-
1.
The modulation of potassium channels by estrogens facilitates neuroprotection.
Li, XT
Frontiers in cell and developmental biology. 2022;:998009
Abstract
Estrogens, the sex hormones, have the potential to govern multiple cellular functions, such as proliferation, apoptosis, differentiation, and homeostasis, and to exert numerous beneficial influences for the cardiovascular system, nervous system, and bones in genomic and/or non-genomic ways. Converging evidence indicates that estrogens serve a crucial role in counteracting neurodegeneration and ischemic injury; they are thereby being considered as a potent neuroprotectant for preventing neurological diseases such as Alzheimer's disease and stroke. The underlying mechanism of neuroprotective effects conferred by estrogens is thought to be complex and multifactorial, and it remains obscure. It is well established that the K+ channels broadly expressed in a variety of neural subtypes determine the essential physiological features of neuronal excitability, and dysfunction of these channels is closely associated with diverse brain deficits, such as ataxia and epilepsy. A growing body of evidence supports a neuroprotective role of K+ channels in malfunctions of nervous tissues, with the channels even being a therapeutic target in clinical trials. As multitarget steroid hormones, estrogens also regulate the activity of distinct K+ channels to generate varying biological actions, and accumulated data delineate that some aspects of estrogen-mediated neuroprotection may arise from the impact on multiple K+ channels, including Kv, BK, KATP, and K2P channels. The response of these K+ channels after acute or chronic exposure to estrogens may oppose pathological abnormality in nervous cells, which serves to extend our understanding of these phenomena.
-
2.
[Latest Findings on Prediction and Prevention of Preeclampsia].
Ye, YZ, Zhou, QJ, Xiao, XR, Xiong, Y, Li, XT
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition. 2022;(6):1012-1015
Abstract
Preeclampsia, a progressive disease involving multiple systems, afflicts pregnancy specifically. It contributes to severe maternal and perinatal morbidity and mortality. It has been reported that preeclampsia initiates from a mismatch between the utero-placental supply and demand, which subsequently triggers the release of placental syncytiotrophoblast stress-derived factors and an imbalance of proangiogenic/antiangiogenic factors, eventually causing maternal systemic endothelial lesions and systemic inflammatory response. Currently, treatments available for preeclampsia are very limited in number. Hence, prediction and prevention carry special significance. Herein, we reviewed the current understanding of preeclampsia, especially findings on the prediction and prevention of preeclampsia published within the past 5 years. We discussed the Fetal Medicine Foundation (FMF) screening model based on placental growth factor (PlGF) and the effects of aspirin, calcium, exercise, and termination of pregnancy in preventing preeclampsia. The efficacy and safety of other new preventive measures still need further validation.
-
3.
[Application value of plasma proteomics in the diagnosis and pathogenesis of high altitude polycythemia].
Li, XT, A, XR
Zhonghua yi xue za zhi. 2022;(45):3624-3629
Abstract
Objective: To explore the application value of plasma proteomics in the diagnosis and pathogenesis of high altitude polycythemia (HAPC). Methods: Ten patients with HAPC in Qinghai Provincial People's Hospital from January 2020 to January 2021 were selected as the experimental group, including 4 males and 6 females, aged (46±4) years. Ten healthy controls at the same altitude in the same period were selected as the control group, including 5 males and 5 females, aged (44±4) years. The differential proteins were identified and quantified by high performance liquid chromatography-mass spectrometry (HPLC-MS), and the gene ontology (GO) functional enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis and interaction network analysis were conducted for the selected differential proteins. Results: A total of 117 differential proteins with quantitative values were screened from the experimental group and the control group, 45 significantly up-regulated proteins with quantitative values only in the experimental group, 40 significantly down-regulated proteins with quantitative values only in the control group, and 32 differentially expressed proteins with quantitative values in both experimental and control groups were detected. Compared with the control group, 11 of the 32 differentially expressed proteins in the experimental group were down-regulated and 21 were up-regulated. The results of GO functional enrichment analysis showed that the biological processes involved by differential proteins mainly included immune response, complement activation, activated protein cascade and coagulation system. The results of KEGG function enrichment analysis showed that the main biochemical metabolic pathways and signal transduction pathways involved by differential proteins were axon guidance, lysosomes, cell adhesion molecules, lipid and atherosclerosis, hematopoietic cell lineage and cholesterol metabolism. The abundant domains are mainly in immunoglobulin-like domain, EGF-like domain, fibronectin type Ⅲ superfamily, serine proteases, Sushi/SCR/CCP superfamily. The results of differential protein interaction analysis showed that the interaction score was>700, and the top 10 differential proteins with the largest number of nodes were MPO, RPS27A, ARG1, GM2A, TIMP1, CRP, FABP5, HBB, S100A7 and RHOA, respectively. Conclusion: Plasma proteomics analysis technique is helpful to identify the related protein markers in the development of HAPC, and provide reference for the diagnosis and pathogenesis of HAPC.
-
4.
Alzheimer's disease therapy based on acetylcholinesterase inhibitor/blocker effects on voltage-gated potassium channels.
Li, XT
Metabolic brain disease. 2022;(3):581-587
Abstract
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder with progressive loss of memory and other cognitive functions. The pathogenesis of this disease is complex and multifactorial, and remains obscure until now. To enhance the declined level of acetylcholine (ACh) resulting from loss of cholinergic neurons, acetylcholinesterase (AChE) inhibitors are developed and successfully approved for AD treatment in the clinic, with a limited therapeutic effectiveness. At present, it is generally accepted that multi-target strategy is potently useful for designing novel drugs for AD. Accumulated evidence reveals that Kv channels, which are broadly expressed in brain and possess crucial functions in modulating the neuronal activity, are inhibited by several acetylcholinesterase (AChE) inhibitors, such as tacrine, bis(7)-tacrine, donepezil and galantamine. Inhibition of Kv channels by these AChE inhibitors can generate neuroprotective effects by either mitigating Aβ toxicity and neuronal apoptosis, or facilitating cell proliferation. These inhibitory effects provide additional explanations for clinical beneficial effectiveness of AChE inhibitors, meaning that Kv channel is a promising candidate target for novel drugs for AD therapy.
-
5.
Beneficial effects of carvedilol modulating potassium channels on the control of glucose.
Li, XT
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:113057
Abstract
The increased prevalence of hypertensive patients with type 2 diabetes mellitus (T2DM) is evident worldwide, leading to a higher risk of cardiovascular disease onset, which is substantially associated with disabilities and mortality in the clinic. In order to achieve the satisfyingly clinical outcomes and prognosis, the comprehensive therapies have been conducted with a beneficial effect on both blood pressure and glucose homeostasis, and clinical trials reveal that some kind of antihypertensive drugs such as angiotensin converting enzyme inhibitors (ACE-I) may, at least in part, meet the dual requirement during the disease management. As a nonselective β-blocker, carvedilol is employed for treating many cardiovascular diseases in clinical practice, including hypertension, angina pectoris and heart failure, and also exhibit the effectiveness for glycemic control and insulin resistance. Apart from alleviating sympathetic nervous system activity, several causes, such as lowering oxygen reactive species, may contribute to the effects of carvedilol on controlling plasma glucose levels, suggesting a feature of this drug having multiple targets. Interestingly, numerous distinct K+ channels expressed in pancreatic β-cells and peripheral insulin-sensitive tissues, which play a sentential role in glucose metabolism, are subjected to extensive modulation of carvdilol, establishing a linkage between K+ channels and drug's effects on the control of glucose. A variety of evidence shows that the impact of carvedilol on different K+ channels, including Kv, KAch, KATP and K2 P, can lead to positive influences for glucose homeostasis, contributing to its clinical beneficial effectiveness in treatment of hypertensive patients with T2DM. This review focus on the control of plasma glucose conferred by carvedilol modulation on K+ channels, providing the novel mechanistic explanation for drug's actions.
-
6.
The Protective Effect of Dexmedetomidine Against Ischemia-Reperfusion Injury after Hepatectomy: A Meta-Analysis of Randomized Controlled Trials.
Huang, YQ, Wen, RT, Li, XT, Zhang, J, Yu, ZY, Feng, YF
Frontiers in pharmacology. 2021;:747911
Abstract
Background: Hepatic inflow occlusion proceeded to reduce blood loss during hepatectomy induces ischemia-reperfusion (IR) injury in the remnant liver. Dexmedetomidine, a selective α2-adrenoceptor agonist used as an anesthetic adjuvant, has been shown to attenuate IR injury in preclinical and clinical studies. However, a meta-analysis is needed to systematically evaluate the protective effect of perioperative dexmedetomidine use on IR injury induced by hepatectomy. Methods: A prospectively registered meta-analysis following Cochrane and PRISMA guidelines concerning perioperative dexmedetomidine use on IR injury after hepatectomy was performed via searching Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov, Web of Science, CNKI, WanFang, and Sinomed for eligible randomized controlled trials up to 2021.3.31. The main outcome is postoperative liver function. Risk of bias was assessed by the Cochrane Risk of Bias tool. Review Manager 5.3 and Stata12.0 were applied to perform data analyses. Results: Eight RCTs enrolling 468 participants were included. Compared with 0.9% sodium chloride, dexmedetomidine decreased serum concentration of ALT (WMD = -66.54, 95% CI: -92.10--40.98), AST (WMD= -82.96, 95% CI: -106.74--59.17), TBIL (WMD = -4.51, 95% CI: -7.32--1.71), MDA (WMD = -3.09, 95% CI: -5.17--1.01), TNF-α (WMD = -36.54, 95% CI: -61.33--11.95) and IL-6 (WMD = -165.05, 95% CI: -225.76--104.34), increased SOD activity (WMD = 24.70, 95% CI: 18.09-31.30) within postoperative one day. There was no significant difference in intraoperative or postoperative recovery parameters between groups. Conclusions: Perioperative administration of dexmedetomidine can exert a protective effect on liver IR injury after hepatectomy. Additional studies are needed to further evaluate postoperative recovery outcomes of dexmedetomidine with different dosing regimens.
-
7.
[Dragon-tiger fighting needling therapy in treatment of painful diabetic peripheral neuropathy: a randomized controlled trial].
Deng, XM, Liu, SW, Lei, J, Li, XT, Jiang, HY
Zhongguo zhen jiu = Chinese acupuncture & moxibustion. 2021;(1):23-6
Abstract
OBJECTIVE To compare the clinical therapeutic effect on painful diabetic peripheral neuropathy (PDPN) between dragon-tiger fighting needling and pregabalin capsules. METHODS A total of 60 patients with PDPN were randomized into an observation group and a control group, 30 cases in each one. On the base of treatment with routine anti-hyperglycaemic measures and nutritional neurotherapy, the dragon-tiger fighting needling was exerted at Sanyinjiao (SP 6), Zusanli (ST 36), Yinlingquan (SP 9) and Xuehai (SP 10) in the observation group, once daily. Pregabalin capsules were prescribed for oral administration in the control group, 75 mg, twice a day. The treatment for 2 weeks was as one course and 2 courses of treatment were required in total. The score of visual analogue scale (VAS), the score of MOS item short form health survey (SF-36) and nerve conduction velocity before and after treatment were compared between the two groups. The clinical therapeutic effect was evaluated in the two groups. RESULTS After treatment, VAS score was reduced as compared with before treatment in the two groups (P<0.05). The reducing range of VAS score in the observation group was larger than the control group (P<0.05). After treatment, the sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity (MNCV) of median nerve and posterior tibial nerve were all improved as compared with before treatment in the two groups (P<0.05). SNCV and MNCV in the observation group were higher than the control group (P<0.05). After treatment, the score of each item in SF-36 was increased as compared with before treatment in the two groups (P<0.05) and the score of each item in SF-36 in the observation group was higher than the control group (P<0.05). The total effective rate was 86.7% (26/30) in the observation group, better than 60.0% (18/30) in the control group (P<0.05). CONCLUSION The dragon-tiger fighting needling therapy relieves painful symptoms, improves the quality of life and increases nerve conduction velocity in the patients with diabetic peripheral neuropathy, and the therapeutic effect is better than oral administration of pregabalin capsules.
-
8.
Serological investigation of IgG and IgE antibodies against food antigens in patients with inflammatory bowel disease.
Wang, HY, Li, Y, Li, JJ, Jiao, CH, Zhao, XJ, Li, XT, Lu, MJ, Mao, XQ, Zhang, HJ
World journal of clinical cases. 2019;7(16):2189-2203
-
-
-
Free full text
Plain language summary
Crohn's disease and ulcerative colitis are relapsing gut inflammatory diseases that are usually referred to as Inflammatory Bowel Disease (IBD). It may be triggered by an imbalance in immune response in response to environmental factors such as diet. The aim of this retrospective study was to evaluate the presence of IgG and IgE mediated antibodies to food antigens in IBD patients. There were one hundred and thirty-seven IBD patients participating in this study, including forty Ulcerative colitis patients and ninety-seven Crohn's disease patients against fifty healthy controls to test serum IgG antibodies to fourteen specific food antigens and serum IgE antibodies to fourteen specific food antigens. There were significantly higher IgG antibodies in response to food antigens in Crohn's disease patients than in Ulcerative colitis patients and healthy controls. Food antigens such as tomato, corn, egg, rice, and soybean exhibited varying levels of IgG antibody responses in Crohn's disease patients and ulcerative colitis patients. Smokers were more likely to develop IgG reactions. Further robust research is needed to examine more IgG-specific food antigens to help manage IBD with an elimination rotation diet. The results of this study can help healthcare professionals understand the importance of diagnosing food intolerances when treating IBD.
Abstract
BACKGROUND Food antigens have been shown to participate in the etiopathogenesis of inflammatory bowel disease (IBD), but their clinical value in IBD is still unclear. AIM: To analyze the levels of specific immunoglobulin G (IgG) and E (IgE) antibodies against food antigens in IBD patients and to determine their clinical value in the pathogenesis of IBD. METHODS We performed a retrospective study based on patients who visited the First Affiliated Hospital of Nanjing Medical University between August 2016 and January 2018. A total of 137 IBD patients, including 40 patients with ulcerative colitis (UC) and 97 patients with Crohn's disease (CD), and 50 healthy controls (HCs), were recruited. Serum food-specific IgG antibodies were detected by semi-quantitative enzyme-linked immunosorbent assay, and serum food-specific IgE antibodies were measured by Western blot. The value of food-specific IgG antibodies was compared among different groups, and potent factors related to these antibodies were explored by binary logistic regression. RESULTS Food-specific IgG antibodies were detected in 57.5% of UC patients, in 90.72% of CD patients and in 42% of HCs. A significantly high prevalence and titer of food-specific IgG antibodies were observed in CD patients compared to UC patients and HCs. The number of IgG-positive foods was greater in CD and UC patients than in HCs (CD vs HCs, P = 0.000; UC vs HCs, P = 0.029). The top five food antigens that caused positive specific IgG antibodies in CD patients were tomato (80.68%), corn (69.32%), egg (63.64%), rice (61.36%), and soybean (46.59%). The foods that caused positive specific IgG antibodies in UC patients were egg (60.87%), corn (47.83%), tomato (47.83%), rice (26.09%), and soybean (21.74%). Significantly higher levels of total food-specific IgG were detected in IBD patients treated with anti-TNFα therapy compared to patients receiving steroids and immunosuppressants (anti-TNFα vs steroids, P = 0.000; anti-TNFα vs immunosuppressants, P = 0.000; anti-TNFα vs steroids + immunosuppressants, P = 0.003). A decrease in food-specific IgG levels was detected in IBD patients after receiving anti-TNFα therapy (P = 0.007). Patients who smoked and CD patients were prone to developing serum food-specific IgG antibodies [Smoke: OR (95%CI): 17.6 (1.91-162.26), P = 0.011; CD patients: OR (95%CI): 12.48 (3.45-45.09), P = 0.000]. There was no difference in the prevalence of food-specific IgE antibodies among CD patients (57.1%), UC patients (65.2%) and HCs (60%) (P = 0.831). CONCLUSION CD patients have a higher prevalence of food-specific IgG antibodies than UC patients and HCs. IBD patients are prone to rice, corn, tomato and soybean intolerance. Smoking may be a risk factor in the occurrence of food-specific IgG antibodies. Food-specific IgG antibodies may be a potential method in the diagnosis and management of food intolerance in IBD.
-
9.
Human CYP2C8: structure, substrate specificity, inhibitor selectivity, inducers and polymorphisms.
Lai, XS, Yang, LP, Li, XT, Liu, JP, Zhou, ZW, Zhou, SF
Current drug metabolism. 2009;(9):1009-47
Abstract
Human CYP2C8 is a key member of the CYP2C family and metabolizes more than 60 clinical drugs. A number of active site residues in CYP2C8 have been identified based on homology modeling and site-directed mutagenesis studies. In the structure of CYP2C8, the large active site cavity exhibits a trifurcated topology that approximates a T or Y shape, which is consistent with the finding that CYP2C8 can efficiently oxidize relatively large substrates such as paclitaxel and cerivastatin. The active site cavity of CYP2C8 contains at least 48 amino acid residues and many of them are important for substrate binding. The structures of CYP2C8 in complex with distinct ligands have revealed that the enzyme can bind divergent substrates and inhibitors without extensive conformational changes. CYP2C8 is a major catalyst in the metabolism of paclitaxel, amodiaquine, troglitazone, amiodarone, verapamil and ibuprofen, with a secondary role in the biotransformation of cerivastatin and fluvastatin. CYP2C8 also metabolises endogenous compounds such as retinoids and arachidonic acid. Many drugs are inhibitors of CYP2C8 and inhibition of this enzyme may result in clinical drug interactions. The pregnane X receptor, constitutive androstane receptor, and glucocorticoid receptor are likely to involve the regulation of CYP2C8. A number of genetic mutations in the CYP2C8 gene have been identified in humans and some of them have functional impact on the clearance of drugs. Further studies are needed to delineate the role of CYP2C8 in drug development and clinical practice.