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1.
Curr Alzheimer Res ; 21(2): 141-154, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766828

RESUMO

BACKGROUND: As individuals age, they may develop Alzheimer's disease (AD), which is characterized by difficulties in speech, memory loss, and other issues related to neural function. Cycloastragenol is an active ingredient of Astragalus trojanus and has been used to treat inflammation, aging, heart disease, and cancer. OBJECTIVES: This study aimed to explore the potential therapeutic benefits of cycloastragenol in rats with experimentally induced AD. Moreover, the underlying molecular mechanisms were also evaluated by measuring Nrf2 and HO-1, which are involved in oxidative stress, NFκB and TNF-α, which are involved in inflammation, and BCL2, BAX, and caspase-3, which are involved in apoptosis. METHODS: Sprague-Dawley rats were given 70 mg/kg of aluminum chloride intraperitoneally daily for six weeks to induce AD. Following AD induction, the rats were given 25 mg/kg of cycloastragenol daily by oral gavage for three weeks. Hippocampal sections were stained with hematoxylin/ eosin and with anti-caspase-3 antibodies. The Nrf2, HO-1, NFκB, TNF-α, BCL2, BAX, and caspase-3 gene expressions and protein levels in the samples were analyzed. RESULTS: Cycloastragenol significantly improved rats' behavioral test performance. It also strengthened the organization of the hippocampus. Cycloastragenol significantly improved behavioral performance and improved hippocampal structure in rats. It caused a marked decrease in the expression of NFκB, TNF-α, BAX, and caspase-3, which was associated with an increase in the expression of BCL2, Nrf2, and HO-1. CONCLUSION: Cycloastragenol improved the structure of the hippocampus in rats with AD. It enhanced the outcomes of behavioral tests, decreased the concentration of AChE in the brain, and exerted antioxidant and anti-inflammatory effects. Antiapoptotic effects were also noted, leading to significant improvements in cognitive function, memory, and behavior in treated rats.


Assuntos
Doença de Alzheimer , Apoptose , Inflamação , Estresse Oxidativo , Ratos Sprague-Dawley , Sapogeninas , Animais , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Ratos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Sapogeninas/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Modelos Animais de Doenças
2.
Biomol Biomed ; 24(5): 1186-1198, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-38461536

RESUMO

Hepatocellular carcinoma (HCC) affects approximately 800,000 individuals globally each year. Despite advancements in HCC treatments, there is still a pressing need to identify new drugs that can combat resistance. One potential option is echinacoside, a natural caffeic acid glycoside with antioxidant, anti-inflammatory, antidepressant, and antidiabetic properties. Therefore, we aimed to investigate the ability of echinacoside to exhibit antitumor activity against HCC in rats through ameliorating hepatic fibrosis and tumor invasion. Rats were given thioacetamide to induce HCC, and some were given 30 mg/kg of echinacoside twice a week for 16 weeks. The liver impairment was assessed by measuring serum α-fetoprotein (AFP) and examining liver sections stained with Masson trichrome or anti-transforming growth factor (TGF)-ß1 antibodies. The hepatic expression of mRNA and protein levels of TGF-ß1, ß-catenin, SMAD4, matrix metalloproteinase-9 (MMP9), phosphoinositide 3-kinases (PI3K), mammalian target of rapamycin (mTOR), connective tissue growth factor 2 (CCN2), E-Cadherin, platelets derived growth factor (PDGF)-B and fascin were also analyzed. Echinacoside improved the survival rate of rats by decreasing serum AFP and the number of hepatic nodules. Examination of micro-images indicated that echinacoside can reduce fibrosis. It also significantly decreased the expression of TGF-ß1, ß-catenin, SMAD4, MMP9, PI3K, mTOR, CCN2, PDGF-B, and fascin while enhancing the expression of E-Cadherin. In conclusion, echinacoside exhibits a protective effect against HCC by increasing survival rates and decreasing tumor growth. It also acts as an inhibitor of the hepatic tissue fibrosis pathway by reducing the expression of TGF-ß1, ß-catenin, SMAD4, PI3K, CCN2, PDGF-B and mTOR. Additionally, it prevents tumor invasion by suppressing MMP9 and fascin, and increasing the expression of E-Cadherin.


Assuntos
Carcinoma Hepatocelular , Glicosídeos , Cirrose Hepática , Neoplasias Hepáticas , Tioacetamida , Fator de Crescimento Transformador beta1 , Animais , Tioacetamida/toxicidade , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Hepatocelular/metabolismo , Ratos , Masculino , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Glicosídeos/farmacologia , Glicosídeos/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/prevenção & controle , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Invasividade Neoplásica , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Ratos Sprague-Dawley , Serina-Treonina Quinases TOR/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , beta Catenina/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo
3.
Cureus ; 16(1): e51997, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38205087

RESUMO

Background and objectives Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor with a poor prognosis. It is currently the second most common cause of cancer-related mortality. Arctiin, a compound found in plants commonly used as a vegetable in Asian countries and as an ingredient in traditional European dishes, possesses various properties, including anti-proliferative, anti-senescence, anti-oxidative, anti-tumor, toxic, anti-adipogenic, and anti-bacterial effects. Our study aims to investigate the potential antitumor activity of arctiin against HCC in rats by inhibiting cell fibrosis and apoptosis. Methods Rats were induced with HCC by administering thioacetamide. Arctiin was orally administered to some rats twice a week for 16 weeks at a dose of 30 mg/kg. The liver impairment was evaluated by measuring serum α-fetoprotein (AFP) and examining liver sections stained with Masson trichrome or anti-hypoxia-induced factor-1α (HIF-1α) antibodies. The hepatic expression of messenger RNA and protein levels of HIF-1α, protein kinase C (PKC), extracellular signal-regulated kinase (ERK), ß-catenin, and mothers against decapentaplegic homolog 4 (SMAD4) were analyzed. Results Our study demonstrated that arctiin can potentially increase the survival rate of rats. This is achieved through a reduction in serum AFP levels and hepatic nodules. We also observed that arctiin has the ability to inhibit the formation of fibrotic tissues and necrotic nodules in HCC rats. Additionally, arctiin can significantly decrease the expression of HIF-1α, PKC, ERK, ß-catenin, and SMAD4. Conclusion Arctiin has demonstrated potential anti-tumor properties that could ameliorate HCC. Studies have shown that it may increase survival rates and reduce the number of tumors and AFP levels. Arctiin works by inhibiting HCC-induced hypoxia, thus blocking the expression of HIF-1α. It also helps to slow down tumor fibrosis by decreasing the expression of ß-catenin and SMAD4. Furthermore, arctiin has been found to downregulate PKC and ERK, reducing hepatic tissue apoptosis.

4.
Sensors (Basel) ; 23(13)2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37447876

RESUMO

The use of augmented reality (AR) technology is growing in the maintenance industry because it can improve efficiency and reduce costs by providing real-time guidance and instruction to workers during repairs and maintenance tasks. AR can also assist with equipment training and visualization, allowing users to explore the equipment's internal structure and size. The adoption of AR in maintenance is expected to increase as hardware options expand and development costs decrease. To implement AR for job aids in mobile applications, 3D spatial information and equipment details must be addressed, and calibrated using image-based or object-based tracking, which is essential for integrating 3D models with physical components. The present paper suggests a system using AR-assisted deep reinforcement learning (RL)-based model for NanoDrop Spectrophotometer training and maintenance purposes that can be used for rapid repair procedures in the Industry 4.0 (I4.0) setting. The system uses a camera to detect the target asset via feature matching, tracking techniques, and 3D modeling. Once the detection is completed, AR technologies generate clear and easily understandable instructions for the maintenance operator's device. According to the research findings, the model's target technique resulted in a mean reward of 1.000 and a standard deviation of 0.000. This means that all the rewards that were obtained in the given task or environment were exactly the same. The fact that the reward standard deviation is 0.000 shows that there is no variability in the outcomes.


Assuntos
Realidade Aumentada , Aplicativos Móveis , Cirurgia Assistida por Computador , Humanos , Cirurgia Assistida por Computador/métodos
5.
Cureus ; 14(10): e30519, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36415369

RESUMO

Mucopolysaccharidosis type III-B (MPS III), also known as Sanfilippo syndrome, is a rare autosomal recessive lysosomal storage disease that primarily affects the brain and spinal cord. In this report, we describe the case of an eight-year-old female child who presented to the emergency room with an asthma exacerbation. She had coarse facial features, thick eyebrows, deep-seated eyes, thinning coarse hair, and macrocephaly. Moreover, she suffered from hepatosplenomegaly, generalized muscular atrophy, global developmental delay, and scoliosis. Urinary glycosaminoglycans (GAGs) were within normal limits. Full genetic testing confirmed the diagnosis of Sanfilippo syndrome type B with a deficiency of alpha-N-acetylglucosaminidase caused by a homozygous mutation c.889C>T, p.(Arg297*) in the NAGLU (N-acetyl-alpha-glucosaminidase) gene. Chromosomal microarray analysis (CMA) showed a copy number variant (CNV) within the 1q24 region. Thus far, CNVs similar in size and position have not been reported in the literature, making this a novel mutation.

6.
Cureus ; 14(7): e26737, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35967136

RESUMO

Background Ectopic pregnancy is a life-threatening medical condition wherein pregnancy occurs outside the uterus. This study primarily aimed to evaluate the efficacy of methotrexate (MTX) in treating patients diagnosed with early ectopic pregnancy between 2016 and 2021. Second, it aimed to investigate the clinical outcomes of subsequent pregnancies following ectopic pregnancy treatment. Methods A retrospective cohort study was carried out at a tertiary care centre in Jeddah, Saudi Arabia. The sample for this study comprised 59 patients who were diagnosed with ectopic pregnancy and treated with MTX at King Abdulaziz Medical City, Jeddah, between 2016 and 2021. The data were stored in the Microsoft Office Excel format and analyzed using the SPSS software. Results There were 10 reported cases of ruptured ectopic pregnancy; seven of these underwent surgery, while three were successfully treated conservatively using MTX. Success rates of 55.9% and 93.8% were recorded after administering the first and second dose of MTX, respectively, based on beta-human chorionic gonadotrophin (ß-hCG) drop between day 4 and day 7. Among those treated with MTX, 37.3% of the patients reported a successful subsequent pregnancy, of which 54.5% delivered a live, healthy infant and 13.6% had a second ectopic pregnancy. Conclusion MTX proved effective in treating ectopic pregnancy, with a ß-hCG drop of more than 15%. Patients who received a second dose of MTX showed a higher drop in ß-hCG level, indicating greater success as a cumulative effect. The clinical outcome after MTX treatment of ectopic pregnancy was shown to be significant with a p-value <0.05.

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