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1.
J Ethnopharmacol ; 300: 115671, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36055476

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Kalyanaka ghrita (KG) is an Ayurvedic formulation traditionally used in the treatment of Daurbalya (debility) and Smritidaurbalya (impairment of intellectual activities). Clinical studies have reported the effect of KG in the treatment of Manasmandata or Buddhimandyata which is associated with impaired learning, social adjustment and maturation. AIM OF THE STUDY: The present study aims to standardization of KG and validation of its use in experimental models of neurodegeneration. MATERIALS AND METHODS: KG was Standardized for biomarkers curcumin, gallic acid, tannic acid, chebulagic acid, and berberine. In male wistar rats, neurodegeneration was induced by administration of intracerebroventricular Amyloid ß (Aß1-42). The effect of KG (oral and intranasal treatment) was evaluated through behavioral parameters such as Morris water maze, social recognition test, novel object recognition, locomotor activity, and molecular parameters, brain acetylcholinesterase, brain-derived neurotrophic factor (BDNF), inflammatory cytokines, oxidative stress markers, and antioxidants. Brain histopathology was performed for studying the architecture of the brain and plaque formation. RESULTS AND DISCUSSION: A novel HPLC method has been developed for the standardization of KG. Treatment with KG significantly improved cognition and memory and increased brain BDNF and antioxidant status in Aß1-42 induced rats. It also reduced brain acetylcholinesterase, oxidative stress, and inflammatory cytokines and prevented neuronal damage. There were more marked effects with intra-nasal administration compared to oral treatment. CONCLUSION: The findings suggest that KG has neuroprotective potential and along with its nootropic property could be a promising therapy for neurodegenerative diseases like Alzheimer's disease.


Assuntos
Doença de Alzheimer , Berberina , Curcumina , Fármacos Neuroprotetores , Nootrópicos , Acetilcolinesterase , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/toxicidade , Animais , Antioxidantes , Berberina/farmacologia , Fator Neurotrófico Derivado do Encéfalo , Curcumina/farmacologia , Citocinas/farmacologia , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Nootrópicos/farmacologia , Ratos , Ratos Wistar , Taninos/farmacologia
2.
J Ethnopharmacol ; 301: 115803, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36216194

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Commelina benghalensis Linn is a perennial plant with upright stems reaching a height of 1 m. Its stem is commonly used to induce abortion in traditional medicine. However, there are insignificant scientific data to evaluate such a claim. AIM OF THE STUDY: The study was conducted to determine the abortifacient and toxicological potential of ethanol extract of Commelina benghalensis Linn stem (EECBS) via selected proinflammatory and oxidative stress biomarkers in pregnant Wistar rats. MATERIALS AND METHODS: To determine the phytochemicals responsible for EECBS's toxicity and abortifacient effects, high-performance liquid chromatography-photodiode array detection (HPLC-PDA) and gas chromatography-mass spectrometry (GC-MS) was used. The abortion rate was determined by monitoring the markers of reproductive system failure in the experimental model. To assess rat hepatotoxicity, biochemical markers and immunohistopathological parameters were used. RESULTS: Results demonstrated the presence of isomeric benzene-mesitylene compounds in EECBS. Also, EECBS significantly altered the markers of liver function and oxidative damage while eliciting a significantly reduced (P < 0.05) number of live fetuses, number of corpora lutea, progesterone, estradiol, and luteinizing hormone, whereas the number of dead fetuses percentage vaginal opening, and post-implantation loss increased significantly (P < 0.05). Estrogenicity studies indicated a significant (P < 0.05) increase in uterine weight, uterine glucose, and ALP dose-dependently. Moreover, EECBS also caused a vaginal hemorrhage preceding the parturition. Also, EECBS treatment significantly increased levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and significantly elevated the expression of COX-2 protein in the liver. CONCLUSION: The current investigation established Commelina benghalensis Linn stem's abortifacient activity. Continuous use, on the other hand, may cause liver damage in pregnant rats by disrupting antioxidant defense mechanisms, promoting the production of pro-inflammatory cytokines, and increasing COX-2 expression. Hence, caution should be excised while consuming this plant's stem for medication purposes, especially during the gestational period.


Assuntos
Abortivos , Doença Hepática Induzida por Substâncias e Drogas , Commelina , Animais , Feminino , Humanos , Gravidez , Ratos , Abortivos/toxicidade , Commelina/química , Ciclo-Oxigenase 2 , Citocinas/farmacologia , Judeus , Estresse Oxidativo , Extratos Vegetais/toxicidade , Ratos Wistar
3.
J Environ Sci (China) ; 124: 481-490, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36182156

RESUMO

Triclosan (TCS) is a ubiquitous antimicrobial used in daily consumer products. Previous reports have shown that TCS could induce hepatotoxicity, endocrine disruption, disturbance on immune function and impaired thyroid function. Kidney is critical in the elimination of toxins, while the effects of TCS on kidney have not yet been well-characterized. The aim of the present study was to investigate the effects of TCS exposure on kidney function and the possible underlying mechanisms in mice. Male C57BL/6 mice were orally exposed to TCS with the doses of 10 and 100 mg/(kg•day) for 13 weeks. TCS was dissolved in dimethyl sulfoxide (DMSO) and diluted by corn oil for exposure. Corn oil containing DMSO was used as vehicle control. Serum and kidney tissues were collected for study. Biomarkers associated with kidney function, oxidative stress, inflammation and fibrosis were assessed. Our results showed that TCS could cause renal injury as was revealed by increased levels of renal function markers including serum creatinine, urea nitrogen and uric acid, as well as increased oxidative stress, pro-inflammatory cytokines and fibrotic markers in a dose dependent manner, which were more significantly in 100 mg/(kg•day) group. Mass spectrometry-based analysis of metabolites related with lipid metabolism demonstrated the occurrence of lipid accumulation and defective fatty acid oxidation in 100 mg/(kg•day) TCS-exposed mouse kidney. These processes might lead to lipotoxicity and energy depletion, thus resulting in kidney fibrosis and functional decline. Taken together, the present study demonstrated that TCS could induce lipid accumulation and fatty acid metabolism disturbance in mouse kidney, which might contribute to renal function impairment. The present study further widens our insights into the adverse effects of TCS.


Assuntos
Anti-Infecciosos , Transtornos do Metabolismo dos Lipídeos , Triclosan , Animais , Óleo de Milho/metabolismo , Óleo de Milho/farmacologia , Creatinina/metabolismo , Creatinina/farmacologia , Citocinas/metabolismo , Citocinas/farmacologia , Dimetil Sulfóxido/metabolismo , Dimetil Sulfóxido/farmacologia , Ácidos Graxos/metabolismo , Fibrose , Rim/metabolismo , Metabolismo dos Lipídeos , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Transtornos do Metabolismo dos Lipídeos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nitrogênio/metabolismo , Triclosan/toxicidade , Ureia , Ácido Úrico/metabolismo , Ácido Úrico/farmacologia
4.
Front Immunol ; 13: 1027064, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330527

RESUMO

Aflatoxin B1 (AFB1) is kind of a common mycotoxin in food and feedstuff. Aquafeeds are susceptible to contamination of AFB1. In teleost fish, the spleen and head kidney are key immune organ. Moreover, the fish skin is a critical mucosal barrier system. However, there was little study on the effects of dietary AFB1 on the immune response of these immune organs in fish. This study aimed to explore the impacts of oral AFB1 on the immune competence and its mechanisms in the skin, spleen, and head kidney of grass carp. Our work indicated that dietary AFB1 reduced antibacterial compounds and immunoglobulins contents, and decreased the transcription levels of antimicrobial peptides in grass carp immune organs. In addition, dietary AFB1 increased the transcription levels of pro-inflammatory cytokines and reduced the transcription levels of anti-inflammatory cytokines in the grass carp immune organs, which might be regulated by NF-κB and TOR signaling, respectively. Meanwhile, we evaluated the content of AFB1 in the grass carp diet should not exceed 29.48 µg/kg diet according to the levels of acid phosphatase and lysozyme. In summary, dietary AFB1 impaired immune response in grass carp skin, spleen, and head kidney.


Assuntos
Carpas , Doenças dos Peixes , Infecções por Bactérias Gram-Negativas , Animais , Aeromonas hydrophila/fisiologia , NF-kappa B , Aflatoxina B1/toxicidade , Imunidade Inata , Ração Animal/análise , Dieta , Transdução de Sinais , Citocinas/farmacologia
5.
Int J Mol Sci ; 23(21)2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36361533

RESUMO

The ex vivo expansion and maintenance of long-term hematopoietic stem cells (LT-HSC) is crucial for stem cell-based gene therapy. A combination of stem cell factor (SCF), thrombopoietin (TPO), FLT3 ligand (FLT3) and interleukin 3 (IL3) cytokines has been commonly used in clinical settings for the expansion of CD34+ from different sources, prior to transplantation. To assess the effect of IL3 on repopulating capacity of cultured CD34+ cells, we employed the commonly used combination of STF, TPO and FILT3 with or without IL3. Expanded cells were transplanted into NSG mice, followed by secondary transplantation. Overall, this study shows that IL3 leads to lower human cell engraftment and repopulating capacity in NSG mice, suggesting a negative effect of IL3 on HSC self-renewal. We, therefore, recommend omitting IL3 from HSC-based gene therapy protocols.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Interleucina-3 , Animais , Humanos , Camundongos , Antígenos CD34 , Células Cultivadas , Citocinas/farmacologia , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas , Interleucina-3/farmacologia , Fator de Células-Tronco/farmacologia , Trombopoetina/farmacologia
6.
Arthritis Res Ther ; 24(1): 254, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397156

RESUMO

BACKGROUND: EC-18, a synthetic monoacetyldiaglyceride, exhibits protective effects against lung inflammation, allergic asthma, and abdominal sepsis. However, there have been no investigations to determine whether EC-18 has preventive potential in autoimmune diseases, especially rheumatoid arthritis (RA). METHODS: To investigate the efficacy of EC-18 on the development of RA, EC-18 was administered in a collagen-induced arthritis (CIA) murine model and disease severity and the level of inflammatory cytokines in the joint were investigated. The effect of EC-18 on the inflammation-related factors was investigated by flow cytometry, ELISA, western blot, and real-time PCR in splenocytes from mice and in peripheral blood mononuclear cells from healthy and patients with RA. The effect of EC-18 on osteoclastogenesis was investigated. RESULTS: EC-18 effectively reduced the clinical and histological severity of arthritis, similar to Janus kinase inhibitors include tofacitinib and baricitinib, in CIA. Furthermore, EC-18 exhibited a synergistic effect with methotrexate in preventing CIA. Treatment with EC-18 effectively reduced the production of inflammatory cytokines in immune cells and osteoclast differentiation in mice and patients with RA. CONCLUSION: These results suggest that EC-18 may be an effective strategy for RA.


Assuntos
Artrite Experimental , Artrite Reumatoide , Camundongos , Animais , Osteogênese , Citocinas/farmacologia , Leucócitos Mononucleares/patologia , Artrite Reumatoide/tratamento farmacológico
7.
Viruses ; 14(11)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36366477

RESUMO

Yellow fever (YF) may cause lesions in different organs. There are no studies regarding the in situ immune response in the human lung and investigating immunopathological aspects in fatal cases can help to better understand the evolution of the infection. Lung tissue samples were collected from 10 fatal cases of human yellow fever and three flavivirus-negative controls who died of other causes and whose lung parenchymal architecture was preserved. In YFV-positive fatal cases, the main histopathological changes included the massive presence of diffuse alveolar inflammatory infiltrate, in addition to congestion and severe hemorrhage. The immunohistochemical analysis of tissues in the lung parenchyma showed significantly higher expression of E-selectin, P-selectin, ICAM-1, VCAM-1 in addition to cytokines such as IL-4, IL-10, IL-13, TNF- α, IFN-γ and TGF-ß compared to the negative control. The increase in immunoglobulins ICAM-1 and VCAM-1 results in strengthening of tissue transmigration signaling. E-selectin and P-selectin actively participate in this process of cell migration and formation of the inflammatory infiltrate. IFN-γ and TNF-α participate in the process of cell injury and viral clearance. The cytokines IL-4 and TGF-ß, acting in synergism, participate in the process of tissue regeneration and breakdown. The anti-inflammatory cytokines IL-4, IL-10 and IL-13 also act in the reduction of inflammation and tissue repair. Our study indicates that the activation of the endothelium aggravates the inflammatory response by inducing the expression of adhesion molecules and cytokines that contribute to the rolling, recruitment, migration and eliciting of the inflammatory process in the lung parenchyma, contributing to the fatal outcome of the disease.


Assuntos
Molécula 1 de Adesão Intercelular , Febre Amarela , Humanos , Molécula 1 de Adesão de Célula Vascular/análise , Molécula 1 de Adesão de Célula Vascular/metabolismo , Interleucina-13 , Interleucina-10 , Interleucina-4 , Citocinas/farmacologia , Endotélio/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Pulmão/metabolismo , Fator de Crescimento Transformador beta
8.
Biomed Res Int ; 2022: 2369650, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36193302

RESUMO

Conventional breeding of wild (Cucumis melo var. makuwa Makino (CM)) and cultivated (Cucumis melo var. reticulatus (CR)) melons is aimed at improving their biological traits. Here, we prepared a nontoxic, bioactive extract of vitalmelon (F1 hybrid) and evaluated its antiadipogenic and antiobesity effects in fully differentiated 3T3-L1 adipocytes and high-fat diet- (HFD-) induced obese C57BL/6 mice. In fully differentiated 3T3-L1 adipocytes, the vitalmelon extract reduced the DMI- (dexamethasone, 3-isobutyl-1-methylxanthine, and insulin-) induced increases in lipid droplet number and intracellular glucose and triglyceride levels. In addition, the extract inhibited 3T3-L1 preadipocyte differentiation by downregulating PPAR-γ and target genes LPL, CD36, HMGCR, and L-FABP. To investigate the inhibitory effects of the vitalmelon extract on lipid metabolism, we measured serum lipid, hormone, and cytokine concentrations; lipolytic activity; lipid accumulation; and adipogenesis in HFD-fed mice treated with the extract. The HFD+vitalmelon-fed mice showed lower blood cholesterol, free fatty acid, sugar, leptin, and insulin concentrations but higher blood adiponectin concentrations than the HFD-fed mice. Moreover, the HFD+vitalmelon-fed mice showed lower abdominal fat levels, smaller fat cells, lower weight, and fewer lipid droplets in the liver tissue than the HFD-fed mice. Therefore, in HFD-fed mice, vitalmelon regulated lipid metabolism through PPAR-γ, highlighting its potential as a promising antiobesity functional food.


Assuntos
Adipogenia , Fármacos Antiobesidade , 1-Metil-3-Isobutilxantina/farmacologia , Células 3T3-L1 , Adiponectina/farmacologia , Animais , Fármacos Antiobesidade/farmacologia , Colesterol , Citocinas/farmacologia , Dexametasona/farmacologia , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos não Esterificados , Frutas/metabolismo , Glucose/farmacologia , Insulina , Leptina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , PPAR gama/metabolismo , Extratos Vegetais/farmacologia , Açúcares , Triglicerídeos
9.
Front Immunol ; 13: 1018047, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36203567

RESUMO

The current global platelet supply is often insufficient to meet all the transfusion needs of patients, in particular for those with alloimmune thrombocytopenia. To address this issue, we have developed a strategy employing a combination of approaches to achieve more efficient production of functional megakaryocytes (MKs) and platelets collected from cord blood (CB)-derived CD34+ hematopoietic cells. This strategy is based on ex-vivo expansion and differentiation of MKs in the presence of bone marrow niche-mimicking mesenchymal stem cells (MSCs), together with two other key components: (1) To enhance MK polyploidization, we used the potent pharmacological Rho-associated coiled-coil kinase (ROCK) inhibitor, KD045, resulting in liberation of increased numbers of functional platelets both in-vitro and in-vivo; (2) To evade HLA class I T-cell-driven killing of these expanded MKs, we employed CRISPR-Cas9-mediated ß-2 microglobulin (ß2M) gene knockout (KO). We found that coculturing with MSCs and MK-lineage-specific cytokines significantly increased MK expansion. This was further increased by ROCK inhibition, which induced MK polyploidization and platelet production. Additionally, ex-vivo treatment of MKs with KD045 resulted in significantly higher levels of engraftment and donor chimerism in a mouse model of thrombocytopenia. Finally, ß2M KO allowed MKs to evade killing by allogeneic T-cells. Overall, our approaches offer a novel, readily translatable roadmap for producing adult donor-independent platelet products for a variety of clinical indications.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Trombocitopenia , Animais , Citocinas/farmacologia , Sangue Fetal , Megacariócitos , Camundongos , Linfócitos T , Quinases Associadas a rho
10.
Sci Rep ; 12(1): 16800, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36207368

RESUMO

De novo hepatitis B virus (HBV) reactivation occurs during direct-acting antiviral (DAA) treatment in hepatitis C virus (HCV)-infected patients with resolved HBV infection. We evaluated the predictive factors, mechanical insight, and differences of cytokine levels during anti-cancer/immunosuppressive and DAA. Eleven, 35, and 19 HCV-infected patients with previous HBV infection with HBV reactivation during DAA treatment, previous HBV infection without HBV reactivation during DAA treatment, and without HBV infection resolution receiving DAA treatment, respectively, were enrolled. Clinical data and baseline cytokine levels were analyzed. Low baseline serum interleukin (IL)-1ß levels predicted de novo HBV reactivation during DAA treatment (odds ratio: 47.6, 95% confidence interval: 6.94-333.3). HCV-infected patients with the IL-1ß gene single nucleotide polymorphism rs16944 AA allele had significantly higher IL-1ß levels; no HCV-infected patient with the IL-1ß AA allele experienced HBV reactivation during DAA treatment. Compared to HCV-infected patients with HBV infection resolution, non-HCV infected patients with or without HBV reactivation during anti-cancer/immunosuppressive therapy or bone marrow transplantation had remarkably lower baseline IL-1ß levels. Low IL-1ß levels were not associated with HBV reactivation. IL-1ß levels before DAA for HCV-infected patients with resolved HBV infection could predict HBV reactivation during DAA treatment.


Assuntos
Antineoplásicos/uso terapêutico , Coinfecção , Hepatite B , Hepatite C Crônica , Hepatite C , Interleucina-1beta/sangue , Antivirais , Citocinas/farmacologia , Hepacivirus/genética , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Hepatite B/genética , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/genética , Hepatite C Crônica/tratamento farmacológico , Humanos , Terapia de Imunossupressão , Interleucinas/farmacologia , Ativação Viral
11.
Biomed Pharmacother ; 155: 113773, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36271555

RESUMO

Influenza A virus (IAV) continues to threaten human health. To date, two classes of antiviral drugs have been approved to treat IAV infection, but the continuous emergence of the drug-resistant IAV mutant reinforces the need to develop new antiviral drugs. In this study, we aimed to investigate the anti-IAV activity of an aqueous mixture of Agrimonia pilosa and Galla rhois extracts (APRG64). We demonstrated that APRG64 significantly reduced the IAV-induced cytopathic effect, the transcription/expression of viral proteins, and the production of infectious viral particles. Among nine major components of APRG64, apigenin was identified as the main ingredient responsible for the anti-IAV activity. Interestingly, APRG64 and apigenin inhibited the cell attachment and entry of virus and polymerase activity. Importantly, intranasal administration of APRG64 or apigenin strongly reduced viral loads in the lungs of IAV-infected mice. Furthermore, oral administration of APRG64 significantly reduced the level of viral RNAs and the expression level of pro-inflammatory cytokines in the lungs, which protected mice from IAV-induced mortality. In conclusion, APRG64 could be an attractive antiviral drug to treat IAV infection.


Assuntos
Agrimonia , Vírus da Influenza A , Influenza Humana , Humanos , Camundongos , Animais , Apigenina/farmacologia , Antivirais/farmacologia , Extratos Vegetais/farmacologia , Proteínas Virais , Citocinas/farmacologia , Replicação Viral
12.
Int J Mol Sci ; 23(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36232495

RESUMO

Head trauma is the most common cause of disability in young adults. Known as a silent epidemic, it can cause a mosaic of symptoms, whether neurological (sensory-motor deficits), psychiatric (depressive and anxiety symptoms), or somatic (vertigo, tinnitus, phosphenes). Furthermore, cranial trauma (CT) in children presents several particularities in terms of epidemiology, mechanism, and physiopathology-notably linked to the attack of an immature organ. As in adults, head trauma in children can have lifelong repercussions and can cause social and family isolation, difficulties at school, and, later, socio-professional adversity. Improving management of the pre-hospital and rehabilitation course of these patients reduces secondary morbidity and mortality, but often not without long-term disability. One hypothesized contributor to this process is chronic neuroinflammation, which could accompany primary lesions and facilitate their development into tertiary lesions. Neuroinflammation is a complex process involving different actors such as glial cells (astrocytes, microglia, oligodendrocytes), the permeability of the blood-brain barrier, excitotoxicity, production of oxygen derivatives, cytokine release, tissue damage, and neuronal death. Several studies have investigated the effect of various treatments on the neuroinflammatory response in traumatic brain injury in vitro and in animal and human models. The aim of this review is to examine the various anti-inflammatory therapies that have been implemented.


Assuntos
Lesões Encefálicas Traumáticas , Inflamação , Animais , Encéfalo/patologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Criança , Citocinas/farmacologia , Modelos Animais de Doenças , Humanos , Inflamação/complicações , Microglia , Oxigênio/farmacologia
13.
Int J Mol Sci ; 23(19)2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36232676

RESUMO

Intraocular pressure (IOP) is considered an important modifiable risk factor for glaucoma, which is known as the second leading cause of blindness worldwide. However, lowering the IOP is not always sufficient to preserve vision due to other non-IOP-dependent mechanisms being involved. To improve outcomes, adjunctive therapies with IOP-independent targets are required. To date, no studies have shown the effect of citicoline on the trabecular meshwork (TM), even though it is known to possess neuroprotective/enhancement properties and multifactorial mechanisms of action. Given that reactive oxygen species seem to be involved in glaucomatous cascade, in this present study, an advanced millifluidic in vitro model was used to evaluate if citicoline could exert a valid TM protection against oxidative stress. To this end, the cellular behavior, in terms of viability, apoptosis, mitochondrial state, senescence and pro-inflammatory cytokines, on 3D human TM cells, treated either with H2O2 alone or cotreated with citicoline, was analyzed. Our preliminary in vitro results suggest a counteracting effect of citicoline eye drops against oxidative stress on TM cells, though further studies are necessary to explore citicoline's potential as a TM-target therapy.


Assuntos
Glaucoma , Malha Trabecular , Citidina Difosfato Colina/farmacologia , Citocinas/farmacologia , Glaucoma/tratamento farmacológico , Humanos , Peróxido de Hidrogênio/farmacologia , Pressão Intraocular , Soluções Oftálmicas/farmacologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/farmacologia
14.
Int J Mol Sci ; 23(19)2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36232768

RESUMO

Antibiotics are broadly restricted in modern husbandry farming, necessitating the need for efficient and low-cost immunomodulatory preparations in antibiotic-free and healthful farming. As is known to all, CpG oligonucleotides (CpG-ODNs, an effective innate immunostimulatory agent) recognized by TLR9 in mammals (while TLR21 in avians) could collaborate with some united agent to induce stronger immune responses, but the cost is prohibitively expensive for farmers. Here, considering the coordination between TLR2 and TLR9/TLR21, we firstly proposed the idea that the well-fermented Lactococcus lactis could be utilized as a CpG-plasmid carrier (LACpG10) to enhance the host's innate immunity against pathogenic invasion. In the present study, after obtaining LACpG10-HL from homogenized and lyophilized recombinant strain LACpG10, we treated primary chicken lymphocytes, two cell lines (HD11 and IPEC-J2), and chickens with LACpG10-HL, CpG plasmids (pNZ8148-CpG10), and other stimulants, and respectively confirmed the effects by conducting qRT-PCR, bacterial infection assays, and a zoological experiment. Our data showed that LACpG10-HL could induce excellent innate immunity by regulating autophagy reactions, cytokine expression, and motivating PRRs. Interestingly, despite having no direct antiseptic effect, LACpG10-HL improved the antibacterial capacities of lymphocytes and enterocytes at the first line of defense. Most importantly, water-supplied LACpG10-HL treatment reduced the average adverse event rates, demonstrating that LACpG10-HL maintained its excellent immunostimulatory and protective properties under farming conditions. Our research not only contributes to revealing the satisfactory effects of LACpG10-HL but also sheds new light on a cost-effective solution with optimal immune effects in green, antibiotic-free, and healthful husbandry farming.


Assuntos
Anti-Infecciosos Locais , Receptor Toll-Like 9 , Adjuvantes Imunológicos/farmacologia , Animais , Antibacterianos/farmacologia , Anti-Infecciosos Locais/farmacologia , Galinhas/metabolismo , Citocinas/farmacologia , Imunidade Inata , Mamíferos/metabolismo , Oligodesoxirribonucleotídeos/farmacologia , Receptor 2 Toll-Like , Receptor Toll-Like 9/metabolismo , Água/farmacologia
15.
Food Funct ; 13(22): 11811-11824, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36306140

RESUMO

Gastrointestinal dysfunction is associated with a disturbance of immune homeostasis, changes in the intestinal microbiome, alteration of the composition of the bile acid pool, and dynamic imbalance of group 3 innate lymphoid cells (ILC3s). Curcumin (CUR), a polyphenolic compound isolated from turmeric, has been known to attenuate intestinal inflammation in potential therapies for gastrointestinal diseases. It was hypothesized that CUR could target the gut microbiome to modulate bile acid (BA) metabolism and the function of ILC3s in ameliorating lipopolysaccharide (LPS)-induced imbalance of intestinal homeostasis in chickens. Seven hundred and twenty 1-day-old crossbred chickens were randomly divided into four treatments, namely CON_saline (basal diet + saline control), CUR_saline (basal diet + 300 mg kg-1 curcumin + saline), CON_LPS (basal diet + LPS), and CUR_LPS (basal diet + 300 mg kg-1 curcumin + LPS), each consisting of 6 replicates of 30 birds. On days 14, 17, and 21, the chickens in the CON_LPS and CUR_LPS treatments were intraperitoneally injected with LPS at 0.5 mg per kg BW. Dietary CUR supplementation significantly decreased LPS-induced suppression of growth performance and injury to the intestinal tight junctions and decreased the vulnerability to LPS-induced acute inflammatory response by inhibiting pro-inflammatory (interleukin-1ß and tumor necrosis factor-α) cytokines. CUR reshaped the cecal microbial community and BA metabolism, contributing to regulation of the intestinal mucosal immunity by promoting the anti-inflammatory (interleukin 10, IL-10) cytokines and enhancing the concentrations of primary and secondary BA metabolites (chenodexycholic acid, lithocholic acid). LPS decreased farnesoid X receptor (FXR) and G protein-coupled receptor class C group 5 member A synthesis, which was reversed by CUR administration, along with an increase in interleukin 22 (IL-22) production from ILC3s. Dietary supplementation of CUR increased the prevalence of Butyricicoccus and Enterococcus and enhanced the tricarboxylic acid cycle of intestinal epithelial cells. In addition, curcumin supplementation significantly increased sirtuin 1 and sirtuin 5 transcription and protein expression, which contributes to regulating mitochondrial metabolic and oxidative stress responses to alleviate LPS-induced enteritis. Our findings demonstrated that curcumin played a pivotal role in regulating the structure of the intestinal microbiome for health promotion and the treatment of intestinal dysbiosis. The beneficial effects of CUR may be attributed to the modulation of the BA-FXR pathway and inhibition of inflammation that induces IL-22 secretion by ILC3s in the intestinal lamina propria.


Assuntos
Curcumina , Microbioma Gastrointestinal , Animais , Ácidos e Sais Biliares/farmacologia , Galinhas/fisiologia , Curcumina/farmacologia , Citocinas/genética , Citocinas/farmacologia , Homeostase , Imunidade Inata , Inflamação/induzido quimicamente , Lipopolissacarídeos/efeitos adversos , Linfócitos
16.
Assay Drug Dev Technol ; 20(7): 300-316, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36269233

RESUMO

Propolis is rich in natural bioactive compounds, and considering its importance for many skin therapies, emulgel was prepared. This study examines how a propolis extract (PE) and Passiflora edulis seed (PS) oil emulgel affect rat deep skin wound healing. Based on preset criteria of maximum drug content and optimum drug permeation through the stratum corneum along with drug retention in the skin layers, an optimized emulgel formula based on Box-Behnken factorial design was prepared and used for subsequent in vitro and in vivo evaluations. In vivo wound-healing activities of emulgel and control treatments were investigated in a rat model. The optimized emulgel formula exhibited superior healing activity compared with plain PE suspension-treated rats on day 14 of wounding. Histopathological investigations of hematoxylin and eosin and Masson's Trichrome-stained skin sections supported this effect. Emulgel promotes cutaneous wound healing through a variety of mechanisms, including anti-inflammatory through modulation of cytokines tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 production, and promotion of collagen fiber formation, all of which contribute to tissue remodeling. Furthermore, when compared with propolis suspension, emulgel showed significant antioxidant and anti-inflammatory effects. Emulgel significantly increased the skin's hydroxyproline level, antioxidant potential, wound contraction, increased penetration, and localized propolis deposition across the skin. Incorporation of PS oil into the emulgel accelerates the tissue regeneration process. The findings suggest that 5% propolis emulgel could be used as an alternative to treat wounds.


Assuntos
Passiflora , Própole , Cicatrização , Animais , Ratos , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Colágeno/metabolismo , Colágeno/farmacologia , Citocinas/metabolismo , Citocinas/farmacologia , Amarelo de Eosina-(YS)/farmacologia , Hematoxilina/farmacologia , Hidroxiprolina/farmacologia , Interleucina-6/farmacologia , Passiflora/química , Passiflora/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Óleos Vegetais/farmacologia , Óleos Vegetais/uso terapêutico , Própole/farmacologia , Própole/uso terapêutico , Fator de Necrose Tumoral alfa/farmacologia , Cicatrização/efeitos dos fármacos
17.
Biochem Biophys Res Commun ; 631: 102-109, 2022 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-36183550

RESUMO

Radiation-induced intestinal injury (RIII) is one of the most common abdominal and pelvic radiation therapy complications. RIII seriously affects the treatment and prognosis of cancer patients, and there are no effective interventions. Radiation can cause intestinal tissue damage, inflammatory cell infiltration, and pro-inflammatory cytokine release. We established an RIII mouse model by subjecting C57BL/6 mice to abdominal irradiation. Our results show that both pyroptosis and ferroptosis play a key role in RIII. VX-765 and Ferrostatin-1 (Fer-1) can inhibit these two types of programmed cell death and ameliorate RIII, respectively. Activation of the nuclear factor-κB (NF-κB) signaling pathway exacerbates the chemotaxis of inflammatory cells. In the present study, we hypothesized that the activation of NF-κB signaling pathway plays an important role in intestinal inflammatory injury. We demonstrated that the nuclear expression levels of the NF-κB subunit p65 increased after irradiation treatment. Reduced release of inflammatory factors and intestinal tissue damage was observed after pretreatment with pyrrolidinedithiocarbamate ammonium (PDTC). Moreover, after PDTC treatment, the indicators related to pyroptosis and ferroptosis were reversed. Collectively, these results suggest that the activation of the intestinal NF-κB signaling pathway may be associated with pyroptosis, ferroptosis, and subsequent intestinal injury after irradiation.


Assuntos
Compostos de Amônio , Ferroptose , Lesões por Radiação , Animais , Citocinas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Prolina/análogos & derivados , Piroptose , Pirrolidinas , Tiocarbamatos
18.
Rev. esp. quimioter ; 35(Supl. 3): 6-9, Oct. 2022. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-210739

RESUMO

In response to SARS-CoV-2 infection, the immune system physiologically upregulates to try to clear the virus from the body; failure to compensate for this inflammatory response with an anti-inflammatory response leads to dysregulation of the immune system that ultimately leads to a situation of uncontrolled hyperinflammation called cytokine storm. This cytokine storm can cause ARDS or multi-organ failure leading to patient death. This review exposes the different mechanisms of the inflammatory response in COVID-19 infection and the therapeutic options to treat this process. (AU)


Assuntos
Humanos , Pandemias , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/complicações , Vírus da SARS , Citocinas/farmacologia , Anti-Inflamatórios/uso terapêutico
19.
Front Immunol ; 13: 1036821, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311806

RESUMO

Taurine has various biological functions in fish, playing an essential role in growth, resistance to oxidative stress, and intestine immunity. Here, we evaluated the effects of exogenous taurine added to low-fishmeal diets on the growth, anti-oxidative stress, intestine immunity, and Streptococcus agalactiae resistance in juvenile golden pompano (Trachinotus ovatus). Our study showed that exogenous taurine supplementation of 1.2% (T3 group) greatly enhanced the weight gain rate and specific growth rate (SGR) of juvenile golden pompano, significantly upregulating growth-related factor expression in the brain and liver, as well as the levels of growth-related parameters in the serum. Polynomial regression analysis using SGR estimated the optimal dietary taurine level for golden pompano at 1.18%. Moderate exogenous taurine also increased the muscular thickness and villus length within the intestine, maintained intestinal physical barrier stability, activated the Nrf2/Keap-1/HO-1 signaling pathway, increased intestinal antioxidant enzyme gene expression and antioxidant enzyme activity in the serum, and upregulated immunoglobulin and complement levels in parallel with declining reactive oxygen species (ROS) levels in the serum. Antioxidant factor expression was also upregulated in the intestine. Furthermore, supplementation suppressed NF-κB signaling and intestinal pro-inflammatory cytokine gene expression, increased anti-inflammatory cytokine gene expression, and improved intestine immunity. Finally, taurine supplementation improved the survival rate of golden pompano challenged with S. agalactiae. Overall, our findings provide additional information and support for the rational use of taurine in healthy aquatic animal farming.


Assuntos
Antioxidantes , Perciformes , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Streptococcus agalactiae , Ração Animal/análise , Perciformes/genética , Suplementos Nutricionais/análise , Taurina/farmacologia , Imunidade Inata , Dieta/veterinária , Peixes/metabolismo , Intestinos , Citocinas/farmacologia
20.
Biochem Pharmacol ; 205: 115287, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36209839

RESUMO

The increased resistance of human malaria parasite Plasmodium falciparum (Pf) to currently used drugs necessities the development of novel anti-malarials. Here, we examine the potential of erythritol, a sugar substitute for therapeutic intervention. Erythritol is a permeant of Plasmodium falciparum aquaglyceroporin (PfAQP) which is a multifunctional channel responsible for maintaining hydro-homeostasis. We show that erythritol effectively inhibited growth and progression of asexual blood stage malaria parasite, and effect invasion and egress processes. It also inhibited the liver stage (sporozoites) and transmission stage parasite (gametocytes) development. Interestingly, erythritol inhibited in vivo growth of malaria parasite in mouse experimental model. It was more effective in inhibiting parasite growth both in vivo and in vitro when tested together with a known anti-malarial 'artesunate'. Additionally, erythritol showed cytokine-modulating effect which suggests its direct effect on the host immune system. Ammonia detection assay demonstrated that erythritol uptake effects the amount of ammonia release across the parasite. Our functional complementation assays suggest that PfAQP expression in yeast mutant restores its growth in hyperosmotic conditions but showed reduced growth in the presence of erythritol. Osmotic lysis assay suggests that erythritol creates osmotic stress for killing the parasite. Overall, our data bestow erythritol as a promising lead compound with an attractive antimalarial profile and could possibly be combined with known drugs without losing its efficacy. We propose the use of erythritol based sweet candies for protection against malaria specially in children living in the endemic area.


Assuntos
Antimaláricos , Aquagliceroporinas , Criança , Camundongos , Humanos , Animais , Antimaláricos/farmacologia , Plasmodium falciparum , Aquagliceroporinas/farmacologia , Eritritol/farmacologia , Edulcorantes , Amônia/farmacologia , Citocinas/farmacologia
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