bluuebunny/crossref_metadata_2025 huggingface dataset:
Disordered Eating Behaviors Related to Food Addiction/Eating Addiction in Inpatients with Obesity and the General Population: The Italian Version of the Addiction-like Eating Behaviors Scale (AEBS-IT)
Authors: Rossi Alessandro Alberto , Mannarini Stefania , Castelnuovo Gianluca , Pietrabissa Giada
Published: December 2022

Purpose. The purpose of this research is to test the psychometric properties and factorial structure of the Addiction-like Eating Behaviors Scale (AEBS) in an Italian sample of adults with severe obesity seeking treatment for weight reduction and the general population, and to examine the measurement invariance of the tool by comparing a clinical and a nonclinical sample. Methods. A confirmatory factor analysis (CFA) was initially conducted to test the factorial structure of the Italian version of the AEBS (AEBS-IT) on a total of 953 participants. Following this, the measurement invariance and psychometric properties of the tool AEBS-IT were assessed on both inpatients with severe obesity (n = 502) and individuals from the general population (n = 451). Reliability and convergent validity analysis were also run. Results. CFA revealed a bi-factor structure for the AEBS-IT, which also showed good reliability and positive correlations with food addiction (through the mYFAS2.0 symptom count), binge-eating symptoms, compulsive eating behavior, and dysfunctional eating patterns and the individuals’ body mass index (BMI). Moreover, the tool was invariant across populations. Conclusion. This study provided evidence that the AEBS-IT is a valid and reliable measure of FA in both clinical and nonclinical samples.
Probing the Double-Layered Cotyledon Cell Structure of Navy Beans: Barrier Effect of the Protein Matrix on In Vitro Starch Digestion
Authors: Do Duc Toan , Singh Jaspreet , Johnson Stuart , Singh Harjinder
Published: December 2022

The microstructure of legumes plays a crucial role in regulating starch digestion and postprandial glycemic responses. Starch granules are double encapsulated within the outer cell wall and the inner protein matrix of legume cotyledon cells. Despite progress in understanding the role of cell walls in delaying starch digestion, the role of the protein matrix has received little research attention. The aim of this study was to evaluate if the protein matrix and cell wall may present combined physical barriers retarding enzyme hydrolysis of intracellular starch. Intact cotyledon cells were isolated from navy beans and used to assess the barrier effect of the protein matrix on the digestion of starch under conditions simulating the upper gastrointestinal tract. The cells were pretreated with pepsin at 37 °C and pH 2.0 for 1, 4, or 24 h and without pepsin for 24 h (control) to facilitate removal of the intracellular protein matrix prior to cooking and simulated in vitro digestion. A longer pretreatment time resulted in a lower protein content of the cells and a higher initial rate and extent of starch hydrolysis. We suggest that in addition to the primary cell wall barrier, the protein matrix provides a secondary barrier restricting the accessibility of α-amylase to starch. This study provides a new fundamental understanding of the relationship between the structural organization of legume cotyledon cells and starch digestion that could inform the design of novel low glycemic index foods.
Molecular Mechanism of Cyanidin-3-O-Glucoside Disassembling Aβ Fibril In Silico
Authors: Gao Jihui , Fu Jiahui , Gao Xiaoyu , Yang Dong
Published: December 2022

The deposition of β-amyloid (Aβ) in the brain leads to neurotoxic effects and subsequent Alzheimer’s disease (AD). While AD is becoming more and more prevalent in modern society, therapeutic efforts targeting Aβ could be a promising solution. Currently, two natural products are reported to disintegrate preformed Aβ fibril in vitro. Meanwhile, the chemical driving force behind this phenomenon remains unknown. Taking cyanidin-3-O-glucoside (Cy-3G) as an example, here we studied its interaction with different Aβ polymorphs in silico. Negative charges on different Aβ polymorphs draw the interaction with the flavylium cation on Cy-3G. Our results show that Aβ in a single peptide form in solution exposed more hydrophobic solvent accessible surface area than its fibril structure (per protomer), and Cy-3G interacts more intensively with the single peptide form than fibril as indicated by more hydrogen bonding formed and more amino acid residues involved in their hydrophobic interactions. Thus, the single Aβ peptide aggregation into fibril and fibril dissociation into single peptide equilibrium could be disturbed by the preferential binding of Cy-3G to the monomeric Aβ peptide, which leads to the disassembly of the pathogenic Aβ fibril. This study offers a novel perspective of Cy-3G alleviated AD syndrome beyond its dogmatic antioxidant activity.
The Association between Methionine Intake and Diabetes in Chinese Adults—Results from the China Health and Nutrition Survey
Authors: Sun Xiaomin , Chen Yingxin , Shu Jing , Li Zhongying , Yu Dongmei , Peng Wen , Yan Alice F. , Wang Youfa , Shi Zumin
Published: December 2022

This study aimed to evaluate the association between methionine intake and diabetes prevalence in Chinese adults and explore whether the association was source-specific. Data from 12,849 adults aged ≥20 years old were used from the China Health and Nutrition Survey during 1997–2011. Diabetes was diagnosed as self-reported and/or when blood tests results met the diagnostic criteria. A 3-day, 24-h recall was used to assess different sources of methionine. Multivariable mixed linear regression was used to examine the associations. Across the quartiles of total methionine intake, the odds ratio (ORs, 95% CI) of diabetes were 1.00, 1.49 (1.21 to 1.82), 1.72 (1.37 to 2.15), and 2.53 (1.97 to 3.23). In the subgroup analysis, similar trends were observed in both animal and plant methionine. There was a significant interaction between urbanization and diabetes. The positive association was only significant in those who lived in low or medium urbanization areas. The ORs (95% CI) were 1.00, 1.27 (0.85 to 1.88), 1.56 (1.01 to 2.39), and 1.79 (1.09 to 2.95) for medium urbanization, respectively. No interaction was identified when stratified by different methionine sources. In conclusion, methionine intake was positively associated with diabetes independent of food source, and it was modified by urbanization levels.
Nutrient Patterns and Its Association and Metabolic Syndrome among Chinese Children and Adolescents Aged 7–17
Authors: Shi Jia , Fang Hongyun , Cheng Xue , Guo Qiya , Ju Lahong , Piao Wei , Xu Xiaoli , Yu Dongmei , Zhao Liyun , He Li
Published: December 2022

This study was designed to explore the associations between nutrient patterns (NPs) and metabolic syndrome (MetS) and its five components among Chinese children and adolescents aged 7–17. The required data of participants were collected from the China National Nutrition and Health Surveillance of Children and Lactating Mothers in 2016–2017. Ultimately, 13,071 participants were included. Nutrient patterns were obtained by means of factor analysis. Multivariate logistic regression analysis was conducted to evaluate the association between nutrient patterns with MetS and its components. After adjusting covariates, the results of logistic regression models revealed that high-carbohydrate patterns were associated with the presence of abdominal obesity. The high-animal protein pattern was negatively associated with high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C). The high-sodium-and-fat pattern had a negative relationship with elevated blood pressure (BP) and was positively associated with low HDL-C. The high-Vitamin D-and-Vitamin B12 pattern had protective effects on MetS, high TG, and low HDL-C. Further large-scale longitudinal investigations are necessary in the future.
Gut Microbiome and Serum Metabolome Profiles of Capsaicin with Cognitive Benefits in APP/PS1 Mice
Authors: Li Jun , Liao Xiaojun , Yin Xuedong , Deng Zimeng , Hu Guangfen , Zhang Weiwei , Jiang Feng , Zhao Liang
Published: December 2022

Capsaicin, a natural bioactive component, has been reported to improve cognition and ameliorate the pathology of Alzheimer’s disease (AD). Studies have linked AD to alterations in gut microbiota composition and serum metabolites. In the present study, we examined the alterations in serum metabolome and gut microbiome in APPswe/PS1dE9 (APP/PS1) mice treated with capsaicin. Capsaicin treatments resulted in a significant increase in the abundance of Akkermansia, Faecalibaculum, Unclassified_f_Atopobiaceae, and Gordonibacter and a significant decrease in the abundance of Adlercreutzia, Peptococcaceae, Alistipes, Oscillibacter and Erysipelatoclostridium. Furthermore, the species Akkermansia muciniphila (A. muciniphila) was significantly enriched in capsaicin-treated APP/PS1 mice (p = 0.0002). Serum metabolomic analysis showed that capsaicin-treated APP/PS1 mice had a significant higher level of tryptophan (Trp) metabolism and a significantly lower level of lipid metabolism compared with vehicle-treated mice. Capsaicin altered serum metabolites, including Kynurenine (Kyn), 5-Hydroxy-L-tryptophan (5-HIT), 5-Hydroxyindoleacetic acid (5-HIAA), indoxylsulfuric acid, lysophosphatidyl cholines (LysoPCs), and lysophosphatidyl ethanolamine (LysoPE). Significant correlations were observed between the gut bacteria and serum metabolite. With regard to the increased abundance of A. muciniphila and the ensuing rise in tryptophan metabolites, our data show that capsaicin alters both the gut microbiota and blood metabolites. By altering the gut microbiome and serum metabolome, a diet high in capsaicin may reduce the incidence and development of AD.
UPLC-MS/MS Analysis of Naturally Derived Apis mellifera Products and Their Promising Effects against Cadmium-Induced Adverse Effects in Female Rats
Authors: Amr Alaa , Abd El-Wahed Aida , El-Seedi Hesham R. , Khalifa Shaden A. M. , Augustyniak Maria , El-Samad Lamia M. , Abdel Karim Ahmed E. , El Wakil Abeer
Published: December 2022

Honeybee products arouse interest in society due to their natural origin and range of important biological properties. Propolis (P) and royal jelly (RJ) attract scientists’ attention because they exhibit antioxidant, anti-inflammatory, anti-bacterial, anti-tumor, and immunomodulatory abilities. In this study, we tested whether P and RJ could mitigate the adverse effects of cadmium (Cd) exposure, with particular emphasis on the reproductive function in female rats. In this line, one week of pretreatment was established. Six experimental groups were created, including (i) the control group (without any supplementation), (ii) the Cd group (receiving CdCl2 in a dose of 4.5 mg/kg/day), (iii) the P group (50 mg of P/kg/day), (iv) RJ group (200 mg of RJ/kg/day), (v) P + Cd group (rats pretreated with P and then treated with P and Cd simultaneously), (vi) RJ + Cd group (animals pretreated with RJ before receiving CdCl2 simultaneously with RJ). Cd treatment of rats adversely affected a number of measured parameters, including body weight, ovarian structure and ultrastructure, oxidative stress parameters, increased ovarian Cd content and prolonged the estrous cycle. Pretreatment and then cotreatment with P or RJ and Cd alleviated the adverse effects of Cd, transferring the clusters in the PCA analysis chart toward the control group. However, clusters for cotreated groups were still distinctly separated from the control and P, or RJ alone treated groups. Most likely, investigated honeybee products can alter Cd absorption in the gut and/or increase its excretion through the kidneys and/or mitigate oxidative stress by various components. Undoubtedly, pretreatment with P or RJ can effectively prepare the organism to overcome harmful insults. Although the chemical composition of RJ and P is relatively well known, focusing on proportion, duration, and scheme of treatment, as well as the effects of particular components, may provide interesting data in the future. In the era of returning to natural products, both P and RJ seem valuable materials for further consideration as anti-infertility agents.
Acinetobacter baumannii during COVID-19: What Is the Real Pandemic?
Authors: Rangel Karyne , De-Simone Salvatore Giovanni
Published: December 2022

The novel Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, has had a monumental impact on public health globally [...]
Chemical and Biological Investigations of Allium scorodoprasum L. Flower Extracts
Authors: Đorđevski Nikoleta , Uba Abdullahi Ibrahim , Zengin Gokhan , Božunović Jelena , Gašić Uroš , Ristanović Elizabeta , Ćirić Ana , Nikolić Biljana , Stojković Dejan
Published: December 2022

This study was designed to investigate the impact of different extraction solvent systems on the chemical composition and biological activities of Allium scorodoprasum L. (Amaryllidaceae)—the medicinal plant that was traditionally used as a remedy in the medieval period in the Balkans. Targeted chemical analysis of nine different extracts was performed by UHPLC(−)HESI–QqQ-MS/MS. Antimicrobial and antibiofilm activities of the extracts were investigated on sixteen clinical isolates of bacteria, yeasts and dermatomycetes, all isolated from infected human skin and corneal formations. Cytotoxicity and wound-healing properties were tested on human immortalized keratinocytes (HaCaT cell line). Antioxidant activity was assessed by six different assays, while beneficial potential against certain neurodegenerative diseases and type 2 diabetes was determined in selected enzyme inhibition assays coupled with molecular modeling. The results showed that the obtained extracts were rich in phenolic compounds, especially flavonoid glycosides such as rutin and kaempferol 3-O-glucoside. All of the extracts showed antimicrobial, wound-healing, antioxidant and anti-enzymatic properties. This study is the first of its kind, linking the medieval medicinal use of wild-growing flowers of A. scorodoprasum with contemporary in vitro scientific approaches.
In Vitro Efficacy of Extracts and Isolated Bioactive Compounds from Ascomycota Fungi in the Treatment of Colorectal Cancer: A Systematic Review
Authors: Luque Cristina , Cepero Ana , Perazzoli Gloria , Mesas Cristina , Quiñonero Francisco , Cabeza Laura , Prados Jose , Melguizo Consolación
Published: December 2022

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Despite the advances and success of current treatments (e.g., chemotherapy), there are multiple serious side effects which require the development of new treatment strategies. In recent years, fungi have gained considerable attention as a source of extracts and bioactive compounds with antitumor capabilities because of their antimicrobial and antioxidant properties and even their anti-inflammatory and antiviral activities. In the present review, a systematic search of the existing literature in four electronic databases was carried out in which the antitumor activity against CRC cells of Ascomycota fungi extracts or compounds was tested. The systematical research in the four databases resulted in a total of 883 articles. After applying exclusion and inclusion criteria, a total of 75 articles were finally studied. The order Eurotiales was the most studied (46% of the articles), and the ethyl acetate extraction was the most used method (49% of the papers). Penicillium extracts and gliotoxin and acetylgliotoxin G bioactive compounds showed the highest cytotoxic activity. This review also focuses on the action mechanisms of the extracts and bioactive compounds of fungi against CRC, which were mediated by apoptosis induction and the arrest of the cell cycle, which induces a notable reduction in the CRC cell proliferation capacity, and by the reduction in cell migration that limits their ability to produce metastasis. Thus, the ability of fungi to induce the death of cancer cells through different mechanisms may be the basis for the development of new therapies that improve the current results, especially in the more advanced stages of the CCR.
Gold Nanoparticles Encapsulated Resveratrol as an Anti-Aging Agent to Delay Cataract Development
Authors: Chen Qifang , Gu Peilin , Liu Xuemei , Hu Shaohua , Zheng Hong , Liu Ting , Li Chongyi
Published: December 2022

Nanoparticle-based drug delivery systems, which can overcome the challenges associated with poor aqueous solubility and other harmful side effects of drugs, display potent applications in cataract treatment. Herein, we designed a nanosystem of gold nanoparticles containing resveratrol (RGNPs) as an anti-aging agent to delay cataracts. The spherical RGNPs had a superior ability to inhibit hydrogen peroxide-mediated oxidative stress damage, including reactive oxygen species (ROS) production, malondialdehyde (MDA) generation, and glutathione (GSH) consumption in the lens epithelial cells. Additionally, the present data showed that RGNPs could delay cellular senescence induced by oxidative stress by decreasing the protein levels of p16 and p21, reducing the ratio of BAX/BCL-2 and the senescence-associated secretory phenotype (SASP) in vitro. Moreover, the RGNPs could also clearly relieve sodium selenite-induced lens opacity in a rat cataract model. Our data indicated that cell senescence was reduced and cataracts were delayed upon treatment with RGNPs through activating the Sirt1/Nrf2 signaling pathway. Our findings suggested that RGNPs could serve as an anti-aging ingredient, highlighting their potential to delay cataract development.
Combinatory Effect and Modes of Action of Chrysin and Bone Marrow-Derived Mesenchymal Stem Cells on Streptozotocin/Nicotinamide-Induced Diabetic Rats
Authors: Sayed Hesham M. , Awaad Ashraf S. , Abdel Rahman Fatma El-Zahraa S. , Al-Dossari M. , Abd El-Gawaad N. S. , Ahmed Osama M.
Published: December 2022

The purpose of this study was to see how chrysin and/or bone marrow-derived mesenchymal stem cells (BM-MSCs) affected streptozotocin (STZ)/nicotinamide (NA)-induced diabetic rats as an animal model of type 2 diabetes mellitus (T2DM). Male Wistar rats were given a single intraperitoneal (i.p.) injection of 60 mg STZ/kg bodyweight (bw) 15 min after an i.p. injection of NA (120 mg/kg bw) to induce T2DM. The diabetic rats were given chrysin orally at a dose of 100 mg/kg bw every other day, BM-MSCs intravenously at a dose of 1 × 106 cells/rat/week, and their combination for 30 days after diabetes induction. The rats in the diabetic group displayed impaired oral glucose tolerance and a decrease in liver glycogen content and in serum insulin, C-peptide, and IL-13 levels. They also had significantly upregulated activities in terms of liver glucose-6-phosphatase and glycogen phosphorylase and elevated levels of serum free fatty acids, IL-1β, and TNF-α. In addition, the diabetic rats exhibited a significant elevation in the adipose tissue resistin protein expression level and a significant decrease in the expression of adiponectin, insulin receptor-beta subunit, insulin receptor substrate-1, and insulin receptor substrate-2, which were associated with a decrease in the size of the pancreatic islets and in the number of β-cells and insulin granules in the islets. The treatment of diabetic rats with chrysin and/or BM-MSCs significantly improved the previously deteriorated alterations, with chrysin combined with BM-MSCs being the most effective. Based on these findings, it can be concluded that combining chrysin with BM-MSCs produced greater additive therapeutic value than using them separately in NA/STZ-induced T2DM rats.
The Potential of Purple Waxy Corn Cob (Zea mays L.) Extract Loaded-Sericin Hydrogel for Anti-Hyperpigmentation, UV Protection and Anti-Aging Properties as Topical Product Applications
Authors: Kanpipit Nattawadee , Nualkaew Natsajee , Thapphasaraphong Suthasinee
Published: December 2022

Sericin-hydrogel formulations incorporating purple waxy corn (Zea mays L.) cob extract (PWCC) were developed as potential topical skin cosmetic products. Sericin has wound healing properties, protects against ultraviolet (UV) radiation, and exhibits anti-inflammatory, anti-oxidation, and anti-tyrosinase activities. PWCC is a rich source of anthocyanins with antioxidants, UV protective, anti-inflammatory, and collagen-enhancing activities. Six hydrogel formulations (S1–S6) were investigated for anti-melanogenesis on the B16F10 melanoma cell line and UV-protection on human keratinocytes (HaCaT) and anti-aging activities on normal human dermal fibroblasts (NHDFs). The results showed that the hydrogel formulations enhanced the anthocyanin permeation through the skin. The S4 formulation indicated the highest inhibition of tyrosinase activity and reduced the melanin pigment, increased the cell viability of the UV-induced HaCaT cells, the inhibition of collagenase and elastase, and increased the collagen type I production without cytotoxicity. Therefore, the PWCC loaded-sericin hydrogels show a high potential as a novel anti-hyperpigmentation, UV protection, and anti-aging products for topical applications.
Afatinib Reverses EMT via Inhibiting CD44-Stat3 Axis to Promote Radiosensitivity in Nasopharyngeal Carcinoma
Authors: Huang Huichao , Huang Fangling , Liang Xujun , Fu Ying , Cheng Zhe , Huang Yan , Chen Zhuchu , Duan Yankun , Chen Yongheng
Published: December 2022

Background: Afatinib, a second-generation tyrosine kinase inhibitor (TKI), exerts its radiosensitive effects in nasopharyngeal carcinoma (NPC). However, the detailed mechanism of afatinib-mediated sensitivity to radiation is still obscure in NPC. Methods: Quantitative phosphorylated proteomics and bioinformatics analysis were performed to illustrate the global phosphoprotein changes. The activity of the CD44-Stat3 axis and Epithelial-Mesenchymal Transition (EMT)-linked markers were evaluated by Western blotting. Wound healing and transwell assays were used to determine the levels of cell migration upon afatinib combined IR treatment. Cell proliferation was tested by CCK-8 assay. A pharmacological agonist by IL-6 was applied to activate Stat3. The xenograft mouse model was treated with afatinib, radiation or a combination of afatinib and radiation to detect the radiosensitivity of afatinib in vivo. Results: In the present study, we discovered that afatinib triggered global protein phosphorylation alterations in NPC cells. Further, bioinformatics analysis indicated that afatinib inhibited the CD44-Stat3 signaling and subsequent EMT process. Moreover, functional assays demonstrated that afatinib combined radiation treatment remarkably impeded cell viability, migration, EMT process and CD44-Stat3 activity in vitro and in vivo. In addition, pharmacological stimulation of Stat3 rescued radiosensitivity and biological functions induced by afatinib in NPC cells. This suggested that afatinib reversed the EMT process by blocking the activity of the CD44-Stat3 axis. Conclusion: Collectively, this work identifies the molecular mechanism of afatinib as a radiation sensitizer, thus providing a potentially useful combination treatment and drug target for NPC radiosensitization. Our findings describe a new function of afatinib in radiosensitivity and cancer treatment.
Effects of Statin Combinations on Zika Virus Infection in Vero Cells
Authors: Españo Erica , Kim Jeong-Ki
Published: December 2022

The Zika virus (ZIKV) remains a global health concern. Thus far, no antiviral or vaccine has been approved to prevent or treat ZIKV infection. In a previous study, we found that lipophilic statins can inhibit ZIKV production in Vero cells. These statins appear to have different potencies against ZIKV infection. Here, we determined whether combinations of statins would have synergistic effects to maximize the efficacy of the statins and to reduce potential side effects. Specifically, we used a modified fixed-ratio assay for the combinations of atorvastatin (ATO) or fluvastatin (FLU) with mevastatin (MEV) or simvastatin (SIM). All combinations with MEV tended towards synergy, especially with higher fractions of MEV in the combinations. The ATO + SIM combination tended towards additivity. The FLU + SIM combination also tended towards additivity except for one combination which had the highest fraction of FLU over SIM among the tested combinations. Overall, certain combinations of ATO or FLU with SIM or MEV may be synergistic. More exhaustive combinatorial assays in vitro and in vivo could help define whether combining lipophilic statins would be beneficial and safe for treating ZIKV infections.
Two-Step Targeted Drug Delivery via Proteinaceous Barnase-Barstar Interface and Doxorubicin-Loaded Nano-PLGA Outperforms One-Step Strategy for Targeted Delivery to HER2-Overexpressing Cells
Authors: Komedchikova Elena N. , Kolesnikova Olga A. , Tereshina Ekaterina D. , Kotelnikova Polina A. , Sogomonyan Anna S. , Stepanov Alexey V. , Deyev Sergey M. , Nikitin Maxim P. , Shipunova Victoria O.
Published: December 2022

Nanoparticle-based chemotherapy is considered to be an effective approach to cancer diagnostics and therapy in modern biomedicine. However, efficient tumor targeting remains a great challenge due to the lack of specificity, selectivity, and high dosage of chemotherapeutic drugs required. A two-step targeted drug delivery strategy (DDS), involving cancer cell pre-targeting, first with a first nontoxic module and subsequent targeting with a second complementary toxic module, is a solution for decreasing doses for administration and lowering systemic toxicity. To prove two-step DDS efficiency, we performed a direct comparison of one-step and two-step DDS based on chemotherapy loaded PLGA nanoparticles and barnase*barstar interface. Namely, we developed and thoroughly characterized the two-step targeting strategy of HER2-overexpressing cancer cells. The first targeting block consists of anti-HER2 scaffold polypeptide DARPin9_29 fused with barstar. Barstar exhibits an extremely effective binding to ribonuclease barnase with Kaff = 1014 M−1, thus making the barnase*barstar protein pair one of the strongest known protein*protein complexes. A therapeutic PLGA-based nanocarrier coupled to barnase was used as a second targeting block. The PLGA nanoparticles were loaded with diagnostic dye, Nile Blue, and a chemotherapeutic drug, doxorubicin. We showed that the two-step DDS increases the performance of chemotherapy-loaded nanocarriers: IC50 of doxorubicin delivered via two-step DDS was more than 100 times lower than that for one-step DDS: IC50 = 43 ± 3 nM for two-step DDS vs. IC50 = 4972 ± 1965 nM for one-step DDS. The obtained results demonstrate the significant efficiency of two-step DDS over the classical one-step one. We believe that the obtained data will significantly change the direction of research in developing targeted anti-cancer drugs and promote the creation of new generation cancer treatment strategies.
Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery
Authors: Brar Harpinder K. , Jose Jiney , Wu Zimei , Sharma Manisha
Published: December 2022

Glioblastoma multiforme (GBM) is an aggressive brain tumor with high mortality rates. Due to its invasiveness, heterogeneity, and incomplete resection, the treatment is very challenging. Targeted therapies such as tyrosine kinase inhibitors (TKIs) have great potential for GBM treatment, however, their efficacy is primarily limited by poor brain distribution due to the presence of the blood–brain barrier (BBB). This review focuses on the potential of TKIs in GBM therapy and provides an insight into the reasons behind unsuccessful clinical trials of TKIs in GBM despite the success in treating other cancer types. The main section is dedicated to the use of promising drug delivery strategies for targeted delivery to brain tumors. Use of brain targeted delivery strategies can help enhance the efficacy of TKIs in GBM. Among various drug delivery approaches used to bypass or cross BBB, utilizing nanocarriers is a promising strategy to augment the pharmacokinetic properties of TKIs and overcome their limitations. This is because of their advantages such as the ability to cross BBB, chemical stabilization of drug in circulation, passive or active targeting of tumor, modulation of drug release from the carrier, and the possibility to be delivered via non-invasive intranasal route.
Lactobacilli as a Vector for Delivery of Nanobodies against Norovirus Infection
Authors: Yuki Yoshikazu , Zuo Fanglei , Kurokawa Shiho , Uchida Yohei , Sato Shintaro , Sakon Naomi , Hammarström Lennart , Kiyono Hiroshi , Marcotte Harold
Published: December 2022

Passive administration of neutralizing antibodies (Abs) is an attractive strategy for the control of gastrointestinal infections. However, an unanswered practical concern is the need to assure the stability of sufficient amounts of orally administered neutralizing Abs against intestinal pathogens (e.g., norovirus) in the harsh environment of the gastrointestinal tract. To this end, we expressed a single-domain Ab (VHH, nanobody) against norovirus on the cell surface of Lactobacillus, a natural and beneficial commensal component of the gut microbiome. First, we used intestinal epithelial cells generated from human induced pluripotent stem cells to confirm that VHH 1E4 showed neutralizing activity against GII.17 norovirus. We then expressed VHH 1E4 as a cell-wall–anchored form in Lactobacillus paracasei BL23. Flow cytometry confirmed the expression of VHH 1E4 on the surface of lactobacilli, and L. paracasei that expressed VHH 1E4 inhibited the replication of GII.17 norovirus in vitro. We then orally administered VHH 1E4-expressing L. paracasei BL23 to germ-free BALB/c mice and confirmed the presence of lactobacilli with neutralizing activity in the intestine for at least 10 days after administration. Thus, cell-wall-anchored VHH-displaying lactobacilli are attractive oral nanobody deliver vectors for passive immunization against norovirus infection.
A Micro-Configured Multiparticulate Reconstitutable Suspension Powder of Fixed Dose Rifampicin and Pyrazinamide: Optimal Fabrication and In Vitro Quality Evaluation
Authors: Rampedi Penelope N. , Ogunrombi Modupe O. , Wesley-Smith James , Adeleke Oluwatoyin A.
Published: December 2022

The scarcity of age-appropriate pharmaceutical formulations is one of the major challenges impeding successful management of tuberculosis (TB) prevalence in minors. To this end, we designed and assessed the quality of a multiparticulate reconstitutable suspension powder containing fixed dose rifampicin and pyrazinamide (150 mg/300 mg per 5 mL) which was prepared employing solid–liquid direct dispersion coupled with timed dehydration, and mechanical pulverization. The optimized formulation had a high production yield (96.000 ± 3.270%), displayed noteworthy powder flow quality (9.670 ± 1.150°), upon reconstitution the suspension flow property was non-Newtonian and was easily redispersible with gentle manual agitation (1.720 ± 0.011 strokes/second). Effective drug loading was attained for both pyrazinamide (97.230 ± 2.570%w/w) and rifampicin (97.610 ± 0.020%w/w) and drug release followed a zero-order kinetic model (R2 = 0.990) for both drugs. Microscopic examinations confirmed drug encapsulation efficiency and showed that the particulates were micro-dimensional in nature (n < 700.000 µm). The formulation was physicochemically stable with no chemically irreversible drug-excipient interactions based on the results of characterization experiments performed. Findings from organoleptic evaluations generated an overall rating of 4.000 ± 0.000 for its attractive appearance and colour 5.000 ± 0.000 confirming its excellent taste and extremely pleasant smell. Preliminary cytotoxicity studies showed a cell viability above 70.000% which indicates that the FDC formulation was biocompatible. The optimized formulation was environmentally stable either as a dry powder or reconstituted suspension. Accordingly, a stable and palatable FDC antimycobacterial reconstitutable oral suspension powder, intended for flexible dosing in children and adolescents, was optimally fabricated.
Curcumin Attenuates Damage to Rooster Spermatozoa Exposed to Selected Uropathogens
Authors: Tvrdá Eva , Petrovičová Michaela , Benko Filip , Ďuračka Michal , Galovičová Lucia , Slanina Tomáš , Kačániová Miroslava
Published: December 2022

Artificial insemination, as an essential pillar of the modern poultry industry, primarily depends on the quality of semen collected from stud roosters. Since the collection and storage of ejaculates is not a sterile process, antimicrobial agents have become essential supplements to semen extenders. While the use of traditional antibiotics has been challenged because of rising bacterial resistance, natural biomolecules represent an appealing alternative because of their antibacterial and antioxidant properties. As such, this study strived to compare the effects of 50 μmol/L curcumin (CUR) with 31.2 µg/mL kanamycin (KAN) as a conventional antibiotic on rooster sperm quality in the presence of Salmonella enterica, Escherichia coli and Pseudomonas aeruginosa. Changes in sperm structural integrity and functional activity were monitored at 2 and 24 h of culture. Computer-assisted semen analysis revealed significant sperm motility preservation following treatment with KAN, particularly in the case of Salmonella enterica and Pseudomonas aeruginosa (p < 0.001) after 24 h. On the other hand, CUR was more effective in opposing ROS overproduction by all bacteria (p < 0.05), as determined by luminol-based luminometry, and maintained sperm mitochondrial activity (p < 0.001 in the case of Salmonella enterica; p < 0.05 with respect to Escherichia coli and Pseudomonas aeruginosa), as assessed by the fluorometric JC-1 assay. The TUNEL assay revealed that CUR readily preserved the DNA integrity of rooster sperm exposed to Salmonella enterica (p < 0.01) and Escherichia coli (p < 0.001). The bacteriological analysis showed higher efficiency of KAN in preventing the growth of all selected bacterial species (p < 0.0001) as opposed to CUR. In conclusion, CUR provided protection to rooster spermatozoa against alterations caused by uropathogens, most likely through its antioxidant activity. Hence, CUR supplementation to poultry semen extenders in combination with properly selected antibacterial substances may become an interesting strategy in the management of bacterial contamination during semen storage.
Anticancer Drug Conjugates Incorporating Estrogen Receptor Ligands
Authors: Zlotos Darius P. , Kronenberger Thales , Laufer Stefan A.
Published: December 2022

Hormone-dependent cancers, such as certain types of breast cancer are characterized by over-expression of estrogen receptors (ERs). Anticancer drug conjugates combining ER ligands with other classes of anticancer agents may not only benefit from dual action at both anti-cancer targets but also from selective delivery of cytotoxic agents to ER-positive tumor cells resulting in less toxicity and adverse effects. Moreover, they could also take advantage of overcoming resistance typical for anti-hormonal monotherapy such as tamoxifen. In this review, we discuss the design, structures and pharmacological effects of numerous series of drug conjugates containing ER ligands such as selective ER modulators (tamoxifen, 4-hydroxytamoxifen, endoxifen), selective ER degraders (ICI-164384) and ER agonists (estradiol) linked to diverse anti-cancer agents including histone-deacetylase inhibitors, DNA-alkylating agents, antimitotic agents and epidermal growth factor receptor inhibitors.
Current Progress and Outlook of Nano-Based Hydrogel Dressings for Wound Healing
Authors: Zhang Xiao , Wei Pengyu , Yang Zhengyang , Liu Yishan , Yang Kairui , Cheng Yuhao , Yao Hongwei , Zhang Zhongtao
Published: December 2022

Wound dressing is an important tool for wound management. Designing wound dressings by combining various novel materials and drugs to optimize the peri-wound environment and promote wound healing is a novel concept. Hydrogels feature good ductility, high water content, and favorable oxygen transport, which makes them become some of the most promising materials for wound dressings. In addition, nanomaterials exhibit superior biodegradability, biocompatibility, and colloidal stability in wound healing and can play a role in promoting healing through their nanoscale properties or as carriers of other drugs. By combining the advantages of both technologies, several outstanding and efficient wound dressings have been developed. In this paper, we classify nano-based hydrogel dressings into four categories: hydrogel dressings loaded with a nanoantibacterial drug; hydrogel dressings loaded with oxygen-delivering nanomedicines; hydrogel dressings loaded with nanonucleic acid drugs; and hydrogel dressings loaded with other nanodelivered drugs. The design ideas, advantages, and challenges of these nano-based hydrogel wound dressings are reviewed and analyzed. Finally, we envisaged possible future directions for wound dressings in the context of relevant scientific and technological advances, which we hope will inform further research in wound management.
Antimicrobial Proteins: Structure, Molecular Action, and Therapeutic Potential
Authors: Hassan Mohamed , Flanagan Thomas W. , Kharouf Naji , Bertsch Christelle , Mancino Davide , Haikel Youssef
Published: December 2022

Second- and third-line treatments of patients with antibiotic-resistant infections can have serious side effects, such as organ failure with prolonged care and recovery. As clinical practices such as cancer therapies, chronic disease treatment, and organ transplantation rely on the ability of available antibiotics to fight infection, the increased resistance of microbial pathogens presents a multifaceted, serious public health concern worldwide. The pipeline of traditional antibiotics is exhausted and unable to overcome the continuously developing multi-drug resistance. To that end, the widely observed limitation of clinically utilized antibiotics has prompted researchers to find a clinically relevant alternate antimicrobial strategy. In recent decades, the discovery of antimicrobial peptides (AMPs) as an excellent candidate to overcome antibiotic resistance has received further attention, particularly from scientists, health professionals, and the pharmaceutical industry. Effective AMPs are characterized by a broad spectrum of antimicrobial activities, high pathogen specificity, and low toxicity. In addition to their antimicrobial activity, AMPs have been found to be involved in a variety of biological functions, including immune regulation, angiogenesis, wound healing, and antitumor activity. This review provides a current overview of the structure, molecular action, and therapeutic potential of AMPs.
Nanodecoys: A Quintessential Candidate to Augment Theranostic Applications for a Plethora of Diseases
Authors: Chatterjee Sampreeti , Harini Karthick , Girigoswami Agnishwar , Nag Moupriya , Lahiri Dibyajit , Girigoswami Koyeli
Published: December 2022

Nanoparticles (NPs) designed for various theranostic purposes have hugely impacted scientific research in the field of biomedicine, bringing forth hopes of a future revolutionized area called nanomedicine. A budding advancement in this area is the conjugation of various cell membranes onto nanoparticles to develop biomimetic cells called ‘Nanodecoys’ (NDs), which can imitate the functioning of natural cells. This technology of coating cell membranes on NPs has enhanced the working capabilities of nano-based techniques by initiating effective navigation within the bodily system. Due to the presence of multiple functional moieties, nanoparticles coated with cell membranes hold the ability to interact with complex biological microenvironments inside the body with ease. Although developed with the initial motive to increase the time of circulation in the bloodstream and stability by coating membranes of red blood cells, it has further outstretched a wide range of cell lines, such as mesenchymal stem cells, beta cells, thrombocytes, white blood cells, and cancer cells. Thus, these cells and the versatile properties they bring along with them open up a brand-new domain in the biomedical industry where different formulations of nanoparticles can be used in appropriate dosages to treat a plethora of diseases. This review comprises recent investigations of nanodecoys in biomedical applications.
Silica Hydrogels as Platform for Delivery of Hyaluronic Acid
Authors: Parfenyuk Elena , Dolinina Ekaterina
Published: December 2022

Hyaluronic acid (HA) is chondroprotective and anti-inflammatory drug used clinically for treatment of inflammatory disorders (arthritis, skin diseases, bowel diseases, etc.). In addition, HA is a crucial ingredient in the cosmetic products used to eliminate the unpleasant consequences of inflammatory skin diseases. The main disadvantages that limit its use are its low mechanical properties and its rapid biodegradation. In this paper, silica hydrogels are considered as a promising matrix for HA to improve its properties. The hybrid HA-silica hydrogels were synthesized by the sol–gel method. Morphology of the hydrogels was investigated by optical microscopy and scanning electron microscopy methods. Taking into account their potential applications for topical and injectable delivery, much attention was paid to investigation of deformation properties of the hydrogels under shear, compression, and tension. Their resistance to enzymatic degradation in vitro was estimated. Kinetics and mechanisms of HA release from the hybrid hydrogels in vitro were also studied. It was found that the indicated properties can be controlled by synthesis conditions, HA molecular weight, and its loading in the hydrogels. Silica hydrogels are a prospective platform for the development of new soft formulations and cosmetic compositions of HA with improved pharmacological and consumer properties.
Tailoring Apixaban in Nanostructured Lipid Carrier Enhancing Its Oral Bioavailability and Anticoagulant Activity
Authors: Zaky Mohamed F. , Megahed Mohamed A. , Hammady Taha M. , Gad Shadeed , Ghorab Mamdouh Mostafa , El-Say Khalid M.
Published: December 2022

Apixaban (Apx), an oral anticoagulant drug, is a direct factor Xa inhibitor for the prophylaxis against venous thromboembolism. Apx has limited oral bioavailability and poor water solubility. The goal of this study was to improve the formulation of an Apx-loaded nanostructured lipid carrier (NLC) to increase its bioavailability and effectiveness. As solid lipid, liquid lipid, hydrophilic, and lipophilic stabilizers, stearic acid, oleic acid, Tween 80, and lecithin were used, respectively. Utilizing Box–Behnken design, the effects of three factors on NLC particle size (Y1), zeta potential (Y2), and entrapment efficiency percent (Y3) were examined and optimized. The optimized formula was prepared, characterized, morphologically studied, and pharmacokinetically and pharmacodynamically assessed. The observed responses of the optimized Apx formula were 315.2 nm, −43.4 mV, and 89.84% for Y1, Y2, and Y3, respectively. Electron microscopy revealed the homogenous spherical shape of the NLC particles. The in vivo pharmacokinetic study conducted in male Wistar rats displayed an increase in AUC and Cmax by 8 and 2.67 folds, respectively, compared to oral Apx suspension. Moreover, the half-life was increased by 1.94 folds, and clearance was diminished by about 8 folds, which makes the NLC formula a promising sustained release system. Interestingly, the pharmacodynamic results displayed the superior effect of the optimized formula over the drug suspension with prolongation in the cuticle bleeding time. Moreover, both prothrombin time and activated partial thromboplastin time are significantly increased. So, incorporating Apx in an NLC formula significantly enhanced its oral bioavailability and pharmacodynamic activity.
Docosahexaenoic Acid Ameliorates Contextual Fear Memory Deficits in the Tg2576 Alzheimer’s Disease Mouse Model: Cellular and Molecular Correlates
Authors: Badesso Sara , Cartas-Cejudo Paz , Espelosin Maria , Santamaria Enrique , Cuadrado-Tejedor Mar , Garcia-Osta Ana
Published: December 2022

Docosahexaenoic acid (DHA), the most abundant polyunsaturated fatty acid in the brain, is essential for successful aging. In fact, epidemiological studies have demonstrated that increased intake of DHA might lower the risk for developing Alzheimer’s disease (AD). These observations are supported by studies in animal models showing that DHA reduces synaptic pathology and memory deficits. Different mechanisms to explain these beneficial effects have been proposed; however, the molecular pathways involved are still unknown. In this study, to unravel the main underlying molecular mechanisms activated upon DHA treatment, the effect of a high dose of DHA on cognitive function and AD pathology was analyzed in aged Tg2576 mice and their wild-type littermates. Transcriptomic analysis of mice hippocampi using RNA sequencing was subsequently performed. Our results revealed that, through an amyloid-independent mechanism, DHA enhanced memory function and increased synapse formation only in the Tg2576 mice. Likewise, the IPA analysis demonstrated that essential neuronal functions related to synaptogenesis, neuritogenesis, the branching of neurites, the density of dendritic spines and the outgrowth of axons were upregulated upon-DHA treatment in Tg2576 mice. Our results suggest that memory function in APP mice is influenced by DHA intake; therefore, a high dose of daily DHA should be tested as a dietary supplement for AD dementia prevention.
Investigation of Optical-Switching Mechanism Using Guided Mode Resonances
Authors: Rehman Atiq Ur , Khan Yousuf , Irfan Muhammad , Butt Muhammad A.
Published: December 2022

Recently, photonic crystals have paved the way to control photonic signals. Therefore, this research numerically investigated the design of the optical switch using the guided-mode resonances in photonic crystals operating in a communication window around 1.55 μm. The design of the device is based on a dielectric slab waveguide to make it compatible with optical waveguides in photonic circuits. Moreover, two signals are used and are termed as the data signal and control signal. The data signal is coupled into the optical waveguide using an out-of-the-plane vertical coupling mechanism, whereas the control signal is index-guided into the optical waveguide to amplify the data signal. The switching parameters of the optical switch are adjusted by changing the number of the photonic crystal periods and implementing a varying radius PhC-cavity within the middle of the PhC-lattice, where the optical characteristics in terms of resonant wavelength, reflection peaks, linewidth, and quality factor of the data signal can be adjusted. The numerical simulations are carried out in open-source finite difference time domain-based software. Congruently, 7% optical amplification is achieved in the data signal with a wavelength shift of 0.011 μm and a quality factor of 12.64. The amplification of the data signal can be utilized to implement an optical switching mechanism. The device is easy to implement and has great potential to be used in programmable photonics and optical integrated circuits.