bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspartame and Its Metabolites Cause Oxidative Stress and Mitochondrial and Lipid Alterations in SH-SY5Y Cells
Authors: Griebsch Lea Victoria , Theiss Elena Leoni , Janitschke Daniel , Erhardt Vincent Konrad Johannes , Erhardt Tobias , Haas Elodie Christiane , Kuppler Konstantin Nicolas , Radermacher Juliane , Walzer Oliver , Lauer Anna Andrea , Matschke Veronika , Hartmann Tobias , Grimm Marcus Otto Walter , Grimm Heike Sabine
Published: March 2023

Due to a worldwide increase in obesity and metabolic disorders such as type 2 diabetes, synthetic sweeteners such as aspartame are frequently used to substitute sugar in the diet. Possible uncertainties regarding aspartame’s ability to induce oxidative stress, amongst others, has led to the recommendation of a daily maximum dose of 40 to 50 mg per kg. To date, little is known about the effects of this non-nutritive sweetener on cellular lipid homeostasis, which, besides elevated oxidative stress, plays an important role in the pathogenesis of various diseases, including neurodegenerative diseases such as Alzheimer’s disease. In the present study, treatment of the human neuroblastoma cell line SH-SY5Y with aspartame (271.7 µM) or its three metabolites (aspartic acid, phenylalanine, and methanol (271.7 µM)), generated after digestion of aspartame in the human intestinal tract, resulted in significantly elevated oxidative stress associated with mitochondrial damage, which was illustrated with reduced cardiolipin levels, increased gene expression of SOD1/2, PINK1, and FIS1, and an increase in APF fluorescence. In addition, treatment of SH-SY5Y cells with aspartame or aspartame metabolites led to a significant increase in triacylglycerides and phospholipids, especially phosphatidylcholines and phosphatidylethanolamines, accompanied by an accumulation of lipid droplets inside neuronal cells. Due to these lipid-mediating properties, the use of aspartame as a sugar substitute should be reconsidered and the effects of aspartame on the brain metabolism should be addressed in vivo.
Cross-Sectional Association of Dietary Patterns and Supplement Intake with Presence and Gray-Scale Median of Carotid Plaques—A Comparison between Women and Men in the Population-Based Hamburg City Health Study
Authors: Assies Julia Maria , Sältz Martje Dorothea , Peters Frederik , Behrendt Christian-Alexander , Jagodzinski Annika , Petersen Elina Larissa , Schäfer Ines , Twerenbold Raphael , Blankenberg Stefan , Rimmele David Leander , Thomalla Götz , Makarova Nataliya , Zyriax Birgit-Christiane
Published: March 2023

This population-based cross-sectional cohort study investigated the association of the Mediterranean and DASH (Dietary Approach to Stop Hypertension) diet as well as supplement intake with gray-scale median (GSM) and the presence of carotid plaques comparing women and men. Low GSM is associated with plaque vulnerability. Ten thousand participants of the Hamburg City Health Study aged 45–74 underwent carotid ultrasound examination. We analyzed plaque presence in all participants plus GSM in those having plaques (n = 2163). Dietary patterns and supplement intake were assessed via a food frequency questionnaire. Multiple linear and logistic regression models were used to assess associations between dietary patterns, supplement intake and GSM plus plaque presence. Linear regressions showed an association between higher GSM and folate intake only in men (+9.12, 95% CI (1.37, 16.86), p = 0.021). High compared to intermediate adherence to the DASH diet was associated with higher odds for carotid plaques (OR = 1.18, 95% CI (1.02, 1.36), p = 0.027, adjusted). Odds for plaque presence were higher for men, older age, low education, hypertension, hyperlipidemia and smoking. In this study, the intake of most supplements, as well as DASH or Mediterranean diet, was not significantly associated with GSM for women or men. Future research is needed to clarify the influence, especially of the folate intake and DASH diet, on the presence and vulnerability of plaques.
Activation of AMPK Entails the Protective Effect of Royal Jelly against High-Fat-Diet-Induced Hyperglycemia, Hyperlipidemia, and Non-Alcoholic Fatty Liver Disease in Rats
Authors: Felemban Alaa Hasanain , Alshammari Ghedeir M. , Yagoub Abu ElGasim Ahmed , Al-Harbi Laila Naif , Alhussain Maha H. , Yahya Mohammed Abdo
Published: March 2023

This study examined the mechanism underlying the protective effect of royal jelly (RJ) against high-fat-diet (HFD)-mediated non-alcoholic liver disease (NAFLD) in rats. Adult male rats were divided into five groups (n = 8 each): control fed a standard diet, control + RJ (300 mg/kg), HFD, HFD + RJ (300 mg/kg), and HFD + RJ + CC (0.2 mg/kg). The treatment with RJ reduced weight gain, increased fat pads, and attenuated fasting hyperglycemia, hyperinsulinemia, and glucose tolerance in the HFD-fed rats. It also reduced the serum levels of liver function enzymes, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and leptin but significantly increased the serum levels of adiponectin. In addition, and with no effect on lipid excretion in stool, RJ significantly decreased the hepatic mRNA expression of SREBP1, serum, hepatic cholesterol, and triglycerides but increased hepatic mRNA levels of PPARα. Furthermore, RJ reduced the hepatic levels of TNF-α, IL-6, and malondialdehyde (MDA) in the livers of these rats. Of note, with no effect on the mRNA levels of AMPK, RJ stimulated the phosphorylation of AMPK and increased the levels of superoxide dismutase (SOD) and total glutathione (GSH) in the livers of the control and HFD-fed rats. In conclusion, RJ attenuates NAFLD via its antioxidant potential and adiponectin-independent activation of liver AMPK.
COntrolling NUTritional Status (CONUT) as Predictive Score of Hospital Length of Stay (LOS) and Mortality: A Prospective Cohort Study in an Internal Medicine and Gastroenterology Unit in Italy
Authors: Rinninella Emanuele , Borriello Raffaele , D’Angelo Marco , Galasso Tiziano , Cintoni Marco , Raoul Pauline , Impagnatiello Michele , Annicchiarico Brigida Eleonora , Gasbarrini Antonio , Mele Maria Cristina
Published: March 2023

Background: Hospital malnutrition affects nearly 30% of patients in medical wards and correlates with worse outcomes. An early assessment is necessary to stratify the risk of short-term outcomes and mortality. The predictive role of COntrolling NUTritional status (CONUT) score in this context has not yet been elucidated in Western countries. We aimed to test CONUT at admission as a predictive score of hospital outcomes, in an Internal Medicine and Gastroenterology Department of an Italian Tertiary Care University hospital. Methods: We prospectively enrolled patients admitted to our center, stratifying them into the four CONUT classes (normal = 0–1; mild = 2–4; moderate = 5–8; severe = 9–12 points) according to serum albumin (g/dL), total lymphocyte count (/mm3), and total cholesterol (mg/dL); the primary outcome measure was length of stay (LOS) and the secondary one was in-hospital mortality. Results: Out of a total of 203 patients enrolled, 44 (21.7%) patients had a normal status (0–1), 66 (32.5%) had a mild impairment (2–4), 68 (33.5%) had a moderate impairment (5–8), and 25 (12.3%) a severe impairment (9–12). The mean LOS was 8.24 ± 5.75 days; nine patients died. A moderate-severe CONUT correlated with a higher LOS at the univariate [HR 1.86 (95% CI 13.9–3.47); p < 0.0001] and multivariate analysis [HR 1.52 (95% CI 1.10–2.09); p = 0.01]. The CONUT score was also a predictor of mortality, with an AUC of 0.831 (95% CI 0.680–0.982) and with an optimal cut-off at 8.5 points. Nutritional supplementation within 48 h from admission correlated with lower mortality [OR 0.12 (95% CI 0.02–0.56) p = 0.006]. Conclusions: CONUT is a reliable and simple predictor of LOS and in-hospital mortality in medical wards.
Nutritional Considerations in Celiac Disease and Non-Celiac Gluten/Wheat Sensitivity
Authors: Abdi Fardowsa , Zuberi Saania , Blom Jedid-Jah , Armstrong David , Pinto-Sanchez Maria Ines
Published: March 2023

A gluten-free diet (GFD) is the only available treatment for celiac disease (CeD), and it may also improve symptoms in non-celiac gluten/wheat sensitivity (NCGWS). In CeD, gluten triggers an immune reaction leading to enteropathy, malabsorption, and symptoms; in NCGWS, the mechanism leading to symptoms is unknown, and neither wheat nor gluten triggers enteropathy or malabsorption. A strict GFD is, therefore, necessary for CeD, but a gluten-restricted diet (GRD) may suffice to achieve symptom control for NCGWS. Regardless of this distinction, the risk of malnutrition and macro- and micronutrient deficiencies is increased by the adoption of a GFD or GRD. Thus, patients with CeD or NCGWS should undergo nutritional assessment and subsequent monitoring, based on evidence-based tools, under the care of a multidisciplinary team involving physicians and dietitians, for the long-term management of their nutrition. This review gives an overview of available nutrition assessment tools and considerations for the nutritional management of CeD and NCGWS populations.
Diet as a Factor Supporting Lung Cancer Treatment—A Systematic Review
Authors: Polański Jacek , Świątoniowska-Lonc Natalia , Kołaczyńska Sylwia , Chabowski Mariusz
Published: March 2023

The purpose of this study was to summarize the evidence from epidemiological studies concerning associations between diet and the effectiveness of treatment for lung cancer. For this review, a literature search has been conducted in the EMBASE and PubMed databases, including papers published between 1977 and June 2022. The term “lung cancer” was used in conjunction with “diet”. Footnotes from the selected papers were also analyzed. The present study is in line with the recommendations included in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The review included studies involving adults, including randomized controlled trials (RCTs) and cohort and observational studies. In total, 863 papers were found, with duplicates excluded. Ultimately, 20 papers were reviewed. The present systematic review indicates that vitamin A, ascorbic acid (vitamin C), vitamin E, selenium, and zinc—as antioxidants—can strengthen the body’s antioxidant barrier. Furthermore, preoperative immunonutrition may not only improve perioperative nutritional status following induction chemoradiotherapy in lung cancer surgery patients but also reduce the severity of postoperative complications. Similarly, a protein supply may exert a beneficial effect on human health by increasing average body weight and muscle mass. Omega-3 fatty acid content in the diet and the consumption of their main source, fish, may have some regulatory effect on inflammation in patients with lung cancer treated with chemotherapy and radiotherapy. In addition, n-3 fatty acids inhibit tumor cell proliferation and may reduce the toxicity of chemotherapy. Increased energy and protein intake are strongly associated with improved quality of life, functional outcomes, hand grip strength, symptoms, and performance in patients with lung cancer. The use of a supportive diet should be the standard of care, alongside pharmaceutical therapy, in treatment for patients with lung cancer.
Changes in Diet and Physical Activity among 18–65-Year-Olds after the First National COVID-19 Lockdown in Denmark
Authors: Matthiessen Jeppe , Biltoft-Jensen Anja , Stockmarr Anders , Fagt Sisse , Christensen Tue
Published: March 2023

COVID-19 lockdowns affected everyday life significantly and made it challenging to achieve or maintain a healthy lifestyle. The aim of the present study was to examine longitudinal changes in Danish adults’ eating habits and physical activity (PA) assessed during and after the first national lockdown in 2020. Furthermore, changes in body weight were examined during the first lockdown period. The whole diet (semi-quantitative Food Frequency Questionnaire), sociodemographic factors, moderate-to-vigorous intensity PA (MVPA), leisure screen time, anthropometrics, change in body weight, and stress level were assessed with a self-administered web-based questionnaire among 839 18–65-year-old Danes during and 5–6 months after the lockdown. Both favorable (decreased intake of saturated fat) and unfavorable (decreased intake of whole grain and fish, and increased intake of red meat) changes were found in the diet after the lockdown, while favorable changes in MVPA (increase in couples) and leisure screen time (decrease with a combined effect of family status and education) were found for PA. More Danish adults reported to gain weight (mean 3.0 kg) than to lose weight (mean 3.5 kg) during the first lockdown period (27% vs. 15%). The study showed favorable changes in PA and mixed results regarding diet among Danish adults after the lockdown. Furthermore, the first lockdown period unfavorably impacted the body weight of many Danes.
Serum Fibroblast Growth Factor 21 Is Markedly Decreased following Exercise Training in Patients with Biopsy-Proven Nonalcoholic Steatohepatitis
Authors: Stine Jonathan G. , Welles Jaclyn E. , Keating Shelley , Hussaini Zeba , Soriano Christopher , Heinle J. Wes , Geyer Nathaniel , Chinchilli Vernon M. , Loomba Rohit , Kimball Scot R.
Published: March 2023

Background and Aims: Exercise remains a key component of nonalcoholic fatty liver disease (NAFLD) treatment. However, mechanisms underpinning the improvements in NAFLD seen with exercise are unclear. Exercise improved liver fat and serum biomarkers of liver fibrosis in the NASHFit trial. We investigated exercise’s mechanism of benefit by conducting a post hoc analysis of these data to determine the relationship between serum fibroblast growth factor (FGF) 21, which is implicated in NAFLD development, and exercise. Methods: In the 20 wk NASHFit trial, patients with nonalcoholic steatohepatitis (NASH) were randomized to receive moderate-intensity aerobic exercise training or standard clinical care. Mediterranean-informed dietary counseling was provided to each group. Change in serum FGF21 was measured after an overnight fast. Results: There was a significant improvement in serum FGF21 with exercise training compared to standard clinical care (p = 0.037) with serum FGF21 reducing by 22% (−243.4 +/−349 ng/mL) with exercise vs. a 34% increase (+88.4 ng/mL +/−350.3 ng/mL) with standard clinical care. There was a large inverse association between change in serum FGF21 and change in cardiorespiratory fitness (VO2peak) (r = −0.62, 95% CI −0.88 to −0.05, p = 0.031), and on multivariable analysis, change in VO2peak remained independently associated with change in FGF21 (β = −44.5, 95% CI −83.8 to −5.11, p = 0.031). Conclusions: Serum FGF21 is markedly decreased in response to aerobic exercise training, offering a novel mechanism to explain the observed reduction in liver fat and improvement in serum biomarkers of liver fibrosis in patients with NASH who do exercise.
Both Saccharomyces boulardii and Its Postbiotics Alleviate Dextran Sulfate Sodium-Induced Colitis in Mice, Association with Modulating Inflammation and Intestinal Microbiota
Authors: Xu Xinge , Wu Jingwei , Jin Yuxin , Huang Kunlun , Zhang Yuanyuan , Liang Zhihong
Published: March 2023

Objective: To investigate the effect of Saccharomyces boulardii and its freeze-dried and spray-dried postbiotics on the intervention and potential mechanism of dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. [Methods] After the acclimation period of C67BL/6J mice, a colitis model was constructed by applying 2% DSS for 7 d, followed by 7 d of intervention. Subsequently, the disease activity index (DAI), organ index, colon length, colon HE staining of pathological sections, ELISA for blood inflammatory factors (Interleukin (IL)-1β, IL-6, IL-10, Tumor necrosis factor (TNF)-α), Real time quantitative polymerase chain reaction (RT-qPCR) to determine the levels of colonic inflammatory factors (IL-1β, IL-6, IL-10, TNF-α), Occludin gene expression, and intestinal flora were assessed to evaluate the protective effects of S. boulardii and its postbiotics on colitis in mice. Results: Compared with the DSS group, S. boulardii and the postbiotics interventions effectively improved colonic shortening and tissue damage, increased the expression of intestinal tight junction protein, reduced the secretion of pro-inflammatory factors, increased the secretion of anti-inflammatory factors, and maintained the homeostasis of intestinal microorganisms. Postbiotics intervention is better than probiotics. Conclusions: S. boulardii and its postbiotics can effectively alleviate DSS-induced colitis in mice through modulating host immunity and maintaining intestinal homeostasis. Postbiotics are promising next-generation biotherapeutics for ulcerative colitis treatment.
Benefits of Supplementation with L-arginine, Citrulline and Watermelon on Vascular and Metabolic Health
Authors: Figueroa Arturo , Wong Alexei
Published: March 2023

The endothelium is crucial in controlling blood pressure and preventing cardiovascular diseases [...]
Hepatitis E Virus in Finland: Epidemiology and Risk in Blood Donors and in the General Population
Authors: Mättö Jaana , Putkuri Niina , Rimhanen-Finne Ruska , Laurila Päivi , Clancy Jonna , Ihalainen Jarkko , Ekblom-Kullberg Susanne
Published: March 2023

Autochthonous hepatitis E (HEV) cases have been increasingly recognized and reported in Europe, caused predominantly by the zoonotic HEV genotype 3. The clinical picture is highly variable, from asymptomatic to acute severe or prolonged hepatitis in immunocompromised patients. The main route of transmission to humans in Europe is the ingestion of undercooked pork meat. Transfusion-transmitted HEV infections have also been reported. The aim of the study was to determine the HEV epidemiology and risk in the Finnish blood donor population. A total of 23,137 samples from Finnish blood donors were screened for HEV RNA from individual samples and 1012 samples for HEV antibodies. Additionally, laboratory-confirmed hepatitis E cases in 2016–2022 were extracted from national surveillance data. The HEV RNA prevalence data was used to estimate the risk of transfusion transmission of HEV in the Finnish blood transfusion setting. Four HEV RNA-positive were found, resulting in 1:5784 (0.02%) RNA prevalence. All HEV RNA-positive samples were IgM-negative, and genotyped samples represented genotype HEV 3c. HEV IgG seroprevalence was 7.4%. From the HEV RNA rate found in this study and data on blood component usage in Finland in 2020, the risk estimate for a severe transfusion-transmitted HEV infection is 1:1,377,000 components or one in every 6–7 years. In conclusion, the results indicate that the risk of transfusion-transmitted HEV (HEV TTI) in Finland is low. However, continuous follow-up of the HEV epidemiology in relation to the transfusion risk landscape in Finland is necessary, as well as promoting awareness in the medical community of the small risk for HEV TTI, especially for immunocompromised patients.
A Descriptive Analysis of Direct Oral Anticoagulant Drugs Dosing Errors Based on Spontaneous Reports from the EudraVigilance Database
Authors: Morgovan Claudiu , Dobrea Carmen Maximiliana , Chis Adriana Aurelia , Juncan Anca Maria , Arseniu Anca Maria , Rus Luca Liviu , Gligor Felicia Gabriela , Ardelean Simona Alexandrina , Stoicescu Laurentiu , Ghibu Steliana , Frum Adina
Published: March 2023

Direct oral anticoagulant drugs (DOACs) interfere with the coagulation process, thus improving patient care for those who require anticoagulant treatment. This study presents a descriptive analysis of adverse reactions (ADRs) attributed to DOAC dosage errors (overdose, underdose, and improper dose). The analysis was performed based on the Individual Case Safety Reports from the EudraVigilance (EV) database. Results show that data reported for rivaroxaban, apixaban, edoxaban, and dabigatran are mostly regarding underdosing (51.56%) compared to overdosing (18.54%). The most dosage error reports were identified for rivaroxaban (54.02%), followed by apixaban (33.61%). Dabigatran and edoxaban had similar percentages (6.26% and 6.11%, respectively) regarding dosage error reports. Since coagulation issues can become life-threatening events, and factors such as advanced age and renal failure can influence the pharmacokinetics of drugs, the correct usage of DOACs is of utmost importance for the management and prevention of venous thromboembolism. Thus, the collaboration and the complementarity of knowledge of physicians and pharmacists may offer a reliable solution for DOAC dose management and improve patient care.
Special Issue “In Vivo Nuclear Molecular Imaging in Drug Development and Pharmacological Research”
Authors: Yue Xuyi
Published: March 2023

Nuclear molecular imaging is increasingly important in aiding diagnosis, monitoring disease progression, and assessing response to treatment [...]
Physicochemical Characterization and Evaluation of Gastrointestinal In Vitro Behavior of Alginate-Based Microbeads with Encapsulated Grape Pomace Extracts
Authors: Martinović Josipa , Lukinac Jasmina , Jukić Marko , Ambrus Rita , Planinić Mirela , Šelo Gordana , Klarić Ana-Marija , Perković Gabriela , Bucić-Kojić Ana
Published: March 2023

Grape pomace is a byproduct of wineries and a rich source of phenolic compounds that can exert multiple pharmacological effects when consumed and enter the intestine where they can then be absorbed. Phenolic compounds are susceptible to degradation and interaction with other food constituents during digestion, and encapsulation may be a useful technique for protecting phenolic bioactivity and controlling its release. Therefore, the behavior of phenolic-rich grape pomace extracts encapsulated by the ionic gelation method, using a natural coating (sodium alginate, gum arabic, gelatin, and chitosan), was observed during simulated digestion in vitro. The best encapsulation efficiency (69.27%) was obtained with alginate hydrogels. The physicochemical properties of the microbeads were influenced by the coatings used. Scanning electron microscopy showed that drying had the least effect on the surface area of the chitosan-coated microbeads. A structural analysis showed that the structure of the extract changed from crystalline to amorphous after encapsulation. The phenolic compounds were released from the microbeads by Fickian diffusion, which is best described by the Korsmeyer–Peppas model among the four models tested. The obtained results can be used as a predictive tool for the preparation of microbeads containing natural bioactive compounds that could be useful for the development of food supplements.
Applications of Stimuli-Responsive Hydrogels in Bone and Cartilage Regeneration
Authors: Ni Xiaoqi , Xing Xin , Deng Yunfan , Li Zhi
Published: March 2023

Bone and cartilage regeneration is an area of tremendous interest and need in health care. Tissue engineering is a potential strategy for repairing and regenerating bone and cartilage defects. Hydrogels are among the most attractive biomaterials in bone and cartilage tissue engineering, mainly due to their moderate biocompatibility, hydrophilicity, and 3D network structure. Stimuli-responsive hydrogels have been a hot topic in recent decades. They can respond to external or internal stimulation and are used in the controlled delivery of drugs and tissue engineering. This review summarizes current progress in the use of stimuli-responsive hydrogels in bone and cartilage regeneration. The challenges, disadvantages, and future applications of stimuli-responsive hydrogels are briefly described.
The CRISPR/Cas9 System Delivered by Extracellular Vesicles
Authors: Zhu Xinglong , Gao Mengyu , Yang Yongfeng , Li Weimin , Bao Ji , Li Yi
Published: March 2023

Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) systems can precisely manipulate DNA sequences to change the characteristics of cells and organs, which has potential in the mechanistic research on genes and the treatment of diseases. However, clinical applications are restricted by the lack of safe, targeted and effective delivery vectors. Extracellular vesicles (EVs) are an attractive delivery platform for CRISPR/Cas9. Compared with viral and other vectors, EVs present several advantages, including safety, protection, capacity, penetrating ability, targeting ability and potential for modification. Consequently, EVs are profitably used to deliver the CRISPR/Cas9 in vivo. In this review, the advantages and disadvantages of the delivery form and vectors of the CRISPR/Cas9 are concluded. The favorable traits of EVs as vectors, such as the innate characteristics, physiological and pathological functions, safety and targeting ability of EVs, are summarized. Furthermore, in terms of the delivery of the CRISPR/Cas9 by EVs, EV sources and isolation strategies, the delivery form and loading methods of the CRISPR/Cas9 and applications have been concluded and discussed. Finally, this review provides future directions of EVs as vectors of the CRISPR/Cas9 system in clinical applications, such as the safety, capacity, consistent quality, yield and targeting ability of EVs.
Nanofibrous Scaffolds for Diabetic Wound Healing
Authors: Yusuf Aliyu Anna , Adeleke Oluwatoyin A.
Published: March 2023

Chronic wounds are one of the secondary health complications that develop in individuals who have poorly managed diabetes mellitus. This is often associated with delays in the wound healing process, resulting from long-term uncontrolled blood glucose levels. As such, an appropriate therapeutic approach would be maintaining blood glucose concentration within normal ranges, but this can be quite challenging to achieve. Consequently, diabetic ulcers usually require special medical care to prevent complications such as sepsis, amputation, and deformities, which often develop in these patients. Although several conventional wound dressings, such as hydrogels, gauze, films, and foams, are employed in the treatment of such chronic wounds, nanofibrous scaffolds have gained the attention of researchers because of their flexibility, ability to load a variety of bioactive compounds as single entities or combinations, and large surface area to volume ratio, which provides a biomimetic environment for cell proliferation relative to conventional dressings. Here, we present the current trends on the versatility of nanofibrous scaffolds as novel platforms for the incorporation of bioactive agents suitable for the enhancement of diabetic wound healing.
Prospects of Using Protein Engineering for Selective Drug Delivery into a Specific Compartment of Target Cells
Authors: Rosenkranz Andrey A. , Slastnikova Tatiana A.
Published: March 2023

A large number of proteins are successfully used to treat various diseases. These include natural polypeptide hormones, their synthetic analogues, antibodies, antibody mimetics, enzymes, and other drugs based on them. Many of them are demanded in clinical settings and commercially successful, mainly for cancer treatment. The targets for most of the aforementioned drugs are located at the cell surface. Meanwhile, the vast majority of therapeutic targets, which are usually regulatory macromolecules, are located inside the cell. Traditional low molecular weight drugs freely penetrate all cells, causing side effects in non-target cells. In addition, it is often difficult to elaborate a small molecule that can specifically affect protein interactions. Modern technologies make it possible to obtain proteins capable of interacting with almost any target. However, proteins, like other macromolecules, cannot, as a rule, freely penetrate into the desired cellular compartment. Recent studies allow us to design multifunctional proteins that solve these problems. This review considers the scope of application of such artificial constructs for the targeted delivery of both protein-based and traditional low molecular weight drugs, the obstacles met on the way of their transport to the specified intracellular compartment of the target cells after their systemic bloodstream administration, and the means to overcome those difficulties.
Efficient Delivery of Gemcitabine by Estrogen Receptor-Targeted PEGylated Liposome and Its Anti-Lung Cancer Activity In Vivo and In Vitro
Authors: Tang Huan , Zhang Zheng , Zhu Ming , Xie Yizhuo , Lv Zhe , Liu Rui , Shen Yujia , Pei Jin
Published: March 2023

Lung cancer is one of the main causes of cancer-related deaths. At present, the main treatment method for lung cancer is chemotherapy. Gemcitabine (GEM) is widely applied in lung cancer treatment, but its lack of targeting ability and serious side effects limit its application. In recent years, nanocarriers have become the focus of research to solve the above problems. Here, we prepared estrone (ES)-modified GEM-loaded PEGylated liposomes (ES-SSL-GEM) for enhanced delivery by identifying the overexpressed estrogen receptor (ER) on lung cancer A549 cells. We studied the characterization, stability, release behavior, cytotoxicity, targeting ability, endocytosis mechanism, and antitumor ability to prove the therapeutic effect of ES-SSL-GEM. The results showed that ES-SSL-GEM presented a uniform particle size of 131.20 ± 0.62 nm, a good stability, and a slowly released behavior. Moreover, ES-SSL-GEM enhanced tumor-targeting ability, and the endocytosis mechanism studies confirmed that the ER-mediated endocytosis had the most crucial effect. Furthermore, ES-SSL-GEM had the best inhibitory effect on A549 cell proliferation and significantly suppressed the tumor growth in vivo. These results suggest that ES-SSL-GEM is a promising agent for treating lung cancer.
A Review on Dry Eye Disease Treatment: Recent Progress, Diagnostics, and Future Perspectives
Authors: Mondal Himangsu , Kim Ho-Joong , Mohanto Nijaya , Jee Jun-Pil
Published: March 2023

Dry eye disease is a multifactorial disorder of the eye and tear film with potential damage to the ocular surface. Various treatment approaches for this disorder aim to alleviate disease symptoms and restore the normal ophthalmic environment. The most widely used dosage form is eye drops of different drugs with 5% bioavailability. The use of contact lenses to deliver drugs increases bioavailability by up to 50%. Cyclosporin A is a hydrophobic drug loaded onto contact lenses to treat dry eye disease with significant improvement. The tear is a source of vital biomarkers for various systemic and ocular disorders. Several biomarkers related to dry eye disease have been identified. Contact lens sensing technology has become sufficiently advanced to detect specific biomarkers and predict disease conditions accurately. This review focuses on dry eye disease treatment with cyclosporin A-loaded contact lenses, contact lens biosensors for ocular biomarkers of dry eye disease, and the possibility of integrating sensors in therapeutic contact lenses.
Does Green Exfoliation of Graphene Produce More Biocompatible Structures?
Authors: Papanikolaou Eirini , Simos Yannis V. , Spyrou Konstantinos , Patila Michaela , Alatzoglou Christina , Tsamis Konstantinos , Vezyraki Patra , Stamatis Haralambos , Gournis Dimitrios P. , Peschos Dimitrios , Dounousi Evangelia
Published: March 2023

Graphene has been studied thoroughly for its use in biomedical applications over the last decades. A crucial factor for a material to be used in such applications is its biocompatibility. Various factors affect the biocompatibility and toxicity of graphene structures, including lateral size, number of layers, surface functionalization, and way of production. In this work, we tested that the green production of few-layer bio-graphene (bG) enhances its biocompatibility compared to chemical-graphene (cG). When tested against three different cell lines in terms of MTT assays, both materials proved to be well-tolerated at a wide range of doses. However, high doses of cG induce long-term toxicity and have a tendency for apoptosis. Neither bG nor cG induced ROS generation or cell cycle modifications. Finally, both materials affect the expression of inflammatory proteins such as Nrf2, NF-kB and HO-1 but further research is required for a safe result. In conclusion, although there is little to choose between bG and cG, bG’s sustainable way of production makes it a much more attractive and promising candidate for biomedical applications.
Targeting Glioblastoma-Associated Macrophages for Photodynamic Therapy Using AGuIX®-Design Nanoparticles
Authors: Lerouge Lucie , Gries Mickaël , Chateau Alicia , Daouk Joël , Lux François , Rocchi Paul , Cedervall Jessica , Olsson Anna-Karin , Tillement Olivier , Frochot Céline , Acherar Samir , Thomas Noémie , Barberi-Heyob Muriel
Published: March 2023

Glioblastoma (GBM) is the most difficult brain cancer to treat, and photodynamic therapy (PDT) is emerging as a complementary approach to improve tumor eradication. Neuropilin-1 (NRP-1) protein expression plays a critical role in GBM progression and immune response. Moreover, various clinical databases highlight a relationship between NRP-1 and M2 macrophage infiltration. In order to induce a photodynamic effect, multifunctional AGuIX®-design nanoparticles were used in combination with a magnetic resonance imaging (MRI) contrast agent, as well as a porphyrin as the photosensitizer molecule and KDKPPR peptide ligand for targeting the NRP-1 receptor. The main objective of this study was to characterize the impact of macrophage NRP-1 protein expression on the uptake of functionalized AGuIX®-design nanoparticles in vitro and to describe the influence of GBM cell secretome post-PDT on the polarization of macrophages into M1 or M2 phenotypes. By using THP-1 human monocytes, successful polarization into the macrophage phenotypes was argued via specific morphological traits, discriminant nucleocytoplasmic ratio values, and different adhesion abilities based on real-time cell impedance measurements. In addition, macrophage polarization was confirmed via the transcript-level expression of TNFα, CXCL10, CD-80, CD-163, CD-206, and CCL22 markers. In relation to NRP-1 protein over-expression, we demonstrated a three-fold increase in functionalized nanoparticle uptake for the M2 macrophages compared to the M1 phenotype. The secretome of the post-PDT GBM cells led to nearly a three-fold increase in the over-expression of TNFα transcripts, confirming the polarization to the M1 phenotype. The in vivo relationship between post-PDT efficiency and the inflammatory effects points to the extensive involvement of macrophages in the tumor zone.
Nanosystems, Drug Molecule Functionalization and Intranasal Delivery: An Update on the Most Promising Strategies for Increasing the Therapeutic Efficacy of Antidepressant and Anxiolytic Drugs
Authors: Antunes Jéssica L. , Amado Joana , Veiga Francisco , Paiva-Santos Ana Cláudia , Pires Patrícia C.
Published: March 2023

Depression and anxiety are high incidence and debilitating psychiatric disorders, usually treated by antidepressant or anxiolytic drug administration, respectively. Nevertheless, treatment is usually given through the oral route, but the low permeability of the blood–brain barrier reduces the amount of drug that will be able to reach it, thus consequently reducing the therapeutic efficacy. Which is why it is imperative to find new solutions to make these treatments more effective, safer, and faster. To overcome this obstacle, three main strategies have been used to improve brain drug targeting: the intranasal route of administration, which allows the drug to be directly transported to the brain by neuronal pathways, bypassing the blood–brain barrier and avoiding the hepatic and gastrointestinal metabolism; the use of nanosystems for drug encapsulation, including polymeric and lipidic nanoparticles, nanometric emulsions, and nanogels; and drug molecule functionalization by ligand attachment, such as peptides and polymers. Pharmacokinetic and pharmacodynamic in vivo studies’ results have shown that intranasal administration can be more efficient in brain targeting than other administration routes, and that the use of nanoformulations and drug functionalization can be quite advantageous in increasing brain–drug bioavailability. These strategies could be the key to future improved therapies for depressive and anxiety disorders.
Suppression of Nonlinear Optical Effects in DWDM-PON by Frequency Modulation Non-Coherent Detection
Authors: Xin Lei , Xu Xiao , Du Liuge , Sun Chonglei , Gao Feng , Zhao Jia
Published: March 2023

We propose a simple and cost-effective method, using a direct frequency modulation (FM) and noncoherent detection (NCD) scheme, to suppress the nonlinear optical effects in dense wavelength division multiplexed (DWDM) optical communication. The FM transmitter comprises a directly modulated distributed feedback laser and a saturable semiconductor optical amplifier. In the NCD receiver, an optical slope filter as the FM to intensity modulation (IM) signal convertor is placed before a conventional photodetector. Because the FM signal has more evenly distributed optical power, bit-pattern-dependent nonlinear effects are consequently suppressed. After analyzing the nonlinear effects in the FM-NCD system and traditional IM direct detection (IM-DD) system, we found that the minimum achievable BER of the proposed FM-NCD scheme is 40 dB smaller. Moreover, a 2 Tbps (10 Gb/s × 200 channels) capacity was achieved by the FM-NCD system in 100 km DWDM passive optical networks (PONs), which is twice the capacity of the IM-DD system (10 Gb/s × 100 channels) under the same condition. These results indicate that WDM-PONs with the cost-effective FM-NCD scheme are strong candidates for future broad access networks and show great potential for the combination of optical access and metro networks for future generations of PONs.
Analysis of the Emission Features in CdSe/ZnS Quantum Dot-Doped Polymer Fibers
Authors: Peng Xuefeng , Wu Zhijian , Ye Chen , Ding Yang , Liu Wei
Published: March 2023

The emission features of Cdse/ZnS quantum dots doped step-index polymer optical fibers are computationally analyzed in this paper. Spontaneous emission and amplified spontaneous emission were calculated by a theoretical model based on the rate equations in terms of time, fiber length, and wavelength. All the calculated parameters are derived from experiments. Through the comparative analysis of the calculated and experimental results of spontaneous emission, we found that the pump power and overlap between the emission and absorption cross-sections may be the two main reasons for the red shift of the output spectra. When the pump power exceeds the threshold of amplified spontaneous emission, the width of the output spectra will rapidly decrease, the output wavelength will fall back toward the maximum emission cross-section, and the final output wavelength will still be affected by the doping concentration and pump power, while amplified spontaneous emission will not be generated when the total number of doped quantum dots is less than 1.27 × 1012.
Exclusive Effect in Rydberg Atom-Based Multi-Band Microwave Communication
Authors: You Shuhang , Cai Minghao , Zhang Haoan , Xu Zishan , Liu Hongping
Published: March 2023

We have demonstrated a Rydberg atom-based two-band communication with the optically excited Rydberg state coupled to another pair of Rydberg states by two microwave fields, respectively. The initial Rydberg state is excited by a three-color electromagnetically-induced absorption in rubidium vapor cell via cascading transitions, with all of them located in infrared bands: a 780 nm laser servers as a probe to monitor the optical transmittancy via transition 5S1/2→5P3/2, 776 nm and 1260 nm lasers are used to couple the states 5P3/2 and 5D5/2 and states 5D5/2 and 44F7/2. Experimentally, we show that two channel communications carried on the two microwave transitions influence each other irreconcilably, so that they cannot work at their most sensitive microwave-optical conversion points simultaneously. For a remarkable communication quality for both channels, the two microwave fields both have to make concessions to reach a common microwave-optical gain. The optimized balance for the two microwave intensities locates at EMW1=6.5 mV/cm and EMW2=5.5 mV/cm in our case. This mutual exclusive influence is theoretically well-explained by an optical Bloch equation considering all optical and microwave field interactions with atoms.
Non-Collinear Attosecond Streaking without the Time Delay Scan
Authors: Xu Peng , Wang Xianglin , Cao Huabao , Yuan Hao , Pi Liang-Wen , Wang Yishan , Fu Yuxi , Bai Yonglin , Zhao Wei
Published: March 2023

Attosecond streaking provides an extremely high temporal resolution for characterizing light pulses and photoionization processes with attosecond (10−18 s) accuracy, which employs a laser as a streaking field to deflect electrons generated by photoionization. The current attosecond streaking requires a time delay scan between the attosecond pulses and streaking field with attosecond accuracy and a femtosecond range, which is difficult to realize real-time measurement. In this study, we theoretically propose a non-collinear attosecond streaking scheme without the time delay scan, enabling real-time and even the potential to perform single-shot attosecond pulse measurement. In the proposal, time-delay information is projected into longitudinal space, both horizontally and vertically, enabling attosecond pulse characterization with temporal-spatial coupling. From our calculation, down to 70 as pulses with pulse front and wavefront tilt are characterized with high accuracy. Our study not only provides a method toward real-time attosecond pulse measurement, but also an approach for attosecond pump-probe experiments without time delay scan.
Extracts of Ulva lactuca Induce Responses against Penicillium digitatum on Oranges
Authors: Salim Douaa , Al-Alam Josephine , Merah Othmane , Chbani Asma , de Caro Pascale
Published: March 2023

Penicillium digitatum causes severe damage to postharvest and stored citrus fruits, making it necessary to seek acceptable solutions limiting environmental and sanitary impacts. The seaweed liquid extracts (SLEs) obtained from the green macroalgae Ulva lactuca have previously shown anti-fungal activities towards postharvest green mold due to P. digitatum. Moreover, treatment with aqueous and ethanolic extracts had an influence on disease incidence and lesion severity on wounded oranges “Valentia late”. Therefore, we studied the abilities of the U. lactuca extracts and chlorophyll a (as a standard) to activate defense mechanisms in oranges. The analyses showed modifications in the protein concentrations and activities of β-1,3-glucanase and peroxidase in orange tissues, with a maximum activity level reached at 72 h after treatments. It appears that the SLEs were able to fight P. digitatum infections in the absence of direct contact with the pathogen, reflecting that the induction of host resistance is also a probable mode of action. Ulva lactuca fractions are rich in chlorophyll a, polyphenols, organic acids and ulvans, which might be the key molecules involved in the defense mechanism of oranges’ albedo. The use of these natural substances could be an alternative way to control postharvest citrus rot.
Optimization of Polyolefin-Bonded Hydroxyapatite Graphite for Sustainable Industrial Applications
Authors: Bakhsh Ahmed A.
Published: March 2023

As a means of introducing environmental responsibility to industrial applications, the usage of biobased composite materials has been encouraged in recent years. Polymer nanocomposites utilize polyolefins increasingly as a matrix, owing to the diversity in their features and prospective applications, even though typical polyester blend materials, such as glass and composite materials, have garnered greater attention from researchers. The mineral hydroxy-apatite, or Ca10(PO4)6(OH)2, is the primary structural component of bone and tooth enamel. Increased bone density and strength result from this procedure. As a result, nanohms are fabricated from eggshells into rods with very tiny particle sizes. Although there have been many papers written on the benefits of HA-loaded polyolefins, the reinforcing effect of HA at low loadings has not yet been taken into account. The purpose of this work was to examine the mechanical and thermal characteristics of polyolefin-HA nanocomposites. These nanocomposites were built out of HDPE and LDPE (LDPE). As an extension of this work, we investigated what would happen when HA is added to LDPE composites at concentrations as high as 40% by weight. Carbonaceous fillers, including graphene, carbon nanotubes, carbon fibers, and exfoliated graphite, all play significant roles in nanotechnology owing to the extraordinary enhancements in their thermal, electrical, mechanical, and chemical properties. The purpose of this study was to examine the effects of adding a layered filler, such as exfoliated graphite (EG), to microwave zones that might have real-world applications for their mechanical, thermal, and electrical characteristics. Mechanical and thermal properties were significantly enhanced by the incorporation of HA, notwithstanding a minor decrease in these attributes at a loading of 40% HA by weight. A higher load-bearing capability of LLDPE matrices suggests their potential usage in biological contexts.
Decoding the Role of Extracellular Polymeric Substances in Enhancing Nitrogen Removal from High-Ammonia and Low-C/N Wastewater in a Sequencing Batch Packed-Bed Biofilm Reactor
Authors: Fan Zheng , Zhou Xin
Published: March 2023

Although the role of extracellular polymeric substances (EPSs) as a viscous high-molecular polymer in biological wastewater treatment has been recognized, in-depth knowledge of how EPSs affect nitrogen removal remains limited in biofilm-based reactors. Herein, we explored EPS characteristics associated with nitrogen removal from high-ammonia (NH4+-N: 300 mg/L) and low carbon-to-nitrogen ratio (C/N: 2–3) wastewater in a sequencing batch packed-bed biofilm reactor (SBPBBR) under four different operating scenarios for a total of 112 cycles. Scanning electron microscopy (SEM), atomic force microscopy (AFM), and Fourier-transform infrared (FTIR) analysis revealed that the distinct physicochemical properties, interface microstructure, and chemical composition of the bio-carrier were conducive to biofilm formation and microbial immobilization and enrichment. Under the optimal conditions (C/N: 3, dissolved oxygen: 1.3 mg/L, and cycle time: 12 h), 88.9% ammonia removal efficiency (ARE) and 81.9% nitrogen removal efficiency (NRE) could be achieved in the SBPBBR. Based on visual and SEM observations of the bio-carriers, biofilm development, biomass concentration, and microbial morphology were closely linked with nitrogen removal performance. Moreover, FTIR and three-dimensional excitation–emission matrix (3D-EEM) spectroscopy demonstrated that tightly bound EPSs (TB-EPSs) play a more important role in maintaining the stability of the biofilm. Significant shifts in the number, intensity, and position of fluorescence peaks of EPSs determined different nitrogen removal. More importantly, the high presence of tryptophan proteins and humic acids might promote advanced nitrogen removal. These findings uncover intrinsic correlations between EPSs and nitrogen removal for better controlling and optimizing biofilm reactors.