bluuebunny/crossref_metadata_2025 huggingface dataset:
Imperatorin Positively Regulates Melanogenesis through Signaling Pathways Involving PKA/CREB, ERK, AKT, and GSK3β/β-Catenin
Authors: Kim Taejin , Hyun Chang-Gu
Published: October 2022

The present study investigated the melanogenic effects of imperatorin and isoimperatorin and the underlying mechanisms of imperatorin using a mouse melanoma B16F10 model. Interestingly, treatment with 25 μM of either imperatorin or isoimperatorin, despite their structural differences, did not produce differences in melanin content and intracellular tyrosinase activity. Imperatorin also activated the expression of melanogenic enzymes, such as tyrosinase (TYR) and tyrosinase-related proteins TYRP-1 and TYRP-2. Mechanistically, imperatorin increases melanin synthesis through the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA)/cAMP-responsive element-binding protein (CREB)-dependent upregulation of microphthalmia-associated transcription factor (MITF), which is a key transcription factor in melanogenesis. Furthermore, imperatorin exerted melanogenic effects by downregulating extracellular signal-regulated kinase (ERK) and upregulating phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/glycogen synthesis kinase-3β (GSK-3β). Moreover, imperatorin increased the content of β-catenin in the cell cytoplasm and nucleus by reducing the content of phosphorylated β-catenin (p-β-catenin). Finally, we tested the potential of imperatorin in topical application through primary human skin irritation tests. These tests were performed on the normal skin (upper back) of 31 volunteers to determine whether 25 or 50 µM of imperatorin had irritation or sensitization potential. During these tests, imperatorin did not induce any adverse reactions. Taken together, these findings suggest that the regulation of melanogenesis by imperatorin can be mediated by signaling pathways involving PKA/CREB, ERK, AKT, and GSK3β/β-catenin and that imperatorin could prevent the pathogenesis of pigmentation diseases when used as a topical agent.
Essential Roles of Peroxiredoxin IV in Inflammation and Cancer
Authors: Thapa Pratik , Ding Na , Hao Yanning , Alshahrani Aziza , Jiang Hong , Wei Qiou
Published: October 2022

Peroxiredoxin IV (Prx4) is a 2-Cysteine peroxidase with ubiquitous expression in human tissues. Prx4 scavenges hydrogen peroxide and participates in oxidative protein folding in the endoplasmic reticulum. In addition, Prx4 is secreted outside the cell. Prx4 is upregulated in several cancers and is a potential therapeutic target. We have summarized historical and recent advances in the structure, function and biological roles of Prx4, focusing on inflammatory diseases and cancer. Oxidative stress is known to activate pro-inflammatory pathways. Chronic inflammation is a risk factor for cancer development. Hence, redox enzymes such as Prx4 are important players in the crosstalk between inflammation and cancer. Understanding molecular mechanisms of regulation of Prx4 expression and associated signaling pathways in normal physiological and disease conditions should reveal new therapeutic strategies. Thus, although Prx4 is a promising therapeutic target for inflammatory diseases and cancer, further research needs to be conducted to bridge the gap to clinical application.
Utilization of a Novel Immunofluorescence Instrument Prototype for the Determination of the Herbicide Glyphosate
Authors: Takács Eszter , Gémes Borbála , Szendrei Fanni , Keszei Csaba , Barócsi Attila , Lenk Sándor , Domján László , Mörtl Mária , Székács András
Published: October 2022

An enzyme-linked fluorescent immunoassay (ELFIA) method has been developed for the quantitative analytical determination of the herbicide active ingredient glyphosate in environmental matrices (surface water, soil, and plant tissues). Glyphosate, as a ubiquitous agricultural pollutant, is a xenobiotic substance with exposure in aquatic and terrestrial ecosystems due its extremely high worldwide application rate. The immunoassay developed in Project Aquafluosense is part of a fluorescence-based instrumentation setup for the in situ determination of several characteristic water quality parameters. The 96-well microplate-based competitive immunoassay method applies fluorescence signal detection in the concentration range of 0–100 ng/mL glyphosate. Application of the fluorescent signal provides a limit of detection of 0.09 ng/mL, which is 2.5-fold lower than that obtained with a visual absorbance signal. Beside the improved limit of detection, determination by fluorescence provided a wider and steeper dynamic range for glyphosate detection. No matrix effect appeared for the undiluted surface water samples, while plant tissues and soil samples required dilution rates of 1:10 and 1:100, respectively. No cross-reaction was determined with the main metabolite of glyphosate, N-aminomethylphosphonic acid, and related compounds.
A Flexible NO2 Gas Sensor Based on Single-Wall Carbon Nanotube Films Doped with a High Level of Nitrogen
Authors: Tian Xiao-Han , Zhou Tian-Ya , Meng Yu , Zhao Yi-Ming , Shi Chao , Hou Peng-Xiang , Zhang Li-Li , Liu Chang , Cheng Hui-Ming
Published: October 2022

Carbon nanotubes (CNTs) are considered a promising candidate for the detection of toxic gases because of their high specific surface area and excellent electrical and mechanical properties. However, the detecting performance of CNT-based detectors needs to be improved because covalently bonded CNTs are usually chemically inert. We prepared a nitrogen-doped single-wall CNT (SWCNT) film by means of gas-phase fluorination followed by thermal annealing in NH3. The doped nitrogen content could be changed in the range of 2.9–9.9 at%. The N-doped SWCNT films were directly used to construct flexible and transparent gas sensors, which can work at a low voltage of 0.01 V. It was found that their NO2 detection performance was closely related to their nitrogen content. With an optimum nitrogen content of 9.8 at%, a flexible sensor had a detection limit of 500 ppb at room temperature with good cycling ability and stability during bending.
Effects of Different Extraction Methods on the Gelatinization and Retrogradation Properties of Highland Barley Starch
Authors: Nie Mengzi , Piao Chunhong , Li Jiaxin , He Yue , Xi Huihan , Chen Zhiying , Wang Lili , Liu Liya , Huang Yatao , Wang Fengzhong , Tong Litao
Published: October 2022

The purpose of this study was to compare the gelatinization and retrogradation properties of highland barley starch (HBS) using different extraction methods. We obtained HBS by three methods, including alkali extraction (A-HBS), ultrasound extraction (U-HBS) and enzyme extraction (E-HBS). An investigation was carried out using a rapid viscosity analyzer (RVA), texture profile analysis (TPA), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier-transform infrared spectrometry (FTIR). It is shown that the different extraction methods did not change the crystalline type of HBS. E-HBS had the lowest damaged starch content and highest relative crystallinity value (p < 0.05). Meanwhile, A-HBS had the highest peak viscosity, indicating the best water absorption (p < 0.05). Moreover, E-HBS had not only higher G′ and G″ values, but also the highest gel hardness value, reflecting its strong gel structure (p < 0.05). These results confirmed that E-HBS provided better pasting stability and rheological properties, while U-HBS provides benefits of reducing starch retrogradation.
Design, Synthesis, Anti-Varicella-Zoster and Antimicrobial Activity of (Isoxazolidin-3-yl)Phosphonate Conjugates of N1-Functionalised Quinazoline-2,4-Diones
Authors: Łysakowska Magdalena , Głowacka Iwona E. , Andrei Graciela , Schols Dominique , Snoeck Robert , Lisiecki Paweł , Szemraj Magdalena , Piotrowska Dorota G.
Published: October 2022

Dipolar cycloaddition of the N-substituted C-(diethoxyphosphonyl)nitrones with N3-allyl-N1-benzylquinazoline-2,4-diones produced mixtures of diastereoisomeric 3-(diethoxyphosphonyl)isoxazolidines with a N1-benzylquinazoline-2,4-dione unit at C5. The obtained compounds were assessed for antiviral and antibacterial activities. Several compounds showed moderate inhibitory activities against VZV with EC50 values in the range of 12.63–58.48 µM. A mixture of isoxazolidines cis-20c/trans-20c (6:94) was found to be the most active against B. cereus PCM 1948, showing an MIC value 0.625 mg/mL, and also was not mutagenic up to this concentration.
An Innovative Chiral UPLC-MS/MS Method for Enantioselective Determination and Dissipation in Soil of Fenpropidin Enantiomers
Authors: Li Rui , Zhang Yanqing , Li Yanhong , Chen Zihao , Wang Zhen , Wang Minghua
Published: October 2022

As a chiral piperidine fungicide, fenpropidin has been widely used to control plant diseases. However, there are rare studies that have investigated fenpropidin at the enantiomer level. In this study, the single-factor analysis combined with a Box-Behnken design was used to obtain the optimal enantio-separation parameters of the fenpropidin enantiomers on ultra-performance liquid chromatography-tandem mass spectrometry. The absolute configuration of two fenpropidin enantiomers was confirmed for the first time using electron circular dichroism and optical activity. On the Lux cellulose-3 column, S-(-)-fenpropidin flowed out before R-(+)-fenpropidin. The enantio-separation mechanism was revealed by molecular docking. A modified QuEChERS method was developed for the trace determination of the fenpropidin enantiomers in seven food and environmental substrates. The average recoveries were 71.5–106.1% with the intra-day and inter-day relative standard deviations of 0.3–8.9% and 0.5–8.0%. The method was successfully verified by enantioselective dissipation of fenpropidin in soil under the field. R-(+)-fenpropidin dissipated faster than S-(-)-fenpropidin, and the half-lives were 19.8 d and 22.4 d. This study established a brand-new effective chiral analysis method for the fenpropidin enantiomers, providing a basis for accurate residue monitoring and the risk assessment of fenpropidin.
Amauroderma rugosum Extract Suppresses Inflammatory Responses in Tumor Necrosis Factor Alpha/Interferon Gamma-Induced HaCaT Keratinocytes
Authors: Shiu Polly Ho-Ting , Li Jingjing , Zheng Chengwen , Rangsinth Panthakarn , Li Renkai , Cheung Queenie Tze-Lam , Lau Angel Heng-Yee , Chan Jacqueline Cho-Ki , Kwan Yiu-Wa , Cheung Timothy Man-Yau , Leung George Pak-Heng
Published: October 2022

Keratinocytes form the physical barrier of the skin and play an important role in the inflammatory process. Amauroderma rugosum is an edible mushroom; however, its pharmacological properties have seldom been studied. Although the anti-inflammatory effect of the organic solvent extract of Amauroderma rugosum has been previously reported, it is not known whether the aqueous extract has a similar effect. In addition, the effect of Amauorderma rugosum extract on skin has never been explored. Therefore, the objectives of the present study were to evaluate the anti-inflammatory effects of the aqueous extract of Amauroderma rugosum on HaCaT keratinocytes, to explore its mechanisms of action, and to study the possible active ingredients involved. The results showed that the aqueous extract of Amauroderm rugosum at a concentration of 1.5 mg/mL was non-toxic to HaCaT cells and inhibited the release of cytokine interleukin-1β, and chemokines interleukin-8 and monocyte chemoattractant protein-1 in tumor necrosis factor (TNF)-α- and interferon (IFN)-γ-stimulated HaCaT cells. Amauroderma rugosum extract reduced the intracellular levels of reactive oxygen species. In addition, Amauroderma rugosum extract reduced the total protein expression of nuclear factor-kappa B (NF-κB) and B-cells inhibitor alpha in HaCaT keratinocytes and inhibited the phosphorylation of mitogen-activated protein kinase kinase (MEK) 1/2, extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (Akt), and mammalian target of rapamycin (mTOR) in TNF-α- and INF-γ-stimulated HaCaT keratinocytes. Chemical analysis revealed that the aqueous extract of Amauroderma rugosum contains polysaccharides, triterpenes, and phenolic compounds. Anti-inflammatory compounds, such as gallic acid, guanosine, and uridine, were also present. The anti-inflammatory effect of Amauroderma rugosum could be mimicked by a combination of gallic acid, guanosine, and uridine. In conclusion, our study suggests that the aqueous extract of Amauroderma rugosum exerts anti-inflammatory effects on keratinocytes through its antioxidant and inhibitory effects on MEK/ERK-, Akt/mTOR-, and NF-κB-dependent signaling pathways.
Synthesis and Antifungal Activity of New butenolide Containing Methoxyacrylate Scaffold
Authors: Zhang Qian , Li Yihao , Zhao Bin , Xu Leichuan , Ma Haoyun , Wang Mingan
Published: October 2022

In order to improve the antifungal activity of new butenolides containing oxime ether moiety, a series of new butenolide compounds containing methoxyacrylate scaffold were designed and synthesized, based on the previous reports. Their structures were characterized by 1H NMR, 13C NMR, HR-MS spectra, and X-ray diffraction analysis. The in vitro antifungal activities were evaluated by the mycelium growth rate method. The results showed that the inhibitory activities of these new compounds against Sclerotinia sclerotiorum were significantly improved, in comparison with that of the lead compound 3–8; the EC50 values of V-6 and VI-7 against S. sclerotiorum were 1.51 and 1.81 mg/L, nearly seven times that of 3–8 (EC50 10.62 mg/L). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observation indicated that compound VI-3 had a significant impact on the structure and function of the hyphal cell of S. sclerotiorum mycelium and the positive control trifloxystrobin. Molecular simulation docking results indicated that the introduction of methoxyacrylate scaffold is beneficial to improving the antifungal activity of these compounds against S. sclerotiorum, which can be used as the lead for further structure optimization.
Optimization of Microwave-Assisted Pectin Extraction from Cocoa Pod Husk
Authors: Sarah Maya , Hasibuan Isti Madinah , Misran Erni , Maulina Seri
Published: October 2022

Optimization of pectin extraction from cocoa pod husk was carried out to examine independent variables that affect the quality of pectin obtained and determine the best conditions for the extraction process. In this study, three independent variables thought to contribute to microwave-assisted pectin extraction were used, namely, extraction time (20, 25, and 30 min), microwave power (180, 300, and 450 W), and citric acid concentration (2.5%, 5%, and 10%). Response surface methodology was applied using central composite design (CCD) to examine the effect of independent variables on the parameter measured. Among the seven parameters measured, namely, yield, temperature, moisture content, ash content, equivalent weight, methoxyl content, and galacturonic acid content, the statistical analysis test showed that the model equations that were suitable for predicting response values were temperature, moisture content, and ash content. Therefore, the optimization of conditions was only reviewed for these three parameters. Optimization results concluded that the factors that had the most significant effect on temperature, moisture content, and ash content were extraction time and microwave power. Optimal conditions for pectin extraction were at 30 min extraction time, 450 W microwave power, and 10% solvent concentration, resulting in a temperature of 104 °C, moisture content of 6%, and ash content of 8%. Other parameter values measured under these conditions were a yield of 21.10%, equivalent weight of 602.40 mg/mol, methoxyl content of 6.07%, and galacturonic acid content of 72.86%. Pectin extracted from cocoa pod husk using this method has the potential to be further applied, especially in the food and pharmaceutical industries.
Quercetin: Its Antioxidant Mechanism, Antibacterial Properties and Potential Application in Prevention and Control of Toxipathy
Authors: Qi Weidong , Qi Wanxiang , Xiong Dongwei , Long Miao
Published: October 2022

Quercetin, as a flavonol compound found in plants, has a variety of biological activities. It is widely present in nature and the human diet, with powerful oxidative properties and biological activities. In this review, the antioxidant mechanism and broad-spectrum antibacterial properties of quercetin are revealed; the intervention effects of quercetin on pesticide poisoning and the pathway of action are investigated; the toxic effects of main mycotoxins on the collection and the detoxification process of quercetin are summarized; whether it is able to reduce the toxicity of mycotoxins is proved; and the harmful effects of heavy metal poisoning on the collection, the prevention, and control of quercetin are evaluated. This review is expected to enrich the understanding of the properties of quercetin and promote its better application in clinical practice.
The Role of Endophytes in Combating Fungal- and Bacterial-Induced Stress in Plants
Authors: Muthu Narayanan Manjula , Ahmad Norhayati , Shivanand Pooja , Metali Faizah
Published: October 2022

Plants are subjected to multifaceted stresses that significantly jeopardize crop production. Pathogenic microbes influence biotic stress in plants, which ultimately causes annual crop loss worldwide. Although the use of pesticides and fungicides can curb the proliferation of pathogens in plants and enhance crop production, they pollute the environment and cause several health issues in humans and animals. Hence, there is a need for alternative biocontrol agents that offer an eco-friendly mode of controlling plant diseases. This review discusses fungal- and bacterial-induced stress in plants, which causes various plant diseases, and the role of biocontrol defense mechanisms, for example, the production of hydrolytic enzymes, secondary metabolites, and siderophores by stress-tolerant fungi and bacteria to combat plant pathogens. It is observed that beneficial endophytes could sustain crop production and resolve the issues regarding crop yield caused by bacterial and fungal pathogens. The collated literature review indicates that future research is necessary to identify potential biocontrol agents that can minimize the utility of synthetic pesticides and increase the tenable agricultural production.
Current Research of Phytochemical, Medicinal and Non-Medicinal Uses of Uncaria gambir Roxb.: A Review
Authors: Munggari Indah Putri , Kurnia Dikdik , Deawati Yusi , Julaeha Euis
Published: October 2022

Uncaria gambir Roxb. is a plant from Southeast Asia and is widely used as an alternative medicine with various applications. This plant has been widely used in traditional medicine. This paper aims to provide information on U. gambir, a summary of data on phytochemicals and on medical and nonmedical activities. Phytochemical studies reveal biologically active constituents such as flavonoids, phenolics, and alkaloids. Various studies have shown that extracts and compounds obtained from U. gambir have medical uses for their antioxidant, antibacterial, anti-helminthic, anticancer, antifungal, anti-inflammatory, anti-hyperglycemic, anti-hyperuricemic, anti-lipid peroxidation, antihyperlipidemic and other properties. In addition, this extract has other uses, such as adsorbent for dyes and metal ions, as well as corrosion inhibition. Thus, U. gambir, which is commonly used in traditional medicine, is a potential plant for many therapeutic applications and prospects for drug development as well as other applications such as adsorbent and corrosion inhibition.
Christmas Tree Bio-Waste as a Power Source of Bioactive Materials with Anti-Proliferative Activities for Oral Care
Authors: Tylkowski Bartosz , Konopka Piotr , Maj Malgorzata , Kazmierski Lukasz , Skrobanska Monika , Montane Xavier , Giamberini Marta , Bajek Anna , Jastrzab Renata
Published: October 2022

According to the American Cancer Society, roughly 54,000 new cases of oral cavity or oropharyngeal cancers have been detected in the United States of America in 2021, and they will cause about 10,850 deaths. The main therapies for cancer management, such as surgery and radio- and chemotherapy, have some own benefits, albeit they are often destructive for surrounding tissues; thus, deep investigations into non-surgical treatments for oral cavities are needed. Biologically active compounds (BACs) extracted from European Spruce needles were analyzed to determine the total phenolic and flavonoid content and were used as additional ingredients for oral hygiene products. An anti-proliferation investigation was carried out using extracts containing BACs with the use of several cell lines (cancer and a normal one). ESI-MS studies on BACs showed that luteolin, a natural flavonoid compound with anti-tumorigenic properties against various types of tumors, is the predominant component of the extracts. MTT, BrdU, and LIVE/DEAD studies demonstrated that BAC extracts obtained from Christmas tree needles possess anticancer properties against squamous cell carcinoma (with epithelial origins). We proved that BAC extracts contain high amounts of luteolin, which induces cytotoxicity toward cancer cells; along with their high selectivity, robustness, and nontoxicity, they are very promising materials in oral health applications.
Chemical Composition, Antioxidant Activity, Cytoprotective and In Silico Study of Ethanolic Extracts of Bougainvillea × buttiana (Var. Orange and Rose)
Authors: Petricevich Vera L. , Cedillo-Cortezano Mayra , Abarca-Vargas Rodolfo
Published: October 2022

Bougainvillea × buttiana is a plant widely used in traditional Mexican medicine and other parts of the world for the treatment of various health disorders. In this study, the antioxidant and cytoprotective activities of three ethanolic extracts of B. × buttiana (BxbO (Orange), BxbR1 (Rose1) and BxbR2 (Rose2)) were investigated. Antioxidant activities were determined by the oxygen radical absorbance capacity (ORAC), DPPH free radicals scavenging activity, and radical scavenging effects on nitric oxide (NO). The in vitro cytoprotective effect of the extracts against oxidative stress induced by hydrogen peroxide-(H2O2) in a model of L929 cells was also determined as well as NO uptake with or without H2O2 through the MTT assay. The results revealed that there was a difference between the compounds present in each of the extracts, with the 2-Hydroxycinnamic acid compound being observed in all the extracts. The 2-Hydroxycinnamic acid compound was tested in silico to predict its biological (PASSonline) and toxicological (Osiris Property Explorer) activity. All extracts with 1 to 4 mg/mL inhibited the activity of the NO radical. In cells exposed to 1 mg/mL of extracts followed by H2O2 exposure, cell protection ranged from 66.96 to 83.46%. The treatment of the cells with extracts prevented the morphological changes caused by H2O2. The 2-Hydroxycinnamic acid compound showed a probability of in silico antioxidant and cytoprotective activity greater than 0.5 and 0.6, respectively. Therefore, the results demonstrated that Bxb extracts exert antioxidant and protective activities against H2O2-induced oxidative stress in L929 cells.
Biopolymers-Derived Materials for Supercapacitors: Recent Trends, Challenges, and Future Prospects
Authors: Appiah Eugene Sefa , Dzikunu Perseverance , Mahadeen Nashiru , Ampong Daniel Nframah , Mensah-Darkwa Kwadwo , Kumar Anuj , Gupta Ram K. , Adom-Asamoah Mark
Published: October 2022

Supercapacitors may be able to store more energy while maintaining fast charging times; however, they need low-cost and sophisticated electrode materials. Developing innovative and effective carbon-based electrode materials from naturally occurring chemical components is thus critical for supercapacitor development. In this context, biopolymer-derived porous carbon electrode materials for energy storage applications have gained considerable momentum due to their wide accessibility, high porosity, cost-effectiveness, low weight, biodegradability, and environmental friendliness. Moreover, the carbon structures derived from biopolymeric materials possess unique compositional, morphological, and electrochemical properties. This review aims to emphasize (i) the comprehensive concepts of biopolymers and supercapacitors to approach smart carbon-based materials for supercapacitors, (ii) synthesis strategies for biopolymer derived nanostructured carbons, (iii) recent advancements in biopolymer derived nanostructured carbons for supercapacitors, and (iv) challenges and future prospects from the viewpoint of green chemistry-based energy storage. This study is likely to be useful to the scientific community interested in the design of low-cost, efficient, and green electrode materials for supercapacitors as well as various types of electrocatalysis for energy production.
Intracellular Enzyme-Instructed Self-Assembly of Peptides (IEISAP) for Biomedical Applications
Authors: Lin Fengming , Jia Chenyang , Wu Fu-Gen
Published: October 2022

Despite the remarkable significance and encouraging breakthroughs of intracellular enzyme-instructed self-assembly of peptides (IEISAP) in disease diagnosis and treatment, a comprehensive review that focuses on this topic is still desirable. In this article, we carefully review the advances in the applications of IEISAP, including the development of various bioimaging techniques, such as fluorescence imaging, photoacoustic imaging, magnetic resonance imaging, positron-emission tomography imaging, radiation imaging, and multimodal imaging, which are successfully leveraged in visualizing cancer tissues and cells, bacteria, and enzyme activity. We also summarize the utilization of IEISAP in disease treatments, including anticancer, antibacterial, and antiinflammation applications, among others. We present the design, action modes, structures, properties, functions, and performance of IEISAP materials, such as nanofibers, nanoparticles, nanoaggregates, and hydrogels. Finally, we conclude with an outlook towards future developments of IEISAP materials for biomedical applications. It is believed that this review may foster the future development of IEISAP with better performance in the biomedical field.
Understanding the Liquid States of Cyclic Hydrocarbons Containing N, O, and S Atoms via the 3D-RISM-KH Molecular Solvation Theory
Authors: Roy Dipankar , Kovalenko Andriy
Published: October 2022

The 3D-reference interaction site model (3D-RISM) molecular solvation theory in combination with the Kovalenko–Hirata (KH) closure is extended to seven heterocyclic liquids to understand their liquid states and to test the performance of the theory in solvation free energy (SFE) calculations of solutes in select solvents. The computed solvent site distribution profiles were compared with the all-atom molecular dynamics (MD) simulations, showing comparable performances. The computational results were compared against the structural parameters for liquids, whenever available, as well as against the experimental SFEs. The liquids are found to have local ordered structures held together via weak interactions in both the RISM and MD simulations. The 3D-RISM-KH computed SFEs are in good agreement with the benchmark values for the tetrahydrothiophene-S,S-dioxide, and showed comparatively larger deviations in the case of the SFEs in the tetrahydrofuran continuum.
Occurrence and Characteristics of Staphylococcus aureus Strains along the Production Chain of Raw Milk Cheeses in Poland
Authors: Gajewska Joanna , Chajęcka-Wierzchowska Wioleta , Zadernowska Anna
Published: October 2022

Cheeses produced from unpasteurized milk by traditional production methods may contain many groups of microorganisms, including Staphylococcus aureus. The aim of this study was to determine the occurrence of S. aureus in the artisanal cheese production chain from unpasteurized milk. We investigated the prevalence of S. aureus strains isolated from various stages of artisanal cheese of unpasteurized milk production from farms in the northeastern and southern parts of Poland and characterized them. Characterization included antimicrobial susceptibility by microbroth dilution and biofilm formation by in vitro assay. Among all strains, the presence of enterotoxigenic genes and genes involved with biofilm formation and antibiotic resistance were screened by PCR-based methods. A total of 180 samples were examined. A high percentage of strains were resistant to penicillin (54/58.1%) and tobramycin (32/34.4%). Some tested isolates also showed resistance to the macrolide class of antibiotics: azithromycin, clarithromycin, and erythromycin at 17/18.3%, 15/16.1%, and 21/22.6%, respectively. Among tested isolates, we also found phenotypic resistance to oxacillin (9/9.7%) and cefoxitin (12/12.9%). The blaZ gene encoding penicillin resistance was the most common gene encoding antibiotic resistance among the tested strains. All isolates showing phenotypic resistance to cefoxitin possessed the mecA gene. The study also evaluated the prevalence of biofilm-associated genes, with eno the most frequently associated gene. Eighty-nine out of 93 S. aureus isolates (95.7%) possessed at least one enterotoxin-encoding gene. The results of this study showed that production of raw milk cheeses may be a source of antibiotic resistance and virulent S. aureus. Our results suggest that artisanal cheese producers should better control production hygiene.
Easy and Fast Production of Solketal from Glycerol Acetalization via Heteropolyacids
Authors: Julião Diana , Mirante Fatima , Balula Salete S.
Published: October 2022

This work presents an effective and fast procedure to valorize the main waste produced from the biodiesel industry, i.e., the glycerol. The acetalization of glycerol with acetone represents an effective strategy to produce the valuable solketal, a fuel additive component. In this work, the catalytic efficiency of different commercial heteropolyacids (HPAas) was compared under a solvent-free system. The HPAs used were H3[PW12O40] (PW12), H3[PMo12O40] (PMo12) and H4[SiW12O40] (SiW12). The influence of reactional parameters such as reactants stoichiometry, catalyst concentration and reaction temperature were investigated in order to optimize experimental conditions to increase cost-efficiency and sustainability. HPAs demonstrated to be highly efficient for this type of reaction, presenting a high and fast glycerol conversion, with high selectivity to solketal under sustainable conditions (solvent-free system and room temperature medium). The activity of HPAs using 3% to glycerol weight and a glycerol/acetone ratio of 1:15 followed the order: PW12 (99.2%) > PMo12 (91.4%) > SiW12 (90.7%) as a result of the strong acidic sites after 5 min. In fact, only 5 min of reaction were needed to achieve 97% of solketal product in the presence of the PW12 as a catalyst. This last system presents an effective, selective and sustainable catalytic system to valorize glycerol.
Preliminary Structure–Activity Relationship Study of the MMV Pathogen Box Compound MMV675968 (2,4-Diaminoquinazoline) Unveils Novel Inhibitors of Trypanosoma brucei brucei
Authors: Dize Darline , Tata Rolland Bantar , Keumoe Rodrigue , Kouipou Toghueo Rufin Marie , Tchatat Mariscal Brice , Njanpa Cyrille Ngansop , Tchuenguia Vianey Claire , Yamthe Lauve Tchokouaha , Fokou Patrick Valere Tsouh , Laleu Benoît , Duffy James , Bishop Ozlem Tastan , Boyom Fabrice Fekam
Published: October 2022

New drugs are urgently needed for the treatment of human African trypanosomiasis (HAT). In line with our quest for novel inhibitors of trypanosomes, a small library of analogs of the antitrypanosomal hit (MMV675968) available at MMV as solid materials was screened for antitrypanosomal activity. In silico exploration of two potent antitrypanosomal structural analogs (7-MMV1578647 and 10-MMV1578445) as inhibitors of dihydrofolate reductase (DHFR) was achieved, together with elucidation of other antitrypanosomal modes of action. In addition, they were assessed in vitro for tentative inhibition of DHFR in a crude trypanosome extract. Their ADMET properties were also predicted using dedicated software. Overall, the two diaminoquinazoline analogs displayed approximately 40-fold and 60-fold more potency and selectivity in vitro than the parent hit, respectively (MMV1578445 (10): IC50 = 0.045 µM, SI = 1737; MMV1578467 (7): IC50 = 0.06 µM; SI = 412). Analogs 7 and 10 were also strong binders of the DHFR enzyme in silico, in all their accessible protonation states, and interacted with key DHFR ligand recognition residues Val32, Asp54, and Ile160. They also exhibited significant activity against trypanosome protein isolate. MMV1578445 (10) portrayed fast and irreversible trypanosome growth arrest between 4–72 h at IC99. Analogs 7 and 10 induced in vitro ferric iron reduction and DNA fragmentation or apoptosis induction, respectively. The two potent analogs endowed with predicted suitable physicochemical and ADMET properties are good candidates for further deciphering their potential as starting points for new drug development for HAT.
Carbazole Derivatives as Potential Antimicrobial Agents
Authors: Patil Siddappa A. , Patil Shivaputra A. , Ble-González Ever A. , Isbel Stephen R. , Hampton Sydney M. , Bugarin Alejandro
Published: October 2022

Microbial infection is a leading cause of death worldwide, resulting in around 1.2 million deaths annually. Due to this, medicinal chemists are continuously searching for new or improved alternatives to combat microbial infections. Among many nitrogen-containing heterocycles, carbazole derivatives have shown significant biological activities, of which its antimicrobial and antifungal activities are the most studied. In this review, miscellaneous carbazole derivatives and their antimicrobial activity are discussed (articles published from 1999 to 2022).
Chinese Cordyceps: Bioactive Components, Antitumor Effects and Underlying Mechanism—A Review
Authors: Liu Yan , Guo Zhi-Jian , Zhou Xuan-Wei
Published: October 2022

Chinese Cordyceps is a valuable source of natural products with various therapeutic effects. It is rich in various active components, of which adenosine, cordycepin and polysaccharides have been confirmed with significant immunomodulatory and antitumor functions. However, the underlying antitumor mechanism remains poorly understood. In this review, we summarized and analyzed the chemical characteristics of the main components and their pharmacological effects and mechanism on immunomodulatory and antitumor functions. The analysis revealed that Chinese Cordyceps promotes immune cells’ antitumor function by via upregulating immune responses and downregulating immunosuppression in the tumor microenvironment and resetting the immune cells’ phenotype. Moreover, Chinese Cordyceps can inhibit the growth and metastasis of tumor cells by death (including apoptosis and autophagy) induction, cell-cycle arrest, and angiogenesis inhibition. Recent evidence has revealed that the signal pathways of mitogen-activated protein kinases (MAPKs), nuclear factor kappaB (NF-κB), cysteine–aspartic proteases (caspases) and serine/threonine kinase Akt were involved in the antitumor mechanisms. In conclusion, Chinese Cordyceps, one type of magic mushroom, can be potentially developed as immunomodulator and anticancer therapeutic agents.
Synthesis and Characterization of Newly Designed and Highly Solvatochromic Double Squaraine Dye for Sensitive and Selective Recognition towards Cu2+
Authors: Tang Linjun , Sharma Shubham , Pandey Shyam S.
Published: October 2022

Synthesis and characterization of a novel and zwitterionic double squaraine dye (DSQ) with a unique D-A-A-D structure is being reported. Contrary to the conventional mono and bis-squaraine dyes with D-A-D and D-A-D-A molecular frameworks reported so far, DSQ dye demonstrated strong solvatochromism allowing for the multiple ion sensing using a single probe by judicious selection of the suitable solvent system. The DSQ dye exhibited a large solvatochromic shift of about 200 nm with color changes from the visible to NIR region with metal ion sensitivity. Utilization of a binary solvent consisted of dimethylformamide and acetonitrile (1:99, v/v), highly selective detection of Cu2+ ions with the linearity range from 50 μM to 1 nM and a detection limit of 6.5 × 10−10 M has been successfully demonstrated. Results of the Benesi–Hildebrand and Jobs plot analysis revealed that DSQ and Cu2+ ions interact in the 2:1 molecular stoichiometry with appreciably good association constant of 2.32 × 104 M−1. Considering the allowed limit of Cu2+ ions intake by human body as recommended by WHO to be 30 μM, the proposed dye can be conveniently used for the simple and naked eye colorimetric monitoring of the drinking water quality.
Factors Influencing the Bioavailability of Organic Molecules to Bacterial Cells—A Mini-Review
Authors: Smułek Wojciech , Kaczorek Ewa
Published: October 2022

The bioavailability of organic compounds to bacterial cells is crucial for their vital activities. This includes both compounds that are desirable to the cells (e.g., sources of energy, carbon, nitrogen, and other nutrients) and undesirable compounds that are toxic to the cells. For this reason, bioavailability is an issue of great importance in many areas of human activity that are related to bacteria, e.g., biotechnological production, bioremediation of organic pollutants, and the use of antibiotics. This article proposes a classification of factors determining bioavailability, dividing them into factors at the physicochemical level (i.e., those related to the solubility of a chemical compound and its transport in aqueous solution) and factors at the microbiological level (i.e., those related to adsorption on the cell surface and those related to transport into the cell). Awareness of the importance of and the mechanisms governing each of the factors described allows their use to change bioavailability in the desired direction.
Zeolites as Adsorbents and Photocatalysts for Removal of Dyes from the Aqueous Environment
Authors: Rakanović Marina , Vukojević Andrijana , Savanović Maria M. , Armaković Stevan , Pelemiš Svetlana , Živić Fatima , Sladojević Slavica , Armaković Sanja J.
Published: October 2022

This study investigated the potential of zeolites (NH4BETA, NH4ZSM-5, and NaY) to remove two frequently used dyes, methylene blue (MB) and rhodamine B (RB), from an aqueous environment. The removal of dyes with zeolites was performed via two mechanisms: adsorption and photocatalysis. Removal of dyes through adsorption was achieved by studying the Freundlich adsorption isotherms, while photocatalytic removal of dyes was performed under UV irradiation. In both cases, the removal experiments were conducted for 180 min at two temperatures (283 K and 293 K), and dye concentrations were determined spectrophotometrically. Additionally, after photodegradation, mineralization was analyzed as chemical oxygen demand. A computational analysis of the structures of MB and RB was performed to gain a deeper understanding of the obtained results. The computational analysis encompassed density functional theory (DFT) calculations and analysis of two quantum-molecular descriptors addressing the local reactivity of molecules. Experimental results have indicated that the considered zeolites effectively remove both dyes through both mechanisms, especially NH4BETA and NH4ZSM-5, due to the presence of active acidic centers on the outer and inner surfaces of the zeolite. The lowest efficiency of dye removal was achieved in the presence of NaY zeolite, which has a lower SiO2/Al2O3 ratio. A more efficient reduction was completed for RB dye, which agrees with the computationally obtained information about reactivity.
Chemistry and the Potential Antiviral, Anticancer, and Anti-Inflammatory Activities of Cardiotonic Steroids Derived from Toads
Authors: El-Seedi Hesham R. , Yosri Nermeen , El-Aarag Bishoy , Mahmoud Shaymaa H. , Zayed Ahmed , Du Ming , Saeed Aamer , Musharraf Syed G. , El-Garawani Islam M. , Habib Mohamed R. , Tahir Haroon Elrasheid , Hegab Momtaz M. , Zou Xiaobo , Guo Zhiming , Efferth Thomas , Khalifa Shaden A. M.
Published: October 2022

Cardiotonic steroids (CTS) were first documented by ancient Egyptians more than 3000 years ago. Cardiotonic steroids are a group of steroid hormones that circulate in the blood of amphibians and toads and can also be extracted from natural products such as plants, herbs, and marines. It is well known that cardiotonic steroids reveal effects against congestive heart failure and atrial fibrillation; therefore, the term "cardiotonic" has been coined. Cardiotonic steroids are divided into two distinct groups: cardenolides (plant-derived) and bufadienolides (mainly of animal origin). Cardenolides have an unsaturated five-membered lactone ring attached to the steroid nucleus at position 17; bufadienolides have a doubly unsaturated six-membered lactone ring. Cancer is a leading cause of mortality in humans all over the world. In 2040, the global cancer load is expected to be 28.4 million cases, which would be a 47% increase from 2020. Moreover, viruses and inflammations also have a very nebative impact on human health and lead to mortality. In the current review, we focus on the chemistry, antiviral and anti-cancer activities of cardiotonic steroids from the naturally derived (toads) venom to combat these chronic devastating health problems. The databases of different research engines (Google Scholar, PubMed, Science Direct, and Sci-Finder) were screened using different combinations of the following terms: “cardiotonic steroids”, “anti-inflammatory”, “antiviral”, “anticancer”, “toad venom”, “bufadienolides”, and “poison chemical composition”. Various cardiotonic steroids were isolated from diverse toad species and exhibited superior anti-inflammatory, anticancer, and antiviral activities in in vivo and in vitro models such as marinobufagenin, gammabufotalin, resibufogenin, and bufalin. These steroids are especially difficult to identify. However, several compounds and their bioactivities were identified by using different molecular and biotechnological techniques. Biotechnology is a new tool to fully or partially generate upscaled quantities of natural products, which are otherwise only available at trace amounts in organisms.
Exploring Nitric Oxide (NO)-Releasing Celecoxib Derivatives as Modulators of Radioresponse in Pheochromocytoma Cells
Authors: Brandt Florian , Ullrich Martin , Seifert Verena , Haase-Kohn Cathleen , Richter Susan , Kniess Torsten , Pietzsch Jens , Laube Markus
Published: October 2022

COX-2 can be considered as a clinically relevant molecular target for adjuvant, in particular radiosensitizing treatments. In this regard, using selective COX-2 inhibitors, e.g., in combination with radiotherapy or endoradiotherapy, represents an interesting treatment option. Based on our own findings that nitric oxide (NO)-releasing and celecoxib-derived COX-2 inhibitors (COXIBs) showed promising radiosensitizing effects in vitro, we herein present the development of a series of eight novel NO-COXIBs differing in the peripheral substitution pattern and their chemical and in vitro characterization. COX-1 and COX-2 inhibition potency was found to be comparable to the lead NO-COXIBs, and NO-releasing properties were demonstrated to be mainly influenced by the substituent in 4-position of the pyrazole (Cl vs. H). Introduction of the N-propionamide at the sulfamoyl residue as a potential prodrug strategy lowered lipophilicity markedly and abolished COX inhibition while NO-releasing properties were not markedly influenced. NO-COXIBs were tested in vitro for a combination with single-dose external X-ray irradiation as well as [177Lu]LuCl3 treatment in HIF2α-positive mouse pheochromocytoma (MPC-HIF2a) tumor spheroids. When applied directly before X-ray irradiation or 177Lu treatment, NO-COXIBs showed radioprotective effects, as did celecoxib, which was used as a control. Radiosensitizing effects were observed when applied shortly after X-ray irradiation. Overall, the NO-COXIBs were found to be more radioprotective compared with celecoxib, which does not warrant further preclinical studies with the NO-COXIBs for the treatment of pheochromocytoma. However, evaluation as radioprotective agents for healthy tissues could be considered for the NO-COXIBs developed here, especially when used directly before irradiation.
Natural Phytocompounds from Common Indian Spices for Identification of Three Potential Inhibitors of Breast Cancer: A Molecular Modelling Approach
Authors: Hazra Samik , Ray Anindya Sundar , Rahaman Chowdhury Habibur
Published: October 2022

Breast cancer is the second most common cancer-related cause of death for women throughout the globe. In spite of some effective measures, the main concerns with traditional anti-cancer chemotherapy are its low bioavailability, physical side effects, acquired resistance of cancer cells and non-specific targeting. Now researchers have taken the initiative to establish natural product-based therapy methods and to identify viable hits for future lead optimization in the development of breast cancer medication. Our study aims to identify the potent phytocompounds from five very popular Indian spices (Zingiber officinale Roscoe, Cuminum cyminum L., Piper nigrum L., Curcuma longa L., and Allium sativum L.). From these spices, a total of 200 phytocompounds were identified and screened against three target genes, namely, cyclin-dependent kinase 8 (CDK 8), progesterone receptor (PR) and epidermal growth factor receptor (EGFR), through structure-based virtual screening using iGEMDOCK 2.1 software. Based on the binding affinity score, the top three phytocompounds against each target protein (cynaroside (−149.66 Kcal/mol), apigetrin (−139.527 Kcal/mol) and curcumin (−138.149 Kcal/mol) against CDK8; apigetrin (−123.298 Kcal/mol), cynaroside (−118.635 Kcal/mol) and xyloglucan (−113.788 Kcal/mol) against PR; cynaroside (−119.18 Kcal/mol), apigetrin (−105.185 Kcal/mol) and xyloglucan (−105.106 Kcal/mol) against EGFR) were selected. Apigetrin, cynaroside, curcumin, and xyloglucan were finally identified for further docking analysis with the respective three target proteins. Autodock 4.2 was applied to screen the optimal binding position and to assess the relative intensity of binding interactions. In addition, the ADME/T property checks and bioactivity scores analysis of were performed to understand the suitability of these four phytocompounds to be potential candidates for developing effective and non-toxic anticancer agents. Based on this in silico analysis, we believe this study could contribute to current efforts to develop new drugs for treating breast cancer.
Virtual Extensive Read-Across: A New Open-Access Software for Chemical Read-Across and Its Application to the Carcinogenicity Assessment of Botanicals
Authors: Viganò Edoardo Luca , Colombo Erika , Raitano Giuseppa , Manganaro Alberto , Sommovigo Alessio , Dorne Jean Lou CM , Benfenati Emilio
Published: October 2022

Read-across applies the principle of similarity to identify the most similar substances to represent a given target substance in data-poor situations. However, differences between the target and the source substances exist. The present study aims to screen and assess the effect of the key components in a molecule which may escape the evaluation for read-across based only on the most similar substance(s) using a new open-access software: Virtual Extensive Read-Across (VERA). VERA provides a means to assess similarity between chemicals using structural alerts specific to the property, pre-defined molecular groups and structural similarity. The software finds the most similar compounds with a certain feature, e.g., structural alerts and molecular groups, and provides clusters of similar substances while comparing these similar substances within different clusters. Carcinogenicity is a complex endpoint with several mechanisms, requiring resource intensive experimental bioassays and a large number of animals; as such, the use of read-across as part of new approach methodologies would support carcinogenicity assessment. To test the VERA software, carcinogenicity was selected as the endpoint of interest for a range of botanicals. VERA correctly labelled 70% of the botanicals, indicating the most similar substances and the main features associated with carcinogenicity.