bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of High Fiber Rye, Compared to Refined Wheat, on Gut Microbiota Composition, Plasma Short Chain Fatty Acids, and Implications for Weight Loss and Metabolic Risk Factors (the RyeWeight Study)
Authors: Iversen Kia Nøhr , Dicksved Johan , Zoki Camille , Fristedt Rikard , Pelve Erik A. , Langton Maud , Landberg Rikard
Published: April 2022

Consumption of whole grain and cereal fiber have been inversely associated with body weight and obesity measures in observational studies but data from large, long-term randomized interventions are scarce. Among the cereals, rye has the highest fiber content and high rye consumption has been linked to increased production of gut fermentation products, as well as reduced risks of obesity and metabolic disease. The effects on body weight and metabolic risk factors may partly be mediated through gut microbiota and/or their fermentation products. We used data from a randomized controlled weight loss trial where participants were randomized to a hypocaloric diet rich in either high fiber rye foods or refined wheat foods for 12 weeks to investigate the effects of the intervention on gut microbiota composition and plasma short chain fatty acids, as well as the potential association with weight loss and metabolic risk markers. Rye, compared to wheat, induced some changes in gut microbiota composition, including increased abundance of the butyrate producing Agathobacter and reduced abundance of [Ruminococcus] torques group, which may be related to reductions in low grade inflammation caused by the intervention. Plasma butyrate increased in the rye group. In conclusion, intervention with high fiber rye foods induced some changes in gut microbiota composition and plasma short chain fatty acid concentration, which were associated with improvements in metabolic risk markers as a result of the intervention.
Astragalus membranaceus Enhances Myotube Hypertrophy through PI3K-Mediated Akt/mTOR Signaling Phosphorylation
Authors: Yeh Tzu-Shao , Lei Tze-Huan , Liu Jen-Fang , Hsu Mei-Chich
Published: April 2022

Astragalus membranaceus (AM) is classified as a high-class traditional herbal medicine, which has strengthened vitality and multifunctional pharmacological activities, but limited empirical evidence is available to support its effects in muscular hypertrophy. It evokes skeletal muscle hypertrophy by increasing anabolic pathway, which is essential to prevent sarcopenia in elderly population. In this study, we examined the effects of AM on skeletal muscle hypertrophy by focusing on the molecular mechanism. We employed an in vitro model to investigate whether AM-treated skeletal muscle, as represented by myotube C2C12 cells, was hypertrophic, and to further investigate the efficacy of AM-activated phosphorylation of PI3K/Akt/mTOR signaling that must occur prior to myotube hypertrophy. The results showed that the myotubes formed larger multinucleated myotubes with increased diameter and thickness (1.16-fold relative to control group, p < 0.05). Administration of PI3K and mTOR inhibitors abolished AM-induced muscular hypertrophy. Moreover, AM-induced PI3K-mediated myotube hypertrophy was accompanied by the activation of Akt and mTOR signaling. We concluded that the AM is a nutritional activator to enhance muscular hypertrophy by increasing PI3K/Akt/mTOR signaling phosphorylation. As the AM is effective in myotube hypertrophy, AM and its derivatives may be promising candidates for ergogenic aid to prevent sarcopenia.
iTRAQ-Based Quantitative Proteomics Reveals the Energy Metabolism Alterations Induced by Chlorogenic Acid in HepG2 Cells
Authors: Takahashi Shoko , Saito Kenji , Li Xuguang , Jia Huijuan , Kato Hisanori
Published: April 2022

Epidemiological studies have suggested that coffee consumption is associated with a decrease in the risk of developing obesity and diabetes; however, the detailed mechanisms underlying these effects of coffee consumption remain poorly understood. In this study, we examined the effects of chlorogenic acid on energy metabolism in vitro. Hepatocellular carcinoma G2 (HepG2) cells were cultured in a medium containing chlorogenic acid. Chlorogenic acid increased the activity of mitochondrial enzymes, including citrate synthase, isocitrate dehydrogenase, and malate dehydrogenase (MDH), which are involved in the tricarboxylic acid (TCA) cycle. Proteome analysis using the isobaric tags for the relative and absolute quantitation (iTRAQ) method revealed the upregulation of proteins involved in the glycolytic system, electron transport system, and ATP synthesis in mitochondria. Therefore, we propose a notable mechanism whereby chlorogenic acid enhances energy metabolism, including the TCA cycle, glycolytic system, electron transport, and ATP synthesis. This mechanism provides important insights into understanding the beneficial effects of coffee consumption.
What about TSH and Anti-Thyroid Antibodies in Patients with Autoimmune Thyroiditis and Celiac Disease Using a Gluten-Free Diet? A Systematic Review
Authors: Malandrini Sabrina , Trimboli Pierpaolo , Guzzaloni Gabriele , Virili Camilla , Lucchini Barbara
Published: April 2022

The prevalence of celiac disease (CD) in patients with chronic autoimmune thyroiditis (CAIT) is estimated to be between 2 and 7.8%. A gluten-free diet (GFD) in patients with CD is suggested to have a beneficial effect on CAIT. Thus, the present systematic review was undertaken to achieve more robust evidence about the change in thyroid stimulating hormone (TSH) and thyroid-specific antibodies (T-Ab) levels obtained in CD patients following a GFD. A specific search strategy was planned. The last search was performed on March 2022. The following data were mainly searched for in order to be extracted: sample size, mean and/or median with standard deviation (SD), and error (SE), individually, of thyroid hormones and T-Ab at baseline and after GFD, and the duration of the study. The initial search retrieved 297 records and 6 articles met the inclusion criteria. In total, 50 patients with both CD and CAIT and 45 controls were reported. The effects of a GFD on the thyroid hormonal and immunological profile could be extracted only in a part of the studies. Two studies were case reports. A low risk of bias was observed. These findings advise further studies, ideally randomized, in order to better investigate the potential relationship between GFD and thyroid homeostasis. The level of evidence is not still sufficient to recommend GFD to patients with CAIT.
Potential Effects of Sucralose and Saccharin on Gut Microbiota: A Review
Authors: del Pozo Susana , Gómez-Martínez Sonia , Díaz Ligia E. , Nova Esther , Urrialde Rafael , Marcos Ascensión
Published: April 2022

Artificial sweeteners are additives widely used in our diet. Although there is no consensus, current evidence indicates that sucralose and saccharin could influence the gut microbiota. The aim of this study was to analyze the existing scientific evidence on the effects of saccharin and sucralose consumption on gut microbiota in humans. Different databases were used with the following search terms: sweeteners, non-caloric-sweeteners, sucralose, splenda, saccharin, sugartwin, sweet’n low, microbiota, gut microbiota, humans, animal model, mice, rats, and/or in vitro studies. In vitro and animal model studies indicate a dose-dependent relationship between the intake of both sweeteners and gut microbiota affecting both diversity and composition. In humans, long-term study suggests the existence of a positive correlation between sweetener consumption and some bacterial groups; however, most short-term interventions with saccharin and sucralose, in amounts below the ADI, found no significant effect on those groups, but there seems to be a different basal microbiota-dependent response of metabolic markers. Although studies in vitro and in animal models seem to relate saccharin and sucralose consumption to changes in the gut microbiota, more long-term studies are needed in humans considering the basal microbiota of participants and their dietary and lifestyle habits in all population groups. Toxicological and basal gut microbiota effects must be included as relevant factors to evaluate food safety and nutritional consequences of non-calorie sweeteners. In humans, doses, duration of interventions, and number of subjects included in the studies are key factors to interpret the results.
Human Dento-Facial Evolution: Cranial Capacity, Facial Expression, Language, Oral Complications and Diseases
Authors: Nowzari Hessam , Jorgensen Michael
Published: April 2022

Objectives: To review dento-facial evolution based on fossil data, comparative anatomy, developmental biology and genetics. Modern human evolution reveals profound insight into the technical and biological challenges faced by clinicians in daily practice of dentistry. Materials and Methods: An analysis and review of the literature is presented to further explain the evolutionary forces that have shaped hominins. Results: Modern human evolutionary morphological and biological adaptations allowed improvement of cognitive ability, facial expression, smile and language. However, the increased cranial capacity correlates inversely with a decrease in size of the maxillary and mandibular bones, weakening of the muscles and facial shortening, contributing to dento-facial complications. Moreover, the distinctive differences in origin and development of the dento-facial components have further contributed to these maladies. In addition, human lifestyle transition from nomadic to sedentary increased the incidence of oral diseases. Conclusions: Knowledge of human evolutionary patterns can improve the quality of response by clinicians to biological challenges. The limitations in current treatment modalities can be explained, in part, due to the complexity of the life forms that resulted from evolution. Although there are no rules to predict how evolutionary forces will shape modern humans, the evolution of the dento-facial complex reveals profound insight into our connection to other forms of life and nature.
Prevalence of Tick-Borne Pathogens in Questing Ixodes ricinus and Dermacentor reticulatus Ticks Collected from Recreational Areas in Northeastern Poland with Analysis of Environmental Factors
Authors: Grochowska Anna , Dunaj-Małyszko Justyna , Pancewicz Sławomir , Czupryna Piotr , Milewski Robert , Majewski Piotr , Moniuszko-Malinowska Anna
Published: April 2022

Ticks, such as Ixodes ricinus and Dermacentor reticulatus, act as vectors for multiple pathogens posing a threat to both human and animal health. As the process of urbanization is progressing, those arachnids are being more commonly encountered in urban surroundings. In total, 1112 I. ricinus (n = 842) and D. reticulatus (n = 270) ticks were collected from several sites, including recreational urban parks, located in Augustów and Białystok, Poland. Afterwards, the specimens were examined for the presence of Borrelia spp., Babesia spp., Anaplasma phagocytophilum, Rickettsia spp., Bartonella spp., and Coxiella burnetii using the PCR method. Overall obtained infection rate reached 22.4% (249/1112). In total, 26.7% (225/842) of I. ricinus was infected, namely with Borrelia spp. (25.2%; 212/842), Babesia spp. (2.0%; 17/842), and A. phagocytophilum (1.2%; 10/842). Among D. reticulatus ticks, 8.9% (24/270) were infected, specifically with Babesia spp. (7.0%; 19/270), A. phagocytophilum (1.1%; 3/270), and Borrelia burgdorferi s.l. (0.7%; 2/270). No specimen tested positively for Rickettsia spp., Bartonella spp., or Coxiella burnetii. Co-infections were detected in 14 specimens. Results obtained in this study confirm that I. ricinus and D. reticulatus ticks found within the study sites of northeastern Poland are infected with at least three pathogens. Evaluation of the prevalence of pathogens in ticks collected from urban environments provides valuable information, especially in light of the growing number of tick-borne infections in humans and domesticated animals.
Ecological Niche Model of Bacillus cereus Group Isolates Containing a Homologue of the pXO1 Anthrax Toxin Genes Infecting Metalworkers in the United States
Authors: Deka Mark A. , Marston Chung K. , Garcia-Diaz Julia , Drumgoole Rahsaan , Traxler Rita M.
Published: April 2022

While Bacillus cereus typically causes opportunistic infections in humans, within the last three decades, severe and fatal infections caused by isolates of the B. cereus group harboring anthrax toxin genes have been reported in the United States. From 1994 to 2020, seven cases of anthrax-like illness resulting from these isolates have been identified. With one exception, the cases have occurred in the Gulf States region of the United States among metalworkers. We aimed to develop an ecological niche model (ENM) to estimate a spatial area conducive to the survival of these organisms based on the presence of known human infections and environmental variables. The estimated ecological niche for B. cereus was modeled with the maximum entropy algorithm (Maxent). Environmental variables contributing most to the model were soil characteristics (cation exchange capacity, carbon content, soil pH), temperature, enhanced vegetation index (EVI), and land surface temperature (LST). Much of the suitable environments were located throughout the Gulf Coast Plain, Texas Backland Prairies, East Central Texas Plains, Edwards Plateau, Cross Timbers, Mississippi Alluvial Plain, and Central Great Plains. These findings may provide additional guidance to narrow potential risk areas to efficiently communicate messages to metalworkers and potentially identify individuals who may benefit from the anthrax vaccine.
Predictive Models for Weekly Cattle Mortality after Arrival at a Feeding Location Using Records, Weather, and Transport Data at Time of Purchase
Authors: Wisnieski Lauren , Amrine David E. , Renter David G.
Published: April 2022

Feedlot mortality negatively affects animal welfare and profitability. To the best of our knowledge, there are no publications on predictive models for weekly all-cause mortality in feedlot cattle. In this study, random forest models to predict weekly mortality for cattle purchase groups (n = 14,217 purchase groups; 860,545 animals) from arrival at the feeding location (Day 1) to Day 42 and cumulative mortality from Day 43 until slaughter were built using records, weather, and transport data available at the time of purchase. Models were evaluated by calculating the root mean squared error (RMSE) and accuracy (as defined as the percent of purchase groups that had predictions within 0.25% and 0.50% of actual mortality). The models had high accuracy (>90%), but the RMSE estimates were high (range = 1.0% to 4.1%). The best predictors were maximum temperature and purchase weight, although this varied by week. The models performed well among purchase groups with low weekly mortality but performed poorly in high mortality purchase groups. Although high mortality purchase groups were not accurately predicted utilizing the models in this study, the models may potentially have utility as a screening tool for very low mortality purchase groups after arrival. Future studies should consider building iterative models that utilize the strongest predictors identified in this study.
Viral Etiological Agent(s) of Respiratory Tract Infections in Symptomatic Individuals during the Second Wave of COVID-19 Pandemic: A Single Drive-Thru Mobile Collection Site Study
Authors: Kozinska Aleksandra , Wegrzynska Karolina , Komiazyk Magdalena , Walory Jaroslaw , Wasko Izabela , Baraniak Anna
Published: April 2022

One of the tools to contain the SARS-CoV-2 pandemic was to increase the number of performed tests and to improve the access to diagnostics. To this effect, mobile collection sites (MCSs) were established. This study was performed on samples collected at the MCS between November 2020 and March 2021. We aimed to confirm/exclude SARS-CoV-2, differentiate SARS-CoV-2 variants, and detect other respiratory pathogens. SARS-CoV-2 and other respiratory viruses were identified by RT-qPCRs. A total of 876 (46.35%) SARS-CoV-2 positive specimens in the diagnostic tests were identified. The wild-type variant was determined in 667 (76.14%) samples; the remaining 209 (23.86%) samples specimens were identified as Alpha variant. A total of 51 (5.6%) non-SARS-CoV-2 cases were detected in retrospective studies. These accounted for 33 cases of mono-infection including rhinovirus (RV), human adenovirus (HAdV), human metapneumovirus (HMPV), enterovirus (EV), and influenza virus, and 18 cases of co-infection (SARS-CoV-2 with RV or HAdV or HMPV, and RV with EV). Our research shows that the results obtained from the MCS have value in epidemiological studies, reflecting national trends on a micro scale. Although the spread of COVID-19 is a major public health concern, SARS-CoV-2 is not the only pathogen responsible for respiratory infections.
Outer Membrane Vesicles of Avian PathogenicEscherichia coli Mediate the Horizontal Transmission of blaCTX-M-55
Authors: Li Chao , Wen Renqiao , Mu Rongrong , Chen Xuan , Ma Peng , Gu Kui , Huang Zheren , Ju Zijing , Lei Changwei , Tang Yizhi , Wang Hongning
Published: April 2022

The CTX-M-55 type extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae is increasing in prevalence worldwide without the transmission mechanism being fully clarified, which threatens public and livestock health. Outer membrane vesicles (OMVs) have been shown to mediate the gene horizontal transmission in some species. However, whether blaCTX-M-55 can be transmitted horizontally through OMVs in avian pathogenic Escherichia coli (APEC) has not been reported yet. To test this hypothesis, an ESBL-producing APEC was isolated and whole-genome sequencing (WGS) was performed to analyze the location of blaCTX-M-55. Ultracentrifugation and size exclusion chromatography was used to isolate and purify OMVs, and the transfer experiment of blaCTX-M-55 via OMVs was performed finally. Our results showed that the blaCTX-M-55 was located on an IncI2 plasmid. The number and diameter of OMVs secreted by ESBL-producing APEC treated with different antibiotics were significantly varied. The transfer experiment showed that the OMVs could mediate the horizontal transfer of blaCTX-M-55, and the frequency of gene transfer ranged from 10−5 to 10−6 CFU/mL with the highest frequency observed in the Enrofloxacin treatment group. These findings contribute to a better understanding of the antibiotics in promoting and disseminating resistance in the poultry industry and support the restrictions on the use of antibiotics in the poultry industry.
New Genetic Bomb Trigger: Design, Synthesis, Molecular Dynamics Simulation, and Biological Evaluation of Novel BIBR1532-Related Analogs Targeting Telomerase against Non-Small Cell Lung Cancer
Authors: Tawfik Haytham O. , El-Hamaky Anwar A. , El-Bastawissy Eman A. , Shcherbakov Kirill A. , Veselovsky Alexander V. , Gladilina Yulia A. , Zhdanov Dmitry D. , El-Hamamsy Mervat H.
Published: April 2022

Telomeres serve a critical function in cell replication and proliferation at every stage of the cell cycle. Telomerase is a ribonucleoprotein, responsible for maintaining the telomere length and chromosomal integrity of frequently dividing cells. Although it is silenced in most human somatic cells, telomere restoration occurs in cancer cells because of telomerase activation or alternative telomere lengthening. The telomerase enzyme is a universal anticancer target that is expressed in 85–95% of cancers. BIBR1532 is a selective non-nucleoside potent telomerase inhibitor that acts by direct noncompetitive inhibition. Relying on its structural features, three different series were designed, and 30 novel compounds were synthesized and biologically evaluated as telomerase inhibitors using a telomeric repeat amplification protocol (TRAP) assay. Target compounds 29a, 36b, and 39b reported the greatest inhibitory effect on telomerase enzyme with IC50 values of 1.7, 0.3, and 2.0 μM, respectively, while BIBR1532 displayed IC50 = 0.2 μM. Compounds 29a, 36b, and 39b were subsequently tested using a living-cell TRAP assay and were able to penetrate the cell membrane and inhibit telomerase inside living cancer cells. Compound 36b was tested for cytotoxicity against 60 cancer cell lines using the NCI (USA) procedure, and the % growth was minimally impacted, indicating telomerase enzyme selectivity. To investigate the interaction of compound 36b with the telomerase allosteric binding site, molecular docking and molecular dynamics simulations were used.
Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox
Authors: Kane Aidan , Carter Dee A.
Published: April 2022

Fungal infections impact the lives of at least 12 million people every year, killing over 1.5 million. Wide-spread use of fungicides and prophylactic antifungal therapy have driven resistance in many serious fungal pathogens, and there is an urgent need to expand the current antifungal arsenal. Recent research has focused on improving azoles, our most successful class of antifungals, by looking for synergistic interactions with secondary compounds. Synergists can co-operate with azoles by targeting steps in related pathways, or they may act on mechanisms related to resistance such as active efflux or on totally disparate pathways or processes. A variety of sources of potential synergists have been explored, including pre-existing antimicrobials, pharmaceuticals approved for other uses, bioactive natural compounds and phytochemicals, and novel synthetic compounds. Synergy can successfully widen the antifungal spectrum, decrease inhibitory dosages, reduce toxicity, and prevent the development of resistance. This review highlights the diversity of mechanisms that have been exploited for the purposes of azole synergy and demonstrates that synergy remains a promising approach for meeting the urgent need for novel antifungal strategies.
Development and Characterization of Eudragit® EPO-Based Solid Dispersion of Rosuvastatin Calcium to Foresee the Impact on Solubility, Dissolution and Antihyperlipidemic Activity
Authors: Inam Sana , Irfan Muhammad , Lali Noor ul ain , Khalid Syed Haroon , Asghar Sajid , Khan Ikram Ullah , Khan Salah-Ud-Din , Iqbal Muhammad Shahid , Zaheer Imran , Khames Ahmed , Abou-Taleb Heba A. , Abourehab Mohammad A. S.
Published: April 2022

Poor solubility is the major challenge involved in the formulation development of new chemical entities (NCEs), as more than 40% of NCEs are practically insoluble in water. Solid dispersion (SD) is a promising technology for improving dissolution and, thereby, the bioavailability of poorly soluble drugs. This study investigates the influence of a pH-sensitive acrylate polymer, EPO, on the physicochemical properties of rosuvastatin calcium, an antihyperlipidemic drug. In silico docking was conducted with numerous polymers to predict drug polymer miscibility. The screened-out polymer was used to fabricate the binary SD of RoC in variable ratios using the co-grinding and solvent evaporation methods. The prepared formulations were assessed for physiochemical parameters such as saturation solubility, drug content and in vitro drug release. The optimized formulations were further ruled out using solid-state characterization (FTIR, DSC, XRD and SEM) and in vitro cytotoxicity. The results revealed that all SDs profoundly increased solubility as well as drug release. However, the formulation RSE-2, with a remarkable 71.88-fold increase in solubility, presented 92% of drug release in the initial 5 min. The molecular interaction studied using FTIR, XRD, DSC and SEM analysis evidenced the improvement of in vitro dissolution. The enhancement in solubility of RoC may be important for the modulation of the dyslipidemia response. Therefore, pharmacodynamic activity was conducted for optimized formulations. Our findings suggested an ameliorative effect of RSE-2 in dyslipidemia and its associated complications. Moreover, RSE-2 exhibited nonexistence of cytotoxicity against human liver cell lines. Convincingly, this study demonstrates that SD of RoC can be successfully fabricated by EPO, and have all the characteristics that are favourable for superior dissolution and better therapeutic response to the drug.
Chiral Recognition R- and RS- of New Antifungal: Complexation/Solubilization/Dissolution Thermodynamics and Permeability Assay
Authors: Volkova Tatyana V. , Simonova Olga R. , Levshin Igor B. , Perlovich German L.
Published: April 2022

Novel potential antifungal of 1,2,4-triazole class have been synthesized as pure enantiomer (R-98) and racemic (RS-186). The effect of 2-hydroxypropyl-β-cyclodextrin (CD) on the solubility and permeability of RS-186 and R-98 in terms of chiral recognition was investigated. Phase solubility studies were carried out at 4 temperatures in 0–0.05 M CD concentration range for pH 2.0 and pH 7.4. AL- and AL−-type phase-solubility profiles were obtained for both compounds in pH 2.0 and pH 7.4. The racemic formed more stable complexes with CD as compared to R-isomer. Disclosing of chiral discrimination was facilitated using the approach based on the complex consideration of the derived complexation/solubilization/inherent dissolution thermodynamic functions, including the differential parameters between the racemic compound and R-enantiomer. The differences in the thermodynamic parameters determined by the chirality were discussed in terms of the driving forces of the processes and the main interactions of the compounds with CD in solution. The membrane permeability of both samples in the presence of CD was accessed in order to evaluate the specificity of enantioselective transport through the lipophilic membrane. The solubility/permeability interrelation was disclosed. The investigated compounds were classified as medium permeable in pure buffers and low permeable in the presence of 0.01 M CD. The obtained results can be useful for the design of pharmaceutical products in the form of liquid formulations based on the investigated substances.
Ovarian Follicular Growth through Intermittent Vaginal Gonadotropin Administration in Diminished Ovarian Reserve Women
Authors: Hsu Chao-Chin , Hsu Isabel , Lee Li-Hsuan , Hsu Rosie , Hsueh Yuan-Shuo , Lin Chih-Ying , Chang Hui Hua
Published: April 2022

It is a challenge to obtain enough oocytes during in vitro fertilization (IVF) in women who have a poor ovarian response (POR) in achieving conception. We have adopted the characteristics of the first uterine pass effect, which we pioneered in employing the vaginal administration of gonadotropins in women receiving IVF treatments. In our previous study employing vaginal administration, faster absorption and slower elimination of gonadotropins were demonstrated, and, female subjects presented proper ovarian follicle growth and pregnancy rates. In this study, during 2016–2020, 300 to 675 IU of gonadotropins were administered vaginally every three days in 266 POR women for their controlled ovarian hyperstimulation (COH). The injections were performed with needles angled at 15–30° towards the middle-upper portions of the bilateral vaginal wall, with an injection depth of 1–2 mm. For the COH results, these women, on average, received 3.0 ± 0.9 vaginal injections and a total dose of 1318.4 ± 634.4 IU gonadotropins, resulting in 2.2 ± 1.9 mature oocytes and 1.0 ± 1.2 good embryos. Among these embryos, 0.9 ± 1.0 were transferred to reach a clinical pregnancy rate of 18.1% and a live birth rate of 16.7%. In conclusion, the intermittent vaginal administration of gonadotropins proved to be effective in POR women for their IVF treatments.
Assessment of the Extrusion Process and Printability of Suspension-Type Drug-Loaded AffinisolTM Filaments for 3D Printing
Authors: Mora-Castaño Gloria , Millán-Jiménez Mónica , Linares Vicente , Caraballo Isidoro
Published: April 2022

Three-dimensional (3D) printing technology enables the design of new drug delivery systems for personalised medicine. Polymers that can be molten are needed to obtain extruded filaments for Fused Deposition Modelling (FDM), one of the most frequently employed techniques for 3D printing. The aim of this work was to evaluate the extrusion process and the physical appearance of filaments made of a hydrophilic polymer and a non-molten model drug. Metformin was used as model drug and Affinisol™ 15LV as the main carrier. Drug-loaded filaments were obtained by using a single-screw extruder and, subsequently, their printability was tested. Blends containing up to a 60% and 50% drug load with 5% and 7.5% of auxiliary excipients, respectively, were successfully extruded. Between the obtained filaments, those containing up to 50% of the drug were suitable for use in FDM 3D printing. The studied parameters, including residence time, flow speed, brittleness, and fractal dimension, reflect a critical point in the extrusion process at between 30–40% drug load. This finding could be essential for understanding the behaviour of filaments containing a non-molten component.
Tolmetin Sodium Fast Dissolving Tablets for Rheumatoid Arthritis Treatment: Preparation and Optimization Using Box-Behnken Design and Response Surface Methodology
Authors: Elsayed Mahmoud M. A. , Aboelez Moustafa O. , Elsadek Bakheet E. M. , Sarhan Hatem A. , Khaled Khaled Ali , Belal Amany , Khames Ahmed , Hassan Yasser A. , Abdel-Rheem Amany A. , Elkaeed Eslam B. , Raafat Mohamed , Elsadek Mahmoud Elkot Mostafa
Published: April 2022

Tolmetin sodium (TLM) is a non-steroidal anti-inflammatory drug (NSAIDs). TLM is used to treat inflammation, skeletal muscle injuries, and discomfort associated with bone disorders. Because of the delayed absorption from the gastro intestinal tract (GIT), the currently available TLM dosage forms have a rather protracted start to the effect, according to pharmacokinetic studies. The aim of this study was to create a combination for TLM fast dissolving tablets (TLM-FDT) that would boost the drug’s bioavailability by increasing pre-gastric absorption. The TLM-FDTs were developed using a Box-Behnken experimental design with varied doses of crospovidone (CP), croscarmellose sodium (CCS) as super-disintegrants, and camphor as a sublimating agent. In addition, the current study used response surface approach to explore the influence of various formulation and process factors on tablet qualities in order to verify an optimized TLM-FDTs formulation. The optimized TLM-FDTs formula was subsequently evaluated for its in vivo anti-inflammatory activity. TLM-FDTs have good friability, disintegration time, drug release, and wetting time, as well as fast disintegration and dissolution behavior. Significant increase in drug bioavailability and reliable anti-inflammatory efficacy were also observed, as evidenced by considerable reductions in paw thickness in rats following carrageenan-induced rat paw edema. For optimizing and analyzing the effect of super-disintegrants and sublimating agents in the TLM-FDTs formula, the three-factor, three-level full factorial design is a suitable tool. TLM-FDTs are a possible drug delivery system for enhancing TLM bioavailability and could be used to treat rheumatoid arthritis.
Correction: Kazmi et al. Formulation and Evaluation of Kaempferol Loaded Nanoparticles against Experimentally Induced Hepatocellular Carcinoma: In Vitro and In Vivo Studies. Pharmaceutics 2021, 13, 2086
Authors: Kazmi Imran , Al-Abbasi Fahad A. , Afzal Muhammad , Altayb Hisham N. , Nadeem Muhammad Shahid , Gupta Gaurav
Published: April 2022

In the original publication [...]
Nanocarrier Drug Delivery Systems: Characterization, Limitations, Future Perspectives and Implementation of Artificial Intelligence
Authors: Alshawwa Samar Zuhair , Kassem Abeer Ahmed , Farid Ragwa Mohamed , Mostafa Shaimaa Khamis , Labib Gihan Salah
Published: April 2022

There has been an increasing demand for the development of nanocarriers targeting multiple diseases with a broad range of properties. Due to their tiny size, giant surface area and feasible targetability, nanocarriers have optimized efficacy, decreased side effects and improved stability over conventional drug dosage forms. There are diverse types of nanocarriers that have been synthesized for drug delivery, including dendrimers, liposomes, solid lipid nanoparticles, polymersomes, polymer–drug conjugates, polymeric nanoparticles, peptide nanoparticles, micelles, nanoemulsions, nanospheres, nanocapsules, nanoshells, carbon nanotubes and gold nanoparticles, etc. Several characterization techniques have been proposed and used over the past few decades to control and predict the behavior of nanocarriers both in vitro and in vivo. In this review, we describe some fundamental in vitro, ex vivo, in situ and in vivo characterization methods for most nanocarriers, emphasizing their advantages and limitations, as well as the safety, regulatory and manufacturing aspects that hinder the transfer of nanocarriers from the laboratory to the clinic. Moreover, integration of artificial intelligence with nanotechnology, as well as the advantages and problems of artificial intelligence in the development and optimization of nanocarriers, are also discussed, along with future perspectives.
An Overview of Cell Membrane Perforation and Resealing Mechanisms for Localized Drug Delivery
Authors: He Stephanie , Singh Davindra , Helfield Brandon
Published: April 2022

Localized and reversible plasma membrane disruption is a promising technique employed for the targeted deposition of exogenous therapeutic compounds for the treatment of disease. Indeed, the plasma membrane represents a significant barrier to successful delivery, and various physical methods using light, sound, and electrical energy have been developed to generate cell membrane perforations to circumvent this issue. To restore homeostasis and preserve viability, localized cellular repair mechanisms are subsequently triggered to initiate a rapid restoration of plasma membrane integrity. Here, we summarize the known emergency membrane repair responses, detailing the salient membrane sealing proteins as well as the underlying cytoskeletal remodeling that follows the physical induction of a localized plasma membrane pore, and we present an overview of potential modulation strategies that may improve targeted drug delivery approaches.
Evaluating Students’ COVID-19 Knowledge, Attitudes and Practices (COVKAP) during the COVID-19 Pandemic
Authors: Axon David R. , Cernasev Alina , Desai Meghana , Connor Sharon E. , Jonkman Lauren J. , Sekar M. Chandra
Published: April 2022

The COVID-19 pandemic led to significant disruption in students’ lives through lockdowns, restricted movement, remote instruction, and mixed information. Therefore, this study aimed to capture the knowledge, attitudes, and practices of student pharmacists during 2020–2021. A 43-item COVID-19 Knowledge, Attitudes, and Practices (COVKAP) survey previously developed was administered at four schools of pharmacy across the U.S. during Fall 2020 and Spring 2021. A total of 418 responses were analyzed from graduating classes of 2021–2024. There were no significant differences in correct COVID-19 knowledge responses across the four graduating years. Respondents’ attitudes around COVID-19 were homogenous with the exception for their belief in their preparedness to administer COVID-19 vaccines. Respondents reported wearing masks daily (76.8%), infrequently visiting restaurants (82.1%), practicing social distancing daily (45.7%), and referring to medical journals for information (72%). In conclusion, during the pandemic, student pharmacists experienced significant changes in their academic lives. Their knowledge and subsequent attitudes and practices were consistent with the state of evidence during Fall 2020 and Spring 2021. Subsequently, as newer information has emerged, the authors suggest that the COVKAP survey may be modified and administered frequently to address student needs and concerns as the pandemic evolves.
Effects of Atmospheric Turbulence on Optical Wireless Communication in NEOM Smart City
Authors: Alatawi Ayshah S. , Youssef Albashir A. , Abaza Mohamed , Uddin Mohammad Ammad , Mansour Ali
Published: April 2022

The foundation of any smart city requires an innovative and robust communication infrastructure. Many research communities envision free-space optical communication (FSO) as a promising backbone technology for the services and applications provided by such cities. However, the channel through which the FSO signal travels is the atmosphere. Therefore, the FSO performance is limited by the local weather conditions. The variation in meteorological variables leads to variations of the refractive index along the transmission path. These index inhomogeneities (i.e., atmospheric turbulence) can significantly degrade the performance of FSO systems. Thus, a practical implementation of the FSO link must carefully consider the atmospheric turbulence effect. This paper aims to investigate the feasibility of FSO communication for NEOM, a promising smart city in Saudi Arabia. We study the effect of weather conditions on FSO links using the micrometeorology model, taking into account actual weather data. The FSO performance in winter and summer was compared in terms of the bit error rate, signal-to-noise ratio (SNR), link availability, and transmission distance. The study shows that the atmospheric turbulence strength is moderate and strong in winter and summer, respectively. The temperature has the biggest impact on the FSO system when compared to the other meteorological elements included in this study. Furthermore, at transmission distances less than 300 m, atmospheric turbulence does not significantly affect the FSO for the operating wavelength of 1550 nm. Furthermore, it has been shown that at transmission distances greater than 300 m, the SNR in summer is more than 18% higher than in winter. The findings of this research enable understanding of the effect of turbulence caused by NEOM weather on the FSO link, thus assisting engineers in establishing a reliable FSO backbone link by adjusting the relevant parameters.
Improving the Stochastic Feedback Cooling of a Mechanical Oscillator Using a Degenerate Parametric Amplifier
Authors: Ye Xiaoqian , Huang Sumei , Deng Li , Chen Aixi
Published: April 2022

Cooling of a macroscopic mechanical resonator to extremely low temperatures is a necessary condition to observe a variety of macroscopic quantum phenomena. Here, we study the stochastic feedback cooling of a mechanical resonator in an optomechanical system with a degenerate optical parametric amplifier (OPA). In the bad-cavity limit, we find that the OPA can enhance the cooling of the movable mirror in the stochastic feedback cooling scheme. The movable mirror can be cooled from 132 mK to 0.033 mK, which is lower than that without the OPA by a factor of about 5.
A Scoping Review of the Efficacy of Diode Lasers Used for Minimally Invasive Exposure of Impacted Teeth or Teeth with Delayed Eruption
Authors: Borzabadi-Farahani Ali
Published: April 2022

Background: The use of diode lasers for oral surgery soft tissue procedures is associated with less pain and bleeding, quick recovery, and better surgical site visibility. Objectives: This scoping review identifies and analyses the evidence evaluating the efficacy of the diode laser surgical exposure of impacted teeth or teeth with delayed eruption (both with no overlaying bone) vs. conventional scalpel surgical exposure. Materials and Methods: The PubMed/Medline, SCOPUS, and Google Scholar databases were searched up to January 2022 for randomized clinical trials and case-control studies comparing diode laser impacted-tooth surgical exposure vs. conventional surgical methods. Furthermore, the surgical exposure of an impacted mandibular canine or premolars with a 940 nm (InGaAsP) diode laser was presented. Results: The literature search revealed no high-quality evidence. However, four prospective studies were identified. Diode laser application was associated with less pain or analgesic need, minimal/no bleeding, and no need for suturing after surgery. The laser wavelengths used were 808, 810, 935, and 980 nm. A comparison of the study outcomes was not possible; all the studies had methodological issues and their funding sources were not mentioned. Conclusions: Adequately powered clinical trials are needed for comparing outcomes from diode laser surgical exposure vs. conventional methods, identifying the ideal laser characteristics, and assessing the long-term periodontal health of laser-exposed teeth and any potential risks.
Optical Frequency Comb-Based Direct Two-Photon Cooling for Cold Atom Clock
Authors: Dan Lin , Xu Hao , Guo Ping , Zhao Jianye
Published: April 2022

The performance of the cold atom clock based on coherent population trapping (CPT) improved when the temperature decreased. In order to obtain a lower temperature in the cold atom clock, we proposed a cooling scheme in this paper that employs direct two-photon transition using optical frequency combs (OFCs). Two trains of time-delayed pulses from opposite directions were utilized to interact with atoms. It was found that the temperature of the cold atoms reached the minimum if the pulse area was π and the time delay between the absorption pulse and the stimulated emission pulse was in the range from 0.7τ to τ. In this paper, it was confirmed that the proposed cooling process allowed for faster and more efficient momentum exchange between light and atoms, and the proposed cooling process could be applied to the atoms or molecules that could not be cooled to desired temperature through the single-photon cooling process. The 87Rb cooling, together with the CPT interrogating scheme using OFCs reduced the ratio value of linewidth/contrast, and the frequency stability of the cold atom clock hence improved by more than six times as per our calculation.
In Vitro Study of the Biological Potential of Wastewater Obtained after the Distillation of Four Bulgarian Oil-Bearing Roses
Authors: Ilieva Yana , Dimitrova Lyudmila , Georgieva Almira , Vilhelmova-Ilieva Neli , Zaharieva Maya Margaritova , Kokanova-Nedialkova Zlatina , Dobreva Ana , Nedialkov Paraskev , Kussovski Vesselin , Kroumov Alexander D. , Najdenski Hristo , Mileva Milka
Published: April 2022

The wastewater after rose oil distillation is usually discharged into the drainage systems and it represents a serious environmental problem. While being rich in polyphenols, which have beneficial biological activity and application in the pharmaceutical industry, limited research has been carried out about the biological activity of the specific wastewaters per se. Wastewaters after distillation of the four Bulgarian oil-bearing roses Rosa damascena Mill., R. alba L., R. centifolia L., and R. gallica L. exerted significant antioxidant activity and good antiherpes simplex virus type-1 (HSV-1) activity while maintaining a good toxicological safety profile (low cytotoxic effect) towards normal cell lines. More precisely, the non-tumorigenic cells were a human (HEK-293 embryonic kidney cells) and a mouse cell line (CCL-1 fibroblasts, which are recommended as a standard for cytotoxicity evaluation in Annex C of ISO 10993-5). The concentrations that achieved antioxidant and radical scavenging effects (0.04–0.92% v/v) were much lower than most of the maximum tolerated concentrations for the tissue culture cells (0.2–3.4% v/v). The wastewaters had a weak antiproliferative effect against Staphylococcus aureus. None of the wastewaters had activity against Gram-negative bacteria or a bactericidal or antifungal effect. We can conclude that these four species, which are the most preferred species worldwide for producing high-quality rose oil, have the potential to be developed as promising antioxidant and antiherpesvirus nutraceuticals.
Vernalization Requirement, but Not Post-Vernalization Day Length, Conditions Flowering in Carrot (Daucus carota L.)
Authors: Wohlfeiler Josefina , Alessandro María Soledad , Morales Andrés , Cavagnaro Pablo Federico , Galmarini Claudio Rómulo
Published: April 2022

Carrots require a certain number of cold hours to become vernalized and proceed to the reproductive stage, and this phenomenon is genotype-dependent. Annual carrots require less cold than biennials to flower; however, quantitative variation within annuals and biennials also exists, defining a gradient for vernalization requirement (VR). The flowering response of carrots to day length, after vernalization has occurred, is controversial. This vegetable has been described both as a long-day and a neutral-day species. The objective of this study was to evaluate flowering time and frequency in response to different cold treatments and photoperiod regimes in various carrot genotypes. To this end, three annual genotypes from India, Brazil, and Pakistan, and a biennial carrot from Japan, were exposed to 7.5 °C during 30, 60, 90, or 120 days, and then transferred to either long day (LD) or short day (SD) conditions. Significant variation (p < 0.05) among the carrot genotypes and among cold treatments were found, with increased flowering rates and earlier onset of flowering being associated with longer cold exposures. No significant differences in response to photoperiod were found, suggesting that post-vernalization day length does not influence carrot flowering. These findings will likely impact carrot breeding and production of both root and seed, helping in the selection of adequate genotypes and sowing dates to manage cold exposure and day-length for different production purposes.
Adnate Leaf-Base and the Origin of Ribs in Succulent Stems of Euphorbia L.
Authors: Arévalo-Rodrigues Gustavo , Hurbath Fernanda , Prado Erika , Galvão Isabella , Cordeiro Inês , Demarco Diego
Published: April 2022

Stem succulence evolved independently in many plant lineages as an adaptation to arid environments. One of the most interesting cases is the convergence between Cactaceae and Euphorbia, which have anatomical adaptations mostly to increase photosynthetic capability and water storage. Our goal was to describe the shoot development in two succulent species of Euphorbia using light microscopy coupled with high-resolution X-ray-computed tomography. Collateral cortical bundles were observed associated with the stem ribs in both species. The analysis of vasculature demonstrated that these bundles are, in fact, leaf traces that run axially along a portion of the internode. That structural pattern is due to an ontogenetic alteration. During shoot development, the leaf-bases remain adnate to the stem near the SAM, forming an axial component. When the internode elongates, the leaf bundles stretch as cortical bundles. The meristematic activity associated with the bundles forms the stem ribs, as leaf veins near the node, and induce rib formation along the entire internode even in the portion where the leaf traces join the stele. In addition, heterochronic shifts are also involved in the evolution of the shoot system in these Euphorbia, being related to early deciduous reduced leaves and the transference of the main photosynthetic function to the stem. This study demonstrates for the first time the influence of leaf developmental shifts and stem rib formation in Euphorbia and sheds new light on the evolution of stem succulence.