Focal Point of Fanconi Anemia Signaling

Among human genetic diseases, Fanconi Anemia (FA) tops all with its largest number of health complications in nearly all human organ systems, suggesting the significant roles played by FA genes in the maintenance of human health. With the accumulated research on FA, the encoded protein products by FA genes have been building up to the biggest cell defense signaling network, composed of not only 22+ FA proteins but also ATM, ATR, and many other non-FA proteins. The FA D2 group protein (FANCD2) and its paralog form the focal point of FA signaling to converge the effects of its upstream players in response to a variety of cellular insults and simultaneously with downstream players to protect humans from contracting diseases, including aging and cancer. In this review, we update and discuss how the FA signaling crucially eases cellular stresses through understanding its focal point.

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Δ 9-Tetrahydrocannabinol Toxicity and Validation of Cannabidiol on Brain Dopamine Levels: An Assessment on Cannabis Duplicity

Natural Products and Bioprospecting ◽

10.1007/s13659-020-00263-z ◽

2020 ◽

Vol 10 (5) ◽

pp. 285-296

Author(s):

Swapnali Chetia ◽

Gaurab Borah

Keyword(s):

Human Health ◽

Present Review ◽

Health Evaluation ◽

Anti Psychotic ◽

Brain Dopamine ◽

Drastic Effect ◽

Health Complications ◽

Reported Data ◽

Therapeutic Medium ◽

The Brain

Abstract Δ9-tetrahydrocannabinol (THC) of cannabis is the main psychoactive component which is a global significant concern to human health. Evaluation on THC reported its drastic effect on the brain dopaminergic (DAergic) system stimulating mesolimbic DA containing neurons thereby increasing the level of striatal DA. Cannabidiol (CBD), with its anxiolytic and anti-psychotic property, is potent to ameliorate the THC-induced DAergic variations. Legal authorization of cannabis use and its analogs in most countries led to a drastic dispute in the elicitation of cannabis products. With a recent increase in cannabis-induced disorder rates, the present review highlighted the detrimental effects of THC and the effects of CBD on THC induced alterations in DA synthesis and release. Alongside the reported data, uses of cannabis as a therapeutic medium in a number of health complications are also being briefly reviewed. These evaluated reports led to an anticipation of additional research contradictory to the findings of THC and CBD activity in the brain DAergic system and their medical implementations as therapeutics. Graphic Abstract

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Environmental exposure to pesticides and cancer risk in multiple human organ systems

Toxicology Letters ◽

10.1016/j.toxlet.2013.11.009 ◽

2014 ◽

Vol 230 (2) ◽

pp. 157-165 ◽

Cited By ~ 70

Author(s):

Tesifón Parrón ◽

Mar Requena ◽

Antonio F. Hernández ◽

Raquel Alarcón

Keyword(s):

Cancer Risk ◽

Environmental Exposure ◽

Human Organ ◽

Organ Systems

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A Survey of Strategies to Modulate the Bone Morphogenetic Protein Signaling Pathway: Current and Future Perspectives

Stem Cells International ◽

10.1155/2016/7290686 ◽

2016 ◽

Vol 2016 ◽

pp. 1-15 ◽

Cited By ~ 12

Author(s):

Jonathan W. Lowery ◽

Brice Brookshire ◽

Vicki Rosen

Keyword(s):

Bone Morphogenetic Proteins ◽

Bmp Signaling ◽

Protein Signaling ◽

Bone Morphogenetic Protein Signaling ◽

Human Organ ◽

Morphogenetic Protein ◽

Organ Systems ◽

Bmp Pathway ◽

Wide Perspective ◽

The Relationship

Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the TGF-βfamily of ligands and are unequivocally involved in regulating stem cell behavior. Appropriate regulation of canonical BMP signaling is critical for the development and homeostasis of numerous human organ systems, as aberrations in the BMP pathway or its regulation are increasingly associated with diverse human pathologies. In this review, we provide a wide-perspective on strategies that increase or decrease BMP signaling. We briefly outline the current FDA-approved approaches, highlight emerging next-generation technologies, and postulate prospective avenues for future investigation. We also detail how activating other pathways may indirectly modulate BMP signaling, with a particular emphasis on the relationship between the BMP and Activin/TGF-βpathways.

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Endocrine cells of the adenohypophysis in severe acute respiratory syndrome (SARS)This paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.

Biochemistry and Cell Biology ◽

10.1139/o10-022 ◽

2010 ◽

Vol 88 (4) ◽

pp. 723-730 ◽

Cited By ~ 13

Author(s):

Lan Wei ◽

Shen Sun ◽

Jing Zhang ◽

Hong Zhu ◽

Yun Xu ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Endocrine Cells ◽

Peer Review Process ◽

Serum Levels ◽

Staining Intensity ◽

Thyroid Stimulating Hormone ◽

Human Organ ◽

Organ Systems ◽

Quantitative Image ◽

Stimulating Hormone

It is known that severe acute respiratory syndrome (SARS), a severe infectious illness, which caused an epidemic in Asia in 2003, has extensive and complex effects on human organ systems. It has been reported that the serum levels of prolactin (PRL), follicle stimulating hormone (FSH), and luteinizing hormone (LH) of SARS patients are significantly higher than those of control groups, while estradiol (E2), pregnancy hormone (P), and thyroid stimulating hormone (TSH) are considerably lower than those of normal controls. This phenomenon suggests that the adenohypophyseal endocrine cells in SARS patients may be damaged. However, up to now there has been no direct histological investigation on the endocrine cells of patients’ pituitary. Here we investigated the endocrine cells in the adenohypophysis obtained from autopsies of 5 SARS patients. The immunohistochemistry and quantitative image results showed that compared with control cases, both the number of positive cells and the staining intensity of immunoreactivity for growth hormone, TSH, and adrenocorticotrophic hormone in these cells were remarkably decreased, while that of PRL, FSH, and LH were significantly increased in all SARS cases studied. These findings indicated that alterations occurred in the patients’ adenohypophyseal endocrine cells, and these changes were consistent with the serum levels of relevant endocrine hormones reported previously. It appears that changes in these endocrine cells and their hormones are affected by the severity of this new infectious disease.

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CRISPR-Cas9 genome editing in human cells works via the Fanconi Anemia pathway

10.1101/136028 ◽

2017 ◽

Cited By ~ 17

Author(s):

Chris D Richardson ◽

Katelynn R Kazane ◽

Sharon J Feng ◽

Nicholas L Bray ◽

Axel J Schäfer ◽

...

Keyword(s):

Dna Repair ◽

Genome Editing ◽

Fanconi Anemia ◽

High Efficiency ◽

Genetic Diseases ◽

Dermal Fibroblasts ◽

Human Cells ◽

Individual Gene ◽

Break Site ◽

Repair Pathways

AbstractCRISPR-Cas9 genome editing creates targeted double strand breaks (DSBs) in eukaryotic cells that are processed by cellular DNA repair pathways. Co-administration of single stranded oligonucleotide donor DNA (ssODN) during editing can result in high-efficiency (>20%) incorporation of ssODN sequences into the break site. This process is commonly referred to as homology directed repair (HDR) and here referred to as single stranded template repair (SSTR) to distinguish it from repair using a double stranded DNA donor (dsDonor). The high efficacy of SSTR makes it a promising avenue for the treatment of genetic diseases1,2, but the genetic basis of SSTR editing is still unclear, leaving its use a mostly empiric process. To determine the pathways underlying SSTR in human cells, we developed a coupled knockdown-editing screening system capable of interrogating multiple editing outcomes in the context of thousands of individual gene knockdowns. Unexpectedly, we found that SSTR requires multiple components of the Fanconi Anemia (FA) repair pathway, but does not require Rad51-mediated homologous recombination, distinguishing SSTR from repair using dsDonors. Knockdown of FA genes impacts SSTR without altering break repair by non-homologous end joining (NHEJ) in multiple human cell lines and in neonatal dermal fibroblasts. Our results establish an unanticipated and central role for the FA pathway in templated repair from single stranded DNA by human cells. Therapeutic genome editing has been proposed to treat genetic disorders caused by deficiencies in DNA repair, including Fanconi Anemia. Our data imply that patient genotype and/or transcriptome profoundly impact the effectiveness of gene editing treatments and that adjuvant treatments to bias cells towards FA repair pathways could have considerable therapeutic value.

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Cafe-au-lait spots as a clinical sign of syndromes

Research Society and Development ◽

10.33448/rsd-v10i9.17607 ◽

2021 ◽

Vol 10 (9) ◽

pp. e14310917607

Author(s):

Adriana Amaral Carvalho ◽

Daniella Reis Barbosa Martelli ◽

Maria Fernanda Amaral Carvalho ◽

Mário Sérgio Oliveira Swerts ◽

Hercílio Martelli Júnior

Keyword(s):

Health Professionals ◽

Literature Search ◽

Genetic Diseases ◽

Signs And Symptoms ◽

Final Diagnosis ◽

Extensive Literature ◽

Clinical Symptomatology ◽

Café Au Lait Spots ◽

Organ Systems ◽

Extensive Literature Search

Several studies describe the frequent association of cafe-au-lait spots with neurofibromatosis. However, many other genetic diseases might be associated with the presence of café-au-lait spots. Several genetic diseases are rare. In most cases, syndromes present themselves as a set of signs and symptoms that may present varied penetrance, therefore largely reducing the percentage of final diagnosis. Exploration of clinical symptomatology is essential for the understanding and diagnosis of syndromes. In this review, we conduct an extensive literature search looking for research that investigated diseases that may be present simultaneously with the cafe-au-lait spots. A total of 60 genetic diseases were found, all of them rare. These syndromes were evaluated based on their most relevant features and described in a summary of the typical, general, and head and neck findings. The available OMIM number, mode of inheritance, chromosome, mutated genes, and affected proteins were also listed. The considerable variety of diseases associated with the presence of cafe-au-lait spots and the fact that many of these conditions affect various organ systems with diverse phenotypic presentations is a diagnostic and therapeutic challenge. The objective of this study was to provide health professionals with an instrument containing a broad spectrum of genetic diseases coincident with the presence of cafe-au-lait spots in order to facilitate the differential and final diagnosis of these syndromes.

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