Physiological action and biochemical components of snake venom

U ovom radu opisala sam pregled otkrića otrova, njegovih svojstava i strukture, kroz povijest pa do danas. Pošto govoriti, odnosno pisati, o toksinima nije lako, morali smo proći i osnovnu podjelu zmija. Podjela prema dentaciji najjednostavnija je i opće prihvaćena. Prema njoj razlikujemo tri skupine: prednježljebozubice (Elapide), stražnježljebozubice (Colubride) i cjevozubice ( Viperide i Atraktaspidide). Prema dentaciji možemo ih podijeliti i na to koju „vrstu“ otrova posjeduju i kako ju ubrizgavaju. „Vrsta“ je pod navodnicima, jer zapravo niti jedna vrsta otrova nije u potpunosti čista. Zmije poput čegrtuša sa velikim udjelom hemotoksičnih komponenti u otrovu često zadrže i nešto neurotoksičnih komponenti. Isto vrijedi i za zmije poput taipana kod kojih prevladavaju neurotoksične komponente. Kada je prvi problem bio uspješno riješen, definiranje proteina i njihova uloga, moglo se krenuti na detaljnije istraživanje samih toksina. Utvrđeno je da je 90% građe toksina upravo proteinska te da za njihove analize mogu primijeniti sada utvrđene tehnike za analizu proteina. Prvenstveno se koristila kromatografija. Jedne od češćih bile su kromatografija ionskom izmjenom i gel filtracija (kromatografija na stupcu) koje su odvajale proteine na temelju različitog ionskog naboja ili određene molekulske mase.This work contains overview of history of discovery, structure and properties of snake venoms. Because writing about snake toxins is not an easy task, we needed to make some kind of classification of snakes themselves. The most common classification is based on their dentition. According to this classification there are three groups of snakes: front-fanged (proteroglyphous - Elapids), rear-fanged (opistoglyphous - Colubrids) and tubular-fanged (solenoglyphous – Vipers and atractaspids). Because of their dentition, we can differ which “kind” of poison snakes posses and how they inject it. “Kind” has quotation marks because no poison is completely pure. Snakes like rattlesnakes with big percentage of cytotoxic compounds in their venom always have some neurotoxic compounds. The same holds true for snakes like taipans, with big percentage of neurotoxic compounds, but also some cytotoxic components. When the first problem was solved, i.e. definition of proteins and their function, it was possible to move on to the research of toxins. It was discovered that 90% of snake toxin is made of proteins. The most often used method in this research was chromatography, specially ion exchange chromatography and gel filtration in which proteins can be divided on the basis of their ionic charge or molecular weight

Physiological action and biochemical components of snake venom

U ovom radu opisala sam pregled otkrića otrova, njegovih svojstava i strukture, kroz povijest pa do danas. Pošto govoriti, odnosno pisati, o toksinima nije lako, morali smo proći i osnovnu podjelu zmija. Podjela prema dentaciji najjednostavnija je i opće prihvaćena. Prema njoj razlikujemo tri skupine: prednježljebozubice (Elapide), stražnježljebozubice (Colubride) i cjevozubice ( Viperide i Atraktaspidide). Prema dentaciji možemo ih podijeliti i na to koju „vrstu“ otrova posjeduju i kako ju ubrizgavaju. „Vrsta“ je pod navodnicima, jer zapravo niti jedna vrsta otrova nije u potpunosti čista. Zmije poput čegrtuša sa velikim udjelom hemotoksičnih komponenti u otrovu često zadrže i nešto neurotoksičnih komponenti. Isto vrijedi i za zmije poput taipana kod kojih prevladavaju neurotoksične komponente. Kada je prvi problem bio uspješno riješen, definiranje proteina i njihova uloga, moglo se krenuti na detaljnije istraživanje samih toksina. Utvrđeno je da je 90% građe toksina upravo proteinska te da za njihove analize mogu primijeniti sada utvrđene tehnike za analizu proteina. Prvenstveno se koristila kromatografija. Jedne od češćih bile su kromatografija ionskom izmjenom i gel filtracija (kromatografija na stupcu) koje su odvajale proteine na temelju različitog ionskog naboja ili određene molekulske mase.This work contains overview of history of discovery, structure and properties of snake venoms. Because writing about snake toxins is not an easy task, we needed to make some kind of classification of snakes themselves. The most common classification is based on their dentition. According to this classification there are three groups of snakes: front-fanged (proteroglyphous - Elapids), rear-fanged (opistoglyphous - Colubrids) and tubular-fanged (solenoglyphous – Vipers and atractaspids). Because of their dentition, we can differ which “kind” of poison snakes posses and how they inject it. “Kind” has quotation marks because no poison is completely pure. Snakes like rattlesnakes with big percentage of cytotoxic compounds in their venom always have some neurotoxic compounds. The same holds true for snakes like taipans, with big percentage of neurotoxic compounds, but also some cytotoxic components. When the first problem was solved, i.e. definition of proteins and their function, it was possible to move on to the research of toxins. It was discovered that 90% of snake toxin is made of proteins. The most often used method in this research was chromatography, specially ion exchange chromatography and gel filtration in which proteins can be divided on the basis of their ionic charge or molecular weight

Influence of different diet regimes on behaviour of lemurs Lemur catta Linnaeus, 1758 and Varecia variegata Kerr, 1792

Malobrojna su istraživanja o utjecaju režima prehrane na ponašanje jedinki u zatočeništvu. Cilj ovog istraživanja, na dvije grupe lemura prstenastorepih i čupavouhih lemura, je utvrditi povezanost zdrave prehrane na bazi povrća s ponašanjem jedinki. Utvrđeno je da prehrana u prirodi sadrži složene ugljikohidrate (vlakna), a voće iz uzgoja u zoološkim vrtovima sadrži više jednostavnih ugljikohidrata (glukoza, fruktoza). Prehrana je mogući uzrok fizioloških nedostataka jedinki u zatočeništvu. Provela sam prethodna promatranja i kreirala tablicu ponašanja prilagođenu našim grupama. Grupe su promatrane jednako ujutro i popodne u trajanju od tri sata (jedan prije hranjenja i dva poslije), a opažena ponašanja bilježila sam svake dvije minute. Rezultati su pokazali da su obje grupe više vremena provodile u odmaranju i probavljanju hrane, čija se konzumacija također značajno povećala, te u prosocijalnim (pozitivnim međusobnim) interakcijama. Promjenom prehrane u grupi čupavouhih lemura došlo je do značajnog pada agonističkih (negativnih, agresivnih) ponašanja. Odgovori obaju promatranih grupa ovisili su o sastavu grupe i u detaljima se razlikuju, no generalni zaključak je da prehrana utječe na ponašanje i nužna su detaljnija istraživanja varijabli koje su se pokazale ključne u ovom istraživanju.There are a few researches about influence of diet regimes on animal behaviour in captivity. Aim of this research, on two groups black and white ruff-eared and ring-tailed lemurs, is to confirm the influence of healthy vegetable based diet on behaviour of individuals. It is known that diet in nature contains complex carbohydrates (fibers), and that fruit in the zoos contains much more simple carbohydrates (glucose, fructose). Diet could be the cause of physiological limitations of individuals in captivity. I did preliminary monitoring and created the table of behaviours for our groups. Monitoring was equal for morning and afternoon sessions in duration of three hours (one before feeding and two after), recording behaviours every two minutes. The results have shown that both groups spent more time resting and digesting, the feeding rate had grown, and their prosocial interactions (positive mutual) increased. The diet change in black and white ruff-eared lemurs caused the significant decrease of agonistic (aggressive) behaviours. The response of both groups depended on group formation and they differed in details, but general conclusion is that diet has influence on the behaviour and it is necessary to test important variables from this research in other circumstances

Physiological action and biochemical components of snake venom

U ovom radu opisala sam pregled otkrića otrova, njegovih svojstava i strukture, kroz povijest pa do danas. Pošto govoriti, odnosno pisati, o toksinima nije lako, morali smo proći i osnovnu podjelu zmija. Podjela prema dentaciji najjednostavnija je i opće prihvaćena. Prema njoj razlikujemo tri skupine: prednježljebozubice (Elapide), stražnježljebozubice (Colubride) i cjevozubice ( Viperide i Atraktaspidide). Prema dentaciji možemo ih podijeliti i na to koju „vrstu“ otrova posjeduju i kako ju ubrizgavaju. „Vrsta“ je pod navodnicima, jer zapravo niti jedna vrsta otrova nije u potpunosti čista. Zmije poput čegrtuša sa velikim udjelom hemotoksičnih komponenti u otrovu često zadrže i nešto neurotoksičnih komponenti. Isto vrijedi i za zmije poput taipana kod kojih prevladavaju neurotoksične komponente. Kada je prvi problem bio uspješno riješen, definiranje proteina i njihova uloga, moglo se krenuti na detaljnije istraživanje samih toksina. Utvrđeno je da je 90% građe toksina upravo proteinska te da za njihove analize mogu primijeniti sada utvrđene tehnike za analizu proteina. Prvenstveno se koristila kromatografija. Jedne od češćih bile su kromatografija ionskom izmjenom i gel filtracija (kromatografija na stupcu) koje su odvajale proteine na temelju različitog ionskog naboja ili određene molekulske mase.This work contains overview of history of discovery, structure and properties of snake venoms. Because writing about snake toxins is not an easy task, we needed to make some kind of classification of snakes themselves. The most common classification is based on their dentition. According to this classification there are three groups of snakes: front-fanged (proteroglyphous - Elapids), rear-fanged (opistoglyphous - Colubrids) and tubular-fanged (solenoglyphous – Vipers and atractaspids). Because of their dentition, we can differ which “kind” of poison snakes posses and how they inject it. “Kind” has quotation marks because no poison is completely pure. Snakes like rattlesnakes with big percentage of cytotoxic compounds in their venom always have some neurotoxic compounds. The same holds true for snakes like taipans, with big percentage of neurotoxic compounds, but also some cytotoxic components. When the first problem was solved, i.e. definition of proteins and their function, it was possible to move on to the research of toxins. It was discovered that 90% of snake toxin is made of proteins. The most often used method in this research was chromatography, specially ion exchange chromatography and gel filtration in which proteins can be divided on the basis of their ionic charge or molecular weight

Genetics of breast cancer: Contribution of BRCA1/2 genes alterations to hereditary predisposition

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Mahonia aquifolium Extracts Promote Doxorubicin Effects against Lung Adenocarcinoma Cells In Vitro

Mahonia aquifolium and its secondary metabolites have been shown to have anticancer potential. We performed MTT, scratch, and colony formation assays; analyzed cell cycle phase distribution and doxorubicin uptake and retention with flow cytometry; and detected alterations in the expression of genes involved in the formation of cell-cell interactions and migration using quantitative real-time PCR following treatment of lung adenocarcinoma cells with doxorubicin, M. aquifolium extracts, or their combination. MTT assay results suggested strong synergistic effects of the combined treatments, and their application led to an increase in cell numbers in the subG1 phase of the cell cycle. Both extracts were shown to prolong doxorubicin retention time in cancer cells, while the application of doxorubicin/extract combination led to a decrease in MMP9 expression. Furthermore, cells treated with doxorubicin/extract combinations were shown to have lower migratory and colony formation potentials than untreated cells or cells treated with doxorubicin alone. The obtained results suggest that nontoxic M. aquifolium extracts can enhance the activity of doxorubicin, thus potentially allowing the application of lower doxorubicin doses in vivo, which may decrease its toxic effects in normal tissues

Molecular signature of response to preoperative radiotherapy in locally advanced breast cancer

Background: Radiation therapy is an indispensable part of various treatment modalities for breast cancer. Specifically, for non-inflammatory locally advanced breast cancer (LABC) patients, preoperative radiotherapy (pRT) is currently indicated as a second line therapy in the event of lack of response to neoadjuvant chemotherapy. Still approximately one third of patients fails to respond favourably to pRT. The aim of this study was to explore molecular mechanisms underlying differential response to radiotherapy (RT) to identify predictive biomarkers and potential targets for increasing radiosensitivity.Methods: The study was based on a cohort of 134 LABC patients, treated at the Institute of Oncology and Radiology of Serbia (IORS) with pRT, without previous or concomitant systemic therapy. Baseline transcriptional profiles were established using Agilent 60 K microarray platform in a subset of 23 formalin-fixed paraffin-embedded (FFPE) LABC tumour samples of which 11 radiotherapy naïve and 3 post-radiotherapy samples passed quality control and were used for downstream analysis. Biological networks and signalling pathways underlying differential response to RT were identified using Ingenuity Pathways Analysis software. Predictive value of candidate genes in the preoperative setting was further validated by qRT-PCR in an independent subset of 60 LABC samples of which 42 had sufficient quality for data analysis, and in postoperative setting using microarray data from 344 node-negative breast cancer patients (Erasmus cohort, GSE2034 and GSE5327) treated either with surgery only (20%) or surgery with RT (80%).Results: We identified 192 significantly differentially expressed genes (FDR < 0.10) between pRT-responsive and non-responsive tumours, related to regulation of cellular development, growth and proliferation, cell cycle control of chromosomal replication, glucose metabolism and NAD biosynthesis II route. APOA1, MAP3K4, and MMP14 genes were differentially expressed (FDR < 0.20) between pRT responders and non-responders in preoperative setting, while MAP3K4 was further validated as RT-specific predictive biomarker of distant metastasis free survival (HR = 2.54, [95%CI:1.42–4.55], p = 0.002) in the postoperative setting.Conclusions: This study pinpoints MAP3K4 as a putative biomarker of response to RT in both preoperative and postoperative settings and a potential target for radiosensitising combination therapy, warranting further pre-clinical studies and prospective clinical validation

A prospective follow up of serum uric acid levels in school children

Na dvije kontrole, u razmaku od tri godine, odre­đena je razina mokraćne kiseline u serumima 381 učenika (starih prosječno 11,4 odnosno 14,3 godine). Uz to su ispitivani i brojni drugi parametri (broj eritrocita, MCV, MCH, MCHC, trigliceridi, holesterol itd.), od kojih je analiziran odnos mokraćne kiseline i tjelesne težine. Analiziran je i odnos navedenih parametara prema istim, dobivenim u ranijem radu, u kom su ispitivana djeca stara 6,4 godine (prvi razred osnovne škole). Nađen je statistički značajan porast razine mokraćne kiseline u dječaka starih 14,4 godine te pojava korelacije razine mokraćne kiseline i tjelesne težine u oba spola (r = 0,35) te dobi (nasuprot manjku te povezanosti u mlađih dobnih skupina djece od 6,4, odnosno 11,4 godine starosti).In 381 children serum uric acid levels were measured at the age of 11.4 and 14.3. Numerous other parameters were also measured (as the erythrocytes, MCV, MCH, MCHC, tryglicerides, cholesterol etc) but only the relation among uric acid levels and body weight was analysed. The relation of these parameters and the data we have got in our previous work (in first grade elementary school children aged 6.4 years) is also discussed. We found significant increase of uric acid levels in boys aged 14.4 and an association between the serum uric acid levels and the body weight appears in both sexes at this age (r=0.35). (Opposite to the lack of this association in younger children, aged 6.4, and 11.4)

A prospective follow up of serum uric acid levels in school children

Na dvije kontrole, u razmaku od tri godine, odre­đena je razina mokraćne kiseline u serumima 381 učenika (starih prosječno 11,4 odnosno 14,3 godine). Uz to su ispitivani i brojni drugi parametri (broj eritrocita, MCV, MCH, MCHC, trigliceridi, holesterol itd.), od kojih je analiziran odnos mokraćne kiseline i tjelesne težine. Analiziran je i odnos navedenih parametara prema istim, dobivenim u ranijem radu, u kom su ispitivana djeca stara 6,4 godine (prvi razred osnovne škole). Nađen je statistički značajan porast razine mokraćne kiseline u dječaka starih 14,4 godine te pojava korelacije razine mokraćne kiseline i tjelesne težine u oba spola (r = 0,35) te dobi (nasuprot manjku te povezanosti u mlađih dobnih skupina djece od 6,4, odnosno 11,4 godine starosti).In 381 children serum uric acid levels were measured at the age of 11.4 and 14.3. Numerous other parameters were also measured (as the erythrocytes, MCV, MCH, MCHC, tryglicerides, cholesterol etc) but only the relation among uric acid levels and body weight was analysed. The relation of these parameters and the data we have got in our previous work (in first grade elementary school children aged 6.4 years) is also discussed. We found significant increase of uric acid levels in boys aged 14.4 and an association between the serum uric acid levels and the body weight appears in both sexes at this age (r=0.35). (Opposite to the lack of this association in younger children, aged 6.4, and 11.4)

Supplementary material for the article: Živković, M. B.; Matić, I. Z.; Rodić, M. V.; Novaković, I. T.; Krivokuća, A. M.; Sladić, D. M.; Krstić, N. M. Anticancer Potential of New Steroidal Thiazolidin-4-One Derivatives. Mechanisms of Cytotoxic Action and Effects on Angiogenesis in Vitro. Journal of Steroid Biochemistry and Molecular Biology 2017, 174, 72–85. https://doi.org/10.1016/j.jsbmb.2017.07.031

Supplementary material for: [https://doi.org/10.1016/j.jsbmb.2017.07.031]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2550]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3191