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Molecular Neurodegeneration Nov 2022The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely... (Review)
Review
The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely resolved, they have been recognized for their signaling engagements and trafficking abilities, navigating a number of molecules between endosome, Golgi compartments, and the cell surface. Strikingly, recent studies connected all the VPS10p-D receptors to Alzheimer's disease (AD) development. In addition, they have been also associated with diseases comorbid with AD such as diabetes mellitus and major depressive disorder. This systematic review elaborates on genetic, functional, and mechanistic insights into how dysfunction in VPS10p-D receptors may contribute to AD etiology, AD onset diversity, and AD comorbidities. Starting with their functions in controlling cellular trafficking of amyloid precursor protein and the metabolism of the amyloid beta peptide, we present and exemplify how these receptors, despite being structurally similar, regulate various and distinct cellular events involved in AD. This includes a plethora of signaling crosstalks that impact on neuronal survival, neuronal wiring, neuronal polarity, and synaptic plasticity. Signaling activities of the VPS10p-D receptors are especially linked, but not limited to, the regulation of neuronal fitness and apoptosis via their physical interaction with pro- and mature neurotrophins and their receptors. By compiling the functional versatility of VPS10p-D receptors and their interactions with AD-related pathways, we aim to further propel the AD research towards VPS10p-D receptor family, knowledge that may lead to new diagnostic markers and therapeutic strategies for AD patients.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Depressive Disorder, Major; Protein Transport; Nerve Growth Factors
PubMed: 36397124
DOI: 10.1186/s13024-022-00576-2 -
Molecular Biology Reports Nov 2022Angiotensin-converting enzyme 2 (ACE2) is known as the major viral entry site for SARS-CoV-2. However, viral tissue tropism and high rate of infectivity do not directly... (Review)
Review
BACKGROUND
Angiotensin-converting enzyme 2 (ACE2) is known as the major viral entry site for SARS-CoV-2. However, viral tissue tropism and high rate of infectivity do not directly correspond with the level of ACE2 expression in the organs. It may suggest involvement of other receptors or accessory membrane proteins in SARSCoV-2 cell entry.
METHODS AND RESULTS
A systematic search was carried out in PubMed/Medline, EMBASE, and Cochrane Library for studies reporting SARS-CoV-2 cell entry. We used a group of the MeSH terms including "cell entry", "surface receptor", "ACE2", and "SARS-CoV-2". We reviewed all selected papers published in English up to end of February 2022. We found several receptors or auxiliary membrane proteins (including CD147, NRP-1, CD26, AGTR2, Band3, KREMEN1, ASGR1, ANP, TMEM30A, CLEC4G, and LDLRAD3) along with ACE2 that facilitate virus entry and transmission. Expression of Band3 protein on the surface of erythrocytes and evidence of binding with S protein of SARS-CoV-2 may explain asymptomatic hypoxemia during COVID19 infection. The variants of SARS-CoV-2 including the B.1.1.7 (Alpha), B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.617.2+ (Delta+), and B.1.1.529 (Omicron) may have different potency to bond with these receptors.
CONCLUSIONS
The high rate of infectivity of SARS-CoV-2 may be due to its ability to enter the host cell through a group of cell surface receptors. These receptors are potential targets to develop novel therapeutic agents for SARS-CoV-2.
Topics: Humans; Angiotensin-Converting Enzyme 2; Asialoglycoprotein Receptor; COVID-19; Protein Binding; Receptors, Virus; SARS-CoV-2; Spike Glycoprotein, Coronavirus
PubMed: 35754059
DOI: 10.1007/s11033-022-07700-x -
The Japanese Dental Science Review Dec 2023To evaluate the effectiveness of antiseptic mouthwashes in reducing SARS-CoV-2 load clinically and in vitro. A systematic electronic search (MEDLINE/Scopus/Cochrane) was... (Review)
Review
To evaluate the effectiveness of antiseptic mouthwashes in reducing SARS-CoV-2 load clinically and in vitro. A systematic electronic search (MEDLINE/Scopus/Cochrane) was conducted to identify prospective clinical and in vitro studies published between 2019 included and 16 June 2023 assessing the effectiveness of mouthwashes in reducing SARS-CoV-2 load in saliva or surrogates. Data were summarized in tables and a network meta-analysis was performed for clinical trials. Thirty-five studies (14 RCTs, 21 in vitro) fulfilled the inclusion criteria. The risk of bias was judged to be high for 2 clinical and 7 in vitro studies. The most commonly test product was chlorhexidine alone or in combination with other active ingredients, followed by povidone-iodine, hydrogen peroxide and cetylpyridinium chloride. Overall, the descriptive analysis revealed the effectiveness of the mouthwashes in decreasing the salivary viral load both clinically and in vitro. Network meta-analysis demonstrated a high degree of heterogeneity. Among these studies, only chlorhexidine 0.20% was associated to a significant Ct increase in the saliva 5 min after rinsing compared to non-active control (p = 0.027). Data from clinical and in vitro studies suggested the antiviral efficacy of commonly used mouthwashes. Large well-balanced trials are needed to identify the best rinsing protocols.
PubMed: 37854066
DOI: 10.1016/j.jdsr.2023.09.003 -
JAMA Neurology Dec 2022There are many known acquired risk factors for cerebral palsy (CP), but in some cases, CP is evident without risk factors (cryptogenic CP). Early CP cohort studies... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
There are many known acquired risk factors for cerebral palsy (CP), but in some cases, CP is evident without risk factors (cryptogenic CP). Early CP cohort studies report a wide range of diagnostic yields for sequence variants assessed by exome sequencing (ES) and copy number variants (CNVs) assessed by chromosomal microarray (CMA).
OBJECTIVE
To synthesize the emerging CP genetics literature and address the question of what percentage of individuals with CP have a genetic disorder via ES and CMA.
DATA SOURCES
Searched articles were indexed by PubMed with relevant queries pertaining to CP and ES/CMA (query date, March 15, 2022).
STUDY SELECTION
Inclusion criteria were as follows: primary research study, case series with 10 or more nonrelated individuals, CP diagnosis, and ES and/or CMA data used for genetic evaluation. Nonblinded review was performed.
DATA EXTRACTION AND SYNTHESIS
Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for assessing data quality and validity. Data were extracted by a single observer.
MAIN OUTCOMES AND MEASURES
A separate meta-analysis was performed for each modality (ES, CMA). The primary outcome was proportion/molecular diagnostic yield (number of patients with a discovered genetic disorder divided by the total number of patients in the cohort), evaluated via meta-analysis of single proportions using random-effects logistic regression. A subgroup meta-analysis was conducted, using risk factor classification as a subgroup. A forest plot was used to display diagnostic yields of individual studies.
RESULTS
In the meta-analysis of ES yield in CP, the overall diagnostic yield of ES among the cohorts (15 study cohorts comprising 2419 individuals from 11 articles) was 23% (95% CI, 15%-34%). The diagnostic yield across cryptogenic CP cohorts was 35% (95% CI, 27%-45%), compared with 7% (95% CI, 4%-12%) across cohorts with known risk factors (noncryptogenic CP). In the meta-analysis of CMA yield in CP, the diagnostic yield of CMA among the cohorts (5 study cohorts comprising 294 individuals from 5 articles) was 5% (95% CI, 2%-12%).
CONCLUSIONS AND RELEVANCE
Results of this systematic review and meta-analysis suggest that for individuals with cryptogenic CP, ES followed by CMA to identify molecular disorders may be warranted.
Topics: Humans; Pathology, Molecular; Cerebral Palsy; Microarray Analysis; Exome Sequencing; DNA Copy Number Variations
PubMed: 36279113
DOI: 10.1001/jamaneurol.2022.3549 -
Current Hypertension Reports Jul 2023Accumulating data on the consumption of plant-based diets and their impact on blood pressure indicate a consensus that plant-based diets are linked to reduced blood... (Review)
Review
PURPOSE OF REVIEW
Accumulating data on the consumption of plant-based diets and their impact on blood pressure indicate a consensus that plant-based diets are linked to reduced blood pressure. The suggested mechanisms of action are manifold, and, in this systematic review, we provide a summary of the most recent findings on plant-based diets and their impact on blood pressure, along with an analysis of the molecules accountable for the observed effects.
RECENT FINDINGS
The overwhelming majority of intervention studies demonstrate that plant-based diets result in lower blood pressure readings when compared to diets that are based on animal products. The various mechanisms of action are being clarified. The data discussed in this systematic review allow us to conclude that plant-based diets are associated with lower blood pressure and overall better health outcomes (namely, on the cardiovascular system) when compared to animal-based diets. The mechanisms of action are being actively investigated and involve many macro- and micronutrients plentiful in plants and the dishes prepared with them.
Topics: Animals; Humans; Blood Pressure; Hypertension; Diet; Cardiovascular System; Diet, Vegetarian
PubMed: 37178356
DOI: 10.1007/s11906-023-01243-7 -
Critical Reviews in Oncology/hematology May 2023Pancreato-biliary and gynecological adenocarcinomas need better tools to predict clinical outcome. Potential prognostic mesenchymal(-like) transcriptome-based subtypes... (Review)
Review
Pancreato-biliary and gynecological adenocarcinomas need better tools to predict clinical outcome. Potential prognostic mesenchymal(-like) transcriptome-based subtypes have been identified in these cancers. In this systematic review, we include studies into molecular subtyping and summarize biological and clinical features of the subtypes within and across sites of origin, searching for suggestions to improve classification and prognostication. PubMed and Embase were searched for original research articles describing potential mesenchymal(-like) mRNA-based subtypes in pancreato-biliary or gynecological adenocarcinomas. Studies limited to supervised clustering were excluded. Fourty-four studies discussing cholangiocarcinomas, gallbladder, ampullary, pancreatic, ovarian, and endometrial adenocarcinomas were included. There was overlap in molecular and clinical features in mesenchymal(-like) subtypes across all adenocarcinomas. Approaches including microdissection were more likely to identify prognosis-associated subtypes. To conclude, molecular subtypes in pancreato-biliary and gynecological adenocarcinomas share biological and clinical characteristics. Furthermore, separation of stromal and epithelial signals should be applied in future studies of biliary and gynecological adenocarcinomas.
Topics: Humans; Pancreatic Neoplasms; Adenocarcinoma; Prognosis; Bile Duct Neoplasms; Bile Ducts, Intrahepatic
PubMed: 37004743
DOI: 10.1016/j.critrevonc.2023.103982 -
Biomedicines Dec 2022Lafora disease (LD) is a neurodegenerative condition characterized by the accumulation of polyglucosan bodies (PBs) throughout the brain. Alongside metabolic and... (Review)
Review
BACKGROUND
Lafora disease (LD) is a neurodegenerative condition characterized by the accumulation of polyglucosan bodies (PBs) throughout the brain. Alongside metabolic and molecular alterations, neuroinflammation has emerged as another key histopathological feature of LD.
METHODS
To investigate the role of astrocytes and microglia in LD, we performed a systematic review according to the PRISMA statement. PubMed, Scopus, and Web-of-Science database searches were performed independently by two reviewers.
RESULTS
Thirty-five studies analyzing the relationship of astrocytes and microglia with LD and/or the effects of anti-inflammatory treatments in LD animal models were identified and included in the review. Although LD has long been dominated by a neuronocentric view, a growing body of evidence suggests a role of glial cells in the disease, starting with the finding that these cells accumulate PBs. We discuss the potential meaning of glial PB accumulations, the likely factors activating glial cells, and the possible contribution of glial cells to LD neurodegeneration and epilepsy.
CONCLUSIONS
Given the evidence for the role of neuroinflammation in LD, future studies should consider glial cells as a potential therapeutic target for modifying/delaying LD progression; however, it should be kept in mind that these cells can potentially assume multiple reactive phenotypes, which could influence the therapeutic response.
PubMed: 36551859
DOI: 10.3390/biomedicines10123103 -
International Journal of Molecular... Mar 2024Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor in adults. Despite important advances in understanding the molecular... (Review)
Review
Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor in adults. Despite important advances in understanding the molecular pathogenesis and biology of this tumor in the past decade, the prognosis for GBM patients remains poor. GBM is characterized by aggressive biological behavior and high degrees of inter-tumor and intra-tumor heterogeneity. Increased understanding of the molecular and cellular heterogeneity of GBM may not only help more accurately define specific subgroups for precise diagnosis but also lay the groundwork for the successful implementation of targeted therapy. Herein, we systematically review the key achievements in the understanding of GBM molecular pathogenesis, mechanisms, and biomarkers in the past decade. We discuss the advances in the molecular pathology of GBM, including genetics, epigenetics, transcriptomics, and signaling pathways. We also review the molecular biomarkers that have potential clinical roles. Finally, new strategies, current challenges, and future directions for discovering new biomarkers and therapeutic targets for GBM will be discussed.
Topics: Humans; Glioblastoma; Pathology, Molecular; Brain Neoplasms; Biomarkers; Gene Expression Profiling; Biomarkers, Tumor
PubMed: 38474286
DOI: 10.3390/ijms25053040 -
Frontiers in Medicine 2022Systemic Sclerosis (SSc) is a rare autoimmune disease whose pathogenesis is still poorly understood. The Transforming Growth Factor β superfamily is considered pivotal...
BACKGROUND
Systemic Sclerosis (SSc) is a rare autoimmune disease whose pathogenesis is still poorly understood. The Transforming Growth Factor β superfamily is considered pivotal and a crucial role has been suggested for the type III receptor, Endoglin (ENG). The aim of this systematic review is to investigate and combine the current clinical and molecular available data, to suggest novel hints for further studies.
METHODS
We followed PRISMA guidelines; the search was performed on three databases (MEDLINE, Web of Science, Embase) in date November 2nd, 2021. Subsequent to the exclusion of duplicates, we applied as inclusion criteria: 1. focus on the relationship between ENG and SSc; 2. English language. As exclusion criteria: 1. ENG exclusively as a cellular biomarker; 2. no focus on ENG-SSc relationship; 3. review articles and 4. abstracts that did not add novel data. Eligibility was assessed independently by each author to reduce biases. We divided records into clinical and molecular works and subgrouped them by their study features and aim.
RESULTS
We selected 25 original papers and 10 conference abstracts. Molecular studies included 6 articles and 4 abstracts, whereas clinical studies included 17 articles and 6 abstracts; 2 articles presented both characteristics. Molecular studies were focussed on ENG expression in different cell types, showing an altered ENG expression in SSc-affected cells. Clinical studies mainly suggested that different disease phenotypes can be related to peculiar disregulations in soluble ENG concentrations.
DISCUSSION
Concerning the possible limits of our search, boolean operators in our strings might have been uneffective. However, the use of different strings in different databases should have reduced this issue at a minimum. Another bias can be represented by the selection step, in which we excluded many articles based on the role of Endoglin as a histological vascular marker rather than a signaling receptor. We tried to reduce this risk by performing the selection independently by each author and discussing disagreements. Our systematic review pointed out that ENG has a pivotal role in activating different TGFβ-stimulated pathways that can be crucial in SSc pathogenesis and progression.
PubMed: 36059817
DOI: 10.3389/fmed.2022.964526 -
International Journal of Environmental... Nov 2022This scoping review aims to provide a comprehensive overview of human melioidosis in Southeast Asia as well as to highlight knowledge gaps in the prevalence and risk... (Review)
Review
This scoping review aims to provide a comprehensive overview of human melioidosis in Southeast Asia as well as to highlight knowledge gaps in the prevalence and risk factors of this life-threatening disease using available evidence-based data for better diagnosis and treatment. Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) was used as the guideline for this review. The literature search was conducted on 23 March 2022 through two electronic databases (PubMed and Scopus) using lists of keywords referring to the Medical Subject Headings (MeSH) thesaurus. A total of 38 articles related to human melioidosis were included from 645 screened articles. These studies were carried out between 1986 and 2019 in six Southeast Asian countries: Thailand, Cambodia, Malaysia, Myanmar, Singapore, and Vietnam. Melioidosis has been reported with a high disease prevalence among high-risk populations. Studies in Thailand (48.0%) and Cambodia (74.4%) revealed disease prevalence in patients with septic arthritis and children with suppurative parotitis, respectively. Other studies in Thailand (63.5%) and Malaysia (54.4% and 65.7%) showed a high seroprevalence of melioidosis among Tsunami survivors and military personnel, respectively. Additionally, this review documented soil and water exposure, diabetes mellitus, chronic renal failure, thalassemia, and children under the age of 15 as the main risk factors for melioidosis. Human melioidosis is currently under-reported in Southeast Asia and its true prevalence is unknown.
Topics: Child; Humans; Seroepidemiologic Studies; Asia, Southeastern; Melioidosis; Malaysia; Risk Factors
PubMed: 36497549
DOI: 10.3390/ijerph192315475