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Biomolecules Mar 2022Proteases and protease inhibitors (P/PIs) are involved in many biological processes in human skin, yet often only specific families or related groups of P/PIs are...
Proteases and protease inhibitors (P/PIs) are involved in many biological processes in human skin, yet often only specific families or related groups of P/PIs are investigated. Proteomics approaches, such as mass spectrometry, can define proteome signatures (including P/PIs) in tissues; however, they struggle to detect low-abundance proteins. To overcome these issues, we aimed to produce a comprehensive proteome of all P/PIs present in normal and diseased human skin, in vivo, by carrying out a modified systematic review using a list of P/PIs from MEROPS and combining this with key search terms in Web of Science. Resulting articles were manually reviewed against inclusion/exclusion criteria and a dataset constructed. This study identified 111 proteases and 77 protease inhibitors in human skin, comprising the serine, metallo-, cysteine and aspartic acid catalytic families of proteases. P/PIs showing no evidence of catalytic activity or protease inhibition, were designated non-peptidase homologs (NPH), and no reported protease inhibitory activity (NRPIA), respectively. MMP9 and TIMP1 were the most frequently published P/PIs and were reported in normal skin and most skin disease groups. Normal skin and diseased skin showed significant overlap with respect to P/PI profile; however, MMP23 was identified in several skin disease groups, but was absent in normal skin. The catalytic profile of P/PIs in wounds, scars and solar elastosis was distinct from normal skin, suggesting that a different group of P/PIs is responsible for disease progression. In conclusion, this study uses a novel approach to provide a comprehensive inventory of P/PIs in normal and diseased human skin reported in our database. The database may be used to determine either which P/PIs are present in specific diseases or which diseases individual P/PIs may influence.
Topics: Antiviral Agents; Humans; Peptide Hydrolases; Protease Inhibitors; Proteome; Proteomics
PubMed: 35327667
DOI: 10.3390/biom12030475 -
Canadian Family Physician Medecin de... Oct 2023To assess the benefits and harms of lipid-lowering therapies used to prevent or manage cardiovascular disease including bile acid sequestrants (BAS), ezetimibe,...
OBJECTIVE
To assess the benefits and harms of lipid-lowering therapies used to prevent or manage cardiovascular disease including bile acid sequestrants (BAS), ezetimibe, fibrates, niacin, omega-3 supplements, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, and statins.
DATA SOURCES
MEDLINE, the Cochrane Database of Systematic Reviews, and a grey literature search.
STUDY SELECTION
Systematic reviews of randomized controlled trials published between January 2017 and March 2022 looking at statins, ezetimibe, PCSK9 inhibitors, fibrates, BAS, niacin, and omega-3 supplements for preventing cardiovascular outcomes were selected. Outcomes of interest included major adverse cardiovascular events (MACE), cardiovascular mortality, all-cause mortality, and adverse events.
SYNTHESIS
A total of 76 systematic reviews were included. Four randomized controlled trials were also included for BAS because no efficacy systematic review was identified. Statins significantly reduced MACE (6 systematic reviews; median risk ratio [RR]=0.74; interquartile range [IQR]=0.71 to 0.76), cardiovascular mortality (7 systematic reviews; median RR=0.85, IQR=0.83 to 0.86), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.88 to 0.92). Major adverse cardiovascular events were also significantly reduced by ezetimibe (3 systematic reviews; median RR=0.93, IQR=0.93 to 0.94), PCSK9 inhibitors (14 systematic reviews; median RR=0.84, IQR=0.83 to 0.87), and fibrates (2 systematic reviews; mean RR=0.86), but these interventions had no effect on cardiovascular or all-cause mortality. Fibrates had no effect on any cardiovascular outcomes when added to a statin. Omega-3 combination supplements had no effect on MACE or all-cause mortality but significantly reduced cardiovascular mortality (5 systematic reviews; median RR=0.93, IQR=0.93 to 0.94). Eicosapentaenoic acid ethyl ester alone significantly reduced MACE (1 systematic review, RR=0.78) and cardiovascular mortality (2 systematic reviews; RRs of 0.82 and 0.82). In primary cardiovascular prevention, only statins showed consistent benefits on MACE (6 systematic reviews; median RR=0.75, IQR=0.73 to 0.78), cardiovascularall-cause mortality (7 systematic reviews, median RR=0.83, IQR=0.81 to 0.90), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.87 to 0.91).
CONCLUSION
Statins have the most consistent evidence for the prevention of cardiovascular complications with a relative risk reduction of about 25% for MACE and 10% to 15% for mortality. The addition of ezetimibe, a PCSK9 inhibitor, or eicosapentaenoic acid ethyl ester to a statin provides additional MACE risk reduction but has no effect on all-cause mortality.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Proprotein Convertase 9; Cardiovascular Diseases; PCSK9 Inhibitors; Niacin; Systematic Reviews as Topic; Ezetimibe; Lipids; Fibric Acids; Primary Health Care; Anticholesteremic Agents
PubMed: 37833094
DOI: 10.46747/cfp.6910701 -
Scientific Reports May 2021Although a considerable volume of data supporting induction or aggravation of psoriasis because of angiotensin-converting enzyme (ACE) inhibitor use exists, it remains... (Meta-Analysis)
Meta-Analysis
Although a considerable volume of data supporting induction or aggravation of psoriasis because of angiotensin-converting enzyme (ACE) inhibitor use exists, it remains insufficient for definitive conclusions. Therefore, we aimed to evaluate the association between ACE inhibitor use and psoriasis incidence through a systematic literature review and meta-analysis. We searched for qualifying studies across PubMed, Web of Science, and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between ACE inhibitor use and psoriasis incidence. Eight studies with a total of 54,509 patients with a psoriasis diagnosis were included in this meta-analysis. The pooled OR for psoriasis incidence among ACE inhibitor users was 1.52 (95% CI, 1.16-2.00) compared to that among non-users. From subgroup analysis by continent, the OR for ACE inhibitor users versus non-users was 2.37 (95% CI 1.28-4.37) in Asia. Per the subgroup analysis by climate, the OR for ACE inhibitor users vs non-users in dry climate was 3.45 (95% CI: 2.05-5.79) vs 1.32 (95% CI 1.01-1.73) in temperate climate. Our results reveal a significant association between ACE inhibitor use and psoriasis incidence.
Topics: Angiotensin-Converting Enzyme Inhibitors; Humans; Incidence; Psoriasis
PubMed: 33976340
DOI: 10.1038/s41598-021-89490-z -
Cancer Causes & Control : CCC Jun 2022Antihypertensive medications may impact colorectal cancer risk. We conducted a systematic review and meta-analysis of associations, with colorectal cancer risk, of five... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Antihypertensive medications may impact colorectal cancer risk. We conducted a systematic review and meta-analysis of associations, with colorectal cancer risk, of five classes of antihypertensive medications: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), and diuretics.
METHODS
A systematic search was conducted in MEDLINE, Embase, Web of Science, and the Cochrane library to identify relevant studies evaluating associations of ACEIs, ARBs, BBs, CCBs, and diuretics with colorectal cancer risk. Meta-analytic risk ratios (RRs) and corresponding 95% confidence intervals (95% CIs) were calculated using the inverse variance method.
RESULTS
No overall significant associations with colorectal cancer risk were observed; ACEIs (5 studies) RR 1.05, 95% CI 0.91-1.23, ARBs (5 studies) RR 0.94, 95% CI 0.80-1.11, BBs (4 studies) RR 1.00, 95% CI 0.92-1.08, CCBs (4 studies) RR 1.02, 95% CI 0.88-1.18, and diuretics (6 studies) RR 1.02, 95% CI 0.90-1.17. There was considerable heterogeneity across studies, partly explained by differences in study design and location. When stratified by study location, there was significantly reduced colorectal cancer risk for ARB use in Asian populations (2 studies, RR 0.69, 95% CI 0.58-0.83).
CONCLUSION
No significant colorectal cancer risk with ACEIs, BBs, CCBs, or diuretics was observed. ARB use may be associated with decreased risk of colorectal cancer in Asian populations, although additional studies in diverse populations are needed to confirm associations and help understand possible reasons for geographical differences.
Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Colorectal Neoplasms; Diuretics; Humans; Hypertension
PubMed: 35314908
DOI: 10.1007/s10552-022-01570-1 -
Journal of Stroke and Cerebrovascular... Apr 2024Investigate the efficacy and safety of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) on stroke prevention. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Investigate the efficacy and safety of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) on stroke prevention.
BACKGROUND
PCSK9i reduce low-density lipoprotein cholesterol (LDL-C) and lipoprotein a (LpA) levels. Their efficacy in reducing the risk of major cardiovascular events has been shown in multiple randomized clinical trials (RCT). However, clinical equipoise remains on the magnitude and mechanisms by which PCSK9i decrease the risk of stroke.
METHODS
We performed a systematic search of biomedical databases from inception to January 15, 2024, to identify RCTs that investigated the efficacy of PCSK9i versus placebo for major cardiovascular event prevention. The primary outcome was total stroke. The safety outcome was the risk of adverse neurological events, as defined by each trial. Effect size was represented by risk ratio (RR), and analysis was done using random-effects meta-analysis. Heterogeneity was assessed by I and Cochrane Q statistics. Meta-regression analyses were performed to assess the association between LDL-C and LpA reduction and stroke risk.
RESULTS
Overall, 20 studies with 93,093 patients were included. The quality of the evidence was moderate and heterogeneity for all comparisons was low (I < 25 %). The mean age was 60.1 years for the PCSK9i group and 59.6 years for the placebo group, with a mean follow-up time of 60.1 weeks. PCSK9i reduced the LDL-C levels by 11 % and LpA levels by 8 %. PCSK9i were associated with a significant reduction in stroke risk (RR 0.75, 95 % CI 0.66-0.86, I = 0 %), without an increase in mortality (RR 0.97, 95 % CI 0.87-1.08, I = 0 %). The risk of adverse neurological events was similar between groups (RR 0.99, 95 % CI 0.84-1.18, I = 11 %). In meta-regression analyses, the stroke risk was not associated with the magnitude of the effect of PCSK9i on LDL-C (LDL C β = -0.01, 95 % CI = -0.03-0.02) and LpA (β = -0.01, 95 % CI = -0.06-0.04) levels.
CONCLUSIONS
PCSK9i significantly reduced the stroke risk, without increasing mortality or the risk of adverse neurological events. Our findings also suggest that the beneficial effect of PCSK9i on stroke risk is mediated by LDL-C- and LpA-independent mechanisms.
Topics: Humans; Middle Aged; PCSK9 Inhibitors; Cholesterol, LDL; Antibodies, Monoclonal, Humanized; Stroke; Anticholesteremic Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cardiovascular Diseases; Proprotein Convertase 9
PubMed: 38336118
DOI: 10.1016/j.jstrokecerebrovasdis.2024.107633 -
The Annals of Pharmacotherapy Apr 2021Discuss the literature and describe strategies to overcome barriers of inpatient initiation of sacubitril/valsartan in patients with heart failure with reduced ejection...
OBJECTIVE
Discuss the literature and describe strategies to overcome barriers of inpatient initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF).
DATA SOURCES
A PubMed, EMBASE, and Google Scholar literature search (January 2014 to June 2020) limited to English language articles was conducted with the following terms: , , , , , , , , and .
STUDY SELECTION AND DATA EXTRACTION
Included articles described inpatient initiation of sacubitril/valsartan or described its impact on BNP, NT-proBNP, diuretic dosing, or cost of care.
DATA SYNTHESIS
A total of 20 studies were identified based on included search terms.
CONCLUSIONS
Sacubitril/valsartan should be considered for hemodynamically stable patients with HFrEF (New York Heart Association class II or III), potassium <5.2 mmol/L, without a history of angioedema, and after a 36-hour washout from angiotensin-converting enzyme (ACE) inhibitor or aliskiren, if applicable. An appropriate dose can be determined based on the patient's previous ACE inhibitor or angiotensin receptor blocker dose and/or blood pressure along with patient-specific factors. To overcome barriers of use, the following are recommended: NT-proBNP or BNP with establishment of a new baseline 1 month after initiation may be used for prognosis or diagnosis; careful monitoring of diuretic requirements; utilization of multiple strategies to overcome cost barriers; and use of interdisciplinary care.
Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Blood Pressure; Clinical Trials as Topic; Drug Combinations; Heart Failure; Hospitalization; Humans; Inpatients; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Valsartan
PubMed: 32741197
DOI: 10.1177/1060028020947446 -
Frontiers in Endocrinology 2023To assess the relationship between use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and the risk of gout among patients with type 2 diabetes mellitus (T2DM). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the relationship between use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and the risk of gout among patients with type 2 diabetes mellitus (T2DM).
METHODS
A systemic review and meta-analysis were designed by reviewing articles published between 2000 January 1 and 2022 December 31 using PubMed system and Web of Science system based on the PRISMA 2020 guidelines. The end point of interest was gout (including gout flares, gout events, starting uric-acid lowering therapy and starting anti-gout drugs use) among patients with T2DM using SGLT2i versus not using SGLT2i. A random-effects model was utilized to measure the pooled hazard ratio (HR) with 95% confidence interval (CI) for the risk of gout associated with SGLT2i use.
RESULTS
Two prospective post-hoc analyses of randomized controlled trials and 5 retrospective electronic medical record-linkage cohort studies met the inclusion criteria. The meta-analysis demonstrated that there was a decreased risk of developing gout for SGLT2i use as comparing with non-use of SGLT2i among patients with T2DM (pooled HR=0.66 and 95%CI=0.57-0.76).
CONCLUSIONS
This meta-analysis demonstrates that SGLT2i use is associated with a 34% decreased risk of developing gout among patients with T2DM. SGLT2i may be the treatment options for patients with T2DM who are at high risk of gout. More randomized controlled trials and real-world data are needed to confirm whether there is a class effect of SGLT2i for the risk reduction of gout among patients with T2DM.
Topics: Sodium-Glucose Transporter 2 Inhibitors; Gout; Diabetes Mellitus, Type 2; Humans; Male; Female; Middle Aged; Placebos; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor
PubMed: 37288295
DOI: 10.3389/fendo.2023.1158153 -
Phytomedicine : International Journal... Jan 2023The therapeutic benefits of Niaoduqing granules (NDQG) in kidney diseases has been comprehensively studied, but its adverse drug reactions remain unexplored. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The therapeutic benefits of Niaoduqing granules (NDQG) in kidney diseases has been comprehensively studied, but its adverse drug reactions remain unexplored.
OBJECTIVE
To evaluate the safety of NDQG in kidney disease treatment.
METHODS
The literature was searched in Embase, Medline via PubMed, Cochrane Library database, Wanfang database, Chinese National Knowledge Infrastructure, SinoMed, and Chinese VIP Database from inception to January 15, 2022, for randomized controlled trials (RCTs) and observational studies. The ClinicalTrials.gov website was searched for ongoing trials. The frequency and characteristics of adverse drug reactions (ADRs) were the primary and secondary outcomes, respectively. Subgroup analysis were conducted to explore the effects of clinical trial types, different kidney diseases, drug combinations and dosage on the safety of NDQG.
RESULTS
This review included 132 trials comprising 115 RCTs and 17 cohort studies. Additionally, 118 studies reported ADR rates with complete data, including 10381 participants. Regarding ADR frequency, no significant difference was observed between NDQG (7.26%) and control (8.39%) groups (RR = 0.890, 95% confidence interval (CI): 0.788-1.007); with no heterogeneity among the studies (I = 0.0%, P = 0.958). ADR frequency in patients with chronic kidney disease (65 trials, n = 5823) was significantly lower in the NDQG treatment group than in the control group (RR = 0.810, 95% CI: 0.67-0.969, I = 0.0%, P = 0.993); however, for patients with diabetic nephropathy there was no difference between both groups (26 trials, n = 2166, RR = 1.077, 95% CI: 0.802-1.446, I = 0.0%, P = 0.611). Similarly, the incidence of ADR in patients on dialysis and patients with pyelonephritis and nephrotic syndrome was the same for both groups, with 95% CI overlapping the line. For different interventions, including NDQG monotherapy or its combination with other commonly used drugs (including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statin drugs, and compound α-keto acid) or dialysis, the incidence of ADR showed no significant difference between the experimental and control arms. The ADR in the NDQG group primarily affected the gastrointestinal system (64.74%), central and peripheral nervous system (9.07%), whole body (5.79%), and skin and appendages (4.53%). The most common clinical manifestations were diarrhea, nausea, and vomiting.
CONCLUSIONS
Our meta-analysis showed that compared with supportive therapy, the incidence of ADR was similar when NDQG was added. However, current evidence is not definitive and more well-designed and conducted RCTs are warranted to definitively establish the reliable evidence.
PROTOCOL REGISTRATION NUMBER
PROSPERO CRD 42018104227.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Renal Insufficiency, Chronic; Nephrotic Syndrome; Skin; Drug-Related Side Effects and Adverse Reactions
PubMed: 36610168
DOI: 10.1016/j.phymed.2022.154535 -
Pharmacological Research Mar 2022Antidiabetic medications (ADMs) may modify prostate cancer (PCa) risk in patients with diabetes mellitus (DM). Accordingly, the current study assessed the possible... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antidiabetic medications (ADMs) may modify prostate cancer (PCa) risk in patients with diabetes mellitus (DM). Accordingly, the current study assessed the possible associations between ADMs and the risk of PCa in diabetics.
METHODS
A systematic literature search (PubMed, Embase and Cochrane Library) identified studies evaluating the associations between ADMs and incidence of PCa. A meta-analysis followed PRISMA was performed using odds ratio (OR) with 95% confidence interval (CI) as effect measures.
RESULTS
In total of 47 studies involving 3094,152 patients with diabetes were included. Results of meta-analysis of the observational studies suggested no significant association between metformin, thiazolidinediones, sulfonylureas, insulin or dipeptidyl peptidase-4 inhibitors administration and the risk of PCa (All p-values > 0.05). Separate analysis of randomized controlled trials (RCTs) revealed a significant reduction in PCa risk with thiazolidinediones (OR = 0.55, p = 0.04) or glucagon-like peptide-1 receptor agonists (GLP-1RA) administration (OR = 0.53, p = 0.006), whereas no significant association was found in SGLT2 inhibitors (p = 0.3).
CONCLUSION
Thiazolidinediones or GLP-1RA administration may have benefits in PCa based on RCTs, however, further research is needed to confirm these findings.
Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Hypoglycemic Agents; Male; Prostatic Neoplasms; Thiazolidinediones
PubMed: 35074527
DOI: 10.1016/j.phrs.2022.106094 -
International Journal of Antimicrobial... Jul 2023Data indicate that certain combination antiretroviral treatment (cART) regimens, particularly protease inhibitor (PI)-based regimens, and cART initiation before... (Meta-Analysis)
Meta-Analysis Review
Maternal antiretroviral treatment for HIV infection and risk of small-for-gestational-age birth: A systematic review and meta-analysis of protease inhibitor-based treatment and timing of treatment.
BACKGROUND
Data indicate that certain combination antiretroviral treatment (cART) regimens, particularly protease inhibitor (PI)-based regimens, and cART initiation before conception may be associated with adverse pregnancy outcomes. The risk of having a small-for-gestational-age (SGA) infant was examined among pregnant HIV-infected mothers on 1) PI-based compared to non-PI-based cART, and 2) any cART initiated before compared to after conception.
METHODS
A search was conducted using PubMed, Embase, and the Cochrane Library, and a systematic review was performed of studies published since Dec 1, 1995. Effect estimates with 95% confidence intervals (CIs) were extracted and meta-analyses with random-effects models were conducted. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool.
FINDINGS
Of 783 identified studies, 28 fulfilled the inclusion criteria. Meta-analysis indicated that PI-based cART was associated with a possible slightly increased risk of SGA compared with non-PI-based cART (pooled odds ratio [OR]: 1·09; CI: 0·76, 1·55). Initiation of cART before conception was also associated with a possible slightly increased risk of SGA compared with after conception (pooled OR: 1·08; CI: 0·95, 1·22). The overall certainty of evidence was very low and low for the first and second research questions, respectively.
INTERPRETATION
Although the benefits of cART largely outweigh the risks, these findings indicate the possibility of slightly increased risks of having an SGA infant. This indicates that careful monitoring of fetuses exposed to PI-based cART or cART before pregnancy might be reasonable. Based on the uncertainty of evidence, further research may change this conclusion.
Topics: Pregnancy; Infant; Female; Humans; HIV Infections; Anti-HIV Agents; Pregnancy Outcome; Protease Inhibitors
PubMed: 37121443
DOI: 10.1016/j.ijantimicag.2023.106823