Učinak zamjene obroka od pšeničnih mekinja obrokom sa sjemenkama kima na nesenje, kvalitetu jaja i masnokiselinski profil u kokoši nesilica

The objective of the present study was to investigate the effect of substituting wheat bran (WB) with cumin seed meal (CSM) on laying performance, egg quality characteristics and egg-yolk fatty acids profile in laying hens. A total of 180 Bovans hens at 55 weeks of age were divided randomly into three treatments. The CSM was incorporated into a standard corn- and soybean meal-based diet by replacing 0, 50, and 100% of WB [i.e., 100% WB (control), 50% WB+50% CSM and 100% CSM] from 55 to 61 weeks of age. Body weight was measured at the beginning and end of the experiment. Feed intake, hen-day egg production and egg weight were recorded daily. At 61 weeks of age, 30 eggs were taken at random from each treatment group to determine the egg quality characteristics. Replacing 100% of WB by CSM did not affect body weight, however, hen-day egg production, egg weight and egg mass significantly increased, while feed conversion ratio significantly decreased (P<0.05). Haugh unit, shell thickness and yolk color significantly increased by CSM substitution in comparison with 100% WB. Plasma concentrations of total cholesterol, triglycerides, LDL-cholesterol and glutamic oxalacetic transaminase (GOT) significantly decreased by replacing WB with CSM, while, plasma HDL-cholesterol significantly increased. Furthermore, the liver malondialdehyde (MDA) concentration significantly decreased, while vitamin E, linoleic acid and alpha-linolenic acid significantly increased (P<0.05) due to CSM inclusion. Therefore, it could be concluded that substitution of WB with CSM could improve laying performance and egg quality characteristics, and reduce lipid peroxidation in laying hens.Cilj ovoga rada bio je istražiti učinak zamjene obroka s pšeničnim mekinjama (WB) obrokom sa sjemenkama kima (CSM) na nesenje, kvalitetu jaja te profil masnih kiselina u žumanjku jajeta kokoši nesilica. Ukupno je 180 Bovans kokoši u dobi od 55 tjedana slučajnim odabirom podijeljeno u tri pokusne skupine, u kojima su sjemenke kima dodane u standardni obrok s kukuruzom i sojom zamjenjujući 0, 50 i 100 % pšeničnih mekinja. Tako je kontrolna skupina hranjena obrocima sa 100 % pšeničnih mekinja, druga skupina s 50 % obroka s pšeničnim mekinjama i 50 % obroka sa sjemenkama kima, a treća skupina obrokom koji je sadržavao 100 % sjemenki kima. Pokusno razdoblje je trajalo od 55. do 61. tjedna starosti nesilica. Tjelesna je masa mjerena na početku i na kraju pokusa. Unos hrane, dnevna proizvodnja jaja i njihova masa bilježili su se svaki dan. U dobi od 61 tjedna iz svake je skupine slučajnim odabirom uzeto 30 jaja kako bi se odredila njihova kvaliteta. zamjenjujući 100 % obrok od pšeničnih mekinja sjemenke kima nisu utjecale na tjelesnu masu, no ipak su dnevna proizvodnja, težina i masa jaja znakovito porasle, dok se stopa konverzije hrane znakovito smanjila (P<0,05). Haugh-ova jedinica, debljina ljuske i boja žumanjka znakovito su porasle u skupinama u kojima su pšenične mekinje zamijenjene sjemenkama kima u odnosu na kontrolnu skupinu. Ukupni kolesterol, trigliceridi, LDL-kolesterol i glutaminska oksalooctena transaminaza (GOT) znakovito su sniženi u skupinama u kojima su pšenične mekinje zamijenjene sjemenkama kima, dok je HDL-kolesterol znakovito povišen. nadalje, koncentracija malondialdehida (MDA) u jetri znakovito je snižena, dok su vitamin E, linolna i alfa-linolna kiselina znakovito porasli (P<0,05) uslijed dodanih sjemenki kima. Može se zaključiti da zamjena obroka s pšeničnim mekinjama obrokom sa sjemenkama kima može poboljšati nesenje i kvalitetu jaja te smanjiti lipidnu peroksidaciju u kokoši nesilica

Discovery of novel class of histone deacetylase inhibitors as potential anticancer agents

Selective inhibition of histone deacetylases (HDACs) is an important strategy in the field of anticancer drug discovery. However, lack of inhibitors that possess high selectivity toward certain HDACs isozymes is associated with adverse side effects that limits their clinical applications. We have initiated a collaborative initiatives between multi-institutions aimed at the discovery of novel and selective HDACs inhibitors. To this end, a phenotypic screening of an in-house pilot library of about 70 small molecules against various HDAC isozymes led to the discovery of five compounds that displayed varying degrees of HDAC isozyme selectivity. The anticancer activities of these molecules were validated using various biological assays including transcriptomic studies. Compounds 15, 14, and 19 possessed selective inhibitory activity against HDAC5, while 28 displayed selective inhibition of HDAC1 and HDAC2. Compound 22 was found to be a selective inhibitor for HDAC3 and HDAC9. Importantly, we discovered a none-hydroxamate based HDAC inhibitor, compound 28, representing a distinct chemical probe of HDAC inhibitors. It contains a trifluoromethyloxadiazolyl moiety (TFMO) as a non-chelating metal-binding group. The new compounds showed potent anti-proliferative activity when tested against MCF7 breast cancer cell line, as well as increased acetylation of histones and induce cells apoptosis. The new compounds apoptotic effects were validated through the upregulation of proapoptotic proteins caspases3 and 7 and downregulation of the antiapoptotic biomarkers C-MYC, BCL2, BCL3 and NFĸB genes. Furthermore, the new compounds arrested cell cycle at different phases, which was confirmed through downregulation of the CDK1, 2, 4, 6, E2F1 and RB1 proteins. Taken together, our findings provide the foundation for the development of new chemical probes as potential lead drug candidates for the treatment of cancer

Design, synthesis and mechanistic anticancer activity of new acetylated 5-aminosalicylate-thiazolinone hybrid derivatives

The development of hybrid compounds has been widely considered as a promising strategy to circumvent the difficulties that emerge in cancer treatment. The well-established strategy of adding acetyl groups to certain drugs has been demonstrated to enhance their therapeutic efficacy. Based on our previous work, an approach of accommodating two chemical entities into a single structure was implemented to synthesize new acetylated hybrids (HH32 and HH33) from 5-aminosalicylic acid and 4-thiazolinone derivatives. These acetylated hybrids showed potential anticancer activities and distinct metabolomic profile with antiproliferative properties. The in-silico molecular docking predicts a strong binding of HH32 and HH33 to cell cycle regulators, and transcriptomic analysis revealed DNA repair and cell cycle as the main targets of HH33 compounds. These findings were validated using in vitro models. In conclusion, the pleiotropic biological effects of HH32 and HH33 compounds on cancer cells demonstrated a new avenue to develop more potent cancer therapies

Bacterial translocation in an experimental intestinal obstruction model: C-reactive protein reliability? Translocação bacteriana no modelo experimental de obstrução intestinal: A proteína C-reativa é confiável?

BACKGROUND: Bacterial translocation occurs in preseptic conditions such as intestinal obstruction through unclear mechanism. The C-reactive protein is an acute phase reactant and a marker of ischemia. METHODS: 45 albino male rats were divided into 3 groups each 15 rats. GI control, GII simple intestinal-obstruction and GIII strangulated obstruction. Outcome measures were: (1) Bacteriologic count and typing for intestinal contents, intestinal wall, liver, mesenteric lymph nodes and blood (cardiac and portal) (2) Histopathologic: mucosal injury score, inflammatory cell infiltrate in the wall, MLN, liver, (3) Biochemical: serum CRP, IL-10, mucosal stress pattern (glutathione peroxidase-malonyldialdhyde tissue levels). RESULTS: (1) Intestinal obstruction associates with BT precursors (Bact-overgrowth, mucosal-acidosis, immuno-incomptence), (2) Bacterial translocation (frequency and density) was found higher in strangulated I.O, that was mainly enteric (aerobic and anaerobic) and mostly E.coli, (3) The pathogen commonality supports the gut origin hypothesis but the systemic inflammatory response goes with the cytokine generating one. (4) The CRP median values for GI, II, III were 0.5, 6.9, 8.5 mg/L, for BT +ve 8 mg/L and 0.75 mg/L for BT -ve rats. CONCLUSION: Bacterial translocation occurs bi-directional (systemic-portal) in intestinal obstruction and the resultant inflammatory response pathogenesis is mostly 3 hit model. The CRP is a non selective marker of suspected I.O cases. However, it is a reliable marker of BT, BT density and vascular compromise during I.O.<br>OBJETIVO: Translocação bacteriana ocorre em condições pré-sépticas como na obstrução intestinal por mecanismo não esclarecido. A proteína C-reativa é um marcador de ischemia em fase aguda. A proposição é investigar os possíveis efeitos da obstrução intestinal no equilíbrio ecológico microbiano. MÉTODOS: 45 ratos machos albinos foram distribuídos em três grupos de 15 ratos. GI controle, GII obstrução intestinal simples e GIII obstrução estrangulada. As medidas adotadas foram: (1) Contagem bacteriológica do conteúdo intestinal, parede intestinal, fígado, linfonodos mesentéricos e sangue (coração e portal) (2) Avaliação histopatológica da lesão da mucosa, infiltrado celular inflamatório da parede, linfonodos mesentéricos, fígado, (3) Avaliação bioquímica. RESULTADOS: (1) Obstrução intestinal está associada a precursora translocação bacteriana (crescimento bacteriano, acidose da mucosa, imuno-incompetência), (2) Translocação bacteriana (freqüência e densidade) foi maior na obstrução intestinal estrangulada, principalmente entérica (aeróbios e anaeróbios), sobretudo E.coli, (3) A ocorrência comum é de origem intestinal. CONCLUSÃO: A translocação bacteriana na obstrução intestinal é bi-direcional (sistêmica e portal) A proteina C-reativa não é um marcador seletivo na suspeita de obstrução intestinal. Contudo é marcador confiável da translocação bacteriana, na densidade e comprometimento durante a obstrução intestinal

Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors

AbstractIntroduction Altered epigenetic map is frequently observed in cancer and recent investigations have demonstrated a pertinent role of epigenetic modifications in the response to many anticancer drugs including the DNA damaging agents. Topoisomerase I (Top I) is a well-known nuclear enzyme that is critical for DNA function and cell survival and its inhibition causes DNA strand breaks and cell cycle arrest. Inhibitors of human Top I have proven to be a prosperous chemotherapeutic treatment for a vast number of cancer patients. While the treatment is efficacious in many cases, resistance and altered cellular response remain major therapeutic issues.Areas covered This review highlights the evidence available till date on the influence of different epigenetic modifications on the response to Top I inhibitors as well as the implications of targeting epigenetic alterations for improving the efficacy and safety of Top I inhibitors.Expert opinion The field of epigenetic research is steadily growing. With its assistance, we could gain better understanding on how drug response and resistance work. Epigenetics can evolve as possible biomarkers and predictors of response to many medications including Top I inhibitors, and could have significant clinical implications that necessitate deeper attention.HIGHLIGHTSEpigenetic alterations, including DNA methylation and histone modifications, play a pertinent role in the response to several anticancer treatments, including DNA damaging agents like Top I inhibitors.Although camptothecin derivatives are used clinically as Top I inhibitors for management of cancer, certain types of cancer have inherent and or acquired resistance that limit the curative potential of them.Epigenetic modifications like DNA hypomethylation can either increase or decrease sensitivity to Top I inhibitors by different mechanisms.The combination of Top I inhibitors with the inhibitors of histone modifying enzymes can result in enhanced cytotoxic effects and sensitization of resistant cells to Top I inhibitors.MicroRNAs were found to directly influence the expression of Top I and other proteins in cancer cells resulting in positive or negative alteration of the response to Top I inhibitors.lncRNAs and their genetic polymorphisms have been found to be associated with Top I function and the response to its inhibitors.Clinical trials of epigenetic drugs in combination with Top I inhibitors are plentiful and some of them showed potentially promising outcomes

The Role of HDACs in the Response of Cancer Cells to Cellular Stress and the Potential for Therapeutic Intervention

Throughout the process of carcinogenesis, cancer cells develop intricate networks to adapt to a variety of stressful conditions including DNA damage, nutrient deprivation, and hypoxia. These molecular networks encounter genomic instability and mutations coupled with changes in the gene expression programs due to genetic and epigenetic alterations. Histone deacetylases (HDACs) are important modulators of the epigenetic constitution of cancer cells. It has become increasingly known that HDACs have the capacity to regulate various cellular systems through the deacetylation of histone and bounteous nonhistone proteins that are rooted in complex pathways in cancer cells to evade death pathways and immune surveillance. Elucidation of the signaling pathways involved in the adaptive responses to cellular stress and the role of HDACs may lead to the development of novel therapeutic agents. In this article, we overview the dominant stress types including metabolic, oxidative, genotoxic, and proteotoxic stress imposed on cancer cells in the context of HDACs, which guide stress adaptation responses. Next, we expose a closer view on the therapeutic interventions and clinical trials that involve HDACs inhibitors, in addition to highlighting the impact of using HDAC inhibitors in combination with stress-inducing agents for the management of cancer and to overcome the resistance to current cancer therapy

Detection of OXA-48-Carbapenemase-Producing Enterobacteriaceae using ChromID OXA-48 in Critical Care Patients in Egypt

Carbapenems are a class of beta-lactam antibiotics with broad spectrum of activity. They are often considered as a last resort in treatment of infections caused by multidrug resistant organisms. Carbapenemase-producing Enterobacteriaceae (CPE) have been reported worldwide. Class D OXA-48 carbapenemases is rapidly disseminating in Enterobacteriaceae leading to high mortality from resistant and invasive CPE infections. In the present study, we attempted to isolate OXA-48 carbapenemase-producing Enterobacteriaceae from different clinical specimens obtained from hospitalized patients at different ICU of kasr Kasr Al-Ainy hospital, Cairo University. Initial screening for carbapenemase-producing Enterobacteriaceae was done using ertapenem disc diffusion method and direct inoculation of the specimens into ChromID OXA-48. The phenotypic Modified Hodge Test (MHT) was used for confirmation of carbapenemse production among screened carbapenem resistant isolates.Out of 112 collected samples, 94 Enterobacteriaceae were isolated. Fifty five isolates (58.5%) were ertapenem disc resistant and 50 isolates (53%) showed positive growth on ChromID OXA-48. Fifty two (94.5%) out of 55 suspected carbapenemase-producing isolates by disc diffusion method and the 50 isolates (100%) grown on ChromID OXA-48 were MHT positive. Our study underlines the need to detect OXA-48 CPE as early as possible to minimize its spread in ICU and apply appropriate infection control measures