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Nutrients Sep 2023Hypertension is the leading preventable risk factor for cardiovascular disease and all-cause mortality worldwide. However, studies have shown increased risk of mortality... (Meta-Analysis)
Meta-Analysis Review
Hypertension is the leading preventable risk factor for cardiovascular disease and all-cause mortality worldwide. However, studies have shown increased risk of mortality from heart disease and stroke even within the normal blood pressure (BP) range, starting at BPs above 110-115/70-75 mm Hg. Nutraceuticals, such as vitamins and minerals, have been studied extensively for their efficacy in lowering BP and may be of benefit to the general, normotensive population in achieving optimal BP. Our study investigated the effects of six nutraceuticals (Vitamins: C, D, E; Minerals: Calcium, Magnesium, Potassium) on both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in this population. We performed a systematic review and pairwise meta-analysis for all six supplements versus placebo. Calcium and magnesium achieved significant reductions in both SBP and DBP of -1.37/-1.63 mm Hg and -2.79/-1.56 mm Hg, respectively. Vitamin E and potassium only yielded significant reductions in SBP with values of -1.76 mm Hg and -2.10 mm Hg, respectively. Vitamins C and D were not found to significantly lower either SBP or DBP. Future studies should determine optimal dosage and treatment length for these supplements in the general, normotensive population.
Topics: Humans; Vitamins; Blood Pressure; Magnesium; Calcium; Dietary Supplements; Hypertension; Minerals; Hypotension; Calcium, Dietary; Potassium; Antihypertensive Agents
PubMed: 37836507
DOI: 10.3390/nu15194223 -
Translational Psychiatry Jul 2023Obsessive-compulsive disorder (OCD) is a frequent and debilitating mental illness. Although efficacious treatment options are available, treatment resistance rates are...
Obsessive-compulsive disorder (OCD) is a frequent and debilitating mental illness. Although efficacious treatment options are available, treatment resistance rates are high. Emerging evidence suggests that biological components, especially autoimmune processes, may be associated with some cases of OCD and treatment resistance. Therefore, this systematic literature review summarizing all case reports/case series as well as uncontrolled and controlled cross-sectional studies investigating autoantibodies in patients with OCD and obsessive-compulsive symptoms (OCS) was performed. The following search strategy was used to search PubMed: "(OCD OR obsessive-compulsive OR obsessive OR compulsive) AND (antib* OR autoantib* OR auto-antib* OR immunoglob* OR IgG OR IgM OR IgA)". Nine case reports with autoantibody-associated OCD/OCS were identified: five patients with anti-neuronal autoantibodies (against N-methyl-D-aspartate-receptor [NMDA-R], collapsin response mediator protein [CV2], paraneoplastic antigen Ma2 [Ma2], voltage gated potassium channel complex [VGKC], and "anti-brain" structures) and four with autoantibodies associated with systemic autoimmune diseases (two with Sjögren syndrome, one with neuropsychiatric lupus, and one with anti-phospholipid autoantibodies). Six patients (67%) benefited from immunotherapy. In addition, eleven cross-sectional studies (six with healthy controls, three with neurological/psychiatric patient controls, and two uncontrolled) were identified with inconsistent results, but in six studies an association between autoantibodies and OCD was suggested. In summary, the available case reports suggest an association between OCD and autoantibodies in rare cases, which has been supported by initial cross-sectional studies. However, scientific data is still very limited. Thus, further studies on autoantibodies investigated in patients with OCD compared with healthy controls are needed.
Topics: Humans; Autoantibodies; Cross-Sectional Studies; Obsessive-Compulsive Disorder; Receptors, N-Methyl-D-Aspartate; Brain
PubMed: 37400462
DOI: 10.1038/s41398-023-02545-9 -
Therapeutic Advances in Chronic Disease 2024The effectiveness and side effects between different medical treatments in patients with primary hyperaldosteronism have not been systematically studied.
BACKGROUND
The effectiveness and side effects between different medical treatments in patients with primary hyperaldosteronism have not been systematically studied.
OBJECTIVE
To analyze the efficacy between different mineralocorticoid receptor antagonists (MRAs) and epithelial sodium channel (ENaC) inhibitors in a network meta-analysis (NMA) framework, while also evaluating adverse events.
DESIGN
Systematic review and NMA.
DATA SOURCES AND METHODS
The systematic review and NMA was reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, MEDLINE, the Cochrane library, and Excerpta Medica database (EMBASE) were searched for randomized controlled trials (RCTs) involving adult patients with primary hyperaldosteronism until 23 June 2023. Studies that compared the efficacy and side effects of different medical treatments of primary hyperaldosteronism were included. The primary outcomes included the effect on blood pressure, serum potassium, and major adverse cardiovascular events. The secondary outcomes were adverse events related to MRAs (hyperkalemia and gynecomastia). Frequentist NMA and pairwise meta-analysis were conducted.
RESULTS
A total of 5 RCTs comprising 392 participants were included. Eplerenone, esaxerenone, and amiloride were compared to spironolactone and demonstrated comparable effect on the reduction of systolic blood pressure. In comparison to spironolactone, eplerenone exhibited a less pronounced effect on reducing diastolic blood pressure [-4.63 mmHg; 95% confidence interval (CI): -8.87 to -0.40 mmHg] and correcting serum potassium (-0.2 mg/dL; 95% CI: -0.37 to -0.03 mg/dL). Spironolactone presented a higher risk of gynecomastia compared with eplerenone (relative risk: 4.69; 95% CI: 3.58-6.14).
CONCLUSION
The present NMA indicated that the blood pressure reduction and potassium-correcting effects of the three MRAs may demonstrate marginal differences, with confidence levels in the evidence being very low. Therefore, further research is needed to explore the efficacy of these MRAs, especially regarding their impact on mortality and cardiovascular outcomes.
TRIAL REGISTRATION
PROSPERO (CRD: 42023446811).
PubMed: 38511069
DOI: 10.1177/20406223241239775 -
Journal of Orthopaedic Surgery and... Mar 2024The lack of effective understanding of the pain mechanism of McCune-Albright syndrome (MAS) has made the treatment of pain in this disease a difficult clinical... (Review)
Review
BACKGROUND
The lack of effective understanding of the pain mechanism of McCune-Albright syndrome (MAS) has made the treatment of pain in this disease a difficult clinical challenge, and new therapeutic targets are urgently needed to address this dilemma.
OBJECTIVE
This paper summarizes the novel mechanisms, targets, and treatments that may produce pain in MAS and fibrous dysplasia (polyfibrous dysplasia, or FD).
METHODS
We conducted a systematic search in the PubMed database, Web of Science, China Knowledge Network (CNKI) with the following keywords: "McCune-Albright syndrome (MAS); polyfibrous dysplasia (FD); bone pain; bone remodeling; G protein coupled receptors; GDNF family receptors; purinergic receptors and glycogen synthase kinase", as well as other keywords were systematically searched. Papers published between January 2018 and May 2023 were selected for finding. Initial screening was performed by reading the titles and abstracts, and available literature was screened against the inclusion and exclusion criteria.
RESULTS
In this review, we systematically analyzed the cutting-edge advances in this disease, synthesized the findings, and discussed the differences. With regard to the complete mechanistic understanding of the pain condition in FD/MAS, in particular, we collated new findings on new pathways, neurotrophic factor receptors, purinergic receptors, interferon-stimulating factors, potassium channels, protein kinases, and corresponding hormonal modulation and their respective strengths and weaknesses.
CONCLUSION
This paper focuses on basic research to explore FD/MAS pain mechanisms. New nonneuronal and molecular mechanisms, mechanically loaded responsive neurons, and new targets for potential clinical interventions are future research directions, and a large number of animal experiments, tissue engineering techniques, and clinical trials are still needed to verify the effectiveness of the targets in the future.
Topics: Animals; Fibrous Dysplasia, Polyostotic; Fibrous Dysplasia of Bone; Pain; Bone Remodeling; China
PubMed: 38515135
DOI: 10.1186/s13018-024-04687-y -
Frontiers in Neuroscience 2023Xenon exhibits significant neuroprotection against a wide range of neurological insults in animal models. However, clinical evidence that xenon improves outcomes in...
INTRODUCTION
Xenon exhibits significant neuroprotection against a wide range of neurological insults in animal models. However, clinical evidence that xenon improves outcomes in human studies of neurological injury remains elusive. Previous reviews of xenon's method of action have not been performed in a systematic manner. The aim of this review is to provide a comprehensive summary of the evidence underlying the cellular interactions responsible for two phenomena associated with xenon administration: anesthesia and neuroprotection.
METHODS
A systematic review of the preclinical literature was carried out according to the PRISMA guidelines and a review protocol was registered with PROSPERO. The review included both models of the central nervous system and mammalian studies. The search was performed on 27th May 2022 in the following databases: Ovid Medline, Ovid Embase, Ovid Emcare, APA PsycInfo, and Web of Science. A risk of bias assessment was performed utilizing the Office of Health Assessment and Translation tool. Given the heterogeneity of the outcome data, a narrative synthesis was performed.
RESULTS
The review identified 69 articles describing 638 individual experiments in which a hypothesis was tested regarding the interaction of xenon with cellular targets including: membrane bound proteins, intracellular signaling cascades and transcription factors. Xenon has both common and subtype specific interactions with ionotropic glutamate receptors. Xenon also influences the release of inhibitory neurotransmitters and influences multiple other ligand gated and non-ligand gated membrane bound proteins. The review identified several intracellular signaling pathways and gene transcription factors that are influenced by xenon administration and might contribute to anesthesia and neuroprotection.
DISCUSSION
The nature of xenon NMDA receptor antagonism, and its range of additional cellular targets, distinguishes it from other NMDA antagonists such as ketamine and nitrous oxide. This is reflected in the distinct behavioral and electrophysiological characteristics of xenon. Xenon influences multiple overlapping cellular processes, both at the cell membrane and within the cell, that promote cell survival. It is hoped that identification of the underlying cellular targets of xenon might aid the development of potential therapeutics for neurological injury and improve the clinical utilization of xenon.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: 336871.
PubMed: 37521706
DOI: 10.3389/fnins.2023.1225191 -
Biomedicine & Pharmacotherapy =... Jan 2024Development of therapeutic agents that have fewer adverse effects and have higher efficacy for diseases, such as cancer, metabolic disorders, neurological diseases,... (Review)
Review
Development of therapeutic agents that have fewer adverse effects and have higher efficacy for diseases, such as cancer, metabolic disorders, neurological diseases, infections, cardiovascular diseases, and respiratory diseases, are required. Recent studies have focused on identifying novel sources for pharmaceutical molecules to develop therapies against these diseases. Among the sources for potentially new therapies, animal venom-derived molecules have generated much interest. Various animal venom-derived proteins and peptides have been isolated, identified, synthesized, and tested to develop drugs. Venom-derived peptides have several biomedical properties, such as proapoptotic, cell migration, and autophagy regulation activities in cancer cell models; induction of vasodilation by nitric oxide and regulation of angiotensin II; modification of insulin response by controlling calcium and potassium channels; regulation of pain receptor activity; modulation of immune cell activity; alteration of motor neuron activity; degradation or inhibition of β-amyloid plaque formation; antibacterial, antifungal, antiviral, and antiprotozoal activities; increase in sperm motility and potentiation of erectile function; reduction of intraocular pressure; anticoagulation, fibrinolytic, and antithrombotic activities; etc. This systematic review compiles these biomedical properties and potential biomedical applications of synthesized animal venom-derived peptides reported in the latest research. In addition, the limitations and areas of opportunity in this research field are discussed so that new studies can be developed based on the data presented.
Topics: Animals; Male; Venoms; Sperm Motility; Peptides; Angiotensin II
PubMed: 38113629
DOI: 10.1016/j.biopha.2023.116015 -
Molecular Medicine Reports Feb 2024Liddle syndrome is an autosomal dominant form of monogenic hypertension that is caused by mutations in , or , which respectively encode the α, β and γ subunits of...
Liddle syndrome is an autosomal dominant form of monogenic hypertension that is caused by mutations in , or , which respectively encode the α, β and γ subunits of the epithelial sodium channel. In the present study, DNA was extracted from leukocytes in peripheral blood obtained from all members of a family with Liddle syndrome. Whole‑exome sequencing and Sanger sequencing were performed to assess the candidate variant and a co‑segregation analysis was conducted. A frameshift mutation in (NM_ 000336: c.1806dupG, p.Pro603Alafs*5) in the family was identified, characterized by early‑onset hypertension and hypokalemia. The mutation led to the truncation of the β subunit of the epithelial sodium channel and a lack of the conservative PY motif. Furthermore, a systematic review of follow‑up data from patients with Liddle syndrome with mutations was performed. The follow‑up data of 108 patients with pathogenic mutations from 47 families were summarized. Phenotypic heterogeneity was evident in patients with Liddle syndrome and early‑onset hypertension was the most frequent symptom. Patients responded well to targeted amiloride therapy with significant improvements in blood pressure and serum potassium concentration. The present study demonstrates that confirmatory genetic testing and targeted therapy can prevent premature onset of clinical endpoint events in patients with Liddle syndrome.
Topics: Humans; Liddle Syndrome; Epithelial Sodium Channels; Frameshift Mutation; Mutation; Hypertension; Potassium
PubMed: 38099339
DOI: 10.3892/mmr.2023.13142