Megastigmane glycosides from the traditional Uighur medicine Cydonia oblonga Mill.

Phytochemical investigation on the fruits of Cydonia oblonga Mill., a traditional Uighur medicine, led to the isolation of seven undescribed and nine known megastigmane glycosides. Their structures including absolute configurations were characterized by an extensive analysis of spectroscopic data including HRESIMS and NMR, combined with ECD calculations. Additionally, compounds 1, 2, 4, and 6-16 exhibited anti-inflammatory activity by inhibiting the secretion of cytokines TNF-α and IL-6 in RAW264.7 cells induced by lipopolysaccharides (LPS) with inhibitory rates of 10.79%-44.58% at 20 µM.

Clerodane diterpenoids from the Uygur medicine Salvia deserta with immunosuppressive activity.

Six undescribed clerodane diterpenoids along with five known ones were isolated from the aerial parts of Salvia deserta, a traditional Uygur medicine. Their chemical structures including absolute configurations were elucidated by extensive spectroscopic analysis (including 1D and 2D NMR, HRESIMS, and IR), combined with calculated ECD method and single-crystal X-ray diffraction analysis. All the compounds possessed a terminal α,ß-unsaturated-γ-lactone moiety, and were assayed for their immunosuppressive activity via inhibiting the secretion of cytokines TNF-α and IL-6 in macrophages RAW264.7. Among them, (5R,8R,9S,10R)-18-nor-cleroda-2,13-dien-16,15-olide-4-one obviously suppressed the secretion of TNF-α and IL-6 with IC50 values of 8.55 and 13.65 µM, respectively.

Rhodol-derived turn-on fluorescent chemosensor for ultrasensitive detection of nitroreductase activity in bacteria and bioimaging in oral cancer cells.

The detection of intracellular nitroreductase (NTR) activity is important for the study of hypoxia in organisms. In the present study, a Rhodol-derived fluorescent chemosensor (Rhod-NO2) was synthesized in a one-step procedure. Rhod-NO2 exhibits 110-fold fluorescence enhancement in the presence of NTR. Moreover, Rhod-NO2 demonstrates high NTR selectivity and sensitivity (LOD, 0.6 ng/mL). The mode of Rhod-NO2 binding to NTR was also revealed by molecular docking. In addition, the reaction and luminescence mechanisms were evaluated by MS and TDDFT theoretical calculations, respectively. Finally, Rhod-NO2 was successfully applied to monitor NTR production during Escherichia coli (E. coli) growth, and to visually analyze NTR production in malignant oral cancer cells under hypoxia. Thus, Rhod-NO2 represents a new molecular tool to further understanding of the biological function of NTR.

A highly responsive, sensitive NIR fluorescent probe for imaging of superoxide anion in mitochondria of oral cancer cells.

Superoxide anion (O2•-) is an important biomarker for reactive oxygen species (ROS) generated through physiological and pathological processes. However, due to the short half-life of O2•- and high autofluorescence of cell tissues, in situ real-time tracking and monitoring of endogenous O2•- can be difficult. In this paper, a fluorescent probe IFP-O2 was developed to detect endogenous O2•- in cells. The probe could instantaneously react with O2•- to produce fluorescence off-on effect; its detection limit was as low as 10 nM. Cell experiments also showed that the probe had low toxicity and mitochondrial targeting ability. The article presents, for the first time, a probe that can be employed to measure endogenous O2•- in oral cancer Cal-27 cells and is a promising tool for monitoring and evaluating apoptosis.

One step synthesis of red-emitting fluorescence turn-on probe for nitroreductase and its application to bacterial detection and oral cancer cell imaging.

Nitroreductase (NTR) belongs to a class of flavin mononucleotide-dependent and flavin adenine dinucleotide-dependent cytoplasmic enzymes; its contents in tumor cells increase during hypoxia. The development of fluorescent probes for detection of NTR activity is of great significance for the study of the state of hypoxia in living organisms. In this paper, a red-emitting fluorescence turn-on probe EBI-NO2 was synthesized using a one-step method. The fluorescence of the probe was enhanced by 60 folds in the presence of NTR. The probe also had high selectivity towards NTR, and its detection limit was as low as 1 ng/mL. The reaction mechanism was verified using MS, molecular docking and theoretical calculations. In addition, it was successfully applied in real-time monitoring of NTR produced during growth of Escherichia coli (BL21) and in visualization of NTR in oral cancer cells (Cal-27) under hypoxia. This work provides a new imaging tool that can be applied to investigate the physiological and pathological changes in hypoxia oral cells.

A novel near-infrared fluorescent probe for the dynamic monitoring of the concentration of glutathione in living cells.

In this study, a water-soluble, near-infrared fluorescent probe (EQR-S) was designed for the measurement of the glutathione (GSH) concentration. Responses of different interfering substances to the developed probe were investigated, and the luminescence mechanism was examined by theoretical calculations. Results revealed that EQR-S can be applied for the rapid, sensitive determination of the GSH concentration with a detection limit of 69 nM. Based on the above advantages, EQR-S was successfully applied to investigate the fluctuation in the GSH concentration of living cells under high-temperature stress.

Progress in the study of association between cellular senescence and organ fibrosis / 药学学报

Deformation or failure of organs is the final stage involving fibrosis, caused by fibrous scars composed of excess extracellular matrix proteins. Cellular senescence means a stable stagnation state with no proliferation, during which the senescent cells maintain biochemical metabolism but promote excessive expression of extracellular matrix proteins due to secreting inflammatory factors, which contribute to the development of various organ fibrosis including myocardial fibrosis, and pulmonary fibrosis. It has been shown that both the incidence of organ fibrosis and the number of senescent cells increase with age. This review mainly summarizes mechanisms of cellular senescence and its contribution to the process of various organ fibrosis. Current anti-fibrotic drug therapy focused on cellular senescence is discussed. Cellular senescence has profound implications in the pathogenesis of fibrotic diseases and provides a new target for new effective treatments.

The effect of short-term exposure to ambient NO2 on lung function and fractional exhaled nitric oxide in 33 chronic obstructive pulmonary disease patients / 中华预防医学杂志

Objectives@#To investigate the effect of short-term exposure to ambient NO2 has influence on lung function and fractional exhaled nitric oxide (FeNO) in chronic obstructive pulmonary disease (COPD) patients.@*Methods@#A panel of doctor-diagnosed stable COPD patients (n=33) were recruited and repeatedly measured for lung function and FeNO from December 2013 to October 2014. The patients who lived in Beijing for more than one year and aged between 60 and 85 years old were included in the study. We excluded patients with asthma, bronchial tensor, lung cancer and other respiratory disorders other than chronic obstructive pulmonary disease and occupational exposure and chest trauma surgery patients. Because the frequency of each subject visiting to the hospital was different, a total of 170 times of lung function measurements and 215 times of FeNO measurements were conducted. At the same time, the atmospheric NO2 data of Beijing environmental monitoring station near the residence of each patient during the study period were collected from 1 day to 7 days lag before the measurement. Effects of short-term NO2 exposure on lung function and FeNO in COPD patients were estimated by linear mixed-effects models.@*Results@#The subjects' forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), and exhaled NO of subjects were (3.26±0.83) L, (1.66±0.61) L, (4.13±1.77) L/s, and (48.99±14.30) μg/m3, respectively. The concentration of NO2 was (70.3±34.2) μg/m3 and the interquartile range (IQR) was 39.0 μg/m3. Short-term exposure to NO2 resulted in a significant decrease in FVC among COPD patients' which was most obvious in 2 days lag. Every quartile range increased in NO2 (39 μg/m3, 2 day) would cause a 1.84% (95%CI: -3.20%- -0.48%) reduction in FVC. The effects of exposure to higher concentration of NO2 (≥58.0 μg/m3) on FVC estimate was -2.32% (95%CI: -4.15%- -0.48%)(P=0.02). No significant relevance of FeNO and NO2 was observed in this study.@*Conclusions@#Short term exposure to ambient NO2 may bring down pulmonary function in COPD patients.

Calcitonin gene-related peptide protects rats from cerebral ischemia/reperfusion injury via a mechanism of action in the MAPK pathway.

The aim of the present study was to investigate the protective function and underlying mechanism of calcitonin gene-related peptide (CGRP) on cerebral ischemia/reperfusion damage in rats. Adult male Wistar rats were selected for the establishment of an ischemia/reperfusion injury model through the application of a middle cerebral artery occlusion. Animals were randomly divided into 6 groups of 24 animals. Drugs were administered according to the design of each group; animals were administered CGRP, CGRP8-37, PD98059 and SB20358. The neurobehavioral scores of the rat cerebral ischemia model in each group were calculated. The infarction range of the rat brain tissues was observed by 2,3,5-triphenyltetrazolium chloride staining. The expression levels of three proteins, phosphorylated c-Jun N-terminal kinase (JNK)/JNK, phosphorylated extracellular signal-regulated protein kinase (ERK)/ERK and p-p38/p38, in the mitogen-activated protein kinase (MAPK) pathway in the brain tissues was detected by western blotting. The results showed that CGRP could improve the neurobehavioral function of the ischemic rats and reduce the infarction range. Western blotting results confirmed that the function of the CGRP was mediated mainly through the reduction of the JNK and p38 phosphorylation and the promotion of ERK phosphorylation. Therefore, the present study confirmed that an increase in the exogenous CRGP could effectively improve ischemia/reperfusion injury of the brain tissue. The mechanisms of action were achieved through a reduction in JNK and p38 phosphorylation and an increase in ERL phosphorylation in the MAPK pathway. These mechanisms were interdependent.

Effect of air pollution on health service demand of the elderly and middle-age patients with hypertension,cardiovascular and cerebrovascular diseases:based on analysis of data from CHARLS / 北京大学学报(医学版)

Objective:To study the association of air pollution with health service demand of the elderly and middle-age patients with cardiovascular and cerebrovascular diseases,and to provide a scientific ba-sis for development of environmental protection policy and health service policy of the Chinese govern-ment.Methods:This study included survey data on self-evaluated health,outpatient service demand and inpatient service demand of the patients with hypertension,heart disease and stroke in 62 cities of 1 7 provinces from China Health and Retirement Longitudinal Study(CHARLS)in 201 1 and 201 3,and com-bined it with the data on the annual concentrations of inhalable particulate matter(PM1 0 ),sulfur dioxide (SO2 )and nitrogen dioxide(NO2 )of those provinces and cities.Conditional Logistic regression was car-ried out to assess the possible effects of air pollutants on self-evaluated health and health service utiliza-tion.Results:The results showed that turning points existed in the effects of concentrations of NO2 and SO2 on the health service demand of the patients with hypertension,heart disease and stroke.The inpa-tient service demand of the hypertension patients increased with NO2 concentration when it was lower than 35.1 μg/m3 and decreased with NO2 concentration for higher value.Self-evaluated health of the patients with heart disease and stroke decreased with SO2 concentration when it was lower than 63.8 μg/m3 and increased with SO2 concentration for higher value.In addition,no evidence was found for the association between PM1 0 and health service demand.Conclusion:Air pollution may have effects on health service demand of the patients with hypertension,cardiovascular and cerebrovascular diseases,and different air pollutants at high or low concentration may have different health effects.

Dipeptidyl peptidase IV activity in patients with ACE-inhibitor-associated angioedema.

Bradykinin and substance P have been implicated as mediators in angiotensin-converting enzyme inhibitor (ACEI)-associated angioedema. Studies investigating the metabolism of bradykinin in sera from patients with a history of ACEI-associated angioedema and controls suggest that there is a defect in a non-ACE, non-kininase I pathway of bradykinin degradation, such as the aminopeptidase P (APP)/dipeptidyl peptidase IV (DPPIV) pathway. This study tested the hypothesis that serum APP or DPPIV activity is decreased in patients with ACEI-associated angioedema. APP and DPPIV activity were measured in sera collected from patients during ACEI-associated angioedema, from patients with a remote history of ACEI-associated angioedema, and from normotensive and untreated hypertensive controls. The effects of acute and chronic ACEI and corticosteroid treatment on serum DPPIV activity were also assessed. DPPIV activity was similar in normotensive volunteers (37.8 +/- 6.3 nmol/mL per min), in untreated hypertensive subjects who had been exposed previously to ACEI without angioedema (36.2 +/- 4.3 nmol/mL per min), in hypertensive patients with a remote history of angioedema (35.1 +/-8.5 nmol/mL per min), and in chronically ACEI-treated hypertensive subjects (36.1 +/- 5.6 nmol/mL per min). DPPIV activity decreased with increasing age (R(2)=0.10, P=0.016). Subject group significantly affected DPPIV activity (F=6.208, P=0.016) such that DPPIV activity was significantly lower in patients with ACEI-associated angioedema (26.9 +/- 4.1 nmol/mL per min) than in normotensive controls, in previously ACEI-exposed untreated hypertensive volunteers, or in ACEI-treated hypertensive volunteers, even after controlling for age. There was no effect of acute ACE inhibition or corticosteroids on DPPIV activity. With respect to APP activity, there was no difference between groups. These results suggest that DPPIV activity is depressed in individuals with hypertension during acute ACEI-associated angioedema.