Design,synthesis, and evaluation of the antiproliferative activity of hydantoin-derived antiandrogen-genistein conjugates

Androgen receptor (AR) signaling is vital to the viability of all forms of prostate cancer (PCa). With the goal of investigating the effect of simultaneous inhibition and depletion of AR on viability of PCa cells, we designed, synthesized and characterized the bioactivities of bifunctional agents which incorporate the independent cancer killing properties of an antiandrogen and genistein, and the AR downregulation effect of genistein within a single molecular template. We observed that a representative conjugate, 9b, is much more cytotoxic to both LNCaP and DU145 cells relative to the antiandrogen and genistein building blocks as single agents or their combination. Moreover, conjugate 9b more effectively down regulates cellular AR protein levels relative to genistein and induces S phase cell cycle arrest. The promising bioactivities of these conjugates warrant further investigation.     

Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride

Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.     

Comparative analysis of the MyTH4-FERM myosins reveals insights into the determinants of actin track selection in polarized epithelia

MyTH4-FERM (MF) myosins evolved to play a role in the creation and function of a variety of actin-based membrane protrusions that extend from cells. Here we performed an analysis of the MF myosins, Myo7A, Myo7B, and Myo10, to gain insight into how they select for their preferred actin networks. Using enterocytes that create spatially separated actin tracks in the form of apical microvilli and basal filopodia, we show that actin track selection is principally guided by the mode of oligomerization of the myosin along with the identity of the motor domain, with little influence from the specific composition of the lever arm. Chimeric variants of Myo7A and Myo7B fused to a leucine zipper parallel dimerization sequence in place of their native tails both selected apical microvilli as their tracks, while a truncated Myo10 used its native antiparallel coiled-coil to traffic to the tips of filopodia. Swapping lever arms between the Class 7 and 10 myosins did not change actin track preference. Surprisingly, fusing the motor-neck region of Myo10 to a leucine zipper or oligomerization sequences derived from the Myo7A and Myo7B cargo proteins USH1G and ANKS4B, respectively, re-encoded the actin track usage of Myo10 to apical microvilli with significant efficiency.     

Quality of Life in Rural Communities: Residents Living Near to Tembeling,Pahang and Muar Rivers,Malaysia

The main aim of this study is to identify the quality of life (QoL) among communities residing near the Tembeling, Pahang and Muar Rivers in Malaysia. This quantitative study used a constructed questionnaire as main tool to collect data on the QoL of river communities. A total of 240 villagers were selected as respondents. The results indicated that the dimensions of settlement, safety, involvement and social relationships, as well as education scored highest, while dimensions of physical environment, financial and job security yielded moderate scores. Dimensions of infrastructure facilities yielded a low mean score. Recommendations are provided, in the hope that our results may be useful for strategies that could enhance QoL of these river communities.     

A “hit-and-run” affair – A possible link for cancer progression in virally driven cancers

BackgroundIt is well-known that certain cancers are caused by viruses. However, viral oncogenesis is complex and only a small fraction of the infected people develop cancer. Indeed, a number of environmental factors can contribute to virally infected cells developing cancer hallmarks, promoting tumorigenesis.Scope of reviewThe hit-and-run theory proposes that viruses facilitate the accumulation of mutations and promote genomic instability until the virus becomes dispensable for tumour maintenance. Indeed, several studies have reported viral genome, episome and/or oncogene loss in tumour cells without losing malignant phenotype.Major conclusionsThe current evidence supports the clear contribution of certain viruses to develop cancers. Importantly, the evidence supporting the sustained maintenance of malignancy after the loss of viral “presence” is sufficient to support the hit-and-run hypothesis of viral cancer development. Long-term tracking of vaccination outcome over the decades will test this theory.General significanceIf the hit-and-run theory is true, viruses might cause more cancers than previously thought and will have implications in the prevention of many cancers through implementing vaccination programs.     

Childhood Asthma and Mental Retardation

Four hundred consecutive outpatients seen at the Children''s Psychiatric Research Institute, London, Ont., were investigated to determine whether there is a negative correlation between childhood asthma and mental retardation. Of these, 380 were mentally retarded and 20 were of normal intelligence. Only two cases of childhood asthma were found. One of these had an I.Q. of 108 and the other 78, so that no case of asthma was found in the mentally retarded group. On the basis of a reported prevalence rate for asthma of 1.76%, one would expect six or seven cases among the 400. By contrast, among the approximately 800 parents there were 11 cases of chronic asthma, a figure which is approximately the expected number.     

Proteomics as a tool for tapping potential of entomopathogens as microbial insecticides

Biopesticides are collective pest control harnessing the knowledge of the target pest and its natural enemies that minimize the risks of synthetic pesticides. A subset of biopesticides; bioinsecticides, are specifically used in controlling insect pests. Entomopathogens (EPMs) are micro‐organisms sought after as subject for bioinsecticide development. However, lack of understanding of EPM mechanism of toxicity and pathogenicity slowed the progress of bioinsecticide development. Proteomics is a useful tool in elucidating the interaction of entomopathogenic fungi, entomopathogenic bacteria, and entomopathogenic virus with their target host. Collectively, proteomics shed light onto insect host response to EPM infection, mechanism of action of EPM’s toxic proteins and secondary metabolites besides characterizing secreted and membrane‐bound proteins of EPM that more precisely describe relevant proteins for host recognition and mediating pathogenesis. However, proteomics requires optimized protein extraction methods to maximize the number of proteins for analysis and availability of organism's genome for a more precise protein identification.     

Crystal and molecular structures of syn and anti isomers of [MoO(μ-NAr)(S2CNR2)]2 (R = Et, Pr; Ar = Ph, p-tolyl)

Crystallographic studies have been carried out on four complexes of the type, [MoO(μ-NAr)(S₂CNR₂)]₂ (R = Et, Pr; Ar = Ph, p-tol). Each contains a binuclear molybdenum(V) centre bridged by two imido ligands, with each molybdenum atom also carrying terminal dithiocarbamate and oxo moieties. Syn and anti structural types are seen which result in significant differences within the Mo₂N₂ core; that in the anti structures being planar, while fold angles of 151.1° and 164.6° are observed in the syn complexes.     

The effect of silicon on lodging of rice in presence of added nitrogen

Summary Effect of silicon on lodging of rice induced by added N was studied in the field with three varieties of rice. The resistance to lodging was measured with a special equipment by applying a pulling force to the rice stalk until it broke or bent to about 30° angle with the surface of the soil The added silicon significantly increased the rigidity of rice stalk and this increase was remarkably higher at lower doses of nitrogen. The larger quantities of nitrogen greatly reduced the efficiency of silicon in imparting rigidity to plants. Different varieties responded differently.