ARTICLE | doi:10.20944/preprints201801.0123.v1
Subject: Earth Sciences, Geology Keywords: geobody modeling, object-based facies modeling (OBFM), variogram analysis, farewell formation, paleo-depositional environment
Online: 15 January 2018 (10:01:00 CET)
The early-mid Paleocene Farewell Formation is stratigraphically distributed across the southern Taranaki Basin (STB) which is also encountered within the Maui Gas Field. Using available 3D seismic and well log data, a challenging task to delineate the spatial distribution and geobody patterns of the potential reservoir sands of the formation was performed. Object based modeling coupled with sequential indicator simulation were used to analyze the spatial distribution of facies configuration and a conceptual model was developed based on the outputs from the structurally- modeled grids. The facies modeling followed a hierarchical object-based mechanism which was set to perform with constraints like channel geometry and heterogeneity within the formation. The resultant 3D geobody model showed that the distributary channels, mainly braided geobodies flowed from northeast cutting through several regional normal-fault systems to the southwest. Overbank facies was adhered to the fringe of the channels whereas the floodplain facies was at the periphery of the model. Meandering channel-sand facies were mostly observed at the center of the model flowing in a more random manner, occupying major flow directions of northwest to southwest and southeast to northwest within the model.
ARTICLE | doi:10.20944/preprints202107.0564.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Neurological activity; GC-MS; ADMET profile; Molecular Docking; Beta-amyloid precursor protein; Alzheimer’s disease
Online: 26 July 2021 (10:27:40 CEST)
Medicinal plants possess a surplus of novel and biologically active secondary metabolites that are responsible for counteracting diseases. Traditionally, Gomphandra tetrandra (Wall.) Sleumer is used to treat mental disorders. The present research was designed to explore phytochemicals from the ethanol leaf extract of Gomphandra tetrandra (Wall.) Sleumer to identify the potential pharmacophore(s) in the treatment of neurological disorders. The chemical compounds of the experimental plant were identified through GC-MS analysis. Besides, in-vitro antioxidant activity was assessed using different methods. Furthermore, in-vivo neurological activity was assessed in Swiss-albino mice. Computer aided analysis was appraised to determine the best-fit phytoconstituent of a total of fifteen identified compounds in the experimental plant extract against beta-amyloid precursor protein. The experimental extract revealed fifteen compounds in GC-MS analysis and the highest content was 9, 12, 15-octadecatrienoic acid (Z, Z, Z). Also, the extract showed potent anti-oxidant activity in in-vitro assays. Furthermore, in in-vivo neurological assays, the extract disclosed significant (p<0.05) neurological activity. The most favorable phytochemicals as neurological agents were selected via ADMET profiling and molecular docking was studied with beta-amyloid precursor protein. Moreover, in the computer aided study, 1, 5-Diphenyl-2H-1, 2, 4-triazoline-3-thione (Pub Chem CID: 2802516) was more active than other identified compounds with strong binding affinity to beta-amyloid precursor protein. The present in vivo and in silico studies revealed neuropharmacological features of G. tetrandra leaves extract as a natural agent against neurological disorders, especially Alzheimer’s disease.
ARTICLE | doi:10.20944/preprints202105.0142.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Cancer Immunotherapy; Cancer Vaccine; Cancer Antigens; CRISPR-Cas9; Engineered T Cells.
Online: 7 May 2021 (11:10:13 CEST)
The mechanisms involved in immune responses to cancer have been extensively studied for several decades and, considerable attention has been paid to harnessing the immune system's therapeutic potential. Cancer immunotherapy has established itself as a promising new treatment option for a variety of cancer types. Various strategies including cancer vaccines, monoclonal antibodies (mAbs), adoptive T-cell-cancer therapy and immune test therapy have gained prominence through immunotherapy. However, it remains to be accomplished the full potential of cancer immunotherapy. In spite of having startling aspects, the cancer immunotherapies have some difficulties including the inability to effectively targeting the cancer antigens and the abnormalities in patient response. With the advancement of technology, this system has changed the genome-based immunotherapy process in the human body including generation of engineered T cells. Due to its high specificity, CRISPR-Cas9 has become a simple and flexible genome-editing tool to target nearly any genomic locus. Recently, the CD19-mediated CAR-T cell (chimeric antigen receptor T cell) therapy has opened a new avenue for the treatment of human cancer, though low efficiency is a major drawback of this process. Thus, increasing the efficiency of the CAR-T cell (engineered T cells that induce the chimeric antigen receptor) by using CRISPR-Cas9 technology could be a better weapon to fight against the cancer. In this review, we have broadly focused on the use of CRISPR-Cas9 technology for the modification of the T-cell, which can specifically recognize cancer cells and be used as immune therapeutics against cancer. We have also demonstrated the other potential strategies for the treatment of cancer.
ARTICLE | doi:10.20944/preprints202105.0211.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Colorectal cancer; SYK; Prognostic Significance; Genetic Alteration; Molecular dynamics simulations
Online: 10 May 2021 (15:20:54 CEST)
Background: Colorectal cancer is considered the third most fetal among all type of cancer. Spleen tyrosine kinase (SYK) is a non-receptor type tyrosine-protein that plays crucial role in signaling mediated via immune receptor. We adopted an onco-informatics analysis to evaluate the SYK expression and prognostic value of SYK in colorectal cancer, and identification of potential phytochemicals which may inhibit overexpression of SYK protein as well as minimized colorectal cancer. Materials & Methods: Differential expression of SYK gene was analyzed using the several transcriptomic databases including Oncomine, UALCAN, GENT2 and GEPIA2. The server, cBioPortal was used to analyze mutation and copy number alterations whereas GENT2, GEPIA, OncoLnc and PrognoScan were employed to examine the survival rate. A protein-protein interaction network of SYK and co-expressed genes of SYK was conducted via GeneMANIA. Considering SYK gene encoding protein as drug target, selected phytochemicals were assessed by molecular docking using PyRx 0.8 packages. YASARA molecular dynamics simulators were applied for the post validation of the molecular docking data. Results: We have observed significant overexpression of mRNA expression levels of SYK gene colorectal adenocarcinoma (COAD) samples compared with normal tissues. Significant methylation level and various genetic alterations are assembled in SYK gene which can lead to the development of colorectal cancer. As a result, lower level of SYK expression was related to the more chances of patients’ survival by which all the outcomes from the multiple bioinformatics platforms and web resources have demonstrated the significant evidences that the SYK kinsase can possess as a potential biomarker for the treatment of colorectal cancer. Here, aromatic phytochemicals namely, Kaempferol and Glabridin targeting SYK showed more stability compared to controls and may be useful for the treatment of colorectal cancer. Conclusion: Our study showed dysregulated expression of SYK in colorectal cancer and potentiality to act as a biomarker for the prognosis of CRC. Moreover, we have shown phytochemicals (Kaempferol and Glabridin) target SYK as potential treatment strategies and drug repositioning potentiality in colorectal cancer.