RESUMO
This study presents the contents of α-methylenecyclopropylglycine, a potentially toxic amino acid, in the peel, pulp and seed fractions of two well-known litchi varieties, namely Shahi and China, over a span of three harvest-seasons. For analysing α-methylenecyclopropylglycine, an LC-MS/MS-based method was validated. The method-accuracies fell within 75-110 % (RSD, <15 %) at 0.1 mg/kg (LOQ) and higher levels. A comparative evaluation of the results in peel, pulp and seed at 30 days before harvest (DBH), 15-DBH, and edible-ripe stage revealed that α-methylenecyclopropylglycine content increased as the litchi seeds grew towards maturity, regardless of the cultivar. In arils, at maturity, the concentration of α-methylenecyclopropylglycine ranged from not-detected to 11.7 µg/g dry weight. The Shahi cultivar showed slightly higher α-methylenecyclopropylglycine content in comparison to China litchi. This paper presents the first known analysis of combined seasonal data on different fruit components at various growth stages for the two chosen litchi cultivars grown in India.
Assuntos
Frutas , Litchi , Sementes , Espectrometria de Massas em Tandem , Litchi/química , Litchi/crescimento & desenvolvimento , Litchi/metabolismo , Frutas/química , Frutas/crescimento & desenvolvimento , China , Sementes/química , Sementes/crescimento & desenvolvimento , Glicina/análogos & derivados , Glicina/análise , Cromatografia Líquida de Alta Pressão , Ciclopropanos/análiseRESUMO
BACKGROUND: Silent myocardial infarction (SMI) frequently goes undetected, yet it is associated with increased cardiovascular morbidity and mortality. The impact of intensive systolic blood pressure (SBP) lowering on the risk of SMI in those with hypertension remains uncertain. METHODS: In this post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), participants with serial electrocardiograms (ECGs) during the trial were included. SPRINT investigated the benefit of intensive SBP lowering, aiming for < 120 mmHg compared to the standard SBP goal of < 140 mmHg. Incident SMI was defined as evidence of new MI on an ECG without adjudicated recognized myocardial infarction (RMI). RESULTS: During a median follow-up of 3.9 years, a total of 234 MI events (55 SMI and 179 RMI) occurred. Intensive, compared to standard, SBP lowering resulted in a lower rate of SMI (incidence rate 1.1 vs. 2.3 cases per 1000 person-years, respectively; HR [95% CI]: 0.48 [0.27-0.84]). Similarly, intensive, compared to standard, BP lowering reduced the risk of RMI (incidence rate 4.6 vs. 6.5 cases per 1000 person-years, respectively; HR [95% CI]: 0.71 [0.52-0.95]). No significant differences were noted between the strength of the association of intensive BP control on lowering the risk of SMI and RMI (p-value for HR differences = 0.23). CONCLUSIONS: This study shows that in adults with hypertension, the benefits of intensive SBP lowering, compared with standard BP lowering, go beyond the prevention of RMI to include the prevention of SMI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01206062.
Assuntos
Anti-Hipertensivos , Eletrocardiografia , Hipertensão , Infarto do Miocárdio , Humanos , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/complicações , Masculino , Feminino , Hipertensão/tratamento farmacológico , Hipertensão/complicações , Anti-Hipertensivos/uso terapêutico , Eletrocardiografia/métodos , Pessoa de Meia-Idade , Idoso , Incidência , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Seguimentos , Fatores de RiscoRESUMO
C-reactive protein (CRP) binds to phosphocholine (PCh)-containing substances and subsequently activates the complement system to eliminate the ligand. The PCh-binding function of CRP has been conserved throughout evolution from arthropods to humans. Human CRP, in its structurally altered conformation at acidic pH, also binds to amyloid-ß (Aß) and prevents the formation of Aß fibrils. It is unknown whether the Aß-binding function of CRP has also been evolutionarily conserved. The aim of this study was to determine whether CRP isolated from American horseshoe crab Limulus polyphemus was also anti-amyloidogenic and whether this function required structural alteration of Limulus CRP (Li-CRP). Two CRP species Li-CRP-I and Li-CRP-II were purified from hemolymph by employing PCh-affinity chromatography and phosphoethanolamine-affinity chromatography, respectively. Both Li-CRP-I and Li-CRP-II bound to immobilized Aß at physiological pH. Unlike human CRP, Li-CRP did not require any changes in its overall structure to bind to Aß. Both Li-CRP-I and Li-CRP-II bound to Aß in the fluid phase also and prevented the fibrillation of Aß. Additionally, ion-exchange chromatography of purified Li-CRP indicated that a variety of Li-CRP molecules of different subunit compositions were present in Limulus hemolymph, raising the possibility that the presence of various Li-CRP species in hemolymph facilitates the recognition of a range of proteins with differing amyloidogenicity. We conclude that the binding of CRP to Aß is an ancient function of CRP. In invertebrates, the Aß-binding function of CRP can protect the host from toxicity caused by amyloidogenic and pathogenic proteins. In humans, the Aß-binding function of CRP can protect against inflammatory diseases in which the host proteins are ectopically deposited on either host cells or foreign cells in an inflammatory milieu since immobilized proteins may expose Aß-like structures after deposition at places where they are not supposed to be.
Assuntos
Peptídeos beta-Amiloides , Amiloide , Proteína C-Reativa , Caranguejos Ferradura , Animais , Proteína C-Reativa/metabolismo , Proteína C-Reativa/química , Caranguejos Ferradura/metabolismo , Humanos , Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Ligação Proteica , Hemolinfa/metabolismo , Evolução Molecular , Fosforilcolina/metabolismoRESUMO
Post-transcriptional and post-translational modification of transcription factors (TFs) and pathway enzymes significantly affect the stress-stimulated biosynthesis of specialized metabolites (SM). Protein phosphorylation is one of the conserved and ancient mechanisms that critically influences many biological processes including specialized metabolism. The phosphorylation of TFs and enzymes by protein kinases (PKs), especially the Mitogen-Activated Protein Kinases (MAPKs), is well-studied in plants. While the roles of MAPKs in plant growth and development, phytohormone signaling, and immunity are well elucidated, significant recent advances have also been made in understanding the involvement of MAPKs in specialized metabolism. However, a comprehensive review highlighting the significant progress in the past several years is notably missing. This review focuses on MAPK-mediated regulation of several important SM, including phenylpropanoids (flavonoids and lignin), terpenoids (artemisinin and other terpenoids), alkaloids (terpenoid indole alkaloids and nicotine), and other nitrogen- and sulfur-containing SM (camalexin and indole glucosinolates). In addition to MAPKs, other PKs also regulate SM biosynthesis. For comparison, we briefly discuss the regulation by other PKs, such as sucrose non-fermenting-1 (SNF)-related protein kinases (SnRKs) and calcium-dependent protein kinases (CPKs). Furthermore, we provide future perspectives in this active area of research.
RESUMO
We report the design, synthesis, photoswitching and computational studies of N-methyl arylazo-3,5-(di-2-pyridyl)pyrazole and its N-alkyl pyridinium derivatives with an ionic center proximally located to the azo group. Besides achieving excellent photoswitching characteristics, particularly at longer wavelengths, and tuning Z isomer stability due to the effects of counter ions and pH, the utility of neutral and ionic photoswitches for pH modulation by light was achieved.
RESUMO
The ever-increasing demand for sustainable energy has drawn attention towards photovoltaic efficiency and reliability. In this context, the shading and associated hotpot degradation within PV modules has become an important area of research and development. The experimental approach of this paper aims to investigate single cell shading in high efficiency monocrystalline silicon PV PERC modules. Prior to the outdoor experiment, the PV module underwent experimental testing under STC to determine variation in electrical and thermal behaviour due to partial shading. The indoor experiments are performed using Sun-simulator and the I-V and P-V curves are analysed. Further, the outdoor experiments were performed under realistic conditions. In both cases, results showed that during 40-60% shading in single cell leads to critical shading scenario causing significant drop in power output in comparison with their unshaded conditions. The maximum power loss of 36.34% and 42% is recorded for indoor and outdoor experiments. The outdoor experiments recorded hotspot temperature of 85-90.1 °C under respective 40% and 60% critical shading scenarios. The efficiency recorded in the time interval of 11:00:00 and 11:30:00 was highest for the solar radiations between 940 and 990 W/m2. The maximum drop in efficiency is recorded from noon till 13:30:00 time of the day. Development of hotspot is directly related to the failure or malfunction of protecting system. Hence the importance of type of PV technology, amount of shading, and critical shading scenario is presented in the study. This study is important for researcher and manufacture to consider single cell shading in PV technology.
RESUMO
Evaluating the chronic course of chronic kidney disease (CKD) and identifying associated risk factors is essential for effective management. This study aims to identify risk factors and monitor the decline in renal function through prolonged follow-up of CKD patients. This retrospective cohort study included 410 CKD patients diagnosed between 2015 and 2022. Data collected included demographics, comorbidities, and repeated measurements of glomerular filtration rate (GFR) and proteinuria. Statistical analyses examined the association between GFR decline and risk factors such as age, diabetes, hypertension, and proteinuria during the follow-up period. The cohort showed a progressive decline in GFR over time. Significant associations were found between GFR decline and age, diabetes, hypertension, and higher proteinuria levels (P < 0.001). Age was associated with a 0.32 ml/min decline in GFR per 1.73 m², while the coefficients for hypertension and diabetes were -2.98 and -4.21, respectively. A strong correlation was found between proteinuria and GFR decline (ß = -6.78, P < 0.001). Early identification and management of risk factors are crucial for slowing CKD progression. These findings underscore the need for targeted interventions to preserve renal function and improve patient outcomes.
RESUMO
India's mango productivity is hindered by many factors but more importantly due to limited understanding of the genomic complexities behind regular bearing habit. This study is the first to quantify carbohydrate fractions, protein content, and macro and micronutrient storage pools, their transportation, and contributions to regular 'Totapuri' and alternate bearer 'Bombay Green' mango varieties during the 'off' year. Deep RNA sequencing was used to assess gene expression dynamics between buds and flowers of these varieties. Differential pathway analysis showed the greatest number of differentially expressed genes in metabolic processes (1377), followed by oxido-reductase (879), hormone (80), oxidative stress (77), starvation (39), alternate bearing (8), flowering (3), meristem (3), and cellular component (2) pathways. In silico analysis showed that among 15 genes, twelve genes up-regulated in Totapuri and three in Bombay Green, confirmed by qRT-PCR. Additionally, 202 SNPs were identified in 32 alternate bearing-related genes. The study confirmed the reproductive bud's strong ability to import sugars, protein, and starch in the regular bearer variety, enhancing flowering and fruiting during off years. The mineral nutrients and biochemical constituent of the bud and leaf tissue in contrasting genotypes, showed the potential role for regular bearing in mango.
RESUMO
Aim & objective: Combinatorial delivery of Doxorubicin (DOX) and Baicalein (BAC) has a potential to improve breast cancer treatment by mitigating the cardiotoxicity induced by DOX. The nanoformulation has been optimized and subjected to pharmacokinetic studies using LC-MS/MS.Materials & methods: Nanoformulation bearing DOX and BAC was optimized using quality by design approach and method validation was done following USFDA guidelines.Results: The particle size, PDI and zeta potential of developed nanoformulation were 162.56 ± 2.21 nm, 0.102 ± 0.03 and -16.5 ± 1.21 mV, respectively. DOX-BAC-SNEDDs had a higher AUC0-t values of 6128.84 ± 68.71 and 5896.62 ± 99.31 ng/mL/h as compared with DOX-BAC suspension.Conclusion: These findings hold promise for advancing breast cancer treatment and facilitating therapeutic drug monitoring.
[Box: see text].
RESUMO
Cordycepin (3'-deoxyadenosine) is a bioactive nucleoside analog synthesized by Cordyceps militaris. Liquid fermentation of C. militaris by addition in different concentrations of five additives singly was evaluated. Glycine at 15.00 g/L after 20 d enhanced the cordycepin of 1773.33 mg/L (15-fold increment over control). Adenine at 4.00 g/L and 6.00 g/L in the liquid media showed significantly higher cordycepin i.e.1596.66 mg/L and 1550.00 mg/L (3-fold increment over control) after 40 d. Tryptone supplementation 14.00 g/L significantly higher cordycepin 784.33 mg/L (6.70-fold increment over control) and 912.66 mg/L production after 20 and 40 d of inoculation. Peanut oil at 10.00 g/L produced 585.66 mg/L (5-fold increment over control) cordycepin after 20 d and after 40 d, also addition of peanut oil at 20.00 g/L and 30.00 g/L in the media showed 631.66 and 624.31 mg/L cordycepin content. Supplementation of mono-sodium glutamate at 0.30 g/L produced significantly highest cordycepin i.e. 614 mg/L and 635.00 mg/L cordycepin after 20 and 40 d, respectively.
Assuntos
Cordyceps , Meios de Cultura , Desoxiadenosinas , Fermentação , Desoxiadenosinas/biossíntese , Desoxiadenosinas/metabolismo , Cordyceps/metabolismo , Cordyceps/química , Cordyceps/crescimento & desenvolvimento , Meios de Cultura/química , Óleo de Amendoim , Adenina/metabolismo , Peptonas/metabolismoRESUMO
Glioblastoma (GBM) is an aggressive brain cancer with limited therapeutic options. Natural killer (NK) cells are innate immune cells with strong anti-tumor activity and may offer a promising treatment strategy for GBM. We compared the anti-GBM activity of NK cells engineered to express interleukin (IL)-15 or IL-21. Using multiple in vivo models, IL-21 NK cells were superior to IL-15 NK cells both in terms of safety and long-term anti-tumor activity, with locoregionally administered IL-15 NK cells proving toxic and ineffective at tumor control. IL-21 NK cells displayed a unique chromatin accessibility signature, with CCAAT/enhancer-binding proteins (C/EBP), especially CEBPD, serving as key transcription factors regulating their enhanced function. Deletion of CEBPD resulted in loss of IL-21 NK cell potency while its overexpression increased NK cell long-term cytotoxicity and metabolic fitness. These results suggest that IL-21, through C/EBP transcription factors, drives epigenetic reprogramming of NK cells, enhancing their anti-tumor efficacy against GBM.
Assuntos
Neoplasias Encefálicas , Proteína delta de Ligação ao Facilitador CCAAT , Glioblastoma , Interleucinas , Células Matadoras Naturais , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Glioblastoma/imunologia , Glioblastoma/genética , Glioblastoma/patologia , Glioblastoma/terapia , Interleucinas/genética , Interleucinas/metabolismo , Interleucinas/imunologia , Humanos , Animais , Camundongos , Proteína delta de Ligação ao Facilitador CCAAT/metabolismo , Proteína delta de Ligação ao Facilitador CCAAT/genética , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Linhagem Celular Tumoral , Interleucina-15/genética , Interleucina-15/metabolismo , Interleucina-15/imunologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Leishmaniasis, attributed to the protozoan parasite Leishmania, manifests in diverse clinical forms, including cutaneous, mucocutaneous, and visceral leishmaniasis; VL constitutes a significant global health menace. Prevalent in tropical and subtropical regions, this affliction disproportionately impacts individuals below the poverty threshold, transmitted through the bite of female sandflies. Existing treatments, such as pentavalent antimony, miltefosine, and Amphotericin B, exhibit limitations. Despite the emergence of liposomal Amphotericin B (AmBisome) as a promising antileishmanial agent, its utility is impeded by adverse effects, elevated production expenses, and cytotoxicity. To address these challenges, our investigation introduces a potential remedyâa citrate-coated gold Amphotericin B nanoparticle formulation. Characterized using dynamic light scattering and transmission electron microscopy, this pioneering formulation exhibited efficacy against L. donovani Ag83 promastigotes as demonstrated by MTT cell viability testing. Evaluating internal reactive oxygen species (ROS) levels and dual staining with acridine orange and ethidium bromide unveiled its consequential impact on cell death. Significantly, our study discloses this novel nanoformulation's unprecedented inhibition of the trypanothione reductase enzyme. The findings posit the citrate-coated gold Amphotericin B nanoformulation as a promising and targeted antileishmanial agent, representing potential advancements in leishmaniasis therapeutics.
Assuntos
Anfotericina B , Antiprotozoários , Ouro , Nanopartículas Metálicas , Ouro/química , Ouro/farmacologia , Anfotericina B/farmacologia , Anfotericina B/química , Antiprotozoários/farmacologia , Antiprotozoários/química , Antiprotozoários/síntese química , Nanopartículas Metálicas/química , Tamanho da Partícula , Nanoconjugados/química , Teste de Materiais , Leishmania donovani/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Sobrevivência Celular/efeitos dos fármacos , Testes de Sensibilidade Parasitária , Espécies Reativas de Oxigênio/metabolismo , HumanosRESUMO
INTRODUCTION: Reducing childhood mortality by curtailing the incidence of vaccine preventable diseases is contingent upon a robust and high-performing routine immunization system. According to the available data, the full immunization coverage (FIC) in the state of Bihar (India) has reached ~ 71%. While the government aspires to reach 90% FIC, a systematic evidence-based investigation of the reasons behind underimmunization as well as the identification of drivers and enablers to reach and sustain 90% FIC is critical. This study aimed to review the factors leading to underimmunized children in the state of Bihar and develop a forward-looking roadmap to reach and sustain 90% FIC by adopting a system strengthening approach. METHOD: We conducted a desk review, followed by extensive stakeholder interviews and field visits to document and analyze the data and evidence relevant to routine immunization system performance in the state of Bihar. The stakeholders included the State Immunization Officer, District Immunization Officers, Block-level health officials, representatives from development agencies, healthcare workers, and caregivers. A total of eighty-six structured interviews were conducted, which included qualitative and quantitative parameters. RESULT: While positive results were observed from the assessment of Bihar's immunization system, the implementation of targeted strategies for supply, service delivery and demand can provide a means to achieve FIC of 90%. The roadmap developed by the Government of Bihar enlists 40 + interventions across key thematic areas and has been prioritized over a 5-year time horizon as short, medium, and long-term milestones to achieve 90% FIC. These interventions include strengthening the data availability and quality, improving the governance and review mechanism, augmenting the capacity of health workers involve with immunization programme, and initiatives to increase demand for immunization services. CONCLUSION: The Bihar's Immunization Roadmap development project work follows a methodical approach to assess and identify intervention to improve immunization coverage and can provide information and reference to other states and countries that are aiming to formulate similar action plans.
Assuntos
Programas de Imunização , Cobertura Vacinal , Humanos , Índia , Programas de Imunização/organização & administração , Cobertura Vacinal/estatística & dados numéricos , Lactente , Pré-EscolarRESUMO
Antimicrobial resistance (AMR), the ability of bacterial species to develop resistance against exposed antibiotics, has gained immense global attention in the past few years. Bacterial infections are serious health concerns affecting millions of people annually worldwide. Therefore, developing novel antibacterial agents that are highly effective and avoid resistance development is imperative. Among various strategies, recent developments in nanozyme technology have shown promising results as antibacterials in several antibiotic-sensitive and resistant bacterial species. Nanozymes offer several advantages over corresponding natural enzymes, such as inexpensive, stable, multifunctional, tunable catalytic properties, etc. Although the use of nanozymes as antibacterial agents has provided promising results, the specific biomolecule-conjugated nanozymes have shown further improvement in catalytic performance and associated antibacterial efficacy. The exclusive design of functional nanozymes with theranostic potential is found to simultaneously inhibit the growth and image of AMR bacterial species. This review comprehensively summarizes the history of nanozymes, their classification, biomolecules conjugated nanozyme, and their mechanism of enzyme-mimetic activity and associated antibacterial activity in antibiotic-sensitive and resistant species. The futureneeds to effectively engineer the existing or new nanozymes to curb AMR have also been discussed.
Assuntos
Antibacterianos , Antibacterianos/química , Antibacterianos/farmacologia , Humanos , Nanoestruturas/química , Bactérias/efeitos dos fármacos , CatáliseRESUMO
Erythrocytes undergo several changes during human aging and age-related diseases and, thus, have been studied as biomarkers of the aging process. The present study aimed to explore the antioxidant ability of metal and metal oxide nanoparticles (NPs) such as iron oxide (Fe3O4), gold (Au), and silver (Ag) to mitigate age-related oxidative stress in human erythrocytes. Metal and metal oxide NPs behave like antioxidative enzymes, directly influencing redox pathways and thus have better efficiency. Additionally, biopolymer coatings such as dextran enhance the biocompatibility of these NPs. Therefore, dextran-coated Fe3O4, Au, and Ag NPs were synthesized using wet chemical methods and were characterized. Their hemocompatibility and ability to protect erythrocytes from age-induced oxidative stress were investigated. The Fe3O4 and Au NPs were observed to protect erythrocytes from hydrogen peroxide and age-induced oxidative damage, including decreased antioxidant levels, reduced activity of antioxidative enzymes, and increased amounts of oxidative species. Pretreatment with NPs preserved the morphology and membrane integrity of the erythrocyte. However, Ag NPs induced oxidative stress in erythrocytes similar to hydrogen peroxide. Therefore, dextran-coated Fe3O4 and Au nanoparticles have the potential to be employed as antioxidant therapies against age-related oxidative stress.
Assuntos
Antioxidantes , Dextranos , Eritrócitos , Ouro , Nanopartículas Metálicas , Estresse Oxidativo , Prata , Estresse Oxidativo/efeitos dos fármacos , Humanos , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Dextranos/farmacologia , Prata/farmacologia , Antioxidantes/farmacologia , Ouro/farmacologia , Compostos Férricos/farmacologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Peróxido de Hidrogênio/metabolismoRESUMO
Exploring efficient systems to recover CO2 from the atmosphere could be a way to address the global carbon emissions issue. Herein, we report the synthesis of nanosilica (NS) functionalized with polyamidoamine (PAMAM) dendrimers (NS-PAMAM) as efficient adsorbents for CO2 capture under simulated direct air capture (DAC) (400 ppm CO2 in helium at 30 °C) and indoor air (≥400 ppm, 50 ± 3% RH at 30 °C) conditions. The results inferred that the 1st (NS-G1.0), 2nd (NS-G2.0), 3rd (NS-G3.0), and 4th (NS-G4.0) generations of the NS-PAMAM dendrimers exhibited excellent performance for CO2 capture. Compared to the other generations, NS-G3.0 demonstrated superior CO2 adsorption capacities of 0.50 mmol g-1 under simulated dry CO2 conditions (400 ppm in He), 1.02 mmol g-1 under indoor air (dry) CO2 conditions (≥400 ppm, 26 ± 3% RH), and 1.54 mmol g-1 under indoor air (humid) CO2 conditions (≥400 ppm, 50 ± 3% RH). The study included the evaluation of CO2 adsorption-desorption performance of the NS-PAMAM dendrimers under varying structural and chemical parameters, kinetics, regeneration at low temperature (80 °C), as well as CO2 adsorption under humid conditions. Additionally, NS-G3.0 displayed a substantially superior performance with stable CO2 capture displayed during ten short temperature swing adsorption (TSA) cycles, making it a promising candidate for CO2 capture from ambient air. Finally, we demonstrated the recovery and reutilization of the captured CO2 for both the synthesis of formate via carbonate hydrogenation and for the production of calcium carbonate pellets.
RESUMO
Past one decade has witnessed a tremendous growth in the field of carbenes stabilized low-valent silicon compounds unravelling very exciting properties of these molecules. Herein, we have employed a bicyclic (alkyl)(amino)carbene, (MeBICAAC) to explore the low-valent chemistry of silicon compounds. The reduction of bicyclic (alkyl)(amino)carbene-SiCl4 complex, [(MeBICAAC)SiCl4] (1) with KC8 afforded low-valent Si complexes, including Si(III) radical [(MeBICAAC)SiCl3] (2) and a complex with silicon center in a formal zero-valent state, [(MeBICAAC)2Si] (3). Similarly, the reduction of in-situ generated MeBICAAC adduct of Me2SiCl2 with one equivalent of KC8 led to the formation of [(MeBICAAC)SiMe2Cl] (4) complex having an unpaired electron. These complexes have been characterized by IR, UV-Vis., NMR, HRMS, EPR and their solid-state structures were also elucidated by single crystal X-ray crystallography. Further, DFT calculations revealed the lower energy singlet state for complexes 1, 3 and doublet state for complexes 2, 4.
RESUMO
Long-term stress is a significant risk factor for cardiovascular diseases, including atherosclerosis and endothelial dysfunction. Moreover, prolonged stress has shown to negatively regulate central BDNF expression. The role of central BDNF in CNS disorders is well studied until recently the peripheral BDNF was also found to be involved in endothelial function regulation and atherosclerosis. The peripheral BDNF and its role in chronic stress-induced atherosclerosis and endothelial dysfunction remain unclear. Therefore, we aimed to elucidate the role of BDNF and its modulation by the HDAC inhibitor valproic acid (VA) in chronic unpredictable stress (CUS)-induced atherosclerosis and endothelial dysfunction. We demonstrated that a 10-week CUS mouse model substantially decreases central and peripheral BDNF expression, resulting in enhanced serum lipid indices, plaque deposition, fibrosis, and CD68 expression in thoracic aortas. Further, parameters associated with endothelial dysfunction such as increased levels of endothelin-1 (ET-1), adhesion molecules like VCAM-1, M1 macrophage markers, and decreased M2 macrophage markers, eNOS expression, and nitrite levels in aortas, were also observed. VA (50 mg/kg, 14 days, i. p.) was administered to mice following 8 weeks of CUS exposure until the end of the experimental procedure. VA significantly prevented the decrease in BDNF, eNOS and nitrite levels, reduced lesion formation and fibrosis in thoracic aortas and increased ET-1, and VCAM-1 followed by M2 polarization in VA-treated mice. The study highlights the potential of epigenetic modulation of BDNF as a therapeutic target, in stress-induced cardiovascular pathologies and suggests that VA could be a promising agent for mitigating CUS-induced endothelial dysfunction and atherosclerosis by BDNF modulation.