RESUMO
Parkinson's disease (PD) is the second most common neurodegenerative disease which is still incurable. Sea cucumber-derived compounds have been reported to be promising candidate drugs for treating age-related neurological disorders. The present study evaluated the beneficial effects of the Holothuria leucospilota (H. leucospilota)-derived compound 3 isolated from ethyl acetate fraction (HLEA-P3) using Caenorhabditis elegans PD models. HLEA-P3 (1 to 50 µg/mL) restored the viability of dopaminergic neurons. Surprisingly, 5 and 25 µg/mL HLEA-P3 improved dopamine-dependent behaviors, reduced oxidative stress and prolonged lifespan of PD worms induced by neurotoxin 6-hydroxydopamine (6-OHDA). Additionally, HLEA-P3 (5 to 50 µg/mL) decreased α-synuclein aggregation. Particularly, 5 and 25 µg/mL HLEA-P3 improved locomotion, reduced lipid accumulation and extended lifespan of transgenic C. elegans strain NL5901. Gene expression analysis revealed that treatment with 5 and 25 µg/mL HLEA-P3 could upregulate the genes encoding antioxidant enzymes (gst-4, gst-10 and gcs-1) and autophagic mediators (bec-1 and atg-7) and downregulate the fatty acid desaturase gene (fat-5). These findings explained the molecular mechanism of HLEA-P3-mediated protection against PD-like pathologies. The chemical characterization elucidated that HLEA-P3 is palmitic acid. Taken together, these findings revealed the anti-Parkinson effects of H. leucospilota-derived palmitic acid in 6-OHDA induced- and α-synuclein-based models of PD which might be useful in nutritional therapy for treating PD.
Assuntos
Holothuria , Doenças Neurodegenerativas , Doença de Parkinson , Animais , Doença de Parkinson/metabolismo , Caenorhabditis elegans/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , alfa-Sinucleína/farmacologia , Holothuria/metabolismo , Ácido Palmítico/farmacologia , Doenças Neurodegenerativas/tratamento farmacológico , Oxidopamina , Animais Geneticamente Modificados , Neurônios Dopaminérgicos , Modelos Animais de DoençasRESUMO
Obesity is a multifactorial disease characterized by an excessive accumulation of fat, which in turn poses a significant risk to health. Bioactive compounds obtained from macroalgae have demonstrated their efficacy in combating obesity in various animal models. The green macroalgae Caulerpa lentillifera (CL) contains numerous active constituents. Hence, in the present study, we aimed to elucidate the beneficial anti-obesity effects of extracts derived from C. lentillifera using a Caenorhabditis elegans obesity model. The ethanol (CLET) and ethyl acetate (CLEA) extracts caused a significant decrease in fat consumption, reaching up to approximately 50-60%. Triglyceride levels in 50 mM glucose-fed worms were significantly reduced by approximately 200%. The GFP-labeled dhs-3, a marker for lipid droplets, exhibited a significant reduction in its level to approximately 30%. Furthermore, the level of intracellular ROS displayed a significant decrease of 18.26 to 23.91% in high-glucose-fed worms treated with CL extracts, while their lifespan remained unchanged. Additionally, the mRNA expression of genes associated with lipogenesis, such as sbp-1, showed a significant down-regulation following treatment with CL extracts. This finding was supported by a significant decrease (at 16.22-18.29%) in GFP-labeled sbp-1 gene expression. These results suggest that C. lentillifera extracts may facilitate a reduction in total fat accumulation induced by glucose through sbp-1 pathways. In summary, this study highlights the anti-obesity potential of compounds derived from C. lentillifera extracts in a C. elegans model of obesity, mediated by the suppression of lipogenesis pathways.
Assuntos
Caulerpa , Alga Marinha , Animais , Caenorhabditis elegans/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo , Glucose/metabolismoRESUMO
Halymenia durvillei is a red alga distributed along the coasts of Southeast Asian countries including Thailand. Previous studies have shown that an ethyl acetate fraction of H. durvillei (HDEA), containing major compounds including n-hexadecanoic acid, 2-butyl-5-hexyloctahydro-1H-indene, 3-(hydroxyacetyl) indole and indole-3-carboxylic acid, possesses high antioxidant and anti-lung cancer activities. The present study demonstrated that HDEA could protect mouse skin fibroblasts (L929) and human immortalized keratinocytes (HaCaT) against photoaging due to ultraviolet A and B (UVA and UVB) by reducing intracellular reactive oxygen species (ROS) and expressions of matrix metalloproteinases (MMP1 and MMP3), as well as increasing Nrf2 nuclear translocation, upregulations of mRNA transcripts of antioxidant enzymes, including superoxide dismutase (SOD), heme oxygenase (HMOX) and glutathione S-transferase pi1 (GSTP1), and procollagen synthesis. The results indicate that HDEA has the potential to protect skin cells from UV irradiation through the activation of the Nrf2 pathway, which leads to decreasing intracellular ROS and MMP production, along with the restoration of skin collagen.
Assuntos
Antioxidantes , Produtos Biológicos , Rodófitas , Raios Ultravioleta , Animais , Humanos , Camundongos , Antioxidantes/farmacologia , Linhagem Celular , Células HaCaT , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Rodófitas/química , Produtos Biológicos/farmacologia , Raios Ultravioleta/efeitos adversosRESUMO
Chest computed tomography (CT) has been the preferred imaging modality during the pandemic owing to its sensitivity in detecting COVID-19 infections. Recently, a large number of COVID-19 imaging datasets have been deposited in public databases, leading to rapid advances in COVID-19 research. However, the application of these datasets beyond COVID-19-related research has been little explored. The authors believe that they could be used in anatomical research to elucidate the link between anatomy and disease and to study disease-related alterations to normal anatomy. Therefore, the present study was designed to investigate the prevalence of six well-known anatomical variants in the thorax using open-access CT images obtained from over 1000 Iranian COVID-19 patients aged between 6 and 89 years (60.9% male and 39.1% female). In brief, we found that the azygos lobe, tracheal bronchus, and cardiac bronchus were present in 0.8%, 0.2%, and 0% of the patients, respectively. Variations of the sternum, including sternal foramen, episternal ossicles, and sternalis muscle, were observed in 9.6%, 2.9%, and 1.5%, respectively. We believe anatomists could benefit from using open-access datasets as raw materials for research because these datasets are freely accessible and are abundant, though further research is needed to evaluate the uses of other datasets from different body regions and imaging modalities. Radiologists should also be aware of these common anatomical variants when examining lung CTs, especially since the use of this imaging modality has increased during the pandemic.
Assuntos
COVID-19 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico por imagem , Criança , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Pandemias , Tórax , Tomografia Computadorizada por Raios X/métodos , Adulto JovemRESUMO
Background: There is a link between diabetic peripheral neuropathy (DPN) progression and the increase in the cross-sectional area (CSA) of the tibial nerve at the ankle. Nevertheless, no prior meta-analysis has been conducted to evaluate its usefulness for the diagnosis of DPN. Methods: We searched Google Scholar, Scopus, and PubMed for potential studies. Studies had to report tibial nerve CSA at the ankle and diabetes status (DM, DPN, or healthy) to be included. A random-effect meta-analysis was applied to calculate pooled tibial nerve CSA and mean differences across the groups. Subgroup and correlational analyses were conducted to study the potential covariates. Results: The analysis of 3295 subjects revealed that tibial nerve CSA was 13.39 mm2 (CI: 10.94−15.85) in DM patients and 15.12 mm2 (CI: 11.76−18.48) in DPN patients. The CSA was 1.93 mm2 (CI: 0.92−2.95, I2 = 98.69%, p < 0.01) larger than DPN-free diabetic patients. The diagnostic criteria of DPN and age were also identified as potential moderators of tibial nerve CSA. Conclusions: Although tibial nerve CSA at the ankle was significantly larger in the DPN patients, its clinical usefulness is limited by the overlap between groups and the inconsistency in the criteria used to diagnose DPN.
Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Humanos , Neuropatias Diabéticas/diagnóstico por imagem , Ultrassonografia , Nervo Tibial/diagnóstico por imagem , Tornozelo , Articulação do TornozeloRESUMO
BACKGROUND: Anconeus epitrochlaeris muscle and Osborne's ligament are anatomical variants that are occasionally found at the cubital tunnel of the elbow. In certain individuals, these two structures may compress the ulnar nerve resulting in a cubital tunnel syndrome. Although these variants have been reported extensively, its prevalence is still unclear and its contribution to cubital tunnel syndrome is debatable. The aim of this study is to generate weighted frequency values of the anconeus epitrochlearis and Osborne's ligament, as well as to identify any association of these two structures with gender, side, ethnicity and the development of cubital tunnel syndrome. METHODS: An anatomical study and a meta-analysis were performed to more accurately study the prevalence of anconeus epitrochlearis and Osborne's ligament. A total of 40 original studies including the present study met the inclusion criteria for meta-analysis and 6 case reports for descriptive analysis. RESULTS: Crude pooled prevalence estimate of the anconeus epitrochlearis was significantly higher (p < 0.001) in healthy subjects (14.2%) than in subjects diagnosed with cubital tunnel syndrome (4.5%). No significant difference was found for gender, side or laterality. The anconeus epitrochlearis was significantly more common in Europeans populations (18.2%) when compared with North American (6.8%) (p = 0.012) and Asian populations (7.5%) (p < 0.001). Anconeus epitrochlearis had a tendency to be hypertrophied when associated with cubital tunnel syndrome. The definition of Osborne's ligament is unclear, resulting in inconsistent reported prevalence across studies. CONCLUSION: The present study provides a more accurate estimate of anconeus epitrochlearis across the populations. There was a negative correlation between the presence of anconeus epitrochlearis and the development cubital tunnel syndrome, supporting the idea that the muscle may be protective against cubital tunnel syndrome. Future studies are needed to give proper definition of Osborne's ligament and accurately study its prevalence across populations.
Assuntos
Síndrome do Túnel Ulnar , Síndrome do Túnel Ulnar/epidemiologia , Cotovelo , Humanos , Ligamentos , Músculo Esquelético , PrevalênciaRESUMO
The azygos lobe (AL) is an accessory lobe of the right lung with prevalence between 0.4 and 1.2%. The aim of the present review is to provide a better estimate of the frequency of the AL and to examine its relationships with other variables such as population, diagnostic methods, and co-occurring illnesses. Studies published between 1899 and October 2020 were searched through three electronic databases; Google Scholar, PubMed, and JSTOR. Titles, abstracts, and full texts of the retrieved entries were screened to determine their appropriateness for inclusion. A total of 88 studies relating to 1,033,083 subjects met the inclusion criteria. A random-effects meta-analysis yielded an overall prevalence of 0.30% (95% CI: 0.0024-0.0035, I2 = 97.9%). Linear regression and subgroup analysis revealed a negative correlation (ρ = -0.540, p <0.001) between AL prevalence and sample size; studies with smaller sample sizes had higher prevalences. The AL prevalence in individuals with congenital pulmonary defects, 5.2% (95% CI: 0.0018-0.0086, I2 = 0%), was 17 times higher than the overall prevalence (z = 6.65, p <0.001), suggesting associations with other abnormalities and possibly a genetic predisposition. In addition to an evidence-based synthesis of AL prevalence, this study demonstrates publication bias and small-study effects in the anatomy literature. Awareness of the AL is crucial for radiologists when they interpret unusual radiological findings and for surgeons when they operate in the region.
Assuntos
Variação Anatômica , Pulmão/anatomia & histologia , Humanos , Prevalência , Fatores de RiscoRESUMO
Parkinson's disease (PD) is a currently incurable neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta and α-synuclein aggregation. Accumulated evidence indicates that the saponins, especially from ginseng, have neuroprotective effects against neurodegenerative disorders. Interestingly, saponin can also be found in marine organisms such as the sea cucumber, but little is known about its effect in neurodegenerative disease, including PD. In this study, we investigated the anti-Parkinson effects of frondoside A (FA) from Cucumaria frondosa and ginsenoside Rg3 (Rg3) from Panax notoginseng in C. elegans PD model. Both saponins were tested for toxicity and optimal concentration by food clearance assay and used to treat 6-OHDA-induced BZ555 and transgenic α-synuclein NL5901 strains in C. elegans. Treatment with FA and Rg3 significantly attenuated DAergic neurodegeneration induced by 6-OHDA in BZ555 strain, improved basal slowing rate, and prolonged lifespan in the 6-OHDA-induced wild-type strain with downregulation of the apoptosis mediators, egl-1 and ced-3, and upregulation of sod-3 and cat-2. Interestingly, only FA reduced α-synuclein aggregation, rescued lifespan in NL5901, and upregulated the protein degradation regulators, including ubh-4, hsf-1, hsp-16.1 and hsp-16.2. This study indicates that both FA and Rg3 possess beneficial effects in rescuing DAergic neurodegeneration in the 6-OHDA-induced C. elegans model through suppressing apoptosis mediators and stimulating antioxidant enzymes. In addition, FA could attenuate α-synuclein aggregation through the protein degradation process.
Assuntos
Caenorhabditis elegans/fisiologia , Ginsenosídeos/farmacologia , Glicosídeos/farmacologia , Doença de Parkinson/patologia , Triterpenos/farmacologia , Animais , Animais Geneticamente Modificados , Apoptose/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/química , Ginsenosídeos/toxicidade , Glicosídeos/química , Glicosídeos/toxicidade , Longevidade/efeitos dos fármacos , Degeneração Neural/complicações , Degeneração Neural/patologia , Oxidopamina , Doença de Parkinson/complicações , Proteólise/efeitos dos fármacos , Triterpenos/química , Triterpenos/toxicidade , alfa-Sinucleína/metabolismoRESUMO
The pathological finding of amyloid-ß (Aß) aggregates is thought to be a leading cause of untreated Alzheimer's disease (AD). In this study, we isolated 2-butoxytetrahydrofuran (2-BTHF), a small cyclic ether, from Holothuria scabra and demonstrated its therapeutic potential against AD through the attenuation of Aß aggregation in a transgenic Caenorhabditis elegans model. Our results revealed that amongst the five H. scabra isolated compounds, 2-BTHF was shown to be the most effective in suppressing worm paralysis caused by Aß toxicity and in expressing strong neuroprotection in CL4176 and CL2355 strains, respectively. An immunoblot analysis showed that CL4176 and CL2006 treated with 2-BTHF showed no effect on the level of Aß monomers but significantly reduced the toxic oligomeric form and the amount of 1,4-bis(3-carboxy-hydroxy-phenylethenyl)-benzene (X-34)-positive fibril deposits. This concurrently occurred with a reduction of reactive oxygen species (ROS) in the treated CL4176 worms. Mechanistically, heat shock factor 1 (HSF-1) (at residues histidine 63 (HIS63) and glutamine 72 (GLN72)) was shown to be 2-BTHF's potential target that might contribute to an increased expression of autophagy-related genes required for the breakdown of the Aß aggregate, thus attenuating its toxicity. In conclusion, 2-BTHF from H. scabra could protect C. elegans from Aß toxicity by suppressing its aggregation via an HSF-1-regulated autophagic pathway and has been implicated as a potential drug for AD.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/antagonistas & inibidores , Furanos/farmacologia , Holothuria/química , Fármacos Neuroprotetores/farmacologia , Paralisia/prevenção & controle , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Animais Geneticamente Modificados , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Sítios de Ligação , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/antagonistas & inibidores , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Modelos Animais de Doenças , Furanos/química , Furanos/isolamento & purificação , Regulação da Expressão Gênica , Humanos , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Paralisia/genética , Paralisia/metabolismo , Paralisia/patologia , Agregados Proteicos/efeitos dos fármacos , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
PURPOSE: Anatomical variants in the posterior compartment of forearm and hand are not uncommon. Physicians should be aware of variations in this region for correct diagnosis and treatment of diseased hands. METHODS: During a routine dissection at our department, an extremely rare case of deep hand extensor muscle was discovered. RESULTS: A complete extensor digitorum profundus complex was found in the fourth extensor compartment in addition to the extensor indicis proprius. The complex consisted of two muscle bellies originating from the lateral aspect of distal ulna and the adjacent interosseous membrane. The first belly resembled the conventional extensor indicis proprius. The second belly gave off two tendon slips: one inserted to the index and middle fingers and the other formed aponeurosis before inserting to the ring and little fingers. CONCLUSION: To our knowledge, a complete extensor digitorum profundus complex which inserts to all medial four digits has never been reported in humans. Awareness of variations in this region is critical for surgeons operating in the forearm and hand. The present case also provides insights into the evolutionary and developmental origin of these structures.
Assuntos
Variação Anatômica , Aponeurose/anormalidades , Dedos/anormalidades , Antebraço/anormalidades , Músculo Esquelético/anormalidades , Idoso de 80 Anos ou mais , Cadáver , Dissecação , Humanos , MasculinoRESUMO
BACKGROUND: Caesalpinia mimosoides, a vegetable consumed in Thailand, has been reported to exhibit in vitro antioxidant properties. The in vivo antioxidant and anti-aging activities have not been investigated. The aim of this research was to study the antioxidant activity of C. mimosoides extracts in Caenorhabditis elegans, a widely used model organism in this context. METHODS: C. elegans were treated with C. mimosoides extracts in a various concentrations. To investigate the protective effects of the extract against oxidative stress, wild-type N2 were used to determine survival rate under oxidative stress and intracellular ROS. To study underlying mechanisms, the mutant strains with GFP reporter gene including TJ356, CF1553, EU1 and LD4 were used to study DAF-16, SOD-3, SKN-1 and GST-4 gene, respectively. Lifespan and aging pigment of the worms were also investigated. RESULTS: A leaf extract of C. mimosoides improved resistance to oxidative stress and reduced intracellular ROS accumulation in nematodes. The antioxidant effects were mediated through the DAF-16/FOXO pathway and SOD-3 expression, whereas the expression of SKN-1 and GST-4 were not altered. The extract also prolonged lifespan and decreased aging pigments, while the body length and brood size of the worms were not affected by the extract, indicating low toxicity and excluding dietary restriction. CONCLUSIONS: The results of this study establish the antioxidant activity of C. mimosoides extract in vivo and suggest its potential as a dietary supplement and alternative medicine to defend against oxidative stress and aging, which should be investigated in intervention studies.
Assuntos
Antioxidantes/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Caesalpinia/química , Longevidade/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Tamanho Corporal/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/metabolismo , Flavonoides/análise , Sequestradores de Radicais Livres/farmacologia , Metanol , Naftoquinonas , Fenóis/análise , Folhas de Planta/química , Espécies Reativas de Oxigênio , Reprodução/efeitos dos fármacosRESUMO
BACKGROUND: Saponins have been shown to possess many pharmacological properties, including altered fat metabolism. The black sea cucumber, Holothuria leucospilota, is a marine animal that contains a specialized organ called a Cuvierian tubule that produces and secrete the bioactive saponins into the tubules and body wall. Therefore, the aims of this study are to investigate the anti-obesity effect of saponins extracted from body wall and Cuvierian tubules of H. leucospilota. RESULTS: The butanol extracts of H. leucospilota body wall and Cuvierian tubules containing high amounts of saponins significantly reduced fat deposition and triglyceride levels in Caenorhabditis elegans fed with 50 mmol L-1 glucose. Moreover, the saponin-enriched extracts of H. leucospilota significantly restored the lifespan of 2% glucose-fed worms (18.71%). Green fluorescence protein-labeled sbp-1 gene expression and nuclear translocation of daf-16 were also significantly decreased in H. leucospilota treatment. The saponin-enriched extracts downregulated the messenger RNA expressions of genes involved in fat storage and metabolism, including sbp-1, cebp, and daf-16 but upregulated the expression of nhr-49 gene. CONCLUSION: Our results suggest that H. leucospilota-derived saponins may mediate the reduction of glucose-induced fat accumulation through sbp-1, cebp, daf-16 and nhr-9 pathways. Therefore, the H. leucospilota extracts could be used as nutraceuticals for anti-obesity prevention. © 2019 Society of Chemical Industry.
Assuntos
Modelos Animais de Doenças , Gorduras/metabolismo , Holothuria/química , Lipogênese/efeitos dos fármacos , Obesidade/tratamento farmacológico , Saponinas/farmacologia , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Humanos , Obesidade/genética , Obesidade/metabolismo , Triglicerídeos/metabolismoRESUMO
Subdivision of cloaca into urogenital and anorectal passages has remained controversial because of disagreements about the identity and role of the septum developing between both passages. This study aimed to clarify the development of the cloaca using a quantitative 3D morphological approach in human embryos of 4-10 post-fertilisation weeks. Embryos were visualised with Amira 3D-reconstruction and Cinema 4D-remodelling software. Distances between landmarks were computed with Amira3D software. Our main finding was a pronounced difference in growth between rapidly expanding central and ventral parts, and slowly or non-growing cranial and dorsal parts. The entrance of the Wolffian duct into the cloaca proved a stable landmark that remained linked to the position of vertebra S3. Suppressed growth in the cranial cloaca resulted in an apparent craniodorsal migration of the entrance of the Wolffian duct, while suppressed growth in the dorsal cloaca changed the entrance of the hindgut from cranial to dorsal on the cloaca. Transformation of this 'end-to-end' into an 'end-to-side' junction produced temporary 'lateral (Rathke's) folds'. The persistent difference in dorsoventral growth straightened the embryonic caudal body axis and concomitantly extended the frontally oriented 'urorectal (Tourneux's) septum' caudally between the ventral urogenital and dorsal anorectal parts of the cloaca. The dorsoventral growth difference also divided the cloacal membrane into a well-developed ventral urethral plate and a thin dorsal cloacal membrane proper, which ruptured at 6.5 weeks. The expansion of the pericloacal mesenchyme followed the dorsoventral growth difference and produced the genital tubercle. Dysregulation of dorsal cloacal development is probably an important cause of anorectal malformations: too little regressive development may result in anorectal agenesis, and too much regression in stenosis or atresia of the remaining part of the dorsal cloaca.
Assuntos
Cloaca/embriologia , Sistema Urogenital/embriologia , Embrião de Mamíferos , HumanosRESUMO
OBJECTIVES: Parkinson's disease (PD) is associated with aggregation of α-synuclein and selective death of dopaminergic (DA) neurons in the substantia nigra, thereby leading to cognitive and motor impairments. Nowadays, the drugs commonly used for PD treatment, such as levodopa, provide only symptomatic relief. Therefore, seeking new drugs against PD, especially from plants and marine organisms, is one of the major research areas to be explored. This study aimed to investigate the anti-Parkinson activity of the extracts from the sea cucumber, Holothuria scabra, by using Caenorhabditis elegans as a model. METHODS: H. scabra was solvent-extracted and subdivided into six fractions including whole body-ethyl acetate (WBEA), body wall-ethyl acetate (BWEA), viscera-ethyl acetate (VIEA), whole body-butanol (WBBU), body wall-butanol (BWBU), and viscera-butanol (VIBU). The extracts were tested in C. elegans BZ555 strain expressing the green fluorescent protein (GFP) specifically in the DA neurons and NL5901 strain expressing human α-synuclein in the muscle cells. RESULTS: WBEA, BWEA, and WBBU fractions of H. scabra extracts at 500â µg/ml significantly attenuated DA neuron-degeneration induced by selective cathecholamine neurotoxin 6-hydroxydopamine (6-OHDA) in the BZ555 strain. Moreover, the extracts also reduced α-synuclein aggregation and restored lipid content in NL5901, as well as improved food-sensing behavior and prolonged lifespan in the 6-OHDA-treated wild-type strain. DISCUSSION: The study indicated that the H. scabra extracts have anti-Parkinson potential in the C. elegans model. These findings encourage further investigations on using the H. scabra extract, as well as its active constituent compounds, as a possible preventive and/or therapeutic intervention against PD.
Assuntos
Antiparkinsonianos/farmacologia , Produtos Biológicos/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Holothuria/química , Doença de Parkinson/tratamento farmacológico , Animais , Caenorhabditis elegans/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Degeneração Neural/induzido quimicamente , Degeneração Neural/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Oxidopamina/toxicidade , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismoRESUMO
PURPOSE: The aim of the study was to investigate the anatomy and histology of Linburg-Comstock variation, or the anomalous connection between flexor pollicis longus and flexor digitorum profundus to the index finger, in Thai population. METHODS: One hundred and thirty cadaveric upper limbs were dissected. Skin and superficial fascia on the anterior distal forearm and hand were removed. The tendons of the flexor pollicis longus and flexor digitorum profundus to the index finger were identified for the possible occurrence of the intertendinous connection. For histological analysis, selected specimens were sampled, and were stained with hematoxylin and eosin. RESULTS: Out of 130 dissected upper limbs, interconnection between the two tendons was found in 32 limbs (25%). The connection was classified into three types including fibrous, tendinous, and musculotendinous. In 29 cases (22%), the connection was simply the thickening of synovial sheath between the two tendons. In two cases (1%) the connection was found as an additional tendinous slip of dense regular collagen bundles running from the flexor pollicis longus to flexor digitorum profundus of the index. In one case (1%), there was an aberrant reversed musculotendinous unit running from flexor pollicis longus, and later joined the first lumbrical. CONCLUSIONS: This study provides a detailed anatomo-histological description of the interconnection between flexor pollicis longus and flexor digitorum profundus to the index finger. Its etiology could either be congenital or secondarily acquired. Surgeons should be aware of this connection for better diagnosis, surgical planning and treatment of diseased hands.
Assuntos
Dedos/anormalidades , Deformidades Congênitas da Mão/patologia , Tendões/anormalidades , Variação Anatômica , Cadáver , Dissecação , Humanos , Síndrome , TailândiaRESUMO
BACKGROUND: Although such local herb as Streblus asper (family Moraceae) has long been recognized for traditional folk medicines and important ingredient of traditional longevity formula, its anti-neurodegeneration or anti-aging activity is little known. This study aimed to investigate the neuroprotective effect of S. asper leaf extracts (SA-EE) against toxicity of glutamate-mediated oxidative stress, a crucial factor contributing to the neuronal loss in age-associated neurodegenerative diseases and the underlying mechanism as well as to evaluate its longevity effect. METHODS: Using mouse hippocampal HT22 as a model for glutamate oxidative toxicity, we carried out MTT and LDH assays including Annexin V-FITC/propidium iodide staining to determine the SA-EE effect against glutamate-induced cell death. Antioxidant activities of SA-EE were evaluated using the radical scavenging and DCFH-DA assays. To elucidate the underlying mechanisms, SA-EE treated cells were analyzed for the expressions of mRNA and proteins interested by immunofluorescent staining, western blot analysis and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) techniques. The longevity effect of SA-EE was examined on C. elegans by lifespan assay. RESULTS: We demonstrate that a concentration-dependent reduction of glutamate-induced cytotoxicity was significant after SA-EE treatment as measured by MTT and LDH assays. Annexin V-FITC/propidium iodide and immunofluorescent staining showed that co-treatment of glutamate with SA-EE significantly reduced apoptotic-inducing factor (AIF)-dependent apoptotic cell death. DCFH-DA assay revealed that this extract was capable of dose dependently attenuating the ROS caused by glutamate. Western blot analysis and qRT-PCR showed that nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels in the nucleus, as well as mRNA levels of antioxidant-related genes under Nrf2 regulation were significantly increased by SA-EE. Furthermore, this extract was capable of extending the lifespan of C. elegans. CONCLUSIONS: SA-EE possesses both longevity effects and neuroprotective activity against glutamate-induced cell death, supporting its therapeutic potential for the treatment of age-associated neurodegenerative diseases.
Assuntos
Ácido Glutâmico/toxicidade , Moraceae , Neurônios/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caenorhabditis elegans , Linhagem Celular , Sobrevivência Celular , Etanol , Hipocampo/citologia , Longevidade/efeitos dos fármacos , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/citologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Folhas de Planta/química , Substâncias Protetoras/química , Transdução de Sinais/efeitos dos fármacosRESUMO
Plumbagin, (5-hydroxy-2-methyl-1,4-naphthoquinone), a natural substance found in the roots of plant species in the genus Plumbago, has been used as a traditional medicine against many diseases. In this study, Caenorhabditis elegans was used as a model for testing the anthelmintic effect of plumbagin. The compound exhibited a nematicidal effect against all stages of C. elegans: L4 was least susceptible, while L1 was most susceptible to plumbagin with an LC(50) of 220 and 156 µM, respectively. Plumbagin inhibited C. elegans development from L1 to adult stages with an IC(50) of 235 µM, and body length was also reduced at concentrations of 25 and 50 µg/ml. Brood sizes decreased from 203±6 to 43±6 and 18±3 eggs per hatch in plumbagin-treated worms at 10, 25, 50 µg/ml, respectively. Furthermore, plumbagin was lethal to strains resistant to the nematicides levamisole, albendazole, and ivermectin, indicating that it possesses a strong and unique nematicidal action. Plumbagin decreased the number of mitochondria in hypodermal and intestinal cells and body wall muscles and damaged the ultrastructure of these tissues. Taken together, plumbagin may be a new drug against parasitic nematodes.
Assuntos
Antinematódeos/farmacologia , Caenorhabditis elegans/metabolismo , Naftoquinonas/farmacologia , Animais , Antinematódeos/química , Caenorhabditis elegans/ultraestrutura , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Naftoquinonas/químicaRESUMO
A total of 100 cadaveric limbs were dissected to study the anatomy of the forearm and hand extensor musculature. Four types of contributions to the index finger were found for the extensor indicis proprius (EIP), including one new type where the double tendons of the EIP inserts volar and radial to the extensor digitorum communis of the index finger (EDC-I). Four variant muscles were identified including the extensor medii proprius (EMP) (in five cadavers), extensor digitorum brevis manus (EDBM) (in one cadaver), extensor indicis et medii communis (EIMC) (in four cadavers) and extensor pollicis et indicis (EPI) (in four cadavers). The absence of the EIP in four cases was substituted by either the EIMC or the EPI. Two unpreviously published cases were found. In one hand, the variant EIMC was present along with the EPI. In another hand, both the EMP and the EDBM were present, and the EMP tendon inserted to the tendon of the EDBM. Awareness of the variations on the dorsum of the hand is essential for diagnosis, surgical planning and treatment of diseased hands.
Assuntos
Variação Anatômica , Mãos/anatomia & histologia , Tendões/anatomia & histologia , HumanosRESUMO
Fasciolosis, caused by Fasciola hepatica and Fasciola gigantica, is one of the most neglected tropical zoonotic diseases. One sustainable control strategy against these infections is the employment of vaccines that target proteins essential for parasites' invasion and nutrition acquiring processes. Cathepsin proteases are the most abundantly expressed proteins in Fasciola spp. that have been tested successfully as vaccines against fasciolosis in experimental as well as large animals because of their important roles in digestion of nutrients, invasion, and migration. Specifically, juvenile-specific cathepsin proteases are the more effective vaccines because they could block the invasion and migration of juvenile parasites whose immune evasion mechanism has not yet been fully developed. Moreover, because of high sequence similarity and identity of cathepsins from juveniles with those of adults, the vaccines can attack both the juvenile and adult stages. In this article, the characteristics and vaccine potentials of juvenile-specific cathepsins, i.e., cathepsins L and B, of Fasciola spp. were reviewed.
Assuntos
Catepsinas/imunologia , Fasciola/enzimologia , Fasciolíase/prevenção & controle , Animais , Catepsina B/imunologia , Catepsina L/imunologia , Fasciola/crescimento & desenvolvimento , Fasciola/imunologia , Fasciolíase/parasitologia , Proteínas de Helminto/imunologia , Estágios do Ciclo de Vida , Peptídeo Hidrolases/imunologia , Caramujos/parasitologia , Vacinas/imunologiaRESUMO
Cathepsin Ls (CatLs), the major cysteine protease secreted by Fasciola spp., are important for parasite digestion and tissue invasion. Fasciola gigantica cathepsin L1H (FgCatL1H) is the isotype expressed in the early stages for migration and invasion. In the present study, a monoclonal antibody (MoAb) against recombinant F. gigantica cathepsin L1H (rFgCatL1H) was produced by hybridoma technique using spleen cells from BALB/c mice immunized with recombinant proFgCatL1H (rproFgCatL1H). This MoAb is an immunoglobulin (Ig)G1 with κ light chain isotype. The MoAb reacted specifically with rproFgCatL1H, the native FgCatL1H at a molecular weight (MW) 38 to 48 kDa in the extract of whole body (WB) of metacercariae and newly excysted juvenile (NEJ) and cross-reacted with rFgCatL1 and native FgCatLs at MW 25 to 28 kDa in WB of 2- and 4-week-old juveniles, adult, and adult excretory-secretory (ES) fractions by immunoblotting and indirect ELISA. It did not cross-react with antigens in WB fractions from other parasites, including Gigantocotyle explanatum, Paramphistomum cervi, Gastrothylax crumenifer, Eurytrema pancreaticum, Setaria labiato-papillosa, and Fischoederius cobboldi. By immunolocalization, MoAb against rFgCatL1H reacted with the native protein in the gut of metacercariae and NEJ and also cross-reacted with CatL1 in 2- and 4-week-old juveniles and adult F. gigantica. Therefore, FgCatL1H and its MoAb may be used for immunodiagnosis of both early and late fasciolosis in ruminants and humans.