Search results for: tumor inhibition

Authors: Mohamed Hafid, Marcel Lacroix

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This study aimed at developing an inverse heat transfer approach for predicting the time-varying freezing front and the temperature distribution of tumors during cryosurgery. Using a temperature probe pressed against the layer of tumor, the inverse approach is able to predict simultaneously the metabolic heat generation and the blood perfusion rate of the tumor. Once these parameters are predicted, the temperature-field and time-varying freezing fronts are determined with the direct model. The direct model rests on one-dimensional Pennes bioheat equation. The phase change problem is handled with the enthalpy method. The Levenberg-Marquardt Method (LMM) combined to the Broyden Method (BM) is used to solve the inverse model. The effect (a) of the thermal properties of the diseased tissues; (b) of the initial guesses for the unknown thermal properties; (c) of the data capture frequency; and (d) of the noise on the recorded temperatures is examined. It is shown that the proposed inverse approach remains accurate for all the cases investigated.

Keywords: cryosurgery, inverse heat transfer, Levenberg-Marquardt method, thermal properties, Pennes model, enthalpy method

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Authors: Nurkhairul Bariyah Baharun, Afzan Adam, Reena Rahayu Md Zin

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Tumor microenvironment (TME) in breast cancer is mainly composed of cancer cells, immune cells, and stromal cells. The interaction between cancer cells and their microenvironment plays an important role in tumor development, progression, and treatment response. The TME in breast cancer includes tumor-infiltrating lymphocytes (TILs) that are implicated in killing tumor cells. TILs can be found in tumor stroma (sTILs) and within the tumor (iTILs). TILs in triple negative breast cancer (TNBC) have been demonstrated to have prognostic and potentially predictive value. The international Immune-Oncology Biomarker Working Group (TIL-WG) had developed a guideline focus on the assessment of sTILs using hematoxylin and eosin (H&E)-stained slides. According to the guideline, the pathologists use “eye balling” method on the H&E stained- slide for sTILs assessment. This method has low precision, poor interobserver reproducibility, and is time-consuming for a comprehensive evaluation, besides only counted sTILs in their assessment. The TIL-WG has therefore recommended that any algorithm for computational assessment of TILs utilizing the guidelines provided to overcome the limitations of manual assessment, thus providing highly accurate and reliable TILs detection and classification for reproducible and quantitative measurement. This study is carried out to develop a TNBC digital whole slide image (WSI) dataset from H&E-stained slides and IHC (CD4+ and CD8+) stained slides. TNBC cases were retrieved from the database of the Department of Pathology, Hospital Canselor Tuanku Muhriz (HCTM). TNBC cases diagnosed between the year 2010 and 2021 with no history of other cancer and available block tissue were included in the study (n=58). Tissue blocks were sectioned approximately 4 µm for H&E and IHC stain. The H&E staining was performed according to a well-established protocol. Indirect IHC stain was also performed on the tissue sections using protocol from Diagnostic BioSystems PolyVue™ Plus Kit, USA. The slides were stained with rabbit monoclonal, CD8 antibody (SP16) and Rabbit monoclonal, CD4 antibody (EP204). The selected and quality-checked slides were then scanned using a high-resolution whole slide scanner (Pannoramic DESK II DW- slide scanner) to digitalize the tissue image with a pixel resolution of 20x magnification. A manual TILs (sTILs and iTILs) assessment was then carried out by the appointed pathologist (2 pathologists) for manual TILs scoring from the digital WSIs following the guideline developed by TIL-WG 2014, and the result displayed as the percentage of sTILs and iTILs per mm² stromal and tumour area on the tissue. Following this, we aimed to develop an automated digital image scoring framework that incorporates key elements of manual guidelines (including both sTILs and iTILs) using manually annotated data for robust and objective quantification of TILs in TNBC. From the study, we have developed a digital dataset of TNBC H&E and IHC (CD4+ and CD8+) stained slides. We hope that an automated based scoring method can provide quantitative and interpretable TILs scoring, which correlates with the manual pathologist-derived sTILs and iTILs scoring and thus has potential prognostic implications.

Keywords: automated quantification, digital pathology, triple negative breast cancer, tumour infiltrating lymphocytes

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Authors: Mahdi Asghari Ozma

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Background and Objective:Maclurapomifera (Rafin.) Schneider, known as osage orange, is a north american native plant which has multiple applications in herbal medicine. The extract of this plant has many therapeutic effects, including antimicrobial, anti-tumor, anti-inflammation, etc., that discussed in this study. Materials and Methods: For this study, the keywords "Maclurapomifera", "osage orange, ""herbal medicine ", and "plant extract" in the databases PubMed and Google Scholar between 2002 and 2021 were searched, and 20 articles were chosen, studied and analyzed. Results: Due to the increased resistance of microbes to antibiotics, the need for antimicrobial plants is increasing. Maclurapomifera is one of the plants with antimicrobial properties that can affect all microbes, especially Gram-negative bacteria, and fungi. This plant also has anti-tumor, anti-inflammatory, anti-oxidant, anti-aging, antiviral, anti-fungal, anti-ulcerogenic, anti-diabetic, and anti-nociceptive effects, which can be used as a substance with many amazing therapeutic applications. Conclusion: These results suggest that the extract of Maclurapomifera can be used in clinical medicine as a remedial agent, which can be substituted for chemical drugs or help them in the treatment of diseases.

Keywords: maclura pomifera, osage orange, herbal medicine, plant extract

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Authors: Maddalena Arigoni, Maria Luisa Ratto, Raffaele A. Calogero, Luca Alessandri

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The presence of tumor heterogeneity, where distinct cancer cells exhibit diverse morphological and phenotypic profiles, including gene expression, metabolism, and proliferation, poses challenges for molecular prognostic markers and patient classification for targeted therapies. Understanding the causes and progression of cancer requires research efforts aimed at characterizing heterogeneity, which can be facilitated by evolving single-cell sequencing technologies. However, analyzing single-cell data necessitates computational methods that often lack objective validation. Therefore, the establishment of benchmarking datasets is necessary to provide a controlled environment for validating bioinformatics tools in the field of single-cell oncology. Benchmarking bioinformatics tools for single-cell experiments can be costly due to the high expense involved. Therefore, datasets used for benchmarking are typically sourced from publicly available experiments, which often lack a comprehensive cell annotation. This limitation can affect the accuracy and effectiveness of such experiments as benchmarking tools. To address this issue, we introduce omics benchmark experiments designed to evaluate bioinformatics tools to depict the heterogeneity in single-cell tumor experiments. We conducted single-cell RNA sequencing on six lung cancer tumor cell lines that display resistant clones upon treatment of EGFR mutated tumors and are characterized by driver genes, namely ROS1, ALK, HER2, MET, KRAS, and BRAF. These driver genes are associated with downstream networks controlled by EGFR mutations, such as JAK-STAT, PI3K-AKT-mTOR, and MEK-ERK. The experiment also featured an EGFR-mutated cell line. Using 10XGenomics platform with cellplex technology, we analyzed the seven cell lines together with a pseudo-immunological microenvironment consisting of PBMC cells labeled with the Biolegend TotalSeq™-B Human Universal Cocktail (CITEseq). This technology allowed for independent labeling of each cell line and single-cell analysis of the pooled seven cell lines and the pseudo-microenvironment. The data generated from the aforementioned experiments are available as part of an online tool, which allows users to define cell heterogeneity and generates count tables as an output. The tool provides the cell line derivation for each cell and cell annotations for the pseudo-microenvironment based on CITEseq data by an experienced immunologist. Additionally, we created a range of pseudo-tumor tissues using different ratios of the aforementioned cells embedded in matrigel. These tissues were analyzed using 10XGenomics (FFPE samples) and Curio Bioscience (fresh frozen samples) platforms for spatial transcriptomics, further expanding the scope of our benchmark experiments. The benchmark experiments we conducted provide a unique opportunity to evaluate the performance of bioinformatics tools for detecting and characterizing tumor heterogeneity at the single-cell level. Overall, our experiments provide a controlled and standardized environment for assessing the accuracy and robustness of bioinformatics tools for studying tumor heterogeneity at the single-cell level, which can ultimately lead to more precise and effective cancer diagnosis and treatment.

Keywords: single cell omics, benchmark, spatial transcriptomics, CITEseq

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Authors: Amar Ranjan, Julieana Durai, Pranay Tanwar

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Background &Introduction: Ovarian cancer is one of the most common malignant tumor in the female. 70% of the cases of ovarian cancer are diagnosed at an advanced stage. The five-year survival rate associated with ovarian cancer is less than 30%. The early diagnosis of ovarian cancer becomes a key factor in improving the survival rate of patients. Presently, CAl25 (carbohydrate antigen125) is used for the diagnosis and therapeutic monitoring of ovarian cancer, but its sensitivity and specificity is not ideal. The introduction of HE4, human epididymis protein 4 has attracted much attention. HE4 has a sensitivity and specificity of 72.9% and 95% for differentiating between benign and malignant adnexal masses, which is better than CA125 detection.  Methods: Serum HE4 and CA -125 were estimated using the chemiluminescence method. Our cases were 40 epithelial ovarian cancer, 9 benign ovarian tumor, 29 benign gynaecological diseases and 13 healthy individuals. This group include healthy woman those who have undergoing family planning and menopause-related medical consultations and they are negative for ovarian mass. Optimal cut off values for HE4 and CA125 were 55.89pmol/L and 40.25U/L respectively (determined by statistical analysis). Results: The level of HE4 was raised in all ovarian cancer patients (n=40) whereas CA125 levels were normal in 6/40 ovarian cancer patients, which were the cases of OC confirmed by histopathology. There is a significant decrease in the level of HE4 with comparison to CA125 in benign ovarian tumor cases. Both the levels of HE4 and CA125 were raised in the nonovarian cancer group, which includes cancer of endometrium and cervix. In the healthy group, HE4 was normal in all patients except in one case of the rudimentary horn, and the reason for this raised HE4 level is due to the incomplete development of uterus whereas CA125 was raised in 3 cases. Conclusions: Findings showed that the serum level of HE4 is an important indicator in the diagnosis of ovarian cancer, and it also distinguishes between benign and malignant pelvic masses. However, a combination of HE4 and CA125 panel will be extremely valuable in improving the diagnostic efficiency of ovarian cancer. These findings of our study need to be validated in the larger cohort of patients.

Keywords: human epididymis protein 4, ovarian cancer, diagnosis, benign lesions

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Authors: Harald Lindorfer, Bettina Frauz, Dietmar Ramhold

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Next to the well-known inhibitors in anaerobic digestion like ammonia, antibiotics or disinfectants, the number of process failures connected with mould growth in the feedstock increased significantly in the last years. It was assumed that mycotoxins are the cause of the negative effects. The financial damage to plants associated with these process failures is considerable. The aim of this study was to find a way of predicting the failures and furthermore strategies for a fast process recovery. In a first step, mould-contaminated feedstocks causing process failures in full-scale digesters were sampled and analysed on mycotoxin content. A selection of these samples was applied to biological inhibition tests. In this test, crystalline cellulose is applied in addition to the feedstock sample as standard substrate. Affected digesters were also sampled and analytical process data as well as operational data of the plants were recorded. Additionally, different mycotoxin substances, Deoxynivalenol, Zearalenon, Aflatoxin B1, Mycophenolic acid and Citrinin, were applied as pure substances to lab-scale digesters, individually and in various combinations, and effects were monitored. As expected, various mycotoxins were detected in all of the mould-contaminated samples. Nevertheless, inhibition effects were observed with only one of the collected samples, after applying it to an inhibition test. With this sample, the biogas yield of the standard substrate was reduced by approx. 20%. This result corresponds with observations made on full-scale plants. However, none of the tested mycotoxins applied as pure substance caused a negative effect on biogas production in lab scale digesters, neither after application as individual substance nor in combination. The recording of the process data in full-scale plants affected by process failures in most cases showed a severe accumulation of fatty acids alongside a decrease in biogas production and methane concentration. In the analytical data of the digester samples, a typical distribution of fatty acids with exceptionally high acetic acid concentrations could be identified. This typical fatty acid pattern can be used as a rapid identification parameter pointing to the cause of the process troubles and enable a fast implication of countermeasures. The results of the study show that more attention needs to be paid to feedstock storage and feedstock conservation before their application to anaerobic digesters. This is all the more important since first studies indicate that the occurrence of mycotoxins will likely increase in Europe due to the ongoing climate change.

Keywords: Anaerobic digestion, Biogas, Feedstock conservation, Fungal mycotoxins, Inhibition, process failure

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Authors: Palak V. Patel, Jessica Pixley, Steven R. Feldman

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Introduction: Basal cell carcinoma (BCC) is the most common skin cancer worldwide and requires substantial resources to treat. When choosing between indicated therapies, providers consider their associated adverse effects, efficacy, cosmesis, and function preservation. The patient’s tumor burden, infiltrative risk, and risk of tumor recurrence are also considered. Treatment cost is often left out of these discussions. This can lead to financial toxicity, which describes the harm and quality of life reductions inflicted by high care costs. Methods: We studied the guidelines set forth by the American Academy of Dermatology for the treatment of BCC. A PubMed literature search was conducted to identify the costs of each recommended therapy. We discuss costs alongside treatment efficacy and side-effect profile. Results: Surgical treatment for BCC can be cost-effective if the appropriate treatment is selected for the presenting tumor. Curettage and electrodesiccation can be used in low-grade, low-recurrence tumors in aesthetically unimportant areas. The benefits of cost-conscious care are not likely to be outweighed by the risks of poor cosmesis or tumor return ($471 BCC of the cheek). When tumor burden is limited, MMS offers better cure rates and lower recurrence rates than surgical excision, and with comparable costs (MMS $1263; SE $949). Surgical excision with permanent sections may be indicated when tumor burden is more extensive or if molecular testing is necessary. The utility of surgical excision with frozen sections, which costs substantially more than MMS without comparable outcomes, is less clear (SE with frozen sections $2334-$3085). Less data exists on non-surgical treatments for BCC. These techniques cost less, but recurrence-risk is high. Side-effects of nonsurgical treatment are limited to local skin reactions, and cosmesis is good. Cryotherapy, 5-FU, and MAL-PDT are all more affordable than surgery, but high recurrence rates increase risk of secondary financial and psychosocial burden (recurrence rates 21-39%; cost $100-270). Radiation therapy offers better clearance rates than other nonsurgical treatments but is associated with similar recurrence rates and a significantly larger financial burden ($2591-$3460 BCC of the cheek). Treatments for advanced or metastatic BCC are extremely costly, but few patients require their use, and the societal cost burden remains low. Vismodegib and sonidegib have good response rates but substantial side effects, and therapy should be combined with multidisciplinary care and palliative measures. Expert-review has found sonidegib to be the less expensive and more efficacious option (vismodegib $128,358; sonidegib $122,579). Platinum therapy, while not FDA-approved, is also effective but expensive (~91,435). Immunotherapy offers a new line of treatment in patients intolerant of hedgehog inhibitors ($683,061). Conclusion: Dermatologists working within resource-compressed practices and with resource-limited patients must prudently manage the healthcare dollar. Surgical therapies for BCC offer the lowest risk of recurrence at the most reasonable cost. Non-surgical therapies are more affordable, but high recurrence rates increase the risk of secondary financial and psychosocial burdens. Treatments for advanced BCC are incredibly costly, but the low incidence means the overall cost to the system is low.

Keywords: nonmelanoma skin cancer, basal cell skin cancer, squamous cell skin cancer, cost of care

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Authors: Reena Murali, David Peter S.

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The small interfering RNA (siRNA) alters the regulatory role of mRNA during gene expression by translational inhibition. Recent studies shows that up regulation of mRNA cause serious diseases like Cancer. So designing effective siRNA with good knockdown effects play an important role in gene silencing. Various siRNA design tools had been developed earlier. In this work, we are trying to analyze the existing good scoring second generation siRNA predicting tools and to optimize the efficiency of siRNA prediction by designing a computational model using Artificial Neural Network and whole stacking energy (ΔG), which may help in gene silencing and drug design in cancer therapy. Our model is trained and tested against a large data set of siRNA sequences. Validation of our results is done by finding correlation coefficient of experimental versus observed inhibition efficacy of siRNA. We achieved a correlation coefficient of 0.727 in our previous computational model and we could improve the correlation coefficient up to 0.753 when the threshold of whole tacking energy is greater than or equal to -32.5 kcal/mol.

Keywords: artificial neural network, double stranded RNA, RNA interference, short interfering RNA

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Authors: Ogemdi Chinwendu Anika, Anna Strzelecka, Yadira Bajón-Fernández, Raffaella Villa

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Anaerobic digestion (AD) has been used since time in memorial to take care of organic wastes in the environment, especially for sewage and wastewater treatments. Recently, the rising demand/need to increase renewable energy from organic matter has caused the AD substrates spectrum to expand and include a wider variety of organic materials such as agricultural residues and farm manure which is annually generated at around 140 billion metric tons globally. The problem, however, is that agricultural wastes are composed of materials that are heterogeneous and too difficult to degrade -particularly lignin, that make up about 0–40% of the total lignocellulose content. This study aimed to evaluate the impact of varying concentrations of lignin on biogas yields and their subsequent response to a commercial yeast-based bioadditive in batch anaerobic digesters. The experiments were carried out in batches for a retention time of 56 days with different lignin concentrations (200 mg, 300 mg, 400 mg, 500 mg, and 600 mg) treated to different conditions to first determine the concentration of the bioadditive that was most optimal for overall process improvement and yields increase. The batch experiments were set up using 130 mL bottles with a working volume of 60mL, maintained at 38°C in an incubator shaker (150rpm). Digestate obtained from a local plant operating at mesophilic conditions was used as the starting inoculum, and commercial kraft lignin was used as feedstock. Biogas measurements were carried out using the displacement method and were corrected to standard temperature and pressure using standard gas equations. Furthermore, the modified Gompertz equation model was used to non-linearly regress the resulting data to estimate gas production potential, production rates, and the duration of lag phases as indicatives of degrees of lignin inhibition. The results showed that lignin had a strong inhibitory effect on the AD process, and the higher the lignin concentration, the more the inhibition. Also, the modelling showed that the rates of gas production were influenced by the concentrations of the lignin substrate added to the system – the higher the lignin concentrations in mg (0, 200, 300, 400, 500, and 600) the lower the respective rate of gas production in ml/gVS.day (3.3, 2.2, 2.3, 1.6, 1.3, and 1.1), although the 300 mg increased by 0.1 ml/gVS.day over that of the 200 mg. The impact of the yeast-based bioaddition on the rate of production was most significant in the 400 mg and 500 mg as the rate was improved by 0.1 ml/gVS.day and 0.2 ml/gVS.day respectively. This indicates that agricultural residues with higher lignin content may be more responsive to inhibition alleviation by yeast-based bioadditive; therefore, further study on its application to the AD of agricultural residues of high lignin content will be the next step in this research.

Keywords: anaerobic digestion, renewable energy, lignin valorisation, biogas

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Authors: Abdul Matin, Muazzama Akhtar, Shahid Nisar, Saddaf Mazzar, Umer Rashid

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Antibiotic resistance is an increasing concern worldwide now a day. Neisseria gonorrhea and Staphylococcus aureus are known to cause major human sexually transmitted and respiratory diseases respectively. Nanotechnology is an emerging discipline and its application in various fields especially in medical sciences is gigantic. In the present study, we synthesized multi-walled carbon nanotubes (MWNTs) using acid oxidation method and solubilized MWNTs were with length predominantly >500 nm and diameters ranging from 40 to 50 nm. The locally synthesized MWNTs were used against gram positive and negative bacteria to determine their impact on bacterial growth. Clinical isolates of Neisseria gonorrhea (isolate: 4C-11) and Staphylococcus aureus (isolate: 38541) were obtained from local hospital and normally cultured in LB broth at 37°C. Both clinical strains can be obtained on request from University of Gujarat. Spectophometric assay was performed to determine the impact of MWNTs on bacterial growth in vitro. To determine the effect of MWTNs on test organisms, various concentration of MWNTs were used and recorded observation on various time intervals to understand the growth inhibition pattern. Our results demonstrated that MWNTs exhibited toxic effects to Staphylococcus aureus while showed very limited growth inhibition to Neisseria gonorrhea, which suggests the resistant potential of Neisseria against nanoparticles. Our results clearly demonstrate the gradual decrease in bacterial numbers with passage of time when compared with control. Maximum bacterial inhibition was observed at maximum concentration (50 µg/ml). Our future work will include further characterization and mode of action of our locally synthesized MWNTs. In conclusion, we investigated and reported for the first time the inhibitory potential of locally synthesized MWNTs on local clinical isolates of Staphylococcus aureus and Neisseria gonorrhea.

Keywords: antibacterial activity, multi walled carbon nanotubes, Neisseria gonorrhea, spectrophotometer assay, Staphylococcus aureus

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Authors: Roberto Cassino, Valeria Dissette, Carlo Alberto Bignozzi, Daniele Pazzi

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Background and Aims: The aim of this work was to investigate, both ‘in vitro’ and ‘in vivo’, if the new SCX technology (SiO2-Ag+Chlorex) can easily defeat infections and it is really more effective than SSD (SilverSulfaDiazine). ‘In vitro’ methods: we tested ‘in vitro’ the effectiveness of both silver materials using a pool of 5 strains: Pseudomonas Aeruginosa, Staphylococcus aureus, Escherichia Coli, Enterococcus hirae and Candida Albicans. 100 µl of this pool have been seeded on Petri dishes and kept for 24 hours in incubation at 37 C°. ‘In vivo’ methods: we enrolled patients with multiple infectious chronic wounds (according with cutting & harding criteria for infection); after a qualitative evaluation of the wounds bacterial population, taking a sample by plug, we included in the study 6 patients for a total of 10 wounds, infected by one or more of the microorganisms used for the ‘in vitro’ test. The protocol consisted of a treatment with a spray powder of SSD every 48 hours for 14 days; in case of worsening we should have to start a new treatment with a spray powder containing silicon dioxide, ionic silver and chlorexidine (SiO2-Ag+Chlorex) every 48 hours for 14 days. We evaluated the number of clinical signs of infection and the disappearance or not of the wound edge erithema. ‘In vitro’ results: SSD demonstrated a wide zone of inhibition within 24 hours, but after 5 days there was no more signs of inhibition; on the contrary SCX had a good inhibition ring that lasted more than 5 days. ‘In vivo’ results: all wounds treated with SSD got worse; the signs of infection increased and the wound edge erithema did not disappear. According with the protocol, we treated then all wounds with SCX and they all improved within the period of observation with complete disappearance of clinical signs of infection and no more wound edge erithema. Conclusions: the study demonstrated the effectiveness of SiO2-Ag+Chlorex, especially in terms of long lasting antimicrobial action. We had the same results ‘in vitro’, so that there has been a perfect correspondence between the laboratory outcomes and the clinical ones.

Keywords: chronic wounds, infections, ionic silver, SSD

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Authors: Ali A. Bazzi, Ameer Hamza, Riley O’Hara, Kimberly Kado, Karen H. Hagglund, Lamia Fathallah, Robert T. Morris

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Introduction: Endometrial Cancer is a common gynecologic malignancy primarily treated with complete surgical staging, which may include complete pelvic and para-aortic lymphadenectomy. The role of lymphadenectomy is controversial, especially the intraoperative indications for the procedure. Three factors are important in decision to proceed with lymphadenectomy: Myometrial invasion, maximum tumor dimension, and histology. Many institutions incorporate these criteria in varying degrees in the decision to proceed with lymphadenectomy. This investigation assesses the use of intraoperatively measured MTD with and without pre-operative histologic grade. Methods: This study compared retrospectively EEC patients with intraoperatively measured MTD ≤2 cm to those with MTD >2 cm from January 1, 2002 to August 31, 2017. This assessment compared those with MTD ≤ 2cm with endometrial biopsy (EB) grade 1-2 to patients with MTD > 2cm with EB grade 3. Lymph node metastasis (LNM), recurrence, and survival were compared in these groups. Results: This study reviewed 222 patient cases. In tumors > 2 cm, LNM occurred in 20% cases while in tumors ≤ 2 cm, LNM was found in 6% cases (p=0.04). Recurrence and mean survival based on last follow up visit in these two groups were not statistically different (p=0.78 and 0.36 respectively). Data demonstrated a trend that when combined with preoperative EB International Federation of Gynecology and Obstetrics (FIGO) grade, a higher proportion of patients with EB FIGO Grade 3 and MTD > 2 cm had LNM compared to those with EB FIGO Grade 1-2 and MTD ≤ 2 cm (43% vs, 11%, p=0.06). LNM was found in 15% of cases in which lymphadenectomy was performed based on current practices, whereas if the criteria of EB FIGO 3 and MTD > 2 cm were used the incidence of LNM would have been 44% cases. However, using this criterion, two patients would not have had their nodal metastases detected. Compared to the current practice, the sensitivity and specificity of the proposed criteria would be 60% and 81%, respectively. The PPV and NPV would be 43% and 90%, respectively. Conclusion: The results indicate that MTD combined with EB FIGO grade can detect LNM in a higher proportion of cases when compared to current practice. MTD combined with EB FIGO grade may eliminate the need of frozen section sampling in a substantial number of cases.

Keywords: endometrial cancer, FIGO grade, lymphadenectomy, tumor size

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Authors: Oseyemi Omowunmi Olubomehin, Olufemi Michael Denton

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Diabetes mellitus is a disease that is related to the digestion of carbohydrates, proteins and fats and how this affects the blood glucose levels. Various synthetic drugs employed in the management of the disease work through different mechanisms. Keeping postprandial blood glucose levels within acceptable range is a major factor in the management of type 2 diabetes and its complications. Thus, the inhibition of carbohydrate-hydrolyzing enzymes such as α-amylase is an important strategy in lowering postprandial blood glucose levels, but synthetic inhibitors have undesirable side effects like flatulence, diarrhea, gastrointestinal disorders to mention a few. Therefore, it is necessary to identify and explore the α-amylase inhibitors from plants due to their availability, safety, and low costs. In the present study, extracts from the leaves of Rauvolfia vomitoria and seeds of Picralima nitida which are used in the Nigeria traditional system of medicine to treat diabetes were tested for their α-amylase inhibitory effect. The powdered plant samples were subjected to phytochemical screening using standard procedures. The leaves and seeds macerated successively using n-hexane, ethyl acetate and methanol resulted in the crude extracts which at different concentrations (0.1, 0.5 and 1 mg/mL) alongside the standard drug acarbose, were subjected to α-amylase inhibitory assay using the Benfield and Miller methods, with slight modification. Statistical analysis was done using ANOVA, SPSS version 2.0. The phytochemical screening results of the leaves of Rauvolfia vomitoria and the seeds of Picralima nitida showed the presence of alkaloids, tannins, saponins and cardiac glycosides while in addition Rauvolfia vomitoria had phenols and Picralima nitida had terpenoids. The α-amylase assay results revealed that at 1 mg/mL the methanol, hexane, and ethyl acetate extracts of the leaves of Rauvolfia vomitoria gave (15.74, 23.13 and 26.36 %) α-amylase inhibitions respectively, the seeds of Picralima nitida gave (15.50, 30.68, 36.72 %) inhibitions which were not significantly different from the control at p < 0.05, while acarbose gave a significant 56 % inhibition at p < 0.05. The presence of alkaloids, phenols, tannins, steroids, saponins, cardiac glycosides and terpenoids in these plants are responsible for the observed anti-diabetic activity. However, the low percentages of α-amylase inhibition by these plant samples shows that α-amylase inhibition is not the major way by which both plants exhibit their anti-diabetic effect.

Keywords: alpha-amylase, Picralima nitida, postprandial hyperglycemia, Rauvolfia vomitoria

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Authors: Chieh-Nan Chen, Ji-Yu Lin, I-Ming Chu

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Polypeptide thermosensitive hydrogel is an excellent candidate as a smart device to deliver drugs and cells due to its remarkable biocompatibility, low gelation concentration, and respond to temperature stimuli, it can be easily injected as a polymer solution into the patient’s body where it undergoes gelation due to an elevation in temperature. Poly (ethylene glycol) monomethyl ether-poly (ethyl-l-glutamate) (mPEG-PELG) contains a hydrophobic side chain –C2H5 which is useful in encapsulating and stabilizing hydrophobic drugs. In this study, we plan to focus on the hydrophobic anti-carcinogenic and anti-inflammatory drug curcumin, which due its insolubility in water, requires a proper carrier for delivery into the body. Our main concept is to use mPEG-PELG to stabilize curcumin, inject the curcumin-loaded hydrogel into the tumor site, and allow the enzymatically-sensitive hydrogel to be degraded by bodily fluids and release the drug. The polymers of interest have been successfully synthesized and characterized by 1H-NMR, FT-IR, SEM, and CMC. Curcumin loading content and drug release were assayed using HPLC. Preliminary results show that these materials have potential as a delivery vehicle for poorly soluble drugs.

Keywords: curcumin, drug release, hydrogel, polypeptide material

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Authors: Alok Kumar Yadav, Saurabh Saraswat, Preeti Sirohi, Manjoo Rani, Sameer Srivastava, Manish Pratap Singh, Nand K. Singh

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The development of antibiotic resistance in bacteria is increasing at an alarming rate, and this is considered as one of the most serious threats in the history of medicine, and an alternative solution should be derived so as to tackle this problem. In many countries, people use the medicinal plants for the treatment of various diseases as these are cheaper, easily available and least toxic. Syzygium cumini is used for the treatment of various kinds of diseases but their mechanism of action is not reported. The antimicrobial activity of Syzygium cumini was tested by the well diffusion assay and zone of inhibition was reported to be 20.06 mm as compared to control with MIC of 0.3 mg/ml. Genomic DNA fragmentation of Bacillus subtilis revealed apoptosis and FE-SEM indicate cell wall cracking on several intervals of time. Propidium iodide staining results showed that few bacterial cells were stained in the control and population of stained cells increase after exposing them for various period of time. Flow cytometric kinetic data analysis on the membrane permeabilization in bacterial cell showed the significant contribution of antimicrobial potential of the seed extract on antimicrobial-induced permeabilization. Two components of Syzygium cumini methanolic seed extract was found to be quite active against four enzymes like PDB ID- 1W5D, 4OX3, 3MFD and 5E2F which have a very crucial role in membrane synthesis in Bacillus subtilis by in silico analysis. Through in silico analysis, lupeol showed highest binding energy for macromolecule 1W5D and 4OX3 whereas stigmasterol showed the highest binding energy for macromolecule 3MFD and 5E2F respectively. It showed that methanolic seed extract of Syzygium cumini can be used for the inhibition of foodborne infections caused by Bacillus subtilis and also as an alternative of prevalent antibiotics.

Keywords: antibiotics, Bacillus subtilis, inhibition, Syzygium cumini

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Authors: Hammad Khan, Wookeun Bae

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The objective of this study was to optimize and control the highly loaded and efficient nitrite production having suitability for autotrophic and heterotrophic denitritation. A lab scale CSTR for partial and full nitritation was operated to treat the livestock manure digester liquor having an ammonium concentration of ~600 mg-NH4+-N/L and biodegradable contents of ~0.35 g-COD/L. The experiments were performed at 30°C, pH: 8.0, DO: 1.5 mg/L and SRT ranging from 7-20 days. After 125 days operation, >95% nitrite buildup having the ammonium loading rate of ~3.2 kg-NH4+-N/m3-day was seen with almost complete ammonium conversion. On increasing the loading rate further (i-e, from 3.2-6.2 kg-NH4+-N/m3-day), stability of the system remained unaffected. On decreasing the pH from 8 to 7.5 and further 7.2, removal rate can be easily controlled as 95%, 75%, and even 50%. Results demonstrated that nitritation stability and desired removal rates are controlled by a balance of simultaneous inhibition by FA & FNA, pH effect and DO limitation. These parameters proved to be effective even to produce an appropriate influent for anammox. In addition, a mathematical model, identified through the occurring biological reactions, is proposed to optimize the full and partial nitritation process. The proposed model present relationship between pH, ammonium and produced nitrite for full and partial nitritation under the varying concentrations of DO, and simultaneous inhibition by FA and FNA.

Keywords: stable nitritation, high loading, autrophic denitritation, hetrotrophic denitritation

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Authors: Hammad Khan, Wookeun Bae

Abstract:

The objective of this study was to optimize, achieve and control the highly loaded and efficient nitrite production having suitability for autotrophic and heterotrophic denitritation. A lab scale CSTR for partial and full nitritation was operated to treat the livestock manure digester liquor having an ammonium concentration of ~600 mg-NH4+-N/L and biodegradable contents of ~0.35 g-COD/L. The experiments were performed at 30°C, pH: 8.0, DO: 1.5 mg/L and SRT ranging from 7-20 days. After 125 days operation, >95% nitrite buildup having the ammonium loading rate of ~3.2 kg-NH4+-N/m3-day was seen with almost complete ammonium conversion. On increasing the loading rate further (i-e, from 3.2-6.2 kg-NH4+-N/m3-day), stability of the system remained unaffected. On decreasing the pH from 8 to7.5 and further 7.2, removal rate can be easily controlled as 95%, 75%, and even 50%. Results demonstrated that nitritation stability and desired removal rates are controlled by a balance of simultaneous inhibition by FA & FNA, pH affect and DO limitation. These parameters proved to be effective even to produce an appropriate influent for anammox. In addition, a mathematical model, identified through the occurring biological reactions, is proposed to optimize the full and partial nitritation process. The proposed model present relationship between pH, ammonium and produced nitrite for full and partial nitritation under the varying concentrations of DO, and simultaneous inhibition by FA and FNA.

Keywords: stable nitritation, high loading, autrophic denitritation, CSTR

Procedia PDF Downloads 238

Authors: Po-Sheng Kuo, Che-Wei Lu, Ssu-Ching Chen

Abstract:

Chlorinated ethenes (CEs) constitute a predominant contaminant in Taiwan's native polluted sites, particularly in groundwater inundated with sulfate salts that substantially impede remediation efforts. The reduction of sulfate by sulfate-reducing bacteria (SRB) impairs the dechlorination efficiency of Dehalococcoides by generating hydrogen sulfide (H₂S), resulting in incomplete chloride degradation and thereby leading to the failure of bioremediation. In order to elucidate interactions between sulfate reduction and dechlorination, this study aims to establish a co-culture system of Dehalococcoides and SRB, overcoming H₂S inhibition by employing the synthesis of ferrous sulfide (FeS), which is commonly utilized in chemical remediation due to its high reduction potential. Initially, the study demonstrates that the addition of ferrous chloride (FeCl₂) effectively removed H₂S production from SRB and enhanced the degradation of trichloroethylene to ethene. This process overcomes the inhibition caused by H₂S produced by SRB in high sulfate environments. Compared to different concentrations of ferrous dosages for the biogenic generation of FeS, the efficiency was optimized by adding FeCl₂ at an equal ratio to the concentration of sulfate in the environment. This was more effective in removing H₂S and crystal particles under 10 times smaller than those synthesized under excessive FeCl₂ dosages, addressing clogging issues in situ remediation. Finally, utilizing Taiwan's indigenous dechlorinating consortium in a simulated high sulfate-contaminated environment, the biodiversity of microbial species was analyzed to reveal a higher species richness within the FeS group, conducive to ecological stability. This study validates the potential of the co-culture system in generating biogenic FeS under sulfate and CEs co-contamination, removing sulfate-reducing products, and improving CE remediation through integrated chemical and biological remediations.

Keywords: biogenic ferrous sulfide, chlorinated ethenes, Dehalococcoides, sulfate-reducing bacteria, sulfide inhibition

Procedia PDF Downloads 51

Authors: Georges F. Hatoum, Thomas H. Temple, Silvio Garcia, Xiaodong Wu

Abstract:

Soft Tissue Sarcomas (STS) represent a diverse group of malignancies with heterogeneous clinical and pathological features. The treatment of extremity STS aims to achieve optimal local tumor control, improved survival, and preservation of limb function. The National Comprehensive Cancer Network guidelines, based on the cumulated clinical data, recommend radiation therapy (RT) in conjunction with limb-sparing surgery for large, high-grade STS measuring greater than 5 cm in size. Such treatment strategy can offer a cure for patients. However, when recurrence occurs (in nearly half of patients), the prognosis is poor, with a median survival of 12 to 15 months and with only palliative treatment options available. The spatially-fractionated-radiotherapy (SFRT), with a long history of treating bulky tumors as a non-mainstream technique, has gained new attention in recent years due to its unconventional therapeutic effects, such as bystander/abscopal effects. Combining single fraction of GRID, the original form of SFRT, with conventional RT was shown to have marginally increased the rate of pathological necrosis, which has been recognized to have a positive correlation to overall survival. In an effort to consistently increase the pathological necrosis rate over 90%, multiple fractions of Lattice RT (LRT), a newer form of 3D SFRT, interdigitated with the standard RT as neoadjuvant therapy was conducted in a preliminary clinical setting. With favorable results of over 95% of necrosis rate in a small cohort of patients, a Phase I/II clinical study was proposed to exam the safety and feasibility of this new strategy. Herein the design of the clinical study is presented. In this single-arm, two-stage phase I/II clinical trial, the primary objectives are >80% of the patients achieving >90% tumor necrosis and to evaluation the toxicity; the secondary objectives are to evaluate the local control, disease free survival and overall survival (OS), as well as the correlation between clinical response and the relevant biomarkers. The study plans to accrue patients over a span of two years. All patient will be treated with the new neoadjuvant RT regimen, in which one of every five fractions of conventional RT is replaced by a LRT fraction with vertices receiving dose ≥10Gy while keeping the tumor periphery at or close to 2 Gy per fraction. Surgical removal of the tumor is planned to occur 6 to 8 weeks following the completion of radiation therapy. The study will employ a Pocock-style early stopping boundary to ensure patient safety. The patients will be followed and monitored for a period of five years. Despite much effort, the rarity of the disease has resulted in limited novel therapeutic breakthroughs. Although a higher rate of treatment-induced tumor necrosis has been associated with improved OS, with the current techniques, only 20% of patients with large, high-grade tumors achieve a tumor necrosis rate exceeding 50%. If this new neoadjuvant strategy is proven effective, an appreciable improvement in clinical outcome without added toxicity can be anticipated. Due to the rarity of the disease, it is hoped that such study could be orchestrated in a multi-institutional setting.

Keywords: lattice RT, necrosis, SFRT, soft tissue sarcoma

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Authors: Constance Chivengwa, Tinashe Mandimutsira, Jephris Gere, Charles Magogo, Irene Chikanza, Jerneja Vidmar, Walter Chingwaru

Abstract:

The use of traditional methods in the management of diarrhoea has remained a common practice among the indigenous African tribes of Southern Africa. Despite the widespread use of traditional medicines in Zimbabwe, very little research validating the activities of phytomedicines against diarrhoea, as claimed by the Shona people of Zimbabwe, has been reported. This study sought to determine the efficacies of the plants that are frequently used to treat stomach complaints, namely Dicoma anomala, Cassia abbreviata, Lannea edulis and Peltophorum africanum against Escherichia coli (an indicator of faecal contamination of water, and whose strains such as EHEC (O157), ETEC and EPEC, are responsible for a number of outbreaks of diarrhoea) and Salmonella spp. Ethanol and aqueous extracts from these plants were obtained, evaporated, dried and stored. The dried extracts were reconstituted and diluted 10-fold in nutrient broth (from 100 to 0.1 microgram/mL) and tested for inhibition against the bacteria. L. edulis exhibited the best antimicrobial effect (minimum inhibition concentration = 10 microgram/mL for both extracts and microorganisms). Runners up to L. edulis were C. abbreviata (20 microgram/mL for both microorganisms) and P. africanum (20 and 30 microgram/mL respectively). Interestingly, D. anomala, which is widely considered panacea in African medicinal practices, showed low antimicrobial activity (60 and 100 microgram/mL respectively). The high antimicrobial activity of L. edulis can be explained by its content of flavonoids, tannins, alkylphenols (cardonol 7 and cardonol 13) and dihydroalkylhexenones. The antimicrobial activities of C. abbreviata can be linked to its content of anthraquinones and triterpenoids. P. africanum is known to contain benzenoids, flavanols, flavonols, terpenes, xanthone and coumarins. This study therefore demonstrated that, among the plants that are used against diarrhoea in African traditional medicine, L. edulis is a clear winner against E. coli and Salmonella spp. Activity guided extraction is encouraged to establish the complement of compounds that have antimicrobial activities.

Keywords: diarrhoea, Escherichia coli, Salmonella, phytomedicine, MIC, Zimbabwe

Procedia PDF Downloads 374

Authors: Ronald Croce, Timothy Quinn, John Miller

Abstract:

Incomplete activation, or activation failure, of motor units during maximal voluntary contractions is often referred to as muscle inhibition (MI), and is defined as the inability of the central nervous system to maximally drive a muscle during a voluntary contraction. The purpose of the present study was to assess the interrelationship amongst peak torque (PT), muscle inhibition (MI; incomplete activation of motor units), and voluntary muscle activation (VMA) of the quadriceps’ muscle group as a function of knee angle and muscle length during maximal voluntary isometric contractions (MVICs). Nine young adult males (mean + standard deviation: age: 21.58 + 1.30 years; height: 180.07 + 4.99 cm; weight: 89.07 + 7.55 kg) performed MVICs in random order with the knee at 15, 55, and 95° flexion. MI was assessed using the interpolated twitch technique and was estimated by the amount of additional knee extensor PT evoked by the superimposed twitch during MVICs. Voluntary muscle activation was estimated by root mean square amplitude electromyography (EMGrms) and mechanomyography (MMGrms) of agonist (vastus medialis [VM], vastus lateralis [VL], and rectus femoris [RF]) and antagonist (biceps femoris ([BF]) muscles during MVICs. Data were analyzed using separate repeated measures analysis of variance. Results revealed a strong dependency of quadriceps’ PT (p < 0.001), MI (p < 0.001) and MA (p < 0.01) on knee joint position: PT was smallest at the most shortened muscle position (15°) and greatest at mid-position (55°); MI and MA were smallest at the most shortened muscle position (15°) and greatest at the most lengthened position (95°), with the RF showing the greatest change in MA. It is hypothesized that the ability to more fully activate the quadriceps at short compared to longer muscle lengths (96% contracted at 15°; 91% at 55°; 90% at 95°) might partly compensate for the unfavorable force-length mechanics at the more extended position and consequent declines in VMA (decreases in EMGrms and MMGrms muscle amplitude during MVICs) and force production (PT = 111-Nm at 15°, 217-NM at 55°, 199-Nm at 95°). Biceps femoris EMG and MMG data showed no statistical differences (p = 0.11 and 0.12, respectively) at joint angles tested, although there were greater values at the extended position. Increased BF muscle amplitude at this position could be a mechanism by which anterior shear and tibial rotation induced by high quadriceps’ activity are countered. Measuring and understanding the degree to which one sees MI and VMA in the QF muscle has particular clinical relevance because different knee-joint disorders, such ligament injuries or osteoarthritis, increase levels of MI observed and markedly reduced the capability of full VMA.

Keywords: electromyography, interpolated twitch technique, mechanomyography, muscle activation, muscle inhibition

Procedia PDF Downloads 347

Authors: Hyeon Su Kim, Sungjin Park, Hae Ryung Chang, Hae Rim Jung, Young Zoo Ahn, Yon Hui Kim, Seungyoon Nam

Abstract:

Ependymoma, one of the most common parenchymal spinal cord tumor, represents 3-6% of all CNS tumor. Especially intracranial ependymomas, which are more frequent in childhood, have a more poor prognosis and more malignant than spinal ependymomas. Although there are growing needs to understand pathogenesis, detailed molecular understanding of pathogenesis remains to be explored. A cancer cell is composed of complex signaling pathway networks, and identifying interaction between genes and/or proteins are crucial for understanding these pathways. Therefore, we explored each ependymoma in terms of differential expressed genes and signaling networks. We used Microsoft Excel™ to manipulate microarray data gathered from NCBI’s GEO Database. To analyze and visualize signaling network, we used web-based PATHOME algorithm and Cytoscape. We show HOX family and NEFL are down-regulated but SCL family is up-regulated in cerebrum and posterior fossa cancers over a spinal cancer, and JAK/STAT signaling pathway and Chemokine signaling pathway are significantly different in the both intracranial ependymoma comparing to spinal ependymoma. We are considering there may be an age-dependent mechanism under different histological pathogenesis. We annotated mutation data of each gene subsequently in order to find potential target genes.

Keywords: systems biology, ependymoma, deg, network analysis

Procedia PDF Downloads 298

Authors: Thampi Rawther, Sean O’Brien, Kamala Kanta Das

Abstract:

Background: Intussusception in the adult is rarely from a benign cause and is almost always pathological. Causes include carcinomas, polyps, Meckel's diverticulum, or colonic diverticulum. Common symptoms include abdominal pain, intestinal obstruction, palpable abdominal mass, GI bleeding, and anemia. Sarcomatoid carcinoma is a rare type of small intestinal malignancy exhibiting carcinomatous and sarcomatous features. It primarily affects older patients, mean age 57, and is 1.5 times more prevalent in men. Method: This is an interesting case report of a patient presenting with intussusception secondary to a sarcomatoid tumor of the small bowel. Conclusion: Surgery is the treatment of choice in adults with intussusception due to the high malignancy potential. Furthermore, surgical resection of the affected bowel is the definitive form of therapy as small bowel sarcomatoid tumors are not responsive to chemotherapy and radiotherapy. Early surgical intervention helps reduce mortality as it allows for early staging, treatment, and monitoring of the tumor. The patient was fortunate to have presented with intussusception, facilitating early surgical intervention, and was found to have a low disease stage.

Keywords: general surgery, small bowel tumour, imaging, unique

Procedia PDF Downloads 80

Authors: Vandana Mohan, Ashwani Koul

Abstract:

Aim: To evaluate the potential of Aqueous Tinospora cordifolia stem extract (Aq.Tc) and Arabinogalactan (AG) on pulmonary carcinogenesis and associated tumor markers. Background: Lung cancer is one of the most frequent malignancy with high mortality rate due to limitation of early detection resulting in low cure rates. Current research effort focuses on identifying some blood-based biomarkers like CEA, ctDNA and LDH which may have potential to detect cancer at an early stage, evaluation of therapeutic response and its recurrence. Medicinal plants and their active components have been widely investigated for their anticancer potentials. Aqueous preparation of T. Cordifolia extract is enriched in the polysaccharide fraction i.e., AG when compared with other types of extract. Moreover, reports are available of polysaccharide fraction of T. Cordifolia in in vitro lung cancer models which showed profound anti-metastatic activity against these cell lines. However, not much has been explored about its effect in in vivo lung cancer models and the underlying mechanism involved. Experimental Design: Mice were randomly segregated into six groups. Group I animals served as control. Group II animals were administered with Aq. Tc extract (200 mg/kg b.w.) p.o.on the alternate days. Group III animals were fed with AG (7.5 mg/kg b.w.) p.o. on the alternate days (thrice a week). Group IV animals were installed with Benzo(a)pyrene (50 mg/kg b.w.), i.p. twice within an interval of two weeks. Group V animals received Aq. Tc extract as in group II along with it B(a)P was installed after two weeks of Aq. Tc administration following the same protocol as for group IV. Group VI animals received AG as in group III along with it B(a)P was installed after two weeks of AG administration. Results: Administration of B(a)P to mice resulted in increased tumor incidence, multiplicity and pulmonary somatic index with concomitant increase in serum/plasma markers like CEA, ctDNA, LDH and TNF-α.Aq.Tc and AG supplementation significantly attenuated these alterations at different stages of tumorigenesis thereby showing potent anti-cancer effect in lung cancer. A pronounced decrease in serum/plasma markers were observed in animals treated with Aq.Tc as compared to those fed with AG. Also, extensive hyperproliferation of alveolar epithelium was prominent in B(a)P induced lung tumors. However, treatment of Aq.Tc and AG to lung tumor bearing mice exhibited reduced alveolar damage evident from decreased number of hyperchromatic irregular nuclei. A direct correlation between the concentration of tumor markers and the intensity of lung cancer was observed in animals bearing cancer co-treated with Aq.Tc and AG. Conclusion: These findings substantiate the chemopreventive potential of Aq.Tc and AG against lung tumorigenesis. Interestingly, Aq.Tc was found to be more effective in modulating the cancer as reflected by various observations which may be attributed to the synergism offered by various components of Aq.Tc. Further studies are in progress to understand the underlined mechanism in inhibiting lung tumorigenesis by Aq.Tc and AG.

Keywords: Arabinogalactan, Benzo(a)pyrene B(a)P, carcinoembryonic antigen (CEA), circulating tumor DNA (ctDNA), lactate dehydrogenase (LDH), Tinospora cordifolia

Procedia PDF Downloads 185

Authors: Hammad Khan, Wookeun Bae

Abstract:

The objective of this study was to optimize and control the highly loaded and efficient nitrite production having suitability for autotrophic and heterotrophic denitritation. A lab scale CSTR for partial and full nitritation was operated to treat the livestock manure digester liquor having an ammonium concentration of ~2000 mg-NH4+-N/L and biodegradable contents of ~0.8 g-COD/L. The experiments were performed at 30°C, pH: 8.0 DO: 1.5 mg/L and SRT ranging from 7-20 days. After 125 days operation, >95% nitrite buildup having the ammonium loading rate of ~3.2 kg-NH4+-N/m3-day was seen with almost complete ammonium conversion. On increasing the loading rate further (i.e. from 3.2-6.2 kg-NH4+-N/m3-day), stability of the system remained unaffected. On decreasing the pH from 8 to7.5 and further 7.2, removal rate can be easily controlled as 95%, 75% and even 50%. Results demonstrated that nitritation stability and desired removal rates are controlled by a balance of simultaneous inhibition by FA and FNA, pH affect and DO limitation. These parameters proved to be effective even to produce an appropriate influent for anammox. In addition, a mathematical model, identified through the occurring biological reactions, is proposed to optimize the full and partial nitritation process. The proposed model presents relationship between pH, ammonium and produced nitrite for full and partial nitritation under the varying concentrations of DO, and simultaneous inhibition by FA and FNA.

Keywords: stable nitritation, high loading, autrophic denitritation, hetrotrophic denitritation

Procedia PDF Downloads 326

Authors: Zoi Konsoula

Abstract:

The increasing prevalence of Alzheimer’s disease (AD) and diabetes mellitus (DM) constitutes them major global health problems. Recently, the inhibition of key enzyme activity is considered a potential treatment of both diseases. Specifically, inhibition of acetylcholinesterase (AChE), the key enzyme involved in the breakdown of the neurotransmitter acetylcholine, is a promising approach for the treatment of AD, while inhibition of α-amylase retards the hydrolysis of carbohydrates and, thus, reduces hyperglycemia. Unfortunately, commercially available AChE and α-amylase inhibitors are reported to possess side effects. Consequently, there is a need to develop safe and effective treatments for both diseases. In the present study, pomegranate peel (PP) was extracted using various solvents of increasing polarity, while two extraction methods were employed, the conventional maceration and the ultrasound assisted extraction (UAE). The concentration of bioactive phytoconstituents, such as total phenolics (TPC) and total flavonoids (TFC) in the prepared extracts was evaluated by the Folin-Ciocalteu and the aluminum-flavonoid complex method, respectively. Furthermore, the anti-neurodegenerative and anti-hyperglycemic activity of all extracts was determined using AChE and α-amylase inhibitory activity assays, respectively. The inhibitory activity of the extracts against AChE and α-amylase was characterized by estimating their IC₅₀ value using a dose-response curve, while galanthamine and acarbose were used as positive controls, respectively. Finally, the kinetics of AChE and α-amylase in the presence of the most inhibitory potent extracts was determined by the Lineweaver-Burk plot. The methanolic extract prepared using the UAE contained the highest amount of phytoconstituents, followed by the respective ethanolic extract. All extracts inhibited acetylcholinesterase in a dose-dependent manner, while the increased anticholinesterase activity of the methanolic (IC₅₀ = 32 μg/mL) and ethanolic (IC₅₀ = 42 μg/mL) extract was positively correlated with their TPC content. Furthermore, the activity of the aforementioned extracts was comparable to galanthamine. Similar results were obtained in the case of α-amylase, however, all extracts showed lower inhibitory effect on the carbohydrate hydrolyzing enzyme than on AChE, since the IC₅₀ value ranged from 84 to 100 μg/mL. Also, the α-amylase inhibitory effect of the extracts was lower than acarbose. Finally, the methanolic and ethanolic extracts prepared by UAE inhibited both enzymes in a mixed (competitive/noncompetitive) manner since the Kₘ value of both enzymes increased in the presence of extracts, while the Vmax value decreased. The results of the present study indicate that PP may be a useful source of active compounds for the management of AD and DM. Moreover, taking into consideration that PP is an agro-industrial waste product, its valorization could not only result in economic efficiency but also reduce the environmental pollution.

Keywords: acetylcholinesterase, Alzheimer’s disease, α-amylase, diabetes mellitus, pomegranate

Procedia PDF Downloads 122

Authors: Samah Lakehal, A. Meliani, F. Z. Benrebiha, C. Chaouia

Abstract:

In the last few years, due to the misuse of antibiotics and an increasing incidence of immunodeficiency-related diseases, the development of microbial drug resistance has become more and more of a pressing problem. Recently, natural products from medicinal plants represent a fertile ground for the development of novel antibacterial agents. Plants essential oils have come more into the focus of phytomedicine. The present study describes antimicrobial activity of Rosmarinus officinalis L. essential oil known medicinally for its powerful antibacterial properties. The essential oil of rosemary obtained by hydrodistillation (using Clevenger type apparatus) growing in Algeria (Djelfa city of south Algeria) was investigated by GC-MS. The essential oil yield of the study was 1.4 %. The major components were found to be camphor, camphene, 1,8-cineole. The essential oil has been tested for antimicrobial activity against eight bacteria (Gram-negative and Gram-positive), and three fungi including Candida albicans. Inhibition of growth was tested by the agar diffusion method based on the determination of the diameter of inhibition. The oil was found to have significant antibacterial activity and therefore can be used as a natural antimicrobial agent for the treatment of several infectious diseases caused by those germs, which have developed resistance to antibiotics.

Keywords: antimicrobial activity, Rosmarinus officinalis L., essential oils, GC/MS, camphor

Procedia PDF Downloads 391

Authors: Hulya Tuba Kiyan, Nilgun Ozturk

Abstract:

Gentiana, a member of Gentianaceae, is represented by approximately 400 species in the world and 12 species in Turkey. Flavonoids, iridoids, triterpenoids and also xanthones are the major compounds of this genus, have been previously reported to have antiinflammatory, antimicrobial, antioxidant, hepatoprotective, hypotensive, hypoglycaemic, DNA repair and immunomodulatory properties. The methanolic extract of the aerial parts of Gentiana brachyphylla Vill. from Turkey was evaluated for its biological activities and its total phenolic content in the present study. According to the antioxidant activity results, G. brachyphylla methanolic extract showed very strong anti-DNA damage antioxidant activity with an inhibition of 81.82%. It showed weak ferric-reducing power with a EC50 value of 0.65 when compared to BHT (EC50 = 0.2). Also, at 0.5 mg/ml concentration, the methanolic extract inhibited ABTS radical cation activity with an inhibition of 20.13% when compared to Trolox (79.01%). Chelating ability of G. brachyphylla was 44.71% whereas EDTA showed 78.87% chelating activity at 0.2 mg/ml. Also G. brachyphylla showed weak 27.21% AChE, 20.23% BChE, strong 67.86% MAO-A and moderate 50.06% MAO-B, weak 19.14% COX-1, 29.11% COX-2 inhibitory activities at 0.25 mg/ml. The total phenolic content of G. brachyphylla was 156.23 ± 2.73 mg gallic acid equivalent/100 g extract.

Keywords: antioxidant activity, cholinesterase inhibitory activity, Gentiana brachyphylla Vill., total phenolic content

Procedia PDF Downloads 201

Authors: Hammad Khan, Wookeun Bae

Abstract:

The objective of this study was to achieve, optimize and control the highly loaded and efficient nitrite production having suitability for autotrophic and heterotrophic denitritation. A lab scale CSTR for partial and full nitritation was operated to treat the livestock manure digester liquor having an ammonium concentration of ~2000 mg-NH4+-N/L and biodegradable contents of ~0.8 g-COD/L. The experiments were performed at 30°C, pH: 8.0, DO: 1.5 mg/L and SRT ranging from 7-20 days. After 125 days operation, >95% nitrite buildup having the ammonium loading rate of ~3.2 kg-NH4+-N/m3-day was seen with almost complete ammonium conversion. On increasing the loading rate further (i-e, from 3.2-6.2 kg-NH4+-N/m3-day), stability of the system remained unaffected. On decreasing the pH from 8 to 7.5 and further 7.2, removal rate can be easily controlled as 95%, 75% and even 50%. Results demonstrated that nitritation stability and desired removal rates are controlled by a balance of simultaneous inhibition by FA & FNA, pH affect and DO limitation. These parameters proved to be effective even to produce an appropriate influent for anammox. In addition, a mathematical model, identified through the occurring biological reactions, is proposed to optimize the full and partial nitritation process. The proposed model present relationship between pH, ammonium and produced nitrite for full and partial nitritation under the varying concentrations of DO, and simultaneous inhibition by FA and FNA.

Keywords: stable nitritation, high loading, autrophic denitritation, hetrotrophic denitritation

Procedia PDF Downloads 273

Authors: Mohammad Jamil Abd AlGhani

Abstract:

The natural native antioxidants N,N-P-methyl phenyl acetone and N,N-phenyl acetone were isolated from the Iraqi crude oil region of Kirkuk by ion exchange and their structure was characterized by spectral and chemical analysis methods. Tetraline was used as a liquid hydrocarbon to detect the efficiency of isolated molecules at elevated temperature (393 K) that it has physicochemical specifications and structure closed to hydrocarbons fractionated from crude oil. The synthesized universal antioxidant 2,6-ditertiaryisobutyl-p-methyl phenol (Unol) with known stochiometric coefficient of inhibition equal to (2) was used as a model for comparative evaluation at the same conditions. Modified chemiluminescence method was used to find the amount of absorbed oxygen and the induction periods in and without the existence of isolated antioxidants molecules. The results of induction periods and quantity of absorbed oxygen during the oxidation process were measured by manometric installation. It was seen that at specific equal concentrations of N,N-phenyl acetone and N, N-P-methyl phenyl acetone in comparison with Unol at 393 K were with (2) and (2.5) times efficient than do Unol. It means that they had the ability to inhibit the formation of new free radicals and prevent the chain reaction to pass from the propagation to the termination step rather than decomposition of formed hydroperoxides.

Keywords: antioxidants, chemiluminescence, inhibition, Unol

Procedia PDF Downloads 200