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Theranostics 2021Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and...
Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants and yeast). Autophagy is generally induced by stress, such as oxygen-, energy- or amino acid-deprivation, irradiation, drugs, . In addition to non-selective bulk degradation, autophagy also occurs in a selective manner, recycling specific organelles, such as mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes and lipid droplets (LDs). This capability makes selective autophagy a major process in maintaining cellular homeostasis. The dysfunction of selective autophagy is implicated in neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure, . Considering the importance of selective autophagy in cell biology, we systemically review the recent advances in our understanding of this process and its regulatory mechanisms. We emphasize the 'cargo-ligand-receptor' model in selective autophagy for specific organelles or cellular components in yeast and mammals, with a focus on mitophagy and ER-phagy, which are finely described as types of selective autophagy. Additionally, we highlight unanswered questions in the field, helping readers focus on the research blind spots that need to be broken.
Topics: Autophagy; Humans; Macroautophagy; Mitophagy; Organelles
PubMed: 33391472
DOI: 10.7150/thno.49860 -
Human Reproduction Update Jul 2023Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as... (Review)
Review
BACKGROUND
Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as well as the elimination of infected or damaged cells throughout life. Quality control through regulation of cell death pathways is particularly important in the germline, which is responsible for the generation of offspring. Women are born with their entire supply of germ cells, housed in functional units known as follicles. Follicles contain an oocyte, as well as specialized somatic granulosa cells essential for oocyte survival. Follicle loss-via regulated cell death-occurs throughout follicle development and life, and can be accelerated following exposure to various environmental and lifestyle factors. It is thought that the elimination of damaged follicles is necessary to ensure that only the best quality oocytes are available for reproduction.
OBJECTIVE AND RATIONALE
Understanding the precise factors involved in triggering and executing follicle death is crucial to uncovering how follicle endowment is initially determined, as well as how follicle number is maintained throughout puberty, reproductive life, and ovarian ageing in women. Apoptosis is established as essential for ovarian homeostasis at all stages of development and life. However, involvement of other cell death pathways in the ovary is less established. This review aims to summarize the most recent literature on cell death regulators in the ovary, with a particular focus on non-apoptotic pathways and their functions throughout the discrete stages of ovarian development and reproductive life.
SEARCH METHODS
Comprehensive literature searches were carried out using PubMed and Google Scholar for human, animal, and cellular studies published until August 2022 using the following search terms: oogenesis, follicle formation, follicle atresia, oocyte loss, oocyte apoptosis, regulated cell death in the ovary, non-apoptotic cell death in the ovary, premature ovarian insufficiency, primordial follicles, oocyte quality control, granulosa cell death, autophagy in the ovary, autophagy in oocytes, necroptosis in the ovary, necroptosis in oocytes, pyroptosis in the ovary, pyroptosis in oocytes, parthanatos in the ovary, and parthanatos in oocytes.
OUTCOMES
Numerous regulated cell death pathways operate in mammalian cells, including apoptosis, autophagic cell death, necroptosis, and pyroptosis. However, our understanding of the distinct cell death mediators in each ovarian cell type and follicle class across the different stages of life remains the source of ongoing investigation. Here, we highlight recent evidence for the contribution of non-apoptotic pathways to ovarian development and function. In particular, we discuss the involvement of autophagy during follicle formation and the role of autophagic cell death, necroptosis, pyroptosis, and parthanatos during follicle atresia, particularly in response to physiological stressors (e.g. oxidative stress).
WIDER IMPLICATIONS
Improved knowledge of the roles of each regulated cell death pathway in the ovary is vital for understanding ovarian development, as well as maintenance of ovarian function throughout the lifespan. This information is pertinent not only to our understanding of endocrine health, reproductive health, and fertility in women but also to enable identification of novel fertility preservation targets.
Topics: Adult; Animals; Female; Humans; Apoptosis; Granulosa Cells; Mammals; Oocytes; Ovarian Follicle; Ovary; Regulated Cell Death; Homeostasis
PubMed: 36857094
DOI: 10.1093/humupd/dmad005 -
European Journal of Nutrition Sep 2020Apple vinegar (AV) has been proclaimed to have different health benefits, such as a weight loss, the ability to lower blood glucose levels, and reducing the risk of...
INTRODUCTION
Apple vinegar (AV) has been proclaimed to have different health benefits, such as a weight loss, the ability to lower blood glucose levels, and reducing the risk of heart diseases. Studies on animals have demonstrated effects of AV consumption, deepening our knowledge of the beneficial effects and side effects.
AIM
The aims of this study were to evaluate the evidence of the effect of AV on metabolic parameters and body weight in humans, furthermore, to evaluate the safety and side effects of ingesting AV, and additionally to evaluate the evidence of the effect of AV on metabolic parameters, safety, and side effects of AV from studies performed on animals (mammals).
METHODS
A systematic literature search was performed. The databases PubMed (MEDLINE), PsycInfo (Ebsco), CINAHL (Ebsco), and Embase (Ovid) were searched for relevant articles. Primary outcomes were glycated hemoglobin, postprandial glucose, and synonyms for blood glucose. Secondary outcomes were waist circumference, visceral fat, high-density lipoprotein, low-density lipoprotein, triglycerides, and total cholesterol. Studies performed on humans and animals were included. The included studies performed on humans were quality assessed for risk of bias using a version of the Cochrane Collaboration's tool.
RESULTS
A total of 487 papers were identified in the literature search. Of these, 13 studies performed on humans and 12 studies performed on animals were included. There may be beneficial health effects from the consumption of AV. The risk of side effects when ingested in recommended quantities and in recommended ways seems inconsiderable.
CONCLUSION
Due to inadequate research of high quality, the evidence for the health effects of AV is insufficient. Therefore, more large-scale, long-term clinical studies with a low risk of bias are needed before definitive conclusions can be made.
Topics: Acetic Acid; Animals; Body Weight; Humans; Intra-Abdominal Fat; Lipids; Malus; Reproducibility of Results; Uncertainty; Waist Circumference
PubMed: 32170375
DOI: 10.1007/s00394-020-02214-3 -
Stem Cell Research & Therapy Aug 2021We explored whether stem cell therapy was effective for animal models and patients with Crohn's disease (CD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We explored whether stem cell therapy was effective for animal models and patients with Crohn's disease (CD).
METHODS
We searched five online databases. The relative outcomes were analyzed with the aid of GetData Graph Digitizer 2.26 and Stata 16.0 software. The SYRCLE risk of bias tool and the MINORS tool were used to assess study quality.
RESULTS
We evaluated 46 studies including 28 animal works (n = 567) and 18 human trials (n = 360). In the animal studies, the disease activity index dramatically decreased in the mesenchymal stem cell (MSC) treatment groups compared to the control group. Rats and mice receiving MSCs exhibited longer colons [mice: standardized mean difference (SMD) 2.84, P = 0.000; rats: SMD 1.44, P = 0.029], lower histopathological scores (mice: SMD - 4.58, p = 0.000; rats: SMD - 1.41, P = 0.000) and lower myeloperoxidase levels (SMD - 6.22, P = 0.000). In clinical trials, stem cell transplantation reduced the CD activity index (SMD - 2.10, P = 0.000), the CD endoscopic index of severity (SMD - 3.40, P = 0.000) and simplified endoscopy score for CD (SMD - 1.71, P = 0.000) and improved the inflammatory bowel disease questionnaire score (SMD 1.33, P = 0.305) compared to control values. CD patients maintained high remission rates for 3-24 months after transplantation.
CONCLUSIONS
Stem cell transplantation is a valuable supplementary therapy for CD.
Topics: Animals; Crohn Disease; Hematopoietic Stem Cell Transplantation; Humans; Mesenchymal Stem Cells; Mice; Rats
PubMed: 34407875
DOI: 10.1186/s13287-021-02533-0 -
Heart Failure Reviews Nov 2021The transverse aortic constriction (TAC) model is frequently used to study adverse cardiac remodeling upon pressure overload. We set out to define the most important... (Meta-Analysis)
Meta-Analysis Review
The transverse aortic constriction (TAC) model is frequently used to study adverse cardiac remodeling upon pressure overload. We set out to define the most important characteristics that define the degree of cardiac remodeling in this model. A systematic review and meta-analyses were performed on studies using the TAC mouse/rat model and reporting echocardiographic outcome parameters. We included all animal studies in which a constriction around the transverse aorta and at least one of the predefined echocardiography or MRI outcome parameters were assessed. A total of 502 articles and > 3000 wild-type, untreated animals undergoing TAC were included in this study and referenced to a control group. The duration of aortic constriction correlated to the degree of adverse remodeling. However, the mouse data is strongly biased by the preferential use of male C57Bl/6 mice (66% of studies). Furthermore, mostly ketamine/xylazine anesthetics, 27G needle constriction, and silk sutures are used. Nonetheless, despite the homogeneity in experimental design, the model contained a substantial degree of heterogeneity in the functional outcome measures. When looking at study quality, only 12% reported randomization, 23% mentioned any sort of blinding, 25% adequately addressed the outcomes, and an amazingly low percentage (2%) showed sample size calculation. Meta-analyses did not detect specific study characteristics that explained the heterogeneity in the reported outcome measures, however this might be related to the strong bias towards the use of specific mouse lines, sex as well as age or to poor reporting of characteristics of study quality.
Topics: Animals; Aorta; Constriction; Echocardiography; Female; Heart Failure; Humans; Male; Mice; Mice, Inbred C57BL; Rats
PubMed: 32335789
DOI: 10.1007/s10741-020-09960-w -
CoDAS Jun 2019to verify the applications of AAT in health by performing a systematic review of the literature.
PURPOSE
to verify the applications of AAT in health by performing a systematic review of the literature.
RESEARCH STRATEGY
a survey was carried out in four databases with the descriptors: animal assisted therapy, horse assisted therapy, speech therapy.
SELECTION CRITERIA
article published between 2010 and 2018, in Portuguese or English, free electronic access and that mentioned the characteristics of the intervention program.
DATA ANALYSIS
criteria: casuistry, area of knowledge, program characteristic, type of research, year and language of publication, nationality, periodical and impact factor.
RESULTS
43 articles published in 30 journals, 16 with impact factor, were reviewed. Clinical studies prevailed (93.02%), 37.20% were from Medicine, the population studied had different diagnoses and ages, 55.81% with adults / elderly. AAT was used preferentially for physical rehabilitation (67.44%) and the main mediator was the dog, mentioned in 72.09% of the articles. Eight (n = 8) programs with a focus on communication intervention were described.
CONCLUSION
There is scientific evidence on the use of AAT published in the period studied, in Brazil and in the world. The programs were used by different health and education professionals. The AAT goals were specific to the profile of the participants, and consistent with the characteristics of the mediator animal and the site.
Topics: Animal Assisted Therapy; Animals; Dogs; Evidence-Based Medicine; Horses; Humans
PubMed: 31271584
DOI: 10.1590/2317-1782/20182018243 -
Brain : a Journal of Neurology Dec 2022Pathogenic variants in the voltage-gated sodium channel gene family lead to early onset epilepsies, neurodevelopmental disorders, skeletal muscle channelopathies,...
Pathogenic variants in the voltage-gated sodium channel gene family lead to early onset epilepsies, neurodevelopmental disorders, skeletal muscle channelopathies, peripheral neuropathies and cardiac arrhythmias. Disease-associated variants have diverse functional effects ranging from complete loss-of-function to marked gain-of-function. Therapeutic strategy is likely to depend on functional effect. Experimental studies offer important insights into channel function but are resource intensive and only performed in a minority of cases. Given the evolutionarily conserved nature of the sodium channel genes, we investigated whether similarities in biophysical properties between different voltage-gated sodium channels can predict function and inform precision treatment across sodium channelopathies. We performed a systematic literature search identifying functionally assessed variants in any of the nine voltage-gated sodium channel genes until 28 April 2021. We included missense variants that had been electrophysiologically characterized in mammalian cells in whole-cell patch-clamp recordings. We performed an alignment of linear protein sequences of all sodium channel genes and correlated variants by their overall functional effect on biophysical properties. Of 951 identified records, 437 sodium channel-variants met our inclusion criteria and were reviewed for functional properties. Of these, 141 variants were epilepsy-associated (SCN1/2/3/8A), 79 had a neuromuscular phenotype (SCN4/9/10/11A), 149 were associated with a cardiac phenotype (SCN5/10A) and 68 (16%) were considered benign. We detected 38 missense variant pairs with an identical disease-associated variant in a different sodium channel gene. Thirty-five out of 38 of those pairs resulted in similar functional consequences, indicating up to 92% biophysical agreement between corresponding sodium channel variants (odds ratio = 11.3; 95% confidence interval = 2.8 to 66.9; P < 0.001). Pathogenic missense variants were clustered in specific functional domains, whereas population variants were significantly more frequent across non-conserved domains (odds ratio = 18.6; 95% confidence interval = 10.9-34.4; P < 0.001). Pore-loop regions were frequently associated with loss-of-function variants, whereas inactivation sites were associated with gain-of-function (odds ratio = 42.1, 95% confidence interval = 14.5-122.4; P < 0.001), whilst variants occurring in voltage-sensing regions comprised a range of gain- and loss-of-function effects. Our findings suggest that biophysical characterisation of variants in one SCN-gene can predict channel function across different SCN-genes where experimental data are not available. The collected data represent the first gain- versus loss-of-function topological map of SCN proteins indicating shared patterns of biophysical effects aiding variant analysis and guiding precision therapy. We integrated our findings into a free online webtool to facilitate functional sodium channel gene variant interpretation (http://SCN-viewer.broadinstitute.org).
Topics: Animals; Channelopathies; Peripheral Nervous System Diseases; Voltage-Gated Sodium Channels; Epilepsy; Phenotype; Mammals
PubMed: 35037686
DOI: 10.1093/brain/awac006 -
Human Reproduction Update Sep 2019A defining feature of sexual reproduction is the transmission of genomic information from both parents to the offspring. There is now compelling evidence that the...
BACKGROUND
A defining feature of sexual reproduction is the transmission of genomic information from both parents to the offspring. There is now compelling evidence that the inheritance of such genetic information is accompanied by additional epigenetic marks, or stable heritable information that is not accounted for by variations in DNA sequence. The reversible nature of epigenetic marks coupled with multiple rounds of epigenetic reprogramming that erase the majority of existing patterns have made the investigation of this phenomenon challenging. However, continual advances in molecular methods are allowing closer examination of the dynamic alterations to histone composition and DNA methylation patterns that accompany development and, in particular, how these modifications can occur in an individual's germline and be transmitted to the following generation. While the underlying mechanisms that permit this form of transgenerational inheritance remain unclear, it is increasingly apparent that a combination of genetic and epigenetic modifications plays major roles in determining the phenotypes of individuals and their offspring.
OBJECTIVE AND RATIONALE
Information pertaining to transgenerational inheritance was systematically reviewed focusing primarily on mammalian cells to the exclusion of inheritance in plants, due to inherent differences in the means by which information is transmitted between generations. The effects of environmental factors and biological processes on both epigenetic and genetic information were reviewed to determine their contribution to modulating inheritable phenotypes.
SEARCH METHODS
Articles indexed in PubMed were searched using keywords related to transgenerational inheritance, epigenetic modifications, paternal and maternal inheritable traits and environmental and biological factors influencing transgenerational modifications. We sought to clarify the role of epigenetic reprogramming events during the life cycle of mammals and provide a comprehensive review of how the genomic and epigenomic make-up of progenitors may determine the phenotype of its descendants.
OUTCOMES
We found strong evidence supporting the role of DNA methylation patterns, histone modifications and even non-protein-coding RNA in altering the epigenetic composition of individuals and producing stable epigenetic effects that were transmitted from parents to offspring, in both humans and rodent species. Multiple genomic domains and several histone modification sites were found to resist demethylation and endure genome-wide reprogramming events. Epigenetic modifications integrated into the genome of individuals were shown to modulate gene expression and activity at enhancer and promoter domains, while genetic mutations were shown to alter sequence availability for methylation and histone binding. Fundamentally, alterations to the nuclear composition of the germline in response to environmental factors, ageing, diet and toxicant exposure have the potential to become hereditably transmitted.
WIDER IMPLICATIONS
The environment influences the health and well-being of progeny by working through the germline to introduce spontaneous genetic mutations as well as a variety of epigenetic changes, including alterations in DNA methylation status and the post-translational modification of histones. In evolutionary terms, these changes create the phenotypic diversity that fuels the fires of natural selection. However, rather than being adaptive, such variation may also generate a plethora of pathological disease states ranging from dominant genetic disorders to neurological conditions, including spontaneous schizophrenia and autism.
Topics: Animals; Biological Evolution; DNA Methylation; Epigenesis, Genetic; Genome; Germ Cells; Heredity; Histone Code; Histones; Humans; Mammals; Mutation; Parents; Phenotype
PubMed: 31374565
DOI: 10.1093/humupd/dmz017 -
The Science of the Total Environment Dec 2022This systematic review aims to summarize the current knowledge on biological effects of micro- and nanoplastics (MNPs) on human health based on mammalian systems. An...
This systematic review aims to summarize the current knowledge on biological effects of micro- and nanoplastics (MNPs) on human health based on mammalian systems. An extensive search of the literature led to a total of 133 primary research articles on the health relevance of MNPs. Our findings revealed that although the study of MNP cytotoxicity and inflammatory response represents a major research theme, most studies (105 articles) focused on the effects of polystyrene MNPs due to their wide availability as a well characterised research material that can be manufactured with a large range of particle sizes, fluorescence labelling as well as various surface modifications. Among the 133 studies covered in this review, 117 articles reported adverse health effects after being exposed to MNPs. Mammalian in vitro studies identified multiple biological effects including cytotoxicity, oxidative stress, inflammatory response, genotoxicity, embryotoxicity, hepatotoxicity, neurotoxicity, renal toxicity and even carcinogenicity, while rodent in vivo models confirmed the bioaccumulation of MNPs in the liver, spleen, kidney, brain, lung and gut, presenting adverse effects at different levels including reproductive toxic effects and trans-generational toxicity. In contrast, the remaining 16 studies indicated an insignificant impact of MNPs on humans. A few studies attempted to investigate the mechanisms or factors driving the toxicity of MNPs and identified several determining factors including size, concentration, shape, surface charge, attached pollutants and weathering process, which, however, were not benchmarked or considered by most studies. This review demonstrates that there are still many inconsistencies in the evaluation of the potential health effects of MNPs due to the lack of comparability between studies. Current limitations hindering the attainment of reproducible conclusions as well as recommendations for future research directions are also presented.
Topics: Animals; Humans; Environmental Pollutants; Mammals; Microplastics; Particle Size; Plastics; Polystyrenes
PubMed: 35987230
DOI: 10.1016/j.scitotenv.2022.158111 -
Animals : An Open Access Journal From... Feb 2021The intent of this review is to summarize the knowledge about selenium and its function in a dog's body. For this purpose, systematic literature search was conducted.... (Review)
Review
The intent of this review is to summarize the knowledge about selenium and its function in a dog's body. For this purpose, systematic literature search was conducted. For mammals, including dogs, a balanced diet and sufficient intake of selenium are important for correct function of metabolism. As for selenium poisoning, there are no naturally occurring cases known. Nowadays, we do not encounter clinical signs of its deficiency either, but it can be subclinical. For now, the most reliable method of assessing selenium status of a dog is measuring serum or plasma levels. Levels in full blood can be measured too, but there are no reference values. The use of glutathione peroxidase as an indirect assay is questionable in canines. Commercial dog food manufactures follow recommendations for minimal and maximal selenium levels and so dogs fed commercial diets should have balanced intake of selenium. For dogs fed home-made diets, complex data are missing. However, subclinical deficiency seems to affect, for example, male fertility or recovery from parasitical diseases. Very interesting is the role of selenium in prevention and treatment of cancer.
PubMed: 33562028
DOI: 10.3390/ani11020418