bluuebunny/crossref_metadata_2025 huggingface dataset:
Determining the Photoelectrical Behavior and Photocatalytic Activity of an h-YMnO3 New Type of Obelisk-like Perovskite in the Degradation of Malachite Green Dye
Authors: López-Alvarez Miguel Ángel , Silva-Jara Jorge Manuel , Silva-Galindo Jazmín Guadalupe , Reyes-Becerril Martha , Velázquez-Carriles Carlos Arnulfo , Macías-Rodríguez María Esther , Macías-Lamas Adriana Macaria , García-Ramírez Mario Alberto , López de Alba Carlos Alberto , Reynoso-García César Alberto
Published: May 2023

YMnO3 is a P-type semiconductor with a perovskite-type structure (ABO3). It presents two crystalline systems: rhombohedral and hexagonal, the latter being the most stable and studied. In the hexagonal system, Mn3+ ions are coordinated by five oxygen ions forming a trigonal bipyramid, and the Y3+ ions are coordinated by five oxygen ions. This arrangement favors its ferroelectric and ferromagnetic properties, which have been widely studied since 1963. However, applications based on their optical properties have yet to be explored. This work evaluates the photoelectric response and the photocatalytic activity of yttrium manganite in visible spectrum wavelengths. To conduct this, a rod-obelisk-shaped yttrium manganite with a reduced indirect bandgap value of 1.43 eV in its hexagonal phase was synthesized through the precipitation method. The synthesized yttrium manganite was elucidated by solid-state techniques, such as DRX, XPS, and UV-vis. It was non-toxic as shown by the 100% leukocyte viability of mice BALB/c.
Visualization and Comparison of the Level of Apurinic/Apyrimidinic Endonuclease 1 in Live Normal/Cancerous and Neuron Cells with a Fluorescent Nanoprobe
Authors: Lu Peng , Cao Xiangjian , Zheng Jinghui , Sun Ying , Tang Ziyu , Zhao Meiping
Published: May 2023

As a major apurinic/apyrimidinic endonuclease and a redox signaling protein in human cells, APE1 plays a crucial role in cellular function and survival. The relationship between alterations of APE1 expression and subcellular localization and the initiation, development and treatment of various cancers has received extensive attention. However, comparing the in-vivo activity of APE1 in normal and cancerous breast live cells remains challenging due to the low efficiency of commonly used liposome transfection methods in delivering DNA substrate probes into human normal breast epithelial cells (MCF-10A). In this work, we develop a DNA/RNA hybrid-based small magnetic fluorescent nanoprobe (25 ± 3 nm) that can be taken up by various live cells under magnetic transfection. The D0/R-nanoprobe demonstrates an outstanding specificity toward APE1 and strong resistance to the cellular background interference. Using this nanoprobe, we are not only able to visualize the intracellular activity of APE1 in breast ductal carcinoma (MCF-7) live cells, but also demonstrate the APE1 activity in MCF-10A live cells for the first time. The method is then extended to observe the changes in APE1 levels in highly metabolically active neuroendocrine cells under normal conditions and severe attacks by reactive oxygen species in real-time. The fluorescent nanoprobe provides a useful tool for studying the dynamic changes of intracellular APE1 in normal or cancerous live cells. It also displays the potential for visible and controllable release of miRNA drugs within live cells for therapeutic purposes.
Green Aromatic Epoxidation with an Iron Porphyrin Catalyst for One-Pot Functionalization of Renewable Xylene, Quinoline, and Acridine
Authors: Corrêa Gabriela A. , Rebelo Susana L. H. , de Castro Baltazar
Published: May 2023

Sustainable functionalization of renewable aromatics is a key step to supply our present needs for specialty chemicals and pursuing the transition to a circular, fossil-free economy. In the present work, three typically stable aromatic compounds, representative of products abundantly obtainable from biomass or recycling processes, were functionalized in one-pot oxidation reactions at room temperature, using H2O2 as a green oxidant and ethanol as a green solvent in the presence of a highly electron withdrawing iron porphyrin catalyst. The results show unusual initial epoxidation of the aromatic ring by the green catalytic system. The epoxides were isolated or evolved through rearrangement, ring opening by nucleophiles, and oxidation. Acridine was oxidized to mono- and di-oxides in the peripheral ring: 1:2-epoxy-1,2-dihydroacridine and anti-1:2,3:4-diepoxy-1,2,3,4-tetrahydroacridine, with TON of 285. o-Xylene was oxidized to 4-hydroxy-3,4-dimethylcyclohexa-2,5-dienone, an attractive building block for synthesis, and 3,4-dimethylphenol as an intermediate, with TON of 237. Quinoline was directly functionalized to 4-quinolone or 3-substituted-4-quinolones (3-ethoxy-4-quinolone or 3-hydroxy-4-quinolone) and corresponding hydroxy-tautomers, with TON of 61.
Hillock Related Degradation Mechanism for AlGaN-Based UVC LEDs
Authors: Chen Juntong , Liu Jianxun , Huang Yingnan , Liu Ruisen , Dai Yayu , Tang Leming , Chen Zheng , Sun Xiujian , Liu Chenshu , Zhang Shuming , Sun Qian , Feng Meixin , Xu Qiming , Yang Hui
Published: May 2023

Heteroepitaxial growth of high Al-content AlGaN often results in a high density of threading dislocations and surface hexagonal hillocks, which degrade the performance and reliability of AlGaN-based UVC light emitting diodes (LEDs). In this study, the degradation mechanism and impurity/defect behavior of UVC LEDs in relation to the hexagonal hillocks have been studied in detail. It was found that the early degradation of UVC LEDs is primarily caused by electron leakage. The prominent contribution of the hillock edges to the electron leakage is unambiguously evidenced by the transmission electron microscopy measurements, time-of-flight secondary ion mass spectrometry, and conductive atomic force microscopy. Dislocations bunching and segregation of impurities, including C, O, and Si, at the hillock edges are clearly observed, which facilitate the trap-assisted carrier tunneling in the multiple quantum wells and subsequent recombination in the p-AlGaN. This work sheds light on one possible degradation mechanism of AlGaN-based UVC LEDs.
The Adsorption Effect of Methane Gas Molecules on Monolayer PbSe with and without Vacancy Defects: A First-Principles Study
Authors: Zhou Xing , Mao Yuliang
Published: May 2023

In this paper, the adsorption effect of methane (CH4) gas molecular on monolayer PbSe with and without vacancy defects is studied based on first-principles calculations. The effects of the adsorption of methane molecular on monolayer PbSe and on the Se vacancy (VSe) and Pb vacancy (VPb) of monolayer PbSe are also explored. Our results show that methane molecules exhibit a good physical adsorption effect on monolayer PbSe with and without vacancy defects. Moreover, our simulations indicate that the adsorption capacity of CH4 molecules on monolayer PbSe can be enhanced by applying strain. However, for the monolayer PbSe with Vse, the adsorption capacity of CH4 molecules on the strained system decreases sharply. This indicates that applying strain can promote the dissociation of CH4 from VSe. Our results show that the strain can be used as an effective means to regulate the interaction between the substrate material and the methane gas molecules.
Investigation of Reducing Interface State Density in 4H-SiC by Increasing Oxidation Rate
Authors: Li Shuai , Luo Jun , Ye Tianchun
Published: May 2023

Detailed investigations of the pre-oxidation phosphorus implantation process are required to increase the oxidation rate in 4H-SiC metal-oxide-semiconductor (MOS) capacitors. This study focuses on the SiO2/SiC interface characteristics of pre-oxidation using phosphorus implantation methods. The inversion channel mobility of a metal-oxide-semiconductor field effect transistor (MOSFET) was decreased via a high interface state density and the coulomb-scattering mechanisms of the carriers. High-resolution transmission electron microscopy (HRTEM) and scanning transmission electron microscopy (STEM) were used to evaluate the SiO2/SiC interface’s morphology. According to the energy-dispersive X-ray spectrometry (EDS) results, it was found that phosphorus implantation reduced the accumulation of carbon at the SiO2/SiC interface. Moreover, phosphorus distributed on the SiO2/SiC interface exhibited a Gaussian profile, and the nitrogen concentration at the SiO2/SiC interface may be correlated with the content of phosphorus. This research presents a new approach for increasing the oxidation rate of SiC and reducing the interface state density.
Towards Bright Single-Photon Emission in Elliptical Micropillars
Authors: Galimov Aidar , Bobrov Michail , Rakhlin Maxim , Serov Yuriy , Kazanov Dmitrii , Veretennikov Alexey , Klimko Grigory , Sorokin Sergey , Sedova Irina , Maleev Nikolai , Zadiranov Yuriy , Kulagina Marina , Guseva Yulia , Berezina Daryia , Nikitina Ekaterina , Toropov Alexey
Published: May 2023

In recent years, single-photon sources (SPSs) based on the emission of a single semiconductor quantum dot (QD) have been actively developed. While the purity and indistinguishability of single photons are already close to ideal values, the high brightness of SPSs remains a challenge. The widely used resonant excitation with cross-polarization filtering usually leads to at least a two-fold reduction in the single-photon counts rate, since single-photon emission is usually unpolarized, or its polarization state is close to that of the exciting laser. One of the solutions is the use of polarization-selective microcavities, which allows one to redirect most of the QD emission to a specific polarization determined by the optical mode of the microcavity. In the present work, elliptical micropillars with distributed Bragg reflectors are investigated theoretically and experimentally as a promising design of such polarization-selective microcavities. The impact of ellipticity, ellipse area and verticality of the side walls on the splitting of the optical fundamental mode is investigated. The study of the near-field pattern allows us to detect the presence of higher-order optical modes, which are classified theoretically. The possibility of obtaining strongly polarized single-photon QD radiation associated with the short-wavelength fundamental cavity mode is shown.
Structural, Electronic and Optical Properties of Some New Trilayer Van de Waals Heterostructures
Authors: Cheng Beitong , Zhou Yong , Jiang Ruomei , Wang Xule , Huang Shuai , Huang Xingyong , Zhang Wei , Dai Qian , Zhou Liujiang , Lu Pengfei , Song Hai-Zhi
Published: May 2023

Constructing two-dimensional (2D) van der Waals (vdW) heterostructures is an effective strategy for tuning and improving the characters of 2D-material-based devices. Four trilayer vdW heterostructures, BP/BP/MoS2, BlueP/BlueP/MoS2, BP/graphene/MoS2 and BlueP/graphene/MoS2, were designed and simulated using the first-principles calculation. Structural stabilities were confirmed for all these heterostructures, indicating their feasibility in fabrication. BP/BP/MoS2 and BlueP/BlueP/MoS2 lowered the bandgaps further, making them suitable for a greater range of applications, with respect to the bilayers BP/MoS2 and BlueP/MoS2, respectively. Their absorption coefficients were remarkably improved in a wide spectrum, suggesting the better performance of photodetectors working in a wide spectrum from mid-wave (short-wave) infrared to violet. In contrast, the bandgaps in BP/graphene/MoS2 and BlueP/graphene/MoS2 were mostly enlarged, with a specific opening of the graphene bandgap in BP/graphene/MoS2, 0.051 eV, which is much larger than usual and beneficial for optoelectronic applications. Accompanying these bandgap increases, BP/graphene/MoS2 and BlueP/graphene/MoS2 exhibit absorption enhancement in the whole infrared, visible to deep ultraviolet or solar blind ultraviolet ranges, implying that these asymmetrically graphene-sandwiched heterostructures are more suitable as graphene-based 2D optoelectronic devices. The proposed 2D trilayer vdW heterostructures are prospective new optoelectronic devices, possessing higher performance than currently available devices.
A Hybrid Triboelectric-Electromagnetic Nanogenerator Based on Arm Swing Energy Harvesting
Authors: Zheng Jiayue , Cao Zhi , Han Chengcheng , Wei Xuelian , Wang Linlin , Wu Zhiyi
Published: May 2023

As wearable devices continue to be updated and iterated, there is an increasing demand for energy supplies that are small, portable and capable of working continuously for extended periods of time. Here, a hybrid triboelectric-electromagnetic nanogenerator (HNG) based on a biomechanical energy harvester is demonstrated. The HNG is designed to be worn on the wrist according to the curve of the wearer’s arm swing. During the swinging of the arm, the magnet covered by the PTFE film will move relative to the curved cavity of the HNG and take on a negative charge by rubbing against the inner wall of the Cu coated cavity, resulting in a change in the potential difference between the two copper electrodes on the inner wall of the curved cavity. The movement of the magnet causes the magnetic flux of the three pairs of coils on both sides of the arc track to change to produce the induced electric potential, which converts the mechanical energy generated by the arm swing into electrical energy. After the rational design, the HNG is integrated into a small size device to achieve the collection of biomechanical energy. Several experiments were conducted to verify the HNG’s usability. Experiments show that the HNG takes 90 s to charge from 0 V to 1.2 V for a 1000 μF capacitor. In addition, the HNG can light up 23 LEDs simultaneously and provide a continuous supply of energy to portable electronic devices, such as temperature sensors and electronic watches after the capacitor has stored the energy. Furthermore, the HNG is experimentally verified by volunteers wearing the HNG to achieve continuous and stable output in all three states of slow swing, fast swing and running swing. This work not only provides a useful reference for human biomechanical energy harvesting, but can also provide a continuous, clean source of energy for wearable devices.
Measurement of Serum Low Density Lipoprotein Cholesterol and Triglyceride-Rich Remnant Cholesterol as Independent Predictors of Atherosclerotic Cardiovascular Disease: Possibilities and Limitations
Authors: Lütjohann Dieter , Klör Hans-Ulrich , Stellaard Frans
Published: May 2023

The serum low density lipoprotein cholesterol (LDL-C) concentration is the dominant clinical parameter to judge a patient’s risk of developing cardiovascular disease (CVD). Recent evidence supports the theory that cholesterol in serum triglyceride-rich lipoproteins (TRLs) contributes significantly to the atherogenic risk, independent of LDL-C. Therefore, combined analysis of both targets and adequate treatment may improve prevention of CVD. The validity of TRL-C calculation is solely dependent on the accuracy of the LDL-C measurement. Direct measurement of serum LDL- C is more accurate than established estimation procedures based upon Friedewald, Martin–Hopkins, or Sampson equations. TRL-C can be easily calculated as total C minus high density lipoprotein C (HDL-C) minus LDL-C. Enhanced serum LDL-C or TRL-C concentrations require different therapeutic approaches to lower the atherogenic lipoprotein C. This review describes the different atherogenic lipoproteins and their possible analytical properties and limitations.
Anaplastic Lymphoma Kinase Receptor: Possible Involvement in Anorexia Nervosa
Authors: Dedoni Simona , Scherma Maria , Camoglio Chiara , Siddi Carlotta , Fratta Walter , Fadda Paola
Published: May 2023

The pathophysiology of Anorexia Nervosa (AN) has not been fully elucidated. Anaplastic lymphoma kinase (ALK) receptor is a protein-tyrosine kinase mainly known as a key oncogenic driver. Recently, a genetic deletion of ALK in mice has been found to increase energy expenditure and confers resistance to obesity in these animals, suggesting its role in the regulation of thinness. Here, we investigated the expression of ALK and the downstream intracellular pathways in female rats subjected to the activity-based anorexia (ABA) model, which reproduces important features of human AN. In the hypothalamic lysates of ABA rats, we found a reduction in ALK receptor expression, a downregulation of Akt phosphorylation, and no change in the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) phosphorylation. After the recovery from body weight loss, ALK receptor expression returned to the control baseline values, while it was again suppressed during a second cycle of ABA induction. Overall, this evidence suggests a possible involvement of the ALK receptor in the pathophysiology of AN, that may be implicated in its stabilization, resistance, and/or its exacerbation.
Walnut (Juglans regia L.) Oligopeptides Alleviate Alcohol-Induced Acute Liver Injury through the Inhibition of Inflammation and Oxidative Stress in Rats
Authors: Liu Rui , Hao Yun-Tao , Zhu Na , Liu Xin-Ran , Mao Rui-Xue , Kang Jia-Wei , Hou Chao , Zhang Ting , Li Yong
Published: May 2023

The study was aimed at investigating the effects of walnut oligopeptides (WOPs) on alcohol-induced acute liver injury and its underlying mechanisms. Male Sprague Dawley (SD) rats were randomly assigned to six groups: normal control, alcohol control, whey protein (440 mg/kg.bw), and three WOPs (220 mg/kg.bw, 440 mg/kg.bw, 880 mg/kg.bw) groups. After 30 days of gavage, ethanol with a volume fraction of 50%, administered at a dose of 7 g/kg.bw., caused acute liver injury. A righting reflex experiment and a blood ethanol concentration evaluation were then performed. Serum biochemical parameters, inflammatory cytokines, liver alcohol metabolism enzymes, oxidative stress biomarkers, liver nuclear factor-κB (NF-κB p65), and cytochrome P4502E1 expression were determined. The results revealed that the intervention of 440 mg/kg and 880 mg/kg WOPs could alleviate the degree of intoxication, decrease blood ethanol concentration, alleviate alcohol-induced hepatic steatosis, enhance the activity of hepatic ethanol metabolizing enzymes and antioxidant capacity, reduce lipid oxidation products and pro-inflammatory factor contents, and inhibit the expression of NF-κBp65 in the livers of rats. The outcomes of the study suggest that WOPs have beneficial effects on liver damage caused by acute ethanol binge drinking, with the high-dose WOPs (880 mg/kg.bw) exerting the most pronounced hepatoprotective effect.
Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota
Authors: Fusco William , Lorenzo Manuel Bernabeu , Cintoni Marco , Porcari Serena , Rinninella Emanuele , Kaitsas Francesco , Lener Elena , Mele Maria Cristina , Gasbarrini Antonio , Collado Maria Carmen , Cammarota Giovanni , Ianiro Gianluca
Published: May 2023

Short-chain fatty acids (SCFAs) play a key role in health and disease, as they regulate gut homeostasis and their deficiency is involved in the pathogenesis of several disorders, including inflammatory bowel diseases, colorectal cancer, and cardiometabolic disorders. SCFAs are metabolites of specific bacterial taxa of the human gut microbiota, and their production is influenced by specific foods or food supplements, mainly prebiotics, by the direct fostering of these taxa. This Review provides an overview of SCFAs’ roles and functions, and of SCFA-producing bacteria, from their microbiological characteristics and taxonomy to the biochemical process that lead to the release of SCFAs. Moreover, we will describe the potential therapeutic approaches to boost the levels of SCFAs in the human gut and treat different related diseases.
Current Findings from the Japan National Health and Nutrition Survey
Authors: Nishi Nobuo , Takimoto Hidemi
Published: May 2023

In this Special Issue, six articles using the Japan National Health and Nutrition Survey (NHNS) were published [...]
Evaluation of Primary DNA Damage in Young Healthy Females Based on Their Dietary Preferences
Authors: Gajski Goran , Matković Katarina , Delić Luka , Gerić Marko
Published: May 2023

DNA damage is known to be associated with many adverse health outcomes, including cancer and chronic diseases, but also with the process of aging. Empirical evidence has shown that environmental exposures, such as certain lifestyle factors, can affect a variety of health-related biomarkers and also impact the stability of DNA through the upregulation of the antioxidant defense system and alteration of its repair capacity. In addition to exercising, diet is an important lifestyle factor that can affect the development of a variety of chronic diseases and growing evidence suggests that plant-based diets, including vegetarianism, may promote health, longevity, and well-being. Therefore, we aimed to assess the primary DNA damage in 32 young healthy females from Zagreb, Croatia, based on their dietary preferences. The participants were divided into two groups: vegetarians and non-vegetarians, where the non-vegetarian group was further divided into omnivores (traditional mixed diet) and pescatarians (consumption of fish and seafood). According to statistical analysis, the DNA damage measured in whole blood cells expressed as the % tail DNA was significantly (p < 0.05) higher in vegetarians (3.6 ± 1.1%) compared to non-vegetarians (2.8 ± 1.0%). When further dividing the participants into specific sub-groups, lower DNA damage was observed amongst omnivorous subjects (3.2 ± 0.8%) compared to vegetarians, with the lowest DNA damage found in females practicing a pescatarian diet (2.4 ± 1.1%). Although a vegetarian diet can lead to a higher intake of specific vitamins and micronutrients, it can also lead to a deficiency of iron, calcium, and total proteins, which may affect genome stability and induce oxidative stress. Even though our results have shown that the pescatarian diet would be more beneficial in terms of maintaining DNA integrity, further research should be carried out to assess how specific dietary preferences affect DNA integrity on a larger scale.
Association between Dietary Patterns and Metabolic Syndrome and Modification Effect of Altitude: A Cohort Study of Tibetan Adults in China
Authors: Wang Haijing , Wang Yanxiang , Shi Zumin , Zhao Lei , Jian Wenxiu , Li Ke , Xu Ruihua , Wu Yan , Xu Fei , Wang Youfa , Peng Wen
Published: May 2023

Little is known about the longitudinal association between dietary patterns (DPs) and metabolic disorders in people living at high altitude areas, such as Tibetans. We constructed the first open cohort, with 1832 Tibetans, and collected data in 2018 and in 2022. The metabolic syndrome (MetS) prevalence was 30.1% (32.3% in men and 28.3% in women). Three different DPs were identified: modern DP (pulses, poultry, offal, and processed meat), urban DP (vegetables, refined grain, beef/mutton, and eggs), and pastoral DP (Tibetan cheese, tsamba, butter/milk tea, and desserts). Participants within the third tertile of the urban DP had a 3.42-fold (95% CI 1.65–7.10) higher risk of MetS than those with the first tertile. Modern DP was positively associated with elevated blood pressure (BP) and elevated triglycerides (TAG), while it was inversely associated with low HDL-C. The urban DP was associated with a higher risk of low HDL-C, but a lower risk of impaired fasting blood glucose (FBG). The pastoral DP was a risk factor for impaired FBG, but protective for central obesity and elevated BP. Associations of modern DP with elevated BP, and pastoral DP with low HDL-C, were modified by altitude. In conclusion, among Tibetan adults, DPs were associated with MetS and its components, and the associations were modified by altitude among Tibetans.
Sustainable Approach of Functional Biomaterials–Tissue Engineering for Skin Burn Treatment: A Comprehensive Review
Authors: Elfawy Loai A. , Ng Chiew Yong , Amirrah Ibrahim N. , Mazlan Zawani , Wen Adzim Poh Yuen , Fadilah Nur Izzah Md , Maarof Manira , Lokanathan Yogeswaran , Fauzi Mh Busra
Published: May 2023

Burns are a widespread global public health traumatic injury affecting many people worldwide. Non-fatal burn injuries are a leading cause of morbidity, resulting in prolonged hospitalization, disfigurement, and disability, often with resulting stigma and rejection. The treatment of burns is aimed at controlling pain, removing dead tissue, preventing infection, reducing scarring risk, and tissue regeneration. Traditional burn wound treatment methods include the use of synthetic materials such as petroleum-based ointments and plastic films. However, these materials can be associated with negative environmental impacts and may not be biocompatible with the human body. Tissue engineering has emerged as a promising approach to treating burns, and sustainable biomaterials have been developed as an alternative treatment option. Green biomaterials such as collagen, cellulose, chitosan, and others are biocompatible, biodegradable, environment-friendly, and cost-effective, which reduces the environmental impact of their production and disposal. They are effective in promoting wound healing and reducing the risk of infection and have other benefits such as reducing inflammation and promoting angiogenesis. This comprehensive review focuses on the use of multifunctional green biomaterials that have the potential to revolutionize the way we treat skin burns, promoting faster and more efficient healing while minimizing scarring and tissue damage.
Development of Novel Small-Molecule Activators of Pyruvate Kinase Muscle Isozyme 2, PKM2, to Reduce Photoreceptor Apoptosis
Authors: Wubben Thomas J. , Chaudhury Sraboni , Watch Brennan T. , Stuckey Jeanne A. , Weh Eric , Fernando Roshini , Goswami Moloy , Pawar Mercy , Rech Jason C. , Besirli Cagri G.
Published: May 2023

Treatment options are lacking to prevent photoreceptor death and subsequent vision loss. Previously, we demonstrated that reprogramming metabolism via the pharmacologic activation of PKM2 is a novel photoreceptor neuroprotective strategy. However, the features of the tool compound used in those studies, ML-265, preclude its advancement as an intraocular, clinical candidate. This study sought to develop the next generation of small-molecule PKM2 activators, aimed specifically for delivery into the eye. Compounds were developed that replaced the thienopyrrolopyridazinone core of ML-265 and modified the aniline and methyl sulfoxide functional groups. Compound 2 demonstrated that structural changes to the ML-265 scaffold are tolerated from a potency and efficacy standpoint, allow for a similar binding mode to the target, and circumvent apoptosis in models of outer retinal stress. To overcome the low solubility and problematic functional groups of ML-265, compound 2’s efficacious and versatile core structure for the incorporation of diverse functional groups was then utilized to develop novel PKM2 activators with improved solubility, lack of structural alerts, and retained potency. No other molecules are in the pharmaceutical pipeline for the metabolic reprogramming of photoreceptors. Thus, this study is the first to cultivate the next generation of novel, structurally diverse, small-molecule PKM2 activators for delivery into the eye.
Therapeutic Potential of Chinese Medicine for Endogenous Neurogenesis: A Promising Candidate for Stroke Treatment
Authors: Li Lin , Li Xiao , Han Rui , Wu Meirong , Ma Yaolei , Chen Yuzhao , Zhang Han , Li Yue
Published: May 2023

Strokes are a leading cause of morbidity and mortality in adults worldwide. Extensive preclinical studies have shown that neural-stem-cell-based treatments have great therapeutic potential for stroke. Several studies have confirmed that the effective components of traditional Chinese medicine can protect and maintain the survival, proliferation, and differentiation of endogenous neural stem cells through different targets and mechanisms. Therefore, the use of Chinese medicines to activate and promote endogenous nerve regeneration and repair is a potential treatment option for stroke patients. Here, we summarize the current knowledge regarding neural stem cell strategies for ischemic strokes and the potential effects of these Chinese medicines on neuronal regeneration.
High Selectivity of 8-Hydroxyquinoline on Leishmania (Leishmania) and Leishmania (Viannia) Species Correlates with a Potent Therapeutic Activity In Vivo
Authors: Lima Sarah Kymberly Santos de , Jesus Jéssica Adriana , Raminelli Cristiano , Laurenti Márcia Dalastra , Passero Luiz Felipe Domingues
Published: May 2023

Leishmaniasis is a neglected disease caused by protozoa of the genus Leishmania, which causes different clinical manifestations. Drugs currently used in the treatment such as pentavalent antimonial and amphotericin B cause severe side effects in patients, and parasite resistance has been reported. Thus, it is necessary and urgent to characterize new and effective alternative drugs to replace the current chemotherapy of leishmaniasis. In this regard, it has been experimentally demonstrated that quinoline derivatives present significative pharmacological and parasitic properties. Thus, the aim of this work was to demonstrate the leishmanicidal activity of 8-hydroxyquinoline (8-HQ) in vitro and in vivo. The leishmanicidal activity (in vitro) of 8-HQ was assayed on promastigote and intracellular amastigote forms of L. (L.) amazonensis, L. (L.) infantum chagasi, L. (V.) guyanensis L. (V.) naiffi, L. (V.) lainsoni, and L. (V.) shawi. Additionally, the levels of nitric oxide and hydrogen peroxide were analyzed. The therapeutic potential of 8-HQ was analyzed in BALB/c mice infected with a strain of L. (L.) amazonensis that causes anergic cutaneous diffuse leishmaniasis. In vitro data showed that at 24 and 72 h, 8-HQ eliminated promastigote and intracellular amastigote forms of all studied species and this effect may be potentialized by nitric oxide. Furthermore, 8-HQ was more selective than miltefosine. Infected animals treated with 8-HQ by the intralesional route dramatically reduced the number of tissue parasites in the skin, and it was associated with an increase in IFN-γ and decrease in IL-4, which correlated with a reduction in inflammatory reaction in the skin. These results strongly support the idea that 8-HQ is an alternative molecule that can be employed in the treatment of leishmaniasis, given its selectivity and multispectral action in parasites from the Leishmania genus.
The Effect of Statins on Ocular Disorders: A Systematic Review of Randomized Controlled Trials
Authors: Lymperopoulou Charoula , Kandarakis Stylianos A. , Tzanaki Ismini , Mylona Ioanna , Xanthos Theodoros , Agouridis Aris P.
Published: May 2023

Aim: Statins have been established in the market not only due to their ability to lower plasma cholesterol levels but also due to their pleiotropic effects. In the literature, there is a controversy regarding the role of statins in ophthalmology. We aimed to systematically address the possible effect of statin therapy on ocular diseases and to identify if there is a beneficial relationship. Methods: We searched PubMed and Cochrane Library databases up to 31 December 2022 for studies evaluating the effect of statins on ocular diseases. We included all relevant Randomized Control Trials (RCTs) that have been conducted in the adult population. PROSPERO registration number: CRD42022364328. Results: Nineteen RCTs were finally considered eligible for this systematic review, with a total of 28,940 participants. Ten studies investigated the role of simvastatin, suggesting a lack of cataractogenic effect and a possible protective role in cataract formation, retinal vascular diseases, and especially diabetic retinopathy, age-related macular disease progression, and non-infectious uveitis. Four studies investigated lovastatin, showing no cataractogenic effect. Three studies examined atorvastatin, revealing conflicting results regarding diabetic retinopathy. Two studies examined rosuvastatin, indicating a possibly harmful effect on lenses and a significant protective effect on retinal microvasculature. Conclusions: Based on our findings, we believe that statins have no cataractogenic effect. There are indications that statins may have a protective role against cataract formation, AMD, diabetic retinopathy progression, and non-infectious uveitis. However, our results were insufficient for any robust conclusion. Future RCTs, with large sample sizes, on the current topic are therefore recommended to provide more solid evidence.
Lactic Acid Bacteria (LAB) and Neuroprotection, What Is New? An Up-To-Date Systematic Review
Authors: Abd Mutalib Nurliana , Syed Mohamad Sharifah Aminah , Jusril Nor Atiqah , Hasbullah Nur Intan , Mohd Amin Mohd Cairul Iqbal , Ismail Nor Hadiani
Published: May 2023

Background: In recent years, the potential role of probiotics has become prominent in the discoveries of neurotherapy against neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. Lactic acid bacteria (LAB) exhibit neuroprotective properties and exert their effects via various mechanisms of actions. This review aimed to evaluate the effects of LAB on neuroprotection reported in the literature. Methods: A database search on Google Scholar, PubMed, and Science Direct revealed a total of 467 references, of which 25 were included in this review based on inclusion criteria which comprises 7 in vitro, 16 in vivo, and 2 clinical studies. Results: From the studies, LAB treatment alone or in probiotics formulations demonstrated significant neuroprotective activities. In animals and humans, LAB probiotics supplementation has improved memory and cognitive performance mainly via antioxidant and anti-inflammatory pathways. Conclusions: Despite promising findings, due to limited studies available in the literature, further studies still need to be explored regarding synergistic effects, efficacy, and optimum dosage of LAB oral bacteriotherapy as treatment or prevention against neurodegenerative diseases.
Special Issue “Gut Microbiota, Inflammatory Bowel Diseases, and Therapeutic Targets”
Authors: Filidou Eirini , Kolios George
Published: May 2023

The gut microbiota and its overall genetic composition, the microbiome, have been the subject of extensive research over the last decade within the fields of genomics, transcriptomics and metabolomics, and their role in various other targeted approaches and advanced technologies has been explored [...]
Pharmacokinetic and Pharmacodynamic Rationale for Extending VEGF Inhibition Increasing Intravitreal Aflibercept Dose
Authors: Veritti Daniele , Sarao Valentina , Di Bin Francesco , Lanzetta Paolo
Published: May 2023

Background: The effects of various dosages and treatment regimens on intravitreal aflibercept concentrations and the proportion of free vascular endothelial growth factor (VEGF) to total VEGF were evaluated using a drug and disease assessment model. The 8 mg dosage received specific attention. Methods: A time-dependent mathematical model was developed and implemented using Wolfram Mathematica software v12.0. This model was used to obtain drug concentrations after multiple doses of different aflibercept dosages (0.5 mg, 2 mg, and 8 mg) and to estimate the time-dependent intravitreal free VEGF percentage levels. A series of fixed treatment regimens were modeled and evaluated as potential clinical applications. Results: The simulation results indicate that 8 mg aflibercept administered at a range of treatment intervals (between 12 and 15 weeks) would allow for the proportion of free VEGF to remain below threshold levels. Our analysis indicates that these protocols maintain the ratio of free VEGF below 0.001%. Conclusions: Fixed q12–q15 (every 12–15 weeks) 8 mg aflibercept regimens can produce adequate intravitreal VEGF inhibition.
Predicting Residence Time and Melt Temperature in Pharmaceutical Hot Melt Extrusion
Authors: Winck Judith , Gottschalk Tobias , Thommes Markus
Published: May 2023

Hot-melt extrusion is increasingly applied in the pharmaceutical area as a continuous processing technology, used to design custom products by co-processing drugs together with functional excipients. In this context, the residence time and processing temperature during extrusion are critical process parameters for ensuring the highest product qualities, particularly of thermosensitive materials. Within this study, a novel strategy is proposed to predict the residence time distribution and melt temperature during pharmaceutical hot-melt extrusion processes based on experimental data. To do this, an autogenic extrusion mode without external heating and cooling was applied to process three polymers (Plasdone S-630, Soluplus and Eudragit EPO) at different specific feed loads, which were set by the screw speed and the throughput. The residence time distributions were modeled based on a two-compartment approach that couples the behavior of a pipe and a stirred tank. The throughput showed a substantial effect on the residence time, whereas the influence of the screw speed was minor. On the other hand, the melt temperatures during extrusion were mainly affected by the screw speed compared to the influence of the throughput. Finally, the compilation of model parameters for the residence time and the melt temperature within design spaces serve as the basis for an optimized prediction of pharmaceutical hot-melt extrusion processes.
Postbiotic Metabolite of Lactiplantibacillus plantarum PD18 against Periodontal Pathogens and Their Virulence Markers in Biofilm Formation
Authors: Butrungrod Widawal , Chaiyasut Chaiyavat , Makhamrueang Netnapa , Peerajan Sartjin , Chaiyana Wantida , Sirilun Sasithorn
Published: May 2023

Alternative methods to reduce infectious diseases caused by bacterial pathogens and their virulence factors, biofilm formations, have arisen to reduce the pressure on existing or currently developed disinfectants and antimicrobial agents. The current strategies for reducing the severity of periodontal pathogen-caused disease by using beneficial bacteria and their metabolites are highly desirable. Probiotic strains of lactobacilli related to foods from Thai-fermented foods were selected and their postbiotic metabolites (PM) were isolated with inhibitory activity on periodontal pathogens and their biofilm formation. The PM from Lactiplantibacillus plantarum PD18 (PD18 PM) with the highest antagonistic effect against Streptococcus mutans, Porphyromonas gingivalis, Tannerella forsythia and Prevotella loescheii was selected from 139 Lactobacillus isolates. The minimal inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC) values of PD18 PM against the pathogens ranged from 1:2 to 1:4. The PD18 PM demonstrated the ability to prevent the biofilm formation of S. mutans and P. gingivalis by showing a significant reduction in viable cells, high percentages of biofilm inhibition at 92.95 and 89.68%, and the highest effective contact times at 5 and 0.5 min, respectively. L. plantarum PD18 PM showed potential as a promising natural adjunctive agent to inhibit periodontal pathogens and their biofilms.
Permeation of Phytochemicals of Selected Psychoactive Medicinal Plants across Excised Sheep Respiratory and Olfactory Epithelial Tissues
Authors: Haasbroek-Pheiffer Anja , Viljoen Alvaro , Steenekamp Jan , Chen Weiyang , Hamman Josias
Published: May 2023

The intranasal route of drug administration offers an opportunity to bypass the blood–brain barrier and deliver compounds directly into the brain. Scientific evidence exists for medicinal plants (e.g., Centella asiatica and Mesembryanthemum tortuosum) to treat central nervous system conditions such as anxiety and depression. The ex vivo permeation of selected phytochemicals (i.e., asiaticoside and mesembrine) has been measured across excised sheep nasal respiratory and olfactory tissue. Permeation studies were conducted on individual phytochemicals and C. asiatica and M. tortuosum crude extracts. Asiaticoside exhibited statistically significantly higher permeation across both tissues when applied alone as compared to the C. asiatica crude extract, while mesembrine permeation was similar when applied alone or as M. tortuosum crude extract. Permeation of all the phytocompounds was similar or slightly higher than that of the drug atenolol across the respiratory tissue. Permeation of all the phytocompounds was similar to or slightly lower than that of atenolol across the olfactory tissue. In general, the permeation was higher across the olfactory epithelial tissue than across the respiratory epithelial tissue and therefore showed potential for direct nose-to-brain delivery of the selected psychoactive phytochemicals.
Radiolabelled Extracellular Vesicles as Imaging Modalities for Precise Targeted Drug Delivery
Authors: Ashique Sumel , Anand Krishnan
Published: May 2023

Extracellular vesicles (ECVs) have been abandoned as bio-inspired drug delivery systems (DDS) in the biomedical field. ECVs have a natural ability to cross over extracellular and intracellular barriers, making them superior to manufactured nanoparticles. Additionally, they have the ability to move beneficial biomolecules among far-flung bodily cells. These advantages and the accomplishment of favorable in vivo results convincingly show the value of ECVs in medication delivery. The usage of ECVs is constantly being improved, as it might be difficult to develop a consistent biochemical strategy that is in line with their useful clinical therapeutic uses. Extracellular vesicles (ECVs) have the potential to enhance the therapy of diseases. Imaging technologies, particularly radiolabelled imaging, have been exploited for non-invasive tracking to better understand their in vivo activity.
Development of a Swellable and Floating Gastroretentive Drug Delivery System (sfGRDDS) of Ciprofloxacin Hydrochloride
Authors: Liang Yu-Kai , Cheng Wen-Ting , Chen Ling-Chun , Sheu Ming-Thau , Lin Hong-Liang
Published: May 2023

Sangelose® (SGL) is a novel hydroxypropyl methylcellulose (HPMC) derivative that has been hydrophobically modified. Due to its high viscosity, SGL has the potential as a gel-forming and release-rate-controlled material for application in swellable and floating gastroretentive drug delivery systems (sfGRDDS). The aim of this study was to develop ciprofloxacin (CIP)-loaded sfGRDDS tablets comprised of SGL and HPMC in order to extend CIP exposure in the body and achieve optimal antibiotic treatment regimes. Results illustrated that SGL-HPMC-based sfGRDDS could swell to a diameter above 11 mm and showed a short floating lag time (<4 s) and long total floating time (>24 h) to prevent gastric emptying. In dissolution studies, CIP-loaded SGL-HPMC sfGRDDS demonstrated a specific biphasic release effect. Among the formulations, the SGL/type-K HPMC 15,000 cps (HPMC 15K) (50:50) group exhibited typical biphasic release profiles, with F4-CIP and F10-CIP individually releasing 72.36% and 64.14% CIP within 2 h dissolution, and sustaining release to 12 h. In pharmacokinetic studies, the SGL-HPMC-based sfGRDDS demonstrated higher Cmax (1.56–1.73 fold) and shorter Tmax (0.67 fold) than HPMC-based sfGRDDS. Furthermore, SGL 90L in GRDDS indicated an excellent biphasic release effect and a maximum elevation of relative bioavailability (3.87 fold). This study successfully combined SGL and HPMC to manufacture sfGRDDS that retain CIP in the stomach for an optimal duration while improving its pharmacokinetic characteristics. It was concluded that the SGL-HPMC-based sfGRDDS is a promising biphasic antibiotic delivery system that can both rapidly achieve the therapeutic antibiotic concentration and maintain the plasma antibiotic concentration for an extended period to maximize antibiotic exposure in the body.
A Method for Risk Assessment Evaluating the Safety, Stability and Efficacy in Clinical Practice of Anticancer Drug Preparations in the Centralized Compounding Unit of the Veneto Institute of Oncology-IRCCS
Authors: Rigamonti Nicoletta , Sebellin Jessica , Pipitone Francesca , Realdon Nicola , Carpanese Debora , Coppola Marina
Published: May 2023

Background. Preparation of injectable anticancer drugs in hospital pharmacies is a high-risk activity that requires a proper risk assessment (RA) and quality assurance system (QAS) to ensure both a decrease in risk associated with chemotherapy compounding and high quality of the final product, especially in terms of its microbiological stability. Methods. At the centralized compounding unit (UFA) of the Italian Hospital IOV-IRCCS, a quick and deductive method was applied to evaluate the “added value” provided by each prescribed preparation, and its RA was calculated applying a formula that integrates different pharmacological, technological and organizational aspects. According to specific RA range values, the preparations were divided into different risk levels, in order to determine the QAS to be adopted, according to the Italian Ministry of Health guidelines, whose adherence was meticulously evaluated through a specific self-assessment procedure. A review of the scientific literature was carried out to integrate the risk-based predictive extended stability (RBPES) of drugs with data concerning their physiochemical and biological stability. Results. Based on the self-assessment comprising all microbiological validations of the working area, personnel and products, the microbiological risk level within the IOV-IRCCS’ UFA was defined through the creation of a transcoding matrix, conferring a microbiological stability to preparations and vial leftovers of a maximum of 7 days. The calculated RBPES were successfully integrated with stability data from the literature, leading to the drafting of a stability table of drugs and preparations in use in our UFA. Conclusions. Our methods allowed us to perform an in-depth analysis of the highly specific and technical process of anticancer drug compounding in our UFA, ensuring a certain grade of quality and safety to preparations, especially in terms of microbiological stability. The resulting RBPES table represents an invaluable tool with positive repercussions at organizational and economic levels.
Mesoporous Silica Nanoparticles as a Gene Delivery Platform for Cancer Therapy
Authors: Khaliq Nisar Ul , Lee Juyeon , Kim Joohyeon , Kim Yejin , Yu Sohyeon , Kim Jisu , Kim Sangwoo , Sung Daekyung , Kim Hyungjun
Published: May 2023

Cancer remains a major global health challenge. Traditional chemotherapy often results in side effects and drug resistance, necessitating the development of alternative treatment strategies such as gene therapy. Mesoporous silica nanoparticles (MSNs) offer many advantages as a gene delivery carrier, including high loading capacity, controlled drug release, and easy surface functionalization. MSNs are biodegradable and biocompatible, making them promising candidates for drug delivery applications. Recent studies demonstrating the use of MSNs for the delivery of therapeutic nucleic acids to cancer cells have been reviewed, along with their potential as a tool for cancer therapy. The major challenges and future interventions of MSNs as gene delivery carriers for cancer therapy are discussed.