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This study investigated the FSH influence on maturation rates of oocytes in vitro maturation (IVM), and expression levels of the follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR) and gonadotropin releasing hormone receptor (GnRHR) of cumulus-oocyte complexes (COCs) response to FSH treatment. 1686 COCs were harvested from 1063 ovaries of sheep. COCs were cultured 26 h at 38.5 °C and 5.0% CO₂ in IVM media supplemented with 0, 5, 10, 20 and 30 IU/ml FSH. They were allocated in to FSH-1 (basal line), FSH-2, FSH-3, FSH-4 and FSH-5 groups. The apoptosis of COCs was assessed by Tunel assay. Expression levels of mRNA and protein for FSHR, LHR and GnRHR in sheep COCs were detected using real time RT-PCR and Western blotting respectively. The results showed that the maturation rates of oocytes were improved gradually when FSH supplement increased from 0 to 10 μg/ml. FSH-3 group showed the highest maturation rate. Apoptosis rates of FSH-treated groups were less than that of FSH-1 group with a minimum of FSH-3 group. Expression levels of FSHR and LHR mRNAs in FSH-3 and FSH-4 were significantly higher than in FSH-1. Expression level of GnRHR mRNA in FSH-3 was higher than in FSH-1 (P < 0.05). Expression levels of FSHR proteins in FSH-3 and FSH-4 groups were higher than that of FSH-1 group. Expression levels of GnRHR proteins increased gradually with a maximal increment of FSH-5. Maturation rates of COCs had significant positive correlations with mRNA and protein levels of FSHR, LHR and GnRHR. In conclusion, FSH could accelerate the maturation rate of sheep oocytes and reduce their apoptosis rate, also increase the expression levels of FSHR, LHR and GnRHR mRNAs, and strengthen expressions of FSHR and GnRHR proteins. 10 IU/ml FSH additions were the optimal dose for IVM of sheep oocytes.

Human milk is a source of glycoconjugates, sialylated forms of which enrich the newborn immature immune system and are crucial for their proper development and well-being. Here, we analyzed the expression of α2,3-/α2,6-sialylated glycotopes on skim milk glycoproteins over lactation. Milk samples were analyzed by lectin-blotting using α2,3- and α2,6- sialic acid specific Maackia amurensis (MAA) and Sambucus nigra (SNA) lectins and sialyl- and asialyl-T antigen specific Artocarpus integrifolia (Jacalin) and Arachis hypogaea (PNA) lectins. The reactivities of MAA, SNA, Jacalin and PNA with milk glycoproteins showed that they are heavily decorated with α2,3-/α2,6-linked sialic acid and sialyl-T antigen and to a lesser degree with asialyl-T antigen. Despite individual differences of particular glycoproteins, a sharp and significant decline of α2,6-sialylated glycotopes and sialyl-T antigens and a weaker but significant decrease of α2,3-sialylated glycotopes and asialyl-T antigens on milk glycoproteins during milk maturation was observed. The expression of α2,3-/α2,6-sialylated glycotopes, sialyl- and asialyl-T antigens corresponds to milk maturation but differs in relation to the analyzed glycoprotein. Sialylated milk glycoproteins are considered as a part of innate immunity provided to neonates. Further investigations are needed to understand if they may be useful in milk banking to control the biochemical quality of milk.

Nanotechnology is a multidisciplinary field evolved within past few decades and playing substantial role in environment, industry, agriculture and pharmacology. Integration of nanotechnology and biotechnology has led to the foundation of nanomedicine. It has provided novel breakthroughs in cure of various ailments and disorders, drug delivery systems, detection and diagnostics of different diseases. However, use of microbially synthesized nanoparticles in health and medicine is still limited. This article highlights the green approach of nanomaterials synthesis using microbes and current status of their applications in biomedical field.

Candida, a commensal and opportunistic fungal pathogen has been typically known for its biofilm forming ability and device-associated hospital acquired infections in human. The study aimed at exploring the in vitro anti-biofilm and anti-metabolic activity of AgNPs against C. albicans (n = 2),C. tropicalis (n = 2) and C. parapsilosis (n = 2) isolated from urine samples. Broth dilution method revealed greater than 50% inhibition at 100 ppm against Ag NPs in 24 h. An overall reduction of 55-86% in biomass (crystal violet staining assay) and 20-73% in metabolic activity (XTT assay) was observed in 24 h old biofilms. However, C. albicans proved to be more susceptible to AgNPs compared to C. tropicalis and C. parapsilosis. Scanning Electron Microscopy revealed patchy growth and deterrence in biofilm biomass when Ag NPs were coated on urinary catheter. Furthermore, viable cell counts of Candida were significantly reduced on AgNPs coated catheter compared to control.

Introduction
The development of inertial sensors in motion capture systems enables precise measurement of motor symptoms in Parkinson's disease (PD). The type of physical activities performed by the PD participants is an important factor to compute objective scores for specific motor symptoms of the disease. The goal of this study is to propose an approach to automatically detect the physical activities over a period time and segment the time stamps for such detected activities.
Methods
A wearable motion capture sensor system using inertial measurement units (IMUs) was used for data collection. Data from the sensors attached to the shoulders, elbows, and wrists were utilized for detecting and segmenting the activities. An unsupervised machine learning algorithm was employed to extract suitable features from the appropriate sensors and classify the data points to the corresponding activity group.
Results
The performance of the proposed technique was evaluated with respect to the manually labeled and segmented activities. The experimental results reveal that the proposed auto detection technique - by obtaining high average scores of accuracy (96%), precision (96%), and recall (98%) - is able to effectively detect the activities during the sitting task and segment them to the proper time stamps.

Among all oral diseases, teeth infection is a commonly encountered problem in dentistry with teeth blackening commonly seen in kids. One of the major causes of teeth blackening are the chromogenic bacteria which form biofilm in the teeth. So far there is no significant and safe treatment available for teeth blackening. The current study focuses on teeth blackening by chromogenic bacteria and various factors promoting the biofilm formation and its treatment by an alternative herbal approach. Distinct colonies isolated from dental swabs of children with black stained teeth were grown individually on oyster shell to identify the particular isolate responsible for tooth discoloration. The interaction of traditionally known substances like NaCl, glucose, charcoal powder, mustard oil, KMnO₄ and H₂O₂ on the growth of bacterium and biofilm forming ability were studied. Further, the leaf and stem extracts of Achyranthus aspera and Alternanthera sessilis (available locally) on the growth and biofilm formation was also evaluated. Finally, the efficacy of the various agents was determined by the reduced biofilm formation as well as change in the membrane potential of the isolates. From our results we propose a non-toxic approach comprising herbal compounds and household reagents against teeth blackening to improve oral hygiene.

Objective
The aim of this study was to determine the effects of Shen-Fu injection treatment on skin flap survival in an experimental random pattern skin flap model in rats.
Materials and methods
Ninety male Sprague-Dawley (SD) rats were randomly assigned to the SFI-treated groups and normal saline-treated (control) group. SFI (10 or 20 ml/kg) or normal saline (10 ml/kg) were administered intraperitoneally once daily. On postoperative day 2, malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor α (TNF-α) and IL-6 were evaluated. Besides, flap survival rate, tissue edema, mean vessel densities, number of neutrophil, flap angiography and vascular endothelial growth factor (VEGF) expression were examined on day 7.
Results
Compared with the control group, the mean survival area in SFI groups were significantly larger showing a possible dose-dependent effect of SFI. SOD activity was increased significantly, as well as the VEGF expression. MDA level, in the test group, however, was decreased. The hematoxylin and eosin (H&E) stained slices revealed that SFI had the angiogenesis promotion effect, meantime inflammation was clearly inhibited in the SFI groups.
Conclusion
This study showed that intraperitoneally administered SFI significantly improved random skin flap survival in rats.

Recently, oxidative stress has been identified as a pivotal pathological factor inducing bone osteoporosis. This phenomenon is responsible for low bone density. It alters bone quality and generates bone fractures. Strontium is found to induce osteoblast activity by stimulating bone formation and reducing bone resorption by restraining osteoclasts. Bioglass (BG) has been used to repair bone defects, and, in combination with strontium (BG-Sr), offers an opportunity to treat this disease. This study investigated the potential role of BG-Sr in improving antioxidant activity and regenerative bone capacity, The effects of both BG-Sr and BG were tested on osteoblast SaOS2 and endothelial EAhy926 cell proliferation in vitro. In vivo, BG-Sr and BG were implanted in the femoral condyles of Wistar rats and compared to that of control groups. Cell proliferation increased significantly by 120% at SaOS2 and 127% at EAhy926. Superoxide Dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GPx) were significantly enhanced in BG-Sr treated rats compared to other groups. Moreover, a significant decrease of thiobarbituric acid-reactive substances (TBARs) was observed. The Ca/P ratio increase improved progressive bone mineralization. According to these results, BG-Sr ameliorated cell proliferation and developed an antioxidative defense against ROS. The histological findings highlight the BG-Sr implications in the osteoporosis treatment confirmed by bone construction. The development of BG-Sr as a therapeutic biomaterial protecting against oxidative stress might make an effective choice for application in tissue engineering.

The authors investigated whether cytosolic free calcium concentration ([Ca²⁺]c) plays a role in hydrogen peroxide-induced pancreatic acinar AR42J cells apoptosis. We analysed mitochondrial depolarization, [Ca²⁺]c determination and caspase-3 activity by fluorimetric methods, and cytochrome c release by subcellular fractionation and western blotting. The data shown that hydrogen peroxide, which causes a sustained [Ca²⁺]c increase, induces mitochondrial depolarization and cytochrome c release, and activation of caspase-3. Dimethyl-BAPTA loading did not affect hydrogen peroxide-evoked mitochondrial apoptosis, suggesting that these responses are independent of increases in [Ca²⁺]c. Treatment with thapsigargin, to induce extensive calcium store depletion and subsequent increases in [Ca²⁺]c, also stimulates mitochondrial depolarization cytochrome c release, and caspase-3 activation. Similar results were observed in AR42J cells loaded with dimethyl-BAPTA, suggesting that activation of apoptosis by thapsigargin does not require rises in [Ca²⁺]c. However, the blockade of mitochondrial calcium entry by pretreating with Ru360 showed protection against hydrogen peroxide- and thapsigargin-induced mitochondrial apoptosis. These results indicate that the apoptosis evoked by hydrogen peroxide and thapsigargin is mediated by mitochondrial calcium uptake.

The ability to detect pathogenic and physiologically relevant molecules in the body with high sensitivity and specificity offers a powerful opportunity in the early diagnosis and treatment of diseases. Early detection and diagnosis can be used to greatly reduce the cost of patient care associated with the advanced stages of many diseases. However, despite their widespread clinical use, these techniques have a number of potential limitations. For example, a number of diagnostic devices have slow response times and are burdensome to patients. Furthermore, these assays are expensive and cost the health care industry billions of dollars every year. Therefore, there is a need to develop more efficient and reliable sensing and detection technologies. A biosensor is commonly defined as an analytical device that uses a biological recognition system to target molecules or macromolecules. Biosensors can be coupled to a physiochemical transducer that converts this recognition into a detectable output signal. Typically biosensors are comprised of three components: (1) the detector, which identifies the stimulus; (2) the transducer, which converts this stimulus to a useful output; and (3) the signal processing system, which involves amplification and display of the output in an appropriate format. The goal of this combination is to utilize the high sensitivity and selectivity of biological sensing for analytical purposes in various fields of research and technology. We review here some of the main advances in this field over the past few years, explore the application prospects, and discuss the issues, approaches, and challenges, with the aim of stimulating a broader interest in developing biosensors and improving their applications in medical diagnosis.

Elevated ferritin levels may lead to oxidative stress, and are associated with coronary artery disease (CAD). Sleep disordered breathing (SDB) is frequently present in atherosclerosis patients, and causes endothelial dysfunction leading to atherosclerotic plaque progression. Hypoxic conditions, such as SDB, may upregulate ferritin. The aim of this study was to evaluate ferritin levels in CAD patients and to correlate ferritin levels with parameters related to CAD progression, including SDB. We studied 27 patients with CAD (defined as >30% coronary narrowing) and 29 controls. We found that ferritin was increased in CAD patients, and was positively correlated with the apnea-hypopnea index (AHI), age, C-reactive protein (CRP), transferrin, hemoglobin, and testosterone levels, and was negatively correlated with O₂ saturation. Nitrites and nitrates, an indirect measure of nitric oxide (*NO) concentration, were lower in CAD patients, and were negatively correlated with ferritin. The increase in ferritin may be related to oxidative stress, suggesting a possible pro-atherosclerotic role of increased ferritin in CAD patients with SDB.

A small molecule EGFR inhibitor, 4-(2-(3-(4-(4-(trifluoromethyl)phenyl)thiazol-2-yl)ureido)vinyl)-1,2-phenylene diacetate ( CIU1) was designed in silico by using caffeic scaffold as core structure. The designed compound showed anti-proliferative action against different solid tumor cell lines, particularly metastatic breast cancer cells. CIU1 inhibited the growth of EGFR-overexpressing MDA-MB-468 triple-negative breast cancer cells and wild-type non-small-cell lung cancer H460 cells with IC₅₀ values of 8.96 μM and 12.98 μM, respectively, these anti-proliferative effects of CIU1 were comparable to gefitinib (a specific EGFR inhibitor) or lapatinib (a dual EGFR and HER2 tyrosine kinase inhibitor). Interestingly CIU1 effectively inhibited the invasive hormone-dependent MCF-7 cancer cells with an IC₅₀ 2.34 μM. The immunoblot analyses revealed that CIU1 induced programmed cell death and suppressed EGFR expression in EGFR-overexpressing breast cancer (MDA-MB468) and lung cancer (PC-9) cells. The findings substantiated our design strategy and demonstrated the potential of CIU1 as new lead for further optimization in the development of anticancer drugs against advanced solid tumors.

Ginger and turmeric rhizomes are used in folk medicine for the treatment of several cerebrovascular diseases with limited scientific basis for their action. Hence, in this study, we investigate the effects of two Zingiberaceae varieties (ginger and turmeric) on ectonucleotidases (NTPDase and 5'-nucleotidase), adenosine deaminase (ADA) and acetylcholinesterase (AChE) activities in synaptosomes of cerebral cortex from l-NAME induced hypertensive rats. The animals were divided into seven groups (n = 10): normotensive control rats; hypertensive rats; hypertensive rats treated with atenolol; normotensive and hypertensive rats treated with 4% supplementation of turmeric and ginger rhizomes, respectively. After 14 days of pre-treatment with both rhizomes the animals were induced with hypertension by oral administration of l-NAME. The results revealed an increase of ATP and AMP hydrolysis as well as ADA and AChE activities of cerebral cortex synaptosomes in induced rats when compared with the control. The supplementation of both rhizomes prevented these alterations by decreasing ATP and AMP hydrolysis and ADA and AChE activities in cerebral cortex. In conclusion, this study demonstrated that both rhizomes interfere with the purinergic and cholinergic neurotransmission in cerebral cortex of hypertensive rats. Therefore, we can suggest that both rhizomes exert neuroprotective potential under hypertensive state.

In the literature, carbamates pesticides (CMs) have been implicated in the increasing prevalence of diseases associated with alterations of the immune response, such as hypersensitivity reactions, some autoimmune diseases and cancers. CMs may initiate, facilitate or exacerbate pathological immune processes, resulting in immunotoxicity by induction of mutations in genes coding for immunoregulatory factors and modifying immune tolerance. In the present study, oxidative stress and inhibition of esterases activities have been introduced as the main mechanisms of CMs induced immune dysregulation. In addition, the evidence on the relationship between CMs pesticide exposure, dysregulation of the immune system and predisposition to different types of cancers are criticized.

Sulfate-reducing bacteria (SRB) are most likely involved in both the initiation and maintenance of inflammatory bowel disease (IBD); unfortunately present antibacterial chemotherapeutics used in the treatment of IBD have been ineffective. Thus, the antimicrobial activity of salicylamide derivatives against two different genera of intestinal SRB, Desulfovibrio and Desulfomicrobium, was investigated. Six 2-(phenylcarbamoyl)phenyl N-[(benzyloxy)carbonyl]alkanoates and three 2-hydroxy-N-[(2S)-1-oxo-1-(phenylamino)alkan-2-yl]benzamides showed MIC values in the range from 0.22 to 0.35 μM against Desulfovibrio piger Vib-7 and in the range from 0.27 to 8.52 μM against Desulfomicrobium sp. Rod-9, while MIC values of ciprofloxacin were 41.2 μM and 39.3 μM. The highest potency against the two strains was observed for 4-chloro-N-{(2S)-1-[(3,4-dichlorophenyl)amino]-3-methyl-1-oxobutan-2-yl}-2-hydroxybenzamide (MIC 0.22 μM and 0.27 μM). 4-Chloro-2-[(4-nitrophenyl)carbamoyl]phenyl (2S)-2-{[(benzyloxy)carbonyl]amino}-3-methylbutanoate showed high activity against D. piger Vib-7 (MIC = 0.26 μM), while 4-chloro-2-[(4-methylphenyl)carbamoyl]phenyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-2-yl)propanoate expressed high activity against Desulfomicrobium sp. Rod-9 (MIC = 0.31 μM). Structure-activity relationships are discussed.

To improve the knowledge in chronophysiology we investigated the causal link between the most important physiological variable studied until now; ten Sarda ewes and ten Sarda goats, pluriparus not pregnant and no lactating, were used. Animals were housed under natural environmental conditions in a common stall, alfalfa hay and water were available ad libitum. Each animal was equipped with an Actiwatch-Mini^® for recording total activity. Blood samples were collected every 4 h over a 48 h period for the assessment of melatonin concentration. Rectal temperature was recorded with a digital thermometer immediately before the blood sampling at each data point. Single cosinor method showed a daily rhythm of studied variables. Higher MESOR and amplitude values of melatonin and rectal temperature were observed in sheep than in goats. The diurnal acrophase of locomotor activity was statistically different from the nocturnal acrophase of melatonin and rectal temperature, with no differences between the two species. Robustness was statistically lower in total locomotor activity in comparison with the others two variables, with a differences due to species in melatonin daily rhythm. In conclusion, in small ruminants, melatonin and rectal temperature daily rhythms are strictly correlated, and are not associated with the locomotor activity rhythm.

pH-dependent sustained-release Tulsion^® microspheres bearing clarithromycin were prepared using quasi-emulsion solvent diffusion method with thermocoat L 30 D 55 as a release retardant. Both, clarithromycin and thermocoat L 30 D 55, were found to be non-hemolytic during in vitro toxicity assay against human red blood cells. Ratiometric optimization of different solvents using phase diagrams was performed on amount of good solvent, bridging liquid, dispersing liquid and poor solvent. The developed microspheres were evaluated for the recovery (67.27 ± 3.3%), average particle size (52.0 ± 0.46 μm) and encapsulation efficiency (61.0 ± 3.1%). Scanning electron microscopy and transmission electron microscopy revealed that the microspheres were smooth in surface and spherical in shape, respectively. The drug release study was conducted at different pH of GIT and it gave a pH dependent release for clarithromycin. The bioavailability study revealed increased AUC (2 fold) and half-life (1.2 fold) of microspheres as compared to plain drug. The manuscript reported the debut work on thermocoat L 30 D 55 based novel drug delivery system, the polymer is safe to be used, quasi emulsion spherical crystallization technique is a good technique to prepare microspheres, the prepared microspheres provides sustain release profile as well as targeting to colon.

Alzheimer's disease (AD) threatens to become the scourge of the 21st century, hence there is an urgent need for the exploration of multipotent drug in the treatment of AD. Rhizophora mucronata, tropical red mangrove has been widely used in traditional oriental medicine as astringent, antiseptic, antibacterial, anti-ulcerogenic and anti-inflammatory agent. The present study aimed to evaluate the neuroprotective effect of the catechin rich methanolic leaf extract of R. mucronata (MERM), against Aβ-induced neurotoxicity. Exposure of PC12 cells to Aβ (25-35) increased cellular oxidative stress, the number of apoptotic cells and caspase-3 activity ultimately leading to neuronal death. Pre-treatment with MERM (50 μg/ml) significantly attenuated cell death, decreased the level of intracellular reactive oxygen and nitrogen species thereby inhibiting lipid peroxidation and protein oxidation. MERM attenuated Aβ (25-35) induced apoptosis by stabilizing the mitochondrial membrane potential, and inhibiting caspase-3 activity. MERM also restored the antioxidant status of the Aβ (25-35) treated cells by effectively scavenging ROS/RNS species. HPTLC analysis of MERM illustrated the presence of (+)-catechin as major constituent. Results conclude that MERM effectively attenuated the neurotoxicity induced by Aβ-associated oxidative stress, implying that MERM can act as a potent drug for the treatment of AD.

Colorectal cancer (CRC) is an important public health problem estimated as the third most commonly diagnosed cancer worldwide. Naphthoquinones are compounds present in different families of plants and interesting for medicinal chemistry due to their activities as potent inhibitors of human cancer growth. In this way, our study aimed to evaluate the cytotoxicity and selectiveness of four 2,3-triazole-1,4-naphthoquinone derivatives (N1-N4) towards the CRC cell line HT-29 and normal human cells. MTT assay showed that N1, N2, N3 and N4 elicited distinct cytotoxic potency, exhibiting EC₅₀ values of 40.6 ± 1.0, 100.1 ± 1.0, 241.9 ± 1.2 and 101.9 ± 1.1, respectively. Later, flow cytometry in HT-29 cells loaded with propidium iodide (5 μM), indicated the ability of N4 (0.5-50 μM) to induce cell membrane damage. Additionally, calcium imaging experiments were conducted in HT-29 cells loaded with 5 μM Fluo-3/AM to assess intracellular Ca²⁺ (iCa²⁺). Our data demonstrated that N4 induces a fast and strong increase of iCa²⁺ in HT-29 cells, mediated by voltage-gated L-type Ca²⁺ channels activation. In conclusion, our study reported on the cytotoxicity and selectiveness of 1,2,3-triazol substituted 1,4-naphthoquinones towards the HT-29 CRC cell line. Furthermore, we have demonstrated the participation of voltage-gated L-type Ca²⁺ channels in the N4 mechanism.

The use of biotherapies as intervention in murine infection with Trypanosoma cruzi is a possible means to understand the effects of these highly diluted medications. This study evaluated the effects of biotherapies that were prepared from rabbit serum uninfected (BSNI_13c group) and chronically infected with Y strain of T. cruzi (BSI_13c group), dynamization 13c, in mice experimentally infected. Parasitological, histopathological, and immunological parameters were evaluated. BSNI_13c group exhibited the best outcome, including decreases in parasitemia and parasite load/inflammation in the heart, with pronounced Th1 response on days 8 and 12 after infection (a.i.) that was attributable to decrease in IL-4 concentrations, with no increases in TNF-α and IFN-γ, associated to decrease in IL-17A compared to control. In contrast, BSI_13c group did not exhibit alterations in parasitemia but a significant decrease in parasite load/inflammation in the heart, with pronounced Th2 response on day 12 a.i. that was attributable to increase in IL-4 concentrations, with no changes in TNF-α and IFN-γ, associated to decrease in IL-17A compared to control. This study suggest that biotherapies that were prepared from rabbit serum uninfected and chronically infected with T. cruzi differentially modulate the immune system in mice infected with this protozoan, providing evidence of the actions of these medications.

Phenazine-1-carboxylic acid has extensive pharmacological activity, including antibiotic and immunomodulatory, but the anticancer activity remains unknown. Treatment of prostate cancer cell line (DU145) with phenazine-1-carboxylic acid stimulated inhibition of cell proliferation in concentration- and time-dependent manner. Dual staining confirmed phenazine-1-carboxylic acid stimulated prostate cancer programmed cell death in time-dependent manner. To investigate the exact mechanism, phenazine-1-carboxylic acid-stimulated oxidative stress and mitochondrial-related apoptotic pathway in human prostate cancer cells were examined in this study. Phenazine-1-carboxylic acid increased the generation of reactive oxygen species (ROS) in prostate cancer cell lines, which triggered the pro-apoptotic JNK signaling. Phosphorylated JNK stimulated the depolarization of mitochondrial membrane potential (ΔΨm) and downregulation of anti-apoptotic protein Bcl-2 related with the upregulation of pro-apoptotic protein Bax. Downregulation of anti-apoptotic Bcl-2 family protein in corresponding with loss of ΔΨm, stimulate the increased production of cytochrome c and programmed cell death inducing factor (AIF) from mitochondria, and ultimately induced the caspase-dependent and caspase-independent programmed cell death. Altogether, the present study suggests that phenazine-1-carboxylic acid showed an antitumor activity in prostate cancer cells by reactive oxygen species production and mitochondrial-related apoptotic pathway. The results of the present study offered an insight into the prospective of phenazine-1-carboxylic acid for prostate cancer therapy.

The effect of the combination of α-pinene and β-caryophyllene on the proliferation of the Trypanosoma evansi was analyzed. These compounds were added individually and in combination at different concentrations to T. evansi cultures, and the in vivo study used mice of 1.0 and 1.5 mL kg^-1 of α-pinene and β-caryophyllene individually and in combination against T. evansi. In order to evaluate the in vitro safety, lymphocytes and VERO cells were assessed using tetrazolium salt (MTT) assay. The trypanocidal effect of α-pinene and β-caryophyllene was observed in vitro when applied independently or combined at 0.5, 1 and 2% concentrations. The combination effect showed a faster trypanocidal effect when compared to chemotherapy (diminazene aceturate - D.A.). Concerning the in vivo evaluation, α-pinene + β-caryophyllene at 1.0 mL kg^-1 was able to extend animal longevity and showed 83.33% curative efficacy, a superior result when compared to D.A. (16.66%). The MTT assay showed that the assessed compounds do not present toxicity to used cells. Also, in vivo safety evaluation of α-pinene + β-caryophyllene at 1.0 mL kg^-1 not altered the aminotransferases levels in serum. Combination between α-pinene and β-caryophyllene shows in vitro and in vivo trypanocidal activity against T. evansi, in a safe dose.

Betahistine dihydrochloride, which is widely prescribed for the treatment of symptoms associated with Meniere's syndrome, is generally administered orally in solid or liquid formulations. There is a strong need of profound investigation of alternative routes of administration of betahistine to overcome difficulties related to oral administration. The aim of this study was to evaluate betahistine cytotoxicity and permeability in vitro and to assess the drug's relevance for incorporation in drug delivery systems for nasal administration. RPMI epithelial model was used to evaluate drug permeability in vitro. The cytotoxicity of betahistine was assessed by MTT test. Chitosan microspheres were used as a betahistine delivery system. RPMI 2650 formed a thick, impermeable cell layer on the apical side of the filter inserts and developed enough TEER values to confirm confluence. According to the obtained results, BET showed high permeability coefficients (Papp values in the range 2.3 × 10^-5 to 19 × 10^-5) and could, therefore, be successfully used in nasal drug delivery formulations. Also, BET exhibited a good safety profile regarding nasal epithelium toxicity. A dose-dependent reduction in cell viability was observed. The microspheres as drug delivery systems affected BET permeation profiles due to the presence of chitosan as an absorption enhancer.

Oxidative stress and NF-κB signaling plays a major role in pathogenesis of osteoarthritis. In the present study, we analyzed the potent role of carnosol against osteoarthritis in cells treated using monosodium iodoacetate (MIA) model through in vitro studies. MIA caused dose-dependent cell death and induced programmed cell death by increasing subG1 accumulation and caspase-3 expressions. MIA caused oxidative stress by increasing reactive oxygen species, lipid peroxidation and further induced NF-κB expression and down regulated Nrf-2 levels. Pre-treatment with carnosol significantly protected the cells by reducing the oxidative stress markers and improved the cell viability up to 98%. Further, carnosol down regulated NF-κB nuclear expression with a concomitant increase in Nrf-2 nuclear localization and up regulated the nuclear Nrf-2 levels. Carnosol also inhibited MIA-induced subG1 accumulation and caspase-3 activation. This study demonstrates that, carnosol might act as potent antioxidant and regulate MIA-induced oxidative stress, NF-κB signaling and programmed cell death by up regulating the Nrf-2 levels.

Glucose is a typical marker of diabetes mellitus but it corresponds also with metabolic syndrome, immune disorders and some types of poisoning. Hence fast, low cost and simple method for its determination is required. Bubble wrap, cheap and available material, was used for immobilization of glucose oxidase (GOx) and peroxidase (POx), the enzymes necessary for colorimetric determination of glucose. Method is based on reaction of enzymes (immobilized in sol-gel membrane inside the bubbles) with substrates glucose and o-phenylenediamine dihydrochloride (o-PD) providing intensive coloration. The color change can be easily tracked by phone integrated camera. Color intensity expressed in red-green-blue (RGB) color model was used for displaying of photos and for gaining numeric data representing concentrations of glucose. The assay exerted good correlation of color intensity with the concentration of glucose, adequately low limit of detection (750 mmol/l) for glucose blood assay, no influence of interferents or matrix substances and by sufficient long term stability of sol-gel membrane. The sensor was found as low-cost simple way to analyze glucose blood levels with promising prospects in the field of portable devices.

This study aimed to investigate the effect of phenylhydrazine-induced hemolytic anemia on testicular functions and protective role of crocin in mice. Forty-nine adult male mice were studied in 7 groups. The control mice received normal saline, three groups were treated with 2, 4, and 6 mg/100 g of phenylhydrazine, and three other groups received 20 mg/100 g of crocin with phenylhydrazine for 35 days. Then, the blood samples were taken to examine oxidative stress of serum, sperm samples were obtained for IVF testing, and testicle tissue samples were taken for morphological studies. Morphometric results indicated a significant reduction in TDI (tubular differentiation index), RI (repopulation index or number of type B spermatogonia), and SI (spermiogenesis index) factors, number of Sertoli and Leydig cells, and diameter of germinal epithelium in the groups receiving phenylhydrazine. Histochemical results indicated some changes in the metabolic cycle of the testicle and results of serum tests showed variations in the peroxidation of lipids and antioxidant capacity of serum. Also, hemolytic anemia significantly reduced testicular parameters and crocin minimized the resulting injuries. It can be concluded that crocin is able to neutralize the complications which are resulting from the hemolytic anemia relating to testicular parameters.

Toxins are produced by bacteria, plants and animals for defense or for predation. Most of the toxins specifically affect the mammalian nervous system by interfering with the transmission of nerve impulses, and such toxins have the potential for misuse by the military or terrorist organizations. This review discusses the origin, structure, toxicity and symptoms, transmission, mechanism(s) of action, symptomatic treatment of the most important toxins and venoms derived from fungi, plants, marine animals, and microorganisms, along with their potential for use in bioweapons and/or biocrime. Fungal trichothecenes and aflatoxins are potent inhibitors of protein synthesis in most eukaryotes and have been used as biological warfare agents. Ricin and abrin are plant-derived toxins that prevent the elongation of polypeptide chains. Saxitoxin, anatoxin, and tetrodotoxin are marine-derived toxins that bind to sodium channels in nerve and muscle tissue and cause muscle paralysis. Most bacterial toxins, such as botulinum and Shiga affect either the nervous system (neurotoxins) or damage cell membranes. Batrachotoxins, which are secreted by poison-dart frogs are extremely potent cardiotoxic and neurotoxic steroidal alkaloids. The aim of this review is to provide basic information to enable further understanding of these toxins and their potential military uses.

In this study we analyzed molecular mechanisms of antioxidative protection of thymol and thyme oil using differentiated PC12 cells, a widely accepted neuronal model. Thymol due to multiple functions is commonly used for clinical applications. However, its action on nervous tissue remains poorly understood. We evaluated the effect of 24 h incubation of the cells with thymol (100 and 400 μM) and equivalent content of thyme oil. Microsomal glutathione transferase 1 (Mgst1) is an important player in anti-oxidative protection because of its transferase and peroxidase activities. Since its expression decreases during aging, we also used stable transfected cells with downregulated Mgst1 (PC12_M). We analyzed cell viability, lipid peroxidation level, glutathione content and expression of key enzymes responsible for cellular reduced glutathione - catalytic subunit of γ-glutamylcysteine ligase and glutathione reductase. Whereas thymol and thyme oil improved antioxidant capacity of control cells, diminished protection was observed in PC12_M line. Increasing interest in natural dietary components has focused attention on plants used as a rich source of bioactive phytochemicals. However, currently available information on the safe amount for thyme oil using appears to be insufficient. Our results indicate that the thyme oil should be used with caution, especially by elderly people.