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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 -
Biologicals : Journal of the... May 2023The treatment of Klebsiella pneumoniae is faced with challenges demanding the development of a vaccination strategy. However, no approved and globally available vaccine... (Review)
Review
The treatment of Klebsiella pneumoniae is faced with challenges demanding the development of a vaccination strategy. However, no approved and globally available vaccine exists yet. This study aimed to systematically review all published data on K. pneumoniae vaccines in animal models. Without time restrictions, electronic databases were searched using appropriate keywords. The retrieved studies were screened and the data of those that matched our inclusion criteria were collected and analyzed. In total, 2027 records were retrieved; of which 35 studies were included for systematic review. The most frequently used animal model was BALB/c mice. Proteins, polysaccharides, and their combinations (conjugates) were the most common vaccine candidates used. The amount of antigen, the route used for immunization, and the challenge strategy was varying in the studies and were chosen based on several factors such as the animal model, the type of antigen, and the schedule of immunization. Almost all studies claimed that their vaccine was effective/protective, indicated by increasing survival rate, reducing organ bacterial load, and eliciting protective antibody and/or cytokine responses. Altogether, the information presented here will assist researchers to have a better look at the K. pneumoniae vaccine candidates and to take more effective steps in the future.
Topics: Animals; Mice; Bacterial Vaccines; Immunization; Klebsiella Infections; Klebsiella pneumoniae; Mice, Inbred BALB C; Models, Animal; Vaccination
PubMed: 37126906
DOI: 10.1016/j.biologicals.2023.101678 -
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 -
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 -
Archives of Dermatological Research Feb 2024Psoriasis is a chronic, inflammatory skin disorder characterized by well-demarcated erythematous lesions with surface scaling. The disease is underpinned by a... (Meta-Analysis)
Meta-Analysis Review
Psoriasis is a chronic, inflammatory skin disorder characterized by well-demarcated erythematous lesions with surface scaling. The disease is underpinned by a dysregulated immune response with a shift in the balance of neutrophils, lymphocytes and platelets. We sought to evaluate the novel systemic inflammatory markers, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as psoriatic indicators. Pubmed, Web of Science and Scopus were systematically searched for relevant studies. Twenty-four studies consisting of a total of 2,275 psoriatic patients (1,301 males and 974 females) and 2,334 healthy controls (1,401 males and 933 females) were identified for inclusion in the quantitative analysis. The NLR and PLR were found to be significantly increased in psoriatic patients [standardized mean difference (SMD) = 0.68, 95% CI 0.56-0.80, p < 0.01, and SMD = 0.37, 95% CI 0.14-0.60, p < 0.01, respectively]. However, no association between the NLR and PLR with psoriasis severity was detected (p = 0.93, and p = 0.83, respectively). In conclusion, the NLR and PLR are simple and cost-effective markers of psoriatic presence, but their value as severity markers requires further study.
Topics: Humans; Female; Male; Neutrophils; Psoriasis; Skin; Lymphocytes
PubMed: 38329632
DOI: 10.1007/s00403-024-02823-6 -
Veterinary Parasitology Jan 2023This review is aimed to (i) appraise the literature on the use of molecular techniques for the detection, quantification and differentiation of gastrointestinal... (Review)
Review
This review is aimed to (i) appraise the literature on the use of molecular techniques for the detection, quantification and differentiation of gastrointestinal helminths (GIH) of equids, (ii) identify the knowledge gaps and, (iii) discuss diagnostic prospects in equine parasitology. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews, we retrieved 54 studies (horses: 50/54; donkeys and zebras: 4/54) from four databases. Polymerase chain reaction (PCR) was employed in all of the studies whereas PCR amplicons were sequenced in only 18 of them. Other techniques used (including modifications of PCR) were reverse line blot, quantitative (q)PCR, restriction fragment length polymorphism, nested-PCR, PCR-directed next-generation sequencing, Southern blotting, single strand conformation polymorphism, PCR-enzyme linked immunosorbent assay, matrix-assisted laser desorption/ionisation-time of flight and random amplification of polymorphic DNA. Most of the studies (53/54) used nuclear ribosomal RNA (including the internal transcribed spacers, intergenic spacer, 5.8 S, 18 S, 28 S and 12 S) as target loci while cytochrome c oxidase subunit 1 and random genomic regions were targeted in only three and one studies, respectively. Overall, to date, the majority of molecular studies have focused on the diagnosis and identification of GIHs of equids (i.e. species of Anoplocephala, Craterostomum, cyathostomins, Oesophagodontus, Parascaris, Strongylus, Strongyloides and Triodontophorus), with a recent shift towards investigations on anthelmintic resistance and the use of high-throughput nemabiome metabarcoding. With the increasing reports of anthelmintic resistance in equid GIHs, it is crucial to develop and apply techniques such as advanced metabarcoding for surveillance of parasite populations in order to gain detailed insights into their diversity and sustainable control. To the best of our knowledge, this is the first systematic review that evaluates molecular investigations published on the diagnosis and quantification of equid GIHs and provides useful insights into important knowledge gaps and future research directions in equid molecular parasitology.
Topics: Animals; Anthelmintics; Helminths; Horse Diseases; Horses; Pathology, Molecular; Strongyloidea; Strongylus
PubMed: 36521296
DOI: 10.1016/j.vetpar.2022.109851 -
Clinical Neurology and Neurosurgery Apr 2017Cerebral small vessel disease is considered hereditary in about 5% of patients and is characterized by lacunar infarcts and white matter hyperintensities on MRI. Several... (Review)
Review
Cerebral small vessel disease is considered hereditary in about 5% of patients and is characterized by lacunar infarcts and white matter hyperintensities on MRI. Several monogenic hereditary diseases causing cerebral small vessel disease and stroke have been identified. The purpose of this systematic review is to provide a guide for determining when to consider molecular genetic testing in patients presenting with small vessel disease and stroke. CADASIL, CARASIL, collagen type IV mutations (including PADMAL), retinal vasculopathy with cerebral leukodystrophy, Fabry disease, hereditary cerebral hemorrhage with amyloidosis, and forkhead box C1 mutations are described in terms of genetics, pathology, clinical manifestation, imaging, and diagnosis. These monogenic disorders are often characterized by early-age stroke, but also by migraine, mood disturbances, vascular dementia and often gait disturbances. Some also present with extra-cerebral manifestations such as microangiopathy of the eyes and kidneys. Many present with clinically recognizable syndromes. Investigations include a thorough family medical history, medical history, neurological examination, neuroimaging, often supplemented by specific examinations e.g of the of vision, retinal changes, as well as kidney and heart function. However molecular genetic analysis is the final gold standard of diagnosis. There are increasing numbers of reports on new monogenic syndromes causing cerebral small vessel disease. Genetic counseling is important. Enzyme replacement therapy is possible in Fabry disease, but treatment options remain overall very limited.
Topics: Alopecia; Animals; Brain; Cerebral Infarction; Cerebral Small Vessel Diseases; Humans; Leukoencephalopathies; Spinal Diseases; Stroke
PubMed: 28254515
DOI: 10.1016/j.clineuro.2017.02.015 -
Acta Parasitologica Mar 2022Microsporidiosis as a zoonotic disease has caused serious health problems in high-risk groups, including immunosuppressed individuals. Among the potential animal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Microsporidiosis as a zoonotic disease has caused serious health problems in high-risk groups, including immunosuppressed individuals. Among the potential animal reservoirs of microsporidia, rodents play a key role due to close-contact with humans and their dispersion in different environments. Therefore, this systematic review and meta-analysis aimed to assess the global status and genetic diversity of microsporidia infection in different rodents.
METHODS
The standard protocol of preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed. Scopus, PubMed, Web of Science, and Google Scholar were searched from 1 January 2000 to 15 April 2021. All peer-reviewed original research articles describing the molecular prevalence of microsporidia infection in rodents were included. Inclusion and exclusion criteria were applied. The point estimates and 95% confidence intervals were calculated using a random-effects model. The variance between studies (heterogeneity) were quantified by I index.
RESULTS
Of 1695 retrieved studies, 22 articles (including 34 datasets) were included for final meta-analysis. The pooled global molecular prevalence (95% CI) of microsporidia infection in rodents was 14.2% (95% CI 10.9-18.3%). The highest prevalence of microsporidia was found in Apodemus spp. 27.3% (95% CI 15-44.5%). Enterocytozoon bieneusi was the most common pathogen (26/34; 76.47% studies) according to PCR-based methods, and the genotype D as the highest reported genotype (15 studies).
CONCLUSIONS
The findings of the study showed a relatively high prevalence of microsporidia infection in rodents as a potential animal reservoir for infecting human. Given the relatively high incidence of microsporidiosis, designing strategies for control, and prevention of microsporidia infection in rodents should be recommended.
Topics: Animals; Enterocytozoon; Feces; Genotype; Microsporidia; Microsporidiosis; Molecular Epidemiology; Prevalence; Public Health; Rodentia
PubMed: 34176043
DOI: 10.1007/s11686-021-00447-8 -
Microbial Genomics Nov 2023(group B , GBS) has recently emerged as an important pathogen among adults. However, it is overlooked in this population, with all global efforts being directed towards...
(group B , GBS) has recently emerged as an important pathogen among adults. However, it is overlooked in this population, with all global efforts being directed towards its containment among pregnant women and neonates. This systematic review assessed the molecular epidemiology and compared how the lineages circulating among non-pregnant populations relate to those of pregnant and neonatal populations worldwide. A systematic search was performed across nine databases from 1 January 2000 up to and including 20 September 2021, with no language restrictions. The Joanna Briggs Institute (JBI) Prevalence Critical Appraisal Tool (PCAT) was used to assess the quality of included studies. The global population structure of GBS from the non-pregnant population was analysed using typing and phylogenetic reconstruction tools. Twenty-four articles out of 13 509 retrieved across 9 databases were eligible. Most studies were conducted in the World Health Organization European region (12/24, 50 %), followed by the Western Pacific region (6/24, 25 %) and the Americas region (6/24, 25 %). Serotype V (23%, 2310/10240) and clonal complex (CC) 1 (29 %, 2157/7470) were the most frequent serotype and CC, respectively. The pilus island PI1 : PI2A combination (29 %, 3931/13751) was the most prevalent surface protein gene, while the tetracycline resistance M (55 %, 5892/10624) was the leading antibiotic resistance gene. This study highlights that, given the common serotype distribution identified among non-pregnant populations (V, III, Ia, Ib, II and IV), vaccines including these six serotypes will provide broad coverage. The study indicates advanced molecular epidemiology studies, especially in resource-constrained settings for evidence-based decisions. Finally, the study shows that considering all at-risk populations in an inclusive approach is essential to ensure the sustainable containment of GBS.
Topics: Pregnancy; Adult; Infant, Newborn; Humans; Female; Streptococcus agalactiae; Molecular Epidemiology; Phylogeny; Anti-Bacterial Agents; Databases, Factual
PubMed: 38019122
DOI: 10.1099/mgen.0.001140 -
PLoS Neglected Tropical Diseases Jan 2017Dengue, the predominant arthropod-borne viral disease affecting humans, is caused by one of four distinct serotypes (DENV-1, -2, -3 or -4). A literature analysis and... (Review)
Review
Dengue, the predominant arthropod-borne viral disease affecting humans, is caused by one of four distinct serotypes (DENV-1, -2, -3 or -4). A literature analysis and review was undertaken to describe the molecular epidemiological trends in dengue disease and the knowledge generated in specific molecular topics in Latin America, including the Caribbean islands, from 2000 to 2013 in the context of regional trends in order to identify gaps in molecular epidemiological knowledge and future research needs. Searches of literature published between 1 January 2000 and 30 November 2013 were conducted using specific search strategies for each electronic database that was reviewed. A total of 396 relevant citations were identified, 57 of which fulfilled the inclusion criteria. All four dengue virus serotypes were present and co-circulated in many countries over the review period (with the predominance of individual serotypes varying by country and year). The number of countries in which more than one serotype circulated steadily increased during the period under review. Molecular epidemiology data were found for Argentina, Bolivia, Brazil, the Caribbean region, Colombia, Ecuador, Mexico and Central America, Paraguay, Peru and Venezuela. Distinct lineages with different dynamics were found in each country, with co-existence, extinction and replacement of lineages occurring over the review period. Despite some gaps in the literature limiting the possibility for comparison, our review has described the molecular epidemiological trends of dengue infection. However, several gaps in molecular epidemiological information across Latin America and the Caribbean were identified that provide avenues for future research; in particular, sequence determination of the dengue virus genome is important for more precise phylogenetic classification and correlation with clinical outcome and disease severity.
Topics: Dengue; Dengue Virus; Humans; Latin America; Molecular Epidemiology; Phylogeny; South America
PubMed: 28068335
DOI: 10.1371/journal.pntd.0005224