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1.
Mar Drugs ; 21(2)2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36827134

RESUMO

Due to the constant growth of the human population and anthropological activity, it has become necessary to use sustainable and affordable technologies that satisfy the current and future demand for agricultural products. Since the nutrients available to plants in the soil are limited and the need to increase the yields of the crops is desirable, the use of chemical (inorganic or NPK) fertilizers has been widespread over the last decades, causing a nutrient shortage due to their misuse and exploitation, and because of the uncontrolled use of these products, there has been a latent environmental and health problem globally. For this reason, green biotechnology based on the use of microalgae biomass is proposed as a sustainable alternative for development and use as soil improvers for crop cultivation and phytoremediation. This review explores the long-term risks of using chemical fertilizers for both human health (cancer and hypoxia) and the environment (eutrophication and erosion), as well as the potential of microalgae biomass to substitute current fertilizer using different treatments on the biomass and their application methods for the implementation on the soil; additionally, the biomass can be a source of carbon mitigation and wastewater treatment in agro-industrial processes.


Assuntos
Microalgas , Solo , Humanos , Fertilizantes/análise , Pegada de Carbono , Carbono , Biotecnologia , Biomassa
2.
Molecules ; 27(16)2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-36014571

RESUMO

In the last decade, algae applications have generated considerable interest among research organizations and industrial sectors. Bioactive compounds, such as carotenoids, and Mycosporine-like amino acids (MAAs) derived from microalgae may play a vital role in the bio and non-bio sectors. Currently, commercial sunscreens contain chemicals such as oxybenzone and octinoxate, which have harmful effects on the environment and human health; while microalgae-based sunscreens emerge as an eco-friendly alternative to provide photo protector agents against solar radiation. Algae-based exploration ranges from staple foods to pharmaceuticals, cosmetics, and biomedical applications. This review aims to identify the effects of UV and UV-vis irradiation on the production of microalgae bioactive compounds through the assistance of different techniques and extraction methods for biomass characterization. The efficiency and results focus on the production of a blocking agent that does not damage the aquifer, being beneficial for health and possible biomedical applications.


Assuntos
Microalgas , Alga Marinha , Aminoácidos/química , Humanos , Microalgas/metabolismo , Protetores Solares/química , Raios Ultravioleta
3.
Molecules ; 27(11)2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35684447

RESUMO

Microalgae are complex photosynthetic organisms found in marine and freshwater environments that produce valuable metabolites. Microalgae-derived metabolites have gained remarkable attention in different industrial biotechnological processes and pharmaceutical and cosmetic industries due to their multiple properties, including antioxidant, anti-aging, anti-cancer, phycoimmunomodulatory, anti-inflammatory, and antimicrobial activities. These properties are recognized as promising components for state-of-the-art cosmetics and cosmeceutical formulations. Efforts are being made to develop natural, non-toxic, and environmentally friendly products that replace synthetic products. This review summarizes some potential cosmeceutical applications of microalgae-derived biomolecules, their mechanisms of action, and extraction methods.


Assuntos
Produtos Biológicos , Cosmecêuticos , Cosméticos , Microalgas , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Biotecnologia , Cosmecêuticos/farmacologia , Cosméticos/metabolismo , Microalgas/metabolismo
4.
Molecules ; 27(18)2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36144740

RESUMO

The photolyase family consists of flavoproteins with enzyme activity able to repair ultraviolet light radiation damage by photoreactivation. DNA damage by the formation of a cyclobutane pyrimidine dimer (CPD) and a pyrimidine-pyrimidone (6-4) photoproduct can lead to multiple affections such as cellular apoptosis and mutagenesis that can evolve into skin cancer. The development of integrated applications to prevent the negative effects of prolonged sunlight exposure, usually during outdoor activities, is imperative. This study presents the functions, characteristics, and types of photolyases, their therapeutic and cosmetic applications, and additionally explores some photolyase-producing microorganisms and drug delivery systems.


Assuntos
Desoxirribodipirimidina Fotoliase , Reparo do DNA , Desoxirribodipirimidina Fotoliase/genética , Desoxirribodipirimidina Fotoliase/metabolismo , Flavoproteínas , Dímeros de Pirimidina , Pirimidinas , Pirimidinonas , Raios Ultravioleta/efeitos adversos
5.
JAMA ; 315(16): 1767-77, 2016 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-27115378

RESUMO

IMPORTANCE: Lyme disease, human granulocytic anaplasmosis (HGA), and babesiosis are emerging tick-borne infections. OBJECTIVE: To provide an update on diagnosis, treatment, and prevention of tick-borne infections. EVIDENCE REVIEW: Search of PubMed and Scopus for articles on diagnosis, treatment, and prevention of tick-borne infections published in English from January 2005 through December 2015. FINDINGS: The search yielded 3550 articles for diagnosis and treatment and 752 articles for prevention. Of these articles, 361 were reviewed in depth. Evidence supports the use of US Food and Drug Administration-approved serologic tests, such as an enzyme immunoassay (EIA), followed by Western blot testing, to diagnose extracutaneous manifestations of Lyme disease. Microscopy and polymerase chain reaction assay of blood specimens are used to diagnose active HGA and babesiosis. The efficacy of oral doxycycline, amoxicillin, and cefuroxime axetil for treating Lyme disease has been established in multiple trials. Ceftriaxone is recommended when parenteral antibiotic therapy is recommended. Multiple trials have shown efficacy for a 10-day course of oral doxycycline for treatment of erythema migrans and for a 14-day course for treatment of early neurologic Lyme disease in ambulatory patients. Evidence indicates that a 10-day course of oral doxycycline is effective for HGA and that a 7- to 10-day course of azithromycin plus atovaquone is effective for mild babesiosis. Based on multiple case reports, a 7- to 10-day course of clindamycin plus quinine is often used to treat severe babesiosis. A recent study supports a minimum of 6 weeks of antibiotics for highly immunocompromised patients with babesiosis, with no parasites detected on blood smear for at least the final 2 weeks of treatment. CONCLUSIONS AND RELEVANCE: Evidence is evolving regarding the diagnosis, treatment, and prevention of Lyme disease, HGA, and babesiosis. Recent evidence supports treating patients with erythema migrans for no longer than 10 days when doxycycline is used and prescription of a 14-day course of oral doxycycline for early neurologic Lyme disease in ambulatory patients. The duration of antimicrobial therapy for babesiosis in severely immunocompromised patients should be extended to 6 weeks or longer.


Assuntos
Anaplasmose , Babesiose , Doença de Lyme , Amoxicilina/uso terapêutico , Anaplasma/isolamento & purificação , Anaplasmose/diagnóstico , Anaplasmose/tratamento farmacológico , Anaplasmose/prevenção & controle , Animais , Antibacterianos/uso terapêutico , Babesiose/diagnóstico , Babesiose/tratamento farmacológico , Babesiose/prevenção & controle , Western Blotting , Cefuroxima/análogos & derivados , Cefuroxima/uso terapêutico , Clindamicina/uso terapêutico , Doxiciclina/uso terapêutico , Esquema de Medicação , Humanos , Técnicas Imunoenzimáticas , Doença de Lyme/diagnóstico , Doença de Lyme/tratamento farmacológico , Doença de Lyme/prevenção & controle , Microscopia , Neutrófilos/microbiologia , Reação em Cadeia da Polimerase , Quinina/uso terapêutico
6.
J Nat Prod ; 77(4): 1005-12, 2014 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-24702233

RESUMO

Chemical investigation of the hexanes extracts of Ageratina jocotepecana afforded (-)-(5S,9S,10S,13S)-labd-7-en-15-oic acid (1), methyl (-)-(5S,9S,10S,13S)-labd-7-en-15-oate (2), (+)-(5S,8R,9R,10S,13R)-8-hydroxylabdan-15-oic acid (3), and (-)-(5S,9S,10S,13Z)-labda-7,13-dien-15-oic acid (5). The coexistence of (13R)- and (13S)-labdanes in this member of the Asteraceae family was demonstrated by vibration circular dichroism measurements of ester 2 and methyl (+)-(5S,8R,9R,10S,13R)-8-hydroxylabdan-15-oate (4) in comparison to the DFT B3LYP/DGDZVP-calculated spectra. In addition, transformation of 1 and 3 with HClO4 in MeOH yielded epimeric methyl (+)-(5S,10S,13S)-labd-8-en-15-oate (6) and methyl (+)-(5S,10S,13R)-labd-8-en-15-oate (7), respectively, confirming the presence of C-13 epimers in this plant. Diterpene 1 showed remarkable antibacterial activity against Bacillus subtilis (MIC 0.15 mg/mL) and Staphylococcus aureus (MIC 0.78 mg/mL), while diterpene 3 exhibited moderate activities against the same organisms.


Assuntos
Ageratina/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Diterpenos/química , Diterpenos/isolamento & purificação , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Dicroísmo Circular , Diterpenos/farmacologia , México , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Staphylococcus aureus/efeitos dos fármacos , Estereoisomerismo
7.
Angew Chem Int Ed Engl ; 53(10): 2662-6, 2014 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-24481645

RESUMO

Described is the development and application of a versatile semisynthetic strategy, based on a combination of sortase-mediated coupling and tetrazine ligation chemistry, which can be exploited for the efficient incorporation of tunable functionality into chimeric recombinant proteins. To demonstrate the scope of the method, the assembly of a set of bivalent ligands, which integrate members of the epidermal growth factor (EGF) ligand family, is described. By using a series of bivalent EGFs with variable intraligand spacing, the differences in structure were correlated with the ability to bias signaling in the ErbB receptor family in a cell motility assay. Biasing away from EGFR-HER2 dimerization with a bivalent EGF was observed to reduce cell motility in an intraligand distance-dependent fashion, thus demonstrating the utility of the approach for acutely perturbing receptor-mediated cell signaling pathways.


Assuntos
Receptores ErbB/química , Células-Tronco Mesenquimais/química , Receptor ErbB-2/química , Receptores ErbB/metabolismo , Humanos , Ligantes , Células-Tronco Mesenquimais/metabolismo , Modelos Moleculares , Receptor ErbB-2/metabolismo
8.
Am J Vet Res ; : 1-5, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38266380

RESUMO

OBJECTIVE: To evaluate the effects of a chemical restraint with isoflurane compared to a physical restraint in hemogram values in psittacines. ANIMALS: 21 adult lilac-crowned parrots (Amazona finschi). METHODS: Subjects were physically restrained for blood sample collection, after this isoflurane anesthesia was administered for 30 minutes at which time a second blood sample was taken. Hemogram values were compared between both samples using a t test in variables with normal distribution and a Wilcoxon test in variables without normal distribution. Statistical significance was established at P < .05. RESULTS: When comparing the analytes of the respective CBCs, a decrease in PCV (P < .001), RBC count (P < .001), WBC count (P = .017), absolute lymphocytes (P = .024), and total proteins (P < .001) was observed in the samples taken under chemical restraint. No significant differences in MCV and absolute values of heterophils, monocytes, or eosinophils were observed. CLINICAL RELEVANCE: Isoflurane causes a decrease in some blood count values in lilac-crowned parrots under isoflurane anesthesia for 30 minutes. Although the magnitude of change could be variable between values, it is important to consider the blood collection method when interpreting the blood count in this species.

9.
Environ Technol ; 34(21-24): 3103-16, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24617069

RESUMO

This paper presents the automation of a real activated sludge wastewater treatment plant, which is located at San Antonio Ajijic in Jalisco, Mexico. The main objective is to create an on-line automatic supervision system, and to regulate the dissolved oxygen concentration in order to improve the performances of the process treating municipal wastewater. An approximate mathematical model is determined in order to evaluate via simulations different control strategies: proportional integral (PI), fuzzy PI and PI Logarithm/Antilogarithm (PI L/A). The controlled variable is dissolved oxygen and the control input is the injected oxygen. Based on this evaluation, the PI L/A controller is selected to be implemented in the real process. After that, the implementation, testing and fully operation of the plant automation are described. With this system, the considered wastewater treatment plant save energy and improves the effluent quality; also, the process monitoring is done online and it is easily operated by the plant users.


Assuntos
Bactérias Aeróbias/metabolismo , Modelos Biológicos , Oxigênio/metabolismo , Esgotos/microbiologia , Águas Residuárias/microbiologia , Poluentes Químicos da Água/metabolismo , Purificação da Água/métodos , Algoritmos , Simulação por Computador , Retroalimentação Fisiológica/fisiologia , Lógica Fuzzy , Análise Numérica Assistida por Computador , Sistemas On-Line , Poluentes Químicos da Água/isolamento & purificação
10.
Cureus ; 15(5): e39383, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37378215

RESUMO

Brucellosis is a zoonotic infectious disease caused by the bacterial genus Brucella and is most commonly transmitted to humans globally via the consumption of contaminated unpasteurized products. In a significant minority of cases, Brucella has been found to be transmitted by contact with infected swine bodily fluids such as blood. Only a small proportion of all cases of brucellosis affects the central nervous system, and of the four species of Brucella that are known to infect humans, Brucella suis is unusual. Neurologic involvement occurs in a limited proportion of cases and can vary in presentation, ranging from encephalitis to radiculitis or from brain abscess to neuritis. In this case report, we present a 20-year-old male with an eight-day history of headache and neck pain and a high fever that started two days after the onset of the headaches. Three weeks prior, he had hunted, killed, butchered, cooked, and eaten a wild boar in the field. A workup was performed, and blood cultures eventually grew Brucella suis. Although an intensive broad-spectrum antibiotic protocol was implemented, his post-therapy course was complicated. He eventually discontinued his antibiotics after one year.

11.
Sci Rep ; 13(1): 1335, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693902

RESUMO

The objective of this article is to propose a scheme to increase the stability zone of a charged particles beam in synchrotrons using a suitable objective function that, when optimized, inhibits the resonances onset in phase space and the dynamic aperture of electrons in storage rings can be improved. The proposed technique is implemented by constructing a quasi-invariant in a neighborhood of the origin of the phase space, then, by using symbolic computation software, sets of coupled differential equations for functions involved in nonlinear dynamics are obtained and solved numerically with periodic boundary conditions. The objective function is constructed by proposing that the innermost momentum solution branch of the polynomial quasi-invariant approaches to the corresponding ellipse of the linear dynamics. The objective function is optimized using a genetic algorithm, allowing the dynamic aperture to be increased. The quality of results obtained with this scheme are compared with particle tracking simulations performed with available software in the field, showing good agreement. The scheme is applied to a synchrotron light source model that can be classified as third generation due to its emittance.

12.
Sci Rep ; 13(1): 23007, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38155154

RESUMO

MBA cell-based synchrotron light sources have enabled an unprecedented increase in beam coherence and brightness, greatly benefiting the scientific disciplines that rely on X-ray techniques. However, controlling the electron dynamics is a theoretical and technological challenge, due to the large number of parameters to adjust and constraints to satisfy when designing modern synchrotrons. Having versatile tools for the description and manipulation of electron dynamics could favor the design of these accelerators and lead to progress on several fronts in the understanding of matter. In this paper, a formalism based on the use of nonlinear geometric surfaces represented by polynomial quasi-invariants, to analyze and optimize the dynamic aperture of electrons in MBA storage rings, is introduced. The formalism considers on- and off-momentum particle dynamics. Within the optimization scheme, different objective functions defined in terms of the nonlinear surfaces, which are minimized using genetic algorithm methods, are proposed. A remarkable horizontal dynamic aperture exceeding 19 mm is obtained for the design particle of a synchrotron model with 86 pm [Formula: see text] rad emittance along with a dynamic aperture above 5 mm for momentum deviations of ± 3[Formula: see text]. According to the results presented, this formalism could be greatly useful for manipulating the dynamical properties of electrons in synchrotrons light sources close to the diffraction limit.

13.
Nat Prod Res ; : 1-5, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37278000

RESUMO

The chemical composition of the essential oils (EOs) from leaves and bark of two morphotypes, white (WM) and black (BM) of Salmea scandens obtained by microwave-assisted extraction (MAE) were analyzed by GC-MS. The major components of the bark EOs were aliphatic hydrocarbons (38.0% in WM, 48.6% in BM) and oxygenated sesquiterpenes (27.6% in WM, 11.3% in BM); in leaves EOs major components were oxygenated sesquiterpenes (43.9% in WM, 45.7% in BM) and oxygenated aliphatics (13.7% in WM, 1.1% in BM) stood out. Nine components have been reported to have antimicrobial and anti-inflammatory potential. The agglomerative hierarchical clustering and principal component analysis confirmed the variability of the EOs. These results suggest that WM may have a better therapeutic effect for treating infectious and inflammatory processes in traditional medicine.

14.
Restor Dent Endod ; 48(3): e29, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37675446

RESUMO

Objectives: This study tested the hypothesis that cryotherapy duration influences lipopolysaccharide (LPS)-induced inflammation in a rat model. Materials and Methods: Six Wistar rats (Rattus norvegicus albinus) were used. Five sites were selected per animal and divided into 5 groups: a negative control group (NC), 2 positive control groups (PC1 and PC2), and 2 experimental groups (E1 and E2). Cryotherapy was applied for 1 minute (E1) or 5 minutes (E2). An acute inflammatory response was induced in the PC and E groups via subcutaneous administration of 0.5 mL/kg. In the PC2 group, a catheter was inserted without additional treatment. For the E1 and E2 groups, 2.5°C saline solution was administered through the implanted catheters for 1 and 5 minutes, respectively. The rats were sacrificed, and samples were obtained and processed for histological analysis, specifically examining the presence of polymorphonuclear neutrophils and hemorrhage. The χ2 test was used to compare the presence of acute inflammation across groups. Dependent variables were compared using the linear-by-linear association test. Results: Inflammation and hemorrhage varied significantly among the groups (p = 0.001). A significantly higher degree of acute inflammation was detected (p = 0.0002) in the PC and E1 samples than in the E2 group, in which cryotherapy was administered for 5 minutes. The PC and E1 groups also exhibited significantly greater numbers of neutrophils (p = 0.007), which were essentially absent in both the NC and E2 groups. Conclusions: Cryotherapy administration for 5 minutes reduced the acute inflammation associated with LPS and catheter implantation.

15.
Micromachines (Basel) ; 14(4)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37420982

RESUMO

This paper proposes a deep learning model based on an artificial neural network with a single hidden layer for predicting the diagnosis of multiple sclerosis. The hidden layer includes a regularization term that prevents overfitting and reduces the model complexity. The purposed learning model achieved higher prediction accuracy and lower loss than four conventional machine learning techniques. A dimensionality reduction method was used to select the most relevant features from 74 gene expression profiles for training the learning models. The analysis of variance test was performed to identify the statistical difference between the mean of the proposed model and the compared classifiers. The experimental results show the effectiveness of the proposed artificial neural network.

16.
Surg Neurol Int ; 14: 437, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38213434

RESUMO

Background: The main objectives of this paper are to outline the essential tools, instruments, and equipment needed to set up a functional microsurgery laboratory that is affordable for low-income hospitals and to identify cost-effective alternatives for acquiring microsurgical equipment, such as refurbished or donated instruments, collaborating with medical device manufacturers for discounted rates, or exploring local suppliers. Methods: Step-by-step instructions were provided on setting up the microsurgery laboratory, including recommendations for the layout, ergonomic considerations, lighting, and sterilization processes while ensuring cost-effectiveness, as well as comprehensive training protocols and a curriculum specifically tailored to enhance microsurgical skills in neurosurgery residents. Results: We explored cost-effective options for obtaining microsurgery simulators and utilizing open-source or low-cost virtual training platforms. We also included guidelines for regular equipment maintenance, instrument sterilization, and establishing protocols for infection control to ensure a safe and hygienic learning environment. To foster collaboration between low-income hospitals and external organizations or institutions that can provide support, resources, or mentorship, this paper shows strategies for networking, knowledge exchange, and establishing partnerships to enhance microsurgical training opportunities further. We evaluated the impact and effectiveness of the low-cost microsurgery laboratory by assessing the impact and effectiveness of the established microsurgery laboratory in improving the microsurgical skills of neurosurgery residents. About microsutures and microanastomosis, after three weeks of training, residents showed improvement in "surgical time" for ten separate simple stitches (30.06 vs. 8.65 min) and ten continuous single stitches (19.84 vs. 6.51 min). Similarly, there was an increase in the "good quality" of the stitches and the suture pattern from 36.36% to 63.63%. Conclusion: By achieving these objectives, this guide aims to empower low-income hospitals and neurosurgery residents with the necessary resources and knowledge to establish and operate an affordable microsurgery laboratory, ultimately enhancing the quality of microsurgical training and patient care in low-income countries.

17.
Biosensors (Basel) ; 13(10)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37887115

RESUMO

Food and waterborne illnesses are still a major concern in health and food safety areas. Every year, almost 0.42 million and 2.2 million deaths related to food and waterborne illness are reported worldwide, respectively. In foodborne pathogens, bacteria such as Salmonella, Shiga-toxin producer Escherichia coli, Campylobacter, and Listeria monocytogenes are considered to be high-concern pathogens. High-concern waterborne pathogens are Vibrio cholerae, leptospirosis, Schistosoma mansoni, and Schistosima japonicum, among others. Despite the major efforts of food and water quality control to monitor the presence of these pathogens of concern in these kinds of sources, foodborne and waterborne illness occurrence is still high globally. For these reasons, the development of novel and faster pathogen-detection methods applicable to real-time surveillance strategies are required. Methods based on biosensor devices have emerged as novel tools for faster detection of food and water pathogens, in contrast to traditional methods that are usually time-consuming and are unsuitable for large-scale monitoring. Biosensor devices can be summarized as devices that use biochemical reactions with a biorecognition section (isolated enzymes, antibodies, tissues, genetic materials, or aptamers) to detect pathogens. In most cases, biosensors are based on the correlation of electrical, thermal, or optical signals in the presence of pathogen biomarkers. The application of nano and molecular technologies allows the identification of pathogens in a faster and high-sensibility manner, at extremely low-pathogen concentrations. In fact, the integration of gold, silver, iron, and magnetic nanoparticles (NP) in biosensors has demonstrated an improvement in their detection functionality. The present review summarizes the principal application of nanomaterials and biosensor-based devices for the detection of pathogens in food and water samples. Additionally, it highlights the improvement of biosensor devices through nanomaterials. Nanomaterials offer unique advantages for pathogen detection. The nanoscale and high specific surface area allows for more effective interaction with pathogenic agents, enhancing the sensitivity and selectivity of the biosensors. Finally, biosensors' capability to functionalize with specific molecules such as antibodies or nucleic acids facilitates the specific detection of the target pathogens.


Assuntos
Técnicas Biossensoriais , Listeria monocytogenes , Nanoestruturas , Microbiologia de Alimentos , Técnicas Biossensoriais/métodos , Listeria monocytogenes/genética , Escherichia coli
18.
J Biol Chem ; 286(31): 27729-40, 2011 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-21622572

RESUMO

The ErbB receptor family is dysregulated in many cancers, and its therapeutic manipulation by targeted antibodies and kinase inhibitors has resulted in effective chemotherapies. However, many malignancies remain refractory to current interventions. We describe a new approach that directs ErbB receptor interactions, resulting in biased signaling and phenotypes. Due to known receptor-ligand affinities and the necessity of ErbB receptors to dimerize to signal, bivalent ligands, formed by the synthetic linkage of two neuregulin-1ß (NRG) moieties, two epidermal growth factor (EGF) moieties, or an EGF and a NRG moiety, can potentially drive homotypic receptor interactions and diminish formation of HER2-containing heterodimers, which are implicated in many malignancies and are a prevalent outcome of stimulation by native, monovalent EGF, or NRG. We demonstrate the therapeutic potential of this approach by showing that bivalent NRG (NN) can bias signaling in HER3-expressing cancer cells, resulting in some cases in decreased migration, inhibited proliferation, and increased apoptosis, whereas native NRG stimulation increased the malignant potential of the same cells. Hence, this new approach may have therapeutic relevance in ovarian, breast, lung, and other cancers in which HER3 has been implicated.


Assuntos
Receptor ErbB-3/metabolismo , Transdução de Sinais , Apoptose , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Ligantes , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neuregulina-1/metabolismo , Fenótipo , Engenharia de Proteínas , Ressonância de Plasmônio de Superfície
19.
J Org Chem ; 77(17): 7428-34, 2012 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-22866873

RESUMO

A strategy for the construction of crystalline molecular rotors involves the assemblage of chemical structures that emulate the elements of macroscopic rotary devices, such as those found in macroscopic gyroscopes and compasses. In this report, we describe an efficient and short synthetic route for preparation of molecular rotors with two pentiptycene-units linked at their central benzene ring by triple bonds to a linearly conjugated phenylene rotator. Five analogous compounds with phenol, alkoxy, or alkoxycarbonyl substituents were synthesized and fully characterized in solution and in the solid-state through various methods, such as cross-polarization magic angle spinning (CPMAS) (13)C NMR and single crystal X-ray diffraction. Molecular and packing structures obtained from single crystal X-ray diffraction and crystallization properties were analyzed with the goal of identifying the key parameters that may hinder or facilitate the formation of dynamically functional, crystalline molecular rotors.

20.
Proc IEEE Conf Decis Control ; 2022: 5633-5638, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37051484

RESUMO

New SARS-CoV-2 variants escaping the effect of vaccines are an eminent threat. The use of antivirals to inhibit the viral replication cycle or immunomodulators to regulate host immune responses can help to tackle the viral infection at the host level. To evaluate the potential use of these therapies, we propose the application of an inverse optimal neural controller to a mathematical model that represents SARS-CoV-2 dynamics in the host. Antiviral effects and immune responses are considered as the control actions. The variability between infected hosts can be large, thus, the host infection dynamics are identified based on a Recurrent High-Order Neural Network (RHONN) trained with the Extended Kalman Filter (EKF). The performance of the control strategies is tested by employing a Monte Carlo analysis. Simulation results present different scenarios where potential antivirals and immunomodulators could reduce the viral load.

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