Food additive salicylates inhibit human and rat placental 3ß-hydroxysteroid dehydrogenase: 3D-QSAR and in silico analysis.

The use of salicylates as flavoring agents in food and beverages is common, but their potential to disrupt the endocrine system remains unclear. Human placental 3ß-hydroxysteroid dehydrogenase 1 (h3ß-HSD1) plays a role in progesterone synthesis and is the potential target. This study evaluated the inhibition of 13 salicylates on h3ß-HSD1, structure-activity relationship (SAR) and compared with rat placental homolog r3ß-HSD4. Salicylates inhibited h3ß-HSD1, depending on carbon chain number in the alcohol moiety and the IC50 values for hexyl, ethylhexyl, homomenthyl, and menthyl salicylates were 53.27, 15.78, 2.35, and 2.31 µM, as mixed inhibitors, respectively, while methyl to benzyl salicylates were ineffective at 100 µM. Interestingly, only hexyl salicylate inhibited r3ß-HSD4 with IC50 of 31.05 µM. Bivariate analysis revealed a negative correlation between IC50 and hydrophobicity (LogP), molecular weight, heavy atoms, and carbon number in the alcohol moiety against h3ß-HSD1. Docking analysis demonstrated that these salicylates bind to cofactor binding sites or between the steroid and cofactor binding sites. Additionally, 3D-QSAR showed distinct binding via hydrogen bond donors and hydrophobic regions. In conclusion, the inhibition of h3ß-HSD1 by salicylates appears to be dependent on factors such as LogP, molecular weight, heavy atoms, and carbon-chain length and there is species-dependent inhibition sensitivity.

Reduced estrogenic risks of a sunscreen additive: Theoretical design and evaluation of functionally improved salicylates.

Salicylic esters (SEs), the widely used ultraviolet (UV) absorbers in sunscreen products, have been found to have health risks such as skin sensitization and estrogenic effects. This study aims to design SE substitutes that maintain high UV absorbance while reducing estrogenicity. Using molecular docking and Gaussian09 software for initial assessments and further application of a combination of two-dimensional and three-dimensional quantitative structure-activity relationships (2D-QSAR and 3D-QSAR, respectively) models, we designed 73 substitutes. The best-performing molecules, ethylhexyl salicylate (EHS)-5 and EHS-15, significantly reduced estrogenicity (44.54 % and 17.60 %, respectively) and enhanced UV absorbance (249.56 % and 46.94 %, respectively). Through screening for human health risks, we found that EHS-5 and EHS-15 were free from skin sensitivity and eye irritation and exhibited reduced skin permeability compared with EHS. Furthermore, the photolysis and synthetic pathways of EHS-5 and EHS-15 were deduced, demonstrating their good photodegradability and potential synthesizability. In addition, we analyzed the mechanisms underlying the changes in estrogenic effects and UV absorption properties. We identified covalent hydrogen bond basicity and acidity Propgen value for atomic molecular properties and the highest occupied molecular orbital eigenvalue as the main factors affecting the estrogenic effect and UV absorbance of SEs, respectively. This study focuses on the design and screening of SEs, exhibiting enhanced functionality, reduced health risks, and synthetic feasibility.

Awareness and Attitude About Ototoxic Drugs Among Medical Doctors in Arar City, Saudi Arabia.

OBJECTIVES: The purpose of this study was to assess the awareness of ototoxicity among medical doctors in Arar City, Saudi Arabia. METHODS: This is a cross-sectional study based on a pre-formed validated questionnaire (Appendix) that included three sections covering participants' demographic data (three questions), their attitudes (five questions), and knowledge (13 questions) regarding drug-induced ototoxicity. RESULTS: After obtaining their informed consent, 213 physicians from government and private sector health facilities in Arar were enrolled in the study. Interns and general practitioners represented 57.8% of the participants; consultants represented 17.8%. Only 71.8% of participants were interested in drug-induced ototoxicity, while 26.3% considered ototoxicity a rare complication. Approximately 90% of the participants were knowledgeable about the adverse effects of drugs on the vestibulocochlear system, and 26.7% reported having experienced cases of drug-induced ototoxicity in their practice. Participants showed an overall knowledge score about ototoxicity of 9.3±3.27 (out of 14). The knowledge score was significantly higher (p-value=0.0007) for participants with more years of clinical experience. The most widely known ototoxic drug for participants was frusemide (72.3%), followed by aminoglycoside (68.5%), while acetaminophen (44.1%) ototoxicity was the least known among participants. CONCLUSION: Awareness of drug-induced ototoxicity is satisfactory among physicians in the Northern Borders region. However, workshops about all types of drugs with ototoxic effects and the main lines for the management of drug-induced ototoxicity are recommended to increase awareness.

Peri-mortem rigidity in a fatal case of severe salicylate poisoning.

INTRODUCTION: There has been a previous case report of peri-arrest muscle rigidity in the setting of severe salicylate poisoning (serum salicylate concentration 1,500 mg/L), described as paratonia or rapid rigor mortis. We present an image of rapid rigor mortis in another fatal salicylate poisoning. CASE SUMMARY: We report a 42-year-old male with severe salicylate poisoning (peak salicylate concentration 1,600 mg/L). During the peri-arrest period, the patient developed isotonic flexion of the upper and lower extremities, the clinical signs of rapid-occurring rigor mortis. Despite resuscitative efforts, the patient died. IMAGE: Our patient is exhibiting peri-arrest rigidity in the upper extremities. DISCUSSION: Peri-mortem rigidity is due to depletion of adenosine triphosphate. Severe salicylate poisoning causes uncoupling of oxidative phosphorylation which prevents the production of adenosine triphosphate, which is required to release myosin from actin to allow the muscle to relax. A limitation of our report is that we did not definitively exclude other uncouplers of oxidative phosphorylation, such as 2,4-dinitrophenol. However, the history of aspirin ingestion was provided by the patient and corroborated by his mother, and it was confirmed by measurement of his salicylate concentration. CONCLUSION: We hypothesize that in our patient, rapid-occurring rigor mortis likely resulted from depletion of adenosine triphosphate. This occurred as a result of uncoupling of oxidative phosphorylation in the mitochondria from severe salicylate poisoning, as adenosine triphosphate is required for muscle relaxation.

Fabrication and application of salicin-polycaprolactone 3D-printed scaffold in the healing of femur bone defects.

Polycaprolactone (PCL) is a suitable material for bone repair due to good biocompatibility and mechanical properties. However, low bioactivity and hydrophobicity pose major challenges for its biomedical applications. To overcome these limitations, PCL-based scaffolds loaded with bioactive agents have been developed. Salicin (Sal) is an anti-inflammatory and analgesic herbal glycoside with osteogenic potential. In the present study, we aimed to produce a Sal-laden PCL (PCL-Sal) scaffold for bone healing applications. Three-dimensional scaffolds were produced and their biocompatibility, and physical-chemical characteristics were determined. The osteogenic potential of the PCL (PCL) and PCL-Sal scaffolds was evaluated using bone marrow mesenchymal stem cells (BMSCs). Scaffolds were implanted into a 5 mm bone defect created in the femur of adult rats, and the new bone fraction was determined using micro-computed tomography scanning at one-month follow-up. PCL-Sal scaffold had a structure, porosity, and fiber diameter suitable for bone construction. It also possessed a higher rate of hydrophilicity and bioactivity compared to the PCL, providing a suitable surface for the proliferation and bone differentiation of BMSCs. Furthermore, PCL-Sal scaffolds showed a higher capacity to scavenge free radicals compared to PCL. The improved bone healing potential of the PCL-Sal scaffold was also confirmed according toin vivoimplantation results. Our findings revealed that the Sal-laden implant could be considered for bone repair due to desirable characteristics of Sal such as hydrophilicity, surface modification for cell attachment, and antioxidant properties.

Risk of bleeding with concomitant use of oral anticoagulants and aspirin: A systematic review and meta-analysis.

PURPOSE: Oral anticoagulants (OACs) and aspirin can trigger bleeding events when used alone or in combination. The purpose of this study was to compare the risk of any type of bleeding in individuals exposed to a combination of OAC and aspirin with the risk in those taking an OAC or aspirin alone. METHODS: MEDLINE and Web of Science were queried in January 2021 for eligible articles. Studies were included if they were either randomized controlled trials (RCTs) or observational studies and evaluated the number of any bleeding events in two groups, one with exposure to both OAC and aspirin and one with exposure to OAC alone or aspirin alone. Pooled odds ratios were calculated using a random-effects model. RESULTS: Forty-two studies were included. In an analysis of 15 RCTs and 19 observational studies evaluating OAC plus aspirin versus OAC alone, a significant difference in the risk of bleeding was observed in the combination groups, with an odds ratio [OR] of, 1.36 (95% CI, 1.15-1.59) for RCTs and an OR of 1.42 (95% CI-, 1.09-1.87) for observational studies. When OAC plus aspirin was compared to aspirin alone, a higher rate of bleeding was found in the combination group (OR, 2.36; 95%CI, 1.91-2.92) in the analysis of 15 RCTs, but no significant difference was found among 10 observational studies (OR, 1.93; 95% Cl, 0.99-3.75). CONCLUSION: The risk of any type of bleeding was significantly increased among patients taking aspirin plus OAC compared to those taking OAC alone in both RCTs and observational studies. Evaluation of RCTs comparing OAC plus aspirin to aspirin alone suggests increased bleeding risk as well.

Association between aspirin use and risk of dementia: a systematic review and meta-analysis.

PURPOSE: Dementia and Alzheimer's disease (AD) pose significant challenges to public health globally with no effective treatment strategies available. Therefore, the research focuses on developing effective prophylaxis to prevent the onset of these diseases. Recent studies have suggested that low-dose aspirin may help reduce the risk of dementia. Nonetheless, evidence regarding the correlation between aspirin consumption and the onset of dementia and AD is limited. This review aims to provide an up-to-date summary of the existing evidence and evaluate the association between aspirin and the onset of dementia and Alzheimer's disease. METHODS: A systematic search of PubMed, Embase, Web of Science, PsycINFO, and CINAHL databases was conducted to find eligible studies published until April 2023. A random-effects meta-analysis of the eligible studies was then performed to assess the link between aspirin use and the onset of dementia and Alzheimer's disease. Additionally, we conducted subgroup analyses to evaluate the overall effect of low-dose (75-100 mg) aspirin consumption on the onset of dementia and AD. RESULTS: A total of 875 studies were identified, with only 22 meeting the inclusion criteria. There was no statistically significant impact of aspirin consumption on the onset of dementia (HR 1.13, 11 studies) or Alzheimer's disease (HR 0.91, 3 studies). Additionally, subgroup analysis showed that taking low doses of aspirin (75-100 mg) did not significantly affect the onset of either dementia (HR 0.96, 13 studies) or Alzheimer's disease (HR 0.85, 2 studies). CONCLUSIONS: Aspirin use does not decrease the risk of dementia or AD, even when taken in low doses. However, the quality of the studies analyzed was inadequate, with only three randomized controlled trials included in the review. Future high-quality studies are needed to assess the effect of aspirin consumption on these diseases. These findings may assist clinicians in selecting appropriate prophylactic strategies for patients at risk of developing dementia and AD.

COVID-19 na doença inflamatória intestinal: devemos ser mais cautelosos com o uso dos salicilatos? / Covid-19 in inflammatory bowel disease: should we be more careful with the use of salicylates?

ABSTRACT Backgrounds: Fortunately, much has been studied about COVID-19 in patients with inflammatory bowel diseases (IBD). Evidence suggests that these patients do not appear to be at increased risk of severe COVID-19. However, there are still some uncertainties regarding the clinical manifestations of COVID-19 in patients with immune-mediated diseases. Objective: This study aimed to describe the main symptoms of COVID-19 and their frequency in IBD patients and evaluate the impact of the IBD therapeutic drugs on clinical presentation of COVID-19 and to determine factors associated with COVID-19 in this population. Methods: Adult patients with IBD from three tertiary-care public, teaching hospitals in Ceará, Northeastern Brazil, were evaluated during one scheduled appointment from March to December 2020. Patients with possible or confirmed COVID-19 were compared with patients without COVID-19. Furthermore, incidences of each symptom were evaluated based on the use of IBD therapeutic drugs. Results: A total of 515 patients with IBD were included in the study: 234 with CD, and 281 with UC. Of these, 174 patients (34%) had possible/confirmed COVID-19 of whom 156 (90%) were symptomatic. Main symptoms were fever (65%) and headache (65%); gastrointestinal symptoms occurred in one third of patients and were higher than COVID-19 in general population. The factors associated with having COVID-19 were female gender (OR 1.71, 95%CI: 1.17-2.50); contact at home (OR 5.07, 95%CI: 3.31-7.78) and outside the home (OR 3.14, 95%CI: 2.10-4.71) with a case of COVID-19; work outside of the home (OR 1.87, 95%CI: 1.26-2.78); family history of COVID-19 (OR 2.29, 95%CI 1.58-3.33) use of salicylate (OR 1.71, 95%CI: 1.17-4.28); and asthma (OR 7.10, 95%CI: 1.46-34.57). Conclusion: IBD patients at high risk of COVID-19 infection may need to avoid salicylate therapy but further studies are necessary to confirm this association.

RESUMO Contexto: Felizmente, muito se tem estudado sobre a COVID-19 em pacientes com doenças inflamatórias intestinais (DII). As evidências sugerem que esses pacientes não parecem ter risco aumentado de COVID-19 grave. Mas ainda se tem algumas incertezas com relação às manifestações clínicas da COVID-19 em portadores de doenças imunomediadas. Objetivo: Este estudo teve como objetivo descrever os principais sintomas da COVID-19 e sua frequência em pacientes com DII e avaliar o impacto dos medicamentos utilizados no tratamento das DII na apresentação clínica da COVID-19. Métodos: Pacientes adultos com DII de três hospitais públicos terciários de ensino do Ceará, Nordeste do Brasil, foram avaliados em consulta ambulatorial no período de março a dezembro de 2020. Pacientes com COVID-19 possível ou confirmada foram comparados com pacientes sem COVID-19. Além disso, as incidências de cada sintoma foram avaliadas com base no uso de medicamentos utilizados para tratamento da DII. Resultados: Foram incluídos no estudo 515 pacientes com DII: 234 com DC e 281 com RCU. Destes, 174 pacientes (34%) tinham COVID-19 possível/confirmado, dos quais 156 (90%) eram sintomáticos. Os principais sintomas foram febre (65%) e dor de cabeça (65%); sintomas gastrointestinais ocorreram em um terço dos pacientes, sendo mais frequentes do que na população geral com COVID-19. Os fatores associados a ter COVID-19 foram sexo feminino (OR 1,71, IC95%: 1,17-2,50); ter contato com caso de COVID-19, tanto intradomiciliar (OR 5,07; IC95%: 3,31-7,78) como fora do domicílio (OR 3,14; IC95%: 2,10-4,71); trabalhar fora de casa (OR 1,87; IC95%: 1,26-2,78); história familiar de COVID-19 (OR 2,29, IC95% 1,58-3,33), uso de salicilato (OR 1,71, IC95%: 1,17-4,28) e asma (OR 7,10; IC95%: 1,46-34,57). Conclusão: Pacientes com DII com alto risco de infecção por COVID-19 podem precisar evitar a terapia com salicilatos, mas mais estudos são necessários para confirmar esta associação.

Risks and benefits of salicylates in food: a narrative review.

Salicylates are generally present in plants as part of their defense system against pathogens and environmental stress. Major dietary sources of salicylates were found in spices and herbs, such as curry and paprika (hot powder). Several studies suggest that these natural salicylates offer health benefits in the human body, such as antidiabetic, anticancer, antiviral, and anti-inflammatory properties. However, despite their advantages, salicylates can be harmful to people with allergies, and high doses of salicylates may cause respiratory alkalosis and gastrointestinal bleeding. Additionally, salicylates can interact with certain drugs, such as nonsteroidal anti-inflammatory drugs and warfarin. This narrative review aimed to consolidate recent information on the content of salicylates in food based on the literature, while also highlighting the benefits and risks associated with salicylate consumption in humans. Based on the literature review and analysis of results, it can be concluded that the dietary intake of salicylates in vegetarians can be relatively high, resulting in concentrations of salicylic acid in the blood and urine that are comparable to those observed in patients taking a low dose of aspirin (75 mg). This suggests that a diet rich in salicylates may have potential benefits in preventing and treating some diseases that require low doses of aspirin.

Incidence of rebound salicylate toxicity following cessation of urine alkalinization.

INTRODUCTION: Management of patients with salicylate toxicity frequently requires urine alkalinization to enhance excretion of salicylate. One strategy for determining when to stop urine alkalinization is to wait for two consecutive serum salicylate concentrations to be less than 300 mg/L (2.17 mmol/L) and declining. When alkalinization of the urine ceases, a rebound in serum salicylate concentration can occur from tissue redistribution or delayed gastrointestinal absorption. Whether this can lead to rebound toxicity is not well understood. METHODS: This was a single-center, retrospective review of cases with a primary ingestion of acetylsalicylic acid reported to the local poison center over a five-year period. Cases were excluded if the product was not listed as the primary ingestion or if there was no serum salicylate concentration documented after discontinuation of intravenous sodium bicarbonate infusion. The primary outcome was the incidence of serum salicylate rebound to a concentration greater than 300 mg/L (2.17 mmol/L) after discontinuation of intravenous sodium bicarbonate infusion. RESULTS: A total of 377 cases were included. Of these, eight (2.1%) had a serum salicylate concentration increase (rebound) after stopping the sodium bicarbonate infusion. All these cases were acute ingestions. Five of the eight cases had rebound serum salicylate concentrations that were greater than 300 mg/L (2.17 mmol/L). Of these five patients, only one reported recurrent symptoms (tinnitus). Prior to stopping urinary alkalinization, the last or the last two serum salicylate concentrations were less than 300 mg/L (2.17 mmol/L) in three and two cases, respectively. CONCLUSIONS: In patients with salicylate toxicity, the incidence of rebound in serum salicylate concentration after cessation of urine alkalinization, is low. Even if serum salicylate rebounds to supratherapeutic concentrations, symptoms are often absent or mild. Routine repeat serum salicylate concentrations after urine alkalinization is stopped may be unnecessary unless symptoms recrudesce.

Salicylic acid and jasmonic acid in elevated CO2-induced plant defense response to pathogens.

Plants respond to elevated CO2 (eCO2) via a variety of signaling pathways that often rely on plant hormones. In particular, phytohormone salicylic acid (SA) and jasmonic acid (JA) play a key role in plant defense against diverse pathogens at eCO2. eCO2 affects the synthesis and signaling of SA and/or JA and variations in SA and JA signaling lead to variations in plant defense responses to pathogens. In general, eCO2 promotes SA signaling and represses the JA pathway, and thus diseases caused by biotrophic and hemibiotrophic pathogens are typically suppressed, while the incidence and severity of diseases caused by necrotrophic fungal pathogens are enhanced under eCO2 conditions. Moreover, eCO2-induced modulation of antagonism between SA and JA leads to altered plant immunity to different pathogens. Notably, research in this area has often yielded contradictory findings and these responses vary depending on plant species, growth conditions, photoperiod, and fertilizer management. In this review, we focus on the recent advances in SA, and JA signaling pathways in plant defense and their involvement in plant immune responses to pathogens under eCO2. Since atmospheric CO2 will continue to increase, it is crucial to further explore how eCO2 may alter plant defense and host-pathogen interactions in the context of climate change in both natural as well as agricultural ecosystems.

Diflunisal Attenuates Virulence Factor Gene Regulation and Phenotypes in Staphylococcus aureus.

Virulence factor expression is integral to pathogenicity of Staphylococcus aureus. We previously demonstrated that aspirin, through its major metabolite, salicylic acid (SAL), modulates S. aureus virulence phenotypes in vitro and in vivo. We compared salicylate metabolites and a structural analogue for their ability to modulate S. aureus virulence factor expression and phenotypes: (i) acetylsalicylic acid (ASA, aspirin); (ii) ASA metabolites, salicylic acid (SAL), gentisic acid (GTA) and salicyluric acid (SUA); or (iii) diflunisal (DIF), a SAL structural analogue. None of these compounds altered the growth rate of any strain tested. ASA and its metabolites SAL, GTA and SUA moderately impaired hemolysis and proteolysis phenotypes in multiple S. aureus strain backgrounds and their respective deletion mutants. Only DIF significantly inhibited these virulence phenotypes in all strains. The kinetic profiles of ASA, SAL or DIF on expression of hla (alpha hemolysin), sspA (V8 protease) and their regulators (sigB, sarA, agr (RNAIII)) were assessed in two prototypic strain backgrounds: SH1000 (methicillin-sensitive S. aureus; MSSA) and LAC-USA300 (methicillin-resistant S. aureus; MRSA). DIF induced sigB expression which is coincident with the significant inhibition of RNAIII expression in both strains and precedes significant reductions in hla and sspA expression. The inhibited expression of these genes within 2 h resulted in the durable suppression of hemolysis and proteolysis phenotypes. These results indicate that DIF modulates the expression of key virulence factors in S. aureus via a coordinated impact on their relevant regulons and target effector genes. This strategy may hold opportunities to develop novel antivirulence strategies to address the ongoing challenge of antibiotic-resistant S. aureus.

Preventive and Curative Effects of Salicylic and Methyl Salicylic Acid Having Antifungal Potential against Monilinia laxa and the Development of Phenolic Response in Apple Peel.

The effects of salicylic acid (SA) and one of its better-known derivatives-methyl salicylic acid (MeSA)-on the infection of apple fruits with the fungus Monilinia laxa, which causes brown rot, were investigated. Since research to date has focused on preventive effects, we also focused on the curative use of SA and MeSA. Curative use of SA and MeSA slowed the progression of the infection. In contrast, preventive use was generally unsuccessful. HPLC-MS was used to analyze the content of phenolic compounds in apple peels in healthy and boundary peel tissues around lesions. The boundary tissue around the lesions of untreated infected apple peel had up to 2.2-times higher content of total analyzed phenolics (TAPs) than that in the control. Flavanols, hydroxycinnamic acids and dihydrochalcones were also higher in the boundary tissue. During the curative treatment with salicylates, the ratio of TAP content between healthy and boundary tissue was lower (SA up to 1.2-times higher and MeSA up to 1.3-times higher content of TAPs in boundary compared to those in healthy tissue) at the expense of also increasing the content in healthy tissues. The results confirm that salicylates and infection with the fungus M. laxa cause an increased content of phenolic compounds. Curative use of salicylates has a greater potential than preventive use in infection control.

Synthesis of New Ester Derivatives of Salicylic Acid and Evaluation of Their COX Inhibitory Potential.

Salicylic acid is an NSAID with serious side effects on the GIS. The side effects of salicylic acid on the GIS are slightly reduced by acetylating salicylic acid. 12 new ester analogs of salicylic acid were synthesized with high yields in this study. The chemical structures of the synthesized compounds were characterized by 1 H-NMR, 13 C-NMR, and HRMS spectra. The inhibitory potential of the compounds was evaluated on COXs by in vitro and in silico studies. The COX2 inhibitory activity of the most potent inhibitor MEST1 (IC50 : 0.048 µM) was found to be much higher than the COX2 inhibitory activity of aspirin (IC50 : 2.60 µM). In docking studies, the strongest inhibitor among the compounds synthesized was predicted to be MEST1, with the lowest binding energy. Docking studies revealed that MEST1 extends from the hydrophobic channel to the top of the cyclooxygenase active site, forming various interactions with residues in the binding pocket.

Acclimation and Compensating Metabolite Responses to UV-B Radiation in Natural and Transgenic Populus spp. Defective in Lignin Biosynthesis.

Plants have evolved to protect leaf mesophyll tissue from damage caused by UV-B radiation by producing an array of UV-absorbing secondary metabolites. Flavonoids (phenolic glycosides) and sinapate esters (hydroxycinnamates) have been implicated as UV-B protective compounds because of the accumulation in the leaf epidermis and the strong absorption in the wavelengths corresponding to UV. Environmental adaptations by plants also generate a suite of responses for protection against damage caused by UV-B radiation, with plants from high elevations or low latitudes generally displaying greater adaptation or tolerance to UV-B radiation. In an effort to explore the relationships between plant lignin levels and composition, the origin of growth elevation, and the hierarchical synthesis of UV-screening compounds, a collection of natural variants as well as transgenic Populus spp. were examined for sensitivity or acclimation to UV-B radiation under greenhouse and laboratory conditions. Noninvasive, ecophysiological measurements using epidermal transmittance and chlorophyll fluorescence as well as metabolite measurements using UPLC-MS generally revealed that the synthesis of anthocyanins, flavonoids, and lignin precursors are increased in Populus upon moderate to high UV-B treatment. However, poplar plants with genetic modifications that affect lignin biosynthesis, or natural variants with altered lignin levels and compositions, displayed complex changes in phenylpropanoid metabolites. A balance between elevated metabolic precursors to protective phenylpropanoids and increased biosynthesis of these anthocyanins, flavonoids, and lignin is proposed to play a role in the acclimation of Populus to UV-B radiation and may provide a useful tool in engineering plants as improved bioenergy feedstocks.

Quantification of Salicylates and Flavonoids in Poplar Bark and Leaves Based on IR, NIR, and Raman Spectra.

Poplar bark and leaves can be an attractive source of salicylates and other biologically active compounds used in medicine. However, the biochemical variability of poplar material requires a standardization prior to processing. The official analytical protocols used in the pharmaceutical industry rely on the extraction of active compounds, which makes their determination long and costly. An analysis of plant materials in their native state can be performed using vibrational spectroscopy. This paper presents for the first time a comparison of diffuse reflectance in the near- and mid-infrared regions, attenuated total reflection, and Raman spectroscopy used for the simultaneous determination of salicylates and flavonoids in poplar bark and leaves. Based on 185 spectra of various poplar species and hybrid powdered samples, partial least squares regression models, characterized by the relative standard errors of prediction in the 4.5-9.9% range for both calibration and validation sets, were developed. These models allow for fast and precise quantification of the studied active compounds in poplar bark and leaves without any chemical sample treatment.

Dietary Intervention Effectiveness, Clinical Outcomes and Nutrient and Salicylate Intakes in Older Adults Living in Long-Term Care Homes: The Results from the Senior's Plate Project.

Optimal nutrition is an important part of the therapeutic process offered to patients in long-term care, as it can significantly influence their nutritional and health status. The aim of this study was to assess the impacts of a dietary intervention on the nutritional status, clinical outcomes and selected nutrient and salicylate intakes among older adults living in a long-term care nursing home. To achieve the research goal, a prospective, non-randomized, baseline-controlled intervention study was conducted. The study was conducted within the framework of the "Senior's Plate Project", a project established in 2018 by the Polish Society of Dietetics. METHODS: A 3 month dietary intervention, which included one serving of supplementary food, served as a second breakfast (Nestle Sinlac). Energy, nutrients and salicylates intakes were estimated on the basis of the menus. Food and beverage intakes among residents were verified by health care personnel. Anthropometric measurements and clinical examinations were conducted according to standard procedures at baseline and after intervention. RESULTS: Of the 38 residents qualified for the study, 29 completed the program. Residents' body mass index (BMI) values ranged from 13.3 kg/m2 to 34 kg/m2. A BMI < 22 kg/m2, indicating underweight, was found in 19 subjects. The dietary intervention resulted in increased body weight (57.8 ± 12.3 vs. 59.4 ± 12.6 kg), BMI (22.4 ± 4.0 vs. 23.0 ± 4.1 kg/m2) and body fat (19.2 ± 8.7 vs. 20.6 ± 8.9 kg). Significant changes in the levels of biochemical parameters, including serum calcium (8.7 vs. 9.5 mg/dL), potassium (4.1 ± 0.6 vs. 4.5 ± 0.5 mmol/L) and zinc (74.1 ± 10.9 vs. 109.0 ± 20.4 µg/dL), were observed. Energy, protein, fat and carbohydrate intakes were significantly higher in the third month of the intervention as compared to the baseline. The estimated medial daily intake of salicylates was low and ranged from 0.34 mg to 0.39 mg. CONCLUSIONS: The dietary intervention resulted in beneficial and significant changes in the nutritional status, biochemical parameters and nutrition of residents of the long-term care home. These results suggest that practical and individualized approaches are required to improve the nutritional status and clinical outcomes of nursing homes residents.

Topical delivery of salicylates.

Salicylates have a long history of use for pain relief. Salicylic acid and methyl salicylate are among the widely used topical salicylates namely for keratolytic and anti-inflammatory actions, respectively. The current review summarises both passive and active strategies, including emerging technologies employed to enhance skin permeation of these two salicylate compounds. The formulation design of topical salicylic acid targets the drug retention in and on the skin based on the different indications including keratolytic, antibacterial and photoprotective actions, while the investigations of topical delivery strategies for methyl salicylate are limited. The pharmacokinetics and metabolisms of both salicylate compounds are discussed. The current overview and future perspectives of the topical delivery strategies are also highlighted for translational considerations of formulation designs.

Promising Antifungal and Antibacterial Agents Based on 5-Aryl-2,2'-bipyridines and Their Heteroligand Salicylate Metal Complexes: Synthesis, Bioevaluation, Molecular Docking.

A series of new 5-aryl-2,2'-bipyridines and their (polyfluoro)salicylate complexes of Cu(II), Co(II) and Mn(II) were synthesized. Their antimicrobial activity was evaluated in vitro against six strains of Trichophytons, E. floccosum, M. canis, C. ablicans and Gram-negative bacteria N. gonorrhoeae. Among azo-ligands, Ph-bipy and Tol-bipy showed promising antifungal activity (minimum inhibitory concentration (MIC)<0.8-27 µM). Their antifungal action was found can be realized via binding Fe(III) ions. Tol-bipy suppressed growth of Gram-positive bacteria S. aureus, S. aureus MRSA and their monospecies biofilms (MIC 6-16 µM). Using molecular docking, the anti-staphylococcal action mechanism based on the inhibition of S. aureus DNA gyrase GyrB was proposed for the lead compounds. Among metal complexes, Cu(II) and Mn(II) complexes based on tetrafluorosalicylic acid and Tol-bipy or Ph-bipy had the high antifungal activity (MIC<0.24-32 µM). Mn(SalF4 -2H)2 (Tol-bipy)2 ] suppressed the growth of seven Candida strains at MIC 12-24 µM. [Cu(Sal-2H)(Ph-bipy)] and [Cu(SalF3 -2H)(Ph-bipy)2 ] showed the promising anti-gonorrhoeae activity (MIC 4.2-5.2 µM). (Cu(SalFn -2H)(Tol-bipy)2 ], [Cu(SalF4 -2H)(Ph-bipy)2 ] and [Cu(SalF3 -2H)(Ph-bipy)2 ]) were found active against the bacteria of S. aureus, S. aureus MRSA and their biofilms (MIC 2.4-41.4 µM). The most active compounds were tested for toxicity in vitro against human embryonic kidney (HEK-293) cells and in vivo experiments with CD-1 mice.

Identification of Salicylates in Willow Bark (Salix Cortex) for Targeting Peripheral Inflammation.

Salix cortex-containing medicine is used against pain conditions, fever, headaches, and inflammation, which are partly mediated via arachidonic acid-derived prostaglandins (PGs). We used an activity-guided fractionation strategy, followed by structure elucidation experiments using LC-MS/MS, CD-spectroscopy, and 1D/2D NMR techniques, to identify the compounds relevant for the inhibition of PGE2 release from activated human peripheral blood mononuclear cells. Subsequent compound purification by means of preparative and semipreparative HPLC revealed 2'-O-acetylsalicortin (1), 3'-O-acetylsalicortin (2), 2'-O-acetylsalicin (3), 2',6'-O-diacetylsalicortin (4), lasiandrin (5), tremulacin (6), and cinnamrutinose A (7). In contrast to 3 and 7, compounds 1, 2, 4, 5, and 6 showed inhibitory activity against PGE2 release with different potencies. Polyphenols were not relevant for the bioactivity of the Salix extract but salicylates, which degrade to, e.g., catechol, salicylic acid, salicin, and/or 1-hydroxy-6-oxo-2-cycohexenecarboxylate. Inflammation presents an important therapeutic target for pharmacological interventions; thus, the identification of relevant key drugs in Salix could provide new prospects for the improvement and standardization of existing clinical medicine.