-
International Journal of Molecular... May 2024Suicide is a major public health priority, and its molecular mechanisms appear to be related to glial abnormalities and specific transcriptional changes. This study... (Review)
Review
Suicide is a major public health priority, and its molecular mechanisms appear to be related to glial abnormalities and specific transcriptional changes. This study aimed to identify and synthesize evidence of the relationship between glial dysfunction and suicidal behavior to understand the neurobiology of suicide. As of 26 January 2024, 46 articles that met the inclusion criteria were identified by searching PubMed and ISI Web of Science. Most postmortem studies, including 30 brain regions, have determined no density or number of total Nissl-glial cell changes in suicidal patients with major psychiatric disorders. There were 17 astrocytic, 14 microglial, and 9 oligodendroglial studies using specific markers of each glial cell and further on their specific gene expression. Those studies suggest that astrocytic and oligodendroglial cells lost but activated microglia in suicides with affective disorder, bipolar disorders, major depression disorders, or schizophrenia in comparison with non-suicided patients and non-psychiatric controls. Although the data from previous studies remain complex and cannot fully explain the effects of glial cell dysfunction related to suicidal behaviors, they provide risk directions potentially leading to suicide prevention.
Topics: Humans; Neuroglia; Suicide; Brain; Biomarkers; Autopsy; Suicidal Ideation; Bipolar Disorder
PubMed: 38891940
DOI: 10.3390/ijms25115750 -
Cells Jun 2024Temporomandibular disorders (TMDs) are a heterogeneous group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory... (Review)
Review
Temporomandibular disorders (TMDs) are a heterogeneous group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory muscles, and associated structures. Mesenchymal stromal/stem cells (MSCs) have emerged as a promising therapy for TMJ repair. This systematic review aims to consolidate findings from the preclinical animal studies evaluating MSC-based therapies, including MSCs, their secretome, and extracellular vesicles (EVs), for the treatment of TMJ cartilage/osteochondral defects and osteoarthritis (OA). Following the PRISMA guidelines, PubMed, Embase, Scopus, and Cochrane Library databases were searched for relevant studies. A total of 23 studies involving 125 , 149 , 470 , and 74 were identified. Compliance with the ARRIVE guidelines was evaluated for quality assessment, while the SYRCLE risk of bias tool was used to assess the risk of bias for the studies. Generally, MSC-based therapies demonstrated efficacy in TMJ repair across animal models of TMJ defects and OA. In most studies, animals treated with MSCs, their derived secretome, or EVs displayed improved morphological, histological, molecular, and behavioral pain outcomes, coupled with positive effects on cellular proliferation, migration, and matrix synthesis, as well as immunomodulation. However, unclear risk in bias and incomplete reporting highlight the need for standardized outcome measurements and reporting in future investigations.
Topics: Animals; Temporomandibular Joint; Mesenchymal Stem Cells; Mesenchymal Stem Cell Transplantation; Temporomandibular Joint Disorders; Humans; Osteoarthritis; Extracellular Vesicles; Disease Models, Animal
PubMed: 38891122
DOI: 10.3390/cells13110990 -
Frontiers in Immunology 2024Multiple investigations and scholarly articles have presented compelling evidence indicating that tertiary lymphoid structures (TLS) play a pivotal role in inhibiting... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple investigations and scholarly articles have presented compelling evidence indicating that tertiary lymphoid structures (TLS) play a pivotal role in inhibiting and controlling the advancement of tumors. While there is an abundance of information highlighting the importance of TLS in different cancer types, their prognostic significance specifically in hepatocellular carcinoma (HCC) cancers remains unclear. Thus, this meta-analysis aimed to explore the prognostic relevance of TLS in HCC.
METHODS
We conducted a thorough search across four databases, namely Web of Science, PubMed, Embase, and the Cochrane Library, to identify pertinent studies. The search utilized the keywords "tertiary lymphoid structures" and "hepatocellular carcinoma." The primary outcomes of interest encompassed overall survival (OS), recurrence-free survival (RFS), early recurrence, and late recurrence. The statistical effect size for these measures was expressed in terms of hazard ratios (HR).
RESULTS
Six studies were incorporated into the analysis. Among them, four studies, encompassing 6 datasets and involving 1490 patients, and three studies, comprising 5 datasets and involving 656 patients, respectively, investigated the correlation between intratumoral and peritumoral TLSs and the prognosis in HCC patients. The meta-analysis revealed that the presence of intratumoral TLSs is linked to longer RFS and reduced early recurrence (HR, 0.60; 95% CI, 0.50-0.67; p <0.001 and HR, 0.49; 95% CI, 0.36-0.65; p <0.001, respectively). However, no significant association was observed with OS and late recurrence. Sensitivity analysis demonstrated the robustness of these findings, and heterogeneities were minimal. Additionally, the meta-analysis did not detect a relationship between peritumoral TLSs and OS or RFS in HCC patients.
CONCLUSION
The presence of intratumoral TLSs is correlated with better RFS and reduced early recurrence in HCC patients. Further investigation is warranted to elucidate the roles of peritumoral TLSs in the prognosis of HCC patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023466793.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Tertiary Lymphoid Structures; Prognosis; Neoplasm Recurrence, Local
PubMed: 38887293
DOI: 10.3389/fimmu.2024.1390938 -
Biomedicine & Pharmacotherapy =... Jul 2024The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation and acetylation offer new perspectives... (Review)
Review
The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation and acetylation offer new perspectives on the pathogenesis and treatment of kidney diseases. lncRNAs, a class of transcripts longer than 200 nucleotides with no protein-coding potential, are now recognized as key regulatory molecules influencing gene expression through diverse mechanisms. They modulate the epigenetic modifications by recruiting or blocking enzymes responsible for adding or removing methyl or acetyl groups, such as DNA, N6-methyladenosine (m6A) and histone methylation and acetylation, subsequently altering chromatin structure and accessibility. In kidney diseases such as acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy (DN), glomerulonephritis (GN), and renal cell carcinoma (RCC), aberrant patterns of DNA/RNA/histone methylation and acetylation have been associated with disease onset and progression, revealing a complex interplay with lncRNA dynamics. Recent studies have highlighted how lncRNAs can impact renal pathology by affecting the expression and function of key genes involved in cell cycle control, fibrosis, and inflammatory responses. This review will separately address the roles of lncRNAs and epigenetic modifications in renal diseases, with a particular emphasis on elucidating the bidirectional regulatory effects and underlying mechanisms of lncRNAs in conjunction with DNA/RNA/histone methylation and acetylation, in addition to the potential exacerbating or renoprotective effects in renal pathologies. Understanding the reciprocal relationships between lncRNAs and epigenetic modifications will not only shed light on the molecular underpinnings of renal pathologies but also present new avenues for therapeutic interventions and biomarker development, advancing precision medicine in nephrology.
Topics: RNA, Long Noncoding; Humans; Epigenesis, Genetic; Histones; Acetylation; DNA Methylation; Kidney Diseases; Chromatin; Animals
PubMed: 38870627
DOI: 10.1016/j.biopha.2024.116922 -
Frontiers in Endocrinology 2024Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma. The majority of PNETs are sporadic,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma. The majority of PNETs are sporadic, but PNETs also occur in hereditary syndromes, primarily multiple endocrine neoplasia type 1 (MEN1). The Knudson hypothesis stated a second, somatic hit in as the cause of PNETs of MEN1 syndrome. In the recent years, reports on genetic somatic events in both sporadic and hereditary PNETs have emerged, providing a basis for a more detailed molecular understanding of the pathophysiology. In this systematic review and meta-analysis, we made a collation and statistical analysis of aggregated frequent genetic alterations and potential driver events in human grade G1/G2 PNETs.
METHODS
A systematic search was performed in concordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) reporting guidelines of 2020. A search in Pubmed for published studies using whole exome, whole genome, or targeted gene panel (+400 genes) sequencing of human G1/G2 PNETs was conducted at the 25 of September 2023. Fourteen datasets from published studies were included with data on 221 patients and 225 G1/G2 PNETs, which were divided into sporadic tumors, and hereditary tumors with pre-disposing germline variants, and tumors with unknown germline status. Further, non-functioning and functioning PNETs were distinguished into two groups for pathway evaluation. The collated genetical analyses were conducted using the 'maftools' R-package.
RESULTS
Sporadic PNETs accounted 72.0% (162/225), hereditary PNETs 13.3% (30/225), unknown germline status 14.7% (33/225). The most frequently altered gene was , with somatic variants and copy number variations in overall 42% (95/225); hereditary PNETs (germline variations in , , , , , , and/or ) 57% (16/30); sporadic PNETs 36% (58/162); unknown germline status 64% (21/33). The point mutations/indels were distributed throughout . Overall, (16%, 37/225) and -variants (12%, 27/225) were also abundant with missense mutations clustered in mutational hotspots associated with histone binding, and translocase activity, respectively. mutations occurred more frequently in PNETs with mutations, p<0.05. While functioning PNETs shared few variated genes, non-functioning PNETs had more recurrent variations in genes associated with the Phosphoinositide 3-kinase, Wnt, NOTCH, and Receptor Tyrosine Kinase-Ras signaling onco-pathways.
DISCUSSION
The somatic genetic alterations in G1/G2 PNETs are diverse, but with distinct differences between sporadic vs. hereditary, and functional vs. non-functional PNETs. Increased understanding of the genetic alterations may lead to identification of more drivers and driver hotspots in the tumorigenesis in well-differentiated PNETs, potentially giving a basis for the identification of new drug targets. (Funded by Novo Nordisk Foundation, grant number NNF19OC0057915).
Topics: Humans; Pancreatic Neoplasms; Neuroendocrine Tumors; Sequence Analysis, DNA; Mutation
PubMed: 38868744
DOI: 10.3389/fendo.2024.1351624 -
Translational Psychiatry Jun 2024Excessive and persistent aggressiveness is the most common behavioral problem that leads to psychiatric referrals among children. While half of the variance in childhood...
Excessive and persistent aggressiveness is the most common behavioral problem that leads to psychiatric referrals among children. While half of the variance in childhood aggression is attributed to genetic factors, the biological mechanism and the interplay between genes and environment that results in aggression remains elusive. The purpose of this systematic review is to provide an overview of studies examining the genetics of childhood aggression irrespective of psychiatric diagnosis. PubMed, PsycINFO, and MEDLINE databases were searched using predefined search terms for aggression, genes and the specific age group. From the 652 initially yielded studies, eighty-seven studies were systematically extracted for full-text review and for further quality assessment analyses. Findings show that (i) investigation of candidate genes, especially of MAOA (17 studies), DRD4 (13 studies), and COMT (12 studies) continue to dominate the field, although studies using other research designs and methods including genome-wide association and epigenetic studies are increasing, (ii) the published articles tend to be moderate in sizes, with variable methods of assessing aggressive behavior and inconsistent categorizations of tandem repeat variants, resulting in inconclusive findings of genetic main effects, gene-gene, and gene-environment interactions, (iii) the majority of studies are conducted on European, male-only or male-female mixed, participants. To our knowledge, this is the first study to systematically review the effects of genes on youth aggression. To understand the genetic underpinnings of childhood aggression, more research is required with larger, more diverse sample sets, consistent and reliable assessments and standardized definition of the aggression phenotypes. The search for the biological mechanisms underlying child aggression will also benefit from more varied research methods, including epigenetic studies, transcriptomic studies, gene system and genome-wide studies, longitudinal studies that track changes in risk/ameliorating factors and aggression-related outcomes, and studies examining causal mechanisms.
Topics: Child; Female; Humans; Male; Aggression; Catechol O-Methyltransferase; Gene-Environment Interaction; Genome-Wide Association Study; Monoamine Oxidase; Receptors, Dopamine D4
PubMed: 38862490
DOI: 10.1038/s41398-024-02870-7 -
What is the role of circRNAs in the pathogenesis of cervical cancer? A systematic literature review.Frontiers in Genetics 2024Cervical Cancer (CC) is one of the most prevalent neoplasms among women, considered the leading cause of gynecological death worldwide, and the fourth most common type...
Cervical Cancer (CC) is one of the most prevalent neoplasms among women, considered the leading cause of gynecological death worldwide, and the fourth most common type of cancer. Regional metastasis is closely related to the low effectiveness of treatment, and validating biomarkers can optimize accuracy in diagnosis and prognosis. Among the potential biomarkers associated with disease metastasis are circular RNAs (circRNAs), whose altered expression has been linked to CC progression. In this context, this systematic review aims to compile information on the clinical-pathological significance and describe the biological function of circRNAs. Inclusion and exclusion criteria were used to include relevant literature, followed by analysis. Additionally, we employed the UALCAN tools to search for host genes of circRNAs and expression data, miRTargetLink 2.0 to predict interactions of microRNA target genes and the Cytoscape software to predict possible interactions of microRNA target genes. According to the research, most circRNAs were found to be overexpressed and described as regulators of processes such as invasion, cell proliferation, apoptosis and migration. They were also implicated in clinical significance, including metastasis, TNM staging and microRNA interactions. CircRNAs may participate in critical processes in tumorigenesis; therefore, understanding the underlying molecular mechanisms of gene regulation in CC can contribute to the accuracy of diagnosis, prognosis and therapy.
PubMed: 38859935
DOI: 10.3389/fgene.2024.1287869 -
Photodiagnosis and Photodynamic Therapy Jun 2024This systematic review assessed the effectiveness of photodynamic therapy (PDT) in patients with recurrent oral squamous cell carcinoma (OSCC). (Review)
Review
BACKGROUND
This systematic review assessed the effectiveness of photodynamic therapy (PDT) in patients with recurrent oral squamous cell carcinoma (OSCC).
METHODS
Clinical studies on recurrent OSCC treated with PDT alone were included. Combined treatment strategies were excluded. The search was performed on Medline/Pubmed, Cochrane Library, Embase, Web of Science and ClinicalTrials.gov, manual search, and grey literature.
RESULTS
The eleven included studies were observational. The risk of bias and methodological quality were evaluated using the Newcastle-Ottawa Quality Assessment Scale. The studies reported the use of hematoporphyrin derivative, Photofrin, Foscan and 5-aminolevulinic acid. Data on treatment response and survival was collected. Secondarily, postoperative courses and patient's quality of life/acceptance were reported whenever available. Photofrin and Foscan were the most used photosensitisers, with more complete responses. Lesions responding less favourably were on posterior regions or deep-seated in the tissue.
CONCLUSIONS
Although treatment response differs between treatment protocols, PDT stands as a viable treatment option to be considered, as it can achieve therapeutic results and disease-free, long-lasting periods. Partial treatment responses may be of interest when achieving eligibility for other treatment strategies. Despite this study's limitations, which considered four photosensitisers, Photofrin was the most used but more recent photosensitisers like Foscan have greater chemical stability, tissue penetration, and may be more efficacious on recurrent OSCC.
PubMed: 38857775
DOI: 10.1016/j.pdpdt.2024.104242 -
Legal Medicine (Tokyo, Japan) Jun 2024Suicidal hanging resulting in decapitation is rarely documented. This discussion involves a case of a 35-year-old man found decapitated in his residence's garden. A... (Review)
Review
INTRODUCTION
Suicidal hanging resulting in decapitation is rarely documented. This discussion involves a case of a 35-year-old man found decapitated in his residence's garden. A systematic literature review on hanging-induced decapitation was conducted to comprehensively investigate and compare the case to existing literature. The study aims to identify frequently described post-mortem findings in cases of suicidal hanging leading to decapitation.
CASE REPORT
A 35-year-old man was found decapitated in his garden, with a jute strap and chimney debris nearby. The cervical region was completely severed along the dorsoventral and craniocaudal plane, exposing internal structures. A ligature mark was present, along with Amussat's sign and Simon's bleeding.
METHODS
The systematic review of the literature followed PRISMA standards, analyzing 3622 publications from Google Scholar, PubMed, and Scopus databases up to 2023. Inclusion criteria comprised cases of complete or incomplete decapitation resulting from hanging, available in full-text and written in English.
RESULTS
16 articles on hanging-induced decapitation met the selection criteria; 22 cases were analyzed. Studies, mostly from Europe, showed a mean victim age of 44.3, all male. Fall height ranged from 1 m to 18 m, with various suspension media. Most cases displayed complete decapitation, primarily between cervical vertebrae C1 and C3. Some cases noted collateral findings.
CONCLUSIONS
Complete crime scene investigation and thorough post-mortem examination are crucial for reconstructing events, especially with confounding elements. Precise evidence collection and literature comparison are essential to understand the case and substantiate the forensic pathologist's hypothesis in court.
PubMed: 38838410
DOI: 10.1016/j.legalmed.2024.102464 -
Clinical Microbiology and Infection :... May 2024The optimal empiric antibiotic regimen for non-ventilator-associated hospital-acquired pneumonia (HAP) is uncertain. (Review)
Review
Empiric antibiotic regimens in adults with non-ventilator-associated hospital-acquired pneumonia: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
The optimal empiric antibiotic regimen for non-ventilator-associated hospital-acquired pneumonia (HAP) is uncertain.
OBJECTIVES
To compare the effectiveness and safety of alternative empiric antibiotic regimens in HAP using a network meta-analysis.
DATA SOURCES
Medline, EMBASE, Cochrane CENTRAL, Web of Science, and CINAHL from database inception to July 06, 2023.
STUDY ELIGIBILITY CRITERIA
RCTs.
PARTICIPANTS
Adults with clinical suspicion of HAP.
INTERVENTIONS
Any empiric antibiotic regimen vs. another, placebo, or no treatment.
ASSESSMENT OF RISK OF BIAS
Paired reviewers independently assessed risk of bias using a modified Cochrane tool for assessing risk of bias in randomized trials.
METHODS OF DATA SYNTHESIS
Paired reviewers independently extracted data on trial and patient characteristics, antibiotic regimens, and outcomes of interest. We conducted frequentist random-effects network meta-analyses for treatment failure and all-cause mortality and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach.
RESULTS
Thirty-nine RCTs proved eligible. Thirty RCTs involving 4807 participants found low certainty evidence that piperacillin-tazobactam (RR compared to all cephalosporins: 0.65; 95% CI: 0.42, 1.01) and carbapenems (RR compared to all cephalosporins: 0.77; 95% CI: 0.53, 1.11) might be among the most effective in reducing treatment failure. The findings were robust to the secondary analysis comparing piperacillin-tazobactam vs. antipseudomonal cephalosporins or antipseudomonal carbapenems vs. antipseudomonal cephalosporins. Eleven RCTs involving 2531 participants found low certainty evidence that ceftazidime and linezolid combination may not be convincingly different from cephalosporin alone in reducing all-cause mortality. Evidence on other antibiotic regimens is very uncertain. Data on other patient-important outcomes including adverse events was sparse, and we did not perform network or pairwise meta-analysis.
CONCLUSIONS
For empiric antibiotic therapy of adults with HAP, piperacillin-tazobactam might be among the most effective in reducing treatment failure. Empiric methicillin-resistant Staphylococcus aureus coverage may not exert additional benefit in reducing mortality.
REGISTRATION
PROSPERO (CRD 42022297224).
PubMed: 38823453
DOI: 10.1016/j.cmi.2024.05.017