Search results for: cancer cell lines

Authors: Francesco Pantano, Marta Fogolari, Michele Iuliani, Sonia Simonetti, Silvia Cavaliere, Marco Russano, Fabrizio Citarella, Bruno Vincenzi, Silvia Angeletti, Giuseppe Tonini

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Background: Although immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of non–small cell lung cancer (NSCLC), these drugs fail to elicit durable responses in the majority of NSCLC patients. The gut microbiota, able to regulate immune responsiveness, is emerging as a promising, modifiable target to improve ICIs response rates. Since the oral microbiome has been demonstrated to be the primary source of bacterial microbiota in the lungs, we investigated its composition as a potential predictive biomarker to identify and select patients who could benefit from immunotherapy. Methods: Thirty-five patients with stage IV squamous and non-squamous cell NSCLC eligible for an anti-PD-1/PD-L1 as monotherapy were enrolled. Saliva samples were collected from patients prior to the start of treatment, bacterial DNA was extracted using the QIAamp® DNA Microbiome Kit (QIAGEN) and the 16S rRNA gene was sequenced on a MiSeq sequencing instrument (Illumina). Results: NSCLC patients were dichotomized as “Responders” (partial or complete response) and “Non-Responders” (progressive disease), after 12 weeks of treatment, based on RECIST criteria. A prevalence of the phylum Candidatus Saccharibacteria was found in the 10 responders compared to non-responders (abundance 5% vs 1% respectively; p-value = 1.46 x 10-7; False Discovery Rate (FDR) = 1.02 x 10-6). Moreover, a higher prevalence of Saccharibacteria Genera Incertae Sedis genus (belonging to the Candidatus Saccharibacteria phylum) was observed in "responders" (p-value = 6.01 x 10-7 and FDR = 2.46 x 10-5). Finally, the patients who benefit from immunotherapy showed a significant abundance of TM7 Phylum Sp Oral Clone FR058 strain, member of Saccharibacteria Genera Incertae Sedis genus (p-value = 6.13 x 10-7 and FDR=7.66 x 10-5). Conclusions: These preliminary results showed a significant association between oral microbiota and ICIs response in NSCLC patients. In particular, the higher prevalence of Candidatus Saccharibacteria phylum and TM7 Phylum Sp Oral Clone FR058 strain in responders suggests their potential immunomodulatory role. The study is still ongoing and updated data will be presented at the congress.

Keywords: oral microbiota, immune checkpoint inhibitors, non-small cell lung cancer, predictive biomarker

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Authors: Pedro F. D. Oliveira, Rangel S. Maia, Aline S. Paula

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As the electric energy consumption grows, the necessity of energy transmission lines increases. One of the problems caused by an oscillatory response to dynamical loads (such as wind effects) in transmission lines is the cable fatigue. Thus, the dynamical behavior of transmission cables understanding and its control is extremely important. The socioeconomic damage caused by a failure in these cables can be quite significant, from large economic losses to energy supply interruption in large regions. Dynamic Vibration Absorbers (DVA) are oscillatory elements used to mitigate the vibration of a primary system subjected to harmonic excitation. The positioning of Stockbridge (DVA for overhead transmission lines) plays an important role in mitigating oscillations of transmission lines caused by airflows. Nowadays, the positioning is defined by technical standards or commercial software. The aim of this paper is to conduct an analysis of multiple DVAs performances in cable conductors of overhead transmission lines. The cable is analyzed by a finite element method and the model is calibrated by experimental results. DVAs performance is analyzed by evaluating total cable energy, and a study of multiple DVAs positioning is conducted. The results are compared to the existing regulations showing situations where proper positioning, different from the standard, can lead to better performance of the DVA. Results also show situations where the use of multiple DVAs is appropriate.

Keywords: dynamical vibration absorber, finite element method, overhead transmission lines, structural dynamics

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Authors: Desta Gebretekle Shiferaw, Balakrishna Kalluraya

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Oxadiazoles and their derivatives with thioether functionalities represent a new and exciting class of physiologically active heterocyclic compounds. Several molecules with these moieties play a vital role in pharmaceuticals because of their diverse biological activities. This paper describes a new class of 1,3,4- oxadiazole-2-thioethers with acetophenone, coumarin, and N-phenyl acetamide residues (S-alkylation), with the hope that the addition of various biologically active molecules will have a synergistic effect on anticancer activity. The structure of the synthesized title compounds was determined by the combined methods of IR, proton-NMR, carbon-13-NMR, and mass spectrometry. Further, all the newly prepared molecules were assessed against their antioxidant activity. Furthermore, four compounds were assessed for their molecular docking interactions and cytotoxicity activity. The synthesized derivatives have shown moderate antioxidant activity compared to the standard BHA. The IC50 of the tilted molecules (11b, 11c, 13b, and 14b) observed for in vitro anti-cancer activities were 11.20, 15.73, 59.61, and 27.66 g/ml at 72-hour treatment time against the A549 cell lines, respectively. The tested compounds' biological evaluation showed that 11b is the most effective molecule in the series.

Keywords: antioxidant activity, cytotoxicity activity, molecular docking, 1, 3, 4-Oxadiazole-2 thioether derivatives

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Authors: S. Zolghadri, M. Naderi, H. Yousefnia, B. Alirzapour, A. R. Jalilian, A. Ramazani

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Nowadays, 68Ga-DOTATOC has been known as a potential agent for the detection of neuroendocrine tumours and it has indicated higher sensitivity compared with the 111In-Octeroetide. The aim of this study was to evaluate the effectiveness of this new agent in the diagnosis of adenocarcinoma breast cancer. 68Ga-DOTATOC was prepared with the radiochemical purity of higher than 98% and by the specific activity of 39.6 TBq/mmol. 37 MBq of the complex was injected intravenously into the BULB/c mice with adenocarcinoma breast cancer. PET/CT images were acquired after 30, 60 and 90 min post injection demonstrated significant accumulation in the tumour sites. Also, considerable activity was observed in the kidney and bladder as the main routs of excretion. Generally, the results showed that 68Ga-DOTATOC can be considered as a suitable complex for diagnosis of the adenocarcinoma breast cancer using PET procedure.

Keywords: adenocarcinoma breast cancer, 68Ga, octreotide, imaging

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Authors: Yi-Fung Lin, Yuan-Mei Liao

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Background: Pain is common among patients with cancer and is also one of the most disturbing symptoms. As this suffering is subjective, if patients proactively participate in their pain self-management, pain could be alleviated effectively. However, not everyone can carry out self-management very well because human behavior is a product of the cognition process. In this process, we can see that "self-efficacy" plays an essential role in affecting human behaviors. Methods: We used the eight steps of concept analysis proposed by Walker and Avant to clarify the concept of “self-efficacy for cancer pain management.” A comprehensive literature review was conducted for relevant publications that were published during the period of 1977 to 2021. We used several keywords, including self-efficacy, self-management, concept analysis, conceptual framework, and cancer pain, to search the following databases: PubMed, CINAHL, Web of Science, and Embase. Results: We identified three defining attributes for the concept of self-efficacy for cancer pain management, including pain management abilities, confidence, and continuous pain monitoring, and recognized six skills related to pain management abilities: problem-solving, decision-making, resource utilization, forming partnerships between medical professionals and patients, planning actions, and self-regulation. Five antecedents for the concept of self-efficacy for cancer pain management were identified: pain experience, existing cancer pain, pain-related knowledge, a belief in pain management, and physical/mental state. Consequences related to self-efficacy for cancer pain management were achievement of pain self-management, well pain control, satisfying quality of life, and containing motivation. Conclusions: This analysis provides researchers with a clearer understanding of the concept of “self-efficacy for cancer pain management.” The findings presented here provide a foundation for future research and nursing interventions to enhance self-efficacy for cancer pain management.

Keywords: cancer pain, concept analysis, self-efficacy, self-management

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Authors: Danni Cheng

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Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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Authors: Jong-Bae Lee, Seongsoo Lee

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This paper proposes an adaptive discharge time control method to balance cell voltages in alternating battery cell discharging method. In the alternating battery cell discharging method, battery cells are periodically discharged in turn. Recovery effect increases battery output voltage while the given battery cell rests without discharging, thus battery operation time of target system increases. However, voltage mismatch between cells leads two problems. First, voltage difference between cells induces inter-cell current with wasted power. Second, it degrades battery operation time, since system stops when any cell reaches to the minimum system operation voltage. To solve this problem, the proposed method adaptively controls cell discharge time to equalize both cell voltages. In the proposed method, battery operation time increases about 19%, while alternating battery cell discharging method shows about 7% improvement.

Keywords: battery, recovery effect, low-power, alternating battery cell discharging, adaptive discharge time control

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Authors: Hatem A. El-Mezayen, Ahmed Abdelmajeed, Fatehya Metwally, Usama Elsaly, Salwa Atef

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Tumor metastasis involves the dissemination of malignant cells into the basement membrane and vascular system contributes to the circulating pool of these markers. In this context our aim has been focused on development of a non-invasive. Circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with and routine laboratory tests for accurate detection of metastatic breast cancer. Methods: Cytokeratin 18 (CK18), Cytokeratin 19 (CK19), and CA15.3 were assayed in metastatic breast cancer (MBC) patients (75), non-MBC patients (50) and healthy control (20). Results: Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named MBC-CTCs = CA15.3 (U/L) × 0.08 + CK 18 % × 2.9 + CK19 × 3.1– 510. That function correctly classified 87% of metastatic breast cancer at cut-off value = 0.55. (i.e great than 0.55 indicates patients with metastatic breast cancer and less than 0.55 indicates patients with non-metastatic breast cancer). Conclusion: MBC-CTCs is a novel, non-invasive and simple can applied to discriminate patients with metastatic breast cancer.

Keywords: metastatic breast cancer, circulating tumor cells, cytokeratin, EpiCam

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Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely

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Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.

Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)

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Authors: Malik SS, Masood N, Mubarik S, Khadim TM

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Introduction: Xeroderma pigmentosum group G (XPG) gene plays a crucial role in the correction of UV-induced DNA damage through nucleotide excision repair pathway. Single nucleotide polymorphisms in XPG gene have been reported to be associated with different cancers. Current case-control study was designed to evaluate the relationship between one of the most frequently found XPG (rs1047768 T>C) polymorphism and breast cancer risk. Methodology: A total of 200 individuals were screened for this polymorphism including 100 pathologically confirmed breast cancer cases and age-matched 100 controls. Genotyping was carried out using Tetra amplification-refractory mutation system (ARMS) PCR and results were confirmed by gel electrophoresis. Results: Conditional logistic regression analysis showed significant association between TC genotype (OR: 8.9, CI: 2.0 – 38.7) and increased breast cancer risk. Although homozygous CC genotype was more frequent in patients as compared to controls, but it was statistically non-significant (OR: 3.9, CI: 0.4 – 35.7). Conclusion: In conclusion, XPG (rs1047768 T>C) polymorphism may contribute towards increased risk of breast cancer but other polymorphisms may also be evaluated to elucidate their role in breast cancer.

Keywords: XPG, breast cancer, NER, ARMS-PCR

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Authors: Daruliza Kernain, Shaharum Shamsuddin, See Too Wei Cun

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CTCF is a unique, highly conserved and ubiquitously expressed 11 zinc finger (ZF) transcriptional factor with multiple target sites. It is able to bind to various target sequences to perform different regulatory roles including promoter activation or repression, creating hormone-responsive gene silencing element, and functional block of enhancer-promoter interactions. The binding of CTCF to the essential binding site is through the combination of different ZF domain. On the other hand, BORIS for brother of the regulator of imprinted sites, which expressed only in the testis and certain cancer cell line is homology to CTCF 11 ZF domains. Since both transcriptional factors share the same ZF domains hence there is a possibility for both to bind to the same target sequences. In this study, the interaction of these two proteins to multi-functional Y-box DNA/RNA-binding factor, YB-1 was determined. The protein-protein interaction between CTCF/YB-1 and BORIS/YB-1 were discovered by Co-immuno-precipitation (CO-IP) technique through reciprocal experiment from RGBM total cell lysate. The results showed that both CTCF and BORIS were able to interact with YB-1 in Glioma RGBM cell line. To the best of our knowledge, this is the first findings demonstrating the ability of BORIS and YB-1 to form a complex in vivo.

Keywords: immunoprecipitation, CTCF/BORIS/YB-1, transcription factor, molecular medicine

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Authors: Hala M. El-hanbuli, Mohammed F. Darweesh

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The incidence rates of any tumor vary hugely with geographical location. Basal Cell Carcinoma (BCC) is one of the most common skin cancer that has many histopathologic subtypes. Objective: The aim was to study the histopathological features of BCC cases that were received in the Pathology Department, Kasr El-Aini hospital, Cairo University, Egypt during the period from Jan 2004 to Dec 2013 and to evaluate the clinical characters through the patient data available in the request sheets. Methods: Slides and data of BCC cases were collected from the archives of the pathology department, Kasr El-Aini hospital. Revision of all available slides and histological classification of BCC according to WHO (2006) was done. Results: A total number of 310 cases of BCC representing about 65% from the total number of malignant skin tumors examined during the 10-years duration in the department. The age ranged from 8 to 84 years, the mean age was (55.7 ± 15.5). Most of the patients (85%) were above the age of 40 years. There was a slight male predominance (55%). Ulcerated BCC was the most common gross picture (60%), followed by nodular lesion (30%) and finally the ulcerated nodule (10%). Most of the lesions situated in the high-risk sites (77%) where the nose was the most common site (35%) followed by the periocular area (22%), then periauricular (15%) and finally perioral (5%). No lesion was reported outside the head. The tumor size was less than 2 centimeters in 65% of cases, and from 2-5 centimeters in the lesions' greatest dimension in the rest of cases. Histopathological reclassification revealed that the nodular BCC was the most common (68%) followed by the pigmented nodular (18.75%). The histologic high-risk groups represented (7.5%) about half of them (3.75%) being basosquamous carcinoma. The total incidence for multiple BCC and 2nd primary was 12%. Recurrent BCC represented 8%. All of the recurrent lesions of BCC belonged to the histologic high-risk group. Conclusion: Basal Cell Carcinoma is the most common skin cancer in the 10-year survey. Histopathological diagnosis and classification of BCC cases are essential for the determination of the tumor type and its biological behavior.

Keywords: basal cell carcinoma, high risk, histopathological features, statistical analysis

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Authors: Christoph Mayer, Dominik Holzmann

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This paper presents the development of a compact, portable and easy to handle solar cell characterization device. The presented device reduces the effort and cost of single solar cell characterization to a minimum. It enables realistic characterization of cells under sunlight within minutes. In the field of photovoltaic research the common way to characterize a single solar cell or a module is, to measure the current voltage curve. With this characteristic the performance and the degradation rate can be defined which are important for the consumer or developer. The paper consists of the system design description, a summary of the measurement results and an outline for further developments.

Keywords: solar cell, photovoltaics, PV, characterization

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Authors: Tejasvi Parupudi, Mochen Li, Lakshya Mittal, Ignacio G. Camarillo, Raji Sundararajan

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With breast cancer becoming a global pandemic, it is very important to assess a woman’s risk profile accurately in a timely manner. Providing an estimate of the risk of developing breast cancer to a woman gives her an opportunity to consider options to decrease this risk. Women at low risk may be suggested yearly screenings whereas women with a high risk of developing breast cancer would be candidates for aggressive surveillance. Fortunately, there is a set of risk factors that are used to predict the probability of a woman being diagnosed with breast cancer in the future. Studying risk factors and understanding how they correlate to cancer is important for early diagnosis, prevention and reducing mortality rates. The effect of crucial risk factors among black and white women was compared in this study. The various risk factors analyzed include breast density, age, cancer in a first-degree relative, menopausal status, body mass index (BMI) and prior breast cancer diagnosis, etc. Breast density, age at first full-term birth and BMI were utilized in this study as important risk factors for the comparison of incidence rates between women of black and white races in the USA. Understanding the differences could lead to the development of solutions to reduce disparity in mortality rates among black women by improving overall access to care.

Keywords: big data, breast cancer, risk factors, incidence rates, mortality, race

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Authors: Gürol Önal, Kevser Dinçer, Salih Yayla

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In this study, performance of proton exchange membrane PEM fuel cell was experimentally investigated. Coating on the anode side of the PEM fuel cell was accomplished with the spin method by using YSZ+SDC. A solution having 0,1 gr YttriaStabilized Zirconia (YSZ) + 0,1 Samarium-Doped Ceria (SDC) + 10 mL methanol was prepared. This solution was taken out and filled into a micro-pipette. Then the anode side of PEM fuel cell was coated with YSZ+ SDC by using spin method. In the experimental study, current, voltage and power performances before and after coating were recorded and then compared to each other. It was found that the efficiency of PEM fuel cell increases after the coating with YSZ+SDC.

Keywords: fuel cell, Polymer Electrolyte Membrane (PEM), membrane, spin method

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Authors: Huda Al-Awisi, Mohammed Al-Azri, Samira Al-Rasbi, Mansour Al-Moundhri

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Cancer diagnosis is invariably a profound and catastrophic life-changing experience for individuals and their families. It has been found that cancer patients and survivors are distressed with the fragility of their life and their mortality. Based on the literature, cancer patients /survivors value their spiritual experience and connecting with unknown power either related to religious belief or not as an important coping mechanism. Health care professionals including nurses are expected to provide spiritual care for cancer patients as holistic care. Yet, nurses face many challenges in providing such care mainly due to lack of clear definition of spirituality. This study aims to explore coping mechanisms of Omani women diagnosed with breast cancer throughout their cancer journey including spirituality using a qualitative approach. A purposive sample of 19 Omani women diagnosed with breast cancer at different stages of cancer treatment modalities were interviewed. Interviews were tape recorded and transcribed verbatim. The framework approach was used to analyze the data. One main theme related to spirituality was identified and called “The power of faith”. For the majority of participants, faith in God (the will of God) was most important in coping with all stages of their breast cancer experience. Some participants thought that the breast cancer is a test from God which they have to accept. Participants also expressed acceptance of death as the eventual end and reward from God. This belief gives them the strength to cope with cancer and seek medical treatment. In conclusion, women participated in this study believed faith in God imposed spiritual power for them to cope with cancer. They connected spirituality with religious beliefs. Therefore, regardless of nurses’ faith in spirituality, the spiritual care needs to be tailored and provided according to each patient individual need.

Keywords: breast cancer, spiritual, religion, coping, diagnosis, oman, women

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Authors: Šárka Hradilová, Aleš Panáček, Radek Zbořil

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Nanotechnologies are considered the most promising fields with high added value, brings new possibilities in various sectors from industry to medicine. With the growing of interest in nanomaterials and their applications, increasing nanoparticle production leads to increased exposure of people and environment with ‘human made’ nanoparticles. Nanoparticles (NPs) are clusters of atoms in the size range of 1–100 nm. Metal nanoparticles represent one of the most important and frequently used types of NPs due to their unique physical, chemical and biological properties, which significantly differ from those of bulk material. Biological properties including toxicity of metal nanoparticles are generally determined by their size, size distribution, shape, surface area, surface charge, surface chemistry, stability in the environment and ability to release metal ions. Therefore, the biological behavior of NPs and their possible adverse effect cannot be derived from the bulk form of material because nanoparticles show unique properties and interactions with biological systems just due to their nanodimensions. Silver and gold NPs are intensively studied and used. Both can be used for instance in surface enhanced Raman spectroscopy, a considerable number of applications of silver NPs is associated with antibacterial effects, while gold NPs are associated with cancer treatment and bio imaging. Antibacterial effects of silver ions are known for centuries. Silver ions and silver-based compounds are highly toxic to microorganisms. Toxic properties of silver NPs are intensively studied, but the mechanism of cytoxicity is not fully understood. While silver NPs are considered toxic, gold NPs are referred to as toxic but also innocuous for eukaryotic cells. Therefore, gold NPs are used in various biological applications without a risk of cell damaging, even when we want to suppress the growth of cancer cells. Thus, gold NPs are toxic or harmless. Because most studies comparing particles of various sizes prepared in various ways, and testing is performed on different cell lines, it is very difficult to generalize. The novelty and significance of our research is focused to the complex biological effects of silver and gold NPs prepared by the same method, have the same parameters and the same stabilizer. That is why we can compare the biological effects of pure nanometals themselves based on their chemical nature without the influence of other variable. Aim of our study therefore is to compare the cytotoxic effect of two types of noble metal NPs focusing on the mechanisms that contribute to cytotoxicity. The study was conducted on murine fibroblasts by selected common used tests. Each of these tests monitors the selected area related to toxicity and together provides a comprehensive view on the issue of interactions of nanoparticles and living cells.

Keywords: cytotoxicity, gold nanoparticles, mechanism of cytotoxicity, silver nanoparticles

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Authors: Yujie Yuan, Yiyang Fan, Hong Fan

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Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

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Authors: Yori Gidron, Laura Caton, Irit Ben-Aharon

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Background: Many patients and even certain clinicians attribute cancer development to psychosocial factors. Yet, empirical data supports more the prognostic role, rather than the etiological role, of psychosocial factors in cancer. Part of the inconsistency may result from not considering possible moderating factors in the etiological role of psychosocial factors. One important candidate moderating factor is the vagal nerve, whose activity is indexed by heart-rate variability (HRV). The vagal nerve may prevent cancer since it reduces inflammation on the one hand, and since it increases anti-tumor immunity on the other hand. This study examined the moderating role of the vagus in the relation between life threatening events (LTE) and cancer development. Method: We re-analyzed data from the Lifelines Dutch longitudinal cohort study of over 150,000 people. The present study included 82,751 adults, who initially were cancer-free. We extracted information on background factors (e.g., age, gender, fat consumption), whether they ever experienced LTE, HRV and cancer diagnosis as reported by patients in annual clinic visits. HRV was derived from brief ECGs. Results: Of the full sample, 1011 people developed cancer during a follow-up. In the full sample, LTE significantly predicted cancer development (R.R = 1.063 p < .01) and HRV significantly predicted a reduced risk of cancer development (R.R = .506 p <.001). Importantly, LTE significantly predicted cancer only when HRV was low (R.R = 1.056, 95% CI: 1.007 - 1.108, p < .05) but not when HRV was high (R.R = 1.014; 95% CI: 0.916 - 1.122, p > 0.05), independent of confounders. Conclusions: To the best of our knowledge, this is the first study showing in a large sample that LTE predict cancer development, and that this occurs only when vagal nerve activity (HRV) is relatively low. These results could result from lack of vagal modulation of inflammation and also from lack of vagal modulation of stress responses. Results are in line with the cancer-protective role of the vagus. HRV needs to be routinely monitored in the population and future intervention trials need to examine whether vagal nerve activation can prevent cancer in people with LTE and with other cancer risk factors.

Keywords: cancer development, life-events, moderation, vagal nerve

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Authors: Nkechi V. Enwuru, Bullum Nkeki, Elizabeth A. Adekoya, Olumide A. Adebesin, Rebecca F. Peters, Victoria A. Aikhomu, Mendie E. U.

Abstract:

Background: Probiotics are live microbial feed supplement beneficial for host. Probiotics and their postbiotic products have been used to prevent or treat various health conditions. However, the products cell viability is often low due to harsh conditions subjected during processing, handling, storage, and gastrointestinal transit. These strongly influence probiotics’ benefits; thus, viability is essential for probiotics to produce health benefits for the host. Microencapsulation is a promising technique with considerable effects on probiotic survival. The study is aimed to formulate a microencapsulated probiotic and evaluate its viability, antimicrobial efficacy, and cytotoxic activity of its postbiotic on the MCF-7 breast cancer cell line. Method: Human and animal raw milk were sampled for lactic acid bacteria. The isolated bacteria were identified using conventional and VITEK 2 systems. The identified lactic acid bacterium was encapsulated using spray-dried and extrusion methods. The free, encapsulated, and chitosan-coated encapsulated probiotics were tested for viability in simulated-gastric intestinal (SGI) fluid and different storage conditions at refrigerated (4oC) and room (25oC) temperatures. The disintegration time and weight uniformity of the spray-dried hard gelatin capsules were tested. The antimicrobial property of free and encapsulated probiotics was tested against enteric pathogenic isolates from antiretroviral therapy (ART) treated HIV-positive patients. The postbiotic of the free cells was extracted, and its cytotoxic effect on the MCF-7 breast cancer cell line was tested through an MTT assay. Result: The Lactobacillus plantarum was isolated from animal raw milk. Zero-size hard gelatin L. plantarum capsules with granules within a size range of 0.71–1.00 mm diameter was formulated. The disintegration time ranges from 2.14±0.045 to 2.91±0.293 minutes, while the average weight is 502.1mg. Simulated gastric solution significantly affected viability of both free and microcapsules. However, the encapsulated cells were more protected and viable due to impermeability in the microcapsules. Furthermore, the viability of free cells stored at 4oC and 25oC were less than 4 log CFU/g and 6 log CFU/g respectively after 12 weeks. However, the microcapsules stored at 4oC achieved the highest viability among the free and microcapsules stored at 25oC and the free cells stored at 4oC. Encapsulated cells were released in the simulated gastric fluid, viable and effective against the enteric pathogens tested. However, chitosan-coated calcium alginate encapsulated probiotics significantly inhibited Shigella flexneri, Candida albicans, and Escherichia coli. The Postbiotic Metabolites (PM) of L. plantarum produced a cytotoxic effect on the MCF-7 breast cancer cell line. The postbiotic showed significant cytotoxic activity similar to 5FU, a standard antineoplastic agent. The inhibition concentration of 50% growth (IC50) of postbiotic metabolite K3 is low and consistent with the IC50 of the positive control (Cisplatin). Conclusions: Lactobacillus plantarum postbiotic exhibited a cytotoxic effect on the MCF-7 breast cancer cell line and could be used as combined adjuvant therapy in breast cancer management. The microencapsulation technique protects the probiotics, improving their viability and delivery to the gastrointestinal tract. Chitosan enhances antibacterial efficacy; thus, chitosan-coated microencapsulated L. plantarum probiotics could be more effective and used as a combined therapy in HIV management of opportunistic enteric infection.

Keywords: probiotics, encapsulation, gastrointestinal conditions, antimicrobial effect, postbiotic, cytotoxicity effect

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Authors: Sourav Sarkar, Manashjit Gogoi

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In the evolving landscape of cancer diagnostics, optical biosensing has emerged as a promising tool due to its sensitivity and specificity. This study explores the potential of CdS/ZnS core-shell quantum dots (QDs) capped with 3-Mercaptopropionic acid (3-MPA), which aids in the linking chemistry of QDs to various cancer antibodies. The QDs, with their unique optical and electronic properties, have been integrated into the biosensor design. Their high quantum yield and size-dependent emission spectra have been exploited to improve the sensor’s detection capabilities. The study presents the design of this QD-enhanced optical biosensor. The use of these QDs can also aid multiplexed detection, enabling simultaneous monitoring of different cancer biomarkers. This innovative approach holds significant potential for advancing cancer diagnostics, contributing to timely and accurate detection. Future work will focus on optimizing the biosensor design for clinical applications and exploring the potential of QDs in other biosensing applications. This study underscores the potential of integrating nanotechnology and biosensing for cancer research, paving the way for next-generation diagnostic tools. It is a step forward in our quest for achieving precision oncology.

Keywords: quantum dots, biosensing, cancer, device

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Authors: A. R. Diniz, P. Borrego, I. Bártolo, N. Taveira

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Cell-to-cell transmission plays a critical role in the spread of HIV-1 infection in vitro and in vivo. Inhibition of HIV-1 cell-associated infection by antiretroviral drugs and neutralizing antibodies (NAbs) is more difficult compared to cell-free infection. Limited data exists on cell-associated infection by HIV-2 and its inhibition. In this work, we determined the ability of entry inhibitors to inhibit HIV-1 and HIV-2 cell-to cell fusion as a proxy to cell-associated infection. We developed a method in which Hela-CD4-cells are first transfected with a Tat expressing plasmid (pcDNA3.1+/Tat101) and infected with recombinant vaccinia viruses expressing either the HIV-1 (vPE16: from isolate HTLV-IIIB, clone BH8, X4 tropism) or HIV-2 (vSC50: from HIV-2SBL/ISY, R5 and X4 tropism) envelope glycoproteins (M.O.I.=1 PFU/cell).These cells are added to TZM-bl cells. When cell-to-cell fusion (syncytia) occurs the Tat protein diffuses to the TZM-bl cells activating the expression of a reporter gene (luciferase). We tested several entry inhibitors including the fusion inhibitors T1249, T20 and P3, the CCR5 antagonists MVC and TAK-779, the CXCR4 antagonist AMD3100 and several HIV-2 neutralizing antibodies (Nabs). All compounds inhibited HIV-1 and HIV-2 cell fusion albeit to different levels. Maximum percentage of HIV-2 inhibition (MPI) was higher for fusion inhibitors (T1249- 99.8%; P3- 95%, T20-90%) followed by co-receptor antagonists (MVC- 63%; TAK-779- 55%; AMD3100- 45%). NAbs from HIV-2 infected patients did not prevent cell fusion up to the tested concentration of 4μg/ml. As for HIV-1, MPI reached 100% with TAK-779 and T1249. For the other antivirals, MPIs were: P3-79%; T20-75%; AMD3100-61%; MVC-65%.These results are consistent with published data. Maraviroc had the lowest IC50 both for HIV-2 and HIV-1 (IC50 HIV-2= 0.06 μM; HIV-1=0.0076μM). Highest IC50 were observed with T20 for HIV-2 (3.86μM) and with TAK-779 for HIV-1 (12.64μM). Overall, our results show that entry inhibitors in clinical use are less effective at preventing Env mediated cell-to-cell-fusion in HIV-2 than in HIV-1 which suggests that cell-associated HIV-2 infection will be more difficult to inhibit compared to HIV-1. The method described here will be useful to screen for new HIV entry inhibitors.

Keywords: cell-to-cell fusion, entry inhibitors, HIV, NAbs, vaccinia virus

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Authors: Mustafa M. Donma, Orkide Donma

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A growing list of cancers might be influenced by obesity. Obesity is associated with an increased risk for the occurrence and development of some cancers. Inflammation can lead to cancer. It is one of the characteristic features of cancer and plays a critical role in cancer development. C-reactive protein (CRP) is under evaluation related to the new and simple prognostic factors in patients with metastatic renal cell cancer. Obesity can predict and promote systemic inflammation in healthy adults. BMI is correlated with hs-CRP. In this study, SII index and CRP values were evaluated in children with normal BMI and those within the range of different obesity grades to detect the tendency towards cancer in pediatric obesity. A total of one hundred and ninety-four children; thirty-five children with normal BMI, twenty overweight (OW), forty-seven obese (OB) and ninety-two morbid obese (MO) participated in the study. Age- and sex-matched groups were constituted using BMI-for age percentiles. Informed consent was obtained. Ethical Committee approval was taken. Weight, height, waist circumference (C), hip C, head C and neck C of the children were measured. The complete blood count test was performed. C-reactive protein analysis was performed. Statistical analyses were performed using SPSS. The degree for statistical significance was p≤0.05. SII index values were progressively increasing starting from normal weight (NW) to MO children. There is a statistically significant difference between NW and OB as well as MO children. No significant difference was observed between NW and OW children, however, a correlation was observed between NW and OW children. MO constitutes the only group, which exhibited a statistically significant correlation between SII index and CRP. Obesity-related bladder, kidney, cervical, liver, colorectal, endometrial cancers are still being investigated. Obesity, characterized as a chronic low-grade inflammation, is a crucial risk factor for colon cancer. Elevated childhood BMI values may be indicative of processes leading to cancer, initiated early in life. Prevention of childhood adiposity may decrease the cancer incidence in adults. To authors’ best knowledge, this study is the first to introduce SII index values during obesity of varying degrees of severity. It is suggested that this index seems to affect all stages of obesity with an increasing tendency and may point out the concomitant status of obesity and cancer starting from very early periods of life.

Keywords: children, C-reactive protein, systemic immune-inflammation index, obesity

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Authors: Ambika Selvaraj

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Magnetic iron oxide nanoparticles (IO) of < 20nm (superparamagnetic) become promising tool in cancer therapy, and integrated nanodevices for cancer detection and screening. The obstacles include particle heterogeneity and cost. It can be overcome by developing monodispersed nanoparticles in economical approach. We have successfully synthesized < 7 nm IO by low temperature controlled technique, in which Fe0 is sandwiched between stabilizer and Fe2+. Size analysis showed the excellent size control from 31 nm at 33°C to 6.8 nm at 10°C. Resultant monodispersed IO were found to be stable for > 50 reuses, proved its applicability in biomedical applications.

Keywords: low temperature synthesis, hybrid iron nanoparticles, cancer therapy, biomedical applications

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Authors: Vitor Rafael Regiani, Carlos Henrique Viesi Do Nascimento Filho, Patricia Matos Biselli-Chicote, Claudia Aparecida Rainho, Luiz Sergio Raposo, José Victor Maniglia, Eny Maria Goloni-Bertollo, Erika Cristina Pavarino

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Promoter hypermethylation of tumor-related genes has been associated with prognosis in early-stage head-and-neck cancers, providing strong evidence that these hypermethylated genes are valuable biomarkers for prognostic evaluation. Hence, we selected the MGMT and RASSF1A genes to examine the methylation status in head and neck squamous cell carcinomas (HNSCC) samples matched with non-tumor tissues (tumor-surrounding tissues or peripheral blood samples). DNA methylation analysis was based on Methylation-Sensitive High Resolution Melting, and the methylation status was correlated with clinic-pathological characteristics of the patients. RASSF1A and MGMT promoter methylation was detected in 43.24% (16/37) and in 44.44% (16/36) of the tumors, respectively. RASSF1A and MGMT methylation was significantly more frequent in tumor tissue than non-tumor tissues, as well as, simultaneous methylation of RASSF1A and MGMT also was higher in tumor tissue than non-tumor tissues. In relation to anatomic site, larynx cancer presented significant methylation of MGMT gene compared to tumor-surrounding tissue. The frequency of RASSF1A and MGMT promoter methylated was higher in tumor tissues in relation to peripheral blood from the same patient. No association was found between methylation and the variables analyzed, including gender, age, smoking or alcohol drinking habits. Clinic-pathological characteristics also showed no association in the presence of methylation. The Kaplan–Meier's method showed no association of methylation and both disease-free and overall survival. In conclusion, the presence of epigenetic abnormalities in normal-appearing tissue corroborates the hypothesis of the ‘field cancerization', or it can reflect preneoplastic and/or preinvasive. Moreover, MGMT methylation may serve as an important laryngeal cancer biomarker because it showed significant difference between laryngeal cancer and surrounding tumor tissues.

Keywords: head and neck cancer, DNA methylation, MGMT promoter methylation, RASSF1A promoter methylation

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Authors: Joseph George, Anne Kotteswara Roa

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Skin disease is one of the most common and popular kinds of health issues faced by people nowadays. Skin cancer (SC) is one among them, and its detection relies on the skin biopsy outputs and the expertise of the doctors, but it consumes more time and some inaccurate results. At the early stage, skin cancer detection is a challenging task, and it easily spreads to the whole body and leads to an increase in the mortality rate. Skin cancer is curable when it is detected at an early stage. In order to classify correct and accurate skin cancer, the critical task is skin cancer identification and classification, and it is more based on the cancer disease features such as shape, size, color, symmetry and etc. More similar characteristics are present in many skin diseases; hence it makes it a challenging issue to select important features from a skin cancer dataset images. Hence, the skin cancer diagnostic accuracy is improved by requiring an automated skin cancer detection and classification framework; thereby, the human expert’s scarcity is handled. Recently, the deep learning techniques like Convolutional neural network (CNN), Deep belief neural network (DBN), Artificial neural network (ANN), Recurrent neural network (RNN), and Long and short term memory (LSTM) have been widely used for the identification and classification of skin cancers. This survey reviews different DL techniques for skin cancer identification and classification. The performance metrics such as precision, recall, accuracy, sensitivity, specificity, and F-measures are used to evaluate the effectiveness of SC identification using DL techniques. By using these DL techniques, the classification accuracy increases along with the mitigation of computational complexities and time consumption.

Keywords: skin cancer, deep learning, performance measures, accuracy, datasets

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Authors: Anik Barua, Rabiul Hossain, Labonno Barua, Rashadul Hossain, Nurul Absar

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Background: Globally, the burden of cancer is increasing consistently. Modern cancer therapies include lots of toxicity in the non-targeted organs reducing the life expectancy of the patients. Hence, scientists are trying to seek noble compounds from natural sources to treat cancer. Objectives: The objectives of the present study are to evaluate the phytochemicals, in vitro antioxidants, and in vivo and in silico anticancer study of various solvent fractions of Tinospora cordifolia (Willd.). Methodology: In this experiment, standard quantitative and qualitative assay methods were used to analyze the phytochemicals. The antioxidant activity was measured using the DPPH and ABTS scavenging methods. The in vivo antitumor activity is evaluated against Ehrlich ascites carcinoma (EAC) cell bearing in Swiss albino mice. In-silico ADME/T and molecular docking study were performed to assess the potential of stated phytochemicals against Transcription Factor STAT3b/DNA Complex of adenocarcinoma. Findings: Phytochemical screening confirmed the presence of flavonoids, alkaloids, glycosides, tannins, and carbohydrates. A significant amount of phenolic (20.19±0.3 mg/g GAE) and flavonoids (9.46±0.18 mg/g GAE) were found in methanolic extract in quantitative screening. Tinospora cordifolia methanolic extract showed promising DPPH and ABTS scavenging activity with the IC50 value of 1222.99 µg/mL and 1534.34 µg/mL, respectively, which was concentration dependent. In vivo anticancer activity in EAC cell-bearing mice showed significant (P < 0.05) percent inhibition of cell growth (60.12±1.22) was found at the highest dose compared with standard drug 5-Fluorouracil (81.18±1.28). Forty-two phytochemicals exhibit notable pharmacokinetics properties and passed drug-likeness screening tests in silico. In molecular docking study, (25S)-3Beta-acetoxy-5-alpha-22-beta-spirost-9(11)-en-12-beta-ol showed docking score (-8.5 kJ/mol) with significant non-bonding interactions with target enzyme. Conclusions: The results were found to be significant and confirmed that the methanolic extract of Tinospora cordifolia has remarkable antitumor activity with antioxidant potential. The Tinospora cordifolia methanolic extract may be considered a potent anticancer agent for advanced research.

Keywords: anticancer, antioxidant, Tinospora cordifolia, EAC cell

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Authors: Rahul Agarwal, Ashutosh Singh

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Colorectal cancer (CRC) also refers as bowel cancer or colon cancer. It involves the development of abnormal growth of cells in colon or rectum part of the body. This work leads to the development of a miRNA database in colorectal cancer. We named this database- miCoRe. This database comprises of all validated colon-rectal cancer miRNAs information from various published literature with an effectual knowledge based information retrieval system. miRNAs have been collected from various published literature reports. MySQL is used for main-framework of miCoRe while the front-end was developed in PHP script. The aim of developing miCoRe is to create a comprehensive central repository of colorectal carcinoma miRNAs with all germane information of miRNAs and their target genes. The current version of miCoRe consists of 238 miRNAs which are known to be implicated in malignancy of CRC. Alongside with miRNA information, miCoRe also contains the information related to the target genes of these miRNA. miCoRe furnishes the information about the mechanism of incidence and progression of the disease, which would further help the researchers to look for colorectal specific miRNAs therapies and CRC specific targeted drug designing. Moreover, it will also help in development of biomarkers for the better and early detection of CRC and will help in better clinical management of the disease.

Keywords: colorectal cancer, database, miCoRe, miRNAs

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Authors: Elham A. Alsadoon, Hamadah B. Alsadoon

Abstract:

Educators try to design learning environments that are preferred by their students. With the wide-spread adoption of cell phones surpassing any other technology, educators should not fail to invest in the power of such technology. This study aimed to explore the current use of cell phones in education among Saudi students in Saudi universities and how students perceive such use. Data was collected from 237 students at King Saud University. Descriptive analysis was used to analyze the data. A T-test for independent groups was used to examine whether there was a significant difference between males and females in their perception of using cell phones in education. Findings suggested that students have a positive attitude toward the use of cell phones in education. The most accepted use was for sending notification to students, which has already been experienced through the Twasel system provided by King Saud University. This electronic system allows instructors to easily send any SMS or email to their students. The use of cell phone applications came in the second rank of using cell phones in education. Students have already experienced the benefits of having these applications handy wherever they go. On the other hand, they did not perceive using cell phones for assessment as practical educational usage. No gender difference was detected in terms of students’ perceptions toward using cell phones in education.

Keywords: cell phone, mobile learning, educational sciences, education

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Authors: Leah Ning

Abstract:

This paper discusses the development of a machine learning algorithm that accurately detects metastatic breast cancer (cancer has spread elsewhere from its origin part) in selected images that come from pathology scans of lymph node sections. Being able to develop an accurate artificial intelligence (AI) algorithm would help significantly in breast cancer diagnosis since manual examination of lymph node scans is both tedious and oftentimes highly subjective. The usage of AI in the diagnosis process provides a much more straightforward, reliable, and efficient method for medical professionals and would enable faster diagnosis and, therefore, more immediate treatment. The overall approach used was to train a convolution neural network (CNN) based on a set of pathology scan data and use the trained model to binarily classify if a new scan were benign or malignant, outputting a 0 or a 1, respectively. The final model’s prediction accuracy is very high, with 100% for the train set and over 70% for the test set. Being able to have such high accuracy using an AI model is monumental in regard to medical pathology and cancer detection. Having AI as a new tool capable of quick detection will significantly help medical professionals and patients suffering from cancer.

Keywords: breast cancer detection, AI, machine learning, algorithm

Procedia PDF Downloads 75