BACKGROUND: Many factors are associated with the development and progression of liver fat and fibrosis; however, genetics and the gut microbiota are representative factors. Moreover, recent studies have indicated a link between host genes and the gut microbiota. This study investigated the effect of patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 (C > G), which has been reported to be most involved in the onset and progression of fatty liver, on liver fat and fibrosis in a cohort study related to gut microbiota in a non-fatty liver population. METHODS: This cohort study included 214 participants from the health check-up project in 2018 and 2022 who had non-fatty liver with controlled attenuation parameter (CAP) values <248 dB/m by FibroScan and were non-drinkers. Changes in CAP values and liver stiffness measurement (LSM), liver-related items, and gut microbiota from 2018 to 2022 were investigated separately for PNPLA3 rs738409 CC, CG, and GG genotypes. RESULTS: Baseline values showed no difference among the PNPLA3 rs738409 genotypes for any of the measurement items. From 2018 to 2022, the PNPLA3 rs738409 CG and GG genotype groups showed a significant increase in CAP and body mass index; no significant change was observed in the CC genotype group. LSM increased in all genotypes, but the rate of increase was highest in the GG genotype, followed by the CG and CC genotypes. Fasting blood glucose levels increased in all genotypes; however, HOMA-IR (Homeostasis Model Assessment of Insulin Resistance) increased significantly only in the GG genotype. HDL (high-density lipoprotein) and LDL (low-density lipoprotein) cholesterol levels significantly increased in all genotypes, whereas triglycerides did not show any significant changes in any genotype. As for the gut microbiota, the relative abundance of Feacalibacterium in the PNPLA3 rs738409 GG genotype decreased by 2% over 4 years, more than 2-fold compared to CC and GG genotypes. Blautia increased significantly in the CC group. CONCLUSION The results suggest that PNPLA3 G-allele carriers of non-fatty liver develop liver fat and fibrosis due to not only obesity and insulin resistance but also the deterioration of gut microbiota, which may require a relatively long course of time, even years.
Humans ; Gastrointestinal Microbiome ; Male ; Female ; Membrane Proteins/metabolism* ; Lipase/genetics* ; Middle Aged ; Liver Cirrhosis/epidemiology* ; Cohort Studies ; Genotype ; Adult ; Non-alcoholic Fatty Liver Disease/microbiology* ; Polymorphism, Single Nucleotide ; Acyltransferases ; Phospholipases A2, Calcium-Independent

As a serious cardiovascular disease, atherosclerosis (AS) causes chronic inflammation and oxidative stress in the body and poses a threat to human health. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospholipase A2 (PLA2) family, and its elevated levels have been shown to contribute to AS. Lp-PLA2 is closely related to a variety of lipoproteins, and its role in promoting inflammatory responses and oxidative stress in AS is mainly achieved by hydrolyzing oxidized phosphatidylcholine (oxPC) to produce lysophosphatidylcholine (lysoPC). Moreover, macrophage apoptosis within plaque is promoted by localized Lp-PLA2 which also promotes plaque instability. This paper reviews those researches of Chinese medicine in treating AS via reducing Lp-PLA2 levels to guide future experimental studies and clinical applications related to AS.
Humans ; 1-Alkyl-2-acetylglycerophosphocholine Esterase ; Medicine, Chinese Traditional ; Atherosclerosis/drug therapy* ; Lipoproteins ; Plaque, Atherosclerotic ; Biomarkers

Ghrelin, a hormone mainly produced and released by the stomach, has numerous functions, including releasing growth hormones, regulating appetite, and processing sugar and lipids. Researchers have made great efforts to study the relationship between ghrelin and metabolic diseases. It is believed that human butyrylcholinesterase (hBChE) could hydrolyze ghrelin to the inactive form (desacyl-ghrelin). However, the low catalytic activity of wild hBChE against ghrelin hinders the clinical application. Recently, a soluble catalytically active hBChE mutant was successfully expressed in Escherichia coli for the first time. We then adopted HotSpot Wizard 3.0 to analyze the mutant structure and rationally selected 10 mutants. Furthermore, we determined the catalytic activities of the mutants against several substrates and the thermostability of these mutants. The results showed that the mutants E197D and A199S improved catalytic activity against ghrelin by 4.6 times and 3.5 times, respectively. The findings provide clues for treating endocrine diseases with the agents for regulating ghrelin.
Ghrelin/genetics* ; Butyrylcholinesterase/genetics* ; Humans ; Escherichia coli/metabolism* ; Mutation ; Catalysis ; Recombinant Proteins/metabolism*

OBJECTIVE: To investigate the association between the expression level of platelet-activating factor acetylhydrolase 1B3 (PAFAH1B3 ) gene in bone marrow CD138⁺ cells of patients with multiple myeloma (MM) treated with autologous hematopoietic stem cell transplantation (AHSCT) and the prognosis within 2 years. METHODS: 147 MM patients treated with AHSCT in The First and The Second Affiliated Hospital of Nantong University from May 2014 to May 2019 were included in the study. Expression level of PAFAH1B3 mRNA in bone marrow CD138⁺ cells of the patients was detected. Patients with disease progression or death during 2 years of follow-up were included in progression group, and the rest were included in good prognosis group. After comparing the clinical data and PAFAH1B3 mRNA expression levels of the two groups, the patients were divided into high PAFAH1B3 expression group and low PAFAH1B3 expression group based on the median PAFAH1B3 mRNA expression level of the enrolled patients. Progression-free survival rate (PFSR) between the two groups was compared by the Kaplan-Meier method. The related factors of prognosis within 2 years were analyzed by univariate analysis and multivariate COX regression analysis. RESULTS: At the end of follow-up, there were 13 patients lost to follow-up. Finally, 44 patients were included in the progression group and 90 patients were included in the good prognosis group. Age in the progression group was higher than that in the good prognosis group, the proportion of patients with CR+VGPR after transplantation in the progression group was lower than that in the good prognosis group, and there was a statistical difference between two groups in the cases distribution of ISS stage (all P<0.05). PAFAH1B3 mRNA expression level and the proportion of patients with LDH>250U/L in the progression group were higher than those in the good prognosis group, and platelet count in the progression group was lower than that in the good prognosis group (all P<0.05). Compared with the low PAFAH1B3 expression group, the 2-year PFSR of the high PAFAH1B3 expression group was significantly lower (log-rank χ²=8.167, P=0.004). LDH>250U/L (HR=3.389, P=0.010), PAFAH1B3 mRNA expression (HR=50.561, P=0.001) and ISS stage Ⅲ(HR=1.000, P=0.003) were independent risk factors for prognosis in MM patients, and ISS stage Ⅰ (HR=0.133, P=0.001) was independent protective factor. CONCLUSION The expression level of PAFAH1B3 mRNA in bone marrow CD138⁺ cells is related to the prognosis of MM patients treated with AHSCT, and detecting PAFAH1B3 mRNA expression can bring some information for predicting PFSR and prognostic stratification of patients.
Humans ; Disease Progression ; Hematopoietic Stem Cell Transplantation ; Multiple Myeloma/drug therapy* ; Prognosis ; Retrospective Studies ; Transplantation, Autologous ; 1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics*

OBJECTIVE: To explore the clinical phenotype and genetic features of two children with MEGDEL syndrome due to variants of the SERAC1 gene. METHODS: Two children who had presented at the Fujian Medical University Union Hospital respectively on July 14, 2020 and July 28, 2018 were selected as the study subjects. Clinical features and results of genetic testing were retrospectively analyzed. RESULTS: Both children had featured developmental delay, dystonia and sensorineural deafness, along with increased urine 3-methylglutaric acid levels. Magnetic resonance imaging revealed changes similar to Leigh-like syndrome. Gene sequencing revealed that both children have harbored pathogenic compound heterozygous variants of the SERAC1 gene, including c.1159C>T and c.442C>T in child 1, and c.1168C>T and exons 4~9 deletion in child 2. CONCLUSION Children with MEGDEL syndrome due to SERAC1 gene variants have variable clinical genotypes. Delineation of its clinical characteristics and typical imaging changes can facilitate early diagnosis and treatment. Discovery of the novel variants has also enriched the spectrum of SERAC1 gene variants.
Humans ; Retrospective Studies ; Metabolism, Inborn Errors ; Hearing Loss, Sensorineural/genetics* ; Dystonia ; Carboxylic Ester Hydrolases

This report presents a case of a male infant, aged 32 days, who was admitted to the hospital due to 2 days of bloody stools and 1 day of fever. Upon admission, venous blood samples were collected, which appeared pink. Blood biochemistry tests revealed elevated levels of triglycerides and total cholesterol. The familial whole genome sequencing revealed a compound heterozygous variation in the LPL gene, with one variation inherited from the father and the other from the mother. The patient was diagnosed with lipoprotein lipase deficiency-related hyperlipoproteinemia. Acute symptoms including bloody stools, fever, and bloody ascites led to the consideration of acute pancreatitis, and the treatment involved fasting, plasma exchange, and whole blood exchange. Following the definitive diagnosis based on the genetic results, the patient was given a low-fat diet and received treatment with fat-soluble vitamins and trace elements, as well as adjustments to the feeding plan. After a 4-week hospitalization, the patient's condition improved and he was discharged. Follow-up showed a decrease in triglycerides and total cholesterol levels. At the age of 1 year, the patient's growth and psychomotor development were normal. This article emphasizes the multidisciplinary diagnosis and treatment of familial hyperlipoproteinemia presenting with symptoms suggestive of acute pancreatitis, including bloody ascites, in the neonatal period.
Humans ; Infant ; Male ; Acute Disease ; Ascites ; Cholesterol ; Hyperlipoproteinemia Type I/genetics* ; Hyperlipoproteinemias ; Lipoprotein Lipase/genetics* ; Pancreatitis ; Triglycerides

Diacylglycerol (DAG) is an intermediate product in lipid metabolism and plays an important physiological role in human body. It is mainly prepared by hydrolyzing lipid with lipase. However, research on the detection method of 1, 2-diacylglycerol (1, 2-DAG) and 1, 3-diacylglycerol (1, 3-DAG) and catalytic specificity of lipase was not enough, which limits its wide application. To address these challenges, an efficient quantitative detection method was first established for 1, 2-DAG (0.025-0.200 g/L) and 1, 3-DAG (0.025-0.150 g/L) by combining supercritical fluid chromatography with evaporative light scattering detector and optimizing the detection and analysis parameters. Based on the molecular docking between Thermomyces lanuginosus lipase (TLL) and triolein, five potential substrate binding sites were selected for site-specific saturation mutation to construct a mutation library for enzyme activity and position specificity screening. The specificity of sn-1, 3 of the I202V mutant was the highest in the library, which was 11.7% higher than the specificity of the wild type TLL. In summary, the position specificity of TLL was modified based on a semi-rational design, and an efficient separation and detection method of DAG isomers was also established, which provided a reference for the study of the catalytic specificity of lipase.
Humans ; Diglycerides ; Molecular Docking Simulation ; Binding Sites ; Catalysis ; Lipase/genetics*

Monoacylglycerol lipase (MGL) is a serine hydrolase that plays a major role in the degradation of endogenous cannabinoid 2-arachidonoylglycerol. The role of MGL in some cancer cells has been confirmed, where inhibition of the MGL activity shows inhibition on cell proliferation. This makes MGL a promising drug target for the treatment of cancer. Recently, the development of covalent inhibitors of MGL has developed rapidly. These drugs have strong covalent binding ability, high affinity, long duration, low dose and low risk of drug resistance, so they have received increasing attention. This article introduces the structure and function of MGL, the characteristics, mechanisms and progress of covalent MGL inhibitors, providing reference for the development of novel covalent small molecule inhibitors of MGL.
Monoacylglycerol Lipases/metabolism* ; Endocannabinoids/metabolism*

Objective: To explore the relationship between extracellular enzymes activity and virulence of Candida glabrata clinical isolates based on the infection model of Galleria mellonella larvae. Methods: Using experimental research methods, 71 strains of non-repetitive Candida glabrata were collected from Qinghai Provincial People's Hospital from June 2021 to January 2022. Bovine serum protein agar medium, egg yolk agar medium, sheep blood agar medium, Tween-80 agar medium and triglyceride agar medium were used to detect the aspartyl protease activity, phospholipase activity, hemolysis activity, esterase activity and lipase activity of Candida glabrata. Median lethal concentration (LC₅₀) was calculated by using 1.25×10⁸ CFU/ml,2.50×10⁸ CFU/ml,3.75×10⁸ CFU/ml,5.00×10⁸ CFU/ml suspension of Candida glabrata ATCC2001 to infect Galleria mellonella larvae. Histopathological and etiological analysis was performed to determine whether the infection model was successfully established. The clinical isolates of Candida glabrata were configured to infect Galleria mellonella larvae with LC₅₀ concentration to detect the pathogenicity of Galleria mellonella larvae.Spearman test or Pearson test were used to analyze the correlation between the extracellular enzyme activity of Candida glabrata clinical isolates and the pathogenicity of Galleria mellonella larvae. Results: 71 strains of Candida glabrata isolated clinically were detected to have low hemolytic activity after 2 days of culture. Aspartyl protease was detected after 4 days of culture, among which 7 strains (9.86%), 19 strains (26.76%) and 45 strains (63.38%) showed low, medium and high aspartyl protease activity. After 7 days of culture, 71 strains did not detect phospholipase, esterase and lipase activities. Candida glabrata on Galleria mellonella larvae of LC₅₀=2.5×10⁸ CFU/ml Fungal spore were found in the intestinal tissue pathological section of Galleria mellonella larvae in the experimental group, and Candida glabrata was identified by the microbial Mass Spectrometry after culture, while no fungi were found in the pathological section and culture of the control group. Spearman test shows that, there was a linear positive correlation between aspartyl protease activity and the survival rate of Galleria mellonella larvae (r = 0.73, P<0.01), the difference was statistically significant.Pearson test shows that, there was no significant linear relationship between hemolytic activity and survival rate of Galleria mellonella larvae (r = 0.16, P = 0.34), the difference was not statistically significant. Conclusion: The clinical isolates of Candida glabrata in this study had aspartyl protease activity and low hemolytic activity, but no phospholipase, esterase and lipase activity. The activity of aspartyl aspartyl protease of Candida glabrata was positively correlated with the pathogenicity of Galleria mellonella larvae.
Animals ; Sheep ; Larva/microbiology* ; Virulence ; Candida glabrata ; Agar ; Moths/microbiology* ; Esterases ; Aspartic Acid Proteases ; Lipase

OBJECTIVES: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a vaso-specific inflammatory marker that exacerbates atherosclerotic through inflammatory responses. It can be used to predict the occurrence of adverse cardiovascular events and to assess the residual risk of cardiovascular diseases. This study aims to investigate the correlation between smoking and serum Lp-PLA2 levels in overweight and obese men, and to provide evidence for preventing the cardiovascular diseases. METHODS: Male subjects, who participated in health examination at the Health Management Center, Third Xiangya Hospital, Central South University from May 1, 2020 to April 30, 2021, were selected. The smoking status and other information were collected by the Self-test Scale of Physical Examination. According to the smoking status, they were divided into a never-smoking group, a current smoking group, a quit smoking group and a passive smoking group. According to the daily smoking amount, the current smoking subjects were divided into a <10 cigarettes group, a 10 to 20 cigarettes group, a 21 to 30 cigarettes group, and a >30 cigarettes group. According to the smoking years, the current smoking subjects were divided into a <5 years group, a 5 to 10 years group, a 11 to 20 years group, and a >20 years group.Serum Lp-PLA2 levels and other clinical indexes in different smoking groups were measured and compared, the correlation between smoking and serum Lp-PLA2 levels in overweight and obese men was analyzed by logistic regression analysis. RESULTS: Serum Lp-PLA2 levels were significantly different between the never-smoking group and the current smoking group (P<0.05). Logistic regression analysis showed that, before adjusting other influencing factors and in terms of smoking status, the current smoking group (OR=1.81, 95% CI 1.27 to 2.58, P<0.01) and the quit smoking group (OR=2.09, 95% CI 1.12 to 3.90, P<0.05) were positively correlated with serum Lp-PLA2 levels compared with the never-smoking group, while the passive smoking group had no correlation with serum Lp-PLA2 levels (OR=1.27, 95% CI 0.59 to 2.73, P>0.05). In terms of daily smoking amount, the 10 to 20 cigarettes group (OR=2.09, 95% CI 1.40 to 3.12, P<0.001) and the 21 to 30 cigarettes group (OR=1.98, 95% CI 1.22 to 3.20, P<0.01) were positively correlated with serum Lp-PLA2 levels compared with the never-smoking group, while the <10 cigarettes group (OR=1.45, 95% CI 0.81 to 2.60, P>0.05) and the >30 cigarettes group (OR=1.17, 95% CI 0.60 to 2.28, P>0.05) had no correlation with serum Lp-PLA2 levels. In terms of smoking years, the 5 to 10 years group (OR=1.94, 95% CI 1.07 to 3.53, P<0.05), the 11 to 20 years group (OR=2.06, 95% CI 1.33 to 3.18, P<0.01), and the >20 years group (OR=1.66, 95% CI 1.11 to 2.47, P<0.05) were positively correlated with serum Lp-PLA2 levels compared with the never-smoking group, while the <5 years group had no correlation with serum Lp-PLA2 levels (OR=1.12, 95% CI 0.38 to 3.33, P>0.05). After adjusting for age and other indicators, the correlation between smoking years and serum Lp-PLA2 levels was the same as before adjustment among the above smoking groups, except that the correlation between the smoking 5 to 10 years group and serum Lp-PLA2 levels was not significant (OR=1.77, 95% CI 0.95 to 3.29, P>0.05). CONCLUSIONS Smoking is correlated with serum Lp-PLA2 levels in overweight and obese men.
Humans ; Male ; 1-Alkyl-2-acetylglycerophosphocholine Esterase ; Overweight ; Cardiovascular Diseases ; Tobacco Smoke Pollution ; Biomarkers ; Obesity ; Smoking ; Risk Factors