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1.
J Immunol Res ; 2024: 6817965, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962578

RESUMO

Therapeutic vaccines based on monocyte-derived dendritic cells have been shown to be promising strategies and may act as complementary treatments for viral infections, cancers, and, more recently, autoimmune diseases. Alpha-type-1-polarized dendritic cells (aDC1s) have been shown to induce type-1 immunity with a high capacity to produce interleukin-12p70 (IL-12p70). In the clinical use of cell-based therapeutics, injectable solutions can affect the morphology, immunophenotypic profile, and viability of cells before delivery and their survival after injection. In this sense, preparing a cell suspension that maintains the quality of aDC1s is essential to ensure effective immunotherapy. In the present study, monocytes were differentiated into aDC1s in the presence of IL-4 and GM-CSF. On day 5, the cells were matured by the addition of a cytokine cocktail consisting of IFN-α, IFN-γ, IL-1ß, TNF-α, and Poly I:C. After 48 hr, mature aDC1s were harvested and suspended in two different solutions: normal saline and Ringer's lactate. The maintenance of cells in suspension was evaluated after 4, 6, and 8 hr of storage. Cell viability, immunophenotyping, and apoptosis analyses were performed by flow cytometry. Cellular morphology was observed by electron microscopy, and the production of IL-12p70 by aDC1s was evaluated by ELISA. Compared with normal saline, Ringer's lactate solution was more effective at maintaining DC viability for up to 8 hr of incubation at 4 or 22°C.


Assuntos
Diferenciação Celular , Sobrevivência Celular , Células Dendríticas , Imunoterapia , Interleucina-12 , Monócitos , Células Dendríticas/imunologia , Humanos , Monócitos/imunologia , Imunoterapia/métodos , Sobrevivência Celular/efeitos dos fármacos , Interleucina-12/metabolismo , Imunofenotipagem , Citocinas/metabolismo , Células Cultivadas , Apoptose , Injeções
2.
Zhonghua Gan Zang Bing Za Zhi ; 32(6): 517-524, 2024 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-38964894

RESUMO

Objective: To measure the overall and lobulated volume of the liver with different degrees of liver fibrosis and to further observe pathological changes such as liver microvasculature, hepatocyte apoptosis, and regeneration in order to understand the macroscopic volume changes of the liver during liver fibrosis and its relationship with liver tissue microscopic pathology in patients with chronic liver disease. Methods: 53 patients with chronic hepatitis B, alcoholic fatty liver disease, autoimmune liver disease, nonalcoholic fatty liver disease, and drug-induced chronic liver disease who underwent both liver biopsy tissue and abdominal magnetic resonance imaging were collected. Patients were divided into early (F1-2), middle (F3-4), and late (F5-6) in accordance with the Ishak fibrosis stage and Masson stain. The liver and spleen volumes were measured using ITK-SNAP software. CD31 immunohistochemical staining was used to reflect intrahepatic angiogenesis. Ki67 and HNF-4α multiplex immunohistochemical staining were used to reflect hepatocyte regeneration. GS staining was used to determine parenchymal extinction lesions. TUNEL staining was used to observe hepatocyte apoptosis. Spearman correlation analysis was used to analyze the relationship between liver volume changes and liver histopathological changes. Results: As liver fibrosis progressed, the total liver volume and right lobe liver volume gradually decreased (P<0.05), while the spleen volume gradually increased (P<0.05). The expression of CD31 and GS gradually increased (P<0.05), and the expression of Ki67 first increased and then decreased (P<0.05). The positivity rate of CD31 was negatively correlated with the right lobe liver volume (r=-0.609, P<0.001) and the total liver volume (r=-0.363, P=0.017). The positivity rate of Ki67 was positively correlated with the right lobe liver volume (r=0.423, P=0.018), while the positivity rate of apoptotic cells was significantly negatively correlated with the total liver volume (r=-0.860, P<0.001). The positivity rate of GS was negatively correlated with the right lobe liver volume (r=-0.440, P=0.002), and the number of PELs was negatively correlated with RV (r=-0.476, P=0.013). The CD31 positive staining area was negatively correlated with the Ki67 positive staining area(r=-0.511, P=0.009). Conclusion: As liver fibrosis progresses, patients with chronic liver disease have a depletion in total liver volume and right lobe liver volume, and this is mainly in correlation with fewer liver cells and liver tissue microvasculature disorders.


Assuntos
Cirrose Hepática , Fígado , Humanos , Cirrose Hepática/patologia , Fígado/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Regeneração Hepática , Doença Crônica , Hepatócitos/patologia , Hepatócitos/metabolismo , Tamanho do Órgão , Apoptose , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia
3.
Int Ophthalmol ; 44(1): 314, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965086

RESUMO

BACKGROUND: Oxidative stress-induced retinal pigment epithelium (RPE) cell damage is a major factor in age-related macular degeneration (AMD). Vitamin D3 (VD3) is a powerful antioxidant and it has been suggested to have anti-aging properties and potential for treating AMD. This study aimed to investigate the effect of VD3 on RPE cell oxidative apoptosis of RPE cells in order to provide experimental evidence for the treatment of AMD. METHODS: Human retinal pigment epithelial cell 19 (ARPE-19) cells were divided into four groups: blank group (untreated), model group (incubated in medium with 400 µmol/L H2O2 for 1 h), VD3 group (incubated in medium with 100 µmol/L VD3 for 24 h), and treatment group (incubated in medium with 400 µmol/L H2O2 for 1 h and 100 µmol/L VD3 for 24 h). Cell viability, cell senescence, ROS content, expression levels of vitamin D specific receptors, Akt, Sirt1, NAMPT, and JNK mRNA expression levels, SOD activity, and MDA, GSH, and GPX levels were measured. RESULTS: We first established an ARPE-19 cell stress model with H2O2. Our control experiment showed that VD3 treatment had no significant effect on ARPE-19 cell viability within 6-48 h. Treating the stressed ARPE-19 cells with VD3 showed mixed results; caspase-3 expression was decreased, Bcl-2 expression was increased, MDA level of ARPE-19 cells was decreased, GSH-PX, GPX and SOD levels were increased, the relative mRNA expression levels of Akt, Sirt1, NAMPT were increased (P < 0.05), and the relative mRNA expression level of JNK was decreased (P < 0.05). CONCLUSION: VD3 can potentially slow the development of AMD.


Assuntos
Apoptose , Sobrevivência Celular , Estresse Oxidativo , Epitélio Pigmentado da Retina , Humanos , Estresse Oxidativo/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Degeneração Macular/metabolismo , Vitaminas/farmacologia , Vitamina D/farmacologia , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Células Cultivadas , Sirtuína 1/metabolismo , Sirtuína 1/genética , Senescência Celular/efeitos dos fármacos , Linhagem Celular , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/toxicidade
4.
Artigo em Chinês | MEDLINE | ID: mdl-38965852

RESUMO

Objective: To explore the effects of hinokiol on the cell cyle and apoptosis of CNE1 nasopharyngeal carcinoma cells and the relevant molecular mechanism. Methods: The CNE1 cells were cultured in vitro and incubated with different concentrations of honokiol, and the cells were divided into blank control group, 10 µmol/L, 20 µmol/L and 40 µmol/L hinokiol treatment groups, and 10 µg/ml cisplatin group. Cell viability was determined by methylthiazolyldiphenyl- tetrazolium bromide (MTT) method, the cell cycle distribution was detected by flow cytometry, mitochondrial membrane potential was detected by mitochondrial membrane potential test kit, apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method, and the proteins expression of proliferating cell nuclear antigen (PCNA) and G1/S specific cyclin D1 (cyclin D1) were detected by immunoblotting. RNA-Seq was conducted in the hinokiol-treated cells. The mRNA expression of yes-associated protein delta (YAP) was detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). The proteins expression of phosphor-YAP (p-YAP) and nuclear YAP were detected by immunoblotting, the nuclear distribution of YAP protein was detected by immunofluorescence in the cells with or without treated with the mammalian STE20-like kinase 1/2 (MST1/2) inhibitor (XMU-MP-1), hinokiol, and XMU-MP-1+hinokiol. Statistical analysis of the data was conducted using GraphPad Prism 8.0 software. Resluts Compared with the control group, the cell viablity of CNE1 cells, the levels of mitochondrial membrane potential, the proteins expression of PCNA and cyclin D1 in hinokiol treatment groups were markedly decreased (all P values<0.05), while the proportion of G0/G1 phase cells and the ratio of TUNEL-positive cells were significantly increased (both P values<0.05). Transcriptome analysis showed that differential genes were mainly enriched in Wnt signaling pathway, tumor necrosis factor pathway, and Hippo signaling pathway. The mRNA level of YAP and the protein expression of YAP in the nucleus were decreased and the level of p-YAP protein was increased in cells treated with hinokiol, which were significantly different from control group (all P values<0.05). Compared with the hinokiol group, XMU-MP-1+hinokiol groups showed the decrease of p-YAP protein expression (1.157±0.076 vs 0.479±0.038, t=37.120, P<0.05), the increase of YAP protein expression in the nucleus (0.143±0.012 vs 0.425±0.031, t=29.181, P<0.05), the reduced proportion of cells in G0/G1 phase [(72.494±3.309)% vs (58.747±2.865)%, t=17.265, P<0.05], and the decrease of apoptosis ratio [(53.158±3.376)% vs (29.621±2.713)%, t=28.584, P<0.05]. Conclusion: Hinokiol can arrest the cell cycle and induce the cell apoptosis of CNE1 cells via Hippo/YAP signaling pathway.


Assuntos
Apoptose , Compostos de Bifenilo , Ciclo Celular , Via de Sinalização Hippo , Lignanas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Transdução de Sinais , Humanos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Carcinoma Nasofaríngeo/metabolismo , Ciclo Celular/efeitos dos fármacos , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Lignanas/farmacologia , Compostos de Bifenilo/farmacologia , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAP , Proteínas Serina-Treonina Quinases/metabolismo , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/metabolismo
5.
Arch Dermatol Res ; 316(7): 455, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967656

RESUMO

Tirbanibulin 1% ointment is a synthetic antiproliferative agent approved in 2021 by the European Union for treating actinic keratoses (AK). Topical tirbanibulin has clinically resolved HPV-57 ( +) squamous cell carcinoma (SCC), HPV-16 ( +) vulvar high-grade squamous intraepithelial lesion, epidermodysplasia verruciformis, and condyloma. We examined how tirbanibulin might affect HPV oncoprotein expression and affect other cellular pathways involved in cell proliferation and transformation. We treated the HeLa cell line, containing integrated HPV-18, with increasing doses of tirbanibulin to determine the effects on cell proliferation. Immunoblotting was performed with antibodies against the Src canonical pathway, HPV 18 E6 and E7 transcription regulation, apoptosis, and invasion and metastasis pathways. Cell proliferation assays with tirbanibulin determined the half-maximal inhibitory concentration (IC50) of HeLa cells to be 31.49 nmol/L. Increasing concentrations of tirbanibulin downregulates the protein expression of Src (p < 0.001), phospho-Src (p < 0.001), Ras (p < 0.01), c-Raf (p < 0.001), ERK1 (p < 0.001), phospho-ERK1 (p < 0.001), phospho-ERK2 (p < 0.01), phospho-Mnk1 (p < 0.001), eIF4E (p < 0.01), phospho-eIF4E (p < 0.001), E6 (p < 0.01), E7 (p < 0.01), Rb (p < 0.01), phospho-Rb (p < 0.001), MDM2 (p < 0.01), E2F1 (p < 0.001), phospho-FAK (p < 0.001), phospho-p130 Cas (p < 0.001), Mcl-1 (p < 0.01), and Bcl-2 (p < 0.001), but upregulates cPARP (p < 0.001), and cPARP/fPARP (p < 0.001). These results demonstrate that tirbanibulin may impact expression of HPV oncoproteins via the Src- MEK- pathway. Tirbanibulin significantly downregulates oncogenic proteins related to cell cycle regulation and cell proliferation while upregulating apoptosis pathways.


Tirbanibulin is Promising Novel Therapy for Human Papillomavirus (HPV)-associated Diseases.Tirbanibulin 1% ointment is an approved synthetic topical ointment for treating actinic keratoses (AK), a precancer of skin cancer. Topical tirbanibulin has previously been reported to clinically resolve human papillomavirus (HPV)-( +) diseases.In this study, we examine how tirbanibulin may affect the HPV and pathways associated with cancer.We treated the HeLa cell line to determine the effects on HPV cell proliferation. Increasing the concentration of tirbanibulin statistically significantly affected numerous cellular pathways often associated with cancer.These results demonstrate that tirbanibulin may impact expression of HPV oncoproteins and thereby kill cancer cells.


Assuntos
Proliferação de Células , Regulação para Baixo , Papillomavirus Humano 18 , Proteínas Oncogênicas Virais , Humanos , Células HeLa , Proliferação de Células/efeitos dos fármacos , Proteínas Oncogênicas Virais/metabolismo , Regulação para Baixo/efeitos dos fármacos , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/tratamento farmacológico , Proteínas E7 de Papillomavirus/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/metabolismo , Quinases da Família src/metabolismo , Quinases da Família src/antagonistas & inibidores , Feminino , Papillomavirus Humano , Proteínas de Ligação a DNA
6.
J Biochem Mol Toxicol ; 38(7): e23762, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38967723

RESUMO

Given the malignancy of gastric cancer, developing highly effective and low-toxic targeted drugs is essential to prolong patient survival and improve patient outcomes. In this study, we conducted structural optimizations based on the benzimidazole scaffold. Notably, compound 8 f presented the most potent antiproliferative activity in MGC803 cells and induced cell cycle arrest at the G0/G1 phase. Further mechanistic studies demonstrated that compound 8 f caused the apoptosis of MGC803 cells by elevating intracellular reactive oxygen species (ROS) levels and activating the mitogen-activated protein kinase (MAPK) signaling pathway, accompanied by corresponding markers change. In vivo investigations additionally validated the inhibitory effect of compound 8 f on tumor growth in xenograft models bearing MGC803 cells without obvious toxicity. Our studies suggest that compound 8 f holds promise as a potential and safe lead compound for developing anti-gastric cancer agents.


Assuntos
Antineoplásicos , Benzimidazóis , Sistema de Sinalização das MAP Quinases , Espécies Reativas de Oxigênio , Neoplasias Gástricas , Benzimidazóis/farmacologia , Benzimidazóis/química , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto , Apoptose/efeitos dos fármacos , Camundongos Nus
7.
Commun Biol ; 7(1): 807, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961177

RESUMO

Glaucoma is the leading cause of irreversible blindness and is characterized by progressive retinal ganglion cell (RGC) loss and retinal nerve fiber layer thinning. Currently, no existing treatment is effective for the preservation of RGCs. MicroRNA-22-3p (miR22) and small extracellular vesicles derived from mesenchymal stem cells (MSC-sEVs) have neuroprotective effects. In this study, we apply miR22-overexpressing MSC-sEVs in an N-methyl-D-aspartic acid (NMDA)-induced RGC injury model to assess their short-term therapeutic effects and explore the underlying mechanisms. We find that mice in the miR22-sEVs-treated group have thicker retinas, fewer apoptotic cells, more reserved RGCs, better retinal function, and lower expression levels of Bax and caspase-3. MiR22-sEVs treatment promotes viability, inhibits apoptosis and inhibits Bax and caspase-3 expression in RGC-5 cells. MiR22 targets mitogen-activated protein kinase kinase kinase 12 to inhibit apoptosis by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Collectively, our results suggest that miR22-sEVs ameliorate NMDA-induced RGC injury through the inhibition of MAPK signaling pathway-mediated apoptosis, providing a potential therapy for glaucoma and other diseases that involve RGC damage.


Assuntos
Vesículas Extracelulares , Sistema de Sinalização das MAP Quinases , Células-Tronco Mesenquimais , MicroRNAs , Células Ganglionares da Retina , Células Ganglionares da Retina/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Células-Tronco Mesenquimais/metabolismo , Vesículas Extracelulares/metabolismo , Camundongos , Apoptose , Camundongos Endogâmicos C57BL , Glaucoma/genética , Glaucoma/metabolismo , Glaucoma/patologia , Glaucoma/terapia , Masculino
8.
BMC Cardiovasc Disord ; 24(1): 333, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961333

RESUMO

BACKGROUND: Oxidative stress may contribute to cardiac ryanodine receptor (RyR2) dysfunction in diabetic cardiomyopathy. Ginsenoside Rb1 (Rb1) is a major pharmacologically active component of ginseng to treat cardiovascular diseases. Whether Rb1 treat diabetes injured heart remains unknown. This study was to investigate the effect of Rb1 on diabetes injured cardiac muscle tissue and to further investigate its possible molecular pharmacology mechanisms. METHODS: Male Sprague-Dawley rats were injected streptozotocin solution for 2 weeks, followed 6 weeks Rb1 or insulin treatment. The activity of SOD, CAT, Gpx, and the levels of MDA was measured; histological and ultrastructure analyses, RyR2 activity and phosphorylated RyR2(Ser2808) protein expression analyses; and Tunel assay were performed. RESULTS: There was decreased activity of SOD, CAT, Gpx and increased levels of MDA in the diabetic group from control. Rb1 treatment increased activity of SOD, CAT, Gpx and decreased the levels of MDA as compared with diabetic rats. Neutralizing the RyR2 activity significantly decreased in diabetes from control, and increased in Rb1 treatment group from diabetic group. The expression of phosphorylation of RyR2 Ser2808 was increased in diabetic rats from control, and were attenuated with insulin and Rb1 treatment. Diabetes increased the apoptosis rate, and Rb1 treatment decreased the apoptosis rate. Rb1 and insulin ameliorated myocardial injury in diabetic rats. CONCLUSIONS: These data indicate that Rb1 could be useful for mitigating oxidative damage, reduced phosphorylation of RyR2 Ser2808 and decreased the apoptosis rate of cardiomyocytes in diabetic cardiomyopathy.


Assuntos
Antioxidantes , Apoptose , Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Ginsenosídeos , Miócitos Cardíacos , Estresse Oxidativo , Ratos Sprague-Dawley , Canal de Liberação de Cálcio do Receptor de Rianodina , Estreptozocina , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/efeitos dos fármacos , Ginsenosídeos/farmacologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/fisiopatologia , Cardiomiopatias Diabéticas/etiologia , Apoptose/efeitos dos fármacos , Antioxidantes/farmacologia , Fosforilação , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Miócitos Cardíacos/metabolismo , Miocárdio/patologia , Miocárdio/metabolismo , Insulina , Malondialdeído/metabolismo
9.
PeerJ ; 12: e17637, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966207

RESUMO

Background: Prostate cancer (PCa) is one of the causes of death in men worldwide. Although treatment strategies have been developed, the recurrence of the disease and consequential side effects remain an essential concern. Diospyros rhodocalyx Kurz, a traditional Thai medicine, exhibits diverse therapeutic properties, including anti-cancer activity. However, its anti-cancer activity against prostate cancer has not been thoroughly explored. This study aims to evaluate the anti-cancer activity and underlying mechanisms of the ethyl acetate extract of D. rhodocalyx Kurz (EADR) related to apoptosis induction in the LNCaP human prostate cancer cell line. Methods: Ethyl acetate was employed to extract the dried bark of D. rhodocalyx Kurz. The cytotoxicity of EADR on both LNCaP and WPMY-1 cells (normal human prostatic myofibroblast cell line) was evaluated using MTS assay. The effect of EADR on the cell cycle, apoptosis induction, and alteration in mitochondrial membrane potential (MMP) was assessed by the staining with propidium iodide (PI), Annexin V-FITC/PI, and JC-1 dye, respectively. Subsequent analysis was conducted using flow cytometry. The expression of cleaved caspase-3, BAX, and Bcl-2 was examined by Western blotting. The phytochemical profiling of the EADR was performed using gas chromatography-mass spectrometry (GC-MS). Results: EADR exhibited a dose-dependent manner cytotoxic effect on LNCaP cells, with IC50 values of 15.43 and 12.35 µg/mL after 24 and 48 h, respectively. Although it also exhibited a cytotoxic effect on WPMY-1 cells, the effect was comparatively lower, with the IC50 values of 34.61 and 19.93 µg/mL after 24 and 48 h of exposure, respectively. Cell cycle analysis demonstrated that EADR did not induce cell cycle arrest in either LNCaP or WPMY-1 cells. However, it significantly increased the sub-G1 population in LNCaP cells, indicating a potential induction of apoptosis. The Annexin V-FITC/PI staining indicated that EADR significantly induced apoptosis in LNCaP cells. Subsequent investigation into the underlying mechanism of EADR-induced apoptosis revealed a reduction in MMP as evidenced by JC-1 staining. Moreover, Western blotting demonstrated that EADR treatment resulted in the upregulation of BAX, downregulation of BCL-2, and elevation of caspase-3 cleavage in LNCaP cells. Notably, the epilupeol was a prominent compound in EADR as identified by GC-MS. Conclusion: The EADR exhibits anti-cancer activity against the LNCaP human prostate cancer cell line by inducing cytotoxicity and apoptosis. Our findings suggest that EADR promotes apoptosis by upregulating pro-apoptotic BAX, whereas downregulation of anti-apoptotic Bcl-2 results in the reduction of MMP and the activation of caspase-3. Of particular interest is the presence of epilupeol, a major compound identified in EADR, which may hold promise as a candidate for the development of therapeutic agents for prostate cancer.


Assuntos
Apoptose , Caspase 3 , Diospyros , Extratos Vegetais , Neoplasias da Próstata , Proteínas Proto-Oncogênicas c-bcl-2 , Proteína X Associada a bcl-2 , Humanos , Masculino , Apoptose/efeitos dos fármacos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Linhagem Celular Tumoral , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Caspase 3/metabolismo , Diospyros/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia
10.
Proc Natl Acad Sci U S A ; 121(28): e2403581121, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38968108

RESUMO

Adverse cardiac outcomes in COVID-19 patients, particularly those with preexisting cardiac disease, motivate the development of human cell-based organ-on-a-chip models to recapitulate cardiac injury and dysfunction and for screening of cardioprotective therapeutics. Here, we developed a heart-on-a-chip model to study the pathogenesis of SARS-CoV-2 in healthy myocardium established from human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and a cardiac dysfunction model, mimicking aspects of preexisting hypertensive disease induced by angiotensin II (Ang II). We recapitulated cytopathic features of SARS-CoV-2-induced cardiac damage, including progressively impaired contractile function and calcium handling, apoptosis, and sarcomere disarray. SARS-CoV-2 presence in Ang II-treated hearts-on-a-chip decreased contractile force with earlier onset of contractile dysfunction and profoundly enhanced inflammatory cytokines compared to SARS-CoV-2 alone. Toward the development of potential therapeutics, we evaluated the cardioprotective effects of extracellular vesicles (EVs) from human iPSC which alleviated the impairment of contractile force, decreased apoptosis, reduced the disruption of sarcomeric proteins, and enhanced beta-oxidation gene expression. Viral load was not affected by either Ang II or EV treatment. We identified MicroRNAs miR-20a-5p and miR-19a-3p as potential mediators of cardioprotective effects of these EVs.


Assuntos
Angiotensina II , COVID-19 , Vesículas Extracelulares , Células-Tronco Pluripotentes Induzidas , Miócitos Cardíacos , SARS-CoV-2 , Humanos , Angiotensina II/farmacologia , COVID-19/virologia , COVID-19/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/virologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Vesículas Extracelulares/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Apoptose/efeitos dos fármacos , Dispositivos Lab-On-A-Chip , MicroRNAs/metabolismo , MicroRNAs/genética , Citocinas/metabolismo
11.
PeerJ ; 12: e17672, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952967

RESUMO

Background: Mitochondrial creatine kinase (MtCK) plays a pivotal role in cellular energy metabolism, exhibiting enhanced expression in various tumors, including colorectal cancer (CRC). Creatine kinase mitochondrial 2 (CKMT2) is a subtype of MtCK; however, its clinical significance, biological functions, and underlying molecular mechanisms in CRC remain elusive. Methods: We employed immunohistochemical staining to discern the expression of CKMT2 in CRC and adjacent nontumor tissues of patients. The correlation between CKMT2 levels and clinical pathological factors was assessed. Additionally, we evaluated the association between CKMT2 and the prognosis of CRC patients using Kaplan-Meier survival curves and Cox regression analysis. Meanwhile, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of CKMT2 in different CRC cell lines. Finally, we explored the biological functions and potential molecular mechanisms of CKMT2 in CRC cells through various techniques, including qRT-PCR, cell culture, cell transfection, western blot, Transwell chamber assays, flow cytometry, and co-immunoprecipitation. Results: We found that CKMT2 was significantly overexpressed in CRC tissues compared with adjacent nontumor tissues. The expression of CKMT2 is correlated with pathological types, tumor size, distant metastasis, and survival in CRC patients. Importantly, CKMT2 emerged as an independent prognostic factor through Cox regression analysis. Experimental downregulation of CKMT2 expression in CRC cell lines inhibited the migration and promoted apoptosis of these cells. Furthermore, we identified a novel role for CKMT2 in promoting aerobic glycolysis in CRC cells through interaction with lactate dehydrogenase B (LDHB). Conclusion: In this study, we found the elevated expression of CKMT2 in CRC, and it was a robust prognostic indicator in CRC patients. CKMT2 regulates glucose metabolism via amplifying the Warburg effect through interaction with LDHB, which promotes the growth and progression of CRC. These insights unveil a novel regulatory mechanism by which CKMT2 influences CRC and provide promising targets for future CRC therapeutic interventions.


Assuntos
Neoplasias Colorretais , Efeito Warburg em Oncologia , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Masculino , Feminino , Linhagem Celular Tumoral , Prognóstico , Creatina Quinase Mitocondrial/metabolismo , Creatina Quinase Mitocondrial/genética , Progressão da Doença , L-Lactato Desidrogenase/metabolismo , L-Lactato Desidrogenase/genética , Pessoa de Meia-Idade , Proliferação de Células , Apoptose , Regulação Neoplásica da Expressão Gênica
12.
PeerJ ; 12: e17619, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952980

RESUMO

Background: Andrographolide (Andro), an extract of Andrographis paniculate (Burm.f.) Wall. ex Nees (Acanthaceae), possesses diverse biologically active properties. However, the precise mechanisms and effects of Andro on pancreatic cancer (PC) remain unclear. Methods: The cytotoxic potential of Andro and underlying mechanism towards PC cells was investigated through in vitro experiments and a xenograft mouse model. PC cells were first subjected to varying concentrations of Andro. The reactive oxygen species (ROS) was assessed using flow cytometry and DCFH-DA staining. The apoptosis rate was detected by flow cytometry. Additionally, western blot was applied to evaluate the expression levels of cleaved-caspase-3, DJ-1, LC3-I, LC3-II, and p62. To further elucidate the involvement of ROS accumulation and autophagy, we employed N-acetylcysteine as a scavenger of ROS and 3-Methyladenine as an inhibitor of autophagy. Results: Andro demonstrated potent anti-proliferative effects on PC cells and induced apoptosis, both in vitro and in vivo. The cytotoxicity of Andro on PC cells was counteracted by DJ-1 overexpression. The reduction in DJ-1 expression caused by Andro led to ROS accumulation, subsequently inhibiting the growth of PC cells. Furthermore, Andro stimulated cytoprotective autophagy, thus weakening the antitumor effect. Pharmacological blockade of autophagy further enhanced the antitumor efficacy of Andro. Conclusion: Our study indicated that ROS accumulation induced by the DJ-1 reduction played a key role in Andro-mediated PC cell inhibition. Furthermore, the protective autophagy induced by the Andro in PC cells is a mechanism that needs to be addressed in future studies.


Assuntos
Apoptose , Autofagia , Diterpenos , Neoplasias Pancreáticas , Proteína Desglicase DJ-1 , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Diterpenos/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Autofagia/efeitos dos fármacos , Proteína Desglicase DJ-1/metabolismo , Proteína Desglicase DJ-1/genética , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus
13.
Front Immunol ; 15: 1372956, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38953033

RESUMO

Our study aimed to elucidate the role of Galectin-1 (Gal-1) role in the immunosuppressive tumor microenvironment (TME) of prostate cancer (PCa). Our previous findings demonstrated a correlation between elevated Gal-1 expression and advanced PCa stages. In this study, we also observed that Gal-1 is expressed around the tumor stroma and its expression level is associated with PCa progression. We identified that Gal-1 could be secreted by PCa cells, and secreted Gal-1 has the potential to induce T cell apoptosis. Gal-1 knockdown or inhibition of Gal-1 function by LLS30 suppresses T cell apoptosis resulting in increased intratumoral T cell infiltration. Importantly, LLS30 treatment significantly improved the antitumor efficacy of anti-PD-1 in vivo. Mechanistically, LLS30 binds to the carbohydrate recognition domain (CRD) of Gal-1, disrupting its binding to CD45 leading to the suppression of T cell apoptosis. In addition, RNA-seq analysis revealed a novel mechanism of action for LLS30, linking its tumor-intrinsic oncogenic effects to anti-tumor immunity. These findings suggested that tumor-derived Gal-1 contributes to the immunosuppressive TME in PCa by inducing apoptosis in effector T cells. Targeting Gal-1 with LLS30 may offer a strategy to enhance anti-tumor immunity and improve immunotherapy.


Assuntos
Apoptose , Galectina 1 , Imunoterapia , Neoplasias da Próstata , Linfócitos T , Microambiente Tumoral , Masculino , Galectina 1/genética , Galectina 1/metabolismo , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Humanos , Animais , Microambiente Tumoral/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Camundongos , Imunoterapia/métodos , Linhagem Celular Tumoral , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo
14.
Gen Physiol Biophys ; 43(4): 291-300, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38953572

RESUMO

This study aims to determine the effect of sevoflurane (Sev) on nasopharyngeal carcinoma (NPC) in malignant behavior and mitochondrial membrane potential (MMP). NPC cells (5-8F and CNE2) were exposed to Sev at different concentrations and then tested for proliferation by CCK-8 and colony formation assays, apoptosis by flow cytometry, and invasion and migration by Transwell assays. In addition, the Warburg effect was examined by measurements of glucose consumption, lactic acid production, and adenosine triphosphate (ATP). Mitochondrial function was evaluated by reactive oxygen species (ROS) production, oxidative stress-related indexes, and mitochondrial membrane potential. Sev suppressed 5-8F and CNE2 cell proliferation, invasion, and migration, and enhanced apoptosis. Moreover, Sev dampened the Warburg effect by reducing glucose consumption, lactic acid production, and ATP, as well as decreasing hexokinase 2 and pyruvate kinases type M2 protein expressions. Also, Sev induced ROS production and malondialdehyde content and reduced superoxide and glutathione peroxidase levels. Finally, Sev caused damage to mitochondrial homeostasis through induction of cleaved caspase-3, cleaved caspase-9, and cytochrome c protein expression and reduction of MMP. Sev inhibits the malignant behavior of NPC cells by regulating MMP.


Assuntos
Potencial da Membrana Mitocondrial , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Sevoflurano , Sevoflurano/farmacologia , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Linhagem Celular Tumoral , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Relação Dose-Resposta a Droga
15.
FASEB J ; 38(13): e23749, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38953707

RESUMO

Pulmonary fibrosis is a formidable challenge in chronic and age-related lung diseases. Myofibroblasts secrete large amounts of extracellular matrix and induce pro-repair responses during normal wound healing. Successful tissue repair results in termination of myofibroblast activity via apoptosis; however, some myofibroblasts exhibit a senescent phenotype and escape apoptosis, causing over-repair that is characterized by pathological fibrotic scarring. Therefore, the removal of senescent myofibroblasts using senolytics is an important method for the treatment of pulmonary fibrosis. Procyanidin C1 (PCC1) has recently been discovered as a senolytic compound with very low toxicity and few side effects. This study aimed to determine whether PCC1 could improve lung fibrosis by promoting apoptosis in senescent myofibroblasts and to investigate the mechanisms involved. The results showed that PCC1 attenuates bleomycin (BLM)-induced pulmonary fibrosis in mice. In addition, we found that PCC1 inhibited extracellular matrix deposition and promoted the apoptosis of senescent myofibroblasts by increasing PUMA expression and activating the BAX signaling pathway. Our findings represent a new method of pulmonary fibrosis management and emphasize the potential of PCC1 as a senotherapeutic agent for the treatment of pulmonary fibrosis, providing hope for patients with pulmonary fibrosis worldwide. Our results advance our understanding of age-related diseases and highlight the importance of addressing cellular senescence in treatment.


Assuntos
Bleomicina , Catequina , Senescência Celular , Camundongos Endogâmicos C57BL , Miofibroblastos , Fibrose Pulmonar , Animais , Bleomicina/toxicidade , Miofibroblastos/metabolismo , Miofibroblastos/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia , Camundongos , Senescência Celular/efeitos dos fármacos , Catequina/farmacologia , Catequina/análogos & derivados , Proantocianidinas/farmacologia , Apoptose/efeitos dos fármacos , Masculino , Biflavonoides/farmacologia , Transdução de Sinais/efeitos dos fármacos
16.
Growth Factors ; 42(2): 62-73, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38954805

RESUMO

BACKGROUND AND OBJECTIVE: Dysregulated expression of Forkhead Box N2 (FOXN2) has been detected in various cancer types. However, the underlying mechanisms by which FOXN2 contributes to the onset and progression of gastric cancer (GC) remain largely unexplored. This study aimed to elucidate the potential role of FOXN2 within GC, its downstream molecular mechanisms, and its feasibility as a novel serum biomarker for GC. METHODS: Tissue samples from GC patients and corresponding non-cancerous tissues were collected. Peripheral blood samples were obtained from GC patients and healthy controls. The expression of FOXN2 was determined using quantitative real-time PCR, western blotting, and immunohistochemistry. The expression of FOXN2 in GC cells was modulated by transfection with small interfering RNA (siRNA) or the pcDNA 3.1 expression vector. Cell proliferation was assessed using the Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine incorporation assays. The migratory and invasive capacities of cells were evaluated by Transwell assays, apoptosis rates were measured by flow cytometry, and the expression of proliferative, apoptotic, and epithelial-mesenchymal transition (EMT) markers were assessed by western blot analysis. RESULTS: FOXN2 was found to be overexpressed in the serum, tissues, and cells of GC, correlating with distant metastasis and TNM staging. FOXN2 demonstrated diagnostic value in differentiating GC patients from healthy individuals, with higher levels of FOXN2 being indicative of poorer survival rates. Silencing FOXN2 in vitro inhibited the proliferation, invasion, migration, and EMT of GC cells, while promoting apoptosis. FOXN2 was shown to regulate the transforming growth factor-beta (TGFß) receptor signaling pathway in GC cells via its interaction with Partitioning Defective 6 Homolog Alpha (PARD6A). CONCLUSION: In summary, our data suggest that FOXN2 acts as an oncogenic factor in GC, modulating the TGFß pathway by binding to PARD6A, thereby influencing gastric carcinogenesis. This study underscores the functional significance of FOXN2 as a potential serum biomarker and therapeutic target in GC.


Assuntos
Biomarcadores Tumorais , Transição Epitelial-Mesenquimal , Fatores de Transcrição Forkhead , Transdução de Sinais , Neoplasias Gástricas , Fator de Crescimento Transformador beta , Humanos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/sangue , Proliferação de Células , Linhagem Celular Tumoral , Apoptose , Movimento Celular , Idoso , Regulação Neoplásica da Expressão Gênica
17.
Med Oncol ; 41(8): 193, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38955918

RESUMO

Preclinical and clinical research showed that immune checkpoint blockade provides beneficial effects for many patients with liver cancer. This study aimed to assess the effect of CTLA-4-specific siRNA on the proliferation, cell cycle, migration, and apoptosis of HePG2 cells. Transfection of siRNA was performed by electroporation. The viability of cells was determined through MTT assay. Flow cytometry was performed to investigate the cell cycle and apoptosis rate, and the wound-healing assay was used to determine HepG2 cells migration. The expression levels of CTLA-4, c-Myc, Ki-67, BCL-2, BAX, caspase-9 (CAS9), and MMP-2,9,13 were measured by qRT-PCR. Transfection of specific CTLA-4-siRNA significantly inhibited the expression of the CTLA-4 gene. Also, our results revealed that CTLA-4 silencing diminished the proliferation and migration as well as induced the apoptosis of HePG2 cells. CTLA-4-siRNA transfection induced the cell cycle arrest in G2 phase. Moreover, CTLA-4-siRNA transfection reduced the expression levels of c-Myc, Ki-67, BCL-2, MMP-2,9,13, and elevated the expression levels of BAX and caspase-9. Our results suggest that silencing CTLA-4 through specific siRNA may be a promising strategy for future therapeutic interventions for treating liver cancer.


Assuntos
Apoptose , Antígeno CTLA-4 , Carcinoma Hepatocelular , Movimento Celular , Proliferação de Células , Neoplasias Hepáticas , RNA Interferente Pequeno , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Células Hep G2 , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Antígeno CTLA-4/metabolismo , Antígeno CTLA-4/genética , Antígeno CTLA-4/antagonistas & inibidores , Movimento Celular/genética , RNA Interferente Pequeno/genética , Inativação Gênica
18.
Drug Dev Res ; 85(5): e22231, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38956926

RESUMO

The close association between inflammation and cancer inspired the synthesis of a series of 1,3,4-oxadiazole derivatives (compounds H4-A-F) of 6-methoxynaphtalene. The chemical structures of the new compounds were validated utilizing Fourier-transform infrared, proton nuclear magnetic resonance, and carbon-13 nuclear magnetic resonance spectroscopic techniques and CHN analysis. Computer-aided drug design methods were used to predict the compounds biological target, ADMET properties, toxicity, and to evaluate the molecular similarities between the design compounds and erlotinib, a standard epidermal growth factor receptor (EGFR) inhibitor. The antiproliferative effects of the new compounds were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, cell cycle analysis, apoptosis detection by microscopy, quantitative reverse transcription-polymerase chain reaction, and immunoblotting, and EGFR enzyme inhibition assay. In silico analysis of the new oxadiazole derivatives indicated that these compounds target EGFR, and that compounds H4-A, H4-B, H4-C, and H4-E show similar molecular properties to erlotinib. Additionally, the results indicated that none of the synthesized compounds are carcinogenic, and that compounds H4-A, H4-C, and H4-F are nontoxic. Compound H4-A showed the best-fit score against EGFR pharmacophore model, however, the in vitro studies indicated that compound H4-C was the most cytotoxic. Compound H4-C caused cytotoxicity in HCT-116 colorectal cancer cells by inducing both apoptosis and necrosis. Furthermore, compounds H4-D, H4-C, and H4-B had potent inhibitory effect on EGFR tyrosine kinase that was comparable to erlotinib. The findings of this inquiry offer a basis for further investigation into the differences between the synthesized compounds and erlotinib. However, additional testing will be needed to assess all of these differences and to identify the most promising compound for further research.


Assuntos
Antineoplásicos , Receptores ErbB , Simulação de Acoplamento Molecular , Naproxeno , Oxidiazóis , Receptores ErbB/antagonistas & inibidores , Humanos , Oxidiazóis/farmacologia , Oxidiazóis/química , Oxidiazóis/síntese química , Naproxeno/farmacologia , Naproxeno/análogos & derivados , Naproxeno/química , Naproxeno/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Cloridrato de Erlotinib/farmacologia , Cloridrato de Erlotinib/química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Proliferação de Células/efeitos dos fármacos
19.
Drug Dev Res ; 85(5): e22229, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38958104

RESUMO

Indole-based agents are frequently used in targeted or supportive therapy of several cancers. In this study, we investigated the anticancer properties of originally synthesized novel indolin-2-one derivatives (6a-d) against Malignant Mesothelioma, Breast cancer, and Colon Cancer cells. Our results revealed that all derivatives were effectively delayed cell proliferation by inhibiting the ERK1/2, AKT, and STAT3 signaling pathways in a concentration-dependent manner. Additionally, these variants induced cell cycle arrest in the S phase, accompanied by elevated levels of p21 and p27 expressions. Derivatives also initiated mitochondrial apoptosis through the upregulation of Bax and downregulation of Bcl-2 proteins, leading to the activation of caspase 3 and PARP cleavage in exposed cells. Remarkably, three of the indolin-2-one derivatives displayed significant selectivity towards Breast and Colon Cancer cells, with compound 6d promising as the most potent and wide spectral one for all cancer cell lines.


Assuntos
Antineoplásicos , Apoptose , Proliferação de Células , Indóis , Humanos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Indóis/farmacologia , Indóis/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos
20.
Trop Anim Health Prod ; 56(6): 195, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963478

RESUMO

This experiment aimed to assess the regulatory effects of treatment with Balanites aegyptiaca fruit ethanol extract (BA-EE) on oxidant/antioxidant status, anti-inflammatory cytokines, and cell apoptosis gene expression in the abomasum of Haemonchus contortus-infected goats. Twenty goat kids were assigned randomly to four equal groups: (G1) infected-untreated, (G2) uninfected-BA-EE-treated, (G3) infected-albendazole-treated, (G4) infected-BA-EE-treated. Each goat in (G1), (G3), and (G4) was orally infected with 10,000 infective third-stage larvae. In the fifth week postinfection, single doses of albendazole (5 mg/kg.BW) and BA-EE (9 g/kg.BW) were given orally. In the ninth week postinfection, the animals were slaughtered to obtain abomasum specimens. The following oxidant/antioxidant markers were determined: malondialdehyde (MDA), glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT). The mRNA gene expression of cytokines (IL-3, IL-6, IL-10, TNF-α) and cell apoptosis markers (Bax, Bcl-2) were estimated. (G1) showed significantly reduced GSH content and GST and SOD activities but a markedly increased MDA level. (G3) and (G4) revealed a markedly lower MDA level with pronouncedly elevated GSH, SOD, and GST levels. The antioxidant properties of BA-EE were superior to those of albendazole. The mRNA gene expressions of IL-3, IL-6, IL-10, TNF-α, and Bax-2 were upregulated in (G1) but downregulated in (G3) and (G4). Bcl-2 and Bcl-2/Bax ratio expression followed a reverse course in the infected and both treated groups. We conclude that BA-EE treatment has a protective role in the abomasum of H. contortus-infected goats. This could be attributed to its antioxidant properties and ability to reduce pro-inflammatory cytokines and cell apoptosis.


Assuntos
Abomaso , Antioxidantes , Apoptose , Citocinas , Doenças das Cabras , Cabras , Hemoncose , Haemonchus , Extratos Vegetais , Animais , Doenças das Cabras/parasitologia , Doenças das Cabras/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Citocinas/metabolismo , Citocinas/genética , Apoptose/efeitos dos fármacos , Hemoncose/veterinária , Hemoncose/parasitologia , Haemonchus/efeitos dos fármacos , Abomaso/parasitologia , Antioxidantes/metabolismo , Anti-Helmínticos/farmacologia , Anti-Helmínticos/administração & dosagem , Distribuição Aleatória , Etanol , Expressão Gênica/efeitos dos fármacos , Albendazol/farmacologia , Albendazol/administração & dosagem , Frutas/química , Lamiaceae/química , Masculino
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