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1.
Journal of Experimental Hematology ; (6): 1745-1749, 2023.
Article in Chinese | WPRIM | ID: wpr-1010032

ABSTRACT

OBJECTIVE@#To establish a MM patient-derived tumor xenograft model (MM-PDX) in zebrafish, and to evaluate the anti-myeloma activity of indirubin-3'-monoxime(I3MO) using this model.@*METHODS@#Zebrafish embryos 2 days after fertilization were transplanted with fluorescence labeled myeloma primary tumor cells, the survival of primary tumor cells in zebrafish was observed at 0,16 and 24 hours after cell injection. The zebrafish embryos after tumor cell transplantation were randomly divided into control group, BTZ treatment and I3MO treatment group. Before and 24 hours after treatment with BTZ and I3MO, the positive area with calcein or Dil in zebrafish were observed under fluorescence microscope to reflect the survival of tumor cells, and it was verified.@*RESULTS@#MM patient derived tumor cells survived in zebrafish. The construction of MM-PDX was successful. Compared with control group, the fluo- rescence area of the BTZ and I3MO treatment groups in zebrafish were significantly decreased(P<0.05), and BTZ and I3MO significantly inhibited the survival of MM cells in zebrafish.@*CONCLUSION@#MM-PDX model was successfully established. Zebrafish model derived from tumor cells of MM patients can be used as a tool for drug screening of MM.


Subject(s)
Animals , Humans , Bortezomib/therapeutic use , Cell Line, Tumor , Disease Models, Animal , Drug Evaluation, Preclinical , Heterografts , Multiple Myeloma/pathology , Xenograft Model Antitumor Assays , Zebrafish
2.
Chinese Journal of Biotechnology ; (12): 3905-3914, 2021.
Article in Chinese | WPRIM | ID: wpr-921475

ABSTRACT

Microfluidic chip technology integrates the sample preparation, reaction, separation and detection on a chip. It consists a network of microchannels, which controls the whole system through fluid. With the advantages of portability, high throughput, and the ability to simulate the microenvironment in vivo, it has a broad application prospect in the research of disease diagnosis, pathogenesis and drug screening. Pulmonary inflammatory disease is a common disease usually caused by bacterial, viral and fungal infections. Early pneumonia is often difficult to diagnose due to lack of obvious respiratory symptoms or the symptoms are mostly atypical, but the disease progresses rapidly. Recently, microfluidic chip technology has been increasingly used to the study of pulmonary inflammatory diseases. In particular, it has been used to develop a "lung-on-a-chip" model, which can reproduce the key structure, function and mechanical properties of human alveolar capillary interface (i.e., the basic functional unit of a living lung), and well simulate the alveoli in vitro. Compared with the cell and animal models, this multifunctional micro experimental platform has great advantages. This article summarizes the advances of using microfluidic chips for the research and diagnosis of pulmonary inflammatory diseases, with the aim to provide new ideas for researchers in this area.


Subject(s)
Animals , Humans , Drug Evaluation, Preclinical , Lung , Microfluidic Analytical Techniques , Microfluidics
3.
China Journal of Chinese Materia Medica ; (24): 320-332, 2021.
Article in Chinese | WPRIM | ID: wpr-878977

ABSTRACT

With the increasing incidence of hepatobiliary diseases, it is particularly important to understand the role of molecular, cellular and physiological factors in the clinical diagnosis and treatment with traditional Chinese medicine(TCM) in the development of liver disease. Appropriate animal models can help us identify the possible mechanisms of relevant diseases. Danio rerio(zebrafish) model was traditionally used to study embryonic development, and has been gradually used in screening and evaluation of liver diseases and relevant drug in recent years. Zebrafish embryos develop rapidly and the digestive organs of 5-day-old juvenile fish are all mature. At this stage, they may develop hepatobiliary diseases induced by developmental defects or compounds. Zebrafish liver is similar to human liver in cell composition, function, signal transduction, response to injury and cell process mediating liver disease. Furthermore, due to the high conservation of genes and proteins between humans and zebrafish, zebrafish becomes an alternative system for studying basic mechanisms of liver disease. Therefore, genetic screening could be performed to identify new genes involving specific disease processes, and chemical screening could be made for drugs in specific processes. This paper briefly introduced the experimental properties of zebrafish as model system, emphasized the study progress of zebrafish models for pathological mechanism of liver diseases, especially fatty liver, and drug screening and evaluation, so as to provide ideas and techniques for the future liver toxicity assessment of TCM.


Subject(s)
Animals , Humans , Drug Evaluation, Preclinical , Liver , Liver Diseases/genetics , Medicine, Chinese Traditional , Zebrafish/genetics
4.
Protein & Cell ; (12): 877-888, 2021.
Article in English | WPRIM | ID: wpr-922482

ABSTRACT

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M


Subject(s)
Humans , Antiviral Agents/therapeutic use , Binding Sites , COVID-19/virology , Coronavirus Papain-Like Proteases/metabolism , Crystallography, X-Ray , Drug Evaluation, Preclinical , Drug Repositioning , High-Throughput Screening Assays/methods , Imidazoles/therapeutic use , Inhibitory Concentration 50 , Molecular Dynamics Simulation , Mutagenesis, Site-Directed , Naphthoquinones/therapeutic use , Protease Inhibitors/therapeutic use , Protein Structure, Tertiary , Recombinant Proteins/isolation & purification , SARS-CoV-2/isolation & purification
5.
Acta cir. bras ; 35(2): e202000203, 2020. graf
Article in English | LILACS | ID: biblio-1100882

ABSTRACT

Abstract Purpose To evaluate the effect of remote ischemic conditioning associated to N-acetylcysteine (NAC) on testicular ischemia∕reperfusion (I∕R) injury in rats. Methods Twenty-five adult male Wistar rats were randomly distributed into five experimental groups (n=5), as follows: Sham, I∕R, Perconditioning (PER), NAC and PER+NAC. Two-hour ischemia was induced by rotating the left testis 720° to clockwise direction, followed by 4 hours of reperfusion. Perconditioning was performed by three I/R cycles of 10 min each on the left limb, 30 min before reperfusion. N-acetylcysteine (150 mg∕kg) was administered 30 min before reperfusion. Results Statistical differences were observed in MDA levels between I/R group with all groups (p<0.01), in addition there was statistical difference between PER and Sham, and PER+ NAC groups (p<0.05) in plasma. Conclusions The protective effect of perconditioning isolated in the reduction of lipid peroxidation related to oxidative stress was demonstrated. However, when Perconditioning was associated with NAC, there was no protective effect against testicular injury of ischemia and reperfusion.


Subject(s)
Animals , Male , Rats , Acetylcysteine/pharmacology , Testis/blood supply , Reperfusion Injury , Free Radical Scavengers/pharmacology , Oxidative Stress/drug effects , Ischemic Preconditioning/methods , Testis/drug effects , Random Allocation , Rats, Wistar , Drug Evaluation, Preclinical , Oxygen Radical Absorbance Capacity
6.
Acta cir. bras ; 35(2): e202000204, 2020. graf
Article in English | LILACS | ID: biblio-1100885

ABSTRACT

Abstract Purpose To investigate the effect of growth arrest-specific protein 6 (Gas6) on acute liver injury in mice and related mechanisms. Methods Thirty C57BL/6 (6-8 weeks old) mice were randomly divided into control, LPS/D-GalN, and LPS/D-GalN+Gas6 groups (10 mice in each group). The LPS/D-GalN group was intraperitoneally administered with LPS (0.25 mg/Kg) and D-GalN (400 mg/Kg) for 5h. The LPS/D-GalN+Gas6 group was intraperitoneally administered with rmGas6 one hour before intraperitoneal application of LPS/D-GalN. All subjects were sacrificed at 5 h for blood and tissue analysis. The expression of protein and mRNA was assessed by western blotting and RT-PCR, respectively. Results Compared with the control group, AST, ALT, IL-1β, TNF-α, IL-6 IL-10, MPO activity were increased in the LPS/D-GalN group. However, they were significantly inhibited by Gas6. Gas6 markedly suppressed the expression of apoptosis-related protein induced by LPS/D-GalN. Moreover, Gas6 attenuated the activation of the NF-κB signaling pathway in acute liver injury induced by LPS/D-GalN. Conclusions Gas6 alleviates acute liver injury in mice through regulating NF-κB signaling pathways. Gas6 can be a potential therapeutic agent in treating LPS/D-GalN-induced acute liver injury in the future.


Subject(s)
Animals , Male , Mice , Lipopolysaccharides/adverse effects , Apoptosis/drug effects , Intercellular Signaling Peptides and Proteins/pharmacology , Chemical and Drug Induced Liver Injury/drug therapy , Liver/drug effects , Anti-Inflammatory Agents/pharmacology , Intercellular Signaling Peptides and Proteins/therapeutic use , Drug Evaluation, Preclinical , Anti-Inflammatory Agents/therapeutic use
7.
Acta cir. bras ; 35(1): e202000106, 2020. graf
Article in English | LILACS | ID: biblio-1088526

ABSTRACT

Abstract Purpose To explore the role of all-trans retinoic acid (ATRA) in renal ischemia/reperfusion injury of diabetic rats. Methods Sixty adult male rats were randomly divided into 6 groups, including sham group (S group), ischemia-reperfusion group (I/R group), ischemia-reperfusion+ATRA group (A group), diabetic group (D group), diabetic ischemia-reperfusion group (DI/R group), diabetic ischemia-reperfusion +ATRA group (DA group). The levels of creatinine (Cr), cystatin C (Cys-C) and β2-microglobulin (β2-MG) were measured. Morphology of renal tissue was observed under light microscope. Results DJ-1, Nrf2, HO-1 and caspase-3 were detected by western blot. DJ-1, Nrf2, HO-1 and caspase-3 in I/R group, D group and DI/R group was higher than that in S group. Compared with I/R group, Nrf2 and HO-1 in A group was decreased, but caspase-3 was increased. However, Nrf2 in DA group was higher than that in DI/R group, HO-1 and caspase-3 in DA group were lower than that in DI/R group. Compared with group S, Cr, Cys-C and β2-MG in I/R group, A group, D group, and DI/R group were higher. Whereas the levels of Cr, Cys-C, β2-MG and renal injury score in DA group were lower than those in DI/R group. Conclusion ATRA has a protective effect on renal ischemia-reperfusion injury in diabetic rats, maybe relating to DJ/Nrf2 pathway.


Subject(s)
Animals , Male , Rats , Tretinoin/therapeutic use , Reperfusion Injury/prevention & control , Diabetes Mellitus, Experimental/chemically induced , NF-E2-Related Factor 2/therapeutic use , Kidney/drug effects , Tretinoin/pharmacology , Reperfusion Injury/pathology , Streptozocin , Disease Models, Animal , Drug Evaluation, Preclinical , NF-E2-Related Factor 2/pharmacology , Kidney/pathology
8.
Acta cir. bras ; 35(1): e202000103, 2020. tab, graf
Article in English | LILACS | ID: biblio-1088520

ABSTRACT

Abstract Purpose To investigate the protective effect of Ganoderma lucidum on testicular torsion/detorsion (T/D)-induced ischemia-reperfusion (I/R) injury. Methods Thirty male Wistar albino rats were randomly categorized into 3 groups: Group 1: sham, Group 2 ( T/D): 2,5 hours of ischemia and 7 days of reperfusion, Group 3 (T/D+ G. lucidum ): 2,5 hours of ischemia and 7 days of reperfusion and 7 days of 20 mg/kg via gastric gavage G. lucidum polysaccharides per day. Biochemical assays of Malondialdehyde (MDA), superoxide dismutase (SOD), Catalase (CAT), Glutathione (GSH) levels , histopathology and expression levels of VEGF and Bcl-2 with immunohistochemical methods were examined in testicular tissue. Results G. lucidum treatment was found to have prevented the T/D-induced I/R injury by decreasing MDA levels of the testis. SOD, CAT and GSH activities were decreased in group 2, while they were increased in group 3 (p<0.001) and significant improvement in the tube diameter was observed in group 3. Bcl-2-positive germinal cells were lowered in group 3 compared to the group 2. VEGF expression showed an increase in group 2, whereas it decreased in group 3. Conclusion The antioxidant G. lucidum is thought to induce angiogenesis by reducing the apoptotic effect in testicular torsion-detorsion.


Subject(s)
Animals , Male , Rats , Spermatic Cord Torsion/complications , Testis/blood supply , Reperfusion Injury/prevention & control , Reishi/chemistry , Antioxidants/therapeutic use , Spermatic Cord Torsion/metabolism , Superoxide Dismutase/metabolism , Testis/drug effects , Testis/pathology , Reperfusion Injury/etiology , Catalase/metabolism , Random Allocation , Rats, Wistar , Vascular Endothelial Growth Factor A/metabolism , Drug Evaluation, Preclinical , Malondialdehyde/metabolism , Antioxidants/pharmacology
9.
Bol. latinoam. Caribe plantas med. aromát ; 19(4): 344-356, 2020. tab, ilus
Article in English | LILACS | ID: biblio-1283652

ABSTRACT

Many chronic diseases require repetitive injections as maintenance treatment. It is therefore important to investigate a possible alternative. A simulated subcutaneous implant prototype was fabricated as a polymer matrix covered by cylinder-shape tubing having a porous membrane. Sucrose, bovine serum albumin, and gelatin were selected as matrix excipients. Eight APIs with different physiochemical properties were used to investigate the releasing mechanism. Drug release was tested through an in vitrodissolution apparatus. Drug release of eight APIs followed zero-order kinetics with a minimum 12-hour duration. Release rates also showed linear correlations with the APIs' solubilities under physiological pH. For releasing mechanism studies, different combinations of matrix and membrane were investigated in detail. A 144-hour continuous zero-order release of caffeine was achieved as the best controlled simulated prototype. The results showed that drug release of our simulated prototype was primarily achieved by drug diffusion rather than dissolution.


Muchas enfermedades crónicas requieren inyecciones repetitivas como tratamiento de mantenimiento. Por lo tanto, es importante investigar una posible alternativa. Se fabricó un prototipo de implante subcutáneo simulado a partir de una matriz de polímero cubierta por un tubo en forma de cilindro que tiene una membrana porosa. La sacarosa, la albúmina de suero bovino y la gelatina se seleccionaron como excipientes matriciales. Se utilizaron ocho APIs con diferentes propiedades fisicoquímicas para investigar el mecanismo de liberación. La liberación del fármaco se probó a través de un aparato de disolución in vitro. La liberación del fármaco de las ocho APIs siguió una cinética de orden cero con una duración mínima de 12 horas. Las tasas de liberación también mostraron correlaciones lineales con las solubilidades de las APIs a pH fisiológico. Para los estudios de mecanismos de liberación, se investigaron en detalle diferentes combinaciones de matriz y membrana. El prototipo simulado con mejor control logró una liberación continua de cafeína de orden cero durante 144 horas. Los resultados mostraron que la liberación del fármaco del prototipo simulado ocurrió principalmente mediante la difusión del fármaco en lugar de la disolución.


Subject(s)
Pharmaceutical Preparations/administration & dosage , Drug Implants/metabolism , In Vitro Techniques , Pilot Projects , Chromatography, High Pressure Liquid , Subcutaneous Tissue , Delayed-Action Preparations , Drug Evaluation, Preclinical , Drug Liberation , Freeze Drying
10.
Protein & Cell ; (12): 723-739, 2020.
Article in English | WPRIM | ID: wpr-827018

ABSTRACT

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.


Subject(s)
Animals , Humans , Mice , Antiviral Agents , Pharmacology , Therapeutic Uses , Betacoronavirus , Physiology , Binding Sites , Cell Line , Coronavirus Infections , Drug Therapy , Virology , Crotonates , Pharmacology , Cytokine Release Syndrome , Drug Therapy , Drug Evaluation, Preclinical , Gene Knockout Techniques , Influenza A virus , Leflunomide , Pharmacology , Mice, Inbred BALB C , Orthomyxoviridae Infections , Drug Therapy , Oseltamivir , Therapeutic Uses , Oxidoreductases , Metabolism , Pandemics , Pneumonia, Viral , Drug Therapy , Virology , Protein Binding , Pyrimidines , RNA Viruses , Physiology , Structure-Activity Relationship , Toluidines , Pharmacology , Ubiquinone , Metabolism , Virus Replication
11.
Protein & Cell ; (12): 723-739, 2020.
Article in English | WPRIM | ID: wpr-828747

ABSTRACT

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.


Subject(s)
Animals , Humans , Mice , Antiviral Agents , Pharmacology , Therapeutic Uses , Betacoronavirus , Physiology , Binding Sites , Cell Line , Coronavirus Infections , Drug Therapy , Virology , Crotonates , Pharmacology , Cytokine Release Syndrome , Drug Therapy , Drug Evaluation, Preclinical , Gene Knockout Techniques , Influenza A virus , Leflunomide , Pharmacology , Mice, Inbred BALB C , Orthomyxoviridae Infections , Drug Therapy , Oseltamivir , Therapeutic Uses , Oxidoreductases , Metabolism , Pandemics , Pneumonia, Viral , Drug Therapy , Virology , Protein Binding , Pyrimidines , RNA Viruses , Physiology , Structure-Activity Relationship , Toluidines , Pharmacology , Ubiquinone , Metabolism , Virus Replication
12.
Protein & Cell ; (12): 723-739, 2020.
Article in English | WPRIM | ID: wpr-828583

ABSTRACT

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.


Subject(s)
Animals , Humans , Mice , Antiviral Agents , Pharmacology , Therapeutic Uses , Betacoronavirus , Physiology , Binding Sites , Cell Line , Coronavirus Infections , Drug Therapy , Virology , Crotonates , Pharmacology , Cytokine Release Syndrome , Drug Therapy , Drug Evaluation, Preclinical , Gene Knockout Techniques , Influenza A virus , Leflunomide , Pharmacology , Mice, Inbred BALB C , Orthomyxoviridae Infections , Drug Therapy , Oseltamivir , Therapeutic Uses , Oxidoreductases , Metabolism , Pandemics , Pneumonia, Viral , Drug Therapy , Virology , Protein Binding , Pyrimidines , RNA Viruses , Physiology , Structure-Activity Relationship , Toluidines , Pharmacology , Ubiquinone , Metabolism , Virus Replication
13.
China Journal of Chinese Materia Medica ; (24): 1219-1224, 2020.
Article in Chinese | WPRIM | ID: wpr-1008559

ABSTRACT

With the rapid outbreak of COVID-19, traditional Chinese medicine(TCM) has been playing an active role against the epidemic. However, the screening of TCM is limited by the development cycle and laboratory conditions, which greatly limits the screening speed. This study established optimization docking models and virtual screening to discovery potential active herbs for the prevention and treatment of the novel coronavirus based on molecular docking technology. The crystal structures of 3 CL protease(Mpro) and papain-like protease(PLP) were obtained from PDB database and homologous modeling respectively, and were used to conduct virtual screening of TCMD 2009 database by CDOCKER program. The ingredients scored in the top 100 were selected respectively, and the candidate herbs were ranked by the numbers of hit molecules. Based on Mpro inhibitors screening, 12 322 potential active components were obtained, and the representative active components included aster pentapeptide A, ligustrazine, salvianolic acid B, etc., and Zingiberis Rhizoma Recens, Asteris Radix et Rhizoma, Notoginseng Radix et Rhizoma, Chuanxiong Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Zingiberis Rhizoma, Dianthi Herba, Rhei Radix et Rhizoma, Cistanches Herba were obtained. While 11 294 potential active ingredients were obtained by PLP inhibitor screening, representative active ingredients included gingerketophenol, ginkgol alcohol, ferulic acid, etc., and Codonopsis Radix, Notopterygii Rhizoma et Radix, Zingiberis Rhizoma Recens, Ginkgo Semen, Chuanxiong Rhizoma, Trichosanthis Fructus, Paeoniae Radix Alba, Psoraleae Fructus, Sophorae Flavescentis Radix, Notoginseng Radix et Rhizoma, Angelicae Sinensis Radix were chosen. By combining the diagnosis and treatment scheme of Hunan province's and angiotensin converting enzyme 2(ACE2) inhibitors screening from literature, present study also discussed the rational application of candidate herbs to this epidemic situation. Trichosanthis Fructus obtained by PLP inhibitors screening and Fritillaria verticillata obtained by ACE2 inhibitors screening were parts of the Sangbei Zhisou Powder and Xiaoxianxiong Decoction, which might be applicable to the syndromes of cough and dyspnea. Rhei Radix et Rhizoma screened by Mpro and Trichosanthis Fructus screened by PLP were contained in Maxing Shigan Decoction and Xuanbai Chengqi Decoction, and could be applied to the syndromes of epidemic virus blocking lung. Mori Folium, Lonicerae Japonicae Flos and Forsythiae Fructus obtained by ACE2 inhibitors screening were included in the Sangju Decoction and Yinqiaosan, which might be applicable to the syndromes of warm pathogen attacking lung and cough and dyspnea. The results of this study are intended to provide a reference for the further development of traditional Chinese medicine to deal with the new epidemic.


Subject(s)
Humans , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Betacoronavirus/drug effects , COVID-19 , Coronavirus Infections/drug therapy , Drug Evaluation, Preclinical , Drugs, Chinese Herbal/pharmacology , Medicine, Chinese Traditional , Molecular Docking Simulation , Pandemics , Peptidyl-Dipeptidase A , Pneumonia, Viral/drug therapy , SARS-CoV-2 , COVID-19 Drug Treatment
14.
Acta cir. bras ; 35(3): e202000303, 2020. tab, graf
Article in English | LILACS | ID: biblio-1130621

ABSTRACT

Abstract Purpose: To evaluate the in vivo response of photobiomodulation therapy associated with norbixin-based poly(hydroxybutyrate) membrane (PHB) in tenotomized calcaneal tendon. Methods: Thirty rats were randomly allocated to six groups (n=5 each): LED groups (L1, L2 and L3) and membrane + LED groups (ML1, ML2 and ML3). The right calcaneal tendons of all animals were sectioned transversely and were irradiated with LED daily, one hour after surgery every 24 hours, until the day of euthanasia. At the end of the experiments the tendons were removed for histological analysis. Results: The histological analysis showed a significant reduction in inflammatory cells in the ML1, ML2 and ML3 groups (p=0.0056, p=0.0018 and p<0.0001, respectively) compared to those in the LED group. There was greater proliferation of fibroblasts in the ML1 (p<0.0001) and L3 (p<0.0001) groups. A higher concentration of type I collagen was also observed in the ML1 group (p=0.0043) replacing type III collagen. Conclusion: Photobiomodulation in association with norbixin-based PHB membrane led to control of the inflammatory process. However, it did not favor fibroblast proliferation and did not optimize type I collagen formation in the expected stage of the repair process.


Subject(s)
Animals , Male , Rats , Achilles Tendon/radiation effects , Carotenoids/pharmacology , Low-Level Light Therapy/methods , Tendinopathy/radiotherapy , Tenotomy/methods , Hydroxybutyrates/pharmacology , Achilles Tendon/surgery , Achilles Tendon/drug effects , Wound Healing/drug effects , Wound Healing/radiation effects , Random Allocation , Collagen/pharmacology , Rats, Wistar , Collagen Type I/analysis , Collagen Type I/drug effects , Collagen Type III/analysis , Collagen Type III/drug effects , Drug Evaluation, Preclinical , Fibroblasts/drug effects , Fibroblasts/chemistry , Prohibitins
15.
Biomédica (Bogotá) ; 39(3): 491-501, jul.-set. 2019. tab, graf
Article in English | LILACS | ID: biblio-1038809

ABSTRACT

Abstract Introduction: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B. Objective: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity. Materials and methods: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively. Results: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity. Conclusion: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.


Resumen Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo [3,2-g ] chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.


Subject(s)
Animals , Male , Mice , Parkinson Disease, Secondary/drug therapy , Monoamine Oxidase Inhibitors/therapeutic use , Antiparkinson Agents/therapeutic use , Parkinson Disease, Secondary/chemically induced , Reserpine/administration & dosage , Carbidopa/administration & dosage , Catalepsy/chemically induced , Levodopa/administration & dosage , Coumarins , Disease Models, Animal , Drug Combinations , Drug Evaluation, Preclinical , Haloperidol , Locomotion/drug effects , Mice, Inbred ICR , Monoamine Oxidase Inhibitors/administration & dosage , Antiparkinson Agents/administration & dosage
16.
Vaccimonitor (La Habana, Print) ; 28(2)mayo.-ago. 2019.
Article in Spanish | LILACS, CUMED | ID: biblio-1094622

ABSTRACT

Con respecto al artículo publicado en la revista Vaccimonitor, volumen 28 número 1 del año 2019, donde se presentan los resultados del estudio toxicológico realizado a la vacuna antimeningocóccica VA-MENGOC-BC® después de 24 y 36 meses de almacenada de 4 a 8°C, quisiera emitir un grupo de consideraciones sobre algunos de los parámetros evaluados en los estudios toxicológicos para vacunas, con el objetivo de optimizar los resultados. En este sentido, podríamos contribuir a un mejor diseño de los estudios toxicológicos preclínicos, para alcanzar un valor predictivo más cercano a lo esperado en los ensayos clínicos. Por otra parte, estas consideraciones pudieran tenerse en cuenta para el análisis de los aspectos éticos, bienestar animal y determinación del punto final humanitario. Los estudios toxicológicos preclínicos de las vacunas se convirtieron en obligatorios desde la última década del pasado siglo XX, donde se han propuesto y diseñado diferentes estudios para cumplir con estos requisitos. Podemos mencionar, por ejemplo, los estudios de seguridad farmacológica, dosis única, tolerancia local y dosis repetida, entre otros.1 En cada uno de ellos existen parámetros a evaluar que se repiten, como son la observación clínica de los animales, peso corporal, consumo de agua y alimentos, así como la respuesta local y sistémica. Sin embargo, la información que pudiéramos obtener de estos parámetros, desde las pruebas de concepto hasta los propios estudios toxicológicos, no es explotada al máximo. Hoy en día, las guías emitidas por la Organización Mundial de la Salud (OMS), en mi opinión, son una de las más completas, porque recogen gran parte de las regulaciones y guías emitidas por otras entidades como la FDA (del inglés: Food and Drug Administration), EMA (del inglés: European Medicine Agency), OECD (del inglés: Organisation for Economic Co-operation and Development), ICH (del inglés: International Committee of Harmonization), entre otras. Contemplan un amplio número de parámetros a investigar en los estudios toxicológicos, que abarcan desde ensayos in vitro hasta in vivo.1 Sobre estos últimos, cada vez más, y para bien, son tenidos en cuenta los aspectos del bienestar animal y el principio de las 3Rs (Reemplazo, Reducción, Refinamiento).1,2 En este sentido, consideramos que se pueden introducir elementos que pudieran potenciar las respuestas de algunos de los parámetros investigados. En nuestro caso los realizamos para brindar nuevos elementos a la seguridad de un producto con años de aplicación, tanto en niños...(AU)


Subject(s)
Humans , Male , Female , Vaccines , Drug Evaluation, Preclinical/methods
17.
The Korean Journal of Physiology and Pharmacology ; : 295-303, 2019.
Article in English | WPRIM | ID: wpr-761807

ABSTRACT

A heart simulator, UT-Heart, is a finite element model of the human heart that can reproduce all the fundamental activities of the working heart, including propagation of excitation, contraction, and relaxation and generation of blood pressure and blood flow, based on the molecular aspects of the cardiac electrophysiology and excitation-contraction coupling. In this paper, we present a brief review of the practical use of UT-Heart. As an example, we focus on its application for predicting the effect of cardiac resynchronization therapy (CRT) and evaluating the proarrhythmic risk of drugs. Patient-specific, multiscale heart simulation successfully predicted the response to CRT by reproducing the complex pathophysiology of the heart. A proarrhythmic risk assessment system combining in vitro channel assays and in silico simulation of cardiac electrophysiology using UT-Heart successfully predicted druginduced arrhythmogenic risk. The assessment system was found to be reliable and efficient. We also developed a comprehensive hazard map on the various combinations of ion channel inhibitors. This in silico electrocardiogram database (now freely available at http://ut-heart.com/) can facilitate proarrhythmic risk assessment without the need to perform computationally expensive heart simulation. Based on these results, we conclude that the heart simulator, UT-Heart, could be a useful tool in clinical medicine and drug discovery.


Subject(s)
Humans , Blood Pressure , Cardiac Electrophysiology , Cardiac Resynchronization Therapy , Cardiotoxicity , Clinical Medicine , Computer Simulation , Drug Discovery , Drug Evaluation, Preclinical , Electrocardiography , Heart , In Vitro Techniques , Ion Channels , Models, Cardiovascular , Relaxation , Risk Assessment
18.
Blood Research ; : 165-174, 2019.
Article in English | WPRIM | ID: wpr-763080

ABSTRACT

Drug resistance in cancer, especially in leukemia, creates a dilemma in treatment planning. Consequently, studies related to the mechanisms underlying drug resistance, the molecular pathways involved in this phenomenon, and alternate therapies have attracted the attention of researchers. Among a variety of therapeutic modalities, mesenchymal stem cells (MSCs) are of special interest due to their potential clinical use. Therapies involving MSCs are showing increasing promise in cancer treatment and anticancer drug screening applications; however, results have been inconclusive, possibly due to the heterogeneity of MSC populations. Most recently, the effect of MSCs on different types of cancer, such as hematologic malignancies, their mechanisms, sources of MSCs, and its advantages and disadvantages have been discussed. There are many proposed mechanisms describing the effects of MSCs in hematologic malignancies; however, the most commonly-accepted mechanism is that MSCs induce tumor cell cycle arrest. This review explains the anti-tumorigenic effects of MSCs through the suppression of tumor cell proliferation in hematological malignancies, especially in acute myeloid leukemia.


Subject(s)
Cell Cycle Checkpoints , Cell Proliferation , Drug Evaluation, Preclinical , Drug Resistance , Hematologic Neoplasms , Leukemia , Leukemia, Myeloid, Acute , Mesenchymal Stem Cells , Population Characteristics
19.
Journal of Korean Academy of Psychiatric and Mental Health Nursing ; : 133-143, 2019.
Article in Korean | WPRIM | ID: wpr-764730

ABSTRACT

PURPOSE: The purpose of this study was to examine the association of multiple addiction risks with life satisfaction, depression, and suicidal ideation in Korean adults. METHODS: This study was descriptive correlational. Data were collected in 800 adults (405 males, 395 females) aged 20 to 69 years recruited using the proportional allocation in a city on April 2017. The structured questionnaire consisted of the Alcohol Use Disorders Identification Test, the Internet Addiction Proneness Scale for adults, the Problem Gambling Severity Index, the Drug Screening Inventory, the Korean version of the Satisfaction with the Life Scale, the Patient Health Questionnaire-9, and the Scale for Suicidal Ideation. RESULTS: Adults with multiple addiction risks had a low level of life satisfaction (p=.003) and high levels of depression and suicidal ideation (p<.001) compared to other participants. Multiple addiction risks were associated with low life satisfaction (β=.12), high depression (β=.21), and suicidal ideation (β=.20). Significant factors of life satisfaction were low suicidal ideation, a simple functioning job, high level of education, and unemployment status. CONCLUSION: Multiple addiction risks are associated with life satisfaction, depression, and suicidal ideation. The comprehensive mental health assessment for multiple addictions should precede the development of preventive multidimensional interventions.


Subject(s)
Adult , Humans , Male , Behavior, Addictive , Depression , Drug Evaluation, Preclinical , Education , Gambling , Internet , Mental Health , Personal Satisfaction , Suicidal Ideation , Unemployment
20.
Biomedical and Environmental Sciences ; (12): 235-241, 2019.
Article in English | WPRIM | ID: wpr-773400

ABSTRACT

OBJECTIVE@#To assess the activities of biapenem against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis.@*METHODS@#Biapenem/clavulanate (BP/CL) was evaluated for in vitro activity against Mycobacterium tuberculosis (Mtb) multidrug-resistant (MDR) isolates, extensively drug-resistant (XDR) isolates, and the H37RV strain. BP/CL activity against the H37Rv strain was assessed in liquid cultures, in macrophages, and in mice..@*RESULTS@#BP/CL exhibited activity against MDR and XDR Mtb isolates in liquid cultures. BP/CL treatment significantly reduced the number of colony forming units (CFU) of Mtb within macrophages compared with control untreated infected macrophages. Notably, BP/CL synergized in pairwise combinations with protionamide, aminosalicylate, and capreomycin to achieve a fractional inhibitory concentration for each pairing of 0.375 in vitro. In a mouse tuberculosis infection model, the efficacy of a cocktail of levofloxacin + pyrazinamide + protionamide + aminosalicylate against Mtb increased when the cocktail was combined with BP/CL, achieving efficacy similar to that of the positive control treatment (isoniazid + rifampin + pyrazinamide) after 2 months of treatment.@*CONCLUSION@#BP/CL may provide a new option to clinically treat MDR tuberculosis.


Subject(s)
Animals , Mice , Anti-Infective Agents , Pharmacology , Therapeutic Uses , Cell Line , Drug Evaluation, Preclinical , Macrophages , Mycobacterium tuberculosis , Thienamycins , Pharmacology , Therapeutic Uses , Tuberculosis, Multidrug-Resistant , Drug Therapy
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