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1.
Endocrinology ; 165(10)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39253786

RESUMO

Prostate cancer progression is driven by androgen receptor (AR) activity, which is a target for therapeutic approaches. Enzalutamide is an AR inhibitor that prolongs the survival of patients with advanced prostate cancer. However, resistance mechanisms arise and impair its efficacy. One of these mechanisms is the expression of AR-V7, a constitutively active AR splice variant. The Mediator complex is a multisubunit protein that modulates gene expression on a genome-wide scale. MED12 and cyclin-dependent kinase (CDK)8, or its paralog CDK19, are components of the kinase module that regulates the proliferation of prostate cancer cells. In this study, we investigated how MED12 and CDK8/19 influence cancer-driven processes in prostate cancer cell lines, focusing on AR activity and the enzalutamide response. We inhibited MED12 expression and CDK8/19 activity in LNCaP (AR+, enzalutamide-sensitive), 22Rv1 (AR-V7+, enzalutamide-resistant), and PC3 (AR-, enzalutamide-insensitive) cells. Both MED12 and CDK8/19 inhibition reduced cell proliferation in all cell lines, and MED12 inhibition reduced proliferation in the respective 3D spheroids. MED12 knockdown significantly inhibited c-Myc protein expression and signaling pathways. In 22Rv1 cells, it consistently inhibited the AR response, prostate-specific antigen (PSA) secretion, AR target genes, and AR-V7 expression. Combined with enzalutamide, MED12 inhibition additively decreased the AR activity in both LNCaP and 22Rv1 cells. CDK8/19 inhibition significantly decreased PSA secretion in LNCaP and 22Rv1 cells and, when combined with enzalutamide, additively reduced proliferation in 22Rv1 cells. Our study revealed that MED12 and CDK8/19 regulate AR activity and that their inhibition may modulate response to enzalutamide in prostate cancer.


Assuntos
Benzamidas , Proliferação de Células , Quinase 8 Dependente de Ciclina , Quinases Ciclina-Dependentes , Complexo Mediador , Nitrilas , Feniltioidantoína , Neoplasias da Próstata , Receptores Androgênicos , Feniltioidantoína/farmacologia , Masculino , Humanos , Receptores Androgênicos/metabolismo , Receptores Androgênicos/genética , Complexo Mediador/metabolismo , Complexo Mediador/genética , Linhagem Celular Tumoral , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Quinases Ciclina-Dependentes/metabolismo , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/antagonistas & inibidores , Quinase 8 Dependente de Ciclina/metabolismo , Quinase 8 Dependente de Ciclina/genética , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
2.
Antioxidants (Basel) ; 13(8)2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39199262

RESUMO

Sperm cryopreservation is a fundamental tool for the conservation of avian genetic resources; however, avian spermatozoa are susceptible to this process. To cope with the high production of reactive oxygen species (ROS), the addition of exogenous antioxidants is beneficial. Pectoliv30 is a substance derived from alperujo, and in this study, its effect was analyzed on seminal quality after its addition to the cryopreservation extender of roosters at different concentrations. For this purpose, 16 Utrerana breed roosters were used, and seminal collection was performed in six replicates, creating a pool for each working day with ejaculates of quality. After cryopreservation, one sample per treatment and replicate was thawed, and several seminal quality parameters were evaluated. Statistical analysis revealed numerous correlations between these variables, both positive and negative according to the correlation matrix obtained. Furthermore, the chi-squared automatic interaction detection (CHAID) decision tree (DT) reported significant differences in the hypo-osmotic swelling test (HOST) variable between groups. Moreover, results for this parameter were more desirable at high concentrations of Pectoliv30. The application of this substance extracted from the by-product alperujo as an antioxidant allows the improvement of the post-thawing seminal quality in roosters and facilitates optimization of the cryopreservation process as a way to improve the conservation programs of different endangered poultry breeds.

3.
Diabetes Metab Syndr ; 18(7): 103095, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39098208

RESUMO

BACKGROUND & AIMS: Asprosin is a promising candidate for novel treatments for metabolic-endocrine disorders. The objective of this systematic review and meta-analysis was to consolidate the existing evidence regarding asprosin levels in patients diagnosed with type 2 diabetes (T2D), metabolic syndrome (MetS), and obesity. METHODS: Scopus, Embase, PubMed, Ovid/Medline, and Web of Science were systematically searched without restrictions. We only used the standardized mean differences (SMD) with their 95 % confidence intervals (95 % CI) as the effect measure. A random-effects model (DerSimonian and Laird method) was used for the meta-analysis. Risk of bias was assessed with the Newcastle-Ottawa Scale and Newcastle-Ottawa Scale for Cross-Sectional Studies. RESULTS: Twenty-six studies (n = 3,787) were included in the meta-analysis. Participants with T2D had higher asprosin values than those without T2D (SMD: 1.64; 95 % CI: 1.08-2.21; I2 = 97 %). Patients with MetS had higher asprosin levels compared to those without MetS (SMD: 0.99; 95 % CI: 0.34-1.64; I2 = 96 %). Patients with obesity had higher asprosin levels than participants without obesity (SMD: 1.49; 95 % CI: 0.23-2.76; I2 = 98 %). CONCLUSIONS: Asprosin is significantly higher in patients with either T2D, MetS, or obesity, compared with controls.

4.
Mikrochim Acta ; 191(9): 526, 2024 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-39120744

RESUMO

A LOx-based electrochemical biosensor for high-level lactate determination was developed. For the construction of the biosensor, chitosan and Nafion layers were integrated by using a spin coating procedure, leading to less porous surfaces in comparison with those recorded after a drop casting procedure. The analytical performance of the resulting biosensor for lactate determination was evaluated in batch and flow regime, displaying satisfactory results in both modes ranging from 0.5 to 20 mM concentration range for assessing the lactic acidosis. Finally, the lactate levels in raw serum samples were estimated using the biosensor developed and verified with a blood gas analyzer. Based on these results, the biosensor developed is promising for its use in healthcare environment, after its proper miniaturization. A pH probe based on common polyaniline-based electrochemical sensor was also developed to assist the biosensor for the lactic acidosis monitoring, leading to excellent results in stock solutions ranging from 6.0 to 8.0 mM and raw plasma samples. The results were confirmed by using two different approaches, blood gas analyzer and pH-meter. Consequently, the lactic acidosis monitoring could be achieved in continuous flow regime using both (bio)sensors.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Ácido Láctico , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Concentração de Íons de Hidrogênio , Ácido Láctico/sangue , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Humanos , Acidose Láctica/sangue , Acidose Láctica/diagnóstico , Quitosana/química , Polímeros de Fluorcarboneto/química , Compostos de Anilina/química , Enzimas Imobilizadas/química , Oxigenases de Função Mista
5.
Rev. colomb. cir ; 39(4): 633-639, Julio 5, 2024. fig
Artigo em Espanhol | LILACS | ID: biblio-1566026

RESUMO

Introducción. La neoplasia sólida pseudopapilar de páncreas, también conocida como tumor de Frantz, es una patología poco frecuente, que comprende menos del 3 % de los tumores pancreáticos, y la mayor incidencia se observa en mujeres jóvenes entre la segunda y tercera década de la vida. Su etiología es desconocida. El tratamiento de elección es la resección quirúrgica sin linfadenectomía cuando se encuentra bien localizado. Inclusive aún cuando hay evidencia de metástasis o invasión local, el manejo quirúrgico sigue siendo el tratamiento de elección. Caso clínico. Mujer de 24 años de edad, con masa abdominal palpable, dolorosa, de tres semanas de evolución. La tomografía computarizada mencionó como presunción diagnóstica un tumor de origen pancreático. En la laparotomía se encontró una masa dependiente del cuerpo del páncreas. Se realizó pancreatectomía distal radical con esplenectomía y omentectomía parcial en bloque. Resultados. Durante la cirugía no se presentaron complicaciones y hasta el sexto mes de seguimiento, la evolución fue adecuada y sin recidiva tumoral. Conclusiones. Ante la presencia de masa abdominal, con compromiso pancreático documentado por tomografía computarizada, se debe considerar el diagnóstico de neoplasia sólida pseudopapilar de páncreas, o tumor de Frantz. El tumor de Frantz es una entidad poco frecuente que generalmente se diagnostica de forma incidental o por síntomas inespecíficos en estadios avanzados. El diagnóstico y manejo de esta neoplasia representa un reto y la resección quirúrgica continúa siendo el tratamiento indicado.


Introduction. Solid pseudopapillary neoplasia of the pancreas, also known as Frantz tumor, is a rare pathology, comprising less than 3% of pancreatic tumors, and the highest incidence is observed in young women between the second and third decades of life. Its etiology is unknown. The treatment of choice is surgical resection without lymphadenectomy when it is well located. Even when there is evidence of metastasis or local invasion, surgical management remains the treatment of choice. Clinical case. A 24-year-old woman presented with a palpable, painful abdominal mass of three weeks' duration. The computed tomography mentioned a tumor of pancreatic origin as a presumptive diagnosis. At laparotomy, a mass dependent on the body of the pancreas was found. Radical distal pancreatectomy with splenectomy and en bloc partial omentectomy was performed. Results. During the surgery there were no complications and until the sixth month of follow-up, the evolution was adequate and without tumor recurrence. Conclusions. In the presence of an abdominal mass, with pancreatic involvement documented by computed tomography, the diagnosis of solid pseudopapillary neoplasia of the pancreas, or Frantz tumor, should be considered, which must be treated surgically. Frantz tumor is a rare entity that is generally diagnosed incidentally or due to nonspecific symptoms in advanced stages. The diagnosis and management of this neoplasia represents a challenge and surgical resection continues to be the indicated treatment.


Assuntos
Humanos , Pancreatectomia , Neoplasias Pancreáticas , Pâncreas , Achados Incidentais , Diagnóstico Diferencial
6.
mSystems ; 9(8): e0041624, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38990071

RESUMO

Medium-chain carboxylates (MCCs) are used in various industrial applications. These chemicals are typically extracted from palm oil, which is deemed not sustainable. Recent research has focused on microbial chain elongation using reactors to produce MCCs, such as n-caproate (C6) and n-caprylate (C8), from organic substrates such as wastes. Even though the production of n-caproate is relatively well-characterized, bacteria and metabolic pathways that are responsible for n-caprylate production are not. Here, three 5 L reactors with continuous membrane-based liquid-liquid extraction (i.e., pertraction) were fed ethanol and acetate and operated for an operating period of 234 days with different operating conditions. Metagenomic and metaproteomic analyses were employed. n-Caprylate production rates and reactor microbiomes differed between reactors even when operated similarly due to differences in H2 and O2 between the reactors. The complete reverse ß-oxidation (RBOX) pathway was present and expressed by several bacterial species in the Clostridia class. Several Oscillibacter spp., including Oscillibacter valericigenes, were positively correlated with n-caprylate production rates, while Clostridium kluyveri was positively correlated with n-caproate production. Pseudoclavibacter caeni, which is a strictly aerobic bacterium, was abundant across all the operating periods, regardless of n-caprylate production rates. This study provides insight into microbiota that are associated with n-caprylate production in open-culture reactors and provides ideas for further work.IMPORTANCEMicrobial chain elongation pathways in open-culture biotechnology systems can be utilized to convert organic waste and industrial side streams into valuable industrial chemicals. Here, we investigated the microbiota and metabolic pathways that produce medium-chain carboxylates (MCCs), including n-caproate (C6) and n-caprylate (C8), in reactors with in-line product extraction. Although the reactors in this study were operated similarly, different microbial communities dominated and were responsible for chain elongation. We found that different microbiota were responsible for n-caproate or n-caprylate production, and this can inform engineers on how to operate the systems better. We also observed which changes in operating conditions steered the production toward and away from n-caprylate, but more work is necessary to ascertain a mechanistic understanding that could be predictive. This study provides pertinent research questions for future work.


Assuntos
Reatores Biológicos , Microbiota , Reatores Biológicos/microbiologia , Caprilatos/metabolismo , Caproatos/metabolismo , Bactérias/metabolismo , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Extração Líquido-Líquido/métodos
7.
New Microbes New Infect ; 60-61: 101439, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38911488

RESUMO

Introduction: Avian influenza A H5N1 is a significant global public health threat. Although relevant, systematic reviews about its prevalence in animals are lacking. Methods: We performed a systematic literature review in bibliographic databases to assess the prevalence of H5N1 in animals. A meta-analysis with a random-effects model was performed to calculate the pooled prevalence and 95 % confidence intervals (95%CI). In addition, measures of heterogeneity (Cochran's Q statistic and I2 test) were reported. Results: The literature search yielded 1359 articles, of which 33 studies were fully valid for analysis, including 96,909 animals. The pooled prevalence for H5N1 in birds (n = 90,045, 24 studies) was 5.0 % (95%CI: 4.0-6.0 %; I2 = 99.21); in pigs (n = 3,178, 4 studies) was 1.0 % (95%CI: 0.0-1.0 %); in cats (n = 2,911, 4 studies) was 0.0 % (95%CI: 0.0-1.0 %); and in dogs (n = 479, 3 studies) was 0.0 % (95%CI: 0.0-2.0 %). Conclusions: While the occurrence of H5N1 in animals might be comparatively limited compared to other influenza viruses, its impact on public health can be substantial when it transmits to humans. This virus can potentially induce severe illness and has been linked to previous outbreaks. Therefore, it is essential to closely monitor and comprehend the factors influencing the prevalence of H5N1 in both avian and human populations to develop effective disease control and prevention strategies.

8.
Infez Med ; 32(2): 183-201, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827825

RESUMO

Introduction: Dengue is a vector-borne disease, especially important in tropical and subtropical areas. The first presentation of many arboviral diseases occurred mainly in animals, including multiple Alphaviruses and Flaviviruses, such as dengue. Objective: To determine the serological and molecular frequency of the dengue virus in animals. Methods: A systematic literature review was carried out in five databases for the proportion of animals infected with dengue, defined by molecular and serological tests. A meta-analysis was performed using a random-effects model to calculate the pooled prevalence and 95% confidence intervals (CI). Cochran?s Q test and the I2 statistic were used to assess the heterogeneity between the two studies. Results: The presence of dengue in bats, primates, birds, sheep, horses, cattle, pigs, rodents and buffaloes, according to serological methods, had a prevalence of 10%, 29%, 8%, 1%, 11%, 0%, 49%, 2%, 7%, respectively. According to molecular methods, the presence of dengue in bats had a seroprevalence of 6.0%. Conclusion: The present study confirms the presence of the Dengue virus in a large group of animal species, with potential implications as possible reservoirs of this virus, raising the possibility of zoonotic transmission.

9.
SAGE Open Med ; 12: 20503121241253957, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774742

RESUMO

Objective: We aimed to review the available evidence on the association between vitamin B12, folate, and homocysteine levels with worse outcomes among COVID-19 patients. Methods: The search was carried out in ten databases simultaneously run on 10 May 2023, without language restrictions. We included cross-sectional, case-control, and cohort studies. The random-effects meta-analysis was performed using the Sidik-Jonkman method and corrected 95% confidence intervals using the truncated Knapp-Hartung standard errors. Standardized mean difference and 95% CI was used as the measure effect size. Results: Thirteen articles were included in this review (n = 2134). Patients with COVID-19 who did not survive had the highest serum vitamin B12 values (SMD: 1.05; 95% CI: 0.31-1.78; p = 0.01, I2 = 91.22%). In contrast, low serum folate values were associated with patients with severe COVID-19 (SMD: -0.77; 95% CI: -1.35 to -0.19; p = 0.02, I2 = 59.09%). The remaining tested differences did not yield significant results. Conclusion: Elevated serum levels of vitamin B12 were associated with higher mortality in patients with COVID-19. Severe cases of COVID-19 were associated with low serum folate levels. Future studies should incorporate a larger sample size.

10.
PLoS One ; 19(5): e0302158, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38696404

RESUMO

High-throughput phenotyping brings new opportunities for detailed genebank accessions characterization based on image-processing techniques and data analysis using machine learning algorithms. Our work proposes to improve the characterization processes of bean and peanut accessions in the CIAT genebank through the identification of phenomic descriptors comparable to classical descriptors including methodology integration into the genebank workflow. To cope with these goals morphometrics and colorimetry traits of 14 bean and 16 forage peanut accessions were determined and compared to the classical International Board for Plant Genetic Resources (IBPGR) descriptors. Descriptors discriminating most accessions were identified using a random forest algorithm. The most-valuable classification descriptors for peanuts were 100-seed weight and days to flowering, and for beans, days to flowering and primary seed color. The combination of phenomic and classical descriptors increased the accuracy of the classification of Phaseolus and Arachis accessions. Functional diversity indices are recommended to genebank curators to evaluate phenotypic variability to identify accessions with unique traits or identify accessions that represent the greatest phenotypic variation of the species (functional agrobiodiversity collections). The artificial intelligence algorithms are capable of characterizing accessions which reduces costs generated by additional phenotyping. Even though deep analysis of data requires new skills, associating genetic, morphological and ecogeographic diversity is giving us an opportunity to establish unique functional agrobiodiversity collections with new potential traits.


Assuntos
Arachis , Phaseolus , Fenótipo , Phaseolus/genética , Phaseolus/anatomia & histologia , Phaseolus/crescimento & desenvolvimento , Arachis/genética , Arachis/crescimento & desenvolvimento , Algoritmos , Banco de Sementes , Aprendizado de Máquina , Inteligência Artificial
11.
Ther Adv Infect Dis ; 11: 20499361241242963, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706456

RESUMO

Background and aims: The presence of fungal infections has been described in patients after recovering from COVID-19. This study aims to conduct a systematic review of studies that reported fungal infections (Mucor spp., Pneumocystis jirovecii, or Aspergillus spp.) in adults after recovering from COVID-19. Methods: We performed a systematic review through PubMed, Web of Science, OVID-Medline, Embase, and Scopus. The study selection process was performed independently and by at least two authors. We performed a risk of bias assessment using the Newcastle-Ottawa Scale for cohort and case-control studies, and the Joanna Briggs Institute's Checklists for Case Series and Case Reports. Results: The systematic search found 33 studies meeting all inclusion criteria. There was a total population of 774 participants, ranging from 21 to 87 years. From them, 746 developed a fungal infection. In 19 studies, Mucor spp. was reported as the main mycosis. In 10 studies, P. jirovecii was reported as the main mycosis. In seven studies, Aspergillus spp. was reported as the main mycosis. Regarding the quality assessment, 12 studies were classified as low risk of bias and the remaining studies as high risk of bias. Conclusion: Patients' clinical presentation and prognosis after recovering from COVID-19 with fungal infection differ from those reported patients with acute COVID-19 infection and those without COVID-19 infection.

12.
BMC Med Educ ; 24(1): 380, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589913

RESUMO

BACKGROUND: Antibiotic resistance has been identified as a global health threat. Knowledge, attitudes, and inappropriate prescription practices of antibiotics by physicians play a crucial role in this problem. In Colombia, research addressing this issue is scarce. METHODS: A cross-sectional study involving 258 physicians was conducted. A scale with questions on sociodemographic aspects, level of education, satisfaction with antibiotic education received, and knowledge, attitudes, and practices was administered. The scale was designed for each item to be analyzed individually or as a total score ranging from 0 to 100 (0 being the lowest and 100 the highest). RESULTS: 31.5% of physicians rated the education received on antibiotics as fair to poor. The knowledge score was 80.1 (IQR 70.5-87.5); however, 25.2% agreed to some extent that amoxicillin is useful in treating most respiratory infections, and 15% agreed that antibiotics are effective in treating upper respiratory infections. Attitudes scored 80.2 (IQR 75.0-86.5), with 99% stating that bacterial resistance is a public health problem in Colombia, but only 56.9% considering it a problem affecting their daily practice. Practices scored 75.5 (IQR 68.8-81.2), and 71.7% affirmed that if they refuse to prescribe antibiotics to a patient who does not need them, the patient can easily obtain them from another physician. General practitioners were found to have lower scores in all three indices evaluated. CONCLUSION: The study reveals enduring misconceptions and concerning practices in antibiotic prescription, particularly among general practitioners. Enhancing knowledge necessitates the implementation of continuous medical education programs that focus on updated antibiotic guidelines, and resistance patterns. Fostering positive attitudes requires a culture of trust and collaboration among healthcare professionals. Practical enhancements can be realized through the establishment of evidence-based prescribing guidelines and the integration of regular feedback mechanisms. Moreover, advocating for the inclusion of antimicrobial stewardship principles in medical curricula is crucial, emphasizing the significance of responsible antibiotic use early in medical education.


Assuntos
Clínicos Gerais , Infecções Respiratórias , Humanos , Estudos Transversais , Colômbia , Antibacterianos/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde , Infecções Respiratórias/tratamento farmacológico , Padrões de Prática Médica , Educação Médica Continuada
13.
Eur J Phys Rehabil Med ; 60(3): 530-539, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38656081

RESUMO

INTRODUCTION: Aging is associated with an increased burden of multi-morbidity and disease related functional loss and disability, widely impacting patients and health care systems. Frailty is a major actor in age-related disability and is an important target for rehabilitation interventions, considering that is a reversible condition. EVIDENCE ACQUISITION: A working group of members of the ISPRM, responding to WHO 2030 call for action to strengthen rehabilitation, was established to assess the quality and implementability of the existing guidelines for the rehabilitation of frailty. Guidelines were retrieved using a systematic search on Pubmed, Scopus and Web of Science and from the reference lists of screened articles. The included guidelines were evaluated using the AGREE II to assess their quality and using the AGREE-REX to assess their clinical credibility and implementability. Guidelines with a score >4 in the AGREE II item evaluating the overall quality of the guideline were considered for endorsement. Finally, nine external reviewers evaluated the applicability of each recommendation from the endorsed guidelines, providing comments about the barriers and facilitators for their implementation in their country. EVIDENCE SYNTHESIS: Ten guidelines were retrieved and evaluated by the working group, of which four guidelines, i.e. the WHO Guidelines on Integrated Care for Older People, the FOCUS guidelines, the Asia-Pacific Clinical Practice Guidelines for the Management of Frailty and the ICFSR International Clinical Practice Guidelines for Identification and Management of Frailty, were considered for endorsement. All these guidelines were rated as of adequate quality and implementability. CONCLUSIONS: The WHO Guidelines on Integrated Care for Older people (24) the ICFSR International Clinical Practice Guidelines for Identification and management of Frailty (15), the FOCUS guidelines (25) and the Asia Pacific Clinical Practice Guidelines (14) for the Management of Frailty have the best quality and applicability of the existing guidelines on the management of frailty, we suggest that should be employed to define the standards of care for patients with frailty. There are barriers for their implementation, as stated by our experts, to take into account, and some of them are country- or region-specific. Screening for frailty, exercise, nutrition, pharmacological management, social and psychological support, management of incontinence, and an overall comprehensive clinical management are the best tools to face upon frailty.


Assuntos
Fragilidade , Guias de Prática Clínica como Assunto , Humanos , Idoso , Fragilidade/reabilitação , Idoso Fragilizado , Avaliação Geriátrica/métodos , Idoso de 80 Anos ou mais , Medicina Física e Reabilitação/normas
14.
BMC Cancer ; 24(1): 346, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38500100

RESUMO

BACKGROUND: The androgen/androgen receptor (AR)-signaling axis plays a central role in prostate cancer (PCa). Upon androgen-binding the AR dimerizes with another AR, and translocates into the nucleus where the AR-dimer activates/inactivates androgen-dependent genes. Consequently, treatments for PCa are commonly based on androgen deprivation therapy (ADT). The clinical benefits of ADT are only transitory and most tumors develop mechanisms allowing the AR to bypass its need for physiological levels of circulating androgens. Clinical failure of ADT is often characterized by the synthesis of a constitutively active AR splice variant, termed AR-V7. AR-V7 mRNA expression is considered as a resistance mechanism following ADT. AR-V7 no longer needs androgenic stimuli for nuclear entry and/or dimerization. METHODS: Our goal was to mechanistically decipher the interaction between full-length AR (AR-FL) and AR-V7 in AR-null HEK-293 cells using the NanoLuc Binary Technology under androgen stimulation and deprivation conditions. RESULTS: Our data point toward a hypothesis that AR-FL/AR-FL homodimers form in the cytoplasm, whereas AR-V7/AR-V7 homodimers localize in the nucleus. However, after androgen stimulation, all the AR-FL/AR-FL, AR-FL/AR-V7 and AR-V7/AR-V7 dimers were localized in the nucleus. CONCLUSIONS: We showed that AR-FL and AR-V7 form heterodimers that localize to the nucleus, whereas AR-V7/AR-V7 dimers were found to localize in the absence of androgens in the nucleus.


Assuntos
Luciferases , Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Masculino , Humanos , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Androgênios , Neoplasias da Próstata/patologia , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Células HEK293 , Neoplasias de Próstata Resistentes à Castração/patologia , Isoformas de Proteínas/genética
15.
Poult Sci ; 103(5): 103630, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38513548

RESUMO

During the poultry sperm cryopreservation process, an excess of reactive oxygen species is generated resulting in oxidative stress which harms the quality of avian spermatozoa. To counteract this effect, the addition of exogenous antioxidants, such as Pectoliv-80A (a by-product of olive oil), to the cryopreservation diluent is interesting. For this purpose, 16 roosters belonging to the Utrerana avian breed were used. Six semen pools (from the 6 different replicates) were divided into 4 aliquots corresponding to different concentrations of Pectoliv-80A that were tested (0, 300, 400, and 500 µg/mL), and the cryopreservation process was carried out. To evaluate post-thawing semen quality, different parameters such as motility, membrane functionality, reactive oxygen species production, lipid peroxidation, and acrosome integrity were studied. A discriminant canonical analysis was used to determine both the differences between the Pectoliv-80A concentration groups and the discriminant power of the aforementioned parameter used for semen evaluation. Total motility and membrane functionality were reported to be the most discriminant variables for differentiating the different antioxidant enrichment groups and concluded that concentrations of 300 µg/mL showed the most desirable quality of post-thawing semen. The present study could lead to the optimization of both cryopreservation and quality evaluation techniques of the sperm of rooster species, that support the conservation program of endangered local breeds.


Assuntos
Antioxidantes , Galinhas , Criopreservação , Azeite de Oliva , Preservação do Sêmen , Espermatozoides , Animais , Masculino , Criopreservação/veterinária , Criopreservação/métodos , Antioxidantes/farmacologia , Azeite de Oliva/química , Azeite de Oliva/farmacologia , Galinhas/fisiologia , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Crioprotetores/farmacologia , Análise do Sêmen/veterinária , Análise Discriminante
17.
Nat Prod Rep ; 41(6): 935-967, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38411238

RESUMO

Covering: September 1964 to June 2023Bacteria and fungi living in symbiosis with insects have been studied over the last sixty years and found to be important sources of bioactive natural products. Not only classic producers of secondary metabolites such as Streptomyces and other members of the phylum Actinobacteria but also numerous bacteria from the phyla Proteobacteria and Firmicutes and an impressive array of fungi (usually pathogenic) serve as the source of a structurally diverse number of small molecules with important biological activities including antimicrobial, cytotoxic, antiparasitic and specific enzyme inhibitors. The insect niche is often the exclusive provider of microbes producing unique types of biologically active compounds such as gerumycins, pederin, dinactin, and formicamycins. However, numerous insects still have not been described taxonomically, and in most cases, the study of their microbiota is completely unexplored. In this review, we present a comprehensive survey of 553 natural products produced by microorganisms isolated from insects by collating and classifying all the data according to the type of compound (rather than the insect or microbial source). The analysis of the correlations among the metadata related to insects, microbial partners, and their produced compounds provides valuable insights into the intricate dynamics between insects and their symbionts as well as the impact of their metabolites on these relationships. Herein, we focus on the chemical structure, biosynthesis, and biological activities of the most relevant compounds.


Assuntos
Produtos Biológicos , Insetos , Microbiota , Insetos/microbiologia , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Animais , Microbiota/fisiologia , Fungos/metabolismo , Fungos/química , Bactérias/metabolismo , Bactérias/efeitos dos fármacos , Simbiose , Estrutura Molecular
18.
Talanta ; 270: 125603, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38194860

RESUMO

The present work introduces two novel approaches to fabricate simple and cost-effective pH and temperature probes. Sinusoidal voltage methodologies were employed to electrodeposit polyaniline (PANI) at different growth times (10-20 min) on the surface of an affordable Sonogel-Carbon electrode to conform a robust pH sensor. The presence of PANI and its phases were corroborated by electrochemical means. The sensibility, reversibility and selectivity of the produced sensor were very adequate to apply it in physiological samples. In this regard, the proposed sensor was evaluated in artificial blood serum as well as untreated plasma samples obtaining outstanding results in comparison with a gold reference technique (error <2 %). In addition, a new composite sonogel material, intrinsically modified with multiwalled carbon nanotubes, was attached on top of an electrode couple to one-step fabricate a new temperature probe, relating resistance of the probe with the surroundings temperature. In this case, an optical microscopy characterization was performed to study the sturdiness of the layer. Remarkably, suitable results in terms of sensitivity and selectivity were obtained. The probes were assessed in artificial and untreated plasma samples as well, with the corresponding validation step (error <1 %) by using a commercial temperature probe.

19.
Foods ; 13(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38275720

RESUMO

The pursuit of developing healthier pasta products without compromising technological properties involves a strategic approach via the customization of raw material formulations and the integration of grain germination and extrusion processes. This study explores the impact of incorporating sprouts from quinoa (Chenopodium quinoa Willd) and kiwicha (Chenopodium pallidicaule Aellen) on the physicochemical properties of pasta by employing a centroid mixture design. The desirability function was utilized to identify the optimal ingredient proportions necessary to achieve specific objectives. The study identified optimal formulations for two pasta variations: pasta with the substitution of sprouted quinoa and cushuro powder (PQC), and pasta with partial substitution of sprouted kiwicha and cushuro powder (PKC). The optimal formulation for PKC was determined as 70% wheat flour (WF), 15% sprouted kiwicha flour (SKF), and 15% cushuro powder (CuP), with a desirability score of 0.68. Similarly, for PQC, the optimal formulation comprised 79% WF, 13% sprouted quinoa flour (SQF), and 8% CuP, with a desirability of 0.63. The optimized pasta formulation exhibited longer cooking times (10 and 8 min), increased weight gain (235% and 244%), and minimal loss of solids (1.4 and 1.2%) for PQC and PKC, respectively. Notably, firmness (2.8 and 2.6 N) and breaking strength values (2 and 2.7 N) for PQC and PKC pasta formulations, respectively, were comparable to those of the control sample (2.7 N and 2.6 N for firmness and fracturability, respectively). This research underscores the potential of tailored formulations and innovative processes to enhance the nutritional profile of pasta while maintaining key technological attributes.

20.
Chemosphere ; 350: 141039, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38147923

RESUMO

Sulfonamides are among the widespread bacterial antibiotics. Despite this, their quick emergence constitutes a serious problem for ecosystems and human health. Therefore, there is an increased interest in developing relevant detection method for antibiotics in different matrices. In this work, a straightforward, green, and cost-effective protocol was proposed for the preparation of a selective molecularly imprinted membrane (MIM) of sulfamethoxazole (SMX), a commonly used antibiotic. Thus, cellulose acetate was used as the functional polymer, while polyethylene glycol served as a pore-former. The developed MIM was successfully characterized through scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The MIM was used as a sensing platform in conjunction with a smartphone for optical readout, enabling on-site, selective, and highly sensitive detection of SMX. In this way, a satisfactory imprinting factor of around 3.6 and a limit of detection of 2 ng mL-1 were reached after applying response surface methodologies, including Box-Behnken and central composite designs. Besides, MIM demonstrated its applicability for the accurate and selective detection of SMX in river waters, wastewater, and drugs. Additionally, the MIM was shown to be a valuable sorbent in a solid-phase extraction protocol, employing a spin column setup that offered rapid and reproducible results. Furthermore, the developed sensing platform exhibited notable regeneration properties over multiple cycles and long shelf-life in different storage conditions. The newly developed methodology is of crucial importance to overcome the limitations of classical imprinting polymers. Furthermore, the smartphone-based platform was used to surpass the typically expensive and complicated methods of detection.


Assuntos
Antibacterianos , Impressão Molecular , Humanos , Impressão Molecular/métodos , Sulfametoxazol , Espectroscopia de Infravermelho com Transformada de Fourier , Ecossistema , Extração em Fase Sólida/métodos , Polímeros/química , Adsorção
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