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Childhood obesity is a chronic inflammatory epidemic that affects children worldwide. Obesity affects approximately 1 in 5 children worldwide. Obesity in children can worsen weight gain and raise the risk of obesity-related comorbidities like diabetes and non-alcoholic fatty liver disease (NAFLD). It can also negatively impact the quality of life for these children. Obesity disrupts immune system function, influencing cytokine (interleukins) balance and expression levels, adipokines, and innate and adaptive immune cells. The altered expression of immune system mediators, including interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-17 (IL-17), interleukin-18 (IL-18), transforming growth factor (TGF), tumor necrosis factor (TNF), and others, caused inflammation, progression, and the development of pediatric obesity and linked illnesses such as diabetes and NAFLD. Furthermore, anti-inflammatory cytokines, including interleukin-2 (IL-2), have been shown to have anti-diabetes and IL-1 receptor antagonist (IL-1Ra) anti-diabetic and pro-NAFLFD properties, and interleukin-10 (IL-10) has been shown to have a dual role in managing diabetes and anti-NAFLD. In light of the substantial increase in childhood obesity-associated disorders such as diabetes and NAFLD and the absence of an effective pharmaceutical intervention to inhibit immune modulation factors, it is critical to consider the alteration of immune system components as a preventive and therapeutic approach. Thus, the current review focuses on the most recent information regarding the influence of pro- and anti-inflammatory cytokines (interleukins) and their molecular mechanisms on pediatric obesity-associated disorders (diabetes and NAFLD). Furthermore, we discussed the current therapeutic clinical trials in childhood obesity-associated diseases, diabetes, and NAFLD.
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Citocinas , Hepatopatia Gordurosa não Alcoólica , Obesidade Infantil , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade Infantil/complicações , Obesidade Infantil/metabolismo , Obesidade Infantil/imunologia , Citocinas/metabolismo , Criança , Diabetes Mellitus/imunologia , Diabetes Mellitus/metabolismo , Inflamação/metabolismo , Inflamação/imunologiaRESUMO
Sarecycline is a new narrow-spectrum tetracycline-class antibiotic approved for the treatment of acne vulgaris. Tetracyclines share a common four-ring naphthacene core and inhibit protein synthesis by interacting with the 70S bacterial ribosome. Sarecycline is distinguished chemically from other tetracyclines because it has a 7-[[methoxy(methyl)amino]methyl] group attached at the C7 position of ring D. To investigate the functional role of this C7 moiety, we determined the X-ray crystal structure of sarecycline bound to the Thermus thermophilus 70S ribosome. Our 2.8-Å resolution structure revealed that sarecycline binds at the canonical tetracycline binding site located in the decoding center of the small ribosomal subunit. Importantly, unlike other tetracyclines, the unique C7 extension of sarecycline extends into the messenger RNA (mRNA) channel to form a direct interaction with the A-site codon to possibly interfere with mRNA movement through the channel and/or disrupt A-site codon-anticodon interaction. Based on our biochemical studies, sarecycline appears to be a more potent initiation inhibitor compared to other tetracyclines, possibly due to drug interactions with the mRNA, thereby blocking accommodation of the first aminoacyl transfer RNA (tRNA) into the A site. Overall, our structural and biochemical findings rationalize the role of the unique C7 moiety of sarecycline in antibiotic action.
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Antibacterianos/farmacologia , Ribossomos/efeitos dos fármacos , Tetraciclinas/farmacologia , Antibacterianos/química , RNA Ribossômico 16S/química , Tetraciclinas/química , Thermus thermophilusRESUMO
Chemical modifications of RNAs have long been established as key modulators of nonprotein-coding RNA structure and function in cells. There is a growing appreciation that messenger RNA (mRNA) sequences responsible for directing protein synthesis can also be posttranscriptionally modified. The enzymatic incorporation of mRNA modifications has many potential outcomes, including changing mRNA stability, protein recruitment, and translation. We tested how one of the most common modifications present in mRNA coding regions, pseudouridine (Ψ), impacts protein synthesis using a fully reconstituted bacterial translation system and human cells. Our work reveals that replacing a single uridine nucleotide with Ψ in an mRNA codon impedes amino acid addition and EF-Tu GTPase activation. A crystal structure of the Thermus thermophilus 70S ribosome with a tRNAPhe bound to a ΨUU codon in the A site supports these findings. We also find that the presence of Ψ can promote the low-level synthesis of multiple peptide products from a single mRNA sequence in the reconstituted translation system as well as human cells, and increases the rate of near-cognate Val-tRNAVal reacting on a ΨUU codon. The vast majority of Ψ moieties in mRNAs are found in coding regions, and our study suggests that one consequence of the ribosome encountering Ψ can be to modestly alter both translation speed and mRNA decoding.
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Biossíntese de Proteínas , Pseudouridina/metabolismo , RNA Bacteriano/genética , RNA Mensageiro/genética , Thermus thermophilus/genética , Códon/genética , Códon/metabolismo , Fases de Leitura Aberta , Elongação Traducional da Cadeia Peptídica , Pseudouridina/genética , Processamento Pós-Transcricional do RNA , RNA Bacteriano/metabolismo , RNA Mensageiro/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Thermus thermophilus/metabolismo , Uridina/metabolismoRESUMO
Egg protein (EP) has a variety of functional properties, such as gelling, foaming, and emulsifying. The gel characteristics provide a foundation for applications in the food industry and research on EP. The proteins denature and aggregate to form a dense three-dimensional gel network structure, with a process influenced by protein concentration, pH, ion type, and strength. In addition, the gelation properties of EP can be altered to varying degrees by applying different treatment conditions to EP. Currently, modification methods for proteins include physical modification (heat-induced denaturation, freeze-thaw modification, high-pressure modification, and ultrasonic modification), chemical modification (glycosylation modification, phosphorylation modification, acylation modification, ethanol modification, polyphenol modification), and biological modification (enzyme modification). Pidan, salted eggs, egg tofu, and other egg products have unique sensory properties, due to the gel properties of EP. In accessions, EP has also been used as a new ingredient in food packaging and biopharmaceuticals due to its gel properties. This review will further promote EP gel research and provide guidance for its full application in many fields.
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Proteínas do Ovo , Proteínas do Ovo/química , Géis/química , PressãoRESUMO
Seafood products have been one of the main drivers behind the popularity of high-pressure processing (HPP) in the food industry owing to a high demand for fresh ready-to-eat seafood products and food safety. This review provides an overview of the advanced knowledge available on the use of HPP for production of wholesome and highly nutritive clean label fish and shellfish products. Out of 653 explored items, 65 articles published during 2016-2021 were used. Analysis of the literature showed that most of the earlier work evaluated the HPP effect on physicochemical and sensorial properties, and limited information is available on nutritional aspects. HPP has several applications in the seafood industry. Application of HPP (400-600 MPa) eliminates common seafood pathogens, such as Vibrio and Listeria spp., and slows the growth of spoilage microorganisms. Use of cold water as a pressure medium induces minimal changes in sensory and nutritional properties and helps in the development of clean label seafood products. This technology (200-350 MPa) is also useful to shuck oysters, lobsters, crabs, mussels, clams, and scallops to increase recovery of the edible meat. High-pressure helps to preserve organoleptic and functional properties for an extended time during refrigerated storage. Overall, HPP helps seafood manufacturers to maintain a balance between safety, quality, processing efficiency, and regulatory compliance. Further research is required to understand the mechanisms of pressure-induced modifications and clean label strategies to minimize these modifications.
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Alimentos Marinhos , Frutos do Mar , Animais , Peixes , Inocuidade dos Alimentos , CarneRESUMO
Staphylococcus aureus is an eminent and opportunistic human pathogen that can colonize in the intestines, skin tissue and perineal regions of the host and cause severe infectious diseases. The presence of complex regulatory network and existence of virulent gene expression along with tuning metabolism enables the S. aureus to adopt the diversity of environments. Two component system (TCS) is a widely distributed mechanism in S. aureus that permit it for changing gene expression profile in response of environment stimuli. TCS usually consist of transmembrane histidine kinase (HK) and cytosolic response regulator. S. aureus contains totally 16 conserved pairs of two component systems, involving in different signaling mechanisms. There is a connection among these regulatory circuits and they can easily have effect on each other's expression. This review has discussed five major types of TCS in S. aureus and covers the recent knowledge of their virulence gene expression. We can get more understanding towards staphylococcal pathogenicity by getting insights about gene regulatory pathways via TCS, which can further provide implications in vaccine formation and new ways for drug design to combat serious infections caused by S. aureus in humans.
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Infecções Estafilocócicas , Staphylococcus aureus , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Histidina Quinase/genética , Humanos , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , VirulênciaRESUMO
Furan (C4H4O) is a volatile, heterocyclic and carcinogenic heterocyclic chemical compound occurring in a wide range of thermally processed foods. Several studies have been conducted to analyze the formation conditions, triggering furan formation via model systems. Furan can be encountered via various pathways including thermal degradation, oxidation of polyunsaturated fatty acids, thermal rearrangement of carbohydrates in the presence of amino acids, thermal degradation of certain amino acids. Furan has been proven to cause cancer in experimental animal models and classified as a possible human carcinogen by International agency for research on cancer based on sufficient evidences. Thus, different strategies should be developed to reduce furan contents in commercially available food stuffs while food processing. This review summarizes some current evidences of furan formation from different precursors, analytical methods for its detection, and its toxicity that might lead to carcinogenicity and genotoxicity with human risk assessment. In addition, furan occurrence in different thermally processed foods entailed by several recent studies as well as furan mitigation strategies during food processing have also been illustrated in this review.
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Furanos , Animais , Carboidratos , Carcinógenos/toxicidade , Ácidos Graxos Insaturados , Manipulação de Alimentos , Furanos/toxicidade , Temperatura Alta , HumanosRESUMO
This study has conducted to determine the concentration levels of furan, furfural and 2-methylfuran in the six commercially available soy sauce varieties by an optimized Gas Chromatography Tripple Quadruple Mass Spectrometry. The extraction of analytes was performed by solid phase microextraction using 50/30 µm CAR/DVB/PDMS fibre in 25 min with 20% NaCl concentration under 35 °C and separation was performed on HP5-MS column. Different concentration levels of furan, furfural and 2-methylfuran were determined which differed significantly at p < 0.05. A total of four metal ions (Iron sulphate, magnesium sulphate, calcium sulphate and sodium sulfite), ascorbic acid and natural antioxidants (epicatechin, epigalactocatechin and kempferol) were added in the soy sauce samples by simulating sterilization conditions. A higher reduction level was given by calcium sulphate with reduction upto 90.68%, 89.07% and 65.42% for furan, furfural and 2-methylfuran, respectively, in comparison with other metal ions. Since iron sulphate and ascorbic acid have triggered formation of furanoic compounds upto high levels instead of reduction. Moreover, from natural antioxidants, epicatechin and kemferol have provided more reduction levels around 89.66%, 90.14% and 78.75% for furan, furfural and 2-methylfuran, respectively by sterilization with catichen and 88.80%, 90.36% and 84.29% for furan, furfural and 2-methylfuran, respectively by sterilization with kempferol than epigalactocatechin. Moreover, this method was also validated in terms of sensitivity, recovery, relative standard deviation and LOD and LOQ for all analytes.
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OBJECTIVE: To identify clinical spectrum, management and outcome of neonatal candidiasis. METHODS: The retrospective study was conducted at the Shifa International Hospital, Islamabad, Pakistan, and comprised microbiological records of all the babies admitted to the Neonatal Intensive Care Unit from January 2009 to January 2014 that were reviewed to identify those with positive candida cultures. Medical records were analysed for demographic and clinical spectrum features, management and outcome. SPSS 16 was used statistical analysis. RESULTS: Of the total 1550 neonatal admissions, 560 (36%) had positive cultures, and, of them, candida was isolated in 49(8.8%) neonates. Among them, 13(26%) had candida albicans and the rest had candida species. Majority were males 34(70%), and preterm with 30(61%) being <37 weeks. The mean birth weight was 2000±873 grams. Mean age at admission was 6±7.6 days. Overall, 39(80%) had ≥2 risk factors. The commonest site of isolation was blood in 41(84%). Besides, 32 (65%) received fluconazole alone for treatment. Mean duration of anti-fungal therapy was 10±5 days (range: 1-21 days). Twelve (24%) neonates expired and the cause of death was candida sepsis in 10(20%) cases. Mortality was not significantly associated with gender, place of birth, gestation, risk factors, length of stay, prior antibiotic exposure or receipt of antifungal prophylaxis except those who were ≤1500 grams (p<0.05). CONCLUSIONS: Approximately one in ten at-risk neonates may develop candida sepsis with high mortality. Early institution of anti-fungal therapy may prove to be life-saving.
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Candidíase/epidemiologia , Candidíase/terapia , Antifúngicos/uso terapêutico , Candidíase/diagnóstico , Feminino , Humanos , Recém-Nascido , Tempo de Internação , Masculino , Paquistão , Estudos Retrospectivos , Fatores de RiscoRESUMO
Triple negative breast cancer (TNBC) is most aggressive type of breast cancer with multiple invasive sub-types and leading cause of women's death worldwide. Lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) causes it to spread rapidly making its treatment challenging due to unresponsiveness towards anti-HER and endocrine therapy. Hence, needing advanced therapeutic treatments and strategies in order to get better recovery from TNBC. Artificial intelligence (AI) has been emerged by giving its high inputs in the automated diagnosis as well as treatment of several diseases, particularly TNBC. AI based TNBC molecular sub-typing, diagnosis as well as therapeutic treatment has become successful now days. Therefore, present review has reviewed recent advancements in the role and assistance of AI particularly focusing on molecular sub-typing, diagnosis as well as treatment of TNBC. Meanwhile, advantages, certain limitations and future implications of AI assistance in the TNBC diagnosis and treatment are also discussed in order to fully understand readers regarding this issue.
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Inteligência Artificial , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/classificação , Feminino , Biomarcadores Tumorais/genéticaRESUMO
Chloramphenicol (CHL) is an antibiotic targeting the peptidyl transferase center in bacterial ribosomes. We synthesized a new analog, CAM-BER, by substituting the dichloroacetyl moiety of CHL with a positively charged aromatic berberine group. CAM-BER suppresses bacterial cell growth, inhibits protein synthesis in vitro, and binds tightly to the 70S ribosome. Crystal structure analysis reveals that the bulky berberine group folds into the P site of the peptidyl transferase center (PTC), where it competes with the formyl-methionine residue of the initiator tRNA. Our toe-printing data confirm that CAM-BER acts as a translation initiation inhibitor in stark contrast to CHL, a translation elongation inhibitor. Moreover, CAM-BER induces a distinct rearrangement of conformationally restrained nucleotide A2059, suggesting that the 23S rRNA plasticity is significantly higher than previously thought. CAM-BER shows potential in avoiding CHL resistance and presents opportunities for developing novel berberine derivatives of CHL through medicinal chemistry exploration.
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Nutrition is an important aspect of a healthy lifestyle for all individuals, including adolescents. The objective of this cross-sectional descriptive survey study was to investigate university students' awareness of immunity enhancing foods, food nutritive values, and eating practices during the COVID-19 pandemic. A total of 839 university students from four different universities in Pakistan participated in the study from October 2021 to January 2022, 397 of which were male and 442 were female. A total of 419 students were studying in medical disciplines while 420 were non-medical students. The students had significant knowledge (p < 0.05) about COVID-19, and nutritional habits were seen in both medical and non-medical students. Results showed that medical students (n-201) were slightly more aware of immunity-enhancing foods and the nutritive values of foods compared to engineering students (n-79). However, eating practices were generally poorly adopted by all of the university students. Male and female students were not significantly different in their mean replies to questions on the nutritive value of food or in their eating habits. Healthy eating practices will aid university students in preventing illnesses connected to nutrition as well as enhancing their immune systems and nutritional well-being both during and post-pandemic. In light of these results, suggestions and implications for nutritional advice and education were explored.
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COVID-19 , Estudantes de Medicina , Adolescente , Feminino , Masculino , Humanos , Paquistão/epidemiologia , Estudos Transversais , Pandemias/prevenção & controle , Universidades , COVID-19/epidemiologia , DietaRESUMO
A wide range of food processing contaminants (FPCs) are usually formed while thermal processing of food products. Furan is a highly volatile compound among FPCs and could be formed in a variety of thermally processed foods. Therefore, identification of possible reasons of furan occurrence in different thermally processed foods, identification of the most consequential sources of furan exposure, factors impacting its formation, and its detection by specific analytical approaches are necessary to indicate gaps and challenges for future research findings. Furthermore, controlling furan formation in processed foods on a factory scale is also challenging, and research advancements are still ongoing in this context. Meanwhile, understanding adverse effects of furan on human health on a molecular level is necessary to gain insights into human risk assessment.
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Contaminação de Alimentos , Manipulação de Alimentos , Humanos , Contaminação de Alimentos/análise , Furanos/análise , Alimento Processado , Medição de RiscoRESUMO
This research work has developed and optimized a sensitive analytical method for separation and quantification of heterocyclic amines (HCAs) mainly including PhIP, Harman, Norharman, IQ, MeIQ, AαC, MeAαC and Trp-P-2 by optimizing UPLC-TQ-XS using electrospray ionization source (ESI+) on ACQUITY UPLC® BEH C18 column in <7 min, from braised beef sample matrix. Meanwhile, modified HCAs extraction by modifying QuEChERS (quick, easy, cheap, efficient, rugged and safe) technique and revisited with solid phase extraction (SPE) for HCAs purification, instead using traditional QuEChERS salts. Moreover, optimized pH conditions of HCA extracts before purification, for better extraction recoveries. Furthermore, this method was validated in terms of method validation parameters. Lastly, simulation of real braised beef model provided the minimum formation of HCAs by optimizing cooking parameters and precursors in a cooking system. Therefore, this method could be applied simultaneously on braised beef matrix either marketed or home cooked for HCAs analysis.
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Compostos Heterocíclicos , Animais , Bovinos , Compostos Heterocíclicos/análise , Projetos de Pesquisa , Aminas/análise , Culinária/métodos , Extração em Fase Sólida , Cromatografia Líquida de Alta PressãoRESUMO
Background: Table olives are becoming well recognized as a source of probiotic bacteria that might be used to create a health-promoting fermented food product by traditional procedures based on the activities of indigenous microbial consortia present in local environments. Methodology. In the present study, the characterization of probiotic bacteria isolated from mince, chunks, and brine of fermented green and black olives (Olea europaea) was done based on morphological, biochemical, and physiological characteristics. Results: Bacterial isolates demonstrated excellent survival abilities at 25, 37, and 45°C and at a variable range of pH. However, the optimum temperature is 37 and the optimum pH is 7 for all three isolates. An antimicrobial susceptibility pattern was found among these isolates through the disc diffusion method. Most of the isolates were susceptible to streptomycin, imipenem, and chloramphenicol, whereas, amoxicillin showed resistance to these isolates, and variable results were recorded for the rest of the antibiotics tested. The growth of the isolates was optimum with the supplementation of 3% NaCl and 0.3% bile salt. The isolated bacteria were able to ferment skimmed milk into yogurt, hence making it capable of producing organic acid. Conclusion: Isolates of Lactobacillus crispatus MB417, Lactococcus lactis MB418 from black olives, and Carnobacterium divergens MB421 from green olives were characterized as potential candidates for use as starter cultures to induce fermentation of other probiotic food products.
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Lactobacillus crispatus , Lactococcus lactis , Olea , Probióticos , Bactérias , Probióticos/farmacologia , Fermentação , Microbiologia de AlimentosRESUMO
Introduction: SARS-CoV-2 has created a significant challenge to healthcare systems, since the disease has spread rapidly, outweighing hospital capacity and exposing Health Care Workers (HCWs) to the risk of infection. The main objective of this study shows the HCW's self-reported use of Personal Protective Equipment (PPE), symptoms, and exposure to revealed and suspected people during the pandemic, as well as the implementation of infection prevention and control (IPC) guidelines that effectively limit the spread of the infection among healthcare personnel. Method: A single-center retrospective cohort study has been done at a tertiary care hospital. There were 3,651 hospital employees of these 1,890 HCWs and 1,761 nonclinical staff among those who were proven or suspected COVID-19 cases and had symptoms were included. The data was gathered using a standardized self-assessment questionnaire. Information about quarantine protocol and line listing was collected through telephonic conversations. Result: The majority of the participants were males (66%). The average age was 32.1±7.62. Out of 432 HCWs, 32.9% with positive SARS-CoV-2 PCR findings were nurses, 19.2% were doctors, and 47.9% were non-clinical employees from the hospital's inpatient and outpatient departments. 31.5% had a higher-risk exposure, 64.1% had a moderate-risk exposure, and 4.4% of practitioners with COVID-19 had a lower-risk exposure. A statistically significant association was found between COVID-19 disease and adherence to PPE and risk exposure. Conclusion: This study represents the healthcare workers' experience with COVID-19 patients in the early stages of the pandemic and emphasizes the measures required to overcome the problems, however, this study highlights that HCWs are being progressively infected with COVID-19 as a result of inadequate/ inappropriate PPE wear.
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In this paper, the effects of acylation modification on the gel behavior of ovalbumin (OVA) under heating induction have been investigated. From the obtained results, the acylated OVA hydrogels exhibited superior gelation properties than the native OVA hydrogels (NOVA-G) in terms of light transmission, gel hardness, resilience and water holding capacity. SEM revealed acylation modifications effectively promoted the formation of uniform and dense network structure of OVA hydrogels. The main intermolecular forces of the acylation-modified OVA hydrogels were hydrophobic interactions and hydrogen bonding. FTIR showed that acylation modifications caused 26.2% decrease in α-helix and 59.2% increase in ß-sheet content compared to NOVA-G. Furthermore, in-vitro release experiments showed that the release rate of curcumin from acylated OVA hydrogels was significantly delayed. Moreover, the above results have shown that acylation modifications can be considered as an effective method to improve the gelation as well as drug release properties of protein hydrogels.
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Temperatura Alta , Hidrogéis , Acilação , Interações Hidrofóbicas e Hidrofílicas , OvalbuminaRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder of an ever-increasing aging population with various pathological features such as ß-amyloid (Aß) aggregation, oxidative stress, an impaired cholinergic system, and neuroinflammation. Several therapeutic drugs have been introduced to slow the progression of AD by targeting the above-mentioned pathways. In addition, emerging evidence suggests that naturally occurring compounds have the potential to serve as adjuvant therapies to alleviate AD symptoms. Carotenoids, a group of natural pigments with antioxidative and anti-inflammatory properties, are proposed to be implicated in neuroprotection. To obtain a comprehensive picture of the effect of carotenoids on AD prevention and development, we critically reviewed and discussed recent evidence from in silico, in vitro, in vivo, and human studies in databases including PubMed, Web of Science, Google Scholar, and Cochrane (CENTRAL). After analyzing the existing evidence, we found that high-quality randomized controlled trials (RCTs) are lacking to explore the neuroprotective role of carotenoids in AD pathogenesis and symptoms, especially carotenoids with solid preclinical evidence such as astaxanthin, fucoxanthin, macular carotenoids, and crocin, in order to develop effective preventive dietary supplements for AD patients to ameliorate the symptoms. This review points out directions for future studies to advance the knowledge in this field.
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Doença de Alzheimer , Fármacos Neuroprotetores , Humanos , Idoso , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/metabolismo , Carotenoides/uso terapêutico , Peptídeos beta-Amiloides/metabolismo , Antioxidantes/uso terapêuticoRESUMO
The present study reports a hydrogel-based sunlight-assisted synthesis of gold nanoparticles (Au NPs) with enhanced antimicrobial and wound healing potential. The hydrogel extracted from the seeds of Cydonia oblonga was used as a reducing and capping agent to synthesize Au NPs for the first time. The as-synthesized Au NPs were characterized for an average size, shape, surface functionalization, antimicrobial, and wound healing capabilities. The cubic and rectangular-shaped Au NPs with an average edge length of 74 ± 4.57 nm depicted a characteristic surface plasmon resonance band at 560 nm. The hydrogel-based Au NPs inhibited the growth of microorganisms in zones with 12 mm diameter. In-vitro experiments showed that a minimum inhibitory concentration of Au NPs (16 µg/mL) was sufficient to mimic the 95% growth of pathogenic microorganisms in 24 h. In vivo treatment of wounds with Au NPs in murine models revealed a 99% wound closure within 5 days. Quantitative PCR analysis performed to decipher the role of Au NPs in enhanced wound healing showed an increase in the expression levels of NANOG and CD-34 proteins.
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Anti-Infecciosos , Nanopartículas Metálicas , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Ouro/farmacologia , Hidrogéis , Nanopartículas Metálicas/uso terapêutico , Camundongos , CicatrizaçãoRESUMO
Here, we report the synthesis, carbonic anhydrase-II (CA-II) inhibition and structure-activity relationship studies of cinnamaldehyde-clubbed thiosemicarbazones derivatives. The derivatives showed potent activities in the range of 10.3 ± 0.62-46.6 ± 0.62 µM. Among all the synthesized derivatives, compound 3n (IC50 = 10.3 ± 0.62 µM), 3g (IC50 = 12.1 ± 1.01 µM), and 3h (IC50 = 13.4 ± 0.52 µM) showed higher inhibitory activity as compared to the standard inhibitor, acetazolamide. Furthermore, molecular docking of all the active compounds was carried out to predict their behavior of molecular binding. The docking results indicate that the most active hit (3n) specifically mediate ionic interaction with the Zn ion in the active site of CA-II. Furthermore, the The199 and Thr200 support the binding of thiosemicarbazide moiety of 3n, while Gln 92 supports the interactions of all the compounds by hydrogen bonding. In addition to Gln92, few other residues including Asn62, Asn67, The199, and Thr200 play important role in the stabilization of these molecules in the active site by specifically providing H-bonds to the thiosemicarbazide moiety of compounds. The docking score of active hits are found in range of - 6.75 to - 4.42 kcal/mol, which indicates that the computational prediction correlates well with the in vitro results.