bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Feeding Practices and Celiac Disease Prevention: Protocol for an Updated and Revised Systematic Review and Meta-Analysis
Authors: Szajewska Hania , Shamir Raanan , Chmielewska Anna , Stróżyk Agata , Zalewski Bartłomiej , Auricchio Renata , Koletzko Sibylle , Korponay-Szabo Ilma , Mearin Luisa , Meijer Caroline , Ribes-Koninckx Carmen , Troncone Riccardo ,   on behalf of the PREVENTCD Study Group
Published: March 2022

Uncertainty remains in regard to when, how, and in what form gluten should be introduced into the diet, particularly of infants genetically predisposed to developing celiac disease (CD). MEDLINE (PubMed), EMBASE, and Cochrane Central Register of Controlled Trials databases will be searched from inception. Randomized controlled trials (RCTs) and observational studies (cohort, case-control, or cross-sectional studies) investigating the association between early feeding practices and the risk of CD and/or CD autoimmunity will be included. In prospective studies, participants will be infants regardless of the risk of developing CD. For retrospective studies, participants will be children or adults with CD or presenting with positive serology indicative of CD. Interventions will be gluten-containing products of any type. Exposures will be breastfeeding and/or the introduction of gluten-containing products of any type. In control groups, there will be no exposure, different degrees of exposure (partial vs. exclusive breastfeeding, different amounts of gluten, etc.), or a placebo. The primary outcome measure will be CD or CD autoimmunity (i.e., anti-transglutaminase or anti-endomysial antibodies). At least two reviewers will independently assess the risk of bias using a validated risk assessment tool depending on study design. Disagreements will be resolved by discussion to achieve a consensus with the involvement of one or more additional reviewers if required. If appropriate, data will be pooled. If not, a narrative synthesis will be performed. The findings will be submitted to a peer-reviewed journal.
Oral Acid Load Down-Regulates Fibroblast Growth Factor 23
Authors: Vidal Angela , Pineda Carmen , Raya Ana I. , Rios Rafael , Espartero Azahara , Muñoz-Castañeda Juan R. , Rodriguez Mariano , Aguilera-Tejero Escolastico , Lopez Ignacio
Published: March 2022

Increased dietary acid load has a negative impact on health, particularly when renal function is compromised. Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that is elevated during renal failure. The relationship between metabolic acidosis and FGF23 remains unclear. To investigate the effect of dietary acid load on circulating levels of FGF23, rats with normal renal function and with a graded reduction in renal mass (1/2 Nx and 5/6 Nx) received oral NH4Cl for 1 month. Acid intake resulted in a consistent decrease of plasma FGF23 concentrations in all study groups when compared with their non-acidotic control: 239.3 ± 13.5 vs. 295.0 ± 15.8 pg/mL (intact), 346.4 ± 19.7 vs. 522.6 ± 29.3 pg/mL (1/2 Nx) and 988.0 ± 125.5 vs. 2549.4 ± 469.7 pg/mL (5/6 Nx). Acidosis also decreased plasma PTH in all groups, 96.5 ± 22.3 vs. 107.3 ± 19.1 pg/mL, 113.1 ± 17.3 vs. 185.8 ± 22.2 pg/mL and 504.9 ± 75.7 vs. 1255.4 ± 181.1 pg/mL. FGF23 showed a strong positive correlation with PTH (r = 0.877, p < 0.0001) and further studies demonstrated that acidosis did not influence plasma FGF23 concentrations in parathyroidectomized rats, 190.0 ± 31.6 vs. 215 ± 25.6 pg/mL. In conclusion, plasma concentrations of FGF23 are consistently decreased in rats with metabolic acidosis secondary to increased acid intake, both in animals with intact renal function and with decreased renal function. The in vivo effect of metabolic acidosis on FGF23 appears to be related to the simultaneous decrease in PTH.
Sweet, Salty, and Umami Taste Sensitivity and the Hedonic Perception of Taste Sensations in Adolescent Females with Anorexia Nervosa
Authors: Hartman-Petrycka Magdalena , Klimacka-Nawrot Ewa , Ziora Katarzyna , Suchecka Wanda , Gorczyca Piotr , Rojewska Katarzyna , Błońska-Fajfrowska Barbara
Published: March 2022

Objective: The aim of this study was to perform analysis of sensitivity to sweet, salty, and umami tastes based on three measurement methods and of the hedonic perception of taste sensations in adolescent females with anorexia nervosa (AN). The aim of the research was to confirm the results of other authors in terms of the perception of sweet and salty taste in patients with AN, and then develop knowledge about the perception of umami taste, which is still insufficiently studied. Method: A total of 110 females with an age ranging from 13 to 19 years, including 50 newly diagnosed patients with a restrictive subtype of AN and 60 healthy controls participated in gustatory research involving analyses of taste perception (recognition thresholds, ability to identify the taste correctly, taste intensity, and hedonic response) applying the sip and spit method. Results: Females with AN showed reduced sensitivity to salty taste and increased sensitivity to umami taste and, more often than healthy controls, wrongly classified the taste of solutions with a low sucrose concentration. Patients with AN assessed the sodium chloride and monosodium glutamate tastes less negatively than did control participants, and they did not show differences in their hedonic assessment of sucrose. Conclusions: The taste sensitivity alterations in females with AN demonstrated in this paper do not entail decreased hedonic assessment of taste experiences. Based on our results, we cannot consider the observed variation in taste sensitivity in patients with AN to be a factor that increases their negative attitude toward food consumption.
A Randomized Controlled Trial Examining the Effects of Mindful Eating and Eating without Distractions on Food Intake over a Three-Day Period
Authors: Seguias Lana , Tapper Katy
Published: March 2022

This study compared the effects of mindful eating and eating without distractions on energy intake and diet over a 3-day period among healthy-weight females. Mindful eating was defined as attending to the sensory properties of one’s food as one eats. Participants (n = 99) were asked to either focus on the sensory properties of their food (MIND), eat without distractions (CON-D) or they were not provided with any instructions (CON-I). All participants completed an online food recall measure at the end of each day. Those in the MIND and CON-D groups also rated strategy adherence at the end of each day. Results showed no significant effects of condition on energy intake (ηp2 = 0.00), saturated fat, added sugar and fiber (ηp2 = 0.03), or fruit and vegetables (ηp2 = 0.04). There was also no significant relationship between energy intake and strategy adherence in the MIND group (r = −0.02). For those in the CON-D group, there was a trend toward a negative relationship between energy intake and strategy adherence (r = −0.31, p = 0.085). Among this population, there was no evidence that asking people to attend to the sensory properties of their food improved their diet. Further research is needed to identify mechanisms underpinning significant effects observed in laboratory studies, to help understand when this strategy is, and is not, likely to be helpful.
Effect of the Consumption of Alcohol-Free Beers with Different Carbohydrate Composition on Postprandial Metabolic Response
Authors: Lamiquiz-Moneo Itziar , Pérez-Calahorra Sofia , Gracia-Rubio Irene , Cebollada Alberto , Bea Ana M. , Fumanal Antonio , Ferrer-Mairal Ana , Prieto-Martín Ascensión , Sanz-Fernández María Luisa , Cenarro Ana , Civeira Fernando , Mateo-Gallego Rocio
Published: March 2022

Background: We investigated the postprandial effects of an alcohol-free beer with modified carbohydrate (CH) composition compared to regular alcohol-free beer. Methods: Two randomized crossover studies were conducted. In the first study, 10 healthy volunteers received 25 g of CH in four different periods, coming from regular alcohol-free beer (RB), alcohol-free beer enriched with isomaltulose and a resistant maltodextrin (IMB), alcohol-free beer enriched with resistant maltodextrin (MB), and a glucose-based beverage. In the second study, 20 healthy volunteers were provided with 50 g of CH from white bread (WB) plus water, or with 14.3 g of CH coming from RB, IMB, MB, and extra WB. Blood was sampled after ingestion every 15 min for 2 h. Glucose, insulin, incretin hormones, TG, and NEFAs were determined in all samples. Results: The increase in glucose, insulin, and incretin hormones after the consumption of IMB and MB was significantly lower than after RB. The consumption of WB with IMB and MB showed significantly less increase in glucose levels than WB with water or WB with RB. Conclusions: The consumption of an alcohol-free beer with modified CH composition led to a better postprandial response compared to a conventional alcohol-free beer.
Red-Fleshed Apples Rich in Anthocyanins and White-Fleshed Apples Modulate the Aorta and Heart Proteome in Hypercholesterolaemic Rats: The AppleCOR Study
Authors: Catalán Úrsula , Pedret Anna , Yuste Silvia , Rubió Laura , Piñol Carme , Sandoval-Ramírez Berner Andrée , Companys Judit , Foguet Elisabet , Herrero Pol , Canela Núria , Motilva Maria-Jose , Solà Rosa
Published: March 2022

The impact of a red-fleshed apple (RFA) rich in anthocyanins (ACNs), a white-fleshed apple (WFA) without ACNs, and an extract infusion from Aronia fruit (AI) equivalent in dose of cyanidin-3-O-galactoside (main ACN) as RFA was determined by the proteome profile of aorta and heart as key cardiovascular tissues. Hypercholesterolaemic Wistar rats were separated into six groups (n = 6/group; three males and three females) and the proteomic profiles were analyzed using nanoliquid chromatography coupled to mass spectrometry. No adverse events were reported and all products were well tolerated. RFA downregulated C1QB and CFP in aorta and CRP in heart. WFA downregulated C1QB and CFP in aorta and C9 and C3 in aorta and heart, among other proteins. AI downregulated PRKACA, IQGAP1, and HSP90AB1 related to cellular signaling. Thus, both apples showed an anti-inflammatory effect through the complement system, while RFA reduced CRP. Regardless of the ACN content, an apple matrix effect was observed that involved different bioactive components, and inflammatory proteins were reduced.
Uncovering Resistance to Hepatitis C Virus Infection: Scientific Contributions and Unanswered Questions in the Irish Anti-D Cohort
Authors: Sugrue Jamie A. , O’Farrelly Cliona
Published: March 2022

Infections caused inadvertently during clinical intervention provide valuable insight into the spectrum of human responses to viruses. Delivery of hepatitis C virus (HCV)-contaminated blood products in the 70s (before HCV was identified) have dramatically increased our understanding of the natural history of HCV infection and the role that host immunity plays in the outcome to viral infection. In Ireland, HCV-contaminated anti-D immunoglobulin (Ig) preparations were administered to approximately 1700 pregnant Irish rhesus-negative women in 1977–1979. Though tragic in nature, this outbreak (alongside a smaller episode in 1993) has provided unique insight into the host factors that influence outcomes after HCV exposure and the subsequent development of disease in an otherwise healthy female population. Despite exposure to highly infectious batches of anti-D, almost 600 of the HCV-exposed women have never shown any evidence of infection (remaining negative for both viral RNA and anti-HCV antibodies). Detailed analysis of these individuals may shed light on innate immune pathways that effectively block HCV infection and potentially inform us more generally about the mechanisms that contribute to viral resistance in human populations.
Pharmacological Effects of Gami-Yukmijihwang-Tang on the Lipopolysaccharide-Induced Hippocampus Oxidation and Inflammation via Regulation of Sirt6
Authors: Kang Jie-Yoon , Lee Jong-Suk , Seol In-Chan , Kim Yoon-Sik , Park Miso S. , Yoo Ho-Ryong
Published: March 2022

Yukmijihwang-Tang is widely used in traditional Korean medicine to treat age-related disorders. In the present study, we re-prescribed Gami-Yukmijihwang-Tang (YJT), which is slightly modified from Yukmijihwang-Tang by adding more medicinal plants to evaluate its pharmacological effects on underlying mechanisms against repeated lipopolysaccharide (LPS)-injection-induced neuroinflammation in the hippocampus regions. C57BL/6J male mice (16–24 weeks old) were divided into six groups: (1) the control group (DW with 0.9% saline injection), (2) LPS group (DW with LPS injection), YJT groups ((3) 100, (4) 200, or (5) 400 mg/kg of YJT with LPS injection), and (6) glutathione (GSH) group (100 mg/kg of GSH with LPS injection), respectively. Mice were orally administrated with various doses of YJT or glutathione (GSH) for the first five days. Neuroinflammation in the hippocampus region was induced by repeated injection of LPS during the last three days. As predicted, LPS not only increased oxidative stress–related markers including malondialdehyde, 4-hydroxynonenal, nitrotryptophan, and hydrogen peroxide, but also drastically enhanced inflammatory reactions including nitric oxide, inducible nitric oxide synthase, p65, and toll-like receptor 4, respectively. YJT administration, on the other hand, notably decreased the above pathological alterations by enhancement of antioxidant capacities such as superoxide dismutase and catalase activities. To explain the underlying pharmacological actions of YJT, we focused on a representative epigenetic regulator, a nicotinamide adenine dinucleotide + (NAD+)–dependent chromatin enzyme, Sirtuin 6 (Sirt6). Neuroinflammation in hippocampus regions depleted Sirt6 at the protein level and this alteration directly affected the nuclear factor erythroid 2–related factor (Nrf2)/hemeoxygenase (HO)-1 signaling pathway in the LPS group; however, YJT significantly recovered the Sirt6 protein levels, and it could recover the abnormal status of Nrf2/HO-1 signaling pathways in the hippocampus regions. Additionally, Sirt6 led to the up-regulation of GSH sub-enzymes of mRNA expression and protein levels of total GSH content. These findings suggest that YJT can protect against LPS-induced neuroinflammation and oxidative stress by regulating the Sirt6-related pathways and normalizing the GSH redox cycle.
Continuous Versus Intermittent Linezolid Infusion for Critically Ill Patients with Hospital-Acquired and Ventilator-Associated Pneumonia: Efficacy and Safety Challenges
Authors: Abou Warda Ahmed E. Abou , Sarhan Rania M. , Al-Fishawy Hussein Saeed , Moharram Ayman N. , Salem Heba F.
Published: March 2022

High variability of linezolid blood concentrations with partial subtherapeutic levels was observed in critically ill patients who received a standard intravenous dose of linezolid, contributing to drug resistance and toxicity. Continuous infusions of linezolid have been suggested as an alternative and provide good serum and alveolar levels without fluctuations in trough concentration. This study aimed to assess the effectiveness and safety of continuous linezolid infusion versus the standard regimen in critically ill patients. A prospective randomized controlled study was conducted on 179 patients with nosocomial pneumonia. Patients were randomized into two groups. The first group received IV linezolid 600 mg twice daily, while the second group received 600 mg IV as a loading dose, followed by a continuous infusion of 1200 mg/day (50 mg/h) for at least 8–10 days. The continuous infusion group showed a higher clinical cure rate than the intermittent infusion group (p = 0.046). Furthermore, efficacy was proven by greater improvement of P/F ratio (p = 0.030) on day 7 of treatment, a lower incidence of developing sepsis after beginning treatment (p = 0.009), and a shorter time to reach clinical cure (p < 0.001). Hematological parameters were also assessed during the treatment to evaluate the safety between the two groups. The incidence of thrombocytopenia was significantly lower in the continuous infusion group than in the intermittent infusion group. In addition, a stepwise logistic regression model revealed that the intermittent infusion of linezolid was significantly associated with thrombocytopenia (OR =4.128; 95% CI = 1.681–10.139; p =0.001). The current study is the first to assess the clinical aspects of continuous infusion of linezolid beyond pharmacokinetic studies. Continuous infusion of linezolid outperforms intermittent delivery in safety and improves clinical effectiveness in critically ill patients with Gram-positive nosocomial pneumonia.
Broad-Spectrum Activity of Small Molecules Acting against Influenza a Virus: Biological and Computational Studies
Authors: Agamennone Mariangela , Superti Fabiana
Published: March 2022

Influenza still represents a problematic disease, involving millions of people every year and causing hundreds of thousands of deaths. Only a few drugs are clinically available. The search for an effective weapon is still ongoing. In this scenario, we recently identified new drug-like compounds with antiviral activity toward two A/H1N1 Influenza virus strains, which were demonstrated to interfere with the processes mediated by hemagglutinin (HA). In the present work, the compound’s ability to act against the A/H3N2 viral strain has been evaluated in hemagglutination inhibition (HI) assays. Two of the five tested compounds were also active toward the A/H3N2 Influenza virus. To validate the scaffold activity, analogue compounds of two broad-spectrum molecules were selected and purchased for HI testing on both A/H1N1 and A/H3N2 Influenza viruses. Forty-three compounds were tested, and four proved to be active toward all three viral strains. A computational study has been carried out to depict the HA binding process of the most interesting compounds.
Electrospun Biomimetic Multifunctional Nanofibers Loaded with Ferulic Acid for Enhanced Antimicrobial and Wound-Healing Activities in STZ-Induced Diabetic Rats
Authors: Anand Sneha , Pandey Prashant , Begum Mohammed Yasmin , Chidambaram Kumarappan , Arya Dilip Kumar , Gupta Ravi Kr. , Sankhwar Ruchi , Jaiswal Shweta , Thakur Sunita , Rajinikanth Paruvathanahalli Siddalingam
Published: March 2022

Diabetic foot ulceration is the most distressing complication of diabetes having no standard therapy. Nanofibers are an emerging and versatile nanotechnology-based drug-delivery system with unique wound-healing properties. This study aimed to prepare and evaluate silk-sericin based hybrid nanofibrous mats for diabetic foot ulcer. The nanofibrous mats were prepared by electrospinning using silk sericin mixed with different proportions of polycaprolactone (PCL) and cellulose acetate (CA) loaded with ferulic acid (FA). The in vitro characterizations, such as surface morphology, mechanical properties, swelling behavior, biodegradability, scanning electron microscopy, and drug release were carried out. The SEM images indicated that nanofibers formed with varied diameters, ranging from 100 to 250 nm, and their tensile strength was found to range from 7 to 15 MPa. In vitro release demonstrated that the nanofibers sustained FA release over an extended time of period. In vitro cytotoxicity showed that the nanofibers possessed a lower cytotoxicity in HaCaT cells. The in vivo wound-healing studies demonstrated an excellent wound-healing efficiency of the nanofibers in diabetic rats. Furthermore, the histopathological studies showed the nanofibers’ ability to restore the skin’s normal structure. Therefore, it was concluded that the prepared silk-sericin-based hybrid nanofibers loaded with FA could be a promising drug-delivery platform for the effective treatment of diabetic foot ulcers.
Chitosan/PVA Hetero-Composite Hydrogel Containing Antimicrobials, Perfluorocarbon Nanoemulsions, and Growth Factor-Loaded Nanoparticles as a Multifunctional Dressing for Diabetic Wound Healing: Synthesis, Characterization, and In Vitro/In Vivo Evaluation
Authors: Lee Yu-Hsiang , Lin Sheng-Jhe
Published: March 2022

Diabetic foot ulcers remain one of the most difficult-to-treat complications of diabetes and may seriously threaten the life of patients since it frequently results in limb loss due to amputation, suggesting that an effective therapeutic strategy is still urgently needed. In this study, a chitosan-based heterogeneous composite hydrogel encapsulating perfluorocarbon emulsions, epidermal growth factor (EGF)-loaded chitosan nanoparticles, and polyhexamethylene biguanide (PHMB) named PEENPPCH was developed for diabetic wound healing. The PEENPPCH could sustainably release EGF and PHMB in an ion-rich environment to exert antibacterial effects and promote cell growth for wound repair. In addition, the PEENPPCH can provide anti-inflammatory effects functioned by its main constituent of chitosan. Moreover, the PEENPPCH can proactively offer oxygen delivery through the incorporation of perfluorocarbon and, therefore, is able to alleviate hypoxia conditions on diabetic wounds. These functionalities enabled a markedly enhanced wound healing efficacy on diabetic rats treated with the PEENPPCHs, including thorough re-epithelization, a reduced inflammatory response, faster collagen deposition, and advanced collagen maturation resulting in a 95% of wound closure degree after 15 days that was 12.6% (p < 0.05) higher than the value of the group treated with the commercial dressing HeraDerm. Given the aforementioned advantages, together with the known merits of hydrogels, the developed PEENPPCH is anticipated to be a feasible tool for clinical diabetic wound treatment.
How Long Do Implanted Triclosan Sutures Inhibit Staphylococcus aureus in Surgical Conditions? A Pharmacological Model
Authors: Daoud Frederic Christopher , Goncalves Ruben , Moore Nicholas
Published: March 2022

(1) Background: Sutures with triclosan (TS) are used to reduce the risk of surgical site infections (SSI), but most clinical trials are inconclusive. The traceability of SSI risk to antimicrobial activity in operated tissues is needed. (2) Objectives: This study aimed to predict triclosan antistaphylococcal activity in operated tissues. (3) Methods: Three TS were exposed to static water for 30 days, and triclosan release was recorded. Polyglactin TS explanted from sheep seven days after cardiac surgery according to 3Rs provided ex vivo acceleration benchmarks. TS immersion up to 7 days in ethanol-water cosolvency and stirring simulated tissue implantation. Controls were 30-day immersion in static water. The release rate over time was measured and fitted to a predictive function. Antistaphylococcal activity and duration were measured by time-kill analysis with pre-immersed polyglactin TS. (4) Fifteen to 60-fold accelerated in vitro conditions reproduced the benchmarks. The rate prediction with double-exponential decay was validated. The antistaphylococcal activity was bactericidal, with TS pre-immersed for less than 12 h before then S. aureus began to grow. The residual triclosan level was more than 95% and played no detectable role. (5) Conclusions: Polyglactin, poliglecaprone, and polydioxanone TS share similar triclosan release functions with parametric differences. Polyglactin TS is antistaphylococcal in surgical conditions for 4 to 12 h.
Methods of Liposomes Preparation: Formation and Control Factors of Versatile Nanocarriers for Biomedical and Nanomedicine Application
Authors: Lombardo Domenico , Kiselev Mikhail A.
Published: March 2022

Liposomes are nano-sized spherical vesicles composed of an aqueous core surrounded by one (or more) phospholipid bilayer shells. Owing to their high biocompatibility, chemical composition variability, and ease of preparation, as well as their large variety of structural properties, liposomes have been employed in a large variety of nanomedicine and biomedical applications, including nanocarriers for drug delivery, in nutraceutical fields, for immunoassays, clinical diagnostics, tissue engineering, and theranostics formulations. Particularly important is the role of liposomes in drug-delivery applications, as they improve the performance of the encapsulated drugs, reducing side effects and toxicity by enhancing its in vitro- and in vivo-controlled delivery and activity. These applications stimulated a great effort for the scale-up of the formation processes in view of suitable industrial development. Despite the improvements of conventional approaches and the development of novel routes of liposome preparation, their intrinsic sensitivity to mechanical and chemical actions is responsible for some critical issues connected with a limited colloidal stability and reduced entrapment efficiency of cargo molecules. This article analyzes the main features of the formation and fabrication techniques of liposome nanocarriers, with a special focus on the structure, parameters, and the critical factors that influence the development of a suitable and stable formulation. Recent developments and new methods for liposome preparation are also discussed, with the objective of updating the reader and providing future directions for research and development.
The Fate of Sialic Acid and PEG Modified Epirubicin Liposomes in Aged versus Young Cells and Tumor Mice Models
Authors: Sui Dezhi , Meng Xianmin , Li Changzhi , Tang Xueying , Qin Ying , Zhang Ning , Ding Junqiang , Liu Xinrong , Deng Yihui , Song Yanzhi
Published: March 2022

In preclinical studies of young mice, nanoparticles showed excellent anti-tumor therapeutic effects by harnessing Peripheral Blood Monocytes (PBMs) and evading the immune system. However, the changes of age will inevitably affect PBMs and the immune system, and there is a serious lack of relevant research. Sialic acid (SA)-octadecylamine (ODA) was synthesized, and SA- or polyethylene glycol (PEG)-modified epirubicin (EPI) liposomes (EPI-SL and EPI-PL, respectively) were prepared to explore differences in antitumor treatment using 8-month-old and 8-week-old Kunming mice. Based on presented data, 8-month-old mice had more PBMs in peripheral blood than 8-week-old mice, and age differences resulted in different anti-tumor treatment effects following EPI-SL and EPI-PL treatment. Following EPI-PL administration, the tumor volume was significantly smaller in 8-week-old mice than in 8-month-old mice (* p < 0.05). Eight-month-old mice treated with EPI-SL (8M-SL) presented no damage to healthy tissue, with a 100% survival rate, and 50% mice in 8M-SL showed ‘shedding’ of tumor tissues from the growth site. Accordingly, 8-month-old mice treated with EPI-SL achieved the best therapeutic effect at different ages and with different liposomes. EPI-SL could improve the antitumor effect of 8-week-old and 8-month-old mice.
Alleviation of Surgery-Induced Osteitis in Sinonasal Cavity by Dexamethasone-Loaded Poly(lactic-co-glycolic acid) (PLGA) Microparticles with Strong Calcium-Binding Affinity
Authors: Hong Seung-No , Kim Minjae , Park Jin-A , Kang Minji , Cha Hyunkyung , Park Sohyun , Kim Joon Kon , Pac Jinyoung , Seo Yuju , Kim Sungwhan , Kim Minju , Kim Dae Woo , Lee Yan
Published: March 2022

For the treatment of sinus surgery-induced osteitis in chronic rhinosinusitis (CRS), oral or intranasal administration of corticoids is generally used, although it has critical limitations and unavoidable side effects. To overcome these limitations, we designed dexamethasone (Dex)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles with bone-specific binding affinity, which could release the encapsulated Dex in a sustained manner on the exposed bone after the surgical wound in the nasal cavity. In a previous report, we prepared poly(butyl methacrylate-co-methacryloyloxyethyl phosphate) (PBMP) with both calcium-binding phosphomonoester groups and PLGA-binding butyl groups to introduce strong calcium-binding property to PLGA particles. In this study, after successful encapsulation of Dex in the PBMP-coated PLGA particles, we applied the Dex-PLGA/PBMP to the treatment of post-operative osteitis in the sinonasal cavity. The Dex-PLGA/PBMP showed more than 5-times higher binding affinity to the hydroxyapatite (HA) surface compared to the non-coated PLGA particles, without altering the morphology and encapsulation efficiency. After establishing the neo-osteogenesis mouse model by mechanical injury of the nasal mucosa, the activity of intranasally administered Dex-PLGA/PBMP was examined to inhibit the formation of undesirable new woven bone during the wound healing process. In addition, significantly lower osteocalcin activity was observed in the group treated with Dex-PLGA/PBMP, indicating decreased activation of osteoblasts. Overall, these results demonstrate that the PLGA/PBMP microparticle strategy has great potential for the treatment of CRS-related osteitis by localized corticoid delivery on the exposed bones with minimal side effects.
Rosinidin Flavonoid Ameliorates Hyperglycemia, Lipid Pathways and Proinflammatory Cytokines in Streptozotocin-Induced Diabetic Rats
Authors: Gilani Sadaf Jamal , Bin-Jumah May Nasser , Al-Abbasi Fahad A. , Nadeem Muhammad Shahid , Imam Syed Sarim , Alshehri Sultan , Ghoneim Mohammed M. , Afzal Muhammad , Alzarea Sami I. , Sayyed Nadeem , Kazmi Imran
Published: March 2022

Diabetes is one of the world’s most important public health issues, impacting both public health and socioeconomic advancement; moreover, current pharmacotherapy is still insufficient. The natural flavonoid rosinidin has a long history of use in pharmaceuticals and nutritional supplements, but its role in diabetes has been unknown. The current study was intended to confirm the anti-diabetic activity of rosinidin in our laboratory setting, along with its mechanism. Streptozotocin (60 mg/kg, ip) treatment used to induce type II diabetes in rats and the test medication rosinidin was then administered orally (at doses of 10 mg/kg and 20 mg/kg) for biochemical and histopathological analysis. Treatment with rosinidin reduced negative consequences of diabetes. Rosinidin exerted a protective effect on a number of characteristics, including anti-diabetic responses (lower blood glucose, higher serum insulin and improved pancreatic function) and molecular mechanisms (favorable effects on lipid profiles, total protein, albumin, liver glycogen, proinflammatory cytokine, antioxidant and oxidative stress markers, AST, ALT and urea). Furthermore, the improved pancreatic architecture observed in tissues substantiated the favourable actions of rosinidin in STZ-induced diabetic rats.
Mineralizing Gelatin Microparticles as Cell Carrier and Drug Delivery System for siRNA for Bone Tissue Engineering
Authors: Hinkelmann Sandra , Springwald Alexandra H. , Schulze Sabine , Hempel Ute , Mitrach Franziska , Wölk Christian , Hacker Michael C. , Schulz-Siegmund Michaela
Published: March 2022

The local release of complexed siRNA from biomaterials opens precisely targeted therapeutic options. In this study, complexed siRNA was loaded to gelatin microparticles cross-linked (cGM) with an anhydride-containing oligomer (oPNMA). We aggregated these siRNA-loaded cGM with human mesenchymal stem cells (hMSC) to microtissues and stimulated them with osteogenic supplements. An efficient knockdown of chordin, a BMP-2 antagonist, caused a remarkably increased alkaline phosphatase (ALP) activity in the microtissues. cGM, as a component of microtissues, mineralized in a differentiation medium within 8–9 days, both in the presence and in the absence of cells. In order to investigate the effects of our pre-differentiated and chordin-silenced microtissues on bone homeostasis, we simulated in vivo conditions in an unstimulated co-culture system of hMSC and human peripheral blood mononuclear cells (hPBMC). We found enhanced ALP activity and osteoprotegerin (OPG) secretion in the model system compared to control microtissues. Our results suggest osteoanabolic effects of pre-differentiated and chordin-silenced microtissues.
Pharmacokinetics of Haloperidol in Critically Ill Patients: Is There an Association with Inflammation?
Authors: Li Letao , Sassen Sebastiaan D. T. , van der Jagt Mathieu , Endeman Henrik , Koch Birgit C. P. , Hunfeld Nicole G. M.
Published: March 2022

Haloperidol is considered the first-line treatment for delirium in critically ill patients. However, clinical evidence of efficacy is lacking and no pharmacokinetic studies have been performed in intensive care unit (ICU) patients. The aim of this study was to establish a pharmacokinetic model to describe the PK in this population to improve insight into dosing. One hundred and thirty-nine samples from 22 patients were collected in a single-center study in adults with ICU delirium who were treated with low-dose intravenous haloperidol (3–6 mg per day). We conducted a population pharmacokinetic analysis using Nonlinear Mixed Effects Modelling (NONMEM). A one-compartment model best described the data. The mean population estimates were 51.7 L/h (IIV 42.1%) for clearance and 1490 L for the volume of distribution. The calculated half-life was around 22 h (12.3–29.73 h) for an average patient. A negative correlation between C-Reactive Protein (CRP) and haloperidol clearance was observed, where clearance decreased significantly with increasing CRP up to a CRP concentration of 100 mg/L. This is the first step towards haloperidol precision dosing in ICU patients and our results indicate a possible role of inflammation.
Therapeutic Treatment Plan Optimization during the COVID-19 Pandemic: A Comprehensive Physicochemical Compatibility Study of Intensive Care Units Selected Drugs
Authors: Tarantini Maria Gloria , Ramos Stéphanie , Secrétan Philippe-Henri , Guichard Laura , Hassani Lamia , Bellanger Agnès , Mayaux Julien , Tilleul Patrick , El Kouari Fadwa , Sadou Yayé Hassane
Published: March 2022

Background: The SARS-CoV-2 pandemic has resulted in a dramatic rise of the demand for medical devices and drugs. In this context, an important shortage of programmable syringe pumps, used to administrate different drugs in intensive care units, was seen. The opportunity of administrating combinations of five intensive care units selected drugs (Sufentanil, Clonidine, Loxapine, Midazolam, and Ketamine) was considered. Methods: The drug mixtures were studied in a pure form or diluted in NaCl 0.9% or G5%. Twenty-six possible combinations of the five drugs were produced in glass vials or polypropylene syringes and stored at 25 °C for 14 days. The LC method was implemented to study drugs combinations in the presence of the degradation products. The clearness and pH were also monitored. Results: All the 26 possible combinations displayed adequate physicochemical stability at 25 °C: at least 3 days and 7 days, respectively, for the dilution in 0.9% NaCl or glucose 5%, and the pure drug products mixtures. Conclusions: The study provided sufficient stability results, covering the medication administration period of at least three days. The combination of more than two drugs offers the advantage of minimizing the individual doses and reduces unwanted side-effects. Hence, this study opens up the possibility of combining the five drugs in one single syringe, which is useful especially under the current circumstances associated with an important shortage of programmable syringe pumps and pharmaceuticals.
Well-Defined Polyethylene Glycol Microscale Hydrogel Blocks Containing Gold Nanorods for Dual Photothermal and Chemotherapeutic Therapy
Authors: Newland Ben , Starke Johannes , Bastiancich Chiara , Gonçalves Diana P. N. , Bray Laura J. , Wang Wenxin , Werner Carsten
Published: March 2022

Local drug delivery offers a means of achieving a high concentration of therapeutic agents directly at the tumor site, whilst minimizing systemic toxicity. For heterogenous cancers such as glioblastoma, multimodal therapeutic approaches hold promise for better efficacy. Herein, we aimed to create a well-defined and reproducible drug delivery system that also incorporates gold nanorods for photothermal therapy. Solvent-assisted micromolding was used to create uniform sacrificial templates in which microscale hydrogels were formed with and without gold nanorods throughout their structure. The microscale hydrogels could be loaded with doxorubicin, releasing it over a period of one week, causing toxicity to glioma cells. Since these microscale hydrogels were designed for direct intratumoral injection, therefore bypassing the blood–brain barrier, the highly potent breast cancer therapeutic doxorubicin was repurposed for use in this study. By contrast, the unloaded hydrogels were well tolerated, without decreasing cell viability. Irradiation with near-infrared light caused heating of the hydrogels, showing that if concentrated at an injection site, these hydrogels maybe able to cause anticancer activity through two separate mechanisms.
Scale-Aware Network with Scale Equivariance
Authors: Ning Mingqiang , Tang Jinsong , Zhong Heping , Wu Haoran , Zhang Peng , Zhang Zhisheng
Published: March 2022

The convolutional neural network (CNN) has achieved good performance in object classification due to its inherent translation equivariance, but its scale equivariance is poor. A Scale-Aware Network (SA Net) with scale equivariance is proposed to estimate the scale during classification. The SA Net only learns samples of one scale in the training stage; in the testing stage, the unknown-scale testing samples are up-sampled and down-sampled, and a group of image copies with different scales are generated to form the image pyramid. The up-sampling adopts interpolation, and the down-sampling adopts interpolation combined with wavelet transform to avoid spectrum aliasing. The generated test samples with different scales are sent to the Siamese network with weight sharing for inferencing. According to the position of the maximum value of the classification-score matrix, the testing samples can be classified and the scale can be estimated simultaneously. The results on the MNIST and FMNIST datasets show that the SA Net has better performance than the existing methods. When the scale is larger than 4, the SA Net has higher classification accuracy than other methods. In the scale-estimation experiment, the SA Net can achieve low relative RMSE on any scale. The SA Net has potential for effective use in remote sensing, optical image recognition and medical diagnosis in cytohistology.
Phase Change Materials with Enhanced Thermal Conductivity and Heat Propagation in Them
Authors: Eletskii Alexander V.
Published: March 2022

The review contains information o; n the properties of phase-change materials (PCM) and the possibilities of their use as the basis of thermal energy storage. Special attention is given to PCMs with a phase transition temperature ranging between 20 and 80 °C since such materials can be effectively used to reduce temperature variations in residential and industrial rooms. Thus, the application of PCMs in the construction industry enables one to considerably reduce the power consumption and reduce the negative environmental impact of industrial facilities. Thermophysical characteristics of the main types of PCMs are presented. The heat balance for a room with walls made of PCM-added materials is estimated. The calculations demonstrate that such structures can stabilize the temperature in practical applications as a result of the usage of such materials. The construction of a thermal accumulator on the basis of PCM is proposed and analyzed. This facility uses water as a working fluid and paraffin as a PCM. The thermal accumulator has a modular structure so that the number of similar modules is determined by the quantity of energy to be stored. The potential of wide application of PCMs as a basis for thermal energy storage is rather limited due to a very low conductivity (less than 1 W/(m K)) inherent to these materials. This drawback can be overcome by adding carbon nanoparticles whose thermal conductivity is four to five orders of magnitude greater than that of the matrix material. The problem of fabrication of polymer composites with enhanced thermal conductivity due to nanocarbon particles doping is discussed in detail.
Effect of Jasmonic Acid Foliar Spray on the Morpho-Physiological Mechanism of Salt Stress Tolerance in Two Soybean Varieties (Glycine max L.)
Authors: Noor Javaria , Ullah Abd , Saleem Muhammad Hamzah , Tariq Akash , Ullah Sami , Waheed Abdul , Okla Mohammad K. , Al-Hashimi Abdulrahman , Chen Yinglong , Ahmed Zeeshan , Ahmad Izhar
Published: March 2022

Jasmonates (JAs) are lipid-derived compounds that function in plants as key signaling compounds during stressful conditions. This study aimed to examine the effects of exogenous fo-liar-JA application (100 μmol L−1) on the morpho-physiological response of two soybean varieties (parachinar-local and swat-84) grown under different NaCl regimes (0, 40, 80, and 120 mM). Results show that exogenous JA application alone and in combination with salt stress altered the growth and metabolism of both soybeans. For instance, they accumulated significant amounts of Na+ and Cl–, while their K+, Mg2+, Fe2+, Mn2+, B3+, and P3+ contents were low. Further, photosynthetic pigments Chl a and Chl b increased at low concentrations of salt and exogenous JA. Car decreased under both salt and exogenous JA as compared with untreated control. In addition, sugar, phenol, and protein content increased under both salt and exogenous JA application. In contrast, the exogenous JA application alleviated the negative impact of salt stress on the growth and metabolism of both soybeans. Further, the high concentrations of soluble protein and phenol in the leaves of both soybeans may contribute to their ability to adapt to salinity. However, molecular studies are necessary to understand the ameliorative role of exogenous JA in the growth and metabolism of salt-treated young seedlings in both soybean varieties.
Persistence of the Strictly Endemic Plants of Forest Margins: The Case of Cirsium alpis-lunae in the Northern Apennines (Italy)
Authors: Fenu Giuseppe , Lazzaro Lorenzo , Lastrucci Lorenzo , Viciani Daniele
Published: March 2022

Narrow endemic plants constitute a pivotal group for conservation, being often reduced to a small contingent of individuals and frequently threatened. However, effective conservation actions require reliable basic information about distribution range, ecological requirements, and population traits. Nevertheless, such knowledge results are incomplete or even completely missing for some neglected or recently described plants, such as Cirsium alpis-lunae, a thistle exclusive to the N-Apennines (Italy). To fill this gap, all sites where C. alpis-lunae grow were monitored, and data on the site and population traits were collected. Our results indicated that this plant is restricted to 16 scattered sites, varied in surface area and number of individuals. Reproductive and juvenile plants showed to be affected by roughly the same variables, in particular the surface of the site, the slope aspect, and the canopy cover. The narrow ecological niche of C. alpis-lunae was mainly determined by the canopy cover, and where coverage increases, the number of individuals decreases. The individuals only grow at forest edges, where the peculiar ecological conditions are limiting factors for the development of forestry cover; some other factors (i.e., high inclination and instability of the substrate) contribute to limiting the development of forestry vegetation and guarantee the persistence of these ecotones. Despite the great difficulties in accessing the sites where this species grows, this study presents, for the first time, a complete picture of the C. alpis-lunae population and yielded important data to identify effective conservation measures.
Dual Beneficial Effects of α-Spinasterol Isolated from Aster pseudoglehnii on Glucose Uptake in Skeletal Muscle Cells and Glucose-Stimulated Insulin Secretion in Pancreatic β-Cells
Authors: Lee Dahae , Kim Ji-Young , Kwon Hak Cheol , Kwon Jaeyoung , Jang Dae Sik , Kang Ki Sung
Published: March 2022

Herein, we determined whether α-Spinasterol, a stigmastane-type phytosterol isolated from Aster pseudoglehnii, potentially impacts glucose uptake and glucose-stimulated insulin secretion in skeletal muscle cells and pancreatic β-cells, respectively. We observed that A. pseudoglehnii and its fractions enhanced glucose uptake, with no toxic effects on C2C12 cells, with the n-hexane fraction exhibiting the most potent effect. α-Spinasterol, isolated from the n-hexane fraction, enhanced glucose uptake with no toxic effects on C2C12 cells. Additionally, α-Spinasterol increased the expression of associated proteins, including insulin receptor substrate-1, AMP-activated protein kinase, and glucose transporter type 4, as determined by Western blotting. Furthermore, α-Spinasterol enhanced insulin secretion in response to high glucose concentrations, with no toxic effects on INS-1 cells; this effect was superior to that demonstrated by gliclazide (positive control), commonly prescribed to treat type 2 diabetes (T2D). α-Spinasterol enhanced the expression of associated proteins, including insulin receptor substrate-2, peroxisome proliferator-activated receptor γ, and pancreatic and duodenal homeobox 1, as determined using Western blotting. The insulin secretory effect of α-Spinasterol was enhanced by a K+ channel blocker and L-type Ca2+ channel agonist and was suppressed by a K+ channel activator and L-type Ca2+ channel blocker. α-Spinasterol isolated from A. pseudoglehnii may improve hyperglycemia by improving glucose uptake into skeletal muscle cells and enhancing insulin secretion in pancreatic β-cells. Accordingly, α-Spinasterol could be a potential candidate for anti-T2D therapy.
The Halophyte Species Solanum chilense Dun. Maintains Its Reproduction despite Sodium Accumulation in Its Floral Organs
Authors: Bigot Servane , Pongrac Paula , Šala Martin , van Elteren Johannes T. , Martínez Juan-Pablo , Lutts Stanley , Quinet Muriel
Published: March 2022

Salinity is a growing global concern that affects the yield of crop species, including tomato (Solanum lycopersicum). Its wild relative Solanum chilense was reported to have halophyte properties. We compared salt resistance of both species during the reproductive phase, with a special focus on sodium localization in the flowers. Plants were exposed to NaCl from the seedling stage. Salinity decreased the number of inflorescences in both species but the number of flowers per inflorescence and sepal length only in S. lycopersicum. External salt supply decreased the stamen length in S. chilense, and it was associated with a decrease in pollen production and an increase in pollen viability. Although the fruit set was not affected by salinity, fruit weight and size decreased in S. lycopersicum. Concentrations and localization of Na, K, Mg, and Ca differed in reproductive structures of both species. Inflorescences and fruits of S. chilense accumulated more Na than S. lycopersicum. Sodium was mainly located in male floral organs of S. chilense but in non-reproductive floral organs in S. lycopersicum. The expression of Na transporter genes differed in flowers of both species. Overall, our results indicated that S. chilense was more salt-resistant than S. lycopersicum during the reproductive phase and that differences could be partly related to dissimilarities in element distribution and transport in flowers.