scholarly journals Impact of Oxysterols on Cell Death, Proliferation, and Differentiation Induction: Current Status

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2301
Author(s):  
Fábio Alessandro de Freitas ◽  
Débora Levy ◽  
Amira Zarrouk ◽  
Gérard Lizard ◽  
Sérgio Paulo Bydlowski
Keyword(s):  
Cell Death ◽  
Adipogenic Differentiation ◽  
Current Status ◽  
Pharmacological Activities ◽  
Oxidation Processes ◽  
Proliferation And Differentiation ◽  
Induction Current ◽  
Enzymatic Pathways ◽  
Derivatives Of ◽  
Oxidized Derivatives Of Cholesterol

Oxysterols are oxidized derivatives of cholesterol produced by enzymatic activity or non-enzymatic pathways (auto-oxidation). The oxidation processes lead to the synthesis of about 60 different oxysterols. Several oxysterols have physiological, pathophysiological, and pharmacological activities. The effects of oxysterols on cell death processes, especially apoptosis, autophagy, necrosis, and oxiapoptophagy, as well as their action on cell proliferation, are reviewed here. These effects, also observed in several cancer cell lines, could potentially be useful in cancer treatment. The effects of oxysterols on cell differentiation are also described. Among them, the properties of stimulating the osteogenic differentiation of mesenchymal stem cells while inhibiting adipogenic differentiation may be useful in regenerative medicine.

A Comprehensive Review on the Therapeutic Versatility of Imidazo [2,1-b]thiazoles

2020 ◽  
Vol 27 (40) ◽  
pp. 6864-6887 ◽  
Author(s):  
Mohd Adil Shareef ◽  
Irfan Khan ◽  
Bathini Nagendra Babu ◽  
Ahmed Kamal
Keyword(s):  
Literature Review ◽  
Medicinal Chemistry ◽  
Therapeutic Agents ◽  
Present Review ◽  
Thiazole Derivatives ◽  
Pharmacological Activities ◽  
Comprehensive Review ◽  
Derivatives Of

Background:: Imidazo[2,1-b]thiazole, a well-known fused five-membered hetrocycle is one of the most promising and versatile moieties in the area of medicinal chemistry. Derivatives of imidazo[2,1-b]thiazole have been investigated for the development of new derivatives that exhibit diverse pharmacological activities. This fused heterocycle is also a part of a number of therapeutic agents. Objective:: To review the extensive pharmacological activities of imidazo[2,1-b]thiazole derivatives and the new molecules developed between 2000-2018 and their usefulness. Method:: Thorough literature review of all relevant papers and patents was conducted. Conclusion:: The present review, covering a number of aspects, is expected to provide useful insights in the design of imidazo[2,1-b]thiazole-based compounds and would inspire the medicinal chemists for a comprehensive and target-oriented information to achieve a major breakthrough in the development of clinically viable candidates.

scholarly journals Damage-Associated Molecular Patterns Modulation by microRNA: Relevance on Immunogenic Cell Death and Cancer Treatment Outcome

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2566
Author(s):  
María Julia Lamberti ◽  
Annunziata Nigro ◽  
Vincenzo Casolaro ◽  
Natalia Belén Rumie Vittar ◽  
Jessica Dal Col
Keyword(s):  
Cell Death ◽  
Tumor Cells ◽  
Cell Activation ◽  
Adaptive Immune Response ◽  
Current Status ◽  
Immunogenic Cell Death ◽  
Basal Expression ◽  
Antigen Presenting ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Immunogenic cell death (ICD) in cancer is a functionally unique regulated form of stress-mediated cell death that activates both the innate and adaptive immune response against tumor cells. ICD makes dying cancer cells immunogenic by improving both antigenicity and adjuvanticity. The latter relies on the spatiotemporally coordinated release or exposure of danger signals (DAMPs) that drive robust antigen-presenting cell activation. The expression of DAMPs is often constitutive in tumor cells, but it is the initiating stressor, called ICD-inducer, which finally triggers the intracellular response that determines the kinetics and intensity of their release. However, the contribution of cell-autonomous features, such as the epigenetic background, to the development of ICD has not been addressed in sufficient depth. In this context, it has been revealed that several microRNAs (miRNAs), besides acting as tumor promoters or suppressors, can control the ICD-associated exposure of some DAMPs and their basal expression in cancer. Here, we provide a general overview of the dysregulation of cancer-associated miRNAs whose targets are DAMPs, through which new molecular mediators that underlie the immunogenicity of ICD were identified. The current status of miRNA-targeted therapeutics combined with ICD inducers is discussed. A solid comprehension of these processes will provide a framework to evaluate miRNA targets for cancer immunotherapy.

scholarly journals MiR-146a-5p targeting SMAD4 and TRAF6 inhibits adipogenensis through TGF-β and AKT/mTORC1 signal pathways in porcine intramuscular preadipocytes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Que Zhang ◽  
Rui Cai ◽  
Guorong Tang ◽  
Wanrong Zhang ◽  
Weijun Pang
Keyword(s):  
Cell Proliferation ◽  
Adipogenic Differentiation ◽  
Signal Pathways ◽  
Pork Quality ◽  
Sequencing Analysis ◽  
Novel Mirna ◽  
Mtorc1 Signaling ◽  
Proliferation And Differentiation ◽  
Mirna Sequencing ◽  
Imf Content

Abstract Background Intramuscular fat (IMF) content is a vital parameter for assessing pork quality. Increasing evidence has shown that microRNAs (miRNAs) play an important role in regulating porcine IMF deposition. Here, a novel miRNA implicated in porcine IMF adipogenesis was found, and its effect and regulatory mechanism were further explored with respect to intramuscular preadipocyte proliferation and differentiation. Results By porcine adipose tissue miRNA sequencing analysis, we found that miR-146a-5p is a potential regulator of porcine IMF adipogenesis. Further studies showed that miR-146a-5p mimics inhibited porcine intramuscular preadipocyte proliferation and differentiation, while the miR-146a-5p inhibitor promoted cell proliferation and adipogenic differentiation. Mechanistically, miR-146a-5p suppressed cell proliferation by directly targeting SMAD family member 4 (SMAD4) to attenuate TGF-β signaling. Moreover, miR-146a-5p inhibited the differentiation of intramuscular preadipocytes by targeting TNF receptor-associated factor 6 (TRAF6) to weaken the AKT/mTORC1 signaling downstream of the TRAF6 pathway. Conclusions MiR-146a-5p targets SMAD4 and TRAF6 to inhibit porcine intramuscular adipogenesis by attenuating TGF-β and AKT/mTORC1 signaling, respectively. These findings provide a novel miRNA biomarker for regulating intramuscular adipogenesis to promote pork quality.

The synthesis of the isomeric N-methyl derivatives of murexine

1981 ◽  
Vol 34 (8) ◽  
pp. 1739 ◽  
Author(s):  
CC Duke ◽  
JV Eichholzer ◽  
JK Macleod
Keyword(s):  
Imidazole Ring ◽  
The Other ◽  
Pharmacological Activities ◽  
Tautomeric Forms ◽  
Methyl Derivatives ◽  
Paramagnetic Ions ◽  
Nucella Emarginata ◽  
Derivatives Of

The two isomeric N-methyl derivatives of murexine have been synthesised by independent routes and shown to be different from an 'N- methylmurexine' reportedly isolated from the mollusc Nucella emarginata. 1H n.m.r. studies have shown a marked difference in the extent of binding to paramagnetic ions of the two N-methyl derivatives of murexine in water while pharmacological results show substantially different pharmacological activities of the two isomers. Both results can be rationalized in terms of the observed activities being associated with the presence of one or the other of the tautomeric forms of the imidazole ring.

scholarly journals Evaluation of Substituted Pyrazole-Based Kinase Inhibitors in One Decade (2011–2020): Current Status and Future Prospects

Molecules ◽  
2022 ◽  
Vol 27 (1) ◽  
pp. 330
Author(s):  
Mohammed I. El-Gamal ◽  
Seyed-Omar Zaraei ◽  
Moustafa M. Madkour ◽  
Hanan S. Anbar
Keyword(s):  
Kinase Inhibitors ◽  
Therapeutic Agents ◽  
Current Status ◽  
Pyrazole Derivatives ◽  
Chronological Order ◽  
Pharmacological Activities ◽  
The Past ◽  
Cancer Types ◽  
Privileged Scaffold ◽  
Almost All

Pyrazole has been recognized as a pharmacologically important privileged scaffold whose derivatives produce almost all types of pharmacological activities and have attracted much attention in the last decades. Of the various pyrazole derivatives reported as potential therapeutic agents, this article focuses on pyrazole-based kinase inhibitors. Pyrazole-possessing kinase inhibitors play a crucial role in various disease areas, especially in many cancer types such as lymphoma, breast cancer, melanoma, cervical cancer, and others in addition to inflammation and neurodegenerative disorders. In this article, we reviewed the structural and biological characteristics of the pyrazole derivatives recently reported as kinase inhibitors and classified them according to their target kinases in a chronological order. We reviewed the reports including pyrazole derivatives as kinase inhibitors published during the past decade (2011–2020).

scholarly journals Ferroptosis: A Novel Therapeutic Target for Ischemia-Reperfusion Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Yunqing Chen ◽  
Hongyan Fan ◽  
Shijun Wang ◽  
Guanmin Tang ◽  
Changlin Zhai ◽  
...  
Keyword(s):  
Cell Death ◽  
Therapeutic Target ◽  
Ischemia Reperfusion Injury ◽  
Close Association ◽  
Ischemia Reperfusion ◽  
Treatment Strategies ◽  
Kidney Injury ◽  
Organ Damage ◽  
Current Treatment ◽  
Current Status

Ischemia-reperfusion (I/R) injury is a major cause of cell death and organ damage in numerous pathologies, including myocardial infarction, stroke, and acute kidney injury. Current treatment methods for I/R injury are limited. Ferroptosis, which is a newly uncovered type of regulated cell death characterized by iron overload and lipid peroxidation accumulation, has been investigated in various diseases. There is increasing evidence of a close association between ferroptosis and I/R injury, with ferroptosis frequently identified as a new therapeutic target for the management of I/R injury. This review summarizes the current status of ferroptosis and discusses its relationship with I/R injury, as well as potential treatment strategies targeting it.

scholarly journals PYRIMIDINES AS POTENT CYTOTOXIC AND ANTI-INFLAMMATORY AGENTS

2017 ◽  
Vol 10 (6) ◽  
pp. 237 ◽  
Author(s):  
Ishwar Bhat K ◽  
Abhishek Kumar
Keyword(s):  
Acetic Acid ◽  
Cytotoxic Activity ◽  
Glacial Acetic Acid ◽  
Antimalarial Activity ◽  
Biological Activities ◽  
Cytotoxic Agents ◽  
Pyrimidine Derivatives ◽  
Pharmacological Activities ◽  
Anti Inflammatory ◽  
Derivatives Of

Objective: Many derivatives of pyrimidine are known for the broad-spectrum biological activities such as antimicrobial, antitumor, antibacterial, antitubercular, anti-inflammatory, and cytotoxic activity. Chalcones with an enone group show potent pharmacological activities such as antiinflammatory, antibacterial, antifungal, and antimalarial activity. A series of pyrimidines from chalcones have been synthesized and screened for anti-inflammatory and cytotoxic activity studies.Methods: Chalcones [1-(4-nitrophenyl)-3-substituted-phenylprop-2-en-1-one] were synthesized from various substituted aldehydes with 4-nitroacetophenone and cyclized with urea and glacial acetic acid to give pyrimidine derivatives [4-(4-nitrophenyl)-6-substituted-phenylpyrimidin-2-ol].Results: Anti-inflammatory and cytotoxic activity studies revealed that some of the synthesized compounds have shown significant activity.Conclusion: The observed results proved that pyrimidines are found to be interesting lead molecules for the synthesis of anti-inflammatory and cytotoxic agents

scholarly journals Targeting ferroptosis in breast cancer

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Zhaoqing Li ◽  
Lini Chen ◽  
Cong Chen ◽  
Yulu Zhou ◽  
Dengdi Hu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Therapeutic Target ◽  
Distinct Type ◽  
Therapeutic Strategies ◽  
Current Status ◽  
Regulated Cell Death ◽  
Promising Therapeutic Target ◽  
Ros Metabolism

Abstract Ferroptosis is a recently discovered distinct type of regulated cell death caused by the accumulation of lipid-based ROS. Metabolism and expression of specific genes affect the occurrence of ferroptosis, making it a promising therapeutic target to manage cancer. Here, we describe the current status of ferroptosis studies in breast cancer and trace the key regulators of ferroptosis back to previous studies. We also compare ferroptosis to common regulated cell death patterns and discuss the sensitivity to ferroptosis in different subtypes of breast cancer. We propose that viewing ferroptosis-related studies from a historical angle will accelerate the development of ferroptosis-based biomarkers and therapeutic strategies in breast cancer.

scholarly journals Role of 1α,25-Dihydroxyvitamin D3 in Adipogenesis of SGBS Cells: New Insights into Human Preadipocyte Proliferation

2018 ◽  
Vol 48 (1) ◽  
pp. 397-408 ◽  
Author(s):  
Ingrid  Felicidade ◽  
Daniele Sartori ◽  
Susan L.M. Coort ◽  
Simone Cristine Semprebon ◽  
Andressa Megumi Niwa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Adipose Tissue ◽  
Lipid Content ◽  
Cell Model ◽  
Adipogenic Differentiation ◽  
Growth Arrest ◽  
Proliferation And Differentiation ◽  
Sgbs Cells

Background/Aims: Compared with non-obese individuals, obese individuals commonly store more vitamin D in adipose tissue. VDR expression in adipose tissue can influence adipogenesis and is therefore a target pathway deserving further study. This study aims to assess the role of 1,25(OH)2D3 in human preadipocyte proliferation and differentiation. Methods: RTCA, MTT, and trypan blue assays were used to assess the effects of 1,25(OH)2D3 on the viability, proliferation, and adipogenic differentiation of SGBS cells. Cell cycle and apoptosis analyses were performed with flow cytometry, triglycerides were quantified, and RT-qPCR was used to assess gene expression. Results: We confirmed that the SGBS cell model is suitable for studying adipogenesis and demonstrated that the differentiation protocol induces cell maturation, thereby increasing the lipid content of cells independently of treatment. 1,25(OH)2D3 treatment had different effects according to the cell stage, indicating different modes of action driving proliferation and differentiation. In preadipocytes, 1,25(OH)2D3 induced G1 growth arrest at both tested concentrations without altering CDKN1A gene expression. Treatment with 100 nM 1,25(OH)2D3 also decreased MTT absorbance and the lipid concentration. Moreover, increased normalized cell index values and decreased metabolic activity were not induced by proliferation or apoptosis. Exposure to 100 nM 1,25(OH)2D3 induced VDR, CEBPA, and CEBPB expression, even in the preadipocyte stage. During adipogenesis, 1,25(OH)2D3 had limited effects on processes such as VDR and PPARG gene expression, but it upregulated CEBPA expression. Conclusions: We demonstrated for the first time that 1,25(OH)2D3 induces changes in preadipocytes, including VDR expression and growth arrest, and increases the lipid content in adipocytes treated for 16 days. Preadipocytes are important cells in adipose tissue homeostasis, and understanding the role of 1,25(OH)2D3 in adipogenesis is a crucial step in ensuring adequate vitamin D supplementation, especially for obese individuals.

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