Molecular mechanisms of crystallization impacting calcium phosphate cements

The biomineral calcium hydrogen phosphate dihydrate (CaHPO 4 ·2H 2 O), known as brushite, is a malleable material that both grows and dissolves faster than most other calcium minerals, including other calcium phosphate phases, calcium carbonates and calcium oxalates. Within the body, this ready formation and dissolution can play a role in certain diseases, such as kidney stone and plaque formation. However, these same properties, along with brushite’s excellent biocompatibility, can be used to great benefit in making resorbable biomedical cements. To optimize cements, additives are commonly used to control crystallization kinetics and phase transformation. This paper describes the use of in situ scanning probe microscopy to investigate the role of several solution parameters and additives in brushite atomic step motion. Surprisingly, this work demonstrates that the activation barrier for phosphate (rather than calcium) incorporation limits growth kinetics and that additives such as magnesium, citrate and bisphosphonates each influence step motion in distinctly different ways. Our findings provide details of how, and where, molecules inhibit or accelerate kinetics. These insights have the potential to aid in designing molecules to target specific steps and to guide synergistic combinations of additives.

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THIOZOLIDINEDIONES IN THE TREATMENT OF PATIENTS WITH EXTENSIVE PSORIASIS AND CONCOMITANT ALIMENTARY OBESITY

Актуальні проблеми сучасної медицини Вісник Української медичної стоматологічної академії ◽

10.31718/2077-1096.20.4.30 ◽

2020 ◽

Vol 20 (4) ◽

pp. 30-34

Author(s):

Ya.O. Yemchenko ◽

K.Ye. Ishcheikin ◽

I.P. Kaidashev

Keyword(s):

Systemic Inflammation ◽

Molecular Mechanisms ◽

Current Data ◽

The Body ◽

Internal Organs ◽

Single View ◽

Multifactorial Diseases ◽

Alimentary Obesity ◽

Inflammatory Processes

Psoriasis is one of the most common chronic recurrent systemic autoimmune multifactorial diseases, affected the skin, joints, internal organs and systems of the body. Despite the significant prevalence of psoriasis and a large number of studies devoted this problem there is still no single view on the pathogenesis of this dermatosis. To clear up the pathogenesis of psoriasis, it seems to be reasonable to focus on the common comorbidities or multimorbidities, which may occur in the course of psoriasis, as this issue is still insufficiently studied. Recent reports have proven the evidences of indisputable link between psoriasis and obesity. The scientific literature extensively covers the issues of identical pathogenetic mechanisms of inflammatory processes in psoriasis and obesity. Given the current data on the role of systemic inflammation underlying the development of both psoriasis and obesity, the study of molecular mechanisms of its development and in particularly the role of proinflammatory nuclear transcription factors, thiazolidinediones have been found out as pathogenetically justified medicine of choice for the therapy of these diseases. In this study, we determined the effectiveness of using 30 mg of pioglitazone daily for 6 months in the course of treatment for patients with extensive psoriasis vulgaris of moderate severity, who were also diagnosed as having concomitant grade І-ІІ alimentary obesity that was supported by clinical and immunological findings evidenced of systemic inflammation. Analyzing the results obtained, we have found out the prolonged therapy with pioglitazone leads to a decrease in systemic inflammation and contributes to a milder recurrent course of psoriasis.

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Molecular mechanisms of control of differentiation of regulatory t-lymphocytes by exogenous melatonin

Доклады Академии наук ◽

10.31857/s0869-56524842224-227 ◽

2019 ◽

Vol 484 (2) ◽

pp. 224-227

Author(s):

N. S. Glebezdina ◽

A. A. Olina ◽

I. V. Nekrasova ◽

E. M. Kuklina

Keyword(s):

T Cells ◽

Molecular Mechanisms ◽

Inhibitory Effect ◽

The Body ◽

Membrane Receptors ◽

Cell Subpopulation ◽

Exogenous Melatonin ◽

Regulatory T Lymphocytes ◽

Treg Differentiation

We investigated the role of epiphyseal hormone melatonin in the differentiation of naive CD4+T cells into regulatory T cells (Treg). The hormone at physiological and pharmacological concentrations inhibited Treg differentiation, decreasing both the proportion of CD4+FOXP3+ cells in the culture and the level of TGF‑β, the key cytokine for this T cell subpopulation. The inhibitory effect of exogenous melatonin was due to its interaction with the membrane receptors MT1 and MT2. At the same time, the signals realized through RORa — the nuclear receptor for melatonin — stimulated Treg formation; however, they were considerably weaker than the signals from the membrane receptors and were overlapped by the latter. Since the Treg subpopulation plays an important role in physiological and pathological processes in the body, the revealed effects of melatonin should be taken into account in its therapeutic use.

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Type 3 Innate Lymphoid Cells as Regulators of the Host-Pathogen Interaction

Frontiers in Immunology ◽

10.3389/fimmu.2021.748851 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ana Valle-Noguera ◽

Anne Ochoa-Ramos ◽

Maria José Gomez-Sánchez ◽

Aranzazu Cruz-Adalia

Keyword(s):

Transgenic Mice ◽

Molecular Mechanisms ◽

Specific Activity ◽

Innate Lymphoid Cells ◽

The Body ◽

Lymphoid Cells ◽

Intracellular Pathogens ◽

Host Pathogen Interaction ◽

Type 3

Type 3 Innate lymphoid cells (ILC3s) have been described as tissue-resident cells and characterized throughout the body, especially in mucosal sites and classical first barrier organs such as skin, gut and lungs, among others. A significant part of the research has focused on their role in combating pathogens, mainly extracellular pathogens, with the gut as the principal organ. However, some recent discoveries in the field have unveiled their activity in other organs, combating intracellular pathogens and as part of the response to viruses. In this review we have compiled the latest studies on the role of ILC3s and the molecular mechanisms involved in defending against different microbes at the mucosal surface, most of these studies have made use of conditional transgenic mice. The present review therefore attempts to provide an overview of the function of ILC3s in infections throughout the body, focusing on their specific activity in different organs.

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Lymphatic system and adipose tissue: Crosstalk in health and disease

Obesity and metabolism ◽

10.14341/omet12776 ◽

2021 ◽

Vol 18 (3) ◽

pp. 336-344

Author(s):

V. V. Klimontov ◽

D. M. Bulumbaeva

Keyword(s):

Endothelial Cells ◽

Adipose Tissue ◽

Molecular Mechanisms ◽

Lymphatic System ◽

Lymphatic Vessels ◽

Inflammatory Cells ◽

The Body ◽

Push Button ◽

Secondary Lymphedema

The lymphatic system (LS) is one of the main integrative systems of the body, providing protective and transport functions. In recent years, interactions between LS and adipose tissue (AT) have been of particular interest. Lymphatic vessels play an important role in metabolic and regulatory functions of AT, acting as a collector of lipolysis products and adipokines. In its turn, hormones and adipocytokines that produced in adipocytes (including leptin, adiponectin, IL-6, TNF-α, etc.) affect the function of lymphatic endothelial cells and control the growth of lymphatic vessels. Cooperation between LS and AT becomes pathogenetically and clinically important in lymphedema and obesity. It is known that both primary and secondary lymphedema are characterized by increased fat accumulation which is associated with the severity of lymphostasis and inflammation. Similarly, in obesity, the drainage function of LS is impaired, which is accompanied by perilymphatic mononuclear infiltration in the AT. The development of these changes is facilitated by endocrine dysfunction of adipocytes and impaired production of adipocytokines. The increase in the production of inflammatory mediators and the disruption of the traffic of inflammatory cells causes a further deterioration in the outflow of interstitial fluid and exacerbates the inflammation of the AT, thereby forming a vicious circle. The role of lymphangiogenesis in AT remodeling in obesity needs further research. Another promising area of research is the study of the role of intestinal LS in the development of obesity and related disorders. It has been shown that the transport of chylomicrons from the intestine depends on the expression of a number of molecular mediators (VEGF-C, DLL-4, neuropilin-1, VEGFR-1, CD36/FAT, etc.)in the endotheliocytes of the intestinal lymphatic vessels, as well as the functioning of «push-button» and “zippering” junctions between endothelial cells. New approach to the treatment of obesity based on blockade of lymphatic chylomicrontransport has been experimentally substantiated. Further identification of the molecular mechanisms and signaling pathways that determine the remodeling of AT in lymphedema and obesity are likely to provide new approaches to the treatment of these diseases.

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Apelin as a nociceptive processes regulator

Ból ◽

10.5604/01.3001.0013.1574 ◽

2019 ◽

Vol 19 (3) ◽

pp. 1-9

Author(s):

Joanna Kujacz ◽

Joanna Mika

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Molecular Mechanisms ◽

Receptor Gene ◽

Clinical Aspect ◽

The Body ◽

Biologically Active ◽

Gene And Protein Expression ◽

Biologically Active Peptide

The aim of this paper is to characterize the biologically active peptide – apelin, and its previously identified APJ receptor. Gene and protein expression of apelin/APJ system has been detected in many tissues and organs of the body such as: adipose tissue, stomach, liver, pancreas, heart, lungs, uterus, ovaries, brain or spinal cord. The results of recently published papers show the role of the apelin/APJ system in numerous physiological and pathological processes in the body, including nociceptive processes. This paper discusses the physiological and molecular mechanisms of the apelin/APJ system, with particular emphasis on its role in inflammatory and neuropathic pain, as well as in the effectiveness of opioids. In addition, the clinical aspect of this system in pain processes is presented.

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Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer

BioMed Research International ◽

10.1155/2018/1691428 ◽

2018 ◽

Vol 2018 ◽

pp. 1-15 ◽

Cited By ~ 65

Author(s):

Federica Pellati ◽

Vittoria Borgonetti ◽

Virginia Brighenti ◽

Marco Biagi ◽

Stefania Benvenuti ◽

...

Keyword(s):

Cancer Cells ◽

Fibre Type ◽

Molecular Mechanisms ◽

Cannabis Sativa ◽

The Body ◽

Alternative Pathways ◽

Receptor Complexes ◽

Cancer Models ◽

Loss Of Appetite

In the last decades, a lot of attention has been paid to the compounds present in medicinal Cannabis sativa L., such as Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and their effects on inflammation and cancer-related pain. The National Cancer Institute (NCI) currently recognizes medicinal C. sativa as an effective treatment for providing relief in a number of symptoms associated with cancer, including pain, loss of appetite, nausea and vomiting, and anxiety. Several studies have described CBD as a multitarget molecule, acting as an adaptogen, and as a modulator, in different ways, depending on the type and location of disequilibrium both in the brain and in the body, mainly interacting with specific receptor proteins CB1 and CB2. CBD is present in both medicinal and fibre-type C. sativa plants, but, unlike Δ9-THC, it is completely nonpsychoactive. Fibre-type C. sativa (hemp) differs from medicinal C. sativa, since it contains only few levels of Δ9-THC and high levels of CBD and related nonpsychoactive compounds. In recent years, a number of preclinical researches have been focused on the role of CBD as an anticancer molecule, suggesting CBD (and CBD-like molecules present in the hemp extract) as a possible candidate for future clinical trials. CBD has been found to possess antioxidant activity in many studies, thus suggesting a possible role in the prevention of both neurodegenerative and cardiovascular diseases. In animal models, CBD has been shown to inhibit the progression of several cancer types. Moreover, it has been found that coadministration of CBD and Δ9-THC, followed by radiation therapy, causes an increase of autophagy and apoptosis in cancer cells. In addition, CBD is able to inhibit cell proliferation and to increase apoptosis in different types of cancer models. These activities seem to involve also alternative pathways, such as the interactions with TRPV and GRP55 receptor complexes. Moreover, the finding that the acidic precursor of CBD (cannabidiolic acid, CBDA) is able to inhibit the migration of breast cancer cells and to downregulate the proto-oncogene c-fos and the cyclooxygenase-2 (COX-2) highlights the possibility that CBDA might act on a common pathway of inflammation and cancer mechanisms, which might be responsible for its anticancer activity. In the light of all these findings, in this review we explore the effects and the molecular mechanisms of CBD on inflammation and cancer processes, highlighting also the role of minor cannabinoids and noncannabinoids constituents of Δ9-THC deprived hemp.

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Role of H3K18ac-regulated nucleotide excision repair-related genes in arsenic-induced DNA damage and repair of HaCaT cells

Human & Experimental Toxicology ◽

10.1177/0960327120903482 ◽

2020 ◽

Vol 39 (9) ◽

pp. 1168-1177 ◽

Cited By ~ 2

Author(s):

AL Zhang ◽

L Chen ◽

L Ma ◽

XJ Ding ◽

SF Tang ◽

...

Keyword(s):

Dna Damage ◽

Nucleotide Excision Repair ◽

Molecular Mechanisms ◽

Excision Repair ◽

The Body ◽

Hacat Cells ◽

Transcriptional Expression ◽

Promoter Regions ◽

Nucleotide Excision

Arsenic is an environmental poison and is a grade I human carcinogen that can cause many types of damage to the body. The skin is one of the main target organs of arsenic damage, but the molecular mechanisms underlying arsenic poisoning are not clear. Arsenic is an epigenetic agent. Histone acetylation is one of the earliest covalent modifications to be discovered and is closely related to the occurrence and development of tumors. To investigate the role of acetylated histone H3K18 (H3K18 ac) in arsenic-induced DNA damage, HaCaT cells were exposed to sodium arsenite (NaAsO2) for 24 h. It was found that arsenic induced the downregulation of xeroderma pigmentosum A, D, and F ( XPA, XPD, and XPF—nucleotide excision repair (NER)-related genes) expression, as well as histone H3K18 ac expression, and aggravated DNA damage. Chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR) analysis showed that H3K18 acetylation in the promoter regions of XPA, XPD, and XPF was downregulated. In addition, the use of the histone deacetylase inhibitor trichostatin A (TSA) partially inhibited arsenic-induced DNA damage, inhibited deacetylation of H3K18 ac in the promoter regions of XPA, XPD, and XPF genes, increased acetylation of H3K18, and promoted the transcriptional expression of NER-related genes. Our study revealed that NaAsO2 induces DNA damage and inhibits the expression of NER-related genes, while TSA increases the H3K18 ac enrichment level and promotes the transcriptional expression of NER, thereby inhibiting DNA damage. These findings provide new ideas for understanding the molecular mechanisms underlying arsenic-induced skin damage.

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Role of Advanced Glycation End Products in Carcinogenesis and their Therapeutic Implications

Current Pharmaceutical Design ◽

10.2174/1381612825666190130145549 ◽

2019 ◽

Vol 24 (44) ◽

pp. 5245-5251 ◽

Cited By ~ 11

Author(s):

David Schröter ◽

Annika Höhn

Keyword(s):

Advanced Glycation End Products ◽

Molecular Mechanisms ◽

The Body ◽

Advanced Glycation ◽

Therapeutic Implications ◽

Age Related ◽

Glycation End Products ◽

End Products ◽

Reduction Strategies

Aging is one of the biggest risk factors for the major prevalent diseases such as cardiovascular diseases, neurodegeneration and cancer, but due to the complex and multifactorial nature of the aging process, the molecular mechanisms underlying age-related diseases are not yet fully understood. Research has been intensive in the last years aiming to characterize the pathophysiology of aging and develop therapies to fight age-related diseases. In this context advanced glycation end products (AGEs) have received attention. AGEs, when accumulated in tissues, significantly increase the level of inflammation in the body which has long been associated with the development of cancer. Here we discuss the classical settings promoting AGE formation, as well as reduction strategies, occurrence and relevance of AGEs in cancer tissues and the role of AGE-interaction with the receptor for advanced glycation end products (RAGE) in cancer initiation and progression.

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Nitric Oxide: Exploring the Contextual Link with Alzheimer’s Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/7205747 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 40

Author(s):

Nicholas Asiimwe ◽

Seung Geun Yeo ◽

Min-Sik Kim ◽

Junyang Jung ◽

Na Young Jeong

Keyword(s):

Nitric Oxide ◽

Molecular Mechanisms ◽

Neurodegenerative Disorder ◽

The Body ◽

Bioactive Molecules ◽

Therapeutic Approaches ◽

Cellular Debris ◽

And Oxidative Stress ◽

Proinflammatory Factors

Neuronal inflammation is a systematically organized physiological step often triggered to counteract an invading pathogen or to rid the body of damaged and/or dead cellular debris. At the crux of this inflammatory response is the deployment of nonneuronal cells: microglia, astrocytes, and blood-derived macrophages. Glial cells secrete a host of bioactive molecules, which include proinflammatory factors and nitric oxide (NO). From immunomodulation to neuromodulation, NO is a renowned modulator of vast physiological systems. It essentially mediates these physiological effects by interacting with cyclic GMP (cGMP) leading to the regulation of intracellular calcium ions. NO regulates the release of proinflammatory molecules, interacts with ROS leading to the formation of reactive nitrogen species (RNS), and targets vital organelles such as mitochondria, ultimately causing cellular death, a hallmark of many neurodegenerative diseases. AD is an enervating neurodegenerative disorder with an obscure etiology. Because of accumulating experimental data continually highlighting the role of NO in neuroinflammation and AD progression, we explore the most recent data to highlight in detail newly investigated molecular mechanisms in which NO becomes relevant in neuronal inflammation and oxidative stress-associated neurodegeneration in the CNS as well as lay down up-to-date knowledge regarding therapeutic approaches targeting NO.

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Requirement for PINCH in Skeletal Myoblast Differentiation

10.21203/rs.3.rs-560801/v1 ◽

2021 ◽

Author(s):

Siyi Xie ◽

Chushan Fang ◽

Yujie Gao ◽

Jie Yan ◽

Lina Luo ◽

...

Keyword(s):

Skeletal Muscle ◽

Skeletal Muscles ◽

Molecular Mechanisms ◽

Myogenic Differentiation ◽

Critical Role ◽

The Body ◽

Myoblast Differentiation ◽

Skeletal Myogenesis ◽

Congenital Myopathies

Abstract Background: Skeletal muscle is composed of bundles of myofibers ensheathed by extracellular matrix networks. Malformation of skeletal muscle during embryonic development results in congenital myopathies. Disease mechanisms of congenital myopathies remain unclear. PINCH, an adaptor of focal adhesion complex, plays essential roles in multiple cellular processes and organogenesis. Elucidation of the molecular mechanisms underlying skeletal myogenesis will offer new insights into pathogenesis of myopathies.Methods: We generated muscle-specific PINCH knock-out mice to study the functional role of PINCH in skeletal myogenesis. Histologic and Transmission Electron Microscopy analysis demonstrated that Impaired myogenic differentiation and maturation in mice with PINCH1 being ablated in skeletal muscle progenitors, and Ablation of PINCH1 and PINCH2 resulted in reduced size of muscle fibers and impaired multinucleation; Cell culture and immunostaining showed that defects in myoblast fusion and cytoskeleton assembly in PINCH double mutant mice; Western blotting showed that defects in expression of cytoskeleton proteins and proteins involved in myogenesis in DMUT skeletal muscles.Results: Double ablation of PINCH1 and PINCH2 resulted in early postnatal lethality with reduced size of skeletal muscles and detachment of diaphragm muscles from the body wall. Myofibers of PINCH mutant myofibers failed to undergo multinucleation and exhibited disrupted sarcomere structures. The mutant myoblasts in culture were able to adhere to newly formed myotubes, but impeded in cell fusion and subsequent sarcomere genesis and cytoskeleton organization. Consistent with this, expression of integrin β1 and some cytoskeleton proteins, and phosphorylation of ERK and AKT were significantly reduced in PINCH mutants. Expression of MRF4, the most highly expressed myogenic factor at late stages of myogenesis, was abolished in PINCH mutants, that could contribute to observed phenotypes. In addition, mice with PINCH1 being ablated in myogenic progenitors exhibited only mild centronuclear myopathic changes, suggesting a compensatory role of PINCH2 in myogenic differentiation, indicating a critical role of PINCH proteins in myogenic differentiation.Conclusion: Our results demonstrated an essential role of PINCH in skeletal myogenic differentiation.

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