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1.
Acta Orthop Traumatol Turc ; 58(1): 77-79, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38525514

RESUMO

Trigger finger causes pain and a persistent functional limitation of the hand, which can lead to permanent blockage of the flexor tendon. Ultrasonography-guided percutaneous release has been widely reported as a successful technique for trigger finger involving the A1 pulley. This article describes for the first time the use of this technique in an unusual location, the A3 pulley of the fifth finger. A 71-year-old patient presented with a 3-month history of pain and blockage in the fifth finger of the right hand and was diagnosed with a grade III trigger finger, according to the Froimson scale. We performed an ultrasonography-guided percutaneous release technique on the A3 pulley to release the flexor tendon of the fifth finger. Ultrasonography-guided percutaneous polectomy to treat trigger finger in the A1 pulley is an effective alternative treatment to surgery and even has certain advantages over it. The anatomical similarity between the A1 and A3 pulleys was the key factor that supported the use of this technique in this clinical case. Based on past experience in similar cases, we conclude that ultrasonography-guided percutaneous polectomy of the A3 pulley of the fifth finger was a surgical technique which could lead to a satisfactory outcome in the treatment of this condition.


Assuntos
Dedo em Gatilho , Humanos , Idoso , Dedo em Gatilho/diagnóstico por imagem , Dedo em Gatilho/cirurgia , Ultrassonografia , Dedos/diagnóstico por imagem , Dedos/cirurgia , Tendões/diagnóstico por imagem , Tendões/cirurgia , Dor
2.
Neuropeptides ; 104: 102413, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38335798

RESUMO

The measurement of neuropeptides using small electrodes for high spatial resolution would provide us with localized information on the release of neuromolecules. The release of Neuropeptide Y (NPY) is related to different neurological diseases such as stress, obesity, and PTSD, among others. In this conference paper, we electrodeposited polypyrrole on carbon fiber microelectrodes in the presence of NPY to develop a molecularly imprinted polypyrrole sensitive to NPY. Optimization of the electrodeposition process resulted in the full coverage of the polymer with nucleation sites on the carbon fiber ridges, achieving completion by the seventh cycle. Electrodeposition was performed for five cycles, and using cyclic voltammetry (CV), we studied the change in the oxidation current peak for polypyrrole due to the presence of NPY. We also observed a change in capacitance due to the presence of NPY, which was studied by electrochemical impedance spectroscopy (EIS). A linear correlation was found between the oxidation peak and the concentration of NPY between 50 ng/mL and 1000 ng/mL. In addition, a linear correlation was also found between microelectrode capacitance and the concentration of NPY between 50 ng/mL and 1000 ng/mL at 100 kHz.


Assuntos
Neuropeptídeo Y , Polímeros , Fibra de Carbono , Microeletrodos , Neuropeptídeo Y/análise , Polímeros/química , Pirróis
3.
Polymers (Basel) ; 16(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38337224

RESUMO

Strawberries (Fragaria xannanasa) are susceptible to mechanical, physical, and physiological damage, which increases their incidence of rot during storage. Therefore, a method of protection is necessary in order to minimize quality losses. One way to achieve this is by applying polymer coatings. In this study, multisystem coatings were created based on polymer nanocapsules loaded with Lippia graveolens essential oil, and it was found to have excellent optical, mechanical, and water vapor barrier properties compared to the control (coating formed with alginate and with nanoparticles without the essential oil). As for the strawberries coated with the multisystem formed from the polymer nanocapsules loaded with the essential oil of Lippia graveolens, these did not present microbial growth and only had a loss of firmness of 17.02% after 10 days of storage compared to their initial value. This study demonstrated that the multisystem coating formed from the polymer nanocapsules loaded with the essential oil of Lippia graveolens could be a viable alternative to preserve horticultural products for longer storage periods.

4.
Front Oncol ; 14: 1304633, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38420017

RESUMO

Background: A heterogeneous geographic distribution of childhood acute lymphoblastic leukemia (ALL) cases has been described, possibly, related to the presence of different environmental factors. The aim of the present study was to explore the geographical distribution of childhood ALL cases in Greater Mexico City (GMC). Methods: A population-based case-control study was conducted. Children <18 years old, newly diagnosed with ALL and residents of GMC were included. Controls were patients without leukemia recruited from second-level public hospitals, frequency-matched by sex, age, and health institution with the cases. The residence address where the patients lived during the last year before diagnosis (cases) or the interview (controls) was used for geolocation. Kulldorff's spatial scan statistic was used to detect spatial clusters (SCs). Relative risks (RR), associated p-value and number of cases included for each cluster were obtained. Results: A total of 1054 cases with ALL were analyzed. Of these, 408 (38.7%) were distributed across eight SCs detected. A relative risk of 1.61 (p<0.0001) was observed for the main cluster. Similar results were noted for the remaining seven ones. Additionally, a proximity between SCs, electrical installations and petrochemical facilities was observed. Conclusions: The identification of SCs in certain regions of GMC suggest the possible role of environmental factors in the etiology of childhood ALL.

5.
Curr Opin Cell Biol ; 86: 102314, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38215516

RESUMO

Cellular stress plays a pivotal role in the onset of numerous human diseases. Consequently, the removal of dysfunctional cells, which undergo excessive stress-induced damage via various cell death pathways, including apoptosis, is essential for maintaining organ integrity and function. The evolutionarily conserved family of cysteine-aspartic-proteases, known as caspases, has been a key player in orchestrating apoptosis. However, recent research has unveiled the capability of these enzymes to govern fundamental cellular processes without triggering cell death. Remarkably, some of these non-lethal functions of caspases may contribute to restoring cellular equilibrium in stressed cells. This manuscript discusses how caspases can function as cellular stress managers and their potential impact on human health and disease. Additionally, it sheds light on the limitations of caspase-based therapies, given our still incomplete understanding of the biology of these enzymes, particularly in non-apoptotic contexts.


Assuntos
Apoptose , Caspases , Humanos , Caspases/metabolismo , Apoptose/fisiologia , Morte Celular
6.
Curr Res Microb Sci ; 6: 100207, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38187997

RESUMO

Bacterial isolated from rhizospheric soil associated with the semi-desertic plant Coronilla juncea L. were screened for 1-aminocyclopropane-1-carboxylate deaminase (ACCD) activity, a common trait for plant-growth-promoting rhizobacteria (PGPR). Among bacterial isolates, strain DBA51 showed phosphate solubilizing index (PSI), producing indole acetic acid (IAA), and with the hemolysis-negative test. Sequencing and analysis of the 16S rDNA gene identified DBA51 as Enterobacter. DBA51 did not show antagonistic activity in vitro against bacterial (Clavibacter michiganensis, Pseudomonas syringae pv. tomato DC3000 and Pectobacterium cacticidum FHLGJ22) and fungal phytopathogens (Alternaria sp., Fusarium oxysporum fsp. lycopersici, Fusarium oxysporum fsp. cubense M5, and Rhizoctonia sp.). Root inoculations with DBA51 in tomato (Solanum lycopersicum L.) and tobacco (Nicotiana tabacum L.) plants were performed under greenhouse conditions. Plant height (20 %) and root biomass (40 %) were significantly enhanced in tomato plants inoculated with DBA51 compared to non-inoculated plants, although for tobacco plants, only root biomass (27 %) showed significant differences with DBA51. In addition, physiological parameters such as photosynthetic rate (µmol CO2 m-2 s-1), stomatal conductance (mol H2O m-2 s-1), and transpiration rate (mmol H2O m-2 s-1) were also evaluated, and no differences were detected between DBA51-inoculated and control treatment in tomato and tobacco leaves. The observed results indicate that the DBA51 strain could be used as a biofertilizer to improve yields of horticultural crops.

7.
Int J Mol Sci ; 24(23)2023 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38069104

RESUMO

CagY is the largest and most complex protein from Helicobacter pylori's (Hp) type IV secretion system (T4SS), playing a critical role in the modulation of gastric inflammation and risk for gastric cancer. CagY spans from the inner to the outer membrane, forming a channel through which Hp molecules are injected into human gastric cells. Yet, a tridimensional structure has been reported for only short segments of the protein. This intricate protein was modeled using different approaches, including homology modeling, ab initio, and deep learning techniques. The challengingly long middle repeat region (MRR) was modeled using deep learning and optimized using equilibrium molecular dynamics. The previously modeled segments were assembled into a 1595 aa chain and a 14-chain CagY multimer structure was assembled by structural alignment. The final structure correlated with published structures and allowed to show how the multimer may form the T4SS channel through which CagA and other molecules are translocated to gastric cells. The model confirmed that MRR, the most polymorphic and complex region of CagY, presents numerous cysteine residues forming disulfide bonds that stabilize the protein and suggest this domain may function as a contractile region playing an essential role in the modulating activity of CagY on tissue inflammation.


Assuntos
Gastrite , Infecções por Helicobacter , Helicobacter pylori , Humanos , Proteínas de Bactérias/metabolismo , Helicobacter pylori/metabolismo , Antígenos de Bactérias/metabolismo , Inflamação
8.
Bol. méd. Hosp. Infant. Méx ; 80(6): 367-373, Nov.-Dec. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1527965

RESUMO

Abstract Background: Determining the effect of reopening schools on pediatric SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection rates increased the need to share the experience of governments in many geographic regions for better future decision-making in similar health emergencies. Methods: Through a prospective study based on a population-based cohort, students from 18,988 schools in the State of Mexico who began returning to school were followed. Daily sanitation filters were implemented in each school and district liaisons were informed on a daily basis through a negative network. Identified cases were confirmed by reverse transcriptase-polymerase chain reaction. Simple case frequencies, percentages, and incidences of COVID-19 were estimated. State incidences were compared with the national incidence. Results: A total of 3,586 cases were confirmed; 2,048 (57.1%) were children. Twenty-four (0.6%) were hospitalized for moderate to severe COVID-19; nine (37.5%) died, and only one was a schoolchild. From week 36, an average infection rate of 0.36 was observed. The highest infection rate in schoolchildren was observed in epidemiologic week 40 (1.01); from this week on, a decrease in the number of cases was observed until week 50. Conclusions: The use of non-pharmaceutical interventions has more advantages than limitations, as long as the strategies are homogeneous and properly implemented to ensure adequate control of infections.


Resumen Introducción: La determinación del efecto de reabrir las escuelas sobre las tasas de infección pediátrica por SARS-CoV-2 (síndrome respiratorio agudo grave coronavirus 2) incrementó la necesidad de trasmitir la experiencia de los gobiernos de muchas regiones geográficas para mejores decisiones futuras en emergencias sanitarias similares. Métodos: Mediante un estudio prospectivo basado en una cohorte poblacional se dio seguimiento a los alumnos de 18,988 escuelas del Estado de México que iniciaron con el regreso a clases. Se implementaron filtros sanitarios diarios en cada escuela y cotidianamente se informaban a los enlaces jurisdiccionales a través de una red negativa. Los casos identificados eran confirmados a través de RT-PCR (reacción en cadena de la polimerasa con transcriptasa inversa). Se estimaron frecuencias simples de casos, porcentajes e incidencias de COVID-19. Las incidencias del estado se compararon con la incidencia nacional. Resultados: Un total de 3,586 casos fueron confirmados; 2,048 (57.1%) correspondieron a niños. Veinticuatro (0.6%) fueron hospitalizados por COVID-19 moderado a grave; nueve (37.5%) fallecieron, y solamente una correspondió a un escolar. A partir de la semana 36 se observó una tasa promedio de infecciones de 0.36. En la semana epidemiológica 40 se observó la mayor tasa de infección en escolares (1.01); a partir de esta semana se observa un declive de los casos hasta la semana 50. Conclusiones: La implementación de intervenciones no farmacéuticas tiene más ventajas que limitaciones, siempre y cuando las estrategias sean homogéneas y correctamente ejecutadas, lo que asegurará un adecuado control en los contagios.

9.
J Vitreoretin Dis ; 7(4): 293-298, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37927327

RESUMO

Purpose: To describe the surgical outcomes of rhegmatogenous retinal detachments (RRDs) associated with giant retinal tears (GRTs) and define factors associated with primary anatomic failure. Methods: This retrospective consecutive study comprised primary GRT-RRD surgeries between 1999 and 2021 at a single institution. Exclusion criteria were a follow-up of less than 3 months and incomplete surgical data. Results: The series included 69 eyes (64 patients). Single-surgery anatomic success (SSAS) was achieved in 75% and final anatomic success (FAS) in 90%. The mean logMAR visual acuity improved from 1.5 ± 1.1 to 0.6 ± 0.9. Preoperative factors significantly associated with redetachment were proliferative vitreoretinopathy (PVR) (odds ratio [OR], 6.2; P < .01), hypotony (OR, 13.6; P < .01), and a 180-degree or larger GRT (OR, 3.3; P = .04). All cases were treated with pars plana vitrectomy (PPV) and perfluoro-N-octane (PFCL). Perfluoropropane (C3F8) was used in 59% and silicone oil in 41%; the redetachment rate was significantly lower in gas cases (15% vs 39%) (P = .02). An encircling band, placed in 84% eyes, had a tendency to reduce redetachment (22% vs 36%) (P = .32). Lensectomy was performed in 61% of phakic eyes, with no effect on redetachment (20% vs 21%) (P = .92). On multivariate analysis, PVR and hypotony were significantly associated with redetachment. Conclusions: PPV with PFCL achieved high SSAS and FAS rates. PVR and hypotony were the main preoperative factors associated with anatomic failure. In cases without PVR, C3F8 tamponade significantly increased SSAS. Encircling scleral buckling showed a nonsignificant tendency toward an increase in SSAS. Lensectomy had no effect on SSAS.

10.
Molecules ; 28(20)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37894621

RESUMO

Essential oils (EOs) are natural antioxidant alternatives that reduce skin damage. However, EOs are highly volatile; therefore, their nanoencapsulation represents a feasible alternative to increase their stability and favor their residence time on the skin to guarantee their effect. In this study, EOs of Rosmarinus officinalis and Lavandula dentata were nanoencapsulated and evaluated as skin delivery systems with potential antioxidant activity. The EOs were characterized and incorporated into polymeric nanocapsules (NC-EOs) using nanoprecipitation. The antioxidant activity was evaluated using the ferric thiocyanate method. The ex vivo effects on pig skin were evaluated based on biophysical parameters using bioengineering techniques. An ex vivo dermatokinetic evaluation on pig skin was performed using modified Franz cells and the tape-stripping technique. The results showed that the EOs had good antioxidant activity (>65%), which was maintained after nanoencapsulation and purification. The nanoencapsulation of the EOs favored its deposition in the stratum corneum compared to free EOs; the highest deposition rate was obtained for 1,8-cineole, a major component of L. dentata, at 1 h contact time, compared to R. officinalis with a major deposition of the camphor component. In conclusion, NC-EOs can be used as an alternative antioxidant for skin care.


Assuntos
Nanocápsulas , Óleos Voláteis , Animais , Suínos , Óleos Voláteis/farmacologia , Antioxidantes/farmacologia , Pele , Eucaliptol , Polímeros
11.
J Pers Med ; 13(10)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37888115

RESUMO

Poorly differentiated sinonasal carcinomas (PDCs) are tumors that have a poor prognosis despite advances in classical treatment. Predictive and prognostic markers and new personalized treatments could improve the oncological outcomes of patients. In this study, we analyzed SOX2 and ßIII-tubulin as biomarkers that could have prognostic and therapeutic impacts on these tumors. The cohort included 57 cases of PDCs: 36 sinonasal undifferentiated carcinoma (SNUC) cases, 13 olfactory neuroblastoma (ONB) cases, and 8 sinonasal neuroendocrine carcinoma (SNEC) cases. Clinical follow-up data were available for 26 of these cases. Sox2 expression was detected using immunohistochemistry in 6 (75%) SNEC cases, 19 (53%) SNUC cases, and 6 (46%) ONB cases. The absence of Sox2 staining correlated with a higher rate of recurrence (p = 0.015), especially distant recurrence. The majority of cases showed ßIII-tubulin expression, with strong positivity in 85%, 75%, and 64% of SNEC, ONB, and SNUC cases, respectively. Tumors with stronger ßIII-tubulin expression demonstrated longer disease-free survival than those with no expression or low expression (p = 0.049). Sox2 and ßIII-tubulin expression is common in poorly differentiated sinonasal tumors and has prognostic and therapeutic utility.

12.
Sci Rep ; 13(1): 12639, 2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37537248

RESUMO

Polymer microfibers are ubiquitous structures across virtually all technological fields. Their applications include, for instance, filter media, tissue regeneration, wound healing and dressing, and reinforcement materials. The most effective methods for fabrication of fibrous micro and nanomaterials rely on electric fields to spin a liquid jet into an ultrafine thread that rapidly dries up forming a fiber. Continuous spinning and collection leads to formation of fiber mats. Here we report a robust yet simple approach for the massive production of liquid threads, which upon acquiring electrical charges in-flight are collected downstream in the form of fibers. The entire process takes place on-line in a single step. The liquid threads are produced through the fragmentation of a polymer solution bulk due to a turbulent interaction of a gas-liquid interface in the interior of an engineered device, a so-called Flow Blurring atomizer. The particularity of this approach consists precisely in such vigorous interaction, at the micrometer scale, which triggers a bubbly motion in the interior of the device, that is a "micro-mixing". Subsequently, the threads are passed through ionized air currents, at ambient conditions, and then stretched to sub-micrometer dimensions by electric fields. Polyvinylpyrrolidone (PVP) as well as carbon nanotubes (CNTs) or graphene oxide sheets (GOSs)-containing PVP fibers, with diameters in the range 100-900 nm, were synthesized via this approach. In the cases studied herein the method was operated at liquid flow rates (i.e. production rates) of 0.2 mL/min but it could be readily increased up to a few tens of mL/min. The method requires further improvement and optimization, nevertheless it is a promising alternative for mass production of polymer fibers.

13.
Molecules ; 28(16)2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37630415

RESUMO

Cancer involves a series of diseases where cellular growth is not controlled. Cancer is a leading cause of death worldwide, and the burden of cancer incidence and mortality is rapidly growing, mainly in developing countries. Many drugs are currently used, from chemotherapeutic agents to immunotherapy, among others, along with organ transplantation. Treatments can cause severe side effects, including remission and progression of the disease with serious consequences. Increased glycolytic activity is characteristic of cancer cells. Triosephosphate isomerase is essential for net ATP production in the glycolytic pathway. Notably, some post-translational events have been described that occur in human triosephosphate isomerase in which functional and structural alterations are provoked. This is considered a window of opportunity, given the differences that may exist between cancer cells and their counterpart in normal cells concerning the glycolytic enzymes. Here, we provide elements that bring out the potential of triosephosphate isomerase, under post-translational modifications, to be considered an efficacious target for treating cancer.


Assuntos
Neoplasias , Triose-Fosfato Isomerase , Humanos , Triose-Fosfato Isomerase/genética , Neoplasias/tratamento farmacológico , Processamento de Proteína Pós-Traducional , Ciclo Celular , Proliferação de Células
14.
J Enzyme Inhib Med Chem ; 38(1): 2231169, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37401012

RESUMO

Trypanosoma cruzi is the causative agent of American trypanosomiasis, which mainly affects populations in Latin America. Benznidazole is used to control the disease, with severe effects in patients receiving this chemotherapy. Previous studies have demonstrated the inhibition of triosephosphate isomerase from T. cruzi, but cellular enzyme inhibition has yet to be established. This study demonstrates that rabeprazole inhibits both cell viability and triosephosphate isomerase activity in T. cruzi epimastigotes. Our results show that rabeprazole has an IC50 of 0.4 µM, which is 14.5 times more effective than benznidazole. Additionally, we observed increased levels of methyl-glyoxal and advanced glycation end products after the inhibition of cellular triosephosphate isomerase by rabeprazole. Finally, we demonstrate that the inactivation mechanisms of rabeprazole on triosephosphate isomerase of T. cruzi can be achieved through the derivatization of three of its four cysteine residues. These results indicate that rabeprazole is a promising candidate against American trypanosomiasis.


Assuntos
Doença de Chagas , Tripanossomicidas , Trypanosoma cruzi , Humanos , Triose-Fosfato Isomerase/química , Triose-Fosfato Isomerase/farmacologia , Rabeprazol/farmacologia , Rabeprazol/uso terapêutico , Reposicionamento de Medicamentos , Doença de Chagas/tratamento farmacológico , Tripanossomicidas/farmacologia
15.
Diseases ; 11(3)2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37489449

RESUMO

In the last decade, artificial intelligence (AI) and AI-mediated technologies have undergone rapid evolution in healthcare and medicine, from apps to computer software able to analyze medical images, robotic surgery and advanced data storage system. The main aim of the present commentary is to briefly describe the evolution of AI and its applications in healthcare, particularly in nutrition and clinical biochemistry. Indeed, AI is revealing itself to be an important tool in clinical nutrition by using telematic means to self-monitor various health metrics, including blood glucose levels, body weight, heart rate, fat percentage, blood pressure, activity tracking and calorie intake trackers. In particular, the application of the most common digital technologies used in the field of nutrition as well as the employment of AI in the management of diabetes and obesity, two of the most common nutrition-related pathologies worldwide, will be presented.

16.
J Clin Med ; 12(12)2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37373758

RESUMO

Research on the use of Acceptance and Commitment Therapy (ACT) for patients with degenerative lumbar pathology awaiting surgery are limited. However, there is evidence to suggest that this psychological therapy may be effective in improving pain interference, anxiety, depression, and quality of life. This is the protocol for a randomized controlled trial (RCT) to evaluate the effectiveness of ACT compared to treatment as usual (TAU) for people with degenerative lumbar pathology who are candidates for surgery in the short term. A total of 102 patients with degenerative lumbar spine pathology will be randomly assigned to TAU (control group) or ACT + TAU (intervention group). Participants will be assessed after treatment and at 3-, 6-, and 12-month follow-ups. The primary outcome will be the mean change from baseline on the Brief Pain Inventory (pain interference). Secondary outcomes will include changes in pain intensity, anxiety, depression, pain catastrophizing, fear of movement, quality of life, disability due to low back pain (LBP), pain acceptance, and psychological inflexibility. Linear mixed models will be used to analyze the data. Additionally, effect sizes and number needed to treat (NNT) will be calculated. We posit that ACT may be used to help patients cope with the stress and uncertainty associated with their condition and the surgery itself.

17.
EMBO Rep ; 24(6): e51716, 2023 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-37039000

RESUMO

Current evidence has associated caspase activation with the regulation of basic cellular functions without causing apoptosis. Malfunction of non-apoptotic caspase activities may contribute to specific neurological disorders, metabolic diseases, autoimmune conditions and cancers. However, our understanding of non-apoptotic caspase functions remains limited. Here, we show that non-apoptotic caspase activation prevents the intracellular accumulation of the Patched receptor in autophagosomes and the subsequent Patched-dependent induction of autophagy in Drosophila follicular stem cells. These events ultimately sustain Hedgehog signalling and the physiological properties of ovarian somatic stem cells and their progeny under moderate thermal stress. Importantly, our key findings are partially conserved in ovarian somatic cells of human origin. These observations attribute to caspases a pro-survival role under certain cellular conditions.


Assuntos
Células-Tronco Adultas , Proteínas Hedgehog , Animais , Humanos , Proteínas Hedgehog/metabolismo , Morte Celular , Apoptose/fisiologia , Caspases/genética , Caspases/metabolismo , Drosophila/metabolismo , Células-Tronco Adultas/metabolismo , Homeostase , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo
18.
Genes (Basel) ; 14(4)2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-37107652

RESUMO

BACKGROUND: The incidence of sporadic colorectal cancer (CRC) among individuals <50 years (early-onset CRC) has been increasing in the United States (U.S.) and Puerto Rico. CRC is currently the leading cause of cancer death among Hispanic men and women living in Puerto Rico (PRH). The objective of this study was to characterize the molecular markers and clinicopathologic features of colorectal tumors from PRH to better understand the molecular pathways leading to CRC in this Hispanic subpopulation. METHODS: Microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutation status were analyzed. Sociodemographic and clinicopathological characteristics were evaluated using Chi-squared and Fisher's exact tests. RESULTS: Of the 718 tumors analyzed, 34.2% (n = 245) were early-onset CRC, and 51.7% were males. Among the tumors with molecular data available (n = 192), 3.2% had MSI, 9.7% had BRAF, and 31.9% had KRAS mutations. The most common KRAS mutations observed were G12D (26.6%) and G13D (20.0%); G12C was present in 4.4% of tumors. A higher percentage of Amerindian admixture was significantly associated with early-onset CRC. CONCLUSIONS: The differences observed in the prevalence of the molecular markers among PRH tumors compared to other racial/ethnic groups suggest a distinct molecular carcinogenic pathway among Hispanics. Additional studies are warranted.


Assuntos
Neoplasias Colorretais , Proteínas Proto-Oncogênicas B-raf , Masculino , Feminino , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Metilação de DNA , Porto Rico/epidemiologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Instabilidade de Microssatélites , Biomarcadores/metabolismo , Hispânico ou Latino/genética
19.
Methods Enzymol ; 683: 291-308, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37087193

RESUMO

Among the biologically relevant reactive oxygen species (ROS), hydrogen peroxide (H2O2) has special properties. H2O2 can diffuse across membranes, has a low reactivity, and is very stable. Deprotonated cysteine residues in proteins can be oxidized by H2O2 into a highly reactive sulfenic acid derivative (-SOH), which can react with another cysteine to form a disulfide. Under higher oxidative stress the sulfenic acid undergo further oxidation to sulfinic acid (Cys-SO2H), which can subsequently be reduced. The sulfinic acid can be hyperoxidized to sulfonic acid (Cys-SO3H), whose reduction is irreversible. Formation of sulfenic acids can have a role in sensing oxidative stress, signal transduction, modulating localization and activity to regulate protein functions. Therefore, there is an emerging interest in trying to understand the pool of proteins that result in these sorts of modification in response to oxidative stress. This is known as the sulfenome and several approaches have been developed in animal and plant cells to analyze the sulfenome under different stress responses. These approaches can be proteomic, molecular, immunological (i.e., antibodies), or expressing genetically encoded probes that specifically react to sulfenic modifications. In this chapter, we describe an additional approach that allows visualization of sulfenic modification in vivo. This is newly developed fluorescent probe DCP-Rho1 can be implemented in any plant cell to analyze the sulfenic modification.


Assuntos
Cisteína , Ácidos Sulfênicos , Animais , Ácidos Sulfênicos/química , Cisteína/química , Corantes Fluorescentes , Células Vegetais/metabolismo , Peróxido de Hidrogênio/química , Proteômica , Ácidos Sulfínicos , Proteínas/química , Oxirredução
20.
Int J Mol Sci ; 24(6)2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36982390

RESUMO

Metabolic reprogramming in cancer is considered to be one of the most important hallmarks to drive proliferation, angiogenesis, and invasion. AMP-activated protein kinase activation is one of the established mechanisms for metformin's anti-cancer actions. However, it has been suggested that metformin may exert antitumoral effects by the modulation of other master regulators of cellular energy. Here, based on structural and physicochemical criteria, we tested the hypothesis that metformin may act as an antagonist of L-arginine metabolism and other related metabolic pathways. First, we created a database containing different L-arginine-related metabolites and biguanides. After that, comparisons of structural and physicochemical properties were performed employing different cheminformatic tools. Finally, we performed molecular docking simulations using AutoDock 4.2 to compare the affinities and binding modes of biguanides and L-arginine-related metabolites against their corresponding targets. Our results showed that biguanides, especially metformin and buformin, exhibited a moderate-to-high similarity to the metabolites belonging to the urea cycle, polyamine metabolism, and creatine biosynthesis. The predicted affinities and binding modes for biguanides displayed good concordance with those obtained for some L-arginine-related metabolites, including L-arginine and creatine. In conclusion, metabolic reprogramming in cancer cells by metformin and biguanides may be also driven by metabolic disruption of L-arginine and structurally related compounds.


Assuntos
Antimaláricos , Metformina , Neoplasias , Humanos , Metformina/farmacologia , Simulação de Acoplamento Molecular , Creatina , Biguanidas , Proteínas Quinases Ativadas por AMP , Buformina , Neoplasias/tratamento farmacológico
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