Therapeutic targeting of HYPDH/PRODH2 with N-propargylglycine offers a Hyperoxaluria treatment opportunity.

N-propargylglycine prevents 4-hydroxyproline catabolism in mouse liver and kidney. N-propargylglycine is a novel suicide inhibitor of PRODH2 and induces mitochondrial degradation of PRODH2. PRODH2 is selectively expressed in liver and kidney and contributes to primary hyperoxaluria (PH). Preclinical evaluation of N-propargylglycine efficacy as a new PH therapeutic is warranted.

Effects of L-ascorbic acid (C6H8O6: Vit-C) on collagen amino acids: DFT study.

Vitamin C plays a very important role in the repair of connective tissue, especially for sports whose training causes the most damage to this tissue. Therefore, many people believe that L-ascorbic acid (C6H8O6: vitamin C) reduces the recovery time between sports exercises. The most abundant form of structural protein in the body is collagen. Collagen is characterized by a high concentration of the three amino acids glycine (Gly), proline (Pro), and hydroxyproline (Hyp), which creates its characteristic triple helix structure. Therefore, in this study, the effect of vitamin C presence on the sequence, interaction, and orientation of amino acids for collagen formation is investigated using computational simulation. This study aimed to investigate the mechanism of action of vitamin C in terms of thermodynamics and structure of the reaction. The calculations are performed using density function theory (DFT) by the base set of B3LYP/6-311++G (p,d). The results show that the presence of vitamin C is effective in the formation of collagen protein for this interaction and the mechanism of amino acid sequence (Gly-Hyp-Pro) is better in the formation of collagen protein in the presence of vitamin C. The presence of Vit-C in the formation and direction of hydroxyproline (Hyp) causes its separation from the prolyl 5-hydroxylase enzyme. In the absence of vitamin C, the reaction stops at this stage and proline cannot be converted into hydroxyproline. The computational data shows vitamin C prevents unwanted interactions and directs amino acid reactions to repair connective tissue (collagen). Therefore, vitamin C acts as a cofactor in the Prolyl 5-Hydroxylase enzyme and causes it to convert proline to hydroxyl.

Optimized Mouse Models for Liver Fibrosis.

Fibrosis is the excessive accumulation of extracellular matrix components due to chronic injury, with collagens as predominant structural components. Liver fibrosis can progress to cirrhosis, which is characterized by a severe distortion of the delicate hepatic vascular architecture, the shunting of the blood supply away from hepatocytes and the resultant functional liver failure. Cirrhosis is associated with a highly increased morbidity and mortality and represents the major hard endpoint in clinical studies of chronic liver diseases. Moreover, cirrhosis is a strong cofactor of primary liver cancer. In vivo models are indispensable tools to study the cellular and molecular mechanisms of liver fibrosis and to develop specific antifibrotic therapies towards clinical translation. Here, we provide a detailed description of select optimized mouse models of liver fibrosis and state-of-the-art fibrosis readouts.

[Determination of hydroxyproline in liver tissue by hydrophilic interaction chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry].

A method for the determination of hydroxyproline (Hyp) in liver tissue of mice by hydrophilic interaction chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry (HILIC-HRMS) was developed. The liver tissue samples of normal mice and liver fibrosis mice induced by carbon tetrachloride were hydrolyzed by concentrated hydrochloric acid. After filtrated and diluted by solution, the diluent was separated on an Hypersil GOLD HILIC column (100 mm×2.1 mm, 3 µm). Water-acetonitrile (28:72, v/v)were used as the mobile phases with isocratic elution. Finally, the target analytes were detected in positive model by HRMS equipped with an electrospray ionization source. The linear range of hydroxyproline was from 0.78 to 100.00 µg/L with the correlation coefficient (R2) of 0.9983. The limit of quantification was 0.78 µg/L. By detecting the spiked samples, the recoveries were in the range of 97.4%-100.9% with the relative standard deviations (RSDs) between 1.4% and 2.0%. In addition, comparison of the measurement results by this method and the chloramine T method was proceeded. It was found that the linear correlation between the two methods was very good, and the Pearson correlation coefficient was 0.927. And this method had simpler operation procedure and higher accuracy than chloramine T method. This method can be used for the quick determination of hydroxyproline in liver tissue samples.

Effect of dimethylaminoethanol and compound amino acid solution on collagen metabolism and free radicals in D-galactose induced aging rat skin / 中华医学美学美容杂志

Objective To study the mechanism of anti-aging effect of dimethylaminoethanol (DMAE) and compound amino acid (AA) injection by mesotheray in D-galactose-induced skin aging rat.Methods Eighty rats were randomly divided into aging treatment group (60 cases),aging control group (10 cases) and normal control group (10 cases).The skin aging models were established by subcutaneous infectim of D-galactose.From the 18th day,the aging treatment group were injected intradermally in the rats' both sides hip skin with 0.2％ DMAE+ AA,0.1％ DMAE+AA,0.2％DMAE,0.1％ DMAE,AA,and saline,once a week.After four weeks,HE,water content,superoxide dismutase (SOD) activity,hydroxyproline (HYP) and malondialdehyde (MDA) content were measured.Results Compared with the aging control group,the epidermal and the dermal thickness and the collagen area of rats skin' increased significantly in 0.2 ％ DMAE+ AA and 0.1％ DMAE+ AA treatment groups (P＜0.05).0.2％ DMAE+AA and 0.1 ％ DMAE+AA treatment groups also had higher SOD activity,HYP content and lower MDA content than other groups (P＜0.05),but no difference was noted among normal control group,0.2％ DMAE+AA and 0.1％ DMAE+AA group (P＞0.05).There were no differences in water content among groups (P＞0.05).Conclusions Intradermal injection with 0.1％ DMAE+ AA and 0.2 ％ DMAE+AA in aging rats may increase the epidermal and the dermal thickness and the collagen of rats skin' improve SOD activity,HYP content and decreased MDA content,indicating that it has ability to clear skin free radicals,enhance antioxidant capacity and skin collagen metabolism,and thus prevent skin aging.

Effect of Cordyceps sinensis and Panax notoginseng compound extracts on Bleomycin-induced pulmonary fibrosis in rats and its mechanisms / 中草药

Objective: To study the effect of Cordyceps sinensis and Panax notoginseng compound extracts (CSPNE) on Bleomycin-induced pulmonary fibrosis (PF) in rats and its mechanisms. Methods: Wistar rats were randomly divided into five groups (18 rats in each group). Rats in model, high- and low-dosage (150 and 75 mg/kg) CSPNE, and Prednisone acetate (3.33 mg/kg) groups were injected with a single dose of Bleomycin hydrochloride through trachea and in control group with the same volume of normal saline. One day after the injection, CSPNE solution of different dosages was respectively ig given to rats daily, while the same volume of normal saline was given to those in the control and model groups. On day 7, 14, and 28 after medication, six rats in per treatment group were randomly killed. Lung samples in every group of rats were measured for lung index, hydroxyproline (Hyp) and malonaldehyde (MDA) contents, and superoxide dismutase (SOD) activities, and serum was analyzed for SOD activities and MDA contents. Lungs were incised to make pathological sections which were stained with HE, and the expression of TGF-β1, Collagen I, and Collagen III in lung tissue was analyzed by means of immunohistochemistry technique. Arterial blood gas detection was observed in every group. Results: CSPNE could significantly decrease the lung index and Hyp contents in the lung tissue of rats with PF. It could enhance SOD activities and reduce MDA contents both in serum and lung tissues. It also decreased the expression of TGF-β1, Collagen I, and Collagen III in lung tissues. In the arterial blood gas detection CSPNE was found to make [p(CO2)] lowered, while [p(O2)] increased in the artery of rats with PF. Conclusion: CSPNE has obvious effect of inhibiting PE of rats, and the mechanism may be associated with its antilipid peroxidation, inhibiting the expression of TGF-β1, reducing the alveolar interstitial collagen deposition, and improving respiratory function as well.

Effect of Haobie Yangyin Ruanjian Decoction on rats with hepatic fibrosis induced by CCl4 composited factor / 中草药

Objective: To observe the effect of Haobie Yangyin Ruanjian Decoction (HYRD) on rats with hepatic fibrosis induced by CCl4 composited factor. Methods: Wistar rats were randomly divided into seven groups: control group, model group, HYRD groups of low, medium, and high doses, positive groups of Fufang Biejia Rungan Tablets, and colchicin. Model of hepatic fibrosis was induced by CCl4 composited factor. Malondialdehyde (MDA), total protein (TP), albumin (ALB) in serum and hydroxyproline (Hyp) in liver were detected by chromatometry; MMP-2 and MMP-9 activities in liver were detected by gelatin zymography; α-SMA expression in liver was evaluated by immunohistochemical method. Results: MDA in serum and Hyp in liver were decreased gradually in HYRD groups compared with those of model group; TP and ALB in serum were increased gradually in HYRD groups compared with those of model group; MMP-2 activity in liver was decreased in HYRD groups compared with those of model group; MMP9 activity had no significant change in each group and α-SMA expression was decreased gradually in HYRD groups compared with those of model group. Conclusion: HYRD can antagonize the hepatic fibrosis induced by CCl4 composited factor.