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Abstract.: The role of nitric oxide (NO) in cellular signaling has become one of the most rapidly growing areas in biology during the past two decades. As a gas and free radical with an unshared electron, nitric oxide participates in various biological processes. The interaction between NO and proteins may be roughly divided into two categories. In many instances, NO mediates its biological effects by activating guanylyl cyclase and elevates intracellular cyclic GMP synthesis from GTP. However, the list of cGMP-independent effects of NO is also growing at a rapid rate. In this review, the importance and relevance of nitrotyrosine formation are stressed. The utilization of intact cell cultures, tissues, and cell-free preparations along with the use of pharmacological, biochemical, and molecular biological approaches to characterize, purify, and reconstitute these NO regulatory pathways could lead to the development of new therapies for various pathological conditions that are characterized by unbalanced production of NO. Keywords:: nitric oxide, inducible nitric oxide synthase (iNOS, NOS-2), nitrotyrosine, peroxidase, hemin

Abstract Objective The objective of this study was to evaluate the anti-tumor effects of Ad/gTRAIL (an adenoviral vector in which expression of GFP and TRAIL is driven by a human telomerase reverse transcriptase promoter, hTERT) on malignant meningiomas and gliomas. Background Gliomas and meningiomas are the two most common types of human brain tumors. Currently there is no effective cure for recurrent malignant meningiomas or for gliomas. Ad/gTRAIL has been shown to be effective in killing selected lung, colon and breast cancer cells, but there have been no studies reporting its antitumor effects on malignant meningiomas. Therefore, we tested the antitumor effect of Ad/gTRAIL for the first time in human malignant meningioma and glioma cell lines, and in intracranial M6 and U87 xenografts. Methods Materials and Methods: Human malignant meningioma and glioma cells were infected with adenoviruses, Ad/gTRAIL and Ad/CMV-GFP. Cell viability was determined by proliferation assay. FACS analysis and quantification of TRAIL were used to measure apoptosis in these cells. We injected Ad/gTRAIL viruses in intracranial M6 and U87 xenografts, and measured the brain tumor volume, quantified apoptosis by TUNEL assay in the brain tumor tissue. Results Our studies demonstrate that in vitro/in vivo treatment with Ad/gTRAIL virus resulted in significant increase of TRAIL activity, and elicited a greater tumor cell apoptosis in malignant brain tumor cells as compared to treatment with the control, Ad/CMV-GFP virus without TRAIL activity. Conclusions We showed for the first time that adenovirus Ad/gTRAIL had significant antitumor effects against high grade malignant meningiomas as well as gliomas. Although more work needs to be done, our data suggests that Ad/gTRAIL has the potential to be useful as a tool against malignant brain tumors.

Esophageal cancer (EC) poses a significant challenge among tract tumors worldwide due to its complex molecular composition, which remains largely unexplored. Kanglaite (KLT), a medicine known for its anti-tumor properties, is emerging as a potential ally in the culinary world. Plasmacytoma Variant translocation 1 (PVT1) plays a significant role in the complex nature of esophageal cancer, showing high expression levels in tumor tissues. During our investigation, we discovered a higher presence of PVT1 in cancer tissues, which led us to explore its functions further. Through manipulating techniques, we found that inhibiting PVT1 not only hinders the growth of esophageal cancer cells but also reduces fibrosis. This is similar to enhancing the texture and flavor of a dish. Our study reveals the interactions at play, highlighting how PVT1 orchestrates the TGF β/Smad pathway – a component in the development of esophageal cancer. Introducing KLT, an expert poised to revolutinize the approach to cancer treatment. Our research demonstrates KLT's effectiveness in regulating the PVT1/TGF-β/Smad axis, uncovering its fibrotic properties, and its ability to hinder the progression of esophageal cancer. With these discoveries, KLT emerges as a promising option for the treatment of esophageal cancer. [ABSTRACT FROM AUTHOR]

Periostin, identified as a matricellular protein and an ECM protein, plays a central role in non-neoplastic diseases. Periostin and its variants have been considered to be normally involved in the progression of most non-neoplastic diseases, including brain injury, ocular diseases, chronic rhinosinusitis, allergic rhinitis, dental diseases, atopic dermatitis, scleroderma, eosinophilic esophagitis, asthma, cardiovascular diseases, lung diseases, liver diseases, chronic kidney diseases, inflammatory bowel disease, and osteoarthrosis. Periostin interacts with protein receptors and transduces signals primarily through the PI3K/Akt and FAK two channels as well as other pathways to elicit tissue remodeling, fibrosis, inflammation, wound healing, repair, angiogenesis, tissue regeneration, bone formation, barrier, and vascular calcification. This review comprehensively integrates the multiple roles of periostin and its variants in non-neoplastic diseases, proposes the utility of periostin as a biological biomarker, and provides potential drug-developing strategies for targeting periostin. [ABSTRACT FROM AUTHOR]

A full-length cDNA encoding a [Ca.sup.2+]-sensing receptor (CaSR) expressed in rat dorsal root ganglia (DRG) was identified using rapid amplification of 5'-cDNA ends and primer extension and then cloned into the plasmid vector pCR3.1. The DNA sequence of the DRG CaSR was 99.9% homologous with published rat kidney CaSR in the coding region and 247 bp upstream of the start site but showed little homology 5' to this site, which maps to exonic junction I/II, supporting the hypothesis that CaSR message arises as a splice variant and showing tissue-to-tissue heterogeneity. Western blot revealed a doublet of 140 and 160 kDa in a thyroparathyroid preparation and a single 140-kDa band in DRG. Deglycosylation using N-glycanase increased the mobility of CaSR protein from both DRG and thyroparathyroid, whereas endo-H was without effect, indicating that the DGR CaSR is a mature form of the receptor. A DRG CaSR-pEGFP fusion product was constructed, and when transfected into HEK-293 cells, it was distributed at the cell membrane and resulted in extracellular [Ca.sup.2+] (0.5-3 mM)-evoked increases in intracellular [Ca.sup.2+], which in some instances exhibited oscillatory behavior. We conclude that DRG CaSR cDNA arises from tissue-specific alternative splicing of a single gene, that the amino acid sequence of DRG CaSR is homologous to other known CaSRs, and that the DRG CaSR undergoes differential posttranslational processing relative to the thyroparathyroid CaSR and is functionally active when transfected into a human-derived cell line. calcium; dorsal root ganglion; posttranscriptional modification; glycosylation

Nitrotyrosine formation in rat kidney after animals received endotoxin for 24 hrs was studied. Findings showed that the marked staining of nitrotyrosine in proximal tubular epithelial cells was in the subapical compartment where the endocytic lysosomal apparatus is located. Therefore, a large portion of nitrotyrosine may come from the hydrolysis of nitrated proteins that are reabsorbed by the proximal tubule during the endotoxin treatment.

The effects of traumatic brain injury (TBI) on cerebral artery contraction and relaxation were analyzed in anesthetized rats after moderate and severe midline fluid percussion TBI or sham injury. Analysis of isolated posterior and middle cerebral arteries from rats with midline fluid percussion TBI indicated the presence of unaltered intrinsic arterial contractile ability. Furthermore, TBI did not alter fundamental responses to applied agonists in rodent pial arterioles.

The calciotropic steroid, 1-alpha,25-dihydroxycholecalciferol (1,25(OH2)D3), accelerates the intracellular Ca2+ mobilization which leads to increased force generation in resistance arteries. Smooth muscle cells have increased levels of intracellular Ca2+. The 1,25(OH2)D3 induces active stress and the activity of verapamil-sensitive Ca2+ channels in the mesenteric resistance arteries. Basal-sensitive Ca2+ channels have increased Ca2+ mobilization and active stress.

1,25-dihydroxyvitamin D3 (1,25{OH}2D3) is important to understand because of its elevation in many conditions associated with heart dysfunction. 1,25{OH}2D3 enhances the expression of the myosin light chain and heavy chain in the aorta, but there is differential distribution and 1,25(OH)2D3 responsiveness of the smooth muscle isoform of the light chain along the arterial tree. The increase in light chain is due to an increase in the smooth muscle isoform of the protein, showing the differentiating effect of 1,25(OH)2D3 in the aorta. 1,25(OH)2D3 also enhances stress generation in the resistant artery.

A study of mesentric arteries isolated from Wistar rats using wire myography and a fura-based method to unravel the mechanism by which extracellular Ca(super 2+) controls vascular smooth muscle force generation revealed that Ca(sub 0) regulates force generation by depressing myofilament Ca(super 2+) sensitivity and lowering Ca(sub i) after to activation of a calcium activated potassium channel. The results comply with the theory that enhancing extracellular Ca(super 2+) over a bodily concentration range downregulates force generation by altering the Ca(sub i)-force relationship.

Political identity directly affects the implementation of the nurturing function of politics and the enhancement of the teaching effect, this paper proposes a path to enhance students’ political identity in the teaching of Daofa based on the multimodal fusion model. The TF-IDF method is utilized to identify political emotions contained in students’ classroom expressions, and LBP is used to extract students’ facial expression features. Based on the above-extracted results, a multimodal feature learner emotion data model is designed, which is also combined with a deep RNN model to identify and analyze students’ learning behaviors in the actual Daofa classroom. Evaluating students’ political identity from five dimensions, the results show that all students have significant differences in the five dimensions, P

To solve the water hazard problem of Jurassic coal seam roof sandstone in Yinxing No.1 Coal Mine of Ningxia Province, the direct relationship between the sedimentary environment of Jurassic coal seam roof sandstone and water abundance was analyzed and the water abundance of sandstone aquifer was evaluated on the basis of combing the geological and hydro-geological conditions of the mine. The mechanism and characteristics of water disaster in Jurassic coal seam roof sandstone were analyzed based on the study of the mechanical properties, mineral composition, water stability characteristics and water-conducting fracture development law of coal seam roof strata. In this paper, we propose the idea of comprehensively applying various measures of “exploration, drainage, discharge, interception and monitoring”, and focusing on the basic exploration work, using hydrophobic and depressurizing technology to control water damage. The water damage control effect of 110301 working face show that it was feasible to control the sandstone water damage on the roof of Jurassic coal seam through hydrophobic depressurization.