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81.
Thanh Q. Bui Huynh Thi Phuong Loan Tran Thi Ai My Duong Tuan Quang Bui Thi Phuong Thuy Vo Duy Nhan Phan Tu Quy Pham Van Tat Duy Quang Dao Nguyen Tien Trung Lam K. Huynh Nguyen Thi Ai Nhung 《RSC advances》2020,10(51):30961
Ribavirin and remdesivir have been preclinically reported as potential drugs for the treatment of SARS-CoV-2 infection, while light silver tetrylene complexes (NHEPh–AgCl and (NHEPh–AgCl)2 with E = C, Si, and Ge) have gained significant interest due to their promising applicability on the cytological scale. Firstly, the structures and bonding states of silver–tetrylene complexes (NHE–Ag) and bis-silver–tetrylene complexes (NHE–Ag-bis) were investigated using density functional theory (DFT) at the BP86 level with the def2-SVP and def2-TZVPP basis sets. Secondly, the inhibitory capabilities of the carbene complexes (NHC–Ag and NHC–Ag-bis) and the two potential drugs (ribavirin and remdesivir) on human-protein ACE2 and SARS-CoV-2 protease PDB6LU7 were evaluated using molecular docking simulation. The carbene ligand NHC bonds in a head-on configuration with AgCl and (AgCl)2, whereas, the other NHE (E = Si and Ge) tetrylene ligands bond in a side-on mode to the metal fragments. The bond dissociation energy (BDE) of the NHE–Ag bond in the complex families follows the order of NHC–Ag > NHSi–Ag > NHGe–Ag and NHSi–Ag-bis > NHGe–Ag-bis > NHC–Ag-bis. The natural bond orbital analysis implies that the [NHEPh→AgCl] and [(NHEPh)2→(AgCl)2] donations are derived mainly from the σ- and π-contributions of the ligands. The docking results indicate that both the ACE2 and PDB6LU7 proteins are strongly inhibited by silver–carbene NHC–Ag, bis-silver–carbene NHC–Ag-bis, ribavirin, and remdesivir with the docking score energy values varying from −17.5 to −16.5 kcal mol−1 and −16.9 to −16.6 kcal mol−1, respectively. The root-mean-square deviation values were recorded to be less than 2 Å in all the calculated systems. Thus, the present study suggests that silver–carbene NHC–Ag and bis-silver–carbene NHC–Ag-bis complexes are potential candidates to inhibit ACE2 and PDB6LU7, and thus potentially conducive to prevent infection caused by the SARS-CoV-2 virus.Simultaneous inhibition of silver–carbene complexes to ACE2 and PDB6LU7 is conducive for the prevention of SARS-CoV-2 infection: a virtual prediction. 相似文献
82.
Ho Duc Viet Hoang Hanh Nhu Thi Vo Hung Quoc Nguyen Khan Viet Pham Ty Viet Le Anh Tuan Van Phan Kiem Nguyen Hien Minh Morita Hiroyuki Nguyen Hoai Thi 《Journal of natural medicines》2020,74(3):591-598
Three new steroidal saponins, aspiletreins A–C (1–3), together with 2H-chromen-2-one (4), and α-tocopherol (5), were isolated from whole Aspidistra letreae plants collected in Vietnam. Their structures were elucidated by a combination of spectroscopic analyses, including 1D- and 2D-NMR, IR, and HRESIMS, and by comparison with the reported data in the literature. Compounds 1–3 exhibited moderate cytotoxicities against the LU-1, HeLa, MDA-MB-231, HepG2, and MKN-7 human cancer cell lines, with IC50 values ranging from 7.69?±?0.40 to 20.46?±?3.11 µM.
相似文献83.
Rivoirard Romain Moncharmont Coralie Assouline Avi Auberdiac Pierre Mery Benoite Falk Alexander Tuan Annède Pierre Trone Jane-Chloé Guy Jean-Baptiste Vial Nicolas Fournel Pierre Merrouche Yacine Chargari Cyrus Magné Nicolas 《European archives of oto-rhino-laryngology》2015,272(3):719-725
European Archives of Oto-Rhino-Laryngology - In the field of radiotherapy, there is very little scientific data on the management of nonagenarians, especially in patients aged 90 years or... 相似文献
84.
Pietro Mesirca Isabelle Bidaud Fran?ois Briec Stéphane Evain Angelo G. Torrente Khai Le Quang Anne-Laure Leoni Matthias Baudot Laurine Marger Antony Chung You Chong Jo?l Nargeot Joerg Striessnig Kevin Wickman Flavien Charpentier Matteo E. Mangoni 《Proceedings of the National Academy of Sciences of the United States of America》2016,113(7):E932-E941
Dysfunction of pacemaker activity in the sinoatrial node (SAN) underlies “sick sinus” syndrome (SSS), a common clinical condition characterized by abnormally low heart rate (bradycardia). If untreated, SSS carries potentially life-threatening symptoms, such as syncope and end-stage organ hypoperfusion. The only currently available therapy for SSS consists of electronic pacemaker implantation. Mice lacking L-type Cav1.3 Ca2+ channels (Cav1.3−/−) recapitulate several symptoms of SSS in humans, including bradycardia and atrioventricular (AV) dysfunction (heart block). Here, we tested whether genetic ablation or pharmacological inhibition of the muscarinic-gated K+ channel (IKACh) could rescue SSS and heart block in Cav1.3−/− mice. We found that genetic inactivation of IKACh abolished SSS symptoms in Cav1.3−/− mice without reducing the relative degree of heart rate regulation. Rescuing of SAN and AV dysfunction could be obtained also by pharmacological inhibition of IKACh either in Cav1.3−/− mice or following selective inhibition of Cav1.3-mediated L-type Ca2+ (ICa,L) current in vivo. Ablation of IKACh prevented dysfunction of SAN pacemaker activity by allowing net inward current to flow during the diastolic depolarization phase under cholinergic activation. Our data suggest that patients affected by SSS and heart block may benefit from IKACh suppression achieved by gene therapy or selective pharmacological inhibition.Pacemaker activity of the sinoatrial node (SAN) controls heart rate under physiological conditions. Abnormal generation of SAN automaticity underlies “sick sinus” syndrome (SSS), a pathological condition manifested when heart rate is not sufficient to meet the physiological requirements of the organism (1). Typical hallmarks of SSS include SAN bradycardia, chronotropic incompetence, SAN arrest, and/or exit block (1–3). SSS carries incapacitating symptoms, such as fatigue and syncope (1–3). A significant percentage of patients with SSS present also with tachycardia-bradycardia syndrome (3). SSS can also be associated with atrioventricular (AV) conduction block (heart block) (1–3). Although aging is a known intrinsic cause of SSS (4), this disease appears also in the absence of any associated cardiac pathology and displays a genetic legacy (1, 2). Heart disease or drug intake can induce acquired SSS (2). Symptomatic SSS requires the implantation of an electronic pacemaker. SSS accounts for about half of all pacemaker implantations in the United States (5, 6). The incidence of SSS has been forecasted to increase during the next 50 y, particularly in the elder population (7). Furthermore, it has been estimated that at least half of SSS patients will need to be electronically paced (7). Although pacemakers are continuously ameliorated, they remain costly and require lifelong follow-up. Moreover, the implantation of an electronic pacemaker remains difficult in pediatric patients (8). Development of alternative and complementary pharmacological or molecular therapies for SSS management could improve quality of life and limit the need for implantation of electronic pacemakers.Recently, the genetic bases of some inherited forms of SSS have been elucidated (recently reviewed in 1, 9) with the discovery of mutations in genes encoding for ion channels involved in cardiac automaticity (4, 9, 10). Notably, loss of function of L-type Cav1.3 Ca2+ channels is central in some inherited forms of SSS. For instance, loss of function in Cav1.3-mediated L-type Ca2+ (ICa,L) current causes the sinoatrial node dysfunction and deafness syndrome (SANDD) (10). Affected individuals with SANDD present with profound deafness, bradycardia, and dysfunction of AV conduction (10). Mutation in ankyrin-B causes SSS by reduced membrane targeting of Cav1.3 channels (11). The relevance of Cav1.3 channels to SSS is demonstrated also by work on the pathophysiology of congenital heart block, where down-regulation of Cav1.3 channels by maternal Abs causes heart block in infants (12). Additionally, recent data show that chronic iron overload induces acquired SSS via a reduction in Cav1.3-mediated ICa,L (13).In mice and humans, Cav1.3 channels are expressed in the SAN, atria, and the AV node but are absent in adult ventricular tissue (14, 15). Cav1.3-mediated ICa,L plays a major role in the generation of the diastolic depolarization in SAN and AV myocytes, thereby constituting important determinants of heart rate and AV conduction velocity (14, 16). The heart rate of mice lacking Cav1.3 channels (Cav1.3−/− mice) fairly recapitulates the hallmarks of SSS and associated symptoms, including bradycardia and tachycardia-bradycardia syndrome (17, 18). In addition, severe AV dysfunction is recorded in Cav1.3−/− mice to variable degrees. Typically, these mice show first- and second-degree AV block (16, 17, 19). Complete AV block with dissociated atrial and ventricular rhythms can also be observed in these animals. The phenotype of Cav1.3−/− mice thus constitutes a unique model for developing new therapeutic strategies against SSS (10).The muscarinic-gated K+ channel (IKACh) is involved in the negative chronotropic effect of the parasympathetic nervous system on heart rate (20, 21). Two subunits of the G-protein activated inwardly rectifying K+ channels (GIRK1 and GIRK4) of the GIRK/Kir3 subfamily assemble as heterotetramers to form cardiac IKACh channels (22). Indeed, both Girk1−/− and Girk4−/− mice lack cardiac IKACh (20, 21, 23). We recently showed that silencing of the hyperpolarization-activated current “funny” (If) channel in mice induces a complex arrhythmic profile that can be rescued by concurrent genetic ablation of Girk4 (24). In this study, we tested the effects of genetic ablation and pharmacological inhibition of IKACh on the Cav1.3−/− mouse model of SSS. We found that Girk4 ablation or pharmacological inhibition of IKACh rescues SSS and AV dysfunction in Cav1.3−/−. Thus, our study shows that IKACh targeting may be pursued as a therapeutic strategy for treatment of SSS and heart block. 相似文献
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88.
Effect of antituberculosis drug resistance on response to treatment and outcome in adults with tuberculous meningitis 总被引:5,自引:0,他引:5
Thwaites GE Lan NT Dung NH Quy HT Oanh DT Thoa NT Hien NQ Thuc NT Hai NN Bang ND Lan NN Duc NH Tuan VN Hiep CH Chau TT Mai PP Dung NT Stepniewska K White NJ Hien TT Farrar JJ 《The Journal of infectious diseases》2005,192(1):79-88
BACKGROUND: Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to 1 or more antituberculosis drugs is an increasingly common clinical problem, although the impact on outcome is uncertain. METHODS: We performed a prospective study of 180 Vietnamese adults admitted consecutively for TBM. M. tuberculosis was cultured from the cerebrospinal fluid (CSF) of all patients and was tested for susceptibility to first-line antituberculosis drugs. Presenting clinical features, time to CSF bacterial clearance, clinical response to treatment, and 9-month morbidity and mortality were compared between adults infected with susceptible and those infected with drug-resistant organisms. RESULTS: Of 180 isolates, 72 (40.0%) were resistant to at least 1 antituberculosis drug, and 10 (5.6%) were resistant to at least isoniazid and rifampicin. Isoniazid and/or streptomycin resistance was associated with slower CSF bacterial clearance but not with any differences in clinical response or outcome. Combined isoniazid and rifampicin resistance was strongly predictive of death (relative risk of death, 11.63 [95% confidence interval, 5.21-26.32]) and was independently associated with human immunodeficiency virus infection. CONCLUSIONS: Isoniazid and/or streptomycin resistance probably has no detrimental effect on the outcome of TBM when patients are treated with first-line antituberculosis drugs, but combined isoniazid and rifampicin resistance is strongly predictive of death. 相似文献
89.
In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain 总被引:35,自引:0,他引:35 下载免费PDF全文
Fallon J Reid S Kinyamu R Opole I Opole R Baratta J Korc M Endo TL Duong A Nguyen G Karkehabadhi M Twardzik D Patel S Loughlin S 《Proceedings of the National Academy of Sciences of the United States of America》2000,97(26):14686-14691
The development of an in vivo procedure for the induction of massive proliferation, directed migration, and neurodifferentiation (PMD) in the damaged adult central nervous system would hold promise for the treatment of human neurodegenerative disorders such as Parkinson's disease. We investigated the in vivo induction of PMD in the forebrain of the adult rat by using a combination of 6-hydroxydopamine lesion of the substantia nigra dopaminergic neurons and infusions of transforming growth factor alpha (TGFalpha) into forebrain structures. Only in animals with both lesion and infusion of TGFalpha was there a rapid proliferation of forebrain stem cells followed by a timed migration of a ridge of neuronal and glial progenitors directed toward the region of the TGFalpha infusion site. Subsequently, increasing numbers of differentiated neurons were observed in the striatum. In behavioral experiments, there was a significant reduction of apomorphine-induced rotations in animals receiving the TGFalpha infusions. These results show that the brain contains stem cells capable of PMD in response to an exogenously administered growth factor. This finding has significant implications with respect to the development of treatments for both acute neural trauma and neurodegenerative diseases. 相似文献