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1.
Molecules ; 27(14)2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35889209

RESUMO

Diabetes mellitus (DM) and its complications are a severe public health concern due to the high incidence, morbidity, and mortality rates. The present study aims to synthesize and characterize silver nanoparticles (AgNPs) using the aqueous leaf extract of Psidium guajava (PGE) for investigating its antidiabetic activity. Psidium guajava silver nanoparticles (PGAg NPs) were prepared and characterized by various parameters. The in vivo study was conducted using PGE and PGAg NPs in Streptozotocin (STZ)-induced diabetic rats to assess their antidiabetic properties. STZ of 55 mg/kg was injected to induce diabetes. The PGE, PGAg NPs at a dose of 200 and 400 mg/kg and standard drug Metformin (100 mg/kg) were administered daily to diabetic rats for 21 days through the oral route. Blood glucose level, body weight changes, lipid profiles, and histopathology of the rats' liver and pancreas were examined. In the diabetic rats, PGE and PGAg NPs produced a drastic decrease in the blood glucose level, preventing subsequent weight loss and ameliorating lipid profile parameters. The histopathological findings revealed the improvements in pancreas and liver cells due to the repercussion of PGE and PGAg NPs. A compelling effect was observed in all doses of PGE and PGAg NPs; however, PGAg NPs exhibited a more promising result. Thus, from the results, it is concluded that the synthesized PGAg NPs has potent antidiabetic activity due to its enhanced surface area and smaller particle size of nanoparticles.


Assuntos
Diabetes Mellitus Experimental , Nanopartículas Metálicas , Psidium , Animais , Glicemia , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Lipídeos , Extratos Vegetais/farmacologia , Folhas de Planta , Prostaglandinas E , Ratos , Prata
2.
Artigo em Chinês | MEDLINE | ID: mdl-35785898

RESUMO

Objective: To establish a solvent desorption gas chromatographymethod for the determination of phenyl glycidyl ether (PGE) . Methods: From October to December 2020, PGE in the air of workplace was collected with carbon tube and desorbed by 25% acetone-carbon disulfide. The target toxicant was separated with the gas chromatography (GC) column and analyzed with flame ionization detector (FID), and quantified by peak area. Results: The linear range of PGE in the air of workplace was 10.0-1109.0 µg/ml, the linear equation was y=1.156x-4.328, with a correlation coefficient of 0.9997. The limit of detection was 3.0 µg/ml. The lower limit of quantification was 10.0 µg/ml. The intar-batch and inter-batch precisionswere 4.9%-6.4% and 6.2%-6.9%, respectively. The recovery rate was ranged from 97.2%-98.8%, the average collection efficiency was 100%, and the average extraction efficiency was 90.1%. The samples could be stored at 4 ℃ for 7 d. Conclusion: This method has high precision and good accuracy, and it is applicable for the determination of PGE in workplace air.


Assuntos
Poluentes Ocupacionais do Ar , Local de Trabalho , Poluentes Ocupacionais do Ar/análise , Cromatografia Gasosa/métodos , Éteres Fenílicos , Prostaglandinas E/análise , Solventes
3.
Zhongguo Zhen Jiu ; 42(7): 733-8, 2022 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-35793881

RESUMO

OBJECTIVE: To compare the clinical efficacy and its effect on serum levels of tumor necrosis factor α(TNF-α), interleukin 1ß(IL-1ß), interleukin 6 (IL-6) and prostaglandin E2 (PGE2) between short needling (close-to-bone needling) and conventional acupuncture for knee osteoarthritis (KOA) with blood stasis obstruction. METHODS: A total of 68 KOA patients with blood stasis obstruction were randomized into a short needling group (34 cases, 3 cases dropped off) and a conventional acupuncture group (34 cases, 3 cases dropped off). The same acupoints (Dubi [ST 35], Neixiyan [EX-LE 4], Binzhong [Extra], Liangqiu [ST 34], etc. on the affected side) were selected in the two groups. In the short needling group, short needling technique was adopted, the needles were slowly inserted and the needle bodies were shaken, thus gradually penetrated to the bone. In the conventional acupuncture group, conventional acupuncture was adopted, the needles were penetrated to the muscle. After qi-arrival, Dubi (ST 35) and Neixiyan (EX-LE 4), Zusanli (ST 36) and Liangqiu (ST 34) were connected with CMNS6-1 electronic acupuncture instrument, with disperse-dense wave, 2 Hz/10 Hz in frequency, the current intensity was based on patients' feeling, the needles were retained for 30 min, at the same time, the knee joint was irradiated for 30 min with a special electromagnetic wave apparatus in the two groups. Once every other day, 3 times a week for 4 weeks. Before and after treatment, the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score, knee joint pain visual analogue scale (VAS) score, inflammatory response related indexes (serum TNF-a, IL-1ß, IL-6 and PGE2) and knee joint ultrasound were observed,and the clinical effect was evaluated in the two groups. RESULTS: After treatment,the pain, stiffness, function scores and total scores of WOMAC were decreased as compared with those before treatment in the two groups (P<0.05), except for the pain score, the changes of above scores in the short needling group were greater than the conventional acupuncture group (P<0.05). After treatment, the VAS scores, serum levels of TNF-a, IL-1ß, IL-6, PGE2 and knee joint synovium thickness, intra-articular effusion were decreased as compared with those before treatment in the two groups (P<0.05), the levels of TNF-a, IL-1ß, IL-6 in the short needling group were lower than the conventional acupuncture group (P<0.05). The total effective rate in the short needling group was 87.1% (27/31), which was superior to 83.9% (26/31) in the conventional acupuncture group (P<0.05). CONCLUSION: Short needling could improve the knee joint function, relieve the pain and inflammatory response, improve the knee joint synovium inflammatory response, reduce the knee joint intra-articular effusion for KOA patients, its effect is better than conventional acupuncture.


Assuntos
Osteoartrite do Joelho , Pontos de Acupuntura , Humanos , Inflamação , Interleucina-6 , Osteoartrite do Joelho/terapia , Dor , Prostaglandinas E
4.
Comput Math Methods Med ; 2022: 7086472, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35770118

RESUMO

The aim of this study was to explore the value of computed tomography (CT) images based on electronic health (E-health) combined with painless gastrointestinal endoscopy (PGE) in the diagnosis of neurocognitive function in patients with combined anesthesia of propofol and butorphanol tartrate. 126 patients undergoing PGE were selected as the research objects, and all were performed with CT perfusion imaging before and after anesthesia to obtain the cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time to peak (TTP). The Montreal Cognitive Assessment (MoCA) was adopted to evaluate the cognitive function of patients. The results showed that after anesthesia, the levels of CBF and CBV in the left and right thalami, frontal lobe, and temporal lobe of the patients were lower than those before anesthesia, while TTP and MTT were higher than those before anesthesia (P < 0.05). The MoCA score after anesthesia was lower than that before anesthesia (P < 0.05). After anesthesia, the CBF, CBV, TTP, and MTT values of the left and right frontal lobes and left and right temporal lobes were significantly positively correlated with MoCA (P < 0.05). In conclusion, the brain CT image parameters based on E-health can clearly display the blood perfusion in the lesion area of the patient, which was beneficial to the PGE-assisted judgment of cognitive dysfunction in patients with propofol tartrate and butorphanol tartrate anesthesia. Therefore, CT-assisted PGE examination based on E-health had a certain clinical value in evaluating the neurocognitive function of patients.


Assuntos
Anestesia , Propofol , Butorfanol , Circulação Cerebrovascular , Eletrônica , Endoscopia Gastrointestinal , Humanos , Propofol/efeitos adversos , Prostaglandinas E , Tomografia Computadorizada por Raios X/métodos
5.
Respir Res ; 23(1): 136, 2022 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-35643499

RESUMO

BACKGROUND: Pulmonary hypertension is a common and serious complication of chronic obstructive pulmonary disease (COPD). Studies suggest that cigarette smoke can initiate pulmonary vascular remodelling by stimulating cell proliferation; however, the underlying cause, particularly the role of vasoactive prostanoids, is unclear. We hypothesize that cigarette smoke extract (CSE) can induce imbalanced vasoactive prostanoid release by differentially modulating the expression of respective synthase genes in human pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs), thereby contributing to cell proliferation. METHODS: Aqueous CSE was prepared from 3R4F research-grade cigarettes. Human PASMCs and PAECs were treated with or without CSE. Quantitative real-time RT-PCR and Western blotting were used to analyse the mRNA and protein expression of vasoactive prostanoid syhthases. Prostanoid concentration in the medium was measured using ELISA kits. Cell proliferation was assessed using the cell proliferation reagent WST-1. RESULTS: We demonstrated that CSE induced the expression of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostanoid synthesis, in both cell types. In PASMCs, CSE reduced the downstream prostaglandin (PG) I synthase (PGIS) mRNA and protein expression and PGI2 production, whereas in PAECs, CSE downregulated PGIS mRNA expression, but PGIS protein was undetectable and CSE had no effect on PGI2 production. CSE increased thromboxane (TX) A synthase (TXAS) mRNA expression and TXA2 production, despite undetectable TXAS protein in both cell types. CSE also reduced microsomal PGE synthase-1 (mPGES-1) protein expression and PGE2 production in PASMCs, but increased PGE2 production despite unchanged mPGES-1 protein expression in PAECs. Furthermore, CSE stimulated proliferation of both cell types, which was significantly inhibited by the selective COX-2 inhibitor celecoxib, the PGI2 analogue beraprost and the TXA2 receptor antagonist daltroban. CONCLUSIONS: These findings provide the first evidence that cigarette smoke can induce imbalanced prostanoid mediator release characterized by the reduced PGI2/TXA2 ratio and contribute to pulmonary vascular remodelling and suggest that TXA2 may represent a novel therapeutic target for pulmonary hypertension in COPD.


Assuntos
Fumar Cigarros , Hipertensão Pulmonar , Doença Pulmonar Obstrutiva Crônica , Proliferação de Células , Células Endoteliais , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/metabolismo , Prostaglandinas/metabolismo , Prostaglandinas E/metabolismo , Prostaglandinas E/farmacologia , Artéria Pulmonar/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , RNA Mensageiro/metabolismo , Tabaco , Remodelação Vascular
6.
Biomed Pharmacother ; 150: 113026, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35658250

RESUMO

Non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric ulcers represent a significant clinical concern and adversely affect the quality of life. Inducible nitric oxide synthase/endothelial nitric oxide synthase (iNOS/eNOS) and asymmetric dimethylarginine/ dimethylarginine dimethylaminohydrolase-1 (ADMA/DDAH-1) signaling are key players in gastric ulcer pathogenesis. This work was planned to explore the role of iNOS/eNOS and ADMA/DDAH-1 signaling in rats with indomethacin-induced gastric ulcer, as potential pathways for the gastro-protective effect of tadalafil. Split into 5 separate groups, rats were assigned to control, tadalafil (10 mg/kg, p.o), indomethacin (single oral dose of 60 mg/kg), indomethacin + pantoprazole (40 mg/kg, p.o), and indomethacin + tadalafil (10 mg/kg, p.o). The results indicated that pretreatment with tadalafil significantly reduced ulcer index (UI), increased preventive index (PI), and counteracted indomethacin-induced histopathological aberrations. Tadalafil significantly reduced the gastric content of NO while it significantly elevated that of GSH and enhanced SOD activity. It significantly reduced the gastric expression of TNF-α and ADMA while it significantly elevated that of COX-2, PGE-2, and DDAH-1. Western blot analysis revealed that pretreatment with tadalafil significantly reduced iNOS protein expression while it significantly elevated that of eNOS. Collectively, these data suggest that tadalafil exerts potential protective effect against indomethacin-induced ulcer through suppression of inflammation, attenuation of oxidative stress, and boosting of antioxidants. Moreover, tadalafil protective effects are mediated via upregulation of PGE-2 with modulating the signaling pathways of ADMA/DDAH-1, and iNOS/eNOS. As a result, the current evidence corroborates the use of tadalafil in controlling gastric ulcers and preventing NSAID gastric side effects.


Assuntos
Indometacina , Úlcera Gástrica , Amidoidrolases/metabolismo , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Arginina/farmacologia , Indometacina/uso terapêutico , Indometacina/toxicidade , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Prostaglandinas E/uso terapêutico , Qualidade de Vida , Ratos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Tadalafila/farmacologia , Tadalafila/uso terapêutico , Úlcera/tratamento farmacológico
7.
Acta Biomater ; 148: 230-243, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35724919

RESUMO

The delivery of salicylic acid or its derivatives to tumor tissue in the form of nanomedicine is critical for the studies on their potential synergistic mechanism in tumor therapy and chemoprevention considering the dangerous bleeding in the high-dose oral administration. To deepen the understanding of their role in adjusting immunosuppressive tumor microenvironment (ITM), herein, we firstly developed a hypoxia-sensitive Fe-5,5'-azosalicylic acid nanoscale coordination polymer nanomedicines (FeNCPs) via a "old drugs new tricks" strategy for synergistic chemodynamic therapy (CDT) and remodulation of ITM to elevate antitumor immunotherapy effect. PEGylated FeNCPs could be reductively cleaved to release 5-aminosalicylic acid (5-ASA) and ferric ions by azo-reductase under hypoxic conditions, which could induce tumor cell death by Fenton reaction-catalysis enhanced CDT and 5-ASA-converted carboxylquinone to promote the production of •OH. Meanwhile, cyclooxygenase-2 (COX-2) and its enzymatic product prostaglandin E2 (PGE2), as immune negative regulatory molecules, can promote tumor progression and immune tolerance. The released 5-ASA as a COX inhibitor could suppress the expression of PGE2, and Fe3+ was employed to reeducate M2-like tumor-associated macrophages (TAMs) to M1-like phenotype, which could initiate antitumor immune response to reach better antitumor immunotherapy. This work broadens the application of salicylic acid derivatives in antitumor immunotherapy, and provides a new strategy for their "old drugs new tricks". STATEMENT OF SIGNIFICANCE: Cyclooxygenase-2 (COX-2) and its enzymatic product prostaglandin E2 (PGE2), as immune negative regulatory molecules, facilitate the differentiation of immune cells into immunosuppressive cells to build the immunosuppressive tumor microenvironment, which can promote tumor progression and immune tolerance. Thus, down-regulation of COX-2/PGE2 expression may be a key approach to tumor treatments. Meanwhile, as a class of inhibitors of COX-2/PGE2, the potential mechanism of aspirin or 5-aminosalicylic acid has been a mystery in tumor therapy and chemoprevention. To expand the application of aspirin family nanomedicine in biomedicine, herein, we firstly developed a hypoxia-sensitive Fe-5,5'-azosalicylic acid nanoscale coordination polymer nanomedicines via a "old drugs new tricks" strategy for synergistic chemodynamic therapy and remodulation of immunosuppressive tumor microenvironment to elevate antitumor immunotherapy effect.


Assuntos
Neoplasias , Microambiente Tumoral , Aspirina/farmacologia , Linhagem Celular Tumoral , Ciclo-Oxigenase 2 , Humanos , Hipóxia , Fatores Imunológicos/farmacologia , Imunoterapia , Mesalamina/farmacologia , Mesalamina/uso terapêutico , Nanomedicina , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Polímeros/farmacologia , Prostaglandinas E/farmacologia , Prostaglandinas E/uso terapêutico , Ácido Salicílico/farmacologia , Ácido Salicílico/uso terapêutico
8.
Sci Rep ; 12(1): 8472, 2022 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-35637203

RESUMO

Neuropathic pain affects millions of people worldwide, yet the molecular mechanisms of how it develops and persists are poorly understood. Given that males have historically been utilized as the primary sex in preclinical studies, less is known about the female neuroinflammatory response to injury, formation of pain, or response to pain-relieving therapies. Macrophages contribute to the development of neuroinflammatory pain via the activation of their cyclooxygenase-2 (COX-2) enzyme, which leads to the production of prostaglandin E2 (PGE2). PGE2 activates nociception and influences additional leukocyte infiltration. Attenuation of COX-2 activity decreases inflammatory pain, most commonly achieved by nonsteroidal anti-inflammatory drugs (NSAIDs), yet NSAIDs are considered ineffective for neuropathic pain due to off target toxicity. Using chronic constriction injury of the rat sciatic nerve, we show that males and females exhibit quantitatively the same degree of mechanical allodynia post injury. Furthermore, a low-dose nanotherapeutic containing the NSAID celecoxib is phagocytosed by circulating monocytes that then naturally accumulate at sites of injury as macrophages. Using this nanotherapeutic, we show that treated males exhibit complete reversal of hypersensitivity, while the same dose of nanotherapeutic in females provides an attenuated relief. The difference in behavioral response to the nanotherapy is reflected in the reduction of infiltrating macrophages at the site of injury. The observations contained in this study reinforce the notion that female neuroinflammation is different than males.


Assuntos
Neuralgia , Caracteres Sexuais , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Celecoxib/farmacologia , Celecoxib/uso terapêutico , Ciclo-Oxigenase 2 , Feminino , Humanos , Masculino , Neuralgia/tratamento farmacológico , Doenças Neuroinflamatórias , Prostaglandinas E , Ratos
9.
Acta Physiol (Oxf) ; 235(4): e13828, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35543087

RESUMO

AIM: Cyclooxygenase-2 (COX-2) activity protects against oxidative stress and apoptosis early in experimental kidney injury. The present study was designed to test the hypothesis that COX-2 activity attenuates fibrosis and preserves microvasculature in injured kidney. The murine unilateral ureteral-obstruction (UUO) model of kidney fibrosis was employed and compared with human nephrectomy tissue with and without chronic hydronephrosis. METHODS: Fibrosis and angiogenic markers were quantified in kidney tissue from wild-type and COX-2-/- mice subjected to UUO for 7 days and in human kidney tissue. COX-enzymes, prostaglandin (PG) synthases, PG receptors, PGE2 , and thromboxane were determined in human tissue. RESULTS: COX-2 immunosignal was observed in interstitial fibroblasts at baseline and after UUO. Fibronectin, collagen I, III, alpha-smooth muscle actin, and fibroblast specific protein-1 mRNAs increased significantly more after UUO in COX-2-/- vs wild-type mice. In vitro, fibroblasts from COX-2-/- kidneys showed higher matrix synthesis. Compared to control, human hydronephrotic kidneys showed (i) fibrosis, (ii) no significant changes in COX-2, COX-1, PGE2 -, and prostacyclin synthases, and prostacyclin and thromboxane receptor mRNAs, (iii) increased mRNA and protein of PGE2 -EP2 receptor level but unchanged PGE2 tissue concentration, and (iv) two- to threefold increased thromboxane synthase mRNA and protein levels, and increased thromboxane B2 tissue concentration in cortex and outer medulla. CONCLUSION: COX-2 protects in the early phase against obstruction-induced fibrosis and maintains angiogenic factors. Increased PGE2 -EP2 receptor in obstructed human and murine kidneys could contribute to protection.


Assuntos
Ciclo-Oxigenase 2 , Rim , Receptores de Prostaglandina E Subtipo EP2 , Obstrução Ureteral , Animais , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Fibrose , Humanos , Rim/metabolismo , Camundongos , Prostaglandinas E/metabolismo , Prostaglandinas I/metabolismo , RNA Mensageiro/metabolismo , Receptores de Prostaglandina E Subtipo EP2/metabolismo , Tromboxanos/metabolismo , Regulação para Cima , Ureter/metabolismo , Obstrução Ureteral/complicações , Obstrução Ureteral/metabolismo
10.
Reprod Toxicol ; 111: 59-67, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35588954

RESUMO

While the effects of delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis, have been studied extensively in the central nervous system, there is limited knowledge about its effects on the female reproductive system. The aim of this study was to assess the effect of THC on the expression and secretion of the angiogenic factor vascular endothelial growth factor (VEGF) in the ovary, and to determine if these effects were mediated by prostaglandins. Spontaneously immortalized rat granulosa cells (SIGCs) were exposed to THC for 24 h. Gene expression, proliferation and TNFα-induced apoptosis were evaluated in the cells and concentrations of VEGF and prostaglandin E2 (PGE2), a known regulator of VEGF production, were determined in the media. To evaluate the role of the prostanoid pathway, cells were pre-treated with cyclooxygenase (COX) inhibitors prior to THC exposure. THC-exposed SIGCs had a significant increase in VEGF and PGE2 secretion, along with an increase in proliferation and cell survival when challenged with an apoptosis-inducing factor. Pre-treatment with COX inhibitors reversed the THC-induced increase in both PGE2 and VEGF secretion. Alterations in granulosa cell function, such as the ones observed after THC exposure, may impact essential ovarian processes including folliculogenesis and ovulation, which could in turn affect female reproductive health and fertility. With the ongoing increase in cannabis use and potency, further study on the impact of cannabis and its constituents on female reproductive health is required.


Assuntos
Cannabis , Fator A de Crescimento do Endotélio Vascular , Animais , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Dronabinol/toxicidade , Feminino , Células da Granulosa/metabolismo , Prostaglandinas E , Ratos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fatores de Crescimento do Endotélio Vascular
11.
Glia ; 70(9): 1666-1680, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35506586

RESUMO

Astrocytes are glial cells that serve homeostatic functions in the central nervous system (CNS). Recent research, however, suggests that under pathological conditions, astrocytes are stimulated by various factors and actively participate in CNS inflammation. In the present study, we found that astrocytes upregulate various inflammatory factors including prostaglandin E2 (PGE2 ) by co-stimulation with tumor necrosis factor-alpha (TNFα) and interleukin-1alpha (IL1α). These TNFα/IL1α-stimulated astrocytes also showed increased Ca2+ release from the endoplasmic reticulum (ER) and increased expression of Orai2, a member of the store-operated calcium channel (SOCC) family. To reveal the role of Orai2, we used astrocytes in which Orai2 was knocked-down (KD) or knocked-out (KO). The expression of the prostaglandin E synthase Ptges and the production of PGE2 were higher in Orai2-KD astrocytes than in WT astrocytes when stimulated with TNFα and IL1α. Orai2-KO astrocytes also showed increased expression of Ptges and increased PGE2 production. The expression of Ptgs2, another PGE2 synthetic enzyme, was also upregulated in Orai2-KO astrocytes. Moreover, Orai2-KO astrocytes showed increased store-operated calcium entry (SOCE) and increased Orai1 expression. These results suggest that Orai2 is upregulated in TNFα/IL1α-stimulated astrocytes and reduces PGE2 production to some extent, modulating CNS inflammation. Our findings may aid in understanding how astrocytes are associated with inflammatory responses, and the identification of new targets that modulate astrocytic reactivity.


Assuntos
Astrócitos , Interleucina-1alfa , Proteína ORAI2 , Prostaglandinas E , Fator de Necrose Tumoral alfa , Animais , Astrócitos/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio , Inflamação , Interleucina-1alfa/metabolismo , Interleucina-1alfa/farmacologia , Camundongos , Proteína ORAI2/metabolismo , Prostaglandinas E/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
13.
Drug Alcohol Depend ; 236: 109491, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35537317

RESUMO

BACKGROUND: Adolescent alcohol misuse is a global problem that can significantly increase the reinstatement of alcohol drinking during re-exposure after abstinence, but the mechanism that causes this increase is unknown. Female adolescents are an understudied population but they are particularly vulnerable to adolescent-onset alcohol abuse. We aimed to determine how adolescent-onset alcohol drinking affects pro-inflammatory mediators endothelin-1 (ET-1), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) in the brain and the role of COX-2 and PGE2 in EtOH reinstatement in adolescent females. METHODS: Adolescent female rats were exposed to a 2-bottle choice paradigm of water vs 5% ethanol (EtOH) every other day over a 21 day period. ET-1 and COX-2 proteins were measured in the dorsal striatum (DS) after a 4 week abstinence from EtOH drinking. The COX-2 inhibitor nimesulide was then administered during abstinence prior to an EtOH reinstatement or sucrose preference or to measure PGE2 content. The PGE2 receptor 1 (EP1) antagonist SC-51089 was then administered prior to EtOH reinstatement during which EtOH intake was measured. RESULTS: EtOH drinking significantly increased ET-1 by 33.8 ± 8.9% and COX-2 by 71.4 ± 24.3% in the DS. Treatment with nimesulide during abstinence attenuated EtOH intake during reinstatement after prolonged abstinence by 40.3 ± 12.4% compared to saline controls. Adolescent EtOH drinking and abstinence increased PGE2 150.5 ± 30.9% in the DS and nimesulide attenuated this increase. SC-51089 treatment during abstinence attenuated EtOH reinstatement by 48.1 ± 8.4% compared to DMSO controls. CONCLUSIONS: These experiments identified a prostaglandin-mediated mechanism that offers a putative pharmacological target to attenuate EtOH reinstatement after adolescent-onset EtOH drinking.


Assuntos
Consumo de Bebidas Alcoólicas , Ciclo-Oxigenase 2/metabolismo , Receptores de Prostaglandina E Subtipo EP1 , Adolescente , Consumo de Bebidas Alcoólicas/metabolismo , Animais , Etanol , Feminino , Humanos , Prostaglandinas E , Ratos
14.
Rev. Odontol. Araçatuba (Online) ; 43(1): 31-40, jan.-abr. 2022. ilus
Artigo em Português | LILACS, BBO - Odontologia | ID: biblio-1361656

RESUMO

Introdução: A Doença Periodontal tem caráter multifatorial, já que depende de condições microbiológicas, imunogenéticas e sistêmicas do hospedeiro. Representa inflamação crônica das estruturas de suporte e proteção dental. Desencadeia uma complexa estimulação imunológica, bem como a produção de citocinas inflamatórias, que mediam a destruição óssea e de tecido conjuntivo, provocando perda dental e complicações à distância. A compreensão da etiopatogênese, permitiu os conceitos de modulação, que referem-se às modificações dos aspectos danosos da resposta inflamatória. Objetivo: O presente artigo tem como objetivo realizar uma revisão dos estudos sobre as principais terapêuticas adjuvantes na modulação da resposta imune frente à doença periodontal. Revisão de Literatura: Foi realizada uma revisão da literatura, onde foram selecionados artigos científicos em inglês, publicados entre os anos 2005 a 2020, por meio das bases de dados PubMed e ScienceDirect. No decorrer das buscas, foram utilizadas as palavraschaves "Inflamation", "Periodontal Disease", "Subantimicrobial Dose of Doxycycline", "Periodontal Disease", "Host Response Modulation". Resultados e Conclusão: A literatura é bem promissora em relação à terapia de controle complementar da doença periodontal. Dessa forma, novas pesquisas nessa área podem trazer inúmeros beneficos aos pacientes, sendo, assim, um novo caminho para o contorno da resistência bacteriana(AU)


Introduction: Periodontal disease has a multifactorial character, depending on the host's microbiological, immunogenetic and systemic conditions. It represents chronic inflammation of dental support and protection structures. It triggers a complex immune stimulation, as well as the production of inflammatory cytokines, which mediate bone and connective tissue destruction, causing tooth loss and complications at a distance. The understanding of etiopathogenesis allowed the concepts of modulation, which refers to the modifications of the harmful aspects of the inflammatory response. This article has the escape of conducting a review of studies on the main mechanisms of modulation against periodontal disease. Objective: This article aims to rev iew the studies on the main modulation mechanisms in the face of periodontal disease. Literature Review: A literature review was carried out in which scientific articles were selected in English, published between 2005 and 2020, through the PubMed and ScienceDirect databases. During the searches, the keywords "Inflammation", "Periodontal Disease", "Subantimicrobial Dose of Doxycycline", "Periodontal Disease", "Host Response Modulation". Results and Conclusion: The literature is very promising with complementary control therapy for periodontal disease. Thus, new research in this area can bring countless benefits to patients, thus being a new way to bypass bacterial resistance(AU)


Assuntos
Doenças Periodontais/terapia , Doxiciclina , Doenças Periodontais , Periodontite , Prostaglandinas E , Dinoprostona , Ácidos Graxos Ômega-3 , Aspirina , Probióticos , Metaloproteinases da Matriz , Inibidores de Metaloproteinases de Matriz
15.
Biosens Bioelectron ; 210: 114211, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35468419

RESUMO

Composite materials have gained significant attention owing to the synergistic effects of their constituent materials, thereby facilitating their utilization in new applications or in improving the existing ones. In this study, a composite based on nickel phthalocyanine (NiTsPc), zinc oxide nanoparticles (ZnONPs), and carbon nanotubes (CNT) was developed and subsequently immobilized on a pyrolytic graphite electrode (PGE). The PGE/NiTsPc-ZnONPs-CNT was identified as a selective catalytic hybrid system for detection of neurotransmitter dopamine (DA). The electrochemical and morphological characterizations were conducted using atomic force microscopy (AFM). Chronoamperometry and differential pulse voltammetry (DPV) were used to detect DA and detection limits of 24 nM and 7.0 nM was found, respectively. In addition, the effects of some possible DA interferents, such as ascorbic acid, uric acid, and serotonin, on DA response were evaluated. Their presence did not show significant variations in the DA electrochemical response. The high specificity and sensitivity of PGE/NiTsPc-ZnONPs-CNT for DA enabled its direct detection in human serum without sample pretreatment as well as in DA-enriched serum samples, whose recovery levels were close to 100%, thereby confirming the effectiveness of the proposed method. In general, PGE/NiTsPc-ZnONPs-CNT is a promising candidate for future applications in clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Grafite , Nanopartículas , Nanotubos de Carbono , Óxido de Zinco , Ácido Ascórbico/química , Dopamina/química , Técnicas Eletroquímicas/métodos , Eletrodos , Grafite/química , Humanos , Indóis , Isoindóis , Nanopartículas/química , Nanotubos de Carbono/química , Níquel , Prostaglandinas E
16.
Stem Cell Res Ther ; 13(1): 168, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477424

RESUMO

BACKGROUND: Fully functional regeneration of skeletal defects by multipotent progenitor cells requires that differentiating cells gain the specific mechano-competence needed in the target tissue. Using cartilage neogenesis as an example, we asked whether proper phenotypic differentiation of mesenchymal stromal cells (MSC) into chondrocytes in vitro will install the adequate biological mechano-competence of native articular chondrocytes (AC). METHODS: The mechano-competence of human MSC- and AC-derived neocartilage was compared during differentiation for up to 35 days. The neocartilage layer was subjected to physiologic dynamic loading in a custom-designed bioreactor and assayed for mechano-sensitive gene and pathway activation, extracellular matrix (ECM) synthesis by radiolabel incorporation, nitric oxide (NO) and prostaglandin E2 (PGE2) production. Input from different pathways was tested by application of agonists or antagonists. RESULTS: MSC and AC formed neocartilage of similar proteoglycan content with a hardness close to native tissue. Mechano-stimulation on day 21 and 35 induced a similar upregulation of mechano-response genes, ERK phosphorylation, NO production and PGE2 release in both groups, indicating an overall similar transduction of external mechanical signals. However, while AC maintained or enhanced proteoglycan synthesis after loading dependent on tissue maturity, ECM synthesis was always significantly disturbed by loading in MSC-derived neocartilage. This was accompanied by significantly higher COX2 and BMP2 background expression, > 100-fold higher PGE2 production and a weaker SOX9 stimulation in response to loading in MSC-derived neocartilage. Anabolic BMP-pathway activity was not rate limiting for ECM synthesis after loading in both groups. However, NFκB activation mimicked the negative loading effects and enhanced PGE2 production while inhibition of catabolic NFκB signaling rescued the load-induced negative effects on ECM synthesis in MSC-derived neocartilage. CONCLUSIONS: MSC-derived chondrocytes showed a higher vulnerability to be disturbed by loading despite proper differentiation and did not acquire an AC-like mechano-competence to cope with the mechanical stress of a physiologic loading protocol. Managing catabolic NFκB influences was one important adaptation to install a mechano-resistance closer to AC-derived neocartilage. This new knowledge asks for a more functional adaptation of MSC chondrogenesis, novel pharmacologic co-treatment strategies for MSC-based clinical cartilage repair strategies and may aid a more rational design of physical rehabilitation therapy after AC- versus MSC-based surgical cartilage intervention.


Assuntos
Cartilagem Articular , Células-Tronco Mesenquimais , Cartilagem Articular/metabolismo , Células Cultivadas , Condrócitos/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , NF-kappa B/metabolismo , Prostaglandinas E/metabolismo , Proteoglicanas/metabolismo
17.
Nat Metab ; 4(4): 444-457, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35361955

RESUMO

Efferocytosis, the clearance of apoptotic cells (ACs) by macrophages, is critical for tissue resolution, with defects driving many diseases. Mechanisms of efferocytosis-mediated resolution are incompletely understood. Here, we show that AC-derived methionine regulates resolution through epigenetic repression of the extracellular signal-regulated kinase 1/2 (ERK1/2) phosphatase Dusp4. We focus on two key efferocytosis-induced pro-resolving mediators, prostaglandin E2 (PGE2) and transforming growth factor beta 1 (TGF-ß1), and show that efferocytosis induces prostaglandin-endoperoxide synthase 2/cyclooxygenase 2 (Ptgs2/COX2), leading to PGE2 synthesis and PGE2-mediated induction of TGF-ß1. ERK1/2 phosphorylation/activation by AC-activated CD36 is necessary for Ptgs2 induction, but this is insufficient owing to an ERK-DUSP4 negative feedback pathway that lowers phospho-ERK. However, subsequent AC engulfment and phagolysosomal degradation lead to Dusp4 repression, enabling enhanced p-ERK and induction of the Ptgs2-PGE2-TGF-ß1 pathway. Mechanistically, AC-derived methionine is converted to S-adenosylmethionine, which is used by DNA methyltransferase-3A (DNMT3A) to methylate Dusp4. Bone-marrow DNMT3A deletion in mice blocks COX2/PGE2, TGF-ß1, and resolution in sterile peritonitis, apoptosis-induced thymus injury and atherosclerosis. Knowledge of how macrophages use AC-cargo and epigenetics to induce resolution provides mechanistic insight and therapeutic options for diseases driven by impaired resolution.


Assuntos
DNA Metiltransferase 3A/metabolismo , Metionina , Fator de Crescimento Transformador beta1 , Animais , Apoptose , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Macrófagos/metabolismo , Metionina/metabolismo , Camundongos , Prostaglandinas E/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
18.
BMC Vet Res ; 18(1): 141, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35436878

RESUMO

BACKGROUND: Hemoderivatives such as autologous conditioned serum (ACS) and platelet-rich plasma (PRP) have been used as potential disease-modifying therapies in musculoskeletal disorders such as osteoarthritis (OA). These therapies are based on the delivery of multiple growth factors and anti-inflammatory cytokines that are known to participate in inflammatory processes. The variability of cytokine content due to the autologous nature of the product, the non-availability for immediate use and need for storage at low temperatures are limitations for its use in the field. An allogeneic freeze-dried conditioned serum (CS) and PRP would provide field clinicians with a more practical approach to use such products in daily practice. Based on in vitro preliminary data, this experimental study aimed to test the in vivo safety of allogeneic freeze-dried CS and PRP in healthy joints, using the horse as a model. RESULTS: Eight horses were randomly assigned and treated with PRP or CS. Horses had three joints injected with ALLO-FD PRP or CS, and three contralateral joints injected with the AUTO version of the same product, by a blinded clinician. Horses were evaluated clinically, and had synovial fluid collected at different time points and evaluated for cell content, PGE2 and protein. Both CS and PRP products triggered a self-limiting and mild inflammatory response in equine healthy joints. This was indicated by the transient increase in nucleated cell count, PGE2 and total protein in synovial fluid. This mild inflammatory response did not result in significant lameness and was not different among the groups. CONCLUSIONS: The allogeneic freeze-dried PRP and CS showed to be overall safe and not dissimilar compared to their autologous frozen version in equine healthy joints. Further studies are necessary to evaluate the modulatory effects of these therapies in a clinical setting.


Assuntos
Plasma Rico em Plaquetas , Animais , Citocinas/metabolismo , Liofilização/veterinária , Cavalos , Injeções Intra-Articulares/veterinária , Prostaglandinas E/metabolismo , Líquido Sinovial/metabolismo
19.
Mediators Inflamm ; 2022: 2127642, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35437426

RESUMO

Gingival inflammation is one of the main causes that can be related to various periodontal diseases. Human gingival fibroblast (HGF) is the major constituent in periodontal connective tissue and secretes various inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), upon lipopolysaccharide stimulation. This study is aimed at investigating the anti-inflammatory mechanism of chlorogenic acid (CGA) on Porphyromonas gingivalis LPS- (LPS-PG-) stimulated HGF-1 cells. The concentration of NO and PGE2, as well as their responsible enzymes, inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2), was analyzed by Griess reaction, ELISA, and western blot analysis. LPS-PG sharply elevated the production and protein expression of inflammatory mediators, which were significantly attenuated by CGA treatment in a dose-dependent manner. CGA treatment also suppressed activation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (MyD88) and nuclear factor- (NF-) κB in LPS-PG-stimulated HGF-1 cells. Furthermore, LPS-PG-induced phosphorylation of extracellular regulated kinase (ERK) and Akt was abolished by CGA treatment, while c-Jun N-terminal kinase (JNK) and p38 did not have any effect. Consequently, these results suggest that CGA ameliorates LPS-PG-induced inflammatory responses by attenuating TLR4/MyD88-mediated NF-κB, phosphoinositide-3-kinase (PI3K)/Akt, and MAPK signaling pathways in HGF-1 cells.


Assuntos
Lipopolissacarídeos , NF-kappa B , Ácido Clorogênico/metabolismo , Ácido Clorogênico/farmacologia , Ciclo-Oxigenase 2/metabolismo , Fibroblastos/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Prostaglandinas E/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor 4 Toll-Like/metabolismo
20.
Nanomedicine ; 43: 102560, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35417772

RESUMO

Chitosan (CHIT) and hyaluronic acid (HA) are two polysaccharides (PSs) with high value in several biomedical applications. In this study, we present a microfluidic method to synthetize CHIT-HA NPs to overcome the disadvantages of the dropwise approach generally used for nanoprecipitation of polyelectrolyte complexes. The proposed microfluidic approach enables to generate monodisperse suspensions of NPs with ≈100 nm of size compared to the dropwise method that generated ≈2 times bigger NPs. Finally, we evaluated the potential of obtained NPs in an inflammatory scenario. The treatment with NPs led to the reduction of the main inflammatory molecules produced by macrophages (PGE2, IL-6, IL-8, MCAF and TNF-α) and fibroblasts (IL-1 α, PGE2, TNF-α) stimulated with lipopolysaccharide or conditioned medium, respectively. This study demonstrates that our approach can be used to enhance the synthesis of nanocarriers based on bioactive macromolecules.


Assuntos
Quitosana , Nanopartículas , Ácido Hialurônico , Microfluídica/métodos , Peso Molecular , Tamanho da Partícula , Polímeros , Prostaglandinas E , Fator de Necrose Tumoral alfa
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