Main molecular mechanisms for noncommunicable diseases

2022 ◽  
pp. 5-25
Author(s):  
Marina Vilar Geraldi ◽  
Paulo Sérgio Loubet Filho ◽  
Andressa Mara Baseggio ◽  
Cinthia Baú Betim Cazarin ◽  
Mario Roberto Marostica Junior
2020 ◽  
Vol 27 (2) ◽  
pp. 120-134 ◽  
Author(s):  
Mithoor Divyashree ◽  
Madhu K. Mani ◽  
Dhanasekhar Reddy ◽  
Ranjith Kumavath ◽  
Preetam Ghosh ◽  
...  

: In this era of multi-drug resistance (MDR), antimicrobial peptides (AMPs) are one of the most promising classes of potential drug candidates to combat communicable as well as noncommunicable diseases such as cancers and diabetes. AMPs show a wide spectrum of biological activities which include antiviral, antifungal, anti-mitogenic, anticancer, and anti-inflammatory properties. Apart from these prospective therapeutic potentials, the AMPs can act as food preservatives and immune modulators. Therefore, AMPs have the potential to replace conventional drugs and may gain a significant global drug market share. Although several AMPs have shown therapeutic potential in vitro or in vivo, in most cases they have failed the clinical trial owing to various issues. In this review, we discuss in brief (i) molecular mechanisms of AMPs in various diseases, (ii) importance of AMPs in pharmaceutical industries, (iii) the challenges in using AMPs as therapeutics and how to overcome, (iv) available AMP therapeutics in market, and (v) AMPs under clinical trials. Here, we specifically focus on the therapeutic AMPs in the areas of dermatology, surgery, oncology and metabolic diseases.


2018 ◽  
Vol 2018 ◽  
pp. 1-24 ◽  
Author(s):  
Bee Ling Tan ◽  
Mohd Esa Norhaizan ◽  
Winnie-Pui-Pui Liew

There are different types of nutritionally mediated oxidative stress sources that trigger inflammation. Much information indicates that high intakes of macronutrients can promote oxidative stress and subsequently contribute to inflammation via nuclear factor-kappa B- (NF-κB-) mediated cell signaling pathways. Dietary carbohydrates, animal-based proteins, and fats are important to highlight here because they may contribute to the long-term consequences of nutritionally mediated inflammation. Oxidative stress is a central player of metabolic ailments associated with high-carbohydrate and animal-based protein diets and excessive fat consumption. Obesity has become an epidemic and represents the major risk factor for several chronic diseases, including diabetes, cardiovascular disease (CVD), and cancer. However, the molecular mechanisms of nutritionally mediated oxidative stress are complex and poorly understood. Therefore, this review aimed to explore how dietary choices exacerbate or dampen the oxidative stress and inflammation. We also discussed the implications of oxidative stress in the adipocyte and glucose metabolism and obesity-associated noncommunicable diseases (NCDs). Taken together, a better understanding of the role of oxidative stress in obesity and the development of obesity-related NCDs would provide a useful approach. This is because oxidative stress can be mediated by both extrinsic and intrinsic factors, hence providing a plausible means for the prevention of metabolic disorders.


Author(s):  
Rondon Ramalho ◽  
Antônio Carlos de Abreu ◽  
Evair Moisés De Lima Santiago ◽  
Gislaine Recaldes de Abreu ◽  
Marcelo Barbosa Neves ◽  
...  

Economic and social development has essential repercussions on the health of populations, as it alters the morbidity and mortality profile and favors the increase in exposures and risks to human health, especially the risk of cancer. Cancer is considered a significant public health problem worldwide, and remains with high incidence rates, being considered a complex disease, with multifactorial causes. The permanent incidence rates of prostate cancer prove to be one of the most prevalent, considered the second most common cancer in men worldwide, and a leading cause of deaths from chronic noncommunicable diseases. Among the different types of cancer, prostate cancer has been the subject of great scientific interest. In this context, animal models are valuable for studying cancer-related aspects, the use of animal models has the potential to increase our understanding of carcinogenesis, tumor biology, and the impact of specific molecular events on tumor biology. Animal models with specific human cancer characteristics can be used to test cancer prevention and treatment strategies. In this review, we aim to show how the use of animal models as an essential tool in the study of the molecular mechanisms of carcinogenesis.


2020 ◽  
Vol 40 (13) ◽  
Author(s):  
Liam Baird ◽  
Masayuki Yamamoto

ABSTRACT The KEAP1-NRF2 pathway is the principal protective response to oxidative and electrophilic stresses. Under homeostatic conditions, KEAP1 forms part of an E3 ubiquitin ligase, which tightly regulates the activity of the transcription factor NRF2 by targeting it for ubiquitination and proteasome-dependent degradation. In response to stress, an intricate molecular mechanism facilitated by sensor cysteines within KEAP1 allows NRF2 to escape ubiquitination, accumulate within the cell, and translocate to the nucleus, where it can promote its antioxidant transcription program. Recent advances have revealed that KEAP1 contains multiple stress sensors and inactivation modalities, which together allow diverse cellular inputs, from oxidative stress and cellular metabolites to dysregulated autophagy, to regulate NRF2 activity. This integration of the KEAP1-NRF2 system into multiple cellular signaling and metabolic pathways places NRF2 activation as a critical regulatory node in many disease phenotypes and suggests that the pharmaceutical modulation of NRF2’s cytoprotective activity will be beneficial for human health in a broad range of noncommunicable diseases.


2019 ◽  
Vol 15 (2) ◽  
pp. 185-201 ◽  
Author(s):  
Manzoor A. Mir ◽  
Syed S. Hamdani ◽  
Bashir A. Sheikh ◽  
Umar Mehraj

Cancer is the second leading cause of death and morbidity in the world among noncommunicable diseases after cardiovascular ailments. With the advancement in science and research, a number of therapies have been developed to treat cancer, including chemotherapy, radiotherapy and immunotherapy. Chemo and radiotherapy have been in use since the last two decades, however these are not devoid of their own intrinsic problems, such as myelotoxicity, cardiotoxicity, nephrotoxicity, neurotoxicity and immunosuppression. Hence, there is an urgent need to develop alternative methods for the treatment of cancer. An increase in the cases of various cancers has encouraged the researchers to discover novel, more effective drugs from plant sources. In this review, fifteen medicinal plants alongside their products with anticancer effects will be introduced and discussed, as well as the most important plant compounds responsible for the anticancer activity of the plant. Several phenolic and alkaloid compounds have been demonstrated to have anticancer effects on various types of cancers. The most fundamental and efficient role exhibited by these secondary plant metabolites against cancer involves removing free radicals and antioxidant effects, induction of apoptosis, cell cycle arrest and inhibition of angiogenesis. Moreover, recent studies have shown that plants and their metabolites may provide an alternative to the existing approaches, including chemotherapies and radiotherapies, in the treatment of cancer. In this review, a brief overview of important secondary metabolites having anticancer activity will be given, along with the major molecular mechanisms involved in the disease. In addition to this, recent advances in secondary metabolites from various medicinal plants in the prevention and treatment of cancer will be explored.


Author(s):  
David P. Bazett-Jones ◽  
Mark L. Brown

A multisubunit RNA polymerase enzyme is ultimately responsible for transcription initiation and elongation of RNA, but recognition of the proper start site by the enzyme is regulated by general, temporal and gene-specific trans-factors interacting at promoter and enhancer DNA sequences. To understand the molecular mechanisms which precisely regulate the transcription initiation event, it is crucial to elucidate the structure of the transcription factor/DNA complexes involved. Electron spectroscopic imaging (ESI) provides the opportunity to visualize individual DNA molecules. Enhancement of DNA contrast with ESI is accomplished by imaging with electrons that have interacted with inner shell electrons of phosphorus in the DNA backbone. Phosphorus detection at this intermediately high level of resolution (≈lnm) permits selective imaging of the DNA, to determine whether the protein factors compact, bend or wrap the DNA. Simultaneously, mass analysis and phosphorus content can be measured quantitatively, using adjacent DNA or tobacco mosaic virus (TMV) as mass and phosphorus standards. These two parameters provide stoichiometric information relating the ratios of protein:DNA content.


Author(s):  
G-A. Keller ◽  
S. J. Gould ◽  
S. Subramani ◽  
S. Krisans

Subcellular compartments within eukaryotic cells must each be supplied with unique sets of proteins that must be directed to, and translocated across one or more membranes of the target organelles. This transport is mediated by cis- acting targeting signals present within the imported proteins. The following is a chronological account of a series of experiments designed and carried out in an effort to understand how proteins are targeted to the peroxisomal compartment.-We demonstrated by immunocryoelectron microscopy that the enzyme luciferase is a peroxisomal enzyme in the firefly lantern. -We expressed the cDNA encoding firefly luciferase in mammalian cells and demonstrated by immunofluorescence that the enzyme was transported into the peroxisomes of the transfected cells. -Using deletions, linker insertions, and gene fusion to identify regions of luciferase involved in its transport to the peroxisomes, we demonstrated that luciferase contains a peroxisomal targeting signal (PTS) within its COOH-terminal twelve amino acid.


Author(s):  
D. P. Bazett-Jones ◽  
M. J. Hendzel

Structural analysis of combinations of nucleosomes and transcription factors on promoter and enhancer elements is necessary in order to understand the molecular mechanisms responsible for the regulation of transcription initiation. Such complexes are often not amenable to study by high resolution crystallographic techniques. We have been applying electron spectroscopic imaging (ESI) to specific problems in molecular biology related to transcription regulation. There are several advantages that this technique offers in studies of nucleoprotein complexes. First, an intermediate level of spatial resolution can be achieved because heavy atom contrast agents are not necessary. Second, mass and stoichiometric relationships of protein and nucleic acid can be estimated by phosphorus detection, an element in much higher proportions in nucleic acid than protein. Third, wrapping or bending of the DNA by the protein constituents can be observed by phosphorus mapping of the complexes. Even when ESI is used with high exposure of electrons to the specimen, important macromolecular information may be provided. For example, an image of the TATA binding protein (TBP) bound to DNA is shown in the Figure (top panel). It can be seen that the protein distorts the DNA away from itself and much of its mass sits off the DNA helix axis. Moreover, phosphorus and mass estimates demonstrate whether one or two TBP molecules interact with this particular promoter TATA sequence.


2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.


2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.


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