-
Frontiers in Pharmacology 2021As lifestyle and diet structure impact our health, non-alcoholic fatty liver disease (NAFLD) is prevalent all over the world. Some phytomedicines containing berberine...
As lifestyle and diet structure impact our health, non-alcoholic fatty liver disease (NAFLD) is prevalent all over the world. Some phytomedicines containing berberine (BBR) have been extensively used for centuries in Ayurvedic and traditional Chinese medicine. The goal of this systematic review is to investigate the preclinical evidence of BBR on NAFLD models. The following relevant databases, including Web of Science, PubMed, the Cochrane Library, and Embase, were retrieved from inception to May 2021. The content involved BBR on different animal models for the treatment of NAFLD. The SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) Animal Experiment Bias Risk Assessment Tool was used to assess the methodological quality and RevMan 5.4 software was used to conduct the meta-analysis based on the Cochrane tool. A total of 31 studies involving 566 animals were included, of which five models and five animal breeds were reported. The results showed that TC, TG, ALT, AST, HDL-C, LDL-C, FBG, FINS, and FFA in the group treated with BBR were significantly restored compared with those in the model group. HOMA-IR had a significant downward trend, but the result was not significantly different (P = 0.08). The subgroup analysis of the different models and different animal breeds indicated that BBR could ameliorate the aforementioned indicator levels, although some results showed no significant difference. Finally, we summarized the molecular mechanisms by which berberine regulated NAFLD/NASH, mainly focusing on activating the AMPK pathway, improving insulin sensitivity and glucose metabolism, regulating mitochondrial function, reducing inflammation and oxidative stress, regulating cell death and ER stress, reducing DNA methylation, and regulating intestinal microenvironment and neurotoxicity. The preclinical evidence suggested that BBR might be an effective and promising drug for treating NAFLD/NASH. In addition, further studies with more well-designed researches are needed to confirm this conclusion.
PubMed: 34566663
DOI: 10.3389/fphar.2021.742465 -
Hepatology International Jun 2024The identification of reliable predictors for hepatitis B surface antigen (HBsAg) seroclearance remains controversial. We aimed to summarize potential predictors for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
The identification of reliable predictors for hepatitis B surface antigen (HBsAg) seroclearance remains controversial. We aimed to summarize potential predictors for HBsAg seroclearance by pegylated interferon-α (PegIFNα) in patients with chronic HBV infection.
METHODS
A systematic search of the Cochrane Library, Embase, PubMed, and Web of Science databases was conducted from their inception to 28 September 2022. Meta-analyses were performed following the PRISMA statement. Predictors of HBsAg seroclearance were evaluated based on baseline characteristics and on-treatment indicators.
RESULTS
This meta-analysis encompasses 27 studies, including a total of 7913 patients. The findings reveal several factors independently associated with HBsAg seroclearance induced by PegIFNα-based regimens. These factors include age (OR = 0.961), gender (male vs. female, OR = 0.537), genotype (A vs. B/D; OR = 7.472, OR = 10.738), treatment strategy (combination vs. monotherapy, OR = 2.126), baseline HBV DNA (OR = 0.414), baseline HBsAg (OR = 0.373), HBsAg levels at week 12 and 24 (OR = 0.384, OR = 0.294), HBsAg decline from baseline to week 12 and 24 (OR = 6.689, OR = 6.513), HBsAg decline from baseline ≥ 1 log IU/ml and ≥ 0.5 log IU/ml at week 12 (OR = 18.277; OR = 4.530), and ALT elevation at week 12 (OR = 3.622). Notably, subgroup analysis suggests no statistical association between HBsAg levels at week 12 and HBsAg seroclearance for treatment duration exceeding 48 weeks. The remaining results were consistent with the overall analysis.
CONCLUSIONS
This is the first meta-analysis to identify predictors of HBsAg seroclearance with PegIFNα-based regimens, including baseline and on-treatment factors, which is valuable in developing a better integrated predictive model for HBsAg seroclearance to guide individualized treatment and achieve the highest cost-effectiveness of PegIFNα.
Topics: Humans; Interferon-alpha; Hepatitis B, Chronic; Hepatitis B Surface Antigens; Antiviral Agents; Polyethylene Glycols; Hepatitis B virus
PubMed: 38461186
DOI: 10.1007/s12072-024-10648-8 -
HPB : the Official Journal of the... May 2015Endoscopic ultrasonography with fine needle aspiration (EUS-FNA) has become an integral tool in the diagnosis of pancreatic cystic lesions (PCLs) and the analysis of... (Review)
Review
BACKGROUND
Endoscopic ultrasonography with fine needle aspiration (EUS-FNA) has become an integral tool in the diagnosis of pancreatic cystic lesions (PCLs) and the analysis of molecular/DNA abnormalities might improve the accuracy of pre-operative diagnosis. A review was conducted of all studies using EUS-FNA aspirates of PCLs to assess the accuracy and added benefit that molecular analysis provides to cytological analysis.
METHODS
A systematic review of the literature was conducted using PRISMA guidelines and electronic databases: PubMed/SCOPUS/EMBASE/Cochrane/CINAHL. Surgical pathology was used as the definitive reference standard. The QUADAS-2 tool was used for quality assessment.
RESULTS
In total, 162 articles were identified; 12 articles met inclusion/exclusion criteria. Ten studies reported on cytology and 8 studies reported k-ras mutational analysis. 362 patients (of 1115 total) had surgical pathology available. The sensitivity and specificity of cytology was 0.42 and 0.99; the sensitivity and specificity of k-ras was 0.39 and 0.95; and the sensitivity and specificity of the combined test of cytology and k-ras was 0.71 and 0.88, respectively.
CONCLUSIONS
k-ras mutational analysis used as an individual screening test has a poor diagnostic accuracy, as does cytology when used alone. The benefit comes with utilization in a combined fashion. More studies are needed to evaluate the correct sequence and utility of these tests for cyst differentiation.
Topics: DNA; DNA Mutational Analysis; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Genes, ras; Humans; Molecular Diagnostic Techniques; Pancreas; Pancreatic Cyst
PubMed: 25428782
DOI: 10.1111/hpb.12364 -
Annals of Global Health Jul 2018Children are susceptible to environmental contaminants and are at risk of developing diseases, more so if the exposure begins at an early age. Epidemiological studies...
BACKGROUND
Children are susceptible to environmental contaminants and are at risk of developing diseases, more so if the exposure begins at an early age. Epidemiological studies have postulated the hypothesis of the fetal origin of disease, which is mediated by epigenetic changes. Epigenetic marks are inheritable; they modulate the gene expression and can affect human health due to the presence of environmental factors.
OBJECTIVE
This review focuses on DNA-methylation and its association with environmental-related diseases in children.
METHODS
A search for studies related to DNA-methylation in children by pre- or post-natal environmental exposures was conducted, and those studies with appropriate designs and statistical analyses and evaluations of the exposure were selected.
FINDINGS
Prenatal and early life environmental factors, from diet to exposure to pollutants, have been associated with epigenetic changes, specifically DNA-methylation. Thus, maternal nutrition and smoking and exposure to air particulate matter, polycyclic aromatic hydrocarbons, arsenic, heavy metals, persistent organic pollutants, and some endocrine disrupters during pregnancy have been associated with genomic and gene-specific newborns' DNA-methylation changes that have shown in some cases sex-specific patterns. In addition, these maternal factors may deregulate the placental DNA-methylation balance and could induce a fetal reprogramming and later-in-life diseases.
CONCLUSIONS
Exposure to environmental pollutants during prenatal and early life can trigger epigenetic imbalances and eventually the development of diseases in children. The integration of epigenetic data should be considered in future risk assessments.
Topics: Child; Child Health; DNA Methylation; Environmental Exposure; Environmental Health; Epigenesis, Genetic; Female; Humans; Maternal Exposure; Risk Factors
PubMed: 30873799
DOI: 10.29024/aogh.909 -
Scientific African Sep 2023The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus's worldwide pandemic has highlighted the urgent need for reliable, quick, and affordable...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus's worldwide pandemic has highlighted the urgent need for reliable, quick, and affordable diagnostic tests for comprehending and controlling the epidemic by tracking the world population. Given how crucial it is to monitor and manage the pandemic, researchers have recently concentrated on creating quick detection techniques. Although PCR is still the preferred clinical diagnostic test, there is a pressing need for substitutes that are sufficiently rapid and cost-effective to provide a diagnosis at the time of use. The creation of a quick and simple POC equipment is necessary for home testing. Our review's goal is to provide an overview of the many methods utilized to identify SARS-CoV 2 in various samples utilizing portable devices, as well as any potential applications for smartphones in epidemiological research and detection. The point of care (POC) employs a range of microfluidic biosensors based on smartphones, including molecular sensors, immunological biosensors, hybrid biosensors, and imaging biosensors. For example, a number of tools have been created for the diagnosis of COVID-19, based on various theories. Integrated portable devices can be created using loop-mediated isothermal amplification, which combines isothermal amplification methods with colorimetric detection. Electrochemical approaches have been regarded as a potential substitute for optical sensing techniques that utilize fluorescence for detection and as being more beneficial to the Minimizing and simplicity of the tools used for detection, together with techniques that can amplify DNA or RNA under constant temperature conditions, without the need for repeated heating and cooling cycles. Many research have used smartphones for virus detection and data visualization, making these techniques more user-friendly and broadly distributed throughout nations. Overall, our research provides a review of different novel, non-invasive, affordable, and efficient methods for identifying COVID-19 contagious infected people and halting the disease's transmission.
PubMed: 37351482
DOI: 10.1016/j.sciaf.2023.e01757 -
The Lancet. Infectious Diseases May 2021Cryptosporidiosis is a common cause of diarrhoea in young children (aged younger than 24 months) in low-resource settings but is currently challenging to diagnose....
BACKGROUND
Cryptosporidiosis is a common cause of diarrhoea in young children (aged younger than 24 months) in low-resource settings but is currently challenging to diagnose. Light-emitting diode fluorescence microscopy with auramine-phenol staining (LED-AP), recommended for tuberculosis testing, can also detect Cryptosporidium species. A lateral-flow test not requiring refrigerator storage (by contrast with most immunochromatographic lateral-flow assays) has also recently been developed for Cryptosporidium spp detection. We aimed to evaluate the diagnostic accuracy and operational feasibility of LED-AP and the lateral-flow test strip for cryptosporidiosis in children.
METHODS
We did a prospective diagnostic accuracy study in two health-care facilities in Ethiopia, in a consecutive series of children younger than 5 years of age with diarrhoea (three or more loose stools within the previous 24 h) or dysentery (at least one loose stool with stains of blood within the previous 24 h). Stool samples were tested for Cryptosporidium spp by LED-AP and the lateral-flow test strip; accuracy of each test was estimated by independent and blind comparison with a composite reference standard comprising quantitative immunofluorescent antibody test (qIFAT), ELISA, and quantitative PCR (qPCR). Quantitative cutoff values for diarrhoea-associated infection were established in an embedded case-control substudy, with cases of cryptosporidiosis coming from the 15 districts in and around Jimma and the eight districts surrounding Serbo, and community controls without diarrhoea in the previous 48 h recruited by weekly frequency matching by geographical district of the household, age group, and enrolment week.
FINDINGS
Stool samples from 912 children with diarrhoea or dysentery and 706 controls from the case-control substudy were tested between Dec 22, 2016, and July 6, 2018. Estimated reference-standard cutoff values for cryptosporidiosis positivity were 2·3 × 10 DNA copies per g of wet stool for qPCR, and 725 oocysts per g for qIFAT. LED-AP had a sensitivity for cryptosporidiosis of 88% (95% CI 79-94; 66 of 75 samples) and a specificity of 99% (98-99; 717 of 726 samples); the lateral-flow test strip had a sensitivity of 89% (79-94; 63 of 71 samples) and a specificity of 99% (97-99; 626 of 635 samples).
INTERPRETATION
LED-AP has high sensitivity and specificity for cryptosporidiosis and should be considered as a dual-use technology that can be easily integrated with existing laboratory infrastructures in low-resource settings. The lateral-flow test strip has similar sensitivity and specificity and provides an alternative that does not require microscopy, although purchase cost of the test strip is unknown as it is not yet available on the market.
FUNDING
Norwegian Research Council GLOBVAC fund, The Bill & Melinda Gates Foundation, Norwegian Society for Medical Microbiology, University of Bergen, and Vestfold Hospital Trust.
Topics: Child; Cryptosporidiosis; Cryptosporidium; Databases, Factual; Diagnostic Tests, Routine; Diarrhea; Ethiopia; Feasibility Studies; Feces; Humans; Immunoassay; Prospective Studies; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity
PubMed: 33278916
DOI: 10.1016/S1473-3099(20)30556-9 -
Cold Spring Harbor Molecular Case... Jun 2019In the current era of personalized medicine, the field of oncology is witnessing a paradigm shift in patient care that is driving a tighter integration of genomic...
In the current era of personalized medicine, the field of oncology is witnessing a paradigm shift in patient care that is driving a tighter integration of genomic analysis modalities in patient care decision. This is driven by the expanding category of targeted therapies that require a broader understanding of the mutational profile of patient samples to more precisely guided personalized treatment decisions. Next-generation sequencing (NGS) has proved to be of tremendous power in detecting and characterizing a broad spectrum of activating or loss-of-function mutations across many gene targets. This power of NGS also results in significant challenges related to technical expertise, bioinformatics, computing infrastructure, laboratory practices, and integration into clinical decision-making. These challenges are particularly relevant to smaller and mid-tier hospital networks that are faced with the need to modernize their clinical practices and offer their patients access to advanced genomic technologies to improve outcomes. Adoption of such personalized medicine relies on information about a patient's cancer genome and the identification of its variants. This is best achieved using NGS. However, there are challenges to the adoption of such a complex technology and workflow, especially in smaller hospital systems. This commentary summarizes key considerations and challenges related to implementation of NGS in a community hospital setting.
Topics: Computational Biology; Genomics; High-Throughput Nucleotide Sequencing; Hospitals, Community; Humans; Medical Oncology; Mutation; Neoplasms; Precision Medicine; Sequence Analysis, DNA
PubMed: 31160354
DOI: 10.1101/mcs.a003707 -
Frontiers in Endocrinology 2024The leading indicator for successful outcomes in fertilization (IVF) is the quality of gametes in oocytes and sperm. Thus, advanced research aims to highlight the... (Review)
Review
Unravelling the role of HAS2, GREM1, and PTGS2 gene expression in cumulus cells: implications for human oocyte development competency - a systematic review and integrated bioinformatic analysis.
The leading indicator for successful outcomes in fertilization (IVF) is the quality of gametes in oocytes and sperm. Thus, advanced research aims to highlight the parameter in assessing these qualities - DNA fragmentation in sperm and oocyte development capacity (ODC) via evaluation of microenvironments involving its maturation process. Regarding oocytes, most evidence reveals the role of cumulus cells as non-invasive methods in assessing their development competency, mainly via gene expression evaluation. Our review aims to consolidate the evidence of GDF-9 derivatives, the HAS2, GREM1, and PTGS2 gene expression in cumulus cells used as ODC markers in relevant publications and tailored to current IVF outcomes. In addition to that, we also added the bioinformatic analysis in our review to strengthen the evidence aiming for a better understanding of the pathways and cluster of the genes of interest - HAS2, GREM1, and PTGS2 in cumulus cell level. Otherwise, the current non-invasive method can be used in exploring various causes of infertility that may affect these gene expressions at the cumulus cell level. Nevertheless, this method can also be used in assessing the ODC in various cohorts of women or as an improvement of markers following targeted tools or procedures by evaluating the advancement of these gene expressions following the targeted intervention.
Topics: Humans; Male; Female; Cyclooxygenase 2; Cumulus Cells; Semen; Oocytes; Gene Expression; Intercellular Signaling Peptides and Proteins; Hyaluronan Synthases
PubMed: 38524634
DOI: 10.3389/fendo.2024.1274376 -
Journal of Cancer Research and Clinical... Jan 2024Accurate and non-invasive estimation of MGMT promoter methylation status in glioblastoma (GBM) patients is of paramount clinical importance, as it is a predictive... (Review)
Review
BACKGROUND
Accurate and non-invasive estimation of MGMT promoter methylation status in glioblastoma (GBM) patients is of paramount clinical importance, as it is a predictive biomarker associated with improved overall survival (OS). In response to the clinical need, recent studies have focused on the development of non-invasive artificial intelligence (AI)-based methods for MGMT estimation. In this systematic review, we not only delve into the technical aspects of these AI-driven MGMT estimation methods but also emphasize their profound clinical implications. Specifically, we explore the potential impact of accurate non-invasive MGMT estimation on GBM patient care and treatment decisions.
METHODS
Employing a PRISMA search strategy, we identified 33 relevant studies from reputable databases, including PubMed, ScienceDirect, Google Scholar, and IEEE Explore. These studies were comprehensively assessed using 21 diverse attributes, encompassing factors such as types of imaging modalities, machine learning (ML) methods, and cohort sizes, with clear rationales for attribute scoring. Subsequently, we ranked these studies and established a cutoff value to categorize them into low-bias and high-bias groups.
RESULTS
By analyzing the 'cumulative plot of mean score' and the 'frequency plot curve' of the studies, we determined a cutoff value of 6.00. A higher mean score indicated a lower risk of bias, with studies scoring above the cutoff mark categorized as low-bias (73%), while 27% fell into the high-bias category.
CONCLUSION
Our findings underscore the immense potential of AI-based machine learning (ML) and deep learning (DL) methods in non-invasively determining MGMT promoter methylation status. Importantly, the clinical significance of these AI-driven advancements lies in their capacity to transform GBM patient care by providing accurate and timely information for treatment decisions. However, the translation of these technical advancements into clinical practice presents challenges, including the need for large multi-institutional cohorts and the integration of diverse data types. Addressing these challenges will be critical in realizing the full potential of AI in improving the reliability and accessibility of MGMT estimation while lowering the risk of bias in clinical decision-making.
Topics: Humans; Glioblastoma; Artificial Intelligence; Reproducibility of Results; DNA Methylation; Brain Neoplasms; DNA Modification Methylases; DNA Repair Enzymes; DNA; Tumor Suppressor Proteins
PubMed: 38291266
DOI: 10.1007/s00432-023-05566-5 -
Antimicrobial Agents and Chemotherapy Feb 2021Molecular testing is rapidly becoming an integral component of global tuberculosis (TB) control. Uncommon mechanisms of resistance escape detection by these platforms...
Systematic Review of Mutations Associated with Isoniazid Resistance Points to Continuing Evolution and Subsequent Evasion of Molecular Detection, and Potential for Emergence of Multidrug Resistance in Clinical Strains of Mycobacterium tuberculosis.
Molecular testing is rapidly becoming an integral component of global tuberculosis (TB) control. Uncommon mechanisms of resistance escape detection by these platforms and undermine our ability to contain outbreaks. This article is a systematic review of published articles that reported isoniazid (INH) resistance-conferring mutations between September 2013 and December 2019. The genes , , and , and the intergenic region '- were considered in this review. Fifty-two articles were included that described 9,306 clinical isolates (5,804 INH resistant [INH] and 3,502 INH susceptible [INH]) from 31 countries. The three most frequently mutated loci continue to be locus 315 of (315; = 4,271), locus -15 of (-15; = 787), and locus -8 of (-8; 106). However, the diagnostic value of -8 is far lower than previously thought, as it only appears in 25 (0.4%) of the INH isolates lacking the first two mutations. I catalogued 45 new loci (29 , nine , and seven ) associated with INH resistance and identified 59 loci (common to this and previous reviews) as a reliable basis for molecular diagnostics. Including all observed mutations provides a cumulative sensitivity of 85.6%. In 14.4% of resistant isolates, no mechanism of resistance was detected, making them likely to escape molecular detection, and in the case of INH monoresistance, likely to convert to multidrug-resistant TB (MDR-TB). Integrating the information cataloged in this study into current diagnostic tools is essential for combating the emergence of MDR-TB, and its exclusion can lead to an unintended selection against common mechanisms and to diversifying evolution. Observation of many low-frequency resistance-conferring mutations points to an advantage of whole-genome sequencing (WGS) for diagnostics. Finally, I provide five recommendations for future diagnostic platforms.
Topics: Antitubercular Agents; Bacterial Proteins; DNA, Bacterial; Drug Resistance, Multiple; Humans; Isoniazid; Microbial Sensitivity Tests; Mutation; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 33361298
DOI: 10.1128/AAC.02091-20