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A comparative study of aromatic secondary metabolites and antioxidant, antimicrobial, and anticancer potential of two lichen species Cladonia coniocraea and Cladonia ramulosa is presented in this paper. HPLC-UV analysis revealed the presence of depsidone fumarprotocetraric acid and depside sekikaic acid as major aromatic metabolites in both tested species but in different amounts. The antioxidant activity was evaluated by free radical scavenging and reducing power assays. In both assays the extracts showed weak activity (IC50>1000 μg/ml, while absorbances for reducing power were from 0.0118 to 0.1675). The total content of phenol and flavonoid in extracts was examined using Folin–Ciocalteu reagent and aluminium chloride method and the obtained values were expressed as pyrocatechol equivalents, and as rutin equivalents, respectively. Further, the antimicrobial activity was estimated by determination of the minimal inhibitory concentration by the broth microdilution method against five bacterial and 10 fungal species. Tested extracts showed similar antimicrobial activity with minimum inhibitory concentration values ranging from 0.156 to 20 mg/ml. Finally, the cytotoxic activity was tested using MTT method on the human epithelial carcinoma (Hela), human lung carcinoma (A549) and human colon carcinoma (LS174) cells. The strongest cytotoxic activity with IC50 value of 185.59 μg/ml expressed extract of C. ramulosa toward Hela cells. Obtained results indicate that these lichens showed the potential for further investigation and possible biopharmaceutical application.

Introduction: Despite the important role of general KRAS mutational status in the selection of an adequate therapeutic protocol in patients with colorectal cancer (CRC), studies that focus on its specific mutations and their significance on progression of disease are scarce. This study aimed to determine the significance of specific KRAS mutations in response to standard chemotherapy protocols with oxaliplatin-based (FOLFOX 4, OXFL) in the first-line and irinotecan-based chemotherapy (FOLFIRI, IFL) in the second-line therapy, and to evaluate the correlation between these mutations and clinicopathological characteristics of CRC patients. Methods: Genomic DNA was extracted from the FFPE tumour tissue sections while the KRAS mutation test was performed by using PCR methods. Results: Prevalence of KRAS gene mutations in CRC patients was 45%. Mutated KRAS was more frequent in later stages of tumor infiltrations (P =0.0017), on the right side of the colon (P= 0.0044), and in patients who developed metastases in the first 6 months after CRC diagnosis than in patients who developed metastases after 24 months (P=0.0083). In a group of patients with a poor therapeutic response to standard chemotherapy the most frequent mutations in KRAS gene were G12D and G12V (63.88%), while in a group of patients with a good response to therapeutic protocols the most prevalent mutation was G12A (66.66%). Conclusion: Our results indicate that there was a significant difference in biological behaviour between tumours harboring different mutations in KRAS gene. Overall, mutation G12A could be a novel prognostic biomarker for CRC patients treated with standard chemotherapy.

Bone loss leading to osteopenia and osteoporosis is a frequent secondary complication of diabetes. This study aimed to evaluate the value of a traditionally used ‘anti-diabetic’ polyherbal mixture as a possible remedy for the prevention of this complication. Diabetes was induced in Wistar female rats with a single intraperitoneal injection of alloxan monohydrate. The animals with blood glucose higher than 20 mmol/L for 14 consecutive days were considered diabetic. For the next 14 days, animals were treated with two concentrations of the polyherbal mixture (10 and 20 g of dry plant material/ kg). Bone histopathology was evaluated using the H&E and Masson’s trichrome staining. Alloxan-induced diabetes triggered bone histological changes characteristic for the development of osteopenia and osteoporosis and treatment with the polyherbal decoction restored these histopathological changes of the bones to the healthy animal level. At the same time, treatment with these tested doses has shown no adverse effects. These findings suggest that this mixture might be used as a remedy for the prevention of diabetic bone loss.

The aim of this study is to investigate the chemical composition of extracts of the lichens Parmelia conspersa and Parmelia perlata and their antimicrobial, antioxidant, and anticancer activities. The phytochemical analysis of the acetone extracts of two Parmelia lichens was determined by (HPLC-UV) method. The predominant phenolic compounds in these extracts were norstictic acid and usnic acids in P. conspersa, while salazinic acid and stictic acid were the major metabolites detected in P. perlata. Besides these compounds, the tested extracts of these lichens contain atranorin and chloroatranorin. The lichen extracts showed comparable and strong antioxidant activity, exhibited higher DPPH and hydroxyl radical scavengings, chelating activity, and inhibitory activity towards lipid peroxidation. The lichen extracts demonstrated important antimicrobial activity against eight strains with MIC values from 19.53 to 312.5 µg/mL. Cytotoxic effects of lichens were tested against Hep2c, RD and L2OB cell lines using MTT method. Cytotoxic effects of P. conspersa and P. perlata extracts toward three cancer cell lines were in the range from 76.33 to 163.39 µg/mL. This is the first report of the detail chemical composition of the lichens P. conspersa and P. perlata. The present study showed that tested extracts of lichens demonstrated a important antimicrobial, antioxidant and anticancer effects. That suggests that these lichens can be used as new sources of the natural antimicrobial agents, antioxidants and anticancer compounds.

The aim of this study is to investigate the chemical composition of methanol extracts of the lichens Pleurosticta acetabulum and Cladonia subulata and their antioxidant, and anticancer activities. The phytochemical analysis of the extracts of lichens was determined by HPLC-UV method. The predominant phenolic compounds in these extracts were norstictic acid and salazinic acids in P. acetabulum, while hypoprotocetraric acid and fumarprotocetraric acid were the major metabolites detected in C. subulata. Total phenolics and flavonoids in the extracts were determined spectrophotometrically, with the varied amount from 21.31 to 73.45 mg GA/g and from 8.48 to 15.42 mg RU/g, respectively. The lichen extracts showed comparable and strong antioxidant activity, exhibited higher DPPH and hydroxyl radical scavengings, inhibitory activity towards lipid peroxidation and reducing power. Cytotoxic effects of lichens were tested against HeLa S3 and LS174 cell lines using MTT method.The cytotoxic effects of P. acetabulum and C. subulata extracts toward two cancer cell lines were in the range from 39.17 to >200 μg/mL IC50 value. The present study showed that the tested extracts of lichens demonstrated important antioxidant and anticancer effects. That suggests that these lichens can be used as new sources of the natural antioxidants and anti-cancer compounds.

One of the commonly used herbal preparation in traditional medicine is made of Rubus fruticosus leaves, Vaccinium myrtillus leaves, Potentilla erecta roots, Geum urbanum aerial parts and Phaseolus vulgaris pods, but little is known about potential toxicity and antitoxicity of these medicinal plants and their accumulated biological effect when used as a herbal mixture. In the present study, possible cytotoxic/genotoxic and anticytotoxic/ antigenotoxic effects of the tested extracts were evaluated using the Allium cepa assay and RBCs antihaemolytic test. Determined by the A. cepa genotoxicity assay, the lowest genotoxic effect was expressed by the herbal mixture extract, and the highest one by P. vulgaris and V. myrtillus. In the A. cepa antigenotoxicity assay, the herbal mixture (45 μg/ml) and P. vulgaris (70 μg/ml) had the highest capacity to reverse chromosomal aberrations caused by ROS. All the extracts in lower concentrations (25, 50 and 100 μg/ml) showed strong antihaemolytic activity. The present study concluded that, although all the extracts expressed high protective activity against cell damage caused by oxidative stress, the most beneficial use of these medicinal plants is when used as a mixture prepared according to a precisely defined recipe.

Pyrimethanil, a synthetic fungicide widely used for the treatment of pre‐ and postharvest fungal diseases on different agricultural crops, was explored for its antifungal activity on different fungal strains. The effect of pyrimethanil on fungal ergosterol was tested by using Aspergillus niger as a model organism. Furthermore, it was investigated, if pyrimethanil can effectively reduce the appearance of Aspergillus rot in wounded cherry tomato fruits. The fungicide cytotoxic effect on different human cell lines was evaluated. In addition, its influence on cell proliferation was studied. A. niger was the most resistant fungal strain (MFC 1.88 μg μL−1) to the effect of pyrimethanil. Addition of ergosterol doubled the MFC on A. niger, indicating that the compound might interfere with ergosterol, main sterol of fungal cell membrane. Disease incidence of A. niger in wounded cherry tomato fruits was not detected with pyrimethanil treatment of 0.75 mg/wound. Some cytotoxic effects of pyrimethanil on human cell lines were recorded already at 50 ng μL−1, while the expression of Ki67 marker of proliferation was decreased with 150 ng μL−1. These results altogether indicate that pyrimethanil is effective in reducing various fungal pathogens, but further use of this fungicide should be reevaluated because of its cytotoxicity.

Matrix accumulation in the tissue is the main pathological feature of fibrosis. TGF-β1 stimulates the production of extracellular matrix protein and induces fibrosis in different tissues. TNF-α is a proinflammatory cytokine produced in the kidneys by proximal tubular cells, mesenchymal cells, interstitial fibroblasts and macrophages. The aim of this study was to investigate the association of TGF-β1 and TNF-α genes polymorphisms with the risk of developing kidney scars in children with vesicoureteral reflux (VUR). DNA samples analyzed in this study were extracted by a phenol-chloroform method from the peripheral blood of 50 children with VUR and 70 healthy controls. The genotyping was performed by the PCR/RFLP method. Results of this study have shown that homozygous genotype T/T is more frequent in the patient group (χ2 = 13.92, p = 0.0009). It can be concluded that the presence of the genotype T/T on the position -509 in the promoter region TGF-β1 gene is a risk factor for the development of kidney scars in children with VUR (TT vs. CT + CC: OR = 19.4615; CI 2.420-156.477; p = 0.0003). However, there was the absence of association of the promoter region polymorphism of the TNF-α gene region with the risk of developing kidney scars of children with VUR.

The purpose of this work was to assess chemical composition, antibacterial activity against Staphylococcus aureus isolates from catheter-associated infections and antioxidant activity of methanol extracts of three lichens collected from Morocco. The phytochemical analysis of the methanol extracts of these lichens was performed by HPLC–UV method, the predominant phenolic compounds were evernic acid, physodalic acid and usnic acid for Evernia prunastri, Pseudevernia furfuracea and Ramalina farinacea, respectively. Total phenolic compounds and total flavonoid content of all extracts were also determined. As a result, Pseudevernia furfuracea extract had the strongest effect and the highest phenolic compounds content. All extracts showed antibacterial activity against all tested strains (MIC values ranging from 0.078 to 0.625 mg/mL), the strongest inhibition was obtained with the extract of Evernia prunastri.

Analysis of allele frequencies of short tandem repeat (STR) loci in ethnically diverse populations is essential for forensic reference database construction and studies on population genetics.To analyse genetic polymorphisms of 22 autosomal STR loci in the Serbian population and to compare them with previously published data from some European and Turkish populations.The study was conducted among 983 unrelated individuals from Serbia. Genotyping was performed using the PowerPlexA total of 280 alleles were detected with corresponding allelic frequencies ranging from 0.0005 to 0.5255. Based on heterozygosity and the polymorphism information content, D1S1656 and Penta E may be considered as the most informative markers. Both the combined power of discrimination (CPD) and the combined power of exclusion (CPE) for the 22 analysed loci were higher than 0.999999. The combined match probability (CPM) for all 22 loci was 6.773688eWith respect to the results, the 22 STR loci are highly polymorphic and discriminating in the Serbian population and could be used for forensic practice and population genetics studies.

One of the commonly prescribed 'anti-diabetic' polyherbal mixtures by European herbalists is made of Rubus fruticosus and Vaccinium myrtillus leaves, Potentilla erecta roots, Geum urbanum aerial parts and Phaseolus vulgaris pods.This study aimed to evaluate the phytochemical composition, antioxidant capacity, potential toxicity, hypoglycemic, hypolipidemic, nephroprotective and hepatoprotective activities of this polyherbal mixture decoction.The phytochemical composition was evaluated using HPLC-UV. The antioxidant activity was assessed using the DPPH test. Potential toxicity was evaluated using the acute and sub-chronic oral toxicity method. Diabetes was induced in Wistar female rats with a single intraperitoneal injection of alloxan monohydrate (150 mg/kg). The animals whose blood glucose was20 mmol/L for 14 consecutive days were considered diabetic. For the next 14 days, D-10 and D-20 groups were treated with the polyherbal mixture (10 and 20 g of dry plant material/kg, respectively). I and M were control groups treated with insulin glargine (13 IU/kg) and metformin (150 mg/kg), respectively. Healthy control (HC) and diabetic control (DC) groups were treated with water. The blood glucose level was measured on days 14, 21 and 28. Lipid profile analysis was done on day 28. Pancreas, kidney and liver histopathology was evaluated using the HE and Masson's trichrome staining. The liver tissue was additionally tested for PAS-positive cells.The HPLC-UV analysis revealed the presence of quinic, gallic and caftaric acid, arbutin, rutin, trifolin, astragalin, hyperoside, isoquercetin and quercitrin. The antioxidant activity of the extract was higher than the reference's one (p 0.01). Treatment with the polyherbal mixture (10 and 20 g/kg) has shown no toxic effects. No major decline in blood sugar was recorded in I and M groups compared to the DC one (22.86 ± 2.58, 28.5 ± 0.42 and 27.82 ± 0.9 mmol/L, respectively). The polyherbal mixture lowered the blood glucose level to the normal value (8.64 ± 4.09, 5.26 ± 1.3 and 6.76 ± 1.54 mmol/L in D-10, D-20 and HC groups, respectively). Furthermore, it decreased the levels of total cholesterol, triglycerides, VLDL, LDL, atherogenic and cardiovascular risk indices (p 0.001) compared to the DC group. In addition, the extract restored histopathological changes of the pancreas, kidneys and liver to the healthy animal level.Treatment with the polyherbal mixture extract was more effective than the standard drugs (insulin and metformin) in the amelioration of hyperglycemia, hyperlipidemia, and histopathological changes of the pancreas, kidney and liver tissue.

Background. Lichens present a complex symbiotic relationship between a filamentous fungus, photoautotrophic partner (algae or cyanobacteria), and bacterial community. The Objective of the Study. This study aimed at investigating the chemical composition and cytotoxic, antioxidant, and antimicrobial activities of acetone extracts of Moroccan Evernia prunastri (E. prunastri), Ramalina farinacea (R. farinacea), and Pseudevernia furfuracea (P. furfuracea). Materials and Methods. The phytochemical analysis was carried out by HPLC-UV. The cytotoxic effect was assessed on human prostate cancer (22RV1), human colon carcinoma (HT-29), human hepatocellular carcinoma (Hep-G2), and Hamster ovarian cancer (CHO) cells lines by WST1 assay. The antioxidant power was assessed by DPPH and FRAP assays. The antibacterial effect was obtained using the broth microdilution method. Results. The findings of phytochemical analysis showed that the lichens studied possess interesting bioactive molecules such as physodalic acid, evernic acid, and usnic acid, as well as protocetraric acid. According to the American National Cancer Institute guidelines, the WST-1 test showed that all crude extracts did not show significant cytotoxic effects against all concerous cell lines, and IC50 values ranged from 42.30 to 140.24 µg/mL. Regarding the antioxidant activity, P. furfuracea extract showed the highest free-radical-scavenging ability (IC50 = 498.40 µg/mL). The most potent antibacterial extract was recorded for P. furfuracea extract with a minimum inhibitory concentration (MIC) ranging from 0.039 to 0.31 mg/mL. Conclusion. In this research work, we report that the studied lichen extracts exhibit an important biological effect, supporting that lichens represent a hopeful source of original natural products for the research of new bioactive molecules having a pharmaceutical interest.

The use of ethnopharmacological therapies is a part of human tradition. For centuries, they have been used in the treatment of diabetes, as well as other illnesses. The aim of this study was to examine the frequency of traditional medicine use in Serbia. The study was conducted as an online survey in February 2018. 130 people were surveyed, 55.38 % of which were people diagnosed with diabetes. The most commonly used herbal substituents were M. piperita L. (21 %), traditional herbal mixtures designed to regulate the primary and secondary diabetes complications (15%), M. chamomilla L. (13 %) and pharmaceutical supplements based on traditional recipes (10 %). 100 % of people with diabetes adhere to contemporary pharmacotherapy, while 25.86 % of people without diabetes do not use pharmacotherapy, but exclusively traditional medicine. There is no significant difference between the diabetic population that uses traditional medicine (51.34 %) and the one who does not (48.61 %), whereas in non-diabetic population the difference is significant (p < 0.05) so that 87.93 % of them regularly use medicinal herbs. More women than men use ethnopharmacological treatments (p < 0.05). The age of the respondents and their education also have an impact on the choice of therapy, so ethnopharmacological approaches are the most often used by faculty educated people aged 30 to 50 years. Moreover, people pay attention to the quality of supplements they use, i.e. 57.96 % of people buy them in pharmacies, 29.55 % with certified sellers, and only 12.49 % at the local market.

The skill of writing with the left or right hand is often taken as a hand lateralization predictor. Taking into consideration that such a manifestation is usually practiced, left-handedness often becomes 'concealed', making it harder to be phenotypically measured. The aim of this study is to determine the predictability of multiple manual skills in relation to the type of handedness. The sample of 756 primary-school students with the aid of Edinburgh Handedness Inventory showed that writing and drawing skills using a particular hand have a very clear mutual correlation (0.86 with the left-handed, and 0.50 with the right-handed). However, the correlation was not determined with other observed unimanual skills, such as throwing, using scissors, using a tooth brush, using a key and holding a glass. In addition to that, writing as such is not a reliable hand lateralization predictor. In relation to hand lateralization, writing shows a low determination coefficient with the left-handed, whereas for other skills R2 varies within the range 0.43-0.66. The numbers are similar to the right-handed, where R2 varies within the range 0.28-0.53, for all skills, except writing and drawing. A conclusion can be drawn that writing is not a reliable predictor of lateralization to left or right, but that those are skills in relation to which there is no cultural pressure.

A study on the morphological variability and ecological differentiation among the species in the genus Daphne was carried out which included seven species from the Balkan Peninsula: Daphne mezereum, D. laureola, D. alpina, D. oleoides, D. malyana, D. cneorum and D. blagayana. In the Balkan Peninsula, the ranges of the species in this genus overlap, which does not occur anywhere else in Europe. Descriptive statistics were measured for 20 quantitative characters of the leves and stems. A comparative analysis of the morpho-anatomical adaptations of these species shows that: D. cneorum, D. malyana and D. oleoides belong to the adaptive type of xerophytes; D. alpina is a xeromesophyte; D. blagayana and D. laureola are mesoxerophytes; and D. mezereum is a mesophyte. Principal component analysis shows the largest contribution to the formation of the variability between the different species is made by characters that are related to leaf shape (leaf length, distance between the largest leaf width and the leaf top, largest width of the leaf, leaf surface area), followed by surface area of abaxial stomata, stem characters (stem cortex thickness and stem diameter) and leaf anatomy characters (thickness of the palisade tissue, thickness mesophyll, number of palisade layers). These features can use to discriminate among the seven studied species, suggesting that leaves and stems of Daphne can represent a source for taxonomically useful characters. Canonical discriminant analysis and the clustering method based on Mahalanobis distances shows that there is significant morphological differentiation among the species studied. The results show that various combinations of morphological and anatomical features contribute to the adaptive capacity of plants to different degrees. The morpho-anatomical features found in all seven species agree with previous infrageneric taxonomic classifications of this genus.

Background: The purpose of this study is to determine the effect of L-ascorbic acid and alpha-tocopherol as well as combination of these vitamins with or without exposure to physical exercise on intensity of lipid peroxidation, activity of xanthine oxidase, activity of total antioxidative system, concentration of glutathione, and activity of catalase in the serum of guinea pigs. Materials and Methods: The experimental measurements of intensity of lipid peroxidation, activity of xanthine oxidase, activity of total antioxidative system, concentration of glutathione, and activity of catalase were done in the serum of guinea pigs. The animals were exposed to the test load to achieve exhaustion and the test was terminated when the animal for the third time to sink into the water. Results: The results of this study demonstrated that endurance exercise of guinea pigs induced oxidative stress response in terms of increased lipid peroxidation and activity of xanthine oxidase in the serum of experimental animals. Our study investigated the antioxidant activity of L-ascorbic acid and alpha-tocopherol also measuring three protective markers in the serum: total antioxidant activity, content of glutathione and activity of catalase. The results obtained show that the vitamins influence the concentrations of above mentioned biochemical parameters, which points out their protective effect of swimming-induced oxidative stress. Conclusion: Single or combined administration of L-ascorbic acid and alpha-tocopherol caused significant inhibition of these markers indicating the important antioxidant activity of the vitamins. Results lead to conclude that the combined treatments with vitamins with or without exposure to physical exercise showed the clear synergistic effect.

In contemporary clinical practice bone substitutes such as implants are used in reconstructive orthopedics and maxillofacial surgery. Judging from physical and chemical properties each implant has some advantages and disadvantages. The idea of bone tissue engineering is to simulate the formation of bone to implants as carriers in combination with osteogenic cells and osteo-stimulative factors (osteoinduction). The design of the implant itself in terms of the chosen carrier with its own characteristics, the type of cells that have been implanted, the type and combination of stimulative factors play an important role in the behavior of the implanted material within a body. Tissue engineering looks promising, however a lot of obstacles have to be surmounted in order to consider it a proper alternative.

The aim of the present study is to investigate the antioxidant properties of the lichen Cetraria aculeata. Antioxidant activity of the methanol and ethyl acetate extracts of lichen was tested by different methods including determination of total phenolics content, determination of total antioxidant capacity, DPPH free radical scavenging activity, inhibitory activity towards lipid peroxidation, ferrous ion chelating ability and hydroxyl radical scavenging activity. The extracts of the lichen C. aculeata showed significant antioxidant activity. The methanol extract showed higher values for total phenolics and total antioxidant capacity compared to the ethyl acetate extract, while the ethyl acetate extract demonstrated better results for DPPH radical scavenging, inhibitory activity towards lipid peroxidation, chelating ability and hydroxyl radical scavenging than the methanol extract. This is the first report of the antioxidant properties of Cetraria aculeata growing in Serbia. The results of antioxidant activity indicate the application of this lichen as source of natural antioxidants that could be used as a possible food supplement, in the pharmaceutical industry and in the treatment of various diseases.

Platelet-rich plasma (PRP) with normal and below-normal physiological concentrations of platelets is designated as diluted PRP (dPRP). The aims of this study are to evaluate whether bone mineral matrix in combination with dPRP possesses osteogenic capacity; and whether the differences in dynamics and osteogenic process pattern depend on different platelet concentrations, to what extent, and also what could be benefits for bone regeneration in clinical practice. Three types of implants were made: BMM-bone mineral matrix alone; dPRP/10-bone mineral matrix mixed with dPRP (concentration of platelets 10 times lower than physiological level) and dPRP/3-bone mineral matrix mixed with dPRP (concentration of platelets 3 times lower than physiological level). A subcutaneous implantation model in Balb/c mice was used. The implants were analyzed using expression analysis of bone-related genes, histochemical, immunohistochemical and histomorphometrical analysis. All types of implants induced creation of necessary preconditions for supporting osteogenic processes, but did not induce visible young bone growth. Implant types dPRP/10 and dPRP/3 showed very similar and significantly better stimulatory effects on osteogenic processes than bone matrix alone. In this study, significant ectopic osteogenic potential of concentration of platelets in PRP that are lower than physiological level in blood plasma in combination with bone mineral matrix was demonstrated. Diluted platelet-rich plasma could be a promising and useful adjuvant therapeutic agent in bone regeneration.

Craniofacial characteristics are used to identify similarities and differences between human populations or within a single population. The aim of this study is to provide data on the differences/similarities between two groups of subjects, left-handed and right-handed children, based on the parameters that determine the phenotypic characteristics of the head and face: head dimensions, face dimensions, hair color, eye color and earlobe shape. The study participants included 1354 students aged 7 to 15 years from regular schools of southeastern Serbia. The instruments used include: the Edinburgh Handedness Questionnaire for handedness determination, the cephalometer, and the questionnaire. 135 students (9.97%) were identified as left-handed, and the differences in the observed parameters were recorded between left-handed and right-handed girls in relation to the cephalic index, nasal index, head breadth, face breadth, and eye color.

Senna (Cassia angustifolia Vahl.) is used in food and pharmaceutical technologies as officinal drugs and natural laxative. The aim of the study was to investigate the effect of toluene and methanol Senna extracts on the viability and proliferation of HeLa cells. The senna leaves were extracted in Soxhlet's extractor and obtained toluene and methanolic extracts were used for determination of effects on viability and proliferation. Cytotoxic effect of different concentrations (0.1%, 0.01%, 0.001% and 0.0001%) extracts was investigated in HeLa cells in vitro. MTT test showed significant cytotoxic activity for toluene extract, especially the concentration of 0.1%, while the tested concentrations metanolic extract did not show cytotoxic activity.

The following review is oriented towards microbes linked to Alzheimer’s disease (AD) and antimicrobial effect of compounds and extracts derived from aquatic organisms against specific bacteria, fungi and viruses which were found previously in patients suffering from AD. Major group of microbes linked to AD include bacteria: Chlamydia pneumoniae, Helicobacter pylori, Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia, Actinomyces naeslundii, spirochete group; fungi: Candida sp., Cryptococcus sp., Saccharomyces sp., Malassezia sp., Botrytis sp., and viruses: herpes simplex virus type 1 (HSV-1), Human cytomegalovirus (CMV), hepatitis C virus (HCV). In the light of that fact, this review is the first to link antimicrobial potential of aquatic organisms against these sorts of microbes. This literature review might serve as a starting platform to develop novel supportive therapy for patients suffering from AD and to possibly prevent escalation of the disease in patients already having high-risk factors for AD occurrence.

Biocompatibility, bioinertness and biofunctionality are prerequisites was that certain materials could be used in implantation. In vivo studies of biomaterials involves the assessing of overall biocompatibility of the newly synthesized biomaterials. In contact with organism, biomaterials represent foreign bodies and organism can react in various desirable and undesirable ways. As response to biomaterials, two types of hypersensitivity reactions are common, type I and type IV. Materials that are routinely used in dentistry can give rise to hypersensitivity reactions in both sensitised patients and members of the dental team. Hypersensitivity reactions to the endovascular prostheses are among the infrequent and unpredictable reactions that may lead to local or systemic complications. After implantation biomaterials initiate a host response which begins with blood-biomaterial interactions and provisional matrix formation and continues with acute/chronic inflammation, granulation tissue emergence, foreign body reaction, development of fibrous capsule and possible fibrosis. Macrophages are cells that regulate the host response to implanted biomaterial at several levels. Evaluation of the effect of the implant includes a large number of biological parameters e.g. thickness and vascularization of fibrous capsule, the number and size of inflammatory cells, cell infiltration in implant, degenerative and necrotic changes in the surrounding tissues, cell apoptosis, proliferation and differentiation, endothelialization, biodegradation, the thrombus formation, calcification. Effects of biomaterial at the site of implantation depend on its size, shape, surface and physicochemical characteristics. Ideal result of implantation would be complete restoration of normal tissue architecture and function after healing of injuries.

1024x768 Phenolic and flavonoid content, as well as the antioxidant activity of methanol and chloroform extracts from the leaves and twigs of Daphne blagayana were determined. The total phenolic content in the chloroform extract of twigs ( 90.26 ±0.69 mg GA/g ) of the plant was higher than that of the other extracts (from 76.56 ±0.89 to 77.45±0.43 mg GA/g). Flavonoids were also more represented in the twigs extracts of D. blagayana. Several different methods were used to determine the antioxidant activity of the tested extracts including total antioxidant capacity, metal chelating activity, hydroxyl radical scavenging activity and inhibitory activity against lipid peroxidation. The highest antioxidant activity was found for the chloroform extract of the plant twigs. A significant correlation between antioxidant activity and phenolic and flavonoid contents was revealed. The results of the present analysis demonstrated, for the first time, that Daphne blagayana leaves and twigs possess high phenolic and flavonoid contents and potential antioxidant activity. This study suggests that Daphne blagayana twigs and leaves may potentially be used as an accessible source of natural antioxidants. Key words : Daphne blagayana, phenols, flavonoids, antioxidant activity. Normal 0 false false false EN-US X-NONE X-NONE

Bipedalism is the main characteristic of humans. During evolutin bipedalism emerged probably as an adaptation to a changing environment. Major changes in skeletal system included femur, pelvis, skull and spine. The significance of bipedal locomotion: Bipedalism freed the forelimbs for carrying objects, creation and usage of tools. In the upright position animals have a broader view of the environment and the early detection of predators is crucial for survival. Bipedal locomotion makes larger distances easier to pass, which is very important in the migration of hominids.

The aim of this study was to investigate the antimicrobial activity and HPLC analysis of the methanol and chloroform extracts of leaves and twigs of endemic species Daphne blagayana collected from the area of Suva Mountain, Serbia. The antimicrobial activity, expressed as the values of MIC, were investigated on the 6 standardized bacterial strains and two strains of fungi. Amracin and ketoconazole are used as standard antibiotics. MIC values of the tested extracts were ranged from 15.62 to 125 μg/ml. The strongest effect of the extracts exhibited against Klebsiella pneumoniae, Staphylococcus aureus and Proteus mirabilis. Results of the HPLC analysis showed the presence of a variety of secondary metabolites, one of which is 7,8-dihydroxycoumarin (daphnetin), which was identified in all the extracts tested. Daphnetin, as biologically active substance, is most responsible for the antimicrobial activity of the tested extracts, but its role can not exclude the influence of other secondary metabolites (phenols and flavonoids) present in the extracts, which may have a synergistic effect.

Animal models are unavoidable and indispensable research tools in the fields of bone tissue engi - neering and experimental orthopaedics. The fact that there is not ideal animal model as well as the differences in the bone microarchitecture and physiology between animals and humans are complicate factors and make model implementation difficult. Therefore, the tendency should be directed towards extrapolation of the results from one animal model to another or from animal model to humans. So far, this is the first paper which provides an overview on the microarchitecture of lower limb long bones and discusses data related to osteon diameter, osteon canal diameter and their orientation, as well as intracortical canals and trabecular tissue microarchitecture in commonly used animal models compared to humans depending on age, gender and anatomical location of the bone. Understanding the differences between animal model and human bone microarchitecture should enable a more accurate extrapolation of experimental results from one animal model to another or from animal models to humans in the fields of bone tissue engineering and experimental orthopaedics. Also, this should be helpful in making decisions on which animal models are the most suitable for particular preclinical testing.

The aim of this study was to investigate antioxidant, antimicrobial and anticancerous activity of Melanelia subaurifera and Melanelia fuliginosa. The phytochemical analysis was determined by HPLC-UV method. Antioxidant activity was evaluated by DPPH and reducing power assay while antimicrobial activity was determined by minimal inhibitory concentration. The cytotoxic activity was tested using MTT method. The method for quantification of 2'-O-methyl anziaic acid and lecanoric acid in these lichens using RF-HPLC was also developed and validated. The depsides (lecanoric acid, gyrophoric acid, atranorin, anziaic acid and 2'-O-methyl anziaic acid), and dibenzofurane (usnic acid) were identified in these lichens. The antioxidant activity (IC50) of lichens extracts ranged from 121.52 to 424.51 μg/ml. 2'-O-Methyl anziaic acid showed the highest antimicrobial activity with MIC ranging from 0.0625 to 1 mg/ml. M. subaurifera extract showed the highest cytotoxic activity against the tested cell lines (IC50 = 9.88 to 31.64 μg/ml).

Implantation of a biomaterial is one of the important trends in solving the problem of bone tissue loss. Calcium hydroxiapatite (HAp), as the most representative bone component is a serious candidate for such implantations. The synthetic polymer poly-L-lactide (PLLA) in HAp/PLLA is often used as a polymeric material, with a role in the substitution of bone tissue collagen fibers. Fibers of PLLA may strengthen HAp and its good bioresorption provides space for tissue remodeling. Differences in porosity, microstructure, compressive consistency as well as bioresorbility of HAp/ PLLA may be achieved by using PLLA with different molecular weights. In this study HAp/PLLA composites with PLLA of different molecular weights (50,000; 160,000 and 430,000) were implanted in mouse peritoneum in order to examine the influence of the molecular weight of PLLA on morphology changes. Microstructural changes of biomaterial (HAp/PLLA) surface were analyzed one week, three weeks and four months after their implantation using Scanning Electron Microscopy. The results showed a significant difference in tissue reactions on the applied biocomposites, depending on their molecular weight. The most intense proliferation of cells was induced by HAp/PLLA 50,000 compared to HAp/PLLA 430,000 and HAp/PLLA 160,000. In the vicinity of HAp/PLLA 430,000 abundant erythrocytes were observed. The differences in biological reactions on the examined biocomposites are significant for their practical applications. HAp/PLLA composite biomaterials of different types and resorption rates require specific designing and programming to become suitable for particular purposes in an organism.

The aim of this study was to investigate the chemical composition of acetone extracts of the lichens Toninia candida and Usnea barbata and in vitro antioxidant, antimicrobial, and anticancer activities of these extracts together with some of their major metabolites. The chemical composition of T. candida and U. barbata extracts was determined using HPLC-UV analysis. The major phenolic compounds in these extracts were norstictic acid (T. candida) and usnic acid (U. barbata). Antioxidant activity was evaluated by free radical scavenging, superoxide anion radical scavenging, reducing power and determination of total phenolic compounds. Results of the study proved that norstictic acid had the largest antioxidant activity. The total content of phenols in the extracts was determined as the pyrocatechol equivalent. The antimicrobial activity was estimated by determination of the minimal inhibitory concentration using the broth microdilution method. The most active was usnic acid with minimum inhibitory concentration values ranging from 0.0008 to 0.5 mg/mL. Anticancer activity was tested against FemX (human melanoma) and LS174 (human colon carcinoma) cell lines using the microculture tetrazolium test. Usnic acid was found to have the strongest anticancer activity towards both cell lines with IC50 values of 12.72 and 15.66 μg/mL.

The present study describes in vitro antimicrobial and antioxidant activities of the methanol extracts which were obtained from the leaves and twigs of the plant Daphne cneorum L. The antimicrobial activity of these extracts was tested against human pathogenic microorganisms using a minimum inhibitory concentration (MIC) values. Total phenolics and flavonoids, as well as the antioxidant activity of the extracts were determined. The two tested extracts showed good antimicrobial and antioxidant activities. The results of a high performance liquid chromatographic (HPLC) method showed that 7,8-dihydroxycoumarin is one of the most abundant secondary metabolite in the tested extracts. The results of this study clearly indicated that the extracts of D. cneorum could be used as a potential source of natural antioxidant and antimicrobial agents.

Daphne malyana Blecic (Thymelaeaceae) is an endemic species of the western part of the Balkan Peninsula. No previous detailed studies exist on D. malyana Blecic. The aim of this study was to provid...

The phytochemical analysis of methanol and chloroform extracts ofUmbilicaria cylindricawas determined by HPLC-UV method. The predominant phenolic compound in both extracts was depsidone, salazinic acid (1). Besides salazinic acid, the tested extracts ofU. cylindricacontain norstictic acid (2), methyl-β-orcinol carboxylate (3), ethyl haematommate (4), atranorin (5), and usnic acid (6), in different amounts and relations. The lichen extracts showed comparable and strong antioxidant activity, exhibited higher DPPH and hydroxyl radical scavengings, chelating activity, and inhibitory activity towards lipid peroxidation. The lichen extracts demonstrated important antimicrobial activity against eight strains with MIC values from 15.62 to 62.50 μg/mL. This is the first report of the detail chemical composition and antioxidant activity of the lichenUmbilicaria cylindrica, and the results suggest that this lichen can be used as a new source of the natural antioxidants and the substances with antimicrobial features.

The aim of this work was the analytical characterization of the ?-orcinol depside, baeomycesic acid in lichens extracts. The extract of Thamnolia vermicularis var. subuliformis was analyzed by the two different methods, namely HPLC-UV and 1H NMR analysis. The results showed that baeomycesic acid was the most abundant depside in the lichens. These results could be of use for rapid identification of this metabolite in other lichen species. Besides baeomycesic acid, three depsides and one monocyclic phenolic compound were isolated from the lichen extract on the chromatographic column. The structure of baeomycesic acid was confirmed by HPLC-UV and spectroscopic methods. In addition, antioxidant and cytotoxic activities of baeomycesic acid were determined. The result of the testing showed that baeomycesic acid exhibited a moderate radical scavenging activity (IC50 = 602.10 ? 0.54 ?g/mL) and good cytotoxic activity. This is the first report of detailed analytical characterization, isolation, as well as antioxidant and cytotoxic activities of baeomycesic acid from Thamnolia vermicularis. These results may be helpful in future industrial production of herbal medicines that include this important natural product.

Daphne malyana Blecic (Thymeleaceae) is an endemic species of the western part of the Balkan Peninsula, distributed in the mountains, canyons and gorges of N. Montenegro, E. Bosnia and W. Serbia. The comparative morphoanatomic investigations have included four distantly separated populations of the species D. malyana, i.e. two from Serbia, from the ravines of Sokoline and Vranjak on Mt. Tara, and two from Montenegro, in the canyons of the Tara and Piva rivers. Comparative morphoanatomical studies have shown the presence of general adaptive characteristics of a specific, conservative xeromorphic type, slightly differing in each population. Principal component analysis (PCA) and canonical discriminant analysis (CDA) of 20 morphoanatomical characteristics of the leaves and stems have shown a clear distinction between the populations from the river Piva canyon (Montenegro) and those from the Sokoline ravine (Serbia), on one side, and those of Vranjak gorge (Serbia) and of the river Tara canyon (Montenegro) on the other side. It may be assumed that the mild morphological variability of the isolated populations of the Balkan endemic species D. malyana in the canyons and gorges seem to have been affected by the microclimate conditions in their habitats.

Handedness (dominant arm) is a term used to describe the ability of using right or left arm not only for writing but also for performing delicate and precise tasks. In fact, dominant arm appears even in prehistoric time. From the aspect of evolution, dominant arm is seen as an ability which correlates with speech development, and as such is related to cerebral lateralization. However, various cognitive disorders are connected to the dominant arm. The influence of inheritance and environment are equally important for the dominant arm, however their influence prevents us to determine how a certain arm becomes dominant.

The aim of this work was to compare the effect of solitary and combined presence of copper (II) and chromium (VI) in food medium, on the reproductive ability and development of the fruit fly Drosophila melanogaster. We used copper (II) sulfate penta-hydrate (CuSO4×5H2O) and potassium-dichromate (K2Cr2O7), which were added at the same concentrations of 500mg/L to the food medium. The flies were exposed to the mentioned compounds during the two generations. The results of the research showed that the average number of adult offspring per one female of the flies exposed only to the influence of copper (II) sulfate or only to potassium-dichromate were on the control level. The flies cultured on the medium containing both tested compounds, had a significantly lower number of offspring compared to the control group (p

Indications exist that paramagnetic calcium phosphates may be able to promote regeneration of bone faster than their regular, diamagnetic counterparts. In this study, analyzed was the influence of paramagnetic cobalt-substituted hydroxyapatite nanoparticles on osteoporotic alveolar bone regeneration in rats. Simultaneously, biocompatibility of the material was tested in vitro, on osteoblastic MC3T3-E1 and epithelial Caco-2 cells in culture. The material was shown to be biocompatible and nontoxic when added to epithelial monolayers in vitro, while it caused a substantial decrease in the cell viability as well as deformation of the cytoskeleton and cell morphology when incubated with the osteoblastic cells. In the course of 6 months after the implantation of the material containing different amounts of cobalt, ranging from 5 to 12 wt%, in the osteoporotic alveolar bone of the lower jaw, the following parameters were investigated: histopathological parameters, alkaline phosphatase and alveolar bone density. The best result in terms of osteoporotic bone tissue regeneration was observed for hydroxyapatite nanoparticles with the largest content of cobalt ions. The histological analysis showed a high level of reparatory ability of the nanoparticulate material implanted in the bone defect, paralleled by a corresponding increase in the alveolar bone density. The combined effect of growth factors from autologous plasma admixed to cobalt-substituted hydroxyapatite was furthermore shown to have a crucial effect on the augmented osteoporotic bone regeneration upon the implantation of the biomaterial investigated in this study. This is accepted peer-reviewed version of the article: Ignjatović, N., Ajduković, Z., Savić, V., Najman, S., Mihailović, D., Vasiljević, P., ... & Uskoković, D. (2013). Nanoparticles of cobalt-substituted hydroxyapatite in regeneration of mandibular osteoporotic bones. Journal of Materials Science: Materials in Medicine, 24(2), 343-354. [https://dx.doi.org/10.1007/s10856-012-4793-1] Published version: [https://vinar.vin.bg.ac.rs/handle/123456789/7410]

The aim of this study is to investigate chemical composition of acetone extracts of the lichens Parmelia caperata, P. saxatilis and P. sulcata and antioxidant, antimicrobial and anticancer activities of some their major metabolites. The phytochemical analysis of acetone extracts of three Parmelia lichens were determined by HPLC-UV method. The predominant phenolic compounds in these extracts were protocetraric and usnic acids (P. caperata) and depsidone salazinic acid (other two species). Besides these compounds, atranorin and chloroatranorin, were also detected in some of these extracts. Antioxidant activity of their isolated metabolites was evaluated by free radical scavenging, superoxide anion radical scavenging and reducing power. As a result of the study salazinic acid had stronger antioxidant activity than protocetraric acid. The antimicrobial activity was estimated by determination of the minimal inhibitory concentration by the broth microdilution method. Both compounds were highly active with minimum inhibitory concentration values ranging from 0.015 to 1mg/ml. Anticancer activity was tested against FemX (human melanoma) and LS174 (human colon carcinoma) cell lines using MTT method. Salazinic acid and protocetraric acid were found to be strong anticancer activity toward both cell lines with IC(50) values ranging from 35.67 to 60.18μg/ml. The present study shows that tested lichen compounds demonstrated a strong antioxidant, antimicrobial, and anticancer effects. That suggest that these lichens can be used as new sources of the natural antimicrobial agents, antioxidants and anticancer compounds.

Simulated body fluid (SBF) is an artificial fluid which has ionic composition and ionic concentration similar to human blood plasma. Purpose This paper compares the interaction between the nanomaterial containing calcium phosphate/poly-DL-lactide-co-glycolide (N-CP/PLGA) and SBF, in order to investigate whether and to what extent inorganic ionic composition of human blood plasma leads to the aforementioned changes in the material. Methods N-CP/PLGA was incubated for 1, 2, 3, and 5 weeks in SBF. The surface of the material was analyzed on SEM-EDS and FTIR spectrometer, while SBF was subjected to pH and electrical conductivity measurement. Results Our results indicate that dissolution of the polymer component of the material N-CP/PLGA and precipitation of the material similar to hydroxyapatite on its surface are based on the morphologic changes seen in this material. Conclusions The mechanism of the apatite formation on the bioceramic surface was intensively studied and was considered crucial in designing the new biomaterials. The results obtained in this work indicate that N-CP/PLGA may be a good candidate for application to bone regeneration.

In the present investigation, methanol, chloroform and petrol ether extracts from the lichen Toninia candida (Weber) Th. Fr, Catillariaceae, were assayed for their antioxidant activity. The phenolic composition of the extracts was determined by HPLC-UV analysis. The predominant phenolic compound in all the extracts was depsidone, norstictic acid. All the tested extracts of T. candida contain, besides norstictic acid, atranorin, stictic, protocetraric and usnic acid, but in different amounts and relations. The lichen extracts showed comparable and strong antioxidant activity, exhibited higher DPPH and hydroxyl radical scavengings, chelating activity and inhibitory activity towards lipid peroxidation. This is the first report of chemical composition and antioxidant antimicrobial activity of the lichen Toninia candida.