bluuebunny/crossref_metadata_2025 huggingface dataset:
Regiospecific Photochemical Synthesis of Methylchrysenes
Authors: Böhme Thomas , Egeland Mari , Lorentzen Marianne , Mady Mohamed F. , Solbakk Michelle F. , Sæbø Krister S. , Jørgensen Kåre B.
Published: December 2022

Methylated polycyclic aromatic hydrocarbons (PAHs) are suspected to be some of the toxic compounds in crude oil towards marine life and are needed as single compounds for environmental studies. 1-, 3- and 6-methylchrysene (3a,b,c) were prepared as single isomers by photochemical cyclization of the corresponding stilbenoids in the Mallory reaction using stoichiometric amounts of iodine in 82-88% yield. 2-methylchrysene (3d) was prepared by photochemical cyclization where the regioselectivity was controlled by elimination of an ortho-methoxy group under acidic oxygen free conditions in 72% yield. These conditions failed to form 4-methylchrysene from the corresponding stilbenoid. All stilbenoids were made from a common naphthyl Wittig salt and suitably substituted benzaldehydes. We have also demonstrated that methylchrysenes can be oxidized to the corresponding chrysenecarboxylic acids by KMnO4 in modest yields.
Benzophenone Derivatives with Histamine H3 Receptor Affinity and Cholinesterase Inhibitory Potency as Multitarget-Directed Ligands for Possible Therapy of Alzheimer’s Disease
Authors: Godyń Justyna , Zaręba Paula , Stary Dorota , Kaleta Maria , Kuder Kamil J. , Latacz Gniewomir , Mogilski Szczepan , Reiner-Link David , Frank Annika , Doroz-Płonka Agata , Olejarz-Maciej Agnieszka , Sudoł-Tałaj Sylwia , Nolte Tobias , Handzlik Jadwiga , Stark Holger , Więckowska Anna , Malawska Barbara , Kieć-Kononowicz Katarzyna , Łażewska Dorota , Bajda Marek
Published: December 2022

The multitarget-directed ligands demonstrating affinity to histamine H3 receptor and additional cholinesterase inhibitory potency represent a promising strategy for research into the effective treatment of Alzheimer’s disease. In this study, a novel series of benzophenone derivatives was designed and synthesized. Among these derivatives, we identified compound 6 with a high affinity for H3R (Ki = 8 nM) and significant inhibitory activity toward BuChE (IC50 = 172 nM and 1.16 µM for eqBuChE and hBuChE, respectively). Further in vitro studies revealed that compound 6 (4-fluorophenyl) (4-((5-(piperidin-1-yl)pentyl)oxy)phenyl)methanone) displays moderate metabolic stability in mouse liver microsomes, good permeability with a permeability coefficient value (Pe) of 6.3 × 10−6 cm/s, and its safety was confirmed in terms of hepatotoxicity in the HepG2 cell line. Therefore, we investigated the in vivo activity of compound 6 in the Passive Avoidance Test and the Formalin Test. While compound 6 did not show a statistically significant influence on memory and learning, it showed analgesic properties in both acute (ED50 = 20.9 mg/kg) and inflammatory (ED50 = 17.5 mg/kg) pain.
Assessment of Micro- and Nanoplastic Composition (Polymers and Additives) in the Gastrointestinal Tracts of Ebro River Fishes
Authors: Garcia-Torné Maria , Abad Esteban , Almeida David , Llorca Marta , Farré Marinella
Published: December 2022

One of the main routes of fish exposure to micro- and nanoplastics (MNPLs) is their ingestion. MNPLs can act as reservoirs of organic contaminants that are adsorbed onto their surfaces, or that can leach from their complex formulations, with potential impacts on biota and along the aquatic food chain. While MNPLs have been reported in fishes worldwide, complete information on MNPL compositions, polymers and additives continues to be scarce. In this work, the presence of MNPLs in the gastrointestinal tracts (GIT) of fish from the Ebro River (Spain) was investigated using a double suspected screening approach to assess and quantify polymers and additives. The sample-preparation procedure consisted of sequential alkaline and acidic digestions with KOH and HNO3, followed by ultrasonic-assisted extraction (USAE) with toluene. The analysis of polymers was carried out with size-exclusion chromatography followed by high-resolution mass spectrometry using an atmospheric pressure photoionization source, operating in negative and positive ionisation modes (SEC-(±)-APPI-HRMS) using full-scan acquisition (FS). Plastic additives were assessed using high-performance liquid chromatography with a C18 analytical column coupled to HRMS equipped with an electrospray ionisation source operating under positive and negative conditions (LC-(±ESI)-HRMS). The acquisition was performed in parallel with full-scan (FS) and data-dependent scan (ddMS2) modes, working under positive and negative ionisation modes. The polymers most frequently detected and quantified in fish GITs were polysiloxanes, polyethylene (PE), polypropylene (PP) and polystyrene (PS). PE was detected in 84% of the samples, with a concentration range from 0.55 to 3545 µg/g. On the other hand, plasticisers such as phthalates and stabilisers such as benzotriazoles were the most frequently identified plastic additives.
Vitamin B12 in Foods, Food Supplements, and Medicines—A Review of Its Role and Properties with a Focus on Its Stability
Authors: Temova Rakuša Žane , Roškar Robert , Hickey Neal , Geremia Silvano
Published: December 2022

Vitamin B12, also known as the anti-pernicious anemia factor, is an essential micronutrient totally dependent on dietary sources that is commonly integrated with food supplements. Four vitamin B12 forms—cyanocobalamin, hydroxocobalamin, 5′-deoxyadenosylcobalamin, and methylcobalamin—are currently used for supplementation and, here, we provide an overview of their biochemical role, bioavailability, and efficacy in different dosage forms. Since the effective quantity of vitamin B12 depends on the stability of the different forms, we further provide a review of their main reactivity and stability under exposure to various environmental factors (e.g., temperature, pH, light) and the presence of some typical interacting compounds (oxidants, reductants, and other water-soluble vitamins). Further, we explore how the manufacturing process and storage affect B12 stability in foods, food supplements, and medicines and provide a summary of the data published to date on the content-related quality of vitamin B12 products on the market. We also provide an overview of the approaches toward their stabilization, including minimization of the destabilizing factors, addition of proper stabilizers, or application of some (innovative) technological processes that could be implemented and contribute to the production of high-quality vitamin B12 products.
Insights on Ferroptosis and Colorectal Cancer: Progress and Updates
Authors: Hu Bangli , Yin Yixin , Li Siqi , Guo Xianwen
Published: December 2022

Patients with advanced-stage or treatment-resistant colorectal cancer (CRC) benefit less from traditional therapies; hence, new therapeutic strategies may help improve the treatment response and prognosis of these patients. Ferroptosis is an iron-dependent type of regulated cell death characterized by the accumulation of lipid reactive oxygen species (ROS), distinct from other types of regulated cell death. CRC cells, especially those with drug-resistant properties, are characterized by high iron levels and ROS. This indicates that the induction of ferroptosis in these cells may become a new therapeutic approach for CRC, particularly for eradicating CRC resistant to traditional therapies. Recent studies have demonstrated the mechanisms and pathways that trigger or inhibit ferroptosis in CRC, and many regulatory molecules and pathways have been identified. Here, we review the current research progress on the mechanism of ferroptosis, new molecules that mediate ferroptosis, including coding and non-coding RNA; novel inducers and inhibitors of ferroptosis, which are mainly small-molecule compounds; and newly designed nanoparticles that increase the sensitivity of cells to ferroptosis. Finally, the gene signatures and clusters that have predictive value on CRC are summarized.
Effect of Ambient Plasma Treatments on Thermal Conductivity and Fracture Toughness of Boron Nitride Nanosheets/Epoxy Nanocomposites
Authors: Choi Won-Jong , Lee Seul-Yi , Park Soo-Jin
Published: December 2022

With the rapid growth in the miniaturization and integration of modern electronics, the dissipation of heat that would otherwise degrade the device efficiency and lifetime is a continuing challenge. In this respect, boron nitride nanosheets (BNNS) are of significant attraction as fillers for high thermal conductivity nanocomposites due to their high thermal stability, electrical insulation, and relatively high coefficient of thermal conductivity. Herein, the ambient plasma treatment of BNNS (PBNNS) for various treatment times is described for use as a reinforcement in epoxy nanocomposites. The PBNNS-loaded epoxy nanocomposites are successfully manufactured in order to investigate the thermal conductivity and fracture toughness. The results indicate that the PBNNS/epoxy nanocomposites subjected to 7 min plasma treatment exhibit the highest thermal conductivity and fracture toughness, with enhancements of 44 and 110%, respectively, compared to the neat nanocomposites. With these enhancements, the increases in surface free energy and wettability of the PBNNS/epoxy nanocomposites are shown to be attributable to the enhanced interfacial adhesion between the filler and matrix. It is demonstrated that the ambient plasma treatments enable the development of highly dispersed conductive networks in the PBNNS epoxy system.
Multiferroic/Polymer Flexible Structures Obtained by Atomic Layer Deposition
Authors: Ramazanov Shikhgasan , Sobola Dinara , Gajiev Gaji , Orudzhev Farid , Kaspar Pavel , Gummetov Adil
Published: December 2022

The paper considers how a film of bismuth ferrite BiFeO3 (BFO) is formed on a polymeric flexible polyimide substrate at low temperature ALD (250 °C). Two samples of BFO/Polyimide with different thicknesses (42 nm, 77 nm) were studied. As the thickness increases, a crystalline BFO phase with magnetic and electrical properties inherent to a multiferroic is observed. An increase in the film thickness promotes clustering. The competition between the magnetic and electrical subsystems creates an anomalous behavior of the magnetization at a temperature of 200 K. This property is probably related to the multiferroic/polymer interface. This paper explores the prerequisites for the low-temperature growth of BFO films on organic materials as promising structural components for flexible and quantum electronics.
Essential Minerals and Metabolic Adaptation of Immune Cells
Authors: Alghamdi Malak , Gutierrez Janelle , Komarnytsky Slavko
Published: December 2022

Modern lifestyles deviated considerably from the ancestral routines towards major shifts in diets and increased sedentarism. The trace elements status of the human body is no longer adequately supported by micronutrient-inferior farmed meats and crop commodities produced by the existing agricultural food systems. This is particular evident in the increased obesogenic adipogenesis and low-grade inflammation that fails to resolve with time. The metabolically restrictive environment of the inflamed tissues drives activation and proliferation of transient and resident populations of immune cells in favor of pro-inflammatory phenotypes, as well as a part of the enhanced autoimmune response. As different stages of the immune activation and resolution depend on the availability of specific minerals to maintain the structural integrity of skin and mucus membranes, activation and migration of immune cells, activation of the complement system, and the release of pro-inflammatory cytokines and chemokines, this review discusses recent advances in our understanding of the contribution of select minerals in optimizing the responses of innate and adaptive immune outcomes. An abbreviated view on the absorption, transport, and delivery of minerals to the body tissues as related to metabolic adaptation is considered.
Low-Dose Oral Iron Replacement Therapy Is Effective for Many Japanese Hemodialysis Patients: A Retrospective Observational Study
Authors: Ogawa Chie , Tsuchiya Ken , Kanemitsu Mineko , Maeda Kunimi
Published: December 2022

Western guidelines recommend the use of intravenous iron supplementation for hemodialysis patients. However, in Japanese patients with well-controlled inflammation, iron replacement may be achieved with oral iron supplementation. This study involved 108 courses in 77 outpatient hemodialysis patients who received low-dose oral iron replacement therapy. Data from baseline to week 28 of treatment were analyzed to identify factors associated with effectiveness. Changes over time in erythrocyte- and iron-related parameters and erythropoiesis-stimulating agent (ESA) dose were investigated in the effective group. A total of 84 courses (77.8%) satisfied the effectiveness criteria. Compared with the effective and ineffective groups, only C-reactive protein (CRP) was significantly different (p < 0.01). ROC curve analysis with efficacy as the endpoint showed a CRP cut point value of ≤0.1 mg/dL (area under the curve, 0.69; 95% confidence interval, 0.57–0.81). The relationship between serum ferritin and hemoglobin fluctuation by reducing the ESA dose showed a positive correlation (p < 0.001). In the ESA maintenance group, the serum ferritin gradually increased and then remained constant at about 60 ng/mL. Our data suggest that patients with CRP ≤ 0.1 mg/dL may benefit from low doses of oral iron supplementation. Approximately 60 ng/mL serum ferritin may be sufficient during stable hematopoiesis.
Euonymus alatus Twig Extract Protects against Scopolamine-Induced Changes in Brain and Brain-Derived Cells via Cholinergic and BDNF Pathways
Authors: Gurung Pallavi , Shrestha Rajeev , Lim Junmo , Thapa Magar Til Bahadur , Kim Han-Hyuk , Kim Yong-Wan
Published: December 2022

In the current study, the therapeutic and preventive effects of Euonymus alatus (EA) twig extract were investigated in a mouse model of cognitive deficit and B35 cells. Twig extract 1 was extracted with 70% ethanol and later twig extract 2 was extracted through liquid-liquid extraction with 70% ethanol and hexane. EA twig 2 (300 mg/kg) along with the standard drug donepezil (5 mg/kg) were orally administered to the mice for 34 days. Scopolamine was given intraperitoneally for 7 days. Administration of EA twig extract 2 significantly improved the passive avoidance test (PAT) in mice. EA twigs extract also restored the scopolamine-reduced brain-derived neurotrophic factor (BDNF)/extracellular regulated kinase (ERK)/cyclic AMP responsive element binding protein (CREB) signaling in B35 cells and the mouse hippocampus. In addition, EA twig extract significantly inhibited the acetylcholine esterase (AChE) activity in B35 cells in a dose-dependent manner. Chromatography and ESI MS analysis of EA twig extract revealed the presence of flavonoids; epicatechin, taxifolin, aromadendrin, and naringenin with catechin being the most abundant. These flavonoids exerted protective effects alone and had the possibility of synergistic effects in combination. Our work unmasks the ameliorating effect of EA twig extract 2 on scopolamine-associated cognitive impairments through the restoration of cholinergic systems and the BDNF/ERK/CREB pathway.
Body Composition of Young Women and the Consumption of Selected Nutrients
Authors: Karpińska Elżbieta , Moskwa Justyna , Puścion-Jakubik Anna , Naliwajko Sylwia , Soroczyńska Jolanta , Markiewicz-Żukowska Renata , Socha Katarzyna
Published: December 2022

The choices of food products and their nutritional value have a significant impact on nutritional status and body composition parameters. Popular and low-cost indicators of nutritional status, such as BMI, may not reflect the actual condition of the body. The aim of the study was to assess the consumption of energy as well as selected nutrients, such as protein, fats, carbohydrates, unsaturated fatty acids, lactose, starch, and dietary fiber, and to evaluate body mass index (BMI) and the parameters of the body composition among young women. Next, correlations were made between these nutrients and the parameters, such as percent body fat (PBF), visceral fat area (VFA), and fitness score (FS). The study group included 478 young women. To assess their consumption, the participants completed 72 h dietary interviews. In addition, the participants had a body composition analysis performed by bioelectric impedance technology by the InBody 720 Body Composition Analyzer (InBody, South Korea). The average energy value of the diets was about 1480 kcal. Most diets contained adequate portions of protein, fat, and carbohydrates. The diets were deficient in terms of unsaturated fatty acids and fiber. We showed that up to 37% of women with normal BMI had excess body fat. Moreover, the % energy from plant protein consumption negatively correlated with PBF and BMI (r = −0.10, p = 0.029, r = −0.10, p = 0.037, respectively) and dietary fiber with PBF, BMI, VFA, and FS (r = −0.17, p = 0.0003, r = −0.12, p = 0.01, r = −0.18, p = 0.0001, r = 0.09, p = 0.041, respectively). Education on the proper consumption of basic nutrients, including plant-based protein and dietary fiber, seems to be essential in preventing overweight and obesity.
Rat Mucosal Immunity following an Intensive Chronic Training and an Exhausting Exercise: Effect of Hesperidin Supplementation
Authors: Ruiz-Iglesias Patricia , Estruel-Amades Sheila , Massot-Cladera Malén , Franch Àngels , Pérez-Cano Francisco J. , Castell Margarida
Published: December 2022

Stressful situations such as a high-intensity exercise or exhausting training programs can act as immune disruptors leading to transitory immunodepression status, which can be accompanied by alterations of the gastrointestinal functions. Hesperidin intake has demonstrated ergogenic activity and is able to influence the intestinal ecosystem and immunity. We aimed to investigate the effect of hesperidin consumption in rats submitted to an intense training and a final exhaustion test, focusing on the functionality of the intestinal immune system and on the cecal microbiota. Rats, supplemented or not with hesperidin, were intensively trained on a treadmill for 5 weeks. Samples were obtained 24 h after a regular training session, and immediately and 24 h after a final exhaustion test. Cecal microbiota and composition and function of mesenteric lymph node (MLN) lymphocytes and mucosal immunoglobulin A (IgA) were determined. Results showed that chronic intense exercise followed by an exhausting test induced changes in the intestinal immune compartment such as the distribution and function of MLN lymphocytes. Although the hesperidin supplementation did not prevent these alterations, it was able to enhance IgA synthesis in the intestinal compartment. This could be important in enhancing the immune intestinal barrier in this stressful situation.
Potential Association of Osteoporosis and Not Osteoporotic Fractures in Patients with Gout: A Longitudinal Follow-Up Study
Authors: Kwon Mi Jung , Park Jae Yong , Kim Sung Gyun , Kim Jwa-Kyung , Lim Hyun , Kim Joo-Hee , Kim Ji Hee , Cho Seong-Jin , Nam Eun Sook , Park Ha Young , Kim Nan Young , Kang Ho Suk
Published: December 2022

Health issues associated with gout and increased occurrence of osteoporosis or fractures have been raised; however, the results are elusive. Herein, we explored the possible link between gout and incident osteoporosis/osteoporotic fractures based on long-term follow-up nationwide data. This study enrolled 16,305 patients with gout and 65,220 controls who were matched by propensity score at a 1:4 ratio on the basis of sex, age, income, and residence from the Korean National Health Insurance Service-Health Screening Cohort database (2002–2015). A Cox proportional hazard model was employed to identify the relevance between gout and incident osteoporosis/fractures, following adjustment for various covariates. In the follow-up period, osteoporosis developed in 761 individuals with gout and 2805 controls (incidence rates: 8.0 and 7.3/1000 person-years, respectively), and each osteoporotic fracture in the distal radius (2.8 vs. 2.7/1000 person-years), hip (1.3 vs. 1.3/1000 person-years), and spine (4.5 vs. 4.5/1000 person-years) occurred in gout and control groups, respectively. After adjustment, the gout group presented an 11% higher development of osteoporosis (95% confidence interval = 1.02–1.20) than the controls (p = 0.011). Subgroup analyses maintained the augment of incident osteoporosis in sufferers with gout, particularly in either men or <60 years. However, no such relevance was identified between gout and incident osteoporotic fractures at any site. In conclusion, gout may result in a slightly elevated likelihood of developing osteoporosis, and not osteoporotic fractures, in the Korean population.
Oregano (Origanum vulgare) Consumption Reduces Oxidative Stress and Markers of Muscle Damage after Combat Readiness Tests in Soldiers
Authors: Shirvani Hossein , Bazgir Behzad , Shamsoddini Alireza , Saeidi Ayoub , Tayebi Seyed Morteza , Escobar Kurt A. , Laher Ismail , VanDusseldorp Trisha A. , Weiss Katja , Knechtle Beat , Zouhal Hassane
Published: December 2022

Military activities often involve high-intensity exercise that can disrupt antioxidant capacity. We investigated the effects of oregano supplementation on muscle damage, oxidative stress, and plasma antioxidant markers of soldiers performing the army combat readiness test (ACRT). Twenty-four healthy male soldiers (age: 24 ± 3 years, height: 167 ± 14 cm, mass: 66 ± 3 kg) were randomized into a placebo group (n = 12) or an oregano supplementation group (n = 12). The participants consumed a capsule containing 500 mg Origanum vulgare immediately after completing the ACRT. Blood sampling was taken before exercise, immediately after exercise, and 60 and 120 min after oregano consumption. Plasma levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (TAC), and glutathione peroxidase (GPX) were measured at the four time points. The time × group interactions were found for CK (p < 0.0001, d = 3.64), LDH (p < 0.0001, d = 1.64), MDA (p < 0.0001, d = 9.94), SOD (p < 0.0001, d = 1.88), TAC (p < 0.0001, d = 5.68) and GPX (p < 0.0001, d = 2.38). In all variables, the difference between placebo and oregano groups were significant at 60 (p < 0.0001) and 120 (p < 0.0001) minutes after ACRT test. The main effect of time was also significant for all the variables (p < 0.0001). Our results suggest that oregano supplementation has the potential to reduce muscle damage and increase oxidative capacity following ACRT. Supplementation with oregano may serve as a dietary strategy to increase preparedness and promote recovery in military recruits.
Impact of Calorie-Restricted Cafeteria Diet and Treadmill Exercise on Sweet Taste in Diet-Induced Obese Female and Male Rats
Authors: Alvarez-Monell Adam , Subias-Gusils Alex , Mariné-Casadó Roger , Boqué Noemi , Caimari Antoni , Solanas Montserrat , Escorihuela Rosa M.
Published: December 2022

The goal of the present study was to evaluate the sweet taste function in obese rats fed with a 30% calorie-restricted cafeteria diet (CAFR) and/or subjected to moderate treadmill exercise (12–17 m/min, 35 min, 5 days per week) for 9 weeks. A two-bottle preference test, a taste reactivity test, and a brief-access licking test were carried out when animals were aged 21 weeks; biometric and metabolic parameters were also measured along the interventions. Two separate experiments for females and males were performed. Behaviorally, CAF diet decreased sucrose intake and preference, as well as perceived palatability, in both sexes and decreased hedonic responses in males. Compared to the CAF diet, CAFR exerted a corrective effect on sweet taste variables in females by increasing sucrose intake in the preference test and licking responses, while exercise decreased sucrose intake in both sexes and licking responses in females. As expected, CAF diet increased body weight and Lee index and worsened the metabolic profile in both sexes, whereas CAFR diet ameliorated these effects mainly in females. Exercise had no noticeable effects on these parameters. We conclude that CAF diet might diminish appetitive behavior toward sucrose in both sexes, and that this effect could be partially reverted by CAFR diet in females only, while exercise might exert protective effects against overconsumption of sucrose in both sexes.
Effects of Flavonoid-Rich Orange Juice Intervention on Major Depressive Disorder in Young Adults: A Randomized Controlled Trial
Authors: Choi Jihee , Kim Jong-Hoon , Park Miey , Lee Hae-Jeung
Published: December 2022

Many individuals are suffering from depression, and various improvements are being proposed. This study was conducted on young people diagnosed with depression and aimed to assess the effects of flavonoid-rich orange juice on the major depressive disorder (MDD) using a randomized controlled trial. In all, 40 young men and women with MDD aged 18–29 years were randomly assigned to a flavonoid-rich orange juice group (FR group) and a flavonoid-low orange cordial group (FL group). The subjects drank the corresponding juice three times a day (190 mL per bottle) for 8 weeks. The blood BDNF, zonulin, and claudin-5 levels significantly increased (p < 0.0001, p < 0.01, and p < 0.05, respectively) in the FR group, and the fatty acid binding protein 2 (FABP2) level was significantly decreased (p < 0.0001) in the FR group after the juice intervention. The FABP2, LPS, and valeric acid levels were negatively correlated with the abundance of Butyricicoccus pullicaecorum, which was higher in the FR group. Orange juice intake improved depressive symptoms in young adults with MDD in the FR group. This B. pullicaecorum can be a potential biomarker for clinical improvement in young adults with MDD patients.
Identifying Cross-Utilization of RSV Vaccine Inventions across the Human and Veterinary Field
Authors: Janse Marga , Soekhradj Swasti , de Jong Rineke , van de Burgwal Linda
Published: December 2022

The respiratory syncytial virus (RSV) has two main variants with similar impact, a human and a bovine variant. The human respiratory syncytial virus (HRSV) is the most frequent cause of acute respiratory disease (pneumonia) in children, leading to hospitalization and causing premature death. In Europe, lower respiratory tract infections caused by HRSV are responsible for 42–45 percent of hospital admissions in children under two. Likewise, the bovine respiratory syncytial virus (BRSV) is a significant cause of acute viral broncho-pneumonia in calves. To date no licensed HRSV vaccine has been developed, despite the high burden of the disease. In contrast, BRSV vaccines have been on the market since the 1970s, but there is still an articulated unmet need for improved BRSV vaccines with greater efficacy. HRSV/BRSV vaccine development was chosen as a case to assess whether collaboration and knowledge-sharing between human and veterinary fields is taking place, benefiting the development of new vaccines in both fields. The genetic relatedness, comparable pathogeneses, and similar severity of the diseases suggests much can be gained by sharing knowledge and experiences between the human and veterinary fields. We analyzed patent data, as most of pharmaceutical inventions, such as the development of vaccines, are protected by patents. Our results show only little cross-utilization of inventions and no collaborations, as in shared IP as an exchange of knowledge. This suggests that, despite the similarities in the genetics and antigenicity of HRSV and BRSV, each fields follows its own process in developing new vaccines.
Exploring the Neuroprotective Mechanism of Curcumin Inhibition of Intestinal Inflammation against Parkinson’s Disease Based on the Gut-Brain Axis
Authors: Zhong Lifan , Cai Benchi , Wang Qitong , Li Xi , Xu Wendi , Chen Tao
Published: December 2022

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease commonly seen in aged people, in which gastrointestinal dysfunction is the most common nonmotor symptom and the activation of the gut–brain axis by intestinal inflammation may contribute to the pathogenesis of PD. In a previous study, curcumin was considered neuroprotective in PD, and this neuroprotective mechanism may act by inhibiting intestinal inflammation. Therefore, the aim of this study was to evaluate the effect of curcumin on motor dysfunction and the loss of dopaminergic neurons in a PD mouse model, induced by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using open field test and pole test behavioral assessments and the immunofluorescence and Western blot methods. Moreover, the effects of curcumin on gastrointestinal dysfunction, gastric barrier function, pro-inflammatory cytokines, and the SIRT1/NRF2 pathway in intestinal tissues in a PD mouse model were assessed using fecal parameters and intestinal dynamics, immunofluorescence, ELISA, and Western blot. A motor impairment study of an MPTP-induced mouse group prior to treatment with curcumin had a lower total movement distance and a slow average speed, while there was no statistical difference in the curcumin group. After treatment with curcumin, the total movement distance and average speed improved, the tyrosine hydroxylase (TH) rate in the substantia nigra pars compacta (SNpc) and striatum were reduced, the pyroptosis of AIM2 and caspase-1 activations were inhibited, and intestinal inflammatory factors and intestinal inflammation were reduced. Curcumin improved gastrointestinal disorders and gastrointestinal barrier function in the MPTP-induced mice and reversed MPTP-induced motor dysfunction and dopaminergic neuron loss in mice. The above effects may be partly dependent on curcumin activation of the SIRT1/NRF2 pathway in the colon. This study provides a potential opportunity to develop new preventive measures and novel therapeutic approaches that could target the gut–brain axis in the context of PD and provide a new intervention in the treatment of Parkinson’s disease.
A Review of Synthetic Access to Therapeutic Compounds Extracted from Psilocybe
Authors: Serreau Raphaël , Amirouche Ammar , Benyamina Amine , Berteina-Raboin Sabine
Published: December 2022

Psychedelics are used for various pathologies of the central nervous system and are currently the subject of much research, some of which relates to the compounds contained in various Psilocybe-type hallucinogenic mushrooms. It is difficult, however, to obtain and purify sufficient quantities of these compounds from fungi to carry out biological studies, hence the need to develop simple and efficient synthetic routes. We review here the various syntheses used to obtain these molecules, focusing first on the classic historical syntheses, then the use of more recent metallo-catalyzed couplings and finally the known biocatalytic methods for obtaining these molecules. Other access routes are certainly possible and should be the subject of future research given the therapeutic interest of these compounds.
Adjuvant Anti-PD-1 Immunotherapy versus Conventional Therapy for Stage III Melanoma: A Real-World Retrospective Cohort Study
Authors: Li Tong , Xu Yu , Sun Wei , Yan Wangjun , Wang Chunmeng , Hu Tu , Zhang Xiaowei , Luo Zhiguo , Liu Xin , Chen Yong
Published: December 2022

The use of adjuvant therapy has provided survival benefits in patients with advanced melanoma. This study aimed to explore the recurrence and prognosis of the PD-1 inhibitor, conventional interferon (IFN), or observation (OBS) on resected stage III acral and cutaneous melanoma patients through a retrospective analysis. Patients with resected stage III melanoma at Fudan University Shanghai Cancer Center from 2017 to 2021 were enrolled with all of their clinicopathologic characteristics collected. They were divided into three groups: PD-1 inhibitor, IFN, and OBS. Survival analyses were performed to indicate the significance of different adjuvant therapies. A total of 199 patients were enrolled (PD-1 n = 126; IFN n = 31; and OBS n = 42), with their median follow-up times being 21 months, 24 months, and 49 months, respectively. The PD-1 inhibitor significantly improved relapse-free survival (p = 0.027) and overall survival (p = 0.033) compared with conventional treatment (IFN+OBS). The superiority of the PD-1 inhibitor was witnessed in stage IIIC/D (p = 0.000) acral (p = 0.05) melanoma patients with ulceration (p = 0.011) or lymph node macrometastasis (p = 0.010). The PD-1 inhibitor significantly reduced local recurrence and systemic metastasis compared with conventional therapy (p = 0.002). In conclusion, adjuvant anti-PD-1 immunotherapy can achieve better survival outcomes in acral and cutaneous melanoma patients compared with conventional treatment, without considering adverse events. More clinical benefits were seen in later-stage acral melanoma patients with ulceration or lymph node macrometastasis.
Drug Repurposing at the Interface of Melanoma Immunotherapy and Autoimmune Disease
Authors: Spitschak Alf , Gupta Shailendra , Singh Krishna P. , Logotheti Stella , Pützer Brigitte M.
Published: December 2022

Cancer cells have a remarkable ability to evade recognition and destruction by the immune system. At the same time, cancer has been associated with chronic inflammation, while certain autoimmune diseases predispose to the development of neoplasia. Although cancer immunotherapy has revolutionized antitumor treatment, immune-related toxicities and adverse events detract from the clinical utility of even the most advanced drugs, especially in patients with both, metastatic cancer and pre-existing autoimmune diseases. Here, the combination of multi-omics, data-driven computational approaches with the application of network concepts enables in-depth analyses of the dynamic links between cancer, autoimmune diseases, and drugs. In this review, we focus on molecular and epigenetic metastasis-related processes within cancer cells and the immune microenvironment. With melanoma as a model, we uncover vulnerabilities for drug development to control cancer progression and immune responses. Thereby, drug repurposing allows taking advantage of existing safety profiles and established pharmacokinetic properties of approved agents. These procedures promise faster access and optimal management for cancer treatment. Together, these approaches provide new disease-based and data-driven opportunities for the prediction and application of targeted and clinically used drugs at the interface of immune-mediated diseases and cancer towards next-generation immunotherapies.
Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition Temperature
Authors: Aikawa Shohei , Tanaka Hironori , Ueda Hiroshi , Maruyama Masato , Higaki Kazutaka
Published: December 2022

Brick dust molecules are usually poorly soluble in water and lipoidal components, making it difficult to formulate them in dosage forms that provide efficient pharmacological effects. A co-amorphous system is an effective strategy to resolve these issues. However, their glass transition temperatures (Tg) are relatively lower than those of polymeric amorphous solid dispersions, suggesting the instability of the co-amorphous system. This study aimed to formulate a stable co-amorphous system for brick dust molecules by utilizing sodium taurocholate (NaTC) with a higher Tg. A novel neuropeptide Y5 receptor antagonist (AntiY5R) and NaTC with Tg of 155 °C were used as the brick dust model and coformer, respectively. Ball milling formed a co-amorphous system for AntiY5R and NaTC (AntiY5R-NaTC) at various molar ratios. Deviation from the theoretical Tg value and peak shifts in Fourier-transform infrared spectroscopy indicated intermolecular interactions between AntiY5R and NaTC. AntiY5R-NaTC at equal molar ratios resulting in an 8.5-fold increase in AntiY5R solubility over its crystalline form. The co-amorphous system remained amorphous for 1 month at 25 °C and 40 °C. These results suggest that the co-amorphous system formed by utilizing NaTC as a coformer could stably maintain the amorphous state and enhance the solubility of brick dust molecules.
Long-Circulating and Fusogenic Liposomes Loaded with Paclitaxel and Doxorubicin: Effect of Excipient, Freezing, and Freeze-Drying on Quality Attributes
Authors: Roque Marjorie , Geraldes Danilo , da Silva Caroline , Oliveira Mônica , Nascimento Laura
Published: December 2022

Liposomes can increase plasma half-life, enhance targeting, and diminish the side-effects of loaded drugs. On the downside, physical and chemical instabilities of dispersions often result in a reduced lifespan, which limits their availability on the market. Solid formulations obtained by freeze-drying can immobilize vesicles and provide extended shelf life. For both processes, the choice of excipients and process parameters are crucial to protect the carrier layers against tension caused by freezing and/or dehydration. The aim of this work is to evaluate the influence of freezing and drying parameters, besides excipient choice, to obtain solid long-circulating and fusogenic liposomes (LCFL-PTX/DXR) co-encapsulating paclitaxel (PTX) and doxorubicin (DXR) at a synergistic ratio (1:10). Methods: LCFL-PTX/DXR was evaluated by freeze-drying microscopy (glass transition, Tg’), differential scanning calorimetry (collapse temperature, Tc), freeze-thawing and freeze-drying processes. Freeze-dried samples were evaluated by thermogravimetry (residual moisture) and the resuspended liposomes were characterized in terms of size, polydispersity index (PI), zeta potential (ZP), and drug content. Liposomes morphology was evaluated by cryomicroscopy. Results: Trehalose protected PTX cargo upon freeze-thawing and more than 80% of the original DXR retention. The formulations with trehalose resulted in a cake with 5–7% of moisture content (200–240 nm); 44–60% of PTX retention, and 25–35% of DXR retention, with the variations caused by cryoprotector concentration and process changes. Conclusions: Trehalose protected liposome integrity, maintaining PTX retention and most of DXR upon freeze-thawing. Freeze-drying reduced the retention of both drugs inside all liposomes, whereas formulation with trehalose presented minor losses. Therefore, this frozen formulation is an alternative product option, with no need for manipulation before use.
Treated Dentin Matrix in Tissue Regeneration: Recent Advances
Authors: Bi Fei , Zhang Zhijun , Guo Weihua
Published: December 2022

Tissue engineering is a new therapeutic strategy used to repair serious damage caused by trauma, a tumor or other major diseases, either for vital organs or tissues sited in the oral cavity. Scaffold materials are an indispensable part of this. As an extracellular-matrix-based bio-material, treated dentin matrixes have become promising tissue engineering scaffolds due to their unique natural structure, astonishing biological induction activity and benign bio-compatibility. Furthermore, it is important to note that besides its high bio-activity, a treated dentin matrix can also serve as a carrier and release controller for drug molecules and bio-active agents to contribute to tissue regeneration and immunomodulation processes. This paper describes the research advances of treated dentin matrixes in tissue regeneration from the aspects of its vital properties, biologically inductive abilities and application explorations. Furthermore, we present the concerning challenges of signaling mechanisms, source extension, individualized 3D printing and drug delivery system construction during our investigation into the treated dentin matrix. This paper is expected to provide a reference for further research on treated dentin matrixes in tissue regeneration and better promote the development of relevant disease treatment approaches.
Indene-Derived Hydrazides Targeting Acetylcholinesterase Enzyme in Alzheimer’s: Design, Synthesis, and Biological Evaluation
Authors: Gupta Shraddha Manish , Behera Ashok , Jain Neetesh K. , Kumar Devendra , Tripathi Avanish , Tripathi Shailesh Mani , Mujwar Somdutt , Patra Jeevan , Negi Arvind
Published: December 2022

As acetylcholinesterase (AChE) plays a crucial role in advancing Alzheimer’s disease (AD), its inhibition is a promising approach for treating AD. Sulindac is an NSAID of the aryl alkanoic acid class, consisting of a indene moiety, which showed neuroprotective behavior in recent studies. In this study, newer Indene analogs were synthesized and evaluated for their in vitro AChE inhibition. Additionally, compared with donepezil as the standard drug, these Indene analogs were accessed for their cell line-based toxicity study on SH-SY5Y cell line. The molecule SD-30, having hydrogen bond donor (HBD) at para-position, showed maximum AChE inhibition potential (IC50 13.86 ± 0.163 µM) in the indene series. Further, the SD-30 showed maximum BuChE inhibition potential (IC50 = 48.55 ± 0.136 µM) with a selectivity ratio of 3.50 and reasonable antioxidant properties compared to ascorbic acid (using DPPH assay). SD-30 (at a dose level: of 10 µM, 20 µM) effectively inhibited AChE-induced Aβ aggregation and showed no significant toxicity up to 30 mM against SH-SY5Y cell lines.
Liposomal Amphotericin B for Treatment of Leishmaniasis: From the Identification of Critical Physicochemical Attributes to the Design of Effective Topical and Oral Formulations
Authors: Frézard Frédéric , Aguiar Marta M. G. , Ferreira Lucas A. M. , Ramos Guilherme S. , Santos Thais T. , Borges Gabriel S. M. , Vallejos Virgínia M. R. , De Morais Helane L. O.
Published: December 2022

The liposomal amphotericin B (AmB) formulation, AmBisome®, still represents the best therapeutic option for cutaneous and visceral leishmaniasis. However, its clinical efficacy depends on the patient’s immunological status, the clinical manifestation and the endemic region. Moreover, the need for parenteral administration, its side effects and high cost significantly limit its use in developing countries. This review reports the progress achieved thus far toward the understanding of the mechanism responsible for the reduced toxicity of liposomal AmB formulations and the factors that influence their efficacy against leishmaniasis. It also presents the recent advances in the development of more effective liposomal AmB formulations, including topical and oral liposome formulations. The critical role of the AmB aggregation state and release rate in the reduction of drug toxicity and in the drug efficacy by non-invasive routes is emphasized. This paper is expected to guide future research and development of innovative liposomal formulations of AmB.
Gold-Coated Superparamagnetic Iron Oxide Nanoparticles Functionalized to EGF and Ce6 Complexes for Breast Cancer Diagnoses and Therapy
Authors: Cândido Marcela , Vieira Paula , Campos Andrea , Soares Cristina , Raniero Leandro
Published: December 2022

Superparamagnetic iron oxide nanoparticles (SPIONs) have some limitations in the physiological environment, however, a modification on their surface, such as a core–shell structure with gold (SPIONs@Au), can enhance their applicability. In this study, SPIONs were synthesized by the chemical coprecipitation method, stabilized by sodium citrate, and followed by the gold-coating process. SPIONs@Au were functionalized with EGF-α-lipoic acid and chlorin e6 (Ce6)-cysteamine complexes, composing a Theranostic Nanoprobe (TP). The outcomes showed that the SPIONs@Au had changed in color to red and had an absorption band centered at 530 nm. The coating was verified in the TEM micrographs in bright and dark fields by EDS mapping, which indicated the presence of Au and Fe. The Ce6-cysteamine complex had a resonant band at 670 nm that enabled the diagnosis of biological samples using fluorescence analysis. In the measure of TNBC cell uptake, the maximum value of TP fluorescence intensity was obtained within 4 h of internalization. At 2 h, the incorporation of the TP in the cytoplasm as well as in the nuclei was observed, suggesting that it could be employed as a diagnostic marker. The PTT results showed significant percentages of apoptosis in the TNBC cell line, which confirms the efficacy of the TP.
A Cationic Amphiphilic AIE Polymer for Mitochondrial Targeting and Imaging
Authors: Zhou Junliang , Wang Haiyang , Wang Wen , Ma Zhiwei , Chi Zhenguo , Liu Siwei
Published: December 2022

Mitochondria are important organelles that play key roles in generating the energy needed for life and in pathways such as apoptosis. Direct targeting of antitumor drugs, such as doxorubicin (DOX), to mitochondria into cells is an effective approach for cancer therapy and inducing cancer cell death. To achieve targeted and effective delivery of antitumor drugs to tumor cells, to enhance the therapeutic effect, and to reduce the side effects during the treatment, we prepared a cationic amphiphilic polymer with aggregation-induced emission (AIE) characteristic. The polymer could be localized to mitochondria with excellent organelle targeting, and it showed good mitochondrial targeting with low toxicity. The polymer could also self-assemble into doxorubicin-loaded micelles in phosphate buffer, with a particle size of about 4.3 nm, an encapsulation rate of 11.03%, and micelle drug loading that reached 0.49%. The results of in vitro cytotoxicity experiments showed that the optimal dosage was 2.0 μg/mL, which had better inhibitory effect on tumor cells and less biological toxicity on heathy cells. Therefore, the cationic amphiphilic polymer can partially replace expensive commercial mitochondrial targeting reagents, and it can be also used as a drug loading tool to directly target mitochondria in cells for corresponding therapeutic research.
Growing Season, Cultivar, and Nitrogen Supply Affect Leaf and Fruit Micronutrient Status of Field-Grown Kiwiberry Vines
Authors: Stefaniak Jan , Łata Barbara
Published: December 2022

The N uptake can affect kiwiberry yield and quality; however, the relationship between an increasing N dose and micronutrient accumulation in leaves and fruit is still to be elucidated. Interrelationships between essential nutrients are one of the most important issues in terms of effectiveness in plant mineral nutrition. A pattern in leaf nutrient accumulation throughout the growing period is required to indicate a suitable sampling time for the purpose of nutrient diagnostics and controlled plant feeding. The experiment was conducted on two commercially available cultivars of kiwiberry, ‘Weiki’ and ‘Geneva’, during the 2015–2016 growing seasons with an increasing soil N fertility (30–50–80 mg N kg−1 soil DW) to test the relationship between soil N level and leaf/fruit micronutrient concentration. The leaf Zn, Cu, Fe, and Mn concentrations significantly increased with a higher N supply in ‘Geneva’, while in ‘Weiki’ only Mn increased. Leaf B, Fe, and Mn gradually increased throughout the growing season, while Cu decreased. Between mid-July and the beginning of August, the lowest fluctuations in the micronutrient contents were recorded. The effect of the growing season on leaf micronutrient accumulation was highly significant; except for Fe, significantly higher micronutrient levels were revealed in 2016. Compared to the leaves, the growing season effect was smaller in the case of fruit micronutrient concentrations. Irrespective of cultivar, the increase in N fertilization resulted in a higher fruit Mn concentration and was insignificant in the case of other micronutrients. The results indicate that the N dose may affect the accumulation of micronutrients within a certain range depending on the tissue type and the genotype.