Differential expressions of TGF-β1, HIF-1, VEGF, α-SMA and E-cadherin in renal tissues of a neonatal rat model of hydronephrosis

Purpose: To investigate the differential expressions of transforming growth factor-β1 (TGF-β1), hypoxia inductive factor-1 (HIF-1), vascular endothelial growth factor (VEGF), α-smooth muscle protein (α-SMA) and E-cadherin in renal tissues of neonatal rat model of hydronephrosis.Methods: The neonatal rats (90) were randomly divided into sham group and model group. The rats in the model group were further divided into two subgroups: week 1 and week 12 after relief of obstruction, with 30 rats in each group. Six rats were taken from each group for the determination of renal histopathological changes. Levels of TGF-β1, HIF-1, VEGF, α-SMA and E-cadherin in renal tissues were compared for different pathological grades and at different time points of obstruction relief.Results: With increase in Elder grade, the concentrations of TGF-β1, HIF-1, VEGF and α-SMA in renal tissues of hydronephrosis neonatal rats were gradually increased, while the expression level of Ecadherin gradually decreased (p < 0.05). However, the concentrations of TGF-β1, HIF-1, VEGF and α-SMA in renal tissues were significantly reduced, while the expression level of E-adherin was upregulated with time after relief of obstruction (p < 0.05).Conclusion: These findings are of great significance in determining the degree of kidney injury and recovery, and for the development of drugs for the treatment of renal injury

Branched-chain amino acids catabolism and cancer progression: focus on therapeutic interventions

Branched-chain amino acids (BCAAs), including valine, leucine, and isoleucine, are crucial amino acids with significant implications in tumorigenesis across various human malignancies. Studies have demonstrated that altered BCAA metabolism can influence tumor growth and progression. Increased levels of BCAAs have been associated with tumor growth inhibition, indicating their potential as anti-cancer agents. Conversely, a deficiency in BCAAs can promote tumor metastasis to different organs due to the disruptive effects of high BCAA concentrations on tumor cell migration and invasion. This disruption is associated with tumor cell adhesion, angiogenesis, metastasis, and invasion. Furthermore, BCAAs serve as nitrogen donors, contributing to synthesizing macromolecules such as proteins and nucleotides crucial for cancer cell growth. Consequently, BCAAs exhibit a dual role in cancer, and their effects on tumor growth or inhibition are contingent upon various conditions and concentrations. This review discusses these contrasting findings, providing valuable insights into BCAA-related therapeutic interventions and ultimately contributing to a better understanding of their potential role in cancer treatment

The role of nanotechnology-based approaches for clinical infectious diseases and public health

Given the high incidence of infection and the growing resistance of bacterial and viral infections to the traditional antiseptic, the need for novel antiseptics is critical. Therefore, novel approaches are urgently required to reduce the activity of bacterial and viral infections. Nanotechnology is increasingly being exploited for medical purposes and is of significant interest in eliminating or limiting the activity of various pathogens. Due to the increased surface-to-volume ratio of a given mass of particles, the antimicrobial properties of some naturally occurring antibacterial materials, such as zinc and silver, increase as particle size decreases into the nanometer regime. However, the physical structure of a nanoparticle and the way it interacts with and penetrates the bacteria also appear to provide unique bactericidal mechanisms. To measure the efficacy of nanoparticles (diameter 100 nm) as antimicrobial agents, it is necessary to comprehend the range of approaches for evaluating the viability of bacteria; each of them has its advantages and disadvantages. The nanotechnology-based disinfectants and sensors for SARS-CoV-2 provide a roadmap for creating more effective sensors and disinfectants for detecting and preventing coronaviruses and other infections. Moreover, there is an increasing role of nanotechnology-based approaches in various infections, including wound healing and related infection, nosocomial infections, and various bacterial infections. To meet the demand for patient care, nanotechnology-based disinfectants need to be further advanced with optimum approaches. Herein, we review the current burden of infectious diseases with a focus on SARS-CoV-2 and bacterial infection that significantly burdens developed healthcare systems and small healthcare communities. We then highlight how nanotechnology could aid in improving existing treatment modalities and diagnosis of those infectious agents. Finally, we conclude the current development and future perspective of nanotechnology for combating infectious diseases. The overall goal is to update healthcare providers on the existing role and future of nanotechnology in tackling those common infectious diseases

Assessment of a Novel VEGF Targeted Agent Using Patient-Derived Tumor Tissue Xenograft Models of Colon Carcinoma with Lymphatic and Hepatic Metastases

The lack of appropriate tumor models of primary tumors and corresponding metastases that can reliably predict for response to anticancer agents remains a major deficiency in the clinical practice of cancer therapy. It was the aim of our study to establish patient-derived tumor tissue (PDTT) xenograft models of colon carcinoma with lymphatic and hepatic metastases useful for testing of novel molecularly targeted agents. PDTT of primary colon carcinoma, lymphatic and hepatic metastases were used to create xenograft models. Hematoxylin and eosin staining, immunohistochemical staining, genome-wide gene expression analysis, pyrosequencing, qRT-PCR, and western blotting were used to determine the biological stability of the xenografts during serial transplantation compared with the original tumor tissues. Early passages of the PDTT xenograft models of primary colon carcinoma, lymphatic and hepatic metastases revealed a high degree of similarity with the original clinical tumor samples with regard to histology, immunohistochemistry, genes expression, and mutation status as well as mRNA expression. After we have ascertained that these xenografts models retained similar histopathological features and molecular signatures as the original tumors, drug sensitivities of the xenografts to a novel VEGF targeted agent, FP3 was evaluated. In this study, PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastasis have been successfully established. They provide appropriate models for testing of novel molecularly targeted agents

Analysis and Discussions on the Nonuniformity Problem of SCR Denitration Equipment NO

Combining with an engineering example, from the aspects of SCR inlet NOx concentration distribution, flue gas velocity uniformity, ammonia injection valve opening, ash deposit, abrasion and flue arrangement, the uniformity problem of SCR denitration equipment outlet NOx concentration distribution is analyzed and discussed in a 660MW coal-fired unit. The results show that the uneven distribution of NOx concentration is caused by the combined action of many factors. In the cause analysis and solution formulation, the influence factors need be overall consideration. By adjusting the ammonia injection valve opening, the uniformity of SCR outlet NOx concentration increases by about 30%, the performance of SCR denitration equipment is obviously improved. At the same time, rationalization proposals and solution measures for the improvement of outlet concentration uniformity are given in order to ensure the safe and stable operation of denitration equipment

Landscape and Fruit Developmental Regulation of Alternative Splicing in Tomato by Genome-Wide Analysis

In eukaryotes, alternative splicing (AS) is one of the posttranscriptional regulatory mechanisms that play important roles by generating transcriptome diversity. To obtain a global view of AS and its dynamics during tomato fruit development, we analyzed the AS events using a large amount of transcriptome datasets. Same with other plant species, about half of the expressed multiexonic genes were alternatively spliced in tomato. Besides that, our further analyzation of RNA-seq datasets of ovule and pericarp at early fruit developmental stages reveals that the dynamic alteration of AS events occurred in specific tissues and AS was regulated spatially and temporally during early fruit development in tomato. By investigating the sequence variations at splice sites causing differential AS events between tomato cultivar ‘Moneymaker’ and wild species Solanum pimpinellifolium PI365967, we uncover that AS may play the regulatory roles during domestication of tomato. Taken together, our results provided the global AS pattern in tomato and highlighted the importance of AS during tomato fruit development and domestication

Mutational Profiling of Non-Small-Cell Lung Cancer Resistant to Osimertinib Using Next-Generation Sequencing in Chinese Patients

Purpose. To identify the somatic mutated genes for optimal targets of non-small-cell lung cancer after resistance to osimertinib treatment. Patients and Methods. Study patients all had advanced lung adenocarcinoma and acquired resistance to osimertinib as a second- or third-line treatment. These patients had harboring EGFR T790M mutation before osimertinib treatment, which was confirmed by Amplification Refractory Mutation System (ARMS) PCR or Next-Generation Sequencing (NGS). After resistance to osimertinib treatment, tumor tissue was collected by core needle biopsy. DNA was extracted from 15 × 5 um sliced section of formalin-fixed paraffin-embedded (FFPE) material and NGS was done. The genetic changes were analyzed. Results. A total of 9 Chinese patients were studied, 5 females and 4 males, age 51–89 years. After progression with osimertinib treatment, core needle biopsy was performed and next-generation sequencing was performed. Nine patients had harboring 62 point mutations, 2 altered gene copies, 2 amplifications, and 1 EML4-ALK gene fusion. No MET or HER2 amplification was found in this cohort study. Nine patients still maintained initial EGFR 19 del or L858R activating mutations, while 7 of them kept EGFR T790M mutations. Among the 7 patients, 5 had secondary EGFR C797S and/or C797G mutations, which all happened in the same allele with T790M mutation. All patients were treated with targets therapies, chemotherapy, or best supportive care (BSC) in accordance with NGS genetic results and patients’ performance status; 7 of them are still alive and 2 of them died of disease progression at last follow-up. Conclusions. EGFR C797S/G mutation and the same one presented on the same allele with EGFR T790M mutation were the most common mutation feature and played a key role in resistance to osimertinib in Chinese patients with NSCLC. Tumor cells losing T790M mutation and maintaining EGFR activating mutation might benefit from first-generation EGFR-TKI treatment

CcMYB12 Positively Regulates Flavonoid Accumulation during Fruit Development in Carya cathayensis and Has a Role in Abiotic Stress Responses

Flavonoid, an important secondary metabolite in plants, is involved in many biological processes. Its synthesis originates from the phenylpropane metabolic pathway, and it is catalyzed by a series of enzymes. The flavonoid biosynthetic pathway is regulated by many transcription factors, among which MYB transcription factors are thought to be key regulators. Hickory (Carya cathayensis) is an economic forest tree species belonging to the Juglandaceae family, and its fruit is rich in flavonoids. The transcriptome of exocarp and seed of hickory has previously been sequenced and analyzed by our team, revealing that CcMYB12 (CCA0691S0036) may be an important regulator of flavonoid synthesis. However, the specific regulatory role of CcMYB12 in hickory has not been clarified. Through a genome-wide analysis, a total of 153 R2R3-MYB genes were identified in hickory, classified into 23 subclasses, of which CcMYB12 was located in Subclass 7. The R2R3-MYBs showed a differential expression with the development of hickory exocarp and seed, indicating that these genes may regulate fruit development and metabolite accumulation. The phylogenetic analysis showed that CcMYB12 is a flavonol regulator, and its expression trend is the same as or opposite to that of flavonol synthesis-related genes. Moreover, CcMYB12 was found to be localized in the nucleus and have self-activation ability. The dual-luciferase reporter assay demonstrated that CcMYB12 strongly bonded to and activated the promoters of CcC4H, CcCHS, CcCHI, and CcF3H, which are key genes of the flavonoid synthesis pathway. Overexpression of CcMYB12 in Arabidopsis thaliana could increase the content of total flavonoids and the expression of related genes, including PAL, C4H, CHS, F3H, F3’H, ANS, and DFR, in the flavonoid synthesis pathway. These results reveal that CcMYB12 may directly regulate the expression of flavonoid-related genes and promote flavonoid synthesis in hickory fruit. Notably, the expression level of CcMYB12 in hickory seedlings was significantly boosted under NaCl and PEG treatments, while it was significantly downregulated under acid stress, suggesting that CcMYB12 may participate in the response to abiotic stresses. The results could provide a basis for further elucidating the regulation network of flavonoid biosynthesis and lay a foundation for developing new varieties of hickory with high flavonoid content

Astaxanthin Protects Ochratoxin A-Induced Oxidative Stress and Apoptosis in the Heart via the Nrf2 Pathway

This study assessed the protective mechanism of astaxanthin (ASX) against ochratoxin A- (OTA-) induced cardiac injury in mice. Four groups of mice were established: control group (0.1 mL olive oil+0.1 mL NaHCO2), OTA group (0.1 mL OTA 5 mg/kg body weight), ASX group (0.1 mL ASX 100 mg/kg body weight), and ASX + OTA group (0.1 mL ASX 100 mg/kg body weight, 2 h later, 0.1 mL OTA 5 mg/kg body weight). The test period lasted for 27 days (7 days of dosing, 2 days of rest). Electrocardiogram, body weight, heart weight, tissue pathology, oxidative markers (malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH)), biochemical markers (creatine kinase (CK), creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH)), electron microscopy, TUNEL, and Western blot tests were used to examine the effects of OTA on myocardial injury and ASX detoxification. The results showed that OTA exposure significantly decreased both body weight and heart weight. OTA induced a decrease in heart rate in mice and decreased tissue concentrations of SOD, CAT, and GSH, while increasing serum concentrations of cardiac enzymes (CK, CK-MB, and LDH) and tissue MDA. ASX improved heart rate, cardiac enzymes, and antioxidant levels in mice. The results of tissue pathology and TUNEL assay showed that ASX protects against OTA-induced myocardial injury. In addition, Western blot results showed that the OTA group upregulated Keap1, Bax, Caspase3, and Caspase9, while it downregulated Nrf2, HO-1, and Bcl-2 protein expression. ASX played a protective role by changing the expression of Keap1, Nrf2, HO-1, Bax, Bcl-2, Caspase3, and Caspase9 proteins. These results indicate that the protective mechanism of ASX on the myocardium works through the Keap1-Nrf2 signaling pathway and mitochondria-mediated apoptosis pathway. This study provides a molecular rationale for the mechanism underlying OTA-induced myocardial injury and the protective effect of ASX on the myocardium