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1.
Eur J Pharm Sci ; 198: 106792, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38714237

RESUMO

Non-alcoholic steatohepatitis (NASH) is characterized by liver inflammation, fat accumulation, and collagen deposition. Due to the limited availability of effective treatments, there is a pressing need to develop innovative strategies. Given the complex nature of the disease, employing combination approaches is essential. Hedgehog signaling has been recognized as potentially promoting NASH, and cholesterol can influence this signaling by modifying the conformation of PTCH1 and SMO activity. HSP90 plays a role in the stability of SMO and GLI proteins. We revealed significant positive correlations between Hedgehog signaling proteins (Shh, SMO, GLI1, and GLI2) and both cholesterol and HSP90 levels. Herein, we investigated the novel combination of the cholesterol-lowering agent lovastatin and the HSP90 inhibitor PU-H71 in vitro and in vivo. The combination demonstrated a synergy score of 15.09 and an MSA score of 22.85, as estimated by the ZIP synergy model based on growth inhibition rates in HepG2 cells. In a NASH rat model induced by thioacetamide and a high-fat diet, this combination therapy extended survival, improved liver function and histology, and enhanced antioxidant defense. Additionally, the combination exhibited anti-inflammatory and anti-fibrotic potential by influencing the levels of TNF-α, TGF-ß, TIMP-1, and PDGF-BB. This effect was evident in the suppression of the Col1a1 gene expression and the levels of hydroxyproline and α-SMA. These favorable outcomes may be attributed to the combination's potential to inhibit key Hedgehog signaling molecules. In conclusion, exploring the applicability of this combination contributes to a more comprehensive understanding and improved management of NASH and other fibrotic disorders.

2.
Front Cell Neurosci ; 18: 1336145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699177

RESUMO

The orexins, also referred to as hypocretins, are neuropeptides that originate from the lateral hypothalamus (LH) region of the brain. They are composed of two small peptides, orexin-A, and orexin-B, which are broadly distributed throughout the central and peripheral nervous systems. Orexins are recognized to regulate diverse functions, involving energy homeostasis, the sleep-wake cycle, stress responses, and reward-seeking behaviors. Additionally, it is suggested that orexin-A deficiency is linked to sleepiness and narcolepsy. The orexins bind to their respective receptors, the orexin receptor type 1 (OX1R) and type 2 (OX2R), and activate different signaling pathways, which results in the mediation of various physiological functions. Orexin receptors are widely expressed in different parts of the body, including the skin, muscles, lungs, and bone marrow. The expression levels of orexins and their receptors play a crucial role in apoptosis, which makes them a potential target for clinical treatment of various disorders. This article delves into the significance of orexins and orexin receptors in the process of apoptosis, highlighting their expression levels and their potential contributions to different diseases. The article offers an overview of the existing understanding of the orexin/receptor system and how it influences the regulation of apoptosis.

4.
FASEB J ; 38(4): e23480, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38354025

RESUMO

Accumulating evidence suggests that dysregulation of FOXO3a plays a significant role in the progression of various malignancies, including hepatocellular carcinoma (HCC). FOXO3a inactivation, driven by oncogenic stimuli, can lead to abnormal cell growth, suppression of apoptosis, and resistance to anticancer drugs. Therefore, FOXO3a emerges as a potential molecular target for the development of innovative treatments in the era of oncology. Linagliptin (LNGTN), a DPP-4 inhibitor known for its safe profile, has exhibited noteworthy anti-inflammatory and anti-oxidative properties in previous in vivo studies. Several potential molecular mechanisms have been proposed to explain these effects. However, the capacity of LNGTN to activate FOXO3a through AMPK activation has not been investigated. In our investigation, we examined the potential repurposing of LNGTN as a hepatoprotective agent against diethylnitrosamine (DENA) intoxication. Additionally, we assessed LNGTN's impact on apoptosis and autophagy. Following a 10-week administration of DENA, the liver underwent damage marked by inflammation and early neoplastic alterations. Our study presents the first experimental evidence demonstrating that LNGTN can reinstate the aberrantly regulated FOXO3a activity by elevating the nuclear fraction of FOXO3a in comparison to the cytosolic fraction, subsequent to AMPK activation. Moreover, noteworthy inactivation of NFκB induced by LNGTN was observed. These effects culminated in the initiation of apoptosis, the activation of autophagy, and the manifestation of anti-inflammatory, antiproliferative, and antiangiogenic outcomes. These effects were concomitant with improved liver function and microstructure. In conclusion, our findings open new avenues for the development of novel therapeutic strategies targeting the AMPK/FOXO3a signaling pathway in the management of chronic liver damage.


Assuntos
Carcinoma Hepatocelular , Inibidores da Dipeptidil Peptidase IV , Neoplasias Hepáticas , Animais , Ratos , Linagliptina/farmacologia , Proteínas Quinases Ativadas por AMP , Dietilnitrosamina/toxicidade , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Hipoglicemiantes , Inibidores de Proteases , Antivirais , Anti-Inflamatórios
5.
Neurochem Res ; 49(4): 980-997, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38170385

RESUMO

Diabetic neuropathic pain is one of the most devasting disorders of peripheral nervous system. The loss of GABAergic inhibition is associated with the development of painful diabetic neuropathy. The current study evaluated the potential of 3-Hydroxy-2-methoxy-6-methyl flavone (3-OH-2'MeO6MF), to ameliorate peripheral neuropathic pain using an STZ-induced hyperglycemia rat model. The pain threshold was assessed by tail flick, cold, mechanical allodynia, and formalin test on days 0, 14, 21, and 28 after STZ administration accompanied by evaluation of several biochemical parameters. Administration of 3-OH-2'-MeO6MF (1,10, 30, and 100 mg/kg, i.p) significantly enhanced the tail withdrawal threshold in tail-flick and tail cold allodynia tests. 3-OH-2'-MeO6MF also increased the paw withdrawal threshold in mechanical allodynia and decreased paw licking time in the formalin test. Additionally, 3-OH-2'-MeO6MF also attenuated the increase in concentrations of myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), nitrite, TNF-α, and IL 6 along with increases in glutathione (GSH). Pretreatment of pentylenetetrazole (PTZ) (40 mg/kg, i.p.) abolished the antinociceptive effect of 3-OH-2'-MeO6MF in mechanical allodynia. Besides, the STZ-induced alterations in the GABA concentration and GABA transaminase activity attenuated by 3-OH-2'-MeO6MF treatment suggest GABAergic mechanisms. Molecular docking also authenticates the involvement of α2ß2γ2L GABA-A receptors and GABA-T enzyme in the antinociceptive activities of 3-OH-2'-MeO6MF.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Flavonas , Neuralgia , Ratos , Animais , Hiperalgesia/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Estreptozocina , Simulação de Acoplamento Molecular , Neuralgia/induzido quimicamente , Neuralgia/tratamento farmacológico , Neuralgia/complicações , Analgésicos/farmacologia , Ácido gama-Aminobutírico/farmacologia , Flavonas/farmacologia , Flavonas/uso terapêutico , Biomarcadores
6.
CNS Neurosci Ther ; 30(4): e14525, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-37953501

RESUMO

Depression is a mood disorder characterized by abnormal thoughts. The pathophysiology of depression is related to the deficiency of serotonin (5HT), which is derived from tryptophan (Trp). Mitochondrial dysfunction, oxidative stress, and neuroinflammation are involved in the pathogenesis of depression. Notably, the renin-angiotensin system (RAS) is involved in the pathogenesis of depression, and different findings revealed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may be effective in depression. However, the underlying mechanism for the role of dysregulated brain RAS-induced depression remains speculative. Therefore, this review aimed to revise the conceivable role of ACEIs and ARBs and how these agents ameliorate the pathophysiology of depression. Dysregulation of brain RAS triggers the development and progression of depression through the reduction of brain 5HT and expression of brain-derived neurotrophic factor (BDNF) and the induction of mitochondrial dysfunction, oxidative stress, and neuroinflammation. Therefore, inhibition of central classical RAS by ARBS and ACEIs and activation of non-classical RAS prevent the development of depression by regulating 5HT, BDNF, mitochondrial dysfunction, oxidative stress, and neuroinflammation.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Doenças Mitocondriais , Humanos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Sistema Renina-Angiotensina , Fator Neurotrófico Derivado do Encéfalo , Antagonistas de Receptores de Angiotensina/farmacologia , Depressão/tratamento farmacológico , Doenças Neuroinflamatórias
7.
Int J Mol Sci ; 24(20)2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37895159

RESUMO

Diabetes mellitus is a metabolic disorder associated with various complications encompassing male reproductive dysfunction. The present study aimed to investigate the therapeutic potential of biologically active Lepidium sativum seed oil (LSO) against the testicular dysfunction associated with streptozotocin (STZ)-induced diabetes. Male adults (n = 24) were divided into four groups: control, LSO-administered, diabetic (D), and LSO-treated diabetic (D+LSO) groups. LSO was extracted from L. sativum seeds, and its chemical composition was determined using GC-MS. Serum testosterone levels, testicular enzymatic antioxidants (catalase (CAT) and superoxide dismutase (SOD)), an oxidative stress (OS) biomarker, malondialdehyde (MDA), pro-inflammatory markers (NF-kB, IL-1, IL-6, and TNF-α), and the expression level of NF-kB were assessed. In addition, histopathological changes were evaluated in testicular tissues. The results obtained showed that the chemical composition of LSO indicated its enrichment mainly with γ-tocopherol (62.1%), followed by 2-methylhexacosane (8.12%), butylated hydroxytoluene (8.04%), 10-Methylnonadecane (4.81%), and δ-tocopherol (3.91%). Moreover, LSO administration in the D+LSO mice significantly increased testosterone levels and ameliorated the observed testicular oxidative damage, inflammatory response, and reduced NF-kB expression compared to the diabetic mice. Biochemical and molecular analyses confirmed the histological results. In conclusion, LSO may prevent the progression of diabetes-induced impairment in the testes through inhibition of the OS- and NF-kB-mediated inflammatory response.


Assuntos
Diabetes Mellitus Experimental , Doenças Testiculares , Humanos , Camundongos , Masculino , Animais , Testículo/metabolismo , Lepidium sativum/metabolismo , NF-kappa B/metabolismo , Diabetes Mellitus Experimental/metabolismo , Estresse Oxidativo , Antioxidantes/metabolismo , Doenças Testiculares/metabolismo , Inflamação/metabolismo , Testosterona/metabolismo , Óleos de Plantas/farmacologia , Óleos de Plantas/uso terapêutico , Óleos de Plantas/metabolismo
8.
Cell Stress Chaperones ; 28(6): 657-673, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37796433

RESUMO

Coronavirus disease 2019 (COVID-19) is a recent pandemic caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) leading to pulmonary and extra-pulmonary manifestations due to the development of oxidative stress (OS) and hyperinflammation. The underlying cause for OS and hyperinflammation in COVID-19 may be related to the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidative responses and cellular homeostasis. The Nrf2 pathway inhibits the expression of pro-inflammatory cytokines and the development of cytokine storm and OS in COVID-19. Nrf2 activators can attenuate endothelial dysfunction (ED), renin-angiotensin system (RAS) dysregulation, immune thrombosis, and coagulopathy. Hence, this review aimed to reveal the potential role of the Nrf2 pathway and its activators in the management of COVID-19. As well, we tried to revise the mechanistic role of the Nrf2 pathway in COVID-19.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Fator 2 Relacionado a NF-E2 , Sistema Renina-Angiotensina , Pulmão
9.
Vet Med Sci ; 9(6): 2475-2484, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37772411

RESUMO

BACKGROUND: Dogs are the most popular pet animals worldwide, and their frequent and close contact with humans poses an increased risk of zoonotic parasite transmission. Toxocara canis infection is a highly pervasive and economically significant zoonotic infection transmitted by dogs worldwide, commonly in tropical and subtropical regions, particularly in developing countries. OBJECTIVES: This study evaluates the epidemiological profile and associated risk factors of T. canis exposure among humans and T. canis infection in domestic dogs in two climatically different governorates in Egypt. METHODS: Faecal samples from 360 domiciled dogs were examined using the flotation technique to detect T. canis eggs. In addition, 276 human serum samples were evaluated by enzyme-linked immunosorbent assay over a period of 10 months from May 2021 to February 2022 in the Alexandria and Qena Governorates, Egypt. RESULTS: Shedding of T. canis was identified in 33.33% (120/360) of dogs and the overall seroprevalence in the human population was 20.65% (57/276). Lower Egypt, represented by the Alexandria Governorate, had higher canine infection (39.47%) and human seropositivity (29.87%) rates than those of Upper Egypt, represented by Qena Governorate (26.47% and 9.02% in dogs and humans, respectively). Statistical analysis of the sociodemographic characteristics of the participants revealed that handwashing, washing of vegetables and fruits and sex were associated with human T. canis exposure. CONCLUSION: The prevalence rates of confirmed T. canis infection in the Egyptian dogs population and the associated human seropositivity rates reflect its importance as a public health concern and support the call to increase public awareness of this issue. The risk factors identified in this study can contribute to the development of more effective control and prevention strategies.


Assuntos
Toxocara canis , Humanos , Animais , Cães , Egito/epidemiologia , Estudos Soroepidemiológicos , Prevalência , Fatores de Risco
10.
Pharmaceuticals (Basel) ; 16(8)2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37631038

RESUMO

Idiopathic pulmonary fibrosis (IPF) is an irreversible and life-threatening lung disease of unknown etiology presenting only a few treatment options. TGF-ß signaling orchestrates a cascade of events driving pulmonary fibrosis (PF). Notably, recent research has affirmed the augmentation of TGF-ß receptor (TßR) signaling via HSP90 activation. HSP90, a molecular chaperone, adeptly stabilizes and folds TßRs, thus intricately regulating TGF-ß1 signaling. Our investigation illuminated the impact of alvespimycin, an HSP90 inhibitor, on TGF-ß-mediated transcriptional responses by inducing destabilization of TßRs. This outcome stems from the explicit interaction of TßR subtypes I and II with HSP90, where they are clients of this cellular chaperone. It is worth noting that regulation of proteasome-dependent degradation of TßRs is a critical standpoint in the termination of TGF-ß signal transduction. Oleuropein, the principal bioactive compound found in Olea europaea, is acknowledged for its role as a proteasome activator. In this study, our aim was to explore the efficacy of a combined therapy involving oleuropein and alvespimycin for the treatment of PF. We employed a PF rat model that was induced by intratracheal bleomycin infusion. The application of this dual therapy yielded a noteworthy impediment to the undesired activation of TGF-ß/mothers against decapentaplegic homologs 2 and 3 (SMAD2/3) signaling. Consequently, this novel combination showcased improvements in both lung tissue structure and function while also effectively restraining key fibrosis markers such as PDGF-BB, TIMP-1, ACTA2, col1a1, and hydroxyproline. On a mechanistic level, our findings unveiled that the antifibrotic impact of this combination therapy likely stemmed from the enhanced degradation of both TßRI and TßRII. In conclusion, the utilization of proteasomal activators in conjunction with HSP90 inhibitors ushers in a promising frontier for the management of PF.

11.
J Immunol Res ; 2023: 5544819, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37383608

RESUMO

Chronic helminth infections (CHIs) can induce immunological tolerance through the upregulation of regulatory T cells. In coronavirus disease 2019 (COVID-19), abnormal adaptive immune response and exaggerated immune response may cause immune-mediated tissue damage. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) and CHIs establish complicated immune interactions due to SARS-CoV-2-induced immunological stimulation and CHIs-induced immunological tolerance. However, COVID-19 severity in patients with CHIs is mild, as immune-suppressive anti-inflammatory cytokines counterbalance the risk of cytokine storm. Since CHIs have immunomodulatory effects, therefore, this narrative review aimed to clarify how CHIs modulate the immunoinflammatory response in SARS-CoV-2 infection. CHIs, through helminth-derived molecules, may suppress SARS-CoV-2 entry and associated hyperinflammation through attenuation of the inflammatory signaling pathway. In addition, CHIs may reduce the COVID-19 severity by reducing the SARS-CoV-2 entry points in the initial phase and immunomodulation in the late phase of the disease by suppressing the release of pro-inflammatory cytokines. In conclusion, CHIs may reduce the severity of SARS-CoV-2 infection by reducing hyperinflammation and exaggerated immune response. Thus, retrospective and prospective studies are recommended in this regard.


Assuntos
COVID-19 , Helmintos , Humanos , Animais , SARS-CoV-2 , Estudos Prospectivos , Estudos Retrospectivos , Citocinas
12.
Nutrients ; 15(5)2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36904204

RESUMO

Schistosomiasis is a tropical disease caused by trematode worms. The inflammatory response of the host to schistosome eggs leads to formation of granuloma in the liver and intestine. Praziquantel (PZQ) is still an effective treatment for schistosomiasis, however resistance development may reduce its efficacy. The current study investigated the possible immunomodulatory and anti-inflammatory action of rutin, a natural flavonoid compound isolated from garlic, on liver fibrotic markers in mice infected with S. mansoni in comparison to PZQ. Male albino CD1 mice were infected with 100 ± 2 S. mansoni cercariae/mouse and treated with garlic, rutin, or PZQ. At the end of the experiment, the liver and intestines were harvested for parasitological and histological assessment and to analyze the proinflammatory cytokine. Rutin significantly affects the pathological alterations caused by Schistosoma in the liver. This may be partially explained by a decrease in the number of eggs trapped in the tissues of the liver and a modification in the serum levels of certain cytokines, which are implicated in the formation of Schistosoma granuloma. In conclusion, rutin has strong anti-schistosome properties in vivo, raising the possibility that rutin might be further investigated as a therapy for S. mansoni.


Assuntos
Alho , Esquistossomose mansoni , Esquistossomose , Masculino , Animais , Camundongos , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/patologia , Schistosoma mansoni , Flavonoides/uso terapêutico , Rutina/uso terapêutico , Praziquantel/uso terapêutico , Fígado/patologia , Esquistossomose/patologia , Anti-Inflamatórios/uso terapêutico , Citocinas , Granuloma/patologia
13.
Nutrients ; 14(24)2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36558525

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation and progressive joint dysfunction. Opuntia littoralis (OL) has a high nutritional content and is thought to offer a number of health advantages. We aimed to evaluate the anti-arthritic potential of OL extracts against collagen-induced arthritis (CIA). We designed three OL cladode fractions from the concentrated aqueous extract: hexane, ethyl acetate (EAE), and hydro alcohol (HAE). We investigated the nitric oxide and MDA levels of EAE against lipopolysaccharide-induced RAW264.7 cells; then, we administered EAE to the mice with CIA to confirm the anti-inflammatory effects against RA. HPLC analysis of the OL extracts showed a high concentration of phenolic compounds in EAE. Treatment with EAE (10 and 20 mg/100 g body weight of mice) after 10 days of immunization with collagen showed a significant inhibition of joint inflammation, paw swelling, and edemas. MDA and cytokine levels (IL-1ß, IL-6R, IL-6, IL-17, and IL-23) were significantly reduced. EAE effectively ameliorated COX-2, NF-kB, STAT-3, PTEN, and RANKL expression. OL-EAE therapy significantly upregulated the expression of miR-28 and miR-199a. In conclusion, the anti-inflammatory actions of OL-EAE altered the cellular localization of the inflammatory mediators, therefore preventing joint inflammation via partial epigenetic and metabolic regulations in experimental mice.


Assuntos
Artrite Experimental , Artrite Reumatoide , MicroRNAs , Opuntia , Camundongos , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Modelos Animais de Doenças , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/metabolismo , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/tratamento farmacológico , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Colágeno
14.
Acta Parasitol ; 65(3): 652-660, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32240492

RESUMO

PURPOSE: Schistosomiasis is a disease that afflicts over 220 million people worldwide. To date, there is no vaccine against schistosomiasis and chemotherapy relies basically on a single drug, praziquantel. The current study was undertaken to investigate the therapeutic effects of monophosphoryl lipid A (MPLA) as an adjuvant in soluble egg antigen (SEA)-vaccinated and Schistosoma mansoni-infected mice. METHODS: Mice were divided into two groups of uninfected and Schistosoma mansoni infected. The two groups were treated differently with MPLA, SEA and praziquantel. Study parameters included parasitological, immunological and biochemical parameters. RESULTS: Parasitological parameters revealed that intraperitoneal injection of MPLA into SEA-vaccinated and S. mansoni-infected mice was effective in reducing the worm and egg burden, granuloma count and diameter as well as the total area of infection in their livers versus SEA-untreated but infected ones. In addition, MPLA showed ameliorative action on the elevated liver oxidative stress marker, including malondialdehyde (MDA) and a decrease in the level of the antioxidant enzymes, reduced glutathione (GSH) and catalase (CAT) which may have a role in the liver damage and fibrosis due to S. mansoni infection. CONCLUSION: Treatment with MPLA has multi-functions in attenuating the deleterious impacts of S. mansoni infection in mice livers. Its effects are mediated through a reduction of ova count, worm burden, granuloma diameter and amelioration of antioxidant defense systems, and liver function biomarkers.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Lipídeo A/análogos & derivados , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/prevenção & controle , Receptores Toll-Like/agonistas , Animais , Anti-Helmínticos/uso terapêutico , Antígenos de Helmintos/administração & dosagem , Antígenos de Helmintos/imunologia , Proteínas de Helminto/administração & dosagem , Proteínas de Helminto/imunologia , Lipídeo A/administração & dosagem , Lipídeo A/imunologia , Masculino , Camundongos , Praziquantel/uso terapêutico , Schistosoma mansoni , Vacinação
15.
J Oncol Pharm Pract ; 26(6): 1343-1352, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31865848

RESUMO

INTRODUCTION: Cancer immunotherapy is a complicated field that develops rapidly; in the past decades, immunotherapy has become the standard treatment for several cancer types. The aim of the current study was to estimate the awareness and understanding of cancer immunotherapy and associated immunological concepts among healthcare professionals (HCPs) in eastern Saudi Arabia in order to assess educational needs. METHODS: A cross-sectional questionnaire was conducted among multidisciplinary HCPs in healthcare institutions in eastern Saudi Arabia from April 2019 to June 2019. The survey was designed to assess the awareness and understanding of HCPs' basic scientific knowledge of cancer immunotherapy. The data were analyzed using the Statistical Package for the Social Sciences (SPSS). Reliability was tested through Cronbach's alpha, and a χ2 or Fisher's exact test was used to determine the distribution of categorical variables between groups. RESULTS: The study included 360 HCPs: 43.6% physicians, 21.9% nurses, 20.8% medical laboratory scientists, and 13.6% pharmacists. Only 20.6% of the HCPs considered immunotherapy the best-known cancer therapy. The overall level of awareness of cancer immunotherapy was low (55.8%), and only 6.4% of the participants had a high knowledge rate. The majority of the respondents indicated the importance of studying the science of immunotherapy. Cronbach's alphas for the HCPs' perceptions, self-evaluation rate, and reflection scales were 0.74, 0.90, and 0.66, respectively. Simple linear regression showed a significant relationship between reflection and self-evaluation. CONCLUSIONS: A reliable and consistent study revealed a low level of awareness and understanding of immunotherapy among multidisciplinary HCPs.


Assuntos
Atitude do Pessoal de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/normas , Imunoterapia , Neoplasias/terapia , Inquéritos e Questionários , Adulto , Estudos Transversais , Feminino , Pessoal de Saúde/psicologia , Humanos , Masculino , Neoplasias/epidemiologia , Neoplasias/imunologia , Reprodutibilidade dos Testes , Arábia Saudita/epidemiologia
16.
Exp Parasitol ; 194: 53-59, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30266572

RESUMO

Schistosomiasis is a fatal disease that has a negative impact on health and economics. Praziquantel (PZQ) is the drug of choice for schistosomiasis treatment, but it has no prophylactic effect; therefore, vaccination is an essential requirement in schistosomiasis control. This work was carried out to investigate the possible effect of DNA vaccination against Schistosoma mansoni infection using recombinant S. mansoni fatty acid binding protein (rsmFABP). The smFABP gene was cloned into the eukaryotic expression vector pcDNAI/Amp in order to obtain an smFABP-pcDNAI recombinant plasmid (DNA vaccine) and was used for the intramuscular DNA vaccination of out-bread Swiss albino mice prior to infection with S. mansoni cercariae. Infected groups, either DNA vaccinated or unvaccinated, were treated with PZQ at week 6 post-infection. After 8 weeks post-infection, all mouse groups were sacrificed and parasitological, immunological and histopathological parameters were studied. DNA vaccinated mice showed a high titer of anti-smFABP-IgG antibodies and acquired significant protection (74.2%, p < 0.01) against S. mansoni infection, with a reduction in ova and granuloma counts. DNA vaccinated and PZQ treated animals had higher titers of anti-smFABP-IgG antibodies and decreased (87%, P < 0.001) parenchymal granulomas compared to the DNA vaccinated PZQ untreated group. Infected mice, either non DNA vaccinated or vaccinated, had very high collagen content and fibrous granulomas (74%) compared to the PZQ treated group (10.3% fibrous granuloma) and PZQ treated + DNA vaccinated group (0% fibrous granuloma). In conclusion, DNA vaccination had protective and anti-pathological effects in naive mice and greatly improved the pathological status in PZQ-treated animals, suggesting an immunological and pathological modulating effect of PZQ treatment.


Assuntos
Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Helminto/genética , Schistosoma mansoni/imunologia , Esquistossomose mansoni/prevenção & controle , Vacinas de DNA , Sequência de Aminoácidos , Animais , Biomphalaria , Cricetinae , Proteínas de Ligação a Ácido Graxo/química , Proteínas de Ligação a Ácido Graxo/imunologia , Feminino , Proteínas de Helminto/química , Proteínas de Helminto/imunologia , Fígado/patologia , Mesocricetus , Camundongos , Vacinas de DNA/administração & dosagem
17.
Acta Trop ; 177: 19-24, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28964770

RESUMO

Nanotechnology is a promising arena for generating new applications in Medicine. To successfully functionalised nanoparticles for a given biomedical application, a wide range of chemical, physical and biological factors have to be taken into account. Silica-coated nanoparticles, (SiO2NP) exhibit substantial diagnostic activity owing to their large surface to volume ratios and crystallographic surface structure. This work aimed to evaluate the advantage of bioconjugation of SiO2NP with PAb against Toxoplasma lyzate antigen (TLA) as an innovative diagnostic method for human toxoplasmosis. This cross-sectional study included 120 individuals, divided into Group I: 70 patients suspected for Toxoplasma gondii based on the presence of clinical manifestation. Group II: 30 patients harboring other parasites than T. gondii Group III: 20 apparently healthy individuals free from toxoplasmosis and other parasitic infections served as negative control. Detection of circulating Toxoplasma antigen was performed by Sandwich ELISA and Nano-sandwich ELISA on sera and pooled urine of human samples. Using Sandwich ELISA, 10 out of 70 suspected Toxoplasma-infected human serum samples showed false negative and 8 out of 30 of other parasites groups were false positive giving 85.7% sensitivity and 84.0% specificity, while the sensitivity and specificity were 78.6% and 70% respectively in urine samples. Using Nano-Sandwich ELISA, 7 out of 70 suspected Toxoplasma-infected human samples showed false negative results and the sensitivity of the assay was 90.0%, while 4 out of 30 of other parasites groups were false positive giving 92.0% specificity, while the sensitivity and specificity were 82.6% and 80% respectively in urine samples. In conclusion, our data demonstrated that loading SiO2 nanoparticles with pAb increased the sensitivity and specificity of Nano-sandwich ELISA for detection of T.gondii antigens in serum and urine samples, thus active (early) and light infections could be easily detected.


Assuntos
Antígenos de Protozoários/imunologia , Nanopartículas/química , Toxoplasmose/diagnóstico , Toxoplasmose/imunologia , Adulto , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G , Gravidez , Sensibilidade e Especificidade , Dióxido de Silício , Toxoplasma/imunologia , Adulto Jovem
18.
Microb Pathog ; 107: 243-248, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28373144

RESUMO

In this work, the efficiency of crude MeOH extracts and soluble glycoprotein fraction of Allium sativum purified by size-exclusion chromatography (SEC) on parasitological, histopathological and some biochemical parameters in Schistosoma mansoni infected mice were investigated. Animals were infected by tail immersion with 100 cercariae/each mouse and divided into five groups in addition to the normal control. The results revealed a significant decrease in mean worm burden in all treated mice especially in the group treated with soluble glycoprotein fraction of A. sativum as compared to infected non-treated control with the disappearance of female worms. Administration of the studied extracts revealed remarkable amelioration in the levels of all the measured parameters in S. mansoni infected mice. In addition, treatment of mice with crude A. sativum MeOH extract and soluble glycoprotein fraction of A. sativum decreased significantly the activities of studied enzymes as compared to the infected untreated group. The highest degrees of enhancement in pathological changes was observed in the treated one with soluble glycoprotein fraction of A. sativum compared to the infected group represented by small sized, late fibro-cellular granuloma, the decrease in cellular constituents and degenerative changes in eggs. In conclusion, A. sativum treatment had effective schistosomicidal activities, through reduction of worm burden and tissue eggs, especially when it was given in purified glycoprotein fraction. Moreover, the soluble glycoprotein fraction of A. sativum largely modulates both the size and the number of granulomas.


Assuntos
Cromatografia em Gel/métodos , Alho/química , Glicoproteínas/química , Glicoproteínas/farmacologia , Extratos Vegetais/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/tratamento farmacológico , Fosfatase Alcalina/sangue , Animais , Modelos Animais de Doenças , Feminino , Granuloma/parasitologia , Granuloma/patologia , Fígado/parasitologia , Fígado/patologia , Masculino , Camundongos , Contagem de Ovos de Parasitas , Schistosoma mansoni/patogenicidade , Esquistossomose mansoni/sangue , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/patologia , Esquistossomicidas/farmacologia , Soro/química , Transaminases/sangue , gama-Glutamiltransferase/sangue
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