GSK0660 enhances antitumor immunotherapy by reducing PD-L1 expression.

Blockade of PD-1/PD-L1 immune checkpoint is wildly used for multiple types of cancer treatment, while the low response rate for patients is still completely unknown. As nuclear hormone receptor, PPARδ (peroxisome-proliferator-activated receptor) regulates cell proliferation, inflammation, and tumor progression, while the effect of PPARδ on tumor immune escape is still unclear. Here we found that PPARδ antagonist GSK0660 significantly reduced colon cancer cell PD-L1 protein and gene expression. Luciferase analysis showed that GSK0660 decreased PD-L1 gene transcription activity. Moreover, reduced PD-L1 expression in colon cancer cells led to increased T cell activity. Further analysis showed that GSK0660 decreased PD-L1 expression in a PPARδ dependent manner. Implanted tumor model analysis showed that GSK0660 inhibited tumor immune escape and the combined PD-1 antibody with GSK0660 effectively enhanced colorectal cancer immunotherapy. These findings suggest that GSK0660 treatment could be an effective strategy for cancer immunotherapy.

Ferroptosis is an effective strategy for cancer therapy.

Ferroptosis is a form of intracellular iron-dependent cell death that differs from necrosis, autophagy and apoptosis. Intracellular iron mediates Fenton reaction resulting in lipid peroxidation production, which in turn promotes cell death. Although cancer cell exhibit's ability to escape ferroptosis by multiple pathways such as SLC7A11, GPX4, induction of ferroptosis could inhibit cancer cell proliferation, migration and invasion. In tumor microenvironment, ferroptosis could affect immune cell (T cells, macrophages etc.) activity, which in turn regulates tumor immune escape. In addition, ferroptosis in cancer cells could activate immune cell activity by antigen processing and presentation. Therefore, ferroptosis could be an effective strategy for cancer therapy such as chemotherapy, radiotherapy, and immunotherapy. In this paper, we reviewed the role of ferroptosis on tumor progression and therapy, which may provide a strategy for cancer treatment.

Genome wide identification, structural characterization and phylogenetic analysis of High-Affinity potassium (HAK) ion transporters in common bean (Phaseolus vulgaris L.).

BACKGROUND: High-Affinity Potassium ions represent one of the most important and large group of potassium transporters. Although HAK genes have been studied in a variety of plant species, yet, remain unexplored in common bean. RESULTS: In the current study, 20 HAK genes were identified in common bean genome. Super-family "K_trans" domain was found in all PvHAK genes. Signals for localization of PvHAK proteins were detected in cell membrane. Fifty three HAKs genes, across diverse plant species, were divided into 5 groups based on sequential homology. Twelve pairs of orthologs genes were found in various plant species. PvHAKs genes were distributed unequally on 7 chromosomes with maximum number (7) mapped on chromosome 2 while only 1 PvHAK found on each chromosome 1, 4, and 6. Tandem gene duplication was witnessed in 2 paralog pairs while 1 pair exhibited segmental gene duplication. Five groups were made in PvHAK gene family based on Phylogeny. Maximum PvHAKs (10) were detected in Group-V while group-II composed of only 1 PvHAK gene. Variation was witnessed in number and size of motifs, and structure of PvHAKs associated with different groups. Light and hormone responsive elements contributed 57 and 24% share, respectively, to cis regulatory elements. qRT-PCR based results revealed significant increase in expression of all 4 PvHAK genes under low-potassium stress. CONCLUSION: The current study provides valuable information for further functional characterization and uncovering the molecular mechanism associated with Potassium transportation in plants.

Optimization of Tensile Strength and Young's Modulus of CNT-CF/Epoxy Composites Using Response Surface Methodology (RSM).

Composites such as carbon fiber are used extensively by automotive, aerospace, marine, and energy industries due to their strong mechanical properties. However, there are still many areas it is lacking in testing, especially related to its electrophoretic deposition. In this research work, the tensile strength and Young's modulus of CNT-CF/epoxy composites were measured using the tensile test by varying the electrophoretic deposition (EPD) process parameters. Response surface methodology (RSM) was used to optimize the three main parameters in this EPD process: the volume ratio (water as the basis), deposition voltage, and time to obtain the maximum tensile properties of the composites. There were four volume ratios (0%, 20%, 80% and 100%) used in this design of experiment (DoE) with ratios' pairs of 0%, 100%, and 20%, 80%. For this study, water and methanol were used as the suspension medium. This design's deposition voltage and time were 10 to 20 V and 5 to 15 min. ANOVA further verified the responses' adequacy. The optimum conditions for the first Design of Experiment (DoE) (0% and 100%) were identified as a volume ratio of 99.99% water, deposition voltage of 10 V, and 12.14 min. These conditions provided the maximum strength of these composites with a tensile strength of 7.41 N/mm2 and Young's modulus of 279.9 N/mm2. Subsequently, for the second DoE (20% and 80%), tensile strength of 7.28 N/mm2 and Young's modulus of 274.1 N/mm2 were achieved with the ideal conditions: volume ratio of 44.80% water, deposition voltage of 10.04 V, and time of 6.89 min. It can be concluded that the ideal interaction between these three EPD parameters was necessary to achieve composites with good tensile properties.

Genome wide and evolutionary analysis of heat shock protein 70 proteins in tomato and their role in response to heat and drought stress.

Heat shock protein 70 (HSP70) proteins play a crucial role in mitigating the detrimental effects of abiotic stresses in plants. In the present study, 21 full length non-redundant SlHSP70 genes were detected and characterized in tomato (Solanum lycopersicum L.). The SlHSP70 genes were classified into four groups based on phylogenetic analysis. Similarities were observed in gene features and motif structures of SlHSP70s belonging to the same group. SlHSP70 genes were unevenly and unequally mapped on 11 chromosomes. Segmental and tandem duplication are the main events that have contributed to the expansion of the SlHSP70 genes. A large number of groups and sub-groups were generated during comparative analysis of HSP70 genes in multiple plant species including tomato. These findings indicated a common ancestor which created diverse sub-groups prior to a mono-dicot split. The selection pressure on specific codons was identified through a maximum-likelihood approach and we found some important coding sites in the coding region of all groups. Diversifying positive selection was indirectly associated with evolutionary changes in SlHSP70 proteins and suggests that gene evolution modulated the tomato domestication event. In addition, expression analysis using RNA-seq revealed that 21 SlHSP70 genes were differentially expressed in response to drought and heat stress. SlHSP70-5 was down-regulated by heat treatment and up-regulated by drought stress. Furthermore, the expression of some of the duplicate genes was partially redundant, while others showed functional diversity. Our results indicate the diverse role of HSP70 gene family in S. lycopersicum under drought and heat stress conditions and open the gate for further investigation of HSP70 gene family functions, especially under drought and heat stress.

Emerging advances and current applications of nanoMOF-based membranes for water treatment.

Metal-organic frameworks (MOFs) are significantly tunable materials that can be exploited in a wide range of applications. In recent years, a large number of studies have been focused on synthesizing nano-scale MOFs (nanoMOFs), thus taking advantage of these unique materials in various applications, especially those that are only possible at nano-scale. One of the technologies where nanoMOF materials occupy a central role is the membrane technology as one of the most efficient separation techniques. Therefore, numerous reports can be found on the enhancement of the physicochemical properties of polymeric membranes by using nanoMOFs, leading to remarkably improved performance. One of the most considerable applications of these nanoMOF-based membranes is in water treatment systems, because freshwater scarcity is now an undeniable crisis facing humanity. In this in-depth review, the most prominent synthesis and post-synthesis methods for the fabrication of nanoMOFs are initially discussed. Afterwards, different nanoMOF-based composite membranes such as thin-film nanocomposites (TFN) and mixed-matrix membranes (MMM) and their various fabrication methods are reviewed and compared. Then, the impacts of using MOFs-based membranes for water purification through growing metal-organic frameworks crystals on the support materials and utilization of metal-organic frameworks as fillers in mixed matrix membrane (MMM) are highlighted. Finally, a summary of pros and cons of using nanoMOFs in membrane technology for water treatment purposes and clear future prospects and research potentials are presented.

Computational simulation and modelling of uranium extraction using tributylphosphate through membrane extractor.

Non-disperse solvent extraction is an effective technique for the extraction of metal ions from aqueous solution. In this study, uranium extraction using n-dodecane solvent containing tributylphosphate extractant in a membrane contactor was investigated. A 2D mathematical model was developed for the fluid flow and mass transfer in the hollow fibre membrane extractor. The equations of the created model were solved using the finite element method. The uranium concentration distribution in the extractor at different extractant concentrations as well as feed acidity was studied. The results showed that there is reasonable good agreement between experimental uranium extraction and modelling outputs at different extractant concentrations. Increasing extractant concentration from 5 to 30% led to the enhancement of uranium extraction from 2.60 to 34.13%. Also, there was an increase in the uranium extraction with increasing feed acidity in the range of 1-3 M. Furthermore, based on the radial uranium concentration distribution, it was found that the main mass transfer resistance in the system was microporous membrane section. Finally, it was obtained that the uranium extraction efficiency could be improved significantly by increasing porosity-to-tortuosity ratio. It was concluded that the membrane specification plays the most important role as the dominant mass transfer resistant was in the membrane subdomain.

COVID-19 spread in a classroom equipped with partition - A CFD approach.

In this study, the motion and distribution of droplets containing coronaviruses emitted by coughing of an infected person in front of a classroom (e.g., a teacher) were investigated using CFD. A 3D turbulence model was used to simulate the airflow in the classroom, and a Lagrangian particle trajectory analysis method was used to track the droplets. The numerical model was validated and was used to study the effects of ventilation airflow speeds of 3, 5, and 7 m/s on the dispersion of droplets of different sizes. In particular, the effect of installing transparent barriers in front of the seats on reducing the average droplet concentration was examined. The results showed that using the seat partitions for individuals can prevent the infection to a certain extent. An increase in the ventilation air velocity increased the droplets' velocities in the airflow direction, simultaneously reducing the trapping time of the droplets by solid barriers. As expected, in the absence of partitions, the closest seats to the infected person had the highest average droplet concentration (3.80 × 10-8 kg/m3 for the case of 3 m/s).

TiO2/Ti3C2/g-C3N4 ternary heterojunction for photocatalytic hydrogen evolution.

Photocatalytic hydrogen (H2) generation derived by water has been considered as a renewable energy to solve environmental problems and global energy crises. Thus, it is necessary to explore the most effective photocatalysts by using multi-cocatalysts, due to an intimate interaction between different components. Therefore, we already synthesized the TiO2/Ti3C2/g-C3N4 (TTC) photocatalyst from g-C3N4 and Ti3C2 MXene via a calcination technique, and applied this composite for H2 evolution. By making use of titanium atom from Ti3C2 MXene, titanium dioxide (TiO2) was in-body developed, which leads to form a close heterostructure between metallic material and semiconductors. Besides, g-C3N4 amorphous with highly surface area also contributes to harvest light irradiation during photocatalytic activity. The optimized TTC-450 heterostructure showed a super H2 generation efficiency than those of pure g-C3N4 and other samples. Besides, TTC-450 sample also exhibited great recyclability after 4 runs. The proposed mechanism illustrates the efficient movement of generated electrons in TTC system, which leads to high H2 evolution efficiency. Moreover, the obtained results consistently emphasize the TiO2/Ti3C2/g-C3N4 composite would be a unique material for H2 production and broaden applications of MXene materials.

Evaluation of Multiple Semi-Twisted Tape Inserts in a Heat Exchanger Pipe Using Al2O3 Nanofluid.

The hydrothermal performance of multiple semi-twisted tape inserts inside a heat exchanger pipe is numerically examined in three-dimensions. This study aims to find the optimum case for having the highest heat transfer enhancement with the lowest friction factor using nanofluid (Al2O3/water). A performance evaluation criterion (PEC) is defined to characterize the performance based on both friction factor and heat transfer. It was found that increasing the number of semi-twisted tapes increases the number of swirl flow streams and leads to an enhancement in the local Nusselt number as well as the friction factor. The average Nusselt number increases from 15.13 to 28.42 and the average friction factor enhances from 0.022 to 0.052 by increasing the number of the semi-twisted tapes from 0 to 4 for the Reynolds number of 1000 for the base fluid. By using four semi-twisted tapes, the average Nusselt number increases from 12.5 to 28.5, while the friction factor reduces from 0.155 to 0.052 when the Reynolds number increases from 250 to 1000 for the base fluid. For the Reynolds number of 1000, the increase in nanofluid concentration from 0 to 3% improves the average Nusselt number and friction factor by 6.41% and 2.29%, respectively. The highest PEC is equal to 1.66 and belongs to the Reynolds number of 750 using four semi-twisted tape inserts with 3% nanoparticles. This work offers instructions to model an advanced design of twisted tape integrated with tubes using multiple semi-twisted tapes, which helps to provide a higher amount of energy demand for solar applications.

Prediction of velocity profile of water based copper nanofluid in a heated porous tube using CFD and genetic algorithm.

The heat transfer improvements by simultaneous usage of the nanofluids and metallic porous foams are still an attractive research area. The Computational fluid dynamics (CFD) methods are widely used for thermal and hydrodynamic investigations of the nanofluids flow inside the porous media. Almost all studies dedicated to the accurate prediction of the CFD approach. However, there are not sufficient investigations on the CFD approach optimization. The mesh increment in the CFD approach is one of the challenging concepts especially in turbulent flows and complex geometries. This study, for the first time, introduces a type of artificial intelligence algorithm (AIA) as a supplementary tool for helping the CFD. According to the idea of this study, the CFD simulation is done for a case with low mesh density. The artificial intelligence algorithm uses learns the CFD driven data. After the intelligence achievement, the AIA could predict the fluid parameters for the infinite number of nodes or dense mesh without any limitations. So, there is no need to solve the CFD models for further nodes. This study is specifically focused on the genetic algorithm-based fuzzy inference system (GAFIS) to predict the velocity profile of the water-based copper nanofluid turbulent flow in a porous tube. The most intelligent GAFIS could perform the most accurate prediction of the velocity. Hence, the intelligence of GAFIS is tested for different values of cluster influence range (CIR), squash factor(SF), accept ratio (AR) and reject ratio (RR), the population size (PS), and the percentage of crossover (PC). The maximum coefficient of determination (~ 0.97) was related to the PS of 30, the AR of 0.6, the PC of 0.4, CIR of 0.15, the SF 1.15, and the RR of 0.05. The GAFIS prediction of the fluid velocity was in great agreement with the CFD. In the most intelligent condition, the velocity profile predicted by GAFIS was similar to the CFD. The nodes increment from 537 to 7671 was made by the GAFIS. The new predictions of the GAFIS covered all CFD results.

Photocatalytic degradation of methyl orange dye by Ti3C2-TiO2 heterojunction under solar light.

Photocatalytic activity is a feasible solution to tackle environmental pollution caused by industrial pollutants. In this research, Ti3C2-TiO2 composite with a unique structure was fabricated successfully via a hydrothermal method. Especially, the in-situ transformation of TiO2 from Ti3C2 MXene creates an intimate heterostructure, which leads to prolonging separation and migration of charged carriers. Thus, this Ti3C2-TiO2 composite enhances effectively methyl orange (MO) degradation efficiency (around 99%) after 40 light-exposed minutes. Besides, the optimal concentration of MO solution was estimated at 40 mg/L and Ti3C2-TiO2 photocatalyst also exhibited good stability after five runs. Moreover, the radical trapping test and the MO photodegradation mechanism over Ti3C2-TiO2 system were also demonstrated. This research illustrates the potential of MXenes as effective co-catalysts for photocatalysis and extends the applications of two-dimensional materials.

Extraction of ingredients from tea leaves using oxidative enzymatic reaction and optimization of extraction conditions.

Peroxidase (POD) and polyphenol oxidase (PPO) are used as biocatalyst in many processes such as oxidization reactions, wastewater treatment, phenol synthesis and so on. The purpose of current study is enzymes extraction from biomass (tea leaves) as well as evaluation of their activation. Different parameters including temperature, buffer concentration, buffer type, buffer/tea leaves ratio, addition of high molecular weight polymers and emulsifiers, and pH were optimized in order to obtain the highest enzymes activity. Response Surface Methodology (RSM) procedure is employed for statistical analysis of enzymes extraction. It is understood from the result that PPO and POD possess the highest activity at temperatures of 25 °C and 50 °C, pH 7 and 5, buffer molarity of 0.1, and 0.05, buffer/tea leaves ratio = 5 for both, contact time = 20 min and 10 min, and presence of 6% and 3% PVP, 5% and 0% Tween 80 for PPO and POD, respectively. Amounts of highest activity for PPO and POD biocatalysts were calculated 0.42 U/mL and 0.025493 U/mL, respectively. Moreover, the entire inactivation of PPO took place after 30 min at 40 °C and 60 °C and 20 min at 80 °C. However, POD lost 35% of its activity after 30 min at 40 °C and 60 °C. The amount of 6% POD activity was kept after 45 min at 80 °C. Generally, it was indicated that POD was more resistant to thermal treatment than PPO.

Wave Dispersion Analysis of Fluid Conveying Nanocomposite Shell Reinforced by MWCNTs Considering the Effect of Waviness and Agglomeration Efficiency.

The current paper is aimed to investigate the effects of waviness, random orientation, and agglomeration factor of nanoreinforcements on wave propagation in fluid-conveying multi-walled carbon nanotubes (MWCNTs)-reinforced nanocomposite cylindrical shell based on first-order shear deformable theory (FSDT). The effective mechanical properties of the nanocomposite cylindrical shell are estimated employing a combination of a novel form of Halpin-Tsai homogenization model and rule of mixture. Utilized fluid flow obeys Newtonian fluid law and it is axially symmetric and laminar flow and it is considered to be fully developed. The effect of flow velocity is explored by implementing Navier-Stokes equation. The kinetic relations of nanocomposite shell are calculated via FSDT. Moreover, the governing equations are derived using the Hamiltonian approach. Afterward, a method which solves problems analytically is applied to solve the obtained governing equations. Effects of a wide range of variants such as volume fraction of MWCNTs, radius to thickness ratio, flow velocity, waviness factor, random orientation factor, and agglomeration factor on the phase velocity and wave frequency of a fluid conveying MWCNTs-reinforced nanocomposite cylindrical shell were comparatively illustrated and the results were discussed in detail.

Inflammation targeted chitosan-based hydrogel for controlled release of diclofenac sodium.

Inflammation is a key challenge in the treatment of chronic diseases. Spurred by topical advancement in polymer chemistry and drug delivery, hydrogels that release a drug in temporal, spatial and dosage controlled fashion have been trendy. This research focused on the fabrication of hydrogels with controlled drug release properties to control inflammation. Chitosan and polyvinyl pyrrolidone were used as base polymers and crosslinked with epichlorohydrin to form hydrogel films by solution casting technique. Prepared hydrogels were analyzed by swelling analysis in deionized water, buffer and electrolyte solutions and gel fraction. Functional groups confirmation and development of new covalent and hydrogen bonds, thermal stability (28.49%) and crystallinity were evaluated by FTIR, TGA and WAXRD, respectively. Rheological properties including gel strength and yield stress, elasticity (2309 MPa), porosity (75%) and hydrophilicity (73°) of prepared hydrogels were also evaluated. In vitro studies confirmed that prepared hydrogels have good biodegradability, excellent antimicrobial property and admirable cytotoxicity. Drug release profile (87.56% in 130 min) along with the drug encapsulation efficiency (84%) of prepared hydrogels was also studied. These results paved the path towards the development of hydrogels that can release the drugs with desired temporal patterns.

Recombinant glutathione-S-transferase A3 protein regulates the angiogenesis-related genes of erythrocytes in thiram induced tibial lesions.

Tibial dyschondroplasia (TD) is a skeletal deformity disease in broilers that occurs when vascularization in the growth plate (GP) is below normal. Although, blood vessels have been reported to contribute significantly in bone formation. Therefore, in the current study, we have examined the mRNA expression of angiogenesis-related genes in erythrocytes of thiram induced TD chickens by qRT-PCR and performed histopathological analysis to determine regulatory effect of recombinant Glutathione-S-Transferase A3 (rGSTA3) protein in response to the destructive effect of thiram following the injection of rGSTA3 protein. Histopathology results suggested that, blood vessels of GPs were damaged in thiram induced TD chicken group (D), it also affected the area and density of blood vessels. In the 20 and 50 µg·kg-1 of rGSTA3 protein-administered groups, E and F vessels appeared to be normal and improved on day 6 and 15. Furthermore, qRT-PCR results showed that rGSTA3 protein significantly (P < .05) up-regulated the expression of the most important angiogenesis-related integrin family genes ITGA2, ITGA5, ITGB2, ITGB3, ITGAV. The expression level of other genes including TBXA2R, FYN, IQGAP2, IL1R1, GIT1, RAP1B, RPL17, RAC2, MAML3, PTPN11, VAV1, PTCH1, NCOR2, CLU and ITGB3 up-regulated on dosage of rGSTA3 protein. In conclusion, angiogenesis is destroyed in thiram induced TD broilers, and rGSTA3 protein injection improved the vascularization of GPs by upregulating the angiogenesis related genes most importantly integrin family genes ITGAV, ITGA2, ITGB2, ITGB3, ITGA5.

Transcriptome-based screening of intracellular pathways and angiogenesis related genes at different stages of thiram induced tibial lesions in broiler chickens.

BACKGROUND: The Tibial dyschondroplasia (TD) in fast-growing chickens is mainly caused by improper blood circulation. The exact mechanism underlying angiogenesis and vascularization in tibial growth plate of broiler chickens remains unclear. Therefore, this research attempts to study genes involved in the regulation of angiogenesis in chicken red blood cells. Twenty-four broiler chickens were allotted into a control and thiram (Tetramethyl thiuram disulfide) group. Blood samples were collected on day 2, 6 (8- and 14-days old chickens) and 15 (23 days old chickens). RESULTS: Histopathology and hematoxylin and eosin (H&E) results showed that angiogenesis decreased on the 6th day of the experiment but started to recover on the 15th day of the experiment. Immunohistochemistry (IHC) results confirmed the expressions of integrin alpha-v precursor (ITGAV) and clusterin precursor (CLU). Transcriptome sequencing analysis evaluated 293 differentially expressed genes (DEGs), of which 103 up-regulated genes and 190 down-regulated genes were enriched in the pathways of neuroactive ligand receptor interaction, mitogen-activated protein kinase (MAPK), ribosome, regulation of actin cytoskeleton, focal adhesion, natural killer cell mediated cytotoxicity and the notch signalling pathways. DEGs (n = 20) related to angiogenesis of chicken erythrocytes in the enriched pathways were thromboxane A2 receptor (TBXA2R), interleukin-1 receptor type 1 precursor (IL1R1), ribosomal protein L17 (RPL17), integrin beta-3 precursor (ITGB3), ITGAV, integrin beta-2 precursor (ITGB2), ras-related C3 botulinum toxin substrate 2 (RAC2), integrin alpha-2 (ITGA2), IQ motif containing GTPase activating protein 2 (IQGAP2), ARF GTPase-activating protein (GIT1), proto-oncogene vav (VAV1), integrin alpha-IIb-like (ITGA5), ras-related protein Rap-1b precursor (RAP1B), tyrosine protein kinase Fyn-like (FYN), tyrosine-protein phosphatase non-receptor type 11 (PTPN11), protein patched homolog 1 (PTCH1), nuclear receptor corepressor 2 (NCOR2) and mastermind like protein 3 (MAML3) selected for further confirmation with qPCR. However, commonly DEGs were sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3), ubiquitin-conjugating enzyme E2 R2 (UBE2R2), centriole cilia and spindle-associated protein (CCSAP), coagulation factor XIII A chain protein (F13A1), shroom 2 isoform X6 (SHROOM2), ras GTPase-activating protein 3 (RASA3) and CLU. CONCLUSION: We have found potential therapeutic genes concerned to erythrocytes and blood regulation, which regulated the angiogenesis in thiram induced TD chickens. This study also revealed the potential functions of erythrocytes. 1. Tibial dyschondroplasia (TD) in chickens were more on day 6, which started recovering on day 15. 2. The enriched pathway observed in TD chickens on day 6 was ribosome pathway, on day 15 were regulation of actin cytoskeleton and focal adhesion pathway. 3. The genes involved in the ribosome pathways was ribosomal protein L17 (RPL17). regulation of actin cytoskeleton pathway were Ras-related C3 botulinum toxin substrate 2 (RAC2), Ras-related protein Rap-1b precursor (RAP1B), ARF GTPase-activating protein (GIT1), IQ motif containing GTPase activating protein 2 (IQGAP2), Integrin alpha-v precursor (ITGAV), Integrin alpha-2 (ITGA2), Integrin beta-2 precursor (ITGB2), Integrin beta-3 precursor (ITGB3), Integrin alpha-IIb-like (ITGA5). Focal adhesion Proto-oncogene vav (Vav-like), Tyrosine-protein kinase Fyn-like (FYN).

Transcriptome analysis of MAPK signaling pathway and associated genes to angiogenesis in chicken erythrocytes on response to thiram-induced tibial lesions.

This study was planned to investigate TD (Tibial dyschondroplasia) on the potential MAPK signaling pathway and angiogenesis related genes. Forty-eight broilers were allotted into control (C) and treatment (T) groups of 2, 6 and 15 days as C1, C2, C3, T1, T2 and T3. The histopathology results revealed that tibiotarsus bone of chickens had more lesions on day 6 (T2 group). The chondrocytes were disordered, and the size, shape and proliferation were affected. Transcriptome results revealed that differentially expressed genes (DEGs) identified were 63, 1026, 623, 130, 141 and 146 in C1 (2 days control vs 6 days control); C2 (2 days control vs 15 days control); C3 (6 days control vs 15 days control); T1 (2 days treatment vs 6 days treatment); T2 (2 days treatment vs 15 days treatment) and T3 (6 days treatment vs 15 days treatment) groups respectively. Whereas, 10 angiogenesis related-genes RHOC, MEIS2, BAIAP2, TGFBI, KLF2, CYR61, PTPN11, PLXNC1, HSPH1 and NRP2 were downregulated on day 6 in the treatment group. The pathway which was found enriched in the control and treatment groups was MAPK signaling pathway. Therefore selected 10 MAPK signaling pathway-related genes RAC2, MAP3K1, PRKCB, FLNB, IL1R1, PTPN7, RPS6KA, MAP3K6, GNA12 and HSPA8 which were found significantly downregulated in the treatment group on day 6. It is concluded that angiogenesis and MAPK signaling pathway related genes has an essential role in TD, as those top screened genes found downregulated in the thiram fed chickens when TD observed severed on day 6.

New Zealand Society of Gastroenterology Guidelines on Therapeutic Drug Monitoring in Inflammatory Bowel Disease.

The incidence of inflammatory bowel disease (IBD) in New Zealand has increased over the last several decades. The management of IBD has been transformed since the introduction of monoclonal antibody drugs. Other medications used in the treatment of IBD include amino-salicylates, steroids, thiopurines and methotrexate. Therapeutic drug monitoring (TDM) involves the measurement of serum drug levels or active metabolites and anti-drug antibodies. TDM is essential for a personalised approach to the management of patients with IBD and is used to optimise drug efficacy and reduce the risk of toxicity. In IBD, TDM can be used for checking adherence, evaluating drug toxicity, identifying hypermethylators, assessing loss of response and in decisions regarding treatment escalation or de-escalation. Management decisions in patients on a thiopurine are facilitated by checking TPMT enzyme activity and thiopurine metabolite levels. Measurement of drug trough levels and anti-drug antibodies can result in individualised treatment decisions in patients on biologics. In addition to using TDM in patients who fail therapy, proactive TDM can potentially facilitate early treatment decisions, albeit more work is needed in this area. The clinical benefits of reactive TDM are well documented and this has been shown to be cost effective. Studies have shown that combination therapy in patients on a biologic leads to better clinical outcomes. Effective use of drugs in the treatment of IBD is even more imperative in the New Zealand setting due to relatively fewer options of funded treatment, and the limitations on the use of available drugs. This document represents the current guidelines of the New Zealand Society of Gastroenterology on TDM in IBD.

Life threatening torsades de pointes due to abiraterone-induced hypokaelemia in a patient with metastatic prostate cancer.

We present a case of a 77 year-old gentleman with previous coronary artery bypass grafting, admitted to hospital with recurrent torsades de pointes (TdP) due to abiraterone-induced hypokalaemia and prolonged QTc. The patient was on abiraterone and prednisone for metastatic prostate cancer. He required multiple defibrillations for recurrent TdP. Abiraterone is a relatively novel drug used in metastatic prostate cancer and we discuss this potential adverse effect and its management in this unusual presentation.