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Microbial Cell Factories Oct 2021Recombinant enzyme expression in Escherichia coli is one of the most popular methods to produce bulk concentrations of protein product. However, this method is often...
Recombinant enzyme expression in Escherichia coli is one of the most popular methods to produce bulk concentrations of protein product. However, this method is often limited by the inadvertent formation of inclusion bodies. Our analysis systematically reviews literature from 2010 to 2021 and details the methods and strategies researchers have utilized for expression of difficult to express (DtE), industrially relevant recombinant enzymes in E. coli expression strains. Our review identifies an absence of a coherent strategy with disparate practices being used to promote solubility. We discuss the potential to approach recombinant expression systematically, with the aid of modern bioinformatics, modelling, and 'omics' based systems-level analysis techniques to provide a structured, holistic approach. Our analysis also identifies potential gaps in the methods used to report metadata in publications and the impact on the reproducibility and growth of the research in this field.
Topics: Biotechnology; Escherichia coli; Gene Expression; Inclusion Bodies; Industrial Microbiology; Recombinant Proteins; Research Design; Solubility
PubMed: 34717620
DOI: 10.1186/s12934-021-01698-w -
International Journal of Molecular... Sep 2021Diabetic retinopathy (DR) is one of the main causes of vision loss in middle-aged economically active people. Modifiable (i.e., hyperglycaemia, hypertension,...
Diabetic retinopathy (DR) is one of the main causes of vision loss in middle-aged economically active people. Modifiable (i.e., hyperglycaemia, hypertension, hyperlipidaemia, obesity, and cigarette smoke) and non-modifiable factors (i.e., duration of diabetes, puberty, pregnancy and genetic susceptibility) are involved in the development of DR. Epigenetic mechanisms, modulating the oxidative stress, inflammation, apoptosis, and aging, could influence the course of DR. Herein, we conducted a systematic review of observational studies investigating how epigenetics affects type 2 diabetes retinopathy (T2DR). A total of 23 epidemiological studies were included: 14 studies focused on miRNA, 4 studies on lnc-RNA, one study on both miRNA and lnc-RNA, and 4 studies on global or gene-specific DNA methylation. A direct relation between the dysregulation of miR-21, miR-93, and miR-221 and FPG, HbA1c, and HOMA-IR was identified. A panel of three miRNAs (hsa-let-7a-5p, hsa-miR-novel-chr5_15976, and hsa-miR-28-3p) demonstrated a good sensitivity and specificity for predicting T2DR. Little evidence is available regarding the possible role of the long non-coding dysregulation and gene promoter hypermethylation. Despite these initial, encouraging findings potentially suggesting a role of epigenetics in T2DR, the use in clinical practice for the diagnosis and staging of this complication encounters several difficulties and further targeted investigations are still necessary.
Topics: DNA Methylation; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Epigenesis, Genetic; Humans; Methylenetetrahydrofolate Reductase (NADPH2); MicroRNAs; Promoter Regions, Genetic; RNA, Long Noncoding
PubMed: 34638838
DOI: 10.3390/ijms221910502 -
Reproductive Biomedicine Online Nov 2021Polycystic ovary syndrome (PCOS) is a multifactorial reproductive and endocrine disease, believed to be caused by aberrant steroid biosynthesis pathways involving... (Meta-Analysis)
Meta-Analysis
Polycystic ovary syndrome (PCOS) is a multifactorial reproductive and endocrine disease, believed to be caused by aberrant steroid biosynthesis pathways involving cytochrome P450, 17α-hydroxylase (CYP17A1). This meta-analysis aimed to evaluate the association between CYP17A1 polymorphism rs743572 and PCOS risk. Studies on the CYP17A1 gene were retrieved by searching PubMed, Embase and Web of Science and statistical analyses were performed by STATA software. Fifteen eligible studies were included, dated from January 1994 to 19 November 2020, involving 2277 patients with PCOS and 1913 control individuals. Overall, the results showed that the rs743572 T>C mutation was most likely to be associated with PCOS risk under the recessive model, which was further confirmed by heterogeneity analysis and publication bias detection (CC versus CT + TT, odds ratio [OR] 1.24, 95% confidence interval [CI] 1.02-1.50, P = 0.028, I² = 35.9%). Moreover, subgroup analysis by ethnicity demonstrated that Caucasian but not Asian women carrying the CC genotype of rs743572 had an elevated risk of PCOS (CC versus CT + TT, OR 1.45, 95% CI 1.03-2.06, P = 0.035, I² = 15.10%, six studies). In conclusion, rs743572 is highly likely to be a risk factor for PCOS, and the mutant genotype CC may increase susceptibility to PCOS in Caucasians rather than Asians.
Topics: Asian People; Female; Genetic Predisposition to Disease; Genotype; Humans; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide; Steroid 17-alpha-Hydroxylase; White People
PubMed: 34538754
DOI: 10.1016/j.rbmo.2021.06.012 -
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 -
Amino Acids Oct 2021Collagen peptide supplementation (COL), in conjunction with exercise, may be beneficial for the management of degenerative bone and joint disorders. This is likely due...
Collagen peptide supplementation (COL), in conjunction with exercise, may be beneficial for the management of degenerative bone and joint disorders. This is likely due to stimulatory effects of COL and exercise on the extracellular matrix of connective tissues, improving structure and load-bearing capabilities. This systematic review aims to evaluate the current literature available on the combined impact of COL and exercise. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a literature search of three electronic databases-PubMed, Web of Science and CINAHL-was conducted in June 2020. Fifteen randomised controlled trials were selected after screening 856 articles. The study populations included 12 studies in recreational athletes, 2 studies in elderly participants and 1 in untrained pre-menopausal women. Study outcomes were categorised into four topics: (i) joint pain and recovery from joint injuries, (ii) body composition, (iii) muscle soreness and recovery from exercise, and (iv) muscle protein synthesis (MPS) and collagen synthesis. The results indicated that COL is most beneficial in improving joint functionality and reducing joint pain. Certain improvements in body composition, strength and muscle recovery were present. Collagen synthesis rates were elevated with 15 g/day COL but did not have a significant impact on MPS when compared to isonitrogenous higher quality protein sources. Exact mechanisms for these adaptations are unclear, with future research using larger sample sizes, elite athletes, female participants and more precise outcome measures such as muscle biopsies and magnetic imagery.
Topics: Body Composition; Collagen; Dietary Supplements; Exercise; Humans; Joints; Muscle, Skeletal; Myalgia; Peptides
PubMed: 34491424
DOI: 10.1007/s00726-021-03072-x -
Mediators of Inflammation 2021Statins reportedly have anti-inflammatory effects aside from their lipid-lowering impact. We investigated the effects of statin therapy on the level of C-reactive...
BACKGROUND
Statins reportedly have anti-inflammatory effects aside from their lipid-lowering impact. We investigated the effects of statin therapy on the level of C-reactive protein (CRP) or highly sensitive CRP (hs-CRP), a liver-derived marker of systemic inflammation, among stroke patients.
METHODS
An online search was performed in Scopus, PubMed/MEDLINE, ISI Web of Science, and Google Scholar up to November 2020 to recognize clinical trials investigating the effects of statins on the CRP level in stroke patients.
RESULTS
Overall, nine studies (11 treatment arms) with 1659 participants met the inclusion criteria. Six out of 9 studies (8 out of 11 arms) were categorized as studies with a high-quality methodological approach using the Cochrane Collaboration's tool. Data from 5 treatment arms indicated a significant decrease in CRP concentration, and in one treatment arm, CRP concentration did not suggest any considerable alteration following statin therapy. Moreover, two treatment arms showed a significant reduction in hs-CRP concentration and three treatment arms revealed no significant alteration in hs-CRP concentration following statin therapy. Generally, results were heterogeneous and independent of the type of statin, statin dose, treatment duration, and changes in plasma low-density lipoprotein cholesterol concentration.
CONCLUSION
The results suggest that statin therapy could reduce and, therefore, could be considered in these patients as potential anti-inflammatory agents.
Topics: Anti-Inflammatory Agents; C-Reactive Protein; Cholesterol; Clinical Trials as Topic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Liver; Stroke
PubMed: 34489618
DOI: 10.1155/2021/7104934 -
Medicine Aug 2021Plenty of studies have showed matrix metalloproteinase 14 (MMP14) expression might be associated with the prognosis of gastric cancer (GC). However, no definite... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Plenty of studies have showed matrix metalloproteinase 14 (MMP14) expression might be associated with the prognosis of gastric cancer (GC). However, no definite conclusion has been obtained for the contradictory results.
METHODS
We searched PubMed, Web of science, Embase, and Cochrane library for eligible studies. The association between MMP14 expression and prognostic outcomes of GC was evaluated. Hazard ratio (HR) and 95% confidence interval (CI) were integrated to show the effect of MMP14 expression on the overall survival (OS) or recurrence-free survival (RFS). Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to validate the association of MMP14 expression with OS or RFS in GC. A brief bioinformatics analysis was also performed to determine the prognostic role of MMP14 expression in GC.
RESULTS
High MMP14 expression was associated with shorter OS compared to low MMP14 expression in GC (HR = 1.95, P < .01). Patients with high MMP14 expression tended to have worse differentiation (P = .03), deeper tumor invasion (P < .01), earlier lymph node metastasis (P < .01), earlier distant metastasis (P < .01) and more advanced clinical stage (P < .01) compared to those with low MMP14 expression. The data from TCGA and GEO showed MMP14 was overexpressed in tumor tissues compared to normal tissues (P < .05), and high MMP14 expression was significantly related to shorter OS (HR = 1.70, 95% CI = 1.32-2.20, P < .01) and RFS (HR = 1.45, 95% CI = 1.15-1.83, P < .01) compared to low MMP14 expression in GC. Expression of MMP14 was linked to functional networks involving the biological process, metabolic process, response to stimulus, cell communication and so on. Functional network analysis suggested that MMP14 regulated the protein digestion and absorption, extracellular matrix receptor interaction, focal adhesion, ribosome, spliceosome, and so on.
CONCLUSION
High MMP14 expression was associated with worse prognosis of GC compared to low MMP14 expression. MMP14 expression could serve as a prognostic factor and potential therapeutic target of GC.
Topics: Biomarkers, Tumor; DNA, Neoplasm; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Matrix Metalloproteinase 14; Prognosis; Stomach Neoplasms
PubMed: 34397871
DOI: 10.1097/MD.0000000000026545 -
Cancer Treatment Reviews Sep 2021Programmed cell death ligand 1 (PD-L1) expression is predictive for benefit from immunotherapy in several human malignancies including triple negative breast cancer.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Programmed cell death ligand 1 (PD-L1) expression is predictive for benefit from immunotherapy in several human malignancies including triple negative breast cancer. Lower positivity rates but a larger relative benefit from atezolizumab has been implied when PD-L1 status is assessed at metastatic sites. We aimed to study the discordance of PD-L1 expression between primary tumor and metastasis in breast cancer due to its potential clinical utility.
METHODS
Cochrane Library, Embase, Medline and Web of science were searched for studies reporting on PD-L1 expression in primary and metastatic breast cancer, followed by data extraction. Outcomes included pooled PD-L1 positivity rates in tumor cells, immune cells or both in primary tumor and metastasis, PD-L1 discordance between matched primary tumors and metastasis and direction of discordance.
RESULTS
Of 2552 identified entries following de-duplication, 20 studies fulfilled the predefined inclusion criteria. Pooled PD-L1 positivity rate was higher in primary tumors compared to metastasis when assessed in immune cells (51.2% vs 37.1% p < 0.001) and tumor/immune cells (30.1% vs 14.6% p < 0.001), but not in tumor cells (18.7% vs 17.8% p = 0.65). PD-L1 positivity was lowest when assessed in bone metastases (12%) and highest in lymph nodes (60%). Discordance between primary tumors and metastasis was bidirectional, with higher pooled discordance rates when PD-L1 expression was assessed in immune compared to tumor cells (39.5% vs 13.6%, p < 0.001).
CONCLUSION
The observed considerable discordance between PD-L1 status in primary and metastatic breast cancer emphasizes the importance of appropriate tissue sampling when selecting patients for immunotherapy.
Topics: B7-H1 Antigen; Breast Neoplasms; Female; Humans; Neoplasm Metastasis
PubMed: 34237488
DOI: 10.1016/j.ctrv.2021.102257 -
Drug Design, Development and Therapy 2021Swertiamarin, a seco-iridoid glycoside, is mainly found in Blume () and exhibits therapeutic activities for various diseases. The present study aimed to provide a...
Swertiamarin, a seco-iridoid glycoside, is mainly found in Blume () and exhibits therapeutic activities for various diseases. The present study aimed to provide a review of swertiamarin in terms of its phytochemistry, physicochemical properties, biosynthesis, pharmacology and therapeutic potential. Relevant literature was collected from several scientific databases, including PubMed, ScienceDirect, Scopus and Google Scholar, between 1990 and the present. This review included the distribution of swertiamarin in medicinal plants and its isolation, characterization, physicochemical properties and possible biosynthetic pathways. A comprehensive summary of the pharmacological activities, therapeutic potential and metabolic pathways of swertiamarin was also included after careful screening and tabulation. Based on the reported evidence, swertiamarin meets all five of Lipinski's rules for drug-like properties. Thereafter, the physicochemical properties of swertiamarin were detailed and analyzed. A simple and rapid method for isolating swertiamarin from has been described. The present review proposed that swertiamarin may be biosynthesized by the mevalonate or nonmevalonate pathways, followed by the seco-iridoid pathway. It has also been found that swertiamarin is a potent compound with diverse pharmacological activities, including hepatoprotective, analgesic, anti-inflammatory, antiarthritis, antidiabetic, antioxidant, neuroprotective and gastroprotective activities. The anticancer activity of swertiamarin against different cancer cell lines has been recently reported. The underlying mechanisms of all these pharmacological effects are diverse and seem to involve the regulation of different molecular targets, including growth factors, inflammatory cytokines, protein kinases, apoptosis-related proteins, receptors and enzymes. Swertiamarin also modulates the activity of several transcription factors, and their signaling pathways in various pathological conditions are also discussed. Moreover, we have highlighted the toxicity profile, pharmacokinetics and possible structural modifications of swertiamarin. The pharmacological activities and therapeutic potential of swertiamarin have been extensively investigated. However, more advanced studies are required including clinical trials and studies on the bioavailability, permeability and administration of safe doses to offer swertiamarin as a novel candidate for future drug development.
Topics: Animals; Drug Development; Drug Discovery; Gentianaceae; Humans; Iridoid Glucosides; Plant Extracts; Pyrones
PubMed: 34188450
DOI: 10.2147/DDDT.S299753 -
Frontiers in Endocrinology 2021Immune checkpoint inhibitors (ICIs) are a group of drugs employed in the treatment of various types of malignant tumors and improve the therapeutic effect. ICIs blocks...
Immune checkpoint inhibitors (ICIs) are a group of drugs employed in the treatment of various types of malignant tumors and improve the therapeutic effect. ICIs blocks negative co-stimulatory molecules, such as programmed cell death gene-1 (PD-1) and its ligand (PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), reactivating the recognition and killing effect of the immune system on tumors. However, the reactivation of the immune system can also lead to the death of normal organs, tissues, and cells, eventually leading to immune-related adverse events (IRAEs). IRAEs involve various organs and tissues and also cause thyroid dysfunction. This article reviews the epidemiology, clinical manifestations, possible pathogenesis, and management of ICIs-related thyroid dysfunction.
Topics: Aged; Aged, 80 and over; B7-H1 Antigen; CTLA-4 Antigen; Disease Progression; Female; Genetic Predisposition to Disease; HLA Antigens; Homeostasis; Humans; Immune Checkpoint Inhibitors; Immune System; Immunotherapy; Ligands; Male; Middle Aged; Programmed Cell Death 1 Receptor; T-Lymphocytes; Thyroid Diseases; Thyroid Gland
PubMed: 34177799
DOI: 10.3389/fendo.2021.649863