bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-Dose Administration of Cannabigerol Attenuates Inflammation and Fibrosis Associated with Methionine/Choline Deficient Diet-Induced NASH Model via Modulation of Cannabinoid Receptor
Authors: Aljobaily Nouf , Krutsinger Kelsey , Viereckl Michael J. , Joly Raznin , Menlove Bridger , Cone Brexton , Suppes Ailaina , Han Yuyan
Published: January 2023

Non-Alcoholic Steatohepatitis (NASH) is the progressive form of Non-Alcoholic Fatty Liver Disease (NAFLD). NASH is distinguished by severe hepatic fibrosis and inflammation. The plant-derived, non-psychotropic compound cannabigerol (CBG) has potential anti-inflammatory effects similar to other cannabinoids. However, the impact of CBG on NASH pathology is still unknown. This study demonstrated the therapeutic potential of CBG in reducing hepatic steatosis, fibrosis, and inflammation. Methods: 8-week-old C57BL/6 male mice were fed with methionine/choline deficient (MCD) diet or control (CTR) diets for five weeks. At the beginning of week 4, mice were divided into three sub-groups and injected with either a vehicle, a low or high dose of CBG for two weeks. Overall health of the mice, Hepatic steatosis, fibrosis, and inflammation were evaluated. Results: Increased liver-to-body weight ratio was observed in mice fed with MCD diet, while a low dose of CBG treatment rescued the liver-to-body weight ratio. Hepatic ballooning and leukocyte infiltration were decreased in MCD mice with a low dose of CBG treatment, whereas the CBG treatment did not change the hepatic steatosis. The high dose CBG administration increased inflammation and fibrosis. Similarly, the expression of cannabinoid receptor (CB)1 and CB2 showed decreased expression with the low CBG dose but not with the high CBG dose intervention in the MCD group and were co-localized with mast cells. Additionally, the decreased mast cells were accompanied by decreased expression of transforming growth factor (TGF)-β1. Conclusions: Collectively, the low dose of CBG alleviated hepatic fibrosis and inflammation in MCD-induced NASH, however, the high dose of CBG treatment showed enhanced liver damage when compared to MCD only group. These results will provide pre-clinical data to guide future intervention studies in humans addressing the potential uses of CBG for inflammatory liver pathologies, as well as open the door for further investigation into systemic inflammatory pathologies.
Effectiveness and Components of Web-Based Interventions on Weight Changes in Adults Who Were Overweight and Obese: A Systematic Review with Meta-Analyses
Authors: Shi Yutong , Wakaba Kyohsuke , Kiyohara Kosuke , Hayashi Fumi , Tsushita Kazuyo , Nakata Yoshio
Published: January 2023

Overweight and obesity have reached epidemic proportions worldwide. The COVID-19 pandemic resulted in an increased need for remote implementation of weight-loss interventions; therefore, the effectiveness of web-based interventions needed to be assessed. This study aimed to examine the effectiveness of web-based interventions and their potency in facilitating weight changes in adults who were overweight or obese. We searched PubMed and Ichu-shi Web from the first year of inclusion in each database until the search date (30 September 2020). Among 1466 articles retrieved from the two databases and manual search, 97 were selected to undergo qualitative analysis and 51 articles were subjected to quantitative analysis. Qualitative analysis of 97 articles demonstrated that articles showing significant effectiveness mostly used the following components: social support, self-monitoring for behavior, self-monitoring for the outcome (weight), behavioral goal setting, information about health consequences, and outcome goal setting. Quantitative analysis of 51 articles showed a significant effectiveness of web-based intervention (standardized mean difference, −0.57; 95% confidence interval, −0.75 to −0.40). This study demonstrated the effectiveness of web-based interventions on weight change in adults with overweight and obesity. Subgroup meta-analyses identified personalized information provision and expert advice to be remarkably effective components.
Selected Seeds as Sources of Bioactive Compounds with Diverse Biological Activities
Authors: Sławińska Natalia , Olas Beata
Published: January 2023

Seeds contain a variety of phytochemicals that exhibit a wide range of biological activities. Plant-derived compounds are often investigated for their antioxidant, anti-inflammatory, immunomodulatory, hypoglycemic, anti-hypercholesterolemic, anti-hypertensive, anti-platelet, anti-apoptotic, anti-nociceptive, antibacterial, antiviral, anticancer, hepatoprotective, or neuroprotective properties. In this review, we have described the chemical content and biological activity of seeds from eight selected plant species—blackberry (Rubus fruticosus L.), black raspberry (Rubus coreanus Miq.), grape (Vitis vinifera L.), Moringa oleifera Lam., sea buckthorn (Hippophae rhamnoides L.), Gac (Momordica cochinchinensis Sprenger), hemp (Cannabis sativa L.), and sacha inchi (Plukenetia volubilis L). This review is based on studies identified in electronic databases, including PubMed, ScienceDirect, and SCOPUS. Numerous preclinical, and some clinical studies have found that extracts, fractions, oil, flour, proteins, polysaccharides, or purified chemical compounds isolated from the seeds of these plants display promising, health-promoting effects, and could be utilized in drug development, or to make nutraceuticals and functional foods. Despite that, many of these properties have been studied only in vitro, and it’s unsure if their effects would be relevant in vivo as well, so there is a need for more animal studies and clinical trials that would help determine if they could be applied in disease prevention or treatment.
Lactobacillus plantarum J26 Alleviating Alcohol-Induced Liver Inflammation by Maintaining the Intestinal Barrier and Regulating MAPK Signaling Pathways
Authors: Li Hongxuan , Cheng Shasha , Huo Jiacheng , Dong Kai , Ding Yixin , Man Chaoxin , Zhang Yu , Jiang Yujun
Published: January 2023

Alcoholic liver disease (ALD), as a global health problem, is mainly caused by liver inflammation. Meanwhile, probiotics have been considered as a potential and promising strategy to prevent and alleviate ALD. This study aimed to investigate the ameliorative effect of pre-intaking with Lactobacillus plantarum J26 (L. plantarum J26) on alcohol-induced liver inflammation, with emphasis on the underlying mechanism for alleviating ALD. The results indicated that L. plantarum J26 could reduce the abundance of Gram-negative pathogenic bacteria by regulating the gut microbiota in mice with alcoholic liver injury, thereby reducing the lipopolysaccharide (LPS) content in the intestine. In addition, L. plantarum J26 could also maintain the intestinal barrier, prevent LPS from crossing the intestinal barrier to correct disorders of the gut–liver axis and then inhibit the activation of Toll-like receptor 4 (TLR4)-mediated MAPK signaling pathway, reducing liver inflammation and restoring liver functions. In conclusion, pre-intake of L. plantarum J26 could alleviate alcohol-induced liver inflammation, which may be closely related to the role of intestinal microbiota in regulating and maintaining the intestinal barrier and then regulating the MAPK signaling pathway.
Identification of Kynurenic Acid-Induced Apoptotic Biomarkers in Gastric Cancer-Derived AGS Cells through Next-Generation Transcriptome Sequencing Analysis
Authors: Kim Hun Hwan , Ha Sang Eun , Park Min Yeong , Jeong Se Hyo , Bhosale Pritam Bhagwan , Abusaliya Abuyaseer , Won Chung Kil , Heo Jeong Doo , Ahn Meejung , Seong Je Kyung , Kim Hyun Wook , Kim Gon Sup
Published: January 2023

Understanding the triggers and therapeutic targets for gastric cancer, one of the most common cancers worldwide, can provide helpful information for the development of therapeutics. RNA sequencing technology can be utilized to identify complex disease targets and therapeutic applications. In the present study, we aimed to establish the pharmacological target of Kynurenic acid (KYNA) for gastric cancer AGS cells and to identify the biological network. RNA sequencing identified differentially expressed genes (DEGs) between KYNA-treated and untreated cells. A total of 278 genes were differentially expressed, of which 120 genes were up-regulated, and 158 genes were down-regulated. Gene ontology results confirmed that KYNA had effects such as a reduction in genes related to DNA replication and nucleosome organization on AGS cells. Protein–protein interaction was confirmed through STRING analysis, and it was confirmed that cancer cell growth and proliferation were inhibited through KEGG, Reactome, and Wiki pathway analysis, and various signaling pathways related to cancer cell death were induced. It was confirmed that KYNA treatment reduced the gene expression of cancer-causing AP-1 factors (Fos, Jun, ATF, and JDP) in AGS cell lines derived from gastric cancer. Overall, using next-generation transcriptome sequencing data and bioinformatics tools, we confirmed that KYNA had an apoptosis effect by inducing changes in various genes, including factor AP-1, in gastric cancer AGS cells. This study can identify pharmacological targets for gastric cancer treatment and provide a valuable resource for drug development.
Glutathione Protects against Paraquat-Induced Oxidative Stress by Regulating Intestinal Barrier, Antioxidant Capacity, and CAR Signaling Pathway in Weaned Piglets
Authors: Xiang Xuan , Wang Houfu , Zhou Wentao , Wang Chenyu , Guan Peng , Xu Gang , Zhao Qiang , He Liuqin , Yin Yulong , Li Tiejun
Published: January 2023

Endogenous glutathione (GSH) effectively regulates redox homeostasis in the body. This study aimed to investigate the regulatory mechanism of different dietary levels of GSH supplementation on the intestinal barrier and antioxidant function in a paraquat-induced stress-weaned piglet model. Our results showed that dietary 0.06% GSH supplementation improved the growth performance of weaned piglets under normal and stressful conditions to some degree and decreased the diarrhea rate throughout. Exogenous GSH improved paraquat-induced changes in intestinal morphology, organelle, and permeability and reduced intestinal epithelial cell apoptosis. Moreover, GSH treatment alleviated intestinal oxidative stress damage by upregulating antioxidant (GPX4, CnZnSOD, GCLC, and GCLM) and anti-inflammatory (IL-10) gene expression and downregulating inflammatory cytokines (IFN-γ and IL-12) gene expression. Furthermore, GSH significantly reduced the expression levels of constitutive androstane receptor (CAR), RXRα, HSP90, PP2Ac, CYP2B22, and CYP3A29, and increased the expression levels of GSTA1 and GSTA2 in the jejunum and ileum of paraquat-induced piglets. We conclude that exogenous GSH protects against oxidative stress damage by regulating the intestinal barrier, antioxidant capacity, and CAR signaling pathway.
Gluten-Free Diet in Co-Existent Celiac Disease and Type 1 Diabetes Mellitus: Is It Detrimental or Beneficial to Glycemic Control, Vascular Complications, and Quality of Life?
Authors: Eland Ingo , Klieverik Lars , Mansour Abbas Ali , Al-Toma Abdulbaqi
Published: January 2023

Celiac disease (CeD) is associated with type 1 diabetes mellitus (T1DM), and both have the same genetic background. Most patients with T1DM who develop CeD are either asymptomatic or have mild CeD-related gastrointestinal symptoms. Therefore, children affected by T1DM should undergo screening for asymptomatic CeD. The aim of this review is to highlight the influence of a gluten-free diet (GFD) on glycemic control, growth rate, microvascular complications, and quality of life in patients with T1DM and CeD. PubMed, Google Scholar, Web of Science, and Cochrane Central databases were searched. Reports reviewed were those published from 1969 to 2022 that focused on the interplay of T1DM and CeD and examined the effect of diet on glycemic control, growth rate, and quality of life. The most challenging aspect for a child with T1DM and CeD is that most GFD foods have a high glycemic index, while low glycemic index foods are recommended for T1DM. Interestingly, dietary therapy for CeD could improve the elevated HbA1c levels. Avoiding gluten added to a diabetic dietary regimen in T1DM patients might impose practical limitations and lead to important restrictions in the lifestyle of a young patient. Consequently, non-adherence to GFD in patients with T1DM and CeD is common. GFD in patients with T1DM and CeD seems to lower the incidence of micro- and macrovascular complications, but this requires further investigation. It seems that adherence to GFD in young patients with T1DM and CeD leads to regular growth and a stable body mass index without any negative effect on HbA1c or insulin requirements. Furthermore, the lipid profile and quality of life seem to have improved with the introduction of GFD.
Real-World Intake of Dietary Sugars Is Associated with Reduced Cortisol Reactivity Following an Acute Physiological Stressor
Authors: Di Polito Nicola , Stylianakis Anthea A. , Richardson Rick , Baker Kathryn D.
Published: January 2023

There is increasing academic and clinical interest in understanding the nature of the relation between diet and response to stress exposure as a risk factor for mental illness. Cross-species evidence shows that conditions of chronic and acute stress increase the intake of, and preference for, caloric-dense palatable foods, a phenomenon thought to be explained by the mitigating effects of comfort foods on the activity of the stress-response network. It is largely unknown whether and how real-world dietary intake of saturated fat and sugars impacts stress responsivity in humans. Therefore, here we examined whether real-world dietary intake of saturated fat and sugars predicted salivary cortisol reactivity following an acute physiological stressor. Multilevel modelling of four salivary cortisol measures collected up to 65 min after the stressor on 54 participants (18–49 years old) were analyzed using a quadratic growth curve model. Sugar intake significantly predicted a weaker cortisol response following the Cold Pressor Test (CPT) controlling for BMI and gender, revealing an inhibitory effect of caloric-dense diets on cortisol reactivity to stress. As the consumption of sugar rose individuals had lower post-stressor cortisol levels, a smaller rate of increase in cortisol 20 and 35 min after the CPT, a lower cortisol peak, and an overall weaker quadratic effect. These observations add to a growing body of evidence reporting suppressive effects of high-energy foods on stress-associated glucocorticoids reactivity and are consistent with the comfort food hypothesis, where people are seen as motivated to eat palatable foods to alleviate the detrimental repercussions of stressor exposure.
Sleep Duration, Midday Napping, and Serum Homocysteine Levels: A Gene–Environment Interaction Study
Authors: Mo Tingting , Wang Yufei , Gao Hui , Li Wending , Zhou Lue , Yuan Yu , Zhang Xiaomin , He Meian , Guo Huan , Long Pinpin , Wu Tangchun
Published: January 2023

The associations of sleep duration and midday napping with homocysteine (Hcy) levels, and whether these sleep behaviors modify the association between genetic predisposition and Hcy levels, has yet to be investigated. We included 19,426 participants without severe health conditions at baseline from the Dongfeng–Tongji cohort. In a subgroup of 15,126 participants with genetic data, a genetic risk score (GRS) based on 18 Hcy-related loci was constructed to test the gene–sleep interactions in Hcy. Hcy levels were higher in subjects with a long sleep duration (≥9 h) and midday napping (>90 min), as compared to those who reported a moderate sleep duration (7 to <8 h) and midday napping (1–30 min) (all p values < 0.05). A long sleep duration and midday napping showed a joint effect in increasing Hcy (p for trend < 0.001). Significant interactions regarding Hcy levels were observed for a long sleep duration with GRS and MTHFR rs1801133, and long midday napping with DPEP1 rs12921383 (all p values for interaction < 0.05). Overall findings indicated that a long sleep duration and midday napping were associated with elevated serum Hcy levels, independently and jointly, and amplified the genetic susceptibility to higher Hcy.
The Association between Sugar-Sweetened Beverages and Male Pattern Hair Loss in Young Men
Authors: Shi Xiaojin , Tuan Hsiaohan , Na Xiaona , Yang Haibing , Yang Yucheng , Zhang Yulin , Xi Menglu , Tan Yuefeng , Yang Celi , Zhang Junhan , Zhao Ai
Published: January 2023

We performed this study to investigate the association between sugar-sweetened beverage (SSB) consumption and male pattern hair loss (MPHL) in young men. We conducted this cross-sectional study from January to April 2022 in mainland China. Young people aged 18–45 years (n = 1951) were recruited from 31 provinces in China. We used a self-reported online survey for data collection. We explored the associations between the amount/frequency of SSB consumption and MPHL by using a binary logistic regression model, with adjustments for sociodemographic, hair status, dietary intake, lifestyle, and psychological factors. Among the 1028 participants (27.8 ± 7.2 years) in the final analysis, we found that high SSB consumption is associated with a higher risk of MPHL. We recommend more support to decrease SSB consumption among young people to minimize negative health outcomes.
Five U.S. Dietary Patterns and Their Relationship to Land Use, Water Use, and Greenhouse Gas Emissions: Implications for Future Food Security
Authors: Jennings Rose , Henderson Andrew D. , Phelps Alexis , Janda Kathryn M. , van den Berg Alexandra E.
Published: January 2023

The U.S. agri-food system is a driver of climate change and other impacts. In order to achieve environmental targets that limit global mean temperature rise ≤2 °C, a shift in American dietary patterns is critical. The purpose of this study was twofold: (1) to determine the environmental impact (i.e., land use, water use, and GHG emissions) related to consumption of five U.S. dietary patterns (i.e., Current U.S., the Healthy U.S., Mediterranean, Healthy Vegetarian, and Vegan), and (2) to determine the specific impact of each food group in each dietary pattern on the three environmental indicators. This study utilized existing datasets to synthesize information related to the study’s environmental indicators and food production and connected these data to the current U.S. diet and the USDA-defined diets. Results indicate that the three omnivore diets contributed the greatest to GHG emissions, land use and water use. The Vegan diet scored the lowest across all indicators, although the water required for plant-based protein nearly offset other water gains. For the omnivore diets, red meat and dairy milk contributed the most to each environmental indicator. By considering sustainability as well as health outcomes in their recommendations in the Dietary Guidelines, the USDA can have a critical role in shifting diets necessary to alter climate change trends.
In Vitro Fermentation of Beechwood Lignin–Carbohydrate Complexes Provides Evidence for Utilization by Gut Bacteria
Authors: Ma Xiaochen , Liu Shujun , Wang Hongliang , Wang Yulu , Li Zhen , Gu Tianyi , Li Yulong , Xin Fengjiao , Wen Boting
Published: January 2023

Lignin–carbohydrate complexes (LCCs) are emerging as a new and natural product with pharmacological and nutraceutical potential. It is uncertain, however, whether LCCs have a positive effect on the microbiota of the gut based on the current evidence. Here, the LCC extracted from beechwood (BW-LCC) was used as a substrate for in vitro fermentation. The lignin in BW-LCC consisted of guaiacyl (G) and syringyl (S) units, which are mainly linked by β-O-4 bonds. After 24 h of in vitro fermentation, the pH had evidently declined. The concentrations of acetic acid and propionic acid, the two main short-chain fatty acids (SCFAs), were significantly higher than in the control group (CK). In addition, BW-LCC altered the microbial diversity and composition of gut microbes, including a reduction in the relative abundance of Firmicutes and an increase in the relative abundance of Proteobacteria and Bacteroidetes. The relative abundance of Escherichia coli-Shigella and Bacteroides were the most variable at the genus level. The genes of carbohydrate-active enzymes (CAZymes) also changed significantly with the fermentation and were related to the changes in microbes. Notably, the auxiliary actives (AAs), especially AA1, AA2, and AA3_2, play important roles in lignin degradation and were significantly enriched and concentrated in Proteobacteria. From this study, we are able to provide new perspectives on how gut microbes utilize LCC.
Celiac Disease Predisposition and Genital Tract Microbiota in Women Affected by Recurrent Pregnancy Loss
Authors: Masucci Luca , D’Ippolito Silvia , De Maio Flavio , Quaranta Gianluca , Mazzarella Roberta , Bianco Delia Mercedes , Castellani Roberta , Inversetti Annalisa , Sanguinetti Maurizio , Gasbarrini Antonio , Scambia Giovanni , Di Simone Nicoletta
Published: January 2023

The incidence of Idiopathic Recurrent Pregnancy Loss (RPL) is doubled in patients suffering from Celiac Disease (CD) compared to healthy populations. CD genetic components are HLA class II genes known as HLA-DQ2 and DQ8. Genetically susceptible women can remain asymptomatic even though they are exposed to a doubled risk of RPL compared to the general population. Furthermore, CD has been associated with microbiota alterations. The aim of this study is to evaluate endometrial and vaginal microbiota in HLA-DQ2/DQ8 positive and negative RPL patients compared to healthy pregnant women. Endometrial and vaginal microbiota of 3 subgroups were evaluated: 15 HLA-DQ2/DQ8 positive RPL women, 25 HLA DQ2/DQ8 negative RPL women (for a total of 40 RPL women) and 7 healthy fertile controls with previous uncomplicated pregnancies (all HLA-DQ2/DQ8 negative). The 2 RPL subgroups (HLA-DQ2/DQ8 positive and negative) showed a different endometrial and vaginal composition in the Lactobacillacae family compared to controls: Lactobacillus acidophilus was absent both in the vaginal and endometrial samples of RPL women, while Lactobaciluus iners, which can favor a less stable vaginal microbiota, was found only in RPL women (26.4% in HLA DQ2/DQ8 positive and 22.1% HLA DQ2/DQ8 negative) in both the vaginal and endometrial districts. In conclusion, both HLA DQ2/DQ8 positive-RPL and HLA DQ2/DQ8 negative-RPL women showed different endometrial and vaginal microbiota composition compared to healthy controls.
Dysgeusia in Patients with Breast Cancer Treated with Chemotherapy—A Narrative Review
Authors: Pellegrini Marianna , Merlo Fabio Dario , Agnello Elena , Monge Taira , Devecchi Andrea , Casalone Valentina , Montemurro Filippo , Ghigo Ezio , Sapino Anna , Bo Simona
Published: January 2023

Breast cancer (BC) is the most common cancer worldwide. Chemotherapy (CT) is essential for the treatment of BC, but is often accompanied by several side effects, including taste alterations, due to different mechanisms. Although dysgeusia is usually underestimated by clinicians, it is considered very worrying and disturbing by cancer patients undergoing CT, because it induces changes in dietary choices and social habits, affecting their physical and psychological health, with a profound impact on their quality of life. Several strategies and therapies have been proposed to prevent or alleviate CT-induced dysgeusia. This review aimed to evaluate the available evidence on prevalence, pathophysiological mechanisms, clinical consequences, and strategies for managing dysgeusia in BC patients receiving CT. We queried the National Library of Medicine, the Cochrane Library, Excerpta Medica dataBASE, and the Cumulative Index to Nursing and Allied Health Literature database, performing a search strategy using database-specific keywords. We found that the literature on this topic is scarce, methodologically limited, and highly heterogeneous in terms of study design and criteria for patient inclusion, making it difficult to obtain definitive results and make recommendations for clinical practice.
Exploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer’s Disease
Authors: Schino Ignazio , Cantore Mariangela , de Candia Modesto , Altomare Cosimo D. , Maria Catarina , Barros João , Cachatra Vasco , Calado Patrícia , Shimizu Karina , Freitas Adilson A. , Oliveira Maria C. , Ferreira Maria J. , Lopes José N. C. , Colabufo Nicola A. , Rauter Amélia P.
Published: January 2023

Alzheimer’s Disease (AD) is characterized by a progressive cholinergic neurotransmission imbalance, with a decrease of acetylcholinesterase (AChE) activity followed by a significant increase of butyrylcholinesterase (BChE) in the later AD stages. BChE activity is also crucial for the development of Aβ plaques, the main hallmarks of this pathology. Moreover, systemic copper dyshomeostasis alters neurotransmission leading to AD. In the search for structures targeting both events, a set of novel 6-benzamide purine nucleosides was synthesized, differing in glycone configuration and N7/N9 linkage to the purine. Their AChE/BChE inhibitory activity and metal ion chelating properties were evaluated. Selectivity for human BChE inhibition required N9-linked 6-deoxy-α-d-mannosylpurine structure, while all three tested β-d-derivatives appeared as non-selective inhibitors. The N9-linked l-nucleosides were cholinesterase inhibitors except the one embodying either the acetylated sugar or the N-benzyl-protected nucleobase. These findings highlight that sugar-enriched molecular entities can tune bioactivity and selectivity against cholinesterases. In addition, selective copper chelating properties over zinc, aluminum, and iron were found for the benzyl and acetyl-protected 6-deoxy-α-l-mannosyl N9-linked purine nucleosides. Computational studies highlight molecular conformations and the chelating molecular site. The first dual target compounds were disclosed with the perspective of generating drug candidates by improving water solubility.
RGD Forever!—Past, Present, and Future of a 3-Letter-Code in Radiopharmacy and Life Sciences
Authors: Notni Johannes
Published: January 2023

“RGD” is frequently pictured as a ligand for αvβ3-integrin and useful for molecular targeting of angiogenesis—which is about as simplistic as the idea that laser beams are green or red and particularly useful for arming spaceships. There is, however, much more to RGD. In particular, targeting angiogenesis is likely not the most significant stronghold of RGD-comprising constructs. RGD is the one-letter code of a very short peptide sequence, arginine-lysine-aspartate, which is recognized by eight different integrins, namely, α(IIb)β3, α5β1, α8β1, and the five dimers that αv forms with β1, β3, β5, β6, and β8. These 8 RGD receptors form an own subset among the entire class of 24 known integrins, which furthermore comprises another three distinct groups (4 collagen receptors, 4 laminin receptors, and 8 leukocyte receptors). However, the 8 RGD-recognizing integrins are far from being alike. They do not even share the same tissue prevalences and functions, but are expressed on fundamentally different cell types and fulfill the most diverse biological tasks. For example, α(IIb)β3 is found on platelets and mediates thrombus formation, whereas αvβ6- and αvβ8-integrin are expressed on epithelial cells, activate TFG-β, and thus may promote cancer progression and invasion as well as fibrosis. Recent non-clinical experiments and clinical findings suggest that the highly specific expression of αvβ6-integrin by some carcinoma types, in combination with the availability of the corresponding small-molecule ligands, may open a multitude of new and promising avenues for improved cancer diagnosis and therapy, including, but not limited to, radiopharmaceutical approaches.
Current Knowledge of the Antidepressant Activity of Chemical Compounds from Crocus sativus L.
Authors: Matraszek-Gawron Renata , Chwil Mirosława , Terlecki Karol , Skoczylas Michał Marian
Published: January 2023

Psychotropic effect of Crocus sativus L. (family Iridaceae) biologically active chemical compounds are quite well documented and they can therefore be used in addition to the conventional pharmacological treatment of depression. This systematic review on antidepressant compounds in saffron crocus and their mechanisms of action and side effects is based on publications released between 1995–2022 and data indexed in 15 databases under the following search terms: antidepressant effect, central nervous system, Crocus sativus, cognitive impairement, crocin, crocetin, depression, dopamine, dopaminergic and serotonergic systems, picrocrocin, phytotherapy, neurotransmitters, safranal, saffron, serotonin, and biologically active compounds. The comparative analysis of the publications was based on 414 original research papers. The investigated literature indicates the effectiveness and safety of aqueous and alcoholic extracts and biologically active chemical compounds (alkaloids, anthocyanins, carotenoids, flavonoid, phenolic, saponins, and terpenoids) isolated from various organs (corms, leaves, flower petal, and stigmas) in adjuvant treatment of depression and anxiety. Monoamine reuptake inhibition, N-methyl-d-aspartate (NMDA) receptor antagonism, and gamma-aminobutyric acid (GABA)-α agonism are the main proposed mechanism of the antidepressant action. The antidepressant and neuroprotective effect of extract components is associated with their anti-inflammatory and antioxidant activity. The mechanism of their action, interactions with conventional drugs and other herbal preparations and the safety of use are not fully understood; therefore, further detailed research in this field is necessary. The presented results regarding the application of C. sativus in phytotherapy are promising in terms of the use of herbal preparations to support the treatment of depression. This is particularly important given the steady increase in the incidence of this disease worldwide and social effects.
Targeting Annexin A1 as a Druggable Player to Enhance the Anti-Tumor Role of Honokiol in Colon Cancer through Autophagic Pathway
Authors: Wang Xi , Shao Gang , Hong Xiangyu , Shi Yue , Zheng Yiting , Yu Yucheng , Fu Caiyun
Published: January 2023

Colon cancer is one of the most common digestive tract malignancies, having the second highest mortality rate among all tumors, with a five-year survival of advanced patients of only 10%. Efficient, targeted drugs are still lacking in treating colon cancer, so it is urgent to explore novel druggable targets. Here, we demonstrated that annexin A1 (ANXA1) was overexpressed in tumors of 50% of colon cancer patients, and ANXA1 overexpression was significantly negatively correlated with the poor prognosis of colon cancer. ANXA1 promoted the abnormal proliferation of colon cancer cells in vitro and in vivo by regulating the cell cycle, while the knockdown of ANXA1 almost totally inhibited the growth of colon cancer cells in vivo. Furthermore, ANXA1 antagonized the autophagic death of honokiol in colon cancer cells via stabilizing mitochondrial reactive oxygen species. Based on these results, we speculated that ANXA1 might be a druggable target to control colon cancer and overcome drug resistance.
Effects of Cationic Dendrimers and Their Complexes with microRNAs on Immunocompetent Cells
Authors: Knauer Nadezhda , Pashkina Ekaterina , Aktanova Alina , Boeva Olga , Arkhipova Valeria , Barkovskaya Margarita , Meschaninova Mariya , Karpus Andrii , Majoral Jean-Pierre , Kozlov Vladimir , Apartsin Evgeny
Published: January 2023

Short regulatory oligonucleotides are considered prospective tools for immunotherapy. However, they require an adequate carrier to deliver potential therapeutics into immune cells. Herein, we explore the potential of polycationic dendrimers as carriers for microRNAs in peripheral blood mononuclear cells of healthy donors. As an oligonucleotide cargo, we use a synthetic mimic and an inhibitor of miR-155, an important factor in the development and functioning of immunocompetent cells. Dendrimers bind microRNAs into low-cytotoxic polyelectrolyte complexes that are efficiently uptaken by immunocompetent cells. We have shown these complexes to affect the number of T-regulatory cells, CD14+ and CD19+ cell subpopulations in non-activated mononuclear cells. The treatment affected the expression of HLA-DR on T-cells and PD-1 expression on T- and B-lymphocytes. It also affected the production of IL-4 and IL-10, but not the perforin and granzyme B production. Our findings suggest the potential of dendrimer-mediated microRNA-155 treatment for immunotherapy, though the activity of microRNA-dendrimer constructions on distinct immune cell subsets can be further improved.
Characteristics of Successful International Pharmacy Partnerships
Authors: Prescott Gina M. , Jonkman Lauren , Crutchley Rustin D. , Dey Surajit , Hong Lisa T. , Malhotra Jodie , Seo See-Won , Kawaguchi-Suzuki Marina , Truong Hoai-An , Unni Elizabeth , Tsuchihashi Kayo , Forkan Nubaira , Abrons Jeanine P.
Published: January 2023

Recommendations for global pharmacy collaborations are predominately derived from US institutions. This study utilized semi-structured interviews of global collaborators to assess important partnership components. Interviewees stated personal connections and understanding of each other’s programs/systems were key components. Additionally, collaborators indicate that mutual benefits between partners can exist without the requirement for bidirectional exchange of learning experiences, and request and value partners and learners who are culturally aware, global citizens. This structured interview approach provided key insight into how to develop mutually beneficial, sustainable partnerships and provides additional confirmation that the five pillars of global engagement align with an international audience.
Simulated LCSLM with Inducible Diffractive Theory to Display Super-Gaussian Arrays Applying the Transport-of-Intensity Equation
Authors: Arriaga-Hernandez Jesus , Cuevas-Otahola Bolivia , Oliveros-Oliveros Jacobo , Morín-Castillo María , Martínez-Laguna Ygnacio , Cedillo-Ramírez Lilia
Published: January 2023

We simulate a liquid crystal spatial light modulator (LCSLM), previously validated by Fraunhofer diffraction to observe super-Gaussian periodic profiles and analyze the wavefront of optical surfaces applying the transport-of-intensity equation (TIE). The LCSLM represents an alternative to the Ronchi Rulings, allowing to avoid all the related issues regarding diffractive and refractive properties, and noise. To this aim, we developed and numerically simulated a LCSLM resembling a fractal from a generating base. Such a base is constituted by an active square (values equal to one) and surrounded by eight switched-off pixels (zero-valued). We replicate the base in order to form 1 ×N-pixels and the successive rows to build the 1024×1024 LCSLM of active pixels. We visually test the LCSLM with calibration images as a diffractive object that is mathematically inducible, using mathematical induction over the N×N-shape (1×1, 2×2, 3×3, …, n×n pixels for the generalization). Finally, we experimentally generate periodic super-Gaussian profiles to be visualized in the LCSLM (transmission SLM, 1024×768-pixels LC 2012 Translucent SLM), modifying the TIE as an optical test in order to analyze the optical elements by comparing the results with ZYGO/APEX.
A Bound State in the Continuum Supported by a Trimeric Metallic Metasurface
Authors: Fu Tao , Wang Ziyan , Chen Yonghe
Published: January 2023

A bound state in the continuum (BIC) is a localized state in a continuous spectrum of radiating waves. In this study, the coupled-mode theory is introduced to more precisely interpret a symmetry-protected BIC and the quasi-BIC in a facile trimeric metasurface, compared with Fano formula, which is introduced to generate a high-quality factor resonance in a trimeric metallic slit metasurface. The multipole decomposition method and the near field distribution of the structure further illustrate that the underlying physics of the high-Q is mainly originated from the interference between the electric quadrupole mode and the magnetic toroidal mode. Physical mechanism shows that the resonance arises from the perturbation of symmetry-protected BICs. The result may play a role in the applications of lasers, optical sensors, and low-loss fibers.
Microstructure and Self-Healing Capability of Artificial Skin Composites Using Biomimetic Fibers Containing a Healing Agent
Authors: Sun Qian , Gao Xu , Wang Sai , Shao Rong-Yue , Wang Xin-Yu , Su Jun-Feng
Published: January 2023

The aging and damage of artificial skin materials for artificial intelligence robots are technical problems that need to be solved urgently in their application. In this work, poly (vinylidene fluoride) (PVDF) fibers containing a liquid agent were fabricated directly as biomimetic microvasculars, which were mixed in a glycol–polyvinyl alcohol–gelatin network gel to form biomimetic self-healing artificial skin composites. The self-healing agent was a uniform-viscous buffer solution composed of phosphoric acid, acetic acid, and sodium carboxymethyl cellulose (CMC-Na), which was mixed under 40 °C. Microstructure analysis showed that the fiber surface was smooth and the diameter was uniform. SEM images of the fiber cross-sections showed that there were uniformly distributed voids. With the extension of time, there was no phenomenon of interface separation after the liquid agent diffused into the matrix through the fiber cavity. The entire process of self-healing was observed and determined including fiber breakage and the agent diffusion steps. XRD and FT–IR results indicated that the self-healing agent could enter the matrix material through fiber damage or release and it chemically reacted with the matrix material, thereby changing the chemical structure of the damaged matrix. Self-healing behavior analysis of the artificial skin indicated that its self-healing efficiency increased to an impressive 97.0% with the increase in temperature to 45 °C.
Expansion of Single Chains Released from a Spherical Cavity
Authors: Chu Chia-Cheng , Hsiao Pai-Yi
Published: January 2023

A two-stage model is developed to explain the phenomena of chain expansion, released from a confining cavity. In the first stage, the chain is assumed to expand as a sphere, while in the second stage it expands like a coil. The kinetic equations for the variation of chain size are derived in the two stages by balancing the rate of the free energy change with the rate of the energy dissipation. Langevin dynamics simulations are then performed to examine the theory. We find that the expansion process is dominated by the second stage and the evolution of chain size follows, mainly, the predicted curve for coil expansion, which depends on the chain length and is not sensitive to the confining volume fraction. It permits to define the expansion time for the process. Further study reveals that the chain does undergo a spherical expansion in the first stage with the characteristic time much shorter than the one for the second stage. As a consequence, the first-stage variation of chain size can be regarded as an add-on to the principal curve of expansion designated by the second stage. The scaling behaviors and the associated scaling exponents are analyzed in details. The simulation results well support the theory.
New Polycaprolactone-Containing Self-Healing Coating Design for Enhance Corrosion Resistance of the Magnesium and Its Alloys
Authors: Gnedenkov Andrey S. , Sinebryukhov Sergey L. , Filonina Valeriia S. , Ustinov Alexander Yu. , Sukhoverkhov Sviatoslav V. , Gnedenkov Sergey V.
Published: January 2023

The method of hybrid coating formation on the surface of a bioresorbable wrought magnesium alloy and magnesium obtained by additive technology was proposed. Plasma electrolytic oxidation (PEO) with subsequent treatment of the material using an organic biocompatible corrosion inhibitor and a bioresorbable polymer material was used to obtain the protective layers. The optimal method of surface treatment was suggested. Using SEM/EDX analysis, XRD, XPS, and confocal Raman microspectroscopy, the composition of the formed surface layers was determined. The corrosion protection performance of the formed coatings was studied by potentiodynamic polarization and electrochemical impedance spectroscopy techniques in 0.9 wt.% NaCl and HBSS. Hydrogen evolution and mass loss tests were performed to study the corrosion rate of samples with different types of protective coatings. Sealing the pores of PEO coating with a polymeric material contributes to a significant reduction in the amount of the inhibitor diffusing into a corrosive medium. The best barrier properties were established for the hybrid coating formed with a one-stage application of benzotriazole and polycaprolactone. Such layers reduce the rate of alloy degradation due to active protection.
Polymeric Encapsulate of Streptomyces Mycelium Resistant to Dehydration with Air Flow at Room Temperature
Authors: Mancera-López María Elena , Barrera-Cortés Josefina , Mendoza-Serna Roberto , Ariza-Castolo Armando , Santillan Rosa
Published: January 2023

Encapsulation is one of the technologies applied for the formulation of biological control agents. The function of the encapsulating matrix is to protect the biological material from environmental factors, while dehydration allows for its viability to be prolonged. An advantage of dehydrated encapsulation formulations is that they can be stored for long periods. However, vegetative cells require low-stress dehydration processes to prevent their loss of viability. Herein we describe the fabrication of a dehydrated encapsulate of the Streptomyces CDBB1232 mycelium using sodium alginate with a high concentration of mannuronic acid; sodium alginate was added with YGM medium for mycelium protection purposes. The encapsulation was carried out by extrusion, and its dehydration was carried out in a rotating drum fed with air at room temperature (2–10 L min−1). The drying of the capsules under air flows higher than 4 L min−1 led to viability loss of the mycelium. The viability loss can be decreased up to 13% by covering the alginate capsules with gum arabic. Compared to conventional dehydration processes, air moisture removal can be lengthy, but it is a low-cost method with the potential to be scaled.
Characterization and Comparison of Bioactive Polysaccharides from Grifola frondosa by HPSEC-MALLS-RID and Saccharide Mapping Based on HPAEC-PAD
Authors: Zhu Baojie , Zhang Wenxia , Zhao Jing , Chen Bilian , Liu Fei , Li Shaoping
Published: January 2023

Grifola frondosa polysaccharides (GFPs) from different regions in China were characterized and compared using HPSEC-MALLS-RID and saccharide mapping based on HPAEC-PAD analysis for achieving and improving its quality control. The results showed that HPSEC chromatograms and molecular weight distributions of GFPs were similar. The average contents of each polysaccharide fraction (Peaks 1, 2, and 3) showed that Peak 3 was the main component and much higher than the other two polysaccharide fractions, which also contained protein. The result of saccharide mapping showed that α-1,4-glycosidic, β-1,4-glycosidic and few β-1,3-glycosidic linkages were existed in GFPs. The similarity result showed that HPAEC-PAD fingerprints of the oligosaccharide fragments after hydrolysis by endoglycosidase were certainly different, especially α-amylase with a mean similar index of only 0.781 ± 0.207. The result of hierarchical cluster analysis (HCA) showed that different batches of GFPs from China can be divided into different clusters. Furthermore, immune-enhancing activity based on RAW 264.7 cells showed significant differences among different GFPs. Based on grey relational analysis (GRA), the fractions of Peak 3 were regarded as the major contributors to its immuno-enhancing activity in GFPs. Overall, the implications from these results were found to be stable, comprehensive, and valid for improving the quality control of GFPs.
Enhancing the Antifungal Activity and Ophthalmic Transport of Fluconazole from PEGylated Polycaprolactone Loaded Nanoparticles
Authors: Almehmady Alshaimaa M. , El-Say Khalid M. , Mubarak Manal A. , Alghamdi Haneen A. , Somali Njood A. , Sirwi Alaa , Algarni Rahmah , Ahmed Tarek A.
Published: January 2023

Fungal eye infections are caused mainly by an eye injury and can result in serious eye damage. Fluconazole (FLZ), a broad-spectrum antifungal agent, is a poorly soluble drug with a risk of hepatotoxicity. This work aimed to investigate the antifungal activity, ocular irritation, and transport of FLZ-loaded poly (ε-caprolactone) nanoparticles using a rabbit eye model. Three formulation factors affecting the nanoparticle’s size, zeta potential, and entrapment efficiency were optimized utilizing the Box-Behnken design. Morphological characteristics and antifungal activity of the optimized nanoparticles were studied. The optimized nanoparticles were loaded into thermosensitive in situ hydrogel and hydroxypropylmethylcellulose (HPMC) hydrogel ophthalmic formulations. The rheological behavior, in vitro release and in vivo corneal transport were investigated. Results revealed that the percentage of poly (ε-caprolactone) in the nanoparticle matrix, polymer addition rate, and mixing speed significantly affected the particle size, zeta potential, and entrapment efficiency. The optimized nanoparticles were spherical in shape and show an average size of 145 nm, a zeta potential of −28.23 mV, and a FLZ entrapment efficiency of 98.2%. The antifungal activity of FLZ-loaded nanoparticles was significantly higher than the pure drug. The developed ophthalmic formulations exhibited a pseudoplastic flow, prolonged the drug release and were found to be non-irritating to the cornea. The prepared FLZ pegylated nanoparticles were able to reach the posterior eye segment without eye irritation. As a result, the developed thermosensitive in situ hydrogel formulation loaded with FLZ polymeric nanoparticles is a promising drug delivery strategy for treating deep fungal eye infections.
N, S-Doped Carbon Dots Prepared by Peanut Protein Isolates and Cysteamine as Highly Sensitive Fluorescent Sensors for Fe2+, Fe3+ and Lactoferrin
Authors: Wang Xinxin , Zu Xinyu , Wang Ting , Zhao Yanan , Liang Yan , Wang Xiaochen , Chai Qian , Zhang Yunjuan , Chen Hongzhong , Wang Hua
Published: January 2023

Lactoferrin (LF) is an iron-binding glycoprotein with various biological activities that has been extensively used in food and medical applications. Several methods for detecting LF have been reported, but they still face challenges in terms of sensitivity and simplicity of detection. To achieve an accurate and efficient detection of LF, we developed a method for the determination of LF in lactoferrin supplements using carbon dots (CDs) fluorescent probes. The N, S-doped PPI carbon dots (N, S-PPI-CDs) were prepared using a protein (peanut protein isolate) and cysteamine as precursors. The prepared N, S-PPI-CDs exhibited intense blue fluorescence and good biocompatibility, while the fluorescence intensity of the N, S-PPI-CDs showed a good linear relationship with Fe2+/Fe3+ concentration (0–2 μM). The N, S-PPI-CDs exhibited a high potential ability to rapidly detect Fe2+/Fe3+ within 30 s, with a limit of detection (LoD) of 0.21 μM/0.17 μM. Due to the reversible binding of LF to Fe, the N, S-PPI-CDs showed a high sensitivity and selectivity for LF, with a limit of detection (LoD) of 1.92 μg/mL. In addition, LF was quantified in real sample LF supplements and showed a fluctuation in recovery of less than 2.48%, further demonstrating the effectiveness of the fluorescent N, S-PPI-CDs sensor.