bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review of the Effect of Preparations from Vegetables of the Asteraceae Family and Cucurbitaceae Family on the Cardiovascular System and Its Diseases
Authors: Rolnik Agata , Olas Beata
Published: September 2022

Cardiovascular (CV) system dysfunction can result in the development of cardiovascular diseases (CVDs), a key cause of death around the world. For many people, the most common treatment choices are still based on various plants used in traditional and folk medicine. Interestingly, many of these plants demonstrate various biological activities and pro-health properties; as such, there has been growing scientific interest in their use as medicines, including treatments for CVDs. Due to their varied biological properties, including anti-inflammatory and anticancer potential, the members of the Asteraceae and Cucurbitaceae have long been used in traditional medicine. These properties are believed to derive from the chemical composition of the plants, which includes various flavonoids, phenolic acids, and terpenes. Although many of their pro-health properties have been well described, their effect on the cardiovascular system and CVDs remains unclear. The present work reviews the current literature about the effects of preparations of vegetables of the Asteraceae and Cucurbitaceae families on the cardiovascular system and CVDs. Various species from the two families demonstrate antioxidant and antiplatelet activities in vitro and in vivo, which play key roles in the prophylaxis and treatment of CVDs. Additionally, some species have been evaluated for their anticoagulant activity. This review also describes the biological properties of these vegetables and discusses their anti-hyperlipidemic action, and their potential for obesity prevention and body weight control.
Anti-Osteoporosis Effects of the Fruit of Sea Buckthorn (Hippophae rhamnoides) through Promotion of Osteogenic Differentiation in Ovariectomized Mice
Authors: Park Kun Hee , Hong Joo-Hyun , Kim Seon-Hee , Kim Jin-Chul , Kim Ki Hyun , Park Ki-Moon
Published: September 2022

The fruit of Hippophae rhamnoides has been widely used for medicinal purposes because of its anti-inflammatory, antioxidant, antiplatelet, and antimicrobial effects. Since there are no clear reports on the therapeutic efficacy of H. rhamnoides in osteoporosis, this study aimed to confirm the potential use of H. rhamnoides for the treatment of osteoporosis through its osteogenic differentiation-promoting effect in ovariectomized mice. Through an in vitro study, we compared the effects of the EtOH extract of H. rhamnoides fruits (EHRF) on the differentiation of C3H10T1/2, a mouse mesenchymal stem cell line, into osteoblasts based on alkaline phosphatase (ALP) staining and the relative expression of osteogenesis-related mRNAs. The EHRF significantly stimulated the differentiation of mesenchymal stem cells into osteoblasts and showed 7.5 times (* p < 0.05) higher osteogenesis than in the untreated control. A solvent fractionation process of EHRF showed that the hexane-soluble fraction (HRH) showed 10.4 times (** p < 0.01) higher osteogenesis than in the untreated control. Among the subfractions derived from the active HRH by preparative HPLC fractionation, HRHF4 showed 7.5 times (* p < 0.05) higher osteogenesis than in the untreated naïve cells, and HRH and HRHF4 fractions showed 22.6 times (*** p < 0.001) stronger osteogenesis activity than in the negative control. Osteoporosis was induced by excision of both ovaries in 9-week-old female ICR mice for in vivo analysis, and two active fractions, HRH and HRHF4, were administered orally for three months. During the oral administration period, body weight was measured weekly, and bone mineral density (BMD) and body fat density were measured simultaneously using a DEXA machine once a month. In particular, during the in vivo study, the average BMD of the ovariectomized group decreased by 0.0009 g/cm2, whereas the average BMD of the HRH intake group increased by 0.0033 g/cm2 (* p < 0.05) and that of the HRHF4 intake group increased by 0.0059 g/cm2 (** p < 0.01). The HRH and HRHF4 intake groups significantly recovered the mRNA and protein expression of osteogenic genes, including ALP, Osteopontin, Runx2, and Osterix, in the osteoporosis mouse tibia. These findings suggest that the active fractions of H. rhamnoides fruit significantly promoted osteoblast differentiation in mesenchymal stem cells and increased osteogenic gene expression, resulting in an improvement in bone mineral density in the osteoporosis mouse model. Taken together, H. rhamnoides fruits are promising candidates for the prevention and treatment of osteoporosis.
Ketogenic Diet Treatment of Defects in the Mitochondrial Malate Aspartate Shuttle and Pyruvate Carrier
Authors: Bölsterli Bigna K. , Boltshauser Eugen , Palmieri Luigi , Spenger Johannes , Brunner-Krainz Michaela , Distelmaier Felix , Freisinger Peter , Geis Tobias , Gropman Andrea L. , Häberle Johannes , Hentschel Julia , Jeandidier Bruno , Karall Daniela , Keren Boris , Klabunde-Cherwon Annick , Konstantopoulou Vassiliki , Kottke Raimund , Lasorsa Francesco M. , Makowski Christine , Mignot Cyril , O’Gorman Tuura Ruth , Porcelli Vito , Santer René , Sen Kuntal , Steinbrücker Katja , Syrbe Steffen , Wagner Matias , Ziegler Andreas , Zöggeler Thomas , Mayr Johannes A. , Prokisch Holger , Wortmann Saskia B.
Published: September 2022

The mitochondrial malate aspartate shuttle system (MAS) maintains the cytosolic NAD+/NADH redox balance, thereby sustaining cytosolic redox-dependent pathways, such as glycolysis and serine biosynthesis. Human disease has been associated with defects in four MAS-proteins (encoded by MDH1, MDH2, GOT2, SLC25A12) sharing a neurological/epileptic phenotype, as well as citrin deficiency (SLC25A13) with a complex hepatopathic-neuropsychiatric phenotype. Ketogenic diets (KD) are high-fat/low-carbohydrate diets, which decrease glycolysis thus bypassing the mentioned defects. The same holds for mitochondrial pyruvate carrier (MPC) 1 deficiency, which also presents neurological deficits. We here describe 40 (18 previously unreported) subjects with MAS-/MPC1-defects (32 neurological phenotypes, eight citrin deficiency), describe and discuss their phenotypes and genotypes (presenting 12 novel variants), and the efficacy of KD. Of 13 MAS/MPC1-individuals with a neurological phenotype treated with KD, 11 experienced benefits—mainly a striking effect against seizures. Two individuals with citrin deficiency deceased before the correct diagnosis was established, presumably due to high-carbohydrate treatment. Six citrin-deficient individuals received a carbohydrate-restricted/fat-enriched diet and showed normalisation of laboratory values/hepatopathy as well as age-adequate thriving. We conclude that patients with MAS-/MPC1-defects are amenable to dietary intervention and that early (genetic) diagnosis is key for initiation of proper treatment and can even be lifesaving.
Reduction of Cardiovascular Events and Related Healthcare Expenditures through Achieving Population-Level Targets of Dietary Salt Intake in Japan: A Simulation Model Based on the National Health and Nutrition Survey
Authors: Ikeda Nayu , Yamashita Hitomi , Hattori Jun , Kato Hiroki , Yoshita Katsushi , Nishi Nobuo
Published: September 2022

Reducing population dietary salt intake is expected to help prevent cardiovascular disease and thus constrain increasing national healthcare expenditures in Japan’s super-aged society. We aimed to estimate the impact of achieving global and national salt-reduction targets (8, <6, and <5 grams/day) on cardiovascular events and national healthcare spending in Japan. Using published data including mean salt intake and systolic blood pressure from the 2019 National Health and Nutrition Survey, we developed a Markov model of a closed cohort of adults aged 40–79 years in 2019 (n = 66,955,000) transitioning among six health states based on the disease course of ischemic heart disease (IHD) and stroke. If mean salt intake were to remain at 2019 levels over 10 years, cumulative incident cases in the cohort would be approximately 2.0 million for IHD and 2.6 million for stroke, costing USD 61.6 billion for IHD and USD 104.6 billion for stroke. Compared with the status quo, reducing mean salt intake towards the targets over 10 years would avert 1–3% of IHD and stroke events and save up to 2% of related national healthcare costs. Attaining dietary salt-reduction goals among adults would yield moderate health economic benefits in Japan.
Associations of Dietary Fats with All-Cause Mortality and Cardiovascular Disease Mortality among Patients with Cardiometabolic Disease
Authors: Yang Tingting , Yi Jing , He Yangting , Zhang Jia , Li Xinying , Ke Songqing , Xia Lu , Liu Li
Published: September 2022

Previous studies have shown distinct associations between specific dietary fats and mortality. However, evidence on specific dietary fats and mortality among patients with cardiometabolic disease (CMD) remains unclear. The aim of this study was to estimate the association between consumption of specific fatty acids and survival of patients with CMD and examine whether cardiometabolic biomarkers can mediate the above effects. The study included 8537 participants with CMD, from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999–2014. Cox proportional hazards regression, restricted cubic spline regression, and isocaloric substitution models were used to estimate the associations of dietary fats with all-cause mortality and cardiovascular disease (CVD) mortality among participants with CMD. Mediation analysis was performed to assess the potential mediating roles of cardiometabolic biomarkers. During a median follow-up of 10.3 years (0–27.1 years), 3506 all-cause deaths and 882 CVD deaths occurred. The hazard ratios (HRs) of all-cause mortality among patients with CMD were 0.85 (95% confidence interval (CI), 95% CI, 0.73–0.99; p trend = 0.03) for ω-6 polyunsaturated fatty acids (ω-6 PUFA), 0.86 (95% CI, 0.75–1.00; p trend = 0.05) for linoleic acid (LA), and 0.86 (95% CI, 0.75–0.98; p trend = 0.03) for docosapentaenoic acid (DPA). Isocalorically replacing energy from SFA with PUFA and LA were associated with 8% and 4% lower all-cause mortality respectively. The HRs of CVD mortality among CMD patients comparing extreme tertiles of specific dietary fats were 0.60 (95% CI, 0.48–0.75; p trend = 0.002) for eicosapentaenoic acid (EPA), and 0.64 (95% CI, 0.48–0.85; p trend = 0.002) for DPA and above effects were mediated by levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL), and high density lipoprotein cholesterol (HDL). Restricted cubic splines showed significant negative nonlinear associations between above specific dietary fats and mortality. These results suggest that intakes of ω-6 PUFA, LA, and DPA or replacing SFA with PUFA or LA might be associated with lower all-cause mortality for patients with CMD. Consumption of EPA and DPA could potentially reduce cardiovascular death for patients with CMD, and their effects might be regulated by cardiometabolic biomarkers indirectly. More precise and representative studies are further needed to validate our findings.
Do Lifestyle Interventions before Gastric Bypass Prevent Weight Regain after Surgery? A Five-Year Longitudinal Study
Authors: Vaccaro Salvatore , Itani Leila , Scazzina Francesca , Bonilauri Stefano , Cartelli Concetto Maria , El Ghoch Marwan , Pellegrini Massimo
Published: September 2022

It is unclear whether weight loss (WL) achieved by means of lifestyle interventions (LSIs) before bariatric surgery (BS) can improve long-term WL outcomes after surgery. We aimed to assess the impact of a structured LSI on WL% after gastric bypass (GBP). Two groups of patients were selected from a large cohort of participants with obesity who underwent GBP surgery at Santa Maria Nuova Hospital (Reggio Emilia, Italy). The groups were categorized as those who have or have not received LSI prior to GBP. The LSI group included 91 participants (cases) compared to 123 participants (controls) in the non-LSI group. WL% was measured at follow-up times of 1, 3, 6, 12, 24, 36, 48, and 60 months. The LSI group achieved a clinically significant WL% (−7.5%) before BS, and at the time of surgery, the two groups had similar body weights and demographic statuses. At all points, until the 24-month follow-up, the two groups displayed similar WLs%. With regard to the longer follow-ups, the LSI group maintained weight loss until the last timepoint (60 months), whereas the non-LSI group experienced weight regain at 36, 48, and 60 months. In a real-world context, a structured behavioral LSI prior to GBP seems to prevent longer-term weight regain.
Acceptability of the FIGO Nutrition Checklist in Preconception and Early Pregnancy to Assess Nutritional Status and Prevent Excess Gestational Weight Gain: A Study of Women and Healthcare Practitioners in the UK
Authors: Jacob Chandni Maria , Inskip Hazel M. , Lawrence Wendy , McGrath Carmel , McAuliffe Fionnuala M. , Killeen Sarah Louise , Divakar Hema , Hanson Mark
Published: September 2022

Optimum nutrition and weight before and during pregnancy are associated with a lower risk of conditions such as pre-eclampsia and gestational diabetes. There is a lack of user-friendly tools in most clinical settings to support healthcare practitioners (HCPs) in implementing them. This study aimed to evaluate the acceptability of (1) using a nutrition checklist designed by the International Federation of Gynecology and Obstetrics (FIGO) for nutritional screening of women in the preconception and early pregnancy period and (2) routine discussion of nutrition and weight in clinical care. An online cross-sectional survey was conducted with women (aged 18–45) and HCPs (e.g., general practitioners, obstetricians, and midwives). Quantitative statistical analysis and qualitative content analysis were performed. The concept and content of the checklist were acceptable to women (n = 251) and HCPs (n = 47) (over 80% in both groups). Several barriers exist to implementation such as lack of time, training for HCPs, and the need for sensitive and non-stigmatizing communication. Routine discussion of nutrition was considered important by both groups; however, results suggest that nutrition is not regularly discussed in perinatal visits in the UK. The FIGO nutrition checklist presents a valuable resource for use in clinical practice, offering long-term and intergenerational benefits for both mother and baby.
An Unexpected Reaction between Diaryliodonium Salts and DMSO
Authors: Kepski Konrad , Moran Wesley James
Published: September 2022

Diaryliodonium salts are useful arylating reagents that have been exploited widely. In this Communication, we demonstrate that heating diphenyliodonium triflate in the solvent DMSO leads to an unexpected arylation reaction. It is postulated that arylation of DMSO at oxygen, followed by a thia-Sommelet–Hauser rearrangement, leads to the formation of 2-thiomethylphenols. More substituted diaryliodonium salts and cyclic diaryliodonium salts are shown to be more stable and less likely to react with DMSO. In conclusion, when using iodonium salts dissolved in DMSO, beware of side-reactions.
The Effect of Core Stabilization Training on Improving Gait and Self-Perceived Function in Patients with Knee Osteoarthritis: A Single-Arm Clinical Trial
Authors: Flowers Daniel W. , Brewer Wayne , Mitchell Katy , Ellison Jennifer , Frilot Clifton
Published: September 2022

The treatment of patients with knee osteoarthritis is typically focused on the involved lower extremity. There is a gap in the literature concerning the effectiveness of core stabilization training on the treatment of patients with knee osteoarthritis. This investigation aimed to determine whether core stabilization improved the gait and functional ability of patients with knee osteoarthritis. Eighteen participants with knee osteoarthritis completed the six-week core stabilization intervention. Participants completed the gait motion analysis and the Knee Injury and Osteoarthritis Outcome Score to assess self-perceived function, pre- and post-intervention. Gait speed improved (p = 0.006, d = 0.59), while the external knee adduction moment decreased (p = 0.034, d = −0.90). Moreover, self-reported function improved (p < 0.001, d = 1.26). The gait speed and external knee adduction moment changes met minimal detectable change thresholds, while gait speed also met the minimal clinically important difference. A six-week core stabilization program can thus improve gait speed and reduce the external knee adduction moment, which is tied to disease progression. Increased functional scores post-intervention indicate an important clinical improvement. Core stabilization training is a safe and potentially effective treatment option for this population.
Importance of Rose Bengal Loaded with Nanoparticles for Anti-Cancer Photodynamic Therapy
Authors: Dhaini Batoul , Wagner Laurène , Moinard Morgane , Daouk Joël , Arnoux Philippe , Schohn Hervé , Schneller Perrine , Acherar Samir , Hamieh Tayssir , Frochot Céline
Published: September 2022

Rose Bengal (RB) is a photosensitizer (PS) used in anti-cancer and anti-bacterial photodynamic therapy (PDT). The specific excitation of this PS allows the production of singlet oxygen and oxygen reactive species that kill bacteria and tumor cells. In this review, we summarize the history of the use of RB as a PS coupled by chemical or physical means to nanoparticles (NPs). The studies are divided into PDT and PDT excited by X-rays (X-PDT), and subdivided on the basis of NP type. On the basis of the papers examined, it can be noted that RB used as a PS shows remarkable cytotoxicity under the effect of light, and RB loaded onto NPs is an excellent candidate for nanomedical applications in PDT and X-PDT.
Cu and Zn Interactions with Peptides Revealed by High-Resolution Mass Spectrometry
Authors: Iavorschi Monica , Lupăescu Ancuța-Veronica , Darie-Ion Laura , Indeykina Maria , Hitruc Gabriela , Petre Brîndușa
Published: September 2022

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by abnormal extracellular amyloid-beta (Aβ) peptide depositions in the brain. Among amorphous aggregates, altered metal homeostasis is considered a common risk factor for neurodegeneration known to accelerate plaque formation. Recently, peptide-based drugs capable of inhibiting amyloid aggregation have achieved unprecedented scientific and pharmaceutical interest. In response to metal ions binding to Aβ peptide, metal chelation was also proposed as a therapy in AD. The present study analyzes the interactions formed between NAP octapeptide, derived from activity-dependent neuroprotective protein (ADNP), amyloid Aβ(9–16) fragment and divalent metal ions such as Cu and Zn. The binding affinity studies for Cu and Zn ions of synthetic NAP peptide and Aβ(9–16) fragment were investigated by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), electrospray ion trap mass spectrometry (ESI-MS) and atomic force microscopy (AFM). Both mass spectrometric methods confirmed the formation of metal–peptide complexes while the AFM technique provided morphological and topographic information regarding the influence of metal ions upon peptide crystallization. Our findings showed that due to a rich histidine center, the Aβ(9–16) fragment is capable of binding metal ions, thus becoming stiff and promoting aggregation of the entire amyloid peptide. Apart from this, the protective effect of the NAP peptide was found to rely on the ability of this octapeptide to generate both chelating properties with metals and interactions with Aβ peptide, thus stopping its folding process.
Non-Invasive Iontophoretic Delivery of Cytochrome c to the Posterior Segment and Determination of Its Ocular Biodistribution
Authors: González Iglesias Laura Gisela , Messaoudi Siwar , Kalia Yogeshvar N.
Published: September 2022

The intact porcine eye globe model was used to demonstrate that transscleral iontophoresis could deliver a small protein, cytochrome c (Cyt c), to the posterior segment and to investigate post-iontophoretic biodistribution in the different ocular compartments. The effects of Cyt c concentration (1, 5, and 10 mg/mL), current density (3.5 and 5.5 mA/cm2), and duration of the current application (10 min and 1, 2, and 4 h) were evaluated. The data confirmed that transscleral iontophoresis enhanced the intraocular delivery of Cyt c under all conditions as compared to passive controls (same setup but without the current application). Increasing the Cyt c concentration resulted in a proportional enhancement in the Cyt c delivery. Increasing the current density from 3.5 to 5.5 mA/cm2 increased iontophoretic delivery at a Cyt c concentration of 10 mg/mL but did not appear to do so at 5 mg/mL; this was attributed in part to the effect of melanin binding. Short duration iontophoresis (10 min, 3.5 mA/cm2) of a 10 mg/mL Cyt c solution created a depot in the sclera. When this was followed by a 4 h incubation period, post-iontophoretic Cyt c diffusion from the sclera resulted in a different biodistribution, and Cyt c could be quantified in the posterior segment.
INGAP-Peptide Variants as a Novel Therapy for Type 1 Diabetes: Effect on Human Islet Insulin Secretion and Gene Expression
Authors: Porter James M. , Guerassimoff Léa , Castiello Francisco Rafael , Charette André , Tabrizian Maryam
Published: September 2022

Islet transplantation offers a long-term cure for Type 1 Diabetes (T1D), freeing patients from daily insulin injections. Therapeutic peptides have shown potential to increase the insulin output of pancreatic islets, maximizing the impact of grafted cells. The islet neogenesis-associated protein (INGAP), and its bioactive core (INGAP-P), stimulate beta-cell function and viability, offering the possibility for islet treatment prior to implant. However, dosing efficacy is limited by low circulation time and enzyme degradation. This proof-of-concept study presents the investigation of novel molecular variants of INGAP-P to find a more bioactive form. Custom-designed peptide variants of INGAP-P were synthesized and tested for their effect on the insulin secretion and gene expression of live human islets. We exposed the live islets of five donors to varying glucose concentrations with INGAP-P variants in solution. We identified four peptide variants (I9, I15Tyr, I19 and I15Cys) which displayed statistically significant enhancements over negative controls (representing a 1.6–2.8-fold increase in stimulation index). This is the first study that has assessed these INGAP-P variants in human islets. It highlights the potential for customized peptides for type 1 diabetes therapy and provides a foundation for future peptide-screening experiments.
Brain-Targeted Drug Delivery
Authors: Sousa Flávia
Published: September 2022

At present, brain diseases affect one in six people worldwide, and they include a wide range of neurological diseases from Alzheimer’s and Parkinson’s diseases to epilepsy, brain injuries, brain cancer, neuroinfections and strokes [...]
Assuring the Biofunctionalization of Silicone Covalently Bonded to Rhamnolipids: Antibiofilm Activity and Biocompatibility
Authors: Dardouri Maïssa , Bettencourt Ana , Martin Victor , Carvalho Filomena A. , Colaço Bruno , Gama Adelina , Ramstedt Madeleine , Santos Nuno C. , Fernandes Maria H. , Gomes Pedro S. , Ribeiro Isabel A. C.
Published: September 2022

Silicone-based medical devices composed of polydimethylsiloxane (PDMS) are widely used all over the human body (e.g., urinary stents and catheters, central venous catheters stents) with extreme clinical success. Nevertheless, their abiotic surfaces, being prone to microorganism colonization, are often involved in infection occurrence. Improving PDMS antimicrobial properties by surface functionalization with biosurfactants to prevent related infections has been the goal of different works, but studies that mimic the clinical use of these novel surfaces are missing. This work aims at the biofunctional assessment of PDMS functionalized with rhamnolipids (RLs), using translational tests that more closely mimic the clinical microenvironment. Rhamnolipids were covalently bonded to PDMS, and the obtained surfaces were characterized by contact angle modification assessment, ATR-FTIR analysis and atomic force microscopy imaging. Moreover, a parallel flow chamber was used to assess the Staphylococcus aureus antibiofilm activity of the obtained surfaces under dynamic conditions, and an in vitro characterization with human dermal fibroblast cells in both direct and indirect characterization assays, along with an in vivo subcutaneous implantation assay in the translational rabbit model, was performed. A 1.2 log reduction in S. aureus biofilm was observed after 24 h under flow dynamic conditions. Additionally, functionalized PDMS lessened cell adhesion upon direct contact, while supporting a cytocompatible profile, within an indirect assay. The adequacy of the biological response was further validated upon in vivo subcutaneous tissue implantation. An important step was taken towards biofunctional assessment of RLs-functionalized PDMS, reinforcing their suitability for medical device usage and infection prevention.
How to Completely Squeeze a Fungus—Advanced Genome Mining Tools for Novel Bioactive Substances
Authors: Schüller Andreas , Studt-Reinhold Lena , Strauss Joseph
Published: September 2022

Fungal species have the capability of producing an overwhelming diversity of bioactive substances that can have beneficial but also detrimental effects on human health. These so-called secondary metabolites naturally serve as antimicrobial “weapon systems”, signaling molecules or developmental effectors for fungi and hence are produced only under very specific environmental conditions or stages in their life cycle. However, as these complex conditions are difficult or even impossible to mimic in laboratory settings, only a small fraction of the true chemical diversity of fungi is known so far. This also implies that a large space for potentially new pharmaceuticals remains unexplored. We here present an overview on current developments in advanced methods that can be used to explore this chemical space. We focus on genetic and genomic methods, how to detect genes that harbor the blueprints for the production of these compounds (i.e., biosynthetic gene clusters, BGCs), and ways to activate these silent chromosomal regions. We provide an in-depth view of the chromatin-level regulation of BGCs and of the potential to use the CRISPR/Cas technology as an activation tool.
Exposure–Response Analysis of Osimertinib in Patients with Advanced Non-Small-Cell Lung Cancer
Authors: Rodier Thomas , Puszkiel Alicja , Cardoso Evelina , Balakirouchenane David , Narjoz Céline , Arrondeau Jennifer , Fallet Vincent , Khoudour Nihel , Guidi Monia , Vidal Michel , Declèves Xavier , Csajka Chantal , Alexandre Jérôme , Cadranel Jacques , Fabre Elizabeth , Wislez Marie , Goldwasser François , Blanchet Benoit
Published: September 2022

High interindividual variability (IIV) of the clinical response to epidermal growth factor receptor (EGFR) inhibitors such as osimertinib in non-small-cell lung cancer (NSCLC) might be related to the IIV in plasma exposure. The aim of this study was to evaluate the exposure–response relationship for toxicity and efficacy of osimertinib in unselected patients with advanced EGFR-mutant NSCLC. This retrospective analysis included 87 patients treated with osimertinib. Exposure–toxicity analysis was performed in the entire cohort and survival analysis only in second-line patients (n = 45). No significant relationship between occurrence of dose-limiting toxicity and plasma exposure was observed in the entire cohort (p = 0.23, n = 86). The median overall survival (OS) was approximately two-fold shorter in the 4th quartile (Q4) of osimertinib trough plasma concentration (>235 ng/mL) than in the Q1–Q3 group (12.2 months [CI95% = 8.0–not reached (NR)] vs. 22.7 months [CI95% = 17.1–34.1]), but the difference was not statistically significant (p = 0.15). To refine this result, the exposure–survival relationship was explored in a cohort of 41 NSCLC patients treated with erlotinib. The Q4 erlotinib exposure group (>1728 ng/mL) exhibited a six-fold shorter median OS than the Q1–Q3 group (4.8 months [CI95% = 3.3-NR] vs. 22.8 months (CI95% = 10.6–37.4), p = 0.00011). These results suggest that high exposure to EGFR inhibitors might be related to worse survival in NSCLC patients.
A Novel C@Fe@Cu Nanocomposite Loaded with Doxorubicin Tailored for the Treatment of Hepatocellular Carcinoma
Authors: Saddik Mohammed S. , Elsayed Mahmoud M. A. , Abdel-Rheem Amany A. , El-Mokhtar Mohamed A. , Mosa Eisa S. , Al-Hakkani Mostafa F. , Al-Shelkamy Samah A. , Khames Ali , Daha Mohamed A. , Abdel-Aleem Jelan A.
Published: September 2022

High mortality and morbidity rates are related to hepatocellular carcinoma (HCC), which is the most prevalent type of liver cancer. A new vision for cancer treatment and cancer cell targeting has emerged with the application of nanotechnology, which reduces the systemic toxicity and adverse effects of chemotherapy medications while increasing their effectiveness. It was the goal of the proposed work to create and investigate an anticancer C@Fe@Cu nanocomposite (NC) loaded with Doxorubicin (DOX) for the treatment of HCC. Scanning and transmission electron microscopes (SEM and TEM) were used to examine the morphology of the produced NC. The formulation variables (DOX content, C@Fe@Cu NC weight, and stirring speed) were analyzed and optimized using Box-Behnken Design (BBD) and Response Surface Methodology (RSM). Additionally, X-ray diffraction patterns (XRD) and Fourier Transform Infrared (FTIR) were investigated. Doxorubicin and DOX- loaded C@Fe@Cu NC (DOX-C@Fe@Cu NC) were also assessed against HEPG2 cells for anticancer efficacy (Hepatic cancer cell line). The results revealed the formation of C@Fe@Cu NC with a mean size of 7.8 nm. A D-R model with a mean size of 24.1 nm best fits the adsorption behavior of DOX onto the C@Fe@Cu NC surface. DOX-C@Fe@Cu NC has also been demonstrated to have a considerably lower IC50 and higher cytotoxicity than DOX alone in an in vitro investigation. Therefore, DOX-C@Fe@Cu NC is a promising DOX delivery vehicle for the full recovery of HCC.
In Vitro Biological Activity and In Vivo Human Study of Porcine-Placenta-Extract-Loaded Nanovesicle Formulations for Skin and Hair Rejuvenation
Authors: Tansathien Kritsanaporn , Ngawhirunpat Tanasait , Rangsimawong Worranan , Patrojanasophon Prasopchai , Opanasopit Praneet , Nuntharatanapong Nopparat
Published: September 2022

Porcine placenta extract (PPE) contains many water-soluble macromolecular compounds, such as proteins and growth factors, which have limited transportation through the skin. This study aimed to assess the effect of porcine-placenta-extract (PPE)-loaded nano-transdermal systems for skin repair and hair growth promotion. The potentials of the nanoformulation for cytotoxicity, cell proliferation, intracellular reactive oxygen species (ROS) reduction, lipoxygenase inhibition, intracellular inflammatory cytokine reduction, and cell aggregation were evaluated. PPE-entrapped niosome nanovesicles were produced by thin-film hydration and probe-sonication methods, followed by incorporation in a skin serum formulation. The physicochemical properties of the formulation were examined, and the efficacy of the serum formulation was elucidated in humans. The results showed that PPE had no toxicity and was able to induce cell growth and cell aggregation. In addition, PPE significantly decreased intracellular ROS, inhibited lipoxygenase activity, and reduced the production of intracellular tumor necrosis factor-α. In the in vivo human study, the PPE nanovesicles-loaded serum could improve skin properties by increasing skin hydration. Moreover, it was capable of promoting hair growth by increasing hair elongation and melanin index after application for one month. Consequently, the PPE nanovesicles-loaded serum was effective for skin anti-aging and hair rejuvenation.
Extracellular Vesicles: A New Frontier for Cardiac Repair
Authors: You Benshuai , Yang Yang , Zhou Zixuan , Yan Yongmin , Zhang Leilei , Jin Jianhua , Qian Hui
Published: September 2022

The ability of extracellular vesicles (EVs) to regulate a broad range of cellular processes has recently been used to treat diseases. Growing evidence indicates that EVs play a cardioprotective role in heart disease by activating beneficial signaling pathways. Multiple functional components of EVs and intracellular molecular mechanisms are involved in the process. To overcome the shortcomings of native EVs such as their heterogeneity and limited tropism, a series of engineering approaches has been developed to improve the therapeutic efficiency of EVs. In this review, we present an overview of the research and future directions for EVs-based cardiac therapies with an emphasis on EVs-mediated delivery of therapeutic agents. The advantages and limitations of various modification strategies are discussed, and possible opportunities for improvement are proposed. An in-depth understanding of the endogenous properties of EVs and EVs engineering strategies could lead to a promising cell-free therapy for cardiac repair.
Chlorophyll Fluorescence Imaging (CFI) and Laser-Induced Breakdown Spectroscopy (LIBS) Applied to Investigate Tomato Plants Infected by the Root Knot Nematode (RKN) Meloidogyne incognita and Tobacco Plants Infected by Cymbidium Ringspot Virus
Authors: Senesi Giorgio Saverio , De Pascale Olga , Marangoni Bruno Spolon , Caires Anderson Rodrigues Lima , Nicolodelli Gustavo , Pantaleo Vitantonio , Leonetti Paola
Published: September 2022

Recently, studies on climate change have highlighted the central role of photosynthetic mechanisms in the defense response of plants to abiotic and biotic stresses. Photo-sensing and photo-activation are innovative technologies applied for the early detection of plant pathogens in order to prevent the dramatic impact they may have on plants. Chlorophyll Fluorescence Imaging (CFI) and Laser-Induced Breakdown Spectroscopy (LIBS) analytical techniques can be used to evaluate the amount of chlorophyll in plants, which can be altered in the case of biotic and abiotic stresses. In this work, both techniques were applied to two pathogenic model systems, i.e., roots of susceptible tomato plants infected by Meloidogyne incognita and Nicotiana benthamiana plants infected by cymbidium ringspot virus. Experimental evidence is provided and discussed showing that specific application protocols of both methods can be used successfully for the early detection of symptoms of the pathogen attacks of Meloidogyne incognita on tomato roots and of cymbidium ringspot virus infected plants. In particular, a decrease in chlorophyll content was measured by fluorescence imaging, and an increase in Mg++ content was determined by LIBS in both the leaves and stems of infected tomato plants and the leaves of infected plants, with respect to control (non-infected) plants. Thus, the two techniques used have been shown to be able to discriminate satisfactorily between control and infected plants and to provide some insight on the underlying mechanisms of plant defenses again nematodes and viruses.
Tribological Evaluation of Silica Nanoparticle Enhanced Bilayer Hydrogels as A Candidate for Cartilage Replacement
Authors: Mostakhdemin Mohammad , Nand Ashveen , Ramezani Maziar
Published: September 2022

Polymeric hydrogels can be used as artificial replacement for lesioned cartilage. However, modulating the hydrogel formulation that mimics articular cartilage tissue with respect to mechanical and tribological properties has remained a challenge. This study encompasses the tribological evaluation of a silica nanoparticle (SNP) loaded bilayer nanocomposite hydrogel (NCH), synthesized using acrylamide, acrylic acid, and alginate via modulated free-radical polymerization. Multi-factor pin-on-plate sliding wear experiments were carried out with a steel ball counterface using a linear reciprocating tribometer. Tribological properties of NCHs with 0.6 wt% SNPs showed a significant improvement in the wear resistance of the lubricious layer and a low coefficient of friction (CoF). CoF of both non-reinforced hydrogel (NRH) and NCH at maximum contact pressure ranged from 0.006 to 0.008, which is in the order of the CoF of healthy articular cartilage. Interfacial surface energy was analysed according to Johnson, Kendall, and Robert’s theory, and NCHs showed superior mechanical properties and surface energy compared to NRHs. Lubrication regimes’ models were drawn based on the Stribeck chart parameters, and CoF results were highlighted in the elastoviscous transition regime.
Anti-Colitic Effect of an Exopolysaccharide Fraction from Pediococcus pentosaceus KFT-18 on Dextran Sulfate Sodium-Induced Colitis through Suppression of Inflammatory Mediators
Authors: Lee Jeong-Hun , Chung Kyung-Sook , Shin Ji-Sun , Jung Seang-Hwan , Lee Sangmin , Lee Myung-Ki , Hong Hee-Do , Rhee Young Kyoung , Lee Kyung-Tae
Published: September 2022

We previously reported the immunostimulatory effect of an exopolysaccharide fraction from Pediococcus pentosaceus KFT18 (PE-EPS), a lactic acid bacterium, in macrophages and primary splenocytes, as well as in cyclophosphamide-induced immunosuppressed mice. In this study, the anti-colitic activity of PE-EPS was investigated in a dextran sulfate sodium (DSS)-induced colitis animal model. PE-EPS relieved DSS-induced colitis symptoms, such as stool blood, decreased colon length, crypt disruption, and mucus layer edema. Regarding the molecular mechanism, PE-EPS reduced the enhanced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1) in the colon tissue of colitis-induced mice. Additionally, PE-EPS protected against DSS-induced phosphorylation of p65 and signal transducer and activator of transcription 1 (STAT1). These findings suggested that the exopolysaccharide fraction from Ped. pentosaceus KFT18 can be used to treat inflammatory bowel disease by alleviating colonic inflammation.
Natural Degradation: Polymer Degradation under Different Conditions
Authors: Vetcher Alexandre A. , Iordanskii Alexey L.
Published: September 2022

Natural degradation (ND) is currently one of the main directions of polymer research [...]
Construction of Bio-Based Polyurethanes via Olefin Metathesis and Their Thermal Reversible Behavior
Authors: Liu Zizhao , Gu Gaosheng , Chen Junwu , Duan Zhongyu , Liu Binyuan
Published: September 2022

With the increase in awareness of environmental protection and the shortage of oil resources, bio-based polyurethane has attracted increasing attention due to its ecological friendliness, low cost and easy degradation. In this paper, using Eugenol (Eug) derived from plant essential oils as the raw resource, syringyl ethanol (Syol) was prepared, and three monomers were obtained by the reaction of the Eug or Syol with Hexamethylene diisocyanate (HDI)or 4,4′-methylene di (phenyl isocyanate) (MDI), respectively. Then, three novel bio-based polyurethanes, P(Eug-HDI), P(Syol-HDI) and P(Syol-MDI), were synthesized by olefin metathesis polymerization. The effects of the catalyst type, reaction solvent, reaction temperature, reaction time, molar ratio of catalyst dosage and metal salts on the Eug-HDI olefin metathesis polymerization were investigated in detail. Under the optimal conditions, the yield reached 64.7%. It is worth noting that the addition of metal Ni salts could significantly promote the polymerization, in which NiI2 could increase the yield to 86.6%. Furthermore, the thermal decomposition behaviors of these bio-based polyurethanes were explored by DSC and variable temperature infrared spectroscopy. The test results showed that P(Eug-HDI) had a reversible thermal decomposition and a certain self-healing performance. This paper provided a new method for the preparation of bio-based polyurethane.
Development of Bio-Based Materials: Synthesis, Characterization and Applications
Authors: Delgado-Sánchez Clara , Tenorio-Alfonso Adrián , Cortés-Triviño Esperanza , Borrero-López Antonio M. , Valencia Concepción
Published: September 2022

The need to find suitable biomaterials and procedures from alternative products able to imitate or even enhance the performance of currently used products has become an important focus of research today due to the depletion of non-renewable resources and the increasing concern related to climate change, sustainability and environmental preservation [...]
Antibacterial Activity of Silver Nanoflake (SNF)-Blended Polysulfone Ultrafiltration Membrane
Authors: Prihandana Gunawan Setia , Sriani Tutik , Muthi’ah Aisyah Dewi , Musa Siti Nurmaya , Jamaludin Mohd Fadzil , Mahardika Muslim
Published: September 2022

The aim of this research was to study the possibility of using silver nanoflakes (SNFs) as an antibacterial agent in polysulfone (PSF) membranes. SNFs at different concentrations (0.1, 0.2, 0.3 and 0.4 wt.%) were added to a PSF membrane dope solution. To investigate the effect of SNFs on membrane performance and properties, the water contact angle, protein separation, average pore size and molecular weight cutoffs were measured, and water flux and antibacterial tests were conducted. The antimicrobial activities of the SNFs were investigated using Escherichia coli taken from river water. The results showed that PSF membranes blended with 0.1 wt.% SNFs have contact angles of 55°, which is less than that of the pristine PSF membrane (81°), exhibiting the highest pure water flux. Molecular weight cutoff values of the blended membranes indicated that the presence of SNFs does not lead to enlargement of the membrane pore size. The rejection of protein (egg albumin) was improved with the addition of 0.1 wt.% SNFs. The SNFs showed antimicrobial activity against Escherichia coli, where the killing rate was dependent on the SNF concentration in the membranes. The identified bacterial colonies that appeared on the membranes decreased with increasing SNF concentration. PSF membranes blended with SNF, to a great degree, possess quality performance across several indicators, showing great potential to be employed as water filtration membranes.
Effect of PEG Molecular Weight on the Polyurethane-Based Quasi-Solid-State Electrolyte for Dye-Sensitized Solar Cells
Authors: Sing Liow Kai , Sipaut Coswald Stephen , Fran Mansa Rachel , Ching Ung Mee , Ebrahimi Shamsi
Published: September 2022

Nanosilica was surface modified with polyaniline and incorporated into polyurethane to form a polymer matrix capable of entrapping a liquid electrolyte and functioning as quasi-solid-state electrolyte in the dye-sensitized solar cells. The effect on the S−PANi distribution, surface morphology, thermal stability, gel content, and structural change after varying the PEG molecular weight of the polyurethane matrix was analyzed. Quasi-solid-state electrolytes were prepared by immersing the polyurethane matrix into a liquid electrolyte and the polymer matrix absorbency, conductivity, and ion diffusion were investigated. The formulated quasi-solid-state electrolytes were applied in dye-sensitized solar cells and their charge recombination, photovoltaic performance, and lifespan were measured. The quasi-solid-state electrolyte with a PEG molecular weight of 2000 gmol−1 (PU−PEG 2000) demonstrated the highest light-to-energy conversion efficiency, namely, 3.41%, with an open-circuit voltage of 720 mV, a short-circuit current of 4.52 mA cm−2, and a fill factor of 0.63.
Optimization of the Physical Properties of HDPE/PU Blends through Improved Compatibility and Electron Beam Crosslinking
Authors: Jeong Jin-Oh , Oh Yong-Hyeon , Jeong Sung-In , Park Jong-Seok
Published: September 2022

Polymer blending is a method in which polymers with different properties are mixed so that each advantage appears in one polymer blend. Improved thermal and mechanical properties of blends can be prepared by blending with high-density polyethylene (HDPE) of a non-polar polymer and polyurethane (PU) of a polar polymer. However, a compatibilizer is required because it has the disadvantage that blending has low miscibility due to the different phases. In this study, HDPE/PU blends with new and excellent physical properties were developed through optimal composition with improved compatibility between the HDPE and PU. In addition, the effects of improving the physical properties through electron-beam crosslinking were confirmed. In general, a crosslinking structure of HDPE is formed by electron beam irradiation to increase its thermal stability and strength, but its elongation is rapidly decreased. In particular, the elongation of HDPE irradiated at 100 kGy was about 110%, which was decreased about five times compared to unirradiated HDPE (510%). However, the HDPE/PU blend with improved compatibility (PU 30) showed an elongation of about 450% while maintaining excellent strength (22.5 MPa), which was increased by about four times compared to the HDPE irradiated at 100 kGy. In particular, the thermal stability of PU 30 irradiated at 100 kGy at a high temperature (180 °C) was improved more than six times compared to the HDPE. Therefore, it is possible to develop HDPE/PU blends with new and excellent physical properties by improving compatibility and using electron beam crosslinking technology.
Evaluation of Natural and Modified Castor Oil Incorporation on the Melt Processing and Physico-Chemical Properties of Polylactic Acid
Authors: Darie-Niță Raluca , Irimia Anamaria , Grigoraș Vasile , Mustață Fănică , Tudorachi Niță , Râpă Maria , Ludwiczak Joanna , Iwanczuk Andrzej
Published: September 2022

Bio-based plasticizers derived from renewable resources represent a sustainable replacement for petrochemical-based plasticizers. Vegetable oils are widely available, non-toxic and biodegradable, resistant to evaporation, mostly colorless and stable to light and heat, and are a suitable alternative for phthalate plasticizers. Plasticized poly(lactic acid) (PLA) materials containing 5 wt%, 10 wt%, 15 wt% and 20 wt% natural castor oil (R) were prepared by melt blending to improve the ductility of PLA. Three castor oil adducts with maleic anhydride (MA), methyl nadic anhydride (methyl-5-norbornene-2,3-dicarboxylic anhydride) (NA) and hexahydro-4-methylphthalic anhydride (HA), previously synthesized, were incorporated in a concentration of 15 wt% each in PLA and compared with PLA plasticized with natural R. The physico-chemical properties of PLA/R blends were investigated by means of processability, chemical structure, surface wettability, mechanical, rheological and thermal characteristics. The addition of natural and modified R significantly improved the melt processing by decreasing the melt viscosity by ~95%, increased the surface hydrophobicity, enhanced the flexibility by ~14 times in the case of PLA/20R blend and ~11 times in the case of PLA/15R-MA blend as compared with neat PLA. The TG/DTG results showed that the natural R used up to 20 wt% could significantly improve the thermal stability of PLA, similar to the maleic anhydride-modified R. Based on the obtained results, up to 20 wt% natural R and 15 wt% MA-, HA- or NA-modified R might be used as environmentally friendly plasticizers that can improve the overall properties of PLA, depending on the intended food packaging applications.