Search results for: phenotype switch of smooth muscle cells
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4644

Search results for: phenotype switch of smooth muscle cells

4614 Peptidoglycan Vaccine-On-Chip against a Lipopolysaccharide-Induced Experimental Sepsis Model

Authors: Katerina Bakela, Ioanna Zerva, Irene Athanassakis

Abstract:

Lipopolysaccharide (LPS) is commonly used in murine sepsis models, which are largely associated with immunosuppression (incretion of MDSCs cells and Tregs, imbalance of inflammatory/anti-inflammatory cytokines) and collapse of the immune system. After adapting the LPS treatment to the needs of locally bred BALB/c mice, the present study explored the protective role of Micrococcus luteus peptidoglycan (PG) pre-activated vaccine-on chip in endotoxemia. The established protocol consisted of five daily intraperitoneal injections of 0.2mg/g LPS. Such protocol allowed longer survival, necessary in the prospect of the therapeutic treatment application. The so-called vaccine-on-chip consists of a 3-dimensional laser micro-texture Si-scaffold loaded with BALB/c mouse macrophages and activated in vitro with 1μg/ml PG, which exert its action upon subcutaneous implantation. The LPS treatment significantly decreased CD4+, CD8+, CD3z+, and CD19+ cells, while increasing myeloid-derived suppressor cells (MDSCs), CD25+, and Foxp3+ cells. These results were accompanied by increased arginase-1 activity in spleen cell lysates and production of IL-6, TNF-a, and IL-18 while acquiring severe sepsis phenotype as defined by the murine sepsis scoring. The in vivo application of PG pre-activated vaccine-on chip significantly decreased the percent of CD11b+, Gr1+, CD25+, Foxp3+ cells, and arginase-1 activity in the spleen of LPS-treated animals, while decreasing IL-6 and TNF-a in the serum, allowing survival to all animals tested and rescuing the severity of sepsis phenotype. In conclusion, these results reveal a promising mode of action of PG pre-activated vaccine-on chip in LPS endotoxemia, strengthening; thus, the use of treatment is septic patients.

Keywords: myeloid-derived suppressor cells, peptidoglycan, sepsis, Si-scaffolds

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4613 Design and Simulation of Step Structure RF MEMS Switch for K Band Applications

Authors: G. K. S. Prakash, Rao K. Srinivasa

Abstract:

MEMS plays an important role in wide range of applications like biological, automobiles, military and communication engineering. This paper mainly investigates on capacitive shunt RF MEMS switch with low actuation voltage and low insertion losses. To trim the pull-in voltage, a step structure has introduced to trim air gap between the beam and the dielectric layer with that pull in voltage is trim to 2.9 V. The switching time of the proposed switch is 39.1μs, and capacitance ratio is 67. To get more isolation, we have used aluminum nitride as dielectric material instead of silicon nitride (Si₃N₄) and silicon dioxide (SiO₂) because aluminum nitride has high dielectric constant (εᵣ = 9.5) increases the OFF capacitance and eventually increases the isolation of the switch. The results show that the switch is ON state involves return loss (S₁₁) less than -25 dB up to 40 GHz and insertion loss (S₂₁) is more than -1 dB up to 35 GHz. In OFF state switch shows maximum isolation (S₂₁) of -38 dB occurs at a frequency of 25-27 GHz for K band applications.

Keywords: RF MEMS, actuation voltage, isolation loss, switches

Procedia PDF Downloads 362
4612 Immunoliposomes Conjugated with CD133 Antibody for Targeting Melanoma Cancer Stem Cells

Authors: Chuan Yin

Abstract:

Cancer stem cells (CSCs) represent a subpopulation of cancer cells that possess the characteristics associated with normal stem cells. CD133 is a phenotype of melanoma CSCs responsible for melanoma metastasis and drug resistance. Although adriamycin (ADR) is commonly used drug in melanoma therapy, but it is ineffective in the treatment of melanoma CSCs. In this study, we constructed CD133 antibody conjugated ADR immunoliposomes (ADR-Lip-CD133) to target CD133+ melanoma CSCs. The results showed that the immunoliposomes possessed a small particle size (~150 nm), high drug encapsulation efficiency (~90%). After 72 hr treatment on the WM266-4 melanoma tumorspheres, the IC50 values of the drug formulated in ADR-Lip-CD133, ADR-Lip (ADR liposomes) and ADR are found to be 24.42, 57.13 and 59.98 ng/ml respectively, suggesting that ADR-Lip-CD133 was more effective than ADR-Lip and ADR. Significantly, ADR-Lip-CD133 could almost completely abolish the tumorigenic ability of WM266-4 tumorspheres in vivo, and showed the best therapeutic effect in WM266-4 melanoma xenograft mice. It is noteworthy that ADR-Lip-CD133 could selectively kill CD133+ melanoma CSCs of WM266-4 cells both in vitro and in vivo. ADR-Lip-CD133 represent a potential approach in targeting and killing CD133+ melanoma CSCs.

Keywords: cancer stem cells, melanoma, immunoliposomes, CD133

Procedia PDF Downloads 382
4611 High-Dimensional Single-Cell Imaging Maps Inflammatory Cell Types in Pulmonary Arterial Hypertension

Authors: Selena Ferrian, Erin Mccaffrey, Toshie Saito, Aiqin Cao, Noah Greenwald, Mark Robert Nicolls, Trevor Bruce, Roham T. Zamanian, Patricia Del Rosario, Marlene Rabinovitch, Michael Angelo

Abstract:

Recent experimental and clinical observations are advancing immunotherapies to clinical trials in pulmonary arterial hypertension (PAH). However, comprehensive mapping of the immune landscape in pulmonary arteries (PAs) is necessary to understand how immune cell subsets interact to induce pulmonary vascular pathology. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to interrogate the immune landscape in PAs from idiopathic (IPAH) and hereditary (HPAH) PAH patients. Massive immune infiltration in I/HPAH was observed with intramural infiltration linked to PA occlusive changes. The spatial context of CD11c+DCs expressing SAMHD1, TIM-3 and IDO-1 within immune-enriched microenvironments and neutrophils were associated with greater immune activation in HPAH. Furthermore, CD11c-DC3s (mo-DC-like cells) within a smooth muscle cell (SMC) enriched microenvironment were linked to vessel score, proliferating SMCs, and inflamed endothelial cells. Experimental data in cultured cells reinforced a causal relationship between neutrophils and mo-DCs in mediating pulmonary arterial SMC proliferation. These findings merit consideration in developing effective immunotherapies for PAH.

Keywords: pulmonary arterial hypertension, vascular remodeling, indoleamine 2-3-dioxygenase 1 (IDO-1), neutrophils, monocyte-derived dendritic cells, BMPR2 mutation, interferon gamma (IFN-γ)

Procedia PDF Downloads 173
4610 Robotic Exoskeleton Response During Infant Physiological Knee Kinematics

Authors: Breanna Macumber, Victor A. Huayamave, Emir A. Vela, Wangdo Kim, Tamara T. Chamber, Esteban Centeno

Abstract:

Spina bifida is a type of neural tube defect that affects the nervous system and can lead to problems such as total leg paralysis. Treatment requires physical therapy and rehabilitation. Robotic exoskeletons have been used for rehabilitation to train muscle movement and assist in injury recovery; however, current models focus on the adult populations and not on the infant population. The proposed framework aims to couple a musculoskeletal infant model with a robotic exoskeleton using vacuum-powered artificial muscles to provide rehabilitation to infants affected by spina bifida. The study that drove the input values for the robotic exoskeleton used motion capture technology to collect data from the spontaneous kicking movement of a 2.4-month-old infant lying supine. OpenSim was used to develop the musculoskeletal model, and Inverse kinematics was used to estimate hip joint angles. A total of 4 kicks (A, B, C, D) were selected, and the selection was based on range, transient response, and stable response. Kicks had at least 5° of range of motion with a smooth transient response and a stable period. The robotic exoskeleton used a Vacuum-Powered Artificial Muscle (VPAM) the structure comprised of cells that were clipped in a collapsed state and unclipped when desired to simulate infant’s age. The artificial muscle works with vacuum pressure. When air is removed, the muscle contracts and when air is added, the muscle relaxes. Bench testing was performed using a 6-month-old infant mannequin. The previously developed exoskeleton worked really well with controlled ranges of motion and frequencies, which are typical of rehabilitation protocols for infants suffering with spina bifida. However, the random kicking motion in this study contained high frequency kicks and was not able to accurately replicate all the investigated kicks. Kick 'A' had a greater error when compared to the other kicks. This study has the potential to advance the infant rehabilitation field.

Keywords: musculoskeletal modeling, soft robotics, rehabilitation, pediatrics

Procedia PDF Downloads 118
4609 Effect of Nicorandil in Bile Duct Ligation-Induced Liver Fibrosis in Rats: Role of Hepatic Stellate Cells

Authors: Y. S. Mohamed, L. A. Ahmed, H. A. Salem, A. M. Agha

Abstract:

Liver Fibrosis is one of the most serious conditions that affect the Egyptian society. In the present study, the effect of nicorandil was investigated in experimentally-induced liver fibrosis by bile duct ligation in rats. Nicorandil (3mg/kg/day) was given orally 24 h after bile duct ligation for 14 days till the end of the experiment. Nicorandil group showed a significant improvement in liver function tests (ALT and ALP) as well as a significant decrease in oxidative stress biomarkers (TBARS and GSH), area of fibrosis and activity of hepatic stellate cells as indicated by decreased expression of alpha smooth muscle actin.Moreover, nicorandil treatment decreased HSCs proliferation due to its inhibitory effects on protein kinase C(PKC) and Platelet derived growth factor (PDGF) . Oral administration of either glibenclamide (10 mg/kg/day)(a KATP channel blocker) or L-NAME (30 mg/kg/day) (an inhibitor of nitric oxide synthase) blocked the protective effects of nicorandil. However, nicorandil and L-NAME treated group showed more or less results similar to that of untreated bile duct ligated group. In conclusion, nicorandil was effective against the development of bile duct ligated-induced liver fibrosis in rats where activation of the NO pathway plays an important role in the protective effect nicorandil.

Keywords: hepatic stellate cells, nicorandil, nitric oxide donor, liver fibrosis

Procedia PDF Downloads 611
4608 Exoskeleton Response During Infant Physiological Knee Kinematics And Dynamics

Authors: Breanna Macumber, Victor A. Huayamave, Emir A. Vela, Wangdo Kim, Tamara T. Chamber, Esteban Centeno

Abstract:

Spina bifida is a type of neural tube defect that affects the nervous system and can lead to problems such as total leg paralysis. Treatment requires physical therapy and rehabilitation. Robotic exoskeletons have been used for rehabilitation to train muscle movement and assist in injury recovery; however, current models focus on the adult populations and not on the infant population. The proposed framework aims to couple a musculoskeletal infant model with a robotic exoskeleton using vacuum-powered artificial muscles to provide rehabilitation to infants affected by spina bifida. The study that drove the input values for the robotic exoskeleton used motion capture technology to collect data from the spontaneous kicking movement of a 2.4-month-old infant lying supine. OpenSim was used to develop the musculoskeletal model, and Inverse kinematics was used to estimate hip joint angles. A total of 4 kicks (A, B, C, D) were selected, and the selection was based on range, transient response, and stable response. Kicks had at least 5° of range of motion with a smooth transient response and a stable period. The robotic exoskeleton used a Vacuum-Powered Artificial Muscle (VPAM) the structure comprised of cells that were clipped in a collapsed state and unclipped when desired to simulate infant’s age. The artificial muscle works with vacuum pressure. When air is removed, the muscle contracts and when air is added, the muscle relaxes. Bench testing was performed using a 6-month-old infant mannequin. The previously developed exoskeleton worked really well with controlled ranges of motion and frequencies, which are typical of rehabilitation protocols for infants suffering with spina bifida. However, the random kicking motion in this study contained high frequency kicks and was not able to accurately replicate all the investigated kicks. Kick 'A' had a greater error when compared to the other kicks. This study has the potential to advance the infant rehabilitation field.

Keywords: musculoskeletal modeling, soft robotics, rehabilitation, pediatrics

Procedia PDF Downloads 83
4607 Fast High Voltage Solid State Switch Using Insulated Gate Bipolar Transistor for Discharge-Pumped Lasers

Authors: Nur Syarafina Binti Othman, Tsubasa Jindo, Makato Yamada, Miho Tsuyama, Hitoshi Nakano

Abstract:

A novel method to produce a fast high voltage solid states switch using Insulated Gate Bipolar Transistors (IGBTs) is presented for discharge-pumped gas lasers. The IGBTs are connected in series to achieve a high voltage rating. An avalanche transistor is used as the gate driver. The fast pulse generated by the avalanche transistor quickly charges the large input capacitance of the IGBT, resulting in a switch out of a fast high-voltage pulse. The switching characteristic of fast-high voltage solid state switch has been estimated in the multi-stage series-connected IGBT with the applied voltage of several tens of kV. Electrical circuit diagram and the mythology of fast-high voltage solid state switch as well as experimental results obtained are presented.

Keywords: high voltage, IGBT, solid state switch, bipolar transistor

Procedia PDF Downloads 552
4606 Effect of Two Bouts of Eccentric Exercise on Knee Flexors Changes in Muscle-Tendon Lengths

Authors: Shang-Hen Wu, Yung-Chen Lin, Wei-Song Chang, Ming-Ju Lin

Abstract:

This study investigated whether the repeated bout effect (RBE) of knee flexors (KF) eccentric exercise would be changed in muscle-tendon lengths. Eight healthy university male students used their KF of non-dominant leg and performed a bout of 60 maximal isokinetic (30°/s) eccentric contractions (MaxECC1). A week after MaxECC1, all subjects used the same KF to perform a subsequent bout of MaxECC2. Changes in maximal isokinetic voluntary contraction torque (MVC-CON), muscle soreness (SOR), relaxed knee joint angle (RANG), leg circumference (CIR), and ultrasound images (UI; muscle-tendon length and muscle angle) were measured before, immediately after, 1-5 days after each bout. Two-way ANOVA was used to analyze all the dependent variables. After MaxECC1, all the dependent variables (e.g. MVC-CON: ↓30%, muscle-tendon length: ↑24%, muscle angle: ↑15%) showed significantly change. Following MaxECC2, all the above dependent variables (e.g. MVC-CON:↓21%, tendon length: ↑16%, muscle angle: ↑6%) were significantly smaller than those of MaxECC1. These results of this study found that protective effect conferred by MaxECC1 against MaxECC2, and changes in muscle damage indicators, muscle-tendon length and muscle angle following MaxECC2 were smaller than MaxECC1. Thus, the amount of shift of muscle-tendon length and muscle angle was related to the RBE.

Keywords: eccentric exercise, maximal isokinetic voluntary contraction torque, repeated bout effect, ultrasound

Procedia PDF Downloads 331
4605 Solid Oral Leiomyoma: Clinical Case Report

Authors: Hurtado Zuñiga Yonel Marcos, Ferreira Joao Tiago

Abstract:

Introduction: Leiomyoma is a benign smooth muscle tumor. It is predominantly found between 40-49 years with a small prevalence in men. It is commonly found in the uterus, stomach, and in areas with smooth muscle. It presents as nodular, solitary, variable size, slow growing, and asymptomatic. It is classified into solid, vascular, and epithelioid leiomyoma. Vascular leiomyoma is the most common in the oral cavity. Oral leiomyomas are very rare because a smooth muscle in the oral cavity isn’t common. The most frequent areas of this pathologyaretongue, lip, buccal mucosa, and palate. It may be derived from the vascular walls or excretory ducts of the salivary glands. The diagnosis is made by histologically analysis. The treatment of choice is complete excision. Recurrence is rare. Objective: To report the case of a solid leiomyoma on the dorsum of the tongue and review the literature. Case description: A 78-year-old female patient presented a nodular (ovoid) elevation of 8x6mm, brownish color, with irregular limits and firm consistency located in the dorsal part of the tongue with slight symptoms. An excisional biopsy was performed, photographic record, and 3 weeks post-surgical follow-up. Result: The surgical specimen was submitted to an anatomopathological analysis, resulting in a benign nodule with defined limits compatible with solid leiomyoma of the tongue. Discussion: It is a pathology that presents in a solitary, nodular, well-defined, asymptomatic form; in the oral cavity, leiomyomas are found in the tongue, lip, buccal mucosa, and palate; as in our patient, it was nodular and, in the tongue, with a difference only in the symptomatology. The most prevalent age is 40-49 years and with small predominance in men, unlike our female patient with 78 years. Conclusions: Oral leiomyoma is a rare benign lesion that presents as a solitary nodular nodule; for its diagnosis, an anatomopathological analysis should be performed, and the treatment of choice is total excision with little recurrence.

Keywords: tongue, bening tumor, oral leiomyoma, leiomyoma

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4604 Optimal Rest Interval between Sets in Robot-Based Upper-Arm Rehabilitation

Authors: Virgil Miranda, Gissele Mosqueda, Pablo Delgado, Yimesker Yihun

Abstract:

Muscular fatigue affects the muscle activation that is needed for producing the desired clinical outcome. Integrating optimal muscle relaxation periods into a variety of health care rehabilitation protocols is important to maximize the efficiency of the therapy. In this study, four muscle relaxation periods (30, 60, 90, and 120 seconds) and their effectiveness in producing consistent muscle activation of the muscle biceps brachii between sets of elbow flexion and extension task was investigated among a sample of 10 subjects with no disabilities. The same resting periods were then utilized in a controlled exoskeleton-based exercise for a sample size of 5 subjects and have shown similar results. On average, the muscle activity of the biceps brachii decreased by 0.3% when rested for 30 seconds, and it increased by 1.25%, 0.76%, and 0.82% when using muscle relaxation periods of 60, 90, and 120 seconds, respectively. The preliminary results suggest that a muscle relaxation period of about 60 seconds is needed for optimal continuous muscle activation within rehabilitation regimens. Robot-based rehabilitation is good to produce repetitive tasks with the right intensity, and knowing the optimal resting period will make the automation more effective.

Keywords: rest intervals, muscle biceps brachii, robot rehabilitation, muscle fatigue

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4603 A Novel Co-Culture System for the Cementoblastic Differentiation of SHED

Authors: Manal Farea, Adam Husein, Ahmad S. Halim, Zurairah Berahim, Nurul A. Abdullah, Khairani I. Mokhtar, Kasmawati Mokhtar

Abstract:

Endodontic furcal perforation remains both an endodontic and a periodontal problem. Regeneration of cementum is very essential for the perforation repair. The aim of this study was to investigate the role of Hertwig's epithelial root sheath (HERS) cells on the cementogenic differentiation of stem cells derived from human exfoliated deciduous teeth (SHED) in the presence of chitosan scaffold-TGFβ1. HERS cells were isolated and characterized then co-cultured with SHED with/without chitosan scaffold-TGFβ1. SHED proliferation was assessed by PrestoBlue. Alkaline phosphatase activity, mineralization behaviour and gene/protein expression of cemento/osteoblast phenotype of SHED were evaluated. Results of the present study showed that HERS cells in association with chitosan-TGFβ1 enhanced proliferation and cemento/osteogenic differentiation of SHED. Our novel co-culture system confirmed the potential effect of HERS cells to stimulate the differentiation of SHED along the cementoblastic lineage which was triggered in the presence of chitosan-TGFβ1. This approach possesses a novel therapeutic strategy for future endodontic perforation and periodontitis.

Keywords: cementogenesis, co-culture system, HERS, SHED

Procedia PDF Downloads 542
4602 The Role of Chemerin and Myostatin after Physical Activity

Authors: M. J. Pourvaghar, M. E. Bahram

Abstract:

Obesity and overweight is one of the most common metabolic disorders in industrialized countries and in developing countries. One consequence of pathological obesity is cardiovascular disease and metabolic syndrome. Chemerin is an adipocyne that plays a role in the regulation of the adipocyte function and the metabolism of glucose in the liver and musculoskeletal system. Most likely, chemerin is involved in obesity-related disorders such as type 2 diabetes and cardiovascular disease. Aerobic exercises reduce the level of chemerin and cause macrophage penetration into fat cells and inflammatory factors. Several efforts have been made to clarify the cellular and molecular mechanisms of hypertrophy and muscular atrophy. Myostatin, a new member of the TGF-β family, is a transforming growth factor β that its expression negatively regulates the growth of the skeletal muscle; and the increase of this hormone has been observed in conditions of muscular atrophy. While in response to muscle overload, its levels decrease after the atrophy period, TGF-β is the most important cytokine in the development of skeletal muscle. Myostatin plays an important role in muscle control, and animal and human studies show a negative role of myostatin in the growth of skeletal muscle. Separation of myostatin from Golgi begins on the ninth day of the onset period and continues until birth at all times of muscle growth. Higher levels of myostatin are found in obese people. Resistance training for 10 weeks could reduce levels of plasma myostatin.

Keywords: chemerin, myostatin, obesity, physical activity

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4601 Developing a Thermo-Sensitive Conductive Stretchable Film to Allow Cell Sheet Harvest after Mechanical and Electrical Treatments

Authors: Wei-Wen Hu, Yong-Zhi Zhong

Abstract:

Depositing conductive polypyrrole (PPy) onto elastic polydimethylsiloxane (PDMS) substrate can obtain a highly stretchable conductive film, which can be used to construct a bioreactor to cyclically stretch and electrically stimulate surface cells. However, how to completely harvest these stimulated muscle tissue to repair damaged muscle is a challenge. To address this concern, N-isopropylacrylamide (NIPAAm), a monomer of temperature-sensitive polymer, was added during the polymerization of pyrrole on PDMS so that the resulting P(Py-co-NIPAAm)/PDMS should own both conductivity and thermo-sensitivity. Therefore, cells after stimulation can be completely harvested as cell sheets by reducing temperature. Mouse skeletal myoblast, C2C12 cells, were applied to examine our hypothesis. In electrical stimulation, C2C12 cells on P(Py-co-NIPAAm)/PDMS demonstrated the best myo-differentiation under the electric field of 1 V/cm. Regarding cyclic stretching, the strain equal to or higher than 9% can highly align C2C12 perpendicular to the stretching direction. The Western blotting experiments demonstrated that the cell sheets harvested by cooling reserved more extracellular matrix (ECM) than cells collected by the traditional trypsin digestion method. Immunostaining of myosin heavy chain protein (MHC) indicated that both mechanical and electrical stimuli effectively increased the number of myotubes and the differentiation ratio, and the myotubes can be aligned by cyclic stretching. Stimulated cell sheets can be harvested by cooling, and the alignment of myotubes was still maintained. These results suggested that the deposition of P(Py-co-NIPAAm) on PDMS can be applied to harvest intact cell sheets after cyclic stretching and electrical stimulation, which increased the feasibility of bioreactor for the application of tissue engineering and regenerative medicine.

Keywords: bioreactor, cell sheet, conductive polymer, cyclic stretching, electrical stimulation, muscle tissue engineering, myogenesis, thermosensitive hydrophobicity

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4600 Transgenerational Impact of Intrauterine Hyperglycaemia to F2 Offspring without Pre-Diabetic Exposure on F1 Male Offspring

Authors: Jun Ren, Zhen-Hua Ming, He-Feng Huang, Jian-Zhong Sheng

Abstract:

Adverse intrauterine stimulus during critical or sensitive periods in early life, may lead to health risk not only in later life span, but also further generations. Intrauterine hyperglycaemia, as a major feature of gestational diabetes mellitus (GDM), is a typical adverse environment for both F1 fetus and F1 gamete cells development. However, there is scare information of phenotypic difference of metabolic memory between somatic cells and germ cells exposed by intrauterine hyperglycaemia. The direct transmission effect of intrauterine hyperglycaemia per se has not been assessed either. In this study, we built a GDM mice model and selected male GDM offspring without pre-diabetic phenotype as our founders, to exclude postnatal diabetic influence on gametes, thereby investigate the direct transmission effect of intrauterine hyperglycaemia exposure on F2 offspring, and we further compared the metabolic difference of affected F1-GDM male offspring and F2 offspring. A GDM mouse model of intrauterine hyperglycemia was established by intraperitoneal injection of streptozotocin after pregnancy. Pups of GDM mother were fostered by normal control mothers. All the mice were fed with standard food. Male GDM offspring without metabolic dysfunction phenotype were crossed with normal female mice to obtain F2 offspring. Body weight, glucose tolerance test, insulin tolerance test and homeostasis model of insulin resistance (HOMA-IR) index were measured in both generations at 8 week of age. Some of F1-GDM male mice showed impaired glucose tolerance (p < 0.001), none of F1-GDM male mice showed impaired insulin sensitivity. Body weight of F1-GDM mice showed no significance with control mice. Some of F2-GDM offspring exhibited impaired glucose tolerance (p < 0.001), all the F2-GDM offspring exhibited higher HOMA-IR index (p < 0.01 of normal glucose tolerance individuals vs. control, p < 0.05 of glucose intolerance individuals vs. control). All the F2-GDM offspring exhibited higher ITT curve than control (p < 0.001 of normal glucose tolerance individuals, p < 0.05 of glucose intolerance individuals, vs. control). F2-GDM offspring had higher body weight than control mice (p < 0.001 of normal glucose tolerance individuals, p < 0.001 of glucose intolerance individuals, vs. control). While glucose intolerance is the only phenotype that F1-GDM male mice may exhibit, F2 male generation of healthy F1-GDM father showed insulin resistance, increased body weight and/or impaired glucose tolerance. These findings imply that intrauterine hyperglycaemia exposure affects germ cells and somatic cells differently, thus F1 and F2 offspring demonstrated distinct metabolic dysfunction phenotypes. And intrauterine hyperglycaemia exposure per se has a strong influence on F2 generation, independent of postnatal metabolic dysfunction exposure.

Keywords: inheritance, insulin resistance, intrauterine hyperglycaemia, offspring

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4599 Dialysis Rehabilitation and Muscle Hypertrophy

Authors: Itsuo Yokoyama, Rika Kikuti, Naoko Watabe

Abstract:

Introduction: It has been known that chronic kidney disease (CKD) patients can benefit from physical exercise during dialysis therapy improving aerobic capacity, muscle function, cardiovascular function, and overall health-related quality of life. This study aimed to evaluate the effectiveness of dialysis rehabilitation. Materials and Methods: A total of 55 patients underwent two-hour resistance exercise training during each hemodialysis session for three consecutive months. Various routine clinical data were collected, including the calculation of the planar dimension of the muscle area in both upper legs at the level of the ischial bone. This area calculation was possible in 26 patients who had yearly plain abdominal computed tomography (CT) scans. DICOM files from the CT scans were used with 3D Slicer software for area calculation. An age and sex-matched group of 26 patients without dialysis rehabilitation also had yearly CT scans during the study period for comparison. Clinical data were compared between the two groups: Group A (rehabilitation) and Group B (non-rehabilitation). Results: There were no differences in basic laboratory data between the two groups. The average muscle area before and after rehabilitation in Group A was 212 cm² and 216 cm², respectively. In Group B, the average areas were 230.0 cm² and 225.8 cm². While there was no significant difference in absolute values, the average percentage increase in muscle area was +1.2% (ranging from -7.6% to 6.54%) for Group A and -2.0% (ranging from -12.1% to 4.9%) for Group B, which was statistically significant. In Group A, 9 of 26 were diabetic (DM), and 13 of 26 in Group B were non-DM. The increase in muscle area for DM patients was 4.9% compared to -0.7% for non-DM patients, which was significantly different. There were no significant differences between the two groups in terms of nutritional assessment, Kt/V, or incidence of clinical complications such as cardiovascular events. Considerations: Dialysis rehabilitation has been reported to prevent muscle atrophy by increasing muscle fibers and capillaries. This study demonstrated that muscle volume increased after dialysis exercise, as evidenced by the increased muscle area in the thighs. Notably, diabetic patients seemed to benefit more from dialysis exercise than non-diabetics. Although this study is preliminary due to its relatively small sample size, it suggests that intradialytic physical training may improve insulin utilization in muscle fiber cells, particularly in type II diabetic patients where insulin receptor function and signaling are altered. Further studies are needed to investigate the detailed mechanisms underlying the muscle hypertrophic effects of dialysis exercise.

Keywords: dialysis, excercise, muscle, hypertrophy, diabetes, insulin

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4598 Study into the Interactions of Primary Limbal Epithelial Stem Cells and HTCEPI Using Tissue Engineered Cornea

Authors: Masoud Sakhinia, Sajjad Ahmad

Abstract:

Introduction: Though knowledge of the compositional makeup and structure of the limbal niche has progressed exponentially during the past decade, much is yet to be understood. Identifying the precise profile and role of the stromal makeup which spans the ocular surface may inform researchers of the most optimum conditions needed to effectively expand LESCs in vitro, whilst preserving their differentiation status and phenotype. Limbal fibroblasts, as opposed to corneal fibroblasts are thought to form an important component of the microenvironment where LESCs reside. Methods: The corneal stroma was tissue engineered in vitro using both limbal and corneal fibroblasts embedded within a tissue engineered 3D collagen matrix. The effect of these two different fibroblasts on LESCs and hTCEpi corneal epithelial cell line were then subsequently determined using phase contrast microscopy, histolological analysis and PCR for specific stem cell markers. The study aimed to develop an in vitro model which could be used to determine whether limbal, as opposed to corneal fibroblasts, maintained the stem cell phenotype of LESCs and hTCEpi cell line. Results: Tissue culture analysis was inconclusive and required further quantitative analysis for remarks on cell proliferation within the varying stroma. Histological analysis of the tissue-engineered cornea showed a comparable structure to that of the human cornea, though with limited epithelial stratification. PCR results for epithelial cell markers of cells cultured on limbal fibroblasts showed reduced expression of CK3, a negative marker for LESC’s, whilst also exhibiting a relatively low expression level of P63, a marker for undifferentiated LESCs. Conclusion: We have shown the potential for the construction of a tissue engineered human cornea using a 3D collagen matrix and described some preliminary results in the analysis of the effects of varying stroma consisting of limbal and corneal fibroblasts, respectively, on the proliferation of stem cell phenotype of primary LESCs and hTCEpi corneal epithelial cells. Although no definitive marker exists to conclusively illustrate the presence of LESCs, the combination of positive and negative stem cell markers in our study were inconclusive. Though it is less traslational to the human corneal model, the use of conditioned medium from that of limbal and corneal fibroblasts may provide a more simple avenue. Moreover, combinations of extracellular matrices could be used as a surrogate in these culture models.

Keywords: cornea, Limbal Stem Cells, tissue engineering, PCR

Procedia PDF Downloads 278
4597 Electromyography Pattern Classification with Laplacian Eigenmaps in Human Running

Authors: Elnaz Lashgari, Emel Demircan

Abstract:

Electromyography (EMG) is one of the most important interfaces between humans and robots for rehabilitation. Decoding this signal helps to recognize muscle activation and converts it into smooth motion for the robots. Detecting each muscle’s pattern during walking and running is vital for improving the quality of a patient’s life. In this study, EMG data from 10 muscles in 10 subjects at 4 different speeds were analyzed. EMG signals are nonlinear with high dimensionality. To deal with this challenge, we extracted some features in time-frequency domain and used manifold learning and Laplacian Eigenmaps algorithm to find the intrinsic features that represent data in low-dimensional space. We then used the Bayesian classifier to identify various patterns of EMG signals for different muscles across a range of running speeds. The best result for vastus medialis muscle corresponds to 97.87±0.69 for sensitivity and 88.37±0.79 for specificity with 97.07±0.29 accuracy using Bayesian classifier. The results of this study provide important insight into human movement and its application for robotics research.

Keywords: electromyography, manifold learning, ISOMAP, Laplacian Eigenmaps, locally linear embedding

Procedia PDF Downloads 361
4596 The Biology of Persister Cells and Antibiotic Resistance

Authors: Zikora K. G. Anyaegbunam, Annabel A. Nnawuihe, Ngozi J. Anyaegbunam, Emmanuel A. Eze

Abstract:

The discovery and production of new antibiotics is unavoidable in the fight against drug-resistant bacteria. However, this is only part of the problem; we have never really had medications that could completely eradicate an infection. All pathogens create a limited number of dormant persister cells that are resistant to antibiotic treatment. When the concentration of antibiotics decreases, surviving persisters repopulate the population, resulting in a recurrent chronic infection. Bacterial populations have an alternative survival strategy to withstand harsh conditions or antibiotic exposure, in addition to the well-known methods of antibiotic resistance and biofilm formation. Persister cells are a limited subset of transiently antibiotic-tolerant phenotypic variations capable of surviving high-dose antibiotic therapy. Persisters that flip back to a normal phenotype can restart growth when antibiotic pressure drops, assuring the bacterial population's survival. Persister cells have been found in every major pathogen, and they play a role in antibiotic tolerance in biofilms as well as the recalcitrance of chronic infections. Persister cells has been implicated to play a role in the establishment of antibiotic resistance, according to growing research. Thusthe need to basically elucidate the biology of persisters and how they are linked to antibiotic resistance, and as well it's link to diseases.

Keywords: persister cells, phenotypic variations, repopulation, mobile genetic transfers, antibiotic resistance

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4595 Mouse Knockouts for Elucidating the Role of Cysteine-Rich Angiogenic Inducer 61 in Tendon Development and Maintenance

Authors: Josephine Hai, Jie Jiang, Karen M. Lyons

Abstract:

Of the musculoskeletal tissues, tendon is least understood in terms of biological development. The current study examines Cysteine-rich angiogenic inducer 61, or CCN1, a member of the CCN family of secreted matricellular proteins that regulate cell behavior via intercellular signaling. Though CCN1 is notable in limiting fibrosis by inducing senescence in fibroblasts, little is known about its role in normal fibrous tissue, where it may be essential to the development of ECM-rich structures like tendons. We found that CCN1 knockout mice (using limb-specific Prx1-Cre) exhibited clubfoot and waddling gaits, a unique phenotype not described in any other mutant to date. Histological analysis showed that the Achilles and patellar tendons, where we previously found high CCN1 expression in adult reporter mice, were thicker and denser in the Prx1-Cre knockouts than in their wildtype littermates. We then hypothesized that CCN1 is required directly in tendon progenitor cells for normal tendon development and generated tendon-specific CCN1 knockout mice using Scx-Cre. We observed similar Achilles/patellar tendon morphology among the Scx-Cre and Prx1-Cre mutants, indicating that the phenotype is a direct result of CCN1’s loss in tendon. To further study phenotype onset and progression, we will histologically characterize these tendons across different developmental time-points. We will also perform RNA-seq and qPCR to analyze tenocyte gene expression and expect fibrotic marker upregulation in the Scx-Cre mutants if CCN1 is required to maintain a normal tendon phenotype. Thus, our study aims to elucidate the molecular mechanisms underlying tendon formation and maintenance. Understanding tendons at the most basic level invites novel approaches to tendon repair.

Keywords: development, matricellular, musculoskeletal, tendon

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4594 Characteristics of Phytophthora infestans: The Causal Fungus of Potato Late Blight Disease

Authors: A. E. Elkorany, Eman Elsrgawy

Abstract:

Eighty six isolates of Phytophthora infestans dating back to 2006 were recovered from potato tubers that were on sale in Alexandria markets, Egypt. The isolates were characterized for mating type and colony morphology. Both A1 and A2 mating types were detected in the isolate collection, however, the A2 constituted 5.8% of the total isolates made while the A1 mating type isolates constituted 91.9%. The self-fertile phenotype was also detected but at a lower percentage of 2.3% of the total isolates. This indicated that Mexico, the probable origin of the disease, is no longer the only place where A2 mating type ever exists. The lumpy phenotype was the only trait observed linked to the A2 mating type isolates on rye A agar medium. The self-fertile isolates, however, exhibited colonies of a waxy appearance with little aerial hyphae and the culture were backed full with oospores. The A1 mating colonies were of smooth white abundant aerial hyphae. The metalaxyl resistant isolates were also detected among the analyzed isolates and constituted 4.6% of the total (86) isolates investigated. The appearance of the A2 mating type outside Mexico and the variation revealed in the population of Phytophthora infestans investigated supported the hypothesis of a second worldwide migration of the fungus from its origin which could constitute a threat to potato cultivation around the world.

Keywords: Phytophthora infestans, potato, Egypt, fungus

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4593 Endocrine Therapy Resistance and Epithelial to Mesenchymal Transition Inhibits by INT3 & Quercetin in MCF7 Cell Lines

Authors: D. Pradhan, G. Tripathy, S. Pradhan

Abstract:

Objectives: Imperviousness gainst estrogen treatments is a noteworthy reason for infection backslide and mortality in estrogen receptor alpha (ERα)- positive breast diseases. Tamoxifen or estrogen withdrawal builds the reliance of breast malignancy cells on INT3 flagging. Here, we researched the commitment of Quercetin and INT3 motioning in endocrine-safe breast tumor cells. Methods: We utilized two models of endocrine treatments safe (ETR) breast tumor: Tamoxifen-safe (TamR) and long haul estrogen-denied (LTED) MCF7 cells. We assessed the transitory and intrusive limit of these cells by Transwell cells. Articulation of epithelial to mesenchymal move (EMT) controllers and in addition INT3 receptors and targets were assessed by constant PCR and western smudge investigation. Besides, we tried in-vitro hostile to Quercetin monoclonal Antibodies (mAbs) and Gamma Secretase Inhibitors (GSIs) as potential EMT inversion remedial specialists. At last, we created stable Quercetin overexpressing MCF7 cells and assessed their EMT components and reaction to Tamoxifen. Results: We found that ETR cells procured an Epithelial to Mesenchymal move (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we distinguished more elevated amount of INT3 however lower levels of INT1 and INT3 proposing a change to motioning through distinctive INT3 receptors after obtaining of resistance. Against Quercetin monoclonal antibodies and the GSI PF03084014 were powerful in obstructing the Quercetin/INT3 pivot and in part repressing the EMT process. As a consequence of this, cell relocation and attack were weakened and the immature microorganism like populace was essentially decreased. Hereditary hushing of Quercetin and INT3 prompted proportionate impacts. At long last, stable overexpression of Quercetin was adequate to make MCF7 lethargic to Tamoxifen by INT3 initiation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives intrusive conduct. Hostile to Quercetin mAbs and GSI PF03084014 lessen articulation of EMT particles decreasing cell obtrusiveness. Quercetin overexpression instigates Tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and INT3 warrants further clinical Correlation as substantial restorative methodologies in endocrine-safe breast.

Keywords: endocrine, epithelial, mesenchymal, INT3, quercetin, MCF7

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4592 Investigation of the Controversial Immunomodulatory Potential of Trichinella spiralis Excretory-Secretory Products versus Extracellular Vesicles Derived from These Products in vitro

Authors: Natasa Ilic, Alisa Gruden-Movsesijan, Maja Kosanovic, Sofija Glamoclija, Marina Bekic, Ljiljana Sofronic-Milosavljevic, Sergej Tomic

Abstract:

As a very promising candidate for modulation of immune response in the sense of biasing the inflammatory towards an anti-inflammatory type of response, Trichinella spiralis infection was shown to successfully alleviate the severity of experimental autoimmune encephalomyelitis, the animal model of human disease multiple sclerosis. This effect is achieved via its excretory-secretory muscle larvae (ES L1) products which affect the maturation status and function of dendritic cells (DCs) by inducing the tolerogenic status of DCs, which leads to the mitigation of the Th1 type of response and the activation of a regulatory type of immune response both in vitro and in vivo. ES L1 alone or via treated DCs successfully mitigated EAE in the same manner as the infection itself. On the other hand, it has been shown that T. spiralis infection slows down the tumour growth and significantly reduces the tumour size in the model of mouse melanoma, while ES L1 possesses a pro-apoptotic and anti-survival effect on melanoma cells in vitro. Hence, although the mechanisms still need to be revealed, T. spiralis infection and its ES L1 products have a bit of controversial potential to modulate both inflammatory diseases and malignancies. The recent discovery of T. spiralis extracellular vesicles (TsEVs) suggested that the induction of complex regulation of the immune response requires simultaneous delivery of different signals in nano-sized packages. This study aimed to explore whether TsEVs bare the similar potential as ES L1 to influence the status of DCs in initiation, progression and regulation of immune response, but also to investigate the effect of both ES L1 and TsEVs on myeloid derived suppressor cells (MDSC) which present the regular tumour tissue environment. TsEVs were enriched from the conditioned medium of T. spiralis muscle larvae by differential centrifugation and used for the treatment of human monocyte-derived DCs and MDSC. On DCs, TsEVs induced low expression of HLA DR and CD40, moderate CD83 and CD86, and increased expression of ILT3 and CCR7 on treated DCs, i.e., they induced tolerogenic DCs. Such DCs possess the capacity to polarize T cell immune response towards regulatory type, with an increased proportion of IL-10 and TGF-β producing cells, similarly to ES L1. These findings indicated that the ability of TsEVs to induce tolerogenic DCs favoring anti-inflammatory responses may be helpful in coping with diseases that involve Th1/Th17-, but also Th2-mediated inflammation. In MDSC in vitro model, although both ES L1 and TsEVs had the same impact on MDSC phenotype i.e., they acted suppressive, ES L1 treated MDSC, unlike TsEVs treated ones, induced T cell response characterized by the increased RoRγT and IFN-γ, while the proportion of regulatory cells was decreased followed by the decrease in IL-10 and TGF-β positive cells proportion within this population. These findings indicate the interesting ability of ES L1 to modulate T cells response via MDSC towards pro-inflamatory type, suggesting that, unlike TsEVs which consistently demonstrate the suppresive effect on inflammatory response, it could be used also for the development of new approaches aimed for the treatment of malignant diseases. Acknowledgment: This work was funded by the Promis project – Nano-MDCS-Thera, Science Fund, Republic of Serbia.

Keywords: dendritic cells, myeloid derived suppressor cells, immunomodulation, Trichinella spiralis

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4591 Prevalence of Sarcocystosis in Slaughtered Sheep and Goats

Authors: Shivan N. Hussein, Ihsan K. Zangana

Abstract:

A total of 2358 sheep and 532 goats were examined for the presence of macrocystis of Sarcocystis. For microcysts, different muscle tissues were randomly taken from 118 sheep and 110 goats. Macrocystis were examined through naked eye inspection, while microcysts were examined microscopically by using histopathology, pepsin digestion, mincing & squeezing, and muscle squash method. Overall prevalence of macrocystis was 1.2% in sheep and 2.6% in goats. The intensity rate of the cysts was 4 cysts/ gram in sheep & 3 cysts/ gram in goats, respectively, while the overall prevalence of microcysts in sheep and goats was 96.5%. The infection rate in sheep was 96.6% and in goats was 96.4%. The total intensity rate of microcysts was 32.4 cysts/ field in sheep and 16.8 cysts/ field in goats, respectively. Histopathological examination found different shapes, size, wall thickness, and intensity rates of microcysts in muscle tissues of sheep & goats. The pathological reaction showed mild to moderate granulocytosis, and mononuclear cells infiltrated surrounding the microcysts with necrotizing and degeneration of myofibrils. The largest average size of spindle and round shaped cysts (290 ± 89.7 x 76.1 ± 10 µm and 88.8 ± 10.3 µm) in goats and (127.2 ± 18.9 x 53.3 ± 5.4 µm and 74.4 ± 7.5 µm) in sheep, was detected in the esophageal muscle. Statistically, there was a significant difference (p < 0.05) in the prevalence of macrocystis in sheep and goats, while no significant difference (p > 0.05) was observed in the prevalence of microcysts between both animal species.

Keywords: macrocystis, microcysts, intensity rate, measurement size

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4590 The Effect of Fibre Orientation on the Mechanical Behaviour of Skeletal Muscle: A Finite Element Study

Authors: Christobel Gondwe, Yongtao Lu, Claudia Mazzà, Xinshan Li

Abstract:

Skeletal muscle plays an important role in the human body system and function by generating voluntary forces and facilitating body motion. However, The mechanical properties and behaviour of skeletal muscle are still not comprehensively known yet. As such, various robust engineering techniques have been applied to better elucidate the mechanical behaviour of skeletal muscle. It is considered that muscle mechanics are highly governed by the architecture of the fibre orientations. Therefore, the aim of this study was to investigate the effect of different fibre orientations on the mechanical behaviour of skeletal muscle.In this study, a continuum mechanics approach–finite element (FE) analysis was applied to the left bicep femoris long head to determine the contractile mechanism of the muscle using Hill’s three-element model. The geometry of the muscle was segmented from the magnetic resonance images. The muscle was modelled as a quasi-incompressible hyperelastic (Mooney-Rivlin) material. Two types of fibre orientations were implemented: one with the idealised fibre arrangement, i.e. parallel single-direction fibres going from the muscle origin to insertion sites, and the other with curved fibre arrangement which is aligned with the muscle shape.The second fibre arrangement was implemented through the finite element method; non-uniform rational B-spline (FEM-NURBs) technique by means of user material (UMAT) subroutines. The stress-strain behaviour of the muscle was investigated under idealised exercise conditions, and will be further analysed under physiological conditions. The results of the two different FE models have been outputted and qualitatively compared.

Keywords: FEM-NURBS, finite element analysis, Mooney-Rivlin hyperelastic, muscle architecture

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4589 The Effects of Electrical Muscle Stimulation (EMS) towards Male Skeletal Muscle Mass

Authors: Mohd Faridz Ahmad, Amirul Hakim Hasbullah

Abstract:

Electrical Muscle Stimulation (EMS) has been introduced to the world in the 19th and 20th centuries and has globally gained increasing attention on its usefulness. EMS is known as the application of electrical current transcutaneous to muscles through electrodes to induce involuntary contractions that can lead to the increment of muscle mass and strength. This study can be used as an alternative to help people especially those living a sedentary lifestyle to improve their muscle activity without having to go through a heavy workout session. Therefore, this study intended to investigate the effectiveness of EMS training in 5 weeks interventions towards male body composition. It was a quasi-experimental design, held at the Impulse Studio Bangsar, which examined the effects of EMS training towards skeletal muscle mass among the subjects. Fifteen subjects (n = 15) were selected to assist in this study. The demographic data showed that, the average age of the subjects was 43.07 years old ± 9.90, height (173.4 cm ± 9.09) and weight was (85.79 kg ± 18.07). Results showed that there was a significant difference on the skeletal muscle mass (p = 0.01 < 0.05), upper body (p = 0.01 < 0.05) and lower body (p = 0.00 < 0.05). Therefore, the null hypothesis has been rejected in this study. As a conclusion, the application of EMS towards body composition can increase the muscle size and strength. This method has been proven to be able to improve athlete strength and thus, may be implemented in the sports science area of knowledge.

Keywords: body composition, EMS, skeletal muscle mass, strength

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4588 Development of 3D Neck Muscle to Analyze the Effect of Active Muscle Contraction in Whiplash Injury

Authors: Nisha Nandlal Sharma, Julaluk Carmai, Saiprasit Koetniyom, Bernd Markert

Abstract:

Whiplash Injuries are mostly experienced in car accidents. Symptoms of whiplash are commonly reported in studies, neck pain and headaches are two most common symptoms observed. The whiplash Injury mechanism is poorly understood. In present study, hybrid neck muscle model were developed with a combination of solid tetrahedral elements and 1D beam elements. Solid tetrahedral elements represents passive part of the muscle whereas, 1D beam elements represents active part. To simulate the active behavior of the muscle, Hill-type muscle model was applied to beam elements. To simulate non-linear passive properties of muscle, solid elements were modeled with rubber/foam material model. Some important muscles were then inserted into THUMS (Total Human Model for Safety) THUMS was given a boundary conditions similar to experimental tests. The model was exposed to 4g and 7g rear impacts as these load impacts are close to low speed impacts causing whiplash. The effect of muscle activation level on occupant kinematics during whiplash was analyzed.

Keywords: finite element model, muscle activation, THUMS, whiplash injury mechanism

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4587 Effect of Resistance Training on Muscle Strength, IGF₁, and Physical Performance of Volleyball Players

Authors: Menan M. Elsayed, Hussein A. Heshmat

Abstract:

The aim of the study is to assess the effect of resistance training on muscle strength and physical performance of volleyball players of Physical Education College, Helwan University. The researcher used the experimental method of pre-post measurements of one group of 10 volleyball players. The execution of the program was through the period of 12/8/2018 to 12/10/2018; included 24 training units, 3 training units weekly for 8 weeks. The training program revealed an improvement in post measurement of muscle strength, IGF₁ (insulin-like growth factor 1), and physical performance of players. It may be concluded that the resistance training may include changes in hormones and muscle fibers leading to hypertrophy of the muscle and physical performance. It is recommended to use the results of the study in rationing the loads and training programs.

Keywords: IGF₁, muscle strength, physical performance, resistance training, volleyball players

Procedia PDF Downloads 193
4586 Myoelectric Analysis for the Assessment of Muscle Functions and Fatigue Monitoring of Upper Extremity for Stroke Patients Performing Robot-Assisted Bilateral Training

Authors: Hsiao-Lung Chan, Ching-Yi Wu, Yan-Zou Lin, Yo Chiao, Ya-Ju Chang

Abstract:

Robot-assisted bilateral arm training has demonstrated useful to improve motor control in stroke patients and save human resources. In clinics, the efficiency of this treatment is mostly performed by comparing functional scales before and after rehabilitation. However, most of these assessments are based on behavior evaluation. The underlying improvement of muscle activation and coordination is unknown. Moreover, stroke patients are easier to have muscle fatigue under robot-assisted rehabilitation due to the weakness of muscles. This safety issue is still less studied. In this study, EMG analysis was applied during training. Our preliminary results showed the co-contraction index and co-contraction area index can delineate the improved muscle coordination of biceps brachii vs. flexor carpiradialis. Moreover, the smoothed, normalized cycle-by-cycle median frequency of left and right extensor carpiradialis decreased as the training progress, implying the occurrence of muscle fatigue.

Keywords: robot-assisted rehabilitation, strokes, muscle coordination, muscle fatigue

Procedia PDF Downloads 475
4585 ESDN Expression in the Tumor Microenvironment Coordinates Melanoma Progression

Authors: Roberto Coppo, Francesca Orso, Daniela Dettori, Elena Quaglino, Lei Nie, Mehran M. Sadeghi, Daniela Taverna

Abstract:

Malignant melanoma is currently the fifth most common cancer in the white population and it is fatal in its metastatic stage. Several research studies in recent years have provided evidence that cancer initiation and progression are driven by genetic alterations of the tumor and paracrine interactions between tumor and microenvironment. Scattered data show that the Endothelial and Smooth muscle cell-Derived Neuropilin-like molecule (ESDN) controls cell proliferation and movement of stroma and tumor cells. To investigate the role of ESDN in the tumor microenvironment during melanoma progression, murine melanoma cells (B16 or B16-F10) were injected in ESDN knockout mice in order to evaluate how the absence of ESDN in stromal cells could influence melanoma progression. While no effect was found on primary tumor growth, increased cell extravasation and lung metastasis formation was observed in ESDN knockout mice compared to wild type controls. In order to understand how cancer cells cross the endothelial barrier during metastatic dissemination in an ESDN-null microenvironment, structure, and permeability of lung blood vessels were analyzed. Interestingly, ESDN knockout mice showed structurally altered and more permeable vessels compared to wild type animals. Since cell surface molecules mediate the process of tumor cell extravasation, the expression of a panel of extravasation-related ligands and receptors was analyzed. Importantly, modulations of N-cadherin, E-selectin, ICAM-1 and VAP-1 were observed in ESDN knockout endothelial cells, suggesting the presence of a favorable tumor microenvironment which facilitates melanoma cell extravasation and metastasis formation in the absence of ESDN. Furthermore, a potential contribution of immune cells in tumor dissemination was investigated. An increased recruitment of macrophages in the lungs of ESDN knockout mice carrying subcutaneous B16-F10 tumors was found. In conclusion, our data suggest a functional role of ESDN in the tumor microenvironment during melanoma progression and the identification of the mechanisms that regulate tumor cell extravasation could lead to the development of new therapies to reduce metastasis formation.

Keywords: melanoma, tumor microenvironment, extravasation, cell surface molecules

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