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排序方式: 共有110条查询结果,搜索用时 15 毫秒
1.
Hrushikesh S. Chaudhari Omkar S. Palkar KM Abha Mishra Kalyan K. Sethi 《Journal of biochemical and molecular toxicology》2023,37(9):e23417
During the period of COVID-19, the occurrences of mucormycosis in immunocompromised patients have increased significantly. Mucormycosis (black fungus) is a rare and rapidly progressing fungal infection associated with high mortality and morbidity in India as well as globally. The causative agents for this infection are collectively called mucoromycetes which are the members of the order Mucorales. The diagnosis of the infection needs to be performed as soon as the occurrence of clinical symptoms which differs with types of Mucorales infection. Imaging techniques magnetic resonance imaging or computed tomography scan, culture testing, and microscopy are the approaches for the diagnosis. After the diagnosis of the infection is confirmed, rapid action is needed for the treatment in the form of antifungal therapy or surgery depending upon the severity of the infection. Delaying in treatment declines the chances of survival. In antifungal therapy, there are two approaches first-line therapy (monotherapy) and combination therapy. Amphotericin B ( 1 ) and isavuconazole ( 2 ) are the drugs of choice for first-line therapy in the treatment of mucormycosis. Salvage therapy with posaconazole ( 3 ) and deferasirox ( 4 ) is another approach for patients who are not responsible for any other therapy. Adjunctive therapy is also used in the treatment of mucormycosis along with first-line therapy, which involves hyperbaric oxygen and cytokine therapy. There are some drugs like VT-1161 ( 5 ) and APX001A ( 6 ), Colistin, SCH 42427, and PC1244 that are under clinical trials. Despite all these approaches, none can be 100% successful in giving results. Therefore, new medications with favorable or little side effects are required for the treatment of mucormycosis. 相似文献
2.
V KW Wong T Li B YK Law E DL Ma N C Yip F Michelangeli C KM Law M M Zhang K YC Lam P L Chan L Liu 《Cell death & disease》2013,4(7):e720
Autophagy is an important cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via the turnover of proteins and damaged organelles. However, persistent activation of autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to caspase-independent autophagic cell death. As such, inducing cell death through this autophagic mechanism could be an alternative approach to the treatment of cancers. Recently, we have identified a novel autophagic inducer, saikosaponin-d (Ssd), from a medicinal plant that induces autophagy in various types of cancer cells through the formation of autophagosomes as measured by GFP-LC3 puncta formation. By computational virtual docking analysis, biochemical assays and advanced live-cell imaging techniques, Ssd was shown to increase cytosolic calcium level via direct inhibition of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump, leading to autophagy induction through the activation of the Ca2+/calmodulin-dependent kinase kinase–AMP-activated protein kinase–mammalian target of rapamycin pathway. In addition, Ssd treatment causes the disruption of calcium homeostasis, which induces endoplasmic reticulum stress as well as the unfolded protein responses pathway. Ssd also proved to be a potent cytotoxic agent in apoptosis-defective or apoptosis-resistant mouse embryonic fibroblast cells, which either lack caspases 3, 7 or 8 or had the Bax-Bak double knockout. These results provide a detailed understanding of the mechanism of action of Ssd, as a novel autophagic inducer, which has the potential of being developed into an anti-cancer agent for targeting apoptosis-resistant cancer cells. 相似文献
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Bethell D Se Y Lon C Tyner S Saunders D Sriwichai S Darapiseth S Teja-Isavadharm P Khemawoot P Schaecher K Ruttvisutinunt W Lin J Kuntawungin W Gosi P Timmermans A Smith B Socheat D Fukuda MM 《PloS one》2011,6(5):e19283
Background
The emergence of artemisinin resistance has raised concerns that the most potent antimalarial drug may be under threat. The currently recommended daily dose of artesunate (AS) is 4 mg/kg, and is administered for 3 days together with a partner antimalarial drug. This study investigated the impact of different AS doses on clinical and parasitological responses in malaria patients from an area of known artemisinin resistance in western Cambodia.Methods
Adult patients with uncomplicated P. falciparum malaria were randomized into one of three 7-day AS monotherapy regimens: 2, 4 or 6 mg/kg/day (total dose 14, 28 and 42 mg/kg). Clinical, parasitological, pharmacokinetic and in vitro drug sensitivity data was collected over a 7-day inpatient period and during weekly follow-up to 42 days.Results
143 patients were enrolled (n = 75, 40 and 28 to receive AS 2, 4 and 6 mg/kg/day respectively). Cure rates were high in all treatment groups at 42 days despite almost half the patients remaining parasitemic on Day 3. There was no impact of increasing AS dose on median parasite clearance times, median parasite clearance rates or on the proportion of patients remaining parasitemic on Day 3. However at the lowest dose used (2 mg/kg/d) patients with parasitemia >10,000/µL had longer median (IQR) parasite clearance times than those with parasitemia <10,000/µL (63 (48–75) vs. 84 (66–96) hours, p<0.0001). 19% of patients in the high-dose arm developed neutropenia (absolute neutrophil count <1.0×109/L) by Day 14 and resulted in the arm being halted early.Conclusion
There is no pharmacodynamic benefit of increasing the daily dose of AS (4mg/kg) currently recommended for short-course combination treatment of uncomplicated malaria, even in regions with emerging artemisinin resistance, as long as the partner drug retains high efficacy.Trial Registration
ClinicalTrials.gov . NCT00722150相似文献6.
With cellulosic energy production from biomass becoming popular in renewable energy research, agricultural producers may be called upon to plant and collect corn stover or harvest switchgrass to supply feedstocks to nearby facilities. Determining the production and transportation cost to the producer of corn stover or switchgrass and the amount available within a given distance from the plant will result in a per metric ton cost the plant will need to pay producers in order to receive sufficient quantities of biomass. This research computes up-to-date biomass production costs using recent prices for all important cost components including seed, fertilizer, herbicide, mowing/shredding, raking, baling, storage, handling, and transportation. The cost estimates also include nutrient replacement for corn stover. The total per metric ton cost is a combination of these cost components depending on whether equipment is owned or custom hired, what baling options are used, the size of the farm, and the transport distance. Total costs per dry metric ton for biomass with a transportation distance of 60 km ranges between $63 and $75 for corn stover and $80 and $96 for switchgrass. Using the county quantity data and this cost information, we then estimate biomass supply curves for three Indiana coal-fired electric utilities. This supply framework can be applied to plants of any size, location, and type, such as future cellulosic ethanol plants. Finally, greenhouse gas emissions reductions are estimated from using biomass instead of coal for part of the utility energy and also the carbon tax required to make the biomass and coal costs equivalent. Depending on the assumed CO2 price, the use of biomass instead of coal is found to decrease overall costs in most cases. 相似文献
7.
Protein tyrosine kinase 6 negatively regulates growth and promotes enterocyte differentiation in the small intestine
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Haegebarth A Bie W Yang R Crawford SE Vasioukhin V Fuchs E Tyner AL 《Molecular and cellular biology》2006,26(13):4949-4957
Protein tyrosine kinase 6 (PTK6) (also called Brk or Sik) is an intracellular tyrosine kinase that is expressed in breast cancer and normal epithelial linings. In adult mice, PTK6 expression is high in villus epithelial cells of the small intestine. To explore functions of PTK6, we disrupted the mouse Ptk6 gene. We detected longer villi, an expanded zone of PCNA expression, and increased bromodeoxyuridine incorporation in the PTK6-deficient small intestine. Although differentiation of major epithelial cell types occurred, there was a marked delay in expression of intestinal fatty acid binding protein, suggesting a role for PTK6 in enterocyte differentiation. However, fat absorption was comparable in wild-type and Ptk6-/- mice. It was previously shown that the serine threonine kinase Akt is a substrate of PTK6 and that PTK6-mediated phosphorylation of Akt on tyrosine resulted in inhibition of Akt activity. Consistent with these findings, we detected increased Akt activity and nuclear beta-catenin in intestines of PTK6-deficient mice and decreased nuclear localization of the Akt substrate FoxO1 in villus epithelial cells. PTK6 contributes to maintenance of tissue homeostasis through negative regulation of Akt in the small intestine and is associated with cell cycle exit and differentiation in normal intestinal epithelial cells. 相似文献
8.
Cellulose conversion in dry grind ethanol plants 总被引:2,自引:1,他引:1
Ladisch M Dale B Tyner W Mosier N Kim Y Cotta M Dien B Blaschek H Laurenas E Shanks B Verkade J Schell C Petersen G 《Bioresource technology》2008,99(12):5157-5159
The expansion of the dry grind ethanol industry provides a unique opportunity to introduce cellulose conversion technology to existing grain to ethanol plants, while enhancing ethanol yields by up to 14%, and decreasing the volume while increasing protein content of distiller's grains. The technologies required are cellulose pretreatment, enzyme hydrolysis, fermentation, and drying. Laboratory data combined with compositional analysis and process simulations are used to present a comparative analysis of a dry grind process to a process with pretreatment and hydrolysis of cellulose in distiller's grains. The additional processing steps are projected to give a 32% increase in net present value if process modifications are made to a 100 million gallon/year plant. 相似文献
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10.
Julia E. Maxson Samuel B. Luty Jason D. MacManiman Melissa L. Abel Brian J. Druker Jeffrey W. Tyner 《The Journal of biological chemistry》2014,289(9):5820-5827
Mutations in the CSF3 granulocyte colony-stimulating factor receptor CSF3R have recently been found in a large percentage of patients with chronic neutrophilic leukemia and, more rarely, in other types of leukemia. These CSF3R mutations fall into two distinct categories: membrane-proximal mutations and truncation mutations. Although both classes of mutation have exhibited the capacity for cellular transformation, several aspects of this transformation, including the kinetics, the requirement for ligand, and the dysregulation of downstream signaling pathways, have all been shown to be discrepant between the mutation types, suggesting distinct mechanisms of activation. CSF3R truncation mutations induce overexpression and ligand hypersensitivity of the receptor, likely because of the removal of motifs necessary for endocytosis and degradation. In contrast, little is known about the mechanism of activation of membrane-proximal mutations, which are much more commonly observed in chronic neutrophilic leukemia. In contrast with CSF3R truncation mutations, membrane-proximal mutations do not exhibit overexpression and are capable of signaling in the absence of ligand. We show that the Thr-615 and Thr-618 sites of membrane-proximal mutations are part of an O-linked glycosylation cluster. Mutation at these sites prevents O-glycosylation of CSF3R and increases receptor dimerization. This increased dimerization explains the ligand-independent activation of CSF3R membrane-proximal mutations. Cytokine receptor activation through loss of O-glycosylation represents a novel avenue of aberrant signaling. Finally, the combination of the CSF3R membrane proximal and truncation mutations, as has been reported in some patients, leads to enhanced cellular transformation when compared with either mutation alone, underscoring their distinct mechanisms of action. 相似文献