Nutritional Aspects of Spermidine

Natural polyamines (spermidine and spermine) are small, positively charged molecules that are ubiquitously found within organisms and cells. They exert numerous (intra)cellular functions and have been implicated to protect against several age-related diseases. Although polyamine levels decline in a complex age-dependent, tissue-, and cell type–specific manner, they are maintained in healthy nonagenarians and centenarians. Increased polyamine levels, including through enhanced dietary intake, have been consistently linked to improved health and reduced overall mortality. In preclinical models, dietary supplementation with spermidine prolongs life span and health span. In this review, we highlight salient aspects of nutritional polyamine intake and summarize the current knowledge of organismal and cellular uptake and distribution of dietary (and gastrointestinal) polyamines and their impact on human health. We further summarize clinical and epidemiological studies of dietary polyamines.

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Molecular Age-Related Changes in the Anterior Segment of the Eye

Journal of Ophthalmology ◽

10.1155/2017/1295132 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Luis Fernando Hernandez-Zimbron ◽

Rosario Gulias-Cañizo ◽

María F. Golzarri ◽

Blanca Elizabeth Martínez-Báez ◽

Hugo Quiroz-Mercado ◽

...

Keyword(s):

Aging Process ◽

Molecular Mechanisms ◽

Molecular Level ◽

Current Knowledge ◽

Anterior Segment ◽

Ageing Process ◽

Degenerative Diseases ◽

Mesh Terms ◽

Age Related ◽

Age Dependent

Purpose. To examine the current knowledge about the age-related processes in the anterior segment of the eye at a biological, clinical, and molecular level. Methods. We reviewed the available published literature that addresses the aging process of the anterior segment of the eye and its associated molecular and physiological events. We performed a search on PubMed, CINAHL, and Embase using the MeSH terms “eye,” “anterior segment,” and “age.” We generated searches to account for synonyms of these keywords and MESH headings as follows: (1) “Eye” AND “ageing process” OR “anterior segment ageing” and (2) “Anterior segment” AND “ageing process” OR “anterior segment” AND “molecular changes” AND “age.” Results. Among the principal causes of age-dependent alterations in the anterior segment of the eye, we found the mutation of the TGF-β gene and loss of autophagy in addition to oxidative stress, which contributes to the pathogenesis of degenerative diseases. Conclusions. In this review, we summarize the current knowledge regarding some of the molecular mechanisms related to aging in the anterior segment of the eye. We also introduce and propose potential roles of autophagy, an important mechanism responsible for maintaining homeostasis and proteostasis under stress conditions in the anterior segment during aging.

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A Knockout Mouse Approach Reveals that TCTP Functions as an Essential Factor for Cell Proliferation and Survival in a Tissue- or Cell Type–specific Manner

Molecular Biology of the Cell ◽

10.1091/mbc.e07-02-0188 ◽

2007 ◽

Vol 18 (7) ◽

pp. 2525-2532 ◽

Cited By ~ 140

Author(s):

Sung Ho Chen ◽

Peih-Shan Wu ◽

Chiang-Hung Chou ◽

Yu-Ting Yan ◽

Hsuan Liu ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Types ◽

Cell Type ◽

Cellular Functions ◽

Embryonic Fibroblasts ◽

Embryonic Tissues ◽

Targeted Gene Disruption ◽

Specific Manner ◽

Cell Type Specific ◽

And Control

Translationally controlled Tumor Protein (TCTP) is an evolutionally highly conserved protein which has been implicated in many cellular functions that are related to cell growth, death, and even the allergic response of the host. To address the physiological roles of TCTP, we generated TCTP knockout mice by targeted gene disruption. Heterozygous mutants appeared to be developmentally normal. However, homozygous mutants (TCTP−/−) were embryonic lethal. TCTP−/− embryos were smaller in size than the control littermates at all postimplantation stages examined. Although TCTP is widely expressed in both extraembryonic and embryonic tissues, the most prominent defect of the TCTP−/− embryo at embryonic stage day 5.5 (E5.5) was in its epiblast, which had a reduced number of cells compared with wild-type controls. The knockout embryos also suffered a higher incidence of apoptosis in epiblast starting about E6.5 and subsequently died around E9.5–10.5 with a severely disorganized structure. Last, we demonstrated that TCTP−/− and control mouse embryonic fibroblasts manifested similar proliferation activities and apoptotic sensitivities to various death stimuli. Taken together, our results suggest that despite that TCTP is widely expressed in many tissues or cell types, it appears to regulate cell proliferation and survival in a tissue- or cell type–specific manner.

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Kidney, heart and brain: three organs targeted by ageing and glycation

Clinical Science ◽

10.1042/cs20160823 ◽

2017 ◽

Vol 131 (11) ◽

pp. 1069-1092 ◽

Cited By ~ 30

Author(s):

Marie Frimat ◽

Maité Daroux ◽

Rachel Litke ◽

Rémi Nevière ◽

Frédéric J. Tessier ◽

...

Keyword(s):

Current Knowledge ◽

Therapeutic Option ◽

Enzymatic Reaction ◽

Epidemiological Studies ◽

Accelerated Ageing ◽

Public Health Issue ◽

Age Related ◽

Target Organs ◽

Generic Term ◽

Inflammatory Signalling

Advanced glycation end-product (AGE) is the generic term for a heterogeneous group of derivatives arising from a non-enzymatic reaction between reducing sugars and proteins. In recent years, evidence has accumulated that incriminates AGEs in pathogenic processes associated with both chronic hyperglycaemia and age-related diseases. Regardless of their exogenous or endogenous origin, the accumulation of AGEs and their derivatives could promote accelerated ageing by leading to protein modifications and activating several inflammatory signalling pathways via AGE-specific receptors. However, it remains to be demonstrated whether preventing the accumulation of AGEs and their effects is an important therapeutic option for successful ageing. The present review gives an overview of the current knowledge on the pathogenic role of AGEs by focusing on three AGE target organs: kidney, heart and brain. For each of these organs we concentrate on an age-related disease, each of which is a major public health issue: chronic kidney disease, heart dysfunction and neurodegenerative diseases. Even though strong connections have been highlighted between glycation and age-related pathogenesis, causal links still need to be validated. In each case, we report evidence and uncertainties suggested by animal or epidemiological studies on the possible link between pathogenesis and glycation in a chronic hyperglycaemic state, in the absence of diabetes, and with exogenous AGEs alone. Finally, we present some promising anti-AGE strategies that are currently being studied.

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miRNA-Based Therapeutics in the Era of Immune-Checkpoint Inhibitors

Pharmaceuticals ◽

10.3390/ph14020089 ◽

2021 ◽

Vol 14 (2) ◽

pp. 89

Author(s):

Florian Huemer ◽

Michael Leisch ◽

Roland Geisberger ◽

Nadja Zaborsky ◽

Richard Greil

Keyword(s):

Gene Expression ◽

Immune Checkpoint ◽

Current Knowledge ◽

Checkpoint Inhibitors ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Cellular Functions ◽

Gene Transcripts ◽

A Cell ◽

Cell Type Specific

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to complementary target regions on gene transcripts. Thus, miRNAs fine-tune gene expression profiles in a cell-type-specific manner and thereby regulate important cellular functions, such as cell growth, proliferation and cell death. MiRNAs are frequently dysregulated in cancer cells by several mechanisms, which significantly affect the course of the disease. In this review, we summarize the current knowledge on how dysregulated miRNAs contribute to cancer and how miRNAs can be exploited as predictive factors and therapeutic targets, particularly in regard to immune-checkpoint inhibitor therapies.

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Aim for the Readers! Bromodomains As New Targets Against Chagas’ Disease

Current Medicinal Chemistry ◽

10.2174/0929867325666181031132007 ◽

2019 ◽

Vol 26 (36) ◽

pp. 6544-6563

Author(s):

Victoria Lucia Alonso ◽

Luis Emilio Tavernelli ◽

Alejandro Pezza ◽

Pamela Cribb ◽

Carla Ritagliati ◽

...

Keyword(s):

Drug Discovery ◽

Small Molecules ◽

Chagas Disease ◽

Causative Agent ◽

Current Knowledge ◽

Sequence Similarity ◽

Lysine Acetylation ◽

Specific Manner ◽

Lysine Residues ◽

Antiparasitic Drugs

Bromodomains recognize and bind acetyl-lysine residues present in histone and non-histone proteins in a specific manner. In the last decade they have raised as attractive targets for drug discovery because the miss-regulation of human bromodomains was discovered to be involved in the development of a large spectrum of diseases. However, targeting eukaryotic pathogens bromodomains continues to be almost unexplored. We and others have reported the essentiality of diverse bromodomain- containing proteins in protozoa, offering a new opportunity for the development of antiparasitic drugs, especially for Trypansoma cruzi, the causative agent of Chagas’ disease. Mammalian bromodomains were classified in eight groups based on sequence similarity but parasitic bromodomains are very divergent proteins and are hard to assign them to any of these groups, suggesting that selective inhibitors can be obtained. In this review, we describe the importance of lysine acetylation and bromodomains in T. cruzi as well as the current knowledge on mammalian bromodomains. Also, we summarize the myriad of small-molecules under study to treat different pathologies and which of them have been tested in trypanosomatids and other protozoa. All the information available led us to propose that T. cruzi bromodomains should be considered as important potential targets and the search for smallmolecules to inhibit them should be empowered.

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Bone morphogenetic proteins, breast cancer, and bone metastases: striking the right balance

Endocrine Related Cancer ◽

10.1530/erc-17-0139 ◽

2017 ◽

Vol 24 (10) ◽

pp. R349-R366 ◽

Cited By ~ 19

Author(s):

Catherine Zabkiewicz ◽

Jeyna Resaul ◽

Rachel Hargest ◽

Wen Guo Jiang ◽

Lin Ye

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Bone Morphogenetic Proteins ◽

Therapeutic Potential ◽

Current Knowledge ◽

Breast Tumour ◽

Cellular Functions ◽

Foetal Development ◽

Key Factor ◽

The Right

Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for the regulation of foetal development, tissue differentiation and homeostasis and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which studies have revealed aberrations of both BMP expression and signalling, which correlate clinically with breast cancer progression. Ultimately a BMP profile could provide new prognostic disease markers. As the evidence suggests a role for BMPs in regulating breast tumour cellular function, in particular interactions with tumour stroma and the bone metastatic microenvironment, there may be novel therapeutic potential in targeting BMP signalling in breast cancer. This review provides an update on the current knowledge of BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease-specific bone metastasis.

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Neuroligin-2 as a central organizer of inhibitory synapses in health and disease

Science Signaling ◽

10.1126/scisignal.abd8379 ◽

2020 ◽

Vol 13 (663) ◽

pp. eabd8379

Author(s):

Heba Ali ◽

Lena Marth ◽

Dilja Krueger-Burg

Keyword(s):

Synaptic Transmission ◽

Synapse Formation ◽

Current Knowledge ◽

Protein Complexes ◽

Inhibitory Synapses ◽

Molecular Architecture ◽

Cellular Functions ◽

Altered Expression ◽

Health And Disease ◽

Flow Of Information

Postsynaptic organizational protein complexes play central roles both in orchestrating synapse formation and in defining the functional properties of synaptic transmission that together shape the flow of information through neuronal networks. A key component of these organizational protein complexes is the family of synaptic adhesion proteins called neuroligins. Neuroligins form transsynaptic bridges with presynaptic neurexins to regulate various aspects of excitatory and inhibitory synaptic transmission. Neuroligin-2 (NLGN2) is the only member that acts exclusively at GABAergic inhibitory synapses. Altered expression and mutations in NLGN2 and several of its interacting partners are linked to cognitive and psychiatric disorders, including schizophrenia, autism, and anxiety. Research on NLGN2 has fundamentally shaped our understanding of the molecular architecture of inhibitory synapses. Here, we discuss the current knowledge on the molecular and cellular functions of mammalian NLGN2 and its role in the neuronal circuitry that regulates behavior in rodents and humans.

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Molecular Subtyping of Blastocystis sp. Isolated from Farmed Animals in Southern Italy

Microorganisms ◽

10.3390/microorganisms9081656 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1656

Author(s):

Simona Gabrielli ◽

Marialetizia Palomba ◽

Federica Furzi ◽

Emanuele Brianti ◽

Gabriella Gaglio ◽

...

Keyword(s):

Current Knowledge ◽

Pcr Amplification ◽

Epidemiological Studies ◽

Fallow Deer ◽

Small Subunit ◽

Zoonotic Transmission ◽

Ssu Rrna ◽

Molecular Approaches ◽

Wide Range ◽

Blastocystis Sp

Blastocystis is a common intestinal protist distributed worldwide, infecting humans and a wide range of domestic and wild animals. It exhibits an extensive genetic diversity and, so far, 25 distinct small subunit ribosomal RNA (SSU rRNA) lineages termed subtypes (STs)) have been characterized; among them, 12 have thus far been reported in humans. The aims of the present study were to detect and genetically characterize Blastocystis sp. in synantropic animals to improve our current knowledge on the distribution and zoonotic transmission of Blastocystis STs in Italy. Samples were collected from N = 193 farmed animals and submitted to DNA extraction and PCR amplification of the SSU rRNA. Blastocystis was detected in 60 samples (31.08%) and successfully subtyped. Phylogenetic analysis evidenced that the isolates from fallow deer, goats, and pigs (N = 9) clustered within the ST5; those from pheasants (N = 2) in the ST6; those from chickens (N = 8) in the ST7; those from sheep (N = 6) in the ST10; and those from water buffaloes (N = 9) in the ST14 clade. The comparison between the present isolates from animals and those previously detected in humans in Italy suggested the animal-to-human spillover for ST6 and ST7. The present study represents the widest Blastocystis survey performed thus far in farmed animals in Italy. Further epidemiological studies using molecular approaches are required to determine the occurrence and distribution of Blastocystis STs in other potential animal reservoirs in Italy and to define the pathways of zoonotic transmission.

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The DEAH helicase DHX36 and its role in G-quadruplex-dependent processes

Biological Chemistry ◽

10.1515/hsz-2020-0292 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Philipp Schult ◽

Katrin Paeschke

Keyword(s):

Current Knowledge ◽

Future Research ◽

Transcriptional Level ◽

Cellular Functions ◽

Multiple Functions ◽

Open Questions ◽

G Quadruplex ◽

Cellular Pathways ◽

Nucleic Acid Structures ◽

Dependent Processes

AbstractDHX36 is a member of the DExD/H box helicase family, which comprises a large number of proteins involved in various cellular functions. Recently, the function of DHX36 in the regulation of G-quadruplexes (G4s) was demonstrated. G4s are alternative nucleic acid structures, which influence many cellular pathways on a transcriptional and post-transcriptional level. In this review we provide an overview of the current knowledge about DHX36 structure, substrate specificity, and mechanism of action based on the available models and crystal structures. Moreover, we outline its multiple functions in cellular homeostasis, immunity, and disease. Finally, we discuss the open questions and provide potential directions for future research.

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Relationship between Autism Spectrum Disorder and Pesticides: A Systematic Review of Human and Preclinical Models

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18105190 ◽

2021 ◽

Vol 18 (10) ◽

pp. 5190

Author(s):

Judit Biosca-Brull ◽

Cristian Pérez-Fernández ◽

Santiago Mora ◽

Beatriz Carrillo ◽

Helena Pinos ◽

...

Keyword(s):

Systematic Review ◽

Autism Spectrum Disorder ◽

Experimental Studies ◽

Clinical Signs ◽

Epidemiological Studies ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Preclinical Studies ◽

Preclinical Models ◽

Gestational Exposure

Autism spectrum disorder (ASD) is a complex set of neurodevelopmental pathologies characterized by impoverished social and communicative abilities and stereotyped behaviors. Although its genetic basis is unquestionable, the involvement of environmental factors such as exposure to pesticides has also been proposed. Despite the systematic analyses of this relationship in humans, there are no specific reviews including both human and preclinical models. The present systematic review summarizes, analyzes, and discusses recent advances in preclinical and epidemiological studies. We included 45 human and 16 preclinical studies. These studies focused on Organophosphates (OP), Organochlorine (OC), Pyrethroid (PT), Neonicotinoid (NN), Carbamate (CM), and mixed exposures. Preclinical studies, where the OP Chlorpyrifos (CPF) compound is the one most studied, pointed to an association between gestational exposure and increased ASD-like behaviors, although the data are inconclusive with regard to other ages or pesticides. Studies in humans focused on prenatal exposure to OP and OC agents, and report cognitive and behavioral alterations related to ASD symptomatology. The results of both suggest that gestational exposure to certain OP agents could be linked to the clinical signs of ASD. Future experimental studies should focus on extending the analysis of ASD-like behaviors in preclinical models and include exposure patterns similar to those observed in human studies.

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