bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Impact of Cerebral Microbleeds on Stroke Management
Authors: Sousanidou Anastasia , Tsiptsios Dimitrios , Christidi Foteini , Karatzetzou Stella , Kokkotis Christos , Gkantzios Aimilios , Bairaktaris Chrisostomos , Karapepera Vaia , Bebeletsi Paschalina , Karagiannakidou Ioanna , Marinidis Marinos , Aggelousis Nikolaos , Vadikolias Konstantinos
Published: February 2023

Stroke constitutes a major cause of functional disability and mortality, with increasing prevalence. Thus, the timely and accurate prognosis of stroke outcomes based on clinical or radiological markers is vital for both physicians and stroke survivors. Among radiological markers, cerebral microbleeds (CMBs) constitute markers of blood leakage from pathologically fragile small vessels. In the present review, we evaluated whether CMBs affect ischemic and hemorrhagic stroke outcomes and explored the fundamental question of whether CMBs may shift the risk–benefit balance away from reperfusion therapy or antithrombotic use in acute ischemic stroke patients. A literature review of two databases (MEDLINE and Scopus) was conducted to identify all the relevant studies published between 1 January 2012 and 9 November 2022. Only full-text articles published in the English language were included. Forty-one articles were traced and included in the present review. Our findings highlight the utility of CMB assessments, not only in the prognostication of hemorrhagic complications of reperfusion therapy, but also in forecasting hemorrhagic and ischemic stroke patients’ functional outcomes, thus indicating that a biomarker-based approach may aid in the provision of counseling for patients and families, improve the selection of more appropriate medical therapies, and contribute to a more accurate choice of patients for reperfusion therapy.
Human Milk Oligosaccharides and Infant Neurodevelopment: A Narrative Review
Authors: Berger Paige K. , Ong Margaret L. , Bode Lars , Belfort Mandy B.
Published: February 2023

The objective of this narrative review was to synthesize the literature on human milk oligosaccharides (HMOs) and neurodevelopmental outcomes in human milk-fed infants. We conducted a scoping review of the literature indexed in PubMed reporting observational or interventional studies on HMO exposure in relation to psychometric measures in infants. Studies were characterized based on study design and definitions of HMO exposure and neurodevelopmental outcomes. Six studies were identified; all were observational in design, and five were conducted in full-term infants. Sample sizes ranged from 35–659 infants. HMOs were defined as individual concentrations or relative abundances assessed at 1 and/or 6 months of age. Studies accounted for differences in HMO exposure based on maternal secretor status. Neurodevelopmental outcomes were assessed between 6 and 24 months of age and included four domains. Studies in full-term infants reported that total and individual fucosylated and sialylated HMOs were positively associated with cognitive, language, and motor skill domains between 18 and 24 months of age, while the single study in preterm infants reported no statistically significant findings in the full cohort. The presence of a maternal secretor did not consistently alter the associations between HMO exposure and neurodevelopmental outcomes. Emerging evidence from observational studies suggests that HMO exposure may be beneficial for neurodevelopment in infants.
Implementation of Flexibilities to the National School Lunch and Breakfast Programs and Their Impact on Schools in Missouri
Authors: Moreland Russell Sarah , Jabbari Jason , Farah Saliba Louise , Ferris Dan , Jost Eliot , Frank Tyler , Chun Yung
Published: February 2023

Background: In 2018, the United States Department of Agriculture (USDA) issued flexibilities to the National School Lunch and Breakfast Programs, relaxing the nutrition standards for milk, whole grains, and sodium. This study examines the implementation decision-making among Missouri school food services and the impact of implementing these flexibilities on the meals served. Methods: We developed a survey using the Consolidated Framework of Implementation to determine schools’ implementation of the flexibilities and factors related to implementation. To determine how the implementation of flexibilities affected participation, we merged the survey results with school-level meal county data from the Missouri Department of Elementary and Secondary Education. We used ordinary least squares regression to examine how flexibility adoption related to the number of meals served. Results: Most schools implemented the wheat, milk, and sodium flexibilities. Common reasons for implementation were increasing participation, meeting students’ preferences, expanding menu variety, and saving money. The implementation of flexibilities was associated with more lunches and breakfasts being served per month, particularly among free and reduced-price meals. Conclusions: Continued research is needed to determine how the increased uptake of school meals that do not fully meet dietary guidelines by low-income students results in inequities in health outcomes. The findings can inform the design and implementation of future policies, especially as new rules related to flexibility design are determined.
The Efficacy of Panax ginseng for the Treatment of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Preclinical Studies
Authors: Yang Keungmo , Kim Hee-Hoon , Shim Young-Ri , Song Myeong Jun
Published: February 2023

Although tremendous research has reported the protective effects of natural compounds in nonalcoholic fatty liver disease (NAFLD), there is still no approved drug. This study aimed to examine the efficacy of Panax ginseng in NAFLD in preclinical studies. A total of 41 studies were identified by searching the PubMed, Web of Science, and Cochrane Library databases. The methodological quality was assessed by the risk of bias tool from the Systematic Review Center for Laboratory Animal Experimentation. The standardized mean difference (SMD) with a 95% confidence interval was calculated, and the random effects model was used to examine overall efficacy or heterogeneity. The publication bias was analyzed by Egger’s test. The results showed that Panax ginseng treatment significantly reduced the systemic levels of alanine aminotransferase (SMD: −2.15 IU/L; p < 0.0001), aspartate aminotransferase (SMD: −2.86 IU/L; p < 0.0001), triglyceride (SMD: −2.86 mg/dL; p < 0.0001), total cholesterol (SMD: −1.69 mg/dL; p < 0.0001), low-density lipoprotein (SMD: −1.46 mg/dL; p < 0.0001), and fasting glucose (SMD: −1.45 mg/dL; p < 0.0001) while increasing high-density lipoprotein (SMD: 1.22 mg/dL; p = 0.0002) in NAFLD regardless of animal models or species. These findings may suggest that Panax ginseng is a promising therapeutic agent for NAFLD treatment.
Dietary Impacts on Changes in Diversity and Abundance of the Murine Microbiome during Progression and Treatment of Cancer
Authors: Paden Holly , Kurbatfinski Nikola , Poelstra Jelmer W. , Ormiston Kate , Orchard Tonya , Ilic Sanja
Published: February 2023

The intestinal microbial population is recognized for its impact on cancer treatment outcomes. Little research has reported microbiome changes during cancer progression or the interplay of disease progression, dietary sugar/fat intake, and the microbiome through surgery and chemotherapy. In this study, the murine gut microbiome was used as a model system, and changes in microbiome diversity, richness, and evenness over the progression of the cancer and treatment were analyzed. Mice were categorized into four diet cohorts, combinations of either high or low sucrose and high or low omega-3 fatty acids, and two treatment cohorts, saline vehicle or chemotherapy, for a total of eight groups. Fecal samples were collected at specific timepoints to assess changes due to diet implementation, onset of cancer, lumpectomy, and chemotherapy. Akkermansia muciniphila abundance was very high in some samples and negatively correlated with overall Amplicon Sequence Variant (ASV) richness (r(64) = −0.55, p = 3 × 10−8). Throughout the disease progression, ASV richness significantly decreased and was impacted by diet and treatment. Alpha-diversity and differential microbial abundance were significantly affected by disease progression, diet, treatment, and their interactions. These findings help establish a baseline for understanding how cancer progression, dietary macronutrients, and specific treatments impact the murine microbiome, which may influence outcomes.
Latilactobacillus sakei Wikim0066 Protects Skin through MMP Regulation on UVB-Irradiated In Vitro and In Vivo Model
Authors: Park Jeong-Yong , Lee Ji Yeon , Kim YongGyeong , Kang Chang-Ho
Published: February 2023

Ultraviolet (UV) B exposure induces wrinkle formation, collagen fiber breakdown, and transepidermal water loss (TEWL). UVB irradiation induces the expression of mitogen-activated protein kinase (MAPK), activator protein 1 (AP-1), and nuclear factor kappa B (NF-κB), which affect the expression of matrix metalloproteinases (MMP). We confirmed the effects of Latilactobacillus sakei wikim0066 (wikim0066) on UVB-irradiated Hs68 cells and HR-1 hairless mice cells. wikim0066 restored the production of type I procollagen by regulating the expression of MMP-1 and -3, MAPK, AP-1, and NF-κB in UVB-irradiated Hs68 cells and HR-1 mice. Oral administration of wikim0066 alleviates wrinkle formation, epidermal thickness, and TEWL in UVB-irradiated HR-1 hairless mice. These results indicated that wikim0066 has the potential to prevent UVB-induced wrinkle formation.
Comprehensive Investigation on Associations between Dietary Intake and Blood Levels of Fatty Acids and Colorectal Cancer Risk
Authors: Lu Ying , Li Doudou , Wang Lijuan , Zhang Han , Jiang Fangyuan , Zhang Rongqi , Xu Liying , Yang Nan , Dai Shuhui , Xu Xiaolin , Theodoratou Evropi , Li Xue
Published: February 2023

Background: Increasingly, studies have discovered that different fatty acids (Fas) are linked to colorectal cancer (CRC) risk. Methods: We systematically searched Embase and Medline databases to identify eligible studies that examined the associations of different types of Fas with CRC risk. The effect estimates and their 95% confidence intervals (Cis) were pooled using a random-effects model. Subgroup and sensitivity analyses were performed to examine the robustness of the study findings. Results: This study evaluated the associations of 28 dietary and 18 blood Fas with CRC risk by summarizing the most updated evidence from 54 observational and four Mendelian Randomization (MR) studies. The present findings suggested that high dietary intake of eicosapentaenoic acid (EPA), docosahexanoic acid (DHA), and docosapentaenoic acid (DPA) are related to low risk of CRC, while the n-6/n-3 PUFA ratio and trans-FA are related to high risk of CRC. The summary of all cohort studies found that a high intake of SFA and DHA was a protective factor for CRC, and a high intake of the n-6/n-3 PUFA ratio was a risk factor for CRC. In the subgroup analysis of cancer subsites, we found that the dietary intake of linoleic acid (LA) and trans-FA are risk factors, while DPA is a protective factor for colon cancer. High dietary DHA intake was associated with a lower risk of rectal cancer, while the dietary n-6/n-3 PUFA ratio was associated with a higher risk of rectal cancer. Meta-analysis of blood FA levels showed a significant reverse association between blood pentadecanoic acid and CRC risk, whilst other blood Fas showed no significant association with CRC risk. All included MR studies showed that high plasma arachidonic acid (AA) is associated with increased CRC risk. Conclusions: Current evidence on the dietary intake and blood levels of Fas in relation to CRC risk is less consistent. Future studies are needed to investigate how the metabolism of Fas contributes to CRC development.
Low Weight Polysaccharide of Hericium erinaceus Ameliorates Colitis via Inhibiting the NLRP3 Inflammasome Activation in Association with Gut Microbiota Modulation
Authors: Ren Yilin , Sun Qige , Gao Ruonan , Sheng Yinyue , Guan Tianyue , Li Wang , Zhou Lingxi , Liu Chang , Li Huaxiang , Lu Zhenming , Yu Lihua , Shi Jinsong , Xu Zhenghong , Xue Yuzheng , Geng Yan
Published: February 2023

Ulcerative colitis (UC), one of the typical inflammatory bowel diseases caused by dysregulated immunity, still requires novel therapeutic medicine with high efficacy and low toxicity. Hericium erinaceus has been widely used to treat different health problems especially gastrointestinal sickness in China for thousands of years. Here, we isolated, purified, and characterized a novel low weight polysaccharide (HEP10, Mw: 9.9 kDa) from the mycelia of H. erinaceus in submerged culture. We explored the therapeutic effect of HEP10 on UC and explored its underlying mechanisms. On one hand, HEP10 suppressed the production of TNF-α, IL-1β, IL-6, inducible iNOS, and COX-2 in LPS challenged murine macrophage RAW264.7 cells, as well as in colons from DSS-induced colitis mice. On the other hand, HEP10 treatment markedly suppressed the activation of NLRP3 inflammasome, NF-κB, AKT, and MAPK pathways. Moreover, HEP10 reversed DSS-induced alternation of the gut community composition and structure by significantly increasing Akkermansia muciniphila and also promoting functional shifts in gut microbiota. Structural equation modeling also highlighted that HEP10 can change widely through gut microbiota. In conclusion, HEP10 has a better prebiotic effect than the crude polysaccharides of H. erinaceus, which can be used as a novel dietary supplement and prebiotic to ameliorate colitis.
Sulforaphane Ameliorates Nonalcoholic Fatty Liver Disease Induced by High-Fat and High-Fructose Diet via LPS/TLR4 in the Gut–Liver Axis
Authors: Xu Ye , Huang Xianghui , Huangfu Bingxin , Hu Yanzhou , Xu Jia , Gao Ruxin , Huang Kunlun , He Xiaoyun
Published: February 2023

The gut–liver axis has emerged as a key player in the progression of non-alcoholic fatty liver disease (NAFLD). Sulforaphane (SFN) is a bioactive compound found in cruciferous vegetables; however, it has not been reported whether SFN improves NAFLD via the gut–liver axis. C57BL/6 mice were fed a high-fat and high-fructose (HFHFr) diet, with or without SFN gavage at doses of 15 and 30 mg·kg−1 body weight for 12 weeks. The results showed that SFN reduced weight gain, hepatic inflammation, and steatosis in HFHFr mice. SFN altered the composition of gut microbes. Moreover, SFN enhanced the intestinal tight junction protein ZO-1, reduced serum LPS, and inhibited LPS/TLR4 and ERS pathways to reduce intestinal inflammation. As a result, SFN protected the intestinal integrity and declined the gut-derived LPS translocations to the liver in HFHFr diet-induced mice. SFN decreased the liver LPS levels and inhibited the LPS/TLR4 pathway activations, thus inhibiting the pro-inflammatory cytokines. Notably, Spearman correlation analysis showed that the protective effect of SFN on intestinal barrier integrity and its anti-inflammatory effect on the liver was associated with improved intestinal dysbiosis. Above all, dietary intervention with SFN attenuates NAFLD through the gut–liver axis.
Effects of Spermidine on Mouse Gut Morphology, Metabolites, and Microbial Diversity
Authors: Jiang Dong-Mei , Wang Ze-Long , Yang Jia-Di , Wang Xin , Niu Chun-Yang , Ji Cheng-Weng , Ling Wei-Kang , An Xiao-Guang , Guo Yong-Ni , Sun Qian , Bai Lin , Li De-Bing , Si Xiao-Hui , Kang Bo
Published: February 2023

Spermidine is a class of biologically active organic small molecules that play an important role in maintaining intestinal homeostasis. The specific objective of this study was to explore the effects of spermidine on intestinal morphology, metabolites, and microbial diversity in mice. We showed that 0.3 mmol/L of spermidine significantly promoted the growth of ileal villi (p < 0.05), and 3.0 mmol/L of spermidine significantly increased the body weight of mice and promoted the growth of jejunum villi (p < 0.05). The 16S rDNA sequencing results indicated that 3.0 mmol/L of spermidine affected the balance of the intestinal flora by increasing the abundance of intestinal Lactic acid bacteria and reducing the abundance of harmful bacteria (Turicibacter and Alistipes). Additionally, spermidine affects the levels of microbial metabolites such as succinic acid and Pantetheine. In summary, spermidine affects intestinal morphology and regulates intestinal flora and metabolites, and this study has provided a new understanding of spermidine’s effects on the intestinal tract.
Encystment of Free-Living Amoebae, So Many Blind Spots to Cover
Authors: Samba-Louaka Ascel
Published: February 2023

Due to frequent variations in environmental conditions, free-living amoebae adapt through differentiation into different states. Hence, favorable conditions enable the formation of a feeding and proliferative form named “Trophozoïte” whereas unfavorable situations drive differentiation into resting and resistant single forms such as cysts, spores, or multicellular structures. Transformation into cyst, named “encystment” or “encystation”, is a common feature found in testate, naked, or flagellated free-living amoebae. Although much effort has been made to understand encystment, several blind spots are still present. This short opinion paper highlights some difficulties impeding a better understanding of encystment.
Recombinant Endostatin as a Potential Radiosensitizer in the Treatment of Non-Small Cell Lung Cancer
Authors: Cunningham Charnay , Bolcaen Julie , Bisio Alessandra , Genis Amanda , Strijdom Hans , Vandevoorde Charlot
Published: February 2023

Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer, which is the leading cause of cancer-related deaths worldwide. Over the past decades, tumour angiogenesis has been intensely studied in the treatment of NSCLC due to its fundamental role in cancer progression. Several anti-angiogenic drugs, such as recombinant endostatin (RE), have been evaluated in several preclinical and clinical trials, with mixed and often disappointing results. However, there is currently an emerging interest in RE due to its ability to create a vascular normalization window, which could further improve treatment efficacy of the standard NSCLC treatment. This review provides an overview of preclinical and clinical studies that combined RE and radiotherapy for NSCLC treatment. Furthermore, it highlights the ongoing challenges that have to be overcome in order to maximize the benefit; as well as the potential advantage of combinations with particle therapy and immunotherapy, which are rapidly gaining momentum in the treatment landscape of NSCLC. Different angiogenic and immunosuppressive effects are observed between particle therapy and conventional X-ray radiotherapy. The combination of RE, particle therapy and immunotherapy presents a promising future therapeutic triad for NSCLC.
Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries
Authors: Cicek Betul , Hacimuftuoglu Ahmet , Kuzucu Mehmet , Cetin Ahmet , Yeni Yesim , Genc Sidika , Yildirim Serkan , Bolat Ismail , Kantarci Mecit , Gul Mustafa , Hayme Serhat , Matthaios Dimitris , Vageli Dimitra P. , Doukas Sotirios G. , Tsatsakis Aristidis , Taghizadehghalehjoughi Ali
Published: February 2023

According to population-based studies, lung cancer is the prominent reason for cancer-related mortality worldwide in males and is also rising in females at an alarming rate. Sorafenib (SOR), which is approved for the treatment of hepatocellular carcinoma and renal cell carcinoma, is a multitargeted protein kinase inhibitor. Additionally, SOR is the subject of interest for preclinical and clinical trials in lung cancer. This study was designed to assess in vivo the possible effects of sorafenib (SOR) in diethylnitrosamine (DEN)-induced lung carcinogenesis and examine its probable mechanisms of action. A total of 30 adult male rats were divided into three groups (1) control, (2) DEN, and (3) DEN + SOR. The chemical induction of lung carcinogenesis was performed by injection of DEN intraperitoneally at 150 mg/kg once a week for two weeks. The DEN-administered rats were co-treated with SOR of 10 mg/kg by oral gavage for 42 alternate days. Serum and lung tissue samples were analyzed to determine SRY-box transcription factor 2 (SOX-2) levels. The tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels were measured in lung tissue supernatants. Lung sections were analyzed for cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) histopathologically. In addition, cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) were analyzed by immunohistochemistry and immunofluorescence methods, respectively. SOR reduced the level of SOX-2 that maintenance of cancer stemness and tumorigenicity, and TNF-α and IL-1β levels. Histopathological analysis demonstrated widespread inflammatory cell infiltration, disorganized alveolar structure, hyperemia in the vessels, and thickened alveolar walls in DEN-induced rats. The damage was markedly reduced upon SOR treatment. Further, immunohistochemical and immunofluorescence analysis also revealed increased expression of COX-2 and JNK expression in DEN-intoxicated rats. However, SOR treatment alleviated the expression of these inflammatory markers in DEN-induced lung carcinogenesis. These findings suggested that SOR inhibits DEN-induced lung precancerous lesions through decreased inflammation with concomitant in reduced SOX-2 levels, which enables the maintenance of cancer stem cell properties.
Denosumab Is Superior to Raloxifene in Lowering Risks of Mortality and Ischemic Stroke in Osteoporotic Women
Authors: Liu Ting-Chun , Hsu Chien-Ning , Lee Wen-Chin , Wang Shih-Wei , Huang Chiang-Chi , Lee Yueh-Ting , Fu Chung-Ming , Chen Jin-Bor , Li Lung-Chih
Published: February 2023

Both osteoporosis and cardiovascular disease (CVD) share similar pathways in pathophysiology and are intercorrelated with increased morbidity and mortality in elderly women. Although denosumab and raloxifene are the current guideline-based pharmacological treatments, their impacts on cardiovascular protection are yet to be examined. This study aimed to compare mortality rate and cardiovascular events between denosumab and raloxifene in osteoporotic women. Risks of CVD development and all-cause mortality were estimated using Cox proportional hazard regression. A total of 7972 (3986 in each group) women were recruited between January 2003 and December 2018. No significant difference between denosumab and raloxifene was observed in composite CVDs, myocardial infarction, or congestive heart failure. However, comparison of the propensity score matched cohorts revealed that patients with proportion of days covered (PDC) ≥60% had lower incidence of ischemic stroke in the denosumab group than that in the raloxifene group (aHR 0.68; 95% CI 0.47–0.98; p = 0.0399). In addition, all-cause mortality was lower in the denosumab group than in the raloxifene group (aHR 0.59; 95% CI 0.48–0.72; p = 0.001), except in patients aged <65 y/o in this cohort study. We concluded that denosumab is superior to raloxifene in lowering risks of all-cause mortality and certain ischemic strokes in osteoporotic women.
Synthesis and Properties of Sucrose- and Lactose-Based Aromatic Ester Surfactants as Potential Drugs Permeability Enhancers
Authors: Verboni Michele , Perinelli Diego Romano , Qiu Carol Yingshan , Tiboni Mattia , Aluigi Annalisa , Lucarini Simone , Lam Jenny K. W. , Duranti Andrea
Published: February 2023

The delivery of therapeutics across biological membranes (e.g., mucosal barriers) by avoiding invasive routes (e.g., injection) remains a challenge in the pharmaceutical field. As such, there is the need to discover new compounds that act as drug permeability enhancers with a favorable toxicological profile. A valid alternative is represented by the class of sugar-based ester surfactants. In this study, sucrose and lactose alkyl aromatic and aromatic ester derivatives have been synthesized with the aim to characterize them in terms of their physicochemical properties, structure–property relationship, and cytotoxicity, and to test their ability as permeability enhancer agents across Calu-3 cells. All of the tested surfactants showed no remarkable cytotoxic effect on Calu-3 cells when applied both below and above their critical micelle concentration. Among the explored molecules, lactose p-biphenyl benzoate (URB1420) and sucrose p-phenyl benzoate (URB1481) cause a reversible ~30% decrease in transepithelial electrical resistance (TEER) with the respect to the basal value. The obtained result matches with the increased in vitro permeability coefficients (Papp) calculated for FTIC-dextran across Calu-3 cells in the presence of 4 mM solutions of these surfactants. Overall, this study proposes sucrose- and lactose-based alkyl aromatic and aromatic ester surfactants as novel potential and safe permeation enhancers for pharmaceutical applications.
Pharmacological Profiling of KATP Channel Modulators: An Outlook for New Treatment Opportunities for Migraine
Authors: Dyhring Tino , Jansen-Olesen Inger , Christophersen Palle , Olesen Jes
Published: February 2023

Migraine is a highly disabling pain disorder with huge socioeconomic and personal costs. It is genetically heterogenous leading to variability in response to current treatments and frequent lack of response. Thus, new treatment strategies are needed. A combination of preclinical and clinical data indicate that ATP-sensitive potassium (KATP) channel inhibitors could be novel and highly effective drugs in the treatment of migraine. The subtype Kir6.1/SUR2B is of particular interest and inhibitors specific for this cranio-vascular KATP channel subtype may qualify as future migraine drugs. Historically, different technologies and methods have been undertaken to characterize KATP channel modulators and, therefore, a head-to-head comparison of potency and selectivity between the different KATP subtypes is difficult to assess. Here, we characterize available KATP channel activators and inhibitors in fluorescence-based thallium-flux assays using HEK293 cells stably expressing human Kir6.1/SUR2B, Kir6.2/SUR1, and Kir6.2/SUR2A KATP channels. Among the openers tested, levcromakalim, Y-26763, pinacidil, P-1075, ZM226600, ZD0947, and A-278637 showed preference for the KATP channel subtype Kir6.1/SUR2B, whereas BMS-191095, NN414, and VU0071306 demonstrated preferred activation of the Kir6.2/SUR1 subtype. In the group of KATP channel blockers, only Rosiglitazone and PNU-37783A showed selective inhibition of the Kir6.1/SUR2B subtype. PNU-37783A was stopped in clinical development and Rosiglitazone has a low potency for the vascular KATP channel subtype. Therefore, development of novel selective KATP channel blockers, having a benign side effect profile, are needed to clinically prove inhibition of Kir6.1/SUR2B as an effective migraine treatment.
Numerical Investigation of the Particle Dynamics in a Rotorgranulator Depending on the Properties of the Coating Liquid
Authors: Grohn Philipp , Heinrich Stefan , Antonyuk Sergiy
Published: February 2023

In the pharmaceutical industry, the coating of particles is a widely used technique to obtain desired surface modifications of the final product, e.g., controlled release of the active agents. The production of round, coated particles is particularly important, which is why fluidized bed rotor granulators (FBRG) are often used for this process. In this work, Computational Fluid Dynamics (CFD) coupled with the Discrete Element Method (DEM) is used to investigate the wet particle dynamics, depending on the properties of the coating liquid in a FBRG. The DEM contact model was extended by liquid bridge model to account for capillary and viscous forces during wet contact of particles. The influence of the relative contact velocity on the maximum length of the liquid bridge is also considered in the model. Five different cases were compared, in which the particles were initially wetted, and the liquid loading as well as the surface tension and viscosity of the liquid were changed. The results show that increasing viscosity leads to a denser particle bed and a significant decrease in particle rotational velocities and particle motion in the poloidal plane of the FBRG. Reducing the liquid loading and surface tension results in increased particle movement.
Biopolymers in Mucoadhesive Eye Drops for Treatment of Dry Eye and Allergic Conditions: Application and Perspectives
Authors: Račić Anđelka , Krajišnik Danina
Published: February 2023

Dry eye syndrome and allergic conjunctivitis are the most common inflammatory disorders of the eye surface. Although eye drops are the most usual prescribed dosage form, they are characterized by low ocular availability due to numerous barrier mechanisms of the eye. The use of biopolymers in liquid ophthalmic preparations has numerous advantages, such as increasing the viscosity of the tear film, exhibiting bioadhesive properties, and resisting the drainage system, leading to prolonged retention of the preparation at the site of application, and improvement of the therapeutic effect. Some mucoadhesive polymers are multifunctional excipients, so they act by different mechanisms on increasing the permeability of the cornea. Additionally, many hydrophilic biopolymers can also represent the active substances in artificial tear preparations, due to their lubrication and moisturizing effect. With the modification of conventional ophthalmic preparations, there is a need for development of new methods for their characterization. Numerous methods for the assessment of mucoadhesiveness have been suggested by the literature. This review gives an overview related to the development of mucoadhesive liquid ophthalmic formulations for the treatment of dry eye and allergic conditions.
Casein-Based Nanoparticles: A Potential Tool for the Delivery of Daunorubicin in Acute Lymphocytic Leukemia
Authors: Zahariev Nikolay , Draganova Milena , Zagorchev Plamen , Pilicheva Bissera
Published: February 2023

The aim of this study was to develop casein-based nanoscale carriers as a potential delivery system for daunorubicin, as a pH-responsive targeting tool for acute lymphocytic leukemia. A coacervation technique followed by nano spray-drying was used for the preparation of drug-loaded casein nanoparticles. Four batches of drug-loaded formulations were developed at varied drug–polymer ratios using a simple coacervation technique followed by spray-drying. They were further characterized using scanning electron microscopy, dynamic light scattering, FTIR spectroscopy, XRD diffractometry, and differential scanning calorimetry. Drug release was investigated in different media (pH 5 and 7.4). The cytotoxicity of the daunorubicin-loaded nanoparticles was compared to that of the pure drug. The influence of the polymer-to-drug ratio on the nanoparticles’ properties such as their particle size, surface morphology, production yield, drug loading, entrapment efficiency, and drug release behavior was studied. Furthermore, the cytotoxicity of the drug-loaded nanoparticles was investigated confirming their potential as carriers for daunorubicin delivery.
Advances in Self-Assembled Peptides as Drug Carriers
Authors: Gao Yawen , Wang Lele , Zhang Xue , Zhou Ziling , Shen Xinzhu , Hu Haodong , Sun Rui , Tang Jihui
Published: February 2023

In recent years, self-assembled peptide nanotechnology has attracted a great deal of attention for its ability to form various regular and ordered structures with diverse and practical functions. Self-assembled peptides can exist in different environments and are a kind of medical bio-regenerative material with unique structures. These materials have good biocompatibility and controllability and can form nanoparticles, nanofibers and hydrogels to perform specific morphological functions, which are widely used in biomedical and material science fields. In this paper, the properties of self-assembled peptides, their influencing factors and the nanostructures that they form are reviewed, and the applications of self-assembled peptides as drug carriers are highlighted. Finally, the prospects and challenges for developing self-assembled peptide nanomaterials are briefly discussed.
Dynamical Modulation of Transverse Orbital Angular Momentum in Highly Confined Spatiotemporal Optical Vortex
Authors: Chen Jian , Kuai Siyu , Chen Guoliang , Yu Lihua , Zhan Qiwen
Published: February 2023

Spatiotemporal optical vortices (STOVs) have attracted numerous attention from researchers in recent years due to their intriguing characteristics with transverse orbital angular momentum (OAM) in the spatiotemporal domain. In this work, we numerically analyze the tightly focusing characteristics of higher-order STOVs and present a method to dynamically modulate the transverse OAM in highly confined STOVs. Richards–Wolf vectorial diffraction theory was employed to simulate the three-dimensional spatiotemporal distribution of the focused STOV corresponding to the incident wave packet of topological charge of −2. The simulation results show that the higher-order spatiotemporal vortices in the transversely polarized components of the focused wave packets split into two first-order vortices with topological charge of −1 when the waist radius of the incident wave packet was larger than 40% of the pupil radius of the focusing lens, and the spacing of the two split vortices could be tailored by adjusting the waist radius of the incident wave packet. Meanwhile, the incident spatial waist radius also affected the tilt angle of the phase singularity trace in the z-polarized component of the focused field. The presented method provides a flexible way to dynamically engineer the spatiotemporal vortices in the tightly focused wave packet and may find potential applications in nanophotonics, light–matter interaction, quantum information processing, etc.
Supramolecular Optimization of Sensory Function of a Hemicurcuminoid through Its Incorporation into Phospholipid and Polymeric Polydiacetylenic Vesicles: Experimental and Computational Insight
Authors: Akhmadeev Bulat S. , Retyunskaya Olga O. , Podyachev Sergey N. , Katsyuba Sergey A. , Gubaidullin Aidar T. , Sudakova Svetlana N. , Syakaev Victor V. , Babaev Vasily M. , Sinyashin Oleg G. , Mustafina Asiya R.
Published: February 2023

This work presents the synthesis of a new representative of hemicurcuminoids with a nonyloxy substituent (HCur) as a fluorescent amphiphilic structural element of vesicular aggregates based on phosphatidylcholine (PC), phosphatidylserine (PS), and 10,12-pentacosadiynoic acid (PCDA). Both X-ray diffraction analysis of the single crystal and 1H NMR spectra of HCur in organic solvents indicate the predominance of the enol-tautomer of HCur. DFT calculations show the predominance of the enol tautomer HCur in supramolecular assemblies with PC, PS, and PCDA molecules. The results of the molecular modeling show that HCur molecules are surrounded by PC and PS with a rather weak exposure to water molecules, while an exposure of HCur molecules to water is enhanced under its supramolecular assembly with PCDA molecules. This is in good agreement with the higher loading of HCur into PC(PS) vesicles compared to PCDA vesicles converted into polydiacetylene (PDA) ones by photopolymerization. HCur molecules incorporated into HCur-PDA vesicles exhibit greater planarity distortion and hydration effect in comparison with HCur-PC(PS) ones. HCur-PDA is presented as a dual fluorescence-chromatic nanosensor responsive to a change in pH within 7.5–9.5, heavy metal ions and polylysine, and the concentration-dependent fluorescent response is more sensitive than the chromatic one. Thus, the fluorescent response of HCur-PDA allows for the distinguishing between Cd2+ and Pb2+ ions in the concentration range 0–0.01 mM, while the chromatic response allows for the selective sensing of Pb2+ over Cd2+ ions at their concentrations above 0.03 mM.
Biosorbent Based on Poly(vinyl alcohol)–Tricarboxi-Cellulose Designed to Retain Organic Dyes from Aqueous Media
Authors: Tataru-Farmus Ramona-Elena , Cimpoesu Ramona , Nica Iulia , Suteu Daniela
Published: February 2023

Methylene Blue, a cationic dye, was retained from aqueous solutions using a novel biosorbent made of poly(vinyl alcohol) reticulated with tricarboxi-cellulose produced via TEMPO oxidation (OxC25). The study of the Methylene Blue biosorption process was performed with an emphasis on operational parameters that may have an impact on it (such as biosorbent concentration, pH of the aqueous media, and temperature). The current study focused on three areas: (i) the physic-chemical characterization of the biosorbent (scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX)); (ii) biosorption data modeling to determine the quantitative characteristic parameters employing three equilibrium isotherms (Langmuir, Freundlich, and Dubinin–Radushkevich—DR); and (iii) the study of temperature influence. The results of the study showed that the Langmuir model provided a good fit for the experimental data of biosorption, realizing a maximum capacity of 806.45 mg/g at 20 °C. The free energy of biosorption (E) evaluated by the DR equation was in the range of 6.48–10.86 KJ/mol. The values of the thermodynamic parameters indicated an endothermic process because the free Gibbs energy ranged from −9.286 KJ/mol to −2.208 KJ/mol and the enthalpy was approximately −71.686 KJ/mol. The results obtained encourage and motivate the further study of this biosorption process by focusing on its kinetic aspects, establishing the biosorption’s controlled steps, identifying the mechanism responsible for the retention of textile dyes presented in moderate concentration in aqueous media, and studying the biosorption process in a dynamic regime with a view to applying it to real systems.
Influence of Process Parameters on the Characteristics of Additively Manufactured Parts Made from Advanced Biopolymers
Authors: Pepelnjak Tomaž , Stojšić Josip , Sevšek Luka , Movrin Dejan , Milutinović Mladomir
Published: February 2023

Over the past few decades, additive manufacturing (AM) has become a reliable tool for prototyping and low-volume production. In recent years, the market share of such products has increased rapidly as these manufacturing concepts allow for greater part complexity compared to conventional manufacturing technologies. Furthermore, as recyclability and biocompatibility have become more important in material selection, biopolymers have also become widely used in AM. This article provides an overview of AM with advanced biopolymers in fields from medicine to food packaging. Various AM technologies are presented, focusing on the biopolymers used, selected part fabrication strategies, and influential parameters of the technologies presented. It should be emphasized that inkjet bioprinting, stereolithography, selective laser sintering, fused deposition modeling, extrusion-based bioprinting, and scaffold-free printing are the most commonly used AM technologies for the production of parts from advanced biopolymers. Achievable part complexity will be discussed with emphasis on manufacturable features, layer thickness, production accuracy, materials applied, and part strength in correlation with key AM technologies and their parameters crucial for producing representative examples, anatomical models, specialized medical instruments, medical implants, time-dependent prosthetic features, etc. Future trends of advanced biopolymers focused on establishing target-time-dependent part properties through 4D additive manufacturing are also discussed.
Enrichment of Starch Desserts with the Addition of Apple Juice and Buckwheat Fiber
Authors: Adamczyk Greta , Hanus Paweł , Bobel Inna , Krystyjan Magdalena
Published: February 2023

Buckwheat hulls which are rich in fiber are good ingredients to increase the nutritional value of food products. The aim of this study was to determine the effect of the applied additives in the form of fiber and apple juice on the properties of both potato and corn starch (normal and waxy). In order to characterize the rheological properties of kissel, the pasting characteristic was measured. In the obtained gels, the basic quality parameters were determined. The analysis of texture, color parameters, and also total polyphenol content were determined. Buckwheat hulls, in addition to their high fiber content, are a valuable source of phenolic compounds and can be a great additive in starch desserts. The addition of buckwheat hulls and apple juice improved the nutritional value of the final products but also caused changes in the technological qualities: it increased the initial temperature of potato starch mixtures (by approx. 9 °C); it decreased the viscosity of cold desserts (from 8 to 55%); and increased the hardness of the final product by more than 7 times. In the case of other starches, the recorded changes were much smaller than for potato starch-based products.
Development of Pavement Material Using Crumb Rubber Modifier and Graphite Nanoplatelet for Pellet Asphalt Production
Authors: Lee Jong-Sub , Lee Sang-Yum , Bae Yoon-Shin , Le Tri Ho Minh
Published: February 2023

The purpose of this research was to promote the recycling of pellet asphalt with Crumb Rubber Modifier (CRM) and Graphite Nanoplatelet (GNP) in pothole restoration. In this study, several laboratory tests were carried out on mixes containing CRM content ratios of 5%, 10%, and 20% and GNP content of 3% and 6% in order to identify the ideal mixing ratio of pellet-type asphalt paving materials. The Marshall stability test, the Hamburg wheel tracking test, and the dynamic modulus test were all performed to compare the effectiveness of the proposed method and heated asphalt combinations. Afterward, the full-scale testbed was conducted to verify the practical application between the proposed method and popular pothole-repairing materials. Both laboratory and field test findings confirmed that the asphalt pavement using 5% CRM and 6% GNP improved the resistance to plastic deformation and anti-stripping compared to the generally heated asphalt paving material, thereby extending road life. However, the resistance to fatigue cracking can be slightly reduced by incorporating these additives. Overall, the CRM and GNP asphalt pellet approach is a feasible solution for sustainable pavement maintenance and rehabilitation, particularly in small-scale damage areas such as potholes.
Intrinsically Conducting Polymer Composites as Active Masses in Supercapacitors
Authors: Ul Hoque Md. Ikram , Holze Rudolf
Published: February 2023

Intrinsically conducting polymers ICPs can be combined with further electrochemically active materials into composites for use as active masses in supercapacitor electrodes. Typical examples are inspected with particular attention to the various roles played by the constituents of the composites and to conceivable synergistic effects. Stability of composite electrode materials, as an essential property for practical application, is addressed, taking into account the observed causes and effects of materials degradation.
Analysis of an Adaptive Periodic Low-Frequency Wave Filter Featuring Magnetorheological Elastomers
Authors: Jafari Hamid , Sedaghati Ramin
Published: February 2023

This study aims to enhance and tune wave-propagation properties (Bandgaps) of periodic structures featuring magnetorheological elastomers (MREs). For this purpose, first, a basic model of periodic structures (square unit cell with cross-shaped arms), which does not possess noise filtering properties in the conventional configuration, is considered. A passive attenuation zone is then proposed by adding a cylindrical core mass to the center of the conventional geometry and changing arm angles, which permitted new bandgap areas. It was shown that better wave-filtering performance may be achieved by introducing a large radius of the cylindrical core as well as low negative cross-arm angles. The modified configuration of the unit cell was subsequently utilized as the basic model for the development of magnetoactive metamaterial using a MRE capable of varying the bandgaps areas upon application of an external magnetic field. The finite element model of the proposed MRE-based periodic unit cell was developed, and the Bloch theorem was employed to systematically investigate the ability of the proposed adaptive periotic structure to attenuate low-frequency noise and vibration. Results show that the proposed MRE-based periodic wave filter can provide wide bandgap areas which can be adaptively changed and tuned using the applied magnetic field. The findings in this study can provide an essential guide for the development of novel adaptive periodic structures to filter low-frequency noises in the wide frequency band.
Effects of Interlaminar Failure on the Scratch Damage of Automotive Coatings: Cohesive Zone Modeling
Authors: Huang Minfei , Yang Hanming , Zou Chenqi , Zang Mengyan , Chen Shunhua
Published: February 2023

Interlaminar failure caused by scratches is a common damage mode in automotive coatings and is considered the potential trigger for irreversible destruction, i.e., plowing. This work strives to numerically investigate the mechanisms responsible for the complex scratch behavior of an automotive coating system, considering the interfacial failure. A finite element model is developed by incorporating a large deformation cohesive zone model for scratch-induced debonding simulation, where the mass scaling technique is utilized to minimize computational burden while ensuring accuracy. The delamination phenomenon of the automotive coating is reproduced, and its effects on scratch damage behavior are analyzed. Accordingly, it is revealed that the interlaminar delamination would produce significant stress redistribution, which leads to brittle and ductile damage of the coating and consequently affects the formation of plowing. Eventually, parametric studies on the effects of interfacial properties are performed. They demonstrate that the shear strength and shear fracture energy dominate scratch-induced delamination.
PEDOT: PSS/AuNPs-Based Composite as Voltammetric Sensor for the Detection of Pirimicarb
Authors: Deller Andrei E. , Hryniewicz Bruna M. , Pesqueira Camila , Horta Rayta Paim , da Silva Bruno José Gonçalves , Weheabby Saddam , Al-Hamry Ammar , Kanoun Olfa , Vidotti Marcio
Published: February 2023

An electrochemical sensor for the pesticide Pirimicarb (PMC) has been developed. A screen-printed electrode (SPCE) was used and modified with the conducting polymer poly (3,4-ethylenedioxythiophene) (PEDOT) and gold nanoparticles (AuNPs) to enhance electrochemical proprieties. Electrode characterizations were performed using scattering electron microscopy (SEM) and cyclic voltammetry (CV). With the SPCE/PEDOT:PSS/AuNPs modified electrode, a new peak at 1.0 V appeared in the presence of PMC related to the PMC oxidation. To elucidate the mechanism of PMC oxidation, Gas Chromatography-Mass Spectrometry (GC-MS), where two major peaks were identified, evidencing that the device can both detect and degrade PMC by an electro-oxidation process. Exploring this peak signal, it was possible the sensor development, performing detection from 93.81–750 µmol L−1, limits of quantification (LOQ) and detection (LOD) of 93.91 µmol L−1 and 28.34 µmol L−1, respectively. Thus, it was possible to study and optimization of PMC degradation, moreover, to perform detection at low concentrations and with good selectivity against different interferents using a low-cost printed electrode based on graphite modified with conductive polymer and AuNPs.