-
International Journal of Molecular... Mar 2023Cervical intraepithelial neoplasia grade 2 (CIN2) is an intermediate stage between CIN 1, which is a low-grade lesion, and CIN3, which is the immediate precursor of... (Review)
Review
Cervical intraepithelial neoplasia grade 2 (CIN2) is an intermediate stage between CIN 1, which is a low-grade lesion, and CIN3, which is the immediate precursor of cervical cancer (CC). Traditionally, CIN2 was regarded as a high-grade lesion and was treated with conization or ablative methods. In recent years, there has been a shift in the management of younger patients, who are now more often being managed conservatively due to frequent spontaneous CIN2 regression and possible adverse effects of treatment on future pregnancies. Because the risk of progression to CC still exists with conservative management, a personalized approach is needed to identify patients with a higher probability of progression. In this regard, research has focused on the role of host and human papillomavirus (HPV) gene methylation. This systematic review summarizes the current knowledge regarding conservative CIN2 management focusing on the main methylation markers and its implementation in conservative CIN2 management, and it describes major ongoing longitudinal studies on the subject. The review showed that DNA methylation is an accurate predictor of disease progression and a valid triage tool for HPV-positive women, with CIN2 performing better than triage cytology. Because virtually all CCs are methylation-positive, methylation-negative women at baseline have an extremely low risk of CC.
Topics: Pregnancy; Humans; Female; Human Papillomavirus Viruses; Papillomavirus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; DNA Methylation; DNA; Papillomaviridae
PubMed: 37047452
DOI: 10.3390/ijms24076479 -
Gut Jul 2023Screening for colorectal cancer (CRC) is effective in reducing CRC related mortality. Current screening methods include endoscopy based and biomarker based approaches....
Joint Asian Pacific Association of Gastroenterology (APAGE)-Asian Pacific Society of Digestive Endoscopy (APSDE) clinical practice guidelines on the use of non-invasive biomarkers for diagnosis of colorectal neoplasia.
Screening for colorectal cancer (CRC) is effective in reducing CRC related mortality. Current screening methods include endoscopy based and biomarker based approaches. This guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society of Digestive Endoscopy (APSDE), developed in response to the increasing use of, and accumulating supportive evidence for the role of, non-invasive biomarkers for the diagnosis of CRC and its precursor lesions. A systematic review of 678 publications and a two stage Delphi consensus process involving 16 clinicians in various disciplines was undertaken to develop 32 evidence based and expert opinion based recommendations for the use of faecal immunochemical tests, faecal based tumour biomarkers or microbial biomarkers, and blood based tumour biomarkers for the detection of CRC and adenoma. Comprehensive up-to-date guidance is provided on indications, patient selection and strengths and limitations of each screening tool. Future research to inform clinical applications are discussed alongside objective measurement of research priorities. This joint APAGE-APSDE practice guideline is intended to provide an up-to-date guide to assist clinicians worldwide in utilising non-invasive biomarkers for CRC screening; it has particular salience for clinicians in the Asia-Pacific region.
Topics: Humans; Gastroenterology; Endoscopy, Gastrointestinal; Colorectal Neoplasms; Feces; Biomarkers, Tumor; Early Detection of Cancer
PubMed: 37019620
DOI: 10.1136/gutjnl-2023-329429 -
Animal Nutrition (Zhongguo Xu Mu Shou... Jun 2023The goal of this review article, based on a systematic literature search, is to critically assess the state of knowledge and experimental methodologies used to delineate... (Review)
Review
The goal of this review article, based on a systematic literature search, is to critically assess the state of knowledge and experimental methodologies used to delineate the conversion and metabolism of the 2 methionine (Met) sources DL-methionine (DL-Met) and DL-2-hydroxy-4-(methylthio) butanoic acid (HMTBa). The difference in the chemical structures of HMTBa and DL-Met indicates that these molecules are absorbed and metabolized differently in animals. This review explores the methodologies used to describe the 2-step enzymatic conversion of the 3 enantiomers (D-HMTBa, L-HMTBa and D-Met) to L-Met, as well as the site of conversion at the organ and tissue levels. Extensive work was published documenting the conversion of HMTBa and D-Met into L-Met and, consequently, the incorporation into protein using a variety of in vitro techniques, such as tissue homogenates, cell lines, primary cell lines, and everted gut sacs of individual tissues. These studies illustrated the role of the liver, kidney, and intestine in the conversion of Met precursors into L-Met. A combination of in vivo studies using stable isotopes and infusions provided evidence of the wide conversion of HMTBa to L-Met by all tissues and how some tissues are net users of HMTBa, whereas others are net secreters of L-Met derived from HMTBa. Conversion of D-Met to L-Met in organs other than the liver and kidney is poorly documented. The methodology cited in the literature to determine conversion efficiency ranged from measurements of urinary, fecal, and respiratory excretion to plasma concentration and tissue incorporation of isotopes after intraperitoneal and oral infusions. Differences observed between these methodologies reflect differences in the metabolism of Met sources rather than differences in conversion efficiency. The factors affecting conversion efficiency are explored in this paper and are mostly associated with extreme dietary conditions, such as noncommercial crystalline diets that are very deficient in total sulfur amino acids with respect to requirements. Implications in the diversion of the 2 Met sources toward transsulfuration over transmethylation pathways are discussed. The strengths and weaknesses of some methodologies used are discussed in this review. From this review, it can be concluded that due to the inherent differences in conversion and metabolism of the 2 Met sources, the experimental methodologies (e.g., selecting different organs at different time points or using diets severely deficient in Met and cysteine) can impact the conclusions of the study and may explain the apparent divergences of conclusion found in the literature. It is recommended when conducting studies or reviewing the literature to properly select the experimental models that allow for differences in how the 2 Met precursors are converted to L-Met and metabolized by the animal to enable a proper comparison of their bioefficacy.
PubMed: 37009071
DOI: 10.1016/j.aninu.2023.01.009 -
Sex Differences in Tryptophan Metabolism: A Systematic Review Focused on Neuropsychiatric Disorders.International Journal of Molecular... Mar 2023Tryptophan (Tryp) is an essential amino acid and the precursor of several neuroactive compounds within the central nervous system (CNS). Tryp metabolism, the common... (Review)
Review
Tryptophan (Tryp) is an essential amino acid and the precursor of several neuroactive compounds within the central nervous system (CNS). Tryp metabolism, the common denominator linking serotonin (5-HT) dysfunctions and neuroinflammation, is involved in several neuropsychiatric conditions, including neurological, neurodevelopmental, neurodegenerative, and psychiatric diseases. Interestingly, most of those conditions occur and progress in a sex-specific manner. Here, we explore the most relevant observations about the influence of biological sex on Tryp metabolism and its possible relation to neuropsychiatric diseases. Consistent evidence suggests that women have a higher susceptibility than men to suffer serotoninergic alterations due to changes in the levels of its precursor Tryp. Indeed, female sex bias in neuropsychiatric diseases is involved in a reduced availability of this amino acid pool and 5-HT synthesis. These changes in Tryp metabolism could lead to sexual dimorphism on the prevalence and severity of some neuropsychiatric disorders. This review identifies gaps in the current state of the art, thus suggesting future research directions. Specifically, there is a need for further research on the impact of diet and sex steroids, both involved in this molecular mechanism as they have been poorly addressed for this topic.
Topics: Female; Humans; Male; Tryptophan; Sex Characteristics; Serotonin; Amino Acids; Mental Disorders; Kynurenine
PubMed: 36983084
DOI: 10.3390/ijms24066010 -
Journal of Neuroinflammation Mar 2023Recent literature on multiple sclerosis (MS) demonstrates the growing implementation of optical coherence tomography-angiography (OCT-A) to discover potential... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Recent literature on multiple sclerosis (MS) demonstrates the growing implementation of optical coherence tomography-angiography (OCT-A) to discover potential qualitative and quantitative changes in the retina and optic nerve. In this review, we analyze OCT-A studies in patients with MS and examine its utility as a surrogate or precursor to changes in central nervous system tissue.
METHODS
PubMed and EMBASE were systematically searched to identify articles that applied OCT-A to evaluate the retinal microvasculature measurements in patients with MS. Quantitative data synthesis was performed on all measurements which were evaluated in at least two unique studies with the same OCT-A devices, software, and study population compared to controls. A fixed-effects or random-effects model was applied for the meta-analysis based on the heterogeneity level.
RESULTS
The study selection process yielded the inclusion of 18 studies with a total of 1552 evaluated eyes in 673 MS-associated optic neuritis (MSON) eyes, 741 MS without optic neuritis (MSNON eyes), and 138 eyes without specification for the presence of optic neuritis (ON) in addition to 1107 healthy control (HC) eyes. Results indicated that MS cases had significantly decreased whole image superficial capillary plexus (SCP) vessel density when compared to healthy control subjects in the analyses conducted on Optovue and Topcon studies (both P < 0.0001). Likewise, the whole image vessel densities of deep capillary plexus (DCP) and radial peripapillary capillary (RPC) were significantly lower in MS cases compared to HC (all P < 0.05). Regarding optic disc area quadrants, MSON eyes had significantly decreased mean RPC vessel density compared to MSNON eyes in all quadrants except for the inferior (all P < 0.05). Results of the analysis of studies that used prototype Axsun machine revealed that MSON and MSNON eyes both had significantly lower ONH flow index compared to HC (both P < 0.0001).
CONCLUSIONS
This systematic review and meta-analysis of the studies reporting OCT-A measurements of people with MS confirmed the tendency of MS eyes to exhibit reduced vessel density in the macular and optic disc areas, mainly in SCP, DCP, and RPC vessel densities.
Topics: Humans; Tomography, Optical Coherence; Multiple Sclerosis; Retina; Angiography; Retinal Vessels; Optic Neuritis; Fluorescein Angiography
PubMed: 36973708
DOI: 10.1186/s12974-023-02763-4 -
Cancers Feb 2023To review somatic genetic changes in nephrogenic rests (NR), which are considered to be precursor lesions of Wilms tumors (WT). (Review)
Review
OBJECTIVE
To review somatic genetic changes in nephrogenic rests (NR), which are considered to be precursor lesions of Wilms tumors (WT).
METHODS
This systematic review is written according to the PRISMA statement. PubMed and EMBASE were systematically searched for articles in the English language studying somatic genetic changes in NR between 1990 and 2022.
RESULTS
Twenty-three studies were included in this review, describing 221 NR of which 119 were pairs of NR and WT. Single gene studies showed mutations in and , but not to occur in both NR and WT. Studies investigating chromosomal changes showed loss of heterozygosity of 11p13 and 11p15 to occur in both NR and WT, but loss of 7p and 16q occurred in WT only. Methylome-based studies found differential methylation patterns between NR, WT, and normal kidney (NK).
CONCLUSIONS
Over a 30-year time frame, few studies have addressed genetic changes in NR, likely hampered by technical and practical limitations. A limited number of genes and chromosomal regions have been implicated in the early pathogenesis of WT, exemplified by their occurrence in NR, including , , and genes located at 11p15. Further studies of NR and corresponding WT are urgently needed.
PubMed: 36900155
DOI: 10.3390/cancers15051363 -
Human & Experimental Toxicology 2023This systematic review, conducted according to the PRISMA guidelines, focuses on genotoxicity of oxidative hair dye precursors. The search for original papers published...
This systematic review, conducted according to the PRISMA guidelines, focuses on genotoxicity of oxidative hair dye precursors. The search for original papers published from 2000 to 2021 was performed in Medline, Web of Science, Cochrane registry, Scientific Committee on Consumer Safety of the European Commission and German MAK Commission opinions. Nine publications on genotoxicity of -phenylenediamine (PPD) and toluene-2,5-diamine (-toluylenediamine; PTD) were included, reporting results of 17 assays covering main genotoxicity endpoints. PPD and PTD were positive in bacterial mutation assay, and PPD tested positive also for somatic cell mutations in the Rodent assay . Clastogenicity of PPD and PTD was revealed by chromosomal aberration assay. The alkaline comet assay showed DNA damage after PPD exposure, which was not confirmed where PTD exhibited positive results. PPD induced micronucleus formation , and increased micronucleus frequencies in mice erythrocytes following high dose oral exposure . Based on the results of a limited number of data from the classical genotoxicity assay battery, this systematic review indicates genotoxic potential of hair dye precursors PPD and PTD, which may present an important health concern for consumers and in particular for professional hairdressers.
Topics: Animals; Mice; Hair Dyes; DNA Damage; Comet Assay; Mutation; Oxidative Stress
PubMed: 36879522
DOI: 10.1177/09603271231159803 -
Food Chemistry: X Mar 2023Chloropropanols, one of the major contaminants in food, and the corresponding esters or glycidyl esters (GEs) are of great concern in terms of product safety due to... (Review)
Review
Chloropropanols, one of the major contaminants in food, and the corresponding esters or glycidyl esters (GEs) are of great concern in terms of product safety due to their potential carcinogenicity. During heat processing, glycerol, allyl alcohol, chloropropanol esters, sucralose, and carbohydrate in mixed foodstuffs are probable precursors of chloropropanol. The standard analytical techniques for chloropropanols or their esters are GC-MS or LC-MS following sample derivatization pretreatment. By comparing modern data against that five-year-old before, it appears that the levels of chloropropanols and their esters/GEs in food products have somewhat decreased. 3-MCPD esters or GEs may yet exceed the permitted intake set, however, especially in newborn formula which requires particularly stringent regulatory measures. Citespace (6.1. R2) software was employed in this study to examine the research focii of chloropropanols and their corresponding esters/GEs in the literature.
PubMed: 36845468
DOI: 10.1016/j.fochx.2022.100529 -
Blood Jun 2023The benefit associated with the incorporation of vincristine-corticosteroid pulses in maintenance therapy for pediatric acute lymphoblastic leukemia (ALL) is unclear,... (Meta-Analysis)
Meta-Analysis
The benefit associated with the incorporation of vincristine-corticosteroid pulses in maintenance therapy for pediatric acute lymphoblastic leukemia (ALL) is unclear, particularly in the context of modern intensive therapy. This systematic review and meta-analysis examined the impact of reducing the frequency of vincristine-steroid pulses during maintenance for pediatric patients newly diagnosed with B-cell ALL. Two authors reviewed all eligible studies identified through a comprehensive search, extracted data from 25 publications (12 513 patients), and assessed the risk of bias. We created historical and contemporary subgroups; the latter included trials providing both a version of Protocol III from the early Berlin-Frankfurt-Munster trials and eliminating routine prophylactic cranial radiation. Meta-analysis of event-free survival data suggested no benefit between more frequent or less frequent pulses in contemporary trials (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.85-1.09), which differed significantly from historical trials (HR, 0.79; 95% CI, 0.68-0.91; P = .04). We found no significant impact of reduced pulse frequency on overall survival or relapse risk. There was however increased odds of grade 3+ nonhepatic toxicity in the high-pulse frequency group (odds ratio, 1.31; 95% CI, 1.12-1.52). This systematic review suggests that the previous benefit conferred by frequent pulses of vincristine-steroids in maintenance therapy for pediatric B-cell ALL in historical trials no longer applies in contemporary trials but is associated with toxicity. These results will help guide the development of the next phase of clinical trials in the field of pediatric ALL and question the continued use of pulses in maintenance among patients not in clinical trials, particularly those experiencing toxicity.
Topics: Humans; Child; Vincristine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Adrenal Cortex Hormones; Steroids; Progression-Free Survival; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 36821772
DOI: 10.1182/blood.2022018899 -
BMC Neurology Feb 2023Platelets are the primary peripheral reserve of amyloid precursor protein (APP), providing more than 90% of blood amyloid-beta (Aβ). Some oxidative stress markers and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Platelets are the primary peripheral reserve of amyloid precursor protein (APP), providing more than 90% of blood amyloid-beta (Aβ). Some oxidative stress markers and neurotransmitter markers were also differentially expressed in the peripheral platelets of AD. Therefore, the present study explored the differences in platelet-associated biomarkers between AD and healthy controls using meta-analysis and systematic review to reveal the value of platelet in the pathogenesis and development of AD.
METHODS
We searched all the related studies that probed into the platelets in AD based on PubMed, Embase, and web of science databases from the establishment to November 04, 2021.
RESULTS
Eighty-eight studies were included in the meta-analysis, and the platelets data of 702 AD and 710 controls were analyzed. The results of standardized mean difference (SMD) showed that platelets in AD had lower levels of APP ratio (SMD: -1.89; p < 0.05), ADAM10 (SMD: -1.16; p < 0.05), Na + -K + -ATPase (SMD: -7.23; p < 0.05), but higher levels of HMW/LMW tau (SMD: 0.92; p < 0.05), adenosine A receptor (SMD: 4.27; p < 0.05), MAO-B (SMD: 1.73; p < 0.05), NO (SMD: 4.25; p < 0.05) and ONOO (SMD: 7.33; p < 0.05). In the systematic review, some other platelet markers seem to be meaningful in AD patients.
CONCLUSION
The results of the present meta-analysis and systematic review demonstrated that the alterations of APP metabolic enzymes, oxidative stress markers, and neurotransmitter factors in platelets were similar to their changes in the central nervous system of AD, suggesting that platelet could be a good source of peripheral biomarkers and may play an important role in the pathophysiological development of AD.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Blood Platelets
PubMed: 36774494
DOI: 10.1186/s12883-023-03099-5