Evaluation of mutagenicity of wastewater in the vicinity of pesticide industry

Pesticide industrial wastewater samples were taken from the Chinhat industrial area nearby Lucknow city, India. GC–MS analysis revealed the presence of pesticides lindane, α-endosulfan, β-endosulfan, chlorpyriphos, monocrotophos, dimethoate and malathion. A pesticide mixture and wastewater extracts were studied to determine the mutagenicity by Ames Salmonella test, survival of DNA repair defective E. coli K-12 mutants and bacteriophage λ systems. Wastewater samples were concentrated with XAD-resins as an adsorbent and liquid–liquid extraction procedure. The XAD concentrated sample exhibited maximum mutagenic activity in comparison to liquid–liquid extracted sample. TA98 strain was the most responsive strain for both test samples with (+S9) and without (?S9) metabolic activation, while other strains exhibited weak response. A significant decline of DNA repair defective E. coli K-12 mutants, bacteriophage λ was observed with test samples in the survival. The intracellular damage was highest when treated with XAD concentrated sample as compared to liquid–liquid extract after 6 h treatment.     

Low pH does not modulate antioxidant status of diphenyl ditelluride but exacerbates Fe (II)-induced lipid peroxidation in liver preparation

The relationship of acidosis and lipid peroxidation in liver homogenate was studied and the effect of pH on the antioxidant potential of diphenyl ditelluride is reported. Low pH increased the rate of lipid peroxidation both in the absence and presence of Fe (II), while diphenyl ditelluride (DPDT) inhibited the rate of lipid peroxidation in a concentration-dependent manner at all studied pH values. However, the change in pH did not alter the antioxidant activity of the compound. This study shows acidosis catalyzed oxidative stress in liver homogenate and the antioxidant potential of diphenyl ditelluride.     

Antioxidant and urease inhibitory C-glycosylflavonoids from Celtis africana

Two new C-glycosylflavonoids celtisides A (1) and B (2) have been isolated from n-butanol-soluble fraction of Celtis africana, along with five known C-glycosylflavonoids vitexin (3), orientin (4), isoswertiajaponin (5), isoswertisin (6), and 2″-O-rhamnosyl vitexin (7) reported for the first time from this species. Their structures were assigned from 1D and 2D NMR spectra. These compounds were investigated for biological activities and showed significant antioxidant and urease inhibitory activities.     

Lipoxygenase inhibitory sphingolipids from Launaea nudicaulis

Four new sphingolipids: nudicaulin A [(2S,3S,4R,14E)-2-{[octadecanoyl]amino}tetraeicos-14-ene-1,3,4-triol; 1], nudicaulin B [(2S,3S,4R,14E)-2-{[(2R)-2-hydroxyoctadecanoyl]amino}tetraeicos-14-ene-1,3,4-triol; 2], nudicaulin C [(2S,3S,4R,14E)-2-{[(2R)-2-hydroxyoctadecanoyl]amino}tetraeicos-14-ene-1,3,4-triol-1-O-β-d-glucopyranoside; 3], and nudicaulin D [(2S,3S,4R)-2-{[(2R,3S,12E)-2,3-dihydroxyeicos-12-enoyl]amino}octadecane-1,3,4-triol; 4] together with 1-hexatriacontanol, β-sitosterol, octadecyl 4-hydroxycinnamate, elaidic acid, cholesta-5,22-diene-3,7-diol, oleanolic acid, apigenin, and β-sitosterol 3-O-β-d-glucopyranoside were isolated from the methanolic extract of the whole plant of Launaea nudicaulis. Their structures were elucidated using ¹H and ¹³C NMR spectra and 2D NMR analyses (HMQC, HMBC, and COSY) in combination with mass spectrometry (EI-MS, HR-EI-MS, FAB-MS, and HR-FAB-MS) experiments and comparison with literature data of related compounds. Compounds 1–4 displayed moderate inhibitory potential against enzyme lipoxygenase in concentration-dependent manner with IC₅₀ value ranges 103–193 μM.     

The lncRNAs PCGEM1 and PRNCR1 are not implicated in castration resistant prostate cancer

Long noncoding RNAs (lncRNAs) are increasingly implicated in cancer biology, contributing to essential cancer cell functions such as proliferation, invasion, and metastasis. In prostate cancer, several lncRNAs have been nominated as critical actors in disease pathogenesis. Among these, expression of PCGEM1 and PRNCR1 has been identified as a possible component in disease progression through the coordination of androgen receptor (AR) signaling (Yang et al., Nature 2013, see ref. [1]). However, concerns regarding the robustness of these findings have been suggested. Here, we sought to evaluate whether PCGEM1 and PRNCR1 are associated with prostate cancer. Through a comprehensive analysis of RNA-sequencing data (RNA-seq), we find evidence that PCGEM1 but not PRNCR1 is associated with prostate cancer. We employ a large cohort of >230 high-risk prostate cancer patients with long-term outcomes data to show that, in contrast to prior reports, neither gene is associated with poor patient outcomes. We further observe no evidence that PCGEM1 nor PRNCR1 interact with AR, and neither gene is a component of AR signaling. Thus, we conclusively demonstrate that PCGEM1 and PRNCR1 are not prognostic lncRNAs in prostate cancer and we refute suggestions that these lncRNAs interact in AR signaling.     

Efficacy of subthreshold micropulse laser in the treatment of diabetic macular edema is influenced by pre-treatment central foveal thickness

Purpose

To determine if the severity of diabetic macular edema influences the effectiveness of subthreshold micropulse (STMP) laser treatment.

Methods

A total of 63 eyes of 58 patients with diabetic macular edema were divided into two groups based on their initial central foveal thickness (CFT). Group 1 had CFT ≤400 μm, group 2 had CFT >400 μm. The change from baseline in CFT and visual acuity were compared at 3, 6 and 12 months follow-up. Patients were considered for retreatment with micropulse laser at 3 months if macular edema had not improved. Patients were considered for rescue anti-VEGF injections if there was clinically significant macular edema at 6 months follow-up. Number of laser retreatments, injections, and any adverse effects from STMP laser were recorded.

Results

Group 1 (n=33) experienced an average of 55 μm reduction in CFT and 0.2log MAR gain in visual acuity at 12 months (P<0.001). No patient required rescue anti-VEGF injections. Group 2 (n=30) experienced no significant change in CFT or visual acuity by 6 months despite retreatment with STMP in 19 eyes. From 6 to 12 months follow-up, all the patients in group 2 received rescue Bevacizumab injections that resulted in 307 μm reduction in CFT and 0.3log MAR improvement in visual acuity (P<0.001). No adverse effects from STMP laser were recorded.

Conclusion

Severity of edema can influence the effects of STMP laser. STMP monotherapy is safe and effective in treating edema of mild to moderate severity.     

A sandwich ELISA for phosphoglycerate kinase

Phosphoglycerate kinase (PGK1) is a key enzyme in glycolysis that can also be released from certain cells. In the extracellular milieu, PGK1 reportedly acts as a disulphide reductase to activate plasmin, resulting in the production of angiostatin, a potent angiogenesis inhibitor. Certain cancer cell lines secrete unusually large amounts of PGK1, raising the possibility that serum PGK1 levels can be used to screen for cancer. To facilitate the characterization of the PGK1 secretory pathway and to monitor serum levels of PGK1, we have developed a sensitive sandwich ELISA using an immuno-affinity-purified chicken polyclonal antibody for capturing PGK1 and an immuno-affinity-purified rabbit polyclonal antibody for detecting it. The assay is about 10-fold more sensitive than other reported PGK1 ELISAs. We used the ELISA to quantify the amount of PGK1 released from HeLa cells and PGK1 serum levels in cancer patients. Of 10 cancer patients whose serum was tested, 3 of 4 with pancreatic cancer had 65-900% higher levels of PGK1 than that found in normal serum.     

Synpolydactyly: clinical and molecular advances

Synpolydactyly (SPD) is a rare limb deformity showing a distinctive combination of syndactyly and polydactyly. Of the nine non-syndromic syndactylies, it is clinically and genetically one of the most heterogeneous malformation. SPD families may show clinical features consistent with the Temtamy and McKusick criteria as well as additional phenotypic variants, which vary from case to case. In certain instances, these variants predominate in a given family, while the typical SPD features remain less explicit. We have reviewed all the clinical variants occurring in well-documented SPD families. We conclude that typical SPD features can be delineated from minor clinical variants. Then, we propose to lump all the phenotypic variants, manifesting themselves in SPD families into three categories: (i) typical SPD features, (ii) minor variants, and (iii) unusual phenotypes. Next, we discuss the likely reasons for the occurrence of minor variants and the obvious lack of penetrance in SPD families. Finally, we show that for the SPD phenotype associated with HOXD13 mutations, a straightforward genotype–phenotype correlation is weak. Our lumping and splitting scheme for SPD phenotypic variants could be useful for the understanding of this interesting malformation.     

The direct effects of stored blood products may worsen prognosis of cancer patients; shall we transfuse or not? An explanation of the adverse oncological consequences of blood product transfusion with a testable hypothesis driven experimental research protocol

Francis and colleagues reported an association between blood transfusion and worsened cancer prognosis. Since then there has been much debate over whether there is in fact such an association. We propose a possible mechanism which could explain much of the conflicting clinical and experimental evidence, and which can be readily tested experimentally. It is suggested that the extracellular accumulation of bioactive factors in blood transfusion products can directly and indirectly cause tumour growth and hence a worsening of prognosis. This theory can be applied both in vitro and in vivo. Two separate UK studies have shown that perioperative blood transfusion is associated with worsened prognosis in head and neck squamous cell cancer patients. Furthermore, pilot experiments have shown that as blood ages, endothelial growth factors are leached from the metabolically compromised red cell. We believe that we have provided a rationale to explain the conflicting findings of research to date in this area. That red cells should store endothelial reparative growth factors would seem logical, as would the release of any factors as the metabolic processes of the anucleate red cell decline over time. As a result, leuco-depletion should be promoted and blood transfusion should be avoided if possible.