Experimental Biology and Medicine最新文献

In this study, we aimed to investigate the effect of paraoxonase 1 (PON1) rs662 polymorphism, arylesterase (ARE) activity, and the serum lipid profile in patients with coronavirus disease 2019 (COVID-19) in different stages of the disease considering post-COVID outcomes. A total of 470 COVID-19 patients (235 female and 235 male patients) were recruited into the study, and based on the World Health Organization (WHO) criteria, the patients were divided into three groups: moderate, severe, and critical. PON1 rs662 polymorphism was determined by the Alw 1 enzyme followed by agarose gel electrophoresis. Moreover, serum levels of triglycerides (TG), cholesterol (Chol), high-density lipoprotein-cholesterol (HDL-c), and low-density lipoprotein-cholesterol (LDL-c), as well as the level of the ARE activity of PON1 in the sera of patients were measured at the time of infection and one and three months after hospitalization. There was a significant relationship between the G allele and the severity of the disease. In addition, the probability of death in homozygous individuals (GG) was higher than in heterozygous patients (GA), and it was higher in heterozygous patients than in wild-type individuals (AA). There was also a significant relationship between the decrease in serum lipids and the intensity of COVID-19. On the contrary, at the onset of the disease, the HDL-c level and serum ARE activity were reduced compared to one and three months after COVID-19 infection. The findings of this study indicated the significant impact of PON1 rs662 polymorphism on ARE activity, lipid profiles, disease severity, and mortality in COVID-19 patients.

Renal ischemia-reperfusion injury (IRI) is a common clinical complication of multiple severe diseases. Owing to its high mortality and the lack of effective treatment, renal IRI is still an intractable problem for clinicians. Itaconate, which is a metabolite of cis-aconitate, can exert anti-inflammatory and antioxidant roles in many diseases. As a derivative of itaconate with high cell membrane permeability, 4-octyl itaconate (4-OI) could provide a protective effect for various diseases. However, the role of 4-OI in renal IRI is still unclear. Herein, we examined whether 4-OI afforded kidney protection through attenuating endoplasmic reticulum stress (ERS) via nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. To observe the effects of 4-OI on alleviating renal pathologic injury, improving renal dysfunction, decreasing inflammatory cytokines, and reducing oxidative stress, we utilized C57BL/6J mice with bilateral renal pedicle clamped and HK-2 cells with hypoxia/reoxygenation (H/R) exposure in our study. In addition, through western blot assay, we found 4-OI ameliorated renal IRI-induced ERS, and activated Nrf2 pathway. Moreover, Nrf2-knockout (KO) mice and Nrf2 knockdown HK-2 cells were used to validate the role of Nrf2 signaling pathway in 4-OI-mediated alleviation of ERS caused by renal IRI. We demonstrated that 4-OI relieved renal injury and suppressed ERS in wild-type mice, while the therapeutic role was not shown in Nrf2-KO mice. Similarly, 4-OI could exert cytoprotective effect and inhibit ERS in HK-2 cells after H/R, but not in Nrf2 knockdown cells. Our in vivo and in vitro studies revealed that 4-OI protected renal IRI through attenuating ERS via Nrf2 pathway.

Ventilator-associated pneumonia (VAP) is a serious complication in neonates requiring mechanical ventilation. This study aimed to determine the risk factors associated with the development of VAP in neonates admitted to the neonatal intensive care unit (NICU) of the Affiliated Hospital of Southwest Medical University. In a retrospective observational study, neonates admitted to the NICU from 1 January 2019, to 31 December 2021, requiring ventilation for more than 48 h were included. Neonates who died within 48 h of NICU admission, those without obtainable consent, or identified with a genetic syndrome were excluded. Various neonatal and clinical variables were evaluated. Univariate and multivariate analyses were performed to determine risk factors associated with VAP. Of the total neonates included, several risk factors were identified for VAP, such as being a premature infant and use of dexamethasone and sedatives. Moreover, reintubation was found to decrease the risk of VAP. Some factors like gestational age, birth weight, Apgar scores at 5 min, and other parameters were found not significantly associated with the development of VAP. The study identified several risk factors associated with the development of VAP in neonates. Recognizing these risk factors could help in the prevention and early management of VAP, thus improving the prognosis for these patients. Further studies are needed to validate these findings and explore the mechanistic links between these factors and VAP.

N6-methyladenosine (m6A) RNA methylation plays a pivotal role in immune responses and the onset and advancement of cancer. Nonetheless, the precise impact of m6A modification in lung adenocarcinoma (LUAD) and its associated tumor microenvironment (TME) remains to be fully elucidated. Here, we distinguished distinct m6A modification patterns within two separate LUAD cohorts using a set of 21 m6A regulators. The TME characteristics associated with these two patterns align with the immune-inflamed and immune-excluded phenotypes, respectively. We identified 2064 m6A-related genes, which were used as a basis to divide all LUAD samples into three distinct m6A gene clusters. We applied a scoring system to evaluate the m6A gene signature of the m6A modification pattern in individual patients. To authenticate the categorization significance of m6A modification patterns, we established a correlation between m6A score and TME infiltration profiling, tumor somatic mutations, and responses to immunotherapy. A high level of m6A modification may be associated with the aggressiveness and poor prognosis of LUAD. Further studies should investigate the mechanism of action of m6A regulators and m6A-related genes to improve the diagnosis and treatment of patients with LUAD.

High-throughput genome-wide sequencing has revealed high genomic variability of HPV16 in different geographic regions which is the most predominant genotype in human papillomavirus (HPV)-associated malignancies. Analysis of the HPV16 by whole-genome sequence (WGS) is an advanced method for the identification of mutations in the genome. There is limited information about HPV16 diversity in Pakistan, especially at the genomic level. Till now, WGS for HPV16 has not been previously reported in Pakistan. The current study has sequenced three HPV16 viral genomes, from two cervical and one oral cavity positive sample of women presented with general gynecological problems without any evidence of precancerous or cancerous lesions using an ion ampliseq customized panel. Sequencing analysis detected 38 variations, including single-nucleotide polymorphisms (SNPs) and two Indels, across three samples with the highest number of SNPs present in E1, E2, and L2, respectively. A total of 20 non-synonymous and 11 synonymous mutations with amino acid substitutions (T1421C, G1515A, T2223C, T1389C, G1483A, and T2191C) were identified. The phylogenetic analysis revealed the genomes of HPV16 are closely associated with those reported from Thailand and the United States. These are the first HPV16 WGS from Pakistan. However, more research is needed with a large sample size from diversified areas to assess the carcinogenic consequences and impact of HPV vaccinations.

Antibiotics can kill bacteria, but their continued use can easily lead to drug resistance, particularly the main pathogenic bacteria of periodontitis, Porphyromonas gingivalis. However, to avoid drug resistance, carbon quantum dots (CDs) have great potential as a bioactive material in antimicrobial therapy. Herein, we use ornidazole as raw material to prepare CDs of different sizes by microwave irradiation and screen CDs with fluorescence and bacteriostatic properties. The inhibition experiments and live/dead assays of P. gingivalis exhibited outstanding antibacterial effects. This research aimed to develop nano-level antibacterial active materials that also have fluorescence traceability. This study offers a different method for the development of multifunctional CDs, provides valuable strategies for the treatment of diseases associated with P. gingivalis, and predicts great application prospects in the field of biomedicine.

The influences of TRIM28 on the gastric tumorigenesis together with potential molecular mechanisms remain to be studied. We aimed at exploring the important effects of TRIM28 on gastric cancer (GC) and uncovering underling molecular mechanisms. Through immunohistochemistry analysis of 20 pairs of GC and the peritumoral tissues, the expression level of TRIM28 was determined. A variety of assays were applied to explore the important roles of TRIM28 in GC. Western blotting and qRT-PCR analyses were used to analyze the association between TRIM28 and the Wnt/β-catenin signaling pathway. TRIM28 was highly expressed in GC tissues than peritumoral tissues. And high expression level of TRIM28 in GC was associated with good prognostic effects. In vitro functional assays suggested TRIM28 knockdown enhanced the proliferation and clone formation of GC cell. Moreover, TRIM28 knockdown enhanced the expression level of stemness markers, strengthened sphere-forming and drug-resistance properties of GC cells, suggesting important effect on GC cell stemness. Besides, our analysis showed that the Wnt/β-catenin signaling was involved in the effect of TRIM28 on GC cell stemness property, and blocking Wnt/β-catenin signaling pathway obviously rescued the promotion influence of TRIM28 knockdown. Overall, TRIM28 has an important influence on regulating the stem-like property of GC cell via Wnt/β-catenin signaling, suggesting TRIM28 a promising drug target and a potential predictor of prognosis.

Chemokines critically orchestrate the tumorigenesis, metastasis, and stemness features of cancer cells that lead to poor outcomes. High plasma levels of transforming growth factor-β1 (TGFβ1) correlate with poor prognostic features in advanced lung cancer patients, thus suggesting the importance of TGFβ1 in the lung tumor microenvironment. However, the role of chemokines in TGFβ1-induced tumor stemness features remains unclear. Here, we clarify the previously undocumented role of CXCL1 in TGFβ1-induced lung cancer stemness features. CXCL1 and its receptor CXCR2 were significantly upregulated in TGFβ1-induced lung cancer stem cells (CSCs). CXCL1 silencing (shCXCL1) suppressed stemness gene expression, tumorsphere formation, colony formation, drug resistance, and in vivo tumorigenicity in TGFβ1-induced lung tumorspheres. Immunohistochemistry staining showed that patients with stage II/III lung cancer had higher expression levels of CXCL1. The levels of CXCL1 were positively associated with lymph node metastasis and correlated with the expression of the CSC transcription factor Oct-4. Furthermore, online database analysis revealed that CXCL1 expression was negatively correlated with lung cancer survival in patients. Patients with high TGFβ1/CXCL1/CD44 co-expression had a worse survival rate. We suggest that CXCL1 serves as a crucial factor in TGFβ1-induced stemness features of lung cancer.