<![CDATA[Current Medicinal Chemistry (Volume 31 - Issue 19)]]> https://benthamscience.com/journal/25 RSS Feed for Journals | BenthamScience EurekaSelect (+https://benthamscience.com) 2024-03-20 <![CDATA[Current Medicinal Chemistry (Volume 31 - Issue 19)]]> https://benthamscience.com/journal/25 <![CDATA[Multimodality Cardiac Imaging Biomarkers and Atrial Fibrillation Substrate: Are they Worthwhile?]]>https://benthamscience.com/article/1362782024-03-20 <![CDATA[The Development of Non-natural Type Nucleoside to Stabilize Triplex DNA Formation against CG and TA Inversion Site]]>https://benthamscience.com/article/1317392024-03-20 <![CDATA[Hybrids Diazine: Recent Advancements in Modern Antimicrobial Therapy]]>https://benthamscience.com/article/1310662024-03-20 <![CDATA[Biology of Tenascin C and its Role in Physiology and Pathology]]>https://benthamscience.com/article/1306862024-03-20 <![CDATA[A Review on the Efficacy and Safety of Intrathecal Administration of Novel Medications for Leptomeningeal Metastases in Solid Cancers]]>https://benthamscience.com/article/1316052024-03-20 <![CDATA[Crosstalk between Oxidative Stress and Inflammation Induced by Ionizing Radiation in Healthy and Cancerous Cells]]>https://benthamscience.com/article/1307762024-03-20 <![CDATA[An Update on Parkinson’s Disease and its Neurodegenerative Counterparts]]>https://benthamscience.com/article/1306422024-03-20 Introduction: Neurodegenerative disorders are a group of diseases that cause nerve cell degeneration in the brain, resulting in a variety of symptoms and are not treatable with drugs. Parkinson's disease (PD), prion disease, motor neuron disease (MND), Huntington's disease (HD), spinal cerebral dyskinesia (SCA), spinal muscle atrophy (SMA), multiple system atrophy, Alzheimer's disease (AD), spinocerebellar ataxia (SCA) (ALS), pantothenate kinase-related neurodegeneration, and TDP-43 protein disorder are examples of neurodegenerative diseases. Dementia is caused by the loss of brain and spinal cord nerve cells in neurodegenerative diseases.

Background: Even though environmental and genetic predispositions have also been involved in the process, redox metal abuse plays a crucial role in neurodegeneration since the preponderance of symptoms originates from abnormal metal metabolism.

Method: Hence, this review investigates several neurodegenerative diseases that may occur symptoms similar to Parkinson's disease to understand the differences and similarities between Parkinson's disease and other neurodegenerative disorders based on reviewing previously published papers.

Results: Based on the findings, the aggregation of alpha-synuclein occurs in Parkinson’s disease, multiple system atrophy, and dementia with Lewy bodies. Other neurodegenerative diseases occur with different protein aggregation or mutations.

Conclusion: We can conclude that Parkinson's disease, Multiple system atrophy, and Dementia with Lewy bodies are closely related. Therefore, researchers must distinguish among the three diseases to avoid misdiagnosis of Multiple System Atrophy and Dementia with Lewy bodies with Parkinson's disease symptoms.

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<![CDATA[Emodin Alcohols: Design, Synthesis, Biological Evaluation and Multitargeting Studies with DNA, RNA, and HSA]]>https://benthamscience.com/article/1317642024-03-20Objective: A series of novel emodin alcohols were designed and prepared in an effort to overcome the increasing microorganism resistance.

Methods: Novel emodin alcohols were prepared from commercial emodin and different nitrogen-containing heterocycles via different synthetic strategies, such as O-alkylation and N-alkylation. The antimicrobial activity of synthesized emodin compounds was evaluated in vitro by a two-fold serial dilution technique. The interaction of emodin compound 3d with biomolecule was researched using UV-vis spectroscopic method and fluorescence spectroscopy.

Results: Emodin compound 3d containing 2-methyl-5-nitro imidazole ring showed relatively good antimicrobial activity. Notably, it exhibited equivalent activity against S. aureus in comparison to the reference drug norfloxacin (MIC = 4 μg/mL). The combination of strong active compound 3d with reference drugs showed better antimicrobial activity with less dosage and a broader antimicrobial spectrum than their separate use. Further research displayed that emodin compound 3d could intercalate into S. aureus DNA to form the 3d–DNA complex, which might correlate with the inhibitory activity. The hydrogen bonds were found between S. aureus DNA gyrase and strong active compound 3d during the docking research, which were in accordance with the spectral experiment results. The interaction with yeast RNA of compound 3d could also form a complex via hydrogen bonds. The hydrogen bonds were found to play a major role in the transportation of emodin compound 3d by human serum albumin (HSA), as confirmed by molecular simulation.

Conclusion: This work provides a promising starting point to optimize the structures of emodin derivatives as potent antimicrobial agents.

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<![CDATA[Potential Role of Bone Metabolism Markers in Kidney Transplant Recipients]]>https://benthamscience.com/article/1383662024-03-20 Background: The impact of treatments, suppressing the immune system, persistent hyperparathyroidism, and other risk factors on mineral and bone disorder (MBD) after kidney transplantation is well-known. However, there is limited knowledge about their effect on bone metabolism biomarkers. This study aimed to investigate the influence of kidney transplant on these markers, comparing them to patients undergoing hemodialysis and healthy individuals.

Methods: In this cross-sectional study, three groups were included: kidney transplant patients (n = 57), hemodialysis patients (n = 26), and healthy controls (n = 31). Plasma concentrations of various bone metabolism biomarkers, including Dickkopf-related protein 1, osteoprotegerin, osteocalcin, osteopontin, sclerostin, and fibroblast growth factor 23, were measured. Associations between these biomarkers and clinical and laboratory data were evaluated.

Results: A total of 114 patients participated. Transplant recipients had significantly lower levels of Dickkopf-related protein 1, osteoprotegerin, osteocalcin, osteopontin, sclerostin, and fibroblast growth factor 23 compared to hemodialysis patients. Alkaline phosphatase levels positively correlated with osteopontin (r = 0.572, p < 0.001), while fibroblast growth factor 23 negatively correlated with 25-hydroxyvitamin D (r = -0.531, p = 0.019). The panel of bone biomarkers successfully predicted hypercalcemia (area under the curve [AUC] = 0.852, 95% confidence interval [CI] = 0.679-1.000) and dyslipidemia (AUC = 0.811, 95% CI 0.640-0.982) in transplant recipients.

Conclusion: Kidney transplantation significantly improves mineral and bone disorders associated with end-stage kidney disease by modulating MBD markers and reducing bone metabolism markers, such as Dickkopf-related protein 1, osteoprotegerin, osteocalcin, osteopontin, and sclerostin. Moreover, the panel of bone biomarkers effectively predicted hypercalcemia and dyslipidemia in transplant recipients.

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<![CDATA[Modulation of the HIF-1α-NCOA4-FTH1 Signaling Axis Regulating Ferroptosis-induced Hepatic Stellate Cell Senescence to Explore the Anti-hepatic Fibrosis Mechanism of Curcumol]]>https://benthamscience.com/article/1384712024-03-20 Introduction: Senescence of activated hepatic stellate cells (HSC) reduces extracellular matrix expression to reverse liver fibrosis. Ferroptosis is closely related to cellular senescence, but its regulatory mechanisms need to be further investigated. The iron ions weakly bound to ferritin in the cell are called labile iron pool (LIP), and together with ferritin, they maintain cellular iron homeostasis and regulate the cell's sensitivity to ferroptosis.

Methods: We used lipopolysaccharide (LPS) to construct a pathological model group and divided the hepatic stellate cells into a blank group, a model group, and a curcumol 12.5 mg/L group, a curcumol 25 mg/L group, and a curcumol 50 mg/L group. HIF-1α-NCOA4- FTH1 signalling axis, ferroptosis and cellular senescence were detected by various cellular molecular biology experiments.

Result: We found that curcumol could induce hepatic stellate cell senescence by promoting iron death in hepatic stellate cells. Curcumol induced massive deposition of iron ions in hepatic stellate cells by activating the HIF-1α-NCOA4-FTH1 signalling axis, which further led to iron overload and lipid peroxidation-induced ferroptosis. Interestingly, our knockdown of HIF-1α rescued curcumol-induced LIP and iron deposition in hepatic stellate cells, suggesting that HIF-1α is a key target of curcumol in regulating iron metabolism and ferroptosis. We were able to rescue curcumol-induced hepatic stellate cell senescence when we reduced LIP and iron ion deposition using iron chelators.

Conclusion: Overall, curcumol induces ferroptosis and cellular senescence by increasing HIF-1α expression and increasing NCOA4 interaction with FTH1, leading to massive deposition of LIP and iron ions, which may be the molecular biological mechanism of its anti-liver fibrosis.

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