Search results for: in vitro and in vivo cancer therapy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4952

Search results for: in vitro and in vivo cancer therapy

2852 Assessment of Antioxidant Activities in Roots of Miswak (Salvadora persica) Plants Grown at Two Different Locations in Saudi Arabia

Authors: Mohamed M. Ibrahima, Abdul Aziz A.AL Sahli, Ibrahim A. Alaraidh, Ali A. Al-Homaidan, E.M. Mostafa, G.A. EL-Gaaly

Abstract:

Traditionally, in Middle Eastern countries, many cultures use chewing sticks of arak for medicinal purposes especially, for oral cleanliness care. It was used by Muslims for the treatment of teeth and highly recommended to be used by muslims during the whole day. Therefore, the present work aimed to determine the total phenolic content and total flavonoids in two Miswak extracts obtained from arak roots collected from two different localities in Saudi Arabia. They were extracted with aqueous ethanol (80%) and used to estimate in vitro their antioxidative abilities. The new findings showed that the two tested extracts contained significantly different amounts of both total phenolic content and total flavonoids. According to the increase of total phenolic contents and total flavonoids obtained from the two extracts, Miswak collected from the southern region was found to contain more contents than those collected from the middle region. The results of antioxidant activities of Miswak root extract obtained by using different in vitro methods were varied depending on the technique used. According to the malondialdehyde (MDA) method, hydrogen peroxide (H2O2) scavenging ability and 1,1-diphenyl-2-picrylhydrazyl (DPPH) methods, the two Miswak extracts exhibited to have high to very high antioxidant activities. Mostly, the values of antioxidant activities of Southern region have been shown to be always the highest.

Keywords: Arak, antioxidant, medicinal plants, Saudi Arabia

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2851 Blood Thicker Than Water: A Case Report on Familial Ovarian Cancer

Authors: Joanna Marie A. Paulino-Morente, Vaneza Valentina L. Penolio, Grace Sabado

Abstract:

Ovarian cancer is extremely hard to diagnose in its early stages, and those afflicted at the time of diagnosis are typically asymptomatic and in the late stages of the disease, with metastasis to other organs. Ovarian cancers often occur sporadically, with only 5% associated with hereditary mutations. Mutations in the BRCA1 and BRCA2 tumor suppressor genes have been found to be responsible for the majority of hereditary ovarian cancers. One type of ovarian tumor is Malignant Mixed Mullerian Tumor (MMMT), which is a very rare and aggressive type, accounting for only 1% of all ovarian cancers. Reported is a case of a 43-year-old G3P3 (3003), who came into our institution due to a 2-month history of difficulty of breathing. Family history reveals that her eldest and younger sisters both died of ovarian malignancy, with her younger sister having a histopathology report of endometrioid ovarian carcinoma, left ovary stage IIIb. She still has 2 asymptomatic sisters. Physical examination pointed to pleural effusion of right lung, and presence of bilateral ovarian new growth, which had a Sassone score of 13. Admitting Diagnosis was G3P3 (3003), Ovarian New Growth, bilateral, Malignant; Pleural effusion secondary to malignancy. BRCA was requested to establish a hereditary mutation; however, the patient had no funds. Once the patient was stabilized, TAHBSO with surgical staging was performed. Intraoperatively, the pelvic cavity was occupied by firm, irregularly shaped ovaries, with a colorectal metastasis. Microscopic sections from both ovaries and the colorectal metastasis had pleomorphic tumor cells lined by cuboidal to columnar epithelium exhibiting glandular complexity, displaying nuclear atypia and increased nuclear-cytoplasmic ratio, which are infiltrating the stroma, consistent with the features of Malignant Mixed Mullerian Tumor, since MMMT is composed histologically of malignant epithelial and sarcomatous elements. In conclusion, discussed is the clinic-pathological feature of a patient with primary ovarian Malignant Mixed Mullerian Tumor, a rare malignancy comprising only 1% of all ovarian neoplasms. Also, by understanding the hereditary ovarian cancer syndromes and its relation to this patient, it cannot be overemphasized that a comprehensive family history is really fundamental for early diagnosis. The familial association of the disease, given that the patient has two sisters who were diagnosed with an advanced stage of ovarian cancer and succumbed to the disease at a much earlier age than what is reported in the general population, points to a possible hereditary syndrome which occurs in only 5% of ovarian neoplasms. In a low-resource setting, being in a third world country, the following will be recommended for monitoring and/or screening women who are at high risk for developing ovarian cancer, such as the remaining sisters of the patient: 1) Physical examination focusing on the breast, abdomen, and rectal area every 6 months. 2) Transvaginal sonography every 6 months. 3) Mammography annually. 4) CA125 for postmenopausal women. 5) Genetic testing for BRCA1 and BRCA2 will be reserved for those who are financially capable.

Keywords: BRCA, hereditary breast-ovarian cancer syndrome, malignant mixed mullerian tumor, ovarian cancer

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2850 In vitro Antimicrobial Resistance Pattern of Bovine Mastitis Bacteria in Ethiopia

Authors: Befekadu Urga Wakayo

Abstract:

Introduction: Bacterial infections represent major human and animal health problems in Ethiopia. In the face of poor antibiotic regulatory mechanisms, development of antimicrobial resistance (AMR) to commonly used drugs has become a growing health and livelihood threat in the country. Monitoring and control of AMR demand close coloration between human and veterinary services as well as other relevant stakeholders. However, risk of AMR transfer from animal to human population’s remains poorly explored in Ethiopia. This systematic research literature review attempted to give an overview on AMR challenges of bovine mastitis bacteria in Ethiopia. Methodology: A web based research literature search and analysis strategy was used. Databases are considered including; PubMed, Google Scholar, Ethiopian Veterinary Association (EVA) and Ethiopian Society of Animal Production (ESAP). The key search terms and phrases were; Ethiopia, dairy, cattle, mastitis, bacteria isolation, antibiotic sensitivity and antimicrobial resistance. Ultimately, 15 research reports were used for the current analysis. Data extraction was performed using a structured Microsoft Excel format. Frequency AMR prevalence (%) was registered directly or calculated from reported values. Statistical analysis was performed on SPSS – 16. Variables were summarized by giving frequencies (n or %), Mean ± SE and demonstrative box plots. One way ANOVA and independent t test were used to evaluate variations in AMR prevalence estimates (Ln transformed). Statistical significance was determined at p < 0.050). Results: AMR in bovine mastitis bacteria was investigated in a total of 592 in vitro antibiotic sensitivity trials involving 12 different mastitis bacteria (including 1126 Gram positive and 77 Gram negative isolates) and 14 antibiotics. Bovine mastitis bacteria exhibited AMR to most of the antibiotics tested. Gentamycin had the lowest average AMR in both Gram positive (2%) and negative (1.8%) bacteria. Gram negative mastitis bacteria showed higher mean in vitro resistance levels to; Erythromycin (72.6%), Tetracycline (56.65%), Amoxicillin (49.6%), Ampicillin (47.6%), Clindamycin (47.2%) and Penicillin (40.6%). Among Gram positive mastitis bacteria higher mean in vitro resistance was observed in; Ampicillin (32.8%), Amoxicillin (32.6%), Penicillin (24.9%), Streptomycin (20.2%), Penicillinase Resistant Penicillin’s (15.4%) and Tetracycline (14.9%). More specifically, S. aurues exhibited high mean AMR against Penicillin (76.3%) and Ampicillin (70.3%) followed by Amoxicillin (45%), Streptomycin (40.6%), Tetracycline (24.5%) and Clindamycin (23.5%). E. coli showed high mean AMR to Erythromycin (78.7%), Tetracycline (51.5%), Ampicillin (49.25%), Amoxicillin (43.3%), Clindamycin (38.4%) and Penicillin (33.8%). Streptococcus spp. demonstrated higher (p =0.005) mean AMR against Kanamycin (> 20%) and full sensitivity (100%) to Clindamycin. Overall, mean Tetracycline (p = 0.013), Gentamycin (p = 0.001), Polymixin (p = 0.034), Erythromycin (p = 0.011) and Ampicillin (p = 0.009) resistance increased from the 2010’s than the 2000’s. Conclusion; the review indicated a rising AMR challenge among bovine mastitis bacteria in Ethiopia. Corresponding, public health implications demand a deeper, integrated investigation.

Keywords: antimicrobial resistance, dairy cattle, Ethiopia, Mastitis bacteria

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2849 Pharmacokinetics, Dosage Regimen and in Vitro Plasma Protein Binding of Danofloxacin following Intravenous Administration in Adult Buffaloes

Authors: Zahid Manzoor, Shaukat Hussain Munawar, Zahid Iqbal, Imran Ahmad Khan, Abdul Aziz, Hafiz Muhammad Qasim

Abstract:

The present study was aimed to investigate the pharmacokinetics behavior and optimal dosage regimen of danofloxacin in 8 adult healthy buffaloes of local breed (Nili Ravi) following single intravenous administration at the dose of 2.5 mg/kg body weight. Plasma drug concentrations at various time intervals were measured by HPLC method. In vitro plasma protein binding was determined employing the ultrafiltration technique. The distribution and elimination of danofloxacin was rapid, as indicated by the values (Mean±SD) of distribution half-life (t1/2α = 0.25±0.09 hours) and elimination half life (t1/2β = 3.26±0.43 hours), respectively. Volume of distribution at steady state (Vss) was 1.14±0.12 L/kg, displaying its extensive distribution into various body fluids and tissues. The high value of AUC (9.80±2.14 µg/ml.hr) reflected the vast area of the body covered by drug concentration. The mean residence time was noted to be 4.78±0.52 hours. On the basis of pharmacokinetic parameters, a suitable intravenous regimen for danofloxacin in adult buffaloes would be 6.5 mg/kg to be repeated after 12 hours intervals. The present study is the foremost pharmacokinetic study of danofloxacin in the local species which would provide the valueable contribution in the local manufacturing of danofloxacin in Pakistan in future.

Keywords: danofloxacin, pharmacokinetics, plasma protein binding, buffaloes, dosage regimen

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2848 Anti-Nutritional Factors, In-Vitro Trypsin, Chymotrypsin and Peptidase Multi Enzyme Protein Digestibility of Some Melon (Egusi) Seeds and Their Protein Isolates

Authors: Joan O. Ogundele, Aladesanmi A. Oshodi, Adekunle I. Amoo

Abstract:

Abstract In-vitro multi-enzyme protein digestibility (IVMPD) and some anti-nutritional factors (ANF) of five melon (egusi) seed flours (MSF) and their protein isolates (PI) were carried out. Their PI have potentials comparable to that of soya beans. It is important to know the IVMPD and ANF of these protein sources as to ensure their safety when adapted for use as alternate protein sources to substitute for cow milk, which is relatively expensive in Nigeria. Standard methods were used to produce PI of Citrullus colocynthis, Citrullus vulgaris, African Wine Kettle gourd (Lageneria siceraria I), Basket Ball gourd (Lagenaria siceraria II) and Bushel Giant Gourd (Lageneria siceraria III) seeds and to determine the ANF and IVMPD of the MSF and PI unheated and at 37oC. Multi-enzymes used were trypsin, chymotrypsin and peptidase. IVMPD of MSF ranged from (70.67±0.70) % (C. vulgaris) to (72.07± 1.79) % (L.siceraria I) while for their PI ranged from 74.33% (C.vulgaris) to 77.55% (L.siceraria III). IVMPD of the PI were higher than those of MSF. Heating increased IVMPD of MSF with average value of 79.40% and those of PI with average of 84.14%. ANF average in MSF are tannin (0.11mg/g), phytate (0.23%). Differences in IVMPD of MSF and their PI at different temperatures may arise from processing conditions that alter the release of amino acids from proteins by enzymatic processes. ANF in MSF were relatively low, but were found to be lower in the PI, therefor making the PI safer for human consumption as an alternate source of protein.

Keywords: Anti-nutrients, Enzymatic protein digestibility, Melon (egusi)., Protein Isolates.

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2847 The Modulation of Health and Inflammatory Status in Young Pigs by Grape Waste Enriched in Polyphenols

Authors: Gina Cecilia Pistol, Loredana Calin, Mariana Stancu, Veronica Chedea, Ionelia Taranu

Abstract:

Inflammatory-associated diseases have an increased trend in the past decades. The pharmacological strategies aimed to treat these inflammatory diseases are very expensive and with non-beneficial results. The current trend is to find alternative strategies to counteract or to control inflammatory component of diseases. The grape by-products either seeds or pomace are rich in bioactive compounds (e.g. polyphenols) which may be beneficial in prevention of inflammation associated with cancer progression and other pathologies with inflammatory component. The in vivo models are very useful for studying the immune and inflammatory status. The domestic pig (Sus scrofa domesticus) is related to human from anatomic and physiologic point of view, representing a feasible model for studying the human inflammatory pathologies. Starting from these data, we evaluated the effect of a diet containing 5% grape seed cakes (GS) on piglets blood biochemical parameters and immune pro- and anti-inflammatory biomarkers (IL-1 beta, IL-8, TNF-alpha, IL-6, IFN-gamma, IL-10, IL-4) in spleen and lymph nodes. 12 weaned piglets were fed for 30 days with a control diet or an experimental diet containing 5% GS. At the end of trial, plasma and tissue samples (spleen and lymph nodes) were collected and the biochemical and inflammatory markers were analysed by using biochemistry analyser and ELISA techniques. Our results showed that diet included 5% GS did not influence the health status determined by plasma biochemical parameters. Only a tendency for a slight increase of the biochemical parameters associated with energetic profile (glucose, cholesterol, triglycerides) was observed. Also, GS diet had no effect on pro- and anti-inflammatory cytokines content in spleen and lymph nodes tissue. Further experiments are needed in order to investigate other rate of dietary inclusion which could provide more evidence about the effect of grape bioactive compounds on pigs used as animal model.

Keywords: animal model, inflammation, grape seed by-product, immune organs

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2846 Functional Analysis of Variants Implicated in Hearing Loss in a Cohort from Argentina: From Molecular Diagnosis to Pre-Clinical Research

Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

Abstract:

Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

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2845 Multi-Classification Deep Learning Model for Diagnosing Different Chest Diseases

Authors: Bandhan Dey, Muhsina Bintoon Yiasha, Gulam Sulaman Choudhury

Abstract:

Chest disease is one of the most problematic ailments in our regular life. There are many known chest diseases out there. Diagnosing them correctly plays a vital role in the process of treatment. There are many methods available explicitly developed for different chest diseases. But the most common approach for diagnosing these diseases is through X-ray. In this paper, we proposed a multi-classification deep learning model for diagnosing COVID-19, lung cancer, pneumonia, tuberculosis, and atelectasis from chest X-rays. In the present work, we used the transfer learning method for better accuracy and fast training phase. The performance of three architectures is considered: InceptionV3, VGG-16, and VGG-19. We evaluated these deep learning architectures using public digital chest x-ray datasets with six classes (i.e., COVID-19, lung cancer, pneumonia, tuberculosis, atelectasis, and normal). The experiments are conducted on six-classification, and we found that VGG16 outperforms other proposed models with an accuracy of 95%.

Keywords: deep learning, image classification, X-ray images, Tensorflow, Keras, chest diseases, convolutional neural networks, multi-classification

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2844 For Post-traumatic Stress Disorder Counselors in China, the United States, and around the Globe, Cultural Beliefs Offer Challenges and Opportunities

Authors: Anne Giles

Abstract:

Trauma is generally defined as an experience, or multiple experiences, overwhelming a person's ability to cope. Over time, many people recover from the neurobiological, physical, and emotional effects of trauma on their own. For some people, however, troubling symptoms develop over time that can result in distress and disability. This cluster of symptoms is classified as Post-traumatic Stress Disorder (PTSD). People who meet the criteria for PTSD and other trauma-related disorder diagnoses often hold a set of understandable but unfounded beliefs about traumatic events that cause undue suffering. Becoming aware of unhelpful beliefs—termed "cognitive distortions"—and challenging them is the realm of Cognitive Behavior Therapy (CBT). A form of CBT found by researchers to be especially effective for PTSD is Cognitive Processing Therapy (CPT). Through the compassionate use of CPT, people identify, examine, challenge, and relinquish unhelpful beliefs, thereby reducing symptoms and suffering. Widely-held cultural beliefs can interfere with the progress of recovery from trauma-related disorders. Although highly revered, largely unquestioned, and often stabilizing, cultural beliefs can be founded in simplistic, dichotomous thinking, i.e., things are all right, or all wrong, all good, or all bad. The reality, however, is nuanced and complex. After studying examples of cultural beliefs from China and the United States and how these might interfere with trauma recovery, trauma counselors can help clients derive criteria for preserving helpful beliefs, discover, examine, and jettison unhelpful beliefs, reduce trauma symptoms, and live their lives more freely and fully.

Keywords: cognitive processing therapy (CPT), cultural beliefs, post-traumatic stress disorder (PTSD), trauma recovery

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2843 Impact of Glycation on Proteomics of Human Serum Albumin: Relevance to Diabetes Associated Pathologies

Authors: Alok Raghav, Jamal Ahmad

Abstract:

Background: Serum albumin glycation and advanced glycation end products (AGE) formation correlates in diabetes and its associated complications. Extensive modified human serum albumin is used to study the biochemical, electrochemical and functional properties in hyperglycemic environment with relevance to diabetes. We evaluate Spectroscopic, side chain modifications, amino acid analysis, biochemical and functional group properties in four glucose modified samples. Methods: A series four human serum albumin samples modified with glucose was characterized in terms of amino acid analysis, spectroscopic properties and side chain modifications. The diagnostic technique employed incorporates UV Spectroscopy, Fluorescence Spectroscopy, biochemical assays for side chain modifications, amino acid estimations, electrochemical and optical characterstic of glycated albumin. Conclusion: Glucose modified human serum albumin confers AGEs formation alters biochemical, electrochemical, optical, and functional property that depend on the reactivity of glucose and its concentration used for in-vitro glycation. A biochemical, electrochemical, optical, and functional characterization of modified albumin in-vitro produced AGE product that will be useful to interpret the complications and pathophysiological significance in diabetes.

Keywords: human serum albumin, glycated albumin, adavanced glycation end products, associated pathologies

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2842 The Breast Surgery Movement: A 50 Year Development of the Surgical Specialty

Authors: Lauren Zammerilla Westcott, Ronald C. Jones, James W. Fleshman

Abstract:

The surgical treatment of breast cancer has rapidly evolved over the past 50 years, progressing from Halsted’s radical mastectomy to a public campaign of surgical options, aesthetic reconstruction, and patient empowerment. This article examines the happenings that led to the transition of breast surgery as a subset of general surgery to its own specialized field. Sparked by the research of Dr. Bernard Fisher and the first National Surgical Adjuvant Breast and Bowel Project trial in 1971, the field of breast surgery underwent significant growth over the next several decades, enabling general surgeons to limit their practices to the breast. High surgical volumes eventually led to the development of the first formal breast surgical oncology fellowship in a large community-based hospital at Baylor University Medical Center in 1982. The establishment of the American Society of Breast Surgeons, as well several landmark clinical trials and public campaign efforts, further contributed to the advancement of breast surgery, making it the specialized field of the current era.

Keywords: breast cancer, breast fellowship, breast surgery, surgical history

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2841 The Effect of an Occupational Therapy Programme on Sewing Machine Operators

Authors: N. Dunleavy, E. Lovemore, K. Siljeur, D. Jackson, M. Hendricks, M. Hoosain, N. Plastow, S. Marais

Abstract:

Background: The work requirements of sewing machine operators cause physical and emotional strain. Past ergonomic interventions have been provided to alleviate physical concerns; however, a holistic, multimodal intervention was needed to improve these factors. Aim: The study aimed to examine the effect of an occupational therapy programme on sewing machine operators’ pain, mental health, and productivity within a factory in the South African context. Methods: A pilot randomised control trial was conducted with 22 sewing machine operators within a single factory. Stratified randomisation was used to determine the experimental (EG) and control groups (CG), using measures for pain intensity, level of depression (mental health), and productivity rates as stratification variables. The EG received the multimodal intervention, incorporating education, seating adaptations, and mental health intervention. In three months, the CG will receive the same intervention. Pre- and post-intervention testing have occurred with upcoming three- and six-month follow-ups. Results: Immediate results indicate a statistically significant decrease in pain in both experimental and control groups; no change in productivity scores and depression between the two groups. This may be attributed to external factors. The values for depression further showed no statistical significance between the two groups and within pre-and post-test results. The Statistical Program for Social Sciences (SPSS) version-24 was used as the data analysis testing, where all the tests will be evaluated at a 5% significance level. Contribution of research: The research adds to the body of knowledge informing the Occupational Therapy role in work settings, providing evidence on the effectiveness of workplace-based multimodal interventions. Conclusion: The study provides initial data on the effectiveness of a pilot randomised control trial on pain and mental health in South Africa. Results indicated no quantitative change between the experimental and control groups; however, qualitative data suggest a clinical significance of the findings.

Keywords: ergonomics programme, occupational therapy, sewing machine operators, workplace-based multimodal interventions

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2840 Binding Mechanism of Synthesized 5β-Dihydrocortisol and 5β-Dihydrocortisol Acetate with Human Serum Albumin to Understand Their Role in Breast Cancer

Authors: Monika Kallubai, Shreya Dubey, Rajagopal Subramanyam

Abstract:

Our study is all about the biological interactions of synthesized 5β-dihydrocortisol (Dhc) and 5β-dihydrocortisol acetate (DhcA) molecules with carrier protein Human Serum Albumin (HSA). The cytotoxic study was performed on breast cancer cell line (MCF-7) normal human embryonic kidney cell line (HEK293), the IC50 values for MCF-7 cells were 28 and 25 µM, respectively, whereas no toxicity in terms of cell viability was observed with HEK293 cell line. The further experiment proved that Dhc and DhcA induced 35.6% and 37.7% early apoptotic cells and 2.5%, 2.9% late apoptotic cells respectively. Morphological observation of cell death through TUNEL assay revealed that Dhc and DhcA induced apoptosis in MCF-7 cells. The complexes of HSA–Dhc and HSA–DhcA were observed as static quenching, and the binding constants (K) was 4.7±0.03×104 M-1 and 3.9±0.05×104 M-1, and their binding free energies were found to be -6.4 and -6.16 kcal/mol, respectively. The displacement studies confirmed that lidocaine 1.4±0.05×104 M-1 replaced Dhc, and phenylbutazone 1.5±0.05×104 M-1 replaced by DhcA, which explains domain I and domain II are the binding sites for Dhc and DhcA. Further, CD results revealed that the secondary structure of HSA was altered in the presence of Dhc and DhcA. Furthermore, the atomic force microscopy and transmission electron microscopy showed that the dimensions like height and molecular sizes of the HSA–Dhc and HSA–DhcA complex were larger compared to HSA alone. Detailed analysis through molecular dynamics simulations also supported the greater stability of HSA–Dhc and HSA–DhcA complexes, and root-mean-square-fluctuation interpreted the binding site of Dhc as domain IB and domain IIA for DhcA. This information is valuable for the further development of steroid derivatives with improved pharmacological significance as novel anti-cancer drugs.

Keywords: apoptosis, dihydrocortisol, fluorescence quenching, protein conformations

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2839 ScRNA-Seq RNA Sequencing-Based Program-Polygenic Risk Scores Associated with Pancreatic Cancer Risks in the UK Biobank Cohort

Authors: Yelin Zhao, Xinxiu Li, Martin Smelik, Oleg Sysoev, Firoj Mahmud, Dina Mansour Aly, Mikael Benson

Abstract:

Background: Early diagnosis of pancreatic cancer is clinically challenging due to vague, or no symptoms, and lack of biomarkers. Polygenic risk score (PRS) scores may provide a valuable tool to assess increased or decreased risk of PC. This study aimed to develop such PRS by filtering genetic variants identified by GWAS using transcriptional programs identified by single-cell RNA sequencing (scRNA-seq). Methods: ScRNA-seq data from 24 pancreatic ductal adenocarcinoma (PDAC) tumor samples and 11 normal pancreases were analyzed to identify differentially expressed genes (DEGs) in in tumor and microenvironment cell types compared to healthy tissues. Pathway analysis showed that the DEGs were enriched for hundreds of significant pathways. These were clustered into 40 “programs” based on gene similarity, using the Jaccard index. Published genetic variants associated with PDAC were mapped to each program to generate program PRSs (pPRSs). These pPRSs, along with five previously published PRSs (PGS000083, PGS000725, PGS000663, PGS000159, and PGS002264), were evaluated in a European-origin population from the UK Biobank, consisting of 1,310 PDAC participants and 407,473 non-pancreatic cancer participants. Stepwise Cox regression analysis was performed to determine associations between pPRSs with the development of PC, with adjustments of sex and principal components of genetic ancestry. Results: The PDAC genetic variants were mapped to 23 programs and were used to generate pPRSs for these programs. Four distinct pPRSs (P1, P6, P11, and P16) and two published PRSs (PGS000663 and PGS002264) were significantly associated with an increased risk of developing PC. Among these, P6 exhibited the greatest hazard ratio (adjusted HR[95% CI] = 1.67[1.14-2.45], p = 0.008). In contrast, P10 and P4 were associated with lower risk of developing PC (adjusted HR[95% CI] = 0.58[0.42-0.81], p = 0.001, and adjusted HR[95% CI] = 0.75[0.59-0.96], p = 0.019). By comparison, two of the five published PRS exhibited an association with PDAC onset with HR (PGS000663: adjusted HR[95% CI] = 1.24[1.14-1.35], p < 0.001 and PGS002264: adjusted HR[95% CI] = 1.14[1.07-1.22], p < 0.001). Conclusion: Compared to published PRSs, scRNA-seq-based pPRSs may be used not only to assess increased but also decreased risk of PDAC.

Keywords: cox regression, pancreatic cancer, polygenic risk score, scRNA-seq, UK biobank

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2838 Exploring the Relationship Between Helicobacter Pylori Infection and the Incidence of Bronchogenic Carcinoma

Authors: Jose R. Garcia, Lexi Frankel, Amalia Ardeljan, Sergio Medina, Ali Yasback, Omar Rashid

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Background: Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that affects nearly half of the population worldwide and humans serve as the principal reservoir. Infection rates usually follow an inverse relationship with hygiene practices and are higher in developing countries than developed countries. Incidence varies significantly by geographic area, race, ethnicity, age, and socioeconomic status. H. pylori is primarily associated with conditions of the gastrointestinal tract such as atrophic gastritis and duodenal peptic ulcers. Infection is also associated with an increased risk of carcinogenesis as there is evidence to show that H. pylori infection may lead to gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. It is suggested that H. pylori infection may be considered as a systemic condition, leading to various novel associations with several different neoplasms such as colorectal cancer, pancreatic cancer, and lung cancer, although further research is needed. Emerging evidence suggests that H. pylori infection may offer protective effects against Mycobacterium tuberculosis as a result of non-specific induction of interferon- γ (IFN- γ). Similar methods of enhanced immunity may affect the development of bronchogenic carcinoma due to the antiproliferative, pro-apoptotic and cytostatic functions of IFN- γ. The purpose of this study was to evaluate the correlation between Helicobacter pylori infection and the incidence of bronchogenic carcinoma. Methods: The data was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate the patients infected versus patients not infected with H. pylori using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale for the purpose of academic research. Standard statistical methods were used. Results:-Between January 2010 and December 2019, the query was analyzed and resulted in 163,224 in both the infected and control group, respectively. The two groups were matched by age range and CCI score. The incidence of bronchogenic carcinoma was 1.853% with 3,024 patients in the H. pylori group compared to 4.785% with 7,810 patients in the control group. The difference was statistically significant (p < 2.22x10-16) with an odds ratio of 0.367 (0.353 - 0.383) with a confidence interval of 95%. The two groups were matched by treatment and incidence of cancer, which resulted in a total of 101,739 patients analyzed after this match. The incidence of bronchogenic carcinoma was 1.929% with 1,962 patients in the H. pylori and treatment group compared to 4.618% with 4,698 patients in the control group with treatment. The difference was statistically significant (p < 2.22x10-16) with an odds ratio of 0.403 (0.383 - 0.425) with a confidence interval of 95%.

Keywords: bronchogenic carcinoma, helicobacter pylori, lung cancer, pathogen-associated molecular patterns

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2837 Virtual Reality for Post COVID-19 Stroke: A Case Report

Authors: Kasra Afsahi, Maryam Soheilifar

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COVID-19 has been associated with stroke and neurological complications. The patient was a 59-year- old male who presented with sudden left hemiparesis and diplopia due to cavernous sinus thrombosis (CST) on 28/03/2020. The COVID-19 test was positive. Multislice CT (MSCT) showed ischemic infarction. He underwent surgical sinectomy 9 days after admission. Physiotherapy began for him in August 2020. Our game-based virtual reality (VR) technology developed for stroke patients was based on upper extremity exercises and function for stroke. After 6 weeks of VR therapy plus conventional physiotherapy exercises (18 sessions, three times per week, 60 minutes each session), there were significant improvements in Brunnstrom Motor Recovery Stage (from “4” to “5”), Fugl-Meyer Scale score of upper extremity section (from 49 to 54), and Modified Barthel Index (from15 to 18). There were no adverse effects. This case with stroke post-COVID-19 due to the CST showed the usefulness of VR therapy used as an adjunct to conventional physiotherapy in improving affected upper extremity.

Keywords: COVID-19, stroke, virtual reality, rehabilitation

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2836 Prevalence and Risk Factors of Musculoskeletal Disorders among Physical Therapist's Seniors versus Internship Students

Authors: A. H. Bekhet, N. Helmy

Abstract:

Background: Physical therapists are knowledgeable in treatment and prevention of musculoskeletal injuries; however, they have occupational musculoskeletal injuries because Physical therapy profession requires effort that may lead to work-related musculoskeletal disorders. No previous studies among physical therapists have been reported in Egypt. We aim to assess the prevalence and risk factors of musculoskeletal disorders among physical therapist’s seniors versus internship students. Method: We conducted a cross-sectional study in faculty of physical therapy Cairo university Prevalence and risk factors of musculoskeletal injuries were assessed using self-administered questionnaire with closed-ended questions. Seniors therapist was defined as a physical therapist with more than 5 years of work experience. Data were analyzed using SPSS 22.0 for Windows. Results: The study included 106 physical therapists (Junior = 72; senior = 34), the mean age of senior therapists was 30.1 (SD 6.3) years and junior therapists were 22.8 (SD 2.4). Female subjects constituted 83.9% of the studied sample. The mean hours of contact with patients was higher among junior therapists 6.4 (SD 2.6) vs. 5.7 (SD 2.1) among senior therapists. The prevalence of a musculoskeletal injury, once or more in their lifetime, was significantly higher among senior therapists (86% vs. 66.7%; p = 0.04). The highest risk factor in increasing the symptoms of the injury among junior therapists was maintaining a position for a prolonged period of time at 28% while performing manual therapy techniques was the highest risk factor among senior therapists at 32%. 53% of senior therapists have limited their patient contact time as a result of their injury in comparison to 25% of junior therapists (p = 0.09). Conclusion: the presented study shows that the prevalence of musculoskeletal injuries, once or more in their lifetime, is significantly higher among senior therapists.

Keywords: musculoskeletal injuries, occupational injuries, physical therapists, work related disorders

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2835 Hydrogen Sulfide Releasing Ibuprofen Derivative Can Protect Heart After Ischemia-Reperfusion

Authors: Virag Vass, Ilona Bereczki, Erzsebet Szabo, Nora Debreczeni, Aniko Borbas, Pal Herczegh, Arpad Tosaki

Abstract:

Hydrogen sulfide (H₂S) is a toxic gas, but it is produced by certain tissues in a small quantity. According to earlier studies, ibuprofen and H₂S has a protective effect against damaging heart tissue caused by ischemia-reperfusion. Recently, we have been investigating the effect of a new water-soluble H₂S releasing ibuprofen molecule administered after artificially generated ischemia-reperfusion on isolated rat hearts. The H₂S releasing property of the new ibuprofen derivative was investigated in vitro in medium derived from heart endothelial cell isolation at two concentrations. The ex vivo examinations were carried out on rat hearts. Rats were anesthetized with an intraperitoneal injection of ketamine, xylazine, and heparin. After thoracotomy, hearts were excised and placed into ice-cold perfusion buffer. Perfusion of hearts was conducted in Langendorff mode via the cannulated aorta. In our experiments, we studied the dose-effect of the H₂S releasing molecule in Langendorff-perfused hearts with the application of gradually increasing concentration of the compound (0- 20 µM). The H₂S releasing ibuprofen derivative was applied before the ischemia for 10 minutes. H₂S concentration was measured with an H₂S detecting electrochemical sensor from the coronary effluent solution. The 10 µM concentration was chosen for further experiments when the treatment with this solution was occurred after the ischemia. The release of H₂S is occurred by the hydrolyzing enzymes that are present in the heart endothelial cells. The protective effect of the new H₂S releasing ibuprofen molecule can be confirmed by the infarct sizes of hearts using the Triphenyl-tetrazolium chloride (TTC) staining method. Furthermore, we aimed to define the effect of the H₂S releasing ibuprofen derivative on autophagic and apoptotic processes in damaged hearts after investigating the molecular markers of these events by western blotting and immunohistochemistry techniques. Our further studies will include the examination of LC3I/II, p62, Beclin1, caspase-3, and other apoptotic molecules. We hope that confirming the protective effect of new H₂S releasing ibuprofen molecule will open a new possibility for the development of more effective cardioprotective agents with exerting fewer side effects. Acknowledgment: This study was supported by the grants of NKFIH- K-124719 and the European Union and the State of Hungary co- financed by the European Social Fund in the framework of GINOP- 2.3.2-15-2016-00043.

Keywords: autophagy, hydrogen sulfide, ibuprofen, ischemia, reperfusion

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2834 The Endocrinology of Obesity and Dejenerative Joint Disease

Authors: Kebret Kebede, Anthony Scinta

Abstract:

Obesity is the most prevalent global problem that continues to rise at alarming rates both in the industrialized and developing countries. Adipose tissue is an endocrine tissue that secretes numerous chemical signals, hormones, lipids, cytokines and coagulation factors as well as prompting insulin resistance which is a primary contributor to Type II Diabetes- one of its most common adverse effects on health. Other hormones whose levels are linked to obesity and nutritional state are leptin, IGF-1, and adiponectin. Several studies indicate that obesity is the leading cause of high levels of cholesterol that leads to fatty liver disease, gallstones, hypertension, increased risk for cancer and degenerative joint disease that primarily affects the weight bearing joints of the lower extremities. The activation of inflammatory pathways promotes synovial pathology that results in accelerated degeneration of the joints. The study examines the prevalence of obesity in the US female population in comparison to that of the developing world and its emergence as a significant and potentially modifiable risk factor in degenerative disease of the hip and knee joints that has resulted in staggering healthcare cost. Studies have shown that as the prevalence of obesity rises, we continue to see a rise in degenerative joint disease. The percentage of arthritis cases linked directly to obesity has risen from 3 percent in 1971 to 18 percent in 2002. A person with obesity is around 60 percent more likely to develop arthritis than someone of normal body weight. In women, obesity is associated with increased mortality from breast, cervical, endometrial and ovarian cancer that may accompany debilitating joint diseases and restricted mobility.

Keywords: obesity, endocrine, degenerative, mortality, joint diseases, cancer, debilitating, mobility

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2833 Biomolecular Interaction of Ruthenium(II) Polypyridyl Complexes

Authors: S. N. Harun, H. Ahmad

Abstract:

A series of ruthenium(II) complexes, including two novel compounds [Ru(dppz)2(L)]2+ where dppz = dipyrido-[3,2-a:2’,3’-c]phenazine, and L = 2-phenylimidazo[4,5-f][1,10]phenanthroline (PIP) or 2-(4-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline (p-HPIP) have been synthesized and characterized. The previously reported complexes [Ru(bpy)2L]2+ and [Ru(phen)2L]2+ were also prepared. All complexes were characterized by elemental analysis, 1H-NMR spectroscopy, ESI-Mass spectroscopy and FT-IR spectroscopy. The photophysical properties were analyzed by UV-Visible spectroscopy and fluorescence spectroscopy. [Ru(dppz)2(PIP)]2+ and [Ru(dppz)2(p-HPIP)]2+ displayed ‘molecular light-switch’ effect as they have high emission in acetonitrile but no emission in water. The cytotoxicity of all complexes against cancer cell lines Hela and MCF-7 were investigated through standard MTT assay. [Ru(dppz)2(PIP)]2+ showed moderate toxicity on both MCF-7 and Hela with IC50 of 37.64 µM and 28.02 µM, respectively. Interestingly, [Ru(dppz)2(p-HPIP)]2+ exhibited remarkable cytotoxicity results with IC50 of 13.52 µM on Hela and 11.63 µM on MCF-7 cell lines which are comparable to the infamous anti-cancer drug, cisplatin. The cytotoxicity of this complex series increased as the ligands size extended in order of [Ru(bpy)2(L)]2+ < [Ru(phen)2(L)]2+ < [Ru(dppz)2(L)]2+.

Keywords: ruthenium, cytotoxicity, molecular light-switch, anticancer

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2832 Early Detection of Lymphedema in Post-Surgery Oncology Patients

Authors: Sneha Noble, Rahul Krishnan, Uma G., D. K. Vijaykumar

Abstract:

Breast-Cancer related Lymphedema is a major problem that affects many women. Lymphedema is the swelling that generally occurs in the arms or legs caused by the removal of or damage to lymph nodes as a part of cancer treatment. Treating it at the earliest possible stage is the best way to manage the condition and prevent it from leading to pain, recurrent infection, reduced mobility, and impaired function. So, this project aims to focus on the multi-modal approaches to identify the risks of Lymphedema in post-surgical oncology patients and prevent it at the earliest. The Kinect IR Sensor is utilized to capture the images of the body and after image processing techniques, the region of interest is obtained. Then, performing the voxelization method will provide volume measurements in pre-operative and post-operative periods in patients. The formation of a mathematical model will help in the comparison of values. Clinical pathological data of patients will be investigated to assess the factors responsible for the development of lymphedema and its risks.

Keywords: Kinect IR sensor, Lymphedema, voxelization, lymph nodes

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2831 The Effects of Zinc Oxide Nanoparticles Loaded with Indole-3-Acetic Acid and Indole-3-Butyric Acid on in vitro Rooting of Apple Microcuttings

Authors: Shabnam Alizadeh, Hatice Dumanoglu

Abstract:

Plant tissue culture is a substantial plant propagation technique for mass clonal production throughout the year, regardless of time in fruit species. However, the rooting achievement must be enhanced in the difficult-to-root genotypes. Classical auxin applications in clonal propagation of these genotypes are inadequate to solve the rooting problem. Nanoparticles having different physical and chemical properties from bulk material could enhance the rooting success of controlled release of these substances when loaded with auxin due to their ability to reach the active substance up to the target cells as a carrier system.The purpose of this study is to investigate the effects of zinc oxide nanoparticles loaded with indole-3-acetic acid (IAA-nZnO) and indole-3-butyric acid (IBA-nZnO) on in vitro rooting of microcuttings in a difficult-to-root apple genotype (Malus domestica Borkh.). Rooting treatments consisted of IBA or IAA at concentrations of 0.5, 1.0, 2.0, 3.0 mg/L; nZnO, IAA-nZnO and IBA-nZnO at doses of 0.0, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0 mg/L were used. All components were added to the Murashige and Skoog (MS) basal medium at strength ½ with 2% sucrose and 0.7% agar before autoclaving. In the study, no rooting occurred in control and nZnO applications. Especially, 1.0 mg/L and 2.0 mg/L IBA-nZnO nanoparticle applications (containing 0.5 mg/L and 0.9 mg/L IBA), respectively with rooting rates of 40.3% and 70.4%, rooting levels of 2.0±0.4 and 2.3±0.4, 2.6±0.7 and 2.5±0.6 average root numbers and 20.4±1.6 mm and 20.2±3.4 mm average root lengths put forward as effective applications.

Keywords: Auxin, Malus, nanotechnology, zinc oxide nanoparticles

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2830 Virtual Screening and in Silico Toxicity Property Prediction of Compounds against Mycobacterium tuberculosis Lipoate Protein Ligase B (LipB)

Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

Abstract:

The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

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2829 Screening of Selected Medicinal Plants from Jordan for Their Protective Properties against Oxidative DNA Damage and Mutagenecity

Authors: Karem H. Alzoubi, Ahmad S. Alkofahi, Omar F. Khabour, Nizar M. Mhaidat

Abstract:

Herbal medicinal products represent a major focus for drug development and industry and it holds a significant share in drug-market all over the globe. In here, selected medicinal plant extracts from Jordan with high antioxidative capacity were tested for their protective effect against oxidative DNA damage using in vitro 8-hydroxydeoxyguanisine and sister chromatid exchanges (SCEs) assays in cultured human lymphocytes. The following plant extracts were tested Cupressus sempervirens L., Psidium guajava (L.) Gaerth., Silybum marianum L., Malva sylvestris L., Varthemia iphionoides Boiss., Eminium spiculatum L. Blume, Pistachia palaestina Boiss., Artemisia herba-alba Asso, Ficus carica L., Morus alba Linn , Cucumis sativus L., Eucalyptus camaldulensis Dehnh., Salvia triloba L., Zizyphus spina-christi L. Desf., and Laurus nobilis L. A fractionation scheme for the active plant extracts of the above was followed. Plants extract fractions with best protective properties against DNA damage included hexane fraction of S. marianum L. (aerial parts), chloroform fractions of P. palaestina Boiss. (Fruits), ethanolic fractions of E. camaldulensis Dehnh (leaves), S. triloba L. (leaves), and ethanolic fractions of Z. spina-christi L. Desf. (Fruits/leaves). On the other hand, the ethanolic extracts of V. iphionoides Boiss was found to increase oxidative DNA damage. Results of the SCEs are undergoing. In conclusion, plant extracts with antioxidative DNA damage properties might have clinical applications in cancer prevention.

Keywords: medicinal plants extract, fractionation, oxidative DNA damage, 8-hydroxydeoxyguanisine, SCEs, Jordan

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2828 Neuron Point-of-Care Stem Cell Therapy: Intrathecal Transplant of Autologous Bone Marrow-Derived Stem Cells in Patients with Cerebral Palsy

Authors: F. Ruiz-Navarro, M. Matzner, G. Kobinia

Abstract:

Background: Cerebral palsy (CP) encompasses the largest group of childhood movement disorders, the patterns and severity varies widely. Today, the management focuses only on a rehabilitation therapy that tries to secure the functions remained and prevents complications. However the treatments are not aimed to cure the disease. Stem cells (SCs) transplant via intrathecal is a new approach to the disease. Method: Our aim was to performed a pilot study under the condition of unproven treatment on clinical practice to assessed the safety and efficacy of Neuron Point-of-care Stem cell Therapy (N-POCST), an ambulatory procedure of autologous bone marrow derived SCs (BM-SCs) harvested from the posterior superior iliac crest undergo an on-site cell separation for intrathecal infusion via lumbar puncture. Results: 82 patients were treated in a period of 28 months, with a follow-up after 6 months. They had a mean age of 6,2 years old and male predominance (65,9%). Our preliminary results show that: A. No patient had any major side effects, B. Only 20% presented mild headache due to LP, C. 53% of the patients had an improvement in spasticity, D. 61% improved the coordination abilities, 23% improved the motor function, 15% improved the speech, 23% reduced the number of convulsive events with the same doses or less doses of anti-convulsive medication and 94% of the patients report a subjective general improvement. Conclusions: These results support previous worldwide publications that described the safety and effectiveness of autologous BM-SCs transplant for patients wit CP.

Keywords: autologous transplant, cerebral palsy, point of care, childhood movement disorders

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2827 Evaluation in Vitro and in Silico of Pleurotus ostreatus Capacity to Decrease the Amount of Low-Density Polyethylene Microplastics Present in Water Sample from the Middle Basin of the Magdalena River, Colombia

Authors: Loren S. Bernal., Catalina Castillo, Carel E. Carvajal, José F. Ibla

Abstract:

Plastic pollution, specifically microplastics, has become a significant issue in aquatic ecosystems worldwide. The large amount of plastic waste carried by water tributaries has resulted in the accumulation of microplastics in water bodies. The polymer aging process caused by environmental influences such as photodegradation and chemical degradation of additives leads to polymer embrittlement and properties change that require degradation or reduction procedures in rivers. However, there is a lack of such procedures for freshwater entities that develop over extended periods. The aim of this study is evaluate the potential of Pleurotus ostreatus a fungus, in reducing lowdensity polyethylene microplastics present in freshwater samples collected from the middle basin of the Magdalena River in Colombia. The study aims to evaluate this process both in vitro and in silico by identifying the growth capacity of Pleurotus ostreatus in the presence of microplastics and identifying the most likely interactions of Pleurotus ostreatus enzymes and their affinity energies. The study follows an engineering development methodology applied on an experimental basis. The in vitro evaluation protocol applied in this study focused on the growth capacity of Pleurotus ostreatus on microplastics using enzymatic inducers. In terms of in silico evaluation, molecular simulations were conducted using the Autodock 1.5.7 program to calculate interaction energies. The molecular dynamics were evaluated by using the myPresto Portal and GROMACS program to calculate radius of gyration and Energies.The results of the study showed that Pleurotus ostreatus has the potential to degrade low-density polyethylene microplastics. The in vitro evaluation revealed the adherence of Pleurotus ostreatus to LDPE using scanning electron microscopy. The best results were obtained with enzymatic inducers as a MnSO4 generating the activation of laccase or manganese peroxidase enzymes in the degradation process. The in silico modelling demonstrated that Pleurotus ostreatus was able to interact with the microplastics present in LDPE, showing affinity energies in molecular docking and molecular dynamics shown a minimum energy and the representative radius of gyration between each enzyme and its substract. The study contributes to the development of bioremediation processes for the removal of microplastics from freshwater sources using the fungus Pleurotus ostreatus. The in silico study provides insights into the affinity energies of Pleurotus ostreatus microplastic degrading enzymes and their interaction with low-density polyethylene. The study demonstrated that Pleurotus ostreatus can interact with LDPE microplastics, making it a good agent for the development of bioremediation processes that aid in the recovery of freshwater sources. The results of the study suggested that bioremediation could be a promising approach to reduce microplastics in freshwater systems.

Keywords: bioremediation, in silico modelling, microplastics, Pleurotus ostreatus

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2826 Myeloid Zinc Finger 1/Ets-Like Protein-1/Protein Kinase C Alpha Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma

Authors: Jer-Yuh Liu, Je-Chiuan Ye, Jin-Ming Hwang

Abstract:

Protein kinase C alpha (PKCα) is a key signaling molecule in human cancer development. As a therapeutic strategy, targeting PKCα is difficult because the molecule is ubiquitously expressed in non-malignant cells. PKCα is regulated by the cooperative interaction of the transcription factors myeloid zinc finger 1 (MZF-1) and Ets-like protein-1 (Elk-1) in human cancer cells. By conducting tissue array analysis, herein, we determined the protein expression of MZF-1/Elk-1/PKCα in various cancers. The data show that the expression of MZF-1/Elk-1 is correlated with that of PKCα in hepatocellular carcinoma (HCC), but not in bladder and lung cancers. In addition, the PKCα down-regulation by shRNA Elk-1 was only observed in the HCC SK-Hep-1 cells. Blocking the interaction between MZF-1 and Elk-1 through the transfection of their binding domain MZF-160–72 decreased PKCα expression. This step ultimately depressed the epithelial-mesenchymal transition potential of the HCC cells. These findings could be used to develop an alternative therapeutic strategy for patients with the PKCα-derived HCC.

Keywords: protein kinase C alpha, myeloid zinc finger 1, ets-like protein-1, hepatocellular carcinoma

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2825 Regenerative Therapeutic Effect of Statin Nanoparticle-Loaded Adipose-Derived Stem Cells on Myocardial Infarction

Authors: Masaaki Ii, Takashi Saito, Yasuhiko Tabata, Shintaro Nemoto

Abstract:

Background: Clinical trials of autologous adipose-derived stem cell (AdSC) therapy for ischemic heart diseases (IHD) are now on-going. We have investigated the hypothesis that combination of AdSCs and statin, an agent with pleiotropic effects, could augment the therapeutic effect on myocardial infarction (MI). Methods and Results: Human AdSC functions with different doses of simvastatin-conjugated nanoparticle (STNP) uptake were evaluated by in vitro assays. STNP promoted the migration activity without changing the proliferation activity, and also up-regulated growth factors. Next, MI was induced by LAD ligation in nude mice, and the mice were assigned in the following groups 3 days after MI: 1) PBS (control), 2) NP-AdSCs (50000 cells), 3) STNP, and 4) STNP-AdSCs (50000 cells). Cardiac functional recovery assessed by echocardiography was improved at 4 weeks after surgery in STNP-AdSC group. Masson’s trichrome-stained sections revealed that LV fibrosis length was reduced, and the number of TUNEL-positive cardiomyocytes was less in STNP-AdSC group. Surprisingly, a number of de novo endogenous Nkx-2.5/GATA4 positive immature cardiomyocytes as well as massive vascular formation were observed in outer layer of infarcted myocardium despite of a few recruited/retained transfused STNP-AdSCs 4 weeks after MI in STNP-AdSC group. Finally, massive myocardial regeneration was observed 8 weeks after MI. Conclusions: Intravenously injected small number of statin nanoparticle-loaded hAdSCs exhibited a potent therapeutic effect inducing endogenous cardiac tissue regeneration.

Keywords: statin, drug delivery system, stem cells, cardiac regeneration

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2824 A Comparison of Clinical and Pathological TNM Staging in a COVID-19 Era

Authors: Sophie Mills, Leila L. Touil, Richard Sisson

Abstract:

Introduction: The TNM classification is the global standard for the staging of head and neck cancers. Accurate clinical-radiological staging of tumours (cTNM) is essential to predict prognosis, facilitate surgical planning and determine the need for other therapeutic modalities. This study aims to determine the accuracy of pre-operative cTNM staging using pathological TNM (pTNM) and consider possible causes of TNM stage migration, noting any variation throughout the COVID-19 pandemic. Materials and Methods: A retrospective cohort study examined records of patients with surgical management of head and neck cancer at a tertiary head and neck centre from November 2019 to November 2020. Data was extracted from Somerset Cancer Registry and histopathology reports. cTNM and pTNM were compared before and during the first wave of COVID-19, as well as with other potential prognostic factors such as tumour site and tumour stage. Results: 119 cases were identified, of which 52.1% (n=62) were male, and 47.9% (n=57) were female with a mean age of 67 years. Clinical and pathological staging differed in 54.6% (n=65) of cases. Of the patients with stage migration, 40.4% (n=23) were up-staged and 59.6% (n=34) were down-staged compared with pTNM. There was no significant difference in the accuracy of cTNM staging compared with age, sex, or tumour site. There was a statistically highly significant (p < 0.001) correlation between cTNM accuracy and tumour stage, with the accuracy of cTNM staging decreasing with the advancement of pTNM staging. No statistically significant variation was noted between patients staged prior to and during COVID-19. Conclusions: Discrepancies in staging can impact management and outcomes for patients. This study found that the higher the pTNM, the more likely stage migration will occur. These findings are concordant with the oncology literature, which highlights the need to improve the accuracy of cTNM staging for more advanced tumours.

Keywords: COVID-19, head and neck cancer, stage migration, TNM staging

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2823 Effect of Rhythmic Auditory Stimulation on Gait in Patients with Stroke

Authors: Mohamed Ahmed Fouad

Abstract:

Background: Stroke is the most leading cause to functional disability and gait problems. Objectives: The purpose of this study was to determine the effect of rhythmic auditory stimulation combined with treadmill training on selected gait kinematics in stroke patients. Methods: Thirty male stroke patients participated in this study. The patients were assigned randomly into two equal groups, (study and control). Patients in the study group received treadmill training combined with rhythmic auditory stimulation in addition to selected physical therapy program for hemiparetic patients. Patients in the control group received treadmill training in addition to the same selected physical therapy program including strengthening, stretching, weight bearing, balance exercises and gait training. Biodex gait trainer 2 TM was used to assess selected gait kinematics (step length, step cycle, walking speed, time on each foot and ambulation index) before and after six weeks training period (end of treatment) for both groups. Results: There was a statistically significant increase in walking speed, step cycle, step length, percent of the time on each foot and ambulation index in both groups post-treatment. The improvement in gait parameters post-treatment was significantly higher in the study group compared to the control. Conclusion: Rhythmic auditory stimulation combined with treadmill training is effective in improving selected gait kinematics in stroke patients when added to the selected physical therapy program.

Keywords: stroke, rhythmic auditory stimulation, treadmill training, gait kinematics

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