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International Journal of Molecular... Aug 2023The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical...
The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.
Topics: Humans; Drugs, Investigational; Nerve Growth Factor; Neuralgia, Postherpetic; Pregabalin; Randomized Controlled Trials as Topic
PubMed: 37629168
DOI: 10.3390/ijms241612987 -
Vaccine Jan 2024To systematically review immunogenicity and safety data of maternal group B streptococcal (GBS) vaccines in published clinical trials until July 2023. (Review)
Review
PURPOSE
To systematically review immunogenicity and safety data of maternal group B streptococcal (GBS) vaccines in published clinical trials until July 2023.
METHODS
EMBASE, MEDLINE, Cochrane Library and clinicaltrial.gov. databases were searched for clinical studies that reported immunogenicity and/or safety of GBS vaccine in non-pregnant adults, pregnant women and infants between 1st of January 1996 to 31st of July 2023. Pairs of reviewers independently selected, data extracted, and assessed the risk of bias of the studies. Discrepancies were resolved by consensus. (PROSPERO CRD42020185213).
RESULTS
We retrieved 1472 records from the literature search; 20 studies and 6 sub-studies were included, involving 4440 non-pregnant participants and 1325 pregnant women with their newborns. There was a significantly higher IgG Geometric Mean Concentration (GMC) and IgG placental transfer ratios in vaccinated compared to placebo groups, with peak response 4-8 weeks after vaccination. Placental transfer ratio varied from 0.4 to 1.4 across five studies. The different clinical trials used different assays that limited direct comparison. There were no significant differences in the risk of serious adverse events (adjusted OR 0.73; 95 % CI 0.49-1.07), serious adverse events leading to withdrawal (adjusted OR 0.44; 95 % CI 0.13-1.51), and systemic illness or fever (adjusted OR 1.05; 95 % CI 0.26-4.19) between the vaccine and placebo groups.
CONCLUSIONS
The published clinical trials show significant IgG GMC response in subjects receiving the conjugated capsular polysaccharide and surface subunit protein vaccines compared to placebo. In current clinical trials of experimental GBS maternal vaccines, there have been no observed serious adverse events of special interest directly linked to vaccination.
Topics: Infant; Adult; Humans; Infant, Newborn; Female; Pregnancy; Placenta; Vaccines; Vaccination; Streptococcus agalactiae; Immunoglobulin G; Immunogenicity, Vaccine
PubMed: 38072754
DOI: 10.1016/j.vaccine.2023.11.056 -
Molecular Psychiatry Jul 2023Impairment of insulin action and metabolic dysregulation have traditionally been associated with schizophrenia, although the molecular basis of such association remains... (Meta-Analysis)
Meta-Analysis
Impairment of insulin action and metabolic dysregulation have traditionally been associated with schizophrenia, although the molecular basis of such association remains still elusive. The present meta-analysis aims to assess the impact of insulin action manipulations (i.e., hyperinsulinemia, hypoinsulinemia, systemic or brain insulin resistance) on glutamatergic, dopaminergic, γ-aminobutyric acid (GABA)ergic, and serotonergic pathways in the central nervous system. More than one hundred outcomes, including transcript or protein levels, kinetic parameters, and other components of the neurotransmitter pathways, were collected from cultured cells, animals, or humans, and meta-analyzed by applying a random-effects model and adopting Hedges'g to compare means. Two hundred fifteen studies met the inclusion criteria, of which 180 entered the quantitative synthesis. Significant impairments in key regulators of synaptic plasticity processes were detected as the result of insulin handlings. Specifically, protein levels of N-methyl-D-aspartate receptor (NMDAR) subunits including type 2A (NR2A) (Hedges' g = -0.95, 95%C.I. = -1.50, -0.39; p = 0.001; I = 47.46%) and 2B (NR2B) (Hedges'g = -0.69, 95%C.I. = -1.35, -0.02; p = 0.043; I = 62.09%), and Postsynaptic density protein 95 (PSD-95) (Hedges'g = -0.91, 95%C.I. = -1.51, -0.32; p = 0.003; I = 77.81%) were found reduced in insulin-resistant animal models. Moreover, insulin-resistant animals showed significantly impaired dopamine transporter activity, whereas the dopamine D2 receptor mRNA expression (Hedges'g = 3.259; 95%C.I. = 0.497, 6.020; p = 0.021; I = 90.61%) increased under insulin deficiency conditions. Insulin action modulated glutamate and GABA release, as well as several enzymes involved in GABA and serotonin synthesis. These results suggest that brain neurotransmitter systems are susceptible to insulin signaling abnormalities, resembling the discrete psychotic disorders' neurobiology and possibly contributing to the development of neurobiological hallmarks of treatment-resistant schizophrenia.
Topics: Humans; Animals; Schizophrenia; Insulin; Neurobiology; Disks Large Homolog 4 Protein; Receptors, N-Methyl-D-Aspartate; gamma-Aminobutyric Acid; Neurotransmitter Agents
PubMed: 37085712
DOI: 10.1038/s41380-023-02065-4 -
Pathogens (Basel, Switzerland) Nov 2023Host genetic factors significantly influence susceptibility to SARS-CoV-2 infection and COVID-19 severity. Among these genetic factors are single-nucleotide variants... (Review)
Review
Host genetic factors significantly influence susceptibility to SARS-CoV-2 infection and COVID-19 severity. Among these genetic factors are single-nucleotide variants (SNVs). and genes have been associated with severe COVID-19 in populations from the United Kingdom, Africa, and Latin America. IFNAR1 and IFNAR2 are subunits forming the type I interferon receptor (IFNAR). SNVs in the genes impact protein function, affecting antiviral response and disease phenotypes. This systematic review aimed to describe and variants associated with COVID-19 susceptibility and severity. Accordingly, the current review focused on and studies published between January 2021 and February 2023, utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol. The electronic search was conducted in PubMed databases using Boolean operators and inclusion and exclusion criteria. Of the 170 literature pieces, 11 studies were included. We include case reports of rare SNVs, defined by minor allele frequency (MAF) < 1%, and genome-wide associated studies (GWAS). Variants in and could potentially be new targets for therapies that limit the infection and the resulting inflammation by SARS-CoV-2 infection.
PubMed: 38003785
DOI: 10.3390/pathogens12111320 -
Archives of Academic Emergency Medicine 2024Traumataic brain injury (TBI) represents a significant global health burden. This systematic review delves into the comparison of S100B and Neuron-Specific Enolase (NSE)... (Review)
Review
INTRODUCTION
Traumataic brain injury (TBI) represents a significant global health burden. This systematic review delves into the comparison of S100B and Neuron-Specific Enolase (NSE) regarding their diagnostic and prognostic accuracy in TBI within the adult population.
METHODS
Conducted on October 21, 2023, the search identified 24 studies encompassing 6454 adult patients. QUADAS-2 and QUAPAS tools were employed to assess the risk of bias. The analyses aimed to evaluate the diagnostic and prognostic performance of S100B and NSE based on sensitivity, specificity, and area under the curve (AUC). The outcomes were detecting intracranial injury, mortality, and unfavorable outcome.
RESULTS
Pooled data analysis tended towards favoring S100B for diagnostic and prognostic purposes. S100B exhibited a diagnostic AUC of 0.74 (95% confidence interval (CI): 0.70-0.78), sensitivity of 80% (95% CI: 63%-90%), and specificity of 59% (95% CI: 45%-72%), outperforming NSE with an AUC of 0.66 (95% CI: 0.61-0.70), sensitivity of 74% (95% CI: 53%-88%), and specificity of 46% (95% CI: 24%-69%). Notably, both biomarkers demonstrated enhanced diagnostic value when blood samples were collected within 12 hours post-injury. The analyses also revealed the excellent diagnostic ability of S100B with a sensitivity of 99% (95% CI: 4%-100%) and a specificity of 76% (95% CI: 51%-91%) in mild TBI patients (AUC = 0.89 [0.86-0.91]). In predicting mortality, S100B showed a sensitivity of 90% (95% CI: 65%-98%) and specificity of 61% (95% CI: 39%-79%), slightly surpassing NSE's performance with a sensitivity of 88% (95% CI: 76%-95%) and specificity of 56% (95% CI: 47%-65%). For predicting unfavorable outcomes, S100B exhibited a sensitivity of 83% (95% CI: 74%-90%) and specificity of 51% (95% CI: 30%-72%), while NSE had a sensitivity of 80% (95% CI: 64%-90%) and specificity of 59% (95% CI: 46%-71%).
CONCLUSION
Although neither biomarker has shown promising diagnostic performance in detecting abnormal computed tomography (CT) findings, they have displayed acceptable outcome prediction capabilities, particularly with regard to mortality.
PubMed: 38572218
DOI: 10.22037/aaem.v12i1.2222 -
Scientific Reports Jun 2024To elucidate the correlation of HIF1A with clinicopathologic characteristics in patients with gastric cancer (GC), we conducted a systematic review and meta-analysis. We... (Meta-Analysis)
Meta-Analysis
To elucidate the correlation of HIF1A with clinicopathologic characteristics in patients with gastric cancer (GC), we conducted a systematic review and meta-analysis. We searched PubMed, Embase and Web of Science for studies on GC and HIF1A, covering studies published until January 31st, 2022. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for clinical characteristics based on high and low HIF1A protein levels. We used random-effects and fixed-effects meta-analysis methods to determine mean effect sizes of ORs and evaluated publication heterogeneity with τ, I, and Q values. Additionally, we generated funnel plots to inspect publication bias. Our meta-analysis included 20 publications with 3416 GC patients to estimate the association between high or low HIF1A expression and clinical characteristics. Positive HIF1A expression was significantly associated with T stage progression (OR: 2.46; 95% CI 1.81-3.36; P < 0.01), TNM stage progression (OR: 2.50; 95% CI 1.61-3.87; P < 0.01), lymph node metastasis (OR: 2.06; 95% CI 1.44-2.94; P < 0.01), undifferentiated status (OR: 1.83; 95% CI 1.45-2.32; P < 0.01), M stage progression (OR: 2.34; 95% CI 1.46-3.77; P < 0.01), Borrmann stage progression (OR: 1.48; 95% CI 1.02-2.15; P = 0.04), larger tumor size (OR: 1.27; 95% CI 1.06-1.52; P < 0.01), vascular invasion (OR: 1.94; 95% CI 1.38-2.72; P < 0.01), and higher vascular endothelial growth factor (VEGF) protein expression (OR: 2.61; 95% CI 1.79-3.80; P < 0.01) in our meta-analysis. GC Patients highly expressing HIF1A protein might be prone to tumor progression, poorly differentiated GC cell types, and a high VEGF expression.
Topics: Stomach Neoplasms; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lymphatic Metastasis; Biomarkers, Tumor; Neoplasm Staging; Vascular Endothelial Growth Factor A; Gene Expression Regulation, Neoplastic
PubMed: 38877062
DOI: 10.1038/s41598-024-63019-6 -
PloS One 2024Colibacillosis, a disease caused by Escherichia coli in broiler chickens has serious implications on food safety, security, and economic sustainability. Antibiotics are... (Meta-Analysis)
Meta-Analysis
Colibacillosis, a disease caused by Escherichia coli in broiler chickens has serious implications on food safety, security, and economic sustainability. Antibiotics are required for treating the disease, while vaccination and biosecurity are used for its prevention. This systematic review and meta-analysis, conducted under the COST Action CA18217-European Network for Optimization of Veterinary Antimicrobial Treatment (ENOVAT), aimed to assess the efficacy of E. coli vaccination in broiler production and provide evidence-based recommendations. A comprehensive search of bibliographic databases, including, PubMed, CAB Abstracts, Web of Science and Agricola, yielded 2,722 articles. Following a defined protocol, 39 studies were selected for data extraction. Most of the studies were experimental infection trials, with only three field studies identified, underscoring the need for more field-based research. The selected studies reported various types of vaccines, including killed (n = 5), subunit (n = 8), outer membrane vesicles/protein-based (n = 4), live/live-attenuated (n = 16), and CpG oligodeoxynucleotides (ODN) (n = 6) vaccines. The risk of bias assessment revealed that a significant proportion of studies reporting mortality (92.3%) or feed conversion ratio (94.8%) as outcomes, had "unclear" regarding bias. The meta-analysis, focused on live-attenuated and CpG ODN vaccines, demonstrated a significant trend favoring both vaccination types in reducing mortality. However, the review also highlighted the challenges in reproducing colibacillosis in experimental setups, due to considerable variation in challenge models involving different routes of infection, predisposing factors, and challenge doses. This highlights the need for standardizing the challenge model to facilitate comparisons between studies and ensure consistent evaluation of vaccine candidates. While progress has been made in the development of E. coli vaccines for broilers, further research is needed to address concerns such as limited heterologous protection, practicability for application, evaluation of efficacy in field conditions and adoption of novel approaches.
Topics: Animals; Escherichia coli; Chickens; Poultry Diseases; Escherichia coli Infections; Escherichia coli Vaccines; Vaccination
PubMed: 38517875
DOI: 10.1371/journal.pone.0301029 -
Expert Review of Vaccines 2024Different COVID-19 vaccines are being utilized as boosters. This systematic review and meta-analysis aims to evaluate the reactogenicity of COVID-19 vaccines given as... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Different COVID-19 vaccines are being utilized as boosters. This systematic review and meta-analysis aims to evaluate the reactogenicity of COVID-19 vaccines given as booster doses, according to vaccine type, dose, timing, participant characteristics and primary immunization regimen received.
METHODS
Four databases (MEDLINE, Embase, Web of Science and CENTRAL) were searched for randomized controlled trials between 1 January 2020 and 1 January 2023 according to predetermined criteria.
RESULTS
Twenty-eight studies describing 19 vaccines of four different types (viral vector, inactivated, mRNA and protein sub-unit) were identified. BNT162b2 vaccine (Pfizer-BioNTech) was selected as the control as it was most often compared with other vaccines. Fever, fatigue, headache, injection-site pain, redness, and swelling were the most frequently reported solicited events. mRNA vaccines were the most reactogenic, followed by viral vector vaccines and protein sub-unit vaccines, while inactivated vaccines were the least reactogenic. Full-dose vaccines were more reactogenic than half-dose vaccines. Heterologous BNT162b2 boosters were more reactogenic than boosters with the same vaccine used for primary immunization.
CONCLUSIONS
COVID-19 vaccine booster schedules have distinct reactogenicity profiles, dependent on dose and vaccine type, which may allow targeted recommendations and provide choice for specific populations. Greater standardization of adverse event reporting will aid future studies.
Topics: Humans; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Immunization, Secondary
PubMed: 38376528
DOI: 10.1080/14760584.2024.2315089 -
Vaccines Jan 2024This systematic review investigated the association between platform type and the clinical efficacy of SARS-CoV-2 vaccines using the meta-regression of randomized... (Review)
Review
Effect of Platform Type on Clinical Efficacy of SARS-CoV-2 Vaccines in Prime Vaccination Settings: A Systematic Review and Meta-Regression of Randomized Controlled Trials.
This systematic review investigated the association between platform type and the clinical efficacy of SARS-CoV-2 vaccines using the meta-regression of randomized controlled trials to compare the rates of the first appearance of symptomatic COVID-19 on the platforms. The trial search was conducted using PubMed, ClinicalTrials.gov, and the EU Clinical Trials Register. The main selection criteria included: non-active control, immunocompetent individuals without previous vaccination, and a low risk of bias. The platform effect was summarized with an incidence rate ratio (IRR) and a 95% confidence interval for every platform category against the reference. IRR was obtained by random-effect meta-regression with adjustment for confounding by effect modifiers. The analysis was conducted in per-protocol (PP) and modified intention-to-treat (mITT) sets. Six vaccine types with 35 trials were included. Vector vaccines were a reference category. In the PP set, rates of symptomatic COVID-19 on mRNA and protein subunit vaccines were significantly lower than on the vector: IRR = 0.30 [0.19; 0.46], = 0.001 and 0.63 [0.46; 0.86], = 0.012, respectively. There was no difference for inactivated and virus-like particle vaccines compared to the vector: IRR = 0.98 [0.71; 1.36], = 0.913 and 0.70 [0.41; 1.20], = 0.197, respectively. The rate of cases on DNA vaccines was significantly higher than that on the vector: IRR = 2.58 [1.17; 5.68], = 0.034. Results for the mITT set were consistent. Platform type is an effect modifier of the clinical efficacy of SARS-CoV-2 vaccines.
PubMed: 38400114
DOI: 10.3390/vaccines12020130 -
Drug Discoveries & Therapeutics Jul 2023Traditional medicines are recently being focused on to treat diabetes and its complications because of their lack of toxic and/or side effects. This report describes the...
Traditional medicines are recently being focused on to treat diabetes and its complications because of their lack of toxic and/or side effects. This report describes the effects of 7-O-galloyl-D-sedoheptulose (GS), a polyphenolic compound isolated from Corni Fructus, on type 2 diabetic db/db mice with hepatic and pancreatic damage. We examined several biochemical factors and oxidative stress- and inflammation-related markers. In the serum, levels of glucose, leptin, insulin, C-peptide, resistin, tumor necrosis factor-α, and interleukin-6 were down-regulated, while adiponectin was augmented by GS treatment. In addition, GS suppressed the reactive oxygen species and lipid peroxidation in the serum, liver, and pancreas, but increased the pancreatic insulin and pancreatic C-peptide contents. These results were derived from attenuating the expression of nicotinamide adenine dinucleotide phosphate oxidase subunit proteins, Nox-4 and p22. Augmented nuclear factor (NF)-E2-related factor 2 and heme oxygenase-1 were reduced with a decrease in oxidative stress during GS treatment. NF-κB-related pro-inflammatory factors were also alleviated in hepatic tissue. Moreover, GS modulated the protein expressions of pro-inflammatory NF-κB, cyclooxygenase-2, inducible nitric oxide synthase, c-Jun N-terminal kinase (JNK), phosphor-JNK, activator protein-1, transforming growth factor-β, and fibronectin. Based on these results, we demonstrated that the anti-diabetic action of GS may be due to its anti-oxidative stress property and anti-inflammatory action.
Topics: Mice; Animals; Cornus; Diabetes Mellitus, Type 2; Polyphenols; NF-kappa B; Diabetes Mellitus, Experimental; C-Peptide; Liver; Pancreas; Insulin
PubMed: 37245985
DOI: 10.5582/ddt.2022.01097