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Comprehensive Psychiatry Aug 2024Trichotillomania (TTM) and excoriation disorder (ED) are impairing obsessive-compulsive related disorders that are common in the general population and for which there...
BACKGROUND
Trichotillomania (TTM) and excoriation disorder (ED) are impairing obsessive-compulsive related disorders that are common in the general population and for which there are no clear first-line medications, highlighting the need to better understand the underlying biology of these disorders to inform treatments. Given the importance of genetics in obsessive-compulsive disorder (OCD), evaluating genetic factors underlying TTM and ED may advance knowledge about the pathophysiology of these body-focused repetitive behaviors.
AIM
In this systematic review, we summarize the available evidence on the genetics of TTM and ED and highlight gaps in the field warranting further research.
METHOD
We systematically searched Embase, PsycInfo, PubMed, Medline, Scopus, and Web of Science for original studies in genetic epidemiology (family or twin studies) and molecular genetics (candidate gene and genome-wide) published up to June 2023.
RESULTS
Of the 3536 records identified, 109 studies were included in this review. These studies indicated that genetic factors play an important role in the development of TTM and ED, some of which may be shared across the OCD spectrum, but there are no known high-confidence specific genetic risk factors for either TTM or ED.
CONCLUSIONS
Our review underscores the need for additional genome-wide research conducted on the genetics of TTM and ED, for instance, genome-wide association and whole-genome/whole-exome DNA sequencing studies. Recent advances in genomics have led to the discovery of risk genes in several psychiatric disorders, including related conditions such as OCD, but to date, TTM and ED have remained understudied.
Topics: Humans; Trichotillomania; Obsessive-Compulsive Disorder; Genome-Wide Association Study; Excoriation Disorder
PubMed: 38833896
DOI: 10.1016/j.comppsych.2024.152506 -
IDCases 2024Herpes simplex encephalitis (HSVE) is a potentially fatal infectious central nervous system (CNS) disorder. Thus, early detection is critical in determining the case's...
Herpes simplex encephalitis (HSVE) is a potentially fatal infectious central nervous system (CNS) disorder. Thus, early detection is critical in determining the case's fate. Clinical history and examination, brain computed tomography, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and lumbar puncture have been used to establish a diagnosis. This report describes a case of HSVE with hypocellular cerebrospinal fluid (CSF) and an uncommon form of memory impairment. However, MRI results were consistent with HSVE, and CSF PCR tested positive for HSV-1 DNA that responded to treatment. We routinely advise patients to begin antiviral therapy as soon as possible to avoid complications.
PubMed: 38831962
DOI: 10.1016/j.idcr.2024.e01981 -
Heliyon Jun 2024Nanoparticles have recently become considered as a crucial player in contemporary medicine, with therapeutic uses ranging from contrast agents in imaging to carriers for... (Review)
Review
Nanoparticles have recently become considered as a crucial player in contemporary medicine, with therapeutic uses ranging from contrast agents in imaging to carriers for the transport of drugs and genes into a specific target. Nanoparticles have the ability to have more precise molecular interactions with the human body in order to target specific cells and tissues with minimal adverse effects and maximal therapeutic outcomes. With the least number of side effects and the greatest possible therapeutic benefit, nanoparticles can target particular cells and tissues through more precise molecular interactions with the human body. The majority of global public health problems are now treated with green synthesized silver nanoparticles (AgNPs), which substantially affect the fundamental structure of DNA and proteins and thus display their antimicrobial action. AgNPs can inhibit the proliferation of tumor cells and induce oxidative stress. By inhibiting vascular endothelial growth factor (HIF)-1, pro-inflammatory mediators generated by silver nanoparticles are reduced, mucin hypersecretion is lessened, and gene activity is subsequently regulated to prevent infections. The biogenic synthesis of silver nanoparticles (AgNPs) using various plants and their applications in antibacterial, antifungal, antioxidant, anticancer, anti-inflammatory, and antidiabetic activities have been extensively discussed in this article. Also, because only natural substances are utilized in the manufacturing process, the particles that are created naturally are coated, stabilized, and play a vital role in these biomedical actions. The characterization of AgNPs, possibility of preparing AgNPSs with different shapes using biological method and their impact on functions and toxicities, impact of size, shape and other properties on AgNPs functions and toxicity profiles, limitations, and future prospects of green-mediated AgNPs have also been reported in this study. The major goal of this study is to provide readers with a comprehensive, informed, and up-to-date summary of the various AgNPs production and characterization methods and their under-investigational antioxidant, antibacterial, and anticancer, antidiabetic, antifungal and anti-inflammatory properties. This review provides instructions and suggestions for additional studies based on AgNPs. This evaluation also pushes researchers to look into natural resources like plant parts in order to create useful nanobiotechnology.
PubMed: 38828360
DOI: 10.1016/j.heliyon.2024.e29766 -
Journal of Gynecology Obstetrics and... May 2024To investigate the impact of metabolic syndrome factors on sperm DNA fragmentation (sDF) in males from infertile couples. (Review)
Review
PURPOSE
To investigate the impact of metabolic syndrome factors on sperm DNA fragmentation (sDF) in males from infertile couples.
METHODS
A systematic literature search was performed across ten databases for literature published from January 1, 2013 until September 13, 2023. The protocol has been registered on PROSPERO (CRD42023458359), and the literature search strategy is adhered to the PRISMA framework. Studies that evaluated sDF, as indicated by DNA fragmentation index (%DFI), in males from infertile couples in relation to metabolic syndrome factors were included. Meta-analysis, using random effects model and Bayesian framework network, was performed, and data were presented as Standardized Mean Differences (SMD) with corresponding 95 % Confidence Interval (CI).
RESULTS
Of the 2579 citations identified, eleven studies were included in this meta-analysis. The findings revealed that the %DFI was not associated with overall metabolic syndrome factors (p-tot = 0.235; SMD = 0.57 [95 %CI: -0.37, 1.52]), metabolic syndrome status (p-tot = 0.337; SMD = 0.08 [95 %CI: -0.08, 0.24), increased body mass index (p-tot = 0.237; SMD = 0.71 [95 %CI: -0.47, 1.89]), or glycaemic profile (p-tot = 0.93; SMD = 0.13 [95 %CI: -2.72, 2.98]). High levels of heterogeneity were observed (p < 0.01) in all subgroups, except for metabolic syndrome status.
CONCLUSION
The association between metabolic syndrome factors and sDF is conflicting. However, interpreting the association requires caution, as confounding factors, indicated by high heterogeneity, may conceal the outcome. Metabolic syndrome may influence other factors contributing to male infertility, highlighting the importance of promoting a healthy lifestyle.
PubMed: 38825166
DOI: 10.1016/j.jogoh.2024.102807 -
European Urology Oncology May 2024Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also... (Review)
Review
BACKGROUND AND OBJECTIVE
Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also directly in biologic fluids (ie, liquid biopsies), mainly blood. Liquid biopsies may represent a safer and less invasive alternative for monitoring patients treated for mPCa. Current research focuses on the description and validation of novel predictive biomarkers to improve precision medicine in mPCa. Our aim was to systematically review the current evidence on liquid biopsy biomarkers for predicting treatment response in mPCa.
METHODS
We systematically searched Medline, Web of Science, and evidence-based websites for publications on circulating biomarkers in mPCa between March 2013 and February 2024 for review. Endpoints were: prediction of overall survival, biochemical or radiographic progression-free survival after treatment (chemotherapy, androgen deprivation therapy, androgen receptor pathway inhibitors [ARPIs], immunotherapy, or PARP inhibitors [PARPIs]). For each biomarker, the level of evidence (LOE) for clinical validity was attributed: LOE IA and IB, high level of evidence; LOE IIB and IIC, intermediate level; and LOE IIIC and LOE IV-VD, weak level.
KEY FINDINGS AND LIMITATIONS
The predictive value of each biomarker for the response to several therapies was evaluated in both metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). In patients with mCRPC, BRCA1/2 or ATM mutations predicted response to ARPIs (LOE IB) and PARPIs (LOE IIB), while AR-V7 transcripts or AR-V7 protein levels in circulating tumor cells (CTCs) predicted response to ARPIs and taxanes (LOE IB). CTC quantification predicted response to cabazitaxel, abiraterone, and radium-223 (LOE IIB), while TP53 alterations predicted response to Lu prostate-specific membrane antigen radioligand treatment (LOE IIB). AR copy number in circulating tumor DNA before the first treatment line and before subsequent lines predicted response to docetaxel, cabazitaxel, and ARPIs (LOE IIB). In mHSPC, DNA damage in lymphocytes was predictive of the response to radium-223 (LOE IIB).
CONCLUSIONS AND CLINICAL IMPLICATIONS
BRCA1/2, ATM, and AR alterations detected in liquid biopsies may help clinicians in management of patients with mPCa. The other circulating biomarkers did not reach the LOE required for routine clinical use and should be validated in prospective independent studies.
PATIENT SUMMARY
We reviewed studies assessing the value of biomarkers in blood or urine for management of metastatic prostate cancer. The evidence indicates that some biomarkers could help in selecting patients eligible for specific treatments.
PubMed: 38824003
DOI: 10.1016/j.euo.2024.05.003 -
World Journal of Stem Cells May 2024Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy. Glioma stem cells (GSCs), a subset within tumors,...
BACKGROUND
Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy. Glioma stem cells (GSCs), a subset within tumors, contribute to resistance, tumor heterogeneity, and plasticity. Recent studies reveal GSCs' role in therapeutic resistance, driven by DNA repair mechanisms and dynamic transitions between cellular states. Resistance mechanisms can involve different cellular pathways, most of which have been recently reported in the literature. Despite progress, targeted therapeutic approaches lack consensus due to GSCs' high plasticity.
AIM
To analyze targeted therapies against GSC-mediated resistance to radio- and chemotherapy in gliomas, focusing on underlying mechanisms.
METHODS
A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to September 30, 2023. The search strategy utilized relevant Medical Subject Heading terms and keywords related to including "glioma stem cells", "radiotherapy", "chemotherapy", "resistance", and "targeted therapies". Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated resistance to radiotherapy resistance (RTR).
RESULTS
In a comprehensive review of 66 studies on stem cell therapies for SCI, 452 papers were initially identified, with 203 chosen for full-text analysis. Among them, 201 were deemed eligible after excluding 168 for various reasons. The temporal breakdown of studies illustrates this trend: 2005-2010 (33.3%), 2011-2015 (36.4%), and 2016-2022 (30.3%). Key GSC models, particularly U87 (33.3%), U251 (15.2%), and T98G (15.2%), emerge as significant in research, reflecting their representativeness of glioma characteristics. Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) (27.3%) and Notch (12.1%) pathways, suggesting their crucial roles in resistance development. Targeted molecules with mTOR (18.2%), CHK1/2 (15.2%), and ATP binding cassette G2 (12.1%) as frequent targets underscore their importance in overcoming GSC-mediated resistance. Various therapeutic agents, notably RNA inhibitor/short hairpin RNA (27.3%), inhibitors ( LY294002, NVP-BEZ235) (24.2%), and monoclonal antibodies ( cetuximab) (9.1%), demonstrate versatility in targeted therapies. among 20 studies (60.6%), the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance (51.5%), followed by reductions in carmustine resistance (9.1%) and doxorubicin resistance (3.0%), while resistance to RTR is reduced in 42.4% of studies.
CONCLUSION
GSCs play a complex role in mediating radioresistance and chemoresistance, emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.
PubMed: 38817336
DOI: 10.4252/wjsc.v16.i5.604 -
Cureus Apr 2024Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer often diagnosed at advanced stages, highlighting the urgent need for early detection strategies. This... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer often diagnosed at advanced stages, highlighting the urgent need for early detection strategies. This systematic review explores the potential of fecal and urinary biomarkers for early PDAC detection. A comprehensive search identified eight relevant studies investigating various biomarkers, including proteins, metabolites, microbial profiles, DNA mutations, and non-coding RNAs. Promising findings suggest that urinary biomarkers related to metabolic alterations, inflammatory processes, fecal microbiome profiles, and fecal miRNAs hold diagnostic potential even at early stages of PDAC. Combining biomarkers into panels may enhance diagnostic accuracy. Challenges such as validation in larger cohorts, standardization of protocols, and regulatory approval must be addressed for clinical translation. Despite these hurdles, non-invasive urinary and fecal biomarkers represent a promising avenue for improving PDAC outcomes through early detection.
PubMed: 38813271
DOI: 10.7759/cureus.59248 -
PloS One 2024Familial Pancreatic Cancer (FPC) presents a notable risk, with 3-10% of pancreatic adenocarcinoma cases having a family history. Studies link FPC to syndromes like HBOC,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Familial Pancreatic Cancer (FPC) presents a notable risk, with 3-10% of pancreatic adenocarcinoma cases having a family history. Studies link FPC to syndromes like HBOC, suggesting BRCA1/BRCA2 mutations play a role. BRCA gene functions in DNA repair impact FPC management, influencing sensitivity to therapies like PARP inhibitors. Identifying mutations not only aids FPC treatment but also reveals broader cancer risks. However, challenges persist in selectively applying genetic testing due to cost constraints. This Systematic Review focuses on BRCA1/BRCA2 significance in FPC, diagnostic criteria, prognostic value, and limitations.
METHOD
Original articles published from 2013 to January 2023 were sourced from databases such as Scopus, PubMed, ProQuest, and ScienceDirect. Inclusion criteria comprised observational cohort or diagnostic studies related to the role of BRCA1/2 mutation in correlation to familial pancreatic cancer (FPC), while article reviews, narrative reviews, and non-relevant content were excluded. The assessment of bias used ROBINS-I, and the results were organized using PICOS criteria in a Google spreadsheet table. The systematic review adhered to the PRISMA 2020 checklist.
RESULT
We analyzed 9 diagnostic studies encompassing 1325 families and 4267 patients from Italy, USA, and Poland. Despite the limitation of limited homogenous PICO studies, our findings effectively present evidence. BRCA1/2 demonstrates benefits in detecting first-degree relatives FPC involvement with 2.26-10 times higher risk. These mutation findings also play an important role since with the BRCA1/2 targeted therapy, Poly-ADP Ribose Polymerase inhibitors (PARP) may give better outcomes of FPC treatment. Analysis of BRCA1 and BRCA2 administration's impact on odds ratio (OR) based on six and five studies respectively. BRCA1 exhibited non-significant effects (OR = 1.26, P = 0.51), while BRCA2 showed significance (OR = 1.68, P = 0.04). No heterogeneity observed, indicating consistent results. Further research on BRCA1 is warranted.
CONCLUSION
Detecting the BRCA1/2 mutation gene offers numerous advantages, particularly in its correlation with FPC. For diagnostic and prognostic purposes, testing is strongly recommended for first-degree relatives, who face a significantly higher risk (2.26-10 times) of being affected. Additionally, FPC patients with identified BRCA1/2 mutations exhibit a more favorable prognosis compared to the non-mutated population. This is attributed to the availability of targeted BRCA1/2 therapy, which maximizes treatment outcomes.
Topics: Humans; Pancreatic Neoplasms; Germ-Line Mutation; BRCA2 Protein; BRCA1 Protein; Genetic Predisposition to Disease; Carcinoma
PubMed: 38809921
DOI: 10.1371/journal.pone.0299276 -
International Journal of Colorectal... May 2024Circulating tumour DNA (ctDNA) has emerged as a promising biomarker in various cancer types, including locally advanced rectal cancer (LARC), offering potential insights... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Circulating tumour DNA (ctDNA) has emerged as a promising biomarker in various cancer types, including locally advanced rectal cancer (LARC), offering potential insights into disease progression, treatment response and recurrence. This review aims to comprehensively evaluate the utility of ctDNA as a prognostic biomarker in LARC.
METHODS
PubMed, EMBASE and Web of Science were searched as part of our review. Studies investigating the utility of ctDNA in locally advanced rectal cancer (LARC) were assessed for eligibility. Quality assessment of included studies was performed using the Newcastle Ottawa Scale (NOS) risk of bias tool. Outcomes extracted included basic participant characteristics, ctDNA details and survival data. A meta-analysis was performed on eligible studies to determine pooled recurrence-free survival (RFS).
RESULTS
Twenty-two studies involving 1676 participants were included in our analysis. Methodological quality categorised by the Newcastle Ottawa Scale was generally satisfactory across included studies. ctDNA detected at various time intervals was generally associated with poor outcomes across included studies. Meta-analysis demonstrated a pooled hazard ratio of 8.87 (95% CI 4.91-16.03) and 15.15 (95% CI 8.21-27.95), indicating an increased risk of recurrence with ctDNA positivity in the post-neoadjuvant and post-operative periods respectively.
CONCLUSION
Our systematic review provides evidence supporting the prognostic utility of ctDNA in patients with LARC, particularly in identifying patients at higher risk of disease recurrence in the post-neoadjuvant and post-operative periods.
Topics: Humans; Biomarkers, Tumor; Circulating Tumor DNA; Disease-Free Survival; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Rectal Neoplasms
PubMed: 38809315
DOI: 10.1007/s00384-024-04656-1 -
Archives of Toxicology May 2024Indoor air pollution is becoming a rising public health problem and is largely resulting from the burning of solid fuels and heating in households. Burning these fuels... (Review)
Review
Indoor air pollution is becoming a rising public health problem and is largely resulting from the burning of solid fuels and heating in households. Burning these fuels produces harmful compounds, such as particulate matter regarded as a major health risk, particularly affecting the onset and exacerbation of respiratory diseases. As exposure to polluted indoor air can cause DNA damage including DNA sd breaks as well as chromosomal damage, in this paper, we aim to provide an overview of the impact of indoor air pollution on DNA damage and genome stability by reviewing the scientific papers that have used the comet, micronucleus, and γ-H2AX assays. These methods are valuable tools in human biomonitoring and for studying the mechanisms of action of various pollutants, and are readily used for the assessment of primary DNA damage and genome instability induced by air pollutants by measuring different aspects of DNA and chromosomal damage. Based on our search, in selected studies (in vitro, animal models, and human biomonitoring), we found generally higher levels of DNA strand breaks and chromosomal damage due to indoor air pollutants compared to matched control or unexposed groups. In summary, our systematic review reveals the importance of the comet, micronucleus, and γ-H2AX assays as sensitive tools for the evaluation of DNA and genome damaging potential of different indoor air pollutants. Additionally, research in this particular direction is warranted since little is still known about the level of indoor air pollution in households or public buildings and its impact on genetic material. Future studies should focus on research investigating the possible impact of indoor air pollutants in complex mixtures on the genome and relate pollutants to possible health outcomes.
PubMed: 38805047
DOI: 10.1007/s00204-024-03785-4