bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of the Temperature and Termination(-O) on the Friction and Adhesion Properties of MXenes Using Molecular Dynamics Simulation
Authors: Deng Yao , Chen Yu , Liu Hanxu , Yan Xin
Published: February 2022

Two-dimensional transition metal carbides and nitrides (MXenes) are widely applied in the fields of electrochemistry, energy storage, electromagnetism, etc., due to their extremely excellent properties, including mechanical performance, thermal stability, photothermal conversion and abundant surface properties. Usually, the surfaces of the MXenes are terminated by –OH, –F, –O or other functional groups and these functional groups of MXenes are related surface properties and reported to affect the mechanical properties of MXenes. Thus, understanding the effects of surface terminal groups on the properties of MXenes is crucial for device fabrication as well as composite synthesis using MXenes. In this paper, using molecular dynamics (MD) simulation, we study the adhesion and friction properties of Ti2C and Ti2CO2, including the indentation strength, adhesion energy and dynamics of friction. Our indentation fracture simulation reveals that there are many unbroken bonds and large residual stresses due to the oxidation of oxygen atoms on the surface of Ti2CO2. By contrast, the cracks of Ti2C keep clean at all temperatures. In addition, we calculate the elastic constants of Ti2C and Ti2CO2 by the fitting force–displacement curves with elastic plate theory and demonstrate that the elastic module of Ti2CO2 is higher. Although the temperature had a significant effect on the indentation fracture process, it hardly influences maximum adhesion. The adhesion energies of Ti2C and Ti2CO2 were calculated to be 0.3 J/m2 and 0.5 J/m2 according to Maugis–Dugdale theory. In the friction simulation, the stick-slip atomic scale phenomenon is clearly observed. The friction force and roughness (Ra) of Ti2C and Ti2CO2 at different temperatures are analyzed. Our study provides a comprehensive insight into the mechanical behavior of nanoindentation and the surface properties of oxygen functionalized MXenes, and the results are beneficial for the further design of nanodevices and composites.
Measuring Exciton Fine-Structure in Randomly Oriented Perovskite Nanocrystal Ensembles Using Nonlinear Optical Spectroscopy: Theory
Authors: Liu Albert
Published: February 2022

Lead halide perovskite nanocrystals (PNCs) exhibit unique optoelectronic properties, many of which originate from a purported bright-triplet exciton fine-structure. A major impediment to measuring this fine-structure is inhomogeneous spectral broadening, which has limited most experimental studies to single-nanocrystal spectroscopies. It is shown here that the linearly polarized single-particle selection rules in PNCs are preserved in nonlinear spectroscopies of randomly oriented ensembles. Simulations incorporating rotational averaging demonstrate that techniques such as transient absorption and two-dimensional coherent spectroscopy are capable of resolving exciton fine-structure in PNCs, even in the presence of inhomogeneous broadening and orientation disorder.
Colloidal Processing of Mn3O4-Carbon Nanotube Nanocomposite Electrodes for Supercapacitors
Authors: Yang Wenjuan , Zhitomirsky Igor
Published: February 2022

This investigation addresses the challenges in the development of efficient nanostructured Mn3O4 cathodes for supercapacitors. A high areal capacitance and the ability to avoid a time-consuming activation procedure for electrodes with high active mass loading of 40 mg cm−2 are reported. This facilitates practical applications of Mn3O4 based electrodes. The highest capacitance of 6.11 F cm−2 (153 F g−1) is obtained from cyclic voltammetry at a scan rate of 2 mV s−1 and 6.07 F cm−2 (151.9 F g−1) from the chronopotentiometry at a current density of 3 mA cm−2 in a potential window of 0.9 V in a neutral Na2SO4 electrolyte. The new approach is based on the application of rhamnolipids (RL) as a capping agent for the synthesis of Mn3O4 particles and a co-dispersant for Mn3O4 and carbon nanotubes, which are used as conductive additives. The size and shape of the Mn3O4 particles are influenced by RL. The enhanced performance of the electrodes is linked to the chemical structure and properties of RL molecules, which exert influence on Mn3O4 particle size and shape during synthesis, reduce agglomeration, facilitate RL adsorption on Mn3O4 and carbon nanotubes, and influence their co-dispersion and mixing at the nanometric scale.
Lactobacillus acidophilus DDS-1 Modulates the Gut Microbial Co-Occurrence Networks in Aging Mice
Authors: Vemuri Ravichandra , Martoni Christopher J. , Kavanagh Kylie , Eri Rajaraman
Published: February 2022

Age-related alterations in the gut microbiome composition and its impacts on the host’s health have been well-described; however, detailed analyses of the gut microbial structure defining ecological microbe–microbe interactions are limited. One of the ways to determine these interactions is by understanding microbial co-occurrence patterns. We previously showed promising abilities of Lactobacillus acidophilus DDS-1 on the aging gut microbiome and immune system. However, the potential of the DDS-1 strain to modulate microbial co-occurrence patterns is unknown. Hence, we aimed to investigate the ability of L. acidophilus DDS-1 to modulate the fecal-, mucosal-, and cecal-related microbial co-occurrence networks in young and aging C57BL/6J mice. Our Kendall’s tau correlation measures of co-occurrence revealed age-related changes in the gut microbiome, which were characterized by a reduced number of nodes and associations across sample types when compared to younger mice. After four-week supplementation, L. acidophilus DDS-1 differentially modulated the overall microbial community structure in fecal and mucosal samples as compared to cecal samples. Beneficial bacteria such as Lactobacillus, Oscillospira, and Akkermansia acted as connectors in aging networks in response to L. acidophilus DDS-1 supplementation. Our findings provided the first evidence of the DDS-1-induced gut microbial ecological interactions, revealing the complex structure of microbial ecosystems with age.
High-Dose Vitamin C Supplementation as a Legitimate Anti-SARS-CoV-2 Prophylaxis in Healthy Subjects—Yes or No?
Authors: Gruber-Bzura Beata M.
Published: February 2022

Vitamin C has a number of acitvities that could contribute to its immune-modulating effects. The only question is whether we should provide ourselves with only the right level of it, or do we need much more during a pandemic? The possibility of reducing the incidence of viral diseases in a well-nourished population through the use of dietary supplements based on vitamin C is not supported in the literature. Despite this, the belief that an extra intake of vitamin C can increase the efficacy of the immune system is still popular and vitamin C is advertised as a remedy to prevent infectious disease. This article refers to the justification of the use of vitamin C in high doses as an anti-SARS-CoV-2 prophylaxis in healthy subjects. Does it make sense or not? As it turns out, any effects of vitamin C supplementation may be more prominent when the baseline vitamin C level is low, for example in physically active persons. People with hypovitaminosis C are more likely to respond to vitamin C administration. No studies regarding prevention of COVID-19 with high-dose vitamin C supplementation in healthy subjects were found.
Cyanidin-3-O-Glucoside Supplement Improves Sperm Quality and Spermatogenesis in a Mice Model of Ulcerative Colitis
Authors: Xiao Yuhang , Xu Baojun , Bordiga Matteo , Li Haiwei , Travaglia Fabiano , Bai Shun , Chen Jiali , Bai Weibin
Published: February 2022

Impaired fertility and low sperm quality are the global health problem with high attention. It has been noted that inflammation may impact fertility by affecting testicular spermatogenesis. Cyanidin-3-O-glucoside is a natural functional pigment with various health benefits. Nevertheless, studies on the mechanism by which C3G protects male reproduction in mice with ulcerative colitis remain scarce. The purpose of this study is to illustrate the potential mechanism of C3G for improving impaired fertility caused by colitis. A DSS-induced colitis model was applied to assess the effects of sperm quality with colitis and the health benefit role of C3G. Results indicated that C3G-treated mice exhibited higher body weight, longer colon length, less crypt damage and focal inflammation infiltration. Being consistent with that, low sperm count, low testis weight, high inflammation levels and abnormal thickness of seminiferous epithelium also observed in the DSS group were significantly recovered upon C3G treatment. These findings suggested that colitis has a close link to impaired fertility. Further analysis found that C3G could significantly suppress the inflammatory mediators in serum. Results conjointly indicated that C3G might improve the impaired fertility of mice with colitis by inhibiting inflammatory cytokines through the blood–testis barrier. C3G could be a promising daily supplement for ameliorating impaired fertility caused by colitis.
The Role of Medicinal and Aromatic Plants against Obesity and Arthritis: A Review
Authors: Paul Alok K. , Jahan Rownak , Paul Anita , Mahboob Tooba , Bondhon Tohmina A. , Jannat Khoshnur , Hasan Anamul , Nissapatorn Veeranoot , Wilairatana Polrat , de Lourdes Pereira Maria , Wiart Christophe , Rahmatullah Mohammed
Published: February 2022

Obesity is a significant health concern, as it causes a massive cascade of chronic inflammations and multiple morbidities. Rheumatoid arthritis and osteoarthritis are chronic inflammatory conditions and often manifest as comorbidities of obesity. Adipose tissues serve as a reservoir of energy as well as releasing several inflammatory cytokines (including IL-6, IFN-γ, and TNF-α) that stimulate low-grade chronic inflammatory conditions such as rheumatoid arthritis, osteoarthritis, diabetes, hypertension, cardiovascular disorders, fatty liver disease, oxidative stress, and chronic kidney diseases. Dietary intake, low physical activity, unhealthy lifestyle, smoking, alcohol consumption, and genetic and environmental factors can influence obesity and arthritis. Current arthritis management using modern medicines produces various adverse reactions. Medicinal plants have been a significant part of traditional medicine, and various plants and phytochemicals have shown effectiveness against arthritis and obesity; however, scientifically, this traditional plant-based treatment option needs validation through proper clinical trials and toxicity tests. In addition, essential oils obtained from aromatic plants are being widely used as for complementary therapy (e.g., aromatherapy, smelling, spicing, and consumption with food) against arthritis and obesity; scientific evidence is necessary to support their effectiveness. This review is an attempt to understand the pathophysiological connections between obesity and arthritis, and describes treatment options derived from medicinal, spice, and aromatic plants.
Contributing Factors to Low Energy Availability in Female Athletes: A Narrative Review of Energy Availability, Training Demands, Nutrition Barriers, Body Image, and Disordered Eating
Authors: Jagim Andrew R. , Fields Jennifer , Magee Meghan K. , Kerksick Chad M. , Jones Margaret T.
Published: February 2022

Relative Energy Deficiency in sport is experiencing remarkable popularity of late, particularly among female athletes. This condition is underpinned by low energy availability, which is a byproduct of high energy expenditure, inadequate energy intake, or a combination of the two. Several contributing factors exist that may predispose an athlete to low energy availability, and therefore a holistic and comprehensive assessment may be required to identify the root causes. The focus of the current narrative review is to discuss the primary contributing factors as well as known risk factors for low energy availability among female athletes to help practitioners increase awareness on the topic and identify future areas of focus.
Impacts of the Seattle Sweetened Beverage Tax on the Perceived Healthfulness of Sweetened Beverages
Authors: Sawyer Lauren , Oddo Vanessa M. , Fretts Amanda , Knox Melissa A. , Chan Nadine , Saelens Brian E. , Jones-Smith Jessica C.
Published: February 2022

Sweetened beverage taxes are associated with significant reductions in the purchase of sweetened beverages. However, it is unclear whether these taxes play a role in shifting perceptions about sweetened beverages and their health impacts. We utilized pre- and post-tax survey data collected from residents in Seattle, WA, a city that implemented a sweetened beverage tax in 2018 and from residents in an untaxed comparison area. We used income-stratified difference-in-difference linear probability models to compare net changes in the perceived healthfulness of overall sweetened beverage consumption and of different types of sugary beverages over time and across income groups. We found significant increases in the percentage of Seattle respondents with lower incomes who agreed that sweetened beverage consumption raises the risk of diabetes (DD = 9 percentage points (pp) (95% CI: 5 pp, 13 pp); p = 0.002), heart disease (DD = 7 pp (95% CI: 2 pp, 12 pp); p = 0.017), and serious health problems (DD = 12 pp (95% CI: 5 pp, 19 pp); p = 0.009), above and beyond changes in the comparison area. The most prominent changes in perceived health impacts of sweetened beverages were found among lower-income Seattle respondents, while fewer changes were found among higher-income Seattle respondents. Future work could examine the relationship between exposure to pro-tax messaging and changes in consumer perceptions of sweetened beverages.
Metabolic Bone Disease in Children with Intestinal Failure and Long-Term Parenteral Nutrition: A Systematic Review
Authors: Gatti Simona , Quattrini Sara , Palpacelli Alessandra , Catassi Giulia N. , Lionetti Maria Elena , Catassi Carlo
Published: February 2022

Metabolic bone disease (MBD) is a possible complication of intestinal failure (IF), with a multi-factorial pathogenesis. The reduction of bone density (BMD) may be radiologically evident before manifestation of clinical signs (bone pain, vertebral compression, and fractures). Diagnosis relies on dual-energy X-ray absorptiometry (DXA). Incidence and evolution of MBD are not homogeneously reported in children. The aim of this systematic review was to define the prevalence of MBD in IF children and to describe risk factors for its development. A comprehensive search of electronic bibliographic databases up to December 2021 was conducted. Randomized controlled trials; observational, cross-sectional, and retrospective studies; and case series published between 1970 and 2021 were included. Twenty observational studies (six case-control) were identified and mostly reported definitions of MBD based on DXA parameters. Although the prevalence and definition of MBD was largely heterogeneous, low BMD was found in up to 45% of IF children and correlated with age, growth failure, and specific IF etiologies. Data demonstrate that long-term follow-up with repeated DXA and calcium balance assessment is warranted in IF children even when PN dependence is resolved. Etiology and outcomes of MBD will be better defined by longitudinal prospective studies focused on prognosis and therapeutic perspectives.
The Role of Nutrients in Prevention, Treatment and Post-Coronavirus Disease-2019 (COVID-19)
Authors: Motti Maria Letizia , Tafuri Domenico , Donini Lorenzo , Masucci Maria Teresa , De Falco Valentina , Mazzeo Filomena
Published: February 2022

SARS-CoV-2 virus, infecting human cells via its spike protein, causes Coronavirus disease 2019 (COVID-19). COVID-19 is characterized by shortness of breath, fever, and pneumonia and is sometimes fatal. Unfortunately, to date, there is still no definite therapy to treat COVID-19. Therefore, the World Health Organization (WHO) approved only supportive care. During the COVID-19 pandemic, the need to maintain a correct intake of nutrients to support very weakened patients in overcoming disease arose. The literature available on nutrient intake for COVID-19 is mainly focused on prevention. However, the safe intake of micro- and/or macro-nutrients can be useful either for preventing infection and supporting the immune response during COVID-19, as well as in the post-acute phase, i.e., “long COVID”, that is sometimes characterized by the onset of various long lasting and disabling symptoms. The aim of this review is to focus on the role of nutrient intake during all the different phases of the disease, including prevention, the acute phase, and finally long COVID.
Habitual Dietary Fiber Intake, Fecal Microbiota, and Hemoglobin A1c Level in Chinese Patients with Type 2 Diabetes
Authors: Fu Jiongxing , Xu Kelin , Ni Xumin , Li Xiaoqiang , Zhu Xiaofeng , Xu Wanghong
Published: February 2022

High-fiber diet interventions have been proven to be beneficial for gut microbiota and glycemic control in diabetes patients. However, the effect of a low level of fiber in habitual diets remains unclear. This study aims to examine the associations of habitual dietary fiber intake with gut microbiome profiles among Chinese diabetes patients and identify differential taxa that mediated associations of dietary fiber with HbA1c level. Two cross-sectional studies and one longitudinal study were designed based on two follow-up surveys in a randomized trial conducted during 2015–2017. The study included 356 and 310 participants in the first and second follow-ups, respectively, with 293 participants in common in both surveys. Dietary fiber intake was calculated based on a 3-day 24-h diet recall at each survey and was classified into a lower or a higher group according to the levels taken based on the two surveys using 7.2 g/day as a cut-off value. HbA1c was assayed to assess glycemic status using a cut-off point of 7.0% and 8.0%. Microbiome was profiled by 16S rRNA sequencing. A high habitual dietary fiber intake was associated with a decrease in α-diversity in both the cross-sectional and longitudinal analyses. At the first follow–up, phylum Firmicutes and Fusobacteria were negatively associated with a higher dietary fiber intake (p < 0.05, Q < 0.15); at the second follow-up, genus Adlercreutzia, Prevotella, Ruminococcus, and Desulfovibrio were less abundant in patients taking higher dietary fiber (p < 0.05, Q < 0.15); genus Desulfovibrio and Ruminococcaceae (Unknown), two identified differential taxa by HbA1c level, were negatively associated with dietary fiber intake in both the cross-sectional and longitudinal analyses, and mediated the dietary fiber-HbA1c associations among patients taking dietary fiber ≥ 7.2 g/day (mediation effect β [95%CI]: −0.019 [−0.043, −0.003], p = 0.018 and −0.019 [−0.046, −0.003], p = 0.016). Our results suggest that habitual dietary fiber intake has a beneficial effect on gut microbiota in Chinese diabetes patients. Further studies are needed to confirm our results.
Association of Infants Small for Gestational Age with Anemia under Five Years Old in Two Large Longitudinal Chinese Birth Cohorts
Authors: Li Nan , An Hang , Jin Ming , Li Zhiwen , Zhang Yali , Zhang Le , Liu Jianmeng , Ye Rongwei
Published: February 2022

Babies who are born small for their gestational age (SGA) have low iron reserves, thus probably increasing the risk of offspring anemia. We studied two longitudinal birth cohorts to evaluate the association of SGA with the risk of anemia during early childhood. Cohort 1 was recruited from five counties in northern China involving 17,180 singleton infants born during 2006–2009 and cohort 2 from 21 counties or cities in southern China involving 180,619 children born during 1993–1996. Anemia was diagnosed by hemoglobin at 6 and 12 months in cohort 1 and at 55 months in cohort 2. The overall incidences of SGA were 7.07% and 5.73% in cohort 1 and cohort 2, respectively. SGA was associated with increased anemia at 6 months (adjusted odds ratio (OR): 1.52; 95% confidence interval (CI): 1.24, 1.86) and 12 months (adjusted OR: 1.42; 95% CI: 1.13, 1.79) in cohort 1 and at 55 months (adjusted OR: 1.11; 95% CI: 1.05, 1.17) in cohort 2. The positive associations for anemia at 6, 12, and 55 months persisted in both logistics and multiple linear models. Our results support a gradually decreased association between SGA and the increased risk of childhood anemia with a longer follow-up time in infants and children.
Physical and Dietary Intervention with Opuntia ficus-indica (Nopal) in Women with Obesity Improves Health Condition through Gut Microbiota Adjustment
Authors: Corona-Cervantes Karina , Parra-Carriedo Alicia , Hernández-Quiroz Fernando , Martínez-Castro Noemí , Vélez-Ixta Juan Manuel , Guajardo-López Diana , García-Mena Jaime , Hernández-Guerrero César
Published: February 2022

Obesity is a multifactorial disease resulting in excessive accumulation of fat. Worldwide, obesity is an important public health problem, affecting a large proportion of the world population. The tender cactus Opuntia ficus-indica, commonly known in Mexico as “nopal”, is widely distributed in this country, Latin America, South Africa, and the Mediterranean area. Nopal cladodes are commonly marketed in different forms as fresh, frozen, or pre-cooked, and used as fresh green vegetable. The aim of this study was to evaluate the capability of nopal to improve the health condition of participants affected by obesity, in a physical and dietary intervention, through gut microbiota modification. These results were contrasted with the effect of nopal in the gut microbiota of normal weight participants. We describe the association among biochemical, anthropometric markers, and the gut microbiota diversity found in fecal samples of the obese and normal weight groups. The results presented in this work suggest that caloric restriction, addition of nopal to the diet and physical activity, promote changes in the gut microbiota in obese women, improving the host metabolism, as suggested by the correlation between some bacterial species with biochemical and anthropometrical parameters.
The Reporting Frequency of Ketoacidosis Events with Dapagliflozin from the European Spontaneous Reporting System: The DAPA-KETO Study
Authors: di Mauro Gabriella , Mascolo Annamaria , Gaio Mario , Rafaniello Concetta , De Angelis Antonella , Berrino Liberato , Paolisso Giuseppe , Rossi Francesco , Capuano Annalisa
Published: February 2022

Dapagliflozin was associated with an increased risk of diabetic ketoacidosis that has led to the European withdrawal of the authorization for the type 1 diabetes. However, it is still used for the treatment of type 2 diabetes. Therefore, we aim to evaluate the occurrence of dapagliflozin-induced ketoacidosis events by using the European spontaneous reporting system. The reporting odds ratios (ROR) were computed to assess the reporting frequency of ketoacidosis events for dapagliflozin compared to Dipeptidyl peptidase-4 (DPP-4) inhibitors, insulins, or all other Sodium-glucose cotransporter-2 (SGLT-2) inhibitors. A total of 2406 cases with dapagliflozin reported at least one event of ketoacidosis. The three most reported events were: diabetic ketoacidosis (1412; 55.39%), ketoacidosis (476; 18.67%), and euglycaemic diabetic ketoacidosis (296; 11.61%). Dapagliflozin was associated with the higher reporting frequency of ketoacidosis events compared to DPP-4 inhibitors (ROR 12.07, 95%CI 11.67–13.81) or insulins (ROR 7.59, 95%CI 7.13–7.89). A lower reporting frequency was instead observed compared to other SGLT2 inhibitors (ROR 0.91, 95%CI 0.87–0.96). Considering the higher reporting frequency of ketoacidosis observed with dapagliflozin then DPP-4 inhibitors or insulins, attention should be given to patients treated with this drug.
Tumor Necrosis Factor-α Mediates Lung Injury in the Early Phase of Endotoxemia
Authors: Chen Kung-Yen , Chang Chao-Yuan , Hsu Hao-Jen , Shih Hung-Jen , Huang I-Tao , Patel Hemal H. , Huang Chun-Jen
Published: February 2022

Endotoxemia induces lung injury. We assessed the therapeutic efficacy between triple cytokine (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], and IL-6) inhibition (mediated by KCF18 peptide) and single cytokine (TNF-α) inhibition (mediated by SEM18 peptide) on alleviating lung injury in the early phase of endotoxemia. Mice receiving endotoxin (Endo group), endotoxin plus KCF18 (EKCF group), or endotoxin plus SEM18 (ESEM) were monitored and euthanized at 24 h after endotoxin. Our data demonstrated altered lung function (decreases in tidal volume, minute ventilation, and dynamic compliance; and by contrast, increases in airway resistance and end expiration work) and histology (increases in injury scores, leukocyte infiltration, vascular permeability, and tissue water content) in the Endo group with significant protection observed in the EKCF and ESEM groups (all p < 0.05). Levels of inflammation (macrophage activation and cytokine upregulations), oxidation (lipid peroxidation), necroptosis, pyroptosis, and apoptosis in EKCF and ESEM groups were comparable and all were significantly lower than in the Endo group (all p < 0.05). These data demonstrate that single cytokine TNF-α inhibition can achieve therapeutic effects similar to triple cytokines TNF-α, IL-1β, and IL-6 inhibition on alleviating endotoxin-induced lung injury, indicating that TNF-α is the major cytokine in mediating lung injury in the early phase of endotoxemia.
l-Arginine and Beetroot Extract Supplementation in the Prevention of Sarcopenia
Authors: Córdova-Martínez Alfredo , Caballero-García Alberto , Bello Hugo J. , Pons-Biescas Antoni , Noriega David C. , Roche Enrique
Published: February 2022

Aging is associated with a significant decline in neuromuscular function, leading to a reduction in muscle mass and strength. The aim of the present report was to evaluate the effect of supplementation with nitric oxide precursors (l-arginine and beetroot extract) in muscular function during a training period of 6 weeks in elderly men and women. The study (double-blind, placebo-controlled) involved 66 subjects randomly divided into three groups: placebo, arginine-supplemented and beetroot extract-supplemented. At the end of this period, no changes in anthropometric parameters were observed. Regarding other circulating parameters, urea levels were significantly (p < 0.05) lower in women of the beetroot-supplemented group (31.6 ± 5.9 mg/dL) compared to placebo (41.3 ± 8.5 mg/dL) after 6 weeks of training. In addition, the circulating creatine kinase activity, as an index of muscle functionality, was significantly (p < 0.05) higher in women of the arginine- (214.1 ± 162.2 mIU/L) compared to the beetroot-supplemented group (84.4 ± 36.8 mIU/L) at the end of intervention. No significant effects were noticed with l-arginine or beetroot extract supplementation regarding strength, endurance and SPPB index. Only beetroot extract supplementation improved physical fitness significantly (p < 0.05) in the sprint exercise in men after 6 weeks (2.33 ± 0.59 s) compared to the baseline (2.72 ± 0.41 s). In conclusion, beetroot seems to be more efficient during short-term training while supplementing, preserving muscle functionality in women (decreased levels of circulating creatine kinase) and with modest effects in men.
Characterization of Novel Lytic Myoviridae Phage Infecting Multidrug-Resistant Acinetobacter baumannii and Synergistic Antimicrobial Efficacy between Phage and Sacha Inchi Oil
Authors: Wintachai Phitchayapak , Voravuthikunchai Supayang
Published: February 2022

Multidrug-resistant (MDR) strains of Acinetobacter baumannii have become a major cause of hospital-acquired infections, resulting in an increase in morbidity and mortality worldwide. Many alternative treatments, including phage therapy, are attractive approaches for overcoming problems posed by antibiotic resistance. A newly isolated phage, vWUPSU-specific MDR A. baumannii, showed a narrow host range against MDR A. baumannii. This research was conducted to isolate, characterize, and apply the phage with sacha inchi oil as an alternative antimicrobial agent. Genome analysis suggested that phage vWUPSU is a novel phage belonging to the family Myoviridae, order Caudoviridae. This phage prevented biofilm formation and eradicated preformed biofilms in a dose-dependent manner. In addition, a synergistic antimicrobial effect of the interaction between phage vWUPSU and sacha inchi oil on planktonic cells was observed. The combination of phage and sacha inchi oil significantly inhibited and removed biofilms, compared with the effects of either single treatment. The results of this work indicate that phage vWUPSU could potentially be applied to control MDR A. baumannii. The antibacterial and antibiofilm activities of the combination of phage vWUPSU and sacha inchi oil have attracted significant interests in the development of antibacterial phage products as beneficial treatment options.
Recent Advances in the Therapeutic Efficacy of Artesunate
Authors: Ruwizhi Ngonidzashe , Maseko Rejoice Bethusile , Aderibigbe Blessing Atim
Published: February 2022

Artesunate, a semisynthetic artemisinin derivative, is well-known and used as the first-line drug for treating malaria. Apart from treating malaria, artesunate has also been found to have biological activity against a variety of cancers and viruses. It also exhibits antidiabetic, anti-inflammatory, anti-atherosclerosis, immunosuppressive activities, etc. During its administration, artesunate can be loaded in liposomes, alone or in combination with other therapeutic agents. Administration routes include intragastrical, intravenous, oral, and parenteral. The biological activity of artesunate is based on its ability to regulate some biological pathways. This manuscript reports a critical review of the recent advances in the therapeutic efficacy of artesunate.
Nanomedicine as a Promising Tool to Overcome Immune Escape in Breast Cancer
Authors: Navarro-Ocón Alba , Blaya-Cánovas Jose L. , López-Tejada Araceli , Blancas Isabel , Sánchez-Martín Rosario M. , Garrido María J. , Griñán-Lisón Carmen , Calahorra Jesús , Cara Francisca E. , Ruiz-Cabello Francisco , Marchal Juan A. , Aptsiauri Natalia , Granados-Principal Sergio
Published: February 2022

Breast cancer is the most common type of malignancy and leading cause of cancer death among women worldwide. Despite the current revolutionary advances in the field of cancer immunotherapy, clinical response in breast cancer is frequently below expectations, in part due to various mechanisms of cancer immune escape that produce tumor variants that are resistant to treatment. Thus, a further understanding of the molecular events underlying immune evasion in breast cancer may guarantee a significant improvement in the clinical success of immunotherapy. Furthermore, nanomedicine provides a promising opportunity to enhance the efficacy of cancer immunotherapy by improving the delivery, retention and release of immunostimulatory agents in targeted cells and tumor tissues. Hence, it can be used to overcome tumor immune escape and increase tumor rejection in numerous malignancies, including breast cancer. In this review, we summarize the current status and emerging trends in nanomedicine-based strategies targeting cancer immune evasion and modulating the immunosuppressive tumor microenvironment, including the inhibition of immunosuppressive cells in the tumor area, the activation of dendritic cells and the stimulation of the specific antitumor T-cell response.
Magnetic Solid Nanoparticles and Their Counterparts: Recent Advances towards Cancer Theranostics
Authors: Cerqueira Mónica , Belmonte-Reche Efres , Gallo Juan , Baltazar Fátima , Bañobre-López Manuel
Published: February 2022

Cancer is currently a leading cause of death worldwide. The World Health Organization estimates an increase of 60% in the global cancer incidence in the next two decades. The inefficiency of the currently available therapies has prompted an urgent effort to develop new strategies that enable early diagnosis and improve response to treatment. Nanomedicine formulations can improve the pharmacokinetics and pharmacodynamics of conventional therapies and result in optimized cancer treatments. In particular, theranostic formulations aim at addressing the high heterogeneity of tumors and metastases by integrating imaging properties that enable a non-invasive and quantitative assessment of tumor targeting efficiency, drug delivery, and eventually the monitoring of the response to treatment. However, in order to exploit their full potential, the promising results observed in preclinical stages need to achieve clinical translation. Despite the significant number of available functionalization strategies, targeting efficiency is currently one of the major limitations of advanced nanomedicines in the oncology area, highlighting the need for more efficient nanoformulation designs that provide them with selectivity for precise cancer types and tumoral tissue. Under this current need, this review provides an overview of the strategies currently applied in the cancer theranostics field using magnetic nanoparticles (MNPs) and solid lipid nanoparticles (SLNs), where both nanocarriers have recently entered the clinical trials stage. The integration of these formulations into magnetic solid lipid nanoparticles—with different composition and phenotypic activity—constitutes a new generation of theranostic nanomedicines with great potential for the selective, controlled, and safe delivery of chemotherapy.
Development and Optimization of Nanolipid-Based Formulation of Diclofenac Sodium: In Vitro Characterization and Preclinical Evaluation
Authors: Zafar Ameeduzzafar , Alruwaili Nabil K , Imam Syed Sarim , Yasir Mohd , Alsaidan Omar Awad , Alquraini Ali , Rawaf Alenazy , Alsuwayt Bader , Anwer Md. Khalid , Alshehri Sultan , Ghoneim Mohammed M.
Published: February 2022

In the present research study, we formulate bilosomes (BMs) of diclofenac (DC) for oral delivery for enhancement of therapeutic efficacy (anti-inflammatory disease). The BMS were prepared by thin film hydration method and optimized by Box–Behnken design (BBD) using cholesterol (A), lipid (B), surfactant (C), and bile salt (D) as formulation factors. Their effects were evaluated on vesicle size (Y1) and entrapment efficacy (Y2). The optimized DC-BMs-opt showed a vesicle size of 270.21 ± 3.76 nm, PDI of 0.265 ± 0.03, and entrapment efficiency of 79.01 ± 2.54%. DSC study result revealed that DC-BMs-opt exhibited complete entrapment of DC in BM matrix. It also depicted significant enhancement (p < 0.05) in release (91.82 ± 4.65%) as compared to pure DC (36.32 ± 4.23%) and DC-liposomes (74.54 ± 4.76%). A higher apparent permeability coefficient (2.08 × 10−3 cm/s) was also achieved compared to pure DC (6.6 × 10−4 cm/s) and DC-liposomes (1.33 × 10−3 cm/s). A 5.21-fold and 1.43-fold enhancement in relative bioavailability was found relative to pure DC and DC liposomes (DC-LP). The anti-inflammatory activity result showed a significant (p < 0.05) reduction of paw edema swelling compared to pure DC and DC-LP. Our findings revealed that encapsulation of DC in BMs matrix is a good alternative for improvement of therapeutic efficacy.
Nanomicelle-Microsphere Composite as a Drug Carrier to Improve Lung-Targeting Specificity for Lung Cancer
Authors: Zhang Qianqian , Bao Jianwei , Duan Tijie , Hu Minxing , He Yuting , Wang Junwei , Hu Rongfeng , Tang Jihui
Published: February 2022

Lung cancer is the second-most common cancer and has the highest mortality among all cancer types. Nanoparticle (NP) drug delivery systems have been used to improve the therapeutic effectiveness of lung cancer, but rapid clearance and poor targeting limit their clinical utility. Here, we developed a nanomicelle-microsphere composite, in which doxorubicin (DOX) was loaded with spermine (Spm) modified poly (ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) micelles, and then the nanomicelles were noncovalently adsorbed on the surface of poly (lactic-co-glycolic acid) (PLGA) microspheres. The attachment was confirmed by scanning electron microscopy and confocal microscopy. In vitro cell experiments, MTT assays and intracellular uptake assays were used to demonstrate the cytotoxicity and the cellular uptake of micelles in A549 cells. In vivo biodistribution studies were conducted, an orthotopic lung cancer implantation model based on C57BL/6 mice was established, and then real-time fluorescence imaging analysis was used to study the targeted efficacy of the complex. A nanomicelle-microsphere composite was successively constructed. Moreover, Spm-modified micelles significantly enhanced cytotoxicity and displayed more efficient cellular uptake. Notably, an orthotopic lung cancer implantation model based on C57BL/6 mice was also successively established, and in vivo biodistribution studies confirmed that the complex greatly improved the distribution of DOX in the lungs and displayed notable tumor targeting. These results suggested that the nanomicelle-microsphere composite has potential application prospects in the targeted treatment of lung cancer.
Effect of Thrombopoietin Receptor Agonist on Pregnant Mice
Authors: Nakai Kensaku , Misugi Takuya , Kitada Kohei , Kurihara Yasushi , Tahara Mie , Hamuro Akihiro , Nakano Akemi , Koyama Masayasu , Kira Yukimi , Tachibana Daisuke
Published: February 2022

Thrombopoietin receptor agonists (TPO-RAs) are an effective treatment for refractory immune thrombocytopenia (ITP). However, the use of TPO-RAs is limited for ITP in pregnant women due to concerns about fetal toxicity. In this study, we examined the effects of romiplostim, one of the TPO-RAs, on pregnant mice. The mice were injected subcutaneously with romiplostim (1, 5, 10, 30, and 100 μg/kg) on gestational days (GD) 1, 8, and 15. We evaluated maternal and fetal platelet and megakaryocyte counts (MK), fetal weight at birth, placental morphology, and miscarriage rates. Romiplostim increased platelet and MK counts in pregnant mice at all doses and in fetuses at doses above 10 µg/kg. Fetal weight at birth was slightly reduced at a dose of 100 μg/kg, but there were no significant differences in placental weight, spiral artery wall thickness, placental growth factor signal changes, or the rate of resorption at that dosage. The dose of romiplostim used clinically for ITP patients (1–10 μg/kg) did not show any adverse effects on pregnant mice. Although the results of the present study are encouraging, until there are more conclusive data, the use of romiplostim should be evaluated individually in severe, life-threatening cases, and all relevant ethical aspects should be considered.
Targeting Protein Kinases and Epigenetic Control as Combinatorial Therapy Options for Advanced Prostate Cancer Treatment
Authors: Bagheri Soghra , Rahban Mahdie , Bostanian Fatemeh , Esmaeilzadeh Fatemeh , Bagherabadi Arash , Zolghadri Samaneh , Stanek Agata
Published: February 2022

Prostate cancer (PC), the fifth leading cause of cancer-related mortality worldwide, is known as metastatic bone cancer when it spreads to the bone. Although there is still no effective treatment for advanced/metastatic PC, awareness of the molecular events that contribute to PC progression has opened up opportunities and raised hopes for the development of new treatment strategies. Androgen deprivation and androgen-receptor-targeting therapies are two gold standard treatments for metastatic PC. However, acquired resistance to these treatments is a crucial challenge. Due to the role of protein kinases (PKs) in the growth, proliferation, and metastases of prostatic tumors, combinatorial therapy by PK inhibitors may help pave the way for metastatic PC treatment. Additionally, PC is known to have epigenetic involvement. Thus, understanding epigenetic pathways can help adopt another combinatorial treatment strategy. In this study, we reviewed the PKs that promote PC to advanced stages. We also summarized some PK inhibitors that may be used to treat advanced PC and we discussed the importance of epigenetic control in this cancer. We hope the information presented in this article will contribute to finding an effective treatment for the management of advanced PC.
Vardenafil Oral Dispersible Films (ODFs) with Advanced Dissolution, Palatability, and Bioavailability
Authors: Abou-Taleb Heba A. , Mustafa Wesam W. , Makram Tarek Saad , Abdelaty Lamiaa N. , Salem Hesham , Abdelkader Hamdy
Published: February 2022

Oral, quick response, and on demand, also known as a spontaneous oral treatment for erectile dysfunction, is highly needed by both patients and physicians. Vardenafil is selective (fewer side effects) and more effective in difficult-to-treat conditions than sildenafil. This study aims at fostering the dual objectives of using biomolecules such as artificial sweetening agents to solubilize and mask the bitterness of vardenafil loaded on biodegradable polymeric materials (PVA, MC, SA, and PVP K30) to fabricate oral, fast-dissolving films (vardenafil ODFs) in the mouth without the need for water to ingest the dosage form. Furthermore, coprecipitated-dispersed mixtures of vardenafil and three sweeteners (sorbitol, acesulfame K, and sucralose) were prepared and characterized using FTIR, DSC, and solubility studies. Moreover, eight different vardenafil ODFs were prepared using the solvent-casting method. Modified gustatory sensation test, in vitro disintegration, and release studies were performed. In addition, the optimized ODF (F8) was compared with the commercial film-coated tablets pharmacokinetically (relative bioavailability, onset, and duration of actions were estimated). The results indicated that the three sweetening agents had comparable solubilizing capacity. However, both sucralose- and acesulfame K-based ODFs have a more enhanced sweet and palatable taste than sorbitol-sweetened ODF. The SA- and PVP K30-based ODFs showed significantly faster disintegration times and release rates than MC. In conclusion, PVA has good film-forming properties, but a higher ratio of PVA adversely affected the disintegration and release characteristics. The % relative bioavailability for ODF was 126.5%, with a superior absorption rate constant (Ka) of 1.2-fold. The Cmax and estimated Tmax were compared to conventional film-coated tablets.
Pleiotropic Long-Term Effects of Atorvastatin on Posttraumatic Joint Contracture in a Rat Model
Authors: Wegner Erik , Slotina Ekaterina , Mickan Tim , Truffel Sebastian , Arand Charlotte , Wagner Daniel , Ritz Ulrike , Rommens Pol M. , Gercek Erol , Drees Philipp , Baranowski Andreas
Published: February 2022

The antifibrotic effect of atorvastatin has already been demonstrated in several organ systems. In the present study, a rat model was used to investigate the effect of atorvastatin on posttraumatic joint contracture. Forty-eight Sprague Dawley rats were equally randomized into an atorvastatin group and a control group. After initial joint trauma, knee joints were immobilized for intervals of 2 weeks (n = 16) or 4 weeks (n = 16) or immobilized for 4 weeks with subsequent remobilization for another 4 weeks (n = 16). Starting from the day of surgery, animals received either atorvastatin or placebo daily. After euthanasia at week 2, 4 or 8, joint contracture was determined, histological examinations were performed, and gene expression was assessed. The results suggest that the joint contracture was primarily arthrogenic. Atorvastatin failed to significantly affect contracture formation and showed a reduction in myofibroblast numbers to 98 ± 58 (control: 319 ± 113, p < 0.01) and a reduction in joint capsule collagen to 60 ± 8% (control: 73 ± 9%, p < 0.05) at week 2. Gene expression of α-smooth muscle actin (α-SMA), collagen type I, transforming growth factor β1 (TGF-β1) and interleukin-6 (IL-6) was not significantly affected by atorvastatin. Atorvastatin decreases myofibroblast number and collagen deposition but does not result in an improvement in joint mobility.
Optimization of the Micellar-Based In Situ Gelling Systems Posaconazole with Quality by Design (QbD) Approach and Characterization by In Vitro Studies
Authors: Durgun Meltem Ezgi , Mesut Burcu , Hacıoğlu Mayram , Güngör Sevgi , Özsoy Yıldız
Published: February 2022

Background: Fungal ocular infections can cause serious consequences, despite their low incidence. It has been reported that Posaconazole (PSC) is used in the treatment of fungal infections in different ocular tissues by diluting the oral suspension, and successful results were obtained despite low ocular permeation. Therefore, we optimized PSC-loaded ocular micelles and demonstrated that the permeation/penetration of PSC in ocular tissues was enhanced. Methods: The micellar-based in situ gels based on the QbD approach to increase the ocular bioavailability of PSC were developed. Different ratios of Poloxamer 407 and Poloxamer 188 were chosen as CMAs. Tsol/gel, gelling capacity and rheological behavior were chosen as CQA parameters. The data were evaluated by Minitab 18, and the formulations were optimized with the QbD approach. The in vitro release study, ocular toxicity, and anti-fungal activity of the optimized formulation were performed. Results: Optimized in situ gel shows viscoelastic property and becomes gel form at physiological temperatures even when diluted with the tear film. In addition, it has been shown that the formulation had high anti-fungal activity and did not have any ocular toxicity. Conclusions: In our previous studies, PSC-loaded ocular micelles were developed and optimized for the first time in the literature. With this study, the in situ gels of PSC for ocular application were developed and optimized for the first time. The optimized micellar-based in situ gel is a promising drug delivery system that may increase the ocular permeation and bioavailability of PSC.
Electrospun Poly(lactide) Fibers as Carriers for Controlled Release of Biochanin A
Authors: Gajić Ivana , Stojanović Sanja , Ristić Ivan , Ilić-Stojanović Snežana , Pilić Branka , Nešić Aleksandra , Najman Stevo , Dinić Ana , Stanojević Ljiljana , Urošević Maja , Nikolić Vesna , Nikolić Ljubiša
Published: February 2022

The aim of this study is to investigate the possibility of using electrospun polylactide (PLA) fibers as a carrier of the phytoestrogen biochanin A. Polylactide fibers were prepared with different contents of biochanin A by using an electrospinning method at specific process parameters. The obtained electrospun polylactide fibers, as carriers of biochanin A, were characterized by means of different methods. The presented results showed that the mechanical properties of PLA have not changed significantly in the presence of biochanin A. Scanning electron microscopy showed that the fine fiber structure is retained without visible deformations and biochanin A crystals on the surface of the fibres. The analysis by infrared spectroscopy showed that there are no strong interactions between polylactide and biochanin A molecules, which is a good prerequisite for the diffusion release of biochanin A from PLA fibers.The release of biochanin A from PLA fibers in buffer solution pH 7.4 at 37 °C was monitored by applying the HPLC method. The rate and time of the release of biochanin A from PLA fibers is in correlation with the amount of the active ingredient in the matrix of the carrier and follows zero-order kinetics. PLA fibers with biochanin A exhibit concentration-dependent activity on proliferation and migration of L929 fibroblasts in direct culture system in vitro, and proved to be suitable for a potential formulation for use in wound healing.