Critical Reviews in Eukaryotic Gene Expression最新文献

The objective of this study is to assess the prevalence of antibiotic-resistant genes (ARGs) in the intestines of infants and the factors affecting their distribution. Breast milk and infant stool samples were collected from nine full-term, healthy mother-infant pairs. The bacterial distribution and various types of ARGs present in the samples were analyzed using metagenomic next-generation sequencing. Over a period spanning from 2 to 240 d after birth, a total of 273 types of ARGs were identified in both infant feces and breast milk, exhibiting a trend of increasing prevalence over time. High concentrations of representative ARG populations were identified in the intestines of infants, especially at 12-15 d after birth. These populations included APH3-Ib, tetW/N/W, mphA, and Haemophilus influenzae PBP3, and multiple ARG Escherichia coli soxS that were resistant to common clinically used aminoglycoside, tetracycline, macrolide, and beta-lactam antibiotics. Gammaproteobacteria and Bacilli, especially Enterococcus, Staphylococcus, Acinetobacter, Streptococcus, and Escherichia were among the identified ARG carriers. Maternal age and body mass index (present and before pregnancy), infant sex, maternal consumption of probiotic yogurt during pregnancy, and lactation might be substantial factors influencing the occurrence of ARG-carrying bacteria and ARG distribution in the infant feces. These results indicate that environmental factors may influence the distribution of ARG-carrying bacteria and ARGs themselves in infants during early life. Providing appropriate recommendations regarding maternal age, body mass index during pregnancy, and use of probiotic products could potentially mitigate the transmission of antibiotic-resistant microbiota and ARGs, thereby diminishing the risk of antibiotic-resistant infections and safeguarding children's health.

Neuroblastoma is a malignant tumor of neuroblasts, immature nerve cells found in several areas of the body. It usually affects children under age of 5. As usual, the tumor has ability to grow rapidly and to expand vastly which ultimately leads to death. Mostly, management decisions can be drawn by the prediction of the stage of the disease as well as age at the time of its diagnosis. There are four main stages of neuroblastoma, and treatment is according to the low and high risk of the disease. Several cytotoxic agents along with other therapies (antibody therapy, gene therapy, and even immunological therapies, antiangiogenic therapy, etc.) are used. Immunotherapy also has an important treatment option used nowadays for neuroblastoma. The discovery of major neuroblastoma-predisposition gene anaplastic lymphoma kinase cause somatic transformation or gene strengthening in diagnosed neuroblastoma. Promising new antiangiogenic strategies have also been introduced for the treatment of neuroblastoma with multiple mylomas. To manage numerous myelomas and cancers, including neuroblastoma, bone marrow transplantation and peripheral blood stem cell transplantation may be used.

Lung adenocarcinoma (LUAD) severely affects human health, and cisplatin (DDP) resistance is the main obstacle in LUAD treatment, the mechanism of which is unknown. Bioinformatics methods were utilized to predict expression and related pathways of AURKB in LUAD tissues, as well as the upstream regulated microRNAs. qRT-PCR assayed expression of AURKB and microRNA-486-5p. RIP and dual-luciferase experiments verified the binding and interaction between the two genes. CCK-8 was used to detect cell proliferation ability and IC50 values. Flow cytometry was utilized to assess the cell cycle. Comet assay and western blot tested DNA damage and γ-H2AX protein expression, respectively. In LUAD, AURKB was upregulated, but microRNA-486-5p was downregulated. The targeted relationship between the two was confirmed by RIP and dual-luciferase experiments. Cell experiments showed that AURKB knock-down inhibited cell proliferation, reduced IC50 values, induced cell cycle arrest, and caused DNA damage. The rescue experiment presented that high expression of microRNA-486-5p could weaken the impact of AURKB overexpression on LUAD cell behavior and DDP resistance. microRNA-486-5p regulated DNA damage to inhibit DDP resistance in LUAD by targeting AURKB, implying that microRNA-486-5p/AURKB axis may be a possible therapeutic target for DDP resistance in LUAD patients.

Gestational diabetes mellitus (GDM) complicated with preeclampsia can lead to polyhydramnios, ketosis. Herein, we explored that CPEB4 in cancer progression of preeclampsia and its underlying mechanism. All the serum samples were collected from patients with preeclampsia. These was the induction of CPEB4 in patients with preeclampsia. The serum of CPEB4 mRNA expression was positive correlation with Proteinuria, systolic blood pressure and diastolic blood pressure in patients. The serum of CPEB4 mRNA expression was also negative correlation with body weight of infant in patients. The serum of CPEB4 mRNA expression also was negative correlation with GPX4 level and GSH activity level in patients. The serum of CPEB4 mRNA expression was positive correlation with iron content in patients. CPEB4 gene inhibited trophoblast cell proliferation. CPEB4 gene promoted trophoblast cell ferroptosis by mitochondrial damage. CPEB4 gene induced PFKFB3 expression by the inhibition of PFKFB3 Ubiquitination. PFKFB3 inhibitor reduced the effects of CPEB4 on cell proliferation and ferroptosis of trophoblast cell. Taken together, the CPEB4 promoted trophoblast cell ferroptosis through mitochondrial damage by the induction of PFKFB3 expression, CPEB4 as an represents a potential therapeutic strategy for the treatment of preeclampsia or various types of GDM.

Water is the most limiting factor for plant growth and crop productivity. Drought stress adversely affects crop yield throughout the world. Up to 50% of crop yield in Pakistan is severely affected by the shortage of water. Cotton is an important cash crop for Pakistan known as "white gold." It accounts for 8.2% of the value added in agriculture and about 3.2% of GDP. Besides, being the world's fourth-largest cotton producer, our yield per acre ranks 13th in the world. If we look at the Pakistan scenario, water deficiency is one of the major yield-limiting factors. Limitations related to conventional breeding and the advancements in plant genomics and biotechnology applications have opened new horizons to plant improvements. Therefore, in the current study, we carry out a comparative analysis to evaluate the morphological, physiological biochemical and molecular parameters in transgenic plants containing GaUSP-1, GaUSP-2 and GaZinc Finger genes under different drought stress conditions. Data showed that transgenic plants showed more tolerance as compared to non-transgenic plants. Transgenic and non-transgenic assist us in our better understanding of the drought-responsive mechanism and its effect on different plant growth traits, so, in this way, we would be able to explore drought tolerance mechanism and this will open the doors for the identification of drought-related genes.

A major subtype of renal cancer is clear cell renal cell carcinoma (ccRCC). Krüppel-like factor 3 (KLF3) dysfunction is also revealed leading to poor prognosis in multiple cancer types. However, dysregulation and molecular dynamics of KLF3 underlying ccRCC progression still remains elusive. Here KLF3 gene and protein expressions in ccRCC were explored using data cohorts from The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), Clinical Proteomic Tumor Analysis Consortium (CPTAC) and verified them in our patient cohort. Correlations of KLF3 expression with clinicopathological features, epigenetic modification, and immune microenvironment characteristics were further investigated. KLF3 was significantly down-regulated expressed in ccRCC tissues compared to adjacent normal controls. Adverse pathological parameters and poor prognosis were associated with lower expression of KLF3. Mechanically, KLF3 regulation was mainly attributed to CpG island methylation. KLF3-high expression subgroup was significantly enriched in cell signaling pathways most associated with EMT markers, angiogenesis, inflammatory response, apoptosis, TGF-β, degradation of ECM, G2M checkpoint, and PI3K-AKT-mTOR. Based on GDSC database, KLF3 upregulation was identified to be associated with higher sensitivities towards PI3K-Akt-mTOR pathway inhibitors such as PI-103, PIK-93, and OSI-027. In addition, patients with down-regulated KLF3 expressions were found more sensitive towards Trametinib, Cetuximab, and Erlotinib. Collectively, our findings suggest that KLF3 may act as a suitable biomarker for prognosis prediction, tumor microenvironment (TME) phenotype identification, thereby helping ccRCC patients to make better therapeutic decisions.

There is a wide variety of cancer cells that can be linked to the presence of TPX2. However, there is not a lot of evidence regarding its role in the development and maintenance of clear cell renal cell carcinoma (ccRCC). In our study, bioinformatics analysis was performed to obtain differentially expressed mRNAs and miR-NAs in ccRCC. Survival curves predicted correlation of TPX2 expression with patient survival. The upstream regulatory miRNA of TPX2 was predicted to be miRNA-27b-3p through database, and dual luciferase assay verified the targeted relationship. qRT-PCR and Western blot were employed for examination of TPX2 mRNA and protein expression in ccRCC cells. Proliferation, invasion, migration and cell cycle were detected by CCK-8, colony formation, wound healing, Transwell, and flow cytometry assays. The results showed that TPX2 showed very high expression in ccRCC, and patients with higher TPX2 expression had shorter relative survival. Low miRNA-27b-3p expression was found in ccRCC. Knockdown of TPX2 or forced expression of miRNA-27b-3p in ccRCC cells inhibited cell proliferation, migration, invasion, and arrested cell division in G0/G1 phase. Dual luciferase reporter presented that miRNA-27b-3p targeted TPX2 to inhibit its expression. Rescue experiments demonstrated that the miRNA-27b-3p/ TPX2 axis affected the biological functions of ccRCC cells. Concurrent overexpression of miRNA-27b-3p and TPX2 inhibited the facilitating effect of TPX2 on ccRCC cell growth. The results revealed novel regulatory mechanisms involved in ccRCC progression, hoping that it may spark an insight for later discovery about the new therapeutic targets for ccRCC.

Destruction of the tumor (cancerous) cells may be caused by live viruses, which have replicative ability and replicate selectively in tumor cells, known as oncolytic virotherapy. In comparison of conservative cancer therapy, tumor-selective replicating viruses have more advantages. These viruses have introduced new methodologies for the human cancer treatment. Numerous strategies are used in development of virotherapeutics. Virotherapy is not unusual concept, but modern advances in technology of genetic modification of oncolytic viruses have improved the ability of targeting tumor cells more specifically, it triggered the development of novel ammunition to fight cancer. An effective virotherapeutic approach with oncolytic viruses exhibits the feasibility and safety under clinical approach. New strategies are being explored to overcome basic obstacles and challenges in virotherapy. Administration of oncolytic viruses, logically, will successfully augment new treatments against many kinds of tumors. Some encouraging antitumor responses shown by combination therapy are provoking strong immunity against established cancer. Chief developments in oncolytic virotherapy have seen in past several years. Significant understandings have been provided by findings on the interface among immune comebacks and viruses, whereas potential results have shown in clinical trials.