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Open Veterinary Journal May 2024The intracytoplasmic sperm injection (ICSI) technique has low efficiency in cattle. This has mainly been attributed to the oocyte activation failure due to oocyte and/or...
BACKGROUND
The intracytoplasmic sperm injection (ICSI) technique has low efficiency in cattle. This has mainly been attributed to the oocyte activation failure due to oocyte and/or sperm factors.
AIM
Our aim was to evaluate the effect of conventional ICSI and Piezo-ICSI with bull or human sperm on bovine oocyte activation and embryo development and to assess its relationship with the phospholipase C zeta (PLCɀ) activity of both species.
METHODS
matured bovine oocytes were randomly divided into five groups and were fertilized as follows: conventional ICSI using bovine sperm with chemical activation (control), conventional ICSI using bovine sperm, Piezo-ICSI using bovine sperm, conventional ICSI using human sperm, and Piezo-ICSI using human sperm. PLCɀ activity was determined in bull and human sperm samples.
RESULTS
Within the groups using bull sperm, the oocytes fertilized by conventional ICSI had the lowest values of 2 pronuclei (PN) formation and cleavage, Piezo-ICSI increased both percentages and ICSI + chemical activation presented the highest 2 PN, cleavage, and blastocyst rates ( < 0.05). Within the groups using human sperm, the oocytes fertilized by Piezo-ICSI presented higher 2 PN and cleavage rates than those activated by conventional ICSI ( < 0.05). Piezo-ICSI with human sperm increased bovine oocyte activation as much as conventional ICSI + chemical activation with bovine sperm ( < 0.05). Higher values of PLCɀ activity were found in human sperm compared with bovine sperm ( < 0.05).
CONCLUSION
Our results suggest that the higher stability of the bovine sperm in combination with its relatively low content of PLCɀ impairs bovine oocyte activation after ICSI.
Topics: Cattle; Sperm Injections, Intracytoplasmic; Male; Animals; Humans; Oocytes; Spermatozoa; Female; Phosphoinositide Phospholipase C
PubMed: 38938440
DOI: 10.5455/OVJ.2024.v14.i5.14 -
BMC Nephrology Jun 2024Sarcoidosis is a multisystemic inflammatory disease, characterized by the presence of non-caseating, epithelioid granulomas. Glomerular disease in patients with...
BACKGROUND
Sarcoidosis is a multisystemic inflammatory disease, characterized by the presence of non-caseating, epithelioid granulomas. Glomerular disease in patients with sarcoidosis is rare and membranous nephropathy (MN) is cited as the most common. The association between the two diseases remained unclear. This article reported a case of co-occurrence of sarcoidosis and anti-PLA2R-associated MN, to provide a possible relationship between these two entities.
CASE PRESENTATION
A 61-year-old Chinese Han woman with a history of sarcoidosis was admitted to our hospital for nephrotic syndrome. Her sarcoidosis was diagnosed according to the adenopathy observed on the computed tomography scan and the biopsy of lymph nodes. The MN presented with nephrotic syndrome with a PLA2R antibody titer of 357RU/ml, and the final diagnosis was based on a renal biopsy. The patient's sarcoidosis was remitted after treatment with prednisone. One year later MN was diagnosed, and she was treated with prednisone combined with calcineurin inhibitors, based on a full dose of renin-angiotensin system (RAS) inhibitor. The patient's sarcoidosis had been in remission while the MN was recurrent, and her renal function deteriorated to end-stage renal disease 6 years later due to discontinuation of immunosuppression. A genetic test led to the identification of the HLA-DRB1*0301 and HLA-DRB1*150 genes associated with both sarcoidosis and MN, which provides a new possible explanation of the co-occurrence of these two diseases.
CONCLUSION
This case suggested for the first time a potential genetic connection between idiopathic MN and sarcoidosis which needs further studies in the future.
Topics: Humans; Glomerulonephritis, Membranous; Female; Middle Aged; Receptors, Phospholipase A2; Sarcoidosis; Genetic Predisposition to Disease; Autoantibodies
PubMed: 38937663
DOI: 10.1186/s12882-024-03649-0 -
Neuropeptides Jun 2024Central nervous system (CNS) disorders are one of the leading health problems today, accounting for a large proportion of global morbidity and mortality. Most these... (Review)
Review
Central nervous system (CNS) disorders are one of the leading health problems today, accounting for a large proportion of global morbidity and mortality. Most these disorders are characterized by high levels of oxidative stress and intense inflammatory responses in degenerated neuronal tissues. While extensive research has been conducted on CNS diseases, but few breakthroughs have been made in treatment methods. To date, there are no disease-modifying drugs available for CNS treatment, underscoring the urgent need for finding effective medications. Bee venom (BV), which is produced by honeybee workers' stingers, has been a subject of interest and study across various cultures. Over the past few decades, extensive research has focused on BV and its therapeutic potentials. BV consists a variety of substances, mainly proteins and peptides like melittin and phospholipase A2 (PLA2). Research has proven that BV is effective in various medical conditions, including pain, arthritis and inflammation and CNS disorders such as Multiple sclerosis, Alzheimer's disease and Parkinson's disease. This review provides a comprehensive overview of the existing knowledge concerning the therapeutic effects of BV and its primary compounds on various CNS diseases. Additionally, we aim to shed light on the potential cellular and molecular mechanisms underlying these effects.
PubMed: 38936137
DOI: 10.1016/j.npep.2024.102451 -
International Immunopharmacology Jun 2024With the increasing frequency of global heatwaves, the incidence of heatstroke (HS) is significantly rising. The liver plays a crucial role in metabolism and is an organ...
With the increasing frequency of global heatwaves, the incidence of heatstroke (HS) is significantly rising. The liver plays a crucial role in metabolism and is an organ highly sensitive to temperature. Acute liver injury (ALI) frequently occurs in patients with HS, yet the exact mechanisms driving ALI in HS are still unknown. In this basic study, we investigated the specific molecular mechanisms by which cytosolic phospholipase A2 (cPLA2) mediates ferroptosis, contributing to the development of ALI following HS. We utilized a mouse model of HS and divided the mice into healthy control and HS groups for a series of experiments. Firstly, we assessed oxidative damage markers in tissues and cells, as well as ferroptosis biomarkers. Additionally, we conducted a non-targeted metabolomics analysis to validate the role of key enzymes in metabolism and the ferroptosis pathway. Our results indicated that ferroptosis contributed to the progression of ALI after HS. Administering the ferroptosis inhibitor liproxstatin-1 (10 mg/kg) post-HS onset significantly inhibits HS-induced ALI progression. Mechanistically, heatstroke triggered cPLA2 activation and increased the levels of its metabolic product, arachidonic acid, thereby further promoted the occurrence of ferroptosis. Furthermore, heatstroke mediated cPLA2 activation might involve enhancing transient receptor potential vanilloid subtype 1 (TRPV1) receptor function. Overall, these results highlighted the critical role that cPLA2-mediated ferroptosis plays in the development of ALI following HS, indicating that inhibiting cPLA2 may present a novel therapeutic approach to prevent ALI after HS by limiting liver cell death.
PubMed: 38936054
DOI: 10.1016/j.intimp.2024.112539 -
Allergy Jun 2024Hereditary angioedema (HAE) is a rare genetic disorder characterized by local, self-limiting edema due to temporary increase in vascular permeability. HAE with normal C1...
BACKGROUND
Hereditary angioedema (HAE) is a rare genetic disorder characterized by local, self-limiting edema due to temporary increase in vascular permeability. HAE with normal C1 esterase inhibitor (C1INH) activity includes the form with mutations in the F12 gene encoding for coagulation factor XII (FXII-HAE) causing an overproduction of bradykinin (BK) leading to angioedema attack. BK binding to B2 receptors (BK2R) leads to an activation of phospholipase C (PLC) and subsequent generation of second messengers: diacylglycerols (DAGs) and possibly the endocannabinoids (eCBs), 2-arachidonoylglycerol (2-AG) and anandamide (AEA), and eCB-related N-acylethanolamines [palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)]. To date, there are no data on the role of these lipid mediators in FXII-HAE.
METHODS
Here, we analyzed plasma levels of PLC, DAGs, and eCBs in 40 patients with FXII-HAE and 40 sex- and age-matched healthy individuals.
RESULTS
Plasma PLC activity was increased in FXII-HAE patients compared to controls. Concentrations of DAG 18:1-20:4, a lipid second messenger produced by PLC, were higher in FXII-HAE compared to controls, and positively correlated with PLC activity and cleaved high molecular kininogen (cHK). Also the concentrations of the DAG metabolite, 2-AG were altered in FXII-HAE. AEA and OEA were decreased in FXII-HAE patients compared to controls; by contrast, PEA, was increased. The levels of all tested mediators did not differ between symptomatic and asymptomatic patients. Moreover, C1INH-HAE patients had elevated plasma levels of PLC, which correlated with cHK, but the levels of DAGs and eCBs were the same as controls.
CONCLUSIONS
BK overproduction and BKR2 activation are linked to alteration of PLCs and their metabolites in patients with FXII-HAE. Our results may pave way to investigations on the functions of these mediators in the pathophysiology of FXII-HAE, and provide new potential biomarkers and therapeutic targets.
PubMed: 38935036
DOI: 10.1111/all.16197 -
Journal of Clinical Apheresis Jun 2024Membranous nephropathy is the most common cause of nephrotic syndrome (NS) in non-diabetic adults; in 80% of patients it is idiopathic (PMN). PMN has an autoimmune...
Membranous nephropathy is the most common cause of nephrotic syndrome (NS) in non-diabetic adults; in 80% of patients it is idiopathic (PMN). PMN has an autoimmune pathogenesis, 70%-85% of patients have increased titer of antibodies to the podocyte membrane antigen PLA2R. The etiological, prognostic and predictive role of the Ab anti-PLA2R is demonstrated. Standard therapy consists in anti-CD20 monoclonal antibody rituximab (RTX) combined with steroids or immunosuppressants according to the risk of progressive loss of kidney function. The immunosuppressive therapies are potentially associated to severe adverse events that lead to protocol suspension. Given their pivotal pathogenetic role, serum clearance of anti-PLA2R with plasmapheresis could have a beneficial impact on NS, particularly in patients not requiring or tolerating standard therapies. In this series, we present three cases of PMN anti-PLA2R related treated with a RTX plus plasmapheresis approach and demonstrate its overall effective role on anti-PLA2R titer and clinical outcomes.
Topics: Humans; Plasmapheresis; Glomerulonephritis, Membranous; Receptors, Phospholipase A2; Rituximab; Male; Middle Aged; Female; Adult; Autoantibodies; Immunosuppressive Agents
PubMed: 38934513
DOI: 10.1002/jca.22134 -
Neural Regeneration Research Jun 2024Diabetic retinopathy is a prominent cause of blindness in adults, with early retinal ganglion cell (RGC) loss contributing to visual dysfunction or blindness. In the...
Diabetic retinopathy is a prominent cause of blindness in adults, with early retinal ganglion cell (RGC) loss contributing to visual dysfunction or blindness. In the brain, defects in y-aminobutyric acid (GABA) synaptic transmission are associated with pathophysiological and neurodegenerative disorders, whereas glucagon-like peptide-1 (GLP-1) has demonstrated neuroprotective effects. However, it is not yet clear whether diabetes causes alterations in inhibitory input to RGCs and whether and how GLP-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to RGCs. In the present study, we used the patch-clamp technique to record GABA subtype A receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) in RGCs from streptozotocin-induced diabetes model rats. We found that early diabetes (4 weeks of hyperglycemia) decreased the frequency of GABAergic mIPSCs in RGCs without altering their amplitude, suggesting a reduction in the spontaneous release of GABA to RGCs. Topical administration of GLP-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency, subsequently enhancing the survival of RGCs. Concurrently, the protective effects of GLP-1 on RGCs in diabetic rats were eliminated by topical administration of exendin-9-39, a specific GLP-1 receptor antagonist, or SR95531, a specific antagonist of the GABA subtype A receptor. Furthermore, extracellular perfusion of GLP-1 was found to elevate the frequencies of GABAergic mIPSCs in both ON- and OFF-type RGCs. This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of GLP-1 receptor activation. Moreover, multielectrode array recordings revealed that GLP-1 functionally augmented the photoresponses of ON-type RGCs. Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of GLP-1. These results suggest that GLP-1 facilitates the release of GABA onto RGCs through the activation of GLP-1 receptor, leading to the de-excitation of RGC circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy. Collectively, our findings indicate that the GABA system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy. Furthermore, the topical administration of GLP-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.
PubMed: 38934389
DOI: 10.4103/NRR.NRR-D-24-00001 -
Nutrients Jun 2024Atherosclerosis is one of the most important causes of cardiovascular diseases. A disintegrin and metalloprotease (ADAM)10 and ADAM17 have been identified as important...
Atherosclerosis is one of the most important causes of cardiovascular diseases. A disintegrin and metalloprotease (ADAM)10 and ADAM17 have been identified as important regulators of inflammation in recent years. Our study investigated the effect of inhibiting these enzymes with selective inhibitor and propolis on atherosclerosis. In our study, C57BL/6J mice ( = 16) were used in the control and sham groups. In contrast, ApoE mice ( = 48) were used in the case, water extract of propolis (WEP), ethanolic extract of propolis (EEP), GW280264X (GW-synthetic inhibitor), and solvent (DMSO and ethanol) groups. The control group was fed a control diet, and all other groups were fed a high-cholesterol diet for 16 weeks. WEP (400 mg/kg/day), EEP (200 mg/kg/day), and GW (100 µg/kg/day) were administered intraperitoneally for the last four weeks. Animals were sacrificed, and blood, liver, aortic arch, and aortic root tissues were collected. In serum, total cholesterol (TC), triglycerides (TGs), and glucose (Glu) were measured by enzymatic colorimetric method, while interleukin-1β (IL-1β), paraoxonase-1 (PON-1), and lipoprotein-associated phospholipase-A2 (Lp-PLA2) were measured by ELISA. Tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), myeloperoxidase (MPO), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-12 (IL-12) levels were measured in aortic arch by ELISA and ADAM10/17 activities were measured fluorometrically. In addition, aortic root and liver tissues were examined histopathologically and immunohistochemically (ADAM10 and sortilin primary antibody). In the WEP, EEP, and GW groups compared to the case group, TC, TG, TNF-α, IL-1β, IL-6, IL-12, PLA2, MPO, ADAM10/17 activities, plaque burden, lipid accumulation, ADAM10, and sortilin levels decreased, while IL-10 and PON-1 levels increased ( < 0.003). Our study results show that propolis can effectively reduce atherosclerosis-related inflammation and dyslipidemia through ADAM10/17 inhibition.
Topics: Animals; ADAM10 Protein; Mice, Inbred C57BL; Propolis; Inflammation; Dyslipidemias; Mice; Male; Amyloid Precursor Protein Secretases; Atherosclerosis; Cholesterol, Dietary; Diet, High-Fat; Membrane Proteins; Disease Models, Animal
PubMed: 38931216
DOI: 10.3390/nu16121861 -
Nutrients Jun 2024Gut microbiota might affect the severity and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to characterize gut dysbiosis and...
Gut microbiota might affect the severity and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to characterize gut dysbiosis and clinical parameters regarding fibrosis stages assessed by magnetic resonance elastography. This study included 156 patients with MASLD, stratified into no/mild fibrosis (F0-F1) and moderate/severe fibrosis (F2-F4). Fecal specimens were sequenced targeting the V4 region of the 16S rRNA gene and analyzed using bioinformatics. The genotyping of , , and was assessed by allelic discrimination assays. Our data showed that gut microbial profiles between groups significantly differed in beta-diversity but not in alpha-diversity indices. Enriched and , and depleted were found in the F2-F4 group versus the F0-F1 group. Compared to F0-F1, the F2-F4 group had elevated plasma surrogate markers of gut epithelial permeability and bacterial translocation. The bacterial genera, polymorphisms, old age, and diabetes were independently associated with advanced fibrosis in multivariable analyses. Using the Random Forest classifier, the gut microbial signature of three genera could differentiate the groups with high diagnostic accuracy (AUC of 0.93). These results indicated that the imbalance of enriched pathogenic genera and decreased beneficial bacteria, in association with several clinical and genetic factors, were potential contributors to the pathogenesis and progression of MASLD.
Topics: Humans; Gastrointestinal Microbiome; Liver Cirrhosis; Female; Male; Middle Aged; Severity of Illness Index; Membrane Proteins; Lipase; Aged; RNA, Ribosomal, 16S; Dysbiosis; Fatty Liver; Feces; Adult; Genetic Variation; Elasticity Imaging Techniques; Bacteria; Acyltransferases; 17-Hydroxysteroid Dehydrogenases; Phospholipases A2, Calcium-Independent
PubMed: 38931155
DOI: 10.3390/nu16121800 -
Microorganisms May 2024() is an anaerobic, spore-forming Gram-positive rod responsible for necrotizing gangrene, bacteremia in patients with cancer or gastrointestinal tract infection....
() is an anaerobic, spore-forming Gram-positive rod responsible for necrotizing gangrene, bacteremia in patients with cancer or gastrointestinal tract infection. virulence is due in large part to toxin production. In 2014, a new enterotoxin, BEC (binary enterotoxin of ) encoded by and genes, distinct from enterotoxin (CPE) encoded by the gene, has been described. BEC-producing strains can be causative agents of acute gastroenteritis in humans. We present herein the case of a 64-year-old man who presented to the emergency department of Toulouse University Hospital with pneumonia and septic shock, without digestive symptoms. Blood cultures showed bacteremia and despite appropriate antibiotic treatment the patient passed away 7 h after admission. The characterization of the strain by whole genome sequencing revealed the presence of typical genes of : gene (alpha-toxin, phospholipase C) and (theta-toxin, perfringolysine). Surprisingly, this strain also harbored and genes encoding the recently described BEC toxin. Interestingly, alpha-toxin typing of our isolate and other published BEC isolates showed that they belonged to different PLC subtypes, confirming the high genetic diversity of these strains. To our knowledge, it is the first clinical case reporting bacteremia due to a BEC-producing isolate.
PubMed: 38930477
DOI: 10.3390/microorganisms12061095