bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Humeral Head and Shaft Fractures: Outcome Following Intramedullary Nailing and Plating
Authors: Souleiman Firas , Theopold Jan , Henkelmann Ralf , Osterhoff Georg , Pastor Torsten , Gueorguiev Boyko , Fakler Johannes , Hepp Pierre
Published: January 2023

Background and Objectives: Combined fractures of the humeral head and shaft (FHS) are rare but frequently involve an intermuscular fracture as its characteristic pattern. The aim of this retrospective study was to investigate intramedullary nailed and plated FHS in terms of outcomes and complications. Materials and Methods: The present study included patients with FHS, treated via either intramedullary nailing or plating within a period of 10 years, with a minimum follow-up of 12 months. Functional outcome was assessed using the age- and sex-adapted Constant–Murley Score (CMS-K). Rates of complications and revision surgeries were registered. Results: Twenty-five patients (18 females, 7 males, age 60.1 ± 14.2 years, range 23–76 years) were included in the study. Nailing was performed in 16 patients (12 females, 4 males, age 62.6 ± 12.4 years), whereas plating was executed in nine patients (6 females, 3 males, age 55.8 ± 17.0 years). Follow-up among all patients was 45.1 ± 26.3 months (range 12–97 months). CMS-K was 70.3 ± 32.3 in the nailing group, with reoperation in four cases, and 76.0 ± 31.0 in the plating group, with one reoperation (p = 0.42). Patients with no metaphyseal fragment displacement (n = 19; CMS-K 76.7 ± 17.3) demonstrated significantly better functional outcomes versus those with secondary displacement of the metaphyseal fragments (n = 6; CMS-K 60.0 ± 17.1), p = 0.046. Conclusions: Comparable acceptable clinical outcome is obtained when comparing nailing with additional open cerclage or lag-screw fixation techniques versus plating with open reduction. However, a higher revision rate was observed after nailing. The correct metaphyseal fragment fixation seems to be crucial to avoid loss of reduction and hence the need for revision surgery, as well as a worse outcome.
The Addition of Hypomethylating Agents to Low-Intensity Induction Chemotherapy Does Not Improve Outcomes in Elderly Acute Myeloid Leukemia Patients: A Single-Center Retrospective Study
Authors: Liu Dan , Wang Xiaoyu , Tong Juan , Zhou Li , Chen Erling , Zhou Ziwei , Xue Lei , Zhang Xuhan , Sun Guangyu , Zheng Changcheng
Published: January 2023

Background and Objectives: This study aimed to evaluate whether the addition of hypomethylating agents (HMA) to low-intensity chemotherapy can enhance the clinical efficacy of induction treatment for elderly acute myeloid leukemia (AML) patients who are unsuitable for standard induction therapy. Materials and Methods: This study retrospectively analyzed 117 patients over 60 years old who were initially diagnosed with AML and received low-intensity induction treatment in the Department of Hematology in Anhui provincial hospital from January 2015 to December 2020. Twenty-three patients were excluded, and the remaining 94 patients were divided into two groups according to the selection of induction regimens. Results: Forty-four patients received HMA combined with low-intensity chemotherapy, and the other 50 patients received only low-intensity induction chemotherapy. Forty-three patients (45.7%) obtained complete remission (CR) after the initial induction treatment. The CR rate in the HMA plus low-intensity chemotherapy group was 34.1% (15/44), and in the single low-intensity chemotherapy group was 56.0% (28/50) (p = 0.04). The 30 days cumulative early death rates were 9.1% (95% CI: 3.5–22.4%) in the HMA plus low-intensity chemotherapy group and 6.0% (95% CI: 2.0–17.5%) in the single low-intensity chemotherapy group, respectively (p = 0.59), and the one-year cumulative relapse rates were 21.1% (95% Cl: 9.8–41.9%) and 33.3% (95% Cl: 20.3–51.5%), respectively (p = 0.80). The one-year overall survival (OS) rates for patients in the HMA plus low-intensity chemotherapy group and the single low-intensity chemotherapy group were 37.3% (95% Cl: 23.1–51.5%) and 55.4% (95% Cl: 40.5–67.9%), respectively (p = 0.098), and the one-year event-free survival (EFS) rates were 8.5% (95% Cl: 2.2–20.6%) and 20.6% (95% Cl: 9.1–35.3%), respectively (p = 0.058). Conclusions: This study showed that the addition of HMA to low-intensity induction chemotherapy does not improve prognosis in elderly AML patients who are unsuitable for standard induction chemotherapy.
Concepts and Misconceptions Concerning the Influence of Divalent Ions on the Performance of Reverse Electrodialysis Using Natural Waters
Authors: Veerman Joost
Published: January 2023

Divalent ions have a negative effect on the obtained power and efficiency of the reverse electrodialysis (RED) process when using natural waters. These effects can largely be attributed to the interaction between the various ions and the membranes, resulting in a decreased membrane voltage, an increased membrane resistance, and uphill transport of divalent ions. The aim of this study was to investigate the causes of these differences and, if possible, to find underlying causes. The approach mainly followed that in literature articles that specifically focused on the effect of divalent ions on RED. It transpired that seven publications were useful because the methodology was well described and sufficient data was published. I found two widely shared misconceptions. The first concerns the role of the stack voltage in uphill transport of divalent ions; itis often thought that the open circuit voltage (OCV) must be taken into account, but it is plausible that the voltage under working conditions is the critical factor. The second debatable point concerns the methodology used to make a series of solutions to study the effect of divalent ions. Typically, solutions with a constant number of moles of salt are used; however, it is better to make a series with a constant ratio of equivalents of those salts. Moreover, it is plausible that the decreased voltage can be explained by the inherently lower Donnan potential of multi-charged ions and that increased resistance is caused by the fact that divalent ions—with a lower mobility there than the monovalent ions—occupy relatively much of the available space in the gel phase of the membrane. While both resistance and voltage play a decisive role in RED and probably also in other membrane processes like electrodialysis (ED), it is remarkable that there are so few publications that focus on measurements on individual membranes. The implications of these results is that research on the effect of divalent ions in RED, ED and similar processes needs to be more structured in the future. Relatively simple procedures can be developed for the determination of membrane resistance in solutions of mixtures of mono- and divalent salts. The same applies to determining the membrane potential. The challenge is to arrive at a standard method for equipment, methodology, and the composition of the test solutions.
Using Kinetic Modelling to Infer Adaptations in Saccharomyces cerevisiae Carbohydrate Storage Metabolism to Dynamic Substrate Conditions
Authors: Lao-Martil David , Verhagen Koen J. A. , Valdeira Caetano Ana H. , Pardijs Ilse H. , van Riel Natal A. W. , Wahl S. Aljoscha
Published: January 2023

Microbial metabolism is strongly dependent on the environmental conditions. While these can be well controlled under laboratory conditions, large-scale bioreactors are characterized by inhomogeneities and consequently dynamic conditions for the organisms. How Saccharomyces cerevisiae response to frequent perturbations in industrial bioreactors is still not understood mechanistically. To study the adjustments to prolonged dynamic conditions, we used published repeated substrate perturbation regime experimental data, extended it with proteomic measurements and used both for modelling approaches. Multiple types of data were combined; including quantitative metabolome, 13C enrichment and flux quantification data. Kinetic metabolic modelling was applied to study the relevant intracellular metabolic response dynamics. An existing model of yeast central carbon metabolism was extended, and different subsets of enzymatic kinetic constants were estimated. A novel parameter estimation pipeline based on combinatorial enzyme selection supplemented by regularization was developed to identify and predict the minimum enzyme and parameter adjustments from steady-state to dynamic substrate conditions. This approach predicted proteomic changes in hexose transport and phosphorylation reactions, which were additionally confirmed by proteome measurements. Nevertheless, the modelling also hints at a yet unknown kinetic or regulation phenomenon. Some intracellular fluxes could not be reproduced by mechanistic rate laws, including hexose transport and intracellular trehalase activity during substrate perturbation cycles.
Simultaneous Quantification of Serum Lipids and Their Association with Type 2 Diabetes Mellitus-Positive Hepatocellular Cancer
Authors: Yue Zhihong , Pei Lin , Meng Guangyan , Zhang Aimin , Li Meng , Jia Mei , Wang Hui , Cao Linlin
Published: January 2023

Type 2 diabetes mellitus (T2DM) has been recognized as one of the most important and independent risk factors for hepatocellular cancer (HCC). However, there is still a lack of ideal tumor markers for HCC detection in the T2DM population. Serum lipids have been revealed as potential tumor markers for HCC. In this study, our objective was to develop a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to detect several lipids including 8,15-dihydroxy-5,9,11,13-eicosatetraenoic acid (8,15-DiHETE), hexadecanedioic acid (HDA), 15-keto-13,14-dihydroprostaglandin A2 (DHK-PGA2), ricinoleic acid (RCL), octadecanedioic acid (OA) and 16-hydroxy hexadecanoic acid (16OHHA) in serum and explore their diagnostic potential for T2DM-positive [T2DM(+)] HCC. A robust LC-MS/MS method was established for the measurement of 8,15-DiHETE, HDA, DHK-PGA2, RCL, OA, and 16OHHA. The methodology validation was conducted, and the results suggested the reliability of this LC-MS/MS method for targeted lipids. Several serum lipids, including 8,15-DiHETE, HDA, DHK-PGA2, and OA were increased in T2DM(+) HCC patients. A biomarker signature that incorporated HDA, DHK-PGA2, and AFP was established and showed good diagnostic potential for T2DM(+) HCC, and the area under the ROC curve (AUC) was 0.87 for diagnosing T2DM(+) HCC from T2DM individuals. Additionally, the biomarker signature diagnosed small-size (AUC = 0.88) and early-stage (AUC = 0.79) tumors with high efficacy. Moreover, the biomarker signature could differentiate T2DM(+) HCC from other T2DM(+) tumors, including pancreatic, gastric and colorectal cancer (AUC = 0.88) as well. In conclusion, our study develops a novel tool for early diagnosis of T2DM(+) HCC in T2DM patients.
Changes in Lipoprotein Particles in the Blood Serum of Patients with Lichen Planus
Authors: Ilves Liis , Ottas Aigar , Raam Liisi , Zilmer Mihkel , Traks Tanel , Jaks Viljar , Kingo Külli
Published: January 2023

Lichen planus is a chronic inflammatory mucocutaneous disease that belongs to the group of papulosquamous skin diseases among diseases like psoriasis, a widely studied disease in dermatology. The aim of the study was to identify the changes between the blood sera of lichen planus patients and healthy controls to widen the knowledge about the metabolomic aspect of lichen planus and gain a better understanding about the pathophysiology of the disease. We used high-throughput nuclear magnetic resonance (NMR) spectroscopy to measure the levels of blood serum metabolites, lipoproteins and lipoprotein particles. Dyslipidemia has relatively recently been shown to be one of the comorbidities of lichen planus, but the changes in the components of lipoproteins have not been described yet. We found statistically significant changes in the concentrations of 16 markers regarding lipoproteins, which included the components of intermediate-density lipoproteins, low-density lipoproteins and large low-density lipoproteins. We propose that the detected changes may increase the risk for specific comorbidities (e.g., dyslipidemia) and resulting cardiovascular diseases, as the turnover and hepatic uptake of the altered/modified lipoprotein particles are disturbed.
The Contribution of Actinobacteria to the Degradation of Chlorinated Compounds: Variations in the Activity of Key Degradation Enzymes
Authors: Emelyanova Elena V. , Ramanaiah Sudarsu V. , Prisyazhnaya Nataliya V. , Shumkova Ekaterina S. , Plotnikova Elena G. , Wu Yonghong , Solyanikova Inna P.
Published: January 2023

Bacteria make a huge contribution to the purification of the environment from toxic stable pollutants of anthropogenic and natural origin due to the diversity of their enzyme systems. For example, the ability to decompose 3-chlorobenzoate (3CBA) by the four representative genera of Actinobacteria, such as Rhodococcus, Gordonia, Microbacterium, and Arthrobacter, was studied. In most cases, the formation of 4-chlorocatechol as the only key intermediate during the decomposition of 3CBA was observed. However, Rhodococcus opacus strain 1CP was an exception, whose cells decomposed 3CBA via both 3-chloro- and 4-chlorocatechol. The enzyme 3-Chlorobenzoate 1,2-dioxygenase (3CBDO) induced during the growth of these bacteria in the presence of 3CBA differed significantly in substrate specificity from the benzoate dioxygenases induced upon growth in the presence of benzoate. The R. opacus 6a strain was found to contain genes encoding chlorocatechol 1,2-dioxygenase, chloromuconate cycloisomerase, and dienelactone hydrolase, whose nucleotide sequence was 100% consistent with the sequences of the corresponding genes encoding the enzymes of the modified 4-chlorocatechol ortho-cleavage pathway of the strain R. opacus 1CP. However, the gene encoding chloromuconolactone dehalogenase (clcF) was not found in the representatives of the actinomycete genera, including Gordonia and Arthrobacter. A linear mega-plasmid carrying 3-chlorocatechol degradation genes remained stable after maintaining the R. opacus 1CP strain on an agar-rich medium for 25 years. In general, a similar plasmid was absent in actinobacteria of other genera, as well as in closely related species of R. opacus 6a.
Pepsin and Trypsin Treatment Combined with Carvacrol: An Efficient Strategy to Fight Pseudomonas aeruginosa and Enterococcus faecalis Biofilms
Authors: Mechmechani Samah , Gharsallaoui Adem , Karam Layal , EL Omari Khaled , Fadel Alexandre , Hamze Monzer , Chihib Nour-Eddine
Published: January 2023

Biofilms consist of microbial communities enclosed in a self-produced extracellular matrix which is mainly responsible of biofilm virulence. Targeting this matrix could be an effective strategy to control biofilms. In this work, we examined the efficacy of two proteolytic enzymes, pepsin and trypsin, to degrade P. aeruginosa and E. faecalis biofilms and their synergistic effect when combined with carvacrol. The minimum dispersive concentrations (MDCs) and the contact times of enzymes, as well as the minimal inhibitory concentrations (MICs) and contact times of carvacrol, were determined against biofilms grown on polystyrene surfaces. For biofilms grown on stainless steel surfaces, the combined pepsin or trypsin with carvacrol treatment showed more significant reduction of both biofilms compared with carvacrol treatment alone. This reduction was more substantial after sequential treatment of both enzymes, followed by carvacrol with the greatest reduction of 4.7 log CFU mL−1 (p < 0.05) for P. aeruginosa biofilm and 3.3 log CFU mL−1 (p < 0.05) for E. faecalis biofilm. Such improved efficiency was also obvious in the epifluorescence microscopy analysis. These findings demonstrate that the combined effect of the protease-dispersing activity and the carvacrol antimicrobial activity could be a prospective approach for controlling P. aeruginosa and E. faecalis biofilms.
Antiparasitic Activity of Hippeastrum Species and Synergistic Interaction between Montanine and Benznidazole against Trypanosoma cruzi
Authors: Piñeiro Mauricio , Ortiz Javier E. , Spina Zapata Renata M. , Barrera Patricia A. , Sosa Miguel A. , Roitman Germán , Bastida Jaume , Feresin Gabriela E.
Published: January 2023

Background: Hippeastrum species have a wide range of biological properties. In Argentina, this genus comprises ten widely distributed species. Purpose: To evaluate the antiparasitic and anticholinesterase activities and chemical profiles of seven Argentinean Hippeastrum species and determine the synergism between the major isolated alkaloid—montanine—and benznidazole in anti-Trypanosoma cruzi activity. Methods: The antiparasitic activity was evaluated through antiproliferative and viability assays against T. cruzi epimastigotes. Synergism assays were performed using the Chou–Talalay method. AChE and BuChE inhibitory activities were also assessed. The alkaloid composition was obtained using GC-MS analysis. Results: All extracts showed strong growth inhibition of T. cruzi epimastigote proliferation. The extracts from H. aglaiae, H. aulicum, and H. hybrid stand out for their potent and total growth inhibition, which was comparable to benznidazole. The H. reticulatum extract showed strong Acetylcholinesterase (AChE) inhibitory activities, while five species showed moderate Butyrylcholinesterase (BuChE) inhibition. Fifteen alkaloids were identified by means of GC-MS. Regarding the synergism assessment, the highest synergistic effect was obtained from the combination of montanine and benznidazole. Conclusion: Hippeastrum species bulb extracts from Argentina were shown to be a good source of antiparasitic alkaloids and cholinesterase inhibitors. The synergism between montanine and benznidazole emerges as a potential combination for future studies to treat Chagas disease.
Diabetes and SARS-CoV-2 Infection: The Potential Role of Antidiabetic Therapy in the Evolution of COVID-19
Authors: Pinchera Biagio , Schiano Moriello Nicola , Buonomo Antonio Riccardo , Di Filippo Isabella , Tanzillo Anastasia , Buzzo Giorgio , Villari Riccardo , Gentile Ivan ,   Federico II COVID Team
Published: January 2023

Diabetes mellitus represents one of the most frequent comorbidities among patients with COVID-19, constituting a risk factor for a more severe prognosis than that of non-diabetic patients. However, the pathophysiological mechanism underlying this unfavorable outcome is still not completely clear. The goal of our study was to evaluate the potential role of antidiabetic therapy in the evolution of COVID-19.
An Outlook on Dental Practices to Avoid the Oral Transmission of COVID-19
Authors: Alsulami Manal , Kattan Waad , Alsamadani Lama , Alahmari Ghadah , Al Juhani Wasan , Almabadi Maha
Published: January 2023

The oral microbiome plays an important role in the maintenance of immune homeostasis, whereas its association with SARS-CoV-2 infection remains under investigation. Since the oral path is one of the transmission routes for COVID-19, we attempt to show the relationship between the oral microbiome, COVID-19 infection, and oral hygiene. We highlight the importance of oral hygiene to control the infection, especially for ICU cases with COVID-19. Moreover, we present the current strategies adapted by in-person dental clinics to overcome the spread of COVID-19. New emerging policies and protocols suggested during the pandemic and their future implementation to minimize virus transmission are also summarized in this review.
How Do Lactobacilli Search and Find the Vagina?
Authors: Reid Gregor
Published: January 2023

With the advent of omics technology and the improved culturing of anaerobic microbes, there is a good understanding of the microorganisms present in a healthy and diseased vagina. This has led to the identification of a select few Lactobacillus species associated with health. However, the origin of these species and how they reach the vagina remains unclear, as does their timing of colonization. In an effort to create badly needed therapies for women, these gaps in knowledge need to be addressed.
Editorial for Special Issue “Sustainable Production of Metals for Low-Carbon Technologies”
Authors: Park Ilhwan , Silwamba Marthias
Published: January 2023

In 2015, 193 governments agreed to act on climate change by drastically reducing carbon dioxide (CO2) emissions as envisaged in the sustainable development goal (SDG) number 13 [...]
Molecular Liquids versus Ionic Liquids: The Interplay between Inter-Molecular and Intra-Molecular Hydrogen Bonding as Seen by Vaporisation Thermodynamics
Authors: Verevkin Sergey P. , Zaitsau Dzmitry H. , Ludwig Ralf
Published: January 2023

In this study, we determined the enthalpies of vaporisation for a suitable set of molecular and ionic liquids using modern techniques for vapour pressure measurements, such as the quartz crystal microbalance, thermogravimetric analysis (TGA), and gas chromatographic methods. This enabled us to measure reasonable vapour pressures, avoiding the problem of the decomposition of the ionic liquids at high temperatures. The enthalpies of vaporisation could be further analysed by applying the well-known “group contribution” methods for molecular liquids and the “centerpiece” method for ionic liquids. This combined approach allowed for the dissection of the enthalpies of vaporisation into different types of molecular interaction, including hydrogen bonding and the dispersion interaction in the liquid phase, without knowing the existing species in both the liquid and gas phases.
The Potential Value of Debarking Water as a Source of Polyphenolic Compounds for the Specialty Chemicals Sector
Authors: Peeters Kelly , Esakkimuthu Esakkiammal Sudha , Tavzes Črtomir , Kramberger Katja , Miklavčič Višnjevec Ana
Published: January 2023

Forest-based industries produce huge quantities of bark during their primary processing activities. In Nordic pulp and paper industries, where a wet debarking process is used for bark removal, toxic debarking water and bark press water are produced as a by-product. However, polyphenols represent an important fraction of the debarking water and bark press water. These polyphenolic compounds are of commercial interest in chemical specialty sectors since polyphenols have been proven to have diverse health benefits, and after collecting them from waste sources, they can act as alternatives to oil-based chemicals. Determining the economic potential of polyphenolic compounds, identifying their molecular structure, and determining the antioxidant capacity of these compounds present in debarking water and bark can support the identification of their potential applications. The results show that water extractions from bark have a lower efficiency than (partial) alcoholic extractions. Nevertheless, a considerable amount of low-molecular polyphenolic compounds, which are of interest for high-end applications, was found in all extracts. Bark press water has a highly versatile range of polyphenolic compounds and showed some antioxidant activity, making it a great source for the collection of polyphenolic compounds, in contrast to debarking water, which had a much lower polyphenolic content and low antioxidant activity.
Identification of Secondary Metabolites of Interest in Pleurotus djamor Using Agave tequilana Bagasse
Authors: Cruz-Moreno Byanka A. , Pérez Ana Angélica Feregrino , García-Trejo Juan Fernando , Pérez-García Sergio Alfonso , Gutiérrez-Antonio Claudia
Published: January 2023

Agro-industrial residues represent more than 60% of organic wastes worldwide, which could be used to generate other by-products or to be incorporated into other production chains. For example, bagasse is a waste from the tequila industry in Mexico that could be implemented for mushroom cultivation. Additionally, the substrate influences the growth, development, and production of secondary metabolites of fungi. This work presents a comparative experiment that studies the metabolite production in Pleurotus djamor mushrooms on agave bagasse and barley straw (traditional substrate). The biological efficiency (BE), yield, phenolics and flavonoids, antioxidant capacity, tannins, and the identification of low molecular weight metabolites were evaluated. Five treatments were proposed according to the following mixtures of agave bagasse: barley straw: T1 (1:0), T2 (3:1), T3 (1:1), T4 (1:3), and T5 (0:1). T2 had the highest yield (13.39 ± 3.23%), BE (56.7 ± 13.71%), and flavonoids (44.25 mg rutin equivalent (RE)/g); T3 obtained the highest phenol content (230.27 mg GAE/g); and T1 the highest tannins content (0.23 mg (+) catechin equivalent (CE)/g). Finally, T1 and T5 are the ones that present the greatest number of primary metabolites, including hydroxycitric acid, 2-deoxy-D-galactose, D-mannose, paromomycin, palmitic acid, pyrrole, mannitol, and DL arabinose, while in T2, T3, and T4 only two chemical compounds were found present (palmitic acid and pyrrole in T2, silicic acid and pyrrole in T3 and 2-deoxy-D-galactose and quinoline in T4). The cultivation substrate influences the concentration of bioactive molecules in the fruiting bodies of P. djamor. Additionally, P. djamor’s degradation of agave bagasse residue generates a potential application for agro-industrial residue management at a low cost.
Synthesis, DFT Studies, Molecular Docking and Biological Activity Evaluation of Thiazole-Sulfonamide Derivatives as Potent Alzheimer’s Inhibitors
Authors: Khan Shoaib , Ullah Hayat , Taha Muhammad , Rahim Fazal , Sarfraz Maliha , Iqbal Rashid , Iqbal Naveed , Hussain Rafaqat , Ali Shah Syed Adnan , Ayub Khurshid , Albalawi Marzough Aziz , Abdelaziz Mahmoud A. , Alatawi Fatema Suliman , Khan Khalid Mohammed
Published: January 2023

Alzheimer’s disease is a major public brain condition that has resulted in many deaths, as revealed by the World Health Organization (WHO). Conventional Alzheimer’s treatments such as chemotherapy, surgery, and radiotherapy are not very effective and are usually associated with several adverse effects. Therefore, it is necessary to find a new therapeutic approach that completely treats Alzheimer’s disease without many side effects. In this research project, we report the synthesis and biological activities of some new thiazole-bearing sulfonamide analogs (1–21) as potent anti-Alzheimer’s agents. Suitable characterization techniques were employed, and the density functional theory (DFT) computational approach, as well as in-silico molecular modeling, has been employed to assess the electronic properties and anti-Alzheimer’s potency of the analogs. All analogs exhibited a varied degree of inhibitory potential, but analog 1 was found to have excellent potency (IC50 = 0.10 ± 0.05 µM for AChE) and (IC50 = 0.20 ± 0.050 µM for BuChE) as compared to the reference drug donepezil (IC50 = 2.16 ± 0.12 µM and 4.5 ± 0.11 µM). The structure-activity relationship was established, and it mainly depends upon the nature, position, number, and electron-donating/-withdrawing effects of the substituent/s on the phenyl rings.
Molecular Docking of Bacterial Protein Modulators and Pharmacotherapeutics of Carica papaya Leaves as a Promising Therapy for Sepsis: Synchronising In Silico and In Vitro Studies
Authors: Usmani Juveria , Kausar Hina , Akbar Saleem , Sartaj Ali , Mir Showkat R. , Hassan Mohammed Jaseem , Sharma Manju , Ahmad Razi , Rashid Summaya , Ansari Mohd Nazam
Published: January 2023

Sepsis is a serious health concern globally, which necessitates understanding the root cause of infection for the prevention of proliferation inside the host’s body. Phytochemicals present in plants exhibit antibacterial and anti-proliferative properties stipulated for sepsis treatment. The aim of the study was to determine the potential role of Carica papaya leaf extract for sepsis treatment in silico and in vitro. We selected two phytochemical compounds, carpaine and quercetin, and docked them with bacterial proteins, heat shock protein (PDB ID: 4PO2), surfactant protein D (PDB ID: 1PW9), and lactobacillus bacterial protein (PDB ID: 4MKS) against imipenem and cyclophosphamide. Quercetin showed the strongest interaction with 1PW9 and 4MKS proteins. The leaves were extracted using ethanol, methanol, and water through Soxhlet extraction. Total flavonoid content, DPPH assay, HPTLC, and FTIR were performed. In vitro cytotoxicity of ethanol extract was screened via MTT assay on the J774 cell line. Ethanol extract (EE) possessed the maximum number of phytocomponents, the highest amount of flavonoid content, and the maximum antioxidant activity compared to other extracts. FTIR analysis confirmed the presence of N-H, O-H, C-H, C=O, C=C, and C-Cl functional groups in ethanol extract. Cell viability was highest (100%) at 25 µg/mL of EE. The present study demonstrated that the papaya leaves possessed antibacterial and cytotoxic activity against sepsis infection.
Capacitive NO2 Detection Using CVD Graphene-Based Device
Authors: Ju Wonbin , Lee Sungbae
Published: January 2023

A graphene-based capacitive NO2 sensing device was developed by utilizing the quantum capacitance effect. We have used a graphene field-effect transistor (G-FET) device whose geometrical capacitance is enhanced by incorporating an aluminum back-gate electrode with a naturally oxidized aluminum surface as an insulating layer. When the graphene, the top-side of the device, is exposed to NO2, the quantum capacitance of graphene and, thus, the measured capacitance of the device, changed in accordance with NO2 concentrations ranging from 1–100 parts per million (ppm). The operational principle of the proposed system is also explained with the changes in gate voltage-dependent capacitance of the G-FET exposed to various concentrations of NO2. Further analyses regarding carrier density changes and potential variances under various concentrations of NO2 are also presented to strengthen the argument. The results demonstrate the feasibility of capacitive NO2 sensing using graphene and the operational principle of capacitive NO2 sensing.
Biocompatibility Evaluation of Carbon Nanohorns in Bone Tissues
Authors: Ueda Katsuya , Ma Chuang , Izumiya Makoto , Kuroda Chika , Ishida Haruka , Uemura Takeshi , Saito Naoto , Aoki Kaoru , Haniu Hisao
Published: January 2023

With the advent of nanotechnology, the use of nanoparticles as drug delivery system (DDS) has attracted great interest. We aimed to apply carbon nanohorns (CNHs) as DDS in the development of new treatments for bone diseases. We evaluated the in vitro and in vivo cellular responses of CNHs in bone-related cells compared with carbon blacks (CBs), which are similar in particle size but differ in surface and structural morphologies. Although in vitro experiments revealed that both CNHs and CBs were incorporated into the lysosomes of RAW264-induced osteoclast-like cells (OCs) and MC3T3-E1 osteoblast-like cells (OBs), no severe cytotoxicity was observed. CNHs reduced the tartrate-resistant acid phosphatase activity and expression of the differentiation marker genes in OCs at noncytotoxic concentrations, whereas the alkaline phosphatase activity and differentiation of OBs increased. Under calcification of OBs, CNHs increased the number of calcified nodules and were intra- and extracellularly incorporated into calcified vesicles to form crystal nuclei. The in vivo experiments showed significant promotion of bone regeneration in the CNH group alone, with localized CNHs being found in the bone matrix and lacunae. The suppression of OCs and promotion of OBs suggested that CNHs may be effective against bone diseases and could be applied as DDS.
A Fusion of Molecular Imprinting Technology and Siloxane Chemistry: A Way to Advanced Hybrid Nanomaterials
Authors: Woźnica Marcin , Sobiech Monika , Luliński Piotr
Published: January 2023

Molecular imprinting technology is a well-known strategy to synthesize materials with a predetermined specificity. For fifty years, the “classical” approach assumed the creation of “memory sites” in the organic polymer matrix by a template molecule that interacts with the functional monomer prior to the polymerization and template removal. However, the phenomenon of a material’s “memory” provided by the “footprint” of the chemical entity was first observed on silica-based materials nearly a century ago. Through the years, molecular imprinting technology has attracted the attention of many scientists. Different forms of molecularly imprinted materials, even on the nanoscale, were elaborated, predominantly using organic polymers to induce the “memory”. This field has expanded quickly in recent years, providing versatile tools for the separation or detection of numerous chemical compounds or even macromolecules. In this review, we would like to emphasize the role of the molecular imprinting process in the formation of highly specific siloxane-based nanomaterials. The distinct chemistry of siloxanes provides an opportunity for the facile functionalization of the surfaces of nanomaterials, enabling us to introduce additional properties and providing a way for vast applications such as detectors or separators. It also allows for catalyzing chemical reactions providing microreactors to facilitate organic synthesis. Finally, it determines the properties of siloxanes such as biocompatibility, which opens the way to applications in drug delivery and nanomedicine. Thus, a brief outlook on the chemistry of siloxanes prior to the discussion of the current state of the art of siloxane-based imprinted nanomaterials will be provided. Those aspects will be presented in the context of practical applications in various areas of chemistry and medicine. Finally, a brief outlook of future perspectives for the field will be pointed out.
Astaxanthin Supplemented with High-Intensity Functional Training Decreases Adipokines Levels and Cardiovascular Risk Factors in Men with Obesity
Authors: Saeidi Ayoub , Nouri-Habashi Akbar , Razi Omid , Ataeinosrat Ali , Rahmani Hiwa , Mollabashi Shirin Shirzad , Bagherzadeh-Rahmani Behnam , Aghdam Shahin Mahmoudi , Khalajzadeh Leila , Al Kiyumi Maisa Hamed , Hackney Anthony C. , Laher Ismail , Heinrich Katie M. , Zouhal Hassane
Published: January 2023

The aim of this study was to investigate the effects of 12 weeks of high-intensity training with astaxanthin supplementation on adipokine levels, insulin resistance and lipid profiles in males with obesity. Sixty-eight males with obesity were randomly stratified into four groups of seventeen subjects each: control group (CG), supplement group (SG), training group (TG), and training plus supplement group (TSG). Participants underwent 12 weeks of treatment with astaxanthin or placebo (20 mg/d capsule daily). The training protocol consisted of 36 sessions of high-intensity functional training (HIFT), 60 min/sessions, and three sessions/week. Metabolic profiles, body composition, anthropometrical measurements, cardio-respiratory indices and adipokine [Cq1/TNF-related protein 9 and 2 (CTRP9 and CTRP2) levels, and growth differentiation factors 8 and 15 (GDF8 and GDF15)] were measured. There were significant differences for all indicators between the groups (p < 0.05). Post-hoc analysis indicated that the levels of CTRP9, CTRP2, and GDF8 were different from CG (p < 0.05), although levels of GDF15 were similar to CG (p > 0.05). Levels of GDF8 were similar in the SG and TG groups (p > 0.05), with reductions of GDF15 levels in both training groups (p < 0.05). A total of 12 weeks of astaxanthin supplementation and exercise training decreased adipokines levels, body composition (weight, %fat), anthropometrical factors (BMI), and improved lipid and metabolic profiles. These benefits were greater for men with obesity in the TSG group.
HSP27 Interacts with Nonstructural Proteins of Porcine Reproductive and Respiratory Syndrome Virus and Promotes Viral Replication
Authors: Song Chunhui , Liu Hanze , Cao Zhi , Shan Hu , Zhang Qiaoya
Published: January 2023

Heat shock protein 27 (HSP27) is a multifunctional protein and belongs to the small HSP family. It has been shown that HSP27 is involved in viral replication as a cellular chaperone, but the function of HSP27 during porcine reproductive and respiratory syndrome virus (PRRSV) infections remains unexplored. Here, we found that PRRSV replication can induce HSP27 expression and phosphorylation in vitro. HSP27 overexpression promoted PRRSV replication, whereas its knockdown reduced PRRSV proliferation. Additionally, suppressing HSP27 phosphorylation reduced PRRSV replication and the level of viral double-stranded RNA (dsRNA), a marker of the viral replication and transcription complexes (RTCs). Furthermore, HSP27 can interact with multiple viral nonstructural proteins (nsps), including nsp1α, nsp1β, nsp5, nsp9, nsp11 and nsp12. Suppressing the phosphorylation of HSP27 almost completely disrupted its interaction with nsp1β and nsp12. Altogether, our study revealed that HSP27 plays an important role in PRRSV replication.
Quantitative Risk Evaluation of Antimicrobial-Resistant Vibrio parahaemolyticus Isolated from Farmed Grey Mullets in Singapore
Authors: Ong Hong Ming Glendon , Zhong Yang , Hu Cheng Cheng , Ong Kar Hui , Khor Wei Ching , Schlundt Joergen , Aung Kyaw Thu
Published: January 2023

Vibrio parahaemolyticus is a causative pathogen for gastroenteritis involving the consumption of undercooked or raw seafood. However, there is a paucity of data regarding the quantitative detection of this pathogen in finfish, while no study reported the enumeration of haemolytic antimicrobial-resistant (AMR) V. parahaemolyticus. In this study, ampicillin-, penicillin G- and tetracycline-resistant and non-AMR haemolytic V. parahaemolyticus isolates were monitored and quantified in grey mullet samples reared locally from different premises within the food chain (farm and retail). Occurrence data for haemolytic V. parahaemolyticus were 13/45 (29%) in farm fish samples, 2/6 (one third) from farm water samples and 27/45 (60%) from retail fish samples. Microbial loads for haemolytic V. parahaemolyticus microbial loads ranged from 1.9 to 4.1 Log CFU/g in fish samples and 2.0 to 3.0 Log CFU/g in farm water samples. AMR risk assessments (ARRAs) for both the full farm-to-home and partial retail-to-home chains in the risk modelling framework were conducted, specifically for ampicillin, penicillin G, tetracycline and haemolytic (non-AMR) scenarios. The haemolytic ARRA predicted an average probability of illness of 2.9 × 10−4 and 4.5 × 10−5 per serving for the farm-to-home and retail-to-home chains, respectively, translating to 57 and 148 cases annually. The ratios of the average probability of illness per year for the three ARRAs to the haemolytic ARRA were 1.1 × 10−2 and 3.0 × 10−4 (ampicillin and penicillin G, respectively) for the farm-to-home chain and 1.3, 1.6 and 0.4 (ampicillin, penicillin G and tetracycline, respectively) for the retail-to-home chain. Sensitivity analysis showed that the initial concentrations of haemolytic V. parahaemolyticus in the gills and intestines of the fish and the cooking and washing of the fish cavity were the major variables influencing risk outputs in all modelled ARRAs. The findings of this study are useful for relevant stakeholders to make informed decisions regarding risk management to improve overall food safety.
Chlamydia Peritonitis Mimicking Juvenile Carcinomatous Peritonitis Diagnosed by Exploratory Laparoscopy: A Case Report
Authors: Nishida Haruka , Takahashi Yuko , Takehara Kohei , Yatsuki Keita , Ichinose Takayuki , Ishida Tsuyoshi , Hiraike Haruko , Sasajima Yuko , Nagasaka Kazunori
Published: January 2023

Chlamydia trachomatis infections may occur in multiple organs, including the lungs, lymph nodes, peritoneal cavity, and genitourinary systems. This disease results in significant ascites, the swelling of lymph nodes, and elevated tumor markers (CA125), sometimes mimicking an ovarian malignancy. At our hospital, we often perform examination laparoscopic surgery in cases of suspected gynecologic cancers before initial treatment. In this paper, we report the case of a 19-year-old woman who came to our hospital because of an ovarian tumor and ascites. There was no history of sexual intercourse (self-reported). We suspected ovarian cancer from image inspections, so we performed laparoscopic surgery for diagnosis. The final pathological diagnosis was acute-to-chronic inflammation of the bilateral fallopian tubes, and a cytologic examination of the ascites was negative for malignant cells. The C. trachomatis antigen was positive on vaginal examination after the operation. Based on this result, we diagnosed this patient with C. trachomatis infection. Chlamydia peritonitis should be a differential diagnosis for cancer peritonitis in juvenile patients with abnormal ascites. Exploratory laparoscopy should help confirm the pathological diagnosis.
Excretory/Secretory Proteome of Females and Males of the Hookworm Ancylostoma ceylanicum
Authors: Uzoechi Samuel C. , Rosa Bruce A. , Singh Kumar Sachin , Choi Young-Jun , Bracken Bethany K. , Brindley Paul J. , Townsend R. Reid , Sprung Robert , Zhan Bin , Bottazzi Maria-Elena , Hawdon John M. , Wong Yide , Loukas Alex , Djuranovic Sergej , Mitreva Makedonka
Published: January 2023

The dynamic host-parasite mechanisms underlying hookworm infection establishment and maintenance in mammalian hosts remain poorly understood but are primarily mediated by hookworm’s excretory/secretory products (ESPs), which have a wide spectrum of biological functions. We used ultra-high performance mass spectrometry to comprehensively profile and compare female and male ESPs from the zoonotic human hookworm Ancylostoma ceylanicum, which is a natural parasite of dogs, cats, and humans. We improved the genome annotation, decreasing the number of protein-coding genes by 49% while improving completeness from 92 to 96%. Compared to the previous genome annotation, we detected 11% and 10% more spectra in female and male ESPs, respectively, using this improved version, identifying a total of 795 ESPs (70% in both sexes, with the remaining sex-specific). Using functional databases (KEGG, GO and Interpro), common and sex-specific enriched functions were identified. Comparisons with the exclusively human-infective hookworm Necator americanus identified species-specific and conserved ESPs. This is the first study identifying ESPs from female and male A. ceylanicum. The findings provide a deeper understanding of hookworm protein functions that assure long-term host survival and facilitate future engineering of transgenic hookworms and analysis of regulatory elements mediating the high-level expression of ESPs. Furthermore, the findings expand the list of potential vaccine and diagnostic targets and identify biologics that can be explored for anti-inflammatory potential.
Birth Outcomes of Anticancer Drug Prescriptions during Pregnancy: A Case Series from a Japanese Claims Database
Authors: Tajima Kentaro , Ishikawa Tomofumi , Tsuchiya Masami , Kikuchi Masafumi , Obara Taku , Mano Nariyasu
Published: January 2023

We aimed to evaluate the adverse birth outcomes of anticancer drug prescription during pregnancy using a Japanese claims database from 2005 to 2019. We applied validated claims-based algorithms to identify pregnant women with birth outcomes, and evaluated drug prescription during pregnancy. The causal relationship between anticancer drugs and adverse birth outcomes was evaluated using the Council for International Organizations of Medical Sciences Working Group VI criteria. Thirteen women with anticancer drugs prescription during pregnancy were identified (mean age: 34.6 years). Atrial/ventricular septal defect was observed in one infant after exposure to cyclophosphamide and doxorubicin for breast cancer in the second and third trimesters. One woman on several anticancer drugs (cyclophosphamide, cytarabine, daunorubicin, l-asparaginase, methotrexate, nelarabine, and vincristine) for acute lymphoblastic leukemia, one on imatinib for chronic myeloid leukemia, and one on cisplatin and fluorouracil for cervical cancer had miscarriages after exposure in the first trimester. A relationship between those anticancer drugs and miscarriage could not be ruled out, while no relationship was identified regarding the atrial/ventricular septal defect considering the period of exposure and organogenesis. Our results suggest increased risk of miscarriage with the use of several anticancer drugs such as methotrexate, imatinib, cisplatin, and fluorouracil in the first trimester.
Nanotechnology-Based RNA Vaccines: Fundamentals, Advantages and Challenges
Authors: Pozharov Vitaly P. , Minko Tamara
Published: January 2023

Over the past decades, many drugs based on the use of nanotechnology and nucleic acids have been developed. However, until recently, most of them remained at the stage of pre-clinical development and testing and did not find their way to the clinic. In our opinion, the main reason for this situation lies in the enormous complexity of the development and industrial production of such formulations leading to their high cost. The development of nanotechnology-based drugs requires the participation of scientists from many and completely different specialties including Pharmaceutical Sciences, Medicine, Engineering, Drug Delivery, Chemistry, Molecular Biology, Physiology and so on. Nevertheless, emergence of coronavirus and new vaccines based on nanotechnology has shown the high efficiency of this approach. Effective development of vaccines based on the use of nucleic acids and nanomedicine requires an understanding of a wide range of principles including mechanisms of immune responses, nucleic acid functions, nanotechnology and vaccinations. In this regard, the purpose of the current review is to recall the basic principles of the work of the immune system, vaccination, nanotechnology and drug delivery in terms of the development and production of vaccines based on both nanotechnology and the use of nucleic acids.
Advances in the Application of Preclinical Models in Photodynamic Therapy for Tumor: A Narrative Review
Authors: Yu Rong , Maswikiti Ewetse Paul , Yu Yang , Gao Lei , Ma Chenhui , Ma Huanhuan , Deng Xiaobo , Wang Na , Wang Bofang , Chen Hao
Published: January 2023

Photodynamic therapy (PDT) is a non-invasive laser light local treatment that has been utilized in the management of a wide variety of solid tumors. Moreover, the evaluation of efficacy, adverse reactions, the development of new photosensitizers and the latest therapeutic regimens are inseparable from the preliminary exploration in preclinical studies. Therefore, our aim was to better comprehend the characteristics and limitations of these models and to provide a reference for related research. Methods: We searched the databases, including PubMed, Web of Science and Scopus for the past 25 years of original research articles on the feasibility of PDT in tumor treatment based on preclinical experiments and animal models. We provided insights into inclusion and exclusion criteria and ultimately selected 40 articles for data synthesis. Results: After summarizing and comparing the methods and results of these studies, the experimental model selection map was drawn. There are 7 main preclinical models, which are used for different research objectives according to their characteristics. Conclusions: Based on this narrative review, preclinical experimental models are crucial to the development and promotion of PDT for tumors. The traditional animal models have some limitations, and the emergence of organoids may be a promising new insight.