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1.
Front Endocrinol (Lausanne) ; 14: 1261781, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38144564

RESUMO

Introduction: Endometriosis is a painful disease that affects around 5% of women of reproductive age. In endometriosis, ectopic endometrial cells or seeded endometrial debris grow in abnormal locations including the peritoneal cavity. Common manifestations of endometriosis include dyspareunia, dysmenorrhea, chronic pelvic pain and often infertility and symptomatic relief or surgical removal are mainstays of treatment. Endometriosis both promotes and responds to estrogen imbalance, leading to intestinal bacterial estrobolome dysregulation and a subsequent induction of inflammation. Methods: In the current study, we investigated the linkage between gut dysbiosis and immune metabolic response in endometriotic mice. Ovariectomized BALB/c mice received intraperitoneal transplantation of endometrial tissue from OVX donors (OVX+END). Control groups included naïve mice (Naïve), naïve mice that received endometrial transplants (Naive+END) and OVX mice that received the vehicle (OVX+VEH). Colonic content was collected 2 weeks post-transplantation for 16s rRNA pyrosequencing and peritoneal fluid was collected to determine the phenotype of inflammatory cells by flow cytometry. Results: We noted a significant increase in the number of peritoneal fluid cells, specifically, T cells, natural killer (NK) cells, and NKT cells in OVX+END mice. Phylogenetic taxonomy analysis showed significant dysbiosis in OVX+END mice, with an increase in abundance of Phylum Tenericutes, Class Mollicutes, Order Aneroplasmatales, and Genus Aneroplasma, and a decrease in Order Clostridiales, and Genus Dehalobacterium, when compared to OVX+VEH controls. The metabolomic profile showed an increase in some tricarboxylic acid cycle (TCA)-related metabolites accompanied by a reduction in short-chain fatty acids (SCFA) such as butyric acid in OVX+END mice. Additionally, the mitochondrial and ATP production of immune cells was enforced to a maximal rate in OVX+END mice when compared to OVX+VEH mice. Conclusion: The current study demonstrates that endometriosis alters the gut microbiota and associated immune metabolism.


Assuntos
Endometriose , Humanos , Feminino , Camundongos , Animais , Disbiose , RNA Ribossômico 16S , Filogenia , Camundongos Endogâmicos BALB C
2.
J Egypt Natl Canc Inst ; 35(1): 42, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38123741

RESUMO

BACKGROUND: Limited data are available on metabolic syndrome and its relation to breast cancer risk in Egypt. We aimed to study metabolic syndrome and its individual components as risk of breast cancer. METHODS: This case-control study recruited 112 breast cancer cases and 112 age-matched controls from Assiut University. In addition to demographic, clinical, and anthropoemetric characteristics, blood samples were collected from both study groups to evaluate metabolic syndrome and its individual components. RESULTS: Mean age of breast cancer cases and control groups was 46.10 ± 4.34 and 45.66 ± 4.68 years, respectively. According to Joint Interim Statement (JIS) criteria for clinical diagnosis of metabolic syndrome, the overall prevalence of metabolic syndrome in all participants was 42.9%, and prevalence in breast cancer cases and control group was 57.14% and 28.6%, respectively, OR 33.33, 95% CI (1.91-5.81). BMI was more likely to be higher in breast cancer patients with a linear trend, p < 0.001. For individual components of metabolic syndrome, breast cancer cases were more likely to have high fasting blood glucose level, systolic and/or diastolic blood pressure, high triglycerides level, and low HDL-C as compared to the control group. CONCLUSION: Metabolic syndrome and its components were found to be associated with the risk of breast cancer. We believe that prevention or reversal of metabolic syndrome by raising community awareness for lifestyle changes could be an effective way in minimizing the toll of the disease.


Assuntos
Neoplasias da Mama , Síndrome Metabólica , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Fatores de Risco , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Estudos de Casos e Controles , Triglicerídeos
3.
BMC Sports Sci Med Rehabil ; 15(1): 24, 2023 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-36872326

RESUMO

BACKGROUND: Children with cerebral palsy (CP) have motor deficits caused by spasticity, weakness, contractures, diminished selective motor control (SMC), and poor balance. The purpose of the current study was to evaluate the influence of mirror feedback on lower extremity selective motor control and balance in children with hemiplegic cerebral palsy. Understanding the relationship between SMC and balance will help children with hemiplegic CP receive more appropriate therapies. METHODS: Forty-seven children of both sexes diagnosed with hemiplegic CP participated in the study. Group1 (Gr1 - control group) received conventional physical therapy training while group 2 (Gr2 - intervention group) received conventional physical therapy training in addition to bilateral lower extremity mirror therapy (MT). The primary outcome measure used was Selective Control Assessment of Lower Extremity scale (SCALE), while the secondary outcome measure was the Pediatric Balance Scale (PBS). RESULTS: There were significant differences in Selective Control Assessment of Lower Extremity Scale (SCALE) and Pediatric Balance Scale (PBS) between both groups in favor of Gr2. After treatment, both groups improved significantly, yet Gr2 outperformed Gr1 by a large margin. CONCLUSION: Mirror therapy may be a useful addition to home-based motor interventions for children with hemiplegic CP due to its relative simplicity, low cost, and high patient adherence. Additionally, it may help children improve their selective motor skills and balance. TRIAL REGISTRATION: Current Controlled Trials using African Clinical Trials Registry website with ID number PACTR202105604636415 retrospectively registered on 21/01/202.

4.
Front Pharmacol ; 14: 1106733, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36909201

RESUMO

Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of insults, such as bacterial and viral infections, including SARS-CoV-2, leading to high mortality. In the murine model of ARDS induced by Staphylococcal enterotoxin-B (SEB), our previous studies showed that while SEB triggered 100% mortality, treatment with Resveratrol (RES) completely prevented such mortality by attenuating inflammation in the lungs. In the current study, we investigated the metabolic profile of SEB-activated immune cells in the lungs following treatment with RES. RES-treated mice had higher expression of miR-100 in the lung mononuclear cells (MNCs), which targeted mTOR, leading to its decreased expression. Also, Single-cell RNA-seq (scRNA seq) unveiled the decreased expression of mTOR in a variety of immune cells in the lungs. There was also an increase in glycolytic and mitochondrial respiration in the cells from SEB + VEH group in comparison with SEB + RES group. Together these data suggested that RES alters the metabolic reprogramming of SEB-activated immune cells, through suppression of mTOR activation and its down- and upstream effects on energy metabolism. Also, miR-100 could serve as novel potential therapeutic molecule in the amelioration of ARDS.

5.
Eur J Phys Rehabil Med ; 59(2): 183-191, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36762919

RESUMO

BACKGROUND: Trigeminal neuralgia (TN) is defined as intense, abrupt, often unilateral, stabbing, short, repeated episodes of pain in one or more distributional branches of the trigeminal nerve. AIM: To see how electromagnetic therapy (EMT) compared to low-level laser therapy (LLLT) affect TN in diabetes patients. DESIGN: This is a randomized controlled trial. SETTING: Physical therapy and Neurology Outpatients Clinics at Faculty of Physical Therapy. POPULATION: One hundred and forty diabetic patients with TN were evaluated for eligibility. As a result, 126 diabetic patients with TN were included in this trial. They were randomly divided into three equal-sized groups using random allocation software. Due to travel to another country, two patients did not complete the treatment protocol, and four opted out of the post-therapy evaluation. So, 120 volunteer diabetic patients with TN of both sexes were diagnosed for the participation in this study by a neurologist (N.=40 in each group). METHODS: For two months, participants in the control group A received the medication only (oral hypoglycemic drugs, Analgesics, vitamin B12), participants in the study group B received the medications as in group A in addition to LLLT, and participants in the study group C received medication as in group A in addition to electromagnetic therapy (EMT). The primary outcome was the amplitude of compound muscle action potentials of temporalis and masseter muscles by using NEXUS 10 (Mind media). The secondary outcome was pain intensity by using the Visual Analog Scale (VAS). RESULTS: According to the results of this study, there is a statistically significant difference in visual analog scale scores and the amplitude of compound muscle action potentials of the temporalis and masseter muscles among groups in favor of group B. CONCLUSIONS: After treatment, all groups improved significantly, with the laser group outperforming the electromagnetic group by a large margin. For irradiation, LLLT was more effective than EMT in reducing diabetic patients' trigeminal pain, and increasing masseter and temporalis muscles compound action potential amplitude in diabetic patients with TN. CLINICAL REHABILITATION IMPACT: LLLT was more effective than EMT at reducing diabetic patient's trigeminal pain, and increasing masseter and temporalis muscles compound action potential amplitude in diabetic patients with TN patients after two months of interventions.


Assuntos
Diabetes Mellitus , Terapia com Luz de Baixa Intensidade , Magnetoterapia , Neuralgia do Trigêmeo , Masculino , Feminino , Humanos , Neuralgia do Trigêmeo/radioterapia , Resultado do Tratamento , Dor
6.
Front Immunol ; 13: 805770, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265071

RESUMO

Asthma is a chronic respiratory disease highly prevalent worldwide. Recent studies have suggested a role for microbiome-associated gut-lung axis in asthma development. In the current study, we investigated if Resveratrol (RES), a plant-based polyphenol, can attenuate ovalbumin (OVA)-induced murine allergic asthma, and if so, the role of microbiome in the gut-lung axis in this process. We found that RES attenuated allergic asthma with significant improvements in pulmonary functions in OVA-exposed mice when tested using plethysmography for frequency (F), mean volume (MV), specific airway resistance (sRaw), and delay time(dT). RES treatment also suppressed inflammatory cytokines in the lungs. RES modulated lung microbiota and caused an abundance of Akkermansia muciniphila accompanied by a reduction of LPS biosynthesis in OVA-treated mice. Furthermore, RES also altered gut microbiota and induced enrichment of Bacteroides acidifaciens significantly in the colon accompanied by an increase in butyric acid concentration in the colonic contents from OVA-treated mice. Additionally, RES caused significant increases in tight junction proteins and decreased mucin (Muc5ac) in the pulmonary epithelium of OVA-treated mice. Our results demonstrated that RES may attenuate asthma by inducing beneficial microbiota in the gut-lung axis and through the promotion of normal barrier functions of the lung.


Assuntos
Asma , Microbiota , Animais , Asma/metabolismo , Modelos Animais de Doenças , Inflamação/metabolismo , Pulmão/metabolismo , Camundongos , Ovalbumina/efeitos adversos , Resveratrol/farmacologia
7.
Ir J Med Sci ; 191(2): 637-639, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33970393

RESUMO

OBJECTIVE: The General Medical Council (GMC) and Irish Medical Council (IMC) recommend the presence of a chaperone for all intimate examinations and that it should be clearly documented. The aim of this report is to assess doctors' compliance with obtaining a chaperone and documenting their presence, determining possible causes of non-compliance and implement interventions to increase compliance. METHODS: Prospective audit of patients seen in the breast clinic in Beaumont hospital over the week starting 8th February 2021. The medical charts were reviewed for documentation of chaperone presence. Doctors were surveyed using (SurveyMonkey) for causes of non-compliance. Interventions included a stamp in the medical notes for chaperone presence and details, an educational email with GMC and IMC guidelines, and posters put up in clinic rooms. The intervention was reassessed at 1-week and 6-week intervals. RESULTS: In the assessment phase, 126 patients were recruited. A chaperone was present 100% of the time where a male doctor examined a female patient; however, chaperone presence was not documented in any of the medical charts (0/126). A survey was sent to 22 breast surgery doctors to explore causes of non-compliance. Response rate was 95%, 50% did not know documentation was necessary, and 25% forgot to document. One week after intervention, 64 patients were recruited. Chaperone documentation increased to 80% (51/64). Reassessment at six weeks included 120 patients, and chaperone documentation rate was 74% (89/120).


Assuntos
Documentação , Auditoria Médica , Instituições de Assistência Ambulatorial , Feminino , Hospitais , Humanos , Masculino , Exame Físico
8.
Pharmacol Res ; 167: 105548, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33722710

RESUMO

Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of agents, including Staphylococcal Enterotoxin B (SEB). Interestingly, a significant proportion of patients with COVID-19, also develop ARDS. In the absence of effective treatments, ARDS results in almost 40% mortality. Previous studies from our laboratory demonstrated that resveratrol (RES), a stilbenoid, with potent anti-inflammatory properties can attenuate SEB-induced ARDS. In the current study, we investigated the role of RES-induced alterations in the gut and lung microbiota in the regulation of ARDS. Our studies revealed that SEB administration induced inflammatory cytokines, ARDS, and 100% mortality in C3H/HeJ mice. Additionally, SEB caused a significant increase in pathogenic Proteobacteria phylum and Propionibacterium acnes species in the lungs. In contrast, RES treatment attenuated SEB-mediated ARDS and mortality in mice, and significantly increased probiotic Actinobacteria phylum, Tenericutes phylum, and Lactobacillus reuteri species in both the colon and lungs. Colonic Microbiota Transplantation (CMT) from SEB-injected mice that were treated with RES as well as the transfer of L. reuteri into recipient mice inhibited the production of SEB-mediated induction of pro-inflammatory cytokines such as IFN-γ and IL-17 but increased that of anti-inflammatory IL-10. Additionally, such CMT and L. reuteri recipient mice exposed to SEB, showed a decrease in lung-infiltrating mononuclear cells, cytotoxic CD8+ T cells, NKT cells, Th1 cells, and Th17 cells, but an increase in the population of regulatory T cells (Tregs) and Th3 cells, and increase in the survival of mice from SEB-mediated ARDS. Together, the current study demonstrates that ARDS induced by SEB triggers dysbiosis in the lungs and gut and that attenuation of ARDS by RES may be mediated, at least in part, by alterations in microbiota in the lungs and the gut, especially through the induction of beneficial bacteria such as L. reuteri.


Assuntos
Anti-Inflamatórios/farmacologia , Colo/efeitos dos fármacos , Enterotoxinas , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Síndrome do Desconforto Respiratório/prevenção & controle , Resveratrol/farmacologia , Superantígenos , Animais , Linhagem Celular , Colo/imunologia , Colo/metabolismo , Colo/microbiologia , Citocinas/metabolismo , Modelos Animais de Doenças , Disbiose , Feminino , Mediadores da Inflamação/metabolismo , Limosilactobacillus reuteri/efeitos dos fármacos , Limosilactobacillus reuteri/crescimento & desenvolvimento , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/microbiologia , Camundongos Endogâmicos C3H , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/microbiologia
9.
Int J Mol Sci ; 21(17)2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32872332

RESUMO

Acute Respiratory Distress Syndrome (ARDS) causes up to 40% mortality in humans and is difficult to treat. ARDS is also one of the major triggers of mortality associated with coronavirus-induced disease (COVID-19). We used a mouse model of ARDS induced by Staphylococcal enterotoxin B (SEB), which triggers 100% mortality, to investigate the mechanisms through which Δ9-tetrahydrocannabinol (THC) attenuates ARDS. SEB was used to trigger ARDS in C3H mice. These mice were treated with THC and analyzed for survival, ARDS, cytokine storm, and metabolome. Additionally, cells isolated from the lungs were used to perform single-cell RNA sequencing and transcriptome analysis. A database analysis of human COVID-19 patients was also performed to compare the signaling pathways with SEB-mediated ARDS. The treatment of SEB-mediated ARDS mice with THC led to a 100% survival, decreased lung inflammation, and the suppression of cytokine storm. This was associated with immune cell apoptosis involving the mitochondrial pathway, as suggested by single-cell RNA sequencing. A transcriptomic analysis of immune cells from the lungs revealed an increase in mitochondrial respiratory chain enzymes following THC treatment. In addition, metabolomic analysis revealed elevated serum concentrations of amino acids, lysine, n-acetyl methionine, carnitine, and propionyl L-carnitine in THC-treated mice. THC caused the downregulation of miR-185, which correlated with an increase in the pro-apoptotic gene targets. Interestingly, the gene expression datasets from the bronchoalveolar lavage fluid (BALF) of human COVID-19 patients showed some similarities between cytokine and apoptotic genes with SEB-induced ARDS. Collectively, this study suggests that the activation of cannabinoid receptors may serve as a therapeutic modality to treat ARDS associated with COVID-19.


Assuntos
Apoptose/efeitos dos fármacos , Betacoronavirus/fisiologia , Agonistas de Receptores de Canabinoides/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Citocinas/imunologia , Dronabinol/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Idoso , Animais , Líquido da Lavagem Broncoalveolar/imunologia , COVID-19 , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Enterotoxinas/efeitos adversos , Feminino , Humanos , Pulmão/imunologia , Pulmão/virologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , MicroRNAs/genética , Pessoa de Meia-Idade , Pandemias , Pneumonia/tratamento farmacológico , Pneumonia/virologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/virologia , SARS-CoV-2 , Transdução de Sinais/efeitos dos fármacos
10.
Br J Pharmacol ; 177(22): 5078-5095, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32754917

RESUMO

BACKGROUND AND PURPOSE: Staphylococcal enterotoxin-B (SEB) is one of the most potent bacterial superantigens that exerts profound toxic effects by inducing a cytokine storm. Inhaled SEB can cause acute respiratory distress syndrome (ARDS), which is often fatal and with no effective treatments. EXPERIMENTAL APPROACH: Efficacy of Δ9 -tetrahydrocannabinol (THC) was tested in a mouse model of SEB-mediated ARDS, in which lung inflammation, alterations in gut/lung microbiota and production of short-chain fatty acids (SCFAs) was measured. Gene dysregulation of lung epithelial cells was studied by transcriptome arrays. Faecal microbiota transplantation (FMT) was performed to confirm the role of microbiota in suppressing ARDS. KEY RESULTS: While SEB triggered ARDS and 100% mortality in mice, THC protected the mice from fatality. Pyrosequencing analysis revealed that THC caused significant and similar alterations in microbiota in the lungs and gut of mice exposed to SEB. THC significantly increased the abundance of beneficial bacterial species, Ruminococcus gnavus, but decreased pathogenic microbiota, Akkermansia muciniphila. FMT confirmed that THC-mediated reversal of microbial dysbiosis played crucial role in attenuation of SEB-mediated ARDS. THC treatment caused an increase in SCFA, of which propionic acid was found to inhibit the inflammatory response. Transcriptome array showed that THC up-regulated several genes like lysozyme1 and lysozyme2, ß-defensin-2, claudin, zonula-1, occludin-1, Mucin2 and Muc5b while down-regulating ß-defensin-1. CONCLUSION AND IMPLICATIONS: The study demonstrates for the first time that THC attenuates SEB-mediated ARDS and toxicity by altering the microbiota in the lungs and the gut as well as promoting antimicrobial and anti-inflammatory pathways.


Assuntos
Microbioma Gastrointestinal , Síndrome do Desconforto Respiratório , Animais , Clostridiales , Citocinas , Dronabinol/farmacologia , Enterotoxinas , Camundongos , Síndrome do Desconforto Respiratório/induzido quimicamente
11.
Front Pharmacol ; 11: 893, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612530

RESUMO

Acute Respiratory Distress Syndrome (ARDS) is a life-threatening complication that can ensue following Staphylococcus aureus infection. The enterotoxin produced by these bacteria (SEB) acts as a superantigen thereby activating a large proportion of T cells leading to cytokine storm and severe lung injury. Δ9Tetrahydrocannabinol (THC), a psychoactive ingredient found in Cannabis sativa, has been shown to act as a potent anti-inflammatory agent. In the current study, we investigated the effect of THC treatment on SEB-induced ARDS in mice. While exposure to SEB resulted in acute mortality, treatment with THC led to 100% survival of mice. THC treatment significantly suppressed the inflammatory cytokines, IFN-γ and TNF-α. Additionally, THC elevated the induction of regulatory T cells (Tregs) and their associated cytokines, IL-10 and TGF-ß. Moreover, THC caused induction of Myeloid-Derived Suppressor Cells (MDSCs). THC acted through CB2 receptor as pharmacological inhibitor of CB2 receptors blocked the anti-inflammatory effects. THC-treated mice showed significant alterations in the expression of miRNA (miRs) in the lung-infiltrated mononuclear cells (MNCs). Specifically, THC caused downregulation of let7a-5p which targeted SOCS1 and downregulation of miR-34-5p which caused increased expression of FoxP3, NOS1, and CSF1R. Together, these data suggested that THC-mediated alterations in miR expression in the lungs may play a critical role in the induction of immunosuppressive Tregs and MDSCs as well as suppression of cytokine storm leading to attenuation of SEB-mediated lung injury.

12.
Environ Sci Pollut Res Int ; 27(7): 6824-6836, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31875294

RESUMO

Radionuclide sorption by natural and modified clays is extensively accepted to be an important process from the radioactive waste point of view. This work focused on modification of natural attapulgite with a layered double hydroxide to produce a novel chemisorbent for Sr2+, Ni2+, and Co2+ removal from multicomponent solution. The structural and surface characteristics of both attapulgite (ATP) and modified attapulgite (LDH-ATP) were investigated using XRD, FTIR, SEM, and thermal analysis. Comparison of sorption features of Sr2+, Ni2+, and Co2+ onto ATP and LDH-ATP was achieved; the results indicated that LDH-ATP was the most efficient sorbent for Sr2+, Ni2+, and Co2+. Kinetic studies established that the sorption is fast and reaching >90% within 30 min. The sorption of Sr2+, Ni2+, and Co2+ are well defined by non-linear pseudo-second-order model and controlled by an intra-particle diffusion mechanism. The diffusivity was determined using homogeneous surface diffusion (HSDM) model and found in the order 10-13 m2/min; this confirmed that the sorption of the three ions is chemisorption process. LDH-ATP can be employed as a candidate chemisorbent for the removal of some metal ions from waste solution.


Assuntos
Compostos de Magnésio/química , Modelos Químicos , Compostos de Silício/química , Poluentes Químicos da Água , Adsorção , Cobalto/análise , Cinética , Níquel/análise , Estrôncio/análise
13.
J Cell Mol Med ; 22(5): 2644-2655, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29512867

RESUMO

Staphylococcal enterotoxin B (SEB) is a potent superantigen produced by Staphylococcus aureus that triggers a strong immune response, characterized by cytokine storm, multi-organ failure, and often death. When inhaled, SEB can cause acute lung injury (ALI) and respiratory failure. In this study, we investigated the effect of resveratrol (RES), a phytoallexin, on SEB-driven ALI and mortality in mice. We used a dual-exposure model of SEB in C3H/HeJ mice, which caused 100% mortality within the first 5 days of exposure, and treatment with RES resulted in 100% survival of these mice up to 10 days post-SEB exposure. RES reduced the inflammatory cytokines in the serum and lungs, as well as T cell infiltration into the lungs caused by SEB. Treatment with RES also caused increased production of transforming growth factor-beta (TGF-ß) in the blood and lungs. RES altered the miRNA profile in the immune cells isolated from the lungs. Of these, miR-193a was strongly induced by SEB and was down-regulated by RES treatment. Furthermore, transfection studies and pathway analyses revealed that miR-193a targeted several molecules involved in TGF-ß signalling (TGFß2, TGFßR3) and activation of apoptotic pathways death receptor-6 (DR6). Together, our studies suggest that RES can effectively neutralize SEB-mediated lung injury and mortality through potential regulation of miRNA that promote anti-inflammatory activities.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/genética , MicroRNAs/metabolismo , Substâncias Protetoras/uso terapêutico , Resveratrol/uso terapêutico , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Sequência de Bases , Líquido da Lavagem Broncoalveolar , Citocinas/sangue , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Enterotoxinas , Feminino , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C3H , MicroRNAs/genética , Substâncias Protetoras/farmacologia , Resveratrol/farmacologia
14.
Int J Biol Macromol ; 107(Pt B): 2342-2350, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29055707

RESUMO

Tannase is considered one of the most important industrial enzymes that find great applications in various sectors. Production of tannases through solid state fermentation (SSF) using agro-industrial wastes is an eco-friendly and cheap technology. Tannase was produced by the yeast Kluyveromyces marxianus using olive pomace as a solid support under SSF. It was purified using ammonium sulfate fractional precipitation followed by Sephadex G-200 gel filtration resulting in 64.6% enzyme yield with 1026.12U/mg specific activity and 24.21 purification fold. Pure tannase had molecular weight of 65 KDa and 66.62 KDa by SDS-PAGE and gel filtration, respectively. It showed a maximal activity at 35°C having two different pH optima, one of which is acidic (4.5) and the other one is alkaline (8.5). The enzyme was stable in the acidic range of pH (4.0-5.5) for 30min, and thermostable within the temperature range 30-70°C. Using tannic acid, the enzyme had a Km value of 0.77mM and Vmax of 263.20µmolemin-1ml-1. The effect of different metal ions on enzymatic activity was evaluated. HPLC analysis data indicated that the purified enzyme could carry out 24.65% tannic acid conversion with 5.25 folds increase in gallic acid concentration within 30min only.


Assuntos
Hidrolases de Éster Carboxílico/química , Ácido Gálico/química , Kluyveromyces/enzimologia , Sulfato de Amônio/química , Hidrolases de Éster Carboxílico/genética , Hidrolases de Éster Carboxílico/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Fermentação , Ácido Gálico/metabolismo , Olea/química
15.
Pharmacology ; 94(1-2): 41-50, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25171542

RESUMO

AIM: The identification and application of stem cells to treat central nervous system disorders represent a dramatic evolution and expansion into the realms of neurorestoration and neuroregeneration. The aim of this study was to assess the possible ameliorative effect of mesenchymal stem cells (MSCs) in comparison to gabapentin on pentylenetetrazole (PTZ)-induced epileptogenesis and its consequences. METHODS: Thirty-two rats were divided into 4 equal groups; group I: saline-injected group, group II: PTZ group, which received 13 intraperitoneal (i.p.) injections of PTZ (30 mg/kg) 3 times/week, groups III and IV: groups received PTZ and were treated with i.p. gabapentin (200 mg/kg) 60 min before each PTZ injection (group III) or a single intravenous injection of 10(6) MSCs/rat at day 22 (group IV). RESULTS: Treatment with either gabapentin or MSCs demonstrated a significant improvement in the PTZ-induced epileptogenesis and its severe consequences, i.e. oxidative stress damage, motor and cognitive impairments. Moreover, they enhanced the GABA neurotransmitter levels. Meanwhile, MSC administration to chronic epileptic rats afforded more ameliorative effects on PTZ-induced epileptogenesis and its severe consequences in comparison to gabapentin. CONCLUSION: These data indicate that MSCs were superior to gabapentin in ameliorating PTZ-induced epileptogenesis and verified the potential use of MSCs in seizure control, motor and cognitive impairments, oxidative stress, and the impairing GABA level in experimentally induced epilepsy.


Assuntos
Aminas/farmacologia , Ácidos Cicloexanocarboxílicos/farmacologia , Epilepsia/prevenção & controle , Transplante de Células-Tronco Mesenquimais/métodos , Convulsões/prevenção & controle , Ácido gama-Aminobutírico/farmacologia , Animais , Modelos Animais de Doenças , Feminino , Gabapentina , Humanos , Injeções Intraperitoneais , Injeções Intravenosas , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Pentilenotetrazol , Ratos , Ratos Wistar , Cordão Umbilical/citologia , Ácido gama-Aminobutírico/metabolismo
16.
Artigo em Inglês | MEDLINE | ID: mdl-23563639

RESUMO

New bis (pyridylurea) ligand, H2L, was synthesized by the reaction of ethylpyridine-2-carbamate (EPC) and p-phenylenediamine. The ligand was characterized by elemental analysis, IR, (1)H NMR, electronic and mass spectra. Reaction of the prepared ligand with Co(2+), Ni(2+), Cu(2+), Fe(3+), VO(2+) and UO2(2+) ions afforded mono, bi- and trinuclear metal complexes. Also, new mixed ligand complexes of the ligand H2L and 8-hydroxyquinoline (8-HQ) with Co(2+), Ni(2+), Cu(2+) and Fe(3+) ions were synthesized. The ligand behaves as bi- and tetradentate toward the transition metal ions, coordination via the pyridine N, the carbonyl O and/or the amidic N atoms in a non, mono- and bis-deprotonated form. The complexes were characterized by elemental and thermal analyses, IR, electronic and mass spectra as well as conductance and magnetic susceptibility measurements. The results showed that the metal complexes exhibited different geometrical arrangements such as square planar, tetrahedral, octahedral and square pyramidal arrangements. The Coats-Redfern equation was used to calculate the kinetic and thermodynamic parameters for the different thermal decomposition steps of some complexes. 3D molecular modeling of the ligand, H2L and a representative complex were studied.


Assuntos
Derivados de Benzeno/química , Complexos de Coordenação/química , Piridinas/química , Ureia/análogos & derivados , Espectroscopia de Ressonância de Spin Eletrônica , Ligantes , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Elementos de Transição/química
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