Phospholipase A2 Research Articles

Functionally overlapping intra- and extralysosomalpathways promote bis(monoacylglycero)phosphate synthesis in mammalian cells.

Bis(monoacylglycero)phosphate (BMP) is a major phospholipid constituent of intralumenal membranes in late endosomes/lysosomes, where it regulates the degradation and sorting of lipid cargo. Recent observations suggest that the Batten disease-associated protein CLN5 functions as lysosomal BMP synthase. Here, we show that transacylation reactions catalyzed by cytosolic and secreted enzymes enhance BMP synthesis independently of CLN5. The transacylases identified in this study are capable of acylating the precursor lipid phosphatidylglycerol (PG), generating acyl-PG, which is subsequently hydrolyzed to BMP. Extracellularly, acyl-PG and BMP are generated by endothelial lipase in cooperation with other serum enzymes of the pancreatic lipase family. The intracellular acylation of PG is catalyzed by several members of the cytosolic phospholipase A2 group IV (PLA2G4) family. Overexpression of secreted or cytosolic transacylases was sufficient to correct BMP deficiency in HEK293 cells lacking CLN5. Collectively, our observations suggest that functionally overlapping pathways promote BMP synthesis in mammalian cells.

Diagnostic Utility of Combining Homocysteine, Lipoprotein-Associated Phospholipase A2, and the C-Reactive Protein-to-Albumin Ratio for Assessing Carotid Atherosclerosis and Plaque Stability in Patients with Essential Hypertension.

The objective of this study is to determine the diagnostic utility of combining homocysteine (HCY), lipoprotein-associated phospholipase A2 (LP-PLA2), and the C-reactive protein-to-albumin ratio (CAR) for carotid atherosclerosis (CAS) and plaque stability in patients with essential hypertension (EH). A total of 280 patients with EH were divided into 2 groups according to ultrasound diagnosis: CAS (n = 106) and non-CAS (N-CAS [n = 174]). The CAS group was further segmented into plaque-stable (n = 50) and plaque non-stable (n = 56) groups. General data were collected for all patients. Risk factors associated with CAS and plaque instability in patients with EH, and the diagnostic utility of HCY, LP-PLA2, and CAR testing alone, or in combination, for assessing CAS and plaque instability were determined. Mean age, systolic blood pressure (SBP), duration of EH, smoking, total cholesterol high-density lipoprotein cholesterol, HCY, LP-PLA2 levels, and CAR were higher in the CAS group than those in the N-CAS group (P < 0.05). SBP, duration of EH, HCY and LP-PLA2 levels, and CAR were independent risk factors for CAS (P < 0.05). In addition, HCY, LP-PLA2, and CAR alone demonstrated significant diagnostic efficacy (P < 0.001) but were inferior to the combined diagnostic utility of the 3 parameters (P < 0.001). HCY and LP-PLA2 levels, and CAR were higher in the plaque non-stable than in the plaque-stable group (P < 0.05). Duration of EH, low-density lipoprotein cholesterol, HCY, LP-PLA2, and CAR independently influenced plaque instability in patients with CAS (P < 0.05). The combined diagnostic utility of HCY, LP-PLA2, and CAR (P < 0.001) was superior to that of each parameter alone and demonstrated more pronounced diagnostic efficacy (P < 0.001). HCY, LP-PLA2, and CAR were independent risk factors for CAS and plaque instability in patients with EH. HCY, LP-PLA2, and CAR demonstrated significant diagnostic efficacy for CAS and plaque instability, and combination of the 3 demonstrated the most pronounced diagnostic efficacy.

Dynamics of Ischemia/Reperfusion Injury Markers During Normothermic Liver Machine Perfusion

Background. A comprehensive mechanistic assessment of normothermic machine perfusion (NMP) is an essential step toward identifying biomarkers to assess liver viability. Although some studies have evaluated the effect of NMP on inflammation markers, there are other key pathological mechanisms involved in ischemia/reperfusion injury (IRI) that have not yet been evaluated. Methods. Eight human donor livers preserved by NMP were included to analyze IRI during preservation. Concentrations of several biomarkers involved in different biological processes of IRI were measured in the perfusate. Results. Perfusate levels of intercellular adhesion molecule 1, P-selectin, vascular cell adhesion molecule 1, metalloproteinase with thrombospondin motif type 1, member 13, phospholipase A2 group VII, and syndecan-1 progressively increased during NMP. Noteworthy, perfusate lactate levels showed a strong correlation with C-X-C motif chemokine ligand 10 (P = 0.001), intercellular adhesion molecule 1 (P = 0.01), and urokinase plasminogen activator (P = 0.001). Conclusions. Perfusate lactate correlates with the main underlying biological mechanisms occurring in the NMP environment. Moreover, several IRI biomarkers accumulate during NMP, which may limit the extent of the benefits of this technology.

Lipoprotein-associated phospholipase A2 and its possible association with COPD development: a case-control study.

The association of lipoprotein-associated phospholipase A2 (Lp-PLA2) with various cardiovascular events has been well-established. However, the exploration of its potential involvement in Chronic obstructive pulmonary disease (COPD) is currently limited. Therefore, our study aims to examine the relationship between Lp-PLA2 and pulmonary conditions, including emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction, to provide further evidence of a possible association with COPD development. Using data from the Southwest Hospital Health Management Center, spanning January 2013 to July 2024, we analyze relationship of serum Lp-PLA2 levels with diffuse pulmonary emphysema and pulmonary functions. In univariate analysis, group differences were assessed with t-tests for numerical variables and Chi-square tests for categorical data. Variables found to be statistically significant (two-sided P < 0.05) in univariate analysis were subsequently included as covariates in multivariate analysis, performed using a binary logistic regression model. Odds ratios and 95% confidence intervals were calculated to assess the differences. We established 2 case-control populations: the Imaging population (1056 subjects, mean age 57.666 ± 8.700 years old, 89.9% male) selected from 24,670 initial records, and the Pulmonary Function population (279 subjects, mean age 52.082 ± 11.473 years old, 71.4% male) selected from 1868 initial records. Univariate analysis revealed that serum Lp-PLA2 levels were significantly higher in patients with diffuse pulmonary emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction compared to those without (454.682 ± 141.382U/L vs. 423.330 ± 140.658U/L, P < 0.001; 475.059 ± 157.181U/L vs. 420.824 ± 142.119U/L, P = 0.006; 475.31 ± 148.980U/L vs. 439.036 ± 157.977U/L, P = 0.049, respectively). Multivariate analysis further showed higher Lp-PLA2 levels were associated with increased risks of diffuse pulmonary emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction. Using Lp-PLA2 ≤ 300 U/L as reference, odds ratios for the aforementioned conditions showed a gradually increasing trend with every 100U/L increase in Lp-PLA2 levels. Our preliminary study suggests that Lp-PLA2 is independently associated with diffuse pulmonary emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction, which are commonly seen in COPD development. These findings indicated a possible association between Lp-PLA2 and COPD, though further validation is needed in a large cohort of COPD patients.

A case of PLA2R-positive membranous nephropathy with subsequent development of IgG4-related disease.

Membranous nephropathy (MN) is a common cause of adult-onset nephrotic syndrome. It is also known as a minor but established renal manifestation of Immunoglobulin G4-related disease (IgG4-RD). Previous reports suggest that MN can also be an initial manifestation of IgG4-RD, all of which are phospholipase A2 receptor (PLA2R)-negative MN. We describe a case of PLA2R-positive MN that subsequently developed other manifestations of IgG4-RD. A 60-year-old male with nephrotic syndrome was diagnosed as primary MN with positive staining for PLA2R on the initial renal biopsy, which remained in partial remission with supportive therapy using angiotensin II receptor blocker (ARB) without steroid. About 1year later, a renal mass was detected during an annual checkup, and contrast-enhanced computed tomography revealed low-density masses in bilateral kidneys and the head of the pancreas. The findings of endoscopic biopsy of the pancreatic mass were consistent with autoimmune pancreatitis (AIP) and the second renal biopsy showed the findings of MN with tubulointerstitial nephritis, both of which led to a diagnosis of IgG4-RD. The second renal biopsy also showed positive PLA2R. The patient received oral glucocorticoid therapy for IgG4-RD, which improved IgG4-related AIP and renal masses and also resulted in complete remission of MN. To our knowledge, this is the first reported case of PLA2R-positive MN with subsequent development of IgG4-RD. It is sometimes difficult to determine whether PLA2R-positive MN occurring with IgG4-RD is primary MN or secondary MN associated with IgG4-RD. The possibility of developing IgG4-RD should be considered even when preceding MN is PLA2R-positive, suggesting of primary MN.

Myotoxicity of Crotoxin on C2C12 Myoblasts and its Inhibition by Crotalus Neutralizing Factor versus Enhanced Resistance in Myotubes: Exploring Toxicity and Membrane Potential.

Crotalus Neutralizing Factor (CNF) is a γ-type Phospholipase A2 (PLA2) inhibitor present in the blood of Crotalus durissus terrificus snake. Particularly, CNF inhibits the toxic action of Crotoxin (CTX), which is a major neurotoxin found in C. d. terrificus venom. CTX induces also myotoxic action and demonstrates high selectivity for skeletal muscle fibers. Consequently, CTX can diffuse beyond the site of infection, which can potentially evoke rhabdomyolysis. The present study has evaluated the effects of CTX on myoblasts and myotubes of muscle cells C2C12 in vitro and the effect of CNF on CTX-induced damage. Cytotoxicity assays were performed by measuring the mitochondrial enzyme dehydrogenase levels. Furthermore, creatine kinase and lactate dehydrogenase levels were used as indicators of muscle damage. Crotoxin has been found to have cytotoxic effects on C2C12 myoblast cells, while CNF has not shown toxic effects on these cells. Furthermore, the findings have shown CNF (50 μg/mL) to abolish CTX toxicity in myoblasts. The myotubes, differentiated cells, showed no change in mitochondrial respiration when exposed to CNF or CTX, showing greater resistance to the toxic actions of crotoxin. The data have confirmed the potential of CNF as an anti-myotoxic agent to prevent CTX-damaged myoblasts and increase resistance to the toxic effects of crotoxin on differentiated cells.

Hyperglycosylation impairs the inhibitory activity of rCdtPLI2, the first recombinant beta-phospholipase A2 inhibitor

Crotoxin, a phospholipase A2 (PLA2) complex and the major Crotalus venom component, is responsible for the main symptoms described in crotalic snakebite envenomings and a key target for PLA2 inhibitors (PLIs). PLIs comprise the alpha, beta and gamma families, and, due to a lack of reports on beta-PLIs, this study aimed to heterologously express CdtPLI2 from Crotalus durissus terrificus venom gland to improve the knowledge of the neglected beta-PLI family. Thereby, recombinant CdtPLI2 (rCdtPLI2) was produced in the eukaryotic Pichia pastoris system to keep some native post-translational modifications. rCdtPLI2 (~41 kDa) presents both N- and O-linked glycans. Alpha-mannosidase digested-rCdtPLI2 (1 mol) strongly inhibited (73 %) CB-Cdc catalytic activity (5 mol), demonstrating that glycosylations performed by P. pastoris affect rCdtPLI2 action. Digested-rCdtPLI2 also inhibited PLA2s from diverse Brazilian snake venoms. Furthermore, rCdtPLI2 (1 mol) abolished the catalytic activity of Lmr-PLA2 (5 mol) and reduced the CTx-Cdc (5 mol) enzyme activity by 65 %, suppressing basic and acidic snake venom PLA2s. Additionally, crotalic antivenom did not recognize rCdtPLI2, suggesting a lack of neutralization by antivenom antibodies. These findings demonstrate that studying snake venom components may reveal interesting novel molecules to be studied in the snakebite treatment and help to understand these underexplored inhibitors.

In vitro anticoagulant effects of Bungarus venoms on human plasma which are effectively neutralized by the PLA2-inhibitor varespladib.

Bungarus (krait) envenomings are well-known for their life-threatening neurotoxic effects. However, their impact on coagulation remains largely unexplored experimentally or clinically. This study, examined the effect of begins to examine venoms from four Bungarus species-B. caeruleus, B. candidus, B. fasciatus, and B. flaviceps on human platelet poor plasma coagulation parameters using thromboelastography and coagulation inhibition assays. B. flaviceps completely inhibited clotting, while B. caeruleus only delayed clot formation. In contrast, B. candidus and B. fasciatus did not affect clotting. Subsequent examinations into the anticoagulant biochemical mechanisms demonstrated divergent pathphysiological pathways. B. caeruleus venom anticoagulant effects were prevented by the addition of an excess of phospholipids, with anticoagulation thereby the result of phospholipid depletion. In contrast B. flaviceps anticoagulation was not affected by the addition of an excess of phospholipids. Further investigations demonstrated that B. flaviceps mediates its anticoagulant toxicity through the inactivation of coagulation enzymes. The anticoagulant effects of both B. flaviceps and B. caeruleus were nullified by varespladib, a phospholipase A2 (PLA2) inhibitor, revealing the toxin class involved. These results uncover previously unrecognized and unexplored anticoagulant effects of Bungarus venoms.

A newly identified secretory phospholipase A2 group XIIA homolog (LcPLA2XIIA) in Larimichthys crocea exhibits antimicrobial and antitumor activities

The phospholipase A2 (PLA2) superfamily has attracted increasing attention in recent years due to the multiple physiological and pathological functions exerted by its members. Up to date, the knowledge about the biological role of PLA2XIIA subfamily members remains limited. In this study, a new member of PLA2XIIA subfamily, LcPLA2XIIA, was characterized in large yellow croaker. Different from most members of the PLA2 superfamily with positive charge, LcPLA2XIIA encodes an anionic protein, which is similar to other members of PLA2XIIA subfamily. LcPLA2XIIA is highly expressed in the intestine, and afterwards, it is up-regulated after with Pseudomonas plecoglossicida or Staphylococcus aureus. LcPLA2XIIA exhibits strong inhibitory activity against these two bacteria. The results indicate that LcPLA2XIIA plays an important role in the antimicrobial immune responses of large yellow croaker. LcPLA2XIIA displays strong binding activity to all the tested bacteria. It specifically interacts with LTA, a unique component on the surface of Gram-positive bacteria. It also significantly promotes bacterial agglutination in the presence of Ca2+. These findings reveal that the binding and agglutinating abilities of LcPLA2XIIA to bacteria contribute greatly to its antibacterial activity. In addition, LcPLA2XIIA significantly inhibits the proliferation of infectious hematopoietic necrosis virus instead of recombinant human adenovirus type 5. It also suppresses the growth of human colorectal adenocarcinoma cells by inducing apoptosis, but it has no obvious inhibitory effect on the growth of epithelioma papulosum cyprinid cells. This study provides new insights into the antibacterial activity, and the mechanism of LcPLA2XIIA in large yellow croaker, and antiviral and antitumor functions of PLA2XIIA subfamily members.

The role and mechanism of BmsPLA2-1-1 in the IMD pathway in silkworm, Bomybx mori

Lepidoptera are a major source of pests in agriculture and forestry, investigating the immune mechanisms of their model species, Bombyx mori, can provide valuable insights into improving pest management. Although the phospholipase A2 (PLA2) and immune deficiency (IMD) pathway have been extensively investigated, their relationship remains unclear. Here, we found that bacterial infection of silkworm larvae significantly upregulated BmsPLA2-1-1 expression and knockdown of BmRelish in the IMD pathway suppressed this response. Likewise, reducing BmsPLA2-1-1 expression significantly downregulated IMD pathway-related genes, including BmRelish, BmImd, and BmPGRP. In contrast, overexpression of BmsPLA2-1-1 significantly upregulated BmRelish and BmImd expression, suggesting a functional crosstalk between BmsPLA2-1-1 and the IMD pathway in silkworms. Additionally, BmPLA2-1-1 interacted with BmHsp60, BmCNBP, BmCfp1, and BmPFD3. Reducing BmRelish resulted in decreased expression of BmHsp60A, BmCfp1, and BmPFD3, but not BmCNBP, in infected larvae. Overexpression BmHsp60A, BmCfp1, or BmPFD3 led to a significant upregulation of BmRelish and BmImd expression. These suggest that BmHsp60A, BmCfp1, and BmPFD3 are involved in functional crosstalk between BmsPLA2-1-1 and the IMD pathway in silkworms. These findings demonstrate the functional crosstalk and mechanism between BmsPLA2-1-1 and the IMD pathway, revealing a new mechanism in the insect immune network.

Hepatoprotective and neuroprotective effects of quinacrine against bile duct ligation-induced hepatic encephalopathy in rats: Role of bone morphogenetic proteins signaling

AimsThis study aimed to assess the potential protective effect of quinacrine, an FDA approved antimalarial drug with reported anti-inflammatory effects, on hepatic encephalopathy (HE) in a bile duct ligation (BDL) experimental model and to investigate the mechanisms responsible for this effect, namely those associated with the liver-brain axis, particularly, bone morphogenetic protein 2 (BMP2) signaling. Materials and methodsFive groups of rats were selected at random: sham, BDL, (BDL+ quinacrine 5), (BDL+ quinacrine 10), and (quinacrine 10 + sham). Daily Intraperitoneal (I.P.) administration of quinacrine was initiated on the surgery day and continued for 28 days. Key findingsResults showed that rats that underwent BDL exhibited marked elevation of serum liver enzymes, ammonia, total bilirubin, together with oxidative stress, inflammation, dysregulated farnesoid x receptor (FXR), dysregulated BMP2 signaling and escalated fibrotic markers indicating hepatotoxicity, cholestasis and fibrosis. Besides, neurotoxicity was detected as manifested by cognitive deficits and dysregulation of hippocampal FXR, BMP2 signaling, WNT3A signaling, brain derived neurotrophic factor (BDNF), phospholipase A2 (PLA2) and glial fibrillary acidic protein (GFAP). In contrast, co-treatment with quinacrine mitigated BDL-induced hepatotoxicity, cholestasis, fibrosis, and neurotoxicity. Notably, quinacrine improved learning and memory and restored FXR, BMP2 signaling in the liver and hippocampus. In addition, quinacrine restored hippocampal WNT3A signaling, BDNF, whereas it downregulated expression of hippocampal PLA2 and GFAP. SignificanceThese findings demonstrated implication of BMP2 signaling in the molecular process of BDL-induced HE and proposed that quinacrine has potential hepatoprotective and neuroprotective properties against HE.

Application of Human Plasma Targeted Lipidomics and Analysis of Toxic Elements to Capture the Metabolic Complexities of Hypothyroidism.

Hypothyroidism (HT) affects millions worldwide and can lead to various lipid disorders. The metabolic complexity and the influence of toxic elements in autoimmune and non-autoimmune HT subtypes are not fully understood. This study aimed to investigate the relationships between plasma lipidome, toxic elements, and clinical classifications of HT in unexposed individuals. Samples were collected from 120 adults assigned to a study group with Hashimoto's disease and non-autoimmune HT, and a healthy control group. Quantification of 145 pre-defined lipids was performed by using triple quadrupole tandem mass spectrometry (TQ MS/MS) in multiple reactions monitoring (MRM) mode via positive electrospray ionization (ESI). Levels of toxic elements were determined using inductively coupled plasma mass spectrometry (ICP-MS). Significant associations between altered levels of several components of the plasma lipidome and Al, Cd, Ni, As, and Pb with HT were found. We show metabolic differences in lysophosphatidylcholines (LPC) and phosphatidylcholines (PC) between HT and controls, with distinct predicted activation patterns for lysolecithin acyltransferase and phospholipase A2. There are significant changes in the lipidome profiles of healthy subjects compared to euthyroid HT patients treated with L-thyroxine, which are related to the type of hypothyroidism and non-occupational exposure to toxic elements.

Isolation, Characterization, and Anti-Inflammatory Effects of β-Sitosterol-β-D-Glucoside from Hygrophila auriculata: Experimental Validation, Molecular Docking, and Molecular Dynamics Simulations.

Hygrophila auriculata (K. Schum) Heine is known to treat various common aliment e.g. rheumatoid arthritis, kidney infections, jaundice, edema, and gout. This study aims to isolate bioactive components from the methanolic extract, assess their anti-inflammatory effects, and investigate their interactions with drug targets through docking and molecular dynamics simulations. Methanolic extract of H. auriculata furnished stigmast-5-en-3-ol-β-D-glucopyranoside (HA-06) which was characterized by using IR, NMR and mass spectral data. HA-06 alleviated carrageenan-induced inflammation in rats, while the methanolic extract of H. auriculata produced comparable results. The findings were similar to those of the positive control, indomethacin. The chemical structure of HA-06 was optimized using DFT at the B3LYP level and subsequently used for molecular docking against anti-inflammatory drug targets. HA-06 exhibited strong affinity towards phospholipase A2 and glucocorticoid receptor exhibiting binding energies of -11.25 kcal/mol and -11.07 kcal/mol, respectively.Molecular dynamics simulation was used to assess the dynamical stability of these two complexes and their native co-crystallized ligands. Principal component analysis, radius of gyration, free energy landscapes, solvent-accessible-surface-area, and root-mean square deviation/fluctuation all indicated stable interactions. Therefore, HA-06 could be a promising candidate for development into an effective therapy against inflammatory diseases targeting phospholipase A2 and glucocorticoid receptor.

Clinicopathological Features of Membranous Nephropathy Complicated by IgA Nephropathy: A Retrospective Analysis of Seven Cases.

Aims/Background Both membranous nephropathy (MN) and immunoglobulin A nephropathy (IgAN) are immune complex-mediated glomerular diseases, but the concurrent occurrence of these two conditions in the same patient is not common, a phenomenon that is currently not supported by clinical data in terms of treatment and prognosis. This study explores the clinical and pathological characteristics, as well as the treatment outcomes, of patients affected by MN and IgAN simultaneously. Methods The clinical data, pathological features, and diagnostic and therapeutic information of seven cases of MN complicated by IgAN, treated between December 2015 and December 2022, were retrospectively analyzed. Results Among the seven cases, there were two male and five female patients, with an average age of 57.3 ± 9.2 years. All patients presented with clinical manifestations of proteinuria and edema upon admission, with an average 24-hour urine protein of 3716.6 ± 1519.4 mg/24 h. Phospholipase A2 receptor (PLA2R) expression was detected in all seven cases, and nephrotic syndrome was clinically diagnosed in five cases. Additionally, all seven cases showed microscopic hematuria, with intermittent gross hematuria in two cases. All seven patients included in this study underwent renal biopsy. After disease staging, the patients had MN stages I-III and IgAN stages II-III. Pathological findings revealed abnormal glomerular basement membrane (GBM) and diffuse immunoglobulin G (IgG) deposition in the subepithelial space, predominantly of the IgG4 subtype. Simultaneously, there was diffuse mesangial zone deposition of immunoglobulin A (IgA) to varying degrees, co-localization of complement component C3 and IgA, and mesangial cell proliferation. Treatment strategies included angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in combination with steroids or immunosuppressive therapies such as tacrolimus, cyclophosphamide, and rituximab. After 2-6 months of treatment, all patients achieved complete remission with a favourable prognosis. Conclusion MN accompanied by IgAN tends to occur more frequently in middle-aged and elderly individuals, with a relatively low incidence. The latent feature of the comorbidities manifests as a form of IgAN superimposed on the background of MN. Utilizing ACEI or ARB in combination with steroids or various immunosuppressive therapies represents a potentially effective treatment strategy.

Membranous glomerulopathy in women: clinical repercussions

Introduction: Membranous glomerulopathy is one of the most common causes of nephrotic syndrome in adults, with particular prevalence in women. This condition is characterized by thickening of the glomerular basement membrane, resulting in significant proteinuria and other clinical complications. The disease may have primary etiologies, such as the presence of antibodies against the phospholipase A2 receptor, or secondary to conditions such as infections, neoplasias and autoimmune diseases. In women, the clinical repercussions of membranous glomerulopathy may be more complex, since the interaction between hormones and immunological factors may influence the course of the disease and the response to treatment. Methodology: The research was conducted using the PRISMA checklist, with data collection from articles published in the last 10 years in the PubMed, SciELO and Web of Science databases. Five descriptors were used: "membranous glomerulopathy", "nephrotic syndrome", "women", "treatment" and "clinical implications". Inclusion criteria consisted of studies that addressed membranous glomerulopathy specifically in women, articles that presented clinical data, and peer-reviewed studies. Exclusion criteria included publications not related to the female population, articles with insufficient data, and non-original reviews. Results: The review revealed that membranous glomerulopathy in women is associated with a higher incidence of complications, including venous thrombosis and arterial hypertension. Treatments ranged from immunosuppressive to targeted therapies, with varied results in terms of remission and adverse effects. The quality of life of patients was significantly affected by the disease, highlighting the need for multidisciplinary management. Conclusion: Membranous glomerulopathy in women presents unique characteristics and clinical challenges, which demand special attention in diagnosis and treatment. Understanding the clinical repercussions and personalizing therapeutic approaches are essential to improve the quality of life of patients affected by this complex condition.

Association between lipoprotein-associated phospholipase A2 gene Val279Phe homozygous genotypes and variant angina in Japanese women

Abstract Background The role of the lipoprotein-associated phospholipase A2 gene (PLA2G7) in the pathogenesis of cardiovascular diseases remains controversial. The PLA2G7 gene normally produces a protein called "plasma platelet activating factor-acetylhydrolase"(PAF-AH). Homozygotes of rs76863441, which is PLA2G7 Val279Phe polymorphism, produce none of PAF-AH, and heterozygotes produce less than half of the normal levels. This polymorphism is rare outside of Asia and is particularly common in Japan, where homozygous mutations account for 4% of the population. The association between rs76863441 and risk of myocardial infarction was significant in ethnicity for Japanese population, but not in other countries. Variant angina is a severe case of coronary artery spasm (CSA) and causes an acute myocardial infarction. It is widely accepted that variant angina is more common in Japanese than in other races. Purpose The aim of this study was to examine the possible association between rs76863441 and variant angina. Methods rs76863441 was analyzed by direct sequencing in 62 patients with variant angina (43 men and 19 women with a mean age of 60.0±11.6 years). In all patients, ST segment elevation was recorded on ECG and coronary angiography was performed. Acetylcholine provocation test was performed in 31 patients. We compared genotypes of rs76863441 between variant angina patients and 872 healthy volunteers without a history of heart diseases living in the same area, who participated in the Iwaki Health Promotion Project, which has been conducted by the Hirosaki University School of Medicine since 2005. These volunteers had undergone Japonica Arrays, which is the SNP array for the Japanese population. Results Homozygotes genotype for rs76863441, heterozygotes genotype, and wild genotype were present in 4 (6.5%), 22 (35.5%), and 36 (58.1%) of the variant angina group, respectively, and in 30 (3.4%), 246 (28.2%), and 596 (68.3%) of the control group, respectively. Statistically, there were no significant differences in genotypes between the variant angina group and the control group. Next, males and females were analyzed separately. In males, there were no significant differences in homozygous mutations (1 out of 43 patients (2.3%) in the variant angina group vs. 11 out of 327 patients (3.4%) in the control group, P=1.00). However, in females, there was a significant difference in homozygous mutations (3 out of 19 (15.8%) in the variant angina group vs. 19 out of 545 (3.4%) in the control group, P=0.033). Conclusions These findings indicate that homozygotes of rs76863441, which has PAF-AH deficiency, may be associated with the pathogenesis of variant angina in Japanese women. Further functional analyses of this mutation are of great interest.Genotypes of rs76863441Gender disparities of rs76863441

Effect of Statin Treatment on Lipoprotein-Associated Phospholipase A2 Mass and Activity: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials.

The goal of this meta-analysis was to establish whether statin treatment reduces Lp-PLA2 mass concentration and/or activity. PubMed, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases were searched using MESH terms and keywords. Randomized controlled trials (RCT) with either parallel or cross-over design examining the effect of statins on Lp-PLA2 mass and/or activity were included in meta-analysis. Out of 256 articles, 10 RCT were selected for meta-analysis. Statin therapy significantly reduced both Lp-PLA2 mass (WMD -44.46 ng/mL; 95%CI -59.01, -29.90; p < 0.001; I2 = 93%) and activity (WMD -39.37 nmol/min/mL; 95%CI -69.99, -8.75; p = 0.01; I2 = 100%). The sensitivity analysis was robust for Lp-PLA2 mass and was also positive for two studies concerning Lp-PLA2 activity. Statin therapy significantly reduced both Lp-PLA2 mass and activity.

Comparative Metabolome and Transcriptome Analysis Reveals the Possible Roles of Rice Phospholipase A Genes in the Accumulation of Oil in Grains.

The phospholipase A (PLA) gene family plays a crucial role in the regulation of plant growth, development and stress response. Although PLA genes have been identified in various plant species, their specific functions and characteristics in oil quality formation of rice grains (Oryza sativa L.) have not been studied yet. Here, we identified and characterized 35 rice PLA genes, which were divided into three subgroups based on gene structures and phylogenetic relationships. These genes are distributed unevenly across 11 rice chromosomes. The promoter sequence of rice PLAs contain multiple plant hormones and stress-related elements. Gene expression analyses in various tissues and under stress conditions indicated that PLAs may be involved in rice growth, development and stress response. In addition, metabolomics, transcriptomics and qRT-PCR analyses between two rice varieties Guang8B (G8B, high oil content) and YueFengB (YFB, low oil content) revealed that the different expressional levels of rice PLA genes were closely related to the differences in the oil content between 'G8B' and 'YFB' grains. The findings of this study provide potential novel insights into the molecular information of the phospholipase A gene family in rice, and underscore the potential functions of PLA genes in rice oil content accumulation, providing valuable resources for future genetic improvement and breeding strategies.

RNA-seq and whole-genome re-sequencing reveal Micropterus salmoides growth-linked gene and selection signatures under carbohydrate-rich diet and varying temperature

This study was performed on Micropterus salmoides to determine growth-linked gene and single nucleotide polymorphism (SNP) markers under carbohydrate diet and varying temperature through RNA-seq and whole-genome re-sequencing. The results showed that growth-related genes were primarily enriched in the fat digestion and absorption signaling pathway, playing a role in lipid transport and metabolism. Fatty acid binding protein 6, bile salt-activated lipase-like, lysophosphatidylcholine acyltransferase 2, phospholipase A2, minor isoenzyme-like, and phospholipase A2, group IB (pancreas) were identified as the crucial genes. The differentially expressed genes between high and low temperatures were enriched in the pentose phosphate pathway, with carbohydrate transport and metabolism were most affected by temperature. Major facilitator superfamily domain containing 10, phosphogluconate dehydrogenase, fructose-1,6-bisphosphatase 1a, and spinster homolog 3 transcript variant X1(spns3) were the shared genes affected by temperature. From all the common genes, 10 growth-associated SNP markers were identified. The TT genotype at rs7781 was associated with lower body weight, while AA genotype at rs31434173 and CC genotype at rs31435313 showed positive correlation with body weight. Analogously, the GG genotype at rs31436887 and AA genotype at rs31438769 also found to characterize better growth performance. At low temperature, individuals with the AA genotype at rs11506587 and rs31435313 exhibited the slowest growth. For the genotypes labeled with rs11510589, the GG individual grew faster than the AA individual, whereas the opposite phenomenon occurred in these genotypes when labeled with rs11511314. The genotypes at rs32970704 and rs32967921 showed no growth correlation. The AA genotype at rs31435313 in spns3 had the slowest growth under a carbohydrate-rich diet regardless of the temperature. Our study presents candidate genes and SNP markers associated with growth influenced by carbohydrate and temperature, providing basis for the development of M. salmoides strain that better accepts carbohydrate diets at varying temperature.

3-O-Ethyl Ascorbic Acid and Cannabigerol in Modulating the Phospholipid Metabolism of Keratinocytes

Phospholipids and their metabolites play an important role in maintaining the membrane integrity and the metabolic functions of keratinocytes under physiological conditions and in the regeneration process after exposure to high-energy UVB radiation. Therefore, in the search for compounds with a protective and regenerative effect on keratinocyte phospholipids, the effectiveness of two antioxidant compounds has been tested: a stable derivative of ascorbic acid, 3-O-ethyl ascorbic acid (EAA) and cannabigerol (CBG), both of which are primarily located in the membrane structures of keratinocytes. In addition, this study has demonstrated that EAA and CBG, especially in a two-component combination, enhance the antioxidant properties of keratinocytes and reduce lipid peroxidation assessed at the level of MDA (malondialdehyde)/neuroprostanes. Moreover, by reducing the activity of enzymes that metabolise phospholipids, free PUFAs (polyunsaturated fatty acids) and endocannabinoids (PLA2; phospholipase A2, COX1/2; cyclooxygenases 1/2, LOX-5; lipoxygenase 5, FAAH; fatty acid amide hydrolase, MAGL; monoacylglycerol lipase), antioxidants have been found to regulate the levels of endocannabinoids (AEA; anandamide, 2-AG; 2-arachidonoylglycerol, PEA; palmitoylethanolamide) and eicosanoids (PGD2; prostaglandin D2, PGE2; prostaglandin E2, 15-d-PGJ2; 15-deoxy-Δ12,14-prostaglandin J2, 15-HETE; 15-hydroxyeicosatetraenoic acid), that are enhanced by UVB radiation. The metabolic effect of both groups of PUFA metabolites is mainly related to the activation of G protein-related receptors (CB1/2; cannabinoid receptor 1 and 2, PPARγ; peroxisome proliferator-activated receptor gamma, TRPV1; transient receptor potential cation channel subfamily V member 1), the expression of which is reduced under the influence of EAA, CBG, and especially the two-component combination. It promotes the regeneration of keratinocyte metabolism disrupted by UVB, particularly in relation to redox balance and inflammation.