bluuebunny/crossref_metadata_2025 huggingface dataset:
New Solid Forms of Nitrofurantoin and 4-Aminopyridine Salt: Influence of Salt Hydration Level on Crystal Packing and Physicochemical Properties
Authors: Boycov Denis E. , Drozd Ksenia V. , Manin Alex N. , Churakov Andrei V. , Perlovich German L.
Published: December 2022

The crystallization of the poorly soluble drug nitrofurantoin (NFT) with 4-aminopyridine (4AmPy) resulted in three multicomponent solid forms with different hydration levels: anhydrous salt [NFT+4AmPy] (1:1), salt monohydrate [NFT+4AmPy+H2O] (1:1:1), and salt tetrahydrate [NFT+4AmPy+H2O] (1:1:4). Each salt was selectively prepared by liquid-assisted grinding in the presence of acetonitrile or ethanol/water mixture at a specific composition. The NFT hydrated salts were characterized using single crystal X-ray diffraction. The [NFT+4AmPy+H2O] salt (1:1:1) crystallized as an isolated site hydrate, while the [NFT+4AmPy+H2O] salt (1:1:4) crystallized as a channel hydrate. The dehydration processes of the NFT salt hydrates were investigated using differential scanning calorimetry and thermogravimetric analysis. A powder dissolution experiment was carried out for all NFT multicomponent solid forms in pH 7.4 phosphate buffer solution at 37 °C.
Reversible On-Off Photoswitching of DNA Replication Using a Dumbbell Oligodeoxynucleotide
Authors: Wang Yu , Ji Heming , Ma Jian , Luo Hang , He Yujian , Tang Xinjing , Wu Li
Published: December 2022

In most organisms, DNA extension is highly regulated; however, most studies have focused on controlling the initiation of replication, and few have been done to control the regulation of DNA extension. In this study, we adopted a new strategy for azODNs to regulate DNA extension, which is based on azobenzene oligonucleotide chimeras regulated by substrate binding affinity, and the conformation of the chimera can be regulated by a light source with a light wavelength of 365 nm. The results showed that the primer was extended with Taq DNA polymerase after visible light treatment, and DNA extension could be effectively hindered with UV light treatment. We also verify the reversibility of the photoregulation of primer extension through photoswitching of dumbbell asODNs by alternate irradiation with UV and visible light. Our method has the advantages of fast and simple, green response and reversible operations, providing a new strategy for regulating gene replication.
Volumetric, Compressibility and Viscometric Approach to Study the Interactional Behaviour of Sodium Cholate and Sodium Deoxycholate in Aqueous Glycyl Glycine
Authors: Kumari Santosh , Chauhan Suvarcha , Singh Kuldeep , Umar Ahmad , Fouad Hassan , Alissawi Mohammed S. , Akhtar Mohammad Shaheer
Published: December 2022

Viscosity, speed of sound (u), and density (ρ) have been measured in aqueous glycyl glycine solution over a temperature range from 293.15 to 313.15 K with a 5 K interlude to evaluate the volumetric and compressibility properties of bio-surfactants, namely sodium cholate (NaC; 1–20 mmol∙kg−1) and sodium deoxycholate (NaDC; 1–10 mmol∙kg−1). Density and viscosity findings provide information on both solute–solute and solute–solvent types of interactions. Many other metrics, such as apparent molar adiabatic compression (κS,φ), isentropic compressibility (κS), and apparent molar volume (Vφ), have been calculated from speed of sound and density measurements, utilising experimental data. The results show that the zwitterionic end group in the glycyl glycine strongly interacts with NaDC and NaC, promoting its micellization. Since the addition of glycyl glycine causes the bio-surfactant molecules to lose their hydrophobic hydration, the observed concentration-dependent changes in apparent molar volume and apparent molar adiabatic compression are likely attributable to changes in water–water interactions. Viscous relaxation time (τ) increases significantly with a rise in bio-surfactant concentration and decreases with increasing temperature, which may be because of structural relaxation processes resulting from molecular rearrangement. All of the estimated parameters have been analysed for their trends with regard to the different patterns of intermolecular interaction present in an aqueous glycyl glycine solution and bio-surfactant system.
Applications of Essential Oils and Plant Extracts in Different Industries
Authors: Bolouri Parisa , Salami Robab , Kouhi Shaghayegh , Kordi Masoumeh , Asgari Lajayer Behnam , Hadian Javad , Astatkie Tess
Published: December 2022

Essential oils (EOs) and plant extracts are sources of beneficial chemical compounds that have potential applications in medicine, food, cosmetics, and the agriculture industry. Plant medicines were the only option for preventing and treating mankind’s diseases for centuries. Therefore, plant products are fundamental sources for producing natural drugs. The extraction of the EOs is the first important step in preparing these compounds. Modern extraction methods are effective in the efficient development of these compounds. Moreover, the compounds extracted from plants have natural antimicrobial activity against many spoilage and disease-causing bacteria. Also, the use of plant compounds in cosmetics and hygiene products, in addition to their high marketability, has been helpful for many beauty problems. On the other hand, the agricultural industry has recently shifted more from conventional production systems to authenticated organic production systems, as consumers prefer products without any pesticide and herbicide residues, and certified organic products command higher prices. EOs and plant extracts can be utilized as ingredients in plant antipathogens, biopesticides, and bioherbicides for the agricultural sector. Considering the need and the importance of using EOs and plant extracts in pharmaceutical and other industries, this review paper outlines the different aspects of the applications of these compounds in various sectors.
The Role of Hydrogen Sulfide in the Development and Progression of Lung Cancer
Authors: Yang Yi-Lun , Zhang Ka , Zhou Ze-Tao , Jiang Zhi-Liang , Liu Yi , Zhang Yan-Xia , Liu Zhi-Hui , Ji Xin-Ying , Wu Dong-Dong
Published: December 2022

Lung cancer is one of the 10 most common cancers in the world, which seriously affects the normal life and health of patients. According to the investigation report, the 3-year survival rate of patients with lung cancer is less than 20%. Heredity, the environment, and long-term smoking or secondhand smoke greatly promote the development and progress of the disease. The mechanisms of action of the occurrence and development of lung cancer have not been fully clarified. As a new type of gas signal molecule, hydrogen sulfide (H2S) has received great attention for its physiological and pathological roles in mammalian cells. It has been found that H2S is widely involved in the regulation of the respiratory system and digestive system, and plays an important role in the occurrence and development of lung cancer. H2S has the characteristics of dissolving in water and passing through the cell membrane, and is widely expressed in body tissues, which determines the possibility of its participation in the occurrence of lung cancer. Both endogenous and exogenous H2S may be involved in the inhibition of lung cancer cells by regulating mitochondrial energy metabolism, mitochondrial DNA integrity, and phosphoinositide 3-kinase/protein kinase B co-pathway hypoxia-inducible factor-1α (HIF-1α). This article reviews and discusses the molecular mechanism of H2S in the development of lung cancer, and provides novel insights for the prevention and targeted therapy of lung cancer.
Deep Eutectic Solvents as Catalysts for Cyclic Carbonates Synthesis from CO2 and Epoxides
Authors: Mańka Dorota , Siewniak Agnieszka
Published: December 2022

In recent years, the chemical industry has put emphasis on designing or modifying chemical processes that would increasingly meet the requirements of the adopted proecological sustainable development strategy and the principles of green chemistry. The development of cyclic carbonate synthesis from CO2 and epoxides undoubtedly follows this trend. First, it represents a significant improvement over the older glycol phosgenation method. Second, it uses renewable and naturally abundant carbon dioxide as a raw material. Third, the process is most often solvent-free. However, due to the low reactivity of carbon dioxide, the process of synthesising cyclic carbonates requires the use of a catalyst. The efforts of researchers are mainly focused on the search for new, effective catalysts that will enable this reaction to be carried out under mild conditions with high efficiency and selectivity. Recently, deep eutectic solvents (DES) have become the subject of interest as potential effective, cheap, and biodegradable catalysts for this process. The work presents an up-to-date overview of the method of cyclic carbonate synthesis from CO2 and epoxides with the use of DES as catalysts.
Atroposelective Amination of Indoles via Chiral Center Induced Chiral Axis Formation
Authors: Wang Yong , Yan Jingxue , Jiang Yiqing , Wei Zexuan , Tu Zhenlin , Dong Chao , Lu Tao , Chen Yadong , Feng Jie
Published: December 2022

The construction of an N–C chiral axis for N-aryl indole derivatives is meaningful as they widely exist in functionalized molecules. This work provides a novel method for this purpose via amination of amino acid derivatives at the C2 position of the indole and chiral center induced chiral axis formation. The protocol of this transformation is easily accessible, not requiring metal or an organic chiral catalyst, endowing this method with great potential in the construction of axis chiral N-aryl indoles.
The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment
Authors: Rahmani Arshad Husain , Almatroudi Ahmad , Allemailem Khaled S. , Khan Amjad Ali , Almatroodi Saleh A.
Published: December 2022

Cancer is a main culprit and the second-leading cause of death worldwide. The current mode of treatment strategies including surgery with chemotherapy and radiation therapy may be effective, but cancer is still considered a major cause of death. Plant-derived products or their purified bioactive compounds have confirmed health-promoting effects as well as cancer-preventive effects. Among these products, flavonoids belong to polyphenols, chiefly found in fruits, vegetables and in various seeds/flowers. It has been considered to be an effective antioxidant, anti-inflammatory and to play a vital role in diseases management. Besides these activities, flavonoids have been revealed to possess anticancer potential through the modulation of various cell signaling molecules. In this regard, fisetin, a naturally occurring flavonoid, has a confirmed role in disease management through antioxidant, neuro-protective, anti-diabetic, hepato-protective and reno-protective potential. As well, its cancer-preventive effects have been confirmed via modulating various cell signaling pathways including inflammation, apoptosis, angiogenesis, growth factor, transcription factor and other cell signaling pathways. This review presents an overview of the anti-cancer potential of fisetin in different types of cancer through the modulation of cell signaling pathways based on in vivo and in vitro studies. A synergistic effect with anticancer drugs and strategies to improve the bioavailability are described. More clinical trials need to be performed to explore the anti-cancer potential and mechanism-of-action of fisetin and its optimum therapeutic dose.
Effects of Cocrystallization on the Structure and Properties of Melt-Cast Explosive 2,4-Dinitroanisole: A Computational Study
Authors: Wang Defu , Yang Lei , Zhu Weihua
Published: December 2022

Melt-cast explosive 2,4-dinitroanisole (DNAN) crystal and its cocrystals DNAN/1,3-dinitrobenzene (DNB) and DNAN/2-nitroaniline (NA) were used to identify the effects of cocrystallization on the crystal structure, non-covalent interactions, and melting points of the DNAN crystal through density functional theory and molecular dynamics. The components DNB and NA with subtle structure variations between the nitro group and amino group can significantly affect the non-covalent interactions, especially the π-π stacking and H-bonds, which can lead to different crystal stacking styles. The melting points of the DNAN crystal are decreased through the cocrystallization, which expands the utilization of the DNAN-based melt cast explosives. Our study deciphers the effects caused by the cocrystallization on the structure and properties of melt cast explosives and may help to design and optimize novel melt-cast explosives.
LC-MS/MS-Based Metabolomic Profiling of Constituents from Glochidion velutinum and Its Activity against Cancer Cell Lines
Authors: Shah Syed Luqman , Bashir Kashif , Rasheed Hafiz Majid , Rahman Jamil Ur , Ikram Muhammad , Shah Abdul Jabbar , Majrashi Kamlah Ali , Alnasser Sulaiman Mohammed , Menaa Farid , Khan Taous
Published: December 2022

This study aimed to establish the phytochemical profile of Glochidion velutinum and its cytotoxic activity against prostate cancer (PC-3) and breast cancer (MCF-7) cell lines. The phytochemical composition of G. velutinum leaf extract and its fractions was established with the help of total phenolic and flavonoid contents and LC-MS/MS-based metabolomics analysis. The crude methanolic extract and its fractions were studied for pharmacological activity against PC-3 and MCF-7 cell lines using the MTT assay. The total phenolic content of the crude extract and its fractions ranged from 44 to 859 µg GAE/mg of sample whereas total flavonoid contents ranged from 20 to 315 µg QE/mg of sample. A total of forty-eight compounds were tentatively dereplicated in the extract and its fractions. These phytochemicals included benzoic acid derivatives, flavans, flavones, O-methylated flavonoids, flavonoid O- and C-glycosides, pyranocoumarins, hydrolysable tannins, carbohydrate conjugates, fatty acids, coumarin glycosides, monoterpenoids, diterpenoids, and terpene glycosides. The crude extract (IC50 = 89 µg/mL), the chloroform fraction (IC50 = 27 µg/mL), and the water fraction (IC50 = 36 µg/mL) were found to be active against the PC-3 cell line. However, the crude extract (IC50 = 431 µg/mL), the chloroform fraction (IC50 = 222 µg/mL), and the ethyl acetate fraction (IC50 = 226 µg/mL) have shown prominent activity against breast cancer cells. Moreover, G. velutinum extract and its fractions presented negligible toxicity to normal macrophages at the maximum tested dose (600 µg/mL). Among the compounds identified through LC-MS/MS-based metabolomics analysis, epigallocatechin gallate, ellagic acid, isovitexin, and rutin were reported to have anticancer activity against both prostate and breast cancer cell lines and might be responsible for the cytotoxic activities of G. velutinum extract and its bioactive fractions.
Electrochemical Characterization and Voltammetric Determination of Methylisothiazolinone on a Boron-Doped Diamond Electrode
Authors: Jakubczyk Magdalena , Michalkiewicz Slawomir , Skorupa Agata , Krajcarz Kinga
Published: December 2022

The electrochemical properties of methylisothiazolinone (MIT), the most widely used preservative, were investigated by cyclic (CV) and differential pulse voltammetry (DPV) to develop a new method for its determination. To our knowledge, this is the first demonstration of a voltammetric procedure for the determination of MIT on a boron-doped diamond electrode (BDDE) in a citrate–phosphate buffer (C-PB) environment. The anodic oxidation process of methylisothiazolinone, which is the basis of this method, proved to be diffusion-controlled and proceeded with an irreversible two-electron exchange. The radical cations, as unstable primary products, were converted in subsequent chemical reactions to sulfoxides and sulfones, and finally to more stable final products. Performed determinations were based on the DPV technique. A linear calibration curve was obtained in the concentration range from 0.7 to 18.7 mg L−1, with a correlation coefficient of 0.9999. The proposed procedure was accurate and precise, allowing the detection of MIT at a concentration level of 0.24 mg L−1. It successfully demonstrated its suitability for the determination of methylisothiazolinone in household products without the need for any separation steps. The proposed method can serve as an alternative to the prevailing chromatographic determinations of MIT in real samples.
Discovery of Novel and Selective G-Protein Coupled Receptor 120 (GPR120) Agonists for the Treatment of Type 2 Diabetes Mellitus
Authors: Wang Xuekun , Li Xu , Wei Shiting , Wang Min , Xu Yao , Hu Weidi , Gao Zhenzhen , Liu Renmin , Wang Shiben , Ji Guoxia
Published: December 2022

Diabetes mellitus (DM), a chronic metabolic disorder characterized by high blood glucose, not only poses a serious threat to human life and health, but also places an economic burden on society. Currently available antidiabetic pharmacological agents have some adverse effects, which have stimulated researchers to explore novel antidiabetic agents with different mechanisms of action. G-protein Coupled Receptor 120 (GPR120), also known as free fatty acid receptor 4 (FFAR4), which is activated by medium-chain and long-chain fatty acids, has emerged as an interesting potential target for the treatment of metabolic disorders. Herein, we designed and synthesized a series of novel GPR120 agonists based on the structure of TUG-891, which is susceptible to β-oxidation and loses its GPR120 agonistic activity in vivo. Among the designed compounds, 14d showed excellent agonistic activity and selectivity and could improve glucose tolerance in normal mice in a dose-dependent manner. In addition, the compound 14d displayed good antidiabetic effects in diet-induced obese (DIO) mice and elevated insulin levels. Molecular simulations illustrated that compound 14d could enter the active site of GPR120 and interact with ARG99, which plays an important role in GPR120 activation. Based on these observations, compound 14d may be a promising lead compound deserving of further biological evaluation and structural modifications.
Self-Supplying Guide RNA-Mediated CRISPR/Cas12a Fluorescence System for Sensitive Detection of T4 PNKP
Authors: Yuan Xiuhua , Yuan Hui , Liu Bingxin , Liu Yeling
Published: December 2022

Sensitive detection methods for T4 polynucleotide kinase/phosphatase (T4 PNKPP) are urgently required to obtain information on malignancy and thereby to provide better guidance in PNKP-related diagnostics and drug screening. Although the CRISPR/Cas12a system shows great promise in DNA-based signal amplification protocols, its guide RNAs with small molecular weight often suffer nuclease degradation during storage and utilization, resulting in reduced activation efficiency. Herein, we proposed a self-supplying guide RNA-mediated CRISPR/Cas12a system for the sensitive detection of T4 PNKP in cancer cells, in which multiple copies of guide RNA were generated by in situ transcription. In this assay, T4 PNKP was chosen as a model, and a dsDNA probe with T7 promoter region and the transcription region of guide RNA were involved. Under the action of T4 PNKP, the 5′-hydroxyl group of the dsDNA probe was converted to a phosphate group, which can be recognized and digested by Lambda Exo, resulting in dsDNA hydrolysis. The transcription template was destroyed, which resulted in the failure to generate guide RNA by the transcription pathway. Therefore, the CRISPR/Cas12a system could not be activated to effectively cleavage the F-Q-reporter, and the fluorescence signal was turned off. In the absence of T4 PNKP, the 5′-hydroxyl group of the substrate DNA cannot be digested by Lambda Exo. The intact dsDNA acts as the transcription template to generate a large amount of guide RNA. Finally, the formed Cas12a/gRNA complex triggered the reverse cleavage of Cas12a on the F-Q-reporter, resulting in a “turn-on” fluorescence signal. This strategy displayed sharp sensitivity of T4 PNKP with the limit of detection (LOD) down to 0.0017 mU/mL, which was mainly due to the multiple regulation effect of transcription amplification. In our system, the dsDNA simultaneously serves as the T4 PNKP substrate, transcription template, and Lambda Exo substrate, avoiding the need for multiple probe designs and saving costs. By integrating the target recognition, Lambda Exo activity, and trans-cleavage activity of Cas12a, CRISPR/Cas12a catalyzed the cleavage of fluorescent-labeled short-stranded DNA probes and enabled synergetic signal amplification for sensitive T4 PNKP detection. Furthermore, the T4 PNKP in cancer cells has been evaluated as a powerful tool for biomedical research and clinical diagnosis, proving a good practical application capacity.
Simultaneous Determination of Escitalopram Impurities including the R-enantiomer on a Cellulose tris(3,5-Dimethylphenylcarbamate)-Based Chiral Column in Reversed-Phase Mode
Authors: Szabó Zoltán-István , Bartalis-Fábián Ágnes , Tóth Gergő
Published: December 2022

A high-performance liquid chromatographic method was developed for the simultaneous determination of the related substances—three potential synthesis-related chemical impurities and the distomer—of escitalopram. The separation capacity of seven different polysaccharide-type chiral columns, including three amylose-based (Lux Amylose-1, Lux i-Amylose-1, Lux Amylose-2) and four cellulose-based columns (Lux Cellulose-1, Lux Cellulose-2, Lux Cellulose-3, and Lux Cellulose-4) were screened in the polar organic and reversed-phase modes. Lux Cellulose-1, based on cellulose tris(3,5-dimethylphenylcarbamate) as the chiral selector with an acetonitrile-water mixture containing 0.1% diethylamine was identified as the most promising separation system. Using the “one factor at a time” optimization approach, the effect of column temperature, flow rate, and mobile phase constituents on separation performance was evaluated, and the critical resolution values were determined. A U-shaped retention pattern was obtained when plotting the retention factors of the citalopram enantiomers versus the water content of the binary mobile phases on the Lux Cellulose-1 column. A thermodynamic analysis revealed enthalpy-driven enantioseparation in both the polar organic and reversed-phase modes. For further method optimizations, an L9 orthogonal array table was employed. Using the optimized parameters (Lux Cellulose-1 column with 0.1% (v/v) diethylamine in water/acetonitrile 55/45 (v/v); 0.8 mL/min flow rate at 25 °C), baseline separations were achieved between all compounds. Our newly developed HPLC method was validated according to the ICH guidelines and its application was tested with a commercially available pharmaceutical formulation. The method proved to be suitable for routine quality control of related substances and the enantiomeric purity of escitalopram.
Chickpea and Lupin Sprouts, Stimulated by Different LED Lights, As Novel Examples of Isoflavones-Rich Functional Food, and Their Impact on Breast and Prostate Cells
Authors: Galanty Agnieszka , Zagrodzki Paweł , Miret Marina , Paśko Paweł
Published: December 2022

Among all legumes sprouts’ active compounds, isoflavones seem to be the most important; nevertheless, their high content is not always associated with beneficial effects. These compounds may prevent or stimulate hormone-dependent cancers due to their estrogen-like activity. Different LED light quality can change the synthesis of active compounds and significantly influence the biological activity of the sprouts. This study aimed to evaluate the effects of LED light (red, blue, green, yellow), as well as total darkness, and natural light conditions (as reference), on isoflavones content, determined by HPLC-UV-VIS, during 10 days of harvesting of chickpea and lupin sprouts. Due to the ambiguous estrogenic potential of isoflavones, the impact of these sprouts on normal and cancer prostate and breast cells was evaluated. Yellow LED light resulted in the highest sum of isoflavones in chickpea sprouts (up to 1 g/100 g dw), while for green LED light, the isoflavones sum was the lowest. The exact opposite effect was noted for lupin sprouts, with the predominance of green over the yellow LED light. The examined sprouts were of high safety to non-neoplastic breast and prostate cells, with interesting cytotoxic effects on breast MCF7 and prostate DU145 cancer cells. No clear relationship was observed between the activity and isoflavones content.
Carbazole and Diketopyrrolopyrrole-Based D-A π-Conjugated Oligomers Accessed via Direct C–H Arylation for Opto-Electronic Property and Performance Study
Authors: Zhang Xiaofeng , Feng Lingwei , Zhang Kai , Liu Shi-Yong
Published: December 2022

Five carbazole and diketopyrrolopyrrole-based donor-acceptor (D-A) new π-conjugated oligomers (π-COs) with gradually elongated lengths are facilely synthesized via a single pot of direct C–H arylation with merits of atom- and step-economy. The structure-property-performance correlations of these π-COs and their parent polymer are studied in detail by opto-electronic characterizations and bulk heterojunction (BHJ) organic photovoltaic (OPV) devices. It is found that the π-COs having longer lengths enable better performance in OPVs owing to the enhanced intermolecular interaction with the elongation of the conjugations. The above results not only highlight the powerful synthetic strategy here provided, but also reveal that π-COs with unique properties might find promising application in OPVs.
Impact of Dispersion Force Schemes on Liquid Systems: Comparing Efficiency and Drawbacks for Well-Targeted Test Cases
Authors: Martin Evelyne , Amiehe Essomba Iréné Bérenger , Ishisone Kana , Boero Mauro , Ori Guido , Massobrio Carlo
Published: December 2022

First-principles molecular dynamics (FPMD) calculations were performed on liquid GeSe4 with the aim of inferring the impact of dispersion (van der Waals, vdW) forces on the structural properties. Different expressions for the dispersion forces were employed, allowing us to draw conclusions on their performances in a comparative fashion. These results supersede previous FPMD calculations obtained in smaller systems and shorter time trajectories by providing data of unprecedented accuracy. We obtained a substantial agreement with experiments for the structure factor regardless of the vdW scheme employed. This objective was achieved by using (in addition to FPMD with no dispersion forces) a selection of vdW schemes available within density functional theory. The first two are due to Grimme, D2 and D3, and the third one is devised within the so-called maximally localized Wannier functions approach (MLWF). D3 results feature a sizeable disagreement in real space with D2 and MLWF in terms of the partial and total pair correlation functions as well as the coordination numbers. More strikingly, total and partial structure factors calculated with D3 exhibit an unexpected sharp increase at low k. This peculiarity goes along with large void regions within the network, standing for a phase separation of indecipherable physical meaning. In view of these findings, further evidence of unconventional structural properties found by employing D3 is presented by relying on results obtained for a complex ionic liquid supported on a solid surface. The novelty of our study is multifold: new, reliable FPMD data for a prototypical disordered network system, convincing agreement with experimental data and assessment of the impact of dispersion forces, with emphasis on the intriguing behavior of one specific recipe and the discovery of common structural features shared by drastically dissimilar physical systems when the D3 vdW scheme is employed.
Phytochemical Compounds and Nanoparticles as Phytochemical Delivery Systems for Alzheimer’s Disease Management
Authors: Bakrim Saad , Aboulaghras Sara , El Menyiy Naoual , El Omari Nasreddine , Assaggaf Hamza , Lee Learn-Han , Montesano Domenico , Gallo Monica , Zengin Gokhan , AlDhaheri Yusra , Bouyahya Abdelhakim
Published: December 2022

Alzheimer’s disease remains one of the most widespread neurodegenerative reasons for dementia worldwide and is associated with considerable mortality and morbidity. Therefore, it has been considered a priority for research. Indeed, several risk factors are involved in the complexity of the therapeutic ways of this pathology, including age, traumatic brain injury, genetics, exposure to aluminum, infections, diabetes, vascular diseases, hypertension, dyslipidemia, and obesity. The pathophysiology of Alzheimer’s disease is mostly associated with hyperphosphorylated protein in the neuronal cytoplasm and extracellular plaques of the insoluble β-amyloid peptide. Therefore, the management of this pathology needs the screening of drugs targeting different pathological levels, such as acetylcholinesterase (AchE), amyloid β formation, and lipoxygenase inhibitors. Among the pharmacological strategies used for the management of Alzheimer’s disease, natural drugs are considered a promising therapeutic strategy. Indeed, bioactive compounds isolated from different natural sources exhibit important anti-Alzheimer effects by their effectiveness in promoting neuroplasticity and protecting against neurodegeneration as well as neuroinflammation and oxidative stress in the brain. These effects involve different sub-cellular, cellular, and/or molecular mechanisms, such as the inhibition of acetylcholinesterase (AchE), the modulation of signaling pathways, and the inhibition of oxidative stress. Moreover, some nanoparticles were recently used as phytochemical delivery systems to improve the effects of phytochemical compounds against Alzheimer’s disease. Therefore, the present work aims to provide a comprehensive overview of the key advances concerning nano-drug delivery applications of phytochemicals for Alzheimer’s disease management.
Multicomponent Characterization of the Flower Bud of Panax notoginseng and Its Metabolites in Rat Plasma by Ultra-High Performance Liquid Chromatography/Ion Mobility Quadrupole Time-of-Flight Mass Spectrometry
Authors: Yang Xiaonan , Xiong Ying , Wang Hongda , Jiang Meiting , Xu Xiaoyan , Mi Yueguang , Lou Jia , Li Xiaohang , Sun He , Zhao Yuying , Li Xue , Yang Wenzhi
Published: December 2022

The flower bud of Panax notoginseng (PNF) consumed as a tonic shows potential in the prevention and treatment of cardiovascular diseases. To identify the contained multi-components and, in particular, to clarify which components can be absorbed and what metabolites are transformed, unveiling the effective substances of PNF is of vital significance. A unique ultrahigh-performance liquid chromatography/ion mobility quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS) profiling approach and efficient data processing by the UNIFITM bioinformatics platform were employed to comprehensively identify the multi-components of PNF and the related metabolites in the plasma of rats after oral administration (at a dose of 3.6 g/kg). Two MS2 data acquisition modes operating in the negative electrospray ionization mode, involving high-definition MSE (HDMSE) and data-dependent acquisition (DDA), were utilized aimed to extend the coverage and simultaneously ensure the quality of the MS2 spectra. As a result, 219 components from PNF were identified or tentatively characterized, and 40 thereof could be absorbed. Moreover, 11 metabolites were characterized from the rat plasma. The metabolic pathways mainly included the phase I (deglycosylation and oxidation). To the best of our knowledge, this is the first report that systematically studies the in vivo metabolites of PNF, which can assist in better understanding its tonifying effects and benefit its further development.
Potential Antioxidant Activity of Apigenin in the Obviating Stress-Mediated Depressive Symptoms of Experimental Mice
Authors: Alghamdi Adel , Almuqbil Mansour , Alrofaidi Mohammad A. , Burzangi Abdulhadi S. , Alshamrani Ali A. , Alzahrani Abdullah R. , Kamal Mehnaz , Imran Mohd. , Alshehri Sultan , Mannasaheb Basheerahmed Abdulaziz , Alomar Nasser Fawzan , Asdaq Syed Mohammed Basheeruddin
Published: December 2022

This study aimed to examine the antidepressant properties of apigenin in an experimental mouse model of chronic mild stress (CMS). Three weeks following CMS, albino mice of either sex were tested for their antidepressant effects using the tail suspension test (TST) and the sucrose preference test. The percentage preference for sucrose solution and the amount of time spent immobile in the TST were calculated. The brain malondialdehyde (MDA) levels, catalase activity, and reduced glutathione levels were checked to determine the antioxidant potential of treatments. When compared to the control, animals treated with apigenin during the CMS periods showed significantly shorter TST immobility times. Apigenin administration raised the percentage preference for sucrose solution in a dose-dependent manner, which put it on par with the widely used antidepressant imipramine. Animals treated with apigenin displayed a significantly (p ˂ 0.05) greater spontaneous locomotor count (281) when compared to the vehicle-treated group (245). Apigenin was also highly effective in significantly (p ˂ 0.01) lowering plasma corticosterone levels (17 vs. 28 µg/mL) and nitrite (19 vs. 33 µg/mL) produced by CMS in comparison to the control group. During CMS, a high dose (50 mg/kg) of apigenin was given, which greatly increased the reduced glutathione level while significantly decreasing the brain’s MDA and catalase activity when compared to the control group. As a result, we infer that high doses of apigenin may have potential antidepressant effects in animal models via various mechanisms.
HS-GC-IMS and PCA to Characterize the Volatile Flavor Compounds in Three Sweet Cherry Cultivars and Their Wines in China
Authors: Liu Baoxiang , Yang Yang , Ren Likun , Su Zhengbo , Bian Xin , Fan Jing , Wang Yuanyuan , Han Bing , Zhang Na
Published: December 2022

The aim of this research was to characterize differences and sources of volatile flavor compounds by using headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) and principal component analysis (PCA). Three sweet cherry fruits from different cultivars (cv. Tie, Van, and Lap) and their wines that were produced by the same yeast were detected. The results showed that 27 flavor compounds were identified in cherry fruits, including 10 alcohols, 7 esters, 7 aldehydes, 2 ketones, and 1 organic acid. Twenty-three flavor compounds were identified in cherry wines, including nine esters, eight alcohols, three aldehydes, two organic acids, and one ketone. In cherry fruits, aldehydes, several alcohols, and one ketone were the most prevalent in cv. Tie, and the majority of esters and alcohols in cv. Van. After fermentation, ethanol, butanol, butanal, ethyl propionate, propionaldehyde, 3-hydroxy-2-butanone, and acetic acid increased, whereas 1-hexanol, 3-methyl-3-buten-1-ol, 1-penten-3-ol, ethyl acetate, methyl acetate, (E)-2-hexenal and hexanal decreased. Few differences were detected in the type and content of volatile compounds in cherry wines from cv. Tieton (WT) and cv. Van (WV). Almost all aldehydes are derived from cherry fruits, which cannot be produced during wine-making, and other volatile compounds are almost all produced by saccharomyces cerevisiae. The volatile compounds of cherry wines were determined by row materials and fermentation cultures. Flavor fingerprints were established by HS-GC-IMS and PCA, which provided a theoretical foundation for the evaluation and improvement of flavor quality in cherry wine-making.
Screening of the Active Compounds against Neural Oxidative Damage from Ginseng Phloem Using UPLC-Q-Exactive-MS/MS Coupled with the Content-Effect Weighted Method
Authors: Gao Xiao-Chen , Zhang Nan-Xi , Shen Jia-Ming , Lv Jing-Wei , Zhang Kai-Yue , Sun Yao , Li Hang , Wang Yue-Long , Cheng Duan-Duan , Zhao Meng-Ya , Zhang Hui , Li Chun-Nan , Sun Jia-Ming
Published: December 2022

The neuroprotective properties of ginsenosides have been found to reverse the neurological damage caused by oxidation in many neurodegenerative diseases. However, the distribution of ginsenosides in different tissues of the main root, which was regarded as the primary medicinal portion in clinical practice was different, the specific parts and specific components against neural oxidative damage were not clear. The present study aims to screen and determine the potential compounds in different parts of the main root in ginseng. Comparison of the protective effects in the main root, phloem and xylem of ginseng on hydrogen peroxide-induced cell death of SH-SY5Y neurons was investigated. UPLC-Q-Exactive-MS/MS was used to quickly and comprehensively characterize the chemical compositions of the active parts. Network pharmacology combined with a molecular docking approach was employed to virtually screen for disease-related targets and potential active compounds. By comparing the changes before and after Content-Effect weighting, the compounds with stronger anti-nerve oxidative damage activity were screened out more accurately. Finally, the activity of the selected monomer components was verified. The results suggested that the phloem of ginseng was the most effective part. There were 19 effective compounds and 14 core targets, and enriched signaling pathway and biological functions were predicted. After Content-Effect weighting, compounds Ginsenosides F1, Ginsenosides Rf, Ginsenosides Rg1 and Ginsenosides Rd were screened out as potential active compounds against neural oxidative damage. The activity verification study indicated that all four predicted ginsenosides were effective in protecting SH-SY5Y cells from oxidative injury. The four compounds can be further investigated as potential lead compounds for neurodegenerative diseases. This also provides a combined virtual and practical method for the simple and rapid screening of active ingredients in natural products.
Association of Ultrasonography and Health Education during Antenatal Visits among Pregnant Women to Reduce Unnecessary Caesarean Section in Bangladesh: Study Protocol for a Cluster Randomized Control Trial
Authors: Shirin Habiba , Moriyama Michiko , Huq K.A.T.M. Ehsanul , Rahman Md Moshiur , Masud Sumaya Binte , Begum Rowshan Ara , Misty Kamrunnahar , Hawlader Mohammad Delwer Hossain
Published: December 2022

The rate of caesarean section (C/S) has been increasing globally. The proposed study aims to evaluate the effects of ultrasonography (USG) and health education in reducing unnecessary C/S among pregnant women. The secondary objectives are to increase antenatal care (ANC) and post-natal care (PNC) visit rates, increase USG use, increase institutional (hospitals and clinics) delivery, reduce delivery related complications and reduce the number of still births. This is a prospective, open-label, two-arm cluster randomized controlled trial (RCT). A total of 288 pregnant women are enrolled from two urban and two rural hospitals in Bangladesh. Women were screened during their first ANC visits, then written informed consent was taken from the participants. Women in intervention hospitals receive eight ANC visits, two additional USG, and health education eight times during their ANC visits. In contrast, participants at control hospitals receive usual care consisting of four ANC visits and two USG during their ANC visits. The primary outcome is to compare the rate of unnecessary C/S during PNC visits. This study obtained approval from the Institutional Review Board of North South University (2021/OR-NSU/IRB/0804), Bangladesh in November 2021 and was registered in clinicalTrails.gov (#NCT05135026).
Preclinical PET and MR Evaluation of 89Zr- and 68Ga-Labeled Nanodiamonds in Mice over Different Time Scales
Authors: Winter Gordon , Eberhardt Nina , Löffler Jessica , Raabe Marco , Alam Md. Noor A. , Hao Li , Abaei Alireza , Herrmann Hendrik , Kuntner Claudia , Glatting Gerhard , Solbach Christoph , Jelezko Fedor , Weil Tanja , Beer Ambros J. , Rasche Volker
Published: December 2022

Nanodiamonds (NDs) have high potential as a drug carrier and in combination with nitrogen vacancies (NV centers) for highly sensitive MR-imaging after hyperpolarization. However, little remains known about their physiological properties in vivo. PET imaging allows further evaluation due to its quantitative properties and high sensitivity. Thus, we aimed to create a preclinical platform for PET and MR evaluation of surface-modified NDs by radiolabeling with both short- and long-lived radiotracers. Serum albumin coated NDs, functionalized with PEG groups and the chelator deferoxamine, were labeled either with zirconium-89 or gallium-68. Their biodistribution was assessed in two different mouse strains. PET scans were performed at various time points up to 7 d after i.v. injection. Anatomical correlation was provided by additional MRI in a subset of animals. PET results were validated by ex vivo quantification of the excised organs using a gamma counter. Radiolabeled NDs accumulated rapidly in the liver and spleen with a slight increase over time, while rapid washout from the blood pool was observed. Significant differences between the investigated radionuclides were only observed for the spleen (1 h). In summary, we successfully created a preclinical PET and MR imaging platform for the evaluation of the biodistribution of NDs over different time scales.
One-Pot Facile Synthesis of CuO–CdWO4 Nanocomposite for Photocatalytic Hydrogen Production
Authors: Althabaiti Shaeel Ahmed , Malik Maqsood Ahmad , Kumar Khanna Manoj , Bawaked Salem Mohamed , Narasimharao Katabathini , Al-Sheheri Soad Zahir , Fatima Bushra , Siddiqui Sharf Ilahi
Published: December 2022

Hydrogen (H2) is a well-known renewable energy source that produces water upon its burning, leaving no harmful emissions. Nanotechnology is utilized to increase hydrogen production using sacrificial reagents. It is an interesting task to develop photocatalysts that are effective, reliable, and affordable for producing H2 from methanol and acetic acid. In the present study, CuO, CdWO4, and CuO–CdWO4 nanocomposite heterostructures were prepared using a cost-efficient, enviro-friendly, and facile green chemistry-based approach. The prepared CuO, CdWO4, and CuO–CdWO4 nanocomposites were characterized using X-ray diffraction pattern, Fourier-transform infrared spectroscopy, diffuse reflectance ultraviolet–visible spectroscopy, scanning electron microscopy, transmission electron microscopy, selected area electron diffraction (SAED) pattern, N2 physisorption, photoluminescence, and X-ray photoelectron spectroscopy techniques. The synthesized photocatalysts were utilized for photocatalytic H2 production using aqueous methanol and acetic acid as the sacrificial reagents under visible light irradiation. The influence of different variables, including visible light irradiation time, catalyst dosage, concentration of sacrificial reagents, and reusability of catalysts, was studied. The maximum H2 was observed while using methanol as a sacrificial agent over CuO–CdWO4 nanocomposite. This enhancement was due to the faster charge separation, higher visible light absorption, and synergistic effect between the CuO–CdWO4 nanocomposite and methanol.
Engineered Nanoparticles, Natural Nanoclay and Biochar, as Carriers of Plant-Growth Promoting Bacteria
Authors: Pavlicevic Milica , Abdelraheem Wael , Zuverza-Mena Nubia , O’Keefe Tana , Mukhtar Salma , Ridge Gale , Ranciato John , Haynes Christy , Elmer Wade , Pignatello Joseph , Pagano Luca , Caldara Marina , Marmiroli Marta , Maestri Elena , Marmiroli Nelson , White Jason C.
Published: December 2022

The potential of biochar and nanoparticles to serve as effective delivery agents for beneficial bacteria to crops was investigated. Application of nanoparticles and biochar as carriers for beneficial bacteria improved not only the amount of nitrogen-fixing and phosphorus-solubilizing bacteria in soil, but also improved chlorophyll content (1.2–1.3 times), cell viability (1.1–1.5 times), and antioxidative properties (1.1–1.4 times) compared to control plants. Treatments also improved content of phosphorus (P) (1.1–1.6 times) and nitrogen (N) (1.1–1.4 times higher) in both tomato and watermelon plants. However, the effect of biochars and nanoparticles were species-specific. For example, chitosan-coated mesoporous silica nanoparticles with adsorbed bacteria increased the phosphorus content in tomato by 1.2 times compared to a 1.1-fold increase when nanoclay with adsorbed bacteria was applied. In watermelon, the situation was reversed: 1.1-fold increase in the case of chitosan-coated mesoporous silica nanoparticles and 1.2 times in case of nanoclay with adsorbed bacteria. Our findings demonstrate that use of nanoparticles and biochar as carriers for beneficial bacteria significantly improved plant growth and health. These findings are useful for design and synthesis of novel and sustainable biofertilizer formulations.
LnNP@ZIF8 Smart System for In Situ NIR-II Ratiometric Imaging-Based Tumor Drug Resistance Evaluation
Authors: Wang Qingyuan , Zhang Zhizheng , Qiu Dehui , Mao Xuanxiang , Zhou Zhaoxi , Xia Tiansong , Wei Jifu , Ding Qiang , Zhang Xiaobo
Published: December 2022

Just-in-time evaluation of drug resistance in situ will greatly facilitate the achievement of precision cancer therapy. The rapid elevation of reactive oxygen species (ROS) is the key to chemotherapy. Hence, suppressed ROS production is an important marker for chemotherapy drug resistance. Herein, a NIR-II emission smart nanoprobe (LnNP@ZIF8, consisting of a lanthanide-doped nanoparticle (LnNP) core and metal-organic framework shell (ZIF8)) is constructed for drug delivery and in vivo NIR-II ratiometric imaging of ROS for tumor drug resistance evaluation. The drug-loaded nanoprobes release therapeutic substances for chemotherapy in the acidic tumor tissue. As the level of ROS increases, the LnNPs shows responsively descending fluorescence intensity at 1550 nm excited by 980 nm (F1550, 980Ex), while the fluorescence of the LnNPs at 1060 nm excited by 808 nm (F1060, 808Ex) is stable. Due to the ratiometric F1550, 980Ex/F1060, 808Ex value exhibiting a linear relationship with ROS concentration, NIR-II imaging results of ROS change based on this ratio can be an important basis for determining tumor drug resistance. As the chemotherapy and resistance evaluation are explored continuously in situ, the ratiometric imaging identifies drug resistance successfully within 24 h, which can greatly improve the timeliness of accurate treatment.
Cation-Exchange in Metal-Organic Framework as a Strategy to Obtain New Material for Ascorbic Acid Detection
Authors: Bodylska Weronika , Fandzloch Marzena , Szukiewicz Rafał , Lukowiak Anna
Published: December 2022

Ascorbic acid (AA) is an important biomolecule, the deficiency or maladjustment of which is associated with the symptoms of many diseases (e.g., cardiovascular disease or cancer). Therefore, there is a need to develop a fluorescent probe capable of detecting AA in aqueous media. Here, we report the synthesis, structural, and spectroscopic characterization (by means of, e.g., XRD, XPS, IR and Raman spectroscopy, TG, SEM, and EDS analyses), as well as the photoluminescent properties of a metal–organic framework (MOF) based on Cu2+ and Eu3+ ions. The ion-exchange process of the extraframework cation in anionic Cu-based MOF is proposed as an appropriate strategy to obtain a new material with a nondisturbed structure and a sensitivity to interaction with AA. Accordingly, a novel Eu[Cu3(μ3-OH)(μ3-4-carboxypyrazolato)3] compound for the selective optical detection of AA with a short detection time of 5 min is described.