The Effects of Dietary Restriction and Aging on in Vivo and in Vitro Binding of Aflatoxin B_1 to Cellular DNA

Laboratory animals maintained on a reduced calorie but nutritionally adequate diet have extended life spans and lowered incidences of spontaneous and chemically induced cancers compared to ad libitum- fed counterparts. Many of the effects of dietary restriction on laboratory animals have been suggested to be related to a deceleration of the aging process. The inhibition of age-related changes in xenobiotic metabolizing enzyme activities by dietary restriction has previously been reported. Alterations of these enzyme activities may cause changes in metabolic activation of carcinogens and, therefore, carcinogen-DNA binding. DNA-repair capability has also been reported to be enhanced in diet-restricted rats. Using AFB1 as a model carcinogen, we have studied in vivo and in vitro hepatic AFB1 -DNA binding, demonstrating that dietary restriction (60% of ad libitum consumption) may decrease the metabolic activation of AFB1, and subsequently reduce AFB 1-DNA binding. Our preliminary results obtained from the AFB 1-DNA binding experiments in isolated hepatocytes suggest that the observed age-dependent reduction in AFB 1-DNA binding which may be attributed to a loss of metabolic activating capability was delayed in the diet-restricted rats.

Experimental study on pharmacodynamics of pudilan xiaoyan oral liquid for preventing and treating respiratory virus infection

Background:Pudilan Xiaoyan Oral Liquid(PDL),a famous traditional Chinese formula for treating acute and chronic inflammation.To evaluate the broad-spectrum antiviral effect of Pudilan Xiaoyan Oral Liquid,and provide a basis for clinical medication.Methods:Its inhibitory effect on different respiratory viruses was observed by cytopathic test.The potential mechanism of the anti-influenza effect was determined by neuraminidase activity.In order to observe the therapeutic effect of PDL on viral pneumonia caused by different respiratory viruses.The viral pneumonia model was established by nasal infection with different respiratory viruses,and then PDL was given Therapeutic and prophylactically to evaluate its pharmacodynamic activity in vivo.Results:The results of in vitro experiments showed that PDL had different inhibitory effects on cytopathic effects caused by different respiratory viruses.And it has obvious inhibitory effect on the neuraminidase activity of influenza A virus,which indicates that it exerts anti-influenza virus effect by inhibiting neuraminidase activity of influenza virus.The results in vivo showed that PDL exhibited an inhibitory effect on pulmonary index(PI)and effectively reduced the degree of lesions in the lungs.The lethal rate of mice was significantly decreased while survival time of mice was dramatically increased by PDL treatment in comparison to infection control,respectively.Conclusions:Our study demonstrates that PDL had a significant protection and treatment effect for respiratory virus infection in vitro and in vivo.

Arsenic Induced Inhibition of δ-aminolevulinate DehydrataseActivity in Rat Blood and its Response To Meso2,3-dimercaptosuccinic Acid andMonoisoamyl DMSA

Objective The objective of this study was to investigate arsenic induced changes in blood 8-aminolevulinic acid dehydratase (ALAD) after in vitro and in vivo exposure to this element and its response to co-administration of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) either individually or in combination. Methods Rat whole blood was exposed to varying concentrations (0.1, 0.2 and 0.5 mmol/L) of arsenic (III) or arsenic (V), to assess their effects on blood ALAD activity. Varying concentrations of MiADMSA and DMSA (0.1,0.5 and 1.0 mmol/L) were also tried in combination to determine its ability to mask the effect of arsenic induced (0.5 mmol/L) inhibition of blood ALAD in vitro. In vitro and in vivo experiments were also conducted to determine the effects of DMSA and MiADMSA either individually or in combination with arsenic, on blood ALAD activity and blood arsenic concentration. Results In vitro experiments showed significant inhibition of the enzyme activity when 0.1-0.5 mmol/L of arsenic (III and V) was used. Treatment with MiADMSA increased ALAD activity when blood was incubated at the concentration of 0.1 mmol/L arsenic (III) and 0.1 mmol/L MiADMSA. No effect of 0.1 mmol/L MiADMSA on ALAD activity was noticed when the arsenic concentration was increased to 0.2 and 0.5 mmol/L. Similarly, MiADMSA at a lower concentration (0.1 mmol/L) was partially effective in the turnover of ALAD activity against 0.5 mmol/L arsenic (III), but at two higher concentrations (0.5 and 1.0 mmol/L) a complete restoration of ALAD activity was observed. DMSA at all the three concentrations (0.1,0.5 and 1.0 mmol/L) was effective in restoring ALAD activity to the normal value. Conclusions The results thus suggest that arsenic has a distinct effect on ALAD activity. Another important toxicological finding of the present study, based on in vivo experiments further suggests that combined administration of DMSA and MiADMSA could be more beneficial for reducing blood ALAD inhibition and blood arsenic concentration than the individual treatment.

Pharmacokinetics and correlation between in vitro release and in vivo absorption of bio-adhesive pellets of panax notoginseng saponins

The present study was designed to prepare and compare bio-adhesive pellets of panax notoginseng saponins(PNS) with hydroxy propyl methyl cellulose(HPMC), chitosan, and chitosan : carbomer, explore the influence of different bio-adhesive materials on pharmacokinetics behaviors of PNSbio-adhesive pellets, and evaluate the correlation between in vivo absorption and in vitro release(IVIVC). In order to predict the in vivo concentration-time profile by the in vitro release data of bio-adhesive pellets, the release experiment was performed using the rotating basket method in p H 6.8 phosphate buffer. The PNS concentrations in rat plasma were analyzed by HPLC-MS-MS method and the relative bioavailability and other pharmacokinetic parameters were estimated using Kinetica4.4 pharmacokinetic software. Numerical deconvolution method was used to evaluate IVIVC. Our results indicated that, compared with ordinary pellets, PNS bio-adhesive pellets showed increased oral bioavailability by 1.45 to 3.20 times, increased Cmax, and extended MRT. What's more, the release behavior of drug in HPMC pellets was shown to follow a Fickian diffusion mechanism, a synergetic function of diffusion and skeleton corrosion. The in vitro release and the in vivo biological activity had a good correlation, demonstrating that the PNS bio-adhesive pellets had a better sustained release. Numerical deconvolution technique showed the advantage in evaluation of IVIVC for self-designed bio-adhesive pellets with HPMC. In conclusion, the in vitro release data of bio-adhesive pellets with HPMC can predict its concentration-time profile in vivo.

Effect of mechanical stresses on degradation behavior of high-purity magnesium in bone environments

High-purity(HP)magnesium(Mg)has emerged as a promising biomaterial for supporting functional bone tissue.Our previous study found that mechanical stresses and the surrounding fibrotic tissue(subcuta-neous)both play crucial roles in the degradation of HP Mg.However,due to challenges in the degradation and regeneration process in vivo,it remains unclear how stress affects HP Mg degradation in bone en-vironments,limiting its further application.In this study,novel loading devices were designed and the effects of tensile and compressive stresses on HP Mg degradation in vivo and in vitro bone environments were quantitatively analyzed.In addition,bone osteointegration around HP Mg was explored preliminar-ily.Tensile stress increases the degradation rate of HP Mg in vivo and in vitro.HP Mg degradation in vivo is more sensitive to stress factors than in vitro,but the sensitivity decreases with corrosion time.The volume loss rate of HP Mg is multilinear with the applied stress and degradation time.The volume of bone tissue surrounding HP Mg is larger in the no-stress group compared to the stressed groups,which is more pronounced with increasing implantation time.These results provide valuable insights for optimiz-ing the design of HP Mg-based implants considering load conditions.This will help to achieve a balance between the degradation rate of the implant and the regeneration rate of the surrounding bone.

Bridging the structure gap between pellets in artificial dissolution media and in gastro-intestinal tract in rats

Changes in structure of oral solid dosage forms(OSDF) elementally determine the drug release and its therapeutic effects.In this research,synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3 D structure of enteric coated pellets recovered from the gastrointestinal tract of rats.The structures of pellets in solid state and in vitro compendium media were measured.Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media.Thus,optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media.The sphericity,pellet volume,pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for2 h were recorded 0.47,1.55 × 10^(8)μm^(3),0.44 × 10^(8)μm^(3)and 27.6%,respectively.After adding pepsin and glass microspheres,the above parameters in vitro reached to 0.44,1.64 × 10^(8)μm^(3)0.38 × 10^(8)μm^(3)and 23.0%,respectively.Omeprazole magnesium pellets behaved similarly.The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3 D structures to ensure better design,characterization and quality control of advanced OSDF.

Anthelmintic, antimicrobial, antioxidant and cytotoxic activity of Caltha palustris var. alba Kashmir, India

The methanolic extract obtained from the root portion of Caltha palustris var. alba was evaluated for its anthelmintic efficacy against gastrointestinal nematodes of sheep under both in vitro and in vivo conditions using worm motility inhibition(WMI) assay and fecal egg count reduction(FECR) assay, respectively. The extract was subjected to antimicrobial activity using agar-well diffusion method against different bacterial strains. In addition the extract was evaluated for cytotoxic and antioxidant activity against cultured THP-1(Leukemia), A-549(Lung), HCT-15(Colon), Cervix(HeLa) and PC-3(Prostrate) cell lines by SRB and DPPH radical scavenging assays. The extract used resulted in mean %WMI of 94.44%, as observed when the worms were put in lukewarm buffer for 30 min after exposure to different treatments. The mean mortality index of the sample was 0.95. The lethal concentration(LC50) was 0.11 mg·mL-1. Cell lines were exposed to concentration of 100 μg·mL-1 of extract for 48 h, which reduced the viability of these cell lines. The same plant extract also showed 55.58% DPPH radical scavenging activity.

The KiSS-1/GPR54 system:Essential roles in physiological homeostasis and cancer biology

KiSS-1,first identified as an anti-metastasis gene in melanoma,encodes C-terminally amidated peptide products,including kisspeptin-145,kisspeptin-54,kisspeptin-14,kisspeptin-13 and kisspeptin-10.These products are endogenous ligands coupled to G protein-coupled receptor 54(GPR54)/hOT7T175/AXOR12.To date,the regulatory activities of the KiSS-1/GPR54 system,such as puberty initiation,antitumor metastasis,fertility in adulthood,hypothalamic-pituitary-gonadal axis(HPG axis)feedback,and trophoblast invasion,have been investigated intensively.Accumulating evidence has demonstrated that KiSS-1 played a key role in reproduction and served as a promising biomarker relative to the diagnosis,identification of therapeutic targets and prognosis in various carcinomas,while few studies have systematically summarized its subjective factors and concluded the functions of KiSS-1/GPR54 signaling in physiology homeostasis and cancer biology.In this review,we retrospectively summarized the regulators of the KiSS-1/GPR54 system in different animal models and reviewed its functions according to physiological homeostasis regulations and above all,cancer biology,which provided us with a profound understanding of applying the KiSS-1/GPR54 system into medical applications.