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Frontiers in Pharmacology 2024Treatment of glomerulonephritis presents several challenges, including limited therapeutic options, high costs, and potential adverse reactions. As a recognized Chinese... (Review)
Review
Treatment of glomerulonephritis presents several challenges, including limited therapeutic options, high costs, and potential adverse reactions. As a recognized Chinese patent medicine, poly-glycosides (TWP) have shown promising benefits in managing autoimmune diseases. To evaluate clinical effectiveness and safety of TWP in treating glomerulonephritis, we systematically searched PubMed, Cochrane Library, Web of Science, and Embase databases for controlled studies published up to 12 July 2023. We employed weighted mean difference and relative risk to analyze continuous and dichotomous outcomes. This meta-analysis included 16 studies that included primary membranous nephropathy (PMN), type 2 diabetic kidney disease (DKD), and Henoch-Schönlein purpura nephritis (HSPN). Analysis revealed that additional TWP administration improved patients' outcomes and total remission rates, reduced 24-h urine protein (24hUP) and decreased relapse events. The pooled results demonstrated the non-inferiority of TWP to glucocorticoids in achieving total remission, reducing 24hUP, and converting the phospholipase A2 receptor (PLA2R) status to negative. For DKD patients, TWP effectively reduced 24hUP levels, although it did not significantly improve the estimated glomerular filtration rate (eGFR). Compared to valsartan, TWP showed comparable improvements in 24hUP and eGFR levels. In severe cases of HSPN in children, significant clinical remission and a reduction in 24hUP levels were observed with the addition of TWP treatment. TWP did not significantly increase the incidence of adverse reactions. Therefore, TWP could offer therapeutic benefits to patients with PMN, DKD, and severe HSPN, with a minimal increase in the risk of side effects.
PubMed: 38841368
DOI: 10.3389/fphar.2024.1339153 -
Journal of Clinical and Experimental... 2022Non-alcoholic fatty liver disease (NAFLD) presents with the accumulation of excessive intra-hepatic fat without significant alcohol intake. Multifactorial pathogenesis... (Review)
Review
Lysosomal Acid Lipase Activity in Non-alcoholic Fatty Liver Disease as a Novel Diagnostic and Therapeutic Target: A Systematic Literature Review of Current Evidence and Future Directions.
BACKGROUND AND AIM
Non-alcoholic fatty liver disease (NAFLD) presents with the accumulation of excessive intra-hepatic fat without significant alcohol intake. Multifactorial pathogenesis is reported to be involved. Reduced lysosomal acid lipase (LAL) activity is suggested as one of the novel-involved pathogenic mechanisms. This review summarizes the available evidence on the role of LAL activity in NAFLD pathogenesis.
METHODS
Four databases namely, PubMed/Medline, Science direct, Cochrane Library, and Google scholar were searched to identify relevant observational records evaluating the role of LAL activity in the pathogenesis of NAFLD. All studies were assessed for their quality by using Newcastle-Ottawa Scale or The Joanna Briggs Institute Critical Appraisal tools for cohort and cross-sectional studies, respectively. The estimates of LAL activity and other clinical outcomes were expressed as mean (SD) and number (%) as presented in the primary studies.
RESULTS
A total of nine good quality studies with 1711 patients with NAFLD and 877 controls from different groups (healthy volunteers, alcoholics, cryptogenic cirrhosis, and HCV-positive) were included. From the NAFLD group, 59.55% were males and the overall mean age ranged between the studies from 12.6 ± 8.5 months in pediatrics to 58.90 ± 13.82 years in adults. In the NAFLD group, the LAL activity varied from 0.53 ± 0.08 to 1.3 ± 0.70 (nmol/spot/hr) between the studies which was less than all control groups except cryptogenic cirrhosis patients (0.5 ± 0.15 nmol/spot/hr). Of the other outcomes of interest, ALT, AST, total cholesterol, triglyceride, and LDL cholesterol were found elevated in NAFLD patients than in controls.
CONCLUSION
The current evidence suggests a potential correlation of reduced LAL activity with NAFLD pathogenesis according to its severity. Large-scale studies are recommended, more importantly in patients with NAFLD having no metabolic or genetic involvement. Further LAL can act as a new non-invasive diagnostic biomarker to identify that specific NAFLD subgroup.
PubMed: 36340307
DOI: 10.1016/j.jceh.2022.04.011 -
Mayo Clinic Proceedings Feb 2007To estimate the association between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and cardiovascular disease (CVD). (Review)
Review
OBJECTIVE
To estimate the association between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and cardiovascular disease (CVD).
METHODS
We searched MEDLINE (January 1, 1985, through September 30, 2006), the Cochrane library (from inception through 2006), conference proceedings, and reference sections of obtained articles and contacted experts for unpublished studies. Eligible studies were cohorts with 1 year or more of follow-up or case-control designs that provided risk estimates for CVD according to blood levels of Lp-PLA2 that were unadjusted or adjusted for conventional CVD risk factors. We used random-effects meta-analysis to estimate the association between Lp-PLA2 and CVD risk and conducted preplanned subgroup analyses to identify risk-subgroup interactions that could explain between-study differences.
RESULTS
We found 14 eligible studies (N = 20,549 patients) that reported either Lp-PLA2 plasma activity (n = 5) or an immunoassay that measured the plasma concentration (n = 9). The meta-analytic estimate from the unadjusted odds ratio for the association between elevated Lp-PLA2 levels and CVD risk was 1.51 (95% confidence interval, 1.30-1.75) and from the odds ratio adjusted for conventional CVD risk factors was 1.60 (95% confidence interval, 1.36-1.89). Differences in study methods explained differences in results across studies.
CONCLUSIONS
Lipoprotein-associated phospholipase A2 is significantly associated with CVD. The risk estimate appears to be relatively unaffected by adjustment for conventional CVD risk factors. Measurement of Lp-PLA2 may be useful in CVD risk stratification. In addition, Lp-PLA2 may represent a potential therapeutic target for CVD risk reduction.
Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Adult; Aged; Biomarkers; Cardiovascular Diseases; Humans; Middle Aged; Phospholipases A2; Risk Assessment
PubMed: 17290721
DOI: 10.4065/82.2.159 -
Atherosclerosis Nov 2008The goal of this systematic review is to assess the cross-sectional relationship of inflammatory markers with the presence and extent of coronary artery calcium (CAC) to... (Review)
Review
OBJECTIVES
The goal of this systematic review is to assess the cross-sectional relationship of inflammatory markers with the presence and extent of coronary artery calcium (CAC) to identify asymptomatic individuals with a higher risk of coronary heart disease (CHD).
BACKGROUND
Markers of subclinical inflammation and subclinical atherosclerosis have both been used to improve detection of individuals at high risk of developing cardiovascular disease. CAC has emerged as a surrogate maker for underlying coronary atherosclerosis, and has been shown to predict future CHD events. Although inflammation is intimately associated with atherosclerosis, and levels of inflammatory markers predict cardiovascular risk, the relationship of subclinical inflammatory markers with the burden of coronary atherosclerosis is not clear.
METHODS
Medline and Pub Med databases were searched for all studies assessing the relationship of inflammatory markers with CAC published till July 2007.
RESULTS
We found 12 studies that met our criteria. CRP, fibrinogen, metallic metalloproteinase-9 (MMP-9), monocyte chemotactic protein 1 (MCP-1), resistin, lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), IL-6, tumor necrosis factor alpha (TNF-alpha) and beta-fibroblast growth factor (bFGF) were used as inflammatory markers. There was a wide variation among studies with regards to population size, inclusion criterias, age range and techniques. It was observed that in almost all studies the relationship between inflammatory markers and CAC was weak, and was mostly found upon univariate analysis in women. However, this association was lost after correction for obesity and BMI. The data on the relationship of inflammation and CAC with progression of atherosclerosis is scarce and did not show any predictive benefits for future CHD.
CONCLUSION
Variable associations between CAC and inflammatory markers were identified. In most studies where a positive relationship was found, this relationship disappeared after appropriate correction for the presence of traditional risk factors. Our data suggests that an approach in which inflammatory markers are used to further characterize risk in individuals with an established coronary artery disease burden is more warranted than using biomarkers as sole risk predictors of future CHD events. Large, well-planned comprehensive studies are required to identify the combined role of measuring inflammatory markers in assessment of atherosclerotic disease.
Topics: Acute-Phase Proteins; Biomarkers; Calcinosis; Coronary Artery Disease; Female; Humans; Inflammation Mediators; Male; Risk Factors
PubMed: 18561934
DOI: 10.1016/j.atherosclerosis.2008.04.045 -
Reproduction in Domestic Animals =... Jun 2011The overall objective of one of the major research programs in the Co-operative Research Centre (CRC) for Beef Genetic Technologies is to 'Improve female reproductive... (Review)
Review
The overall objective of one of the major research programs in the Co-operative Research Centre (CRC) for Beef Genetic Technologies is to 'Improve female reproductive performance' in tropical, northern Australian beef cattle herds. To address this overall objective, a quantitative genetics project focused on investigation of male reproductive traits was designed and linked to three female reproduction-focussed projects, (i) discovery of genes associated with post-partum re-conception and age at puberty; (ii) expression of genes associated with post-partum re-conception; and (iii) early predictors of lifetime female reproductive performance. During the initial planning of this male reproductive traits project, the CRC Scientific Review Committee recommended that the research team investigate and evaluate potentially new, early-life (i.e able to be measured before 2 years of age) predictors of both male and female reproductive performance. To address this recommendation, the following was carried out: (i) criteria for selection of traditional and candidate traits were established; (ii) methodology for tabulation of potential traits/phenotypes that define male and female reproductive function was developed; and (iii) a systematic scientific review of early-life predictors of male and female fertility was prepared. This review concluded that although factors that might be useful in predicting male reproductive performance have been studied for many years, there was relatively little useful information available to meet the objectives of this review. It was also concluded that the direction of future research should be guided not only by previous research which was scarce, but also by speculative hypotheses arising from an understanding of the physiological, endocrinological and genetic processes active in reproduction. A small number of new traits were recommended in addition to traditional sperm morphology, sexual behaviour, anatomical structure and growth traits. Potential additional traits include measurement of gonadotrophin-releasing hormone-stimulated luteinizing hormone (GnRH-stimulated LH); inhibin; several seminal plasma proteins (osteopontin, spermadhesin and seminal plasma proteins BSP30 and phospholipase A(2) could be used in an index); 11β-hydroxysteriod dehydrogenase; and leptin. In addition, the potential also exists to screen animals for a number of genetic markers associated with age of puberty, follicular recruitment and ovulation rate and genes associated with bovine seminal plasma protein and testosterone production. Insulin-like growth factor-1 (IGF-1) measurements are included because of their association with growth parameters, and an additional analysis demonstrated associations with male and female reproductive traits. Some of these factors have been previously evaluated in small numbers of animals of various species under intensive management conditions. Therefore, there is a need to evaluate these factors in much larger numbers of beef cattle grazing semi-extensive tropical production systems in northern Australia to determine their value in improving beef cattle enterprise profitability through improved herd fertility.
Topics: Animals; Australia; Breeding; Cattle; Female; Fertility; Male; Quantitative Trait, Heritable; Reproduction
PubMed: 21332828
DOI: 10.1111/j.1439-0531.2011.01748.x -
International Journal of Molecular... Apr 2016Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of disease ranging from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) and fibrosis.... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of disease ranging from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) and fibrosis. "Obese/Metabolic NAFLD" is closely associated with obesity and insulin resistance and therefore predisposes to type 2 diabetes and cardiovascular disease. NAFLD can also be caused by common genetic variants, the patatin-like phospholipase domain-containing 3 (PNPLA3) or the transmembrane 6 superfamily member 2 (TM6SF2). Since NAFL, irrespective of its cause, can progress to NASH and liver fibrosis, its definition is of interest. We reviewed the literature to identify data on definition of normal liver fat using liver histology and different imaging tools, and analyzed whether NAFLD caused by the gene variants is associated with insulin resistance. Histologically, normal liver fat content in liver biopsies is most commonly defined as macroscopic steatosis in less than 5% of hepatocytes. In the population-based Dallas Heart Study, the upper 95th percentile of liver fat measured by proton magnetic spectroscopy (¹H-MRS) in healthy subjects was 5.6%, which corresponds to approximately 15% histological liver fat. When measured by magnetic resonance imaging (MRI)-based techniques such as the proton density fat fraction (PDFF), 5% macroscopic steatosis corresponds to a PDFF of 6% to 6.4%. In contrast to "Obese/metabolic NAFLD", NAFLD caused by genetic variants is not associated with insulin resistance. This implies that NAFLD is heterogeneous and that "Obese/Metabolic NAFLD" but not NAFLD due to the PNPLA3 or TM6SF2 genetic variants predisposes to type 2 diabetes and cardiovascular disease.
Topics: Humans; Insulin; Insulin Resistance; Lipase; Liver; Magnetic Resonance Imaging; Membrane Proteins; Non-alcoholic Fatty Liver Disease; Obesity; Proton Magnetic Resonance Spectroscopy
PubMed: 27128911
DOI: 10.3390/ijms17050633 -
Microbial Pathogenesis Dec 2020Candida albicans is the main causative agent of oral lesions in HIV-infected patients and its oral colonization is a potential source of systemic dissemination. Although... (Meta-Analysis)
Meta-Analysis Review
Candida albicans is the main causative agent of oral lesions in HIV-infected patients and its oral colonization is a potential source of systemic dissemination. Although the high prevalence of lesions in HIV patients can be explained by the immunosuppressive condition, several studies have reported that natural selection can make C. albicans more virulent in this group of patients. Comparisons of the activity of exoenzymes (phospholipase, proteinase and hemolysin) in C. albicans isolated from HIV-infected and uninfected patients have yielded conflicting results. This study aimed, through a systematic review and meta-analysis, to answer the question: "Is the hydrolytic enzymatic activity of C. albicans, isolated from the oral cavity, different in individuals infected and not infected with HIV?" The question was addressed using the PECO framework: P (Population): children and adults, E (Exposure): HIV infection, C (Comparator): non-HIV-infected patients; O (Outcomes): exoenzymes activity i.e. phospholipase, proteinase and hemolysin. We conducted a systematic search on Pubmed, Embase, Scopus, Livivo, Lilacs, Web of Science, and Science Direct databases, and Google Scholar. The MAStARI tool was used to evaluate the risk of bias in the selected studies. From 2259 studies, 19 were included in this review and 11 comprised the meta-analysis. The activity of phospholipase (M-H = 0.15; Z = 2,76; p = 0.0006) and hemolysin exoenzymes (M-H = 0.07; z = 1,94; p = 0.05) was higher in C. albicans isolated from the oral cavity of HIV-infected patients, whereas the levels of protease activity were not different compared with non-HIV-infected individuals. This study showed a higher phospholipase and hemolysin activity in C. albicans isolates from the oral cavity of HIV-infected patients.
Topics: Adult; Candida albicans; Candidiasis, Oral; Child; HIV Infections; Humans; Phospholipases
PubMed: 32920148
DOI: 10.1016/j.micpath.2020.104477 -
International Urology and Nephrology Sep 2019We aimed to evaluate the prognostic value of serum anti-PLA2R and glomerular PLA2R deposit (gPLA2R) in predicting remission of proteinuria in Primary Membranous... (Meta-Analysis)
Meta-Analysis
PURPOSE
We aimed to evaluate the prognostic value of serum anti-PLA2R and glomerular PLA2R deposit (gPLA2R) in predicting remission of proteinuria in Primary Membranous Nephropathy (PMN) patients.
METHODS
PUBMED, EMBASE, WEB OF SCIENCE, COCHRANE LIBRARY and CNKI were searched from 2008 January to December 2018. Heterogeneity was assessed by Cochran Q test and I. Source of heterogeneity was explored by subgroup analysis and sensitivity analysis.
RESULTS
Totally 2345 patients from 29 cohort studies were eligible for inclusion. The results suggested that PMN patients with negative anti-PLA2R at the time of biopsy had a 1.31 times (95% CI 1.12-1.46, p < 0.05) higher possibility in achieving remission than those with positive anti-PLA2R. The clearance of anti-PLA2R at the end of immunosuppressive therapy showed an even greater chance of achieving remission (RR = 2.86, 95% CI 1.75-4.69, p < 0.05). The relative ratios for complete remission and spontaneous remission with negative anti-PLA2R were 1.65 (95% CI 1.46-1.87, p < 0.05) and 1.93, respectively (95% CI 1.53-2.45, p < 0.05), and heterogeneity percentages were I = 18% and 46%, respectively. The possibility for remission was significantly greater among PMN patients with negative gPLA2R (RR = 1.30, 95% CI 1.13-1.50, p < 0.05). Subgroup analyses revealed that retrospective design of study might be the potential source of heterogeneity.
CONCLUSIONS
Negative anti-PLA2R or gPLA2R might predict higher possibility of remission, and the presence of anti-PLA2R or gPLA2R might serve as a useful biomarker for clinical outcome and predicting response to immunosuppressive therapy in PMN.
Topics: Autoantibodies; Glomerulonephritis, Membranous; Humans; Prognosis; Proteinuria; Receptors, Phospholipase A2
PubMed: 31140029
DOI: 10.1007/s11255-019-02147-9 -
Journal of Clinical Medicine Dec 2021High-density lipoprotein (HDL) functional traits have emerged as relevant elements that may explain HDL antiatherogenic capacity better than HDL cholesterol levels.... (Review)
Review
High-density lipoprotein (HDL) functional traits have emerged as relevant elements that may explain HDL antiatherogenic capacity better than HDL cholesterol levels. These properties have been improved in several lifestyle intervention trials. The aim of this systematic review is to summarize the results of such trials of the most commonly used dietary modifications (fatty acids, cholesterol, antioxidants, alcohol, and calorie restriction) and physical activity. Articles were screened from the Medline database until March 2021, and 118 randomized controlled trials were selected. Results from HDL functions and associated functional components were extracted, including cholesterol efflux capacity, cholesteryl ester transfer protein, lecithin-cholesterol acyltransferase, HDL antioxidant capacity, HDL oxidation status, paraoxonase-1 activity, HDL anti-inflammatory and endothelial protection capacity, HDL-associated phospholipase A2, HDL-associated serum amyloid A, and HDL-alpha-1-antitrypsin. In mainly short-term clinical trials, the consumption of monounsaturated and polyunsaturated fatty acids (particularly omega-3 in fish), and dietary antioxidants showed benefits to HDL functionality, especially in subjects with cardiovascular risk factors. In this regard, antioxidant-rich dietary patterns were able to improve HDL function in both healthy individuals and subjects at high cardiovascular risk. In addition, in randomized trial assays performed mainly in healthy individuals, reverse cholesterol transport with ethanol in moderate quantities enhanced HDL function. Nevertheless, the evidence summarized was of unclear quality and short-term nature and presented heterogeneity in lifestyle modifications, trial designs, and biochemical techniques for the assessment of HDL functions. Such findings should therefore be interpreted with caution. Large-scale, long-term, randomized, controlled trials in different populations and individuals with diverse pathologies are warranted.
PubMed: 34945193
DOI: 10.3390/jcm10245897 -
Nephrologie & Therapeutique Apr 2022The use of traditional immunosuppressive medicines for the treatment of membranous nephropathy is being challenged, owing to its limited efficacy and tolerability.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The use of traditional immunosuppressive medicines for the treatment of membranous nephropathy is being challenged, owing to its limited efficacy and tolerability. Research on M-type phospholipase A2 receptor antibodies has provided a new way for evaluating the efficiency and prognosis of treatment of membranous nephropathy. However, the relationship between rituximab, a monoclonal antibody against CD20, and antiphospholipase A2 receptor antibodies and the drug regimen of rituximab for membranous nephropathy is uncertain. We conducted a meta-analysis to evaluate the efficacy of rituximab treatments in membranous nephropathy and compared the clinical effects of first-line and second-line rituximab therapies.
METHODS
PubMed, Embase, Web of Science, Scopus, the Cochrane Central Register ofControlled Trials, and ClinicalTrials.gov were searched to find articles about rituximab treatment of patients with membranous nephropathy between January 2000 and August 2020. The outcomes included remission, antiphospholipase A2 receptor antibodies, relapse, and adverse events. The Grading of Recommendations Assessment Development and Evaluation criteria were used to evaluate the strength of evidence.
RESULTS
A total of 723 participants from 11 trials were included in this meta-analysis. The other treatments included cyclosporine, cyclophosphamide, steroids, and non-immunosuppressive antiproteinuric treatment. Rituximab significantly improved cumulative remission (P=0.007; Odds Ratio [OR]=3.06; 95% confidence interval [CI]=1.35-6.94) compared with other treatments. It significantly reduced relapse (P<0.00001; OR=0.06; 95% CI=0.02-0.19), antiphospholipase A2 receptor antibody levels (P=0.0009; SMD=-0.52; 95% CI=-0.83 to -0.21), and the proportion of patients positive for anti-PLA2R antibodies (P=0.003; OR=6.11; 95% CI=1.85-20.24) compared with other treatments. Compared with the second-line, first-line rituximab therapy achieved a higher rate of cumulative remission (P=0.03; OR=0.32, 95% CI=0.11-0.91).
CONCLUSIONS
Rituximab can improve the rate of clinical remission in patients with membranous nephropathy. Rituximab was more effective than other treatments in reducing relapse, antiphospholipase A2 receptor antibody levels, and the proportion of patients positive for antiphospholipase A2 receptor antibodies. The clinical remission rate following first-line rituximab therapy was better than that of second-line rituximab therapy for membranous nephropathy.
Topics: Autoantibodies; Autoantigens; Cyclophosphamide; Cyclosporine; Female; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Male; Receptors, Phospholipase A2; Recurrence; Rituximab
PubMed: 35074299
DOI: 10.1016/j.nephro.2021.10.002