ABSTRACT
A series of structurally chiral cyclic imines efficiently yields chiral nitrones and nitroalkanes. This is the first report of the synthesis of nitro groups by CâN bond cleavage of imines through a nitrone intermediate.
ABSTRACT
OBJECTIVES: This study aimed to develop a liver metastasis-related gene prognostic index (LMPI) for pancreatic ductal adenocarcinoma prognosis and therapy. METHODS: The Cancer Genome Atlas data set was used to identify liver metastasis-related hub genes via weighted gene coexpression network analysis. The core genes were identified to construct an LMPI by using the Cox regression method. An immune cell abundance identifier was applied to determine the immune cell abundance. RESULTS: A total of 78 hub liver metastasis-related genes in the black module were significantly enriched in complement and coagulation cascades, fat digestion and absorption, and the PPAR signaling pathway. Then, an LMPI was constructed on the basis of the 5 prognostic genes (MOGAT3, ASGR1, TRPM8, SGSM1, and LOC101927851). Patients with higher LMPI scores had poor overall survival, more co-occurring or mutually exclusive pairs of driver gene mutations, and less benefit from immunotherapy than patients with lower LMPI scores. In addition, a high correlation was also found between LMPI scores and immune infiltration, such as CD4 naive, CD8 T, cytotoxic T, T helper 2, follicular helper T, and natural killer cells. CONCLUSIONS: The core genes of the LMPI developed may be independent factors for predicting prognosis, immune characteristics, and immunotherapy efficacy in pancreatic ductal adenocarcinoma.
Subject(s)
Carcinoma, Pancreatic Ductal , Liver Neoplasms , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/therapy , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/therapy , Liver Neoplasms/genetics , Liver Neoplasms/therapy , Prognosis , Asialoglycoprotein Receptor , Pancreatic NeoplasmsABSTRACT
AIMS: The depressor action of the centrally antihypertensive drug moxonidine has been attributed to activation of I(1)-imidazoline receptor in the rostral ventrolateral medulla (RVLM). The objective of this study was to determine the role of the γ-aminobutyric acid (GABA) mechanisms in the RVLM in mediating the effect of moxonidine in anaesthetized normotensive rats. METHODS AND RESULTS: The relationship between the effects of microinjection or picoinjection of moxonidine and the functional state of GABA receptors at the level of the RVLM or pre-sympathetic neuron was determined. Microdialysis was performed to detect the effect of moxonidine on the release of GABA in the RVLM. Western blot analysis was carried out to test the effect of chronic intracerebroventricular injection of moxonidine on the protein expression of GABA receptors in the RVLM. Pre-treatment with the GABA(A) or GABA(B) receptor antagonist bicuculline (5 pmol) or CGP35348 (200 pmol), respectively, microinjected into the RVLM significantly attenuated the decrease in blood pressure and renal sympathetic nerve activity induced by moxonidine. In 22 moxonidine-sensitive pre-sympathetic neurons in the RVLM, picoinjection of bicuculline (100 fmol/5 nL) significantly attenuated the neuronal inhibition evoked by moxonidine (100 pmol/5 nL). The release of GABA in the RVLM was increased after intravenous moxonidine (50 µg/kg). Central infusion of moxonidine upregulated the protein expression of both GABA(A) and GABA(B) receptors in the RVLM. CONCLUSION: The current data demonstrate that GABAergic mechanisms in the RVLM are responsible for the hypotension and sympathoinhibition of moxonidine.
Subject(s)
Antihypertensive Agents/toxicity , Hypotension/chemically induced , Imidazoles/toxicity , Medulla Oblongata/drug effects , gamma-Aminobutyric Acid/metabolism , Animals , Antihypertensive Agents/administration & dosage , Blood Pressure/drug effects , Blotting, Western , GABA-A Receptor Antagonists/administration & dosage , GABA-B Receptor Antagonists/administration & dosage , Heart Rate/drug effects , Hypotension/metabolism , Hypotension/physiopathology , Imidazoles/administration & dosage , Infusions, Intraventricular , Injections, Intravenous , Injections, Intraventricular , Kidney/innervation , Male , Medulla Oblongata/metabolism , Microdialysis , Microinjections , Neural Inhibition/drug effects , Rats , Rats, Sprague-Dawley , Receptors, GABA-A/drug effects , Receptors, GABA-A/metabolism , Receptors, GABA-B/drug effects , Receptors, GABA-B/metabolism , Sympathetic Nervous System/drug effects , Sympathetic Nervous System/physiopathologyABSTRACT
The absorbance, fluorescence and Scatchard plots methods as well as the effect of phosphate group on the fluorescence intensity of the cordycepin-DNA-EB system were used to study the interaction of the antitumor compound cordycepin and DNA. It is obvious tiat there is hyperchromic effect and hypochromic effect with slight red shift on the subtracted UV spectrum. It proves that the adenine base of cordycepin can be inserted into the double-helix of DNA. The results of the fluorescence intensity that decreases after increases with a little blue shift on the fluorescence spectrum also proved this. At the same time the phosphate can affect the cordycepin-DNA-EB system. Finally that the result depended on the Scatchard equation indicates that cordycepin reacts electrostatically on phosphate backbone of DNA. There also exists an intercalation into the double-helix of DNA.