654,010 results on '"Molecular medicine"'
Search Results
102. Studies from Zunyi Medical University Describe New Findings in Molecular Medicine (Mitochondria: a New Intervention Target for Tumor Invasion and Metastasis).
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- 2024
103. New clues on how the heart makes arteries.
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HEART failure ,MYOCARDIAL infarction ,MYOCARDIUM ,HEART diseases ,VASCULAR endothelial cells - Abstract
A team of researchers at the Max Delbruck Center in Berlin has discovered how new arteries form in the heart, which could improve therapies for regenerating heart muscle after a heart attack or stroke. The researchers found that pre-arterial cells, which develop from specialized "tip cells," play a major role in growing new arteries. This finding challenges previous beliefs about how arteries develop and opens up possibilities for developing treatments that stimulate regenerative pathways to reverse heart muscle damage. The study was supported by the DZHK (Deutsches Zentrum fur Herz-Kreislauf-Forschung). [Extracted from the article]
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- 2024
104. Findings on Hematology Discussed by Investigators at University of Rochester (The 50th Anniversary Of Blood Cells, Molecules And Diseases,, 1975-2024).
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BLOOD cells ,ERYTHROCYTES ,CELL physiology ,EXPERIMENTAL medicine ,ACADEMIC medical centers - Abstract
The University of Rochester has published a report on the 50th anniversary of the journal Blood Cells, Molecules and Diseases. The journal was initiated in 1975 by Marcel Bessis and has evolved into a standard journal for the publication of papers in the field of hematology. Over the years, the journal has focused on disorders of red cells, erythropoiesis, and hematopoiesis. The research concludes that the journal will celebrate its 50th anniversary in October 2024. [Extracted from the article]
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- 2024
105. Hackensack Meridian John Theurer Cancer Center First in State to Launch a Comprehensive Program to Prevent and Pre-empt Cancer at its new Hennessy Institute for Cancer Prevention and Applied Molecular Medicine HICAP.
- Abstract
Hackensack Meridian Health's John Theurer Cancer Center has launched a new program at its Hennessy Institute for Cancer Prevention and Applied Molecular Medicine (HICAP) to improve cancer risk identification and early detection. The program, offered in New Jersey, aims to shift cancer diagnoses to earlier stages and reduce the overall burden of cancer. By utilizing a precision health platform called CancerIQ, individuals can complete a comprehensive cancer risk assessment and receive personalized plans for early detection and prevention. The program combines technology, genomics, and AI to intercept cancer and provide accessible tools for underserved communities. [Extracted from the article]
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- 2024
106. New Findings from Jilin University in the Area of Molecular Medicine Described (The Rhob P.s73f Mutation Leads To Cerebral Palsy Through Dysregulation of Lipid Homeostasis).
- Abstract
A study conducted by researchers at Jilin University in Changchun, China, has identified a mutation called RhoB p.S73F that is associated with cerebral palsy (CP). The study used rabbit models to mimic this mutation and found that it led to symptoms similar to human CP, such as periventricular leukomalacia and spastic-dystonic diplegia. The researchers discovered that the mutation disrupted lipid homeostasis through the LYN-ACAT1 pathway, causing damage to neuronal cells and myelin. This study provides insights into the relationship between RhoB and lipid metabolism and offers potential therapeutic targets for CP. [Extracted from the article]
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- 2024
107. Investigators at Guangxi Medical University Report Findings in Molecular Medicine (Th1 Cells Reduce the Osteoblast-like Phenotype In Valvular Interstitial Cells By Inhibiting Nlrp3 Inflammasome Activation In Macrophages).
- Abstract
Researchers at Guangxi Medical University in Nanning, China have conducted a study on the role of Th1 cells in reducing the calcification of valvular interstitial cells. The study found that Th1 cells inhibit the activation of the NLRP3 inflammasome in macrophages, which protects against valvular interstitial cell calcification. This research provides a potential precision medicine strategy for calcific aortic valve stenosis (CAVS) based on anti-inflammatory mechanisms. The study was supported by the National Natural Science Foundation of China. [Extracted from the article]
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- 2024
108. Surprising mechanism of lupus kidney damage identified.
- Abstract
A Berlin-led research team has discovered that a specialized population of immune cells called innate lymphoid cells (ILCs) play a critical role in causing kidney damage in patients with lupus nephritis. This finding challenges the conventional belief that autoantibodies are solely responsible for the condition. The researchers used single-cell RNA sequencing to identify the genes and functions of various kidney and immune cells. By blocking the activation of ILCs and a protein called GM-CSF, the team was able to reduce kidney tissue damage in mice. These findings may lead to new antibody therapies for severe forms of lupus. [Extracted from the article]
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- 2024
109. New Public Health and Primary Care Data Has Been Reported by a Researcher at Department of Pathology (Diagnosis of Body Fluids Using a Combined Approach of Cytomorphology in Routinely Stained Smears and Cell Blocks: A Boon for Primary Health...).
- Abstract
A recent study conducted in Bihar, India, highlights the challenges in accurately diagnosing cells in body fluids as reactive or malignant mesothelial cells. The study suggests that conventional cytodiagnosis methods often leave behind residue that contains valuable diagnostic information. To address this issue, the researchers propose the use of a cell block method, where the residue is embedded in paraffin and examined alongside routine smears. The study concludes that the application of the cell block technique, along with ancillary techniques such as immunohistochemistry, can improve the sensitivity of diagnosis and provide better patient outcomes, even at the primary health care level. [Extracted from the article]
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- 2024
110. AIM4 AI and Mechanistic Modeling in Molecular Medicine.
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HORMONE receptor positive breast cancer ,TUMOR classification ,ARTIFICIAL intelligence - Abstract
The article discusses a study on motor somatotopy and its impact on imagery strategy success in intracortical brain-computer interfaces (iBCIs), conducted by researchers and published in Clinical Trials Week on August 19, 2024. Topics include the influence of electrode array location on movement imagery strategies, the impact of somatotopic organization on iBCI control, and the differential recording of neural activity related to proximal versus distal arm movements.
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- 2024
111. New Findings in Molecular Medicine Described from Virginia Polytechnic Institute and State University (Virginia Tech) (Immune-enhancing Neutrophils Reprogrammed By Subclinical Low-dose Endotoxin In Cancer Treatment).
- Abstract
A recent report discusses research conducted at Virginia Polytechnic Institute and State University (Virginia Tech) on the immune-enhancing effects of low-dose endotoxin in cancer treatment. The study found that neutrophils, a type of white blood cell, can be reprogrammed by super-low dose endotoxin to adopt a potent immune-enhancing phenotype. These reprogrammed neutrophils were able to reduce tumor burden when transfused into tumor-bearing mice. The findings shed light on the mechanisms behind the immune-enhancing efficacy of low-dose endotoxin and provide a potential avenue for developing neutrophil-based anti-tumor therapeutics. [Extracted from the article]
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- 2024
112. Centre for Host Microbiome Interactions Researcher Details Research in Periodontitis (The promise and challenges of genomics-informed periodontal disease diagnoses).
- Abstract
A recent study from the Centre for Host Microbiome Interactions explores the potential of genomics and molecular medicine in diagnosing periodontitis. The research highlights the advancements in human genomics and molecular medicine that have allowed for a better understanding of human health and disease. The study discusses the association between genomics and periodontal diseases, noting that genetic variation may contribute to approximately one-third of the population variance of periodontitis. The paper also explores the potential use of polygenic risk scores and genetic testing for periodontitis diagnosis. [Extracted from the article]
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- 2024
113. An Exploratory Study Using Next-Generation Sequencing to Identify Prothrombotic Variants in Patients with Cerebral Vein Thrombosis
- Author
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Robert Anton Kramer, Robert Zimmermann, Julian Strobel, Susanne Achenbach, Armin Michael Ströbel, Holger Hackstein, David Alexander Christian Messerer, and Sabine Schneider
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cerebral vein thrombosis ,thrombophilia ,personalized medicine ,next-generation sequencing ,molecular medicine ,neurology ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Prothrombotic hereditary risk factors for cerebral vein thrombosis (CVT) are of clinical interest to better understand the underlying pathophysiology and stratify patients for the risk of recurrence. This study explores prothrombotic risk factors in CVT patients. An initial screening in patients of the outpatient clinic of the Department of Transfusion Medicine and Hemostaseology of the University Hospital Erlangen, Germany, revealed 183 patients with a history of CVT. An initial screening identified a number of common prothrombic risk factors, including Factor V Leiden (rs6025) and Prothrombin G20210A (rs1799963). All patients without relevant findings (58 individuals) were invited to participate in a subsequent genetic analysis of 55 relevant genes using next-generation sequencing (NGS). Three intron variants (ADAMTS13: rs28446901, FN1: rs56380797, rs35343655) were identified to occur with a significantly higher frequency in the CVT patient cohort compared to the general European population. Furthermore, the combined prevalence of at least two of four potentially prothrombic variants (FGA (rs6050), F13A1 (rs5985), ITGB3 (rs5918), and PROCR (rs867186)) was significantly higher in the CVT subjects. The possible impact of the identified variants on CVT is discussed.
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- 2023
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114. The study of the deubiquitinase USP8 in Parkinson's disease pathogenesis
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Alexopoulou, Zoi, Fulga, Tudor, and Tofaris, George
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616.8 ,Neurology ,molecular neurosciences ,Molecular Medicine ,Parkinson's disease ,Medicine ,Neuroscience ,Neurodegeneration - Abstract
Parkinson's disease is the second commonest neurodegenerative disease currently treated symptomatically. It is a multifactorial disease involving mechanisms ranging from protein aggregation to mitochondrial dysfunction, oxidative stress and dopamine dysregulation. The levels of α-synuclein have been causatively linked to the development and progression of Parkinson's disease. Therefore α-synuclein lowering strategies are valid approaches in Parkinson's disease. Neuropathologically, Lewy Bodies in the vulnerable substantia nigra of Parkinson's disease patients are less ubiquitinated and specifically less K-63 ubiquitinated than Lewy bodies in the cortex, suggesting differential activation or regulation of ubiquitin interactors. A targeted screen for such interactors revealed that the Deubiquitinating enzyme Usp8 is upregulated in the substantia nigra of Parkinson's disease brains and is inversely correlated with the degree of total and K-63 ubiquitination. Using genetic knockdown and overexpression techniques, Usp8 was found to colocalize and directly interact with α-synuclein. It was found to de-ubiquitinate α-synuclein and increase its half-life. Its knockdown increased the total and K-63 α-synuclein ubiquitination and decreased its levels by 35% at least partly by increasing its degradation via the lysosome. In vivo in the Drosophila melanogaster, Usp8 knockdown demonstrated protection against α-synuclein toxicity. It rescued in a specific manner the rough eye phenotype, the age-dependent locomotive defect and the loss of dopaminergic neurons caused by the expression of α-synuclein. Specific and effective pharmacological Usp8 inhibition also has the potential to lower α-synuclein levels. Collectively, the evidence produced in my thesis suggests that Usp8 could be a potential target for the future disease-modifying therapies in Parkinson's disease.
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- 2016
115. Proteolysis dependent cell cycle regulation in Caulobacter crescentus.
- Author
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Fatima, Nida I, Fazili, Khalid Majid, and Bhat, Nowsheen Hamid
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- *
CELL cycle regulation , *CAULOBACTER crescentus , *CELL cycle , *BACTERIAL diseases , *BACTERIAL cells - Abstract
Caulobacter crescentus, a Gram-negative alpha-proteobacterium, has surfaced as a powerful model system for unraveling molecular networks that control the bacterial cell cycle. A straightforward synchronization protocol and existence of many well-defined developmental markers has allowed the identification of various molecular circuits that control the underlying differentiation processes executed at the level of transcription, translation, protein localization and dynamic proteolysis. The oligomeric AAA+ protease ClpXP is a well-characterized example of an enzyme that exerts post-translational control over a number of pathways. Also, the proteolytic pathways of its candidate proteins are reported to play significant roles in regulating cell cycle and protein quality control. A detailed evaluation of the impact of its proteolysis on various regulatory networks of the cell has uncovered various significant cellular roles of this protease in C. crescentus. A deeper insight into the effects of regulatory proteolysis with emphasis on cell cycle progression could shed light on how cells respond to environmental cues and implement developmental switches. Perturbation of this network of molecular machines is also associated with diseases such as bacterial infections. Thus, research holds immense implications in clinical translation and health, representing a promising area for clinical advances in the diagnosis, therapeutics and prognosis. [ABSTRACT FROM AUTHOR]
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- 2022
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116. Molekulare Prädiktoren des Tumoransprechens auf neoadjuvante Radiochemotherapie des Rektumkarzinoms.
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Fleischmann, Maximilian, Diefenhardt, Markus, Fokas, Emmanouil, Rödel, Claus, and Rödel, Franz
- Abstract
Copyright of Der Onkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2022
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117. Molecular and Cellular Pediatrics
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molecular medicine ,paediatrics ,translational medicine ,Pediatrics ,RJ1-570 - Published
- 2022
118. Human iPSC-derived renal organoids engineered to report oxidative stress can predict drug-induced toxicity
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M.L. Lawrence, M. Elhendawi, M. Morlock, W. Liu, S. Liu, A. Palakkan, L.F. Seidl, P. Hohenstein, A.K. Sjögren, and J.A. Davies
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Molecular medicine ,Cellular toxicology ,Cell biology ,Science - Abstract
Summary: Advances in regenerative medicine have led to the construction of many types of organoids, which reproduce important aspects of endogenous organs but may be limited or disorganized in nature. While their usefulness for restoring function remains unclear, they have undoubted usefulness in research, diagnostics, and toxicology. In toxicology, there is an urgent need for better models for human kidneys. We used human iPS-cell (hiPSC)-derived renal organoids to identify HMOX1 as a useful marker of toxic stress via the oxidative stress pathway, and then constructed an HMOX1 reporter in hiPSCs. We used two forms of hiPSC-derived HMOX1-reporter renal organoids to probe their ability to detect nephrotoxicants in a panel of blind-coded compounds. Our results highlight the potential usefulness, and some limitations, of HMOX1-reporter renal organoids as screening tools. The results may guide development of similar stress-reporting organoid assays for other stem-cell-derived organs and tissues.
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- 2022
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119. NanoLuc reporters identify COL4A5 nonsense mutations susceptible to drug-induced stop codon readthrough
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Kohei Omachi, Hirofumi Kai, Michel Roberge, and Jeffrey H. Miner
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Biochemistry ,Molecular biology ,Molecular medicine ,Science - Abstract
Summary: Alport syndrome, a disease of kidney, ear, and eye, is caused by pathogenic variants in the COL4A3, COL4A4, or COL4A5 genes encoding collagen α3α4α5(IV) of basement membranes. Collagen IV chains that are truncated due to nonsense variants/premature termination codons (PTCs) cannot assemble into heterotrimers or incorporate into basement membranes. To investigate the feasibility of PTC readthrough therapy for Alport syndrome, we utilized two NanoLuc reporters in transfected cells: full-length for monitoring translation, and a split version for assessing readthrough product function. Full-length assays of 49 COL4A5 nonsense variants identified eleven as susceptible to PTC readthrough using various readthrough drugs. In split-NanoLuc assays, the predicted missense α5(IV) readthrough products of five nonsense mutations could heterotrimerize with α3(IV) and α4(IV). Readthrough was also observed in kidney cells from an engineered Col4a5 PTC mouse model. These results suggest that readthrough therapy is a feasible approach for a fraction of patients with Alport syndrome.
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- 2022
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120. PEGylated talazoparib enhances therapeutic window of its combination with temozolomide in Ewing sarcoma
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Vanessa Del Pozo, Andrew J. Robles, Shaun D. Fontaine, Qianqian Liu, Joel E. Michalek, Peter J. Houghton, and Raushan T. Kurmasheva
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Oncology ,Pharmacology ,Molecular medicine ,Science - Abstract
Summary: Current therapy is ineffective for relapsed and metastatic Ewing sarcoma (EwS) owing to development of drug resistance. Macromolecular prodrugs potentially lead to lower drug exposure in normal tissues and reduced toxicity. We evaluated the efficacy of PEGylated talazoparib (PEG∼TLZ), a PARP1 inhibitor, alone or in combination with the DNA-alkylating agent temozolomide (TMZ) in EwS and other pediatric tumors using conventional testing or single-mouse trial (SMT). A single dose of PEG∼TLZ (10 μmol/kg on day 0) combined with 5 daily doses of TMZ (40 mg/kg starting on day 3/4) produced minimal toxicity, and the combination achieved maintained complete response in EwS and glioblastoma models. The SMT trial with the 3-day interval between PEG∼TLZ and TMZ resulted in objective responses in EwS and other xenografts. Thus, PEG∼TLZ + TMZ demonstrated a broad range of activity in pediatric solid tumor models. Furthermore, the therapeutic window of PEG∼TLZ + TMZ was enhanced compared with the free-TLZ combination.
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- 2022
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121. Recent Advancements in the Discovery of MDM2/MDM2-p53 Interaction Inhibitors for the Treatment of Cancer
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Suresh Thareja, Neha Bhatia, Rakesh Khator, Swanand Kulkarni, Yogesh Singh, and Pradeep Kumar
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Pharmacology ,Drug Discovery ,Organic Chemistry ,Molecular Medicine ,Biochemistry - Abstract
Abstract: Discovery of MDM2 and MDM2-p53 interaction inhibitors changed the direction of anticancer research as it is involved in about 50% of cancer cases globally. Not only the inhibition of MDM2 but also its interaction with p53 proved to be an effective strategy in anticancer drug design and development. Various molecules of natural as well as synthetic origin have been reported to possess excellent MDM2 inhibitory potential. The present review discusses the pathophysiology of the MDM2-p53 interaction loop and MDM2/MDM2-p53 interaction inhibitors from literature covering recent patents. Focus has also been put on characteristic features of the active site of the target and its desired interactions with the currently FDA-approved inhibitor. The designing approach of previously reported MDM2/MDM2-p53 interaction inhibitors, their SAR studies, in silico studies, and the biological efficacy of various inhibitors from natural as well as synthetic origins are also elaborated. An attempt is made to cover recently patented MDM2/MDM2- p53 interaction inhibitors.
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- 2023
122. In-silico Studies, Synthesis, and Evaluation of Anti-inflammatory Activity of Novel Pyrimidine Scaffold
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Sunil Menghani, Ganesh Munde, Nilesh Rarokar, Deweshri Kerzare, Md. Asif Iqbal Chittur, and Pramod Khedekar
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Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Background: The heterocyclic nucleus pyrimidine is present in several natural and synthetic chemical analogues and has proved its broad medicinal applications. Further, pyrimidine in the form of parent structure or basic skeleton of RNA and DNA is involved in controlling the immune functioning, and in turn, inflammatory reactions. Objective: The objective of the present study is to evaluate some novel pyrimidine analogues for antiinflammatory action. Method: Molecular docking studies of Indomethacin and selected analogues were carried out with the COX-2 enzyme (PDB: 4ZOL). The synthesis of derivatives of 4-Phenyl-6-(phenylamino)pyrimidine-2-ol derivatives was begun by following Perkin condensation between substituted acetanilides and substituted aromatic aldehydes to yield an intermediate, which in turn produces the required nucleus for treatment with urea. All synthesized compounds were evaluated for in vivo and in vitro anti-inflammatory activity. Result: The docking interaction reflects a good dock score when compared with indomethacin, a potent Anti-inflammatory drug. In the majority of the compounds, pyrimidine was able to form hydrogen bonding while the rest of the part was involved in hydrophobic bonding. All compounds were synthesized in good yield and confirmed by physical and spectral studies. In vitro studies showed that compounds 5a and 5e were better at controlling inflammation than the conventional treatment Antipyrine, while in vivo data showed that compounds 5a, 5c, 5e, and 5h were better at controlling inflammation than the standard drug Antipyrine. Conclusion: The compound with more than one electron releasing group on the aniline moiety of pyrimidine yields a decent result in the synthetic and experimental studies, but the absence of an electron withdrawing group favours stronger anti-inflammatory activity on the target.
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- 2023
123. Synthesis of Ethyl Methyl 4-aryl-1,4-dihydropyridine-3,5-dicarboxylates as Potential Calcium Channel Blockers for Hypertension
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Ranju Bansal, Priyanka Jain, Gaurav Narang, Anupreet Kaur, Carmen Calle, and Rosalia Carron
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Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Aim: Several new dihydropyridine-based calcium channel blockers have been synthesized and pharmacologically evaluated for the treatment of hypertension Background: Dihydropyridines constitute an important class of calcium channel blockers (CCBs) due to their high potency, wide heterogeneity and tremendous biological usefulness. As a follow-up to our previous studies on 4-aryl-1,4-dihydropyridines as calcium channel blockers for the treatment of hypertension, four new series of methyl ethyl ester substituted 1,4-dihydropyridines are reported. Objectives: The aim of the work was to study the effects of unsymmetrical ester substitutions on calcium channel blocking activity of dihydropyridines (DHPs) while retaining the aminoalkoxy side chain at various positions of the 4-aryl ring. The type and location of the substituents on the 4-aryl ring have been extensively explored to study the structure-activity relationship (SAR) in this series of dihydropyridines as calcium channel blockers. Methodology: The target DHPs were synthesized using modified Hantzsch condensation and further derivatization. The compounds were screened for their inhibitory potential against L-type calcium channels at a single concentration of 10 μM on NG108-15 cells (Neuroblastoma X Glioma). The most potent DHP 12 was also tested for its vasodilatory activity using rat thoracic aortic rings precontracted with KCl (30 mM) and in vivo antihypertensive activity in rats using the tail-cuff method. Results: The newly synthesized DHPs displayed diversified calcium channel blocking activity with compounds 1e, 1h, 2d, 2f, 2h, 6, 9, 11, 12 and 14, producing more than 50% inhibition of veratridine response. 3-imidazolylpropoxy substituted analogue 12 turned out to be the most potent compound of the four series of compounds and produced fairly higher inhibition (78.6%) of veratridine response in comparison to nifedipine (70%) at 10 μM. In addition, compound 12 produced potent vasodilatory and antihypertensive properties. Conclusion: Both location of the side chain and the type of substituent on methyl ethyl ester substituted 4-aryl ring affected the response of dihydropyridine derivatives towards L-type calcium channels.
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- 2023
124. Research Progress of Vitamin K2 Related Signal Pathways: A Literature Review
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Xiao Ouyang and Shimin Li
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Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Abstract: Vitamin K2 products were first applied to Japanese children, which can promote the growth of children's bones and eliminate their growing pain. At the same time, it does little harm to the human body, so it has attracted the attention of some scholars. Later, it was also proved to be effective in treating osteoporosis, especially for postmenopausal women. After years of research, some capabilities of VK2 have been discovered; it has been proved that it has great clinical value in treating osteoporosis, reducing intimal lipid deposition, diabetes, tumor, immune diseases, nervous system diseases and other diseases. There is no doubt that VK2 is an essential nutrient for human health, once vitamin K2 is deficient, it will cause a series of diseases. In recent years, some new evidences show that VK2 can also be used in leukemia and other diseases, which shows that VK2 still has great development potential. As a new adjuvant drug, VK2 has attracted worldwide attention and has been used in the clinic for many years. In this article, we mainly summarized the related research of VK2 in recent years, and expounded on several VK2-related signal pathways and the related mechanisms of these signal pathways in treating various diseases.
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- 2023
125. Chlorogenic Acid: A Dietary Phenolic Acid with Promising Pharmacotherapeutic Potential
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Abhay Kumar Pandey, Amit Kumar Singh, and Rajeev Kumar Singla
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Pharmacology ,Drug Discovery ,Organic Chemistry ,Molecular Medicine ,Biochemistry - Abstract
Abstract: Phenolic acids are now receiving a great deal of interest as pervasive human dietary constituents that have various therapeutic applications against chronic and age-related diseases. One such phenolic acid that is being utilized in traditional medicine is chlorogenic acid (CGA). It is one of the most readily available phytochemicals that can be isolated from the leaves and fruits of plants, such as coffee beans (Coffea arabica L.), apples (Malus spp.), artichoke (Cynara cardunculus L.), carrots (Daucus carota L.), betel (Piper betle L.), burdock (Arctium spp.), etc. Despite its low oral bioavailability (about 33%), CGA has drawn considerable attention due to its wide range of biological activities and numerous molecular targets. Several studies have reported that the antioxidant and anti-inflammatory potentials of CGA mainly account for its broad-spectrum pharmacological attributes. CGA has been implicated in exerting a beneficial role against dysbiosis by encouraging the growth of beneficial GUT microbes. At the biochemical level, its therapeutic action is mediated by free radical scavenging efficacy, modulation of glucose and lipid metabolism, down-regulation of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1β, and interferon-gamma (IFN-γ), upregulation of nuclear factor erythroid 2-related factor 2 (Nrf-2), and inhibition of the activity of nuclear factor- κβ (NF-κβ), thus helping in the management of diabetes, cardiovascular diseases, neurodegenerative disorders, cancer, hypertension etc. This review highlights the natural sources of CGA, its bioavailability, metabolism, pharmacotherapeutic potential, and underlying mechanisms of action for the clinical usefulness of CGA in the management of health disorders.
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- 2023
126. A Deep Dive in the Involvement of the Cerebellum in Epilepsy: A Neuroanatomical and Cellular Approach
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Wilhelm Moreno, Jesús Ernesto Ochoa Monroy, CARMEN RUBIO, and Eric Uribe
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Pharmacology ,Drug Discovery ,Organic Chemistry ,Molecular Medicine ,Biochemistry - Abstract
Objective: The purpose of this article is to describe the state-of-art of neuroanatomical and cellular aspects of the cerebellum in epilepsy. Background: Over the years, cerebellum epileptogenesis has been widely studied. There is growing evidence linking the cerebellum with this pathology by several other structures involved: mainly the limbic system, thalamus, cerebral cortex, red nucleus, and reticular formation. As a result, these anatomical and cellular changes in the cerebellum might trigger the genesis and propagation of seizures. Discussion: We herewith outline the cerebellum's deep nuclei physiological pathways, responsible for seizure spread via ion channels and neurotransmitter dysfunction. Additionally, we describe the shifts in seizures produced after cell death, gene expression, and protein interaction with their respective molecular and anatomical pathways. Conclusion: Finally, we highlight the role played by the cerebellum in seizure propagation to the brain and how it can be counteracted in some subtypes of drug-resistant epilepsy.
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- 2023
127. Organoid Models of Heart Diseases: Find a New Channel in Improvements of Cardiac Regenerative Medicine
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Dmitry Olegovich Bokov, Saade Abdalkareem Jasim, Wanich Suksatan, Fahad Alsaikhan, Mohammed Abed Jawad, Satish Kumar Sharma, Supat Chupradit, and Lakshmi Thangavelu
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Pharmacology ,Drug Discovery ,Organic Chemistry ,Molecular Medicine ,Biochemistry - Abstract
Abstract: We are experiencing a revolution in regenerative medicine. Recent developments in organoid technology have provided unique opportunities for studying human biology and diseases. Indeed, organoid models have revolutionized the in vitro culture tools for biomedical research by creating robust three-dimensional (3D) architecture to recapitulate the primary tissues' cellular heterogeneity, structure, and functions. Such organoid technology enables researchers to re-create human organs and diseases model in a culture dish. It thus holds excellent promises for many translational applications such as regenerative medicine, drug discovery, and precision medicine. This review summarizes the current knowledge on the progression and promotion of organoid models, particularly with the heart disease approach. We discuss the usefulness of clinical applications of cardiac organoids and ultimately highlight the currently advanced therapeutic strategies in vitro model of organoids aimed at personalizing heart disease treatment.
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- 2023
128. Role of Polyphenols in Alleviating Alzheimer’s Disease: A Review
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Veeramuthu Duraipandiyan, Tharsius Raja William Raja, Savarimuthu Ignacimuthu, Udaiyappan Janakiraman, and Soosaimanickam Maria Packiam
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Pharmacology ,Drug Discovery ,Organic Chemistry ,Molecular Medicine ,Biochemistry - Abstract
Abstract: Alzheimer’s Disease (AD) is a successive neurodegenerative disorder in the aged population. Many chemicals and phytochemicals are used to treat AD. Polyphenols which occur widely in various fruits, vegetables, beverages, and some other plant sources are gaining importance in AD treatment. Polyphenols comprise various subcategories, such as phenolic acids, lignans, tannins, stilbenes, hydroxybenzoic acid, hydroxycinnamic acid, and flavonoids. These compounds, as sole entities or in combination, can be used for treating AD because they have an abundance of antioxidants that are reported to be effective in free radical scavenging, metal ion chelating, and anti-inflammatory activities. Polyphenols of various plant origins have been studied, and these have been supported by in vitro assays and in vivo studies in rodents. These molecules protect neurons against oxidative stress and deposition of amyloid-β (Aβ) and tau proteins which play a vital role in the pathogenesis of AD. Consumption of wine and other foods rich in polyphenols has a beneficial effect on the neuronal signaling pathways, playing a vital role in shielding neuronal cells from neurodegeneration. Their ability to reduce free radicals and chelate metals are of great advantage. In this review, we highlight the various polyphenols that inhibit neuronal damage and progression of AD while also providing a cure. Some of the polyphenols covered are hesperidin, resveratrol, curcumin, catechin, kaempferol, and quercetin. The mechanisms of the actions of three polyphenols are also elaborated.
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- 2023
129. A Comparative Analytical Review on Machine Learning Methods in Drugtarget Interactions Prediction
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Zahra Nikraftar and Mohammad Reza Keyvanpour
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Drug Discovery ,Molecular Medicine ,General Medicine - Abstract
Background: Predicting drug-target interactions (DTIs) is an important topic of study in the field of drug discovery and development. Since DTI prediction in vitro studies is very expensive and time-consuming, computational techniques for predicting drug-target interactions have been introduced successfully to solve these problems and have received extensive attention. Objective: In this paper, we provided a summary of databases that are useful in DTI prediction and intend to concentrate on machine learning methods as a chemogenomic approach in drug discovery. Unlike previous surveys, we propose a comparative analytical framework based on the evaluation criteria. Methods: In our suggested framework, there are three stages to follow: First, we present a comprehensive categorization of machine learning-based techniques as a chemogenomic approach for drug-target interaction prediction problems; Second, to evaluate the proposed classification, several general criteria are provided; Third, unlike other surveys, according to the evaluation criteria introduced in the previous stage, a comparative analytical evaluation is performed for each approach. Results: This systematic research covers the earliest, most recent, and outstanding techniques in the DTI prediction problem and identifies the advantages and weaknesses of each approach separately. Additionally, it can be helpful in the effective selection and improvement of DTI prediction techniques, which is the main superiority of the proposed framework. Conclusion: This paper gives a thorough overview to serve as a guide and reference for other researchers by providing an analytical framework which can help to select, compare, and improve DTI prediction methods.
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- 2023
130. Synthesis and Computational Study of Some New 1-(1H-indol-1- yl)ethanone Derivatives on COX-2 Enzyme and Evaluation of In-Vivo Analgesic and Anti-inflammatory Activity
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Arvind Kumar, Deepika Kumar, Mayur Porwal, and Arun Kumar Mishra
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Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Background: Indole and its derivatives play an important role in the synthesis of commercially relevant intermediate molecules required for the synthesis of a wide range of bioactive molecules. Aim: Exploration of the synthesis of novel nonsteroidal anti-inflammatory drugs, as well as their computational studies and pharmacological effects, was aimed as an important component of the present research. Objective: the objective of present work was to synthesize some novel 1-(1H-indol-1-yl)ethanone compounds, analyse their computational effects on the COX-2 enzyme and to test their in vivo analgesic and anti-inflammatory activity. Method: The condensation of 4-(2-(1H-indol-1-yl)-2-oxoethoxy) benzaldehyde with substituted aniline in ethanol in the presence of a catalytic quantity of glacial acetic acid was performed, which yielded the new Indole derivatives. IR, NMR, mass spectroscopy and elemental analysis techniques were used to characterize the structures of new indole derivatives. To estimate the drug-like candidate’s nature, a number of molecular attributes of these derivatives were computed. The synthesized derivatives were docked with a specific reference cyclooxygenase-2 (COX-2) enzyme. The physical similarity of the newly synthesized derivatives (D1-D8) and indomethacin (the reference drug) was determined by evaluating seven physicochemical features by a software. Result: Although the bioavailability/drug likeness was found to be in the standard range, the synthesized compounds exhibited close similarity with those of the reference drug, and subsequent optimization was necessary. Conclusion: The newly synthesized indole derivatives as COX-2 inhibitors were evaluated for their biological properties, which included anti-inflammatory and analgesic efficacy Other: D-7 (1-(1H-indol-1-yl)-2-(4-((4-nitrophenyl)imino)methyl)phenoxy)ethanone) was found to have the strongest anti-inflammatory and analgesic activity amongst the eight target compounds.
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- 2023
131. Assessing the Performance of GOLD, Glide and MM-GBSA on a Dataset of Hydrazide-hydrazone-based Tuberculostatics
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Emilio Mateev, Maya Georgieva, and Alexander Zlatkov
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Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Background: Tuberculosis is considered a global health problem; hence, the screening and synthesis of novel tuberculostatic drugs are a necessity. Molecular docking could drastically reduce the time of hit identification; however, initial validation is required to reduce the false-positive results. Objective: Assessment of several searching and scoring algorithms for a custom dataset of hydrazidehydrazone- based tuberculostatics was conducted to obtain a reliable docking protocol for future virtual screening. Methods: Modification in the scoring functions, size of the grid space, and presence of active waters of a GOLD 5.3 docking protocol was conducted. Subsequently, side-chain flexibility and ensemble docking were carried out to assess the role of protein flexibility in the correlation coefficient. In addition, docking simulations with Glide and free binding energy calculations with MM-GBSA were implemented. The Pearson correlation coefficient between the experimental and the acquired in silico data was calculated after each work step. The major interactions between the top-scored ligands and the active site of 2X22 were visualized applying Discovery Studio. Results: An optimized GOLD 5.3 docking protocol led to a drastically enhanced Pearson correlation coefficient of the training set, from 0.461 to 0.823, as well as an excellent pairwise correlation coefficient in the test set - 0,8405. Interestingly, the Glide docking scores and the free binding energy calculations with MM-GBSA did not achieve reliable results. During the visualization of the top-ranked compounds, it was observed that Lys165 played a major role in the formation of stable complexes. Conclusion: It could be concluded that the performance of the optimized GOLD 5.3 docking protocol demonstrated significantly higher reliability against the hydrazide-hydrazone dataset when compared to Glide docking simulations and MM-GBSA free binding energy calculations. The results could be utilized for future virtual screenings.
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- 2023
132. The Newly Proposed Mechanism of Cardiomyocyte Protection of Carvedilol- Anti-Apoptosis Pattern of Carvedilol in Anoxia by Inducing Autophagy Partly through the AMPK/mTOR Pathway
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Luqiao Wang, Yunzhu Peng, Jingru Li, Chaozhong Li, Guihu Sun, Longjun Li, Yongli Zeng, Huawei Wang, Xinyu Wu, and Ping Yang
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Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Purpose: To investigate the underlying mechanism of cardiomyocyte protection of carvedilol based on autophagy and apoptosis. Methods: Neonatal rat ventricular myocytes (NRVMs) were exposed to various concentrations of carvedilol before anoxia, and pretreated with 3-MA or compound C for inhibiting autophagy or p-AMPK expression. CCK-8 colorimeter and flow cytometry were used to determine the cell viability and apoptotic rates. The variation of mRNA and protein was measured by RT-PCR and Western blot. The presence of autophagosomes was observed by electron microscopy. Results: First, we found that carvedilol increased autophagic marker levels in a concentration-dependent manner and the number of autophagosomes in NRVMs. Moreover, carvedilol substantially enhanced the viability and noticeably reduced the CK, MDA and LDH levels and cell apoptosis rate compared with the anoxia group. In addition, carvedilol decreased the levels of caspase-3 and Bim in mRNA and protein, but such effect was blocked by the special autophagy inhibitor-3-MA, and the number of autophagosomes was significantly decreased when treated with 3-MA, indicating that carvedilol exhibited anti-apoptotic and anti-injury effects by inducing autophagy in anoxia NRVMs, but these effects can be abolished by adding 3-MA to suppress autophagy. Finally, the carvedilol treatment-induced autophagy by enhancing the activation of p-AMPK and inhibiting p-mTOR. Electron microscopy presented that the number of autophagosomes was significantly decreased when treating with compound C, indicating that carvedilol induced autophagy in anoxia NRVMs partly by the AMPK-mTOR signaling pathway. Conclusions: Carvedilol has cardioprotection by inducing autophagy against apoptosis partly through the AMPK/mTOR pathway during anoxia in NRVMs.
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- 2023
133. Cannabinoids Receptors in COVID-19: Perpetrators and Victims
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Hayder M, Al-Kuraishy, Ali I, Al-Gareeb, Athanasios, Alexiou, and Gaber El-Saber, Batiha
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Pharmacology ,Drug Discovery ,Organic Chemistry ,Molecular Medicine ,Biochemistry - Abstract
Abstract: COVID-19 is caused by SARS-CoV-2 and leads to acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and extrapulmonary manifestations in severely affected cases. However, most of the affected cases are mild or asymptomatic. Cannabinoids (CBs) such as tetrahydrocannabinol (THC) and cannabidiol (CBD), which act on G-protein-coupled receptors called CB1 and CB2, have anti-inflammatory effects. Many published studies show that CBs are effective in various inflammatory disorders, viral infections, and attenuation of ALI and ARDS. Therefore, the present narrative review aimed to summarize the possible immunological role of CBs in COVID-19. The effects of CBs are controversial, although they have beneficial effects via CB2 receptors and adverse effects via CB1 receptors against ALI, ARDS, and hyperinflammation, which are hallmarks of COVID-19. The present narrative review has shown that CBs effectively manage ALI and ARDS by suppressing pro-inflammatory cytokines, which are common in COVID-19. Therefore, CBs may be used to manage COVID-19 because of their potent anti-inflammatory effects, suppressing pro-inflammatory cytokines and inhibiting inflammatory signaling pathways.
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- 2023
134. Some New 1,2,4-triazole Derivatives Bearing the Pyrimidine Moiety as Potential Antimycobacterial Agents: Synthesis and Docking Analysis
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Ivaturi Venkata Kasi Viswanath, Ganji Sreekanth Reddy, Anna Venkateswara Rao, Mukkanti Siva Naga Anjaneya Prasad, and Eppakayala Laxminarayana
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Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Background: Pyrimidine and 1,2,4-triazole heterocycles have been linked to a variety of biological and pharmacological properties such as effective bactericides, fungicides, vermicides, insecticides, anticancer and antiviral agents. Accordingly, the synthetic derivatives and analogs of these molecules have attracted attention as potential pharmacological agents. Objective: A novel set of heterocyclic derivatives comprising 1,2,4-triazole, pyrimidine moieties was developed, synthesized, and assessed for their antimicrobial activity. Methods: In this study, we performed ligand-based pharmacophore modeling as a promising design strategy for the design of substituted triazolyl-pyrimidine derivatives as antitubercular agents. The designed compounds were synthesized and characterized by proton, carbon nuclear magnetic resonance spectroscopy, infrared, and mass spectroscopy. Synthesized compounds were screened for anti-TB activity using the agar micro dilution method against M. tuberculosis H37Rv strain. Results: Our results revealed that the target 1,2,4-triazoles 7d, 7e, 7c have potent potency against Gram- (+ve) bacteria S. epidermidis (MICs: 1.7, 3.7, 16.4 μg/mL), whereas final pyrimidines 7c, 7e, 7f, have the strongest antibacterial activity against Gram-(-ve) strain P. aeruginosa (MICs: 3.5, 6.4, 8.4 μg/mL). Among all tested compounds, 7a, 7e, and 7h revealed an outstanding antitubercular activity against M. tuberculosis H37RV strain with MICs of 3.24, 8.93, and 4.70 μg/mL, respectively. The most active ligand 7b reveals highest hydrophobic binding modes with ThrA:127 [2.194 A°], LysA:103 [3.103, 2.164 A°], GlyA:102 [1.713 A°], ArgA:238 [1.713 A°], ValA:101 [2.113 A°] (hydrogen bondings), AspA:129, GluA:201 [Pi-anion], AlaA:246, LeuA:180 [Pi-alkyl] and HisA:179 [3.104 A°] [Pi-Pi], respectively. Conclusion: In this communication, our aim has been verified by the synthesis of 3-methoxy-10,12- dimethyl-8-phenyl-6,7,8,12-tetrahydrobenzo[2,3]oxepino[4,5-d][1,2,4]triazolo[4,3-a] pyrimidine derivatives 7 in which 1,2,4-triazole and pyrimidine moieties with benzoxepine in a single molecular framework were found. After all the above findings, it can be concluded that these molecules become lead molecules for further synthetic and biological evaluation.
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- 2023
135. Research Progress in Competitive Purine Antagonists
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Guo-Wu Rao, Dan-Xia Ying, Peng-Cheng Zhao, and Wen Zhang
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Pharmacology ,Drug Discovery ,Organic Chemistry ,Molecular Medicine ,Biochemistry - Abstract
Abstract: Purine, one of the nucleotides, is an important substance for the metabolism and regulation of the body. Purine plays a key role not only in the composition of coenzymes but also in the supply of energy. Since purine was artificially synthesized, it has always been an important scaffold for respiratory diseases, cardiovascular diseases, and anti- tumor and anti-viral drugs. In addition to being widely used as competitive antagonists in the treatment of diseases, purines can be used in combination with other drugs and as precursors to benefit human life. Unfortunately, few new discoveries have been made in recent years. In this article, purine drugs in the market have been classified according to their different targets. In addition, their mechanism of action and structure-activity relationship have also been introduced. This paper provides details of the signaling pathways through which purine drugs can bind to the respective receptors on the surface of cells and cause consequent reactions within the cell, which finally affect the targeted diseases. The various receptors and biological reactions involved in the signaling for respective disease targets within the cells are discussed in detail.
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- 2023
136. Biomarkers in Hypertension and Hypertension-related Disorders
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Patrícia, de Carvalho Ribeiro, Lucas Felipe, Oliveira, Daniel Mendes, Filho, Ricardo Cambraia, Parreira, Mariana Sousa, Vieira, Bruno Lemes, Marques, Elis Marra, da Madeira Freitas, Walison N, Silva, Helton da Costa, Santiago, Alexander, Birbrair, Henning, Ulrich, Valdo José Dias, da Silva, and Rodrigo R, Resende
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Pharmacology ,Drug Discovery ,Organic Chemistry ,Molecular Medicine ,Biochemistry - Abstract
Abstract: Systemic arterial hypertension (SAH) is a major risk factor for several secondary diseases, especially cardiovascular and renal conditions. SAH has a high prevalence worldwide, and its precise and early recognition is important to prevent the development of secondary outcomes. In this field, the study of biomarkers represents an important approach to diagnosing and predicting the disease and its associated conditions. The use of biomarkers in hypertension and hypertension-related disorders, such as ischemic stroke, intracerebral hemorrhage, transient ischemic attack, acute myocardial infarction, angina pectoris and chronic kidney disease, are discussed in this review. Establishing a potential pool of biomarkers may contribute to a non-invasive and improved approach for their diagnosis, prognosis, risk assessment, therapy management and pharmacological responses to a therapeutic intervention to improve patients' quality of life and prevent unfavorable outcomes.
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- 2023
137. In Silico, In Vitro and In Vivo Assessment of Acetylcholinesterase Inhibitory Activity of Theobromine Derivatives Containing an Arylpiperazine Fragment
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Maya Georgieva, Lily Andonova, Mariyana Atanasova, Iva Valkova, Irini Doytchinova, Rumyana Simeonova, Dimitrina Zheleva-Dimitrova, and Alexander Zlatkov
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Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Background: In the current Alzheimer’s disease therapy as the preferred treatment are applied acetylcholinesterase inhibitors. Aiming to identify the active pharmacophores necessary for increased acetylcholinesterase inhibitory activity, some docking studies have been applied. Methods: In silico docking evaluation of the binding modes, identification of acetylcholinesterase inhibitory activity in vitro through Ellman’s test and ITC protocol, and the in vivo effect. PAMPA evaluation of the GIT and BBB permeability. Results: In the present study, two series previously synthesized in our laboratory, arylpiperazine derivatives of theobromine were docked into the rhAChE active sites. Ellman’s test outlined molecules LA1 and LA7 as the most active, with IC50 of 0.708 and 0.299 μM, respectively. In the acute toxicity test, LA7 given intraperitoneally in mice showed moderate toxicity with LD50 of 87.5 mg/kg. The new compound, administered i.p. for 12 days at doses 2 mg/kg/day and 4 mg/kg/day, respectively, showed a pronounced acetylcholinesterase inhibitory activity in vivo. Conclusion: The corresponding binding modes were identified, where the docking pose for the studied molecules depends on the protonated state of the nitrogen atom of the piperazine moiety. In the best scored pose for LA7, the xanthine moiety is bound into the catalytic active site (CAS) of acetylcholinesterase, while the arylpiperazine fragment is placed into the peripheral binding site (PAS). For the evaluated selected structures, good permeability through the GIT and BBB assessed by PAMPA was also determined.
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- 2023
138. Graviola Protects Against Hepatic Toxicity Associated with DMBA induced Breast Cancer via Restoration of Antioxidants and Attenuation of Inflammatory Pathways
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Gaber El-Saber Batiha, Athanasios Alexiou, Mohamed M. Zeweil, Kadry M. Sadek, Tarek K. Abouzed, Lamiaa Wasef, Hamida Saleh, Sarah M. Albogami, Saqer S. Alotaibi, and Abdulrahman A. Alsayegh
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Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Aims: This study documented hepatic tissue's protective activity against oxidative damage mediated experimental models of breast cancer. Background: Gaviola has a long history of improving the protection mechanism against many diseases as an antioxidant and anticancer dietary agent. Objective: The purpose of this study is to establish changes in hepatic profiling, antioxidants, inflammatory cytokine expression, and DMBA-induced hepatic histopathology of mammalian rats. Method: 7,12-dimethylbenz[a] anthracene (DMBA), PAHs, used orally in female Sprague Dawley rats Fifty-seven days-old with breast cancer single-dose diluted in sesame oil of 20 mg/kg/body weight. The cancer-bearing animals had 45 days gastrogavagated at 200 mg/kg/body weight with Graviola. The serum samples were taken at the end of the experiment. The rats were sacrificed to establish the hepatic protective activity of the Graviola by testing hepatic and oxidative stress markers. Result: Graviola therapy shows that enzymatic and non-enzymatic antioxidants and lipid peroxide levels have increased efficiency and have restored the high activity of hepatic marker enzymes such as ALT, AST, ALP, and GGT. To date, hepatic expression of nuclear factor erythroid 2-like 2 (Nfe2l2) and nuclear factor kappa B subunit 1 (Nfkb1) mediated rats have normalized. In addition, histological observations have demonstrated that Graviola's treatment effectively protects the liver from the oxidative damage caused by DMBA, reinforcing its hepatic defensive nature. Conclusion: Graviola therapy improves the efficiency of both enzymatic and non-enzymatic antioxidants and lipid peroxide levels. It also helps in the restoration of other liver enzymes.
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- 2023
139. Natural Antioxidants of the Underutilized and Neglected Plant Species of Asia and South America
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Wenli Sun, Mohamad Hesam Shahrajabian, Diorge Jonatas Marmitt, and Qi Cheng
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Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Background: Plants have played an essential role in the search for new compounds for the most diverse therapeutic purposes. Recently, more attention has been paid to natural antioxidants because of the possible insecurity of synthetic antioxidants. Objective: The review is aimed at summarizing the most important and common natural antioxidants and their resources from medicinal plants. Method: The research was performed using data bases of PubMed, Google Scholar, Science Direct, Taylor and Francis, etc. to search for all collected scientific publications. Results: The most important medicinal plants with antioxidant activities in Iran are Artemisia, berberry fruit, borage, calendula, coriander, cumin, green tea, hawthorn, jujube, pomegranate, rose, rosemary, black zira, tea, and thyme. Important traditional medicinal plants with antioxidant activities in China are Asparagus, bindii, blueberries, camellia, Chinese bayberry, Chinese bitter melon, Chinese cabbage, Chinese cherry, Chinese jujube, Chinese olive, pomegranate, Chinese rose tea, Chinese toon, Chinese watermelon, black tea, knotweed, Chinese quince, Chinese rhubarb, sumac, wolfberry, dendrobium, drumstick tree, Fiscus species, ginger, ginkgo, goji berry, grape, Jerusalem thorn, kiwifruit seed oil, and liquorice root. Anacardium occidentale L., Ananas comosus (L.) Merril, Baccharis trimera (Less) DC., Carapa guianensis Aubl., Casearia sylvestris Sw., Cordia verbenacea DC., Croton lechleri Müll. Arg., and Eugenia uniflora L. are the main medicinal plants with antioxidant activities in Brazil. Conclusion: Antioxidants are those molecules that are involved in the scavenging of these reactive species causing oxidative stress and are defined as those substances which could prevent the oxidation of the substrate at low concentrations. The main derived exogenous natural antioxidants are derived from medicinal plants, fruits, foods, flowers, and traditional herbal medicines in different parts of the world
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- 2023
140. Effect of Statins on the Blood Lipid Profile in Patients with Different Cardiovascular Diseases: A Systematic Review with Meta-analysis of Randomized Clinical Trials
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Saeed, Aslani, Bahman, Razi, Danyal, Imani, Keyhan, Mohammadi, Tannaz, Jamialahamdi, Željko, Reiner, and Amirhossein, Sahebkar
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Pharmacology ,Drug Discovery ,Organic Chemistry ,Molecular Medicine ,Biochemistry - Abstract
Background: Statins are the main lipid-lowering drugs and are used in the prevention of cardiovascular diseases (CVDs). Since the results have been, to some extent, inconsistent in the clinical trials concerning different types of CVDs, a systematic review and meta-analysis was performed to prove the effect of statins on decreasing elevated levels of total cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in patients with CVDs. Methods: Literature search was performed on major electronic databases (MEDLINE/ PubMed, Scopus, and ISI Web of Science) from inception up to July 2021 to find randomized controlled trials (RCTs) evaluating the effect of different statins on different types of CVDs. The effect size was determined using weighted mean difference (WMD) and corresponding 95% confidence interval (CI). Results: Statin therapy significantly decreased levels of total cholesterol (WMD = -33.37 mg/dl, 95% CI: -45.98 to -20.76, P Conclusion: Statin therapy was found effective in lowering levels of total cholesterol, LDL-C, and TG, and increasing levels of HDL-C in patients with different CVDs.
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- 2023
141. Molecular Docking, ADMET Analysis and Molecular Dynamics (MD) Simulation to Identify Synthetic Isoquinolines as Potential Inhibitors of SARS-CoV-2 MPRO
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Ricardo Silva Porto, Paulo Ricardo dos Santos Correia, Alesson Henrique Donato de Souza, Andres Reyes Chaparro, and Aldo Yair Tenorio Barajas
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Drug Discovery ,Molecular Medicine ,General Medicine - Abstract
Background: The rapidly widespread SARS-CoV-2 infection has affected millions worldwide, thus becoming a global health emergency. Although vaccines are already available, there are still new COVID-19 cases daily worldwide, mainly due to low immunization coverage and the advent of new strains. Therefore, there is an utmost need for the discovery of lead compounds to treat COVID-19. Objective: Considering the relevance of the SARS-CoV-2 MPRO in viral replication and the role of the isoquinoline moiety as a core part of several biologically relevant compounds, this study aimed to identify isoquinoline-based molecules as new drug-like compounds, aiming to develop an effective coronavirus inhibitor. Methods: 274 isoquinoline derivatives were submitted to molecular docking interactions with SARS-CoV-2 MPRO (PDB ID: 7L0D) and drug-likeness analysis. The five best-docked isoquinoline derivatives that did not violate any of Lipinski’s or Veber’s parameters were submitted to ADMET analysis and molecular dynamics (MD) simulations. Results: The selected compounds exhibited docking scores similar to or better than chloroquine and other isoquinolines previously reported. The fact that the compounds interact with residues that are pivotal for the enzyme's catalytic activity, and show the potential to be orally administered makes them promising drugs for treating COVID-19. Conclusion: Ultimately, MD simulation was performed to verify ligand-protein complex stability during the simulation period.
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- 2023
142. The Custom R Group Enumeration with Various R Group Libraries at Designated Sites on Amphotericin B
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Amit K. Goyal, Ajay Mahor, and Devesh M. Sawant
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Drug Discovery ,Molecular Medicine ,General Medicine - Abstract
Background: Amphotericin B is a gold-standard drug, particularly for the treatment of systemic fungal infections. However, its low solubility and permeability limit its application. To improve its bioavailability, AmB may be conjugated with various water-soluble auxiliary groups. Methods: Custom R group Enumeration was used at the designated sites of Amphotericin B. The designated sites taken into consideration are the carboxyl moiety of the aglycone part and the amine moiety of the glycone part of Amphotericin B for Enumeration purposes. The enumerated molecules were subjected to QikProp properties. Results: We identified fourteen hits with improved predicted aqueous solubility and cell permeability. Conclusion: Enumeration might be applicable in improving bioavailability, which could lead to the oral formulation of the Amphotericin B drug.
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- 2023
143. The Effect of Synthetic Curcumin Analogues on Obesity, Diabetes and Cardiovascular Disease: A Literature Review
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Amirhossein Sahebkar, Salime Lavian, Pegah Mardaneh, Mohammad Bagherniya, Seyed Ahmad Emami, and Alexandra E. Butler
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Pharmacology ,Drug Discovery ,Organic Chemistry ,Molecular Medicine ,Biochemistry - Abstract
Abstract: Obesity, as an unfavorable consequence of our modern lifestyle, can promote the emergence of other disorders, like diabetes and cardiovascular disease, that negatively impact quality of life. Therefore, prevention and treatment of obesity and its related comorbidities are critical. Lifestyle modification is the first and most important step but, in practical terms, presents a major challenge to many patients. So, the development of new strategies and therapies is critical for these patients. Although herbal bioactive compounds have recently gained attention for their ability to prevent and treat conditions related to obesity, no ideal pharmacological treatment has been found to treat obesity. Curcumin, one of the compounds extracted from turmeric, is a well-studied active herbal extract; however, its poor bioavailability and solubility in water, instability against temperature, light and pH fluctuations and rapid excretion limit its therapeutic application. Curcumin modification can, however, provide novel analogues with better performance and fewer disadvantages in comparison to the original structure. In the past few years, the positive effects of synthetic analogues of curcumin for the treatment of obesity, diabetes and cardiovascular disorders have been reported. In this review, we evaluate the strengths and weaknesses of the reported artificial derivatives and assess their practicality as therapeutic agents.
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- 2023
144. Design, Synthesis, and Antiproliferative Activity of Novel Flavone Derivatives
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Lata C. Potey, Prafulla M. Sabale, and Vidya P. Sabale
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Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Background: Cancer is a complex disease in which some of the cells grow uncontrollably and spread to other parts of the body. Objective: The present study focuses on molecular docking and synthesis of novel flavone derivatives substituted with heterocyclic rings. Objective: The present study focuses on molecular docking and synthesis of novel flavone derivatives substituted with heterocyclic rings. Methods: The anticancer activity of novel flavones against human aromatase enzyme using human breast cancer cell line MCF-7 through MTT assay was demonstrated. The synthesized compounds for the determination of single or double-strand DNA damage through the single-cell electrophoresis/comet assay were evaluated. Results: In this study, we found that the derivative 3M with Morpholine ring showed the highest anticancer potency against the MCF-7 cell line compared to that of other flavone derivatives. Compound 3T showed less cytotoxicity against the MCF-7 cell line. Conclusion: Based on the findings, flavone scaffolds can be selected as a skeleton for the development of heterocyclic amine-containing flavones with the potential to develop as anticancer drugs.
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- 2023
145. Updates on the Synthetic Strategies and Structure-Activity Relationship of Anticonvulsant Benzothiazole and Benzimidazole Derivatives
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Rajnish Kumar, Bharti Chauhan, Avijit Mazumder, null Salahuddin, Himanshu Singh, Ranjeet Kumar Yadav, and Mohd. Mustaqeem Abdullah
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Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Abstract: Epilepsy is a chronic neurological disorder characterized by periodic and unpredictable seizures affecting the neurobiological, psychological, cognitive, economic, and social well-being of patients. It is one of the causes of concern in developed as well as developing countries as currently marketed drugs are not capable of providing protection against it. Although several heterocyclic moieties have been frequently used as building blocks for the preparation of anticonvulsant drugs, more focused and consistent research on the synthesis of potential molecules with less adverse effects is the need of the hour. It can be concluded on the basis of available research reports that among several heterocyclic compounds, benzo-fused five-membered heterocyclic moieties (benzothiazole and benzimidazole) have been utilized far less than their great potential as building blocks for the synthesis of anticonvulsant drugs. Various reports clearly established that the required pharmacophore model could be easily achieved through benzothiazole and benzimidazole moieties as two hetero atoms and aryl rings are present in the structure. The present study highlights various synthetic approaches for anticonvulsant benzothiazole and benzimidazole derivatives with their structure-activity relationship studies in order to provide a trove of knowledge to medicinal chemists for future research.
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- 2023
146. Cellular Functional, Protective or Damaging Responses Associated with Different Redox Imbalance Intensities: A Comprehensive Review
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Luis Alberto Videla, Rodrigo Valenzuela, Andrea del Campo, and Jessica Zúñiga-Hernandez
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Pharmacology ,Drug Discovery ,Organic Chemistry ,Molecular Medicine ,Biochemistry - Abstract
Abstract: Reactive species (RS) are produced in aerobic and anaerobic cells at different concentrations and exposure times, which may trigger diverse responses depending on the cellular antioxidant potential and defensive devices. Study searches were carried out using the PubMed database of the National Library of Medicine-National Institutes of Health. Cellular RS include reactive oxygen (ROS), nitrogen (RNS), lipid (RLS) and electrophilic species that determine either cell homeostasis or dysfunctional biomolecules. The complexity of redox signalling is associated with the variety of RS produced, the reactivity of the target biomolecules with RS, the multiplicity of the counteracting processes available, and the exposure time. The continuous distortion in the prooxidant/ antioxidant balance favoring the former is defined as oxidative stress, whose intensity determines (i) the basal not harmful unbalance (oxidative eustress) at RS levels in the pM to nM range that supports physiological processes (e.g., immune function, thyroid function, insulin action) and beneficial responses to external interventions via redox signalling; or (ii) the excessive, toxic distortion (oxidative distress) at RS levels exceeding those in the oxidative eustress zone, leading to the unspecific oxidation of biomolecules and loss of their functions causing cell death with associated pathological states. The cellular redox imbalance is a complex phenomenon whose underlying mechanisms are beginning to be understood, although how RS initiates cell signalling is a matter of debate. Knowledge of this aspect will provide a better understanding of how RS triggers the pathogenesis and progression of the disease and uncover future therapeutic measures.
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- 2023
147. The Therapeutic Potential of Panax Ginseng and Ginger on Postsurgical Adhesion Band Formation
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Amir Avan, Majid Khazaei, Seyedeh Elnaz Nazari, Ghazaleh Khalili-Tanha, Leila Mobasheri, Fereshteh Asgharzadeh, Hamideh Naimi, Moein Eskandari, Mohammad-Mostafa Askarnia-Faal, Seyed Mahdi Hassanian Mehr, Masoumeh Gharib, Hamid Reza Ghorbani, Mohsen Aliakbarian, and Gordon A Ferns
- Subjects
Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Background: Peritoneal adhesions (PA) are a common complication of abdominal operations. Previous studies indicate that inhibition of inflammation and fibrosis at sites of peritoneal damage may prevent the development of intra-abdominal adhesions. Zingiber officinalis Roscoe (ginger) and Panax ginseng (P. ginseng) are herbal products with antioxidant and anti-inflammatory effects that can have restorative properties. Objective: This research aimed to examine the impact of ginger and p. ginseng on prevention of PA in a rat model after surgery. Methods: Following a laparotomy, the wall of the cecum was rubbed to induce intra-abdominal adherence in Wistar rats. Ginger (400mg/kg) and P. ginseng (500mg/kg) were orally adminstered to the animals. The animals were sacrificed on the 10th day after surgery, and the Nair and Leach scoring system was used to assess adhesion. The microscopic histology of the induced cecal adhesions was evaluated. An enzyme-linked immunosorbent assay (ELISA) was used to determined tissue levels of transforming growth factor-beta (TGF-β) on homogenized PA tissue. Real-time PCR was performed to quantify the mRNA expression of IL-1β, TNF-α, Col 1a1, and Col 3a1 in rat tissue. Result: The adhesion score and histopathological rating based on the Nair and Leach scoring criteria showed lower adhesion scores in the group of rats treated with P. ginseng compared to the control group (p Conclusion: The study's outcome recommends that P. ginseng could be an effective agent for preventing the PA and inflammation during the post-operative stage.
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- 2023
148. Network Pharmacological Study of Compound Kushen Injection in Esophageal Cancer
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Yutong He, Dongli Guo, Jing Jin, Jianghui Liu, and Meng Ren
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Drug Discovery ,Molecular Medicine ,General Medicine - Abstract
Aim: To provide new methods and ideas for the clinical application of integrated traditional Chinese and Western medicine in the treatment of esophageal cancer. Background: Traditional Chinese medicine compound Kushen injection (CKI) has been widely used in the clinic with adjuvant radiotherapy and chemotherapy. However, the mechanism of action of CKI as adjuvant therapy for esophageal cancer has not yet been described. Method: This study is based on network pharmacology, data mining, and molecular docking technology to explore the mechanism of action of CKI in the treatment of esophageal cancer. We obtained the effective ingredients and targets of CKI from the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) and esophageal cancer-related genes from the Online Mendelian Inheritance in Man (OMIM) and GeneCards databases. Result: CKI mainly contains 58 active components. Among them, the top 5 active ingredients are quercetin, luteolin, naringenin, formononetin, and beta-sitostero. The target protein of the active ingredient was matched with the genes associated with esophageal cancer. The active ingredients targeted 187 esophageal cancer target proteins, including AKT1, MAPK1, MAPK3, TP53, HSP90AA1, and other proteins. Then, we enriched and analyzed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and used AutoDockVina to dock the core targets and compounds. Finally, PyMOL and Ligplot were used for data visualization. Conclusion: This study provides a new method and ideas for the clinical application of integrated traditional Chinese and Western medicine in the treatment of esophageal cancer.
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- 2023
149. Various Carbonic Anhydrases in Physiopathological Events, Carbonic Anhydrase Inhibitors, and Hybrid Compounds
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Ayse Er
- Subjects
Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Abstract: Enzymes are highly specific catalysts that accelerate reactions in biological systems. Carbonic anhydrase (CA) is an enzyme found in plants, microorganisms, and vertebrates. CA catalyses CO2 hydration/ dehydration. There are different families and isoenzymes of CAs. Fifteen α-CA isoenzymes have been reported in humans. The status of CO2 hydration and dehydration is important for a variety of biological processes. CAs play an important role in many physiological and pathological events in several tissue types. Their levels are increased in some diseases; therefore, CA inhibition has been applied as a therapeutic option. However, the high diversity of these isoenzymes is an important consideration. Isoenzyme- specific CA inhibitors can reduce the side effects of treatment. Some agents containing additional sulfonamides approved for other therapeutic applications, such as topiramate, celecoxib/valdecoxib, sulpiride, and famotidine, have inhibitory effects on CA isoenzymes. These bind to the zinc ion in the CA active site. Recently, research has been conducted on the use of a hybrid form of active ingredient and a CA inhibitor. CA inhibitor-NSAID hybrid compounds demonstrated more efficacy than NSAIDs in arthritis, which has attracted further attention of researchers in conducting research on CA-hybrid drugs.
- Published
- 2023
150. Considering the Conception of Nanotechnology Integrated on Herbal Formulation for the Management of Cancer
- Author
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Sudhanshu Mishra, Smriti Ojha, Shalini Yadav, null Ajeet, Babita Aggarwal, and Saurabh Kumar Gupta
- Subjects
Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Abstract: Metastases result from a complicated process in which malignant cells detach from the initial cancerous cells and disseminate to other locations. Few therapy options are available that aim to prevent or counteract metastatic disorders. Identifying novel molecular targets and medications, developing techniques to distribute preexisting chemicals, and combining resources to supervise individualized treatment are all part of this process. Because of its improved sensitivity, accuracy, and multiplexed measurement capacity, nanotechnology has been investigated to recognize extracellular cancer biomarkers, cancer cells, and bioimaging. Nanotechnology is a vast and rapidly expanding field with enormous potential in cancer treatment. Nanoparticles can treat resistant cancers with minimal harm to healthy tissues and organs by targeting cancer stem cells. Nanoparticles can also trigger immune cells, which can help to destroy malignancies. The potential of herbal-based nano formulation as a specialized and high-efficacy therapeutic method opens the path for future research into the screening and use of herbal nanoparticles for cancer treatment. The possible impacts of nanoparticles in the therapy of metastatic cancer, specifically on cell stability, proliferation suppression, eventual interaction with adhesion molecules, and antiangiogenic activity, are discussed in this paper.
- Published
- 2023
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