过氧化氢对PC12细胞plk1基因表达的影响

目的 观察过氧化氢对体外培养的PC12细胞plk1基因表达的影响.方法 采用MTT法观察不同浓度过氧化氢对体外培养的PC12细胞作用6h后,对PC12细胞存活率的影响;Western-blot检测不同浓度过氧化氢作用后,PC12细胞plk1基因蛋白表达水平的变化.结果 与对照组比较,过氧化氢剂量依赖性降低PC12细胞的存活率,增强PC12细胞plk1基因蛋白的表达水平.结论 过氧化氢降低PC12细胞的增殖活力,其机制可能是通过增强Plk1蛋白表达水平来实现.     

内源性硫化氢和基于中医气血理论的血瘀证之间的关系

“Qi” and “blood” are two essential concepts in Chinese medicine (CM). As qi is intangible, the concept of qi is still controversial between CM and Western medicine. However, the endogenous hydrogen sulfide (H₂S) and other gaseous signaling molecules provides a new approach for understanding the essence of qi in CM. Blood stasis syndrome is a common syndrome in CM. According to the CM theory, the incidence of blood stasis syndrome is closely correlated to the reckless movement of qi, as qi and blood are inseparable in regulating physiological functions. In recent years, more and more evidences suggest a close correlation between blood stasis syndrome and microcirculation dysfunction. In this paper, we discuss the relationship between endogenous H₂S and blood stasis syndrome based on qi-blood theory of CM. We found that endogenous H₂S maybe a material basis in concept of qi in CM, while dysfunctional microcirculation is the pathological basis of the blood stasis syndrome. As qi is closely associated with incidence and progression of blood stasis syndrome, endogenous H₂S may play an important role in preventing and treating the blood stasis syndrome by improving the function of microcirculation.     

NO,CO and H2S: What about gasotransmitters in fish and amphibian heart?

The gasotransmitters nitric oxide (NO), carbon monoxide (CO), and hydrogen sulphide (H₂S), long considered only toxicant, are produced in vivo during the catabolism of common biological molecules and are crucial for a large variety of physiological processes. Mounting evidence is emerging that in poikilotherm vertebrates, as in mammals, they modulate the basal performance of the heart and the response to stress challenges. In this review, we will focus on teleost fish and amphibians to highlight the evolutionary importance in vertebrates of the cardiac control elicited by NO, CO and H₂S, and the conservation of the intracellular cascades they activate. Although many gaps are still present due to discontinuous information, we will use examples obtained by studies from our and other laboratories to illustrate the complexity of the mechanisms that, by involving gasotransmitters, allow beat‐to‐beat, short‐, medium‐ and long‐term cardiac homoeostasis. By presenting the latest data, we will also provide a framework in which the peculiar morpho‐functional arrangement of the teleost and amphibian heart can be considered as a reference tool to decipher cardiac regulatory networks which are difficult to explore using more conventional vertebrates, such as mammals.     

Nanomedicine for acute respiratory distress syndrome: The latest application,targeting strategy,and rational design

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air–blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.     

Therapeutic potential of new hydrogen sulfide-releasing hybrids

A new class of hydrogen sulfide (H₂S)-donating hybrids combined with pharmacologically active compounds is presented in this article. The pharmacological profiles of some hybrid lead compounds in the areas of inflammation, H₂S-donating diclofenac (ACS 15); cardiovascular, H₂S-donating aspirin (ACS 14); urology, H₂S-donating sildenafil (ACS 6); and neurodegenerative, H₂S-donating latanoprost (ACS 67) for glaucoma treatment and H₂S-donating levodopa (ACS 84) for Parkinson’s disease, are described. The new H₂S-releasing hybrids demonstrate remarkable improvement in activity and tolerability as compared with the related parent compounds, suggesting an active pharmacological role for H₂S. Finally the mechanism(s) of action of glutathione-dependent and independent, and of gas (H₂S) release (spontaneous or enzymatic) and its implications for clinical pharmacology perspectives will be also discussed.     

Young porcine endocrine pancreatic islets cultured in fibrin show improved resistance toward hydrogen peroxide

Aim: To study the protective effect of a fibrin scaffold toward embedded young porcine endocrine pancreatic islets from hydrogen peroxide within the context of islet encapsulation in transplantation. Methods: After isolation and in vitro maturation, groups of 200 young porcine islet equivalents (IEQ) were embedded in a 200 µL fibrin gel and exposed to 2 concentrations (10 and 100 µM) of hydrogen peroxide (H₂O₂) to investigate the ability of fibrin to protect islets against apoptotic stimuli. As a control, young porcine islets were seeded in tissue culture polystyrene (TCPS) well plates and exposed to the same H₂O₂ concentrations. Islet integrity, viability and function were then investigated. Results: Morphologically, the integrity of islets embedded in fibrin gels was better preserved compared with that of islets cultured in TCPS plates, when exposed to H₂O₂. Immunofluorescence staining showed that insulin and glucagon expression was higher in islets cultured in fibrin. Overall, H₂O₂ incubation led to decreased insulin and glucagon expression. A TUNEL assay revealed elevated numbers of apoptotic cells for islets cultured in TCPS plates when compared with those embedded in fibrin. Islets cultured in TCPS plates and exposed to H₂O₂ had diminished ability to secrete insulin in response to glucose stimulation, whereas islets embedded in fibrin maintained their glucose responsiveness. Insulin trapped in fibrin was extracted and quantified, revealing insulin in the extract. Conclusions/Interpretation: Fibrin has a protective effect on young porcine endocrine pancreatic islets exposed to hydrogen peroxide.     

Mineral metabolism in the aging and the aged.

With the development of accurate and precise techniques for quantifying sodium, potassium, calcium, and magnesium concentrations, a vast literature has been generated indicating that deficits and excesses of these cations in the body create many clinical challenges for the physician. Iron has received its share of attention as the most abundant trace metal in the body, primarily being utilized in the formation of hemoglobin. Zinc is the next most abundant trace element in the body, and evaluation of its role in the biochemistry and pathophysiology of disease is now stimulating a great deal of interest. Deficiencies of the other trace metals also are receiving increasing attention as attempts to evaluate their importance in human nutrition are being made. Studies were not considered reliable until technological advances made it possible, by atomic absorption spectroscopy, neutron activation analysis, and other techniques, to quantify these trace elements accurately and precisely.     

NSAID induced gastrointestinal damage and designing GI-sparing NSAIDs

ABSTRACT

NSAIDs are widely used to treat pain and rheumatic conditions, but they induce adverse events in different body systems, although the major, most frequent events occur in the upper and lower gastrointestinal (GI) tracts.

Areas covered: This review is focused on damage caused by NSAIDs in the upper and lower GI tracts, the different mechanisms of damage and the GI-sparing NSAIDs designed to minimize adverse events based on understanding of these mechanisms.

Expert commentary: Among the new NSAIDs, COX-2 selective inhibitors have been extensively investigated, and some were approved for human use. Celecoxib demonstrated its safety for the entire GI tract, compared to traditional NSAIDs. However, coxibs, like traditional NSAIDs, are toxic to the cardiovascular (CV) system. Other GI-sparing agents include nitric oxide-NSAIDs and phosphatidylcholine-associated NSAIDs. Testing in animal models and humans they showed GI advantages over the parent NSAID compounds, but none obtained regulatory approval or were further investigated. Hydrogen sulfide-releasing NSAIDs are currently under clinical development, and more data are needed before clinical use. Alternative therapies, such as modulating gut microbiota, are being explored. Currently, clinicians must continue prescribing traditional NSAIDs or coxibs, associated with/without proton pump inhibitor therapy, based on the presence of GI/CV risk factors.