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1.
Front Genet ; 15: 1339064, 2024.
Article in English | MEDLINE | ID: mdl-38533208

ABSTRACT

Introduction: Pulmonary fibrosis (PF), a type of interstitial pneumonia with complex etiology and high mortality, is characterized by progressive scarring of the alveolar interstitium and myofibroblastic lesions. In this study, we screened for potential biomarkers in PF and clarified the role of the lncRNA-miRNA-mRNA ceRNA network in the inhibitory effect of SRL-4 on PF. Methods: Healthy male SPF SD rats were randomly divided into three groups, namely, CON, MOD, and SRL-4. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to determine the biological functions of the target genes. A visualized lncRNA-miRNA-mRNA ceRNA network was constructed using Cytoscape, while key genes in the network were identified using the cytoNCA plugin. Results: Seventy-four differentially expressed lncRNAs and 118 differentially expressed mRNAs were identified. Gene Ontology analysis revealed that the target genes were mainly enriched in the cell membrane and in response to organic substances, while Kyoto Encyclopedia of Genes and Genomes analysis showed that the target genes were mainly enriched in the AMPK, PPAR, and cAMP signaling pathways. We elucidated a ceRNA axis, namely, Plcd3-OT1/rno-miR-150-3p/Fkbp5, with potential implications in PF. Key genes, such as AABR07051308.1-201, F2rl2-OT1, and LINC3337, may be important targets for the treatment of PF, while the AMPK, PPAR, and cAMP signaling pathways are potential key targets and important pathways through which SRL-4 mitigates PF. Conclusion: Our findings suggest that SRL-4 improves PF by regulating the lncRNA-miRNA-mRNA network.

2.
Biochem Genet ; 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38349440

ABSTRACT

Hyperlipidemia is an independent risk factor for cardiovascular and cerebrovascular diseases. The transcriptomic data and the gene regulatory networks of hyperlipidemia are largely unclear. We analyzed the changes in liver gene expression and the serum levels of biochemical indicators in rats with hyperlipidemia induced by high-fat diet (HFD). The body weight, liver weight, and the serum levels of TG, TC, HDL-C, LDL-C, ALT, and AST were significantly higher in the hyperlipidemic rats compared to the healthy controls (P < 0.05). In addition, HFD feeding decreased the antioxidant capacity of the liver tissues and significantly increased the arteriosclerosis index (AI) (P < 0.05). There were 584 differentially expressed genes (DEGs) in the hyperlipidemia model compared to the control, with |log2FC|≥ 1 and P-adjust ≤ 0.05 as the thresholds. GO analysis of the DEGs revealed significant enrichment of 382 biological processes (BP), 18 cellular components (CC), and 40 molecular functions (MF). In addition, pathways related to bile secretion, cholesterol metabolism, and steroid hormone biosynthesis were significantly associated with hyperlipidemia. The key genes potentially involved in the blood lipid changes were Agt, Src, Gnai3, Cyp2c7, Cyp2c11, Cyp2c22, Apoa1, Apoe, and Srebf1. The genes and pathways identified in this study are potential intervention targets for hyperlipidemia and warrant further investigation.

3.
J Pharm Sci ; 112(12): 2965-2980, 2023 12.
Article in English | MEDLINE | ID: mdl-37741455

ABSTRACT

Antibody-drug conjugates unite the specificity and long circulation time of an antibody with the toxicity of a chemical cytostatic or otherwise active drug using appropriate chemical linkers to reduce systemic toxicity and increase therapeutic index. This combination of a large biological molecule and a small molecule creates an increase in complexity. Multiple production processes are required to produce the native antibody, the drug and the linker, followed by conjugation of afore mentioned entities to form the final antibody-drug conjugate. The connected processes further increase the number of points of control, resulting in necessity of additional specifications and intensified analytical characterization. By combining scientific understanding of the production processes with risk-based approaches, quality can be demonstrated at those points where control is required and redundant comparability studies, specifications or product characterization are avoided. Over the product development lifecycle, this will allow process qualification to focus on those areas critical to quality and prevent redundant studies. The structure of the module 3 common technical document for an ADC needs to reflect each of the production processes and the combined overall approach to quality. Historically, regulatory authorities have provided varied expectations on its structure. This paper provides an overview of essential information to be included and shows that multiple approaches work as long as adequate cross-referencing is included.


Subject(s)
Immunoconjugates , Immunoconjugates/chemistry , Antibodies, Monoclonal/chemistry
4.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 52(1): 46-53, 2023 Feb 25.
Article in English, Chinese | MEDLINE | ID: mdl-37283117

ABSTRACT

OBJECTIVES: To establish and verify a hysteroscopic scoring system for the diagnosis of chronic endometritis (CE) in infertile patients. METHODS: A total of 238 infertile patients who underwent hysteroscopy and endometrial biopsy in the Reproductive Medicine Center, Shijiazhuang Obstetrics and Gynecology Hospital Affiliated to Hebei Medical University from October 1 to December 31, 2019 were enrolled in the study. According to the results of CD138 immunohistochemistry, the patients were divided into CE group (n=73) and non-CE group (n=165). Univariate and binary logistic regression analyses were used to screen the risk factors of CE and a nomogram was establish for hysteroscopic scoring. Receiver operating characteristic (ROC) curve, calibration curve and Bootstrap resampling method were used to evaluate and verify the system. RESULTS: Univariate and binary logistic regression analyses showed that hyperemia area (HA) degree ≥2, micropolyps, polypoid hyperplasia of endometrium and history of ectopic pregnancy were independent risk factors for CE (all P<0.05). A nomogram was generated to establish a hysteroscopy scoring system based on the above four factors. The area under ROC curve of the hysteroscopy scoring system for predicting CE was 0.801 (95%CI:0.742-0.861), the sensitivity was 74.0% and the specificity was 73.9%. The calibration curve showed that the predicting value of the scoring system was highly consistent with the actual value. In the internal verification, the C-index was 0.7811. The predicting value of the verification group in the calibration curve was basically consistent with the actual value, indicating that the scoring system had good stability. CONCLUSIONS: The hysteroscopic scoring system composed of HA, micropolyp, polypoid hyperplasia of endometrium and history of ectopic pregnancy can effectively and intuitively predict CE, which is conducive to improving the diagnosis of CE.


Subject(s)
Endometritis , Infertility, Female , Pregnancy, Ectopic , Pregnancy , Female , Humans , Endometritis/diagnosis , Endometritis/complications , Endometritis/pathology , Hyperplasia/complications , Hyperplasia/pathology , Sensitivity and Specificity , Endometrium/pathology , Chronic Disease , Infertility, Female/diagnosis , Pregnancy, Ectopic/pathology
5.
J Toxicol Environ Health A ; 80(22): 1193-1198, 2017.
Article in English | MEDLINE | ID: mdl-28949828

ABSTRACT

The seeds of Amygdalus mongolica contain various constituents including flavonoids and vitamin E, which are known to exert antioxidant effects. However, the safety of the oil extract of this compound is not fully known. The aim of this study was to determine the physicochemical properties of A. mongolica oil, identify the constituents and subsequently assess the effectiveness of utilizing this seed extract in hyperlipidemia as an antioxidant agent. In particular, the toxicity and safety of A. mongolica oil were examined with emphasis on effects on blood lipids level and serum lipid peroxidation using a hyperlipidemia rat model. Treatment with 20 ml/kg A. mongolica oil produced no apparent adverse effects after 14 days in normal female and male rats. A dose of 2.5-10 ml/kg A. mongolica oil administered to hyperlipidemic male rats significantly decreased serum total cholesterol (TC), low-density lipoprotein-C (LDL-C), malondialdehyde (MDA), total cholesterol high-density lipoprotein-C (TC/HDL-C), LDL-C/HDL-C, and atherosclerosis index(AI). In contrast, glutathione (GSH) levels and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly increased. Data demonstrated that A. mongolica oil may be utilized in conditions of hyperlipidemia due to its antioxidant effects.


Subject(s)
Hyperlipidemias/drug therapy , Plant Oils/chemistry , Plant Oils/pharmacology , Prunus/chemistry , Rats , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Enzyme Activation/drug effects , Female , Gene Expression Regulation/drug effects , Lipid Peroxidation/drug effects , Lipids/blood , Male , Oxidoreductases/genetics , Oxidoreductases/metabolism , Random Allocation , Rats, Wistar
6.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(1): 220-3, 2013 Jan.
Article in Chinese | MEDLINE | ID: mdl-23586260

ABSTRACT

For determination of elements in the leaves of Prunus mongolica, the samples were digested by nitric acid-perchloric. The contents of Ca, Mg, Fe, Mn, Cu, Zn, Al, Sr, Sn and Pb in the leaves of Prunus mongolica were determined by ICP-AES, at the same time a blank experiment was carried out. The results showed that the recovery rate of the ten elements was between 93% and 110%, and the relative standard deviation was between 0.33% and 2.94%. This method is fast, simple and accurate.


Subject(s)
Minerals/analysis , Plant Leaves/chemistry , Prunus/chemistry , Spectrophotometry, Atomic/methods , Calcium/analysis , Iron/analysis , Magnesium/analysis
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