bluuebunny/crossref_metadata_2025 huggingface dataset:
Biocontrol Potential of the New Codling Moth Granulovirus (CpGV) Strains
Authors: Tsygichko Aleksandra A. , Asaturova Anzhela M. , Lakhova Tatiana N. , Klimenko Alexandra I. , Lashin Sergey A. , Vasiliev Gennady V.
Published: September 2024

The use of CpGV strains as the basis for bioinsecticides is an effective and safe way to control Cydia pomonella. The research is aimed at the identification and study of new CpGV strains. Objects of identification and bioinformatic analysis: 18 CpGV strains. Sequencing was carried out on a NextSeq550. Genome assembly and annotation were carried out using Spades, Samtools 1.9, MinYS, Pilon, Gfinisher, Quast, and Prokka. Comparative genomic analysis was carried out in relation to the reference genome present in the «Madex Tween» strain-producer (biological standard) according to the average nucleotide identity (ANI) criterion. The presence/absence of IAP, cathepsin, MMP, and chitinase in the genetic sequences of the strains was determined using simply phylogeny. Entomopathogenic activity was assessed against C. pomonella according to the criterion of biological efficacy. Thus, molecular genetic identification revealed that 18 CpGV strains belong to a genus of Betabaculovirus. For all the strains under study ANI values of 99% or more were obtained, and the presence of the cathepsin, chitinase, IAP, and MMP genes was noted. The strains BZR GV 1, BZR GV 3, BZR GV 7, BZR GV 10, and BZR GV L-8 showed the maximum biological efficacy: 100% on the 15th day of observation. Strains BZR GV 4, BZR GV 8, and BZR GV 13 showed efficacy at the level of the «Madex Tween» preparation: 89.5% on the 15th day of observation. The strains with the highest mortality rate of the host insect were identified: BZR GV 9, BZR GV 10, BZR GV L-6, and BZR GV L-8.
Synthesis and Characterization of 3,4-Bis[3(2-azidoethoxy)furazan-4-yl]furoxan (DAeTF): A Novel Low-Melting Insensitive Energetic Material
Authors: Wu Yang , Liu Yuezhou , Gao Fulei , Chen Bin , Lu Tingting , Wang Yinglei
Published: September 2024

The synthesis and characterization of low-melting-point insensitive energetic materials are crucial due to their increasing applications in melt–cast explosives. In this work, a furazan-derived energetic compound, 3,4-bis[3(2-azidoethoxy)furazan-4-yl]furoxan (DAeTF), exhibiting insensitive and high-energy characteristics, is rationally designed and synthesized. The structure of DAeTF is characterized by nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, elemental analysis, mass spectrometry, and single-crystal X-ray diffraction. The thermal properties of DAeTF are investigated using differential scanning calorimetry, in situ FTIR spectroscopy and thermogravimetric-differential scanning calorimetry–Fourier transform infrared–mass spectrometry and thermal decomposition mechanism was elucidated in combination with bond energy calculations. The detonation performance of DAeTF is predicted by the EXPLO5 program. The results indicate that DAeTF has thermal stability (Td = 251.7 °C), high energy level (D = 7270 m/s) and significant insensitivity (IS = 60 J). Additionally, its relatively low melting point (Tm = 60.5 °C) facilitates processing and loading. These characteristics indicate that DAeTF is a promising candidate as an insensitive melt–cast explosive in future applications.
The Use of Organoclays as Excipient for Metformin Delivery: Experimental and Computational Study
Authors: Omrani Sondes , Gamoudi Safa , Viseras César , Moussaoui Younes , Sainz-Díaz C. Ignacio
Published: September 2024

This work combines experimental and computational modeling studies for the preparation of a composite of metformin and an organoclay, examining the advantages of a Tunisian clay used for drug delivery applications. The clay mineral studied is a montmorillonite-like smectite (Sm-Na), and the organoclay derivative (HDTMA-Sm) was used as a drug carrier for metformin hydrochloride (MET). In order to assess the MET loading into the clays, these materials were characterized by means of cation exchange capacity assessment, specific surface area measurement, and with the techniques of X-ray diffraction (XRD), differential scanning calorimetry, X-ray fluorescence spectroscopy, and Fourier-transformed infrared spectroscopy. Computational molecular modeling studies showed the surface adsorption process, identifying the clay–drug interactions through hydrogen bonds, and assessing electrostatic interactions for the hybrid MET/Sm-Na and hydrophobic interactions and cation exchange for the hybrid MET/HDTMA-Sm. The results show that the clays (Sm-Na and HDTMA-Sm) are capable of adsorbing MET, reaching a maximum load of 12.42 and 21.97 %, respectively. The adsorption isotherms were fitted by the Freundlich model, indicating heterogeneous adsorption of the studied adsorbate–adsorbent system, and they followed pseudo-second-order kinetics. The calculations of ΔGº indicate the spontaneous and reversible nature of the adsorption. The calculation of ΔH° indicates physical adsorption for the purified clay (Sm-Na) and chemical adsorption for the modified clay (HDTMA-Sm). The release of intercalated MET was studied in media simulating gastric and intestinal fluids, revealing that the purified clay (Sm-Na) and the modified organoclay (HDTMA-Sm) can be used as carriers in controlled drug delivery in future clinical applications. The molecular modeling studies confirmed the experimental phenomena, showing that the main adsorption mechanism is the cation exchange process between proton and MET cations into the interlayer space.
The Expression of Cannabinoid and Cannabinoid-Related Receptors on the Gustatory Cells of the Piglet Tongue
Authors: Zamith Cunha Rodrigo , Grilli Ester , Piva Andrea , Delprete Cecilia , Franciosi Cecilia , Caprini Marco , Chiocchetti Roberto
Published: September 2024

The gustatory system is responsible for detecting and evaluating the palatability of the various chemicals present in food and beverages. Taste bud cells, located primarily on the tongue, communicate with the gustatory sensory neurons by means of neurochemical signals, transmitting taste information to the brain. It has also been found that the endocannabinoid system (ECS) may modulate food intake and palatability, and that taste bud cells express cannabinoid receptors. The purpose of this study was to investigate the expression of cannabinoid and cannabinoid-related receptors in the gustatory cells of the papillae vallatae and foliatae of ten piglets. Specific antibodies against the cannabinoid receptors (CB1R and CB2R), G protein-coupled receptor 55 (GPR55), transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) were applied on cryosections of lingual tissue; the lingual tissue was also processed using Western blot analysis. Cannabinoid and cannabinoid-related receptors were found to be expressed in the taste bud cells and the surrounding epithelial cells. The extra-papillary epithelium also showed strong immunolabeling for these receptors. The results showed that these receptors were present in both the taste bud cells and the extra-gustatory epithelial cells, indicating their potential role in taste perception and chemesthesis. These findings contributed to understanding the complex interactions between cannabinoids and the gustatory system, highlighting the role of the ECS within taste perception and its potential use in animal production in order to enhance food intake.
Testing the Capability of Embedding-Based Alignments on the GST Superfamily Classification: The Role of Protein Length
Authors: Vazzana Gabriele , Savojardo Castrense , Martelli Pier Luigi , Casadio Rita
Published: September 2024

In order to shed light on the usage of protein language model-based alignment procedures, we attempted the classification of Glutathione S-transferases (GST; EC 2.5.1.18) and compared our results with the ARBA/UNI rule-based annotation in UniProt. GST is a protein superfamily involved in cellular detoxification from harmful xenobiotics and endobiotics, widely distributed in prokaryotes and eukaryotes. What is particularly interesting is that the superfamily is characterized by different classes, comprising proteins from different taxa that can act in different cell locations (cytosolic, mitochondrial and microsomal compartments) with different folds and different levels of sequence identity with remote homologs. For this reason, GST functional annotation in a specific class is problematic: unless a structure is released, the protein can be classified only on the basis of sequence similarity, which excludes the annotation of remote homologs. Here, we adopt an embedding-based alignment to classify 15,061 GST proteins automatically annotated by the UniProt-ARBA/UNI rules. Embedding is based on the Meta ESM2-15b protein language. The embedding-based alignment reaches more than a 99% rate of perfect matching with the UniProt automatic procedure. Data analysis indicates that 46% of the UniProt automatically classified proteins do not conserve the typical length of canonical GSTs, whose structure is known. Therefore, 46% of the classified proteins do not conserve the template/s structure required for their family classification. Our approach finds that 41% of 64,207 GST UniProt proteins not yet assigned to any class can be classified consistently with the structural template length.
Molecular Interactions Governing the Rat Aryl Hydrocarbon Receptor Activities of Polycyclic Aromatic Compounds and Predictive Model Development
Authors: Jin Lingmin , Chen Bangyu , Ma Guangcai , Wei Xiaoxuan , Yu Haiying
Published: September 2024

Polycyclic aromatic compounds (PACs) exhibit rat aryl hydrocarbon receptor (rAhR) activities, leading to diverse biological or toxic effects. In this study, the key amino residues and molecular interactions that govern the rAhR activity of PACs were investigated using in silico strategies. The homology model of rAhR was first docked with 90 PACs to yield complexes, and the results of the molecular dynamics simulations of 16 typical complexes showed that the binding energies of the complexes range from −7.37 to −26.39 kcal/mol. The major contribution to the molecular interaction comes from van der Waals forces, and Pro295 and Arg316 become the key residues involved in most complexes. Two QSAR models were further developed to predict the rAhR activity of PACs (in terms of log IEQ for PACs without halogen substitutions and log%-TCDD-max for halogenated PACs). Both models have good predictive ability, robustness, and extrapolation ability. Molecular polarizability, electronegativity, size, and nucleophilicity are identified as the important factors affecting the rAhR activity of PACs. The developed models could be employed to predict the rAhR activity of other reactive PACs. This work provides insight into the mechanisms and interactions of the rAhR activity of PACs and assists in the assessment of their fate and risk in organisms.
A Review of the Occurrence and Recovery of Rare Earth Elements from Electronic Waste
Authors: Liang Binjun , Gu Jihan , Zeng Xiangrong , Yuan Weiquan , Rao Mingjun , Xiao Bin , Hu Haixiang
Published: September 2024

Electronic waste (e-waste) contains valuable rare earth elements (REEs) essential for various high-tech applications, making their recovery crucial for sustainable resource management. This review provides an overview of the occurrence of REEs in e-waste and discusses both conventional and emerging green technologies for their recovery. Conventional methods include physical separation, hydrometallurgy, and pyrometallurgy, while innovative approaches such as bioleaching, supercritical fluid extraction, ionic liquid extraction, and lanmodulin-derived peptides offer improved environmental sustainability and efficiency. The article presents case studies on the extraction of REEs from waste permanent magnets and fluorescent powders, highlighting the specific processes involved. Future research should focus on developing eco-friendly leaching agents, separation materials, and process optimization to enhance the overall sustainability and efficiency of REE recovery from e-waste, addressing both resource recovery and environmental concerns effectively.
Three New Ent-Kaurane Diterpenes with Antibacterial Activity from Sigesbeckia orientalis
Authors: Zhou Zhong-Shun , Wang Zhao-Jie , Tian Bei , Zhu Yan-Yan , Wei Mei-Zhen , Zhao Yun-Li , Luo Xiao-Dong
Published: September 2024

Three novel ent-kaurane diterpenes, namely sigesbeckin A–C (1–3), in conjunction with eight previously identified analogues (4–11), were isolated from Sigesbeckia orientalis. Their chemical structures were resolved through multiple spectroscopic analyses. All compounds were assessed for antimicrobial bioactivity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) strains. In particular, compounds 1 and 5 demonstrated moderate efficacy, with MIC values of 64 μg/mL. Moreover, compounds 3, 5, and 11 were found to synergize with doxorubicin hydrochloride (DOX) and vancomycin (VAN) against MRSA and VRE. The aforementioned findings offer valuable insights for the development of novel alternatives to antibiotics, which can effectively tackle the escalating issue of antibiotic resistance.
Catechol/m-Phenylenediamine Modified Sol–Gel Coating with Enhanced Long-Lasting Anticorrosion Performance on 3003 Al Alloy
Authors: Huang Keqi , Huang Xin , Wang Liyan , Tu Sifan , Yang Zi , Guo Honglei , Lei Bing , Feng Zhiyuan , Meng Guozhe
Published: September 2024

Aluminum alloys, characterized by their low density and high mechanical strength, are widely applied in the manufacturing sector. However, the application of aluminum alloys in extreme environments presents severe corrosion challenges. Sol–gel organic coating techniques have garnered significant attention due to their excellent stability, barrier properties, and cost-effectiveness, as well as their simpler processing. Nevertheless, conventional sol–gel coatings are unable to withstand the corrosive effects of high-chloride and high-halide ion environments such as marine conditions, owing to their inherent structural defects. Therefore, this study proposes the utilization of a simple method to synthesize catechol (CA) and meta-phenylenediamine (MPD)-derived catecholamine compounds to modify sol–gel coatings. Surface characteristics of the modified coatings were analyzed using Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible (UV-Vis) spectroscopy, scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). The thickness of the modified coating was approximately 6.8 μm. The CA/MPD-modified substance effectively densifies the sol–gel coating, enhancing its corrosion protection performance. A 3.5 wt% NaCl solution was used to simulate a marine environment, and electrochemical impedance spectroscopy (EIS) was conducted using an electrochemical workstation to evaluate the coating’s protective properties over a long-term period. The results indicate that the modified coating provides protection for 3003 aluminum alloy for a minimum of 30 days under corrosive conditions, outperforming unmodified sol–gel coatings in terms of corrosion resistance.
Correction: Ortelli et al. Design of TiO2-Based Hybrid Systems with Multifunctional Properties. Molecules 2023, 28, 1863
Authors: Ortelli Simona , Vespignani Maurizio , Zanoni Ilaria , Blosi Magda , Vineis Claudia , Piancastelli Andreana , Baldi Giovanni , Dami Valentina , Albonetti Stefania , Costa Anna Luisa
Published: September 2024

There was an error in the original publication [...]
Hats Off to Modeling! Profiling Early Synthetic Dyes on Historic Woolen Samples with ATR-FTIR Spectroscopy and Multivariate Curve Resolution–Alternating Least Square Algorithm
Authors: Forleo Tiziana , Giannossa Lorena Carla , De Juan Capdevila Anna , Lagioia Giovanni , Mangone Annarosa
Published: September 2024

This research focuses on analyzing wool samples dyed with synthetic dyes from the early 20th century. A methodology to identify and distinguish wool fibers dyed with azo, triphenylmethane, and xanthene dyes, which are no longer in use, using the ATR-FTIR spectra, is presented. Firstly, the dataset was subjected to PCA, which revealed the similarities and differences among the samples, illustrating a distribution pattern based on dye classes. MCR-ALS was employed to extract the spectral profiles of the dyed fibers, thereby enhancing the efficacy of the analytical techniques and extracting the comprehensive information from a single instrument. The combination of ATR-FTIR spectroscopy with chemometric methods, such as PCA and MCR-ALS, has proven to be an effective strategy for identifying and differentiating wool fibers dyed with early azo, triphenylmethane, and xanthene dyes. This approach has demonstrated particular effectiveness in enabling rapid analysis without requiring sampling or pretreatment. Moreover, the analysis is supported by thorough bibliographic research on these no longer used colorants. In order to maximize the potential of non-destructive spectroscopic techniques, such as ATR-FTIR, the approach used has proven to be crucial. This study underscores how chemometric techniques expand the capabilities of spectroscopy, extracting extensive information from a single instrument and aligning with the goals of cultural heritage analysis.
Aging Processes of Working Memory in Different Modalities
Authors: Levi Ohad , Heled Eyal
Published: September 2024

Background: Working memory (WM) involves temporarily storing and manipulating information. Research on the impact of aging on WM has shown inconsistent results regarding the decline in visual and verbal WM, with a lack of studies on tactile WM. This study aimed to assess the effects of aging on WM across verbal, visuospatial, and tactile modalities using span tasks of forward (storage) and backward (manipulation) stages. Methods: A total of 130 participants, divided into four age groups of 20–29, 60–69, 70–79, and 80–89, completed the Digit, Visuospatial, and Tactual Spans. Performance was analyzed using a 3 (Task) × 4 (Group) × 2 (Stage) mixed design repeated measures ANOVA. Results: The analysis revealed significant main effects for modality (p < 0.001, ηp2 = 0.15), age (p < 0.001, ηp2 = 0.48), and stage (p < 0.001, ηp2 = 0.30). Digit Span outperformed the other modalities, while Tactual Span showed the worst performance. Additionally, task performance declined with age, and the forward stage was superior to the backward stage. Interaction effects indicated that Digit Span was less affected by aging compared to the Visuospatial and Tactual Spans (p = 0.004, ηp2 = 0.07). Post hoc analyses further revealed that the Digit Span consistently outperformed the other modalities in both stages, with more pronounced differences observed in the forward stage. Conclusions: Verbal WM is more resilient to aging compared to the other modalities while tactile WM declines with age in a manner similar to verbal and visuospatial WM, suggesting a modality-specific impact of aging on WM.
Effectiveness of the CATCH (Coordinated Approach to Child’s Health) Rainbow Program in Elementary Schools for Change in Fruit and Vegetable Intake
Authors: Muzaffar Henna , Valinskas Ashley , Werner Ashley , Collins Nora , Regan Melanie
Published: September 2024

Background: Nutrition, cooking, and gardening lessons individually and together have been shown to increase fruit and vegetable (FV) consumption in school-aged children. The CATCH Rainbow program incorporated nutrition education, cooking, and gardening lessons aimed at increasing FV consumption in elementary school-aged children and assessed changes in participants’ BMI, self-reported FV consumption, and skin carotenoid levels at baseline and post-intervention. Methods: Two-hundred and twenty-five 4th and 5th graders (mean age: 9.8 years and 52% male participants) at Genoa Elementary School participated in six cooking and six gardening sessions between September 2021 and May 2022. Each nutrition education session was 25 min long, paired with either hands-on cooking activities or gardening skills. At baseline and post-intervention, participants’ height and weight were assessed with a stadiometer/scale, and skin carotenoid measurement was taken by a Veggie Meter® (Longevity Link Corporation (Salt Lake City, UT, USA)). Students also completed the Block Food Frequency Questionnaire to self-report FV consumption at both time points. Focus groups were conducted with children at the end of the program for qualitative feedback. Results: paired samples T-test and regression analysis results indicate no significant decrease in BMI or significant increase in skin carotenoid scores from pre- to post-intervention. However, though not significant, there was an increase in self-reported FV intake by 0.4 servings. Additionally, the qualitative feedback was positive, as children mentioned benefits of healthy eating and expressed enjoyment for growing, cooking, and tasting fruits and vegetables. Conclusions: Results from this study can be used to guide future cooking and gardening programs for elementary school children. Time of the year when implementing these programs and collecting data may impact study outcomes due to seasonal variations in fruit and vegetable intake.
Memory T-Cells Contribute to Calcium Release from Bones during Lactation in Mice
Authors: Wu Di , Cline-Smith Anna , Chrisler Brady , Lubeck Brittani , Perla Ajit , Banerjee Sumona , Fan Ida , Aurora Rajeev
Published: September 2024

Objective: Milk production during lactation places a high demand for calcium that is fulfilled both from maternal bone resorption and diet. While it is known that mammary gland-derived PTHrP drives bone resorption during lactation, the impact of postpartum estrogen loss on bone has been unclear. Methods: We used a case-control study design to test the effect of estrogen loss in lactating mice. Results: In the present study, we show for the first time that estrogen loss during lactation activates memory T-cells (TM) to produce TNFα and IL-17A to aid in bone resorption and calcium release. Our studies reveal a new mechanism for the release of calcium from bone postpartum. The findings provide several new insights. First, the immune system plays a critical role in milk production postpartum. Second, evolutionarily, the pathway serves the physiological purpose of increasing bone resorption to release calcium for breastmilk production postpartum but becomes maladaptive postmenopause, leading to osteoporosis. Finally, these results highlight the crosstalk between the brain–bone–breast–endocrine axis and the immune system during lactation.
The Impact of Flavonoid Supplementation on Serum Oxidative Stress Levels Measured via D-ROMs Test in the General Population: The PREVES-FLAVON Retrospective Observational Study
Authors: Di Lorenzo Giuseppe , Verde Antonio , Scafuri Luca , Costabile Ferdinando , Caputo Vincenza , Di Trolio Rossella , Strianese Oriana , Montanaro Vittorino , Crocetto Felice , Del Giudice Francesco , Baio Raffaele , Tufano Antonio , Verze Paolo , Calabrese Alessia Nunzia , Buonerba Carlo
Published: September 2024

Background: Oxidative stress has emerged as a key contributor to numerous NCDs (non-communicable diseases), including cardiovascular diseases, cancer, and diabetes. This study aims to explore the potential of targeted interventions to mitigate oxidative stress as part of a primary prevention strategy. Methods: The study included 32 healthy participants (11 men, 21 women) aged 45–65 who completed both the initial and follow-up assessments of the Healthy Days Initiative, a community-based wellness program organized by the non-profit Associazione O.R.A. ETS. Through blood analysis, vital sign assessment, lifestyle questionnaires, and individualized recommendations, participants received guidance on improving their health and reducing disease risk. The initiative also offered the opportunity for participants to consume a flavonoid supplement containing quercitrin, rutin, and hesperidin, with the goal of reducing oxidative stress. Participants who opted for supplementation were instructed to take 1–2 tablets daily for two weeks. Data collected included demographic information, anthropometric measurements, vital signs, dietary and lifestyle habits, medical history, WHO-5 Well-Being Index scores, and blood parameters. Results: Significant reductions were observed in glucose levels (from 82 to 74.5 mg/dL), reactive oxygen metabolites (d-ROMs) (from 394.5 to 365.5 U.CARR), and systolic blood pressure (from 133 to 122 mmHg) after the two-week flavonoid intervention. Most participants (26/31) reported no side effects, and the majority (30/31) expressed a willingness to continue using a product combination of quercitrin, rutin, and hesperidin or a similar product long-term. Conclusions: While limited in scope and duration, the PREVES-FLAVON study contributes valuable insights to the growing body of evidence suggesting that flavonoid supplementation may play a significant role in reducing risk factors associated with NCDs in primary prevention settings. By targeting novel risk factors such as oxidative stress, this intervention holds promise for mitigating the global burden of NCDs and promoting healthy aging.
An Overview of Apple Varieties and the Importance of Apple Consumption in the Prevention of Non-Communicable Diseases—A Narrative Review
Authors: Mierczak Karina , Garus-Pakowska Anna
Published: September 2024

Non-communicable diseases such as cardiovascular diseases, cancers, diabetes, and asthma are increasingly common due to factors like industrialization, urbanization, fast-paced life, stress, sedentary lifestyle, and unbalanced diet in the 21st century. These chronic conditions are a global epidemic, being among the top causes of death worldwide. Preventing these diseases through a nutritious diet is crucial, and scientific studies suggest that appropriate fruit intake, particularly apples, can lower the risk of various health issues. Apples, rich in bioactive compounds, vitamins, minerals, and dietary fiber, offer numerous health benefits. Regular consumption of apples helps reduce the risk of atherosclerosis, coronary artery disease, heart attacks, and diabetes, and also provides anti-asthmatic and anti-allergic effects. Apples aid in detoxification, improve digestion, enhance skin, hair, and nail health, and offer protection against cancers, Alzheimer’s, and Parkinson’s disease. Apples have been a dietary staple for centuries, consumed in various forms like juices, sauces, and ciders. The reviewed article emphasizes the health benefits of apples, highlighting their role in preventing civilization diseases. It also discusses the characteristics of common apple varieties and the impact of thermal processing on their nutritional content.
Taraxacum Mongolicum Polysaccharides Reverses Mice Obesity via Activation of AKT/mTOR Pathway
Authors: Yue Xiaoyu , Yu Shilong , Luan Yue , Wang Jianpeng , Zhao Junxing , Zhang Mu , Wang Qin
Published: September 2024

Background/Objectives: The global prevalence of obesity and its associated health complications represent significant public health concerns. Plant polysaccharides have been demonstrated to possess a range of beneficial pharmacological effects. This experiment was designed to elucidate the mechanisms of dietary Taraxacum mongolicum polysaccharides involved in the regulation of obesity and fat browning. Methods: Male C57BL/6J mice were randomly divided into three groups: a control group, a high-fat diet (HFD) group, and an HFD group supplemented with 0.3% TMPs. The mice were fed their respective diets for 10 weeks, after which their body weight, food consumption, and serum lipid levels were measured. Histological analysis was performed to assess lipid deposition in adipose tissue and liver. Western blot was used to assess the expression of proteins involved in the AKT/mTOR pathway. Results: The results show that compared with the HFD group, the TMP supplementation group’s body-weight gain (12.17 ± 1.77) significantly decreased. TMPs also reduced serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol. Histological analysis showed that TMPs reduced lipid deposition in both adipose tissue and the liver. Conclusions: In addition, TMPs increased the expression of phosphorylated AKT and the mechanistic target of rapamycin (mTOR), indicating that TMPs exert their beneficial effects on lipid metabolism via the AKT/mTOR pathway.
Pharmacology of P2X Receptors and Their Possible Therapeutic Potential in Obesity and Diabetes
Authors: Cabral-García Guillermo A. , Cruz-Muñoz José R. , Valdez-Morales Eduardo E. , Barajas-Espinosa Alma , Liñán-Rico Andrómeda , Guerrero-Alba Raquel
Published: September 2024

The role of P2X ionotropic receptors in the behavior of purinergic signaling on pathophysiological processes has been widely studied. In recent years, the important participation of P2X receptors in physiological and pathological processes, such as energy metabolism, characteristic inflammatory responses of the immune system, and nociceptive activity in response to pain stimuli, has been noted. Here, we explore the molecular characteristics of the P2X receptors and the use of the different agonist and antagonist agents recently described, focusing on their potential as new therapeutic targets in the treatment of diseases with emphasis on obesity, diabetes, and some of the complications derived from these pathologies.
Prominent Neuroprotective Potential of Indole-2-N-methylpropargylamine: High Affinity and Irreversible Inhibition Efficiency towards Monoamine Oxidase B Revealed by Computational Scaffold Analysis
Authors: Vrban Lucija , Vianello Robert
Published: September 2024

Background: Monoamine oxidases (MAO) are flavoenzymes that metabolize a range of brain neurotransmitters, whose dysregulation is closely associated with the development of various neurological disorders. This is why MAOs have been the central target in pharmacological interventions for neurodegeneration for more than 60 years. Still, existing drugs only address symptoms and not the cause of the disease, which underlines the need to develop more efficient inhibitors without adverse effects. Methods: Our drug design strategy relied on docking 25 organic scaffolds to MAO-B, which were extracted from the ChEMBL20 database with the highest cumulative counts of unique member compounds and bioactivity assays. The most promising candidates were substituted with the inactivating propargylamine group, while further affinity adjustment was made by its N-methylation. A total of 46 propargylamines were submitted to the docking and molecular dynamics simulations, while the best binders underwent mechanistic DFT analysis that confirmed the hydride abstraction mechanism of the covalent inhibition reaction. Results: We identified indole-2-propargylamine 4fH and indole-2-N-methylpropargylamine 4fMe as superior MAO-B binders over the clinical drugs rasagiline and selegiline. DFT calculations highlighted 4fMe as more potent over selegiline, evident in a reduced kinetic requirement (ΔΔG‡ = −2.5 kcal mol−1) and an improved reaction exergonicity (ΔΔGR = −4.3 kcal mol−1), together with its higher binding affinity, consistently determined by docking (ΔΔGBIND = −0.1 kcal mol−1) and MM-PBSA analysis (ΔΔGBIND = −1.5 kcal mol−1). Conclusions: Our findings strongly advocate 4fMe as an excellent drug candidate, whose synthesis and biological evaluation are highly recommended. Also, our results reveal the structural determinants that influenced the affinity and inhibition rates that should cooperate when designing further MAO inhibitors, which are of utmost significance and urgency with the increasing prevalence of brain diseases.
The Role of Mitochondrial Homeostasis in Mesenchymal Stem Cell Therapy—Potential Implications in the Treatment of Osteogenesis Imperfecta
Authors: Guo Qingling , Zhai Qiming , Ji Ping
Published: September 2024

Osteogenesis imperfecta (OI) is a hereditary disorder characterized by bones that are fragile and prone to breaking. The efficacy of existing therapies for OI is limited, and they are associated with potentially harmful side effects. OI is primarily due to a mutation of collagen type I and hence impairs bone regeneration. Mesenchymal stem cell (MSC) therapy is an attractive strategy to take advantage of the potential benefits of these multipotent stem cells to address the underlying molecular defects of OI by differentiating osteoblasts, paracrine effects, or immunomodulation. The maintenance of mitochondrial homeostasis is an essential component for improving the curative efficacy of MSCs in OI by affecting the differentiation, signaling, and immunomodulatory functions of MSCs. In this review, we highlight the MSC-based therapy pathway in OI and introduce the MSC regulation mechanism by mitochondrial homeostasis. Strategies aiming to modulate the metabolism and reduce the oxidative stress, as well as innovative strategies based on the use of compounds (resveratrol, NAD+, α-KG), antioxidants, and nanomaterials, are analyzed. These findings may enable the development of new strategies for the treatment of OI, ultimately resulting in improved patient outcomes.
Glucose-Lowering Drugs and Primary Prevention of Chronic Kidney Disease in Type 2 Diabetes Patients: A Real-World Primary Care Study
Authors: Rodríguez-Miguel Antonio , Fernández-Fernández Beatriz , Ortiz Alberto , Gil Miguel , Rodríguez-Martín Sara , Ruiz-Hurtado Gema , Fernández-Antón Encarnación , Ruilope Luis M. , de Abajo Francisco J.
Published: September 2024

Background/Objectives: The burden of chronic kidney disease (CKD) is increasing, as is the prevalence of type 2 diabetes mellitus (T2DM). Post-hoc analyses of clinical trials support that sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptors agonists (GLP-1RAs) prevent CKD in T2DM patients. Methods: We used the Spanish primary care database BIFAP to perform a retrospective cohort study with a nested case-control analysis to assess the incidence, risk factors, and the effect of glucose-lowering drugs (GLDs) on the primary prevention of CKD. Results: From a cohort of 515,701 T2DM subjects (2.75 million person-years), we found 89,075 incident CKD cases, yielding an overall incidence rate (95%CI) of 324.3 (322.1–326.5) per 10,000 person-years. In the nested case–control analysis, gout, hyperuricemia, and hyperkalemia were the factors showing the highest AORs. Long-term users (≥3 years) of GLP1-RAs and SGLT-2i, compared to other GLDs, showed a decreased risk for CKD (AOR = 0.85; 95%CI: 0.73–0.99 and AOR = 0.89; 95%CI: 0.74–1.08, respectively), and for incident CKD at KDIGO stages G3-G5 (AOR = 0.72; 95%CI: 0.56–0.94 and AOR = 0.64; 95%CI: 0.46–0.91, respectively). Conclusions: In a real-world primary care setting, the long-term use of GLP-1RAs and SGLT-2i, but not other GLDs, appeared to decrease the risk of incident CKD in T2DM, supporting a role in primary prevention of CKD.
Comparative Biochemical and Pharmacodynamic Analyses of Asarum heterotropoides Fr. Schmidt var. Mandshuricum (Maxim) Kitag and Asarum sieboldii Miq var. Seoulense Nakai Roots
Authors: Li Huiling , Wang Zhiqing , Zhao Guangyuan , Wang Yanhong , Xu Xuanwei , Wang Yingping , Zhang Ze , Wang Guanghui
Published: September 2024

Background:Asarum heterotropoides and Asarum sieboldii are commonly used in traditional Chinese medicine. However, little is known about how they differ in terms of essential oil (EO) and ethanol extract (EE) content and composition. Moreover, the effect of various geographical locations on the essential oil (EO), ethanol extract (EE), and asarinin content of different Asarum samples remains unknown. We tested four root-drying methods, i.e., soil removal and shade drying (P1), water washing and shade drying (P2), and water washing and drying at 30 °C (P3) and 40 °C (P4). We used LC-MS and GC-MS to investigate these differences. We also investigated the pharmacodynamic effects of EO and EE. Results: Overall, the EO, EE and asarinin contents of the analysed samples were 19.21–51.53 μL.g−1, 20.00–45.00 μL.g−1, and 1.268–2.591 mg.g−1, respectively. P1 treatment yielded the lowest volatile oil content compared to the other three treatments. GC-MS analysis revealed 78 EO components. Among the six major EO components, eucarvone, 3,5-dimethoxytoluene, and methyl eugenol were higher in A. heterotropoides than in A. sieboldii. However, the latter had a higher myristicin content. LC-MS analysis identified 888 EE components in roots and leaves of A. heterotropoides and A. sieboldii; 317 differentially accumulated metabolites were identified. EO and EE showed a dose-dependent reduction in the degree of swelling and an increase in the inhibition rate of drug concentration on acetic acid writhing in mice. Asarum EO proved to be more effective than EE in the pharmacodynamic study. Conclusions: We conclude that Asarum species show inter- and intra-specific differences in EO and EE content and composition, which may influence the pharmacodynamics of Asarum root extracts.
Silk Fibroin Nanofibers: Advancements in Bioactive Dressings through Electrospinning Technology for Diabetic Wound Healing
Authors: Aldahish Afaf , Shanmugasundaram Nirenjen , Vasudevan Rajalakshimi , Alqahtani Taha , Alqahtani Saud , Mohammad Asiri Ahmad , Devanandan Praveen , Thamaraikani Tamilanban , Vellapandian Chitra , Jayasankar Narayanan
Published: September 2024

Background: Non-healing diabetic wounds represent a significant clinical challenge globally, necessitating innovative approaches in drug delivery to enhance wound healing. Understanding the pathogenesis of these wounds is crucial for developing effective treatments. Bioactive dressings and polymeric nanofibers have emerged as promising modalities, with silk biomaterials gaining attention for their unique properties in diabetic wound healing. Purpose of Review: The purpose of this review is to examine the challenges and innovations in treating non-healing diabetic wounds, emphasizing the global burden and the need for effective solutions. This review explores the complex mechanisms of wound healing in diabetes and evaluates the therapeutic potential of bioactive dressings and polymeric nanofibers. Special focus is given to the application of silk biomaterials, particularly silk fibroin, for wound healing, detailing their properties, mechanisms, and clinical translation. This review also describes various nanofiber fabrication methods, especially electrospinning technology, and presents existing evidence on the effectiveness of electrospun silk fibroin formulations. Recent Findings: Recent advancements highlight the potential of silk biomaterials in diabetic wound healing, owing to their biocompatibility, mechanical strength, and controlled drug release properties. Electrospun silk fibroin-based formulations have shown promising results in preclinical and clinical studies, demonstrating accelerated wound closure and tissue regeneration. Summary: Non-healing diabetic wounds present a significant healthcare burden globally, necessitating innovative therapeutic strategies. Bioactive dressings and polymeric nanofibers, particularly silk-based formulations fabricated through electrospinning, offer promising avenues for enhancing diabetic wound healing. Further research is warranted to optimize formulation parameters and validate efficacy in larger clinical trials.
Plant Metabolomics: The Future of Anticancer Drug Discovery
Authors: Dabbousy Ranin , Rima Mohamad , Roufayel Rabih , Rahal Mohamad , Legros Christian , Sabatier Jean-Marc , Fajloun Ziad
Published: September 2024

Drug development from medicinal plants constitutes an important strategy for finding natural anticancer therapies. While several plant secondary metabolites with potential antitumor activities have been identified, well-defined mechanisms of action remained uncovered. In fact, studies of medicinal plants have often focused on the genome, transcriptome, and proteome, dismissing the relevance of the metabolome for discovering effective plant-based drugs. Metabolomics has gained huge interest in cancer research as it facilitates the identification of potential anticancer metabolites and uncovers the metabolomic alterations that occur in cancer cells in response to treatment. This holds great promise for investigating the mode of action of target metabolites. Although metabolomics has made significant contributions to drug discovery, research in this area is still ongoing. In this review, we emphasize the significance of plant metabolomics in anticancer research, which continues to be a potential technique for the development of anticancer drugs in spite of all the challenges encountered. As well, we provide insights into the essential elements required for performing effective metabolomics analyses.
Multifaceted Evaluation of Inhibitors of Anti-Apoptotic Proteins in Head and Neck Cancer: Insights from In Vitro, In Vivo, and Clinical Studies (Review)
Authors: Krzykawski Kamil , Kubina Robert , Wendlocha Dominika , Sarna Robert , Mielczarek-Palacz Aleksandra
Published: September 2024

This paper presents a multifaceted assessment of inhibitors of anti-apoptotic proteins (IAPs) in the context of head and neck squamous cell carcinoma (HNSCC). The article discusses the results of in vitro, in vivo, and clinical studies, highlighting the significance of IAPs in the resistance of cancer cells to apoptosis, which is a key factor hindering effective treatment. The main apoptosis pathways, including the intrinsic and extrinsic pathways, and the role of IAPs in their regulation, are presented. The study’s findings suggest that targeting IAPs with novel therapies may offer clinical benefits in the treatment of advanced HNSCC, especially in cases resistant to conventional treatment methods. These conclusions underscore the need for further research to develop more effective and safer therapeutic strategies.
A Modified Cell-Penetrating Peptide Enhances Insulin and Oxytocin Delivery across an RPMI 2650 Nasal Epithelial Cell Barrier In Vitro
Authors: Wong Sara , Brown Alexander D. , Abrahams Abigail B. , Nurzak An Nisaa , Eltaher Hoda M. , Sykes David A. , Veprintsev Dmitry B. , Fone Kevin C. F. , Dixon James E. , King Madeleine V.
Published: September 2024

Background/Objectives: Peptide-based treatments represent an expanding area and require innovative approaches to enhance bioavailability. Combination with cell-penetrating peptides (CPPs) is an attractive strategy to improve non-invasive delivery across nasal epithelial barriers for systemic and direct nose-to-brain transport. We previously developed a modified CPP system termed Glycosaminoglycan-binding Enhanced Transduction (GET) that improves insulin delivery across gastrointestinal epithelium. It contains a membrane docking sequence to promote cellular interactions (P21), a cationic polyarginine domain to stimulate uptake (8R) and an endosomal escaping sequence to maximize availability for onward distribution (LK15). It is synthesized as a single 44-residue peptide (P21-LK15-8R; PLR). Methods: The current research used in vitro assays for a novel exploration of PLR’s ability to improve the transport of two contrasting peptides, insulin (51 residues, net negative charge) and oxytocin (9 residues, weak positive charge) across an RPMI 2650 human nasal epithelial cell barrier cultured at the air–liquid interface. Results: PLR enhanced insulin transcytosis over a 6 h period by 7.8-fold when used at a 2:1 molar ratio of insulin/PLR (p < 0.0001 versus insulin alone). Enhanced oxytocin transcytosis (5-fold) occurred with a 1:10 ratio of oytocin/PLR (p < 0.01). Importantly, these were independent of any impact on transepithelial electrical resistance (TEER) or cell viability (p > 0.05). Conclusions: We advocate the continued evaluation of insulin–PLR and oxytocin–PLR formulations, including longer-term assessments of ciliotoxicity and cytotoxicity in vitro followed by in vivo assessments of systemic and nose-to-brain delivery.
Capped Plasmonic Gold and Silver Nanoparticles with Porphyrins for Potential Use as Anticancer Agents—A Review
Authors: Hlapisi Nthabeleng , Songca Sandile P. , Ajibade Peter A.
Published: September 2024

Photothermal therapy (PTT) and photodynamic therapy (PDT) are potential cancer treatment methods that are minimally invasive with high specificity for malignant cells. Emerging research has concentrated on the application of metal nanoparticles encapsulated in porphyrin and their derivatives to improve the efficacy of these treatments. Gold and silver nanoparticles have distinct optical properties and biocompatibility, which makes them efficient materials for PDT and PTT. Conjugation of these nanoparticles with porphyrin derivatives increases their light absorption and singlet oxygen generation that create a synergistic effect that increases phototoxicity against cancer cells. Porphyrin encapsulation with gold or silver nanoparticles improves their solubility, stability, and targeted tumor delivery. This paper provides comprehensive review on the design, functionalization, and uses of plasmonic silver and gold nanoparticles in biomedicine and how they can be conjugated with porphyrins for synergistic therapeutic effects. Furthermore, it investigates this dual-modal therapy’s potential advantages and disadvantages and offers perspectives for future prospects. The possibility of developing gold, silver, and porphyrin nanotechnology-enabled biomedicine for combination therapy is also examined.
Development of Quercetin Solid Dispersion-Loaded Dissolving Microneedles and In Vitro Investigation of Their Anti-Melanoma Activities
Authors: Khuanekkaphan Monsicha , Netsomboon Kesinee , Fristiohady Adryan , Asasutjarit Rathapon
Published: September 2024

Background: Melanoma is a skin cancer that requires early treatment to prevent metastasis. In particular, the superficial spreading melanoma, excisional surgery with local administration of anti-cancer drugs via microneedles is currently considered a potential combination therapy. Quercetin is a natural flavonoid having activities against melanoma cells. Unfortunately, the therapeutic effect is limited by its poor water solubility. Objectives: This study aimed to develop formulations of solid dispersion-loaded dissolving microneedles (SD-DMNs) of quercetin and to investigate their in vitro activities against melanoma cells. Methods: Quercetin solid dispersions (Q-SDs) were prepared using polyvinylpyrrolidone K30 (PVP) via a solvent technique. The optimized Q-SD was selected for preparing Q-SD-loaded dissolving microneedles (Q-SD-DMNs) using a mold casting method. Results: Q-SDs had higher water solubility than that of quercetin by 5–10 times depending on the ratio of quercetin-to-PVP. The presence of quercetin in the Q-SD and Q-SD-DMN were in an amorphous form. The obtained Q-SD-DMNs had pyramid-shaped microneedles. Their strength depended on the compositions, i.e., ratios of hyaluronic acid-to-sodium carboxymethylcellulose and the content of Q-SD. An optimized Q-SD-DMN increased the in vitro skin permeation of quercetin compared to that of microneedles containing quercetin (without being processed). From the molecular investigations, the optimized Q-SD-DMN reduced the viability of the A375 cells (melanoma cells) through the induction of cell apoptosis. It suppressed Bcl-2 gene expression and led to a lower content of Bcl-2 in the cells. Conclusions: The optimized Q-SD-DMN has a potential for use in further in vivo studies as a synergistic method of melanoma treatment.
Correction: Ibarra et al. Selective Photo-Assisted Eradication of Triple-Negative Breast Cancer Cells through Aptamer Decoration of Doped Conjugated Polymer Nanoparticles. Pharmaceutics 2022, 14, 626
Authors: Ibarra Luis Exequiel , Camorani Simona , Agnello Lisa , Pedone Emilia , Pirone Luciano , Chesta Carlos Alberto , Palacios Rodrigo Emiliano , Fedele Monica , Cerchia Laura
Published: September 2024

In the original publication [...]