Current Research in Pharmacology and Drug Discovery最新文献_第6页

Apigenin attenuates depressive-like behavior via modulating monoamine oxidase A enzyme activity in chronically stressed mice 芹菜素通过调节慢性应激小鼠的单胺氧化酶A酶活性来减轻抑郁样行为

Current Research in Pharmacology and Drug Discovery Pub Date : 2023-01-01 DOI: 10.1016/j.crphar.2023.100161

Juliet N. Olayinka , Oluwole B. Akawa , Emmanuela K. Ogbu , Anthony T. Eduviere , Raymond I. Ozolua , Mahmoud Soliman

{"title":"Apigenin attenuates depressive-like behavior via modulating monoamine oxidase A enzyme activity in chronically stressed mice","authors":"Juliet N. Olayinka , Oluwole B. Akawa , Emmanuela K. Ogbu , Anthony T. Eduviere , Raymond I. Ozolua , Mahmoud Soliman","doi":"10.1016/j.crphar.2023.100161","DOIUrl":"10.1016/j.crphar.2023.100161","url":null,"abstract":"<div><p>Chronic stress is a risk factor for depression and is characterized by elevated levels of brain monoamine oxidase A (MAOA). Mounting evidence has shown that MAOA is a biochemical link between stress and depression. Apigenin (API), a natural flavonoid, as demonstrated <em>in vitro</em> inhibitory effect on MAOA, is suggestive of antidepressant-like activity. However, the <em>in vivo</em> inhibitory effect of API on MAOA and how it affects depression still remain unclear. Here, we report the probable mechanisms of action of API in chronic unpredictable mild stress (CUMS)-induced depression in mice. Treatment with API reversed anhedonia, and reduced anxiety and immobility time in behavioral studies. API reduced brain corticosterone and malondialdehyde (MDA) levels but increased brain levels of glutathione and superoxide dismutase. Furthermore, interleukin-6 and tumor necrosis factor-α were attenuated by API. It also restored cell loss and inhibited the activity of MAOA in the hippocampal brain regions and prefrontal cortex. Comparative binding affinity of API for MAOA (-7.7 kcal/mol) through molecular docking studies was greater than that of reference compound, clorgyline (-6.8 kcal/mol). Favorable hydrophobic interactions important to API binding at MAOA binding cavity was revealed to include conventional hydrogen bond (Cys323 and Tyr444), π-Sulfur (Cys323), π-π Stacked (Tyr407), π-π T-shaped (Phe208), π-lone pair and π-alkyl (Ile335, Ile180) interactions. These results suggest that API is a potent, selective, reversible inhibitor of MAOA with capability of attenuating CUMS-induced depression via inhibiting MAOA enzyme activity and altering other pathomechanisms.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"5 ","pages":"Article 100161"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/82/56/main.PMC10368777.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9889451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Activity-based protein profiling: A graphical review 基于活性的蛋白质分析:一个图形回顾

Current Research in Pharmacology and Drug Discovery Pub Date : 2023-01-01 DOI: 10.1016/j.crphar.2023.100164

Exequiel O.J. Porta, Patrick G. Steel

引用次数: 0

Fucoidan alleviates the hepatorenal syndrome through inhibition organic solute transporter α/β to reduce bile acids reabsorption 褐藻糖胶通过抑制有机溶质转运蛋白α/β减少胆汁酸重吸收缓解肝肾综合征

Current Research in Pharmacology and Drug Discovery Pub Date : 2023-01-01 DOI: 10.1016/j.crphar.2023.100159

Xiaojuan Zhao, Ting Yang, Jiayan Zhou, Yanli Chen, Qian Shen, Jiankang Zhang, Qianqian Qiu

{"title":"Fucoidan alleviates the hepatorenal syndrome through inhibition organic solute transporter α/β to reduce bile acids reabsorption","authors":"Xiaojuan Zhao, Ting Yang, Jiayan Zhou, Yanli Chen, Qian Shen, Jiankang Zhang, Qianqian Qiu","doi":"10.1016/j.crphar.2023.100159","DOIUrl":"10.1016/j.crphar.2023.100159","url":null,"abstract":"<div><p>The high levels of bile acids are a critical factor in hepatorenal syndrome. Organic solute transporter α/β (Ostα/β) participate in bile acids reabsorption in the kidney. Fucoidan has the great potential in protecting against liver and kidney injury. However, whether Ostα/β increase bile acids reabsorption in bile duct ligature (BDL)-induced hepatorenal syndrome and the blockade of fucoidan are still not clear. Male mice that received BDL were given to fucoidan (at 12.5, 25 and 50 mg/kg) through intraperitoneal injection once daily for three weeks. The serum, liver and kidney samples of these experimental mice were collected to carry out biochemical, pathological and Western blot analysis. In this study, fucoidan significantly lowered serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), decreased serum levels of uric acid, creatinine and uric nitrogen, restored the deregulation of the renal urate transporter 1 (URAT1), organic anion transporter 1 (OAT1), and organic cation/carnitine transporter 1/2 (OCTN1/2), consistence with alleviation BDL-induced liver and kidney dysfunction, inflammation and fibrosis in mice. Furthermore, fucoidan significantly hampered Ostα/β and reduced bile acids reabsorption in BDL-induced mice, protected against AML12 and HK-2 cells injury in vitro. These results demonstrate that fucoidan alleviates BDL-induced hepatorenal syndrome through inhibition Ostα/β to reduce bile acids reabsorption in mice. Therefore, suppression of Ostα/β by fucoidan may be a novel strategy for attenuating hepatorenal syndrome.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"5 ","pages":"Article 100159"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b8/1e/main.PMC10320405.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A new triphenylphosphonium-conjugated amphipathic cationic peptide with improved cell-penetrating and ROS-targeting properties 一种新的三苯基鏻偶联的两亲性阳离子肽，具有改善的细胞穿透和ROS靶向性能

Current Research in Pharmacology and Drug Discovery Pub Date : 2023-01-01 DOI: 10.1016/j.crphar.2022.100148

Rezeda A. Ishkaeva , Diana V. Salakhieva , Ruslan Garifullin , Raghad Alshadidi , Alexander V. Laikov , Abdulla A. Yergeshov , Marat I. Kamalov , Timur I. Abdullin

{"title":"A new triphenylphosphonium-conjugated amphipathic cationic peptide with improved cell-penetrating and ROS-targeting properties","authors":"Rezeda A. Ishkaeva , Diana V. Salakhieva , Ruslan Garifullin , Raghad Alshadidi , Alexander V. Laikov , Abdulla A. Yergeshov , Marat I. Kamalov , Timur I. Abdullin","doi":"10.1016/j.crphar.2022.100148","DOIUrl":"10.1016/j.crphar.2022.100148","url":null,"abstract":"<div><p>We study for the first time whether triphenylphosphonium (TPP) moiety can improve cellular delivery and redox properties of amphipathic cationic peptides based on YRFK/YrFK cell-penetrating and cytoprotective motif. TPP moiety was found to increase reducing activity of both stereoisomeric peptides in solution and on electrode surface in association with TPP-mediated intramolecular interactions. Among TPP-conjugated peptides, newly synthesized TPP3-YrFK featured both increased antioxidant efficacy and proteolytic resistance. TPP-conjugated peptides preferably mitigated endogenic ROS in mitochondria and cytoplasm of model glioblastoma cells with increased oxidative status. This anti-ROS effect was accompanied by mild reversible decrease of reduced glutathione level in the cells with relatively weak change in glutathione redox forms ratio. Such low interference with cell redox status is in accordance with non-cytotoxic nature of the compounds. Intracellular concentrations of label-free peptides were analyzed by LC–MS/MS, which showed substantial TPP-promoted penetration of YrFK motif across cell plasma membrane. However, according to ΔΨ<sub>m</sub> analysis, TPP moiety did not profoundly enhance peptide interaction with mitochondrial inner membrane. Our study clarifies the role of TPP moiety in cellular delivery of amphipathic cationic oligopeptides. The results suggest TPP moiety as a multi-functional modifier for the oligopeptides which is capable of improving cellular pharmacokinetics and antioxidant activity as well as targeting increased ROS levels. The results encourage further investigation of TPP3-YrFK as a peptide antioxidant with multiple benefits.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100148"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/af/d3/main.PMC9804109.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10842320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Role of pro-inflammatory cytokines in Alzheimer's disease and neuroprotective effects of pegylated self-assembled nanoscaffolds 促炎细胞因子在阿尔茨海默病中的作用及聚乙二醇化自组装纳米支架的神经保护作用

Current Research in Pharmacology and Drug Discovery Pub Date : 2023-01-01 DOI: 10.1016/j.crphar.2022.100149

Varsha Rani , Rinki Verma , Krishan Kumar , Ruchi Chawla

{"title":"Role of pro-inflammatory cytokines in Alzheimer's disease and neuroprotective effects of pegylated self-assembled nanoscaffolds","authors":"Varsha Rani , Rinki Verma , Krishan Kumar , Ruchi Chawla","doi":"10.1016/j.crphar.2022.100149","DOIUrl":"10.1016/j.crphar.2022.100149","url":null,"abstract":"<div><p>Neurodegeneration and synaptic loss in Alzheimer's disease (AD) lead to impairment in memory functions. Neuroinflammation causes activation of microglia and astrocytes cells that locally and systemically produces inflammatory cytokines which can serve as early diagnostic markers or therapeutic targets in AD. Pro-inflammatory cytokines (Interleukins (IL-1β, IL-6 and IL-10) and tumor necrosis factor (TNF α)) levels were estimated in serum, cerebral tissue, hepatic tissue, and renal tissue in treatment groups of scopolamine-induced amnesia mice model using ELISA protocol. The results showed that cerebral tissue of AD mice exhibited elevated levels of IL1β, IL6, IL10 and TNFα which indicate contribution of pro-inflammatory cytokines in the progression of AD. A significant reduction in the concentration of IL1β, IL-10 and TNF-α were noticed in serum, cerebral tissue and hepatic tissue of animal group treated with marketed memantine tablet (Admenta), pure memantine drug (MEMp), memantine-poly (lactic-co-glycolic acid) self-assembled nanoscaffolds (MEM-PLGA) SANs, Polyethylene Glycol coated memantine-poly (lactic-co-glycolic acid) self-assembled nanoscaffolds [(PEG-MEM-PLGA) SANs] and Polyethylene Glycol coated memantine-poly [(lactic-co-glycolic acid)] self-assembled nanoscaffolds grafted with Bone Marrow Derived Stem Cell ((PEG-MEM-PLGA) SANs-BMSc), whereas a high level of IL-6 was observed in hepatic tissue, cerebral tissue and renal tissues of normal and AD induced mice which showed the emerging potential of IL-6 cytokines that can trigger either neurons survival after injury or causing neurodegeneration and cell apoptosis. The Neuroregenerative potential of stem cells helps in the proliferation of neuronal cell and thus improves cognition in AD animal model.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100149"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/51/main.PMC9804106.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10842321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

The therapeutic potential of carnosine: Focus on cellular and molecular mechanisms 肌肽的治疗潜力：聚焦细胞和分子机制

Current Research in Pharmacology and Drug Discovery Pub Date : 2023-01-01 DOI: 10.1016/j.crphar.2023.100153

Giuseppe Caruso , Lucia Di Pietro , Vincenzo Cardaci , Salvatore Maugeri , Filippo Caraci

{"title":"The therapeutic potential of carnosine: Focus on cellular and molecular mechanisms","authors":"Giuseppe Caruso , Lucia Di Pietro , Vincenzo Cardaci , Salvatore Maugeri , Filippo Caraci","doi":"10.1016/j.crphar.2023.100153","DOIUrl":"10.1016/j.crphar.2023.100153","url":null,"abstract":"<div><p>Carnosine is a naturally occurring endogenous dipeptide composed by the ligation of β-alanine and L-histidine performed particularly by tissues with an increased oxidative metabolism such as muscles and brain. In the last 50 years different studies have assessed the role and function of carnosine through numerous <em>in vitro</em>, <em>in vivo</em>, and clinical studies, demonstrating the multimodal mechanism of action of this dipeptide that includes anti-aggregant, antioxidant, and anti-inflammatory activities. In particular its activity has been investigated in experimental models of cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), and neurodegenerative disorders, such as cerebral ischemia and Alzheimer's disease (AD). In the present review, we examined the protective role that carnosine could exert in the context of T2DM, CVD, and AD, which show common pathogenic mechanisms including oxidative stress, inflammation, and aggregation phenomena. Carnosine's pharmacodynamic profile is multimodal and combines the systemic anti-inflammatory and antioxidant activities with its anti-aggregant and neuroprotective efficacy in the central nervous system. This enlarged pharmacological activity opens a new path to explore the therapeutic potential of carnosine in all the three diseases, and in particular in patients with T2DM, who often show a history of CVD and also have an increased risk to develop mild cognitive impairment and AD.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100153"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/54/main.PMC10333684.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10193256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

A PAM of the α1A-Adrenergic receptor rescues biomarker, long-term potentiation, and cognitive deficits in Alzheimer’s disease mouse models without effects on blood pressure α 1a -肾上腺素能受体的PAM可在不影响血压的情况下拯救阿尔茨海默病小鼠模型的生物标志物、长期增强和认知缺陷

Current Research in Pharmacology and Drug Discovery Pub Date : 2023-01-01 DOI: 10.1016/j.crphar.2023.100160

Robert S. Papay , Shaun R. Stauffer , Dianne M. Perez

{"title":"A PAM of the α1A-Adrenergic receptor rescues biomarker, long-term potentiation, and cognitive deficits in Alzheimer’s disease mouse models without effects on blood pressure","authors":"Robert S. Papay , Shaun R. Stauffer , Dianne M. Perez","doi":"10.1016/j.crphar.2023.100160","DOIUrl":"https://doi.org/10.1016/j.crphar.2023.100160","url":null,"abstract":"<div><p>α<sub>1</sub>-Adrenergic Receptors (ARs) regulate the sympathetic nervous system by the binding of norepinephrine (NE) and epinephrine (Epi) through different subtypes (α<sub>1A</sub>, α<sub>1B</sub>, α<sub>1D</sub>). α<sub>1A</sub>-AR activation is hypothesized to be memory forming and cognitive enhancing but drug development has been stagnant due to unwanted side effects on blood pressure. We recently reported the pharmacological characterization of the first positive allosteric modulator (PAM) for the α<sub>1A</sub>-AR with predictive pro-cognitive and memory properties. In this report, we now demonstrate the <em>in vivo</em> characteristics of Compound 3 (Cmpd-3) in two genetically-different Alzheimer’s Disease (AD) mouse models. Drug metabolism and pharmacokinetic studies indicate sufficient brain penetrance and rapid uptake into the brain with low to moderate clearance, and a favorable inhibition profile against the major cytochrome p450 enzymes. Oral administration of Cmpd-3 (3–9 mg/kg QD) can fully rescue long-term potentiation defects and AD biomarker profile (amyloid β-40, 42) within 3 months of dosing to levels that were non-significant from WT controls and which outperformed donepezil (1 mg/kg QD). There were also significant effects on paired pulse facilitation and cognitive behavior. Long-term and high-dose <em>in vivo</em> studies with Cmpd-3 revealed no effects on blood pressure. Our results suggest that Cmpd-3 can maintain lasting therapeutic levels and efficacy with disease modifying effects with a once per day dosing regimen in AD mouse models with no observed side effects.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"5 ","pages":"Article 100160"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49771530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Anti-emetic effects of thalidomide: Evidence, mechanism of action, and future directions 沙利度胺的止吐作用:证据、作用机制和未来方向

Current Research in Pharmacology and Drug Discovery Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100138

Paul L.R. Andrews , Robin S.B. Williams , Gareth J. Sanger

{"title":"Anti-emetic effects of thalidomide: Evidence, mechanism of action, and future directions","authors":"Paul L.R. Andrews , Robin S.B. Williams , Gareth J. Sanger","doi":"10.1016/j.crphar.2022.100138","DOIUrl":"10.1016/j.crphar.2022.100138","url":null,"abstract":"<div><p>The rationale for using thalidomide (THD) as a treatment for nausea and vomiting during pregnancy in the late 1950s appears to have been based on its sedative or hypnotic properties. In contrast to contemporaneous studies on the anti-emetic activity of phenothiazines, we were unable to identify publications reporting preclinical or clinical evaluation of THD as an anti-emetic. Our survey of the literature revealed a clinical study in 1965 showing THD reduced vomiting in cancer chemotherapy which was substantiated by similar studies from 2000, particularly showing efficacy in the delayed phase of chemotherapy-induced nausea and vomiting. To identify the mechanism(s) potentially involved in thalidomide's anti-emetic activity we reviewed its pharmacology in the light of nausea and vomiting mechanisms and their pharmacology with a particular emphasis on chemotherapy and pregnancy. The process identified the following potential mechanisms: reduced secretion of Growth Differentiation Factor 15, suppression of inflammation/prostaglandin production, downregulation of cytotoxic drug induced upregulation of iNOS, and modulation of BK (K<sub>Ca</sub>1.1) channels and GABA<sub>A</sub>/glutamate transmission at critical points in the emetic pathways (nucleus tractus solitarius, area postrema). We propose ways to investigate these hypothesized mechanisms and discuss the associated challenges (e.g., objective quantification of nausea) in addition to some of the more general aspects of developing novel drugs to treat nausea and vomiting.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100138"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8d/16/main.PMC9780081.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10276779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Cellular and molecular mechanisms, genetic predisposition and treatment of diabetes-induced cardiomyopathy 糖尿病性心肌病的细胞和分子机制、遗传易感性和治疗

Current Research in Pharmacology and Drug Discovery Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100126

Urvashi Sharma, Manodeep Chakraborty, Devid Chutia, Nihar Ranjan Bhuyan

{"title":"Cellular and molecular mechanisms, genetic predisposition and treatment of diabetes-induced cardiomyopathy","authors":"Urvashi Sharma, Manodeep Chakraborty, Devid Chutia, Nihar Ranjan Bhuyan","doi":"10.1016/j.crphar.2022.100126","DOIUrl":"10.1016/j.crphar.2022.100126","url":null,"abstract":"<div><p>Diabetes mellitus is a common disease affecting millions of people worldwide. This disease is not limited to metabolic disorders but also affects several vital organs in the body and can lead to major complications. People with diabetes mellitus are subjected to cardiovascular complications, such as cardiac myopathy, which can further result in major complications such as diabetes-induced cardiac failure. The mechanism underlying diabetes-induced cardiac failure requires further research; however, several contributing factors have been identified to function in tandem, such as reactive oxygen species production, inflammation, formation of advanced glycation end-products, altered substrate utilisation by mitochondria, activation of the renin–angiotensin–aldosterone system and lipotoxicity. Genetic factors such as microRNAs, long noncoding RNAs and circular RNAs, as well as epigenetic processes such as DNA methylation and histone modifications, also contribute to complications. These factors are potential targets for developing effective new therapies. This review article aims to facilitate in depth understanding of these contributing factors and provide insights into the correlation between diabetes mellitus and cardiovascular complications. Some alternative targets with therapeutic potential are discussed to indicate favourable targets for the management of diabetic cardiomyopathy.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100126"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dc/d2/main.PMC9780063.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10437353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Pretomanid for tuberculosis treatment: an update for clinical purposes 用于结核病治疗的Pretomanid:用于临床目的的更新

Current Research in Pharmacology and Drug Discovery Pub Date : 2022-01-01 DOI: 10.1016/j.crphar.2022.100128

Sara Occhineri , Tommaso Matucci , Laura Rindi , Giusy Tiseo , Marco Falcone , Niccolò Riccardi , Giorgio Besozzi

{"title":"Pretomanid for tuberculosis treatment: an update for clinical purposes","authors":"Sara Occhineri , Tommaso Matucci , Laura Rindi , Giusy Tiseo , Marco Falcone , Niccolò Riccardi , Giorgio Besozzi","doi":"10.1016/j.crphar.2022.100128","DOIUrl":"10.1016/j.crphar.2022.100128","url":null,"abstract":"<div><p>Coronavirus disease (COVID-19) pandemic determined a 10 years-set back in tuberculosis (TB) control programs. Recent advances in available therapies may help recover the time lost. While Linezolid (LZD) and Bedaquiline (BDQ), previously Group D second line drugs (SLDs) for TB, have been relocated to Group A, other drugs are currently being studied in regimens for drug resistant TB (DR-TB). Among these, Pretomanid (PA), a recently introduced antimycobacterial drug derived from nitroimidazole with both solid bactericidal and bacteriostatic effect, and with an excellent effectiveness and tolerability profile, is in the spotlight. Following promising data obtained from recently published and ongoing randomized controlled trials (RCTs), the World Health Organization (WHO) determined to include PA in its guidelines for the treatment of rifampicin-resistant (RR), multi drug resistant (MDR) and pre-extensively drug resistant TB (pre-XDR-TB) with BDQ, LZD and Moxifloxacine (MFX) in a 6-month regimen. Although further studies on the subject are needed, PA may also represent a treatment option for drug-susceptible TB (DS-TB), latent TB infection (LTBI) and non tuberculous mycobacteria (NTM). This narrative review aims to examine current implementation options and future possibilities for PA in the never-ending fight against TB.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100128"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/08/2c/main.PMC9461242.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10326730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3