Distinct microRNA expression pattern in breast cancer cells following anti-neoplastic treatment: A systematic review and functional analysis of microRNA target genes.

Breast cancer remains a significant cause of mortality in females worldwide, despite advances in technology and treatment. MicroRNA expression in breast cancer is studied both as potential biomarkers and for therapeutic purposes. Accumulated evidence revealed microRNA profile of various types of cancer cells following antineoplastic treatment. The progression of research in this area provides better understanding on the anti-cancer mechanism of various natural compounds and drugs specifically on the microRNA regulation. Hence, we aim to systematically review differentially expressed microRNA in MCF-7, a commonly studied breast cancer cell line, after treatment with anti-neoplastic agents. Relevant keywords were used to screen for research articles that reported on the differentially expressed microRNAs in experimental models of MCF-7 before and after anti-neoplastic treatment. Target genes of microRNAs were identified from MiRTarbase and further in silico functional analysis of the target genes were performed using DAVID bioinformatic resources. Two upregulated microRNAs (mir-200c and let-7d) and 3 downregulated microRNAs (mir-27a, mir-27b and mir-203) were identified by highest number of studies. Three microRNAs (let-7a, mir-23a and mir-7) showed inconsistent direction of expression. Genes functional analysis revealed the regulatory effect of microRNA on genes related to angiogenesis, hypoxia, P53, FoxO and PI3K-AKT signalling. Clusters of genes associated to the pathway of angiogenesis, cancers, cell proliferation and apoptosis were noted through protein-protein interaction analysis. MicroRNAs, especially the mir-200c, let-7d, mir-27a, mir-27b and mir-203 from this review could be further validated experimentally to serve as molecular target or biomarkers for anti-neoplastic therapy.

Transcriptional profiling of primary prostate tumor in metastatic hormone-sensitive prostate cancer and association with clinical outcomes: correlative analysis of the E3805 CHAARTED trial.

BACKGROUND: The phase III CHAARTED trial established upfront androgen-deprivation therapy (ADT) plus docetaxel (D) as a standard for metastatic hormone-sensitive prostate cancer (mHSPC) based on meaningful improvement in overall survival (OS). Biological prognostic markers of outcomes and predictors of chemotherapy benefit are undefined. PATIENTS AND METHODS: Whole transcriptomic profiling was performed on primary PC tissue obtained from patients enrolled in CHAARTED prior to systemic therapy. We adopted an a priori analytical plan to test defined RNA signatures and their associations with HSPC clinical phenotypes and outcomes. Multivariable analyses (MVAs) were adjusted for age, Eastern Cooperative Oncology Group status, de novo metastasis presentation, volume of disease, and treatment arm. The primary endpoint was OS; the secondary endpoint was time to castration-resistant PC. RESULTS: The analytic cohort of 160 patients demonstrated marked differences in transcriptional profile compared with localized PC, with a predominance of luminal B (50%) and basal (48%) subtypes, lower androgen receptor activity (AR-A), and high Decipher risk disease. Luminal B subtype was associated with poorer prognosis on ADT alone but benefited significantly from ADT + D [OS: hazard ratio (HR) 0.45; P = 0.007], in contrast to basal subtype which showed no OS benefit (HR 0.85; P = 0.58), even in those with high-volume disease. Higher Decipher risk and lower AR-A were significantly associated with poorer OS in MVA. In addition, higher Decipher risk showed greater improvements in OS with ADT + D (HR 0.41; P = 0.015). CONCLUSION: This study demonstrates the utility of transcriptomic subtyping to guide prognostication in mHSPC and potential selection of patients for chemohormonal therapy, and provides proof of concept for the possibility of biomarker-guided selection of established combination therapies in mHSPC.

(22ß,25R)-3ß-Hydroxy-spirost-5-en-7-iminoxy-heptanoic acid exhibits anti-prostate cancer activity through caspase pathway.

Prostate cancer is one of the most common cancers in men. Diosgenin and related compounds are potential cytotoxic agents. Twelve diverse analogues of long chain fatty acid/ester of diosgenin-7-ketoxime have been prepared. Six of the analogues exhibited significant anticancer activity against a panel of human cancer cell lines with IC50 ranging from 12 to 35µM. Compound 16, the best representative of the series exerted S phase arrest in DU145 prostate cancer cells and induced apoptosis through caspase pathway. Additionally, these analogues inhibited lipopolysaccharide induced pro-inflammatory cytokines (TNF-α and IL-6) up to 47.7% and 23.3% respectively. Compound 16 was found to be safe in acute oral toxicity in Swiss albino mice up to 300mg/kg dose. The anticancer and antiinflammatory properties of compound 16 are important and can further be optimized for a better anti-prostate cancer candidate.

Effects of salinity and salinity-induced augmented bioactive compounds in purslane (Portulaca oleracea L.) for possible economical use.

Dry matter (DM), total phenolics, flavonoids, carotenoid contents, and antioxidant activity of 12 purslane accessions were investigated against five levels of salinity (0, 8, 16, 24 and 32dSm(-1)). In untreated plants, the DM contents ranged between 8.0-23.4g/pot; total phenolics contents (TPC) between 0.96-9.12mgGAEg(-1)DW; total flavonoid contents (TFC) between 0.15-1.44mgREg(-1)DW; and total carotenoid contents (TCC) between 0.52BCEg(-1)DW. While FRAP activity ranged from 8.64-104.21mgTEg(-1)DW (about 12-fold) and DPPH activity between 2.50-3.30mgmL(-1) IC50 value. Different levels of salinity treatment resulted in 8-35% increases in TPC; about 35% increase in TFC; and 18-35% increases in FRAP activity. Purslane accessions Ac4, Ac5, Ac6 and Ac8 possessed potentials for salinity-induced augmented production of bioactive compounds which in turn can be harnessed for possible human health benefits.

Synthesis of novel anticancer agents through opening of spiroacetal ring of diosgenin.

Diosgenin has been modified to furostane derivatives after opening the F-spiroacetal ring. The aldehyde group at C26 in derivative 8 was unexpectedly transformed to the ketone 9. The structure of ketone 9 was confirmed by spectroscopy and finally by X-ray crystallography. Five of the diosgenin derivatives showed significant anticancer activity against human cancer cell lines. The most potent molecule of this series i.e. compound 7, inhibited cellular growth by arresting the population at G0/G1 phase of cell division cycle. Cells undergo apoptosis after exposure to the derivative 7 which was evident by increase in sub G0 population in cell cycle analysis. Docking experiments showed caspase-3 and caspase-9 as possible molecular targets for these compounds. This was further validated by cleavage of PARP, a caspase target in apoptotic pathway. Compound 7 was found non-toxic up to 1000mg/kg dose in acute oral toxicity in Swiss albino mice.

An assessment of Pakistani pharmacy and medical students’ knowledge of black box warnings / Una evaluación del conocimiento de estudiantes de medicina y de farmacia en Pakistán sobre alertas de medicamentos / Uma avaliação sobre o acesso de estudantes paquistaneses de medicina e farmácia ao conhecimento das advertências das caixas de tarja preta

Food and Drug Administration delivers the black box warnings (BBW) which should appear on the leaflets of medicines for patient awareness and the prescription of drugs indicating its highly fatal adverse effects to human body. The aim of this study was to assess the knowledge of Pakistani pharmacy and medical students about BBW. A questionnaire containing contents about BBW was given to the 1st, 2nd and 3rd professional year pharmacy and medical students from different pharmacy and medical institutes. A 76 percent survey response rate was observed. It was observed that student’s knowledge about BBW improves in association with the promotion in professional years of pharmacy and medical education. The results indicate that student’s knowledge about black box increases with the study level. Training in black box warnings should be implemented in pharmacy and medical institutions influencing the meaningful ways to educate and train pharmacy and medical students, and help these students to get recent knowledge about black box warnings so that, in future, they may perform an ethical practice in their respective fields.

La Agencia Reguladora de Alimentos y Medicamentos comunica alertas sobre medicamentos (AM), que debieran aparecer en los prospectos de medicinas, para el conocimiento de los pacientes y la prescripción de medicamentos, indicando sus efectos adversos fatales para el cuerpo humano. El objetivo de este estudio es averiguar el conocimiento de estudiantes de medicina y de farmacia sobre AM. Se entregó un cuestionario con contenidos sobre AM a estudiantes de farmacia y de medicina de primero a tercer año de diferentes institutos médicos y farmacéuticos. Se obtuvo un 76 por ciento de respuesta. Se observó que el conocimiento de los estudiantes sobre AM mejora asociado a la promoción en años profesionales de medicina y farmacia. Los resultados indican que el conocimiento de los estudiantes sobre alerta de medicamentos aumenta con el nivel de estudio. Debería implementarse la formación sobre alerta de medicamentos en farmacia y medicina y ayudar a los estudiantes a tener conocimiento actual sobre alerta de medicamentos de forma que, en el futuro, puedan realizar prácticas éticas en sus campos respectivos.

A Food and Drug Administration disponibiliza as advertências das caixas de tarja preta (BBW) que devem aparecer em bulas de medicamentos para conscientização de pacientes e a prescrição de drogas, indicando seus efeitos adversos altamente fatais para o corpo humano. O propósito deste estudo foi o de de inteirar a cerca do conhecimento de estudantes de medicina e farmácia sobre BBW. Um questionário com conteúdos sobre BBW foi dado a estudantes de farmácia e medicina, do 1º, 2º e 3º ano de diferentes instituições de ensino em farmácia e medicina. Foi observada uma taxa de 76 por cento de resposta dos pesquisados. Observou-se que o conhecimento de estudantes sobre BBW melhora quando se associa à promoção para anos seguintes da educação nas faculdades de farmácia e medicina. Os resultados indicam que o conhecimento dos estudantes sobre as caixas de tarja preta aumenta com o nível de estudo. Treinamento com caixas de tarja preta pode ser implementado em instituições de ensino de farmácia e medicina, influenciando de modo significativo as formas de educação e treinamento de estudantes de farmácia e medicina, e,assim, ajudar estes estudantes a obter conhecimentos recentes sobre medicamentos de tarja preta de modo que, no futuro, elas possam exercer uma prática ética em seus respectivos campos de atuação profissional.

Recyclable, strong thermosets and organogels via paraformaldehyde condensation with diamines.

Nitrogen-based thermoset polymers have many industrial applications (for example, in composites), but are difficult to recycle or rework. We report a simple one-pot, low-temperature polycondensation between paraformaldehyde and 4,4'-oxydianiline (ODA) that forms hemiaminal dynamic covalent networks (HDCNs), which can further cyclize at high temperatures, producing poly(hexahydrotriazine)s (PHTs). Both materials are strong thermosetting polymers, and the PHTs exhibited very high Young's moduli (up to ~14.0 gigapascals and up to 20 gigapascals when reinforced with surface-treated carbon nanotubes), excellent solvent resistance, and resistance to environmental stress cracking. However, both HDCNs and PHTs could be digested at low pH (<2) to recover the bisaniline monomers. By simply using different diamine monomers, the HDCN- and PHT-forming reactions afford extremely versatile materials platforms. For example, when poly(ethylene glycol) (PEG) diamine monomers were used to form HDCNs, elastic organogels formed that exhibited self-healing properties.

Synthesis of diosgenin analogues as potential anti-inflammatory agents.

We herein report the synthesis of diosgenin analogues from commercially available diosgenin as the starting material. The structures of newly synthesised compounds were confirmed by (1)H NMR, (13)C NMR and mass spectrometry. All analogues were evaluated for in-vitro anti-inflammatory profile against LPS-induced inflammation in primary peritoneal macrophages isolated from mice by quantification of pro-inflammatory (TNF-α, IL-6 and IL-1ß) cytokines in cell culture supernatant using the ELISA technique followed by in-vitro cytotoxicity study. Among the synthesised analogues, analogue 15 [(E) 26-(3',4',5'-trimethoxybenzylidene)-furost-5en-3ß-acetate)] showed significant anti-inflammatory activity by inhibiting LPS-induced pro-inflammatory cytokines in a dose-dependent manner without any cytotoxicity. Efficacy and safety of analogue 15 were further validated in an in-vivo system using LPS-induced sepsis model and acute oral toxicity in mice. Oral administration of analogue 15 inhibited the pro-inflammatory cytokines in serum, attenuated the liver and lung injury and reduced the mortality rate in sepsis mice. Acute oral toxicity study showed that analogue 15 is non-toxic at higher dose in BALB/c mice. Molecular docking study revealed the strong binding affinity of diosgenin analogues to the active site of the pro-inflammatory proteins. These findings suggested that analogue 15 may be a useful therapeutic candidate for the treatment of inflammatory diseases.

Combating malaria with plant molecules: a brief update.

Malaria is one of the deadliest diseases on the planet affecting about 50% of the population worldwide. It is a leading cause of morbidity and mortality in the developing world. Plasmodium falciparum, a tiny parasite is the major cause of malaria and is possibly the most dangerous stow-away in history. Malaria has become a major economic concern to some of the tropical and sub-tropical countries. Though a number of antimalarials have been developed from plants as such or their semi-synthetic analogues, there is again an alarming situation of drug resistance against most of the antimalarial drugs. Plants have been an excellent source of antimalarial compounds. There are several plant leads exhibiting antimalarial activity better than the existing drugs. A systematic evaluation of these plant based leads is the need of the time to develop safe, effective and affordable new antimalarials. The present review is an update of plant based antimalarial agents.

Use of prebiotics in oral delivery of bioactive compounds: a nanotechnology perspective.

The oral route is considered the most patient-convenient means of drug administration. In recent years there has been a tendency to employ smart carrier systems that enable controlled or timed release of a bioactive material, thereby providing a better dosing pattern and minimizing side effects. Nano-encapsulation systems (nanocarriers) offer important advantages over conventional drug delivery techniques. Nanocarriers can protect the drug from chemical/enzymatic degradation and enhance bioavailability. Prebiotics are ideal ingredients for the nano-encapsulation and oral drug delivery due to their natural ability to protect the encapsulated compound in the upper gasterointestinal (GI) tract. Here the potential of prebiotics for oral delivery of drugs and other bioactives is reviewed.

Chemical constituents and anti-inflammatory activity of leaf essential oil of Nigerian grown Chenopodium album L.

Hydrodistilled leaves of Chenopodiumalbum yielded 0.64 % v/w of essential oil. GC and GC/MS analyses of the oil revealed that the bulk of the oil was constituted by aromatic compounds (60.1 %). The abundant constituents of the oil were: p- cymene (40.9 %), ascaridole (15.5 %), pinane-2-ol (9.9 %), α-pinene (7.0 %), ß-pinene (6.2 %) and α-terpineol (6.2 %). The oil displayed strong anti-inflammatory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA) - induced ear edema in mice.

High prevalence of Pseudomonas species in soil samples from Ternate Island-Indonesia.

In the present study, Ten soil samples were examined and the pH of the soil was recorded. For bacterial isolation, a sterile nutrient and blood agars were used. Gram stain and biochemical tests were done for identification. A total of 384 genus were isolated, 314 (81.8%) were identified as Pseudomonas species of which 245 (78.0%) were Pseudomonas aeruginosa, 42 (13.4%) were Pseudomonas fluorescens, 13 (4.2%) were Pseudomonas mallei, 10 (3.1%) were Pseudomonas putida and 4 (1.3%) were Pseudomonas syringe and are regarded as pathogenic and harmful to man, animal and plants. This study shows that Pseudomonas aeruginosa had a high adaptation capability to grow in soil samples from Ternate, Indonesia. The rest of the bacterial isolates (18.2%) were identified as follows: 24 samples (6.2%) were Micrococcus, 23 samples (6.0%) were E. coli, 12 samples (3.1%) were Pasteurella and 11 samples (2.9%) were Staphylococcus. Pencillium was also isolated.

Modulation of lipid metabolism by Centella asiatica in oxidative stress rats.

A study was carried out to investigate the effects of Centella asiatica leaf on lipid metabolism of oxidative stress rats. The rats were fed 0.1% hydrogen peroxide (H(2)O(2)) with either 0.3% (w/w) C. asiatica extract, 5%C. asiatica powder (w/w), or 0.3% (w/w) alpha-tocopherol for 25 wk. Results of the study showed that C. asiatica powder significantly (P < 0.05) lowered serum low-density lipoprotein compared to that of control rats (rats fed H(2)O(2) only). At the end of the study C. asiatica-fed rats were also found to have significantly (P < 0.05) higher high-density lipoprotein and lower triglyceride level compared to rats fed only normal diet. However, cholesterol level of rats fed both C. asiatica extract and powder was found to be significantly (P < 0.05) higher compared to that of control rats. It was interesting to note that consumption of C. asiatica significantly decreased body and liver weights of the rats. Histological examinations revealed no obvious changes in all rats studied. Quantitative analysis of C. asiatica leaf revealed high concentration of total phenolic compounds, in particular, catechin, quercetin, and rutin.

Differential gene expression of human adipose-derived stem cells in osteogenic induction.

Human adipose-derived stem cells (HADSC) have demonstrated the capacity of differentiating into bone depending on the specific induction stimuli and growth factors. However, investigation on stem cell characteristic after osteogenic differentiation is still lacking. The goal of this study was to investigate the differential expression of sternness and osteogenic genes in non-induced HADSC compared with HADSC after osteogenic induction using quantitative Real Time RT-PCR. Our results showed that OCT-4, REX-1, FZD9, OSC, RUNX, and ALP were up regulated after osteogenic induction. This may indicated that HADSCs after osteogenic induction still possessed some stemness properties.

Effect of some environmental parameters on hydrogen production using C. acetobutylicum.

The aim of this study was to investigate the influence of some environmental factors on bacterial metabolism. Fermentative hydrogen production by C. acetobutylicum, using glucose as the substrate. The effect of initial pH (4-8), inoculum size (1-20% (v/v)) and glucose concentration (1-30 g L(-1)) on hydrogen production were studied. The optimum cultivation temperature for hydrogen production was at 30 degrees C. The results show that substrate concentration and inoculum size resulted in hydrogen yield (Y(P/S)) of 391 mL g(-1) glucose utilized with maximum hydrogen productivity of 77.5 mL/L/h. Higher substrate concentration or inoculum size adversely affects hydrogen production, which decreases hydrogen yield by 15% to 334 mL g(-1) glucose utilized when 30% (v/v) inoculum size was used. The use of 30 g L(-1) substrate concentration resulted in a 75% decrease to 97 mL g(-1) glucose supplied. Concluded that proper Xo/So enhanced the hydrogen production.

Enhancement of biodegradation of crude petroleum-oil in contaminated water by the addition of nitrogen sources.

Addition of nitrogen sources as supplementary nutrient into MSM medium to enhance biodegradation by stimulating the growth four isolates, Acinetobacter faecalis, Staphylococcus sp., Pseudomonas putida and Neisseria elongata isolated from petroleum contaminated groundwater, wastewater aeration pond and biopond at the oil refinery Terengganu Malaysia was investigated. The organic nitrogen sources tested not only supported growth but also enhances biodegradation of 1% Tapis crude oil. All four isolates showed good growth especially when peptone was employed as the organic nitrogen compared to growth in the basal medium. Gas chromatography showed that more then 91, 93, 94 and 95% degradation of total hydrocarbon was observed after 5 days of incubation by isolates Pseudomonas putida, Neisseria elongate, Acinetobacter faecalis and Staphylococcus sp., respectively.

Removal of headspace CO2 increases biological hydrogen production by C. acetobutylicum.

The effect of removal of resultant gas resulted in enhancement of the H2 yield. The technique of CO2 scavenging resulted in H2 yield being improved from 408 mL g(-1) to reach the maximum of 422 mL g'. The highest hydrogen productivity of 87.9 ml L(-1) h(-1) was obtained by CO2 scavenging. Biomass concentration was enhanced to 1.47 g L(-1), Y(P,X) of 287 ml g(-1) L(-1), Y(X/S) of 0.294 and Y(H2/s) of 0.0377 by the use of CO2 scavenging. The results suggested that the presence of the gaseous products in fermentation medium and headspace adversely effect biomass growth and hydrogen production.

Effect of salts addition on hydrogen production by C. acetobutylicum.

The objective of this study is to investigate the effect of salts addition to fermentation medium on hydrogen production, under anaerobic batch culture system. In this study, batch experiments were conducted to investigate the inhibitory effect of both NaCl and sodium acetate on hydrogen production. The optimum pH and temperature for hydrogen production were at initial pH of 7.0 and 30 degrees C. Enhanced production of hydrogen, using glucose as substrate was achieved. In the absence of Sodium Chloride and Sodium Acetate enhanced hydrogen yield (Y(P/S)) from 350 mL g(-1) glucose utilized to 391 mL g(-1) glucose utilized with maximum hydrogen productivity of 77.5 ml/L/h. Results also show that sodium chloride and sodium acetate in the medium adversely affect growth. Hydrogen yield per biomass (Y(P/X)) of 254 ml/L/g, biomass per substrate utilized (Y(X/S)) of 0.268 and (Y(H2/S) of 0.0349. The results suggested that Sodium at any concentration resulted to inhibit the bacterial productivity of hydrogen.

C-erbB-2 or mutant Ha-ras induced malignant transformation of immortalized human ovarian surface epithelial cells in vitro.

Ovarian cancer is believed to develop from the ovarian surface epithelium through the accumulation of aberrations of oncogenes and/or tumor suppressor genes. However, it is unclear how the gene abnormalities are involved in ovarian carcinogenesis. To elucidate the process, we transfected genes reported to show their abnormalities in human ovarian cancers into human ovarian surface epithelial cells. Immortalization of the cells was achieved by the transfection of SV40 large T antigen (LT) and human telomerase reverse transcriptase (hTERT); however, the resultant cells showed no tumorigenesis. Additional transfection of either c-erbB-2 or mutant Ha-ras into the immortalized cells showed the anchorage-independent growth and tumorigenesis in mice with the incidence of 50% and 40%, respectively. Histologically, all the tumours were undifferentiated. In association with the tumorigenesis, the cells expressing c-erbB-2 or mutant Ha-ras demonstrated increased vascular endothelial growth factor secretion under hypoxia and enhanced resistance to apoptosis compared with the immortalized cells. Collectively, the introduction of either c-erbB-2 or mutant Ha-ras in the cells, which were efficiently immortalized by the transfection of LT and hTERT, showed tumorigenicity, suggesting that c-erbB-2 or mutant Ha-ras genes might be involved in ovarian carcinogenesis.

Resource use of insect seed predators during general flowering and seeding events in a Bornean dipterocarp rain forest.

Insect seed predators of 24 dipterocarp species (including the genera ot Dipterocarpus, Dryobalanops and Shorea) and five species belonging to the Moraceae, Myrtaceae, Celastraceae and Sapotaceae were investigated. In a tropical lowland dipterocarp forest in Sarawak, Malaysia, these trees produces seeds irregularly by intensely during general flowering and seeding events in 1996 and/or 1998. Dipterocarp seeds were preyed on by 51 insect species (11 families), which were roughly classified into three taxonomic groups: smaller moths (Trotricidae, Pyralidae, Crambidae, Immidae, Sesiidae, and Cosmopterigidae), scolytids (Scolydae) and weevils (Curdulionidae, Apionidae, Anthribidae, and Attelabidae). Although the host-specificity of invertebrate seed predators has been assumed to be high in tropical forests, it was found that the diet ranges of some insect predators were relatively wide and overlapped one another. Most seed predators that were collected in both study years changes their diets between general flowering and seeding events. The results of cluster analyses based on the number of adult of each predator species that emerged from 100 seeds of each tree species, suggested that the dominant species was not consistent, alternating between the two years.