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Hormone Research in Paediatrics 2023Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder that causes defects in the adrenal cortex enzymes that impair the biosynthesis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder that causes defects in the adrenal cortex enzymes that impair the biosynthesis of cortisol, aldosterone, or both. The most common type is the 21-hydroxylase enzyme deficiency in approximately 95% of cases resulting from CYP21A2 gene mutations or deletions.
OBJECTIVES
This study aimed to systematically review the national differences in CAH incidence and analyze the pooled results to determine disparities and whether ethnicity can predispose people to develop CAH.
METHODS
PubMed, Scopus, and LILACS were used to achieve results until June 22, 2018. Study eligibility criteria included availability of full-text; English, Spanish, or Portuguese languages; incidence or number of new cases; and number of live births or sample population. Only the classic CAH type (salt-wasting and simple-virilizing) was considered, and no distinction was made between the enzyme deficiency types.
RESULTS
This study summarizes the findings of 58 studies and 31 countries (from 1969 to 2017), in which the overall CAH incidence was 1:9,498 (95% confidence interval: 1:9,089, 1:9,945). Countries from the Eastern Mediterranean and Southeast Asia revealed the highest CAH incidence. The lowest incidence was reported in countries of the Western Pacific of Asia. No remarkable difference was observed in the Hispanics/Latino and White groups. However, they manifested a higher incidence of CAH than people identified as Black or of African descent. Published studies on CAH incidence in the sub-Saharan African region and parts of Europe were insufficient.
CONCLUSIONS
This study highlights the at-risk population for CAH and regions that need monitoring for CAH. The highest CAH incidence could be attributed to higher consanguinity, less genetic diversity, or other genetic causes since CAH is an inherited genetic disorder. Cultural practices in some places regarding consanguineous unions or geographic isolation may directly affect the incidence. Newborn screening for CAH may be unavailable in many developing countries, thereby affecting the actual CAH incidence. Therefore, healthcare workers should be trained to recognize CAH at an early stage to reduce its complications and mortality.
Topics: Infant, Newborn; Humans; Adrenal Hyperplasia, Congenital; Neonatal Screening; Adrenal Cortex; Mutation; Steroid 21-Hydroxylase
PubMed: 35973409
DOI: 10.1159/000526401 -
Bone Research Aug 2022Approximately 40% of treatments of chronic and recurrent osteomyelitis fail in part due to bacterial persistence. Staphylococcus aureus, the predominant pathogen in... (Review)
Review
Approximately 40% of treatments of chronic and recurrent osteomyelitis fail in part due to bacterial persistence. Staphylococcus aureus, the predominant pathogen in human osteomyelitis, is known to persist by phenotypic adaptation as small-colony variants (SCVs) and by formation of intracellular reservoirs, including those in major bone cell types, reducing susceptibility to antibiotics. Intracellular infections with S. aureus are difficult to treat; however, there are no evidence-based clinical guidelines addressing these infections in osteomyelitis. We conducted a systematic review of the literature to determine the demonstrated efficacy of all antibiotics against intracellular S. aureus relevant to osteomyelitis, including protein biosynthesis inhibitors (lincosamides, streptogramins, macrolides, oxazolidines, tetracyclines, fusidic acid, and aminoglycosides), enzyme inhibitors (fluoroquinolones and ansamycines), and cell wall inhibitors (beta-lactam inhibitors, glycopeptides, fosfomycin, and lipopeptides). The PubMed and Embase databases were screened for articles related to intracellular S. aureus infections that compared the effectiveness of multiple antibiotics or a single antibiotic together with another treatment, which resulted in 34 full-text articles fitting the inclusion criteria. The combined findings of these studies were largely inconclusive, most likely due to the plethora of methodologies utilized. Therefore, the reported findings in the context of the models employed and possible solutions for improved understanding are explored here. While rifampicin, oritavancin, linezolid, moxifloxacin and oxacillin were identified as the most effective potential intracellular treatments, the scientific evidence for these is still relatively weak. We advocate for more standardized research on determining the intracellular effectiveness of antibiotics in S. aureus osteomyelitis to improve treatments and patient outcomes.
PubMed: 35961964
DOI: 10.1038/s41413-022-00227-8 -
Biochemical Society Transactions Jun 2021Hypoxia is a feature of most solid tumours and predicts for poor prognosis. In radiobiological hypoxia (<0.1% O2) cells become up to three times more resistant to...
Hypoxia is a feature of most solid tumours and predicts for poor prognosis. In radiobiological hypoxia (<0.1% O2) cells become up to three times more resistant to radiation. The biological response to radiobiological hypoxia is one of few physiologically relevant stresses that activates both the unfolded protein and DNA damage responses (UPR and DDR). Links between these pathways have been identified in studies carried out in normoxia. Based in part on these previous studies and recent work from our laboratory, we hypothesised that the biological response to hypoxia likely includes overlap between the DDR and UPR. While inhibition of the DDR is a recognised strategy for improving radiation response, the possibility of achieving this through targeting the UPR has not been realised. We carried out a systematic review to identify links between the DDR and UPR, in human cell lines exposed to <2% O2. Following PRISMA guidance, literature from January 2010 to October 2020 were retrieved via Ovid MEDLINE and evaluated. A total of 202 studies were included. LAMP3, ULK1, TRIB3, CHOP, NOXA, NORAD, SIAH1/2, DYRK2, HIPK2, CREB, NUPR1, JMJD2B, NRF2, GSK-3B, GADD45a, GADD45b, STAU1, C-SRC, HK2, CAV1, CypB, CLU, IGFBP-3 and SP1 were highlighted as potential links between the hypoxic DDR and UPR. Overall, we identified very few studies which demonstrate a molecular link between the DDR and UPR in hypoxia, however, it is clear that many of the molecules highlighted warrant further investigation under radiobiological hypoxia as these may include novel therapeutic targets to improve radiotherapy response.
Topics: Animals; Apoptosis; Cell Line, Tumor; DNA Damage; Humans; Hypoxia; Neoplasms; Protein Serine-Threonine Kinases; Signal Transduction; Unfolded Protein Response
PubMed: 34003246
DOI: 10.1042/BST20200861 -
Nutrients Apr 2023Tocotrienol, a type of vitamin E, is well known for its anti-cancer and other biological activities. This systematic review aims to summarize the involvement of... (Review)
Review
BACKGROUND
Tocotrienol, a type of vitamin E, is well known for its anti-cancer and other biological activities. This systematic review aims to summarize the involvement of endoplasmic reticulum stress (ERS) and subsequent unfolded protein response (UPR) as the underlying molecular mechanisms for the anticancer properties of tocotrienol.
METHOD
A comprehensive literature search was performed in March 2023 using the PubMed, Scopus, Web of Science, and EMBASE databases. In vitro, in vivo, and human studies were considered.
RESULT
A total of 840 articles were retrieved during the initial search, and 11 articles that fit the selection criteria were included for qualitative analysis. The current mechanistic findings are based solely on in vitro studies. Tocotrienol induces cancer cell growth arrest, autophagy, and cell death primarily through apoptosis but also through paraptosis-like cell death. Tocotrienol-rich fractions, including α-, γ- and δ-tocotrienols, induce ERS, as evidenced by upregulation of UPR markers and/or ERS-related apoptosis markers. Early endoplasmic reticulum calcium ion release, increased ceramide level, proteasomal inhibition, and upregulation of microRNA-190b were suggested to be essential in modulating tocotrienol-mediated ERS/UPR transduction. Nevertheless, the upstream molecular mechanism of tocotrienol-induced ERS is largely unknown.
CONCLUSION
ERS and UPR are essential in modulating tocotrienol-mediated anti-cancer effects. Further investigation is needed to elucidate the upstream molecular mechanism of tocotrienol-mediated ERS.
Topics: Humans; Tocotrienols; Endoplasmic Reticulum Stress; Unfolded Protein Response; Apoptosis; Cell Death
PubMed: 37111076
DOI: 10.3390/nu15081854 -
Frontiers in Endocrinology 2021To explore the glycemic control [represented by glycated hemoglobin (HbA1c) concentrations] in children with diabetes mellitus (DM) in east China and middle- and...
Glycated Hemoglobin (HbA1c) Concentrations Among Children and Adolescents With Diabetes in Middle- and Low-Income Countries, 2010-2019: A Retrospective Chart Review and Systematic Review of Literature.
OBJECTIVES
To explore the glycemic control [represented by glycated hemoglobin (HbA1c) concentrations] in children with diabetes mellitus (DM) in east China and middle- and low-income countries, from 2010 to 2019.
METHODS
Retrospective data of children with DM from two hospital-based health records were reviewed. Data on HbA1c concentrations, hospitalization due to diabetic ketoacidosis, and patient demographics were collected and analyzed. A systematic review was subsequently performed to analyze publications that report HbA1c concentrations in patients aged <18 years. Patients' characteristics extracted from each publication were used to generate simulated individual data for pooled analysis. HbA1c estimates were derived from steady-state iterations.
RESULTS
Data of 843 diabetic children (aged 11.2 ± 3.9 years) with 2,658 HbA1c measures were retrieved from the two hospitals during the period 2010-2020. The duration of diabetes in the patients was 4.4 ± 2.8 years, and their HbA1c was 8.1 ± 2.2%. Patients who were internal migrants had significantly higher HbA1c concentration than resident patients (8.4 7.9%). The literature review yielded 1,164 publications, and the majority (74.1%) of patient data were published in high-income countries. The patient data extracted from these publications generated 486,416 HbA1c concentration estimates between 2005 and 2019. The average HbA1c concentration during the 15 years was 9.07 ± 2.15%. The mean HbA1c concentrations among children were 8.23, 8.73, 9.20, and 10.11% in high-income country (HIC), upper-middle income country (UMIC), lower-middle income country (LMIC), and low-income country (LIC) respectively. The mean rate of optimized glycemic control (HbA1c <7.5%) among children was 32.4, 27.5, 21.7, and 12.7% in HIC, UMIC, LMIC, and LIC, respectively.
CONCLUSIONS
The current study indicated that there is substantial room for improvement in glycemic control in children with DM worldwide, especially in middle- and low-income countries.
Topics: Adolescent; Child; Child, Preschool; China; Data Collection; Diabetes Mellitus; Diabetic Ketoacidosis; Electronic Health Records; Female; Glycated Hemoglobin; Hospitalization; Humans; Hypoglycemia; Infant; Infant, Newborn; Male; Models, Statistical; Retrospective Studies
PubMed: 33912137
DOI: 10.3389/fendo.2021.651589 -
International Journal of Molecular... May 2021Bicistronic reporter assays have been instrumental for transgene expression, understanding of internal ribosomal entry site (IRES) translation, and identification of...
Bicistronic reporter assays have been instrumental for transgene expression, understanding of internal ribosomal entry site (IRES) translation, and identification of novel cap-independent translational elements (CITE). We observed a large methodological variability in the use of bicistronic reporter assays and data presentation or normalization procedures. Therefore, we systematically searched the literature for bicistronic IRES reporter studies and analyzed methodological details, data visualization, and normalization procedures. Two hundred fifty-seven publications were identified using our search strategy (published 1994-2020). Experimental studies on eukaryotic adherent cell systems and the cell-free translation assay were included for further analysis. We evaluated the following methodological details for 176 full text articles: the bicistronic reporter design, the cell line or type, transfection methods, and time point of analyses post-transfection. For the cell-free translation assay, we focused on methods of in vitro transcription, type of translation lysate, and incubation times and assay temperature. Data can be presented in multiple ways: raw data from individual cistrons, a ratio of the two, or fold changes thereof. In addition, many different control experiments have been suggested when studying IRES-mediated translation. In addition, many different normalization and control experiments have been suggested when studying IRES-mediated translation. Therefore, we also categorized and summarized their use. Our unbiased analyses provide a representative overview of bicistronic IRES reporter use. We identified parameters that were reported inconsistently or incompletely, which could hamper data reproduction and interpretation. On the basis of our analyses, we encourage adhering to a number of practices that should improve transparency of bicistronic reporter data presentation and improve methodological descriptions to facilitate data replication.
Topics: Animals; Genes, Reporter; Humans; Internal Ribosome Entry Sites; Protein Biosynthesis; Regulatory Sequences, Nucleic Acid; Ribosomes
PubMed: 34068921
DOI: 10.3390/ijms22105193 -
Signal Transduction and Targeted Therapy Oct 2020Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that is highly pathogenic and has caused the recent worldwide pandemic officially named...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that is highly pathogenic and has caused the recent worldwide pandemic officially named coronavirus disease (COVID-19). Currently, considerable efforts have been put into developing effective and safe drugs and vaccines against SARS-CoV-2. Vaccines, such as inactivated vaccines, nucleic acid-based vaccines, and vector vaccines, have already entered clinical trials. In this review, we provide an overview of the experimental and clinical data obtained from recent SARS-CoV-2 vaccines trials, and highlight certain potential safety issues that require consideration when developing vaccines. Furthermore, we summarize several strategies utilized in the development of vaccines against other infectious viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), with the aim of aiding in the design of effective therapeutic approaches against SARS-CoV-2.
Topics: Angiotensin-Converting Enzyme 2; Antibodies, Viral; Betacoronavirus; COVID-19; COVID-19 Vaccines; Clinical Trials as Topic; Coronavirus Infections; Gene Expression Regulation; Humans; Immunity, Innate; Immunization Schedule; Immunogenicity, Vaccine; Middle East Respiratory Syndrome Coronavirus; Pandemics; Patient Safety; Peptidyl-Dipeptidase A; Pneumonia, Viral; Protein Binding; Receptors, Virus; Severe acute respiratory syndrome-related coronavirus; SARS-CoV-2; Severe Acute Respiratory Syndrome; Spike Glycoprotein, Coronavirus; Vaccines, Attenuated; Vaccines, DNA; Vaccines, Subunit; Vaccines, Virus-Like Particle; Viral Vaccines
PubMed: 33051445
DOI: 10.1038/s41392-020-00352-y -
BMC Genomics Aug 2022The histidine metabolism and transport (his) genes are controlled by a variety of RNA-dependent regulatory systems among diverse taxonomic groups of bacteria including...
BACKGROUND
The histidine metabolism and transport (his) genes are controlled by a variety of RNA-dependent regulatory systems among diverse taxonomic groups of bacteria including T-box riboswitches in Firmicutes and Actinobacteria and RNA attenuators in Proteobacteria. Using a comparative genomic approach, we previously identified a novel DNA-binding transcription factor (named HisR) that controls the histidine metabolism genes in diverse Gram-positive bacteria from the Firmicutes phylum.
RESULTS
Here we report the identification of HisR-binding sites within the regulatory regions of the histidine metabolism and transport genes in 395 genomes representing the Bacilli, Clostridia, Negativicutes, and Tissierellia classes of Firmicutes, as well as in 97 other HisR-encoding genomes from the Actinobacteria, Proteobacteria, and Synergistetes phyla. HisR belongs to the TrpR family of transcription factors, and their predicted DNA binding motifs have a similar 20-bp palindromic structure but distinct lineage-specific consensus sequences. The predicted HisR-binding motif was validated in vitro using DNA binding assays with purified protein from the human gut bacterium Ruminococcus gnavus. To fill a knowledge gap in the regulation of histidine metabolism genes in Firmicutes genomes that lack a hisR repressor gene, we systematically searched their upstream regions for potential RNA regulatory elements. As result, we identified 158 T-box riboswitches preceding the histidine biosynthesis and/or transport genes in 129 Firmicutes genomes. Finally, novel candidate RNA attenuators were identified upstream of the histidine biosynthesis operons in six species from the Bacillus cereus group, as well as in five Eubacteriales and six Erysipelotrichales species.
CONCLUSIONS
The obtained distribution of the HisR transcription factor and two RNA-mediated regulatory mechanisms for histidine metabolism genes across over 600 species of Firmicutes is discussed from functional and evolutionary points of view.
Topics: Actinobacteria; Bacteria; DNA; Gene Expression Regulation, Bacterial; Gram-Positive Bacteria; Histidine; Humans; Phylogeny; Riboswitch; Transcription Factors
PubMed: 36008760
DOI: 10.1186/s12864-022-08796-y -
BMJ Open Aug 2019Liver kinase B1 (LKB1) is considered a tumour suppressor that can control cell growth and metabolism. Whether LKB1 expression levels are related to clinicopathology and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Liver kinase B1 (LKB1) is considered a tumour suppressor that can control cell growth and metabolism. Whether LKB1 expression levels are related to clinicopathology and prognosis is controversial. This review aimed to quantitatively examine the latest evidence on this question.
DESIGN
An updated systematic review and meta-analysis on the association between LKB1 expression and prognosis of patients with solid tumours were performed.
DATA SOURCES
Eligible studies were identified through literature searches from database establishment until 15 June 2018 in the following databases: Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure and Wan Fang databases.
ELIGIBILITY CRITERIA
The association between LKB1 expression and clinicopathological characteristics, overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) of patients with solid tumours were reported. Sufficient data were available to calculate the OR or HR and 95% CI.
DATA EXTRACTION AND SYNTHESIS
Relevant data were meta-analysed for OS, DFS, RFS and various clinical parameters.
RESULTS
The systematic review included 25 studies containing 6012 patients with solid tumours. Compared with patients with high LKB1 expression, patients with low expression showed significantly shorter OS in univariate analysis (HR=1.63, 95% CI 1.35 to 1.97, p<0.01) and multivariate analysis (HR=1.61, 95% CI 1.26 to 2.06, p<0.01). In contrast, the two groups showed similar DFS in univariate analysis (HR=1.49, 95% CI 0.73 to 3.01, p=0.27) as well as similar RFS in univariate analysis (HR=1.44, 95% CI 0.65 to 3.17, p=0.37) and multivariate analysis (HR=1.02, 95% CI 0.42 to 2.47, p=0.97). Patients with low LKB1 expression showed significantly worse tumour differentiation (OR=1.71, 95% CI 1.14 to 2.55, p<0.01), larger tumours (OR=1.68, 95% CI 1.24 to 2.27, p<0.01), earlier lymph node metastasis (OR=1.43, 95% CI 1.26 to 1.62, p<0.01) and more advanced tumour, node, metastases (TNM) stage (OR=1.80, 95% CI 1.56 to 2.07, p<0.01).
CONCLUSION
Low LKB1 expression predicts shorter OS, worse tumour differentiation, larger tumours, earlier lymph node metastasis and more advanced TNM stage. Low LKB1 expression may be a useful biomarker of poor clinicopathology and prognosis.
Topics: AMP-Activated Protein Kinase Kinases; Disease-Free Survival; Humans; Neoplasms; Prognosis; Protein Serine-Threonine Kinases; Survival Rate
PubMed: 31383697
DOI: 10.1136/bmjopen-2018-027185 -
Epigenetics Sep 2022Adverse experiences in the perinatal period have been associated with the methylation of the human glucocorticoid receptor gene () and long-term diseases. We conducted a...
Adverse experiences in the perinatal period have been associated with the methylation of the human glucocorticoid receptor gene () and long-term diseases. We conducted a systematic review on the association between adversities in the perinatal period and DNA methylation in the 1 region of the gene in newborns. We explored the MEDLINE, Web of Science, Scopus, Scielo, and Lilacs databases without time or language limitations. Two independent reviewers performed the selection of articles and data extraction. A third participated in the methodological quality assessment and consensus meetings at all stages. Finally, ten studies were selected. Methodological quality was considered moderate in six and low in four. Methylation changes were reported in 41 of the 47 CpG sites of exon 1 . Six studies addressed maternal conditions during pregnancy: two reported methylation changes at the same sites (CpG 10, 13, 20, 21 and 47), and four at one or more sites from CpG 35 to 39. Four studies addressed neonatal parameters and morbidities: methylation changes at the same sites 4, 8, 10, 16, 25, and 35 were reported in two. Hypermethylation associated with stressful conditions prevailed. Hypomethylation was more often associated with protective conditions (maternal-foetal attachment during pregnancy, breast milk intake, higher birth weight or Apgar). In conclusion, methylation changes in several sites of the 1 region of the gene in newborns and very young infants were associated with perinatal stress, but more robust and comparable results are needed to corroborate site-specific associations.
Topics: DNA Methylation; Exons; Female; Humans; Infant; Infant, Newborn; Pregnancy; Protein Processing, Post-Translational; Receptors, Glucocorticoid
PubMed: 34519616
DOI: 10.1080/15592294.2021.1980691