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Current Neuropharmacology 2024Tauroursodeoxycholic acid (TUDCA) is a naturally produced hydrophilic bile acid that has been used for centuries in Chinese medicine. Numerous recent and studies have...
BACKGROUND
Tauroursodeoxycholic acid (TUDCA) is a naturally produced hydrophilic bile acid that has been used for centuries in Chinese medicine. Numerous recent and studies have shown that TUDCA has neuroprotective action in various models of retinal disorders.
OBJECTIVE
To systematically review the scientific literature and provide a comprehensive summary on the neuroprotective action and the mechanisms involved in the cytoprotective effects of TUDCA.
METHODS
A systematic review was conducted in accordance with the PRISMA (The Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Systematic literature search of United States National Library of Medicine (PubMed), Web of Science, Embase, Scopus and Cochrane Library was performed, which covered all original articles published up to July 2022. The terms, "TUDCA" in combination with "retina", "retinal protection", "neuroprotection" were searched. Possible biases were identified with the adopted SYRCLE's tool.
RESULTS
Of the 423 initially gathered studies, 24 articles met inclusion/exclusion criteria for full-text review. Six of them were experiments, 17 studies reported data and one study described both and data. The results revealed the effect of TUDCA on different retinal diseases, such as retinitis pigmentosa (RP), diabetic retinopathy (DR), retinal degeneration (RD), retinal ganglion cell (RGC) injury, Leber's hereditary optic neuropathy (LHON), choroidal neovascularization (CNV), and retinal detachment (RDT). The quality scores of the studies were ranged from 5 to 7 points (total 10 points), according to SYRCLE's risk of bias tool. Both and data suggested that TUDCA could effectively delay degeneration and apoptosis of retinal neurons, preserve retinal structure and function, and its mechanism of actions might be related with inhibiting apoptosis, decreasing inflammation, attenuating oxidative stress, suppressing endoplasmic reticulum (ER) stress, and reducing angiogenesis.
CONCLUSION
This systematic review demonstrated that TUDCA has neuroprotective effect on and models of retinal disorders, reinforcing the currently available evidence that TUDCA could be a promising therapeutic agent in retinal diseases treatment. However, well designed clinical trials are necessary to appraise the efficacy of TUDCA in clinical setting.
Topics: Taurochenodeoxycholic Acid; Animals; Neuroprotective Agents; Humans; Retinal Diseases; Disease Models, Animal
PubMed: 37691227
DOI: 10.2174/1570159X21666230907152207 -
BMC Medical Genomics Apr 2023Wolfram syndrome type 1 gene (WFS1), which encodes a transmembrane structural protein (wolframin), is essential for several biological processes, including proper inner...
BACKGROUND
Wolfram syndrome type 1 gene (WFS1), which encodes a transmembrane structural protein (wolframin), is essential for several biological processes, including proper inner ear function. Unlike the recessively inherited Wolfram syndrome, WFS1 heterozygous variants cause DFNA6/14/38 and wolfram-like syndrome, characterized by autosomal dominant nonsyndromic hearing loss, optic atrophy, and diabetes mellitus. Here, we identified two WFS1 heterozygous variants in three DFNA6/14/38 families using exome sequencing. We reveal the pathogenicity of the WFS1 variants based on three-dimensional (3D) modeling and structural analysis. Furthermore, we present cochlear implantation (CI) outcomes in WFS1-associated DFNA6/14/38 and suggest a genotype-phenotype correlation based on our results and a systematic review.
METHODS
We performed molecular genetic test and evaluated clinical phenotypes of three WFS1-associated DFNA6/14/38 families. A putative WFS1-NCS1 interaction model was generated, and the impacts of WFS1 variants on stability were predicted by comparing intramolecular interactions. A total of 62 WFS1 variants associated with DFNA6/14/38 were included in a systematic review.
RESULTS
One variant is a known mutational hotspot variant in the endoplasmic reticulum (ER)-luminal domain WFS1(NM_006005.3) (c.2051 C > T:p.Ala684Val), and the other is a novel frameshift variant in transmembrane domain 6 (c.1544_1545insA:p.Phe515LeufsTer28). The two variants were pathogenic, based on the ACMG/AMP guidelines. Three-dimensional modeling and structural analysis show that non-polar, hydrophobic substitution of Ala684 (p.Ala684Val) destabilizes the alpha helix and contributes to the loss of WFS1-NCS1 interaction. Also, the p.Phe515LeufsTer28 variant truncates transmembrane domain 7-9 and the ER-luminal domain, possibly impairing membrane localization and C-terminal signal transduction. The systematic review demonstrates favorable outcomes of CI. Remarkably, p.Ala684Val in WFS1 is associated with early-onset severe-to-profound deafness, revealing a strong candidate variant for CI.
CONCLUSIONS
We expanded the genotypic spectrum of WFS1 heterozygous variants underlying DFNA6/14/38 and revealed the pathogenicity of mutant WFS1, providing a theoretical basis for WFS1-NCS1 interactions. We presented a range of phenotypic traits for WFS1 heterozygous variants and demonstrated favorable functional CI outcomes, proposing p.Ala684Val a strong potential marker for CI candidates.
Topics: Humans; Wolfram Syndrome; Cochlear Implants; Cochlear Implantation; Pedigree; Hearing Loss; Deafness
PubMed: 37041640
DOI: 10.1186/s12920-023-01506-x -
Frontiers in Physiology 2021Renal ischemia-reperfusion (I/R) injury is one of the major causes related to acute kidney damage. Melatonin has been shown as a powerful antioxidant, with many animal...
Renal ischemia-reperfusion (I/R) injury is one of the major causes related to acute kidney damage. Melatonin has been shown as a powerful antioxidant, with many animal experiments have been designed to evaluate the therapeutic effect of it to renal I/R injury. This systematic review aimed to assess the therapeutic effect of melatonin for renal I/R injury in animal models. The PubMed, Web of Science, Embase, and Science Direct were searched for animal experiments applying melatonin to treat renal I/R injury to February 2021. Thirty-one studies were included. The pooled analysis showed a greater reduction of blood urea nitrogen (BUN) (21 studies, weighted mean difference (WMD) = -30.00 [-42.09 to -17.91], < 0.00001), and serum creatinine (SCr) (20 studies, WMD = -0.91 [-1.17 to -0.66], < 0.00001) treated with melatonin. Subgroup analysis suggested that multiple administration could reduce the BUN compared with control. Malondialdehyde and myeloperoxidase were significantly reduced, meanwhile, melatonin significantly improved the activity of glutathione, as well as superoxide dismutase. The possible mechanism for melatonin to treat renal I/R injury is inhibiting endoplasmic reticulum stress, apoptosis, inflammation, autophagy, and fibrillation in AKI to chronic kidney disease. From the available data of small animal studies, this systematic review demonstrated that melatonin could improve renal function and antioxidative effects to cure renal I/R injury through, then multiple administration of melatonin might be more appropriate. Nonetheless, extensive basic experiments are need to study the mechanism of melatonin, then well-designed randomized controlled trials to explore the protective effect of melatonin.
PubMed: 35095558
DOI: 10.3389/fphys.2021.791036 -
Environmental Science and Pollution... Jan 2023Environmental pollution caused by persistent organic pollutants (POPs) has increased the challenge for the scientific communities. Polybrominated diphenyl ethers... (Review)
Review
Environmental pollution caused by persistent organic pollutants (POPs) has increased the challenge for the scientific communities. Polybrominated diphenyl ethers (PBDEs), classified as POPs, are widely applied in various materials as brominated flame retardants (BFRs). Because of the nature of these chemical compounds including toxicity, stability, and capability to bioaccumulate and biomagnify, PBDEs have posed a great challenge and risk to human health and wildlife. Therefore, the side effects of exposure to PBDEs as ubiquitous pollutants in the environment on cancer progression were investigated using a systematic review (SR) survey. To achieve this goal, forty studies were considered after defining the search terms and inclusion criteria, and/or exclusion criteria; the eligible records were collected from the international bibliographic databases. Based on the findings of the reviewed records, environmental exposure to the BFRs including PBDEs has a positive association with different mechanisms that induce cancer progression. However, the findings of the reviewed studies were not totally consistent with the mode of action and side effects are yet to be fully elucidated. Several articles have reported that BFRs can be carcinogenic and induce epithelial to mesenchymal transition via different mechanisms. The main mode of action involved in the environmental exposure to BFRs and the risk of cancer progression is endoplasmic reticulum and oxidative stress (OS). Generally, the imbalance of antioxidant mechanisms, reactive nitrogen species (RNSs) and reactive oxygen species (ROSs), during damage in cells, and stress caused OS, which increases tumorigenesis via multiple mechanisms, such as DNA damage, inflammation, and angiogenesis.
Topics: Humans; Halogenated Diphenyl Ethers; Epithelial-Mesenchymal Transition; Environmental Exposure; Environmental Pollutants; Flame Retardants; Carcinogenesis; Environmental Monitoring
PubMed: 36469279
DOI: 10.1007/s11356-022-24538-9 -
Current Oncology (Toronto, Ont.) Nov 2022The endoplasmic reticulum chaperone BiP (also known as GRP-78 or HSPA5) maintains protein folding to allow cell proliferation and survival and has been implicated in... (Meta-Analysis)
Meta-Analysis
The endoplasmic reticulum chaperone BiP (also known as GRP-78 or HSPA5) maintains protein folding to allow cell proliferation and survival and has been implicated in carcinogenesis, tumor progression, and therapy resistance. BiP's association with clinical factors and prognostic potential in breast cancer remains unclear. In this work, three types of analysis were conducted to improve the knowledge of BiP's clinicopathological potential: (1) analysis of publicly available RNA-seq and proteomics datasets stratified as high and low quartiles; (2) a systematic review and meta-analysis of immunohistochemical detection of BIP; (3) confirmation of findings by BiP immunohistochemical detection in two luminal-like breast cancer small cohorts of paired samples (pre- vs. post-endocrine therapy, and primary pre- vs. metastasis post-endocrine therapy). The TCGA PanCancer dataset and CPTAC showed groups with high BiP mRNA and protein associated with HER2, basal-like subtypes, and higher immune scores. The meta-analysis of BiP immunohistochemistry disclosed an association between higher BiP positivity and reduced relapse-free survival. BiP immunohistochemistry confirmed increased BiP expression in metastasis, an association of BiP positivity with HER2 expression, and nuclear BiP localization with higher a tumor stage and poor outcome. Therefore, three independent approaches showed that BiP protein is associated with worse outcomes and holds prognostic potential for breast cancer.
Topics: Humans; Female; Endoplasmic Reticulum Chaperone BiP; Heat-Shock Proteins; Breast Neoplasms; Neoplasm Recurrence, Local; Prognosis
PubMed: 36547124
DOI: 10.3390/curroncol29120710 -
Frontiers in Pharmacology 2020Astragaloside IV (AS-IV) has a variety of biological activities and is widely used to treat kidney diseases. We conducted a systematic review of 24 animal studies...
Astragaloside IV (AS-IV) has a variety of biological activities and is widely used to treat kidney diseases. We conducted a systematic review of 24 animal studies including 424 animals to evaluate the efficacy of AS-IV for diabetic nephropathy (DN); all current possible mechanisms were summarized. A search strategy was applied to eight databases from inception to June 2020. The CAMARADES 10-item quality checklist and Rev-Man 5.3 software were used to analyze the risks of bias of each study and data regarding outcome measures, respectively. The mean study quality score was 5.4 points (range 3-8 points). Meta-analyses data and comparisons between groups showed that AS-IV significantly slowed the progression of pathological signs in the kidney including glomeruli and tubules, increasing creatinine clearance rate, decreasing blood urea nitrogen, serum creatinine, 24-h urinary neutrophil gelatinase-associated lipocalin and N-acetyl--D-glucosaminidase, 24-h urinary albumin, 24-h urinary microalbumin and HbA1c. There were no significant differences between experimental and control groups with respect to mortality or levels of alanine aminotransferase and aspartate aminotransferase. In terms of the possible mechanisms of treatment of DN, AS-IV acts through antifibrotic, antioxidant, and antiapoptotic mechanisms, thereby alleviating endoplasmic reticulum stress, inhibiting mitochondrial fission, and increasing autophagic activity. Taken together, our findings suggest that AS-IV is a multifaceted renoprotective candidate drug for DN.
PubMed: 32695006
DOI: 10.3389/fphar.2020.00988 -
PloS One 2017We performed a systematic review to identify all original publications describing the asymmetric inheritance of cellular organelles in normal animal eukaryotic cells and... (Review)
Review
We performed a systematic review to identify all original publications describing the asymmetric inheritance of cellular organelles in normal animal eukaryotic cells and to critique the validity and imprecision of the evidence. Searches were performed in Embase, MEDLINE and Pubmed up to November 2015. Screening of titles, abstracts and full papers was performed by two independent reviewers. Data extraction and validity were performed by one reviewer and checked by a second reviewer. Study quality was assessed using the SYRCLE risk of bias tool, for animal studies and by developing validity tools for the experimental model, organelle markers and imprecision. A narrative data synthesis was performed. We identified 31 studies (34 publications) of the asymmetric inheritance of organelles after mitotic or meiotic division. Studies for the asymmetric inheritance of centrosomes (n = 9); endosomes (n = 6), P granules (n = 4), the midbody (n = 3), mitochondria (n = 3), proteosomes (n = 2), spectrosomes (n = 2), cilia (n = 2) and endoplasmic reticulum (n = 2) were identified. Asymmetry was defined and quantified by variable methods. Assessment of the statistical reliability of the results indicated only two studies (7%) were judged to have low concern, the majority of studies (77%) were 'unclear' and five (16%) were judged to have 'high concerns'; the main reasons were low technical repeats (<10). Assessment of model validity indicated that the majority of studies (61%) were judged to be valid, ten studies (32%) were unclear and two studies (7%) were judged to have 'high concerns'; both described 'stem cells' without providing experimental evidence to confirm this (pluripotency and self-renewal). Assessment of marker validity indicated that no studies had low concern, most studies were unclear (96.5%), indicating there were insufficient details to judge if the markers were appropriate. One study had high concern for marker validity due to the contradictory results of two markers for the same organelle. For most studies the validity and imprecision of results could not be confirmed. In particular, data were limited due to a lack of reporting of interassay variability, sample size calculations, controls and functional validation of organelle markers. An evaluation of 16 systematic reviews containing cell assays found that only 50% reported adherence to PRISMA or ARRIVE reporting guidelines and 38% reported a formal risk of bias assessment. 44% of the reviews did not consider how relevant or valid the models were to the research question. 75% reviews did not consider how valid the markers were. 69% of reviews did not consider the impact of the statistical reliability of the results. Future systematic reviews in basic or preclinical research should ensure the rigorous reporting of the statistical reliability of the results in addition to the validity of the methods. Increased awareness of the importance of reporting guidelines and validation tools is needed for the scientific community.
Topics: Eukaryotic Cells; Organelles
PubMed: 28562636
DOI: 10.1371/journal.pone.0178645 -
Medicine Jul 2022Stress granules (SGs) are the dense granules formed in the cytoplasm of eukaryotic cells in response to stress stimuli, such as endoplasmic reticulum stress, heat shock,...
BACKGROUND
Stress granules (SGs) are the dense granules formed in the cytoplasm of eukaryotic cells in response to stress stimuli, such as endoplasmic reticulum stress, heat shock, hypoxia, and arsenate exposure. Although SGs have been attracting a lot of research attention, there is still a lack of systematic analysis of SGs in the literature.
METHODS
By analyzing the literature published in the Web of Science database using the R software, we extracted all the information related to SGs from the literature and cited references. The following information was included: publications per year, overall citations, top 10 countries, top 10 authors, co-author collaborations, top 10 institutions, critical areas, and top 10 cited research articles.
RESULTS
A total of 4052 articles related to SGs were selected and screened. These documents have been cited a total of 110,553 times, with an H-index of 126 and an average of 27.28 citations per article. The authors of the literature included in this study were from 89 different countries/regions. The United States and China had the highest number of publications and ranking institutions.
CONCLUSIONS
This article presents essential insights on the characteristics and influence of SGs, demonstrating their indispensable role in immune regulation and other fields.
Topics: Bibliometrics; Databases, Factual; Delivery of Health Care; Humans; Publications; Stress Granules
PubMed: 35866775
DOI: 10.1097/MD.0000000000029200 -
Nutrients Oct 2019In physiological conditions, the gut is heavily infiltrated with various subsets of inflammatory cells, whose activity is tightly controlled by counter-regulatory...
In physiological conditions, the gut is heavily infiltrated with various subsets of inflammatory cells, whose activity is tightly controlled by counter-regulatory mechanisms. Defects in such mechanisms can favour the development of chronic intestinal disorders, such as Crohn's disease (CD) and ulcerative colitis (UC), the principal forms of inflammatory bowel diseases (IBD) in humans, as well as systemic disorders. Over the last years, the frequency of intestinal and systemic immune-inflammatory disorders has increased in previously low incidence areas, likely due to the Westernization of lifestyles, including dietary habits. The Western diet is characterized by high consumption of proteins, saturated fats and sweets, as well as by a broad use of food additives (e.g., emulsifiers, bulking agents), which are used to preserve and enhance food quality. Accumulating evidence suggests that food additives can perturb gut homeostasis, thereby contributing to promote tissue-damaging inflammatory responses. For instance, mice given the emulsifiers carboxymethylcellulose and polysorbate 80 develop dysbiosis with overgrowth of mucus-degrading bacteria. Such an effect triggers colitis in animals deficient in either interleukin-10, a cytokine exerting anti-inflammatory and regulatory functions, or Toll-like receptor 5, a receptor recognizing the bacterial flagellin. Similarly, the polysaccharide maltodextrin induces endoplasmic reticulum stress in intestinal goblet cells, thereby impairing mucus release and increasing host susceptibility to colitis. In this review, we report and discuss the current knowledge about the impact of food additives on gut homeostasis and their potential contribution to the development of inflammatory disorders.
Topics: Animals; Colitis; Diet, Western; Dysbiosis; Food Additives; Gastrointestinal Microbiome; Homeostasis; Humans; Immunity, Mucosal; Intestines; Metabolic Diseases; Risk Assessment; Risk Factors
PubMed: 31581570
DOI: 10.3390/nu11102334 -
Alimentary Pharmacology & Therapeutics Apr 2018Alpha-1 antitrypsin deficiency (AATD) is estimated to affect three million people worldwide. It causes liver disease in a proportion of carriers of the PiS and PiZ...
BACKGROUND
Alpha-1 antitrypsin deficiency (AATD) is estimated to affect three million people worldwide. It causes liver disease in a proportion of carriers of the PiS and PiZ allele due to the formation and retention of polymers within the endoplasmic reticulum of hepatocytes. The reason for this selective penetrance is not known. Although clinical trials are underway, liver transplantation is the only effective treatment for liver disease due to AATD.
AIMS
To report the prevalence and natural history of liver disease among individuals with AATD, and assess the outcomes of liver transplantation through systematic review.
METHODS
A comprehensive search was conducted across multiple databases. Two independent authors selected the articles and assessed bias using the Newcastle-Ottawa Scale. Data were pooled for analysis, where comparable outcomes were reported.
RESULTS
Thirty-five studies were identified related to disease progression and 12 for the treatment of AATD. Seven per cent of children were reported to develop liver cirrhosis, with 16.5% of individuals presenting in childhood requiring liver transplantation. Of those surviving to adulthood, 10.5% had liver cirrhosis and 14.7% required transplantation. Liver transplantation was the only effective treatment reported and outcomes compare favourably to other indications, with 5-year survival reported as over 90% in children and over 80% in adults.
DISCUSSION
The clinical course of liver disease in individuals with AATD remains poorly understood, but affects about 10% of those with AATD. More research is required to identify those patients at risk of developing liver disease at an early stage, and to provide alternative treatments to liver transplantation.
Topics: Adult; Child; Disease Progression; Humans; Liver Cirrhosis; Liver Transplantation; Prevalence; Treatment Outcome; alpha 1-Antitrypsin Deficiency
PubMed: 29446109
DOI: 10.1111/apt.14537