Correction to "Surface Thermal Behavior and RT CO Gas Sensing Application of Oligoacenaphthylene with p-Hydroxyphenylacetic Acid Composite".

[This corrects the article DOI: 10.1021/acsomega.2c03897.].

Ethyl-4-(aryl)-6-methyl-2-(oxo/thio)-3,4-dihydro-1H-pyrimidine-5-carboxylates: Silica supported bismuth(III)triflate catalyzed synthesis and antioxidant activity.

Novel ethyl-4-(aryl)-6-methyl-2-(oxo/thio)-3,4-dihydro-1H-pyrimidine-5-carboxylates were synthesized from one-pot, three-component Biginelli reaction of aryl aldehydes, ethyl acetoacetate and urea/ thiourea by catalytic action of silica supported Bismuth(III) triflate, a Lewis acid. All the synthesized compounds were structurally characterized by spectral (IR, 1H NMR & 13C NMR spectroscopic and Mass spectrometric) and elemental (C, H & N) analyses. The present protocol has deserved novel as, formed the products in high yields with short reaction times, involved eco-friendly methodology and reusable heterogeneous Lewis acid catalyst. The title compounds were screened for in vitro DPPH free radical scavenging antioxidant activity and identified 4i, 4j, 4h & 4f as potential antioxidants. The obtained in vitro results were correlated with molecular docking, ADMET, QSAR, Bioactivity & toxicity risk studies and molecular finger print properties and found that in silico binding affinities were identified in good correlation with in vitro antioxidant activity and studied the structure activity relationship. The molecular docking study has disclosed strong hydrogen bonding interactions of title compounds with aspartic acid (ASP197) aminoacid residue of 2HCK, a complex enzyme of haematopoietic cell kinase and quercetin. Results of toxicology study evaluated for potential risks of compounds have revealed title compounds as safer drugs. In ultimate the study has established ligand's antioxidant potentiality as they effectively binds with ASP197 amino acid of Chain A hence confirms the inhibition of growth of reactive oxygen species in vivo. In addition, the title compounds have been identified as potential blood-brain barrier penetrable entities and efficient central nervous system (CNS) active neuro-protective antioxidant agents.

Surface Thermal Behavior and RT CO Gas Sensing Application of an Oligoacenaphthylene with p-Hydroxyphenylacetic Acid Composite.

The current work describes room-temperature gas sensing performances using an oligoacenaphthylene (OAN)/p-hydroxyphenylacetic acid (p-HPA) composite. Based on inverse gas chromatography (IGC), the London dispersive surface energy γs d is calculated by using 14 representative models. Even when the γs d values of both OAN and the OAN/p-HPA composite are decreased as the temperature increases, the surface of OAN shows a higher value than that of the composite. The Gibbs surface free energy values of both are decreased with an increasing temperature. In our results, higher Lewis basic characters are observed in OAN and the OAN/p-HPA composite and the OAN/p-HPA surface exhibits a higher basicity compared to OAN. Because of the presence of phenolic groups in the OAN/p-HPA composite, the more important basic character drives a significant CO gas sensing ability with a sensitivity of 8.96% and good cycling stability as compared to the pristine counterparts. It is expected that the current study sheds light on a new pathway to exploring polymer composite materials for futuristic diverse and multiple applications, including IGC and gas sensor applications.

Competitive removal mechanism to simultaneously incarcerate bisphenol A, triclosan and 4-tert-octylphenol within beta-cyclodextrin crosslinked citric acid used for encapsulation in polypropylene membrane protected-micro-solid-phase extraction.

Endocrine disrupting compounds (EDCs) are extensively found in the environment and severely impacting human health. In addressing this issue, the beta-cyclodextrin crosslinked citric acid (BCD-CA) had been previously employed in membrane-protected micro-solid phase extraction for sequestering EDCs from water medium; and the findings revealed that BCD-CA possessed a selectivity property. On that account, the potential of BCD-CA towards competitive adsorption of selected EDCs was investigated in terms of adsorption mechanism and selectivity property. Factors that affected the removal efficiencies such as sample pH, sorbent dosage, contact time and initial concentration were evaluated. The characterization results revealed that the carbon percentage of BCD-CA had increased by 2.04%, while the hydrogen percentage had reduced by 1.83%, signifying the successful crosslinking of BCD-CA. Besides, the amount of active BCD was calculated to be 3.2 × 10-7 mol, while the amount of carboxyl group was 2.48 × 10-5 mol per 4 mg of BCD-CA. Moreover, BCD-CA was stable in an aqueous medium with the zeta potential obtained at -36.5 mV and had a high-water retention capacity (∼150%). The competitive adsorption mechanism by BCD-CA with EDCs followed the pseudo-second-order kinetics and Freundlich isotherm, suggesting that the adsorption process was dominated by chemisorption on the heterogeneous surface of the adsorbent. Thermodynamic results revealed that adsorption of 4-tert-octylphenol had the most negative ΔG value, indicating most favorable to be adsorbed by BCD-CA as opposed to triclosan and bisphenol A, which was coherent with the apparent formation constant results. These unique properties manifested the practicality of BCD-CA as a selective adsorbent to detect and remove EDCs from the water medium.

Gallocatechin-silver nanoparticles embedded in cotton gauze patches accelerated wound healing in diabetic rats by promoting proliferation and inhibiting apoptosis through the Wnt/ß-catenin signaling pathway.

BACKGROUND: Diabetes mellitus is a chronic metabolic disorder characterized by elevated plasma glucose levels. It is often defined as a lifestyle disease having severe economic and physiological repercussions on the individual. One of the most prevalent clinical consequences of diabetes is the lagging pace of injury healing leading to chronic wounds, which still to date have limited treatment options. The objective of this research is to look into the wound healing capabilities of gallocatechin (GC) and silver nanoparticles (AgNPs) impregnated patches in diabetic rats. Experimental rats were dressed patches and the wound healing skin region was dissected at the end of the experiment for molecular analysis. The wound healing rate in diabetic rats dressed with CGP2 and CGP3 & silver sulfadiazine (AgS) patches were found to be high. While mRNA and immunofluorescence or immunohistochemistry assays reveal that Wnt3a and ß-catenin levels were higher with Gsk-3ß and c-fos levels were lower in diabetic rats dressed with in CGP2 and CGP3 as compared with diabetic rats dressed with DC+CGP1. Furthermore, apoptosis markers such as caspase-3, caspase-9, and Bax levels were reduced, whereas anti-apoptosis maker (Bcl-2) and proliferation marker (PCNA) levels were increased in diabetic rats dressed with CGP2 and CGP3 as compared with diabetic rats dressed with DC+CGP1. In conclusion, the results demonstrated that GC-AgNPs-CGP (CGP2 & CGP3) dressing on diabetes wound rats decreased changes in Wnt3a/ß-catenin pathways, resulting in lower apoptosis and greater proliferation, so drastically improving diabetic wound healing.

Molecular Insights into Coumarin Analogues as Antimicrobial Agents: Recent Developments in Drug Discovery.

A major global health risk has been witnessed with the development of drug-resistant bacteria and multidrug-resistant pathogens linked to significant mortality. Coumarins are heterocyclic compounds belonging to the benzophenone class enriched in different plants. Coumarins and their derivatives have a wide range of biological activity, including antibacterial, anticoagulant, antioxidant, anti-inflammatory, antiviral, antitumour, and enzyme inhibitory effects. In the past few years, attempts have been reported towards the optimization, synthesis, and evaluation of novel coumarin analogues as antimicrobial agents. Several coumarin-based antibiotic hybrids have been developed, and the majority of them were reported to exhibit potential antibacterial effects. In the present work, studies reported from 2016 to 2020 about antimicrobial coumarin analogues are the focus. The diverse biological spectrum of coumarins can be attributed to their free radical scavenging abilities. In addition to various synthetic strategies developed, some of the structural features include a heterocyclic ring with electron-withdrawing/donating groups conjugated with the coumarin nucleus. The suggested structure-activity relationship (SAR) can provide insight into how coumarin hybrids can be rationally improved against multidrug-resistant bacteria. The present work demonstrates molecular insights for coumarin derivatives having antimicrobial properties from the recent past. The detailed SAR outcomes will benefit towards leading optimization during the discovery and development of novel antimicrobial therapeutics.

Infection Dynamics of ATG8 in Leishmania: Balancing Autophagy for Therapeutics.

In many regions of the world, Leishmaniasis is a cause of substantial mortality and ailment. Due to impediment in available treatment, development of novel and effective treatments is indispensable. Significance of autophagy has been accentuated in infectious disease as well as in Leishmaniasis, and it is having capability to be manifested as a therapeutic target. By evincing autophagy as a novel therapeutic regime, this study emphasized on the critical role of ATG4.1-ATG8 and ATG5-ATG12 complexes in Leishmania species. The objective here was to identify ATG8 as a potential therapeutic target in Leishmania. R71T, P56E, R18P are the significant mutations which shows detrimental effect on ATG8 while Arg276, Arg73, Cys75 of ATG4.1 and Val88, Pro89, Glu116, Asn117, and Gly120 are interacting residues of ATG8. Along with this, we also bring into spotlight an enticing role of Thiabendazole derivatives that interferes with the survival mechanisms by targeting ATG8. Further, the study claims that thiabendazole can be a potential drug candidate to target autophagy process in the infectious disease Leishmaniasis.

Comparative analysis of web-based programs for single amino acid substitutions in proteins.

Single amino-acid substitution in a protein affects its structure and function. These changes are the primary reasons for the advent of many complex diseases. Analyzing single point mutations in a protein is crucial to see their impact and to understand the disease mechanism. This has given many biophysical resources, including databases and web-based tools to explore the effects of mutations on the structure and function of human proteins. For a given mutation, each tool provides a score-based outcomes which indicate deleterious probability. In recent years, developments in existing programs and the introduction of new prediction algorithms have transformed the state-of-the-art protein mutation analysis. In this study, we have performed a systematic study of the most commonly used mutational analysis programs (10 sequence-based and 5 structure-based) to compare their prediction efficiency. We have carried out extensive mutational analyses using these tools for previously known pathogenic single point mutations of five different proteins. These analyses suggested that sequence-based tools, PolyPhen2, PROVEAN, and PMut, and structure-based web tool, mCSM have a better prediction accuracy. This study indicates that the employment of more than one program based on different approaches should significantly improve the prediction power of the available methods.

Therapeutic Implications of Caffeic Acid in Cancer and Neurological Diseases.

Caffeic acid (CA) is found abundantly in fruits, vegetables, tea, coffee, oils, and more. CA and its derivatives have been used for many centuries due to their natural healing and medicinal properties. CA possesses various biological and pharmacological activities, including antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. The potential therapeutic effects of CA are mediated via repression and inhibition of transcription and growth factors. CA possesses potential anticancer and neuroprotective effects in human cell cultures and animal models. However, the biomolecular interactions and pathways of CA have been described highlighting the target binding proteins and signaling molecules. The current review focuses on CA's chemical, physical, and pharmacological properties, including antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. We further described CA's characteristics and therapeutic potential and its future directions.

Development of Protein Rich Pregelatinized Whole Grain Cereal Bar Enriched With Nontraditional Ingredient: Nutritional, Phytochemical, Textural, and Sensory Characterization.

This study was aimed to use extrusion cooking as a pretreatment for non-conventional seeds (Indian horse chestnut flour) to blend them with whole grain flours (whole wheat flour, whole barley flour, and whole corn flour) for the development of a pregelatinized cereal bar (PCB). In this study, date paste (7.5-17.5%) and walnut grits (2.5-12.5%) were incorporated at varying levels to prepare PCB. The PCB was evaluated for its nutritional, color, textural (both three-point bending test and TPA), antioxidant activity, and sensory attributes. The flexural modulus, rupture stress, and fracture strain of PCB increased with the incorporation of a higher proportion of date paste. The protein and fiber content in PCB increased from 7.74 to 9.13% and 4.81 to 5.59% with the incorporation of walnut grits and date paste, respectively. The DPPH, total phenolic content, and water activity of PCB were determined, which progressively enhanced with increased levels of walnut grits and date paste. The correlation between sensory attributes and instrumental texture on PCB was also investigated. The correlation results showed a significant (p < 0.05) positive correlation between texture analysis and sensory hardness, springiness, adhesiveness, and negatively correlated to instrumental and sensory cohesiveness. For sensorial attributes, all PCB samples presented average scores of 7/10 and 4/5 for buying intention. Therefore, whole grain extrudates, date paste, and walnut grits can be efficiently used to develop PCB with improved nutritional, nutraceutical, and economic values.

Bax/Bcl-2 Cascade Is Regulated by the EGFR Pathway: Therapeutic Targeting of Non-Small Cell Lung Cancer.

Non-small cell lung carcinoma (NSCLC) comprises 80%-85% of lung cancer cases. EGFR is involved in several cancer developments, including NSCLC. The EGFR pathway regulates the Bax/Bcl-2 cascade in NSCLC. Increasing understanding of the molecular mechanisms of fundamental tumor progression has guided the development of numerous antitumor drugs. The development and improvement of rationally planned inhibitors and agents targeting particular cellular and biological pathways in cancer have been signified as a most important paradigm shift in the strategy to treat and manage lung cancer. Newer approaches and novel chemotherapeutic agents are required to accompany present cancer therapies for improving efficiency. Using natural products as a drug with an effective delivery system may benefit therapeutics. Naturally originated compounds such as phytochemicals provide crucial sources for novel agents/drugs and resources for tumor therapy. Applying the small-molecule inhibitors (SMIs)/phytochemicals has led to potent preclinical discoveries in various human tumor preclinical models, including lung cancer. In this review, we summarize recent information on the molecular mechanisms of the Bax/Bcl-2 cascade and EGFR pathway in NSCLC and target them for therapeutic implications. We further described the therapeutic potential of Bax/Bcl-2/EGFR SMIs, mainly those with more potent and selectivity, including gefitinib, EGCG, ABT-737, thymoquinone, quercetin, and venetoclax. In addition, we explained the targeting EGFR pathway and ongoing in vitro and in vivo and clinical investigations in NSCLC. Exploration of such inhibitors facilitates the future treatment and management of NSCLC.

Potential Therapeutic Implications of Caffeic Acid in Cancer Signaling: Past, Present, and Future.

Caffeic acid (CA) has been present in many herbs, vegetables, and fruits. CA is a bioactive compound and exhibits various health advantages that are linked with its anti-oxidant functions and implicated in the therapy and prevention of disease progression of inflammatory diseases and cancer. The anti-tumor action of CA is attributed to its pro-oxidant and anti-oxidant properties. CA's mechanism of action involves preventing reactive oxygen species formation, diminishing the angiogenesis of cancer cells, enhancing the tumor cells' DNA oxidation, and repressing MMP-2 and MMP-9. CA and its derivatives have been reported to exhibit anti-carcinogenic properties against many cancer types. CA has indicated low intestinal absorption, low oral bioavailability in rats, and pitiable permeability across Caco-2 cells. In the present review, we have illustrated CA's therapeutic potential, pharmacokinetics, and characteristics. The pharmacological effects of CA, the emphasis on in vitro and in vivo studies, and the existing challenges and prospects of CA for cancer treatment and prevention are discussed in this review.

Therapeutic Outcomes of Isatin and Its Derivatives against Multiple Diseases: Recent Developments in Drug Discovery.

Isatin (1H indole 2, 3-dione) is a heterocyclic, endogenous lead molecule recognized in humans and different plants. The isatin nucleus and its derivatives are owed the attention of researchers due to their diverse pharmacological activities such as anticancer, anti-TB, antifungal, antimicrobial, antioxidant, anti-inflammatory, anticonvulsant, anti-HIV, and so on. Many research chemists take advantage of the gentle structure of isatins, such as NH at position 1 and carbonyl functions at positions 2 and 3, for designing biologically active analogues via different approaches. Literature surveys based on reported preclinical, clinical, and patented details confirm the multitarget profile of isatin analogues and thus their importance in the field of medicinal chemistry as a potent chemotherapeutic agent. This review represents the recent development of isatin analogues possessing potential pharmacological action in the years 2016-2020. The structure-activity relationship is also discussed to provide a pharmacophoric pattern that may contribute in the future to the design and synthesis of potent and less toxic therapeutics.

Impact of Single Amino Acid Substitutions in Parkinsonism-Associated Deglycase-PARK7 and Their Association with Parkinson's Disease.

Parkinsonism-associated deglycase-PARK7/DJ-1 (PARK7) is a multifunctional protein having significant roles in inflammatory and immune disorders and cell protection against oxidative stress. Mutations in PARK7 may result in the onset and progression of a few neurodegenerative disorders such as Parkinson's disease. This study has analyzed the non-synonymous single nucleotide polymorphisms (nsSNPs) resulting in single amino acid substitutions in PARK7 to explore its disease-causing variants and their structural dysfunctions. Initially, we retrieved the mutational dataset of PARK7 from the Ensembl database and performed detailed analyses using sequence-based and structure-based approaches. The pathogenicity of the PARK7 was then performed to distinguish the destabilizing/deleterious variants. Aggregation propensity, noncovalent interactions, packing density, and solvent accessible surface area analyses were carried out on the selected pathogenic mutations. The SODA study suggested that mutations in PARK7 result in aggregation, inducing disordered helix and altering the strand propensity. The effect of mutations alters the number of hydrogen bonds and hydrophobic interactions in PARK7, as calculated from the Arpeggio server. The study indicated that the alteration in the hydrophobic contacts and frustration of the protein could alter the stability of the missense variants of the PARK7, which might result in disease progression. This study provides a detailed understanding of the destabilizing effects of single amino acid substitutions in PARK7.

Sonication-supported synthesis of cobalt oxide assembled on an N-MWCNT composite for electrochemical supercapacitors via three-electrode configuration.

The Co3O4@N-MWCNT composite was synthesized by a sonication-supported thermal reduction process for supercapacitor applications. The structural and morphological properties of the materials were characterized via Raman, XRD, XPS, SEM-EDX, and FE-TEM analysis. The composite electrode was constructed into a three-electrode configuration and examined by using CV, GCD and EIS analysis. The demonstrated electrochemical value of ~ 225 F/g at 0.5 A/g by the electrode made it appropriate for potential use in supercapacitor applications.

Bitter Gourd Honey Ameliorates Hepatic and Renal Diabetic Complications on Type 2 Diabetes Rat Models by Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms.

Honey has several pharmacological effects, including anti-diabetic activity. However, the effectiveness of bitter gourd honey (BGH) in the treatment of diabetes mellitus (DM) is unknown. The aim of this study was to determine the antioxidant, anti-inflammatory, and anti-apoptotic properties of BGH on the kidney and liver of a streptozotocin-induced diabetes rat model. METHODS: A single dose (nicotinamide 110 mg/kg, streptozotocin (STZ) 55 mg/kg, intraperitoneal (i.p.)) was used to induce DM in male rats. For 28 days, normal or diabetic rats were administered 1 g/kg/day and 2 g/kg/day of BGH orally. After the treatment, blood, liver, and kidney samples were collected and analysed for biochemical, histological, and molecular parameters. In addition, liquid chromatography-mass spectrometry (LC-MS) was used to identify the major bioactive components in BGH. RESULTS: The administration of BGH to diabetic rats resulted in significant reductions in alanine transaminase (ALT),aspartate aminotransferase (AST), creatinine, and urea levels. Diabetic rats treated with BGH showed lesser pathophysiological alterations in the liver and kidney as compared to non-treated control rats. BGH-treated diabetic rats exhibited reduced levels of oxidative stress (MDA levels), inflammatory (MYD88, NFKB, p-NFKB, IKKß), and apoptotic (caspase-3) markers, as well as higher levels of antioxidant enzymes (SOD, CAT, and GPx) in the liver and kidney. BGH contains many bioactive compounds that may have antioxidative stress, anti-inflammatory, and anti-apoptotic effects. CONCLUSION: BGH protected the liver and kidney in diabetic rats by reducing oxidative stress, inflammation, and apoptosis-induced damage. As a result, BGH can be used as a potential therapy to ameliorate diabetic complications.

Multifaceted phytogenic silver nanoparticles by an insectivorous plant Drosera spatulata Labill var. bakoensis and its potential therapeutic applications.

The current investigation highlights the green synthesis of silver nanoparticles (AgNPs) by the insectivorous plant Drosera spatulata Labill var. bakoensis, which is the first of its kind. The biosynthesized nanoparticles revealed a UV visible surface plasmon resonance (SPR) band at 427 nm. The natural phytoconstituents which reduce the monovalent silver were identified by FTIR. The particle size of the Ds-AgNPs was detected by the Nanoparticle size analyzer confirms that the average size of nanoparticles was around 23 ± 2 nm. Ds-AgNPs exhibit high stability because of its high negative zeta potential (- 34.1 mV). AFM studies also revealed that the Ds-AgNPs were spherical in shape and average size ranges from 10 to 20 ± 5 nm. TEM analysis also revealed that the average size of Ds-AgNPs was also around 21 ± 4 nm and the shape is roughly spherical and well dispersed. The crystal nature of Ds-AgNPs was detected as a face-centered cube by the XRD analysis. Furthermore, studies on antibacterial and antifungal activities manifested outstanding antimicrobial activities of Ds-AgNPs compared with standard antibiotic Amoxyclav. In addition, demonstration of superior free radical scavenging efficacy coupled with potential in vitro cytotoxic significance on Human colon cancer cell lines (HT-29) suggests that the Ds-AgNPs attain excellent multifunctional therapeutic applications.

Gallocatechin­silver nanoparticle impregnated cotton gauze patches enhance wound healing in diabetic rats by suppressing oxidative stress and inflammation via modulating the Nrf2/HO-1 and TLR4/NF-κB pathways.

This study is designed to investigate the combination of gallocatechin (GC) and silver nanoparticles (AgNPs) for its wound healing ability in diabetic rats. Thirty male Sprague Dawley rats were randomly divided into 5 groups: 1. Normal control rats dressed with blank CGP1; 2. Diabetic rats dressed with blank CGP1; 3. Diabetic rats dressed with 13.06µM of GC; 4. Diabetic rats dressed with 26.12 µM of GC; 5. Diabetic rats dressed with 0.1% silver sulfadiazine patches. GC-AgNPs-CGP dressed diabetic rats showed significant FBG reduction, prevented the body weight losses and reduced the oxidative stress by lowering MDA content and elevated antioxidant enzymes such as SOD, CAT and GPx in wound healing skin of diabetic rats when compared to normal CGP. Besides, mRNA expression of Nrf2, Nqo-1, and Ho-1 was upregulated with downregulated expression of Keap-1 mRNA, which is supported by immunohistochemistry. Furthermore, GC-AgNPs-CGP dressing increased growth factors such as VEGF, EGF, TGF-ß, and FGF-2 while decreasing MMP-2 in the skin of diabetic wound rats. In vitro permeation study demonstrated rapid GC release and permeation with a flux of 0.061 and 0.143 mg/sq.cm/h. In conclusion, the results indicated that GC-AgNPs-CGP dressing on diabetic wound rats modulated oxidative stress and inflammation with elevated growth factors; increased collagen synthesis thereby significantly improved the wound healing and could be beneficial for the management of diabetic wounds.

Ultrasonication-mediated nitrogen-doped multiwalled carbon nanotubes involving carboxy methylcellulose composite for solid-state supercapacitor applications.

In this study, a novel nanohybrid composite containing nitrogen-doped multiwalled carbon nanotubes/carboxymethylcellulose (N-MWCNT/CMC) was synthesized for supercapacitor applications. The synthesized composite materials were subjected to an ultrasonication-mediated solvothermal hydrothermal reaction. The synthesized nanohybrid composite electrode material was characterized using analytical methods to confirm its structure and morphology. The electrochemical properties of the composite electrode were investigated using cyclic voltammetry (CV), galvanic charge-discharge, and electrochemical impedance spectroscopy (EIS) using a 3 M KOH electrolyte. The fabricated composite material exhibited unique electrochemical properties by delivering a maximum specific capacitance of approximately 274 F g-1 at a current density of 2 A g-1. The composite electrode displayed high cycling stability of 96% after 4000 cycles at 2 A g-1, indicating that it is favorable for supercapacitor applications.