Search results for: Cdk5/p25 inhibition

Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz

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T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.

Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3

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Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

Abstract:

Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: copper oxide nanoparticles, green synthesis, nanotechnology, microbial infection

Procedia PDF Downloads 63

Authors: Sharat Chandra, Zilong Wang, Ru-Rong Ji, Andrey Bortsov

Abstract:

Chronic pain (CP) therapeutic approaches have limited efficacy. As a result, doctors are prescribing opioids for chronic pain, leading to opioid overuse, abuse, and addiction epidemic. Therefore, the development of effective and safe CP drugs remains an unmet medical need. Voltage-gated sodium (Nav) channels act as cardiovascular and neurological disorder’s molecular targets. Nav channels selective inhibitors are hard to design because there are nine closely-related isoforms (Nav1.1-1.9) that share the protein sequence segments. We are targeting the Nav1.7 found in the peripheral nervous system and engaged in the perception of pain. The objective of this project was to screen a 1.5 million compound library for identification of inhibitors for Nav1.7 with analgesic effect. In this study, we designed a protocol for identification of isoform-selective inhibitors of Nav1.7, by utilizing the prior information on isoform-selective antagonists. First, a similarity search was performed; then the identified hits were docked into a binding site on the fourth voltage-sensor domain (VSD4) of Nav1.7. We used the FTrees tool for similarity searching and library generation; the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with molecular dynamics simulation (MDS). We reduced our list to 9 compounds based on the MDS root mean square deviation plot and obtained them from a vendor for in vitro and in vivo validation. Whole-cell patch-clamp recordings in HEK-293 cells and dorsal root ganglion neurons were conducted. We used patch pipettes to record transient Na⁺ currents. One of the compounds reduced the peak sodium currents in Nav1.7-HEK-293 stable cell line in a dose-dependent manner, with IC50 values at 0.74 µM. In summary, our computer-aided analgesic discovery approach allowed us to develop pre-clinical analgesic candidate with significant reduction of time and cost.

Keywords: chronic pain, voltage-gated sodium channel, isoform-selective antagonist, similarity search, virtual screening, analgesics development

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Authors: Nélio Veiga, Paula Ferreira, Tiago Correia, Maria J. Correia, Carlos Pereira, Odete Amaral, Ilídio J. Correia

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Introduction: The application of fissure sealants is considered to be an important primary prevention method used in dental medicine. However, the formation of microleakage gaps between tooth enamel and the fissure sealant applied is one of the most common reasons of dental caries development in teeth with fissure sealants. The association between various dental biomaterials may limit the major disadvantages and limitations of biomaterials functioning in a complementary manner. The present study consists in the incorporation of a cariostatic agent – silver diamine fluoride (SDF) – in a resin-based fissure sealant followed by the study of release kinetics by spectrophotometry analysis of the association between both biomaterials and assessment of the inhibitory effect on the growth of the reference bacterial strain Streptococcus mutans (S. mutans) in an in vitro study. Materials and Methods: An experimental in vitro study was designed consisting in the entrapment of SDF (Cariestop^® 12% and 30%) into a commercially available fissure sealant (Fissurit^®), by photopolymerization and photocrosslinking. The same sealant, without SDF was used as a negative control. The effect of the sealants on the growth of S. mutans was determined by the presence of bacterial inhibitory halos in the cultures at the end of the incubation period. In order to confirm the absence of bacteria in the surface of the materials, Scanning Electron Microscopy (SEM) characterization was performed. Also, to analyze the release profile of SDF along time, spectrophotometry technique was applied. Results: The obtained results indicate that the association of SDF to a resin-based fissure sealant may be able to increase the inhibition of S. mutans growth. However, no SDF release was noticed during the in vitro release studies and no statistical significant difference was verified when comparing the inhibitory halo sizes obtained for test and control group.  Conclusions: In this study, the entrapment of SDF in the resin-based fissure sealant did not potentiate the antibacterial effect of the fissure sealant or avoid the immediate development of dental caries. The development of more laboratorial research and, afterwards, long-term clinical data are necessary in order to verify if this association between these biomaterials is effective and can be considered for being used in oral health management. Also, other methodologies for associating cariostatic agents and sealant should be addressed.

Keywords: biomaterial, fissure sealant, primary prevention, silver diamine fluoride

Procedia PDF Downloads 259

Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

Abstract:

Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: biological synthesis, copper oxide nanoparticles, microbial infection, nanotechnology

Procedia PDF Downloads 62

Authors: Eitedal Daoud, Reda M.Daoud, Khaled Abdel-Wahhab, Maha M.Saber, Lobna Saber

Abstract:

Background: Cis-platin is a widely used chemotherapeutic drug to treat many malignant disorders including head and neck malignancies. Oto-nephrotxicity is an important and dose - limiting side effect of cis - platin therapy. Nowadays, more attention had been paid to oto-toxicity caused with cis-platin. Aim of the Work: This study was designed to investigate the potential protective effect of Whey protein (WP) against cis-platin induced ototoxicity compared to the effect of N-acetylcysteine (NAC) in rats. Methodology: Male albino rats were randomly divided into 6 groups: untreated rats (control), rats orally treated with whey protein (1g/kg b.w/day) for seven executive days, rats treated orally with N-acetylcysteine (500 mg/kgb.w /day) for seven executive days, rates intoxicated intraperitoneal (ip) with cis- platin (10 mg/kgb.w. once), rats treated with whey protein (1g/kgb.w./day) for seven executive days) followed by one injection (ip) of cis-platin(10 mg/kg b.w.) one hour after the last oral administration of whey protein, rats treated with N- acetylcysteine (for seven executive days followed by one injection (ip) of cis-platin (10 mg/kgb.w) one hour after the last oral administration of N-acetylcysteine. The organ of Corti, the stria vascularis and spiral ganglia were visualized by light microscopy at different magnifications. Results: Cis-platin intoxicated animals showed a significant decrease in serum level of total antioxidant capacity (TAC),with inhibition in the activity of serum glutathione-s transferase(GST) and paraoxonnase-1 (PON-1) in comparison with control. Group treated with either NAC or WP with cis-platin showed significant elevation in the activity of both GST & PON-1 with increased serum level of TAC when compared with cis-platin intoxicated rats. Animals treated with NAC or WP with cis-platin compared to those treated with cis-platin alone showed marked degree of improvement towards control rats as there was significant drop in the serum level of cortecosterone, nitric oxide (NO), and melandialdehyde (MDA).Histopathologic, in NAC pretreated group there was no changes in stria vascularis or spiral ganglia. In group pretreated with WP, there was no histopathologic alteration detected in the organ of Corti and Reissers membrane but oedema and haemorrhage were founded in the stria vascularis in small focal manner. Conclusion: Our finding showed that Whey protein is a natural dietary supplement product proved its ability of protection of anti-oxidant system and the cochlea against cis-platin induced ototoxicity.

Keywords: anti-oxidant, cis-platin, N-acetylcysteine, ototoxicity, whey protein

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Authors: Jineetkumar Gawad, Chandrakant Bonde

Abstract:

Tuberculosis (TB) is a major worldwide concern whose control has been exacerbated by HIV, the rise of multidrug-resistance (MDR-TB) and extensively drug resistance (XDR-TB) strains of Mycobacterium tuberculosis. The interest for newer and faster acting antitubercular drugs are more remarkable than any time. To search potent compounds is need and challenge for researchers. Here, we tried to design lead for inhibition of Decaprenyl phosphoryl-β-D-ribose 2′-epimerase (DprE1) enzyme. Arabinose is an essential constituent of mycobacterial cell wall. DprE1 is a flavoenzyme that converts decaprenylphosphoryl-D-ribose into decaprenylphosphoryl-2-keto-ribose, which is intermediate in biosynthetic pathway of arabinose. Latter, DprE2 converts keto-ribose into decaprenylphosphoryl-D-arabinose. We had a selection of 23 compounds from azaindole series for computational study, and they were drawn using marvisketch. Ligands were prepared using Maestro molecular modeling interface, Schrodinger, v10.5. Common pharmacophore hypotheses were developed by applying dataset thresholds to yield active and inactive set of compounds. There were 326 hypotheses were developed. On the basis of survival score, ADRRR (Survival Score: 5.453) was selected. Selected pharmacophore hypotheses were subjected to virtual screening results into 1000 hits. Hits were prepared and docked with protein 4KW5 (oxydoreductase inhibitor) was downloaded in .pdb format from RCSB Protein Data Bank. Protein was prepared using protein preparation wizard. Protein was preprocessed, the workspace was analyzed using force field OPLS 2005. Glide grid was generated by picking single atom in molecule. Prepared ligands were docked with prepared protein 4KW5 using Glide docking. After docking, on the basis of glide score top-five compounds were selected, (5223, 5812, 0661, 0662, and 2945) and the glide docking score (-8.928, -8.534, -8.412, -8.411, -8.351) respectively. There were interactions of ligand and protein, specifically HIS 132, LYS 418, TRY 230, ASN 385. Pi-pi stacking was observed in few compounds with basic Imidazo [4,5-b] pyridine ring. We had basic azaindole ring in parent compounds, but after glide docking, we received compounds with Imidazo [4,5-b] pyridine as a basic ring. That might be the new lead in the process of drug discovery.

Keywords: DprE1 inhibitors, in silico drug designing, imidazo [4, 5-b] pyridine, lead, tuberculosis

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Authors: Raghuram Kandimalla, Sanjeeb Kalita, Bhaswati Choudhury, Jibon Kotoky

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The quest for developing an ideal suture material prompted our interest to develop a novel suture with advantageous characteristics to market available ones. We developed novel suture biomaterial from muga silk (Antheraea assama) and ramie (Boehmeria nivea) plant fiber. Field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), attenuated total reflection fourier transform infrared spectroscopy (ATR-FTIR) and thermo gravimetric analysis (TGA) results revealed the physicochemical properties of the fibers which supports the suitability of fibers for suture fabrication. Tensile properties of the prepared sutures were comparable with market available sutures and it found to be biocompatible towards human erythrocytes and nontoxic to mammalian cells. The prepared sutures completely healed the superficial deep wound incisions within seven days in adult male wister rats leaving no rash and scar. Histopathology studies supports the wound healing ability of sutures, as rapid synthesis of collagen, connective tissue and other skin adnexal structures were observed within seven days of surgery. Further muga suture surface modified by exposing the suture to oxygen plasma which resulted in formation of nanotopography on suture surface. Broad spectrum antibiotic amoxicillin was functionalized on the suture surface to prepare an advanced antimicrobial muga suture. Surface hydrophilicity induced by oxygen plasma results in an increase in drug-impregnation efficiency of modified muga suture by 16.7%. In vitro drug release profiles showed continuous and prolonged release of amoxicillin from suture up to 336 hours. The advanced muga suture proves to be effective against growth inhibition of Staphylococcus aureus and Escherichia coli, whereas normal muga suture offers no antibacterial activity against both types of bacteria. In vivo histopathology studies and colony-forming unit count data revealed accelerated wound healing activity of advanced suture over normal one through rapid synthesis and proliferation of collagen, hair follicle and connective tissues.

Keywords: sutures, biomaterials, silk, Ramie

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Authors: J. H. Bang, H. J. Baek, K. I. Kim, B. J. Lee, H. J. Jung, H. J. Jang, S. K. Jung

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Asthma is a chronic inflammatory lung disease characterized by airway hyper responsiveness (AHR), airway obstruction and airway wall remodeling responsible for significant morbidity and mortality worldwide. Genetic and environment factors may result in asthma, but there are no the exact causes of asthma. Chungpye-tang (CPT) has been prescribed as a representative aerosol agent for patients with dyspnea, cough and phlegm in the respiratory clinic at Kyung Hee Korean Medicine Hospital. This Korean herbal medicines have the effect of dispelling external pathogen and dampness pattern. CPT is composed of 4 species of herbal medicines. The 4 species of herbal medicines are Ephedrae herba, Pogostemonis(Agatachis) herba, Caryophylli flos and Zingiberis rhizoma crudus. CPT suppresses neutrophil infiltration and the production of pro-inflammatory cytokines in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Moreover, the anti-inflammatory effects of CPT on a mouse model of Chronic Obstructive Pulmonary Disease (COPD) was proved. Activation of the NF-κB has been proven that it plays an important role in inflammation via inducing transcription of pro-inflammatory genes. Over-expression of NF-κB has been believed be related to many inflammatory diseases such as arthritis, gastritis, asthma and COPD. So we firstly hypothesize whether CPT has an anti-inflammatory effect on asthmatic human airway epithelial tissue via inhibiting NF-κB pathway. In this study, CPT was extracted with distilled water for 3 hours at 100°C. After process of filtration and evaporation, it was freeze dried. And asthmatic human lung tissues were provided by MatTek Corp. We investigated the precise mechanism of the anti-inflammatory effect of CPT by western blotting analysis. We observed whether the decoction extracts could reduce NF-κB activation, COX-2 protein expression and NF-κB-mediated pro-inflammatory cytokines such as TNF-α, eotaxin, IL-4, IL-9 and IL-13 in asthmatic human lung tissue. As results of this study, there was a trend toward decreased NF-κB expression in asthmatic human airway epithelial tissue. We found that the inhibition effects of CPT on COX-2 expression was not determined. IL-9 and IL-13 secretion was significantly reduced in the asthmatic human lung tissue treated with CPT. Overall, our results indicate that CPT has an anti-inflammatory effect through blocking the signaling pathway of NF-κB, thereby CPT may be a potential remedial agent for allergic asthma.

Keywords: Chungpye-tang, allergic asthma, asthmatic human airway epithelial tissue, nuclear factor kappa B (NF-κB) pathway, COX-2

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Authors: Franco Van De Velde, Debora Esposito, Maria E. Pirovani, Mary A. Lila

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The physiology of various inflammatory diseases is a complex process mediated by inflammatory and immune cells such as macrophages and monocytes. Chronic inflammation, as observed in many cardiovascular and autoimmune disorders, occurs when the low-grade inflammatory response fails to resolve with time. Because of the complexity of the chronic inflammatory disease, major efforts have focused on identifying novel anti-inflammatory agents and dietary regimes that prevent the pro-inflammatory process at the early stage of gene expression of key pro-inflammatory mediators and cytokines. The ability of the extracts of three blackberry cultivars (‘Jumbo’, ‘Black Satin’ and ‘Dirksen’), and one strawberry cultivar (‘Camarosa’) to inhibit four well-known genetic biomarkers of inflammation: inducible nitric oxide synthase (iNOS), cyclooxynase-2 (Cox-2), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in an in vitro lipopolysaccharide-stimulated murine RAW 264.7 macrophage model were investigated. Moreover, the effect of latter extracts on the intracellular reactive oxygen species (ROS) and nitric oxide (NO) production was assessed. Assay was conducted with 50 µg/mL crude extract concentration, an amount that is easily achievable in the gastrointestinal tract after berries consumption. The mRNA expression levels of Cox-2 and IL-6 were reduced consistently (more than 30%) by extracts of ‘Jumbo’ and ‘Black Satin’ blackberries. Strawberry extracts showed high reduction in mRNA expression levels of IL-6 (more than 65%) and exhibited moderate reduction in mRNA expression of Cox-2 (more than 35%). The latter behavior mirrors the intracellular ROS production of the LPS stimulated RAW 264.7 macrophages after the treatment with blackberry ‘Black Satin’ and ‘Jumbo’, and strawberry ‘Camarosa’ extracts, suggesting that phytochemicals from these fruits may play a role in the health maintenance by reducing oxidative stress. On the other hand, effective inhibition in the gene expression of IL-1β and iNOS was not observed by any of blackberry and strawberry extracts. However, suppression in the NO production in the activated macrophages among 5–25% was observed by ‘Jumbo’ and ‘Black Satin’ blackberry extracts and ‘Camarosa’ strawberry extracts, suggesting a higher NO suppression property by phytochemicals of these fruits. All these results suggest the potential beneficial effects of studied berries as functional foods with antioxidant and anti-inflammatory roles. Moreover, the underlying role of phytochemicals from these fruits in the protection of inflammatory process will deserve to be further explored.

Keywords: cyclooxygenase-2, functional foods, interleukin-6, reactive oxygen species

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Authors: Takuya Suzuki, Atsushi Shirai, Takashi Seki

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Acupuncture therapy is one of the treatments in traditional Chinese medicine. Recently, some reports have shown the effectiveness of acupuncture. However, its full acceptance has been hindered by the lack of understanding on mechanism of the therapy. Acupuncture applied to Zusanli (ST-36) enhances blood flow volume in superior mesenteric artery (SMA), yielding peripheral vascular resistance – regulated blood flow of SMA dominated by the parasympathetic system and inhibition of sympathetic system. In this study, a lumped-parameter approximation model of blood flow in the systemic arteries was developed. This model was extremely simple, consisting of the aorta, carotid arteries, arteries of the four limbs and SMA, and their peripheral vascular resistances. Here, the individual artery was simplified to a tapered tube and the resistances were modelled by a linear resistance. We numerically investigated contribution of the peripheral vascular resistance of SMA to the systemic blood distribution using this model. In addition to the upstream end of the model, which correlates with the left ventricle, two types of boundary condition were applied; mean left ventricular pressure which correlates with blood pressure (BP) and mean cardiac output which corresponds to cardiac index (CI). We examined it to reproduce the experimentally obtained hemodynamic change, in terms of the ratio of the aforementioned hemodynamic parameters from their initial values before the acupuncture, by regulating the peripheral vascular resistances and the upstream boundary condition. First, only the peripheral vascular resistance of SMA was changed to show contribution of the resistance to the change in blood flow volume in SMA, expecting reproduction of the experimentally obtained change. It was found, however, this was not enough to reproduce the experimental result. Then, we also changed the resistances of the other arteries together with the value given at upstream boundary. Here, the resistances of the other arteries were changed simultaneously in the same amount. Consequently, we successfully reproduced the hemodynamic change to find that regulation of the upstream boundary condition to the value experimentally obtained after the stimulation is necessary for the reproduction, though statistically significant changes in BP and CI were not observed in the experiment. It is generally known that sympathetic and parasympathetic tones take part in regulation of whole the systemic circulation including the cardiac function. The present result indicates that stimulation to ST-36 could induce vasodilation of peripheral circulation of SMA and vasoconstriction of that of other arteries. In addition, it implies that experimentally obtained small changes in BP and CI induced by the acupuncture may be involved in the therapeutic response.

Keywords: acupuncture, hemodynamics, lumped-parameter approximation, modeling, systemic vascular resistance

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Authors: R. Prinsloo

Abstract:

Amniotic fluid stem cells (AFSC) have been shown to contribute towards the amelioration of Acute Renal Failure (ARF), but the mechanisms underlying the renoprotective effect are largely unknown. Therefore, the main goal of the current study was to evaluate the therapeutic efficacy of AFSC in a cisplatin-induced rat model of ARF and to investigate the underlying mechanisms responsible for its renoprotective effect. To study the therapeutic efficacy of AFSC, ARF was induced in Wistar rats by an intra-peritoneal injection of cisplatin, and five days after administration, the rats were randomized into two groups and injected with either AFSC or normal saline intravenously. On day 8 and 12 after cisplatin injection, i.e., day 3 and day7 post-therapy respectively, the blood biochemical parameters, histopathological changes, apoptosis, and expression of pro-apoptotic, anti-apoptotic and autophagy-related proteins in renal tissues were studied in both groups of rats. Administration of AFSC in ARF rats resulted in improvement of renal function and attenuation of renal damage as reflected by significant decrease in blood urea nitrogen, serum creatinine levels, tubular cell apoptosis as assessed by Bax/Bcl2 ratio, and expression of the pro-apoptotic proteins viz. PUMA, Bax, cleaved caspase-3 and cleaved caspase-9 as compared to saline-treated group. Furthermore, in the AFSC-treated group as compared to saline-treated group, there was a significant increase in the activation of autophagy as evident by increased expression of LC3-II, ATG5, ATG7, Beclin1 and phospho-AMPK levels with a concomitant decrease in phospho-p70S6K and p62 expression levels. To further confirm whether the protective effects of AFSC on cisplatin-induced apoptosis were dependent on autophagy, chloroquine, an autophagy inhibitor was administered by the intra-peritoneal route. Chloroquine administration led to significant reduction in the anti-apoptotic effects of the AFSC therapy and further deterioration in the renal structure and function caused by cisplatin. Collectively, our results put forth that AFSC ameliorates cisplatin-induced ARF through induction of autophagy and inhibition of apoptosis. Furthermore, the protective effects of AFSC were blunted by chloroquine, highlighting that activation of autophagy is an important mechanism of action for the protective role of AFSC in cisplatin-induced renal injury.

Keywords: best interest of the child, children's rights, parent and child relationship, parental responsibilities and rights

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Authors: Nelson R. Osungbemiro, O. A. Bello-Olusoji, M. Oladipupo

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This study was carried out to determine the effects of probiotics Pseudomonas fluorescens on the growth performance, histology examination and immune modulation of African Catfish, (Clarias gariepinus) challenged with Clostridium botulinum. P. fluorescens, and C. botulinum isolates were removed from the gut, gill and skin organs of procured adult samples of Clarias gariepinus from commercial fish farms in Akure, Ondo State, Nigeria. The physical and biochemical tests were performed on the bacterial isolates using standard microbiological techniques for their identification. Antibacterial activity tests on P. fluorescens showed inhibition zone with mean value of 3.7 mm which indicates high level of antagonism. The experimental diets were prepared at different probiotics bacterial concentration comprises of five treatments of different bacterial suspension, including the control (T1), T2 (10³), T3 (10⁵), T4 (10⁷) and T5 (10⁹). Three replicates for each treatment type were prepared. Growth performance and nutrients utilization indices were calculated. The proximate analysis of fish carcass and experimental diet was carried out using standard methods. After feeding for 70 days, haematological values and histological test were done following standard methods; also a subgroup from each experimental treatment was challenged by inoculating Intraperitonieally (I/P) with different concentration of pathogenic C. botulinum. Statistically, there were significant differences (P < 0.05) in the growth performance and nutrient utilization of C. gariepinus. Best weight gain and feed conversion ratio were recorded in fish fed T4 (10⁷) and poorest value obtained in the control. Haematological analyses of C. gariepinus fed the experimental diets indicated that all the fish fed diets with P. fluorescens had marked significantly (p < 0.05) higher White Blood Cell than the control diet. The results of the challenge test showed that fish fed the control diet had the highest mortality rate. Histological examination of the gill, intestine, and liver of fish in this study showed several histopathological alterations in fish fed the control diets compared with those fed the P. fluorescens diets. The study indicated that the optimum level of P. fluorescens required for C. gariepinus growth and white blood cells formation is 10⁷ CFU g⁻¹, while carcass protein deposition required 10⁵ CFU g⁻¹ of P. fluorescens concentration. The study also confirmed P. fluorescens as efficient probiotics that is capable of improving the immune response of C. gariepinus against the attack of a virulent fish pathogen, C. botulinum.

Keywords: Clarias gariepinus, Clostridium botulinum, probiotics, Pseudomonas fluorescens

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Authors: Jae-Hyeon Kim, Michael Lee

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Intrinsic and acquired resistance limits the therapeutic benefits of oncogenic BRAF inhibitors in melanoma. MicroRNAs (miRNA) regulate the expression of target mRNAs by repressing their translation. Thus, we investigated miRNA expression patterns in melanoma cell lines to identify candidate biomarkers for acquired resistance to BRAF inhibitor. Here, we used Affymetrix miRNA V3.0 microarray profiling platform to compare miRNA expression levels in three cell lines containing BRAF inhibitor-sensitive A375P BRAF V600E cells, their BRAF inhibitor-resistant counterparts (A375P/Mdr), and SK-MEL-2 BRAF-WT cells with intrinsic resistance to BRAF inhibitor. The miRNAs with at least a two-fold change in expression between BRAF inhibitor-sensitive and –resistant cell lines, were identified as differentially expressed. Averaged intensity measurements identified 138 and 217 miRNAs that were differentially expressed by 2 fold or more between: 1) A375P and A375P/Mdr; 2) A375P and SK-MEL-2, respectively. The hierarchical clustering revealed differences in miRNA expression profiles between BRAF inhibitor-sensitive and –resistant cell lines for miRNAs involved in intrinsic and acquired resistance to BRAF inhibitor. In particular, 43 miRNAs were identified whose expression was consistently altered in two BRAF inhibitor-resistant cell lines, regardless of intrinsic and acquired resistance. Twenty five miRNAs were consistently upregulated and 18 downregulated more than 2-fold. Although some discrepancies were detected when miRNA microarray data were compared with qPCR-measured expression levels, qRT-PCR for five miRNAs (miR-3617, miR-92a1, miR-1246, miR-1936-3p, and miR-17-3p) results showed excellent agreement with microarray experiments. To further investigate cellular functions of miRNAs, we examined effects on cell proliferation. Synthetic oligonucleotide miRNA mimics were transfected into three cell lines, and proliferation was quantified using a colorimetric assay. Of the 5 miRNAs tested, only miR-1246 altered cell proliferation of A375P/Mdr cells. The transfection of miR-1246 mimic strongly conferred PLX-4720 resistance to A375P/Mdr cells, implying that miR-1246 upregulation confers acquired resistance to BRAF inhibition. We also found that PLX-4720 caused much greater G2/M arrest in A375P/Mdr cells transfected with miR-1246mimic than that seen in scrambled RNA-transfected cells. Additionally, miR-1246 mimic partially caused a resistance to autophagy induction by PLX-4720. These results indicate that autophagy does play an essential death-promoting role inPLX-4720-induced cell death. Taken together, these results suggest that miRNA expression profiling in melanoma cells can provide valuable information for a network of BRAF inhibitor resistance-associated miRNAs.

Keywords: microRNA, BRAF inhibitor, drug resistance, autophagy

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Authors: Hani M. Alothaid, Louise Robson, Richmond Muimo

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Cystic fibrosis (CF) is a disease that affects respiratory function and in EU it affects about 1 in 2,500 live births with an average 40-year life expectancy. This disease caused by mutations within the gene encoding the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel leading to dysregulation of epithelial fluid transport and chronic lung inflammation, suggesting functional alterations of immune cells. In airways, CFTR been found to form a functional complex with S100A10 and AnxA2 in a cAMP/PKA dependent manner. The multiprotein complex of AnxA2-S100A10 and CFTR is also regulated by calcineurin. The aim of this study was i) to investigate whether chloride ion (Cl−) channels are activated by Pseudomonas aeruginosa lipopolysaccharide (LPS from PA), ii) if this activation is regulated by cAMP/PKA/calcineurin pathway and iii) to investigate the role of LPS-activated Cl− channels in the release of pro-inflammatory cytokines by immune cells. Human peripheral blood monocytes were used in the study. Whole-cell patch records showed that LPS from PA can activate Cl− channels, including CFTR and outwardly-rectifying Cl− channel (ORCC). This activation appears to require an intact PKA/calcineurin signalling pathway. The Gout in the presence of LPS was significantly inhibited by diisothiocyanatostilbene-disulfonic acid (DIDS), an ORCC blocker (p<0.001). The Gout was further suppressed by CFTR(inh)-172, a specific inhibitor for CFTR channels (p<0.001). Monocytes pre-incubated with PKA inhibitor or calcineurin inhibitor before stimulated with LPS from PA that were resulted in DIDS and CFTR(inh)-172 insensitive currents. Activation of both ORCC and CFTR was however, observed in response to monocytes exposure to LPS. Additionally, ELISA showed that the CFTR and ORCC play a role in mediating the release of pro-inflammatory cytokines such as IL-1β upon exposure of monocytes to LPS. However, this secretion was significantly inhibited due to CFTR and ORCC inhibition. However, Cl− may play a role in IL-1β release independent of cAMP/PKA/calcineurin signalling due to the enhancement of IL-1β secretion even when cAMP/PKA/calcineurin pathway was inhibited. In conclusion, our data confirmed that LPS from PA activates Cl− channels in human peripheral blood monocytes. Our data also confirmed that Cl− channels were involved in IL-1β release in monocytes upon exposure to LPS. However, it has been found that PKA and calcineurin does not seem to influence the Cl− dependent cytokine release.

Keywords: cystic fibrosis, CFTR, Annexin A2, S100A10, PP2B, PKA, outwardly-rectifying Cl− channel, Pseudomonas aeruginosa

Procedia PDF Downloads 177

Authors: Martina Šutovská, Marta Jošková, Ivana Kazimierová, Lenka Pappová, Maroš Adamkov, Soňa Fraňová

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Bronchial asthma is characterized by increased bronchoconstrictor responses to provoking agonists, airway inflammation and remodeling. All these processes involve Ca2+ influx through Ca2+-release-activated Ca2+ channels (CRAC) that are widely expressed in immune, respiratory epithelium and airway smooth muscle (ASM) cells. Our previous study pointed on possible therapeutic potency of CRAC blockers using experimental guinea pigs asthma model. Presented work analyzed complex anti-asthmatic effect of long-term administered CRAC blocker, including impact on allergic inflammation, airways hyperreactivity, and remodeling and mucociliary clearance. Ovalbumin-induced allergic inflammation of the airways according to Franova et al. was followed by 14 days lasted administration of CRAC blocker (3-fluoropyridine-4-carboxylic acid, FPCA) in the dose 1.5 mg/kg bw. For comparative purposes salbutamol, budesonide and saline were applied to control groups. The anti-inflammatory effect of FPCA was estimated by serum and bronchoalveolar lavage fluid (BALF) changes in IL-4, IL-5, IL-13 and TNF-α analyzed by Bio-Plex® assay as well as immunohistochemical staining focused on assessment of tryptase and c-Fos positivity in pulmonary samples. The in vivo airway hyperreactivity was evaluated by Pennock et al. and by organ tissue bath methods in vitro. The immunohistochemical changes in ASM actin and collagen III layer as well as mucin secretion evaluated anti-remodeling effect of FPCA. The measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software determined impact on mucociliary clearance. Long-term administration of FPCA to sensitized animals resulted in: i. Significant decrease in cytokine levels, tryptase and c-Fos positivity similar to budesonide effect; ii.Meaningful decrease in basal and bronchoconstrictors-induced in vivo and in vitro airway hyperreactivity comparable to salbutamol; iii. Significant inhibition of airway remodeling parameters; iv. Insignificant changes in CBF. All these findings confirmed complex anti-asthmatic effect of CRAC channels blocker and evidenced these structures as the rational target in the treatment of allergic bronchial asthma.

Keywords: allergic asthma, CRAC channels, cytokines, respiratory epithelium

Procedia PDF Downloads 521

Authors: Inês N. Peça , A. Bicho, Rui Gardner, M. Margarida Cardoso

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Inorganic/organic nanocomplexes offer tremendous scope for future biomedical applications, including imaging, disease diagnosis and drug delivery. The combination of Fe3O4 with biocompatible polymers to produce smart drug delivery systems for use in pharmaceutical formulation present a powerful tool to target anti-cancer drugs to specific tumor sites through the application of an external magnetic field. In the present study, we focused on the evaluation of the effect of the magnetic field application time on the rate of drug release from iron oxide polymeric nanoparticles. Doxorubicin, an anticancer drug, was selected as the model drug loaded into the nanoparticles. Nanoparticles composed of poly(d-lactide-co-glycolide (PLGA), a biocompatible polymer already approved by FDA, containing iron oxide nanoparticles (MNP) for magnetic targeting and doxorubicin (DOX) were synthesized by the o/w solvent extraction/evaporation method and characterized by scanning electron microscopy (SEM), by dynamic light scattering (DLS), by inductively coupled plasma-atomic emission spectrometry and by Fourier transformed infrared spectroscopy. The produced particles yielded smooth surfaces and spherical shapes exhibiting a size between 400 and 600 nm. The effect of the magnetic doxorubicin loaded PLGA nanoparticles produced on cell viability was investigated in mammalian CHO cell cultures. The results showed that unloaded magnetic PLGA nanoparticles were nontoxic while the magnetic particles without polymeric coating show a high level of toxicity. Concerning the therapeutic activity doxorubicin loaded magnetic particles cause a remarkable enhancement of the cell inhibition rates compared to their non-magnetic counterpart. In vitro drug release studies performed under a non-permanent magnetic field show that the application time and the on/off cycle duration have a great influence with respect to the final amount and to the rate of drug release. In order to determine the mechanism of drug release, the data obtained from the release curves were fitted to the semi-empirical equation of the the Korsmeyer-Peppas model that may be used to describe the Fickian and non-Fickian release behaviour. Doxorubicin release mechanism has shown to be governed mainly by Fickian diffusion. The results obtained show that the rate of drug release from the produced magnetic nanoparticles can be modulated through the magnetic field time application.

Keywords: drug delivery, magnetic nanoparticles, PLGA nanoparticles, controlled release rate

Procedia PDF Downloads 259

Authors: Bill D. Geis

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Even with significantly increased spending, suicide rates continue to climb—with alarming increases among traditionally low-risk groups. This has caused clinicians and researchers to call for a complete rethinking of all assumptions about suicide prevention, assessment, and intervention. A form of therapy--Internal Family Systems Therapy--affords tremendous promise in sustained diminishment of lethal suicide risk. Though a form of therapy that is most familiar to trauma therapists, Internal Family Systems Therapy, involving direct work with suicidal parts, is a promising therapy for meaningful and sustained reduction in suicide deaths. Developed by Richard Schwartz, Internal Family Systems Therapy proposes that we are all influenced greatly by internal parts, frozen by development adversities, and these often-contradictory parts contribute invisibly to mood, distress, and behavior. In making research videos of patients from our database and discussing their suicide attempts, it is clear that many persons who attempt suicide are in altered states at the time of their attempt and influenced by factors other than conscious intent. Suicide intervention using this therapy involves direct work with suicidal parts and other interacting parts that generate distress and despair. Internal Family Systems theory posits that deep experiences of pain, fear, aloneness, and distress are defended by a range of different parts that attempt to contain these experiences of pain through various internal activities that unwittingly push forward inhibition, fear, self-doubt, hopelessness, desires to cut and engage in destructive behavior, addictive behavior, and even suicidal actions. These suicidal parts are often created (and “frozen”) at young ages, and these very young parts do not understand the consequences of this influence. Experience suggests that suicidal parts can create impulsive risk behind the scenes when pain is high and emotional support reduced—with significant crisis potential. This understanding of latent suicide risk is consistent with many of our video accounts of serious suicidal acts—compiled in a database of 1104 subjects. Since 2016, consent has been obtained and records kept of 23 highly suicidal patients, with initial Intention-to-Die ratings (0= no intent, 10 = conviction to die) between 5 and 10. In 67% of these cases using IFST parts-work intervention, these highly suicidal patients’ risk was reduced to 0-1, and 83% of cases were reduced to 4 or lower. There were no suicide deaths. Case illustrations will be offered.

Keywords: suicide, internal family systems therapy, crisis management, suicide prevention

Procedia PDF Downloads 41

Authors: Vanda Ferreira Ribeiro, Daiane Tomacheski, Douglas Naue Simões, Michele Pitto, Ruth Marlene Campomanes Santana

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Indoor environments, such as car cabins and public transportation vehicles are places where users are subject to air quality. Microorganisms (bacteria, fungi, yeasts) enter these environments through windows, ventilation systems and may use the organic particles present as a growth substrate. In addition, atmospheric pollutants can act as potential carbon and nitrogen sources for some microorganisms. Compounds base SEBS copolymers, poly(styrene-b-(ethylene-co-butylene)-b-styrene, are a class of thermoplastic elastomers (TPEs), fully recyclable and largely used in automotive parts. Metals, such as cooper and silver, have biocidal activities and the production of the SEBS compounds by melting blending with these agents can be a good option for producing compounds for use in plastic parts of ventilation systems and automotive air-conditioning, in order to minimize the problems caused by growth of pathogenic microorganisms. In this sense, the aim of this work was to evaluate the effect of copper microparticles as antimicrobial agent in compositions based on SEBS/PP/oil/calcite. Copper microparticles were used in weight proportion of 0%, 1%, 2% and 4%. The compounds were prepared using a co-rotating double screw extruder (L/D ratio of 40/1 and 16 mm screw diameter). The processing parameters were 300 rpm of screw rotation rate, with a temperature profile between 150 to 190°C. SEBS based TPE compounds were injection molded. The compounds emission were characterized by gravimetric fogging test. Compounds were characterized by physical (density and staining by contact), mechanical (hardness and tension properties) and rheological properties (melt volume rate – MVR). Antibacterial properties were evaluated against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) strains. To avaluate the abilities toward the fungi have been chosen Aspergillus niger (A. niger), Candida albicans (C. albicans), Cladosporium cladosporioides (C. cladosporioides) and Penicillium chrysogenum (P. chrysogenum). The results of biological tests showed a reduction on bacteria in up to 88% in E.coli and up to 93% in S. aureus. The tests with fungi showed no conclusive results because the sample without copper also demonstrated inhibition of the development of these microorganisms. The copper addition did not cause significant variations in mechanical properties, in the MVR and the emission behavior of the compounds. The density increases with the increment of copper in compounds.

Keywords: air conditioner, antimicrobial, cooper, SEBS

Procedia PDF Downloads 282

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

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

Keywords: anticancer, antioxidant, Tinospora cordifolia, EAC cell

Procedia PDF Downloads 129

Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

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The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

Procedia PDF Downloads 110

Authors: Randa M. T. Mohamed

Abstract:

Spices have long been used as traditional ingredients in the kitchen for seasoning, coloring, aromatic and food preservative properties. Besides, spices are equally used for therapeutic purposes. The objective of this study was to survey and document the medicinal properties of spices commonly used in the Sudanese kitchen for different food preparations. Also, extracts from reported spices were screened for the presence of secondary metabolites as well as their antioxidant and beta-lactamase inhibitory properties. This study was conducted in the Rekabbya Quartier in Omdurman, Khartoum State, Sudan. Information was collected by carrying out semi-structured interviews. All informants (30) in the present study were women. Spices were purchased from Attareen shop in Omdurman. Essential oils from spices were extracted by hydrodistillation, and ethanolic extracts by maceration. Phytochemical screening was performed by thin-layer chromatography (TLC). The antioxidant capacity of essential oils and ethanolic extracts was investigated through TLC bioautography. Beta lactamase inhibitory activity was performed by the acidimetric test. Ethnobotany study showed that a total of 16 spices were found to treat 36 ailments belonging to 10 categories. The most frequently claimed medicinal uses were for the digestive system diseases treated by 14 spices and respiratory system diseases treated by 8 spices. Gynecological problems were treated with 4 spices. Dermatological diseases were cured by 5 spices, while infections caused by tapeworms and other microbes causing dysentery were treated by 3 spices. 4 spices were used to treat bad breath, bleeding gum and toothache. Headache, eyes infection, cardiac stimulation and epilepsy were treated with one spice each. Other health problems like fatigue and loss of appetite, and low breast milk production were treated by 1, 3 and 2 spices, respectively. The majority (69%, 11/16) of spices were exported from different countries like India, China, Indonesia, Ethiopia, Egypt and Nigeria, while 31% (5/16) was cultivated in Sudan. Essential oils of all spices were rich in terpenes, while ethanolic extracts contained variable classes of secondary metabolites. Both essential oils and ethanolic extracts of all spices exerted considerable antioxidant activity. Only one extract, Syzygium aromaticum, possessed beta-lactamase inhibitory activity. In conclusion, this study could contribute to conserving information on traditional medicinal uses of spices in Sudan. Also, the results demonstrated the potential of some of these spices to exert beneficial antimicrobial and antioxidant effects. Detailed phytochemical and biological assays of these spices are recommended.

Keywords: spices, enthnobotany, antioxidant, betalactamase inhibition

Procedia PDF Downloads 30

Authors: Judit Perjessy, Zsolt Zalan, Ferenc Hegyi, Eniko Horvath-Szanics, Krisztina Takacs, Andras Nagy, Adel Klupacs, Erika Koppany-Szabo, Zhirong Wang, Kaituo Wang, Muying Du, Jianquan Kan

Abstract:

The post-harvest diseases cause great economic losses in the fruit and vegetables; the prevention of these deterioration has great importance. Against the fungi, which cause most of the diseases, are extensively used the fungicides. However, there are increasing consumer concerns over the presence of pesticide residues in food. An alternative and in recent years, increasingly studied method for the prevention of the diseases is biocontrol, where antagonistic microorganisms are used for the control of fungi. The genera of Lactobacillus is well known and extensively studied, but its applicability as biocontrol agents in post-harvest preservation of fruit and vegetables is poorly investigated. However these bacteria can be found on the surface of the plants and have great antimicrobial activity. In our study we have investigated the chitinase activity, the antifungal effect and the applicability of several Lactobacillus strains to select potential biocontrol agents. We investigated the determination of the environmental parameters of a gene (encoding chitinase) expression and we also investigated the relationship between actual antifungal activity and potential chitinase activity. Mixed cultures were also developed to enhance the antifungal activity and determined the optimal mold spore and bacteria concentration ratio for the appropriate efficacy. Five Lactobacillus strains (L. acidophilus N2, L. delbrueckii subsp. bulgaricus B397, L. sp. 2231, L. sake subsp. sake 2471, L. buchneri 1145) possess chitinase-coding gene from the 43 investigated Lactobacillus strains. Proteins with similar molecular weight and separation properties like bacterial chitinases were detected from these strains, which also possess chitin-binding property. Nevertheless, they were inactive, lacks the chitinolytic activity. In point of the cumulative activity of inhibition, our results showed that certain strains were statistically significant in a positive direction compared to other strains, e.g., L. rhamnosus VT1 and L. Casey 154 have shown great general antifungal effect against 11 molds from the genera Penicillium and Botrytis and isolated from spoiled fruit and vegetables. Also, some mixed cultures (L. rhamnosus VT1 - L. Plantarum 299v) showed significant antifungal effects against the indigenous molds on the surface of apple fruit during the industrial storage experiment. Thus, they could be promising for post-harvest biopreservation.

Keywords: biocontrol, chitinase, Lactobacillus, post-harvest

Procedia PDF Downloads 154

Authors: Randa M. T. Mohamed

Abstract:

Spices have long been used as traditional ingredients in the kitchen for seasoning, coloring, aromatic and food preservative properties. Besides, spices are equally used for therapeutic purposes. The objective of this study was to survey and document the medicinal properties of spices commonly used in the Sudanese kitchen for different food preparations. Also, extracts from reported spices were screened for the presence of secondary metabolites as well as their antioxidant and beta-lactamase inhibitory properties. This study was conducted in the Rekabbya Quartier in Omdurman, Khartoum State, Sudan. Information was collected by carrying out semi-structured interviews. All informants (30) in the present study were women. Spices were purchased from Attareen shop in Omdurman. Essential oils from spices were extracted by hydrodistillation and ethanolic extracts by maceration. Phytochemical screening was performed by thin layer chromatography (TLC). The antioxidant capacity of essential oils and ethanolic extracts was investigated through TLC bioautography. Beta lactamase inhibitory activity was performed by the acidimetric test. Ethnobotany study showed that a total of 16 spices were found to treat 36 ailments belonging to 10 categories. The most frequently claimed medicinal uses were for the digestive system diseases treated by 14 spices and respiratory system diseases treated by 8 spices. Gynaecological problems were treated by 4 spices. Dermatological diseases were cured by 5 spices while infections caused by tapeworms and other microbes causing dysentery were treated by 3 spices. 4 spices were used to treat bad breath, bleeding gum and toothache. Headache, eyes infection, cardiac stimulation and epilepsy were treated by one spice each. Other health problem like fatigue and loss of appetite and low breast milk production were treated by 1, 3 and 2 spices respectively. The majority (69%, 11/16) of spices were exported from different countries like India, China, Indonesia, Ethiopia, Egypt and Nigeria while 31% (5/16) was cultivated in Sudan. Essential oils of all spices were rich in terpenes while ethanolic extracts contained variable classes of secondary metabolites. Both essential oils and ethanolic extracts of all spices exerted considerable antioxidant activity. Only one extract, Syzygium aromaticum, possessed beta lactamase inhibitory activity. In conclusion, this study could contribute in conserving information on traditional medicinal uses of spices in Sudan. Also, the results demonstrated the potential of some of these spices to exert beneficial antimicrobial and antioxidant effect. Detailed phytochemical and biological assays of these spices are recommended.

Keywords: spices, ethnobotany, phytoconstituents, antioxidant, beta lactamase inhibition

Procedia PDF Downloads 79

Authors: Zachary Muthii Rukenya, James Mbaria, Peter Mbaabu, Kiama Stephen Gitahi, Ronald Onzago

Abstract:

Aloe turkanensis is one of the widely used medicinal shrub and in Kenya the plant is mainly found in Baringo, Isiolo, Laikipia, Turkana and West Pokot Counties where it is used in ethno-medicine and ethno-veterinary medicine. The Turkana community uses the plant products to manage malaria, wounds, stomach ache, constipation, pain, skin infection, poultry diseases and retained afterbirth in cows. This evaluated the efficacy and safety of the plant obtained from Turkana County, Kenya. Preliminary data on the use of the plant in the county was collected through observation, photographing and interviews. A sample of the whole plant was harvested in Natira sublocation, in ex-Turkana west district in February 2012 after identification by Aloe-working group herbalists who voluntarily provided information on its medicinal uses. Botanical identification was done at Kenya Forest Research Centre in Karura where voucher specimen was deposited. Cold maceration using 70% methanol and distilled water was used for extraction. Bioassays were to determine the effects of the plant extracts on brine shrimp and selected bacterial and fungal cultures. The extracts were tested in-vitro activity against standard cultures of B. cereus (ATCC 11778), S. aureus (ATCC25923), P. aeroginosa (ATCC 27853), E. coli (ATCC 25922) and a human infections clinical isolate of C. albicans. The extracts of Aloe turkanensis inhibited the growth B. cereus (100-200 mg/ml), S. aureus (50-100 mg/ml), P. aeroginosa (200mg/ml), E. coli (400mg/ml) while C. albicans was not affected. The extracts also inhibited the growth of S. aureus and B. cereus with mean diameters of inhibition zones being 19.75±1 mm and 18.5±05 mm reapectively. Phytochemical screening showed the presence of alkaloids, tarpenoids, steroids, quinones, saponins and tannins in the plant extracts. The extract was found to be non-toxic at a concentration of 1000µg/ml with a 100% survival of Brine Shrimp larva. It was concluded that Aloe turkanensis growing the study area has metabolites that inhibit the growth of microorganisms and is however, there is need for further studies to validate the in-vivo bioactivity of the plant and more generate adequate toxicological data.to support conservation, value chain addition of its products and widespread use as a herbal remedy.

Keywords: Aloe turkanensis, bioactivity, cultivated, human infections

Procedia PDF Downloads 321

Authors: Burcin Basyazici

Abstract:

The history of urban regeneration in Istanbul dates to the 1980s and has been generated by various reasons, from political state-based decisions to cultural migrations and/or translocations and economical private sector-based reasons. However, one of the latest regeneration areas in Fikirtepe that have been still under construction for ten years becomes dissimilar to other regeneration areas in Istanbul. The region is located very close to Kadıkoy's downtown area but was still considered a slum due to its inhabitants -who mostly belong to lower-income immigrants. The process begun in 2011 with the decision of the government, and the settlement has been emptied and demolished also by the government -together with the investors and construction companies. Although there has been much research on the process of deconstruction and the relocation of landlords, there hasn’t been any research on what happened after the regeneration. While many high-rise luxurious gated communities were constructed and inhabited in five years, many constructions have stopped due to the latest economic devastation in Turkey. Then the region stayed as an unfinished construction area with its new upper-income and upper-middle-income residents and old low-income landlords. This situation has also changed the commercial activities in Fikirtepe. While some new retail facilities have been offered for new residents, some of the oldest ones have also survived in new-Fikirtepe. This study aims to investigate the urban everyday life of Fikirtepe with relation to its retail-based regeneration with the help of the theories of Bourdieu called cultural capital and cultural omnivorousness. To achieve this aim, after presenting the historical background of urban regeneration in Istanbul, Bourdieu’s conceptualism of cultural capital, habitus, and the consumption tendencies related to those are introduced and discussed within the scope of the Fikirtepe case. To represent the retail-based regeneration in the area, the current situation of retail premises is mapped by comparing to its pre-situation before urban gentrification. To better understand the change of cultural capital and the consumption tendencies of the new residents, eighteen semi-structured in-depth interviews have been conducted with twelve inhabitants from three different luxurious gated communities and six shop owners containing the new ones after regeneration and old ones before it. The interview questions have been structured to understand the motivation of change and/or inhibition of retail premises and the consumption tendencies of the new residents. In conclusion, the study shows that even though the cultural capital has been changed in Fikirtepe, the new residents also tend to act as culturally omnivorous by referring to Bourdieu's theories on multi-cultural tendencies of the upper-class and upper-middle-class societies, that should be questioned regarding the cultural regeneration in in-town urban regeneration areas in metropoles.

Keywords: bourdieu, cultural omnivorousness, fikirtepe, urban regeneration in istanbul

Procedia PDF Downloads 163

Authors: Karin M. Granstrom

Abstract:

Paper mills produce wastewater with a high content of organic substances. Treatment usually consists of sedimentation, biological treatment of activated sludge basins, and chemical precipitation. The resulting sludges are currently a waste problem, deposited in landfills or used as low-grade fuels for incineration. There is a growing awareness of the need for energy efficiency and environmentally sound management of sludge. A resource-efficient method would be to digest the wastewater sludges anaerobically to produce biogas, refine the biogas to biomethane for use in the transportation sector, and utilize the resulting digestate for soil improvement. The biomethane yield of pulp and paper wastewater sludge is comparable to that of straw or manure. As a bonus, the digestate has an improved dewaterability compared to the feedstock biosludge. Limitations of this process are predominantly a weak economic viability - necessitating both sufficiently large-scale paper production for the necessary large amounts of produced wastewater sludge, and the resolving of remaining questions on the certifiability of the digestate and thus its sales price. A way to improve the practical and economical feasibility of using paper mill wastewater for biomethane production and soil improvement is to co-digest it with other feedstocks. In this study, pulp and paper sludge were co-digested with (1) silage and manure, (2) municipal sewage sludge, (3) food waste, or (4) microalgae. Biomethane yield analysis was performed in 500 ml batch reactors, using an Automatic Methane Potential Test System at thermophilic temperature, with a 20 days test duration. The results show that (1) the harvesting season of grass silage and manure collection was an important factor for methane production, with spring feedstocks producing much more than autumn feedstock, and pulp mill sludge benefitting the most from co-digestion; (2) pulp and paper mill sludge is a suitable co-substrate to add when a high nitrogen content cause impaired biogas production due to ammonia inhibition; (3) the combination of food waste and paper sludge gave higher methane yield than either of the substrates digested separately; (4) pure microalgae gave the highest methane yield. In conclusion, although pulp and paper mills are an almost untapped resource for biomethane production, their wastewater is a suitable feedstock for such a process. Furthermore, through co-digestion, the pulp and paper mill wastewater and mill sludges can aid biogas production from more nutrient-rich waste streams from other industries. Such co-digestion also enhances the soil improvement properties of the residue digestate.

Keywords: anaerobic, biogas, biomethane, paper, sludge, soil

Procedia PDF Downloads 259

Authors: Vanlounni Sibounheuang, Wanarat Anusornsangiam, Pattarin Kittiboonyakun, Chanthanom Manithip

Abstract:

In worldwide, one of the most common use of oral anticoagulant is warfarin. Its margin between therapeutic inhibition of clot formation and bleeding complications is narrow. Mahosot Hospital, warfarin clinic had not been established yet. The descriptive study was conducted by investigating drug-related problems of outpatients using warfarin, the value of the international normalized ratio (INR) higher than normal ranges (25.40 % of the total 272 outpatients) were mostly identified at Lao-Luxembourg Heart Centre, Mahosot Hospital, Lao PDR. This result led to the present study conducting qualitative interviews in order to help establish a warfarin clinic at Mahosot Hospital for the better outcomes of patients using warfarin. The purpose of this study was to explore perspectives of healthcare professional providing services for outpatients using warfarin. The face to face, in-depth interviews were undertaken among nine healthcare professionals (doctor=3, nurse=3, pharmacist=3) working at out-patient clinic, Lao-Luxembourg Heart Centre, Mahosot Hospital, Lao PDR. The interview guides were developed, and they were validated by the experts in the fields of qualitative research. Each interview lasted approximately 20 minutes. Three major themes emerged; healthcare professional’s experiences of current practice problems with warfarin therapy, healthcare professionals’ views of medical problems related to patients using warfarin, and healthcare professionals’ perspectives on ways of service improvement. All healthcare professionals had the same views that it’s difficult to achieve INR goal for individual patients because of some important patient barriers especially lack of knowledge about to use warfarin properly and safety, patients not regularly follow-up due to problems with transportations and financial support. Doctors and nurses agreed to have a pharmacist running a routine warfarin clinic and provided counselling to individual patients on the following points: how to take drug properly and safety, drug-drug and food-drug interactions, common side effects and how to manage them, lifestyle modifications. From the interviews, some important components of the establishment of a warfarin clinic included financial support, increased human resources, improved the system of keeping patients’ medical records, short course training for pharmacists. This study indicated the acceptance of healthcare professionals on the important roles of pharmacists and the feasibility of setting up warfarin clinic by working together with the multidisciplinary health care team in order to help improve health outcomes of patients using warfarin at Mahosot Hospital, Lao PDR.

Keywords: perspectives, healthcare professional, warfarin therapy, Mahosot Hospital

Procedia PDF Downloads 100

Authors: Stephanie Remedios, Linda Veronica Rios

Abstract:

Background. Pediatric obesity is a serious health problem linked to multiple physical diseases and ailments, including diabetes, heart disease, and joint issues. While research has shown pediatric obesity can bring about an array of physical illnesses, it is less known how such a condition can affect children’s cognitive development. With childhood overweight and obesity prevalence rates on the rise, it is essential to understand the scope of their cognitive consequences. The present review of the literature tested the hypothesis that poor physical health, such as childhood obesity or malnutrition, negatively impacts a child’s cognitive development. Methodology. A systematic review was conducted to determine the relationship between poor physical health and lower cognitive functioning in children ages 4-16. Electronic databases were searched for studies dating back to ten years. The following databases were used: Science Direct, FIU Libraries, and Google Scholar. Inclusion criteria consisted of peer-reviewed academic articles written in English from 2012 to 2022 that analyzed the relationship between childhood malnutrition and obesity on cognitive development. A total of 17,000 articles were obtained, of which 16,987 were excluded for not addressing the cognitive implications exclusively. Of the acquired articles, 13 were retained. Results. Research suggested a significant connection between diet and cognitive development. Both diet and physical activity are strongly correlated with higher cognitive functioning. Cognitive domains explored in this work included learning, memory, attention, inhibition, and impulsivity. IQ scores were also considered objective representations of overall cognitive performance. Studies showed physical activity benefits cognitive development, primarily for executive functioning and language development. Additionally, children suffering from pediatric obesity or malnutrition were found to score 3-10 points lower in IQ scores when compared to healthy, same-aged children. Conclusion. This review provides evidence that the presence of physical activity and overall physical health, including appropriate diet and nutritional intake, has beneficial effects on cognitive outcomes. The primary conclusion from this research is that childhood obesity and malnutrition show detrimental effects on cognitive development in children, primarily with learning outcomes. Assuming childhood obesity and malnutrition rates continue their current trade, it is essential to understand the complete physical and psychological implications of obesity and malnutrition in pediatric populations. Given the limitations encountered through our research, further studies are needed to evaluate the areas of cognition affected during childhood.

Keywords: childhood malnutrition, childhood obesity, cognitive development, cognitive functioning

Procedia PDF Downloads 118

Authors: Sugandha Asthana, Geetika Vajpayee, Pratibha Kumari, Shanthy Sundaram

Abstract:

An economically important disease of wheat in North Western region of India is Karnal Bunt caused by smut fungus Tilletia indica. This fungal pathogen spreads by air, soil and seed borne sporodia at the time of flowering, which ultimately leads to partial bunting of wheat kernels with fishy odor and taste to wheat flour. It has very serious effects due to quarantine measures which have to be applied for grain exports. Chemical fungicides such as mercurial compounds and Propiconazole applied to the control of Karnal bunt have been only partially successful. Considering the harmful effects of chemical fungicides on man as well as environment, many countries are developing biological control as the superior substitute to chemical control. Repeated use of fungicides can be responsible for the development of resistance in fungal pathogens against certain chemical compounds. The present investigation is based on the isolation and evaluation of antifungal properties of some isolated (from natural manure) and commercial bacterial strains against Tilletia indica. Total 23 bacterial isolates were obtained and antagonistic activity of all isolates and commercial bacterial strains (Bacillus subtilis MTCC8601, Bacillus pumilus MTCC 8743, Pseudomonas aeruginosa) were tested against T. indica by dual culture plate assay (pour plate and streak plate). Test for the production of antifungal volatile organic compounds (VOCs) by antagonistic bacteria was done by sealed plate method. Amongst all s1, s3, s5, and B. subtilis showed more than 80% inhibition. Production of extracellular hydrolytic enzymes such as protease, beta 1, 4 glucanase, HCN and ammonia was studied for confirmation of antifungal activity. s1, s3, s5 and B. subtilis were found to be the best for protease activity and s5 and B. subtilis for beta 1, 4 glucanase activity. Bacillus subtilis was significantly effective for HCN whereas s3, s5 and Bacillus subtilis for ammonia production. Isolates were identified as Pseudomonas aeruginosa (s1) and B. licheniformis (s3, s5) by various biochemical assays and confirmed by16s rRNA sequencing. Use of microorganisms or their secretions as biocontrol agents to avoid plant diseases is ecologically safe and may offer long term of protection to crop. The above study reports the promising effects of these strains in better pathogen free crop production and quality maintenance as well as prevention of the excessive use of synthetic fungicides.

Keywords: antagonistic, antifungal, biocontrol, Karnal bunt

Procedia PDF Downloads 283