-
Biochemical Pharmacology Jan 2024Hepatitis B is an infectious disease caused by the HBV virus. It presents a significant challenge for treatment due to its chronic nature and the potential for... (Review)
Review
Hepatitis B is an infectious disease caused by the HBV virus. It presents a significant challenge for treatment due to its chronic nature and the potential for developing severe complications, including hepatocirrhosis and hepatocellular carcinoma. These complications not only cause physical and psychological distress to patients but also impose substantial economic and social burdens on both individuals and society as a whole. The internalization of HBV relies on endocytosis and necessitates the involvement of various proteins, including heparin sulfate proteoglycans, epidermal growth factor receptors, and NTCP. Among these proteins, NTCP is pivotal in HBV internalization and is primarily located in the liver's basement membrane. As a transporter of bile acids, NTCP also serves as a receptor facilitating HBV entry into cells. Numerous molecules have been identified to thwart HBV infection by stifling NTCP activity, although only a handful exhibit low IC values. In this systematic review, our primary focus dwells on the structure and regulation of NTCP, as well as the mechanism involved in HBV internalization. We underscore recent drug breakthroughs that specifically target NTCP to combat HBV infection. By shedding light on these advances, this review contributes novel insights into developing effective anti-HBV medications.
Topics: Humans; Hepatitis B virus; Virus Internalization; Hepatitis B; Symporters; Liver Neoplasms; Hepatocytes; Hep G2 Cells
PubMed: 38049009
DOI: 10.1016/j.bcp.2023.115956 -
Cureus Sep 2023Atypical hemolytic uremic syndrome (aHUS) is a type of thrombotic microangiopathy and is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute... (Review)
Review
Atypical hemolytic uremic syndrome (aHUS) is a type of thrombotic microangiopathy and is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. The complement cascade plays an integral role in aHUS. Mutations in the complement cascade, especially in the alternative pathway (AP) lead to an unregulated and continuous activation of the cascade. Eculizumab and ravulizumab are humanized monoclonal antibodies that inhibit the complement cascade. This systematic analysis reviews the evidence for both antibodies to compare them in terms of safety and efficacy. This review will also assess the evidence for biomarker associations with interventions, the role of genetic mutations in the prognosis of disease, and the financial burden of both treatment options. An in-depth search was conducted across PubMed, Science Direct, and Cochrane Library following the PRISMA 2020 guidelines. Both eculizumab and ravulizumab were comparable in safety and efficacy but ravulizumab was preferred by patients and their caregivers as it posed a lower financial burden and had less frequent dosing. Soluble complement 5b-9 (sC5b), especially in urine, has the potential to be used as a biomarker to assess response to treatment. Genetic mutations, especially mutations in complement factor I (CFI), membrane cofactor protein (MCP), and complement factor H (CFH), were associated with a higher risk of recurrence, and therefore care should be taken when attempting to discontinue treatment in this subset of patients. Treatment with a monoclonal antibody should be initiated as soon as a genetic mutation is identified. Blinded, double-arm, clinical trials preferably with larger sample sizes are needed to effectively compare both the monoclonal antibodies.
PubMed: 37905269
DOI: 10.7759/cureus.46185 -
Biochimica Et Biophysica Acta.... Nov 2023This study aims to explore the potential biomarkers in the development of diabetes mellitus (DM) into diabetic retinopathy (DR).
Integration of systematic review, lipidomics with experiment verification reveals abnormal sphingolipids facilitate diabetic retinopathy by inducing oxidative stress on RMECs.
OBJECTIVE
This study aims to explore the potential biomarkers in the development of diabetes mellitus (DM) into diabetic retinopathy (DR).
METHODS
Systematic review of diabetic metabolomics was used to screen the differential metabolites and related pathways during the development of DM. Non-targeted lipidomics of rat plasma was performed to explore the differential metabolites in the development of DM into DR in vivo. To verify the effects of differential metabolites in inducing retinal microvascular endothelial cells (RMECs) injury by increasing oxidative stress, high glucose medium containing differential metabolites was used to induce rat RMECs injury and cell viability, malondialdehyde (MDA) contents, superoxide dismutase (SOD) activities, reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were evaluated in vitro. Network pharmacology was performed to explore the potential mechanism of differential metabolites in inducing DR.
RESULTS
Through the systematic review, 148 differential metabolites were obtained and the sphingolipid metabolic pathway attracted our attention. Plasma non-targeted lipidomics found that sphingolipids were accompanied by the development of DM into DR. In vitro experiments showed sphinganine and sphingosine-1-phosphate aggravated rat RMECs injury induced by high glucose, further increased MDA and ROS levels, and further decreased SOD activities and MMP. Network pharmacology revealed sphinganine and sphingosine-1-phosphate may induce DR by regulating the AGE-RAGE and HIF-1 signaling pathways.
CONCLUSIONS
Integrated systematic review, lipidomics and experiment verification reveal that abnormal sphingolipid metabolism facilitates DR by inducing oxidative stress on RMECs. Our study could provide the experimental basis for finding potential biomarkers for the diagnosis and treatment of DR.
Topics: Rats; Animals; Diabetic Retinopathy; Reactive Oxygen Species; Sphingolipids; Lipidomics; Endothelial Cells; Oxidative Stress; Glucose; Superoxide Dismutase; Biomarkers; Diabetes Mellitus
PubMed: 37659619
DOI: 10.1016/j.bbalip.2023.159382 -
Clinical Laboratory Oct 2023Acinetobacter baumannii produce biofilm and efflux pumps. This systematic review study aimed to provide new strategies to inhibit the efflux pumps and biofilm in A.... (Review)
Review
BACKGROUND
Acinetobacter baumannii produce biofilm and efflux pumps. This systematic review study aimed to provide new strategies to inhibit the efflux pumps and biofilm in A. baumannii using nanoparticles.
METHODS
In this research, analyses from 2000 to February 24, 2022, were performed by the Statement of Preferred Reporting Items for Systematic Reviews (PRISMA). Keywords include Acinetobacter baumannii (A. baumannii) AND (biofilm) AND (anti-biofilm activity) AND (nanoparticles) AND (solid lipid NPS) AND (lipid nanocarriers), and in other searches include Acinetobacter baumannii (A. baumanni) AND (efflux pumps) AND (nanoparticles) AND (solid lipid NPS) AND (lipid nanocarriers). Searches were conducted in English databases, including Science Direct, PubMed, Scopus, Ovid, and Cochrane.
RESULTS
At first, 136 studies were extracted, but after removing duplicates, 116 cases remained for further analysis. After evaluating the title and abstract of each study, 95 unrelated studies were excluded. The remaining 25 studies were reviewed based on full texts. Considering the inclusion/exclusion criteria, 19 studies were selected. In this study, metal nanoparticles were the most used nanoparticles for anti-biofilm and efflux pump purposes, and among these nanoparticles, silver nanoparticles (AgNPs) contributed the most.
CONCLUSIONS
The present study shows that nanoparticles have potential and significant effects in inhibiting biofilm and efflux pumps in A. baumannii isolates, which researchers can consider in light of the increasing prevalence of antibiotic resistance.
Topics: Humans; Anti-Bacterial Agents; Membrane Transport Proteins; Acinetobacter baumannii; Metal Nanoparticles; Silver; Biofilms; Lipids; Microbial Sensitivity Tests; Drug Resistance, Multiple, Bacterial; Bacterial Proteins
PubMed: 37844038
DOI: 10.7754/Clin.Lab.2023.230227 -
Journal of Pharmacy Practice Sep 2023Analgesia and sedation are often critical elements of therapy for patients undergoing extracorporeal membrane oxygenation (ECMO). Aside from potential drug-drug... (Review)
Review
Analgesia and sedation are often critical elements of therapy for patients undergoing extracorporeal membrane oxygenation (ECMO). Aside from potential drug-drug interactions, the PK changes associated with ECMO make appropriate analgosedative selection challenging. Ketamine is less lipophilic and has lower protein binding than alternative agents, and may be less impacted by the PK changes during ECMO. To systematically identify all instances of ketamine use during ECMO support in the literature to elucidate associated efficacy and safety outcomes and prevalence of use, as well as commonly used dosing strategies and pharmacokinetic data. Web of Science, Cochrane Library, Scopus, Ovid MEDLINE, PubMed, and OVID Embase were searched through 02/2023 using keywords ketamine and ECMO or extracorporal life support (ECLS). Case reports, case series, and studies were included that had (1) original data, (2) included patients that were on ECMO and continuous infusion ketamine, and (3) reported pertinent ketamine related clinical endpoints or prevalence of use. Of the 307 articles screened, 25 were identified as relevant and 11 met our inclusion criteria. Heterogeneity of patient population, ketamine indication, reported outcomes, and reported safety endpoints were identified in the included articles. Commonly reported information includes indications, pharmacokinetics, dosing, adverse effects and use in pediatrics for ketamine, and suspected opioid sparing effect. Our review has found a lack of consistency in reporting and results in adult and pediatric patients. Increased consistency in reporting and larger studies are required to increase our knowledge of ketamine use in both the adult and pediatric patient population.
PubMed: 37670605
DOI: 10.1177/08971900231198928 -
Clinical and Experimental Medicine Nov 2023Some human polymorphisms of ACE1, ACE2, IFITM3, TMPRSS2 and TNFα genes may have an effect on the susceptibility to SARS-CoV-2 infection and increase the risk to develop... (Meta-Analysis)
Meta-Analysis Review
Genetic polymorphisms of ACE1, ACE2, IFTM3, TMPRSS2 and TNFα genes associated with susceptibility and severity of SARS-CoV-2 infection: a systematic review and meta-analysis.
BACKGROUND
Some human polymorphisms of ACE1, ACE2, IFITM3, TMPRSS2 and TNFα genes may have an effect on the susceptibility to SARS-CoV-2 infection and increase the risk to develop severe COVID-19. We conducted a systematic review of current evidence to investigate the association of genetic variants of these genes with the susceptibility to virus infection and patient prognosis.
METHODS
We systematically searched Medline, Embase and The Cochrane Library for articles published until May 2022, and included observational studies covering genetic association of ACE1, ACE2, IFITM3, TMPRSS2 and TNFα genes with COVID-19 susceptibility or prognosis. We evaluated the methodological quality of included studies, and pooled data as convenient in meta-analysis (MA). Odds ratio (OR) values and 95% confidence intervals were calculated.
RESULTS
We included 35 studies (20 on ACE, 5 each on IFITM3, TMPRSS2, TNFα), enrolling 21,452 participants, of them 9401 were COVID-19 confirmed cases. ACE1 rs4646994 and rs1799752, ACE2 rs2285666, TMPRSS2 rs12329760, IFITM3 rs12252 and TNFα rs1800629 were identifies as common polymorphisms. Our MA showed an association between genetic polymorphisms and susceptibility to SARS-CoV-2 infection for IFITM3 rs12252 CC (OR 5.67) and CT (OR 1.64) genotypes. Furthermore, MA uncovered that both ACE DD (OR 1.27) and IFITM3 CC (OR 2.26) genotypes carriers had a significantly increased risk of developing severe COVID-19.
DISCUSSION
These results provide a critical evaluation of genetic polymorphisms as predictors in SARS-CoV-2 infection. ACE1 DD and IFITM3 CC polymorphisms would lead to a genetic predisposition for severe lung injury in patients with COVID-19.
Topics: Humans; Angiotensin-Converting Enzyme 2; COVID-19; Membrane Proteins; Peptidyl-Dipeptidase A; Polymorphism, Genetic; RNA-Binding Proteins; SARS-CoV-2; Serine Endopeptidases; Tumor Necrosis Factor-alpha
PubMed: 37055652
DOI: 10.1007/s10238-023-01038-9 -
Critical Reviews in Toxicology Dec 2023Metal phosphides are highly toxic pesticides that result in high morbidities and mortalities worldwide. This systematic review included 350 studies that fulfilled the... (Review)
Review
Metal phosphides are highly toxic pesticides that result in high morbidities and mortalities worldwide. This systematic review included 350 studies that fulfilled the eligibility criteria. There were significant rising trends of studies on acute aluminum phosphide (AlP) and zinc phosphide (ZnP) poisoning (-values = <.001), pointing to an increased number of phosphide-intoxicated patients. Acute AlP poisoning studies represented 81%, 89.3%, and 97.7% of all descriptive, analytical, and experimental interventional studies included in this review, respectively. High AlP poisoning mortality explains great research interest in AlP poisoning. Thus, after 2016, nearly half (49.7%) of studies on acute AlP poisoning were issued. Also, 78.82% of experimental interventional studies on AlP poisoning were published after 2016. The trends of in-vitro, animal, and clinical studies on AlP poisoning significantly increased with -values equal to .021, <.001, and <.001, respectively. Seventy-nine treatment modalities for acute AlP poisoning were pooled from 124 studies; 39 management-related case reports, 12 in-vitro studies, 39 animal studies, and 34 clinical studies. All therapeutic modalities were summarized to formulate an integrated and comprehensive overview. For clinicians, therapeutic modalities significantly decreased mortality of acute AlP poisoning in clinical trials included extracorporeal membrane oxygenation (ECMO), N-acetyl cysteine (NAC), vitamin E, glucose-insulin-potassium (GIK) infusion, fresh packed RBCs infusion, and GIT decontamination using oils. However, meta-analyses are needed to provide solid evidence regarding their efficacies. To date, there is no effective antidote nor evidence-based standardized protocol for managing acute AlP poisoning. This article outlined the potential research gaps in phosphide poisoning that might promote and direct future medical research in this context.
Topics: Animals; Pesticides; Evidence Gaps; Antidotes; Acetylcysteine; Aluminum Compounds
PubMed: 37387512
DOI: 10.1080/10408444.2023.2225539 -
European Journal of Nuclear Medicine... Dec 2023The current clinical recommendations posit the deployment of specific approved radiolabeled prostate-specific membrane antigen-ligand positron emission tomography (PSMA... (Meta-Analysis)
Meta-Analysis Review
The diagnostic accuracy of radiolabeled PSMA-ligand PET for tumour staging in newly diagnosed prostate cancer patients compared to histopathology: a systematic review and meta-analysis.
PURPOSE
The current clinical recommendations posit the deployment of specific approved radiolabeled prostate-specific membrane antigen-ligand positron emission tomography (PSMA PET) for detecting metastatic prostate cancer during primary staging. Nevertheless, the precise efficacy of such ligands in localizing intraprostatic tumours (index tumour) and T-staging is not well established. Consequently, the objective of this inquiry is to ascertain the diagnostic accuracy of PSMA-PET in the tumour staging of newly diagnosed prostate cancer by means of a meta-analysis that integrates studies utilizing histological confirmation as the reference standard.
METHODS
In this study, we conducted a systematic literature search of the PubMed, Embase, Web of Science, and Cochrane Library databases using a predefined collection of search terms. These terms included 'PSMA PET', 'primary staging', and 'prostate cancer'. Subsequently, two independent reviewers evaluated all the studies based on predetermined inclusion criteria, extracted pertinent data, and assessed the quality of evidence. Any disparities were resolved by a third reviewer. A random effects Sidik-Jonkman model was applied to conduct a meta-analysis and estimate the diagnostic accuracy on a per-patient basis, along with 95% confidence intervals. Moreover, an appraisal regarding the likelihood of publication bias and the impact of small-study effects was performed utilizing both Egger's test and a graphical examination of the funnel plot.
RESULTS
The present analysis comprised a total of twenty-three scientific papers encompassing 969 patients and involved their analysis by both qualitative and quantitative approaches. The results of this study demonstrated that the estimated diagnostic accuracy of PSMA PET/CT and PSMA PET/MRI, for the detection of intraprostatic tumours, regardless of the type of PSMA-ligand, was 86% (95% CI: 76-96%) and 97% (95% CI: 94-100%), respectively. Furthermore, the diagnostic accuracy for the detection of extraprostatic extension (EPE) was 73% (95% CI: 64-82%) and 77% (95% CI: 69-85%), while the diagnostic accuracy for the detection of seminal vesicle involvement (SVI) was 87% (95% CI: 80-93) and 90% (95% CI: 82-99%), respectively.
CONCLUSION
The present investigation has demonstrated that PSMA PET/MRI surpasses currently recommended multiparametric magnetic resonance imaging (mpMRI) in terms of diagnostic accuracy as inferred from a notable data trajectory, whereas PSMA-PET/CT exhibited comparable diagnostic accuracy for intraprostatic tumour detection and T-staging compared to mpMRI. Nevertheless, the analysis has identified certain potential limitations, such as small-study effects and a potential for publication bias, which may impact the overall conclusions drawn from this study.
Topics: Male; Humans; Positron Emission Tomography Computed Tomography; Neoplasm Staging; Ligands; Gallium Radioisotopes; Prostatic Neoplasms; Positron-Emission Tomography
PubMed: 37597010
DOI: 10.1007/s00259-023-06392-0 -
Perfusion Nov 2023Extracorporeal membrane oxygenation (ECMO) is employed to support critically ill COVD-19 patients. The occurrence of ischemic stroke and intracranial hemorrhage (ICH),... (Meta-Analysis)
Meta-Analysis
PURPOSE
Extracorporeal membrane oxygenation (ECMO) is employed to support critically ill COVD-19 patients. The occurrence of ischemic stroke and intracranial hemorrhage (ICH), as well as the implementation of anticoagulation strategies under the dual influence of ECMO and COVID-19 remain unclear. We conducted a systematic review and meta-analysis to describe the ischemic stroke, ICH and overall in-hospital mortality in COVID-19 patients receiving ECMO and summarize the anticoagulation regimens.
METHODS
EMBASE, PubMed, Cochrane, and Scopus were searched for studies examining ischemic stroke, ICH, and mortality in COVID-19 patients supported with ECMO. The outcomes were incidences of ischemic stroke, ICH, overall in-hospital mortality and anticoagulation regimens. We calculated the pooled proportions and 95% confidence intervals (CIs) to summarize the results.
RESULTS
We analyzed 12 peer-reviewed studies involving 6039 COVID-19 patients. The incidence of ischemic stroke had a pooled estimate of 2.2% (95% CI: 1.2%-3.2%). The pooled prevalence of ICH was 8.0% (95% CI: 6.3%-9.6%). The pooled estimate of overall in-hospital mortality was 40.3% (95% CI: 33.1%-47.5%). The occurrence of ICH was significantly higher in COVID-19 patients supported with ECMO than in other respiratory ECMO [relative risk=1.75 (95% CI: 1.00-3.07)]. Unfractionated heparin was the most commonly used anticoagulant, and anticoagulation monitoring practice varied among centers.
CONCLUSIONS
Ischemic stroke and ICH were common under the double "hit" of COVID-19 and ECMO. The prevalence of ICH was significantly higher in COVID-19 patients supported with ECMO than non-COVID-19 patients requiring ECMO. Individualized anticoagulation regimens may be a good choice to balance thrombosis and bleeding. More detailed research and further exploration are needed to clarify the underlying mechanism and clinical management decisions.
Topics: Humans; Heparin; Extracorporeal Membrane Oxygenation; Ischemic Stroke; COVID-19; Intracranial Hemorrhages; Anticoagulants; Retrospective Studies
PubMed: 36189498
DOI: 10.1177/02676591221130886 -
Targeted Oncology Nov 2023Delta-like ligand 3 (DLL3), a member of the Notch pathway, has been identified as a potential therapeutic target as it is highly expressed in small cell lung cancer...
BACKGROUND
Delta-like ligand 3 (DLL3), a member of the Notch pathway, has been identified as a potential therapeutic target as it is highly expressed in small cell lung cancer (SCLC), a subtype accounting for 15% of lung cancer cases.
OBJECTIVE
A systematic literature review (SLR) was conducted to understand the prevalence and prognostic impact of DLL3 expression on survival of patients with SCLC and treatment response.
PATIENTS AND METHODS
Systematic literature searches were conducted across multiple databases to capture studies of any SCLC population that evaluated DLL3 expression. Specific outcomes of interest included prevalence of DLL3 expression, method of expression analysis, and impact on outcome, including treatment response and survival (overall, progression-free, disease-free) according to varying levels of DLL3 expression/positivity. Standard risk of bias tools were used to evaluate study quality.
RESULTS
Among the 30 included studies, the most common DLL3 testing method was immunohistochemistry (N = 26, 86.7%). For comparability, results focused on the 13 (22.3%) studies that used the Ventana DLL3 (SP347) immunohistochemistry assay. The prevalence of DLL3 positivity ranged from 80.0-93.5% for studies using a threshold of ≥ 1% of tumor cells (N = 4) and 58.3-91.1% for studies with a ≥ 25% threshold (N = 4). DLL3 expression was generally categorized as high using cutoffs of ≥ 50% (prevalence range: 45.8-79.5%; N = 6) or ≥ 75% (prevalence range: 47.3-75.6%; N = 5) of cells with positivity. Two studies used an H-score of ≥ 150 to define high DLL3 expression with prevalence ranging from 33.3-53.1%. No consistent associations were seen between DLL3 expression level and patient age, sex, smoking history, or disease stage. Two studies reported change in DLL3 expression category (high versus low) before and after chemotherapy. No statistically significant differences were reported between DLL3 expression groups and survival (overall, progression-free, or disease-free) or treatment response.
CONCLUSIONS
There is a high prevalence of DLL3 expression in SCLC. Further research and analytical methods may help to characterize different populations of patients with SCLC based on DLL3 expression. While no significant prognostic factor in the included studies was identified, additional cohort studies using standardized methodology, with longer follow-up, are needed to better characterize any potential differences in patient survival or response by DLL3 expression level in SCLC.
Topics: Humans; Small Cell Lung Carcinoma; Lung Neoplasms; Prognosis; Ligands; Prevalence; Membrane Proteins; Intracellular Signaling Peptides and Proteins
PubMed: 37930513
DOI: 10.1007/s11523-023-01008-x