic value of SAA, PCT, and HMGB1 in the context of NEC in newborns. METHODS: The study retrospectively analysed the clinical data of 48 newborns diagnosed with NEC and 50 healthy newborns admitted to the hospital. Clinical, radiological, and laboratory findings, including serum SAA, PCT, and HMGB1 Levels, were collected, and specific detection methods were used. The diagnostic value of the biomarkers was evaluated through statistical analysis, which was performed using chi-square test, t-test, correlation analysis, and receiver operating characteristic (ROC) analysis. RESULTS: The study demonstrated significantly elevated levels of serum SAA, PCT, and HMGB1 Levels in newborns diagnosed with NEC compared with healthy controls. The correlation analysis indicated strong positive correlations among serum SAA, PCT, and HMGB1 Levels and the presence of NEC. ROC analysis revealed promising sensitivity and specificity for serum SAA, PCT, and HMGB1 Levels as potential diagnostic markers. The combined model of the three biomarkers demonstrating an extremely high area under the curve (0.908). CONCLUSION: The diagnostic value of serum SAA, PCT, and HMGB1 Levels in NEC was highlighted. These biomarkers potentially improve the early detection, risk stratification, and clinical management of critical conditions. The findings suggest that these biomarkers may aid in timely intervention and the enhancement of outcomes for neonates affected by NEC.

[Impact of the waist circumference change on new onset of diabetes in the population with impaired fasting glucose].

OBJECTIVE: To explore the impact of the waist circumference change on new onset diabetes (NOD) in the impaired fasting glucose (IFG) population. METHODS: A total of 12 657 subjects who took part in the health examination from 2006 to 2007 and from 2010 to 2011 from the employees of Kailuan Group and met the inclusion criteria were selected as the observation cohort.Of the 12 657 subjects, 10 697 were male, 1960 were female, with age of (49.9 ± 11.3) years old. According to the baseline waist circumference (WC) measurements and its quartile in the health examinations during 2006 to 2007, the observation population was divided into four groups (first, second, third and the fourth quartile groups) . Multiple logistic regression analysis was used to test the relation between the increasing of WC and NOD. RESULTS: The incidences in the IFG population of NOD were 4.27% (1884/12 657) in the total population;4.25% (1581/10 697) in male and 4.44% (303/1960) in females, respectively (P < 0.05) . Along with increasing WC in the 4 quartile groups, the incidences of NOD was progressively increased, which were 2.19% (235/3083) , 3.07% (333/3114) , 4.47% (473/3037) and 7.08% (843/3423) , respectively;2.34% (213/2626) , 3.06% (282/2645) , 4.37% (393/2582), 7.00% (693/2844) in males and 1.38% (22/457) , 3.12% (51/469) , 5.05% (80/455) , 7.45% (150/579) in female (P < 0.05) . Multiple logistic regression analysis showed that compared with the first quartile group, the second, third and fourth quartile group had increased risk of NOD after adjusting for age, gender and other risk factors, the OR (95%CI) values were 1.38(1.13-1.68), 1.79 (1.47-2.09) and 3.10 (2.57-3.75), respectively. CONCLUSION: The incidence of NOD in the IFG population increased as the WC increased.

The novel antitumor compound clinopodiside A induces cytotoxicity via autophagy mediated by the signaling of BLK and RasGRP2 in T24 bladder cancer cells.

In the study, we investigated the anti-cancer effect of clinopodiside A and the underlying mechanisms using T24 bladder cancer cells as an experimental model. We found that the compound inhibited the growth of the bladder cancer cells in vitro and in vivo in a in a concentration- and dose-dependent manner, respectively, which showed a combinational effect when used together with cisplatin. In the bladder cancer cells, clinopodiside A caused autophagy, which was mediated by the signaling of BLK and RasGRP2, independently. Inhibition of the autophagy by chemical inhibitor 3-methyladenine or by the inhibition of the signaling molecules attenuated the cytotoxicity of clinopodiside A. Further analyses showed that clinopodiside A acted in synergism with cisplatin which itself could trigger both autophagy and apoptosis, which occurred with concomitant enhancements in autophagy and the cisplatin-evoked apoptosis. In conclusion, our results suggest that clinopodiside A inhibits the growth of the bladder cancer cells via BLK- and RasGRP2-mediated autophagy. The synergistic effect between clinopodiside A and cisplatin is attributed to the increases in autophagy and autophagy-promoted apoptosis. Clinopodiside A is a promising investigational drug for the treatment of cancer, at least blabber, which can be used alone or in combination with clinical drug(s).

[Surface modification of RGD peptides onto acellularized porcine aortic valve to promote cell adhesion].

OBJECTIVE: To investigate the impact of RGD peptides on cell adhesion to acellularized procine aortic valve. METHODS: The acellular porcine aorta valve (APAV) was prepared by removing the cells and cellular components from porcine aortic valve using trypsin and hyposmosis TritonX-100. With the help of epoxy chloropropane (EC), the decelluarized valve scaffolds were immobilized with YGRGDSP peptide. MFBs were seeded onto four groups [acellularized value (AV) group, EC group, glutaraldehyde+EC (GE) group and EC+ RGD group or GE+RGD group] of coupled, coated and untreated decelluarized valve scaffolds. Ninhydrin reaction, cell count and fluorescent imaging test were employed to examine the efficiency of cell adhesion. RESULTS: More cells were attached to the decellularized valve scaffolds when the cells were coupled with RGD peptides compared with the others. The adhesive effect was correlated with the concentration of the RGD peptide and the attaching time. CONCLUSION: With the help of EC, YGRGDSP peptides can be immobilized by covalent bonding. RGD peptides improve cell adhesion to decellularized valve scaffolds.

TCDD-induced antagonism of MEHP-mediated migration and invasion partly involves aryl hydrocarbon receptor in MCF7 breast cancer cells.

Evidence has shown that the activation of AhR (aryl hydrocarbon receptor) can promote cancer cell metastasis. However, limited studies have been carried out on mixed exposure to endocrine-disrupting chemicals (EDCs), especially in human breast cancer. Therefore, using MCF7 human breast cancer cells, we investigated the effects of coexposure to MEHP (mono 2-ethylhexyl phthalate) and TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) on cell migration and invasion, as well as the roles of AhR and the MMP/slug pathway. Our data suggest that MEHP or TCDD can induce migration and invasion in MCF7 cells, and the promotion is partly AhR dependent. We also observed that MEHP antagonized TCDD to reduce AhR-mediated CYP1A1 expression. Subsequently, we revealed that MEHP recruited AhR to dioxin response element (DRE) sequences and decreased TCDD-induced AhR-DRE binding in CYP1A1 genes. Overall, MEHP is a potential AHR agonist, capable of decreasing TCDD-induced AhR-DRE binding in CYP1A1 genes. The antagonizing effect of coexposure led to the inhibition of the epithelial-mesenchymal transition (EMT) in MCF7 cells. Our study provides new evidence for the potential mechanisms involved in EDCs exposure and their interactions in EMT.