Biomedicine & Aging Pathology最新文献

Purpose

Colorectal cancer (CRC) is among the most common malignancies worldwide. Early diagnosis of the progressive tumor disease and control of the effect of therapy in colorectal carcinoma are most frequently performed.

Methods

The purpose of this present work was to evaluate the synergistic responses of a novel chemopreventive combination regimen namely 5-FU and natural coumarin family, UMB to assess the serum tumor markers CEA, CA 19-9 and CA 72-4 for colorectal carcinoma is described according to recently formulated guidelines, in addition of antioxidant and lipid peroxidation status in the serum of 1,2-dimethylhydrazine induced rat colon carcinogenesis.

Results

Administration of DMH resulted in decreased serum levels of antioxidants such as GST, SOD, CAT, GPx, GR, GSH and lipid peroxidation end products such as TBARS, LOOH and CD with concomitant increase in the levels of colon cancer specific serum markers like CEA, CA 19-9 and CA 72-4 levels. Administration of UMB alone and combined forms of UMB with 5-FU to the colon cancer-bearing rats significantly attenuated these alterations which indicates the anticancer effect that was further confirmed by histopathological analysis.

Conclusions

Overall, these findings substantiate the synergistic potential of UMB with 5-FU against chemically-induced colon cancer in rats.

Walnut contains different polyphenolic compounds with antioxidant activities, and it has long been known for its diverse pharmacological activities. However, anti-aging and anti-inflammatory effects of these have not been investigated. The objective of this work was to investigate the ability of Juglans regia kernels to protect mice skin against ultraviolet (UV) radiations-induced damage in vivo. To study the effect of walnut on collagen, the skin of mice was treated with 5% w/w of ethanolic extract of walnut over 12 weeks. The physical parameters, like wrinkle assessment, biochemical parameters evaluation viz. collagen levels, TBARS, GSH, etc. and histological parameters’ evaluations were performed. Conversely, the extract was not able to revive morphological normality of skin, as compared to the standard group (quercetin treated). Histopathological studies confirmed increased protection of the skin by quercetin treatment, rather than crude extract. The extract may owe its protective effect by the extract due to the MMP-1 inhibition in addition to the suppression of MIP-α, thus, downregulating the inflammatory response.

Objective

It is well established that natural autoantibodies are present in sera of healthy individuals and that the level of these antibodies changes with increasing age in humans. Evaluation of the total serum level of IgG and IgM as the main natural autoantibodies provides us with valuable information on their potential role in the aging process. This study aimed to evaluate and compare the changes in the total serum level of IgG and IgM in healthy individuals of different age groups.

Materials and methods

Blood samples (n = 270) were obtained and included in seven age groups ranging from cord blood to the elderly. The concentration of total serum IgG and IgM was assessed using nephelometry. Moreover, the association between the level of total IgG and IgM, and age was determined.

Results

IgG concentration, despite a slight decrease in under 1-year-old infants, followed a rising trend with increasing age. On the other hand, the mean value of total IgM showed an increasing pattern from cord blood up to the middle age (40 years) after which it started to decrease to its lowest level in the elderly. We also found that the drop in the level of IgM level after the middle age was in line with the changes in the frequency of blood B-1 cells, which we reported in our previous study.

Conclusion

Overall, this study showed that the mean serum levels of total IgG and IgM varied with age. In most cases, the differences between mean values of total antibodies at different age intervals were significant. The total amount of both serum IgG and IgM showed an increasing trend ranging from cord blood up to the middle age samples rejecting their role in physiological and pathological processes. Nonetheless, the declining trend observed for IgM from the middle age to the elderly could be partly responsible for the imperfect immune responses and higher rate of pathological disorders observed along with aging.

The study was conducted to evaluate the hepatoprotective potentials of aqueous extracts of Convolvulus pluricaulis leaves against thiocetamide induced liver damage in rats. The acute oral toxicity study was conducted as per OECD guidelines 420 and the extract was proved to be safe up to the dose of 2000 mg/kg. The total duration of the study was 21 days and animals were divided into six groups. Hepatotoxicity was induced in the animals of all groups except normal control by single dose administration of thioacetamide (100 mg/kg) at first day of the study followed by animals were treated daily with standard drug sylimarine and aqueous extract of Convovulus pluricaulis (200 mg/kg, 400 mg/kg and 600 mg/kg) to respective groups for 21 days. Variations in biochemical parameters like alanine transferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP), total bilurubin, direct bilirubin, albumin, total protein, ions and others parameters like clotting time and weight of the liver were considered to determine beneficial effect of the extract. At the end of the study liver samples were collected and subjected to histopathological evaluation. In control animals treated with Thioacetamide alone there were variations in the above-mentioned parameters. But in the animals treated with aqueous extract and standard drug silymarine, all the parameters were normal possibly due to their beneficial property in protecting the liver against thioacetamde induced hepatotoxicity. The results obtained in the above study suggesting that, the aqueous extract of Convolvulus pluricaulis posses significant hepatoprotective activity.

The objective of the present study was to evaluate the protective effect of trigonelline (TRIG) and sitagliptin (SITA) combination in streptozotocin-nicotinamide induced diabetes in Wistar rats. Diabetes was induced by streptozotocin (65 mg/kg i.p.) injected 15 min after nicotinamide (110 mg/kg, i.p.). The rats were divided into following groups: Group 1: non-diabetic control, Group 2: diabetic control (saline), Groups 3, 4, 5 received TRIG as 25, 50, 100 mg/kg p.o., Groups 6, 7, 8 received SITA as 2.5, 5, 10 mg/kg p.o. respectively. For acute study, serum glucose (SG) levels were measured at 0, 2nd, 4th, 6th and 24th hour after administration. To find out effective combination, acute study of TRIG + SITA combination was done. The doses used are in combination TRIG + SITA as Groups 9, 10, 11 as 70% + 30%, 50% + 50%, 30 + 70%. SG was measured as per above-mentioned pattern. A 28-day subacute study was performed by taking effective percentage combination of TRIG + SITA. For subacute study SG, body weight was measured on 7th, 14th, 21st, 28th day; while serum insulin, HbA_1c and pancreatic histopathological study were done on 28th day. In acute study, TRIG + SITA (50% + 50%) were more effectively 43.08% reduction in SG level at 6 h with onset at 2 h and effect waned at 24 h. Subacute study reveals that the TRIG + SITA (50% + 50%) reduces SG by 54.72% than alone on 28th day. Serum insulin levels, body weight, pancreatic mass were increased with reduction in HbA_1c levels in animals receiving 50% + 50% combination of TRIG + SITA. The concomitant administration of TRIG + SITA (50% + 50%) contributes in the prevention to development diabetes and showed synergistic antihyperglycemic effect.

Background

Plant-derived polysaccharides such as galactomannans (GAL) have very interesting and useful applications in the biomedical and biopharmaceutical field. GAL from fenugreek (Trigonella foenum graecum L.) seeds has been shown to have promising but inconsistent anti-hyperglycemic activity due to variable composition.

Aim

We have isolated and characterized low molecular weight GAL fraction from fenugreek seeds (LMWGAL-TF) and evaluated its anti-hyperglycemic potential.

Materials and methods

LMWGAL-TF was isolated, well characterized (HPLC and LC-MS) and evaluated for anti-hyperglycemic activity after acute and subacute oral treatment in doses of 50, 100 and 200 mg/kg in alloxan-induced hyperglycemia in mice.

Results

The isolated LMWGAL-TF was of 91.5% purity with low molecular weight. LMWGAL-TF showed dose-dependent anti-hyperglycemic activity against alloxan-induced hyperglycemia without body weight gain, and protected mice pancreas from alloxan-induced histological changes.

Conclusions

LMWGAL-TF showed promising and dose-dependent anti-hyperglycemic effects in animal model of DM.

Sensitivity of physiological and biochemical parameters based on aging, pathological conditions and drug combinations on propranolol pharmacokinetics was investigated to define factors contributing to larger inter-individual variability on propranolol pharmacokinetics after oral administration than that after intravenous (iv) administration. Using a physiologically-based pharmacokinetic model, plasma propranolol concentration was simulated with wide-ranging physiological and biochemical parameters. Then calculated AUC and half-life (t_1/2) were compared with those obtained from the basic condition. It was found that the total blood flow through the body (Q_tot), hepatic volume, unbound fraction in the blood and metabolic parameters affected propranolol AUC. Except for Q_tot, effects were greater with after oral administration than iv administration. The propranolol AUC decreased by half with a two-fold increase in hepatic volume after oral administration possibly because of the increased first-pass metabolism. By contrast, some distribution parameters such as the skin tissue-to-blood distribution ratio and blood-to-plasma concentration ratio affected propranolol t_1/2. Finally, propranolol plasma concentrations were simulated in the case that metabolizing activity decreased to one half and one fifth with an assumption of metabolic enzyme inhibition. The simulated propranolol curves correlated well with the previously reported plasma concentration in the absence and presence of quinidine, which is well known to be a potent and selective CYP2D6 inhibitor. Thus, plasma propranolol pharmacokinetics was affected by parameters which related to the hepatic metabolism and the distribution, especially after oral administration.

Introduction

Natural autoantibodies (NAAs) that recognize autoantigens are mainly generated in the absence of any apparent immunization with foreign antigens (Ags). These antibodies maintain the body homeostasis through functions, such as inhibition of tumor angiogenesis, detection of structural changes in autoantigens, and exertion of anti-inflammatory impacts. The human body is shown to go through immunological and physiological changes during aging. However, data regarding the potential variations in the binding activity of NAAs is still scarce. Therefore, in this study, we were about to explore the trend through which the reactivity of serum NAAs with several autoantigens varies with advancing age.

Materials and methods

Serum samples were prepared from healthy individuals of seven age intervals: (0) cord blood, (1) infancy, (2) childhood, (3) adolescence, (4) early adulthood, (5) middle adulthood, and (6) late adulthood (the elderly). The mean immune reactivity (MIR) of the sera with 24 human autoantigens that were obtained from Immunculus research center (Russia) was determined using ELISA and inter-group comparisons were also performed.

Results

In general, the MIR of serum natural antibodies with the autoantigens was shown to follow an upward trend with advancing age so that the lowest and highest MIRs were detected in the cord blood and late adulthood samples, respectively. Moreover, the results of the inter-group comparisons indicated that the MIRs of the first, second, fourth, and sixth groups were significantly higher than those of their previous groups, i.e. zero, first, third, and fifth groups, respectively.

Conclusion

This study showed that the reactivity of human tissue-specific and non-specific NAAs with autoantigens varied along with aging. Regarding the crucial roles NAAs play in maintaining the body homeostasis, the variation in their concentration at different age intervals might account for the immunological and pathological changes that occur in the elderly.

Sleep is a naturally complex dynamic state governed by nervous and signaling systems. Sleep disorders are prevalent and challenging in medicine and psychology, involved in genetic or inherited elements and environmental factors. The determination of the molecular changes during sleep and in sleep disturbance is fundamental to the understanding, diagnosis and therapy as well as pharmaceutical development of sleep disorders. Genetic and environmental contributions to sleep timing and sleep structure by molecular processes provide important insights into sleep deprivation or disorders. In this review, molecular mechanisms during sleep and in sleep-wake transition are overviewed in immune systems, metabolic process and neuronal activity. Current research progress in genetics of sleep disorders is summarized and the therapy or treatment approaches are presented in psychological-behavioural therapy, sleep-assistance devices and medications to introduce the strategy of addressing various sleep disorders. Although the correlation of environmental conditions and genetic changes is still not completely revealed, some advances are already achieved that environmental factors or medications have impacts on gene traits or genes controlling sleep and sleep deprivation by molecular pathways.

Isoorientin (ISO) is a flavonoid compound, and possesses a significant antioxidant potential. However, the effects of ISO on the oxidative damage in normal hepatocytes remain unknown. The present study investigated the protective effects of ISO on H₂O₂-induced apoptosis in buffalo rat liver (BRL-3A) cells. The results showed that H₂O₂ induced cell death in a dose-dependent manner, pretreatment with ISO significantly (P < 0.01) increased the cell viability in a concentration-dependent manner, and no significant toxicity was found in ISO-treated cells. ISO notably decreased the loss of mitochondrial membrane potential (MMP) and the protein expression of Bax, cytochrome c (in the cytosol), cleaved caspase-3 and PARP, and ultimately reduced H₂O₂-induced BRL-3A cells apoptosis. Meanwhile, ISO also remarkably restrained the activation of ERK1/2, JNK and p38, and the inactivation of Akt induced by H₂O₂. Furthermore, ISO significantly reduced H₂O₂-induced reactive oxygen species (ROS) and nitric oxide (NO) production by elevating total superoxide dismutase (T-SOD) and catalase (CAT) levels, and inhibiting the expression of inducible nitric oxide synthase (iNOS). These results demonstrated for the first time that ISO is able to protect BRL-3A cells against H₂O₂-induced apoptosis by inhibiting mitochondrial dysfunction, inactivating MAPK kinases, activating Akt, and scavenging ROS and NO.