Endogenous sulfur dioxide deficiency as a driver of cardiomyocyte senescence through abolishing sulphenylation of STAT3 at cysteine 259.

OBJECTIVE: Cardiomyocyte senescence is an important contributor to cardiovascular diseases and can be induced by stressors including DNA damage, oxidative stress, mitochondrial dysfunction, epigenetic regulation, etc. However, the underlying mechanisms for the development of cardiomyocyte senescence remain largely unknown. Sulfur dioxide (SO2) is produced endogenously by aspartate aminotransferase 2 (AAT2) catalysis and plays an important regulatory role in the development of cardiovascular diseases. The present study aimed to explore the effect of endogenous SO2 on cardiomyocyte senescence and the underlying molecular mechanisms. APPROACH AND RESULTS: We interestingly found a substantial reduction in the expression of AAT2 in the heart of aged mice in comparison to young mice. AAT2-knockdowned cardiomyocytes exhibited reduced SO2 content, elevated expression levels of Tp53, p21Cip/Waf, and p16INk4a, enhanced SA-ß-Gal activity, and elevated level of γ-H2AX foci. Notably, supplementation with a SO2 donor ameliorated the spontaneous senescence phenotype and DNA damage caused by AAT2 deficiency in cardiomyocytes. Mechanistically, AAT2 deficiency suppressed the sulphenylation of signal transducer and activator of transcription 3 (STAT3) facilitated its nuclear translocation and DNA-binding capacity. Conversely, a mutation in the cysteine (Cys) 259 residue of STAT3 blocked SO2-induced STAT3 sulphenylation and subsequently prevented the inhibitory effect of SO2 on STAT3-DNA-binding capacity, DNA damage, and cardiomyocyte senescence. Additionally, cardiomyocyte (cm)-specific AAT2 knockout (AAT2cmKO) mice exhibited a deterioration in cardiac function, cardiomegaly, and cardiac aging, whereas supplementation with SO2 donors mitigated the cardiac aging and remodeling phenotypes in AAT2cmKO mice. CONCLUSION: Downregulation of the endogenous SO2/AAT2 pathway is a crucial pathogenic mechanism underlying cardiomyocyte senescence. Endogenous SO2 modifies STAT3 by sulphenylating Cys259, leading to the inhibition of DNA damage and the protection against cardiomyocyte senescence.

Endogenous Taurine Downregulation Is Required for Renal Injury in Salt-Sensitive Hypertensive Rats via CBS/H2S Inhibition.

Although taurine is known to exert an antihypertensive effect, it is unclear whether it is involved in the mechanism for hypertension-related target organ injury. To reveal the role of endogenous taurine in renal injury formation during salt-sensitive hypertension and clarify its mechanisms, both salt-sensitive Dahl rats and salt-resistant SS-13BN rats were fed a high-salt diet (8% NaCl) and given 2% taurine for 6 weeks. Rat systolic blood pressure (SBP) was measured by the tail-cuff method and artery catheterization. Kidney ultrastructure was observed under an electron microscope. Taurine content and mRNA and protein levels of taurine synthases, cysteine dioxygenase type 1 (CDO1) and cysteine sulfinic acid decarboxylase (CSAD), were decreased in Dahl rats fed a high-salt diet. However, taurine supplementation and the resulting increase in renal taurine content reduced the increased SBP and improved renal function and structural damage in high-salt diet-fed Dahl rats. In contrast, taurine did not affect SS-13BN SBP and renal function and structure. Taurine intervention increased the renal H2S content and enhanced cystathionine-ß-synthase (CBS) expression and activity in Dahl rats fed a high-salt diet. Taurine reduced the renin, angiotensin II, and aldosterone contents and the levels of oxidative stress indices in Dahl rat renal tissues but increased antioxidant capacity, antioxidant enzyme activity, and protein expression. However, taurine failed to achieve this effect in the renal tissue of SS-13BN rats fed a high-salt diet. Pretreatment with the CBS inhibitor HA or renal CBS knockdown inhibited H2S generation and subsequently blocked the effect of taurine on renin, superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2) levels in high-salt-stimulated Dahl renal slices. In conclusion, the downregulation of endogenous taurine production resulted in a decrease in the renal CBS/H2S pathway. This decrease subsequently promoted renin-angiotensin-aldosterone system (RAAS) activation and oxidative stress in the kidney, ultimately contributing to renal injury in salt-sensitive Dahl rats.

Background and fingerprint characteristics of anthropogenic 236U and137Cs in soil and road dust samples collected from Beijing and Zhangjiakou, China.

236U has attracted more attention as an environmental tracer in recent years. However, in-depth study of 236U in terrestrial environments is still rare in China. Data on 236U and 137Cs concentrations in soil and road dust samples collected from Beijing and Zhangjiakou, China were obtained to demonstrate the background and distinct characteristics of anthropogenic 236U and 137Cs. 236U and 137Cs were detected in the range of (1.10-7.90) × 107 atoms g-1 and below the method limits of detection to 5.30 Bq kg-1. A clear characteristic was observed in road dust, where 236U concentrations increased with decreasing of sample particle size. Soil samples showed an irregular characteristic, but the highest 236U concentrations were observed in particle size fraction of <0.053 mm in both samples. This phenomenon was caused by U chemical properties, higher specific surface areas and organic compounds in fine particles. Anthropogenic radionuclides fingerprint characteristics in <0.053 mm samples were specially discussed. 236U/238U atom ratios were detected in the range of (0.627-3.38) × 10-8. A weak correlation between anthropogenic 236U and natural U isotopes were observed. The intermediate correlation between 236U and 137Cs indicated somewhat distinct migration behavior of these two radionuclides in soil after release to the environment. The released amount of 236U from global fallout during the period of atmospheric nuclear weapons testing was roughly estimated to be 1300 ± 448 kg. These results could be used as fingerprint information for anthropogenic 236U migration behavior and tracer application in environment.

Gambogic acid inhibits proliferation and induces apoptosis of human acute T­cell leukemia cells by inducing autophagy and downregulating ß­catenin signaling pathway: Mechanisms underlying the effect of Gambogic acid on T­ALL cells.

The main active compound of Garcinia hanburyi (referred to as gamboge) is gambogic acid (GA), which has long been a Chinese herbal medicine for treating several types of cancer. However, the potential therapeutic role and mechanisms of GA in T­cell acute lymphoblastic leukemia (T­ALL) remain unclear. In the present study, the effects of GA on proliferation, cell cycle, apoptosis, and autophagy in T­ALL cell lines were investigated. The possible mechanisms underlying GA activity were also examined. The results showed that GA inhibited proliferation, induced apoptosis, and activated autophagy in T­ALL cell lines (Jurkat and Molt­4 cells). Findings confirmed that GA has an antileukemia effect against peripheral blood lymphocyte cells in patients with ALL. GA inhibited phospho­GSK3ß S9 (p­GSK3ß S9) protein levels to inactivate Wnt signaling and suppress ß­catenin protein levels. In addition, the inhibitory effect of GA on T­ALL was reversed by overexpression of ß­catenin. Thus, GA can inhibit the growth and survival of T­ALL cells. GA also had antileukemic activity, at least in part, through the downregulation of the Wnt/ß­catenin signaling pathway.

236U and radiocesium in river bank soil and river sediment in Fukushima Prefecture, after the Fukushima Daiichi Nuclear Power Plant accident.

Almost 8 years after the Japanese Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, data for 236U and 236U/238U have mainly remained limited to only a few heavily contaminated samples. In the present study, activities of 236U, 134Cs, and 137Cs, along with 234U, 235U, 238U, in 15 river bank soil and 10 river sediment samples, were measured by ICP-MS/MS and γ spectrometry. The 134Cs activities and 134Cs/137Cs activity ratios (decay-corrected to March 11, 2011) in these 15 river bank soil samples were from 74.8 to 3.88 × 105 Bq kg-1 and from 0.944 to 1.02, respectively; and in these 10 river sediment samples were from 87.1 to 1.86 × 105 Bq kg-1 and from 0.904 to 0.990, respectively. The 236U activities and 236U/238U atom ratios in these soil samples were in the respective ranges of (0.139-17.6) × 10-5 Bq kg-1 and (0.259-3.83) × 10-8; and in these sediment samples were in the respective ranges of (0.884-27.0) × 10-5 Bq kg-1 and (1.12-5.04) × 10-8. For one river sediment core sample, 134Cs and 236U activities decreased with the depth indicating 134Cs and 236U accumulated in the river sediment with time. Unlike 134Cs, no clear evidence of FDNPP accident-derived 236U has been found in this study, although further monitoring is encouraged to establish the background database on 236U/238U for its potential application as a tracer in environmental studies.

First report on global fallout 236U and uranium atom ratios in soils from Hunan Province, China.

More nuclear power plants continue to be built in China. Due to its long half-life, radiotoxicity and potential application as an environmental tracer, 236U is one of the most important artificial radionuclides deserving more study since activity data are important for risk assessment. However, the ultra-trace activity of 236U and its dilution by natural uranium isotopes make it difficult to distinguish its sources and there are only limited global fallout 236U data for present in Chinese environmental samples. In order to understand the background levels for uranium isotopes, especially 236U, and clarify their sources, inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) was applied to analyze uranium isotopes in 48 soil samples from Hunan Province, China. The 234U, 235U, 238U and 236U concentrations were measured as 9.91-33.7, 0.312-1.43, 6.63-28.7 Bq kg-1 and (1.61-21.3) × 107 atoms g-1, while, the 236U/238U, 234U/238U and 235U/238U atom ratios were (0.470-4.91) × 10-8, (5.10-9.31) × 10-5, and (7.11-7.82) × 10-3, respectively. The uranium isotopic fractionation may be due to irrigation of the agricultural lands where the samples were collected. Considering the facts that neither previous nuclear tests nor nuclear accidents had occurred in Hunan Province and the present 236U/238U atom ratios were included in the range of global fallout values in other areas, it may be concluded that 236U in soils from Hunan Province is mainly from global fallout. To the best of the authors' knowledge, the presence of global fallout 236U in soil samples from China has been confirmed for the first time, and these values may be useful as background data for risk assessment in the future.

Isotopic compositions of 236U, 239Pu, and 240Pu in soil contaminated by the Fukushima Daiichi Nuclear Power Plant accident.

Six years after the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, data for 236U and 236U/238U have remained limited to a few heavily contaminated samples. In the present study, activities of 236U, 239Pu, and 240Pu, along with other U isotopes in 46 soil samples both heavily and lightly contaminated by this accident were measured by inductively coupled plasma-mass spectrometry (ICP-MS) and triple-quadrupole ICP-MS. The 236U activities and 236U/238U atom ratios in these soil samples were in the range of (0.469-24.4) × 10-5 Bq kg-1 and ((0.099-1.35) × 10-7), respectively. Higher 240Pu/239Pu atom ratios (0.245-0.312) and 238Pu/239+240Pu activity ratios (0.859-1.62) indicated Pu contamination originated from this accident and global fallout in some samples. For those soil samples along with black substances collected along roads in Fukushima Prefecture, high linear correlations were presented between 236U activities and 239+240Pu activities (Pearson's r = 0.755, p < 0.01), and between 236U activities and 238Pu activities (Pearson's r = 0.844, p < 0.01). The analysis of these soil samples confirmed the release of 236U, although in trace amounts, during the FDNPP accident.

[Influence of photoselective vaporization of the prostate on the sexual function of the patient].

n recent years, photoselective vaporization of the prostate (PVP) has gained a wide clinical application in the treatment of benign prostatic hyperplasia (BPH) for its satisfactory effect, high safety, and low incidence of complications. With the improvement of living conditions, BPH patients are paying more attention to their sexual function, especially erectile function and ejaculatory problems instead of just focusing on the alleviation of lower urinary tract symptoms. Few studies of PVP, however, relate to its association with the sexual function of the patient and there is a certain controversy over the influence of PVP on it in the existing literature. Prevailing views hold that the uprated power in PVP does not affect erectile function or increase the risk of retrograde ejaculation (REj) and that PVP is even better than transurethral resection of the prostate (TURP) in avoiding the risk of REj.

Determination of pesticide residues in tea by gas chromatography/triple quadrupole mass spectrometry with solid-phase extraction.

An analytical method was developed for determination of multipesticide residues, including organophosphorus, organohalogen, pyrethroid, and organonitrogen, in tea at trace levels by GC coupled with triple quadrupole mass chromatography (QqQ-MS/MS). Scan time was selected in order to optimize QqQ-MS/MS conditions. The key parameters for controlling cleanup performance were optimized, including SPE cartridge type and elution solvent volume. Acetonitrile was the extraction solvent, and a novel multilayer SPE cartridge, Cleanert TPT, was used in the cleanup step. The recoveries of the studied pesticides at 5.0, 10.0, and 25.0 microg/kg were in the range of 77.8 to 103.8% with an RSD of less than 14%. Determination coefficient (R2) values between 0.9951 and 0.9998 were obtained for all target compounds. The LOD was between 0.002 and 1.0 microg/kg, and LOQs were 0.0066-3.3 microg/kg, which satisfied the maximum residue limits for pesticides in tea recommended by the European Union and Japan. The optimized method was applied to the analysis of real tea samples obtained from the local market.

[Yimusake Tablet: safe and efficacious for premature ejaculation].

OBJECTIVE: To objectively evaluate the efficacy and safety of Yimusake Tablet in the treatment of premature ejaculation (PE) through a multi-centered large-sample trial. METHODS: We conducted a multi-centered, open, fixed-dose, and self-compared clinical trial among 300 patients with diagnosed PE. The trial lasted 12 weeks, including 4 weeks without any medication and 8 weeks of treatment with Yimusake Tablet, 2 pills (1 g) per night. We observed the intravaginal ejaculation latency time (IELT) before and after treatment, evaluated the safety of medication, and performed a questionnaire investigation on the patients' satisfaction. RESULTS: Of the 300 PE patients, 288 accomplished the clinical trial. The patients ranged in age from 22 to 60 years, averaging at 31.6 years. The mean IELT of the patient was 62.5 seconds at baseline, 168.9 seconds after 4 weeks of treatment with Yimusake Tablet, and 222.2 seconds after 8 weeks of medication. Among the 157 patients with normal erectile function (IIEF >21), the mean IELT was 71.4 seconds before treatment, 147.4 seconds after 4 weeks of medication, and 172.5 seconds after 8 weeks of medication. The patients' satisfaction was significantly increased after treatment. Those complicated by mild to moderate erectile dysfunction achieved different degrees of improvement in the IIEF-5 score, with a mean increase of 3.8. Only a few patients experienced mild adverse events, including constipation, dry mouth, nose bleeding, abdominal pain, and lumbosacral pain, which were all relieved without drug withdrawal. CONCLUSION: Yimusake Tablet is a safe and effective medicine for the treatment of PE.

[Influence of photoselective vaporization of prostate on erectile function in patients with benign prostatic hyperplasia].

OBJECTIVE: To assess the influence of photoselective vaporization of the prostate (PVP) on the erectile function of the patient with benign prostatic hyperplasia (BPH). METHODS: Using IIEF-5, we conducted a questionnaire investigation among 210 BPH patients before and after treated by PVP (n = 80) and transurethral resection of the prostate (TURP, n = 130). We also reviewed the clinical data and compared the pre- and post-operative penile erectile function between the two groups of patients. RESULTS: Follow-up was completed in 76 cases of PVP and 123 of TURP. The baseline data showed no statistically significant differences between the two groups in age, prostate volume, IPSS, QOL, Qmax, post void urine residual volume and IIEF-5 scores (P>0.05). Compared with the IEFF-5 score at the baseline (21.88 +/- 2.46), those at 3, 6 and 12 months after PVP were 16.72 +/- 3.17, 19.34 +/- 2.46 and 19.29 +/- 2. 18, respectively, significantly decreased at 3 months (P = 0.042), but with no remarkable difference at 6 and 12 months (P >0.05). Nor were there significant differences in the IIEF-5 score between the PVP and TURP groups at any time points (P>0.05). At 6 months after surgery, the incidence rates of erectile dysfunction were 11.7% and 13.7% in the TURP and PVP groups, respectively (P>0.05). CONCLUSION: PVP may reduce erectile function in some cases in the early stage after surgery, but this adverse effect does not last long and is basically similar to that of TURP.

Effects of Tongxinluo-facilitated cellular cardiomyoplasty with autologous bone marrow-mesenchymal stem cells on postinfarct swine hearts.

BACKGROUND: Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo (TXL) treatment around the transplantation of mesenchymal stem cells (MSCs) can improve survival and subsequent activities of implanted cells in swine hearts with acute myocardial infarction (AMI) and reperfusion. METHODS: Twenty-eight Chinese mini-pigs were divided into four groups including a control group (n = 7); group 2, administration of low-dose TXL alone from the 3rd day prior to AMI to the 4th day post transplantation (n = 7); group 3, MSCs alone (n = 7) and group 4, TXL + MSCs (n = 7). AMI models were made by occlusion of the left anterior descending coronary artery for 90 minutes. Autologous bone marrow-MSCs (3 x 10(7) cells/animal) were then injected into the post-infarct myocardium immediately after AMI and reperfusion. The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were obtained at baseline (1 week after transplantation) and endpoint (6 weeks after transplantation) by single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Apoptosis was detected by TUNEL assay and the oxidative stress level was investigated in the post-infarct myocardium at endpoint. RESULTS: At endpoint, there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4 than in the control group. In group 4 the survival and differentiation of implanted MSCs were significantly improved more than that seen in group 3 alone (P < 0.0001); the capillary density was also significantly greater than in the control group, group 2 or 3 both in the infarcted zone (P < 0.0001) and the peri-infarct zone (P < 0.0001). MRI showed that parameters at baseline were not significantly different between the 4 groups. At endpoint, regional wall thickening and the left ventricular ejection fraction were increased while the left ventricular mass index, dyskinetic segments and infarcted size were decreased only in group 4 compared with control group (P < 0.0001). SPECT showed that the area of perfusion defect was significantly decreased at endpoint only in group 4 compared with control group (P < 0.0001). TUNEL assay indicated that TXL administration significantly decreased cell apoptosis in peri-infarct myocardium in groups 2 and 4. Furthermore, superoxide dismutase (SOD) significantly increased and malondialdehyde (MDA) decreased in groups 2 and 4 by the administration of TXL. CONCLUSIONS: Our study demonstrates the following: (1) immediate intramyocardial injection of MSCs after AMI and reperfusion resulted in limited survival and differentiation potential of implanted cells in vivo, thus being incapable of beneficially affecting post-hearts; (2) TXL-facilitation resulted in a significant survival and differentiation potential of implanted cells in vivo via inhibition of apoptosis and oxidative stress, accompanied by significant benefits in cardiac function.

[Study on anti-tumor effect of dry and fresh Gekko swinhonis freeze-dried powders on mice sarcoma S180 and acute toxicity testing of two powders].

OBJECTIVE: To investigate the anti-tumor activity of dry Gekko swinhonis freeze-dried powder (DGFP) and fresh G. swinhonis freeze-dried powder (FGFP) on mice sarcoma S180 and acute toxicity testing of the two powders. METHOD: Mice xenotransplant model of sarcoma S180 was established. Eighty mice were randomly divided into 8 groups. Control group were orally administrated by saline, another intraperitoneally injected with 5-Fu, the other six groups were orally administrated by DGFP and FGFP, each at three different doses (low, moderate and high). Rate of restraining tumor, index of thymus and spleen were calculated after 10 days' treatment. Acute toxicity testing tried to figure out LDs and LD, of DGFP and FGFP. RESULT: The restraining tumor rates of DGFP and FGFP each at three doses were 31.4%, 50.8%, 37.7% and 14.8%, 19.1%, 54.7%. DGFP and FGFP elevated the thymic weight and thymic index of the mice to different extent. There were no significant differences among the eight groups in their spleen weight and spleen index. Acute toxicity testing did not figure out LD50 of DGFP and FGFP. In LD0 test, the administrating dosages of DGFP and FGFP given to the mice were both more than 2000 times than those given to patients on clinic. The result showed nothing abnormal in DGFP group. Compared with the DGFP and control group there was only a significant body weight decrease (P < 0.01) in the FGFP group in the first three days. However, on the fifth day and the seventh day there was no significant difference. CONCLUSION: DGFP and FGFP have conspicuous anti-tumor effects in vivo. The mechanism may be related to the elevated cellular immune function. Acute toxicity testing reveals that DGFP and FGFP are quite safe for conventional oral use on clinic.

Combinational numeral fingerprint spectra of Glycyrrhiza and analysis of common peak ratio invariableness in HPLC.

To overcome the instability of traditional Chinese medicine (TCM) fingerprint spectra (FPS) and to build up absolute identification standard of TCM, the construction method of combinational numeral fingerprint spectra (CNFPS) was set up. The analysis of invariableness based on CNFPS was carried out. It can be used as absolute quantitative standard to identify the difference of TCM samples. According to this method, the HPLC FPS of components extracted from Glycyrrhiza root samples by ethanol was analyzed. Stable results and accurate quality evaluation were obtained perfectly. The common peak ratio invariableness is an absolute standard in identifying TCM samples, which is better than the similarity method of the FPS.

[Research of high precision of temperature measurement in microwave hyperthermia therapy].

This paper describes a new method of temperature measurement in microwave field. This method resolves a series of problems such as the microwave field suppression, the linearization of the temperature sensor and the sensor exchangeability.

[Research on the hyperthermia-therapy performances of invasive microwave antennas].

The paper introduces four kinds of 2450 MHz antennas including noninsulted (bare), insulated-open-tip (I.O.T.), dipole-type and sleeve invasive microwave ones. The comparison between the antennas' hyperthermia performances in the muscle tissue phantom made by specific absorption rate (SAR) shows that the sleeve antenna is the best. It has a bigger heating range and a changeless shape and is independent of the inserting depth.