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1.
Nucleic Acids Res ; 52(D1): D376-D383, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-37870448

ABSTRACT

Allosteric regulation, induced by perturbations at an allosteric site topographically distinct from the orthosteric site, is one of the most direct and efficient ways to fine-tune macromolecular function. The Allosteric Database (ASD; accessible online at http://mdl.shsmu.edu.cn/ASD) has been systematically developed since 2009 to provide comprehensive information on allosteric regulation. In recent years, allostery has seen sustained growth and wide-ranging applications in life sciences, from basic research to new therapeutics development, while also elucidating emerging obstacles across allosteric research stages. To overcome these challenges and maintain high-quality data center services, novel features were curated in the ASD2023 update: (i) 66 589 potential allosteric sites, covering > 80% of the human proteome and constituting the human allosteric pocketome; (ii) 748 allosteric protein-protein interaction (PPI) modulators with clear mechanisms, aiding protein machine studies and PPI-targeted drug discovery; (iii) 'Allosteric Hit-to-Lead,' a pioneering dataset providing panoramic views from 87 well-defined allosteric hits to 6565 leads and (iv) 456 dualsteric modulators for exploring the simultaneous regulation of allosteric and orthosteric sites. Meanwhile, ASD2023 maintains a significant growth of foundational allosteric data. Based on these efforts, the allosteric knowledgebase is progressively evolving towards an integrated landscape, facilitating advancements in allosteric target identification, mechanistic exploration and drug discovery.


Subject(s)
Allosteric Site , Knowledge Bases , Humans , Allosteric Regulation , Drug Discovery , Ligands , Proteome , Protein Interaction Maps
2.
Am J Transl Res ; 14(11): 8156-8165, 2022.
Article in English | MEDLINE | ID: mdl-36505328

ABSTRACT

OBJECTIVE: To explore the effect of rapid rehabilitation nursing on inflammation and liver function in patients with primary liver cancer (PLC) after laparoscopic radical resection. METHODS: A total of 124 PLC patients who underwent laparoscopic radical surgery in the Zhuji People's Hospital of Zhejiang Province from April 2019 to July 2021 were enrolled in this retrospective study. Among them, 65 patients who received rapid rehabilitation nursing were assigned into the observation group (OG), and the other 59 with routine nursing were considered to be the control group (CG). The pain before operation (T0), 3 days after operation (T1) and 7 days after operation (T2) was evaluated by visual analogue scale (VAS). The perioperative related indexes and nursing satisfaction were compared. The levels of liver function indexes alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and inflammatory factors C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured before operation, 1 day and 7 days after operation. Finally, the incidence of postoperative complications was counted, the 6-month survival rate of both groups of patients was compared. RESULTS: There was no obvious difference in VAS scores between the two groups at T0 (P>0.050), but the VAS scores at T1 and T2 in the OG were lower than those in the CG (P<0.001). There was no marked difference in the total operation time. Compared with the CG, the time to first exhaust, catheter indwelling and hospitalization in the OG were shorter (P<0.001) and the nursing satisfaction rate was higher (P<0.05). There was no obvious difference in ALT, AST and TBIL on the 1st day after operation (P>0.05); however, on the 7th day after operation, ALT and AST were lower while TBIL was higher in the OG (all P<0.05). There was no marked difference in CRP, IL-6 and TNF-α between the two groups on postoperative day 1 (P>0.05), but the levels were lower in the OG than those in the CG on postoperative day 7 (all P<0.05), and the total incidence of adverse reactions in the OG was lower (P<0.05). There was no statistical difference in the postoperative survival rate between both groups of patients (P>0.05). Age, number of lesions, tumor size, Child-Pugh grade, AST, TBIL, CRP, IL-6, TNF-α were associated with the survival rate of patients. CONCLUSION: Rapid rehabilitation nursing can effectively reduce adverse reactions after laparoscopic radical resection of PLC. Thus, it has a high application value in future clinical treatment.

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