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111.
Justin Anglin Reza Beheshti Zavareh Philipp N. Sander Daniel Haldar Edouard Mullarky Lewis C. Cantley Alec C. Kimmelman Costas A. Lyssiotis Luke L. Lairson 《Bioorganic & medicinal chemistry letters》2018,28(16):2675-2678
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that is extremely refractory to the therapeutic approaches that have been evaluated to date. Recently, it has been demonstrated that PDAC tumors are dependent upon a metabolic pathway involving aspartate aminotransferase 1, also known as glutamate-oxaloacetate transaminase 1 (GOT1), for the maintenance of redox homeostasis and sustained proliferation. As such, small molecule inhibitors targeting this metabolic pathway may provide a novel therapeutic approach for the treatment of this devastating disease. To this end, from a high throughput screen of ~800,000 molecules, 4-(1H-indol-4-yl)-N-phenylpiperazine-1-carboxamide was identified as an inhibitor of GOT1. Mouse pharmacokinetic studies revealed that potency, rather than inherent metabolic instability, would limit immediate cell- and rodent xenograft-based experiments aimed at validating this potential cancer metabolism-related target. Medicinal chemistry-based optimization resulted in the identification of multiple derivatives with >10-fold improvements in potency, as well as the identification of a tryptamine-based series of GOT1 inhibitors. 相似文献
112.
Mohammad Reza Emad Hadi Momeninejad Babak Pourabbas Tahvildari 《Somatosensory & motor research》2017,34(4):213-218
Despite differences in the anatomical and physiological characteristics of the medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (Sol) muscles, it is common practice to investigate them as single triceps surae H-reflex recordings. The aim of this study was to compare the latencies of H-reflex recordings from the Sol, MG, and LG in patients with explicit magnetic resonance imaging (MRI) evidence of unilateral S1 radiculopathy and also compare their diagnostic yield in varied clinical characteristics (i.e., symptom duration and severity of involvement). We found a significant difference between H-reflex latencies of Sol and the two others (p?0.05 for both comparisons). Although Sol had more sensitivity in patients with positive straight leg raising (SLR) of 30°–50° and also the sub-acute phase of the disease, and MG and LG had more sensitivity in the acute phase of the disease and patients with positive SLR of 50°–70°, there were no statistically significant differences between diagnostic ability of the three heads of the triceps surae in various clinical settings and they can be used interchangeably in patients with suspected S1 radiculopathies. 相似文献
113.
Moradi Hamid Reza Hajali Vahid Khaksar Zabihollah Vafaee Farzaneh Forouzanfar Fatemeh Negah Sajad Sahab 《Molecular biology reports》2021,48(7):5647-5660
Molecular Biology Reports - Among different pathological mechanisms, neuronal loss and neurogenesis impairment in the hippocampus play important roles in cognitive decline in Alzheimer’s... 相似文献
114.
Aghamohamadi Elham Asri † Nastaran Odak Aylin Rostami-Nejad Mohammad Chaleshi Vahid Hajinabi Yasaman Eslami Maryam Mohammadian Haftcheshmeh Saeed Gholam-Mostafaei Fahimeh Sadat Asadzadeh-Aghdaei Hamid Masotti Andrea Zali Mohammad Reza 《Molecular biology reports》2022,49(7):6085-6091
Molecular Biology Reports - Celiac disease (CeD) and inflammatory bowel disease (IBD) are accompanied by impaired immune responses. To study the immune regulation of these diseases, we evaluated... 相似文献
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116.
Kidney pain is one of the clinically significant features of renal dysfunction. Mild to severe pain is seen in the lower back area. Painkillers are mostly recommended in these cases to relieve the symptom. Yet, several analgesics are associated with side effects that can worsen the state of the disease. This review is based on the studies conducted in these aspects analgesics used to treat kidney pain and their effectiveness, renal consequences of postoperative analgesia, and pharmacogenetics of these palliatives are briefly summarized in this paper. 相似文献
117.
Zohreh Poursina Asadollah Mohammadi Shadi Zamanian Yazdi Ian Humpson Veda Vakili Reza Boostani Houshang Rafatpanah 《Journal of cellular biochemistry》2019,120(9):15740-15745
Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) disease is a chronic neuroinflammatory disease, which is associated with HTLV-1 infection. There is no effective and satisfactory treatment of HAM/TSP. It has been shown that curcumin exhibits modulatory effects on apoptosis and cytotoxicity-related molecules in HAM/TSP patients. In the present study, we examined the effect of curcumin on the gene expression of caspase-8, caspase-10, and anti-apoptotic protein c-FLIP, in HAM/TSP patients. Furthermore, we compared the expression of these molecules between HAM/TSP and asymptomatic carriers. Real-time PCR was performed to examine the mRNA expression of caspase-8, caspase-10, and c-FLIP in studied groups. The mRNA expression of caspase-8 and caspase-10 was similar before and after curcumin treatment in HAM/TSP patients (P > 0.05). The mRNA expression of c-FLIPL and c-FLIPs was higher after curcumin treatment compared with before treatment and significant differences were observed between the two groups (P = 0.004 and P = 0.044, respectively). The mRNA expression levels of caspase-8, caspase-10, c-FLIPL, and c-FLIPs were not statistically significant between HAM/TSP patients and asymptomatic carriers (P < 0.05). In conclusion, our results showed that curcumin increased the expression of c-FLIP in HAM/TSP patients which might suggest that, this molecule is involved in the apoptosis of HTLV-1-infected cells. Further studies with large sample size could be useful to clarify the role of this supplement in HAM/TSP patients. 相似文献
118.
Nazila Danesh Zahra Navaee Sedighi Sima Beigoli Atena Sharifi-Rad Mohammad Reza Saberi 《Journal of biomolecular structure & dynamics》2018,36(7):1747-1763
The interactions between estradiol and two carrier proteins, i.e. human serum albumin (HSA) and holo-transferrin (HTF) in aqueous solution at pH = 7.4 were studied by three-dimensional fluorescence emission spectroscopy, isothermal titration calorimetry (ITC), zeta-potential, resonance light-scattering and molecular modeling. Extensive fluorescence quenching was observed throughout the interaction between the drug and both proteins. Moreover, conformational changes were determined by observing the rearrangement of Trp residues during binding of estradiol with HSA and HTF at different concentrations. ITC experiments revealed that, in the presence of estradiol, both van der Waals forces and hydrogen bonding became predominant. In addition, other binding parameters such as enthalpy and entropy changes were determined by the zeta potential method. Molecular modeling suggested that estradiol was situated within sub-domain IB sited in the hydrophobic cluster in Site I, whereas the drug was located in the N-terminal of HTF where it was hydrogen bonded with Ala 670. 相似文献
119.
120.
Pourghadamyari H Moohebati M Parizadeh SM Falsoleiman H Dehghani M Fazlinezhad A Akhlaghi S Tavallaie S Sahebkar A Paydar R Ghayour-Mobarhan M Ferns GA 《Cell stress & chaperones》2011,16(3):309-316
Antibody titers to several heat shock proteins (anti-Hsps) have been reported to be associated with the severity and progression of cardiovascular disease. However, there are little data regarding anti-Hsp27 titers in patients with coronary artery disease (CAD). A total of 400 patients with suspected CAD were recruited. Based on the results of coronary angiography, these patients were classified into CAD+ (n = 300) and CAD− (n = 100) groups defined as patients with ≥50% and <50% stenosis of any major coronary artery, respectively. Eighty-three healthy subjects were also recruited as the control group. Serum anti-Hsp27 IgG titers were measured using an in-house enzyme-linked immunosorbent assay. CAD+ patients had significantly higher anti-Hsp27 titers compared with both CAD− and control groups. Anti-Hsp27 titers were also higher in the CAD− group compared with the control group. With regard to the number of affected vessels in the CAD+ group, patients with three-vessel disease had higher anti-Hsp27 titers compared with both two-vessel disease (2VD) and one-vessel disease (1VD) subgroups. However, there was no significant difference between 1VD and 2VD subgroups. In multiple linear regression analysis, the number of narrowed vessels and smoking were significant independent determinants of serum anti-Hsp27 titers. The present findings indicate that serum anti-Hsp27 titers may be associated with the presence and severity of coronary artery disease. 相似文献