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Cureus Jul 2023The gut microbiota has been studied and continues to be a developing area in the pathognomic development of metabolic diseases like diabetes. Treatment with diet... (Review)
Review
The gut microbiota has been studied and continues to be a developing area in the pathognomic development of metabolic diseases like diabetes. Treatment with diet changes, the addition of supplements like prebiotics/probiotics, and the impact of fecal microbial transplantation can be correlated to targeting changes in dysbiosis. Understanding the impacts of various anti-hyperglycemic agents such as metformin and the implications of post-bariatric surgery on the gut microbiota diversity has emerged. These areas of study are crucial to understanding the pathognomic aspects of diabetes disease progression at the microbial level of metabolic and inflammatory mechanisms, which may give more insight into focusing on the role of diet prebiotic/probiotic supplements as potential forms of prospective management in diabetes and the development of more agents that target gut microbiota, which harbors low-grade inflammation. Intestinal dysbiosis was consistently observed in the mechanism of gut microbial change in diabetic individuals, contributing to reduced insulin sensitivity and poor glycemic control. This systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 checklist. We performed a literature search using the PubMed, Google Scholar and Science Direct databases in accordance with the eligibility criteria and ultimately selected 14 articles for final analysis. The Scale for the Assessment of Narrative Review Articles (SANRA) and the PRISMA 2020 checklist were used to assess the quality of selected articles for cross-sectional studies, traditional literature reviews, and systematic reviews, respectively. We collected papers from 2012 to 2022 for this review. We gathered articles from databases, such as this study, which show there is a strong connection between microbiota and diabetes that appears to exist. The objective is to assess and identify any dietary and therapeutic agents that may alter the microbiota and potentially target and modulate insulin sensitivity. This review article will discuss the pathophysiological effects of gut microbiota in diabetes management and the impact of various gut biodiversity therapeutics that can aid in reversing insulin sensitivity.
PubMed: 37554593
DOI: 10.7759/cureus.41559 -
Clinical Chemistry and Laboratory... Feb 2024Dysregulation of hepcidin-iron axis is presumed to account for abnormal iron status in patients with chronic liver disease (CLD). Our aim is to determine the effect of... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Dysregulation of hepcidin-iron axis is presumed to account for abnormal iron status in patients with chronic liver disease (CLD). Our aim is to determine the effect of specific etiologies of CLD and of cirrhosis on serum hepcidin levels.
METHODS
PubMed, Embase, Web of Science were searched for studies comparing serum hepcidin levels in patients with CLD to that in controls using enzyme-linked immunosorbent assay. The study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines. Statistical analysis was carried out with STATA using random effects model to calculate the mean difference (MD) between two groups.
RESULTS
Hepcidin levels were significantly lower in subjects with hepatitis C virus (16 studies) [MD -1.6 (95 % CI: -2.66 to -0.54), p<0.01] and alcoholic liver disease (3 studies) [MD -0.84 (95 % CI: -1.6 to -0.07), p=0.03] than controls. Serum hepcidin was significantly higher in subjects with non-alcoholic fatty liver disease (12 studies) [MD 0.62 (95 % CI: 0.21 to 1.03), p<0.01], but did not differ in subjects with hepatitis B and controls (eight studies) [MD -0.65 (95 % CI: -1.47 to 0.16), p=0.12]. Hepcidin levels were significantly lower in patients with cirrhosis of any etiology (four studies) [MD -1.02 (CI: -1.59 to -0.45), p<0.01] vs. controls (CI: confidence interval).
CONCLUSIONS
Serum hepcidin levels are altered in common forms of CLD albeit not in a consistent direction. Additional study is needed to determine how changes in hepcidin levels are related to dysregulation of iron metabolism in CLD.
Topics: Humans; Hepcidins; Ferritins; Liver Cirrhosis; Iron; Non-alcoholic Fatty Liver Disease
PubMed: 37540837
DOI: 10.1515/cclm-2023-0540 -
Current Neuropharmacology 2024The diathesis-stress paradigm and the cannabinoid-hypothesis have been proposed as possible pathophysiological models of schizophrenia. However, they have historically...
BACKGROUND
The diathesis-stress paradigm and the cannabinoid-hypothesis have been proposed as possible pathophysiological models of schizophrenia. However, they have historically been studied independently of each other.
OBJECTIVE
This PRISMA 2020-compliant systematic review aimed at reappraising the interplay between the hypothalamic-pituitary-adrenal (HPA) axis and the endocannabinoid (eCB) system in psychosis- spectrum disorder risk and outcome.
METHODS
All pathophysiological and outcome clinical studies, concomitantly evaluating the two systems in psychosis-spectrum disorder risk and different stages of illness, were gathered from electronic databases (Pubmed, Web of Science, and Scopus), and discussed.
RESULTS
41 eligible outputs were extracted, focusing on at least a biological measure (9 HPA-related studies: 4 eCB-interventional, 1 HPA-interventional, 1 both HPA-interventional and non-interventional, 3 non-interventional; 2 eCB-related studies: non-interventional), environmental measures only (29 studies: 1 eCB- interventional, 28 non-interventional), and genetic measures (1 study: non-interventional). Independent contributions of aberrancies in the two systems to the physiopathology and outcome of psychosis were confirmed. Also, concomitant alterations in the two systems, either genetically defined (e.g., CNR1 genetic variation), biologically determined (e.g., dysfunctional HPA axis or endocannabinoid signaling), or behaviorally imputed (e.g., cannabis use, stress exposure, and response), were consistently reported in psychosis. Further, a complex biobehavioral perturbation was revealed not only within each system (e.g., cannabis use affecting the eCB tone, stress exposure affecting the HPA axis), but also across the two systems (e.g., THC affecting the HPA axis, childhood trauma affecting the endocannabinoid signaling).
CONCLUSION
There is a need to concomitantly study the two systems' mechanistic contribution to psychosis in order to establish more refined biological relevance.
Topics: Humans; Hypothalamo-Hypophyseal System; Endocannabinoids; Pituitary-Adrenal System; Psychotic Disorders; Schizophrenia
PubMed: 37533248
DOI: 10.2174/1570159X21666230801150032 -
Scientific Reports Aug 2023Osteoarthritis (OA) affects 240 million people worldwide. Neuroimaging has been increasingly used to investigate brain changes in OA, however, there is considerable... (Meta-Analysis)
Meta-Analysis
Osteoarthritis (OA) affects 240 million people worldwide. Neuroimaging has been increasingly used to investigate brain changes in OA, however, there is considerable heterogeneity in reported results. The goal of this systematic review and meta-analysis was to synthesise existing literature and identify consistent brain alterations in OA. Six databases were searched from inception up to June, 2022. Full-texts of original human studies were included if they had: (i) neuroimaging data by site of OA (e.g. hand, knee, hip); (ii) data in healthy controls (HC); (iii) > 10 participants. Activation likelihood estimation (ALE) was conducted using GingerALE software on studies that reported peak activation coordinates and sample size. Our search strategy identified 6250 articles. Twenty-eight studies fulfilled the eligibility criteria, of which 18 were included in the meta-analysis. There were no significant differences in brain structure or function between OA and healthy control contrasts. In exploratory analysis, the right insula was associated with OA vs healthy controls, with less activity, connectivity and brain volume in OA. This region was implicated in both knee and hip OA, with an additional cluster in the medial prefrontal cortex observed only in the contrast between healthy controls and the hip OA subgroup, suggesting a possible distinction between the neural correlates of OA subtypes. Despite the limitations associated with heterogeneity and poor study quality, this synthesis identified neurobiological outcomes associated with OA, providing insight for future research. PROSPERO registration number: CRD42021238735.
Topics: Humans; Osteoarthritis, Hip; Likelihood Functions; Osteoarthritis, Knee; Brain; Neuroimaging
PubMed: 37528135
DOI: 10.1038/s41598-023-39245-9 -
Environmental Research Nov 2023Particulate matter (PM) is a major component of ambient air pollution (AAP), being widely associated with adverse health effects. Epidemiological and experimental... (Review)
Review
The influence of environmental particulate matter exposure during late gestation and early life on the risk of neurodevelopmental disorders: A systematic review of experimental evidences.
Particulate matter (PM) is a major component of ambient air pollution (AAP), being widely associated with adverse health effects. Epidemiological and experimental studies point towards a clear implication of AAP on the development of central nervous system (CNS) diseases. In this sense, the period of most CNS susceptibility is early life, when the CNS is maturing. In humans the last trimester of gestation is crucial for brain maturation while in rodents, due to the shorter gestational period, the brain is still immature at birth, and early postnatal development plays a significant role. The present systematic review provides an updated overview and discusses the existing literature on the relationship between early exposure to PM and neurodevelopmental outcomes in experimental studies. We included 11 studies with postnatal exposure and 9 studies with both prenatal and postnatal exposure. Consistent results between studies suggest that PM exposure could alter normal development, triggering impairments in short-term memory, sociability, and impulsive-like behavior. This is also associated with alterations in synaptic plasticity and in the immune system. Interestingly, differences have been observed between sexes, although not all studies included females. Furthermore, the developmental window of exposure seems to be crucial for effects to be observed in the future. In summary, air pollution exposure during development affects subjects in a time- and sex-dependent manner, the postnatal period being more important and being males apparently more sensitive to exposure than females. Nevertheless, additional experimental investigations should prioritize the examination of learning, impulsivity, and biochemical parameters, with particular attention provided to disparities between sexes.
Topics: Male; Infant, Newborn; Female; Pregnancy; Humans; Particulate Matter; Air Pollutants; Air Pollution; Environmental Exposure; Neurodevelopmental Disorders
PubMed: 37527744
DOI: 10.1016/j.envres.2023.116792 -
Chemosphere Oct 2023This comprehensive study analysed 55 articles published between 2011 and 2022 on the use of metal organic frameworks (MOFs) for phosphate adsorption. The study found... (Meta-Analysis)
Meta-Analysis Review
This comprehensive study analysed 55 articles published between 2011 and 2022 on the use of metal organic frameworks (MOFs) for phosphate adsorption. The study found that the performance of MOFs in phosphate adsorption is influenced by various factors such as the type of MOF, synthesis method, modification/alteration, and operational conditions (initial concentration, adsorbent dose, pH, contact time, and temperature). Most of the MOFs have a wide range of theoretical maximum adsorption capacity for phosphate, but their long-term use in phosphorus recovery may be limited due to the adsorption mechanisms being dominated by inner sphere complexation. The study employed machine learning to construct artificial neural network (ANN) models for predicting phosphate adsorption capacity based on input features from operation and synthesis procedures. The initial phosphate concentration was the most important input from the operational features, while the modulator agent was consistently relevant during MOF synthesis. The models showed strong fitting for most MOF types recorded for the study, such as UIO-66, MIL-100, ZIF-8, Al-MOFs, La-MOFs, and Ce-MOFs. Overall, this study provides valuable insights for the design of MOF adsorbents for phosphate adsorption and offers guidance for future research in this area.
Topics: Phosphates; Metal-Organic Frameworks; Adsorption; Phosphorus; Neural Networks, Computer
PubMed: 37517668
DOI: 10.1016/j.chemosphere.2023.139674 -
Molecular Psychiatry Oct 2023Aberrant anatomical brain connections in attention-deficit/hyperactivity disorder (ADHD) are reported inconsistently across diffusion weighted imaging (DWI) studies.... (Meta-Analysis)
Meta-Analysis
Aberrant anatomical brain connections in attention-deficit/hyperactivity disorder (ADHD) are reported inconsistently across diffusion weighted imaging (DWI) studies. Based on a pre-registered protocol (Prospero: CRD42021259192), we searched PubMed, Ovid, and Web of Knowledge until 26/03/2022 to conduct a systematic review of DWI studies. We performed a quality assessment based on imaging acquisition, preprocessing, and analysis. Using signed differential mapping, we meta-analyzed a subset of the retrieved studies amenable to quantitative evidence synthesis, i.e., tract-based spatial statistics (TBSS) studies, in individuals of any age and, separately, in children, adults, and high-quality datasets. Finally, we conducted meta-regressions to test the effect of age, sex, and medication-naïvety. We included 129 studies (6739 ADHD participants and 6476 controls), of which 25 TBSS studies provided peak coordinates for case-control differences in fractional anisotropy (FA)(32 datasets) and 18 in mean diffusivity (MD)(23 datasets). The systematic review highlighted white matter alterations (especially reduced FA) in projection, commissural and association pathways of individuals with ADHD, which were associated with symptom severity and cognitive deficits. The meta-analysis showed a consistent reduced FA in the splenium and body of the corpus callosum, extending to the cingulum. Lower FA was related to older age, and case-control differences did not survive in the pediatric meta-analysis. About 68% of studies were of low quality, mainly due to acquisitions with non-isotropic voxels or lack of motion correction; and the sensitivity analysis in high-quality datasets yielded no significant results. Findings suggest prominent alterations in posterior interhemispheric connections subserving cognitive and motor functions affected in ADHD, although these might be influenced by non-optimal acquisition parameters/preprocessing. Absence of findings in children may be related to the late development of callosal fibers, which may enhance case-control differences in adulthood. Clinicodemographic and methodological differences were major barriers to consistency and comparability among studies, and should be addressed in future investigations.
Topics: Adult; Humans; Child; White Matter; Attention Deficit Disorder with Hyperactivity; Diffusion Tensor Imaging; Brain; Corpus Callosum; Anisotropy
PubMed: 37479785
DOI: 10.1038/s41380-023-02173-1 -
Chemosphere Oct 2023Glyphosate was classified as a probable human carcinogen (Group 2A) by the International Agency for Research on Cancer (IARC) partially due to strong mechanistic... (Review)
Review
Glyphosate was classified as a probable human carcinogen (Group 2A) by the International Agency for Research on Cancer (IARC) partially due to strong mechanistic evidence in 2015. Since then, numerous studies of glyphosate and its formulations (GBF) have emerged. These studies can be evaluated for cancer hazard identification with the newly described ten key characteristics (KC) of carcinogens approach. Our objective was to assess all in vivo, ex vivo, and in vitro mechanistic studies of human and experimental animals (mammals) that compared exposure to glyphosate/GBF with low/no exposure counterparts for evidence of the ten KCs. A protocol with our methods adhering to PRISMA guidelines was registered a priori (INPLASY202180045). Two blinded reviewers screened all in vivo, ex vivo, and in vitro studies of glyphosate/GBF exposure in humans/mammals reporting any KC-related outcome available in PubMed before August 2021. Studies that met inclusion criteria underwent data extraction conducted in duplicate for each KC outcome reported along with key aspects of internal/external validity, results, and reference information. These data were used to construct a matrix that was subsequently analyzed in the program R to conduct strength of evidence and quality assessments. Of the 2537 articles screened, 175 articles met inclusion criteria, from which we extracted >50,000 data points related to KC outcomes. Data analysis revealed strong evidence for KC2, KC4, KC5, KC6, KC8, limited evidence for KC1 and KC3, and inadequate evidence for KC7, KC9, and KC10. Notably, our in-depth quality analyses of genotoxicity (KC2) and endocrine disruption (KC8) revealed strong and consistent positive findings. For KC2, we found: 1) studies conducted in humans and human cells provided stronger positive evidence than counterpart animal models; 2) GBF elicited a stronger effect in both human and animal systems when compared to glyphosate alone; and 3) the highest quality studies in humans and human cells consistently revealed strong evidence of genotoxicity. Our analysis of KC8 indicated that glyphosate's ability to modulate hormone levels and estrogen receptor activity is sensitive to both exposure concentration and formulation. The modulations observed provide clear evidence that glyphosate interacts with receptors, alters receptor activation, and modulates the levels and effects of endogenous ligands (including hormones). Our findings strengthen the mechanistic evidence that glyphosate is a probable human carcinogen and provide biological plausibility for previously reported cancer associations in humans, such as non-Hodgkin lymphoma. We identified potential molecular interactions and subsequent key events that were used to generate a probable pathway to lymphomagenesis.
Topics: Animals; Humans; Carcinogens; Herbicides; Neoplasms; Lymphoma, Non-Hodgkin; Mammals; Glyphosate
PubMed: 37474029
DOI: 10.1016/j.chemosphere.2023.139572 -
Schizophrenia Bulletin Jan 2024Schizophrenia is highly heritable, with a polygenic effect of many genes conferring risk. Evidence on whether cumulative risk also predicts alterations in brain...
BACKGROUND AND HYPOTHESIS
Schizophrenia is highly heritable, with a polygenic effect of many genes conferring risk. Evidence on whether cumulative risk also predicts alterations in brain morphology and function is inconsistent. This systematic review examined evidence for schizophrenia polygenic risk score (sczPRS) associations with commonly used magnetic resonance imaging (MRI) measures. We expected consistent evidence to emerge for significant sczPRS associations with variation in structure and function, specifically in frontal, temporal, and insula cortices that are commonly implicated in schizophrenia pathophysiology.
STUDY DESIGN
In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched MEDLINE, Embase, and PsycINFO for peer-reviewed studies published between January 2013 and March 2022. Studies were screened against predetermined criteria and National Institutes of Health (NIH) quality assessment tools.
STUDY RESULTS
In total, 57 studies of T1-weighted structural, diffusion, and functional MRI were included (age range = 9-80 years, Nrange = 64-76 644). We observed moderate, albeit preliminary, evidence for higher sczPRS predicting global reductions in cortical thickness and widespread variation in functional connectivity, and to a lesser extent, region-specific reductions in frontal and temporal volume and thickness. Conversely, sczPRS does not predict whole-brain surface area or gray/white matter volume. Limited evidence emerged for sczPRS associations with diffusion tensor measures of white matter microstructure in a large community sample and smaller cohorts of children and young adults. These findings were broadly consistent across community and clinical populations.
CONCLUSIONS
Our review supports the hypothesis that schizophrenia is a disorder of disrupted within and between-region brain connectivity, and points to specific whole-brain and regional MRI metrics that may provide useful intermediate phenotypes.
Topics: Young Adult; Child; Humans; Adolescent; Adult; Middle Aged; Aged; Aged, 80 and over; Schizophrenia; Magnetic Resonance Imaging; Brain; Gray Matter; White Matter
PubMed: 37354489
DOI: 10.1093/schbul/sbad087 -
The Journal of Clinical Endocrinology... Dec 2023Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women...
PURPOSE
Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women globally, with associated cardiometabolic dysfunction. Adipose tissue (AT) dysfunction appears to play an important role in the pathophysiology of PCOS even in patients who do not have excess adiposity.
METHODS
We undertook a systematic review concerning AT dysfunction in PCOS, and prioritized studies that assessed AT function directly. We also explored therapies that targeted AT dysfunction for the treatment of PCOS.
RESULTS
Various mechanisms of AT dysfunction in PCOS were identified including dysregulation in storage capacity, hypoxia, and hyperplasia; impaired adipogenesis; impaired insulin signaling and glucose transport; dysregulated lipolysis and nonesterified free fatty acids (NEFAs) kinetics; adipokine and cytokine dysregulation and subacute inflammation; epigenetic dysregulation; and mitochondrial dysfunction and endoplasmic reticulum and oxidative stress. Decreased glucose transporter-4 expression and content in adipocytes, leading to decreased insulin-mediated glucose transport in AT, was a consistent abnormality despite no alterations in insulin binding or in IRS/PI3K/Akt signaling. Adiponectin secretion in response to cytokines/chemokines is affected in PCOS compared to controls. Interestingly, epigenetic modulation via DNA methylation and microRNA regulation appears to be important mechanisms underlying AT dysfunction in PCOS.
CONCLUSION
AT dysfunction, more than AT distribution and excess adiposity, contributes to the metabolic and inflammation abnormalities of PCOS. Nonetheless, many studies provided contradictory, unclear, or limited data, highlighting the urgent need for additional research in this important field.
Topics: Humans; Female; Adult; Polycystic Ovary Syndrome; Insulin Resistance; Phosphatidylinositol 3-Kinases; Adipose Tissue; Insulin; Cytokines; Obesity; Inflammation; Glucose
PubMed: 37329216
DOI: 10.1210/clinem/dgad356