ABSTRACT
The methylation of histone lysine plays a pivotal role in epigenetic regulation of gene expression. Histone lysine methylation modifications have 5 sites within histone H3(K4, K9, K27, K36, K79)and 1 site within histone H4(K20). Methylation at various sites has been shown to lead to transcriptional activation or silencing. Histone lysine methyltransferases(HKMTs)and histone lysine demethylases(HKDMs)collectively regulate the methylation modification state of histone lysine. It was reported that the mis-regulation of HKDMs is associated with the occurring and resistance of numerous malignant tumors, so more and more attention are received to HKDMs. Therefore, it is great significant in the study and development of HKDMs inhibitors. The inhibitors could be served not only as a tool in the investigation of the biological function, but also could be used as novel anti-cancer agents in the anticancer therapy. In this review, we provide a short summary of the HKDMs inhibitors recently reported and their potential in the treatment of diseases.
ABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of solar infrared ray (IR) radiation on the expressions of c-Jun and collagens I and III in cultured human skin fibroblasts (HSFs) and explore the molecular mechanism by which IR radiation causes aging of the skin.</p><p><b>METHODS</b>Primarily cultured HSFs exposed to IR radiation were examined for changes of the cell viability with MTT assay. The mRNA and protein expressions of c-Jun and collagens I and III was detected with real-time quantitative PCR and immunocytochemistry.</p><p><b>RESULTS</b>MTT assay showed that IR irradiation caused inhibition of cell proliferation compared with the control cells. The mRNA and protein expression of collagen I was decreased significantly by IR irradiation with the increase of the irradiation dose (P<0.01). HSFs irradiated by IR for 12 h showed a dose-dependent reduction of the expression of collagen type III mRNA and protein (P<0.05, P<0.01), but the expression increased dose-dependently in response to IR exposure for 24 h (P<0.05 or 0.01). IR irradiation enhanced the mRNA and protein expression of c-Jun in a dose-dependence manner (P<0.05 or 0.01).</p><p><b>CONCLUSIONS</b>IR irradiation can increase the expression of c-Jun, inhibit the expression of collagen I, and cause disturbance in collagen III expression in human skin fibroblasts, which may be one of the mechanism of IR radiation to initiate and promote skin photoaging.</p>
Subject(s)
Humans , Cell Proliferation , Cell Survival , Cells, Cultured , Collagen Type I , Metabolism , Collagen Type III , Metabolism , Fibroblasts , Metabolism , Radiation Effects , Infrared Rays , Proto-Oncogene Proteins c-jun , Metabolism , RNA, Messenger , Metabolism , Skin , Cell Biology , Skin Aging , Ultraviolet RaysABSTRACT
Small molecule covalent inhibitors, or called as irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity. Nevertheless, these agents may also exhibit larger toxicity once off-target effects arise. This "double-edged swords" property often leads drug researchers to avoid attaching them. In recent years, some problems such as drug resistance are difficult to be solved with reversible inhibitors leading researchers to pay more attention on the covalent inhibitors. In this review, we shall make a short summary to the recent research progress of covalent inhibitors and the interaction modes between covalent inhibitors and their target protein residues.
Subject(s)
Humans , Amino Acids , Chemistry , Antineoplastic Agents , Chemistry , Therapeutic Uses , Antiviral Agents , Chemistry , Therapeutic Uses , Drug Discovery , Drug Resistance , Enzyme Inhibitors , Chemistry , Therapeutic Uses , Hepatitis C , Drug Therapy , Molecular Structure , Neoplasms , Drug Therapy , Protein Binding , Protein Kinase Inhibitors , Chemistry , Therapeutic Uses , ErbB Receptors , Serine Proteinase Inhibitors , Chemistry , Therapeutic UsesABSTRACT
Based on thermodynamic principle, the critical relative humidity of electrolytes is closely related to their solubility. The authors explored the relationship theoretically and calculated critical relative humidity of 21 electrolytes from their solubility in the light of Raoult's law and extended Wilson model. The results indicate that the critical relative humidity values calculated by Raoult's law can not accord with the reported ones and there is a systematic error in the high concentration range; while these calculated by extended Wilson model are comparable to the reported ones.
Subject(s)
Electrolytes , Chemistry , Humidity , Models, Chemical , SolubilityABSTRACT
A linear degradation humidifying model for drug stability experiment is introduced. This new humidifying model is presented as: H(r) = -M1-ln {exp(- MH(r,0)) - [exp(-MH(r,0)) -exp(-MH(r-m)) t(m)-t}. Where H(r) is the relative humidity; t is the time; H(r,m) and t(m) are the final relative humidity and time of the experiment, respectively. M is humidifying constant used in the humidifying program. In the new programmed humidifying model, a linear relationship between the content function of drugs and the relative humidity is obtained, the degradation of drugs can be more uniform within different humidity ranges and the experimental results are more accurate than those in the reported linear humidifying model. The stability of penicillin potassium, as a solid state model, was investigated by the linear degradation programmed humidifying and the exponential heating experiments. The results indicated that the kinetic parameters obtained by the linear degradation programmed humidifying and the exponential heating models were significantly more precise than those obtained by the linear programmed humidifying and the reciprocal heating models.
Subject(s)
Drug Stability , Humidity , Kinetics , Mathematics , Models, Chemical , Penicillins , Chemistry , Technology, Pharmaceutical , Methods , TemperatureABSTRACT
<p><b>AIM</b>To study the influence of light and heat on the stability of procaine hydrochloride injection.</p><p><b>METHODS</b>Accelerated tests upon exposure to light at high temperatures were employed.</p><p><b>RESULTS</b>In experiments with either isothermal heating or exposure to light at high temperatures, the drug degradation rate obeys first-order kinetics. The total rate constant, ktotal, caused by both light and heat can be divided into two parts: ktotal = kdark + klight, where kdark and klight are the rate constants caused by heat and light, respectively. The klight can be expressed as klight = Alight x E x exp(-Ea,light/RT). Where E is the illuminance of light, Alight is an experimental constant related to light sources, and Ea,light is an experimental constant.</p><p><b>CONCLUSION</b>Because the form of klight is similar to the Arrhenius equation, it is suggested that Ea,light might be the observed activation energy of the rate-determining step of the subsequent processes of the photochemical reaction. This viewpoint is supported by the fact that the Ea,light is independent of light sources.</p>
Subject(s)
Drug Stability , Hot Temperature , Injections , Light , Mathematics , Procaine , Chemistry , Radiation EffectsABSTRACT
<p><b>AIM</b>To simplify the study on the effect of relative humidity and temperature on drug stability.</p><p><b>METHODS</b>The stability of penicillin potassium as a model was studied with programmed humidifying and heating.</p><p><b>RESULTS</b>Results of our programmed humidifying and heating experiments are comparable to those of traditional experiment at constant humidity and temperature.</p><p><b>CONCLUSION</b>Programmed humidifying and heating experiments are applicable to drug stability study.</p>
Subject(s)
Drug Stability , Hot Temperature , Humidity , Penicillins , ChemistryABSTRACT
<p><b>AIM</b>To study the effect of both light and heat on the stability of furacilin aqueous solution and the probability of substituting for isothermal accelerated tests by nonisothermal accelerated tests upon exposure to light at high temperatures.</p><p><b>METHODS</b>The isothermal and nonisothermal accelerated tests were employed. The accelerated tests were proceeded in the dark and exposed to light at high temperature. Tungsten, ultraviolet and fluorescent lamps were employed in exposure tests.</p><p><b>RESULTS</b>The degradation of furacilin aqueous solution in isothermal heating experiments or the exposure experiments to light at high temperatures obeys zero-order kinetics. The total degradation rate constant k caused by both light and heat can be divided into two parts: k = kdark + klight, where kdark and klight are the degradation rate constant caused by heat and light, respectively. The klight can be expressed as klight = Alight.exp(-Ea,light/RT).E, where E is the illuminance of light; Alight and Ea,light are both experimental constants. The parameters obtained in nonisothermal accelerated tests were comparable to those obtained in classic isothermal accelerated tests.</p><p><b>CONCLUSION</b>Nonisothermal accelerated tests may substitute for isothermal accelerated tests during the study of the effects of both light and heat on the stability of drugs, in order to save time, labor and drugs.</p>