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排序方式: 共有58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.
Two-photon scanning laser and confocal microscopies were used to image metabolic dynamics of single or cell populations of Saccharomyces cerevisiae strain 28033. Autofluorescence of reduced nicotinamide nucleotides, and mitochondrial membrane potential (DeltaPsim), were simultaneously monitored. Spontaneous, large-scale synchronized oscillations of NAD(P)H and DeltaPsim throughout the entire population of yeasts occurred under perfusion with aerated buffer in a continuous single-layered film of organisms. These oscillations stopped in the absence of perfusion and the intracellular NAD(P)H pool became reduced. Individual mitochondria within a single yeast also showed in-phase synchronous responses with the cell population, in both tetramethylrhodamine ethyl ester (or tetramethylrhodamine methyl ester) and autofluorescence. A single, localized, laser flash also triggered mitochondrial oscillations in single cells suggesting that the mitochondrion may behave as an autonomous oscillator. We conclude that spontaneous oscillations of S. cerevisiae mitochondrial redox states and DeltaPsim occur within individual yeasts, and synchrony of populations of organisms indicates the operation of an efficient system of cell-cell interaction to produce concerted metabolic multicellular behaviour on the minute time scale in both cases. 相似文献
3.
Cytochrome P-448 (mol wt 55,000 Daltons) from rabbit liver was purified to a specific content of 16.6 nmol/mg. Mice were immunised with this preparation, their spleens removed and dissociated lymphocytes hybridised with myeloma cells. Four monoclonal antibodies against cytochrome P-448 were raised and partially characterised. All four antibodies interacted with cytochrome P-448 in intact microsomal fractions and selectively immunoadsorbed cytochrome P-448 from solubilised microsomal preparations. One of the antibodies inhibited benzo[a] pyrene hydroxylase activity in a reconstituted system, one had no effect on activity and two increased activity. The possible applications of such antibodies are discussed. 相似文献
4.
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
5.
Yannick?AllanoreEmail author Didier?Borderie Axel?Périanin Hervé?Lemaréchal Ohvanesse?Garabed?Ekindjian André?Kahan 《Arthritis research & therapy》2004,7(1):R93
We have reported previously that dihydropyridine-type calcium-channel antagonists (DTCCA) such as nifedipine decrease plasma
markers of oxidative stress damage in systemic sclerosis (SSc). To clarify the cellular basis of these beneficial effects,
we investigated the effects in vivo and in vitro of nifedipine on superoxide anion (O2
•-) production by peripheral blood monocytes. We compared 10 healthy controls with 12 patients with SSc, first after interruption
of treatment with DTCCA and second after 2 weeks of treatment with nifedipine (60 mg/day). O2
•- production by monocytes stimulated with phorbol myristate acetate (PMA) was quantified by the cytochrome c reduction method. We also investigated the effects in vitro of DTCCA on O2
•- production and protein phosphorylation in healthy monocytes and on protein kinase C (PKC) activity using recombinant PKC.
After DTCCA had been washed out, monocytes from patients with SSc produced more O2
•- than those from controls. Nifedipine treatment considerably decreased O2
•- production by PMA-stimulated monocytes. Treatment of healthy monocytes with nifedipine in vitro inhibited PMA-induced O2
•- production and protein phosphorylation in a dose-dependent manner. Finally, nifedipine strongly inhibited the activity of
recombinant PKC in vitro. Thus, the oxidative stress damage observed in SSc is consistent with O2
•- overproduction by primed monocytes. This was decreased by nifedipine treatment both in vivo and in vitro. This beneficial property of nifedipine seems to be mediated by its cellular action and by the inhibition of PKC activity.
This supports the hypothesis that this drug could be useful for the treatment of diseases associated with oxidative stress. 相似文献
6.
AIMS: To determine the effects of fresh and freeze-dried extracts of Allium sativum on the physiology and morphology of Candida albicans. METHODS AND RESULTS: Inhibition of growth in glucose-yeast extract-peptone was measured using a multiwell plate reader. Scanning and transmission electron microscopy investigations indicated loss of structural integrity. Gas chromatography-mass spectrometry of extracts was employed to separate and quantify putative inhibitory sulphur-containing components. CONCLUSIONS: Fresh garlic extract has a greater efficacy than garlic powder extract as indicated both by its effects on morphology and inhibition of growth. SIGNIFICANCE AND IMPACT OF THE STUDY: The ubiquitous opportunistic pathogen C. albicans is sensitive to garlic; resistance to the broad spectrum of active principles present is unlikely so that its anticandidal effects may provide an important alternative route to chemotherapy. 相似文献
7.
The effects of the trichothecene mycotoxins (acetyl T-2 toxin, T-2 toxin, HT-2 toxin, palmityl T-2 toxin, diacetoxyscirpenol (DAS), deoxynivalenol (DON), and T-2 tetraol) on bovine platelet function were examined in homologous plasma stimulated with platelet activating factor (PAF). The mycotoxins inhibited platelet function with the following order of potency: acetyl T-2 toxin > palmityl T-2 toxin = DAS > HT-2 toxin = T-2 toxin. While T-2 tetraol was completely ineffective as an inhibitor, DON exhibited minimal inhibitory activity at concentrations above 10×10?4M. The stability of the platelet aggregates formed was significantly reduced in all mycotoxin treated platelets compared to that of the untreated PAF controls. It is suggested that the increased sensitivity of PAF stimulated bovine platelets to the more lipophilic mycotoxins may be related to their more efficient partitioning into the platelet membrane compared to the more hydrophilic compounds. 相似文献
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10.
The murid rodent subfamily Sigmodontinae contains 79 genera which are
distributed throughout the New World. The time of arrival of the first
sigmodontines in South America and the estimated divergence time(s) of the
different lineages of South American sigmodontines have been controversial
due to the lack of a good fossil record and the immense number of extant
species. The "early-arrival hypothesis" states that the sigmodontines must
have arrived in South America no later than the early Miocene, at least 20
MYA, in order to account for their vast present-day diversity, whereas the
"late-arrival hypothesis" includes the sigmodontines as part of the
Plio-Pleistocene Great American Interchange, which occurred approximately
3.5 MYA. The phylogenetic relationships among 33 of these genera were
reconstructed using mitochondrial DNA (mtDNA) sequence data from the ND3,
ND4L, arginine tRNA, and ND4 genes, which we show to be evolving at the
same rate. A molecular clock was calibrated for these genes using published
fossil dates, and the genetic distances were estimated from the DNA
sequences in this study. The molecular clock was used to estimate the dates
of the South American sigmodontine origin and the main sigmodontine
radiation in order to evaluate the "early-" and "late-arrival" scenarios.
We estimate the time of the sigmodontine invasion of South America as
between approximately 5 and 9 MYA, supporting neither of the scenarios but
suggesting two possible models in which the invading lineage was either (1)
ancestral to the oryzomyines, akodonts, and phyllotines or (2) ancestral to
the akodonts and phyllotines and accompanied by the oryzomyines. The
sigmodontine invasion of South America provides an example of the advantage
afforded to a lineage by the fortuitous invasion of a previously
unexploited habitat, in this case an entire continent.
相似文献