Phase I clinical trial of temozolomide and methoxyamine (TRC-102), an inhibitor of base excision repair, in patients with advanced solid tumors.

Temozolomide (TMZ) generates DNA adducts that are repaired by direct DNA and base excision repair mechanisms. Methoxyamine (MX, TRC-102) potentiates TMZ activity by binding to apurinic and apyrimidinic (AP) sites after removal of N3-methyladenine and N7-methylguanine, inhibiting site recognition of AP endonuclease. We conducted a phase I trial to determine the maximum tolerated dose and dose-limiting toxicities (DLTs) of intravenous MX when given with oral TMZ. Patients with advanced solid tumors and progression on standard treatment were enrolled to a standard 3 + 3 dose escalation trial assessing escalating doses of TMZ and MX. Tumor response was assessed per RECIST and adverse events (AEs) by CTCAEv3. Pharmacokinetics (PK) of MX and COMET assays on peripheral blood mononuclear cells were performed. 38 patients were enrolled-median age 59.5 years (38-76), mean number of cycles 2.9 [1-13]. No DLTs were observed. Cycle 1 grade 3 AEs included fatigue, lymphopenia, anemia, INR, leukopenia, neutropenia, allergic reaction, constipation, psychosis and paranoia. Cycle 2-13 grade 4 AEs included thrombocytopenia and confusion. A partial response was seen in 1 patient with a pancreatic neuroendocrine tumor (PNET) and six additional patients, each with different tumor types, demonstrated prolonged stable disease. MX PK was linear with dose and was not affected by concomitant TMZ. TMZ 200 mg/m2 daily × 5 may be safely administered with MX 150 mg/m2 intravenously once on day 1 with minimal toxicity. Further studies assessing this drug combination in select tumor types where temozolomide has activity may be warranted.

Plasticized poly(vinylalcohol) and poly(vinylpyrrolidone) based patches with tunable mechanical properties for cardiac tissue engineering applications.

Polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) are the two most investigated biopolymers for various tissue engineering applications. However, their poor tensile strength renders them unsuitable for cardiac tissue engineering (CTE). In this study, we developed and evaluated PVA-PVP-based patches, plasticized with glycerol or propylene glycol (0.1%-0.4%; v:v), for their application in CTE. The cardiac patches were evaluated for their physico-chemical (weight, thickness, folding endurance, FT-IR, and swelling behavior) and mechanical properties. The optimized patches were characterized for their ability to support in vitro attachment, viability, proliferation, and beating behavior of neonatal mouse cardiomyocytes (CMs). In vivo evaluation of the cardiac patches was done under the subcutaneous skin pouch and heart of rat models. Results showed that the optimized molar ratio of PVA:PVP with plasticizers (0.3%; v-v) resulted in cardiac patches, which were dry at room temperature and had desirable folding endurance of at least 300, a tensile strength of 6-23 MPa and, percentage elongation at break of more than 250%. Upon contact with phosphate-buffered saline, these PVA-PVP patches formed hydrogel patches having the tensile strength of 1.3-3.0 MPa. The patches supported the attachment, viability, and proliferation of primary neonatal mouse CMs and were nonirritant and noncorrosive to cardiac cells. In vivo transplantation of cardiac patches into a subcutaneous pouch and on the heart of rat models revealed them to be biodegradable, biocompatible, and safe for use in CTE applications.

The first comprehensive description of the expression profile of genes involved in differential body growth and the immune system of the Jeju Native Pig and miniature pig.

Sus scrofa provides a major source of animal protein for humans as well as being an excellent biomedical model. This study was carried out to understand, in detail, the genetic and functional variants of Jeju Native Pigs and miniature pigs through differential expression profiling of the genes controlling their immune response, growth performance, and meat quality. The Illumina HiSeq 2000 platform was used for generating 1.3 billion 90 bp paired-end reads, which were mapped to the S. scrofa genome using TopHat2. A total of 2481 and 2768 genes were differentially expressed with 8-log changes in muscle and liver samples, respectively. Five hundred forty-eight genes in muscle and 642 genes in liver samples had BLAST matches within the non-redundant database. GO process and pathway analyses showed enhanced biological processes related to the extracellular structural organization and skeletal muscle cell differentiation in muscle tissue, whereas the liver tissue shares functions related to the inflammatory response. Herein, we identify inflammatory regulatory genes in miniature pigs and growth response genes in Jeju Native Pigs, information which can provide a stronger base for the selection of breeding stock and facilitate further in vitro and in vivo studies for therapeutic purposes.

Phase I study of the combination of quinacrine and erlotinib in patients with locally advanced or metastatic non small cell lung cancer.

Introduction Preclinical data suggest quinacrine acts as an inhibitor of FACT (facilitates chromatin transcription) complex, which may play a role in TKI (tyrosine kinase inhibitor) resistance. The aim of this Phase I study was to study the safety and assess the maximum tolerated dose of quinacrine in combination with erlotinib in non small cell lung cancer (NSCLC). Methods This was a phase I study with standard 3 + 3 dose escalation design with the primary aim of determining the maximum tolerated dose. Two of 3 patients enrolled at dose level 1 experienced dose limiting toxicity (DLT). The next 6 patients were enrolled at dose level - 1 and none of these 6 patients experienced DLT. The dose of 50 mg of quinacrine every other day with 150 mg of erlotinib was established as the maximum tolerated and the recommended phase II dose. One of 3 patients treated at dose level 1 had stable disease. One of 6 patients treated at dose level - 1 had partial response for 6 months, the rest had progressive disease at the time of first assessment. Conclusion Combination of quinacrine and erlotinib was well tolerated but showed limited efficacy in advanced NSCLC.

Transformation of animal genomics by next-generation sequencing technologies: a decade of challenges and their impact on genetic architecture.

For more than a quarter of a century, sequencing technologies from Sanger's method to next-generation high-throughput techniques have provided fascinating opportunities in the life sciences. The continuing upward trajectory of sequencing technologies will improve livestock research and expedite the development of various new genomic and technological studies with farm animals. The use of high-throughput technologies in livestock research has increased interest in metagenomics, epigenetics, genome-wide association studies, and identification of single nucleotide polymorphisms and copy number variations. Such studies are beginning to provide revolutionary insights into biological and evolutionary processes. Farm animals, such as cattle, swine, and horses, have played a dual role as economically and agriculturally important animals as well as biomedical research models. The first part of this study explores the current state of sequencing methods, many of which are already used in animal genomic studies, and the second part summarizes the state of cattle, swine, horse, and chicken genome sequencing and illustrates its achievements during the last few years. Finally, we describe several high-throughput sequencing approaches for the improved detection of known, unknown, and emerging infectious agents, leading to better diagnosis of infectious diseases. The insights from viral metagenomics and the advancement of next-generation sequencing will strongly support specific and efficient vaccine development and provide strategies for controlling infectious disease transmission among animal populations and/or between animals and humans. However, prospective sequencing technologies will require further research and in-field testing before reaching the marketplace.

Insights into phytase-containing transgenic Lemna minor (L.) as a novel feed additive.

This study assessed the effect of supplementation of novel transgenic phytase on growth performance and bone mineralization in Korean native broiler chickens. The experiment was designed using four dietary groups: those with a diet supplemented with (A) recombinant phytase, (B) transgenic phytase from the plant Lemna minor, (C) or wild-type L. minor as well as (D) a control group that was supplemented with commercially available feed. Three hundred 1-day-old Korean native broiler chicks were used and divided into these four dietary treatment groups having three replicates of 25 birds each (n = 75). The results showed increases in growth performance and bone mineralization in Groups B and C; compared with Groups A and D. Hematological analyses revealed notable contrasts in erythrocyte sedimentation rate, red blood cell count, and hemoglobin levels among the experimental groups, whereas no impacts of dietary treatment were observed on total eosinophil, lymphocyte, heterophil, monocyte, and basophil levels. The relative expression profiling of candidate genes showed that the genes involved in growth response, meat quality, and P-Ca metabolism were significantly highly expressed in the phytase-supplemented groups. Hence, it is suggested that dietary supplementation with transgenic phytase plant L. minor for enhancing growth performance is a promising new approach in the broiler feed industry. To the best of our knowledge, we report here the most comprehensive analysis using a broiler model that provides a workable platform for further research on the cost-effective production of feed with different compositions that might be beneficial in the livestock feed industry.

Emerging importance of dietary phytochemicals in fight against cancer: Role in targeting cancer stem cells.

Recent years have seen an unpretending increase in research using dietary phytochemicals for targeting cancer and cancer stem cells (CSCs) due to the limited efficacy of conventional chemotherapy and radiotherapy and numerous associated side effects. A large number of dietary phytochemicals using traditional recommendation and experimental approaches have been demonstrated to have anti-proliferative, anti-metastatic, reactive oxygen species (ROS) inducing, anti-angiogenic, pro-apoptotic effects and efficacy in targeting cellular molecules and pathways implicated in malignancy. Researchers have shown the knack of phytochemicals in interfering with the CSCs self-renewal process. Thus, dietary phytochemicals can play a significant role in the cancer therapy owing to the plethora of targets without toxicity. In this review, we have discussed about the basic knowledge of CSCs, their identification, characterization, mechanism of self-renewal pathways (Wnt/ß-catenin, Hedgehog, and Notch), features that help in the survival of CSCs and use of phytochemicals to replace chemotherapy. Applications of phytochemicals including curcumin, epigallocatechin-3-gallate (EGCG), resveratrol, lycopene, and sulforaphane for their effect on targeting cancer and in particular CSCs along with their molecular mechanisms responsible for pharmacological action are also discussed.

Quality, functionality, and shelf life of fermented meat and meat products: A review.

Fermentation of meat is a traditional preservation method used widely for improving quality and shelf life of fermented meat products. Fermentation of meat causes a number of physical, biochemical, and microbial changes, which eventually impart functional properties, sensory characteristics, and nutritional aspects to these products and inhibit the growth of various pathogenic and spoilage microorganisms. These changes include acidification (carbohydrate catabolism), solubilization and gelation of myofibrillar and sarcoplasmic proteins of muscle, degradation of proteins and lipids, reduction of nitrate into nitrite, formation of nitrosomyoglobin, and dehydration. Dry-fermented sausages are increasingly being used as carrier of probiotics. The production of biogenic amines during fermentation can be controlled by selecting proper starter cultures and other preventive measures such as quality of raw materials, hygienic measures, temperature, etc.

Prognostic potential of neutrophil-to-lymphocyte ratio and lymphocyte nadir in stage III non-small-cell lung cancer.

AIM: Studies have shown increased pretreatment neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios to be predictive of survival in various cancers. Our aim was to evaluate the prognostic role of such inflammatory markers in non-small-cell lung cancer (NSCLC). METHODS: One hundred and sixty-three patients with stage III NSCLC who received definitive treatment were included. Survival analysis was performed using Kaplan-Meier method. Hazard ratios for overall and recurrence-free survival were estimated using Cox proportional hazards model. RESULTS: Both neutrophil-to-lymphocyte >Q75 (4.5) and lymphocyte nadir values

Wogonin suppresses stem cell-like traits of CD133 positive osteosarcoma cell via inhibiting matrix metallopeptidase-9 expression.

BACKGROUND: Several efforts have been deployed to cure osteosarcoma, a high-grade malignant bone tumour in children and adolescents. However, some challenges such as drug resistance, relapse, and tumour metastasis remain owing to the existence of cancer stem cells (CSC). There is an urgent need to develop cost-effective and safe therapies. METHODS: Wogonin, an extract from the root of Scutellaria baicalensis, has long been considered as a promising natural and safe compound for anti-tumourigenesis, particularly to inhibit tumour invasion and metastasis. Hoechst 33,342 staining, wound healing assay, sphere formation assay, western blotting, and gelatin zymography assays were performed in CD133 positive osteosarcoma cell. RESULTS: In this study, we examined the effect of Wogonin on the mobility of human osteosarcoma CSC. Wogonin induces apoptosis of human osteosarcoma CSC, inhibits its mobility in vitro via downregulation of MMP-9 expression, and represses its renewal ability. CONCLUSIONS: We demonstrated that Wogonin decreases the renewal capacity of CSC. By inhibiting the formation of and reducing the size of spheres, Wogonin at a concentration of 40-80 µM effectively minimizes potential risk from CSC. Taken together, we have demonstrated a new approach for developing a potential therapy for osteosarcoma.

An integrated in silico approach for functional and structural impact of non- synonymous SNPs in the MYH1 gene in Jeju Native Pigs.

BACKGROUND: This study was performed to identify the non- synonymous polymorphisms in the myosin heavy chain 1 gene (MYH1) association with skeletal muscle development in economically important Jeju Native Pig (JNP) and Berkshire breeds. Herein, we present an in silico analysis, with a focus on (a) in silico approaches to predict the functional effect of non-synonymous SNP (nsSNP) in MYH1 on growth, and (b) molecular docking and dynamic simulation of MYH1 to predict the effects of those nsSNP on protein-protein association. RESULTS: The NextGENe (V 2.3.4.) tool was used to identify the variants in MYH1 from JNP and Berkshire using RNA seq. Gene ontology analysis of MYH1 revealed significant association with muscle contraction and muscle organ development. The 95 % confidence intervals clearly indicate that the mRNA expression of MYH1 is significantly higher in the Berkshire longissimus dorsi muscle samples than JNP breed. Concordant in silico analysis of MYH1, the open-source software tools identified 4 potential nsSNP (L884T, K972C, N981G, and Q1285C) in JNP and 1 nsSNP (H973G) in Berkshire pigs. Moreover, protein-protein interactions were studied to investigate the effect of MYH1 mutations on association with hub proteins, and MYH1 was found to be closely associated with the protein myosin light chain, phosphorylatable, fast skeletal muscle MYLPF. The results of molecular docking studies on MYH1 (native and 4 mutants) and MYLFP demonstrated that the native complex showed higher electrostatic energy (-466.5 Kcal mol(-1)), van der Walls energy (-87.3 Kcal mol(-1)), and interaction energy (-835.7 Kcal mol(-1)) than the mutant complexes. Furthermore, the molecular dynamic simulation revealed that the native complex yielded a higher root-mean-square deviation (0.2-0.55 nm) and lower root-mean-square fluctuation (approximately 0.08-0.3 nm) as compared to the mutant complexes. CONCLUSIONS: The results suggest that the variants at L884T, K972C, N981G, and Q1285C in MYH1 in JNP might represent a cause for the poor growth performance for this breed. This study is a pioneering in-depth in silico analysis of polymorphic MYH1 and will serve as a valuable resource for further targeted molecular diagnosis and population-based studies conducted for improving the growth performance of JNP.

NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016.

These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Malignant Pleural Mesothelioma (MPM). These NCCN Guidelines Insights discuss systemic therapy regimens and surgical controversies for MPM. The NCCN panel recommends cisplatin/pemetrexed (category 1) for patients with MPM. The NCCN panel also now recommends bevacizumab/cisplatin/pemetrexed as a first-line therapy option for patients with unresectable MPM who are candidates for bevacizumab. The complete version of the NCCN Guidelines for MPM, available at NCCN.org, addresses all aspects of management for MPM including diagnosis, evaluation, staging, treatment, surveillance, and therapy for recurrence and metastasis; NCCN Guidelines are intended to assist with clinical decision-making.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 4.2016.

These NCCN Guidelines Insights focus on recent updates in the 2016 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC; Versions 1-4). These NCCN Guidelines Insights will discuss new immunotherapeutic agents, such as nivolumab and pembrolizumab, for patients with metastatic NSCLC. For the 2016 update, the NCCN panel recommends immune checkpoint inhibitors as preferred agents (in the absence of contraindications) for second-line and beyond (subsequent) therapy in patients with metastatic NSCLC (both squamous and nonsquamous histologies). Nivolumab and pembrolizumab are preferred based on improved overall survival rates, higher response rates, longer duration of response, and fewer adverse events when compared with docetaxel therapy.

Randomized Phase II Trial of Erlotinib Beyond Progression in Advanced Erlotinib-Responsive Non-Small Cell Lung Cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy is clearly beneficial in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). However, acquired resistance develops uniformly and the benefit of continuation of EGFR TKI therapy beyond progression remains unclear. MATERIALS AND METHODS: This was a randomized phase II study of chemotherapy (arm A: pemetrexed or docetaxel) versus chemotherapy plus erlotinib (ERL) (arm B) in patients with progressive NSCLC following clinical benefit from erlotinib. In arm B, chemotherapy was given with erlotinib at an oral daily dose of 150 mg on days 2-19 of each cycle to minimize negative pharmacodynamic interactions. The primary endpoint was that continuation of erlotinib in this patient population could extend progression-free survival (PFS) by 50%. RESULTS: A total of 46 patients were randomized (arm A: 24; arm B: 22). Patient characteristics were well balanced except there were more female patients in arm A (p = .075). The median PFS of patients in arm A was 5.5 months and for those in arm B, 4.4 months (p = .699). The response rates were 13% and 16% in arms A and B, respectively (p = .79). EGFR status data were available for 39 of the 46 patients and no significant difference in PFS was seen for continuing ERL beyond progression in mutation-positive patients. Substantially more toxicity was seen in arm B than arm A. CONCLUSION: There was added toxicity but no benefit with the continuation of ERL beyond progression along with chemotherapy as compared with chemotherapy alone. IMPLICATIONS FOR PRACTICE: The benefits of continuing erlotinib upon progression alongside conventional chemotherapy are unclear. This randomized phase II study, initiated prior to the establishment of routine epidermal growth factor receptor (EGFR) mutation testing, addressed this clinically relevant issue through randomizing patients with prior clinical benefit from erlotinib (thereby enriching for EGFR-mutated tumors) upon progression in the second- or third-line setting to conventional chemotherapy (single-agent pemetrexed or docetaxel) with or without continued erlotinib. The results showed no benefit to continuing erlotinib beyond progression, while significantly more side effects were noted in the combination arm. Along with other recently presented study findings, these results argue against the routine practice of continuing erlotinib in this setting.

Targeted inhibition of osteosarcoma tumor growth by bone marrow-derived mesenchymal stem cells expressing cytosine deaminase/5-fluorocytosine in tumor-bearing mice.

BACKGROUND: Mesenchymal stem cells (MSCs) are considered as an attractive approach for gene or drug delivery in cancer therapy. In the present study, the ability of human bone marrow-derived MSCs expressing the cytosine deaminase/5-fluorocytosine prodrug (CD/5-FC MSCs) to target the human osteosarcoma cell line Cal72 was evaluated. METHODS: The stable CD/5-FC MSC cell line was established by transfection of pEGFP containing the cytosine deaminase gene into MSCs with G418 selection. The anti-tumor effect was verified by a bystander effect assay in vitro and co-injection of Cal72 and CD/5-FC MSCs in cancer-bearing mice. RESULTS: The therapeutic CD/5-FC MSCs retained the characteristics of multipotent cells, such as differentiation into adipocytes/osteocytes and expression of mesenchymal markers (CD90 and CD44), and showed migration toward Cal72 cells to a greater extent than the native MSCs. The bystander effect assay showed that the CD/5-FC MSCs significantly augmented Cal72 cytotoxicity in direct co-culture and in the presence of 5-FC through the application of conditioned medium. In osteosarcoma-bearing mice, the CD/5-FC MSCs inhibited tumor growth compared to control mice subcutaneously injected with only Cal72 cells. CONCLUSIONS: Taken together, these findings suggest that CD/5-FC MSCs may be suitable for targeting human osteosarcoma.

Phenotypic Characterization and Multivariate Analysis to Explain Body Conformation in Lesser Known Buffalo (Bubalus bubalis) from North India.

Phenotypic characterization and body biometric in 13 traits (height at withers, body length, chest girth, paunch girth, ear length, tail length, length of tail up to switch, face length, face width, horn length, circumference of horn at base, distances between pin bone and hip bone) were recorded in 233 adult Gojri buffaloes from Punjab and Himachal Pradesh states of India. Traits were analysed by using varimax rotated principal component analysis (PCA) with Kaiser Normalization to explain body conformation. PCA revealed four components which explained about 70.9% of the total variation. First component described the general body conformation and explained 31.5% of total variation. It was represented by significant positive high loading of height at wither, body length, heart girth, face length and face width. The communality ranged from 0.83 (hip bone distance) to 0.45 (horn length) and unique factors ranged from 0.16 to 0.55 for all these 13 different biometric traits. Present study suggests that first principal component can be used in the evaluation and comparison of body conformation in buffaloes and thus provides an opportunity to distinguish between early and late maturing to adult, based on a small group of biometric traits to explain body conformation in adult buffaloes.

Phase II trial of sorafenib in conjunction with chemotherapy and as maintenance therapy in extensive-stage small cell lung cancer.

OBJECTIVES: Sorafenib is a multi-tyrosine kinase inhibitor of Raf kinase, VEGFR, and PDGFR. Angiogenesis is important for growth and progression of SCLC. This trial was conducted to evaluate whether the combination of cisplatin and etoposide plus concurrent and sequential sorafenib could prolong survival in patients with previously untreated SCLC. METHODS: Previously untreated patients with extensive stage SCLC were treated with cisplatin and etoposide days 1, 2, 3 for four cycles, concurrent with sorafenib 200 mg orally bid starting day 1 cycle 1. Patients with no disease progression after four cycles continued sorafenib 400 mg orally bid as maintenance for maximum of 12 months. The primary endpoint was 1 year survival with response rate and safety as secondary endpoints. RESULTS: A total of 18 patients were enrolled with 17 evaluable patients. One patient had a complete response, seven patients had a partial response (overall response rate of 47 %) and one patient had stable disease. Overall median survival was 7.4 months and 1 year survival was 25 %. The most common treatment-related adverse events included fatigue, anorexia, rash, diarrhea, neutropenia and weight loss. Grade 5 GI bleeding, pulmonary hemorrhage and neutropenia occurred in one pt (6 %) each. Accrual was halted on the basis of safety profile as well as preliminary efficacy data. CONCLUSIONS: The combination of platinum based chemotherapy and sorafenib has significant toxicity at current dose levels and is associated with disappointing efficacy data.

Comparative transcriptomic analysis to identify differentially expressed genes in fat tissue of adult Berkshire and Jeju Native Pig using RNA-seq.

Pork is a major source of animal protein for humans. The subcutaneous, intermuscular and the intramuscular fat are the factors responsible for meat quality. RNA-seq is rapidly adopted for the profiling of the transcriptomes in the studies related to gene regulation. The discovery of differentially expressed genes (DEGs) between adult animals of Jeju Native Pig (JNP) and Berkshire breeds are of particular interest for the current study. RNA-seq was used to investigate the transcriptome profiling in the fat tissue. Sequence reads were obtained from Ilumina HiSeq2000 and mapped to the pig genome using Tophat2. Total 153 DEGs were identified and 71 among the annotated genes, have BLAST matches in the non- redundant database. Metabolic, immune response and protein binding are enriched pathways in the fat tissue. In our study, biological adhesion, cellular, developmental and multicellular organismal processes in fat were up-regulated in JNP as compare to Berkshire. Multicellular organismal process, developmental process, embryonic morphogenesis and skeletal system development were the most significantly enriched terms in fat of JNP and Berkshire breeds (p = 1.17E-04, 0.044, 3.47E-04 and 4.48E-04 respectively). COL10A1, COL11A2, PDK4 and PNPLA3 genes responsible for skeletal system morphogenesis and body growth were down regulated in JNP. This study is the first statistical analysis for the detection of DEGs from RNA-seq data generated from fat tissue sample. This analysis can be used as stepping stone to understand the difference in the genetic mechanisms that might influence the identification of novel transcripts, sequence polymorphisms, isoforms and noncoding RNAs.

Evaluation of the antioxidant, anti-inflammatory, and anticancer activities of Euphorbia hirta ethanolic extract.

This study evaluated the chemical composition, antioxidant, anti-inflammatory and anticancer activities of a Euphorbia hirta L. extract. The antioxidant activities of whole E. hirta ethanol extract were determined by electron spin resonance spectrophotometric analysis of 1,1-diphenyl-2-picryl-hydrazyl (DPPH), hydroxyl, and alkyl radical levels and by using an online high-performance liquid chromatography (HPLC)-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assay. The E. hirta ethanol extract (0.5 mg/mL) exhibited DPPH-scavenging activity of 61.19% ± 0.22%, while the positive control (0.5 mg/mL ascorbic acid) had 100% ± 0.22% activity. The concentration of the extract required to trap 50% of DPPH (IC50) was 0.205 mg/mL. Online HPLC analysis of the extract also showed strong antioxidant activity. The anti-inflammatory activity of the E. hirta extract was assessed in lipopolysaccharide-induced RAW 264.7 macrophages. The anti-inflammatory activity was highest in the presence of 200 µg/mL E. hirta extract, and nitric oxide production was decreased significantly (p < 0.05). The extract also showed selective anticancer activity at a concentration of 100 µg/mL (p < 0.05). These results indicated that E. hirta may warrant further investigation for the development of antioxidant, anti-inflammatory, and anticancer herbal medications.

Efficacious rat model displays non-toxic effect with Korean beechwood creosote: a possible antibiotic substitute.

Wood creosote, an herbal anti-diarrheal and a mixture of major volatile compounds, was tested for its non-toxicological effects, using a rat model, with the objective to use the creosote as an antibiotic substitute. A total of 30 Sprague-Dawley rats were studied to form five groups with 6 rats each. Korea beechwood creosote was supplemented into three test groups with 0.03 g/kg, 0.07 g/kg and 0.1 g/kg body weight/day without antibiotic support, along with a positive control of Apramycin sulphate (at 0.5% of the daily feed) and a negative control. Korean beechwood creosote supplementation showed no negative effect on the body weight gain in comparison to the negative and the positive control groups and the feed conversion ratio was also comparable with that of the control groups. The clinical pathology parameters studied were also under the umbrella of normal range, including liver specific enzymes, blood glucose, total protein, blood urea nitrogen (BUN), which indicated no toxic effect of creosote at the given doses. The non-hepatotoxic effect was also confirmed using hepatic damage specific molecular markers like Tim-p1, Tim-p2 and Tgf-ß1. The results suggested that Korean beechwood may be used as antibiotic substitute in weanling pigs feed without any toxic effect on the body. Although the antimicrobial properties of creosote were not absolutely similar to those of apramycin sulphate, they were comparable.