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Ischemic stroke is a severe cause of disability and death all over the world. To search for effective therapy for ischemic stroke, PC12 cells damaged by oxygenation and glucose deprivation/restoration were employed to assess the protective effects of inotodiol. As a result, inotodiol can improve the cell viability and attenuate the leakage of lactate dehydrogenase. Meanwhile, inotodiol can prevent oxidative stress by reducing reactive oxygen species generation, decreasing the content of malonic dialdehyde, and increasing the activity of superoxide dismutase. In addition, the dysfunction of mitochondria induced by oxygenation and glucose deprivation/restoration was ameliorated through decreasing the level of intracellular calcium and increasing the mitochondrial membrane potential. At the same time, inotodiol can inhibit PC12 cells apoptosis through downregulation of Caspase-3 and Bax as well as upregulation of Bcl-2. These results reveal inotodiol can protect PC12 cells against the injury induced by oxygenation and glucose deprivation/restoration. This investigation gives promising evidences for the therapy of ischemic stroke.

Background/Objectives
To determine effects of gender, age, diet, and smoking status on circadian rhythm characteristics of ascorbic acid (vitamin C).
Subjects/Methods
Ascorbic acid was measured spectrophotometrically in serum collected from 162 healthy volunteers (103 males and 59 females; 7-75 years) every 6 h for 24 h (4 samples). Data were analyzed by single and population mean cosinor. Effects of gender, age, diet (vegetarian vs. omnivore), and smoking status on the rhythm-adjusted mean (MESOR) and circadian amplitude were examined by multiple analysis of variance.
Results
A circadian rhythm is documented with statistical significance by population mean cosinor. In addition to effects of gender and age, the MESOR is affected by diet and smoking status. The circadian amplitude changes nonlinearly as a function of age. The circadian acrophase advances with increasing age.
Conclusion
The present observations confirm a definite circadian rhythm in ascorbic acid concentrations with significant effects of age, diet and smoking status in clinical health. Mapping the circadian rhythm of serum ascorbic acid in health can help explore its role in different pathophysiological conditions as pre-disease conditions may be characterized by alterations in the circadian amplitude and/or phase before there is a change in mean value.

Sickle cell anemia (SCA) is a hereditary disorder that is characterized by tendency of hemoglobin molecules within the erythrocytes to polymerize under hypoxia conditions, deform the red cells, and promote vaso-occlusion and endothelial damage. This disease may be associated with the extracellular release of nucleotides, particularly ATP, ADP and adenosine into the circulation. The aim of this study was to investigate the possible changes in adenine nucleotides and nucleoside metabolizing enzymes as well as their levels in serum of SCA patients. NTPDase, 5'-nucleotidase and adenosine deaminase activities were evaluated in serum obtained from blood samples of 15 SCA treated patients and 15 healthy subjects (control group). The results revealed that there were significant (P < 0.001) elevations in NTPDase, 5'-nucleotidase and ADA activities in serum of SCA treated patients when compared to the control group. Furthermore, no significant (P > 0.05) alteration was observed in ATP, ADP and adenosine levels of both SCA treated and control groups. However, inosine level was significantly (P < 0.05) decreased and hypoxanthine level was higher in SCA treated patients (P < 0.001) when compared to the control group. The results suggest the involvement of purinergic signaling enzymes in the maintenance of the levels of extracellular nucleotides and nucleosides, thus preventing some pathophysiological conditions associated with SCA.

An increased number of sulfate-reducing bacteria is often isolated from faeces of patients with gastrointestinal diseases, which can be the cause of the development of bowel inflammation. Frequent use of antibiotics causes the resistance of intestinal microorganisms and ineffective treatment of these diseases. The antimicrobial activity and biological properties of the selected ring-substituted 8-hydroxyquinoline-2-carboxanilides against Desulfovibrio piger Vib-7 were studied. The addition of these compounds in the cultivation medium inhibited the bacterial growth and the process of sulfate reduction dose-dependently. A significant cytotoxic activity under the influence of ring-substituted 8-hydroxyquinoline-2-carboxanilides was determined. The strongest cytotoxic effect of the derivatives was observed for compounds 8-hydroxy-N-(3-methoxyphenyl)quinoline-2-carboxamide and 8-hydroxy-N-(3-trifluoromethylphenyl)quinoline-2-carboxamide that caused a low survival of D. piger Vib-7 in concentration 17 μM and high toxicity rates.

Background/objective
Chronic pain, sleep disturbances and oxidative stress are implicated in the pathogenesis of fibromyalgia. The aim of this study was to assess the effect of melatonin supplementations on sleep quality, 6-sulfatoxymelatonin (aMT6-s) levels, as well as urinary and serum total antioxidant capacity (TAC) in patients with fibromyalgia.
Methods
Thirty three patients carried out the full study. A baseline period (10 days) was included in the experimental design to collect information about patients' initial status. Then, patients took different doses of melatonin, during 10 consecutive days each. Placebo was given during 10 days either before or between melatonin doses. Objective sleep quality was recorded by actigraphy whereas subjective sleep quality was measured by The Pittsburgh Sleep Quality Index. Quantification of aMT6-s and TAC was achieved by ELISA and colorimetric assay kits, respectively.
Results
Six out of seven sleep parameters evaluated by actigraphy were improved after the intake of melatonin as well as the subjective sleep quality. All the biochemical parameters measured were also elevated after the melatonin administration.
Conclusion
The daily intake of melatonin improved the sleep quality, increased the aMT6-s levels and the total antioxidant capacity in patients with fibromyalgia.

Non-steroidal anti-inflammatory drugs (NSAIDs) play an effective chemopreventive action against a variety of cancers. The present study aimed at targeting pro-inflammatory cyclooxygenase (COX) and NF-kB mediated inflammatory pathways in 9,10-dimethylbenzanthracene (DMBA) induced lung cancer in BALB/C mice and chemoprotective action of NSAIDs. Animals were divided into five groups and treated with NSAIDs, intratracheally, daily for a period of 18 weeks. Group 1 as control, received vehicle treatment; Group 2 received single dose of DMBA (10 mg/kg bw); Group 3, 4 and 5 besides DMBA treatment, also received Aspirin (60 mg/kg bw), Celecoxib (6.0 mg/kg bw) and Etoricoxib (0.6 mg/kg bw), respectively. DMBA induce DNA damage, apoptosis and expression of COX-1, COX-2 and NF-κB using immunofluorescence and blot analysis were done. The present study demonstrated the formation of micronuclei, over-expression of COX-2 and NF-κB in DMBA induced lung tumorigenesis and thereby suggesting a marked role of inflammation in the tumour progression. Results indicate the formation of micronuclei in DMBA group, which were significantly reduced in aspirin treated group, and totally absent in the celecoxib and etoricoxib groups. In conclusion, co-administration of etoricoxib and celecoxib has significantly reduced the inflammatory potential of the growing neoplasm in DMBA induced lung cancer in male BALB/C mice.

The effect of moderate and overtraining exercise on Th1/Th2 balance was evaluated in rat splenocytes. Male Wistar rats were divided into sedentary control (C), moderately trained (MT; V = 20 m/min, 30 min/day, 8 weeks), overtrained (OT; V = 25 m/min, 60 min/day, 11 weeks) and recovered after overtraining (OR) (OT plus 2 weeks recovery) groups. At the end of study, cell viability, proliferation, interleukin 4 (IL-4) and interferon-γ (IFN-γ) secretion were evaluated in non-stimulated, phytohemagglutinin (PHA) and concavaline A (Con A)-stimulated splenocytes. Cell viability increased in MT and OR groups compared to control. Cell proliferation was higher in OR group than other groups. IL-4 concentration in PHA-stimulated cells from MT and OT groups, and IL-4 concentration in Con A-stimulated cells from OR and OT groups, were higher than the control group, but not for IFN-γ. In non-stimulated cells, IFN-γ/ IL-4 ratio was higher than MT and OT groups. In PHA and Con A-stimulated cells, IFN-γ/ IL-4 ratio was lower in exercise groups than control. We previously showed that moderate exercise increases Th1 cytokines in serum, but in splenocytes, Th2 or Th1 response may increase depending on the type of mitogen stimulation. Two-week recovery restored Th1/Th2 balance, only in non-stimulated splenocytes of overtrained animals.

Malaria is a serious global health challenge, and it has infected millions of people worldwide. There is an urgent need for new antimalarial drugs and drug targets for both prophylaxis and chemotherapy. In the present study, we biosynthesized TiO₂ nanoparticles (NPs) using the Momordica charantia leaf aqueous extract as a reducing and stabilizing agent. TiO₂ NPs were characterized by UV, XRD, FTIR, HRTEM, EDX, DLS and Zeta-potential. The maximum activity of mosquitocidal was observed in the synthesized TiO₂ NPs against Anopheles stephensi Liston (Diptera: Culicidae) larvae and pupae, LC₅₀ were 2.50 mg/l (I instar), 2.86 mg/l (II), 3.29 mg/l (III), 3.43 mg/l (IV), and 5.04 mg/l (pupa). The antimalarial activity of M. charantia leaf aqueous extract and TiO₂ NPs were evaluated against CQ-resistant (CQ-r) and CQ sensitive (CQ-s) strains of Plasmodium falciparum. IC₅₀ of M. charantia leaf aqueous extract were 83.64 μg/ml (CQ-s) and 88.14 μg/ml (CQ-r). Synthesized TiO₂ NPs achieved IC₅₀ of 53.42 μg/ml (CQ-s) and 59.71 μg/ml (CQ-r). The TiO₂ NPs did not exhibit any noticeable toxicity on Poecilia reticulata after 24 h of exposure. Overall, our results suggest that the synthesized TiO₂ NPs may be employed to develop newer and safer agents for malaria control.

Fruit of Terminalia chebula Retz. (Combretaceae) has male contraceptive folk medicine reputation but its molecular aspect regarding hypotesticular activity is still in dark. The study focused the hypotesticular efficacy of the most potent fraction out of n-hexane, chloroform and ethyl acetate fractions of hydro-methanolic (3:2) extract of Terminalia chebula in connection with male herbal contraceptive development.
Treatment with above fractions of Terminalia chebula showed a significant diminution in the activities of androgenic key enzymes (Δ5, 3β-HSD, 17β-HSD) and inhibition in serum testosterone level in compare to the control. Significant up regulation of testicular Bax gene and down regulation of Bcl-2 gene indicated the hypotesticular activity of these fractions. Flow-cytometric study focused a significant diminution in sperm viability and sperm mitochondrial status after the treatment with different fractions. Out of these, ethyl acetate fraction showed most promising hypotesticular effect without impairing any toxicity in general which highlighted that the fraction may contains antitesticular agent(s) in threshold levels compare to other fractions as it decreases spermiological, testicular genomic sensors and elevates sperm apoptotic sensors that may lead to male contraception.

A novel and facile in vitro cell sensing system has been developed with one-step electropolymerization of the conducting polypyrrole(PPy) polymer using RGD peptide as the sole dopant on an indium tin oxide (ITO) surface. The resulted RGD peptide-doped polypyrrole (PPy/RGD) composite film had a robust surface, in which PPy provided a biocompatible matrix for cell growth and a conducting interface for electrical detection, while the RGD peptide entrapped in the PPy matrix conferred the desired biomimetic properties. Using the human lung cancer cell A549 as a model, this system can be used to monitor cell behaviors of proliferation and cytotoxicity.

The effect of hydro-alcoholic extract of Curculigo orchoides on hexavalent chromium (Cr VI) induced toxicity in rats was investigated. Sub-acute toxicity studies were performed by OECD guidelines. K₂Cr₂O₇ (30 mg/kg) was administered to all groups except control group for a period of 28 days by oral gavage. Control group received distilled water; treatment groups received C. orchoides (25, 50 and 100 mg/kg). Cr(VI) administration resulted in up-regulation of serum biochemical parameters such as alanine transaminase, aspartate transaminase, alkaline phosphatase, and tissue biochemical markers viz. lipid peroxidation and protein carbonyl content. C. orchioides (100 mg/kg) significantly decreased these enzyme levels. The activities of anti-oxidant enzymes like superoxide dismutase, catalase and glutathione S-transferase were significantly decreased by Cr(VI) administration (50.7%, 43.7% and 37.9%, respectively). Further, mRNA expression studies and histopathology studies confirmed Cr(VI) toxicity. In all cases, C. orchioides promoted significant restoration of enzyme levels in a dose dependent manner. These results suggest the ameliorating effect of C. orchoides on Cr(VI) induced oxidative stress is probably via, modulation of cytokines, transcription factors and apoptotic genes.

The aim of the presented research was to formulate, prepare and evaluate novel film wound dressings containing lidocaine hydrochloride. The conversion of partially substituted fibrous sodium carboxymethylcellulose (CMC) to an acidic form of CMC enabled the formation of an insoluble matrix which consequently provided the prepared films with excellent handling properties in their wet state. The drug concentration which was incorporated into an external layer of the film was 5 mg/cm². The films demonstrated satisfactory mass and drug content uniformity as well as an acidic surface pH advantageous for wound application. An in vitro drug release test proved that the insoluble CMC matrix served as a reliable carrier without slowing down the release of lidocaine hydrochloride - more than 90% of the drug was released during the first 15 min, indicating a quick rate of anesthetic action. The prepared films could be potential wound dressings for comfortable and efficient topical anesthesia before/after procedures on the wound.

To evaluate parallel circadian rhythms in salivary and serum cortisol concentrations during 48-h period, sampling was performed in six clinically healthy dogs of various breeds housed under natural photoperiod in spring (sunrise 05:20, sunset 20:20). Saliva and blood samples were taken every 3 h for a 48-h period to determine the daily changes in salivary and serum cortisol concentrations. The relationship between salivary and serum cortisol level was determined as well. In the two-day period of monitoring, salivary and serum cortisol concentrations showed the same trend. Their levels started to increase at sunrise and reached their peak in the middle of the photophase. Both parameters showed a high robustness of rhythm. A positive correlation between salivary and serum cortisol concentration was observed during the day 1 and 2. Acrophase and robustness of rhythm showed no statistically significant difference between salivary and serum cortisol concentrations. We can claim that salivary cortisol, a measure of free cortisol, follows the circadian rhythm of serum cortisol. Therefore, saliva sampling is a valid and non-invasive technique useful in chronomedicine to estimate free cortisol.

Objective
There is an increasing incidence of Helicobacter pylori eradication therapy failure secondary to antibiotic resistance. In this study, we aimed to assess the P-glycoprotein expression levels among subjects who were H. pylori-positive and received multiple courses of eradication therapy to understand factors that may associate with their non-responses.
Methods
Eleven resistant subjects were recruited during their hospital visit for upper gastrointestinal endoscopies. H. pylori infection status was confirmed by rapid urease test and bacterial culture. P-glycoprotein expressions from the antral and duodenal biopsies were measured by Western blot. The data was compared with H. pylori-negative (n = 54) and H. pylori-positive-treatment naïve (n = 22) that were recruited earlier in another study.
Results
The resistant group showed higher relative antral P-glycoprotein expression compared to the H. pylori-negative group (p = 0.0361). Most subjects demonstrated resistance to clarithromycin (72%), metronidazole (63.6%) or both (54.5%). No significant difference was observed between the P-glycoprotein expression in H. pylori-treatment resistant and H. pylori-positive-treatment naïve groups (p = 0.319).
Conclusion
H. pylori infection induces the expression of P-glycoprotein in the antrum. This study shows a potential protective mechanism which may be exploited through the use of P-glycoprotein inducers, such as rifabutin, may be beneficial in eradication regimens.

Avidity is an important feature of antibodies associated with their pathogenic effects. Anticardiolipin antibodies (aCLs) are the most commonly examined antiphospholipid antibodies, however, their avidity has been investigated only marginally. The aim of the study was to compare the avidity of the antibodies specifically bound to the cardiolipin-coated microtitrate wells with those bound to the wells bearing no cardiolipin in various conditions. We analysed 22 serum samples with high, medium and low levels of aCL IgG. The avidity of aCL IgG was determined in serially diluted sera by the ELISA method in the presence of increasing urea concentrations (from 2 to 8 mol/L) as a chaotropic agent. The serum dilution 1:50 and 1:100 and the concentrations of urea 6 mol/L and 8 mol/L seemed to be suitable for the determination of aCL avidity. The avidity of antibodies specifically bound to the cardiolipin and those bound to the cardiolipin-free wells significantly differed in their avidity. The simultaneous determination of higher-avidity aCL and lower-avidity polyspecific antibodies, whose presence complicates the ELISA methods by an increase of the background signal, might limit the shortcomings of some ELISA methods.

Alzheimer disease (AD) is the most common cause of progressive dementia in the elderly population, with prevalence of 5% after 65 year of age and is increasing to about 30% in people over 85 year. AD is a neurodegenerative and incurable disease. Currently, three inhibitors of acetylcholinesterase (AChE), galantamine, donepezil and rivastigmine, and one inhibitor of N-methyl-d-aspartate (NMDA) receptor are available as drugs for amelioration of the disease. Demand to prepare drugs for the therapy providing at least relieve of symptoms remains. In this experiment, the ability of standards (donepezil, galantamine, huperzine A, tacrine and 7-methoxytacrine) and precursors used for synthesis of new AD drugs (l-tryptophan, pyridoxine B₆, tryptamine, acridine, chinoline, isochinoline, indole, pyridine and piperidine) to inhibit AChE, BChE and BACE or to have the antioxidant properties were determined. The results were compared using statistical expression of the relationship between the performed tests. In this experiment, IC₅₀ for every one method and every compound were found. Beside this, prediction of free energy in a link to ln(IC₅₀) was assessed using in silico tests. This article focuses on possibility to find the most suitable chemical precursors to be used in the next development of drugs for AD.

There is a renewed interest in metabolism alterations and its impact on cancer development and progression. The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation. Elevated fatty acid synthesis is one of the most important aberrations in cancer cell metabolism, and is required both for carcinogenesis and cancer cell survival. We have previously shown that cancer cells explore metabolic pathways especially autophagy and particularly enhanced glycolysis and suppressed oxidative phosphorylation to promote treatment resistance. To support cell proliferation in cancer, lipid metabolism and biosynthetic activities is required and often up-regulated. Here we bring lipid metabolic pathways into focus and summarized details that suggest a new perspective for improving chemotherapeutic responses in cancer treatment, and indicate the need to design more inclusive molecular targeting for a better treatment response.

Effects of atorvastatin on the expression of Cytochrome P450 3A2 and its enzymatic activity in the kidney of diabetic rats were investigated. Diabetes was induced by injection of streptozotocine (50 mg/kg, b.w., i.p.) in male Wistar rats. The animals were assigned into four groups including control (C), non-treated diabetic (D), atorvastatin-treated diabetic (AD) and atorvastatin-treated non-diabetic (A) groups. Metabolism of testosterone was examined in the presence of renal microsomes. The expression of CYP 3A2 at mRNA level was examined by means of PCR technique. The atorvastatin administration resulted in a remarkable improvement of diabetes-induced nephropathy and oxidative stress. Enzyme kinetics analyses showed that both diabetic groups produced significantly (P < 0.05) more 6β-hydroxytestosterone (V_max for D = 34.7 ± 1.3 and for AD = 45.1 ± 2.3 pM/min/mg) than that of the control group (V_max = 21.6 ± 1.5 pM/min/mg). Both diabetes and atorvastatin administration resulted in a significant up regulation of CYP 3A2 mRNA level in the kidney. Our data suggest that due to profound influence of diabetes and atorvastatin on renal metabolism of CYP 3A2 substrate and up-regulation of this gene, there should be adjusted dose regimen for medications which are classified as CYP 3A2 substrates.

Developing plant derived chemopreventive agents that can divert the carcinogenic process and inhibit tumour progression may greatly reduce serious health consequences of cancer. This study investigated the antiproliferative and apoptosis inducing ability of Rubus fairholmianus root acetone (RFRA) on MCF-7 cells. RFRA treatments showed an increase in the in vivo antioxidant levels such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) in mice. The extract showed significant antitumour activity with 76.57% increase in life span of ascites tumour bearing mice and 1.94 cm³ reductions in solid tumour volume at 250 mg/kg. The cytotoxicity spectrum analysis indicated that RFRA is a potent cytocidal agent with varying levels of toxicity (IC₅₀: 57.14-29.36 μg/ml). A significant dose dependent decrease in viability, proliferation and increase in cytotoxicity, caspase 3/7 activity were observed in MCF-7 cells. RFRA (20 μg/ml) induced apoptosis in MCF-7 cells, which was observed by morphology; DNA ladder formation and increased apoptotic population in flow cytometry analysis. These findings strongly suggest the use of R. fairholmianus as natural antioxidant with profound antitumour activities. It can act as a potent cytotoxic agent, which is able to induce apoptosis in MCF-7 cells via caspase 3/7 upregulation.

Fullerenol C₆₀(OH)₂₄ nanoparticles (FNP) are promising radioprotectors in prevention of early and late ionizing radiation injury. The aim of this study was to compare the efficacy of FNP and amifostine (AMI) in protection of rats exposed to whole-body X-ray irradiation (7 or 8 Gy). Both compounds (FNP, 100 mg/kg ip; AMI, 300 mg/kg ip) were given 30 min before irradiation throughout the study. The general radioprotective efficacy of FNP and AMI were evaluated in rats irradiated with an absolutely lethal dose of X-rays (8 Gy) and their survival were monitored during the period of 30 days after irradiation. Both compounds were of comparable efficacy. Tissue-protective effects of tested compounds were assessed in rats irradiated with an sublethal dose of X-rays (7 Gy). For this purpose, the animals were sacrificed on the 7th and 28th day after irradiation. Their lung, heart, liver, kidney, small intestine and spleen were taken for histopathological and semiquantitative analysis. Careful examination of established tissue and vascular alteration revealed better radioprotective effects of FNP compared to those of AMI on the small intestine, lung and spleen, while AMI had better radioprotective effects than FNP in protection of the heart, liver and kidney. Results of this study confirmed high radioprotective efficacy of FNP in irradiated rats that was comparable to that of AMI, a well-known radioprotector.

Telomeres are repetitive DNA located at the ends of chromosomes that preserve genomic stability. Excessive leukocyte telomere shortening is associated with cardio-metabolic disease and increased mortality risk. Although most studies indicate exercise training could attenuate leukocyte telomere attrition, data is somewhat equivocal. The inconsistencies could be partly explained by the different populations of leukocytes isolated for telomere length assessment. Accordingly, average peripheral blood mononuclear cell (PBMC) and whole blood leukocyte telomere length were assessed in 44 endurance athletes and 40 healthy controls using quantitative PCR. While whole blood leukocyte telomeres were, on average, 6.1% longer in endurance athletes compared to controls, PBMC telomere length was similar between the two cohorts in age and sex-adjusted analyses (athletes vs controls, mean T/S ratio ± SE: 3.25 ± 0.05 vs 3.23 ± 0.05, p = 0.72). Other than a weak inverse correlation with sitting (r = -0.25, p = 0.03), no statistically significant correlations were found between PBMC telomere length and exercise parameters. Unlike whole blood leukocytes, PBMC telomere length is not associated with endurance exercise and exercise parameters. These findings suggest the need for future work to quantify short and long telomeres of sorted immune cell populations and to measure them in context with cell counts and exercise traits.

Physical activity has been correlated with transient immune impairment. However, such activities lead to improvement in immunity rather than dysfunction. The major benefit of regular exercise is the reduction of low-grade inflammation which consequently prevents or attenuates metabolic diseases, such as atherosclerosis and type 2 diabetes, neurodegenerative disorders, cancer or even depression. As a major factor responsible for general improvements in the immune system, scientists have examined epigenetics. Epigenetic mechanisms include cytosine methylation, micro-RNA expression and post-transcriptional modifications of histones, which regulate tissue-specific gene expression in response to environmental stimulation. This review will summarize the recent data regarding the impact of exercise and the role of epigenetic mechanisms on gene expression changes in Peripheral Blood Mononuclear Cells (PBMCs).

Previous studies have indicated that polyphenol-rich Chrysanthemum morifolium extract (CME) may inhibit the formation of hyperlipidemic fatty liver in mice. But there has been no report about therapeutic effect on diabetes mellitus. In the present study, we investigated the action of CME and its potential mechanisms. A mouse model with diabetes mellitus was induced by alloxan. The results showed that after treatment of diabetic mice with polyphenol-rich CME 150 and 300 mg/kg for 6 weeks, the levels of fasting blood glucose (FBG) as well as water and food consumption were decreased (P < 0.05 or P < 0.01), the content of hepatic glycogen was increased, especially in the 300 mg/kg group (P < 0.05), but no significant variations in the body-weight gain, fasting serum insulin, and muscular glycogen were observed. Importantly, toxic alloxan treatment might decrease the protein expressions of hepatic peroxisome proliferator-activated receptor (PPAR) α/γ, glycogen synthase (GS), and glucose transporter-2 (Glut-2) (P < 0.05 or P < 0.01), while CME might reverse the changes (P < 0.01). These findings demonstrate that the reduction of PPARα/γ-mediated hepatic glycogen synthesis may involve in the alloxan-induced hyperglycemia, and the hypoglycemic mechanisms of CME may be mainly associated with the increment of hepatic glycogen synthesis via upregulation of PPARα/γ-mediated GS and Glut-2 protein expressions.

The current study explored the in vitro anticancer properties of Mesua ferrea stem bark (SB) extract towards human colon carcinoma HCT116 cells. SB was successively extracted with different solvents using soxhlet apparatus. MTT assay was employed to test toxicity against different cancer and normal cell lines. Active extract (n-Hexane) was fractionated by column chromatography (CC) to get the most active fraction (F-3). Series of in vitro assays were employed to characterize cytotoxic nature of F-3. Antioxidant properties of F-3 were assessed using DPPH, ABTS and FRAP assays followed by GC-MS analysis. Intracellular ROS levels were measured by DCFH-DA fluorescent assay. Finally, cell signalling pathways and their downstream proteins targeted by F-3 were studied using 10-cancer pathway and human apoptosis protein profilers and in silico docking studies. n-Hexane extract and its fraction (F-3) showed potent anti-proliferative effect against HCT 116. Programmed cell death (PCD) studies showed that F-3 modulated the expression of multiple proteins in HCT 116. F-3 showed weak antioxidant activity in all the models, while significant increase in ROS was observed in HCT 116. GC-MS analysis revealed that F-3 was majorly comprised of terpenes. Data of pathway profiler and in silico studies revealed that F-3 down-regulated the expression of NF-κB and HIF-1α pathways. Overall these results demonstrate that anticancer effects of M. ferrea stem bark towards human colon carcinoma are mainly due to its terpenes contents.

There is a lack of data on the state of iodine reserves and the possible consequences of iodine deficits in diabetic patients. The main aims of this study were to: a) obtain information about iodine saturation in patients with type 1 diabetes; b) determine to what extent this saturation differs from the non-diabetic population; and c) determine whether iodine levels are related to several clinical and laboratory parameters characteristic of diabetic syndrome, including thyroid status.
Subjects and methods: A total of 54 males and 51 females treated for type 1 diabetes mellitus (DM1) were included in this cross-sectional study. In addition to iodine saturation determined as the concentration of iodine in the first urine sample of the day, we measured clinical, anthropometric, and biochemical parameters in relation to DM1.
Results: Measured iodine levels were: median 152 μg/l, first quartile 117 μg/l, and third quartile 219 μg/l. More than 50% of iodine levels varied within the optimal saturation range of 100-200 μg/l, while about 14% showed incomplete saturation (200 μg/l).
Multi-dimensional regression showed significant positive relationships; (an OPLS model explaining 9% of the variability) between ioduria and male sex, body weight and height, and serum creatinine levels, which to date have not yet been published. Relationships to the other analyzed parameters (glycated hemoglobin, insulin dose, DM duration, body mass index, microalbuminuria, glomerular filtration rate, thyroid function and volume, thyroid autoimmune markers) were not significant.
Conclusions: Iodine saturation levels in our study group were within the ICCIDD (WHO) recommendations for optimal/good saturation for the non-diabetic population, and patients with diabetic syndrome did not differ with respect to the chosen normal ioduria concentrations, i.e. 100 or 150 μg/l. The question remains, however, whether past attempts to deal with iodine deficits in the Czech Republic are responsible for this satisfactory iodine status of the type 1 diabetic population, or if there are other factors involved.

Mosquitoes (Diptera: Culicidae) represent a key threat for millions of humans and animals worldwide, since they act as vectors for devastating parasites and pathogens. Eco-friendly control tools are a priority. Plant-mediated biosynthesis of nanoparticles is rapid and cost-effective. Here we biosynthesized poly-dispersed silver nanocrystals (AgNPs) using a cheap aqueous leaf extract of Adiantum raddianum. AgNPs were characterized by UV-vis spectrophotometry, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDX) and X-ray diffraction analysis (XRD). The acute toxicity of A. raddianum extract and biosynthesized AgNPs was evaluated against larvae of the malaria vector Anopheles stephensi, the dengue vector Aedes aegypti and the filariasis vector Culex quinquefasciatus. Compared to the leaf aqueous extract, AgNPs showed higher toxicity against An. stephensi, Ae. aegypti and Cx. quinquefasciatus with LC₅₀ values of 10.33, 11.23 and 12.19 μg/ml, respectively. Biosynthesized AgNPs were found safer to non-target organisms Diplonychus indicus, Anisops bouvieri and Gambusia affinis, with respective LC₅₀ values ranging from 517.86 to 635.98 μg/ml. Overall, this study firstly shed light on the potential of A. raddianum as a potential bio-resource for rapid, cheap and effective nanosynthesis of novel mosquitocides.

Protective effects of electromagnetic fields (EMFs) against oxygen and glucose deprivation (OGD)-induced human mesenchymal stem cell (MSC) death were studied. Cell survival, intracellular calcium and ROS/RNS levels were measured after culturing MSCs for 3 h under OGD with or without EMF exposure. The survival rate of cells cultured under OGD condition was significantly reduced compared to control cells, while cells cultured in OGD with 10 Hz/1 mT EMF exposure had higher survival ratio than that in equivalent non-exposed cells. This protective effect of EMF was not observed at different frequency/intensity combinations such as 10 Hz/0.01 mT, 10 Hz/0.1 mT, 50 Hz/1 mT and 100 Hz/1 mT. ROS/RNS levels of cells cultured under OGD conditions significantly increased compared to the control level while 10 Hz/1 mT EMF alleviated this effect. Intracellular calcium levels in OGD group were higher than control while those in OGD plus 10 Hz/1 mT EMF group were significantly lower than OGD group. Addition of Ca²⁺ chelator promoted protective effects of EMF against OGD-induced MSC death. Our results suggest that 10 Hz/1 mT EMF exposure protects MSCs from OGD-induced cell death and the underlying mechanisms of the protection are reduction of intracellular levels of Ca²⁺ and ROS/RNS.

Amyloidosis is a group of diseases caused by the accumulation of insoluble protein aggregates in different parts of the body. Repeated subcutaneous injection of insulin hormones in diabetic patients leads to localized amyloidosis that is found to be cytotoxic. Thus, agents that can dissociate these aggregates are critically needed. In the present study, insulin amyloid dissociation was demonstrated by the treatment of an enzyme lumbrokinase (LK) isolated from earthworm. Thioflavin T (ThT) fluorescence, solution turbidity, particle size analysis, FTIR, CD, atomic force microscopy and cell viability assay were employed to support the dissociation of insulin amyloid in vitro. The small animal optical imaging was used to explore the dissociation of amyloid fibrils in vivo using zebrafish model. The activity of LK towards amyloid dissociation was compared with the standard amyloid fibril degrading agent nattokinase (NK). Our results indicated that LK can be a probable fibril degrading agent for the dissociation of amyloids.

The epidermis is the external layer of the skin and is composed mainly of keratinocytes. Therefore, keratinocytes play an indispensable role as inherent constituents of the skin barrier in physical defenses against environmental threats. Keratinocytes also exert an active protective role against invasion by pathogens. This competency is of particular importance when physical defenses fail as a consequence of skin injury. During the inflammatory phase of healing, keratinocytes act as immuno-modulators, managing inflammation via a rigorously coordinated network of inflammatory cascades, triggered by keratinocyte-receptor communication with the surroundings in a paracrine and autocrine manner. This review summarizes current understandings of the coordinated inflammatory network and focuses on recent progress regarding the role of keratinocytes in early phases of skin wound healing.

Novel benzoylhydrazones were designed and synthesized by condensation of 5-methoxysalicylaldehyde and benzhydrazides with different substituents at 4th position. The structures of the new derivatives were confirmed by elemental and thermal analysis, mass, IR, ¹H NMR and ¹³C NMR spectroscopy. The molecular properties of the compounds, important for drug pharmacokinetics and biodisposition in the human body, were assessed by the Lipinski's rule of five. In silico evaluation of the LogP value and the remaining parameters of drug similarity, as well as the topological polar surface area and absorption percentage, were used only as a first step in the study. The investigated 5-methoxyderivative hydrazones were further tested for in vitro cytotoxicity on three leukemic, two breast cancer and one non-tumor human cell lines using the MTT-dye reduction assay. The bioassay demonstrated that the compounds exhibited concentration-dependent antiproliferative activity at low micromolar concentrations against the used human cell lines. The solid tumor-derived breast cancer cell lines were generally more sensitive to the effects of the hydrazones with IC₅₀ values ranging 0.91 μM-12.07 μM. The results confirm that all compounds are more potent than the standard drug Melphalan and have appropriate properties as potential anti-breast cancer drug candidates.