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1.
J. venom. anim. toxins incl. trop. dis ; 28: e20210040, 2022. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1365074

ABSTRACT

Background: Naja atra is a venomous snake species medically relevant in China. In the current study, we evaluated the composition and toxicological profile of venom collected from farm-raised N. atra. Methods: Venom was collected from third-generation captive bred N. atra on a snake farm in Hunan Province, China. The venom was analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis and nano-liquid chromatography with electrospray ionization tandem mass spectrometry. In addition, hemolytic activity, median lethal dose, serum biochemical and histopathological parameters were accessed. Results: N. atra venom proteome was dominated by phospholipase A2 (46.5%) and three-finger toxins (41.4 %), and a set of common low relative abundance proteins, including cysteine-rich secretory proteins (4.7%), NGF-beta (2.4%), snake venom metalloproteinase (1.5%), glutathione peroxidase (0.6%), vespryn (0.3%), and 5ʹ-nucleotidases (0.2%) were also found. Furthermore, the venom exhibited direct hemolytic activity, neurotoxicity, myotoxicity, and high lethal potency in mice, with a subcutaneous median lethal dose of 1.02 mg/kg. Histopathological analysis and serum biochemical tests revealed that venom caused acute hepatic, pulmonary and renal injury in mice. Conclusion: This study revealed the composition and toxicity of venom collected from farm-raised N. atra, thereby providing a reference for the analysis of venom samples collected from captive-born venomous snakes in the future.(AU)


Subject(s)
Animals , Snake Venoms/toxicity , Phospholipases A2 , Naja naja , Myotoxicity , Nucleotidases
2.
Article in English | WPRIM | ID: wpr-927654

ABSTRACT

Objective@#To explore associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular events in a Chinese population, with a long-term follow-up.@*Methods@#A random sample of 2,031 participants (73.6% males, mean age = 60.4 years) was derived from the Asymptomatic Polyvascular Abnormalities Community study (APAC) from 2010 to 2011. Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). The composite endpoint was a combination of first-ever stroke, myocardial infarction (MI) or all-cause death. Lp-PLA2 associations with outcomes were assessed using Cox models.@*Results@#The median Lp-PLA2 level was 141.0 ng/mL. Over a median follow-up of 9.1 years, we identified 389 events (19.2%), including 137 stroke incidents, 43 MIs, and 244 all-cause deaths. Using multivariate Cox regression, when compared with the lowest Lp-PLA2 quartile, the hazard ratios with 95% confidence intervals for developing composite endpoints, stroke, major adverse cardiovascular events, and all-cause death were 1.77 (1.24-2.54), 1.92 (1.03-3.60), 1.69 (1.003-2.84), and 1.94 (1.18-3.18) in the highest quartile, respectively. Composite endpoints in 145 (28.6%) patients occurred in the highest quartile where Lp-PLA2 (159.0 ng/mL) was much lower than the American Association of Clinical Endocrinologists recommended cut-off point, 200 ng/mL.@*Conclusion@#Higher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population. The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.


Subject(s)
1-Alkyl-2-acetylglycerophosphocholine Esterase/blood , Asians , Cardiovascular Diseases/diagnosis , China/epidemiology , Female , Humans , Longitudinal Studies , Male , Middle Aged , Mortality , Myocardial Infarction/blood , Predictive Value of Tests , Risk Factors , Stroke/blood
3.
Chinese Journal of Nephrology ; (12): 387-396, 2022.
Article in Chinese | WPRIM | ID: wpr-933869

ABSTRACT

Objective:To analyze the clinicopathological characteristics, treatment responses and kidney outcomes of patients with atypical membranous nephropathy (MN), and to provide information for the clinical practice.Methods:The clinical data of patients with atypical MN and synchronous primary MN who were diagnosed, treated and followed up in Peking University First Hospital from January 2008 to June 2020 were retrospectively collected and analyzed. Clinicopathological features, treatment responses and kidney prognosis were compared between the two groups. The expression of phospholipase A2 receptor (PLA2R) in kidney tissues was detected by immunofluorescence. Serum anti-PLA2R antibody was detected by enzyme-linked immunosorbent assay. Clinicopathological indexes were compared between PLA2R-related MN group and non-PLA2R-related MN group. Kaplan-Meier (Log-rank test) survival curve and multivariate Cox regression analysis methods were used to analyze the influencing factors of kidney prognosis in patients with atypical MN. The primary endpoint of renal adverse outcome was renal insufficiency, defined as end-stage renal disease or estimated glomerular filtration rate (eGFR) decline>30% baseline and<60 ml·min -1·(1.73 m 2) -1. Results:A total of 65 atypical MN patients were enrolled in this study. Compared with primary MN ( n=324), patients with atypical MN had younger age ( Z=-4.229, P<0.001), higher proportion of hematuria ( χ2=5.555, P=0.018), higher level of urinary protein ( Z=2.228, P=0.026) and lower level of eGFR ( t=-5.108, P<0.001); the proportion of IgG4 deposition in kidneys was lower ( χ2=8.081, P=0.004), and the proportions of IgA ( χ2=16.969, P<0.001) and IgM ( χ2=9.281, P=0.002) deposition were higher. There was no significant difference on gender, serum albumin, positive proportion of anti-PLA2R antibody, anti-PLA2R antibody level and kidney C3/C1q deposition between the two groups (all P>0.05). The proportions of atypical MN patients receiving renin-angiotensin aldosterone system inhibitors (49.3% vs 57.1%), calcineurin inhibitors (27.7% vs 19.1%) and cyclophosphamide (21.5% vs 23.8%) were comparable to those of primary MN patients (all P>0.05). The rates of clinical remission (80.0% vs 77.2%), partial remission (44.6% vs 44.1%), complete remission (35.4% vs 33.1%), spontaneous remission (36.9% vs 42.6%), response to cyclophosphamide (85.7% vs 81.8%), response to calcineurin inhibitor (88.9% vs 79.0%), and relapse (30.8% vs 26.8%) in atypical MN patients were comparable to those in primary MN patients (all P>0.05). During the follow-up 30.0(21.5, 61.5) months, 15 atypical MN patients (23.1%) had eGFR reduction>30%, among whom 7 patients (10.8%) had eGFR reduction>50% and 3 patients (4.6%) had end-stage kidney disease. There was no significant difference on poor kidney prognosis between the two groups (all P>0.05). Kaplan-Meier survival curve showed that patients with age>39 years old ( χ2=10.092, P=0.001), eGFR≤100 ml·min -1·(1.73 m 2) -1( χ2=5.491, P=0.019), tubular interstitial lesion ( χ2=6.999, P=0.008) and no nephropathy remission ( χ2=22.952, P<0.001) had earlier poor renal prognosis. Multivariate Cox regression analysis showed that no nephropathy remission ( HR=12.604, 95% CI 2.691-59.037, P=0.001) was an independent influencing factor for poor renal prognosis in atypical MN patients. Conclusion:No significant difference is found between atypical MN and primary MN on treatment responses and kidney prognosis, which implies that clinical practice of atypical MN can be performed by referring to the guidelines and experience of primary MN.

4.
Article in Chinese | WPRIM | ID: wpr-933455

ABSTRACT

A 43-year-old male patient with onset of edema caused by nephrotic proteinuria and low titer of anti-M type phospholipase-A 2-receptor (PLA 2R) antibody was diagnosed as idiopathic membranous nephropathy by renal biopsy. Administrated with prednisone 40 mg once a day and cyclosporine 100 mg twice a day as front-line regimen, the patient relapsed after transient partial remission. When treatment was combined with cyclophosphamide 100 mg once a day, the 24-hour total urine protein and titer of anti-PLA 2R antibody were even elevated. Therefore, the patient received rituximab 1 g intravenously in April 2019, October 2019 and October 2020 respectively. CD19 positive B lymphocytes in peripheral blood were eliminated from 71/μl to zero. Immunosuppressants and corticosteroids were withdrawn successively. On the last follow-up in November 2020, the anti-PLA 2R antibody was negative, and the 24-hour total urine protein and serum albumin was 4.4 g and 34 g/L, respectively. This case suggested the potential efficacy of rituximab for refractory membranous nephropathy. Further studies should explore whether the titer of anti-PLA 2R antibody indicates the dose of rituximab.

5.
Journal of Chinese Physician ; (12): 96-101, 2022.
Article in Chinese | WPRIM | ID: wpr-932033

ABSTRACT

Objectives:To investigate the correlation of serum lipoprotein-associated phospholipase A2 (Lp-PLA2) with intra-stent restenosis (ISR) after drug-eluting stent (DES) implantation.Methods:A total of 227 patients with coronary artery disease, who were diagnosed with severe epicardial coronary stenosis by coronary angiography (CAG) and treated by percutaneous coronary intervention (PCI) and DES implantation were enrolled in our study. After follow-up for 1-1.5 years, the CAG was performed and the patients were divided into ISR group and non-ISR (nISR) group according to the consequence of CAG. Biochemical data and multiple serum inflammatory factors such as Lp-PLA2, hypersensitive C-reactive protein (hs-CRP), interleukin 2 (IL-2), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were analyzed before the CAG. Multivariate logistic regression and multiple linear regression were used to analyze the influencing factors of stent restenosis after DES implantation.Results:The level of serum Lp-PLA2 and the proportion of hypertension in ISR group were significantly higher than those in nISR group, and the level of high density lipoprotein cholesterol (HDL-C) was significantly lower than that in nISR group (all P<0.05), but there was no significant difference in other biochemical indexes and inflammatory factors between the two groups (all P>0.05). The minimum lumen diameter of stent segment in ISR group was significantly lower than that in nISR group ( t=14.975, P<0.01), and the stenosis degree of stent segment diameter was significantly higher than that in nISR group ( P<0.01). Multivariate logistic regression analysis showed that Lp-PLA2 remained an independent predictor for ISR (1.011, 95% CI: 1.005-1.017). Only the serum levels of Lp-PLA2 had linear relationship with the degree of ISR by multivariate linear regression analysis ( β=0.790, P<0.01). Conclusions:Serum Lp-PLA2 level is independently associated with an increased risk of ISR in patients with coronary heart disease.

6.
Journal of Chinese Physician ; (12): 35-38,43, 2022.
Article in Chinese | WPRIM | ID: wpr-932021

ABSTRACT

Objective:To investigate the correlation between serum anti phospholipase A2 receptor (PLA 2R) antibody level and the condition and prognosis of patients with primary membranous nephropathy (PMN).Methods:61 patients who were diagnosed as PMN in the laboratory department of Jiangsu Province Hospital of Chinese Medicine from January 2017 to August 2019 were selected and divided into PLA 2R positive group (41 cases) and PLA 2R negative group (20 cases) according to the level of PLA 2R antibody. The gender, age and other general data of the two groups were collected, and the clinical pathological characteristics and prognosis of the two groups were analyzed. Spearman correlation was used to analyze the correlation between the level of PLA 2R antibody and the disease condition and treatment prognosis.Results:The levels of estimate glomerular filtration rate (eGFR), total protein (TP) and albumin (ALB) in PLA 2R positive group were lower than those in PLA 2R negative group, while the levels of 24-h urinary protein and IgG4 were higher in PLA 2R positive group than that in PLA 2R negative group ( P<0.05); Multivariate logistic regression analysis showed that 24-hour urinary protein was an independent risk factor for PLA 2R antibody level ( OR=2.242, P<0.05), while TP and ALB levels were protective factors ( OR=0.840, 0.674, P<0.05); The patients in both groups were followed up for one year by rechecking serological indexes. The complete remission rate and total remission rate of PLA 2R positive group were lower than those of PLA 2R negative group ( P<0.05); Spearman correlation analysis showed that the level of PLA 2R antibody was negatively correlated with the levels of TP, ALB, and prognosis of patients ( r=-0.642, -0.547, -0.357, P<0.05), and positively correlated with the level of 24-hour urinary protein ( r=0.347, P<0.05). PLA 2R in renal tissue of 61 patients was found to be positive in 63.93% (39/61). Conclusions:The level of PLA 2R antibody is closely related to serum albumin, TP, 24 h urinary protein and prognosis of patients with PMN.

7.
Article in Chinese | WPRIM | ID: wpr-930445

ABSTRACT

Objective:To analyze the clinical and prognosis of primary membranous nephropathy (PMN) in children with positive glomerular M-type phospholipase A2 receptor (PLA2R).Methods:A total of 69 children diagnosed with PMN by renal biopsy admitted to the Department of Pediatrics of Eastern Theater Command General Hospital from January 2006 to December 2018 were retrospectively analyzed, including 40 males and 29 females, with an average age of 14.86 years.According to the immunofluorescence of renal pathology, they were divided into PLA2R positive group and PLA2R negative group.Pathological features between 2 groups were compared by the t test, Mann- Whitney U test and Chi- square test.Kaplan-Meier method was used to compare the long-term renal survival rate and cumulative remission rate between 2 groups. Results:A total of 69 pediatric PMN patients were included.The po-sitive rates of serum anti-PLA2R antibody and positive expression of PLA2R in renal tissues were 53.6% (37 cases) and 82.6% (57 cases), respectively.The proportion of children with clinical manifestations of large proteinuria [55 cases(96.5% ) vs.9 cases(75.0%), P=0.034] was significantly higher in the PLA2R positive group than that of the PLA2R negative group.Blood urea nitrogen level was significantly higher in the PLA2R positive group than that of PLA2R negative group[1.14(0.93, 1.54) mg/L vs.0.80 (0.44, 1.18) mg/L, P=0.049], while estimate glomerular filtration rate(eGFR) [162.26 (139.81, 185.53) mL/(min·1.73 m 2) vs.199.52 (157.58, 212.01) mL/(min·1.73 m 2), P=0.034] and serum IgG [3.58 (2.50, 5.43) g/L vs.5.14 (4.35, 6.03) g/L, P=0.016] were significantly lower.The cumulative remission rate was significantly higher in the PLA2R negative group than that of PLA2R positive group ( P<0.001). The 24 h urinary protein ≥50 mg/kg ( HR=0.119, 95% CI: 0.021-0.595, P=0.010)was an independent risk factor for renal prognosis, and PLA2R( HR=0.263, 95% CI: 0.125-0.551, P<0.001) and 24 h urinary protein ≥50 mg/kg ( HR=0.568, 95% CI: 0.125-0.551, P=0.041)were independent predictors of urinary protein remission.PLA2R ( HR=1.020, 95% CI: 0.698-1.682, P=0.656)was not associated with renal prognosis. Conclusions:The severity of PMN in children with positive PLA2R was higher than that in those with negative PLA2R.The long-term cumulative remission rate of PLA2R negative children with PMN was higher than that of PLA2R positive children.

8.
Acta Pharmaceutica Sinica ; (12): 1557-1564, 2022.
Article in Chinese | WPRIM | ID: wpr-929451

ABSTRACT

The remodeling of phospholipid includes two processes: deacylation and reacylation. It realizes the conversion of nascent phospholipids to mature phospholipids by changing the length and types of fatty acids at specific sites of phospholipids, which is a key step in phospholipid metabolism. Phospholipids are not only the basic components of biological membranes, but also participate in the transduction of many molecular signals in cells. Therefore, phospholipid remodeling disorders can affect the structure and function of cell membranes, as well as the activity of membrane proteins, causing a series of intricate signaling cascades, and finally lead to many pathological changes including neurodegeneration. This paper reviews the basic process of phospholipid remodeling and the involvement of its key enzymes, calcium independent group VIA phospholipase A2 (iPLA2β), peroxiredoxin 6 (PRDX6), calcium independent group VIB phospholipase A2 (iPLA2γ) as well as acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1) in the pathology of Parkinson's disease. The mutations in the gene encoding iPLA2β, PLA2G6, have been widely reported to be directly related to hereditary Parkinson disease-14 (PARK14). Here we focus on the molecular mechanism of iPLA2β in the development of Parkinson's disease, mainly involving phospholipid fatty acid metabolism disorders, mitochondrial physiology abnormalities and α-synuclein aggregate formation and other aspects, which will help to understand the role of phospholipid remodeling in Parkinson's disease, and provide new clues for the development of new Parkinson's disease diagnosis and treatment strategies.

9.
Article in Chinese | WPRIM | ID: wpr-939969

ABSTRACT

@#Modulating drug release from liposomes at tumor sites are important for eliciting therapeutic effects of platinum drugs considering their low permeability through liposomal membranes, here a novel secretory phospholipase A2 (sPLA2) responsive-liposome system was constructed for oxaliplatin (L-OHP).Lipid ingredients dipalmitoyl phosphatidylcholine and distearoyl phosphoethanolamine-PEG2k, together with facial amphiphiles (FAs) including lithocholic acid (LCA) or 3-keto lithocholic acid (kLCA) were used to prepare sPLA2 responsive-liposome (LCA-Lip or kLCA-Lip) by thin-film hydration method.The physicochemical properties, sPLA2-responsive drug release and anti-tumor activity were evaluated in vitro.The results indicated L-OHP loaded liposomes modified with FAs had similar particle sizes of approximately 100 nm and narrow size distributions (PDI < 0.11).Compared with non-FAs-containing liposomes (C-Lip), LCA-Lip or kLCA-Lip has a comparable entrapment efficiency and loading efficiency.LCA-Lip or kLCA-Lip didn't show significant higher drug leakage at the presence of 10% or 50% fetal bovine serum (FBS) in media than that in media without FBS.Treated with secretory phospholipase A2 from Colo205 cells culture conditioned medium (CCM sPLA2) for 24 h, FAs modified liposomes released about 70% of carboxyfluorescein (CF), while C-Lip only released 20% of CF.Compared to L-OHP loaded C-Lip, L-OHP-loaded FAs-included formulations had much greater anti-proliferative activity against sPLA2-secreting Colo205 cells.In summary, our results shows that LCA or kLCA promotes responsiveness of liposomes to tumor-related sPLA2 and points to a new way to develop platium drugs-loaded liposomal delivery systems with better release mechanisms.

10.
Electron. j. biotechnol ; 50: 1-9, Mar. 2021. ilus, tab, graf
Article in English | LILACS | ID: biblio-1292302

ABSTRACT

BACKGROUND: Phospholipase D (PLD) is used as the biocatalyst for phosphatidylserine (PS) production. In general, PLD was expressed in insoluble form in Escherichia coli. High-level soluble expression of PLD with high activity in E. coli is very important for industrial production of PLD. RESULTS: Streptomyces chromofuscus PLD coding gene was codon-optimized, cloned without signal peptide, and expressed in E. coli. The optimal recombinant E. coli pET-28a+PLD/BL21(DE3) was constructed with pET-28a without His-tag. The highest PLD activity reached 104.28 ± 2.67 U/mL in a 250-mL shake flask after systematical optimization. The highest PLD activity elevated to 122.94 ± 1.49 U/mL by feeding lactose and inducing at 20 C after scaling up to a 5.0-L fermenter. Substituting the mixed carbon source with 1.0 % (w/v) of cheap dextrin and adding a feeding medium could still attain a PLD activity of 105. 81 ± 2.72 U/mL in a 5.0-L fermenter. Fish peptone from the waste of fish processing and dextrin from the starch are both very cheap, which were found to benefit the soluble PLD expression. CONCLUSIONS: After combinatorial optimization, the high-level soluble expression of PLD was fulfilled in E. coli. The high PLD activity along with cheap medium obtained at the fermenter level can completely meet the requirements of industrial production of PLD.


Subject(s)
Phospholipases/metabolism , Streptomyces/enzymology , Solubility , Streptomyces/genetics , Temperature , Codon , Combinatorial Chemistry Techniques , Escherichia coli
11.
Rev. méd. Chile ; 149(1)ene. 2021.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1389340

ABSTRACT

Background: The discovery of the phospholipase A2 receptor antigen and its highly specific autoantibody (anti-PLA2R Ab) was useful for the diagnosis and follow-up of patients with membranous nephropathy (MN). Thus, some international guidelines recommend not performing renal biopsy in patients with positive serum anti-PLA2R Ab. Aim: To evaluate the prevalence of anti-PLA2R Ab in serum and renal tissue samples from Chilean patients with primary MN. Material and Methods: Twenty-eight patients aged 50 ± 14 years (20 males) with biopsy-proven primary MN plus a negative workup for secondary causes were included. Measurements of serum and renal histologic anti-PLA2R Ab were performed. The relationship between the findings of serum and tissue anti-PLA2R Ab was evaluated. Results: Fifteen patients (54 %) had anti-PLA2R Ab presence in serum and 19 patients (68%) had positive anti-PLA2R Ab in the renal biopsy. All patients with positive serum anti-PLA2R Ab had positive antibodies on immunohistochemistry. Conclusions: Serum anti-PLA2R Ab is potentially useful in the diagnosis of patients with suspected primary MN in Chilean population.

12.
Chinese Journal of Biotechnology ; (12): 2513-2521, 2021.
Article in Chinese | WPRIM | ID: wpr-887817

ABSTRACT

Human secreted phospholipase A2 GIIE (hGIIE) is involved in inflammation and lipid metabolism due to its ability of hydrolyzing phospholipids. To reveal the mechanism of substrate head-group selectivity, we analyzed the effect of mutation of hGIIE on its activity and selectivity. hGIIE structural analysis showed that E54 might be related to its substrate head-group selectivity. According to the sequence alignment, E54 was mutated to alanine, phenylalanine, and lysine. Mutated genes were cloned and expressed in Pichia pastoris X33, and the enzymes with mutations were purified with 90% purity by ion exchange and molecular size exclusion chromatography. The enzymatic activities were determined by isothermal microthermal titration method. The Km of mutant E54K towards 1,2-dihexyl phosphate glycerol decreased by 0.39-fold compared with that of wild type hGIIE (WT), and the Km of E54F towards 1,2-dihexanoyl-sn-glycero-3-phosphocholine increased by 1.93-fold than that of WT. The affinity of mutant proteins with phospholipid substrate was significantly changed, indicating that E54 plays an important role in the substrate head-group selectivity of hGIIE.


Subject(s)
Humans , Kinetics , Mutation , Phospholipases A2, Secretory , Phospholipids , Saccharomycetales , Substrate Specificity
13.
Acta Pharmaceutica Sinica B ; (6): 3150-3164, 2021.
Article in English | WPRIM | ID: wpr-922785

ABSTRACT

The three-dimensional (3D) conformation of chromatin is integral to the precise regulation of gene expression. The 3D genome and genomic variations in non-alcoholic fatty liver disease (NAFLD) are largely unknown, despite their key roles in cellular function and physiological processes. High-throughput chromosome conformation capture (Hi-C), Nanopore sequencing, and RNA-sequencing (RNA-seq) assays were performed on the liver of normal and NAFLD mice. A high-resolution 3D chromatin interaction map was generated to examine different 3D genome hierarchies including A/B compartments, topologically associated domains (TADs), and chromatin loops by Hi-C, and whole genome sequencing identifying structural variations (SVs) and copy number variations (CNVs) by Nanopore sequencing. We identified variations in thousands of regions across the genome with respect to 3D chromatin organization and genomic rearrangements, between normal and NAFLD mice, and revealed gene dysregulation frequently accompanied by these variations. Candidate target genes were identified in NAFLD, impacted by genetic rearrangements and spatial organization disruption. Our data provide a high-resolution 3D genome interaction resource for NAFLD investigations, revealed the relationship among genetic rearrangements, spatial organization disruption, and gene regulation, and identified candidate genes associated with these variations implicated in the pathogenesis of NAFLD. The newly findings offer insights into novel mechanisms of NAFLD pathogenesis and can provide a new conceptual framework for NAFLD therapy.

14.
Acta Pharmaceutica Sinica B ; (6): 3015-3034, 2021.
Article in English | WPRIM | ID: wpr-922781

ABSTRACT

Parkinson's disease (PD), known as one of the most universal neurodegenerative diseases, is a serious threat to the health of the elderly. The current treatment has been demonstrated to relieve symptoms, and the discovery of new small-molecule compounds has been regarded as a promising strategy. Of note, the homeostasis of the autolysosome pathway (ALP) is closely associated with PD, and impaired autophagy may cause the death of neurons and thereby accelerating the progress of PD. Thus, pharmacological targeting autophagy with small-molecule compounds has been drawn a rising attention so far. In this review, we focus on summarizing several autophagy-associated targets, such as AMPK, mTORC1, ULK1, IMPase, LRRK2, beclin-1, TFEB, GCase, ERR

15.
Article in English | WPRIM | ID: wpr-880650

ABSTRACT

OBJECTIVES@#Systemic lupus erythematosus (SLE) is a kind of autoimmune inflammatory connective tissue disease which seriously endangers human health. Genetic factors play a key role in the pathogenesis of SLE. This study aims to investigate a novel phospholipase D2 (PLD2) mutation associated with familial SLE, and further explore the underlying mechanism of the mutation in SLE.@*METHODS@#The blood samples from a SLE patient, the patient's parents, and 147 normal controls were collected and DNA was extracted. Whole genome high-throughput sequencing was performed in the patient and her parents and the results were further analyzed by various bioinformatics methods. The wild type (wt), mutant type (mu), and negative control PLD2 plasmids were further constructed and transfected into 293 cells. The expression level of HRAS protein in 293 cells was detected by Western blotting.@*RESULTS@#In this SLE family, the female SLE patient and her mother, 1 in generation II and 1 in generation III had typical clinical manifestations of SLE, and all of them had lupus nephritis at early stage. The genetic characteristics are consistent with autosomal dominant inheritance. A novel PLD2 heterozygous mutation (c.2722C>T) was found in the patient and her mother, but not in her father and other normal controls. Compared with wtPLD2 plasmid and negative control PLD2 plasmid, the expression of HRAS in 293 cells transfected with muPLD2 plasmid was significantly up-regulated (both @*CONCLUSIONS@#PLD2 c.2722C>T mutation may be one of the pathogeny of SLE in this family.


Subject(s)
Case-Control Studies , Female , High-Throughput Nucleotide Sequencing , Humans , Lupus Erythematosus, Systemic/genetics , Lupus Nephritis , Mutation , Phospholipase D
17.
Article in Chinese | WPRIM | ID: wpr-881375

ABSTRACT

Objective @# To study the role of DNA methylation in oral leukoplakia carcinogenesis.@*Methods@# DNA methylation was detected in forty cases of oral squamous cell carcinoma (OSCC), twenty-eight cases of oral leukoplakia (OLK) and forty cases of healthy oral mucosa. Download the expression profile data of OSCC, OLK and healthy oral mucosa from Gene Expression Omnibus (GEO) database. DNA methylation data and expression profile data were compared for repeatability, DNA methylation data for difference analysis and corresponding expression profile data for IPA pathway analysis.@*Results @#The data analysis showed that DNA methylation had greater flexibility and instability. Ingenuity Pathway Analysis (IPA) analysis showed that genes related to OLK differential methylation sites were mainly concentrated in the process of cell movement and differentiation. Genes related to differential methylation sites of OSCC are mainly enriched in cell proliferation, migration, oxidation regulation, and anti-apoptosis processes. The genes associated with OLK and OSCC differential methylation sites are co-enriched in phosphoinositol metabolism and phospholipase C signaling pathway.@* Conclusion@#DNA methylation is involved in the formation of oral squamous cell carcinoma, and the activation of phosphoinositol metabolism may promote oral leukinoma.

18.
Acta Pharmaceutica Sinica B ; (6): 781-794, 2021.
Article in English | WPRIM | ID: wpr-881169

ABSTRACT

Fibroblast growth factor receptors (FGFRs) have emerged as promising targets for anticancer therapy. In this study, we synthesized and evaluated the biological activity of 66 pyrazolo[3,4-

19.
Acta Pharmaceutica Sinica B ; (6): 3806-3819, 2021.
Article in English | WPRIM | ID: wpr-922442

ABSTRACT

Dioxin-like molecules have been associated with endocrine disruption and liver disease. To better understand aryl hydrocarbon receptor (AHR) biology, metabolic phenotyping and liver proteomics were performed in mice following ligand-activation or whole-body genetic ablation of this receptor. Male wild type (WT) and

20.
Article in Chinese | WPRIM | ID: wpr-942824

ABSTRACT

Objective: To determine the effect of climatic and environmental factors on the incidence of cutaneous leishmaniasis in Qom province in 2018. Methods: In this cross-sectional study, the data on cutaneous leishmaniasis incidence were collected from the Disease Control and Prevention Center in Qom province. Climatic and environmental data including Normalized Difference Vegetation Index (NDVI), Land Surface Temperature (LST), and soil moisture were extracted using satellite images. Data of altitude and sunny hours were provided based on shuttle radar topography mission digital elevation model and hemispherical viewshed algorithm, respectively. The associations of climatic and environmental variables with the incidence of the disease were analyzed by Pearson correlation method. The ArcGIS 10.3 software was used to determine the geographical distribution of these factors. Results: There were positive correlations between cutaneous leishmaniasis incidence and the two climatic factors: LST and sunny hours per day (P=0.041, P=0.016), and it had weak negative correlations with the digital elevation model (P=0.27), soil moisture (P=0.54), and NDVI (P=0.62). The time delay analysis showed that in one-, two-, and three month periods, the correlations increased with a 95% confidence interval. Accordingly, the correlation with the three-month time delay was positive and relatively strong between the cutaneous leishmaniasis incidence and LST and sunny hours (P=0.027, P=0.02); nevertheless, there were negative correlations between the cutaneous leishmaniasis incidence and the soil moisture (P=0.27) and NDVI (P=0.62). Conclusions: As Qom is located in one of the semi-arid climate zones, topography and solar energy are important factors affecting the incidence of cutaneous leishmaniasis in autumn. Therefore, appropriate disease control programs are recommended.

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