bluuebunny/crossref_metadata_2025 huggingface dataset:
Salvia plebeia R. Br. Water Extract Ameliorates Hepatic Steatosis in a Non-Alcoholic Fatty Liver Disease Model by Regulating the AMPK Pathway
Authors: Bae Subin , Lee Yoo-Hyun , Lee Jeongmin , Park Jeongjin , Jun Woojin
Published: December 2022

Salvia plebeia R. Br. (SP), grown from autumn to spring, is used as a medicinal herb from roots to leaves. This herb exhibits antioxidant activities and various physiological effect, including anti-asthma, immune-promoting, anti-obesity, and anti-cholesterol effects. However, the effectiveness of SP against non-alcoholic fatty liver disease (NAFLD) and the associated mechanism have not been elucidated. In this study, alleviation of NAFLD by SP was confirmed in a mouse model of hepatic steatosis induced by a high-fat diet and in HepG2 cells administered free fatty acids (FFA). In the experimental model, intrahepatic lipid accumulation was investigated using the AdipoRedTM assay, Oil Red O staining, biomarker analysis, and hematoxylin and eosin staining. Furthermore, glucose tolerance was examined based on the fasting glucose levels and oral glucose tolerance. The molecular mechanisms related to hepatic steatosis were determined based on marker mRNA levels. Blood FFAs were found to flow into the liver via the action of fatty acid translocase, cluster of differentiation 36, and fatty acid transporter proteins 2 and 5. Salvia plebeia R. Br. water extract (SPW) suppressed the FFAs inflow by regulating the expression of the above-mentioned proteins. Notably, modulating the expression of AMP-activated protein kinase (AMPK) and liver X receptor, which are involved in the regulation of lipid metabolism, stimulated peroxisome proliferator activated receptor α in the nucleus to induce the expression genes involved in β-oxidation and increase β-oxidation in the mitochondria. AMPK modulation also increased the expression of sterol regulatory element binding protein-1c, which activated lipid synthesis enzymes. As a consequence of these events, triglyceride synthesis was reduced and lipid accumulation in hepatocytes was alleviated. Overall, our findings suggested that SPW could ameliorate NAFLD by inhibiting hepatic steatosis through AMPK modulation.
The Role of Food Literacy in Managing Nutritional Precarity in the Migrant Experience: Dietary Lifestyles of Cambodia Migrants in Thailand
Authors: Seng Sary , Feuer Hart Nadav , Charoenratana Sayamol
Published: December 2022

The paper explores the dietary lifestyles of young Cambodian migrants in Thailand to illuminate the role of food literacy in determining nutritional outcomes and well-being, including during crises, such as the COVID-19 pandemic. In this context, food literacy is defined as food skills and abilities to plan, select, and prepare to achieve adequate consumption under new or adverse social and culinary contexts of the migrant experience. In this paper, we consider both how nutritional precarity arises in the migrant experience, and to what extent food literacy can mitigate it under various conditions. The research approach involves a combination of qualitative and quantitative approaches that were adjusted to address the limited mobility for social science research during the COVID-19 pandemic in Thailand. Data collection was conducted through hybrid (online and in-person) ethnography, focus group discussions, food literacy questionnaires, and key informant interviews, often facilitated through internet messaging clients. The findings indicate that, while generally high food literacy may facilitate the transition to the foreign food systems found in migration destinations, optimizing nutrition and well-being requires reinforcement by context-specific food literacy, such as openness to foreign flavors and recipes. Contextual food literacy most directly leads to positive social and health outcomes while simultaneously expanding universal food literacy in the long-term.
The Influence of Nutrition and Physical Activity on Exercise Performance after Mild COVID-19 Infection in Endurance Athletes-CESAR Study
Authors: Śliż Daniel , Wiecha Szczepan , Gąsior Jakub S. , Kasiak Przemysław Seweryn , Ulaszewska Katarzyna , Postuła Marek , Małek Łukasz A. , Mamcarz Artur
Published: December 2022

COVID-19 and imposed restrictions are linked with numerous health consequences, especially among endurance athletes (EA). Unfavorable changes in physical activity and nutrition may affect later sports and competition performance. The aims of this study were: (1) to assess the impact of COVID-19 infection and pandemic restrictions on the nutrition and physical activity of EAs and (2) to compare them with the results of cardiopulmonary exercise testing (CPET). In total, 49 EAs (nmale = 43, nfemale = 6, mean age = 39.9 ± 7.8 year., height = 178.4 ± 6.8 cm, weight = 76.3 ± 10.4 kg; BMI = 24.0 ± 2.6 kg·m−2) underwent pre- and post-COVID-19 CPET and fulfilled the dietary and physical activity survey. COVID-19 infection significantly deteriorated CPET performance. There was a reduction in oxygen uptake and in heart rate post-COVID-19 (both p < 0.001). Consuming processed meat and replacing meat with plant-based protein affected blood lactate concentration (p = 0.035). Fat-free mass was linked with consuming unsaturated fatty acids (p = 0.031). Adding salt to meals influenced maximal speed/power (p = 0.024) and breathing frequency (p = 0.033). Dietary and Fitness Practitioners and Medical Professionals should be aware of possible COVID-19 infection and pandemic consequences among EA. The results of this study are a helpful guideline to properly adjust the treatment, nutrition, and training of EA.
Flavor Wheel Construction and Sensory Profile Description of Human Milk
Authors: Yu Mingguang , Zheng Chengdong , Xie Qinggang , Tang Yuan , Wang Ying , Wang Baosong , Song Huanlu , Zhou Yalin , Xu Yajun , Yang Rongqiang
Published: December 2022

To explore the flavor characteristics of human milk, we constructed a three-tiered human milk flavor wheel based on 53 sensory descriptors belonging to different sensory categories. Fifteen sensory descriptors were selected using M-value and multivariate statistical methods, and the corresponding references were set up to realize qualitative and quantitative sensory evaluation of the human milk samples. To ensure the accuracy and reliability of the sensory evaluation, the performance of the sensory panelists was also tested. The sensory profile analysis indicated that the established sensory descriptors could properly reflect the general sensory properties of the human milk and could also be used to distinguish different samples. Further investigation exposed that the fat content might be an important factor that influence the sensory properties of human milk. To the best of our knowledge, this is the first report on the flavor wheel of human milk.
The Difference in the Prevalence of Metabolic Syndrome According to Meeting Guidelines for Aerobic Physical Activity and Muscle-Strengthening Exercise: A Cross-Sectional Study Performed Using the Korea National Health and Nutrition Examination Survey, 2014–2019
Authors: Kwon Du Ho , Cho Young Gyu , Park Hyun Ah , Koo Ho Seok
Published: December 2022

Physical activity and muscle strengthening are essential for preventing and managing metabolic syndrome. This study was conducted to investigate the relationship between the prevalence of metabolic syndrome and meeting the guidelines for aerobic physical activity (APA), muscle strengthening exercise (MSE), and combined exercise. We used data from 22,467 Koreans aged 40 years or older, who participated in in the Korea National Health and Nutrition Examination Survey (KNHANES) 2014–2019. We used the Global Physical Activity Questionnaire (GPAQ) to measure physical activity and surveyed frequency of MSE through a questionnaire. Metabolic syndrome was defined according to the American heart association and the National Heart, Lung, and Blood Institute. Compared with none exercise group, odds ratios of APA, MSE, and combined exercise group (CEG) on metabolic syndrome prevalence were 0.85 (95% confidence interval (CI), 0.74–0.98), 0.81 (95% CI, 0.67–0.99), and 0.65 (95% CI, 0.54–0.78) among men, respectively. Among women, ORs of APA, MSE, and CEG were 0.83 (95% CI, 0.73–0.93), 0.73 (95% CI, 0.58–0.91), and 0.74 (95% CI, 0.58–0.93), respectively. This study showed that meeting guidelines for APA and MSE was associated with lower prevalence of metabolic syndrome. Furthermore, subjects who met both APA and MSE had the lowest metabolic syndrome prevalence.
Effects of Bifidobacterium with the Ability of 2′-Fucosyllactose Utilization on Intestinal Microecology of Mice
Authors: Mao Bingyong , He Zhujun , Chen Yang , Stanton Catherine , Ross Reynolds Paul , Zhao Jianxin , Chen Wei , Yang Bo
Published: December 2022

In breast milk, 2′-Fucosyllactose (2′FL) is the most abundant breast milk oligosaccharide and can selectively promote the proliferation of bifidobacteria. This study aimed to explore the effect of ifidobacterial with different utilization capacities of 2′FL on the intestinal microecology of mice. Furthermore, the effects of ifidobacterial with different 2′FL utilization capabilities on mice gut microbiota under the competitive pressure of 2′FL as a carbon source were explored. Compared with the control group, 2′FL, Bifidobacterium (B.) bifidum M130R01M51 + 2′FL, B. longum subsp. Longum CCFM752, and CCFM752 + 2′FL treatments significantly decreased the food intake. Moreover, the water intake, body weight, and fecal water content in all groups showed no significant difference compared with the control group. The combination of B. longum subsp. longum CCFM752 and 2′FL can significantly increase the levels of pro-inflammatory and anti-inflammatory factors. B. bifidum M130R01M51 and mixed strains combined with 2′FL significantly increased the contents of acetic acid and isobutyric acid. The results showed that B. bifidum M130R01M51, B. breve FHuNCS6M1, B. longum subsp. longum CCFM752, and B. longum subsp. infantis SDZC2M4 combined with 2′FL significantly increased the species richness of the gut microbiota. Moreover, B. longum subsp. longum CCFM752 and B. longum subsp. infantis SDZC2M4 significantly increased the abundance of Faecalibaculum and Bifidobacterium, respectively. In conclusion, exploring the impact on intestinal microecology can provide theoretical guidance for the development of personalized prebiotics for different bifidobacteria, which has the potential to improve the ecological imbalance of infant gut microbiota.
Association of Vasopressors Dose Trajectories with Enteral Nutrition Tolerance in Patients with Shock: A Prospective Observational Study
Authors: Wang Luping , Zhang Tao , Yao Hua , Xu Qian , Fu Xin , Yang Jing , Wang Bo , Zhang Zhongwei , Jin Xiaodong , Kang Yan , Wu Qin
Published: December 2022

(1) Background: Studies on the long-term patterns of using vasopressors in patients with shock and their correlations with the risk of feeding intolerance (FI) are limited. This study aimed to characterize the norepinephrine equivalent dose (NEQ) trajectories and explore its correlations with FI in patients with shock. (2) Methods: This study prospectively enrolled patients with shock, who received vasopressors from August 2020 to June 2022. The Growth Mixed Model (GMM) was used to traverse longitudinal NEQ data at six-hour intervals and identify the latent trajectories of NEQ use in these patients. Cox proportional hazards regression models were used to examine the correlations of NEQ trajectories with FI. (3) Results: This study included a total of 210 patients with shock recruited from August 2020 to June 2022. Four trajectories of NEQ dose were identified and characterized by low-dose stable NEQ (L-NEQ, n = 98), moderate-dose stable NEQ (M-NEQ, n = 74), high-dose stable NEQ (H-NEQ, n = 21), and rapidly rising NEQ (R-NEQ, n = 17), with NEQ doses of 0.2, 0.4, 0.4, and 0.5 µg/kg/min at enteral nutrition (EN) initiation, respectively. The incidences of FI were 37.76%, 67.57%, 80.95%, and 76.47% in the L-NEQ, M-NEQ, H-NEQ, and R-NEQ groups, respectively (p < 0.001). As compared to the L-NEQ group, the risk of FI occurrence increased in the M-NEQ, H-NEQ, and R-NEQ groups (all p < 0.05). (4) Conclusions: The risk of FI was significantly associated with NEQ trajectories. It might be appropriate to initiate EN when the NEQ dose is stabilized below 0.2 µg/kg/min in patients with shock.
Naringenin and Quercetin Exert Contradictory Cytoprotective and Cytotoxic Effects on Tamoxifen-Induced Apoptosis in HepG2 Cells
Authors: Xu Zhixiang , Jia Yue , Liu Jun , Ren Xiaomin , Yang Xiaoxia , Xia Xueshan , Pan Xuejun
Published: December 2022

Tamoxifen is commonly used to treat estrogen receptor-positive breast cancer and hepatocellular carcinoma. Phytoconstituents are considered candidates for chemopreventive drugs in cancer treatment. However, it remains unknown what would happen if tamoxifen and phytoconstituents were administrated simultaneously. We aimed to observe the synergistic antitumor effects of tamoxifen and naringenin/quercetin on human hepatic carcinoma and to explore the potential underlying molecular mechanisms. The HepG2 cell line was used as an in vitro model. Cell proliferation, invasion, migration, cycle progression and apoptosis were investigated along with reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨm) repression. The signaling pathways involved were identified using real-time quantitative polymerase chain reaction analysis. As the results show, tamoxifen in combination with higher concentrations of naringenin or quercetin significantly inhibited cell growth compared to either agent alone. These antiproliferative effects were accompanied by the inhibition of cell migration and invasion but the stimulation of cell apoptosis and loss of ΔΨm, which depended on the ROS-regulated p53 signaling cascades. Conversely, lower concentrations of naringenin and quercetin inhibited the tamoxifen-induced cell antiproliferative effects by regulating cell migration, invasion, cycle and apoptosis. Taken together, our findings revealed that phytoconstituents exerted contradictory cytoprotective and cytotoxic effects induced by tamoxifen in human hepatic cancer.
Association between Serum Zinc and Toll-like-Receptor- Related Innate Immunity and Infectious Diseases in Well-Nourished Children with a Low Prevalence of Zinc Deficiency: A Prospective Cohort Study
Authors: Liao Sui-Ling , Hua Man-Chin , Tsai Ming-Han , Su Kuan-Wen , Lin Chi , Yao Tsung-Chieh , Chen Li-Chen , Yeh Kuo-Wei , Huang Jing-Long , Lai Shen-Hao
Published: December 2022

Existing reports focus on zinc-associated immunity and infection in malnourished children; however, whether zinc also plays an important role in the immune homeostasis of the non-zinc-deficient population remained unknown. This study aimed to investigate the association between zinc status and toll-like receptor (TLR)-related innate immunity and infectious outcome in well-nourished children. A total of 961 blood samples were collected from 1 through 5 years of age. Serum zinc was analyzed, and mononuclear cells isolated to assess TNF-α, IL-6, and IL-10 production by ELISA after stimulation with TLR ligands. Childhood infections were analyzed as binary outcomes with logistic regression. The prevalence of zinc deficiency was 1.4–9.6% throughout the first 5 years. There was significant association between zinc and TLR-stimulated cytokine responses. Higher serum zinc was associated with decreased risk of ever having pneumonia (aOR: 0.94; 95% CI: 0.90, 0.99) at 3 years, and enterocolitis (aOR: 0.96; 95% CI: 0.93, 0.99) at 5 years. Serum zinc was lower in children who have had pneumonia before 3 years of age (72.6 ± 9 vs. 81.9 ± 13 μg/dL), and enterocolitis before 5 years (89.3 ± 12 vs. 95.5 ± 13 μg/dL). We emphasize the importance of maintaining optimal serum zinc in the young population.
Combination Treatment of Withalongolide a Triacetate with Cisplatin Induces Apoptosis by Targeting Translational Initiation, Migration, and Epithelial to Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma
Authors: Subramanian Chitra , Spielbauer Katie K. , Pearce Robin , Kovatch Kevin J. , Prince Mark E. , Timmermann Barbara N. , Cohen Mark S.
Published: December 2022

Treatment regimens for head and neck squamous cell carcinoma (HNSCC) typically include cisplatin and radiotherapy and are limited by toxicities. We have identified naturally derived withalongolide A triacetate (WGA-TA) from Physalis longifolia as a lead compound for targeting HNSCC. We hypothesized that combining WGA-TA with cisplatin may allow for lower, less toxic cisplatin doses. HNSCC cell lines were treated with WGA-TA and cisplatin. After treatment with the drugs, the cell viability was determined by MTS assay. The combination index was calculated using CompuSyn. The expression of proteins involved in the targeting of translational initiation complex, epithelial to mesenchymal transition (EMT), and apoptosis were measured by western blot. Invasion and migration were measured using the Boyden-chamber assay. Treatment of MDA-1986 and UMSCC-22B cell lines with either WGA-TA or cisplatin alone for 72 h resulted in a dose dependent decrease in cell viability. Cisplatin in combination with WGA-TA resulted in significant synergistic cell death starting from 1.25 μM cisplatin. Combination treatment with WGA-TA resulted in lower cisplatin dosing while maintaining the downregulation of translational initiation complex proteins, the induction of apoptosis, and the blockade of migration, invasion, and EMT transition. These results suggest that combining a low concentration of cisplatin with WGA-TA may provide a safer, more effective therapeutic option for HNSCC that warrants translational validation.
Environmental Factors Determining Body Mass Index (BMI) within 9 Months of Therapy Post Bariatric Surgery—Sleeve Gastrectomy (SG)
Authors: Wawrzyniak Agata , Krotki Monika
Published: December 2022

Treatment of obesity should be multidirectional and include, in addition to bariatric surgery, changing the key factors of lifestyle and eating habits. The study aimed to assess the impact of bariatric surgery and dietary care on anthropometric measurements, blood pressure, changes in lifestyle, and eating habits of patients within 9 months after the procedure, with the selection of environmental factors determining BMI variation. The study included 30 SG patients before surgery (month zero) and at 1, 3, 6, and 9 months after SG. Patients completed a questionnaire regarding age, sex, place of residence, education, professional activity, number of family members, financial situation, family history of obesity, previous forms of therapy, self-assessment of nutritional knowledge, receiving and following nutritional recommendations, eating habits, frequency of body weight control, leisure time. Body weight, height, waist and hip circumference, and systolic and diastolic pressure were measured, and BMI and WHR (Waist to Hip Ratio) were calculated. Within 9 months after the procedure, the patients’ body weight and BMI decreased on average by 26%. Post bariatric surgery, patients changed their eating habits. The influence of bariatric SG surgery and time after surgery was decisive for the normalization of BMI and explained the 33% variation in BMI up to 9 months after the procedure. Other factors important for the normalization of BMI after surgery were: male gender, older age of patients, family obesity (non-modifiable factors), as well as previous forms of therapy related to weight loss before surgery, shortening the intervals between meals and stopping eating at night (modifiable factors). The tested model explained 68% of the BMI variation after SG surgery for all assessed factors. Changes in lifestyle and eating habits in bariatric patients are crucial to maintaining the effect of bariatric surgery.
Dynamical Pair Production at Sub-Barrier Energies for Light Nuclei
Authors: Settlemyre Thomas , Zheng Hua , Bonasera Aldo
Published: December 2022

In the collision of two heavy ions, the strong repulsion coming from the Coulomb field is enough to produce e+e− pair(s) from vacuum fluctuations. The energy is provided by the kinetic energy of the ions and the Coulomb interaction at the production point. If, for instance, the electron is located at the center of mass (C.M.) of the two ions moving along the z-axis, and the positron is at a distance x from the electron, the ions can be accelerated towards each other since the Coulomb barrier is lowered by the presence of the electron. This screening results in an increase in the kinetic energy of the colliding ions and may result in an increase in the fusion probability of light ions above the adiabatic limit.
Targeted Treatment against Lipoprotein (a): The Coming Breakthrough in Lipid Lowering Therapy
Authors: Sosnowska Bożena , Surma Stanisław , Banach Maciej
Published: December 2022

Atherosclerotic cardiovascular diseases (ASCVD) are a very important cause of premature death. The most important risk factor for ASCVD is lipid disorders. The incidence of lipid disorders and ASCVD is constantly increasing, which means that new methods of prevention and treatment of these diseases are still being searched for. In the management of patients with lipid disorders, the primary goal of therapy is to lower the serum LDL-C concentration. Despite the available effective lipid-lowering therapies, the risk of ASCVD is still increased in some patients. A high level of serum lipoprotein (a) (Lp(a)) is a risk factor for ASCVD independent of serum LDL-C concentration. About 20% of Europeans have elevated serum Lp(a) levels, requiring treatment to reduce serum Lp(a) concentrations in addition to LDL-C. Currently available lipid lowering drugs do not sufficiently reduce serum Lp(a) levels. Hence, drugs based on RNA technology, such as pelacarsen, olpasiran, SLN360 and LY3819469, are undergoing clinical trials. These drugs are very effective in lowering the serum Lp(a) concentration and have a satisfactory safety profile, which means that in the near future they will fill an important gap in the armamentarium of lipid-lowering drugs.
The Hidden Pandemic of COVID-19-Induced Organizing Pneumonia
Authors: Bazdyrev Evgeny , Panova Maria , Zherebtsova Valeria , Burdenkova Alexandra , Grishagin Ivan , Novikov Fedor , Nebolsin Vladimir
Published: December 2022

Since the beginning of the COVID-19 pandemic, clinical, radiological, and histopathological studies have provided evidence that organizing pneumonia is a possible consequence of the SARS-CoV2 infection. This post-COVID-19 organizing pneumonia (PCOP) causes persisting dyspnea, impaired pulmonary function, and produces radiological abnormalities for at least 5 weeks after onset of symptoms. While most patients with PCOP recover within a year after acute COVID-19, 5–25% of cases need specialized treatment. However, despite substantial resources allocated worldwide to finding a solution to this problem, there are no approved treatments for PCOP. Oral corticosteroids produce a therapeutic response in a majority of such PCOP patients, but their application is limited by the anticipated high-relapse frequency and the risk of severe adverse effects. Herein, we conduct a systematic comparison of the epidemiology, pathogenesis, and clinical presentation of the organizing pneumonias caused by COVID-19 as well as other viral infections. We also use the clinical efficacy of corticosteroids in other postinfection OPs (PIOPs) to predict the therapeutic response in the treatment of PCOP. Finally, we discuss the potential application of a candidate anti-inflammatory and antifibrotic therapy for the treatment of PCOP based on the analysis of the latest clinical trials data.
Aromatase-Inhibitor-Induced Musculoskeletal Inflammation Is Observed Independent of Oophorectomy in a Novel Mouse Model
Authors: Young Nicholas A. , Hampton Jeffrey , Sharma Juhi , Jablonski Kyle , DeVries Courtney , Bratasz Anna , Wu Lai-Chu , Lustberg Maryam , Reinbolt Raquel , Jarjour Wael N.
Published: December 2022

Aromatase Inhibitors (AIs) block estrogen production and improve survival in patients with hormone-receptor-positive breast cancer. However, half of patients develop aromatase-inhibitor-induced arthralgia (AIIA), which is characterized by inflammation of the joints and the surrounding musculoskeletal tissue. To create a platform for future interventional strategies, our objective was to characterize a novel animal model of AIIA. Female BALB/C-Tg(NFκB-RE-luc)-Xen mice, which have a firefly luciferase NFκB reporter gene, were oophorectomized and treated with an AI (letrozole). Bioluminescent imaging showed significantly enhanced NFκB activation with AI treatment in the hind limbs. Moreover, an analysis of the knee joints and legs via MRI showed enhanced signal detection in the joint space and the surrounding tissue. Surprisingly, the responses observed with AI treatment were independent of oophorectomy, indicating that inflammation is not mediated by physiological estrogen levels. Histopathological and pro-inflammatory cytokine analyses further demonstrated the same trend, as tenosynovitis and musculoskeletal infiltrates were detected in all mice receiving AI, and serum cytokines were significantly upregulated. Human PBMCs treated with letrozole/estrogen combinations did not demonstrate an AI-specific gene expression pattern, suggesting AIIA-mediated pathogenesis through other cell types. Collectively, these data identify an AI-induced stimulation of disease pathology and suggest that AIIA pathogenesis may not be mediated by estrogen deficiency, as previously hypothesized.
New Insights into the Structural Requirements of Isatin-Derived Pro-Apoptotic Agents against Acute Myeloid Leukemia
Authors: Hamdy Ahmed K. , Sakamoto Takashi , Toma Tsugumasa , Sakamoto Masaharu , Abourehab Mohammed A. S. , Otsuka Masami , Fujita Mikako , Tateishi Hiroshi , Radwan Mohamed O.
Published: December 2022

Searching for bioactive compounds within the huge chemical space is like trying to find a needle in a haystack. Isatin is a unique natural compound which is endowed with different bio-pertinent activities, especially in cancer therapy. Herein, we envisaged that adopting a hybrid strategy of isatin and α,β-unsaturated ketone would afford new chemical entities with strong chemotherapeutic potential. Of interest, compounds 5b and 5g demonstrated significant antiproliferative activities against different cancer genotypes according to NCI-60 screening. Concomitantly, their IC50 against HL-60 cells were 0.38 ± 0.08 and 0.57 ± 0.05 µM, respectively, demonstrating remarkable apoptosis and moderate cell cycle arrest at G1 phase. Intriguingly, an impressive safety profile for 5b was reflected by a 37.2 times selectivity against HL-60 over PBMC from a healthy donor. This provoked us to further explore their mechanism of action by in vitro and in silico tools. Conclusively, 5b and 5g stand out as strong chemotherapeutic agents that hold clinical promise against acute myeloid leukemia.
Neuropharmacological Activities of Ceiba aesculifolia (Kunth) Britten & Baker f (Malvaceae)
Authors: Bustos-Gómez Chrystyan Iván , Gasca-Martínez Deisy , Yáñez-Barrientos Eunice , Hidalgo-Figueroa Sergio , Gonzalez-Rivera Maria L. , Barragan-Galvez Juan Carlos , Zapata-Morales Juan Ramón , Isiordia-Espinoza Mario , Corrales-Escobosa Alma Rosa , Alonso-Castro Angel Josabad
Published: December 2022

Ceiba aesculifolia (Kunth) Britten & Baker f (Malvaceae) is used for the folk treatment of mood disorders. C. aesculifolia bark was extracted in ethanol, and the extract (CAE) was chemically standardized using gas chromatography–mass spectrometry (GC-MS). This study evaluated the effects of CAE (10–100 mg/kg p.o.) on anxiolytic-like activity, sedation, locomotor activity, depression-like activity, and spatial working memory using in vivo rodent models. A possible mechanism for the anxiolytic-like and antidepressant-like actions induced by CAE was assessed using neurotransmission pathway inhibitors. Myristic acid was one of the compounds found in CAE using GC-MS. This study also evaluated the anxiolytic-like activity and the sedative actions of myristic acid and assessed a possible mechanism of action using neurotransmission pathway inhibitors and an in silico analysis. CAE elicited anxiolytic-like activity and antidepressant-like effects (ED50 = 57 mg/kg). CAE (10–100 mg/kg) did not affect locomotor coordination or induce sedation. The anxiolytic-like and antidepressant-like actions of CAE were reverted by prazosin, suggesting a possible participation of the noradrenergic system. The anxiolytic-like activity of myristic acid was reverted by the co-administration of prazosin and partially reverted by ketanserin. The docking study revealed that myristic acid can form favorable interactions within 5-HT2A and α1A-adrenoreceptor binding pockets.
Quantitative Mass Spectrometry Imaging of Bleomycin in Skin Using a Mimetic Tissue Model for Calibration
Authors: Traberg Andreas , Pinto Fernanda E. , Hansen Anders C. N. , Haedersdal Merete , Lerche Catharina M. , Janfelt Christian
Published: December 2022

The aim of Quantitative mass spectrometry imaging (Q-MSI) is to provide distribution analysis and quantitation from one single mass-spectrometry-based experiment, and several quantitation methods have been devised for Q-MSI. Mimetic tissue models based on spiked tissue homogenates are considered one of the most accurate ways to perform Q-MSI, since the analyte is present in a well-defined concentration in a sample matrix highly similar to the one of the unknown sample to be analyzed. The delivery of drugs in skin is among the most frequent types of pharmaceutical MSI studies. Here, a mimetic tissue model is extended for use on the skin, which, due to its high collagen content, is different from most other tissue as the homogenates become extremely viscous. A protocol is presented which overcomes this by the addition of water and the handling of the homogenate at an elevated temperature where the viscosity is lower. Using a mimetic tissue model, a method was developed for the quantitative imaging of bleomycin in skin. To compensate for the signal drift and the inhomogeneities in the skin, an internal standard was included in the method. The method was tested on skin from a pig which had had an electropneumatic injection of bleomycin into the skin. Quantification was made at several regions in a cross section of the skin at the injection site, and the results were compared to the results of a quantitative LC-MS on a neighboring tissue biopsy from the same animal experiment. The overall tissue concentration determined by the LC-MS was within the range of the different regions quantified by the Q-MSI. As the model provides the results of the same order of magnitude as a LC-MS, it can either be used to replace LC-MS in skin studies where MSI and LC-MS are today carried out in combination, or it can add quantitative information to skin studies which are otherwise carried out by MSI alone.
The Role of Bronchoalveolar Lavage in Systemic Sclerosis Interstitial Lung Disease: A Systematic Literature Review
Authors: Orlandi Martina , Meliante Laura Antonia , Damiani Arianna , Tofani Lorenzo , Bruni Cosimo , Guiducci Serena , Matucci-Cerinic Marco , Bellando-Randone Silvia , Tomassetti Sara
Published: December 2022

The role of Bronchoalveolar Lavage (BAL) in the evaluation of systemic sclerosis (SSc) interstitial lung disease (ILD) is still controversial. The aim of this systematic literature review was to investigate the use of BAL in SSc-ILD, and to focus on the pros and cons of its real-life application. Methods: PubMed, Cochrane, and Embase were questioned from inception until 31 December 2021. Results: Eighteen papers were finally analyzed. A positive correlation was observed between lung function and BAL cytology; in particular, BAL neutrophilia/granulocytosis was related to lower diffusing capacity for carbon monoxide (DLCO) values and lower forced vital capacity (FVC). Moreover, a positive correlation between BAL cellularity and high-resolution computed tomography (HRCT) findings has been reported by several authors. Cytokines, chemokines, growth factors, coagulation factors, and eicosanoids have all been shown to be present, more often and in higher quantities in SSc-ILD patients than in the health control and, in some cases, they were related to more severe pulmonary disease. There was no consensus regarding the role of BAL cellularity as a predictor of mortality.
Development of an Oral Isoliquiritigenin Self-Nano-Emulsifying Drug Delivery System (ILQ-SNEDDS) for Effective Treatment of Eosinophilic Esophagitis Induced by Food Allergy
Authors: Cao Mingzhuo , Wang Yuan , Jing Heyun , Wang Zeqian , Meng Yijia , Geng Yu , Miao Mingsan , Li Xiu-Min
Published: December 2022

Isoliquiritigenin (ILQ) is a natural flavonoid with various pharmacological activities. In this study, we optimized the preparation method of self-nano-emulsion-loaded ILQ to further improve its bioavailability based on our previous study. In addition, its effect on the treatment of eosinophilic esophagitis was also evaluated. Combined surfactants and co-surfactants were screened, and the optimal formulation of ILQ-SNEDDS was determined according to droplet size, droplet dispersity index (DDI), and drug loading. The formulation was composed of ethyl oleate (oil phase), Tween 80 & Cremophor EL (surfactant, 7:3), and PEG 400 & 1,2-propylene glycol (cosurfactant, 1:1), with a mass ratio of 3:6:1. Its physicochemical properties, including drug loading, droplets’ size, Zeta potential, appearance, and Fourier transform infrared (FTIR) spectroscopy, were characterized. In vitro release profile, in situ intestinal absorption, and in vivo pharmacokinetics were applied to confirm the improvement of oral ILQ bioavailability by NEDDS. Finally, the efficacy of ILQ-SNEDDS in the treatment of food allergy-induced eosinophilic esophagitis (EOE) was further evaluated. When the ILQ drug loading was 77.9 mg/g, ILQ-SNEDDS could self-assemble into sub-spherical uniform droplets with an average size of about 33.4 ± 2.46 nm (PDI about 0.10 ± 0.05) and a Zeta potential of approximately −10.05 ± 3.23 mV. In situ intestinal absorption showed that optimized SNEDDS significantly increased the apparent permeability coefficient of ILQ by 1.69 times, and the pharmacokinetic parameters also confirmed that SNEDDS sharply increased the max plasma concentration and bioavailability of ILQ by 3.47 and 2.02 times, respectively. ILQ-SNEDDS also significantly improved the apparent signs, allergic index, hypothermia and body weight of EoE model mice. ILQ-SNEDDS treatment significantly reduced the levels of inflammatory cytokines, such as TNF-α, IL-4, and IL-5, and the level of PPE-s-IgE in serum, and significantly inhibited the expression of TGF-β1 in esophageal tissue. SNEDDS significantly improved the solubility and bioavailability of ILQ. Additionally, ILQ-SNEDDS treatment attenuated symptomatology of EoE model mice, which was associated with inhibiting the production of TH2 inflammatory cytokines and PPE-s-IgE and the expression of TGF-β1. The above results shows that ILQ-SNEDDS has great potential as a good candidate for the treatment of eosinophilic esophagitis.
Special Issue: Tissue Engineered Biomaterials and Drug Delivery Systems
Authors: Ribeiro Viviana P. , Oliveira Joaquim M. , Reis Rui L.
Published: December 2022

Current advances in biomaterials processing and engineering for drug delivery have allowed interesting progressed in biomedical field [...]
Design, Synthesis and In Vitro Investigation of Cabozantinib-Based PROTACs to Target c-Met Kinase
Authors: Sachkova Anastasia A. , Andreeva Daria V. , Tikhomirov Alexander S. , Scherbakov Alexander M. , Salnikova Diana I. , Sorokin Danila V. , Bogdanov Fedor B. , Rysina Yulia D. , Shchekotikhin Andrey E. , Shchegravina Ekaterina S. , Fedorov Alexey Yu.
Published: December 2022

(1) Background: This investigation aimed at developing a series of c-Met-targeting cabozantinib-based PROTACs. (2) Methods: Purification of intermediate and target compounds was performed using column chromatography, in vitro antiproliferation activity was measured using a standard MTT assay and a c-Met degradation assay was performed via the immunoblotting technique. (3) Results: Several compounds exhibited antiproliferative activity towards different cell lines of breast cancer (T47D, MDA-MB-231, SKBR3, HCC1954 and MCF7) at the same level as parent cabozantinib and 7-demethyl cabozantinib. Two target conjugates, bearing a VHL-ligand as an E3-ligase binding moiety and glycol-based linkers, exhibited the effective inhibition of c-Met phosphorylation and an ability to decrease the level of c-Met in HCC1954 cells at micromolar concentrations. (4) Conclusions: Two compounds exhibit c-Met inhibition activity in the nanomolar range and can be considered as PROTAC molecules due to their ability to decrease the total level of c-Met in HCC1954 cells. The structures of the offered compounds can be used as starting points for further evaluation of cabozantinib-based PROTACs.
Practical Recommendations for the Manipulation of Kinase Inhibitor Formulations to Age-Appropriate Dosage Forms
Authors: Bernsen Emma C. , Hogenes Valery J. , Nuijen Bastiaan , Hanff Lidwien M. , Huitema Alwin D. R. , Diekstra Meta H. M.
Published: December 2022

Over 75 kinase inhibitors (KIs) have been approved for the treatment of various cancers. KIs are orally administrated but mostly lack pediatric age-appropriate dosage forms or instructions for dose manipulation. This is highly problematic for clinical practice in pediatric oncology, as flexible oral formulations are essential to individually set dosages and to adjust it to a child’s swallowability. Most KIs are poorly soluble, categorized in Biopharmaceutics Classification System (BCS) class II or IV, and improperly manipulating the KI formulation can alter pharmacokinetics and jeopardize KI drug safety and efficacy. Therefore, the goals of this review were to provide practical recommendations for manipulating the formulation of the 15 most frequently used KIs in pediatric oncology (i.e., bosutinib, cabozantinib, cobimetinib, crizotinib, dabrafenib, dasatinib, entrectinib, imatinib, larotrectinib, nilotinib, ponatinib, ruxolitinib, selumetinib, sunitinib and trametinib) based on available literature studies and fundamental drug characteristics and to establish a decision tool that supports decisions regarding formulation manipulation of solid oral dosages of KIs that have been or will be licensed (for adult and/or pediatric cancers) but are not included in this review.
Chemical Attachment of 5-Nitrosalicylaldimine Motif to Silatrane Resulting in an Organic–Inorganic Structure with High Medicinal Significance
Authors: Zaltariov Mirela-Fernanda , Turtoi Mihaela , Peptanariu Dragos , Macsim Ana-Maria , Clima Lilia , Cojocaru Corneliu , Vornicu Nicoleta , Ciubotaru Bianca-Iulia , Bargan Alexandra , Calin Manuela , Cazacu Maria
Published: December 2022

Two chemical motifs of interest for medicinal chemistry, silatrane as 1-(3-aminopropyl) silatrane (SIL M), and nitro group attached in position 5 to salicylaldehyde, are coupled in a new structure, 1-(3-{[(2-hydroxy-5-nitrophenyl)methylidene]amino}propyl)silatrane (SIL-BS), through an azomethine moiety, also known as a versatile pharmacophore. The high purity isolated compound was structurally characterized by an elemental, spectral, and single crystal X-ray diffraction analysis. Given the structural premises for being a biologically active compound, different specific techniques and protocols have been used to evaluate their in vitro hydrolytic stability in simulated physiological conditions, the cytotoxicity on two cancer cell lines (HepG2 and MCF7), and protein binding ability—with a major role in drug ADME (Absorption, Distribution, Metabolism and Excretion), in parallel with those of the SIL M. While the latter had a good biocompatibility, the nitro-silatrane derivative, SIL-BS, exhibited a higher cytotoxic activity on HepG2 and MCF7 cell lines, performance assigned, among others, to the known capacity of the nitro group to promote a specific cytotoxicity by a “activation by reduction” mechanism. Both compounds exhibited increased bio- and muco-adhesiveness, which can favor an optimized therapeutic effect by increased drug permeation and residence time in tumor location. Additional benefits of these compounds have been demonstrated by their antimicrobial activity on several fungi and bacteria species. Molecular docking computations on Human Serum Albumin (HSA) and MPRO COVID-19 protease demonstrated their potential in the development of new drugs for combined therapy.
Providers’ Perceived Value of Clinical Pharmacist and Technician Services within Primary Care Clinics
Authors: Abbinanti Alan , Slager Stacey , Turner Kyle , Gurney Erin , Berrett Golden Benjamin , Cox Nicholas
Published: December 2022

Several studies have demonstrated the benefit of clinical pharmacy services in primary care. However, studies are limited on providers’ perceived value of embedded primary care pharmacy teams. The purpose of this project was to determine how primary care clinical pharmacists and technicians provide value to medical providers. Primary care providers in University of Utah health clinics where primary care clinical pharmacists are embedded were invited to participate in one-on-one, semi-structured interviews. Interview sessions were recorded, transcribed, and de-identified. The transcripts were coded and analyzed to determine common themes. Questions were on various topics, including what is of greatest value to them, pharmacy integration into care teams, provider burnout, provider happiness at work, provider workload, and provider retention in the health system. In total, 25 interviews were conducted from nine different clinics (response rates of 19.7% for providers and 81.8% for clinics). Coding revealed themes of increased job satisfaction, enhanced patient care, decreased workload and burnout, and a desire for increased access to clinical pharmacy services. The responses related to clinical pharmacists in primary care were overwhelmingly positive, and providers almost unanimously expressed the need for more pharmacy services in primary care.
An Effective Method for Gas-Leak Area Detection and Gas Identification with Mid-Infrared Image
Authors: Zhao Qi , Nie Xiaoxi , Luo Dong , Wang Jue , Li Qiran , Chen Wei
Published: December 2022

Mid-infrared imaging systems are widely applied in gas-leak detection. However, infrared images generally suffer from low contrast and poor quality. In this paper, an image-enhancement method based on Gaussian filtering and adaptive histogram segmentation is proposed to effectively improve the quality of infrared images. It can effectively improve the quality of infrared images, which contributes to the subsequent gas-image feature extraction. The traditional background modeling algorithm is analyzed, and the ViBe (visual background extractor) algorithm is studied in depth. Based on the advantages and disadvantages of the ViBe algorithm and the characteristics of gas-leak images, a gas-leak region detection method based on the improved ViBe algorithm is proposed. The test results show that it can quickly establish a background model, segment the gas-leak region with motion characteristics, and render the gas-leak region in color based on grayscale mapping to achieve the automatic detection and enhanced display of gas leaks.
Visible to Mid-Infrared Supercontinuum Initiated by Stimulated Raman Scattering of 1.03 μm Ultrashort Pulses in a Gas-Filled Silica Fiber
Authors: Gladyshev Alexey , Yatsenko Yury , Kolyadin Anton , Bufetov Igor
Published: December 2022

Multiband supercontinuum generation covering the bandwidth from 0.65 μm to 3.3 μm was demonstrated in a gas-filled hollow-core silica fiber pumped by chirped ultrashort pulses at 1.03 μm. The development of the SC spectrum into the mid-IR was initiated by cascade stimulated Raman scattering in gaseous D2, which was used as an active medium filling the hollow core. The influence of the Kerr nonlinearity was studied by changing the linear chirp of the pump pulses. The influence of gas pressure and pump pulse energy on the SC generation was investigated. As high as 14% of pump quanta were converted to the wavelength range above 2 μm.
AnaBHEL (Analog Black Hole Evaporation via Lasers) Experiment: Concept, Design, and Status
Authors: Chen Pisin , Mourou Gerard , Besancon Marc , Fukuda Yuji , Glicenstein Jean-Francois , Nam Jiwoo , Lin Ching-En , Lin Kuan-Nan , Liu Shu-Xiao , Liu Yung-Kun , Kando Masaki , Kondo Kotaro , Paganis Stathes , Pirozhkov Alexander , Takabe Hideaki , Tuchming Boris , Wang Wei-Po , Watamura Naoki , Wheeler Jonathan , Wu Hsin-Yeh
Published: December 2022

Accelerating relativistic mirrors have long been recognized as viable settings where the physics mimic those of the black hole Hawking radiation. In 2017, Chen and Mourou proposed a novel method to realize such a system by traversing an ultra-intense laser through a plasma target with a decreasing density. An international AnaBHEL (Analog Black Hole Evaporation via Lasers) collaboration was formed with the objectives of observing the analog Hawking radiation, shedding light on the information loss paradox. To reach these goals, we plan to first verify the dynamics of the flying plasma mirror and characterize the correspondence between the plasma density gradient and the trajectory of the accelerating plasma mirror. We will then attempt to detect the analog Hawking radiation photons and measure the entanglement between the Hawking photons and their “partner particles”. In this paper, we describe our vision and strategy of AnaBHEL using the Apollon laser as a reference, and we report on the progress of our R&D concerning the key components in this experiment, including the supersonic gas jet with a graded density profile, and the superconducting nanowire single-photon Hawking detector. In parallel to these hardware efforts, we performed computer simulations to estimate the potential backgrounds, and derived analytic expressions for modifications to the blackbody spectrum of the Hawking radiation for a perfectly reflecting point mirror, due to the semi-transparency and finite-size effects specific to flying plasma mirrors. Based on this more realistic radiation spectrum, we estimate the Hawking photon yield to guide the design of the AnaBHEL experiment, which appears to be achievable.
Evaluation of Chemical Composition, Sun Protection Factor and Antioxidant Activity of Lithuanian Propolis and Its Plant Precursors
Authors: Stanciauskaite Monika , Marksa Mindaugas , Rimkiene Laura , Ramanauskiene Kristina
Published: December 2022

The growing interest in polyphenols of natural origin and their plant sources encourages the study of their chemical composition and biological activity. Propolis is widely used as a source of phenolic compounds. The aim of this study is to evaluate and compare the chemical composition, antioxidant activity and sun protection factor (SPF) of the ethanolic extracts of the poplar buds, birch buds and pine buds of propolis plant precursors collected in Lithuania. The IC50 concentration of the extracts was evaluated using DPPH and ABTS methods. Extracts of poplar buds, birch buds and propolis showed a lower IC50 concentration by ABTS and DPPH methods compared with pine buds extracts. Poplar buds and propolis extracts showed the highest SPF value, while birch and pine buds extracts showed a lower SPF value. High-performance liquid chromatography (HPLC) analysis results showed that phenolic acids, such as p-coumaric acid and cinnamic acid, and flavonoids, such as pinobanksin and pinocembrin, were identified in all the tested extracts. Salicin has been identified only in poplar buds extracts. The results of antioxidant activity showed that propolis poplar and birch buds are a promising source of biologically active polyphenols.