Hardness Controlled Enzymes and Electronegativity Controlled Enzymes: Role of an Absolute Hardness Electronegativity (.ETA.-.CHI.) Activity Diagram as a Coordinate for Biological Activities.

Abstract Background A large number of preclinical studies have shown that local anesthetics have a direct inhibitory effect on tumor biological activities, including cell survival, proliferation, migration, and invasion. There are few studies on the role of local anesthetics in cancer stem cells. This study aimed to determine the possible role of local anesthetics in glioblastoma stem cell (GSC) self-renewal and the underlying molecular mechanisms. Methods The effects of local anesthetics in GSCs were investigated through in vitro and in vivo assays (i.e., Cell Counting Kit 8, spheroidal formation assay, double immunofluorescence, western blot, and xenograft model). The acyl-biotin exchange method (ABE) assay was identified proteins that are S-acylated by zinc finger Asp-His-His-Cys-type palmitoyltransferase 15 (ZDHHC15). Western blot, co-immunoprecipitation, and liquid chromatograph mass spectrometer-mass spectrometry assays were used to explore the mechanisms of ZDHHC15 in effects of local anesthetics in GSCs. Results In this study, we identified a novel mechanism through which local anesthetics can damage the malignant phenotype of glioma. We found that local anesthetics prilocaine, lidocaine, procaine, and ropivacaine can impair the survival and self-renewal of GSCs, especially the classic glioblastoma subtype. These findings suggest that local anesthetics may weaken ZDHHC15 transcripts and decrease GP130 palmitoylation levels and membrane localization, thus inhibiting the activation of IL-6/STAT3 signaling. Conclusions In conclusion, our work emphasizes that ZDHHC15 is a candidate therapeutic target, and local anesthetics are potential therapeutic options for glioblastoma.

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In vitro biological activities and in vivo hepatoprotective role of brown algae-isolated fucoidans

Environmental Science and Pollution Research ◽

10.1007/s11356-020-11892-9 ◽

2021 ◽

Author(s):

Marwa E. Atya ◽

Amr El-Hawiet ◽

Mohamed A. Alyeldeen ◽

Doaa A. Ghareeb ◽

Mohamed M. Abdel-Daim ◽

...

Keyword(s):

Brown Algae ◽

Biological Activities

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Antiviral Role of Phenolic Compounds against Dengue Virus: A Review

Biomolecules ◽

10.3390/biom11010011 ◽

2020 ◽

Vol 11 (1) ◽

pp. 11

Author(s):

Vanessa Loaiza-Cano ◽

Laura Milena Monsalve-Escudero ◽

Carlos da Silva Maia Bezerra Filho ◽

Marlen Martinez-Gutierrez ◽

Damião Pergentino de Sousa

Keyword(s):

Phenolic Compounds ◽

Dengue Virus ◽

Biological Activities ◽

Antiviral Effect ◽

Health Concern ◽

Host Proteins ◽

Viral Particles ◽

Antiviral Role ◽

Productive Replication

Phenolic compounds have been related to multiple biological activities, and the antiviral effect of these compounds has been demonstrated in several viral models of public health concern. In this review, we show the antiviral role of phenolic compounds against dengue virus (DENV), the most widespread arbovirus globally that, after its re-emergence, has caused multiple epidemic outbreaks, especially in the last two years. Twenty phenolic compounds with anti-DENV activity are discussed, including the multiple mechanisms of action, such as those directed against viral particles or viral proteins, host proteins or pathways related to the productive replication viral cycle and the spread of the infection.

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Development of sensitivity to cAMP-inducing hormones in the rat stomach

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1984.247.3.g231 ◽

1984 ◽

Vol 247 (3) ◽

pp. G231-G239

Author(s):

C. Gespach ◽

Y. Cherel ◽

G. Rosselin

Keyword(s):

Biological Activities ◽

Physiological Role ◽

H2 Receptor Antagonist ◽

Adult Rats ◽

Gastric Glands ◽

Camp Generation ◽

Final Maturation ◽

Noncompetitive Inhibitor ◽

Regulatory Properties

Development of cAMP responses to secretin, pancreatic glucagon, and histamine was measured in gastric glands of fetal (day 20), postnatal (days 1-30), and adult rats (day 65). cAMP stimulation by these hormones was already detected on day 20 of gestation. cAMP generation showed biphasic variations during the 1st days of life and at the onset of weaning (day 20). Anticipated weaning at day 14 triggered precocious maturation (efficacies) of the cAMP-generating systems sensitive to secretin, glucagon, and histamine without changing the potencies of the hormones. During development, the general characteristics (potency and pharmacological or regulatory properties) of the receptor-cAMP systems studied were comparable with those evidenced in adult rats. At days 5, 20, and 65, vasoactive intestinal peptide and the peptide having N-terminal histidine and C-terminal isoleucine amide (PHI) were about 100 times less potent than secretin (EC50 = 1.5 X 10(-9) M secretin). The histamine action could be blocked by the competitive H2-receptor antagonist cimetidine (70-100% inhibition) as well as by the noncompetitive inhibitor somatostatin (37-62% inhibition). The data indicate that these regulatory hormones (secretin, glucagon(s), histamine, and somatostatin) might have a direct effect on gastric glands and may modulate their biological activities (metabolism, differentiation, proliferation, and exocrine and endocrine secretions) from the neonatal period in rats. The important physiological role of weaning on the final maturation of the cAMP-generating systems in rat gastric glands is underlined.

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The Role of 5-Lipoxygenase and Leukotrienes in Shock and Ischemia-Reperfusion Injury

The Scientific World JOURNAL ◽

10.1100/tsw.2007.34 ◽

2007 ◽

Vol 7 ◽

pp. 56-74 ◽

Cited By ~ 5

Author(s):

Antonietta Rossi ◽

Carlo Pergola ◽

Salvatore Cuzzocrea ◽

Lidia Sautebin

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Biological Activities ◽

Ischemia Reperfusion ◽

Targeted Disruption ◽

Pathological Conditions ◽

Metabolic Products ◽

Important Regulator ◽

Multicellular Organisms

The leukotrienes (LTs) are metabolic products of arachidonic acid via the 5-lipoxygenase (5-LO) pathway. The biological activities of LTs suggest that they are mediators of acute inflammatory and immediate hypersensitivity responses. In particular, the 5-LO activation has been proposed to be an important regulator for pathogenesis in multicellular organisms. The role of LTs in tissue damage, associated with septic and nonseptic shock and ischemia-reperfusion, has been extensively studied by the use of 5-LO inhibitors, receptor antagonists, and mice with a targeted disruption of the 5-LO gene (5-LOKO). In particular, several data indicate that LTs regulate neutrophil trafficking in damaged tissue in shock and ischemia-reperfusion, mainly through the modulation of adhesion molecule expression. This concept may provide new insights into the interpretation of the protective effect of 5-LO inhibition, which may be useful in the therapy of pathological conditions associated with septic and nonseptic shock and ischemia-reperfusion injury.

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Biological activities and biological role of triterpene glycosides from holothuroids (Echinodermata)

Echinoderm Studies ◽

10.1201/9781003077909-4 ◽

2020 ◽

pp. 139-181

Author(s):

V.I. Kalinin ◽

M.M. Anisimov ◽

N.G. Prokofieva ◽

S.A. Avilov ◽

Sh.Sh. Afiyatullov ◽

...

Keyword(s):

Biological Activities ◽

Triterpene Glycosides ◽

Biological Role

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Hunting Bioactive Molecules from the Agave Genus: An Update on Extraction and Biological Potential

Molecules ◽

10.3390/molecules26226789 ◽

2021 ◽

Vol 26 (22) ◽

pp. 6789

Author(s):

Misael Bermúdez-Bazán ◽

Gustavo Adolfo Castillo-Herrera ◽

Judith Esmeralda Urias-Silvas ◽

Antonio Escobedo-Reyes ◽

Mirna Estarrón-Espinosa

Keyword(s):

Secondary Metabolites ◽

Biological Activities ◽

Waste Product ◽

Bioactive Molecules ◽

Alcoholic Beverages ◽

Therapeutic Benefits ◽

Biological Potential ◽

Novel Drugs ◽

Ancient Times

Agaves are plants used in the production of alcoholic beverages and fibers. Ever since ancient times, pre-Hispanic cultures in Mexico have used them in traditional medicine to cure different ailments. Over the years, studies of the active principles responsible for the therapeutic benefits of agaves have increased. Leaves and fibers are the main agro-wastes generated in tequila and mezcal production, while fibers are the main waste product in the textile sector. Different investigations have referred to the agro-waste from agave processing as a source of bioactive molecules called secondary metabolites (SM). Among them, phenols, flavonoids, phytosterols, and saponins have been extracted, identified, and isolated from these plants. The role of these molecules in pest control and the prospect of metabolites with the biological potential to develop novel drugs for chronic and acute diseases represent new opportunities to add value to these agro-wastes. This review aims to update the biological activities and recent applications of the secondary metabolites of the genus Agave.

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The Role of m6A Ribonucleic Acid Modification in the Occurrence of Atherosclerosis

Frontiers in Genetics ◽

10.3389/fgene.2021.733871 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jie Fu ◽

Xinghui Cui ◽

Xiaoyun Zhang ◽

Min Cheng ◽

Xiaoxia Li ◽

...

Keyword(s):

Messenger Rna ◽

Biological Activities ◽

Rna Modification ◽

Acid Modification ◽

Rna Methylation ◽

Mrna Metabolism ◽

Modification Process ◽

M6a Rna Methylation ◽

The Relationship

The N6-methyladenosine (m6A) modification is the most abundant epitranscriptomic modification in eukaryotic messenger RNA (mRNA). The m6A modification process is jointly regulated by various enzymes and proteins, such as methyltransferases, demethylases and related m6A-binding proteins. The process is dynamic and reversible, and it plays an essential role in mRNA metabolism and various biological activities. Recently, an increasing number of researchers have confirmed that the onset and development of many diseases are closely associated with the molecular biological mechanism of m6A RNA methylation. This study focuses on the relationship between m6A RNA modification and atherosclerosis (AS). It thoroughly summarizes the mechanisms and processes of m6A RNA modification in AS-related cells and the relationships between m6A RNA modification and AS risk factors, and it provides a reference for exploring new targets for the early diagnosis and treatment of AS.

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CSF-1-Induced DC-SIGN+ Macrophages Work In The Ovarian Endometriosis

10.21203/rs.3.rs-814415/v1 ◽

2021 ◽

Author(s):

Xiaocui Li ◽

Wei Hong ◽

Yunlang Cai ◽

Zhenzhen Zheng ◽

Min An

Keyword(s):

Peripheral Blood ◽

Peritoneal Fluid ◽

Immune Status ◽

Biological Activities ◽

Peripheral Blood Lymphocytes ◽

Enzyme Linked Immunosorbent Assay ◽

Predominant Role ◽

Blood Lymphocytes ◽

Suppressive Phenotype

Abstract BackgroundCSF-1 was found to be accumulated in the lesions and peritoneal fluid of endometriosis patients, and CSF-1 induced THP-1-derived macrophages to polarize toward a suppressive phenotype. Researchers found that macrophages were the predominant cells in the peritoneal fluid (PF) of endometriosis patients, and the primary consensus is that the immune status in the PF of endometriosis patients exhibits a depressed state. Does the cytokine CSF-1 induce monocytes to differentiate into macrophages with a DC-SIGN+ suppressive phenotype in endometriosis?MethodsThe level of CSF-1 in control endometrium (N=11), eutopic endometrium (N=17), and ectopic (N=39) endometrium of endometriosis patients was evaluated by real-time polymerase chain reaction and in the PF of control (N=25) and endometriosis (N=35) patients by enzyme-linked immunosorbent assay. CSF-1 was examined by a MILLIPLEX MAP Mouse Cytokine/Chemokine Magnetic Bead Panel in an in vivo study. DC-SIGN+ suppressive macrophages were detected by immunohistochemical staining of tissues and flow cytometric analysis of the PF of control (N=25) and endometriosis (N=35) patients. The phenotypes and biological activities of the resulting macrophages derived from THP-1 cells induced by CSF-1 were compared by an in vitro coculture system with peripheral blood lymphocytes from normal subjects.Results In this study, we found the proportion of DC-SIGN+ suppressive macrophages was larger in the abdominal immune microenvironment of endometriosis patients. CSF-1 was primarily secreted from the ectopic lesions and peritoneum of mice with endometriosis. And, CSF-1 induced the polarization of macrophages toward a DC-SIGN+ suppressive phenotype; this effect was abolished by the addition of anti-CSF-1R. CSF-1 induced DC-SIGN+ macrophages, leading to a depressed status of peripheral blood lymphocytes, including a high percentage of Treg cells and a low percentage of CD8+ T cells. Similarly, blockade with anti-CSF-1R abrogated this biological effect. This is the first study on the predominant role of DC-SIGN+ suppressive macrophages in the depressed immune status of endometriosis patients.Conclusions This is the first study on the predominant role of DC-SIGN+ suppressive macrophages in the depressed immune status of endometriosis patients. Further study of the mechanism and biological activities of CSF-1-induced DC-SIGN+ suppressive macrophages will enhance our understanding of the physiology of endometriosis and indicate new directions for further study.

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Recent Advancement of Pyrazole Scaffold Based Neuroprotective Agents: A Review

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527320666210602152308 ◽

2021 ◽

Vol 20 ◽

Author(s):

Subham Das ◽

Saleem Akbar ◽

Bahar Ahmed ◽

Rikeshwar Prasad Dewangan ◽

Mohammad Kashif Iqubal ◽

...

Keyword(s):

Biological Activities ◽

Neuroprotective Agents ◽

Wide Range ◽

Recent Developments ◽

Ic50 Values ◽

Structural Activity Relationship ◽

Pharmaceutical Industries ◽

Neurological Conditions ◽

Nitrogen Containing Compounds

: As a source of therapeutic agents, heterocyclic nitrogen-containing compounds and their derivatives are still interesting and essential. Pyrazole, a five-member heteroaromatic ring with two nitrogen atoms, has a major impact on chemical industries as well as pharmaceutical industries. Due to its wide range of biological activities against various diseases, it has been identified as a biologically important heterocyclic scaffold. The treatment of neurological disorders has always been a difficult task. Therefore, identifying therapeutically effective molecules for neurological conditions remains an open challenge in biomedical research and development. For developing novel entities as neuroprotective agents, recently, pyrazole scaffold has attracted medicinal chemists worldwide. The major focus of research in this area is to discover novel molecules as neuroprotective agents with minimal adverse effects and better effectiveness in improving the neurological condition. This review mainly covers recent developments in the neuropharmacological role of pyrazole incorporated compounds, including their structural-activity relationship (SAR), which also further includes IC50 values (in mM as well as in μM), recent patents, and a brief history as neuroprotective agents.

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