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Normal lung cells incur genetic damage over time, which causes unchecked cell growth and ultimately leads to lung cancer. Nearly 85% of lung cancer cases are caused by smoking, but there exists factual evidence that beta-carotene supplements and arsenic in water may raise the risk of developing the illness. Asbestos, polycyclic aromatic hydrocarbons, arsenic, radon gas, nickel, chromium and hereditary factors represent various lung cancer-causing agents. Therefore, deep learning approaches are employed to quicken the crucial procedure of diagnosing lung cancer. The effectiveness of these methods has increased when used to examine cancer histopathology slides. Initially, the data is gathered from the standard benchmark dataset. Further, the pre-processing of the collected images is accomplished using the Gabor filter method. The segmentation of these pre-processed images is done through the modified expectation maximization (MEM) algorithm method. Next, using the histogram of oriented gradient (HOG) scheme, the features are extracted from these segmented images. Finally, the classification of lung cancer is performed by the improved graph neural network (IGNN), where the parameter optimization of graph neural network (GNN) is done by the green anaconda optimization (GAO) algorithm in order to derive the accuracy maximization as the major objective function. This IGNN classifies lung cancer into normal, adeno carcinoma and squamous cell carcinoma as the final output. On comparison with existing methods with respect to distinct performance measures, the simulation findings reveal the betterment of the introduced method.
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Arsênio , Boidae , Neoplasias Pulmonares , Humanos , Animais , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Redes Neurais de Computação , AlgoritmosRESUMO
Background: Excitotoxicity is a condition in which neurons are damaged/injured by the over-activation of glutamate receptors. Excitotoxins play a crucial part in the progression of several neurological diseases. Marsilea quadrifolia Linn (M. quadrifolia) is a very popular aquatic medicinal plant that has been utilised for a variety of therapeutic benefits since ancient times. Its chemical composition is diverse and includes phenolic compounds, tannins, saponins, flavonoids, steroids, terpenoids, alkaloids, carbohydrates and several others that possess antioxidant properties. Objective: The objective of the present study was to investigate the neuroprotective potential of M. quadrifolia against monosodium glutamate (MSG)-induced excitotoxicity in rats. Methods: A high-performance thin-layer chromatography (HPTLC) analysis of chloroform extract of M. quadrifolia (CEMQ) was conducted to identify the major constituents. Further, the in silico docking analysis was carried out on selected ligands. To confirm CEMQ's neuroprotective effects, the locomotor activity, non-spatial memory, and learning were assessed. Results and discussion: The present study confirmed that CMEQ contains quercetin and its derivatives in large. The in-silico findings indicated that quercetin has a better binding affinity (-7.9 kcal/mol) towards the protein target 5EWJ. Animals treated with MSG had 1) a greater reduction in the locomotor score and impairment in memory and learning 2) a greater increase in the blood levels of calcium and sodium and 3) neuronal disorganization, along with cerebral edema and neuronal degeneration in the brain tissues as compared to normal control animals. The changes were however, significantly improved in animals which received standard drug memantine (20 mg/kg) and CEMQ (200 and 400 mg/kg) as compared to the negative control. It is plausible that the changes seen with CEMQ may be attributed to the N-methyl-D-aspartate (NMDA) antagonistic properties. Conclusion: Overall, this study indicated that M. quadrifolia ameliorated MSG-induced neurotoxicity. Future investigations are required to explore the neuroprotective mechanism of M. quadrifolia and its active constituents, which will provide exciting insights in the therapeutic management of neurological disorders.
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Background: Dodonaea viscosa Jacq. (D. viscosa) belongs to the family of Sapindaceae, commonly known as "Sinatha," and is used as a traditional medicine for treating wounds due to its high flavonoids content. However, to date there is no experimental evidence on its flavonoid-rich fraction of D. viscosa formulation as an agent for healing wounds. Objective: The present study aimed to evaluate the wound healing effect of ethyl acetate fraction of D. viscosa leaves on dermal wounds. Methods: The ethyl acetate fraction was produced from a water-ethanol extract of D. viscosa leaves and was quantitatively evaluated using the HPLC technique. The in-vivo wound healing ability of the ethyl acetate fraction of D. viscosa ointment (DVFO, 2.5%w/w and 5%w/w) was investigated in Sprague-Dawley rats utilizing an incision and excision paradigm with povidone-iodine ointment (5% w/w) as a control. The percentage of wound closure, hydroxyproline and hexosamine concentrations, tensile strength and epithelialization duration were measured. Subsequently, histopathology analysis of skin samples as well as western blots were performed for collagen type 3 (COL3A1), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Results: The ethyl acetate fraction of D. viscosa revealed flavonoids with high concentrations of quercetin (6.46% w/w) and kaempferol (0.132% w/w). Compared to the control group, the DVFO (2.5% and 5.0% w/w) significantly accelerated wound healing in both models, as demonstrated by quicker wound contraction, epithelialization, elevated hydroxyproline levels and increased tensile strength. Histopathological investigations also revealed that DVFO treatment improved wound healing by re-epithelialization, collagen formation and vascularization of damaged skin samples. Western blot analysis further demonstrated an up-regulation of COL3A, vascular endothelial growth factor and bFGF protein in wound granulation tissue of the DVFO-treated group (p < 0.01). Conclusion: It is concluded that flavonoid-rich D. viscosa ethyl acetate fraction promotes wound healing by up-regulating the expressions of COL3A, VEGF and bFGF protein in wound granulation tissue. However, extensive clinical and pre-clinical research on the flavonoid-rich fraction of D. viscosa is needed to determine its significant impact in the healing of human wounds.
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Background: Solanum torvum Swartz, a medicinal plant belonging to the family Solanaceae, is an important medicinal plant widely distributed throughout the world and used as medicine to treat diabetes, hypertension, tooth decay, and reproductive problems in traditional systems of medicine around the world including Malaysia. The objective of this study was to investigate hypoglycemic, antilipidemic, and hepatoprotective activities, histopathology of the pancreas, and specific glucose regulating gene expression of the ethanolic extract of S. torvum fruit in streptozotocin-induced diabetic Sprague-Dawley rats. Materials and methods: Acute toxicity study was done according to OECD-423 guidelines. Diabetes was induced by intraperitoneal (i.p.) injection of streptozotocin (55 mg/kg) in male Sprague-Dawley rats. Experimental diabetic rats were divided into six different groups; normal, diabetic control, and glibenclamide at 6 mg/kg body weight, and the other three groups of animals were treated with oral administration of ethanolic extract of S. torvum fruit at 120, 160, and 200 mg/kg for 28 days. The effect of ethanolic extract of S. torvum fruit on body weight, blood glucose, lipid profile, liver enzymes, histopathology of pancreas, and gene expression of glucose transporter 2 (slc2a2), and phosphoenolpyruvate carboxykinase (PCK1) was determined by RT-PCR. Results: Acute toxicity studies showed LD50 of ethanolic extract of S. torvum fruit to be at the dose of 1600 mg/kg body weight. Blood glucose, total cholesterol, triglycerides, low-density lipoproteins, very low-density lipoproteins, serum alanine aminotransferase, and aspartate aminotransferase were significantly reduced, whereas high-density lipoproteins were significantly increased in S. torvum fruit (200 mg/kg)-treated rats. Histopathological study of the pancreas showed an increase in number, size, and regeneration of ß-cell of islets of Langerhans. Gene expression studies revealed the lower expression of slc2a2 and PCK1 in treated animals when compared to diabetic control. Conclusion: Ethanolic extract of S. torvum fruits showed hypoglycemic, hypolipidemic, and hepatoprotective activity in streptozocin-induced diabetic rats. Histopathological studies revealed regeneration of ß cells of islets of Langerhans. Gene expression studies indicated lower expression of slc2a2 and PCK1 in treated animals when compared to diabetic control, indicating that the treated animals prefer the gluconeogenesis pathway.
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The ABCG2 transporter plays a pivotal role in multidrug resistance, however, no clinical trial using specific ABCG2 inhibitors have been successful. Although ABC transporters actively extrude a wide variety of substrates, photodynamic therapeutic agents with porphyrinic scaffolds are exclusively transported by ABCG2. In this work, we describe for the first time a porphyrin derivative (4B) inhibitor of ABCG2 and capable to overcome multidrug resistance in vitro. The inhibition was time-dependent and 4B was not itself transported by ABCG2. Independently of the substrate, the porphyrin 4B showed an IC50 value of 1.6 µM and a mixed type of inhibition. This compound inhibited the ATPase activity and increased the binding of the conformational-sensitive antibody 5D3. A thermostability assay confirmed allosteric protein changes triggered by the porphyrin. Long-timescale molecular dynamics simulations revealed a different behavior between the ABCG2 porphyrinic substrate pheophorbide a and the porphyrin 4B. Pheophorbide a was able to bind in three different protein sites but 4B showed one binding conformation with a strong ionic interaction with GLU446. The inhibition was selective toward ABCG2, since no inhibition was observed for P-glycoprotein and MRP1. Finally, this compound successfully chemosensitized cells that overexpress ABCG2. These findings reinforce that substrates may be a privileged source of chemical scaffolds for identification of new inhibitors of multidrug resistance-linked ABC transporters.
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Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Adenosina Trifosfatases/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Porfirinas/farmacologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/química , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Adenosina Trifosfatases/química , Adenosina Trifosfatases/metabolismo , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Células HEK293 , Humanos , Irinotecano/farmacologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Porfirinas/química , Porfirinas/metabolismo , Ligação Proteica , Conformação Proteica/efeitos dos fármacosRESUMO
The ability of the lymphatic network to absorb large molecules and bypass the first-pass liver metabolism makes it appealing as a delivery system for therapeutic substances. In most cases, the drug is injected into the subcutaneous tissue and must negotiate the tissue space, before being drained via the lymphatics. Tracking the transport of drug molecules through this route is challenging, and computational models of lymphatic drainage can play an important role in assessing the efficacy of a proposed delivery strategy. The three-dimensional computational model we present here of the peripheral lymphatic network and surrounding interstitium is informed by anatomical data, and quantifies the degree to which uptake and transit times are affected by drug particle size, physiological flow rates, and specifics of drug injection.
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Sistema Linfático , Vasos Linfáticos , Transporte Biológico , Sistema Linfático/metabolismoRESUMO
The role of micronutrients in health and disease has increased the curiosity and interest among researchers. The prime focus of this review is the significance of trace elements- calcium, vitamin D, selenium and zinc with cardiovascular health. WHO identified cardiovascular diseases (CVD) as the leading cause of deaths globally. Identifying the risk factors that could be modified and creating new treatment strategies remains to be the main concern for CVD prevention. The data that showed the relationship between trace elements and various ways in which they may contribute to cardiovascular health and disease from clinical trials and observational studies were collected from databases such as PubMed and Embase. Based on these collected data, it shows that either high or low circulating serum levels can be associated with the development of cardiovascular diseases. Micronutrients through diet contribute to improved cardiac health. However, due to our current lifestyle, there is a huge dependency on dietary supplements. Based on the observational studies, it is evident that supplements cause sudden increase in the circulating levels of the nutrients and result in cardiovascular damage. Thus, it is advisable to restrict the use of supplements, owing to the potent risks it may cause. In order to understand the exact mechanism between micronutrients and cardiac health, more clinical studies are required.
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Multidrug resistant bacteria create a challenging situation for society to treat infections. Multidrug resistance (MDR) is the reason for biofilm bacteria to cause chronic infection. Plant-based nanoparticles could be an alternative solution as potential drug candidates against these MDR bacteria, as many plants are well known for their antimicrobial activity against pathogenic microorganisms. Spondias mombin is a traditional plant which has already been used for medicinal purposes as every part of this plant has been proven to have its own medicinal values. In this research, the S. mombin extract was used to synthesise AgNPs. The synthesized AgNPs were characterized and further tested for their antibacterial, reactive oxygen species and cytotoxicity properties. The characterization results showed the synthesized AgNPs to be between 8 to 50 nm with -11.52 of zeta potential value. The existence of the silver element in the AgNPs was confirmed with the peaks obtained in the EDX spectrometry. Significant antibacterial activity was observed against selected biofilm-forming pathogenic bacteria. The cytotoxicity study with A. salina revealed the LC50 of synthesized AgNPs was at 0.81 mg/mL. Based on the ROS quantification, it was suggested that the ROS production, due to the interaction of AgNP with different bacterial cells, causes structural changes of the cell. This proves that the synthesized AgNPs could be an effective drug against multidrug resistant bacteria.
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Anacardiaceae/química , Antibacterianos/farmacologia , Biofilmes , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Nanopartículas Metálicas/química , Prata/química , Animais , Artemia , Bactérias/efeitos dos fármacos , Química Verde , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Nanomedicina , Extratos Vegetais/farmacologia , Folhas de Planta/química , Espécies Reativas de Oxigênio , Raios UltravioletaRESUMO
Continuously increasing energy demand and growing concern about energy resources has attracted much research in the field of clean and sustainable energy sources. In this context, zero-emission fuels are required for energy production to reduce the usage of fossil fuel resources. Here, we present the synthesis of Pd-Ag-decorated reduced graphene oxide (rGO) nanostructures using a green chemical approach with stevia extract for hydrogen production and antibacterial studies under light irradiation. Moreover, bimetallic nanostructures are potentially lime lighted due to their synergetic effect in both scientific and technical aspects. Structural characteristics such as crystal structure and morphological features of the synthesized nanostructures were analyzed using X-ray diffraction and transmission electron microscopy. Analysis of elemental composition and oxidation states was carried out by X-ray photoelectron spectroscopy. Optical characteristics of the biosynthesized nanostructures were obtained by UV-Vis absorption spectroscopy, and Fourier transform infrared spectroscopy was used to investigate possible functional groups that act as reducing and capping agents. The antimicrobial activity of the biosynthesized Pd-Ag-decorated rGO nanostructures was excellent, inactivating 96% of Escherichia coli cells during experiments over 150 min under visible light irradiation. Hence, these biosynthesized Pd-Ag-decorated rGO nanostructures can be utilized for alternative nanomaterial-based drug development in the future.
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Antibacterianos/farmacologia , Nanopartículas Metálicas/química , Nanocompostos/química , Paládio/química , Fotoquímica/métodos , Fitoterapia/métodos , Folhas de Planta/metabolismo , Prata/química , Stevia/metabolismo , Catálise , Citoplasma/metabolismo , Desenho de Fármacos , Escherichia coli/metabolismo , Grafite/química , Química Verde , Hidrogênio/química , Luz , Metais , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Nanomedicina/métodos , Nanoestruturas/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
In the present study, we have developed a green approach for the synthesis of silver nanoparticles (DSAgNPs) using aqueous extract of Durio zibethinus seed and determined its antibacterial, photocatalytic and cytotoxic effects. Surface plasmon resonance confirmed the formation of DSAgNPs with a maximum absorbance (λmax) of 420 nm. SEM and TEM images revealed DSAgNPs were spherical and rod shaped, with a size range of 20 nm and 75 nm. The zeta potential was found to be -15.41 mV. XRD and EDX analyses confirmed the nature and presence of Ag and AgCl. DSAgNPs showed considerable antibacterial activity, exhibited better cytotoxicity against brine shrimp, and shown better photocatalytic activity against methylene blue. Based on the present research work, it can be concluded that DSAgNPs could be used in the field of water treatment, pharmaceuticals, biomedicine, biosensor and nanotechnology in near future.
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Anti-Infecciosos/farmacologia , Bombacaceae/química , Química Verde/métodos , Luz , Nanopartículas Metálicas/química , Extratos Vegetais/química , Sementes/química , Prata/química , Animais , Artemia/efeitos dos fármacos , Catálise , Morte Celular/efeitos dos fármacos , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade MicrobianaRESUMO
The ATP-binding cassette (ABC) drug transporter ABCG2 can actively efflux a wide variety of chemotherapeutic agents out of cancer cells and subsequently reduce the intracellular accumulation of these drugs. Therefore, the overexpression of ABCG2 often contributes to the development of multidrug resistance (MDR) in cancer cells, which is one of the major obstacles to successful cancer chemotherapy. Moreover, ABCG2 is highly expressed in various tissues including the intestine and blood-brain barrier (BBB), limiting the absorption and bioavailability of many therapeutic agents. For decades, the task of developing a highly effective synthetic inhibitor of ABCG2 has been hindered mostly by the intrinsic toxicity, the lack of specificity, and complex pharmacokinetics. Alternatively, considering the wide range of diversity and relatively nontoxic nature of natural products, developing potential modulators of ABCG2 from natural sources is particularly valuable. α-Mangostin is a natural xanthone derived from the pericarps of mangosteen (Garcinia mangostana L.) with various pharmacological purposes, including suppressing angiogenesis and inducing cancer cell growth arrest. In this study, we demonstrated that at nontoxic concentrations, α-mangostin effectively and selectively inhibits ABCG2-mediated drug transport and reverses MDR in ABCG2-overexpressing MDR cancer cells. Direct interactions between α-mangostin and the ABCG2 drug-binding site(s) were confirmed by stimulation of ATPase activity and by inhibition of photolabeling of the substrate-binding site(s) of ABCG2 with [125I]iodoarylazidoprazosin. In summary, our findings show that α-mangostin has great potential to be further developed into a promising modulator of ABCG2 for reversing MDR and for its use in combination therapy for patients with MDR tumors.
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Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Xantonas/química , Xantonas/uso terapêutico , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Linhagem Celular Tumoral , Garcinia mangostana/química , Humanos , Mucosa Intestinal/metabolismoRESUMO
P-glycoprotein (P-gp) is a multidrug transporter that uses energy from ATP hydrolysis to export many structurally dissimilar hydrophobic and amphipathic compounds, including anticancer drugs from cells. Several structural studies on purified P-gp have been reported, but only limited and sometimes conflicting information is available on ligand interactions with the isolated transporter in a dodecyl-maltoside detergent environment. In this report we compared the biochemical properties of P-gp in native membranes, detergent micelles, and when reconstituted in artificial membranes. We found that the modulators zosuquidar, tariquidar, and elacridar stimulated the ATPase activity of purified human or mouse P-gp in a detergent micelle environment. In contrast, these drugs inhibited ATPase activity in native membranes or in proteoliposomes, with IC50 values in the 10-40 nm range. Similarly, a 30-150-fold decrease in the apparent affinity for verapamil and cyclic peptide inhibitor QZ59-SSS was observed in detergent micelles compared with native or artificial membranes. Together, these findings demonstrate that the high-affinity site is inaccessible because of either a conformational change or binding of detergent at the binding site in a detergent micelle environment. The ligands bind to a low-affinity site, resulting in altered modulation of P-gp ATPase activity. We, therefore, recommend studying structural and functional aspects of ligand interactions with purified P-gp and other ATP-binding cassette transporters that transport amphipathic or hydrophobic substrates in a detergent-free native or artificial membrane environment.
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Detergentes/química , Ligantes , Micelas , Subfamília B de Transportador de Cassetes de Ligação de ATP/química , Acridinas/química , Trifosfato de Adenosina/química , Animais , Baculoviridae/metabolismo , Sítios de Ligação , Dibenzocicloeptenos/química , Sistemas de Liberação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Glucosídeos/química , Humanos , Hidrólise , Concentração Inibidora 50 , Insetos , Camundongos , Peptídeos Cíclicos/química , Ligação Proteica , Quinolinas/química , Tetra-Hidroisoquinolinas/química , Verapamil/químicaRESUMO
INTRODUCTION: Vitamin D deficiency has been found to contribute to various cardiac conditions, such as hypertension, coronary artery disease, stroke, and atherosclerosis. However, the clinical cardiovascular benefits after short term supplementation have not been reported. AIM: To study the beneficial effect of Vitamin D supplementation on angina episodes in Vitamin D deficient patients with chronic stable angina on medical management. MATERIALS AND METHODS: A total of 40 patients were studied with group 1 (20 patients) with low Vitamin D levels and group 2 with normal Vitamin D levels. 60000 IU of Vitamin D supplementation was given every week for 8 weeks in group 1. Frequency of anginal episodes and use of sub-lingual nitrates were compared at base-line and after 8 weeks post supplementation. RESULTS: Significant 20% (p <0.05) reduction in anginal episodes and 17.24% (p <0.05) reduction in use of sub-lingual nitrates was noted in group1 after Vitamin D supplementation. The benefits were independent of BP, heart rate and medications, thus, attributing to supplementation. No significant change was noted in group 2. CONCLUSION: Cardiovascular patients need to be evaluated for Vitamin D deficiency. Supplementation to correct Vitamin D levels may have additional cardiovascular benefits like reduction in angina episodes.
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P-Glycoprotein (P-gp) serves as a therapeutic target for the development of inhibitors to overcome multidrug resistance in cancer cells. Although various screening procedures have been practiced so far to develop first three generations of P-gp inhibitors, their toxicity and drug interaction profiles are still a matter of concern. To address the above important problem of developing safe and effective P-gp inhibitors, we have made systematic computational and experimental studies on the interaction of natural phytochemicals with human P-gp. Molecular docking and QSAR studies were carried out for 40 dietary phytochemicals in the drug-binding site of the transmembrane domains (TMDs) of P-gp. Dietary flavonoids exhibit better interactions with homology modeled human P-gp. Based on the computational analysis, selected flavonoids were tested for their inhibitory potential against P-gp transport function in drug resistant cell lines using calcein-AM and rhodamine 123 efflux assays. It has been found that quercetin and rutin were the highly desirable flavonoids for the inhibition of P-gp transport function and they significantly reduced resistance in cytotoxicity assays to paclitaxel in P-gp overexpressing MDR cell lines. Hence, quercetin and rutin may be considered as potential chemosensitizing agents to overcome multidrug resistance in cancer.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Antineoplásicos/farmacologia , Suplementos Nutricionais , Resistencia a Medicamentos Antineoplásicos/genética , Flavonoides/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/química , Sítios de Ligação , Domínio Catalítico , Linhagem Celular Tumoral , Simulação por Computador , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Flavonoides/química , Humanos , Ligantes , Modelos Moleculares , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica , Relação Estrutura-AtividadeRESUMO
Nasal high flow (NHF) therapy is used to treat a variety of respiratory disorders to improve patient oxygenation. A CO2 washout mechanism is believed to be responsible for the observed increase in oxygenation. In this study, experimentally validated Computational Fluid Dynamics simulations of the CO2 concentration within the upper airway during unassisted and NHF assisted breathing were undertaken with the aim of exploring the existence of this washout mechanism. An anatomically accurate nasal cavity model was generated from a CT scan and breathing was reproduced using a Fourier decomposition of a physiologically measured breath waveform. Time dependent CO2 profiles were obtained at the entrance of the trachea in the experimental model, and were used as simulation boundary conditions. Flow recirculation features were observed in the anterior portion of the nasal cavity upon application of the therapy. This causes the CO2 rich gas to vent from the nostrils reducing the CO2 concentration in the dead space and lowering the inspired CO2 volume. Increasing therapy flow rate increases the penetration depth within the nasal cavity of the low CO2 concentration gas. A 65% decrease in inspired CO2 was observed for therapy flow rates ranging from 0 to 60 L min(-1) supporting the washout mechanism theory.
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Dióxido de Carbono/metabolismo , Oxigenoterapia Hiperbárica , Modelos Biológicos , Cavidade Nasal/metabolismo , Traqueia/metabolismo , Adulto , Humanos , Masculino , Cavidade Nasal/fisiopatologia , Traqueia/fisiopatologiaRESUMO
Cancer is a hyperproliferative disorder that involves transformation, dysregulation of apoptosis, proliferation, invasion, angiogenesis and metastasis. During the last 30 years, extensive research has revealed much about the biology of cancer. Chemotherapy and radiotherapy are the mainstays of cancer treatment, particularly for patients who do not respond to surgical resection. However, cancer treatment with drugs or radiation is seriously limited by chemoresistance and radioresistance. Various approaches and strategies are employed to overcome resistance to chemotherapy and radiation treatment. Many plant-derived phytochemicals have been investigated for their chemo- and radio-sensitizing properties. The peoples of South Asian countries such as India, Pakistan, Sri Lanka, Nepal, Bangladesh and Bhutan have a large number of medicinal plants from which they produce various pharmacologically potent secondary metabolites. The medicinal properties of these compounds have been extensively investigated and many of them have been found to sensitize cancer cells to chemo- and radio-therapy. This review focuses on the role of South Asian medicinal compounds in chemo- and radio-sensitizing properties in drug- and radio-resistant cancer cells. Also discussed is the role of South Asian medicinal plants in protecting normal cells from radiation, which may be useful during radiotherapy of tumors to spare surrounding normal cells.
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Monoamine oxidase B inhibitors (MAO-BIs) are used in the early management of Parkinson's disease (PD). Long-term suspected side effects of MAO-B classical inhibitors established the need for safer alternative therapeutic agents. In our study, the flavanone bavachinin (BNN) and its analog bavachin (BVN) found in the seeds of Psoralea corylifolia L. ethanolic extract (PCSEE) were investigated for their human MAO-A and MAO-B (hMAO-A and hMAO-B) inhibition. Both PCSEE and BNN effectively reduced hMAO-B activity more than hMAO-A while BVN had activating effects. BNN showed selective hMAO-B inhibition (IC50 ~ 8.82 µM) more than hMAO-A (IC502009;~ 189.28 µM). BNN in the crude extract was determined by HPLC, also validated by TLC showing a yield of 0.21% PCSEE dry weight. BNN competitively inhibited hMAO-A and hMAO-B, with a lower hMAO-B K i than hMAO-A K i by 10.33-fold, and reduced hMAO-B K m /V max efficiency ratio to be comparable to the standard selegiline. Molecular docking examination of BNN and BVN predicted an indirect role of BNN C7-methoxy group for its higher affinity, selectivity, and reversibility as an MAO-BI. These findings suggest that BNN, which is known to be a potent PPAR-γ agonist, is a selective and competitive hMAO-B inhibitor and could be used in the management of PD.
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ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthusrheedei Wight is a plant used by Muthuvan tribes of Kerala for treating liver related diseases. MATERIALS AND METHODS: The different extracts of Phyllanthus rheedei were analysed on cell lines were viz, PLC/PRF, Hep3B, FLCII10 and HepG2215 for its anti-HBV property. The analysis was done through ELISA, SQRT-PCR and immuno blotting. The most active extract was then divided in to fractions using HPTLC and the most active fraction was further identified. RESULTS: From the screening experiments it was shown that the ethanol extract of this plant has the maximum activity in lowering the viral markers like HBsAg, HBV Core and HBV X protein and whole virions with comparatively lesser cytotoxicity. The dose responses of this particular extract were further established. CONCLUSIONS: This study concluded that the ethanol extract of Phyllanthusrheedei is very much effective in preventing the multiplication of HBV at the cellular level. This study scientifically validated the tribal claim of the use of this plant for severe liver disorders.
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Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Phyllanthus/química , Extratos Vegetais/farmacologia , Linhagem Celular , DNA Viral/genética , Antígenos do Núcleo do Vírus da Hepatite B/metabolismo , Antígenos de Superfície da Hepatite B/metabolismo , Fígado/efeitos dos fármacos , Fígado/virologiaRESUMO
Hypothyroidism is associated with increased oxidative stress. The mechanism underlying the endothelial dysfunction in thyroid disease is not yet clear. This study aims to investigate lipid peroxidation and its association with endothelial dysfunction in overt hypothyroidism (OHT).Plasma malondialdehyde (MDA) as a marker of oxidative stress and plasma nitrates and asymmetric dimethyl arginine levels (ADMA) as markers of endothelial dysfunction were estimated in 25 OHT patients in comparison to 25 euthyroid controls. Plasma MDA, ADMA levels were significantly increased, whereas plasma nitrates were significantly decreased in the patient group compared to control group (p<0.01). Moreover, a significant positive association between plasma MDA and ADMA was found in the patient group (ρ=0.472, p=0.036). Our results reveal the presence of endothelial dysfunction in OHT patients as evidenced by decreased plasma nitrates and increased ADMA levels. Increased levels of MDA represent an increased generation of reactive oxygen species in these patients. A finding of significant direct relation of plasma MDA with ADMA indicates that oxidative stress has a strong impact on endothelial dysfunction in overt hypothyroidism. Further studies focusing on the role of oxidative stress in endothelial dysfunction and the effects of antioxidant supplementation on endothelial function in OHT patients are required.