Oncostatic treatment effect of triple negative breast cancer cell line with copper (I)-nicotinate complex

The treatment of triple-negative breast cancer (TNBC) remains a major challenge. The present study aimed to throw more light on the role of copper (I)-nicotinate complex (CNC) as an antitumor as well as a proapoptotic agent. In this study, the HCC-1806 cell line was used as a model for TNBC. Cell cycle, apoptosis assay, and programmed cell death protein-1 were investigated by flowcytometry. Besides, the comet assay was performed using a fluorescence microscope. The enzyme-linked immunosorbent assay technique was used for the detection of phospho-Chk1 at ser 317 and caspase-3. Moreover, the gene expression of survivin was identified by real-time polymerase chain reaction. Finally, superoxide dismutase (SOD) was calorimetrically assayed. The viability of HCC-1806 cells treated with CNC was decreased in a dose-dependent manner. The tendency for apoptotic machinery was observed through the increase in the sub G0 peak, the percentage of early and late apoptotic phases, and the elevation in caspase-3 levels associated with a downregulation of the survivin gene expression. The antioxidant property of the complex, reflected by elevated SOD activity, may contribute to mediate the cell death pathways. Low concentrations of CNC were found to favor the apoptotis-mediated mechanism. However, one cannot neglect the abundance of cell necrosis–mediated death of cells via CNC, especially at higher concentrations.     

Collision/Reaction Cell ICP-MS with Shielded Torch and Sector Field ICP-MS for the Simultaneous Determination of Selenium Isotopes in Biological Matrices

The determinations of selenium isotopes in biological samples were performed using both inductively coupled plasma collision/reaction cell quadruple mass spectrometer (CRC-ICP-QMS) and inductively coupled plasma sector field mass spectrometers (SF-ICP-MS). To significantly decrease the argon-based interferences at m/z 74 (³⁶Ar³⁸Ar), 76 (³⁸Ar³⁸Ar, ⁴⁰Ar³⁶Ar), 78 (³⁸Ar⁴⁰Ar), and 80 (⁴⁰Ar⁴⁰Ar), the gas-flow rates of a helium and hydrogen mixture used in the collision cell were optimized to 1.0 mL/min H₂ and 3.5 mL/min He. Under the optimized condition, the precisions for natural selenium isotope ratio measurements of both instruments were evaluated and compared using 100 ppb Se standard solution. A modified external calibration quantification method was applied for the simultaneous determination of clinically used enriched selinocompounds (⁷⁷Se-selenate, ⁸²Se-selenite, ⁷⁶Se-methylseleninic acid^IV, ⁷⁸Se-methylselenonic acid^VI) and to examine their fate in rat organs (liver, kidney, and lung).     

Glucokinase regulatory protein genetic variant interacts with omega-3 PUFA to influence insulin resistance and inflammation in metabolic syndrome

Glucokinase Regulatory Protein (GCKR) plays a central role regulating both hepatic triglyceride and glucose metabolism. Fatty acids are key metabolic regulators, which interact with genetic factors and influence glucose metabolism and other metabolic traits. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been of considerable interest, due to their potential to reduce metabolic syndrome (MetS) risk.

Objective

To examine whether genetic variability at the GCKR gene locus was associated with the degree of insulin resistance, plasma concentrations of C-reactive protein (CRP) and n-3 PUFA in MetS subjects.

Design

Homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-B, plasma concentrations of C-peptide, CRP, fatty acid composition and the GCKR rs1260326-P446L polymorphism, were determined in a cross-sectional analysis of 379 subjects with MetS participating in the LIPGENE dietary cohort.

Results

Among subjects with n-3 PUFA levels below the population median, carriers of the common C/C genotype had higher plasma concentrations of fasting insulin (P = 0.019), C-peptide (P = 0.004), HOMA-IR (P = 0.008) and CRP (P = 0.032) as compared with subjects carrying the minor T-allele (Leu446). In contrast, homozygous C/C carriers with n-3 PUFA levels above the median showed lower plasma concentrations of fasting insulin, peptide C, HOMA-IR and CRP, as compared with individuals with the T-allele.

Conclusions

We have demonstrated a significant interaction between the GCKR rs1260326-P446L polymorphism and plasma n-3 PUFA levels modulating insulin resistance and inflammatory markers in MetS subjects. Further studies are needed to confirm this gene-diet interaction in the general population and whether targeted dietary recommendations can prevent MetS in genetically susceptible individuals.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00429195","term_id":"NCT00429195"}}NCT00429195     

Tranilast attenuates methotrexate‐induced renal and hepatic toxicities: Role of apoptosis‐induced tissue proliferation

Drug‐induced organ toxicity is a frequently encountered obstacle in the field of medical practice that limits the use of numerous pharmacologically valuable drugs. Methotrexate (MTX)‐induced organ toxicity is unfortunately the rate‐limiting factor for its clinical application. In the current study, MTX injection induced significant renal and hepatic toxicities manifested on functional, biochemical, and histopathological scales. This was associated with a significant elevation in both renal and hepatic contents of TNF‐related apoptosis–inducing ligand (TRAIL) and caspase‐8, biomarkers of tissue apoptosis. Inline, immunohistochemical analysis confirmed that tissue increased expression of Ki67 as a biomarker of tissue regeneration in both organs. Tranilast (TRAN) is a small molecular weight anti‐inflammatory and antiallergic agent. TRAN's coadministration with MTX in the current study induced a significant tissue recovery via modulation of TRAIL/caspase‐8 signaling and modulation of apoptosis‐induced tissue proliferation confirmed by quantification of Ki67 expression. In conclusion, TRAN can be proposed as an effective drug to attenuate MTX‐induced organ toxicity via modulation of apoptosis‐induced tissue proliferation pathway.     

How much land‐based greenhouse gas mitigation can be achieved without compromising food security and environmental goals?

Feeding 9–10 billion people by 2050 and preventing dangerous climate change are two of the greatest challenges facing humanity. Both challenges must be met while reducing the impact of land management on ecosystem services that deliver vital goods and services, and support human health and well‐being. Few studies to date have considered the interactions between these challenges. In this study we briefly outline the challenges, review the supply‐ and demand‐side climate mitigation potential available in the Agriculture, Forestry and Other Land Use AFOLU sector and options for delivering food security. We briefly outline some of the synergies and trade‐offs afforded by mitigation practices, before presenting an assessment of the mitigation potential possible in the AFOLU sector under possible future scenarios in which demand‐side measures codeliver to aid food security. We conclude that while supply‐side mitigation measures, such as changes in land management, might either enhance or negatively impact food security, demand‐side mitigation measures, such as reduced waste or demand for livestock products, should benefit both food security and greenhouse gas (GHG) mitigation. Demand‐side measures offer a greater potential (1.5–15.6 Gt CO₂‐eq. yr^?1) in meeting both challenges than do supply‐side measures (1.5–4.3 Gt CO₂‐eq. yr^?1 at carbon prices between 20 and 100 US$ tCO₂‐eq. yr^?1), but given the enormity of challenges, all options need to be considered. Supply‐side measures should be implemented immediately, focussing on those that allow the production of more agricultural product per unit of input. For demand‐side measures, given the difficulties in their implementation and lag in their effectiveness, policy should be introduced quickly, and should aim to codeliver to other policy agenda, such as improving environmental quality or improving dietary health. These problems facing humanity in the 21st Century are extremely challenging, and policy that addresses multiple objectives is required now more than ever.     

Synthesis,biological evaluation,and molecular docking investigation of benzhydrol- and indole-based dual PPAR-γ/FFAR1 agonists

Type-2 diabetes mellitus is a progressive cluster of metabolic disorders, representing a global public health burden affecting more than 366?million people worldwide. We recently reported the discovery of three series of novel agents showing balanced activity on two metabolic receptors, peroxisome proliferator activated receptor-γ (PPAR-γ) and free fatty acid receptor 1 (FFAR1), also known as GPCR40. Our designing strategy relied on linking the thiazolidinedione head with known GPCR privilege structures. To further investigate this concept, two new scaffolds, the benzhydrol- and indole-based chemotypes, were introduced here in. Our optimization campaign resulted in three compounds; 15a, 15c, and 15d, with affinities in the low micromolar range on both targets. In vivo study of selected test compounds, revealed that 15c possesses a significant anti-hyperglycemic and anti-hyperlipidemic activities superior to rosiglitazone in fat-fed animal models. Molecular docking analysis was conducted to explain the binding modes of both series. These compounds could lead to the development of the unique antidiabetic agent acting as insulin sensitizer as well as insulin secretagogue.     

Striped catfish (Pangasianodon hypophthalmus) could be suitable for coastal aquaculture

Salinity intrusion in the coastal freshwater rivers due to climate change and construction of the dam in the upstream rivers are alarming in aquaculture. Hence, an experiment was conducted to know the effects of salinity on growth performance, hemato‐biochemical parameters and erythrocytes structure in a commercially cultivable catfish species, striped catfish (Pangasianodon hypophthalmus). Firstly, median lethal concentration (LC₅₀) of salinity for striped catfish was determined and then the fish were exposed to three salinity conditions (4, 8 and 12‰) and a control (0‰). Fish were sacrificed at day 7, 14, 28 and 56 after the start of salinity exposure. The 96 hr LC₅₀ value was found to be 14.87‰. Salinity levels from freshwater to 8‰ showed optimal conditions with high survival rate and good growth performances of fish in terms of weight gain and specific growth rate (SGR). Interestingly, the lowest food conversion ratio (FCR) was found in 4‰ group. The hemoglobin (Hb) level and number of red blood cells (RBCs) were found to be decreased significantly in 8 and 12‰ compared to 0 and 4‰ at the initial days of exposure, while number of white blood cells (WBCs) and glucose level showed opposite scenario. Frequencies of ENA (erythrocytic nuclear abnormalities) and ECA (erythrocytic cellular abnormalities) were significantly increased with increasing salinities in the initial days of exposure. Overall, findings of the present study revealed that striped catfish might be suitable fish species for culture in the brackish water containing salinity up to 10‰.