Search results for: stem cell therapy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5779

Search results for: stem cell therapy

4819 Performance of Osmotic Microbial Fuel Cell in Wastewater Treatment and Electricity Generation: A Critical Review

Authors: Shubhangi R. Deshmukh, Anupam B. Soni

Abstract:

Clean water and electricity are vital services needed in all communities. Bio-degradation of wastewater contaminants and desalination technologies are the best possible alternatives for the global shortage of fresh water supply. Osmotic microbial fuel cell (OMFC) is a versatile technology that uses microorganism (used for biodegradation of organic waste) and membrane technology (used for water purification) for wastewater treatment and energy generation simultaneously. This technology is the combination of microbial fuel cell (MFC) and forward osmosis (FO) processes. OMFC can give more electricity and clean water than the MFC which has a regular proton exchange membrane. FO gives many improvements such as high contamination removal, lower operating energy, raising high proton flux than other pressure-driven membrane technology. Lower concentration polarization lowers the membrane fouling by giving osmotic water recovery without extra cost. In this review paper, we have discussed the principle, mechanism, limitation, and application of OMFC technology reported to date. Also, we have interpreted the experimental data from various literature on the water recovery and electricity generation assessed by a different component of OMFC. The area of producing electricity using OMFC has further scope for research and seems like a promising route to wastewater treatment.

Keywords: forward osmosis, microbial fuel cell, osmotic microbial fuel cell, wastewater treatment

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4818 Visualization as a Psychotherapeutic Mind-Body Intervention through Reducing Stress and Depression among Breast Cancer Patients in Kolkata

Authors: Prathama Guha Chaudhuri, Arunima Datta, Ashis Mukhopadhyay

Abstract:

Background: Visualization (guided imagery) is a set of techniques which induce relaxation and help people create positive mental images in order to reduce stress.It is relatively inexpensive and can even be practised by bed bound people. Studies have shown visualization to be an effective tool to improve cancer patients’ anxiety, depression and quality of life. The common images used with cancer patients in the developed world are those involving the individual’s body and its strengths. Since breast cancer patients in India are more family oriented and often their main concerns are the stigma of having cancer and subsequent isolation of their families, including their children, we figured that positive images involving acceptance and integration within family and society would be more effective for them. Method: Data was collected from 119 breast cancer patients on chemotherapy willing to undergo psychotherapy, with no history of past psychiatric illness. Their baseline stress, anxiety, depression and quality of life were assessed using validated tools. The participants were then randomly divided into three groups: a) those who received visualization therapy with standard imageries involving the body and its strengths (sVT), b) those who received visualization therapy using indigenous family oriented imageries (mVT) and c) a control group who received supportive therapy. There were six sessions spread over two months for each group. The psychological outcome variables were measured post intervention. Appropriate statistical analyses were done. Results:Both forms of visualization therapy were more effective than supportive therapy alone in reducing patients’ depression, anxiety and quality of life.Modified VT proved to be significantly more effective in improving patients’ anxiety and quality of life. Conclusion: Visualization is a valuable therapeutic option for reduction of psychological distress and improving quality of life of breast cancer patients.In order to be more effective, the images used need to be modified according to the sociocultural background and individual needs of the patients.

Keywords: breast cancer, visualization therapy, quality of life, anxiety, depression

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4817 Natural Honey and Effect on the Activity of the Cells

Authors: Abujnah Dukali

Abstract:

Natural honey was assessed in cell culture system for its anticancer activity. Human leukemic cell line HL 60 was treated with honey and cultured for 5 days and cytotoxicity was calculated by MTT assay. Honey showed cytotoxicity with CC50 value of 174.20 µg/ml. Radical modulation activities was assessed by lipid peroxidation assay using egg lecithin. Honey showed antioxidant activity with EC50 value of 159.73 µg/ml. In addition, treatment with HL60 cells also resulted in nuclear DNA fragmentation, as seen in agarose gel electrophoresis. This is a hallmark of cells undergoing apoptosis. Confirmation of apoptosis was performed by staining the cells with Annexin V and FACS analysis. Apoptosis is an active, genetically regulated disassembly of the cell form within. Disassembly creates changes in the phospholipid content of the cytoplasmic membrane outer leaflet. Phosphatidylserine (PS) is translocated from the inner to the outer surface of the cell for phagocytic cell recognition. The human anticoagulant, annexin V, is a Ca2+-dependent phospholipid protein with a high affinity for PS. Annexin V labeled with fluorescein can identify apoptotic cells in the population It is a confirmatory test for apoptosis. Annexin V-positive cells were defined as apoptotic cells. Since honey shows both antioxidant activity and cytotoxicity at almost the same concentration, it can prevent the free radical induced cancer as prophylactic agent and kill the cancer cells by apoptotic process as a chemotherapeutic agent. Everyday intake of honey can prevent the cancer induction.

Keywords: anticancer, cells, DNA, honey

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4816 Highly Concentrated Photo Voltaic using Multi-Junction Concentrator Cell

Authors: Oriahi Love Ndidi

Abstract:

High concentration photovoltaic promises a more efficient, higher power output than traditional photovoltaic modules. One of the driving forces of this high system efficiency has been the continuous improvement of III-V multi-junction solar cell efficiencies. Multi-junction solar cells built from III-V semiconductors are being evaluated globally in concentrated photovoltaic systems designed to supplement electricity generation for utility companies. The high efficiency of this III-V multi-junction concentrator cells, with demonstrated efficiency over 40 percent since 2006, strongly reduces the cost of concentrated photovoltaic systems, and makes III-V multi-junction cells the technology of choice for most concentrator systems today.

Keywords: cost of multi-junction solar cell, efficiency, photovoltaic systems, reliability

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4815 Effects of Intensive Rehabilitation Therapy on Sleep in Children with Developmental Disorders

Authors: Sung Hyun Kim

Abstract:

Introduction: Sleep disturbance is common in children with developmental disorders (D.D.). Sleep disturbance has a variety of negative effects, such as behavior problems, medical problems, and even developmental problems in children with D.D. However, to our best knowledge, there has been no proper treatment for sleep disorders in children with D.D. Therefore, we conduct this study to know the positive effects of intensive rehabilitation therapy in children with D.D. on the degree of sleep disturbance. Method: We prospectively recruited 22 patients with a diagnosis of D.D. during the period of January 2022 through May 2022. The inclusion criteria were as follows: 1) a patient who would participate in the intensive rehabilitation therapy of our institution; 2) the age participant under 18 years at the time of assessment; 3) a child who has consented to participate in the study by signing the consent form by the legal guardian. We investigated the clinical characteristics of participants by the medical record, including sex, age, underlying diagnosis of D.D., and Gross Motor Function Measures (GMFM). Before starting the intensive rehabilitation therapy, we conducted a Sleep disturbance scale for children (SDSC). It contains 26 questions about children’s sleep, and those questions are grouped into six subscales, such as Disorders of initiating and maintaining sleep (DIMS), Sleep Breathing Disorders(SBD), Disorders of arousal(DOA), Sleep-Wake Transition Disorders(SWTD), Disorders of excessive somnolence(DOES) and Sleep Hyperhydrosis(SHY). We used the t-score, which was calculated by comparing the scores of normal children. Twenty two patients received 8 weeks of intensive rehabilitation, including daily physical and occupational therapy. After that, we did follow up with SDSC. The comparison between SDSC before and after intensive rehabilitation was calculated using the paired t-test, and P< 0.05 was considered statistically significant. Results: Demographic data and clinical characteristics of 22 patients are enrolled. Patients were 4.03 ± 2.91 years old, and of the total 22 patients, 14 (64%) were male, and 8 (36%) were female. Twelve patients(45%) were diagnosed with Cerebral palsy(C.P.), and the mean value of participants’ GMFM was 47.82 ± 20.60. Each mean value of SDSC’s subscales was also calculated. DIMS was 62.36 ± 13.72, SBD was 54.18 ± 8.39, DOA was 49.59 ± 7.01, SWTD was 58.95 ± 9.20, DOES was 53.09 ± 15.15, SHY was 52.14 ± 8.82, and the total was 59.86 ± 13.18. These values suggest that children with D.D. have sleep disorders. After 8 weeks of intensive rehabilitation treatment, the score of DIMS showed improvement(p=0.016), but not the other subscale and total score of SDSC. Conclusion: This result showed that intensive rehabilitation could be helpful to patients of D.D. with sleep disorders. Especially intensive rehabilitation therapy itself can be a meaningful treatment in inducing and maintaining sleep.

Keywords: sleep disorder, developmental delay, intensive rehabilitation therapy, cerebral palsy

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4814 Understanding Neuronal and Glial Cell Behaviour in Multi-Layer Nanofibre Systems to Support the Development of an in vitro Model of Spinal Cord Injury and Personalised Prostheses for Repair

Authors: H. Pegram, R. Stevens, L. De Girolamo

Abstract:

Aligned electrospun nanofibres act as effective neuronal and glial cell scaffolds that can be layered to contain multiple sheets harboring different cell populations. This allows personalised biofunctional prostheses to be manufactured with both acellular and cellularised layers for the treatment of spinal cord injury. Additionally, the manufacturing route may be configured to produce in-vitro 3D cell based model of spinal cord injury to aid drug development and enhance prosthesis performance. The goal of this investigation was to optimise the multi-layer scaffold design parameters for prosthesis manufacture, to enable the development of multi-layer patient specific implant therapies. The work has also focused on the fabricating aligned nanofibre scaffolds that promote in-vitro neuronal and glial cell population growth, cell-to-cell interaction and long-term survival following trauma to mimic an in-vivo spinal cord lesion. The approach has established reproducible lesions and has identified markers of trauma and regeneration marked by effective neuronal migration across the lesion with glial support. The investigation has advanced the development of an in-vitro model of traumatic spinal cord injury and has identified a route to manufacture prostheses which target the repair spinal cord injury. Evidence collated to investigate the multi-layer concept suggests that physical cues provided by nanofibres provide both a natural extra-cellular matrix (ECM) like environment and controls cell proliferation and migration. Specifically, aligned nanofibre layers act as a guidance system for migrating and elongating neurons. On a larger scale, material type in multi-layer systems also has an influence in inter-layer migration as cell types favour different material types. Results have shown that layering nanofibre membranes create a multi-level scaffold system which can enhance or prohibit cell migration between layers. It is hypothesised that modifying nanofibre layer material permits control over neuronal/glial cell migration. Using this concept, layering of neuronal and glial cells has become possible, in the context of tissue engineering and also modelling in-vitro induced lesions.

Keywords: electrospinning, layering, lesion, modeling, nanofibre

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4813 Hemodynamic Effects of Magnesium Sulphate Therapy in Critically Ill Infants and Children with Wheezy Chest

Authors: Yasmin Sayed, Hala Hamdy, Hafez Bazaraa, Hanaa Rady, Sherif Elanwary

Abstract:

Intravenous and inhaled magnesium sulfate (MgSO₄) had been recently used as an adjuvant therapy in cases suffering from the wheezy chest. Objective: We aimed to determine the possible change in the hemodynamic state in cases received intravenous or inhaled MgSO₄ in comparison to cases received standard treatment in critically ill infants and children with the wheezy chest. Methods: A randomized controlled trial comprised 81 patients suffering from wheezy chest divided into 3 groups. In addition to bronchodilators and systemic steroids, MgSO₄ was given by inhalation in group A, intravenously in group B, and group C didn't receive MgSO₄. The hemodynamic state was determined by assessment of blood pressure, heart rate, capillary refill time and the need for shock therapy or inotropic support just before and 24 hours after receiving treatment in 3 groups. Results: There was no significant difference in the hemodynamic state of the studied groups before and after treatment. Means of blood pressure were 102.2/63.2, 105.1/64.8 before and after inhaled MgSO₄; respectively. Means of blood pressure were 105.5/64.2, 104.1/64.9 before and after intravenous MgSO₄; respectively. Means of blood pressure were 107.4/62.8, 104.4/62.1 before and after standard treatment, respectively. There was a statistically insignificant reduction of the means of the heart rate in group A and group B after treatment rather than group C. There was no associated prolongation in capillary refill time and/or the need for inotropic support or shock therapy after treatment in the studied groups. Conclusion: MgSO₄ is a safe adjuvant therapy and not associated with significant alteration in the hemodynamic state in critically ill infants and children with the wheezy chest.

Keywords: critically ill infants and children, inhaled MgSO₄, intravenous MgSO₄, wheezy chest

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4812 Computational Approaches to Study Lineage Plasticity in Human Pancreatic Ductal Adenocarcinoma

Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles

Abstract:

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: deconvolution, imaging, microenvironment, PDAC

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4811 A Case Study of Response to Dual Genotype Chronic Hepatitis C/HIV Co-Infection to Fixed Dose Sofosbuvir/Ledipasvir

Authors: Tabassum Yasmin, Hamid Pahlevan

Abstract:

HIV/Hepatitis C co-infection treatments have evolved substantially and they have similar sustained virologic response rates as those of Hepatitis C monoinfected population. There are a few studies on therapy of patients with dual genotypes, especially in HIV/Hepatic C coinfected group. Most studies portrayed case reports of dual genotype chronic Hepatitis C coinfection treatment with Sofosbuvir/Ledipasvir and Ribavirin. A 79-year-old male with a history of HIV on Truvada and Isentress had chronic Hepatitis C with 1a and 2 genotypes. The patient has a history of alcohol intake for 40 years but recently stopped drinking alcohol. He has a history of intravenous drug use in the past and currently is not using any recreational drugs. Patient has Fibro score of 0.7 with Metavir score F2 to F4. AFP is 3.2. The HCV RNA is 493,034 IU/ML. The HBV viral DNA is < 1.30 (not detected). The CD4 is 687CU/MM. The FIB 4 is 3.34 with APRI index 0.717. The HIV viral load is 101 copies/ML. MRI abdomen did not show any liver abnormality. Fixed dose Sofosbuvir/Ledipasvir was used for therapy without Ribavirin. He tolerated medication except for some minor gastrointestinal side effects like abdominal bloating. He demonstrated 100% adherence rate. Patient completed 12 weeks of therapy. HCV RNA was undetectable at 4 and 12 weeks. He achieved SVR at week 12 and subsequently had undetectable RNA for 2 years. Dual genotype prevalence in chronic hepatitis C population is rare, especially in HIV/hepatic coinfection. Our case demonstrates that dual genotypic cases can still be successfully treated with Direct Acting Antiviral agents. The newer agents for therapy for pan genotypes were not available at the time the patient was being treated. We demonstrated that dual agent therapy was still able to maintain SVR in our patient.

Keywords: HIV/Hepatitis C, SVR (sustained virologic response), DAA (direct active antiviral agents, dual genotype

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4810 Anion Exchange Nanocomposite Membrane Doped with ZnO-Nanoparticles for Direct Methanol Alkaline Fuel Cell

Authors: Phumlani Msomi, Patrick Nonjola, Patrick Ndungu, James Ramontja

Abstract:

A series of quaternized poly (2.6 dimethyl – 1.4 phenylene oxide)/ polysulfone (QPPO/PSF) blend anion exchange membrane (AEM) were successfully fabricated and characterized for methanol alkaline fuel cell application. Zinc Oxide (ZnO) nanoparticles were introduced in the polymer matrix to enhance the intrinsic properties of the AEM. To confirm successful fabrication, FT-IR spectroscopy and nuclear magnetic resonance (¹H NMR and HMBC ¹⁵N NMR) were used. The membrane properties were enhanced by the addition of ZnO nanoparticles. The addition of ZnO nanoparticles resulted to a higher ion exchange capacity (IEC) of 3.72 mmol.g⁻¹and a 30-fold ion conductivity (IC) increase of the nanocomposite due to no (zero (0)) methanol permeability at 30 °C and increased water uptake. The QPPO/PSF/2% ZnO composite retained over 80 % of its initial IC when evaluated for alkaline stability at room temperature. The maximum power output reached for the membrane electrode assembly (MEA) constructed with QPPO/PSF/2%ZnO is 69 mW.cm⁻², which is about three times more than the parent QPPO membrane. The above results indicate that QPPO/PSF-ZnO is a good candidate as an anion exchange membrane for fuel cell application.

Keywords: anion exchange membrane, fuel cell, zinc oxide, nanocomposite

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4809 Combined Treatment of Estrogen-Receptor Positive Breast Microtumors with 4-Hydroxytamoxifen and Novel Non-Steroidal Diethyl Stilbestrol-Like Analog Produces Enhanced Preclinical Treatment Response and Decreased Drug Resistance

Authors: Sarah Crawford, Gerry Lesley

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This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

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4808 Development of an Implicit Physical Influence Upwind Scheme for Cell-Centered Finite Volume Method

Authors: Shidvash Vakilipour, Masoud Mohammadi, Rouzbeh Riazi, Scott Ormiston, Kimia Amiri, Sahar Barati

Abstract:

An essential component of a finite volume method (FVM) is the advection scheme that estimates values on the cell faces based on the calculated values on the nodes or cell centers. The most widely used advection schemes are upwind schemes. These schemes have been developed in FVM on different kinds of structured and unstructured grids. In this research, the physical influence scheme (PIS) is developed for a cell-centered FVM that uses an implicit coupled solver. Results are compared with the exponential differencing scheme (EDS) and the skew upwind differencing scheme (SUDS). Accuracy of these schemes is evaluated for a lid-driven cavity flow at Re = 1000, 3200, and 5000 and a backward-facing step flow at Re = 800. Simulations show considerable differences between the results of EDS scheme with benchmarks, especially for the lid-driven cavity flow at high Reynolds numbers. These differences occur due to false diffusion. Comparing SUDS and PIS schemes shows relatively close results for the backward-facing step flow and different results in lid-driven cavity flow. The poor results of SUDS in the lid-driven cavity flow can be related to its lack of sensitivity to the pressure difference between cell face and upwind points, which is critical for the prediction of such vortex dominant flows.

Keywords: cell-centered finite volume method, coupled solver, exponential differencing scheme (EDS), physical influence scheme (PIS), pressure weighted interpolation method (PWIM), skew upwind differencing scheme (SUDS)

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4807 Temporal Changes of Heterogeneous Subpopulations of Human Adipose-Derived Stromal/Stem Cells in vitro

Authors: Qiuyue Peng, Vladimir Zachar

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The application of adipose-derived stromal/stem cells (ASCs) in regenerative medicine is gaining more awareness due to their advanced translational potential and abundant source preparations. However, ASC-based translation has been confounded by high subpopulation heterogeneity, causing ambiguity about its precise therapeutic value. Some phenotypes defined by a unique combination of positive and negative surface markers have been found beneficial to the required roles. Therefore, the immunophenotypic repertoires of cultured ASCs and temporal changes of distinct subsets were investigated in this study. ASCs from three donors undergoing cosmetic liposuction were cultured in standard culturing methods, and the co-expression patterns based on the combination of selected markers at passages 1, 4, and 8 were analyzed by multi-chromatic flow cytometry. The results showed that the level of heterogeneity of subpopulations of ASCs became lower by in vitro expansion. After a few passages, most of the CD166⁺/CD274⁺/CD271⁺ based subpopulations converged to CD166 single positive cells. Meanwhile, these CD29⁺CD201⁺ double-positive cells, in combination with CD36/Stro-1 expression or without, feathered only the major epitopes and maintained prevailing throughout the whole process. This study suggested that, upon in vitro expansion, the phenotype repertoire of ASCs redistributed and stabilized in a way that cells co-expressing exclusively the strong markers remained dominant. These preliminary findings provide a general overview of the distribution of heterogeneous subsets residents within human ASCs during expansion in vitro. It is a critical step to fully characterize ASCs before clinical application, although the biological effects of heterogeneous subpopulations still need to be clarified.

Keywords: adipose-derived stromal/stem cells, heterogeneity, immunophenotype, subpopulations

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4806 Tuberculous Osteomyelitis Mimicking Tumours and Tumour-Like Lesions of Bone: Clinico-Radiologic Study of 22 Patients

Authors: Parveen Kundu, Zile Singh, Kunika Kundu, Swaran Kaur

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Context: Tuberculous osteomyelitis is a relatively uncommon condition that can present with various clinical and radiological features, often mimicking bone tumors or tumor-like lesions. In endemic countries like India, tuberculosis should be considered as a potential differential diagnosis for lytic bone lesions. This study aimed to highlight the different presentations of tuberculosis that can mimic tumors or tumor-like lesions in bone and emphasize the successful outcome of antitubercular therapy (ATT) in treating these cases. Research Aim: The main objective of this research was to explore the varied presentations of tuberculosis that mimic bone tumors or tumor-like lesions both clinically and radiologically, focusing on different bones. The study aimed to raise awareness among clinicians about this possibility and highlight the importance of histopathological confirmation before initiating treatment for lytic bone lesions. Methodology: This study utilized a retrospective review of 22 patients with suspected lytic bone lesions, who were subsequently diagnosed with tuberculous osteomyelitis through histopathological examination. The cases were collected over a period of ten years. Eleven cases required curettage for extensive lesions with sequestrations, while all 22 patients received 12 months of antitubercular therapy. Findings: The study included 14 male and 8 female patients, ranging in age from 3 to 61 years, with an average age of 22.05. The clinical and radiological presentations varied, with examples including bone cysts in the metaphyseal area of long bones, lesions resembling chondroblastomas, giant cell tumors, and osteoid osteoma, as well as multifocal lytic lesions resembling metastasis or multiple myeloma. One patient had lesions in both the clavicle and hand. Lesions mimicking chondromas were also observed in the phalanges of the hand and foot metatarsal. All patients showed resolution of the lesions and no residual disability following ATT. Theoretical Importance: This study highlights the importance of considering tuberculosis as a potential differential diagnosis for lytic bone lesions, particularly in endemic regions. It emphasizes the need for histopathological confirmation to accurately diagnose tuberculous osteomyelitis, as this is considered the gold standard. Data Collection and Analysis Procedures: Data for this study were collected retrospectively from medical records and radiological images of the 22 patients. The cases were analyzed based on clinical presentation, radiological findings, and histopathological confirmation. The outcomes of antitubercular therapy were also assessed. The data were summarized and presented descriptively. Question Addressed: This study aimed to address the question of how tuberculosis can mimic different bone tumors and tumor-like lesions clinically and radiologically. It also aimed to assess the successful outcome of antitubercular therapy in treating these cases. Conclusion: Tuberculous osteomyelitis can present with varied clinical and radiological features, often mimicking bone tumors or tumor-like lesions. Clinicians should consider tuberculosis as a potential diagnosis for lytic bone lesions, especially in endemic areas. Histopathological confirmation is essential for accurate diagnosis. Antitubercular therapy is an effective treatment for tuberculous osteomyelitis, leading to the resolution of the lesions with no residual disability.

Keywords: tuberculosis, tumor, curettage, bone

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4805 Liposomal Encapsulation of Silver Nanoparticle for Improved Delivery and Enhanced Anticancer Properties

Authors: Azeez Yusuf, Alan Casey

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Silver nanoparticles (AgNP) are one of the most widely investigated metallic nanoparticles due to their promising antibacterial activities. In recent years, AgNP research has shifted beyond antimicrobial use to potential applications in the medical arena. This shift coupled with the extensive commercial applications of AgNP will further increase human exposure, and the subsequent risk of adverse effects that may result from repeated exposures and inefficient delivery meaning research into improved AgNP delivery is of paramount importance. In this study, AgNP were encapsulated in a natural bio-surfactant, dipalmitoylphosphatyidyl choline (DPPC), in an attempt to enhance the intracellular delivery and simultaneously mediate the associated cytotoxicity of the AgNP. It was noted that as a result of the encapsulation, liposomal-AgNP (Lipo-AgNP) at 0.625 μg/ml induced significant cell death in THP1 cell lines a notably lower dose than that of the uncoated AgNP induced cytotoxicity. The induced cytotoxicity was shown to result in an increased level of DNA fragmentation resulting in a cell cycle interruption at the S phase of the cell cycle. It was shown that the predominate form of cell death upon exposure to both uncoated and Lipo-AgNP was apoptosis, however, a ROS-independent activation of the executioner caspases 3/7 occurred when exposed to the Lipo-AgNP. These findings showed that encapsulation of AgNP enhances AgNP cytotoxicity and mediates an ROS-independent induction of apoptosis.

Keywords: silver nanoparticles, AgNP, cytotoxicity, encapsulation, liposome

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4804 Antigen-Presenting Cell Characteristics of Human γδ T Lymphocytes in Chronic Myeloid Leukemia

Authors: Piamsiri Sawaisorn, Tienrat Tangchaikeeree, Waraporn Chan-On, Chaniya Leepiyasakulchai, Rachanee Udomsangpetch, Suradej Hongeng, Kulachart Jangpatarapongsa

Abstract:

Human Vγ9Vδ2 T lymphocytes are regarded as promising effector cells for cancer immunotherapy since they have the ability to eliminate several tumor cells through non-peptide antigen recognition and non-major histocompatibility complex (MHC) restriction. An issue of recent interest is the capability to activate γδ T cells by use of a group of drugs, such as pamidronate, that cause accumulation of phosphoantigen which is recognized by γδ T cell receptors. Moreover, their antigen presenting cell-like phenotype and function have been confirmed in many clinical trials. In this study, Vγ9Vδ2 T cells derived from normal peripheral blood mononuclear cells were activated with pamidronate and the expanded Vγ9Vδ2 T cells can recognize and kill chronic myeloid leukemia (CML) cells treated with pamidronate through their cytotoxic activity. To support the strong role played by Vγ9Vδ2 T cells against cancer, we provide the evidence that Vγ9Vδ2 T cells activated with CML cell lysate antigen can efficiently express antigen presenting cell (APC) phenotype and function. In conclusion, pamidronate can be used in intentional activation of human Vγ9Vδ2 T cells and can increase the susceptibility of CML cells to cytotoxicity of Vγ9Vδ2 T cells. The activated Vγ9Vδ2 T cells by cancer cells lysate can show their APC characteristics, and so greatly increase the interest in exploring their therapeutic potential in hematologic malignancy.

Keywords: γδ T lymphocytes, antigen-presenting cells, chronic myeloid leukemia, cancer, immunotherapy

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4803 Trans-Activator of Transcription-Tagged Active AKT1 Variants for Delivery to Mammalian Cells

Authors: Tarana Siddika, Ilka U. Heinemann, Patrick O’Donoghue

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Protein kinase B (AKT1) is a serine/threonine kinase and central transducer of cell survival pathways. Typical approaches to study AKT1 biology in cells rely on growth factor or insulin stimulation that activates AKT1 via phosphorylation at two key regulatory sites (Threonine308, Serine473), yet cell stimulation also activates many other kinases and fails to differentiate the effect of the two main activating sites of AKT1 on downstream substrate phosphorylation and cell growth. While both AKT1 activating sites are associated with disease and used as clinical markers, in some cancers, high levels of Threonine308 phosphorylation are associated with poor prognosis while in others poor survival correlates with high Serine473 levels. To produce cells with specific AKT1 activity, a system was developed to deliver active AKT1 to human cells. AKT1 phospho-variants were produced from Escherichia coli with programmed phosphorylation by genetic code expansion. Tagging of AKT1 with an N-terminal cell penetrating peptide tag derived from the human immunodeficiency virus trans-activator of transcription (TAT) helped to enter AKT1 proteins in mammalian cells. The TAT-tag did not alter AKT1 kinase activity and was necessary and sufficient to rapidly deliver AKT1 protein variants that persisted in human cells for 24 h without the need to use transfection reagents. TAT-pAKT1T308, TAT-pAKT1S473 and TAT-pAKT1T308S473 proteins induced selective phosphorylation of the known AKT1 substrate GSK-3αβ, and downstream stimulation of the AKT1 pathway as evidenced by phosphorylation of ribosomal protein S6 at Serine240/244 in transfected cells. Increase in cell growth and proliferation was observed due to the transfection of different phosphorylated AKT1 protein variants compared to cells with TAT-AKT1 protein. The data demonstrate efficient delivery of AKT1 with programmed phosphorylation to human cells, thus establishing a cell-based model system to investigate signaling that is dependent on specific AKT1 activity and phosphorylation.

Keywords: cell penetrating peptide, cell signaling, protein kinase b (AKT1), phosphorylation

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4802 Investigating the Effect of High Intensity Laser and Dry Needling in Patients with Chronic Neck Pain

Authors: Marzieh Yassin, Azizeh Parandnia, Javad Sarrafzadeh, Reza Salehi

Abstract:

Background: Myofascial trigger points (MTrPs) are one of the main causes of musculoskeletal pain syndromes and are associated with pain, tenderness, and limited range of motion (ROM). This study compared the effectiveness of high-intensity laser therapy (HILT) and dry needling (DN) on pain intensity, pain pressure threshold, cervical range of motion and disability in people with chronic neck pain. Method and Material: 30 patients with chronic neck pain were randomly divided into two groups: a HILT group (n=15) and a DN group (n=15). Treatment sessions were performed for three weeks, and all participants received related intervention twice a week (5 sessions). The pain level was measured using a Visual Analog Scale (VAS); the pain pressure threshold (PPT) was measured using a digital algometer; perceived disability was measured using the neck disability index (NDI); and cervical range of movements (CROMs) were measured using an iPhone app (lateral flexion) and a goniometer (Rotation). Results: In both the dry needling and high-intensity laser therapy groups, the pain and neck disability were significantly decreased (P < 0.05). Also, the pain pressure threshold and cervical range of motions were significantly increased in both groups. However, there was no significant difference between the two groups (P > 0.05). Conclusion: Both high-intensity laser therapy and dry needling can be used to treat chronic neck pain.

Keywords: chronic neck pain, dry needling, high intensity laser therapy (HILT), pain, pain pressure threshold

Procedia PDF Downloads 77
4801 The Clinical and Survival Differences between Primary B-Cell and T/NK-Cell Non-Hodgkin Lymphomas in the Nasopharynx, Nasal Cavity, and Nasal Sinus: A Population-Based Study of 3839 Cases in the Seer Database

Authors: Jiajia Peng, Danni Cheng, Jianqing Qiu, Yufang Rao, Minzi Mao, Ke Qiu, Junhong Li, Fei Chen, Feng Liu, Jun Liu, Xiaosong Mu, Wenxin Yu, Wei Zhang, Wei Xu, Yu Zhao, Jianjun Ren

Abstract:

Background: Currently, primary B-cell non-Hodgkin lymphoma (B-NHL) and T/NK-cell non-Hodgkin lymphoma (NKT-NHL) originated from the nasal cavity (NC), nasopharynx (NP) and nasal sinus (NS) distinguished unclearly in the clinic. Objective: We sought to compare the clinical and survival differences of B-NHL and NKT-NHL that occurred in NC, NP, and NS, respectively. Methods: Retrospective data of patients diagnosed with nasal cavity lymphoma (NCL), nasopharyngeal lymphoma (NPL), and nasal sinus lymphoma (NSL) between 1975 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database were collected. We identified the B/NKT-NHL patients based on the histological type and performed univariate, multivariate, and Kaplan-Meier analyses to investigate the survival rates. Results: Of the identified 3,101 B-NHL and 738 NKT-NHL patients, those with B-NHL in NP were the majority (43%) and had better cancer-specific survival than those in NC and NS from 2010 to 2017 (5-year-CSS, NC vs. NP vs. NS: 81% vs. 83% vs. 82%). In contrast, most of the NKT-NHL originated from NC (68%) and had the highest CSS rate in the recent seven years (2010-2017, 5-year-CSS: 63%). Additionally, the survival outcomes of patients with NKT-NHL-NP (HR: 1.34, 95% CI: 0.62-2.89, P=0.460) who had received surgery were much worse than those of patients with NKT-NHL-NC (HR: 1.07, 95% CI: 0.75-1.52, P=0.710) and NKT-NHL-NS (HR: 1.11, 95% CI: 0.59-2.07, P=0.740). NKT-NHL-NS patients who had radiation performed (HR: 0.38, 95% CI: 0.19-0.73, P=0.004) showed the highest survival rates, while chemotherapy performed (HR: 1.01, 95% CI: 0.43-2.37, P=0.980) presented opposite results. Conclusions: Although B-NHL and NKT-NHL originating from NC, NP and NS had similar anatomical locations, their clinical characteristics, treatment therapies, and prognoses were different in this study. Our findings may suggest that B-NHL and NKT-NHL in NC, NP, and NS should be treated as different diseases in the clinic.

Keywords: nasopharyngeal lymphoma, nasal cavity lymphoma, nasal sinus lymphoma, B-cell non-Hodgkin lymphoma, T/NK-cell non-Hodgkin lymphoma

Procedia PDF Downloads 179
4800 Grading Histopathology Features of Graft-Versus-Host Disease in Animal Models; A Systematic Review

Authors: Hami Ashraf, Farid Kosari

Abstract:

Graft-versus-host disease (GvHD) is a common complication of allogeneic hematopoietic stem cell transplantation that can lead to significant morbidity and mortality. Histopathological examination of affected tissues is an essential tool for diagnosing and grading GvHD in animal models, which are used to study disease mechanisms and evaluate new therapies. In this systematic review, we identified and analyzed original research articles in PubMed, Scopus, Web of Science, and Google Scholar that described grading systems for GvHD in animal models based on histopathological features. We found that several grading systems have been developed, which vary in the tissues and criteria they assess, the severity scoring scales they use, and the level of detail they provide. Skin, liver, and gut are the most commonly evaluated tissues, but lung and thymus are also included in some systems. Our analysis highlights the need for standardized criteria and consistent use of grading systems to enable comparisons between studies and facilitate the translation of preclinical findings to clinical practice.

Keywords: graft-versus-host disease, GvHD, animal model, histopathology, grading system

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4799 Inflammatory Changes in Postmenopausal Women including Th17 and Treg

Authors: Ae Ra Han, Seoung Eun Huh, Ji Yeon Kim, Joanne Kwak-Kim, Sung Ki Lee

Abstract:

Objective: Prevalence of osteoporosis, cardiovascular disorders, and Alzheimer's disease rapidly increase after menopause. Immune activation and inflammation are suggested as an important pathogenesis of these serious diseases. Several pro-inflammatory cytokines are increased in women with surgical or natural menopause. However, the little is known about IL-17 producing T cells and Foxp3+ regulatory T (Treg) cells in post-menopause. Methods: A total of 34 postmenopausal women, who had no active cardiovascular, endocrine and infectious disorders were recruited as study group and healthy premenopausal women participated as controls. Peripheral blood mononuclear cells were isolated. Immuno-morphologic (CD3, CD4, CD8, CD19, CD56/CD16), intracellular cytokine (TNF-alpha, IFN-gamma, IL-10, IL-17), and Treg cell (Foxp3) studies were carried out using flow cytometry. The proportion of peripheral lymphocytes, including IL-17 producing and Foxp3+ Treg cells immune cell in each group were statistically analyzed. Results: The proportion of NK cells was significantly increased in menopausal women as compared to that of controls (P=.005). The ratios of TNF-alpha/IL-10 producing CD3+CD4+ T cells were increased in postmenopausal women. CD3+IL-17+ T cell level was higher in postmenopausal women and CD4+ Foxp3+ Treg cells was lower than that of controls. The ratios of CD3+IL-17+ T cell to CD3+Foxp3+ and to CD4+Foxp3+ Treg cells were significantly increased in postmenopausal women (P=.001). Conclusions: We found enhanced innate immunity and Th1- and Th17-mediated adaptive immunity in postmenopausal women. This may explain increasing prevalence of chronic inflammatory diseases after menopause. Further studies are needed to elucidate what factors contribute to this inflammatory shift in the postmenopause.

Keywords: inflammation, immune cell, menopause, Th17, regulatory T cell

Procedia PDF Downloads 318
4798 The Impact of Kids Science Labs Intervention Program on Independent Thinking and Academic Achievement in Young Children

Authors: Aliya Kamilyevna Salahova

Abstract:

This study examines the effectiveness of the Kids Science Labs intervention program, based on STEM, in fostering independent thinking among preschool and elementary school children and its influence on their academic achievement. Through a comprehensive methodology involving interviews, surveys, observations, case studies, and statistical tests, data were collected from various sources to accurately analyze the program's effects. The findings indicate a significant positive impact on children's independent thinking abilities, leading to improved academic performance in mathematics and science, enhanced learning motivation, and a propensity to critically evaluate problem-solving approaches. This research contributes to the theoretical understanding of how STEM activities can foster independent thinking and academic success in young children, providing valuable insights for the development of educational programs. Introduction: The goal of this study is to investigate the influence of the Kids Science Labs intervention program, grounded in STEM, on the development of independent thinking skills among preschool and elementary school children. By addressing this objective, we aim to explore the program's potential to enhance academic performance in mathematics and science. The study's findings have theoretical significance as they shed light on the ways in which STEM activities can foster independent thinking in young children, thus enabling educators to design effective learning programs that promote academic success. Methodology: This study employs a robust methodology that includes interviews, surveys, observations, case studies, and statistical tests. These methods were carefully selected to collect comprehensive data from multiple sources, such as documents and records, ensuring a thorough analysis of the program's effects. The use of diverse data collection and analysis procedures facilitated an in-depth exploration of the research questions and yielded reliable results. Results: The results indicate that children participating in the Kids Science Labs program experienced a sustained positive impact on their independent thinking abilities. Moreover, these children demonstrated improved academic performance in mathematics and science, displaying higher learning motivation and the capacity to critically evaluate problem-solving methods and seek optimal solutions. Theoretical Importance: This study contributes significantly to the existing theoretical knowledge by elucidating how STEM activities can foster independent thinking and enhance academic success in preschool and elementary school children. The findings have practical implications for educators, empowering them to develop learning programs that stimulate independent thinking, leading to improved academic performance in young children. Discussion: The findings of this research affirm that the Kids Science Labs intervention program is highly effective in fostering independent thinking among preschool and elementary school children. The program's positive impact extends to improved academic performance in mathematics and science, highlighting its potential to enhance learning outcomes. Educators can leverage these findings to develop educational programs that promote independent thinking and elevate academic achievement in young children. Conclusion: In conclusion, the Kids Science Labs intervention program has been found to be highly effective in fostering independent thinking among preschool and elementary school children. Furthermore, participation in the program correlates with improved academic performance in mathematics and science. The study's outcomes underscore the importance of developing educational initiatives that stimulate independent thinking in young children, thereby enhancing their academic success.

Keywords: STEM in preschool, STEM in elementary school, kids science labs, independent thinking, STEM activities in early childhood education

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4797 Effect of Non-Surgical Periodontal Therapy According to Periodontal Severity

Authors: Jungbin Lim, Bohee Kang, Heelim Lee, Sunjin Kim, GeumHee Choi, Jae-Suk Jung, Suk Ji

Abstract:

Nonsurgical periodontal therapies have, for several decades, been the basis of periodontal treatment concepts. The aim of this paper is to investigate the effectiveness of non-surgical periodontal therapy according to the severity of periodontitis disease. Methods: Retrospective data of patients who visited Department of periodontics in Ajou University Medical Center from 2016 to 2022 were collected. Among the patients, those who took full mouth examination of clinical parameters and non-surgical periodontal therapy were chosen for this study. Selected patients were divided into initial, moderate, and severe periodontitis based on severity and complexity of management (2018 World Workshop EFP/AAP consensus). Recall visits with clinical periodontal examination were scheduled for 1,2,3 months or 1,3,6 months after the treatment. The results were evaluated by recordings of mean probing pocket depth (mean PD), mean clinical attachment levels (mean CAL), bleeding on probing (BOP%), mean gingival index (mean GI), mean regression, mean sulcus bleeding index (mean SBI), mean plaque scores (mean PI). All statistical analyses were performed with R software, version 4.3.0. A level of significance, P<0.05, was considered to be statistically significant. Results: A total of 92 patients were included in this study. 15 patients were diagnosed as initial periodontitis, 14 moderate periodontitis, and 63 severe periodontitis. The all parameters except for mean recession decreased over time in all groups. The amount of mean PD decreased were the greatest in severe periodontitis group followed by moderate and initial, which was found to be statistically significant. The changes of mean PD were 0.15±0.05 mm, 0.37±0.06 mm, and 1.01±0.07 mm (initial, moderate, and severe, respectively, P<0.001). When comparing before and after treatment, the reductions in BOP(%), mean GI, mean SBI, and mean PI were statistically significant. Conclusion: All patients who received non-surgical periodontal therapy showed periodontal healing in terms of improvements in clinical parameters, and it was greater in the severe group.

Keywords: periodontology, clinical periodontology, oral treatment, comprehensive preventive dentistry, non-surgical periodontal therapy

Procedia PDF Downloads 71
4796 Fuel Inventory/ Depletion Analysis for a Thorium-Uranium Dioxide (Th-U) O2 Pin Cell Benchmark Using Monte Carlo and Deterministic Codes with New Version VIII.0 of the Evaluated Nuclear Data File (ENDF/B) Nuclear Data Library

Authors: Jamal Al-Zain, O. El Hajjaji, T. El Bardouni

Abstract:

A (Th-U) O2 fuel pin benchmark made up of 25 w/o U and 75 w/o Th was used. In order to analyze the depletion and inventory of the fuel for the pressurized water reactor pin-cell model. The new version VIII.0 of the ENDF/B nuclear data library was used to create a data set in ACE format at various temperatures and process the data using the MAKXSF6.2 and NJOY2016 programs to process the data at the various temperatures in order to conduct this study and analyze cross-section data. The infinite multiplication factor, the concentrations and activities of the main fission products, the actinide radionuclides accumulated in the pin cell, and the total radioactivity were all estimated and compared in this study using the Monte Carlo N-Particle 6 (MCNP6.2) and DRAGON5 programs. Additionally, the behavior of the Pressurized Water Reactor (PWR) thorium pin cell that is dependent on burn-up (BU) was validated and compared with the reference data obtained using the Massachusetts Institute of Technology (MIT-MOCUP), Idaho National Engineering and Environmental Laboratory (INEEL-MOCUP), and CASMO-4 codes. The results of this study indicate that all of the codes examined have good agreements.

Keywords: PWR thorium pin cell, ENDF/B-VIII.0, MAKXSF6.2, NJOY2016, MCNP6.2, DRAGON5, fuel burn-up.

Procedia PDF Downloads 94
4795 Predictive Value of Primary Tumor Depth for Cervical Lymphadenopathy in Squamous Cell Carcinoma of Buccal Mucosa

Authors: Zohra Salim

Abstract:

Objective: To access the relationship of primary tumor thickness with cervical lymphadenopathy in squamous cell carcinoma of buccal mucosa. Methodology: A cross-sectional observational study was carried out on 80 Patients with biopsy-proven oral squamous cell carcinoma of buccal mucosa at Dow University of Health Sciences. All the study participants were treated with wide local excision of the primary tumor with elective neck dissection. Patients with prior head and neck malignancy or those with prior radiotherapy or chemotherapy were excluded from the study. Data was entered and analyzed on SPSS 21. Chi-squared test with 95% C.I and 80% power of the test was used to evaluate the relationship of tumor depth with cervical lymph nodes. Results: 50 participants were male, and 30 patients were female. 30 patients were in the age range of 20-40 years, 36 patients in the range of 40-60 years, while 14 patients were beyond age 60 years. Tumor size ranged from 0.3cm to 5cm with a mean of 2.03cm. Tumor depth ranged from 0.2cm to 5cm. 20% of the participants reported with tumor depth greater than 2.5cm, while 80% of patients reported with tumor depth less than 2.5cm. Out of 80 patients, 27 reported with negative lymph nodes, while 53 patients reported with positive lymph nodes. Conclusion: Our study concludes that relationship exists between the depth of primary tumor and cervical lymphadenopathy in squamous cell carcinoma of buccal mucosa.

Keywords: squamous cell carcinoma, tumor depth, cervical lymphadenopathy, buccal mucosa

Procedia PDF Downloads 234
4794 Optimization of Hydrogel Conductive Nanocomposite as Solar Cell

Authors: Shimaa M. Elsaeed, Reem K. Farag, Ibrahim M. Nassar

Abstract:

Hydrogel conductive polymer nanocomposite fabricated via in-situ polymerization of polyaniline (PANI) inside thermosensitive hydrogels based on hydroxy ethyl meth acrylate (HEMA) copolymer with 2-acrylamido-2-methyl propane sulfonic acid (AMPS). SEM micrographs show the nanometric size of the conductive material (polyaniline, PANI) dispersed in the hydrogel matrix. The swelling parameters of hydrogel are measured. The incorporation of PANI improves the mechanical properties and swelling up to 30,000% without breaking. X-ray diffraction shows that typical polyaniline crystallization is formed in composite, which is advantageous to increase the electrical conductivity of the composite hydrogel. Open-circuit voltage (I-V) curve fill factor of the highest photo-conversion efficiency and enhanced to use in solar cell.

Keywords: hydrogel, solar cell, conductive polymer, nanocomposite

Procedia PDF Downloads 396
4793 Prediction of B-Cell Epitope for 24 Mite Allergens: An in Silico Approach towards Epitope-Based Immune Therapeutics

Authors: Narjes Ebrahimi, Soheila Alyasin, Navid Nezafat, Hossein Esmailzadeh, Younes Ghasemi, Seyed Hesamodin Nabavizadeh

Abstract:

Immunotherapy with allergy vaccines is of great importance in allergen-specific immunotherapy. In recent years, B-cell epitope-based vaccines have attracted considerable attention and the prediction of epitopes is crucial to design these types of allergy vaccines. B-cell epitopes might be linear or conformational. The prerequisite for the identification of conformational epitopes is the information about allergens' tertiary structures. Bioinformatics approaches have paved the way towards the design of epitope-based allergy vaccines through the prediction of tertiary structures and epitopes. Mite allergens are one of the major allergy contributors. Several mite allergens can elicit allergic reactions; however, their structures and epitopes are not well established. So, B-cell epitopes of various groups of mite allergens (24 allergens in 6 allergen groups) were predicted in the present work. Tertiary structures of 17 allergens with unknown structure were predicted and refined with RaptorX and GalaxyRefine servers, respectively. The predicted structures were further evaluated by Rampage, ProSA-web, ERRAT and Verify 3D servers. Linear and conformational B-cell epitopes were identified with Ellipro, Bcepred, and DiscoTope 2 servers. To improve the accuracy level, consensus epitopes were selected. Fifty-four conformational and 133 linear consensus epitopes were predicted. Furthermore, overlapping epitopes in each allergen group were defined, following the sequence alignment of the allergens in each group. The predicted epitopes were also compared with the experimentally identified epitopes. The presented results provide valuable information for further studies about allergy vaccine design.

Keywords: B-cell epitope, Immunotherapy, In silico prediction, Mite allergens, Tertiary structure

Procedia PDF Downloads 156
4792 Pathogenic Effects of IgG and IgM Apoptotic Cell-Reactive Monoclonal Auto-Antibodies on Innate and Adaptive Immunity in Lupus

Authors: Monika Malik, Pooja Arora, Ruchi Sachdeva, Vishnampettai G. Ramachandran, Rahul Pal

Abstract:

Apoptotic debris is believed to be the antigenic trigger in lupus. Whether such debris and autoantibodies induced in lupus-prone mice which specifically recognize its constituents can mediate differential effects on innate and humoral responses in such mice was assessed. The influence of apoptotic blebs and apoptotic cell-reactive monoclonal antibodies on phenotypic markers expressed on bone marrow-derived dendritic cells (BMDCs) and secreted cytokines were evaluated. Sera from lupus-prone and healthy mice immunized with the antibodies were analyzed for anti-self reactivity. Apoptotic blebs, as well as somatically-mutated IgG and non-mutated IgM apoptotic-cell reactive monoclonal antibodies, induced the preferential maturation of BMDCs derived from lupus-prone mice relative to BMDCs derived from healthy mice; antibody specificity and cell genotype both influenced the secretion of inflammatory cytokines. Immunization of lupus-prone mice with IgM and IgG antibodies led to hypergammaglobulinemia; elicited antibodies were self-reactive, and exhibited enhanced recognition of lupus-associated autoantigens (dsDNA, Ro60, RNP68, and Sm) in comparison with adjuvant-induced sera. While ‘natural’ IgM antibodies are believed to contribute to immune homeostasis, this study reveals that apoptotic cell-reactive IgM antibodies can promote inflammation and drive anti-self responses in lupus. Only in lupus-prone mice did immunization with IgG auto-antibodies enhance the kinetics of humoral anti-self responses, resulting in advanced-onset glomerulosclerosis. This study reveals that preferential innate and humoral recognition of the products of cell death in an autoimmune milieu influences the indices associated with lupus pathology.

Keywords: antigen spreading, apoptotic cell-reactive pathogenic IgG, and IgM autoantibodies, glomerulosclerosis, lupus

Procedia PDF Downloads 166
4791 Rituximab Therapy for Musculoskeletal Involvement in Systemic Sclerosis

Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

Abstract:

Objectives. There is very few data on changes of the musculoskeletal manifestations (artritis, arthralgia, muscle weakness, etc.) in systemic sclerosis (SSc) on rituximab (RTX) therapy. The aim of our study was to assess the severity of the musculoskeletal involvement in SSc patients (pts) and its changes during RTX therapy. Methods. Our study included 103 pts with SSc. The mean followup period was 12.6±10.7 months. The mean age was 47±12.9 years, female-87 pts (84%), the diffuse cutaneous subset of the disease had 55 pts (53%). The mean disease duration was 6.2±5.5 years. All pts had interstitial lung disease (ILD) and were positive for ANA, 67% of them were positive for antitopoisomerase-1. All patients received prednisolone at a dose of 11.3±4.5 mg/day, immunosuppressants at inclusion received 47% of them. Pts received RTX due to the ineffectiveness of previous therapy for ILD. The cumulative mean dose of RTX was 1.7±0.6 grams. Arthritis was observed in 22 pts (21%), arthralgias in 47 pts (46%). Muscle weakness was observed in 17 pts (17%). Tendon friction rubs was established in 7 pts (7%). The results at baseline and at the end of the follow up are presented in the form of mean values. Results. There was an improvement of all outcome parameters and musculoskeletal manifestations on RTX therapy. There was a decrease in the number of pts with arthritis from 22 (21%) to 10 (9%), a decrease in the number of pts with arthralgias from 47 (46%) to 31 (30%). The number of pts with muscle weakness decreased from 17 (17%) to 7 (7%). The number of pts with tendon friction rubs decreased from 7 (7%) to 3 (3%). The creatine phosphokinase decreased from 365.5±186 to 70.8±50.4 (p=0.00006). The C-reactive protein (CRP) decreased from 23.2±31.3 to 8.62±7.4 (p=0.001). The dose of prednisolone was reduced from 11.3±4.5 to 9.8±3.5 mg/day (p=0.0004). Conclusion. In our study, musculoskeletal involvement was detected in almost half of the patients with SSc-ILD. There was an improvement of musculoskeletal manifestations despite a small cumulative dose of RTX. We also managed to reduce the dose of glucocorticosteroids. The improvement of musculoskeletal manifestations was accompanied by a decrease in laboratory parameters - creatine phosphokinase and CRP. RTX is effective option for treatment of musculoskeletal manifestations in SSc.

Keywords: arthritis, musculoskeletal involvement, systemic sclerosis, rituximab

Procedia PDF Downloads 79
4790 Oral Health Status in Sickle Cell Anemia Subjects

Authors: Surekha Rathod

Abstract:

Sickle cell disease is a vascular disorder characterized by chronic, ongoing organ damage that is punctuated by episodes of acutely painful vascular complications.1 It is the most common genetic blood disorder in the United States, with about 2000 infants being identified through routine blood screenings annually, and an estimated 104,000-138,000 affected individuals living in the United States. Approximately 0.3%-1.3% of African American are affected by Sickle Cell Diseases (SCD).3 The aim of this paper is to present oral health status of patients with SCD. A total of 200 subjects of both sexes in the age group 18- 40 years were included in this study. The subjects were examined and the following indices were recorded • Oral hygiene index – Simplified (OHI-S). • Probing depths (PD). • Clinical Attachment Levels (CAL). • Gingival Index - Loe and Sillness. • Turesky Gillmore Glickman Modification of the Quigley Hein Plaque Index. (1970) • DMFT index. • Sickle Cell Disease Severity Index. A total of 1478 patients were screened of which 200 subjects were found to be diagnosed with SCD by electrophoresis. The study thus, included 200 subjects (111 females & 89 males) diagnosed with Sickle Cell Disease in the age group of 18-40 years. The probing pocket depths (PPD) were measured in millimeters. 36% had PPD in the range of 2-4mm, 48% had PPD in the range of 4-6mm while 16% had PPD of more than 6mm. Similar results were obtained for the Clinical Attachment Levels (CAL). 29.5 % subjects had CAL 2-4mm, 44.5% had 4-6mm & 26% had CAL 6mm & above. We can thus conclude that although oral health is not a priority for patients with SCD, it is supported by increased plaque accumulation. Because of the chronic anemic state of the patients with SCD, they should be encouraged to pay strict attention to oral hygiene instructions and practice.

Keywords: chronic, genetic, oral, sickle cell disease, vascular

Procedia PDF Downloads 396