bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial Ecology of Artisanal Feta and Kefalograviera Cheeses, Part I: Bacterial Community and Its Functional Characteristics with Focus on Lactic Acid Bacteria as Determined by Culture-Dependent Methods and Phenotype Microarrays
Authors: Tsigkrimani Markella , Bakogianni Magdalini , Paramithiotis Spiros , Bosnea Loulouda , Pappa Eleni , Drosinos Eleftherios H. , Skandamis Panagiotis N. , Mataragas Marios
Published: January 2022

Artisanal cheesemaking is still performed using practices and conditions derived from tradition. Feta and Kefalograviera cheeses are very popular in Greece and have met worldwide commercial success. However, there is a lack of knowledge regarding their lactic acid microecosystem composition and species dynamics during ripening. Thus, the aim of the present study was to assess the microecosystem as well as the autochthonous lactic acid microbiota during the ripening of artisanal Feta and Kefalograviera cheeses. For that purpose, raw sheep’s milk intended for cheesemaking, as well as Feta and Kefalograviera cheeses during early and late ripening were analyzed, and the lactic acid microbiota was identified using the classical phenotypic approach, clustering with PCR-RAPD and identification with sequencing of the 16S-rRNA gene, as well as with the Biolog GEN III microplates. In addition, the functional properties of the bacterial community were evaluated using the Biolog EcoPlates, which consists of 31 different carbon sources. In general, concordance between the techniques used was achieved. The most frequently isolated species from raw sheep’s milk were Enteroroccus faecium, Lactiplantibacillus plantarum and Pediococcus pentosaceus. The microecosystem of Feta cheese in the early ripening stage was dominated by Lp. plantarum and E. faecium, whereas, in late ripening, the microecosystem was dominated by Weissella paramesenteroides. The microecosystem of Kefalograviera cheese in the early ripening stage was dominated by Levilactobacillus brevis and E. faecium, and in late ripening by W. paramesenteroides and E. faecium. Finally, Carbohydrates was the main carbon source category that metabolized by all microbial communities, but the extent of their utilization was varied. Kefalograviera samples, especially at early ripening, demonstrated higher metabolic activity compared to Feta cheese. However, dominating species within microbial communities of the cheese samples were not significantly different.
Dietary Beta-Hydroxy-Beta-Methyl Butyrate Supplementation Inhibits Hepatic Fat Deposition via Regulating Gut Microbiota in Broiler Chickens
Authors: Zhang Shiyu , Tang Zhiyi , Zheng Changbing , Zhong Yinzhao , Zheng Jie , Duan Geyan , Yin Yulong , Duan Yehui , Song Zehe
Published: January 2022

The present study is aimed to explore the effects of different dietary beta-hydroxy-beta-methyl butyrate (HMB) levels (0, 0.05%, 0.10%, or 0.15%) on liver lipid metabolism on Wenshi broiler chickens. Results showed that HMB reduced the liver weight as well as liver concentrations of triacylglycerol (TG) and total cholesterol (TC) (quadratically, p < 0.05), and the lowest values were observed in the 0.10% HMB group. Meanwhile, HMB supplementation significantly altered the expression levels of key genes related to lipid metabolism in the liver of broiler chickens (p < 0.05). Furthermore, 16S rRNA gene sequencing revealed that HMB supplementation could greatly change the richness, diversity, and composition of the broiler gut microbiota, and the Bacteroidetes relative abundance at the phylum level and the Alistipes relative abundance at the genus level were affected (p < 0.05). Correlation analysis further suggested a strong association between Bacteroidetes relative abundance and lipid metabolism-related parameters (p < 0.05). Together, these data suggest that 0.10% HMB supplementation could inhibit hepatic fat deposition via regulating gut microbiota in broilers.
New Insights into the Genome Organization of Yeast Double-Stranded RNA LBC Viruses
Authors: Ramírez Manuel , Martínez Alberto , Molina Felipe
Published: January 2022

The yeasts Torulaspora delbrueckii (Td) and Saccharomyces cerevisiae (Sc) may show a killer phenotype that is encoded in dsRNA M viruses (V-M), which require the helper activity of another dsRNA virus (V-LA or V-LBC) for replication. Recently, two TdV-LBCbarr genomes, which share sequence identity with ScV-LBC counterparts, were characterized by high-throughput sequencing (HTS). They also share some similar characteristics with Sc-LA viruses. This may explain why TdV-LBCbarr has helper capability to maintain M viruses, whereas ScV-LBC does not. We here analyze two stretches with low sequence identity (LIS I and LIS II) that were found in TdV-LBCbarr Gag-Pol proteins when comparing with the homologous regions of ScV-LBC. These stretches may result from successive nucleotide insertions or deletions (indels) that allow compensatory frameshift events required to maintain specific functions of the RNA-polymerase, while modifying other functions such as the ability to bind V-M (+)RNA for packaging. The presence of an additional frameshifting site in LIS I may ensure the synthesis of a certain amount of RNA-polymerase until the new compensatory indel appears. Additional 5′- and 3′-extra sequences were found beyond V-LBC canonical genomes. Most extra sequences showed high identity to some stretches of the canonical genomes and can form stem-loop structures. Further, the 3′-extra sequence of two ScV-LBC genomes contains rRNA stretches. The origin and possible functions of these extra sequences are here discussed.
Nd-Sr Isotopic Study of Magmatic Rocks and 40Ar/39Ar Dating of the Mafic Dike of the Proterozoic Ulan-Sar’dag Ophiolite Mélange (Southern Siberia, East Sayan, Middle Belt, Russia)
Authors: Kiseleva Olga , Serov Pavel , Airiyants Evgenia , Travin Aleksey , Belyanin Dmitriy , Nharara Brain , Zhmodik Sergey
Published: January 2022

We report the first radiogenic Nd-Sr isotope data in the magmatic rocks island-arc ophiolite assemblage from the middle branch of the East Sayan ophiolite complexes to better constrain geodynamic processes in this segment of the CAOB in southern central Siberia. The magmatic rocks belong to the following geochemical types: (1) Ensimatic island-arc boninites; (2) island-arc assemblage; (3) enriched basalts of mid-ocean ridges; and (4) oceanic island-like basalts. The boninites have a positive value εNd (T), which is generated from a depleted mantle source (N-MORB). The island-arc assemblage has negative or slightly positive εNd (T) and was formed from an enriched mantle source due to the subduction of terrigenous rocks. The source of the terrigenous material was most likely the rocks of the Archean TTG (Trondhjemite Tonalite Granodiorite) complex of the Gargan block. Isotopic ratios for E-MOR and OIB-like basalts are characterized by positive or slightly negative values of εNd (T). The mafic dike, which crosscut ophiolite rocks, corresponds to OIB-like basalts. The values of εNd (T), measured 87Sr/86Sr and I (Sr), in the mafic dike correspond to the EM I mantle source. The E-MOR and OIB-like basalts appear to be formed in late-stage asthenospheric mantle melting via the decompression melting processes. The obtained isotope geochemical data for the E-MOR and OIB-like basalts probably indicate the mixing of island-arc melts with asthenospheric melts. We undertook 40Ar/39Ar dating of the mafic dike, which crosscut the ophiolite unit. The mafic dike has a whole-rock 40Ar/39Ar weighted mean plateau age of 799 ± 11 Ma. The dating constrains the minimum age of the ophiolite and island-arc magmatism in the region.
Chemical Profile of Lipophilic Fractions of Different Parts of Zizyphus lotus L. by GC-MS and Evaluation of Their Antiproliferative and Antibacterial Activities
Authors: Zazouli Sofia , Chigr Mohammed , Ramos Patrícia A. B. , Rosa Daniela , Castro Maria M. , Jouaiti Ahmed , Duarte Maria F. , Santos Sónia A. O. , Silvestre Armando J. D.
Published: January 2022

Zizyphus lotus L. is a perennial shrub particularly used in Algerian folk medicine, but little is known concerning the lipophilic compounds in the most frequently used parts, namely, root bark, pulp, leaves and seeds, which are associated with health benefits. In this vein, the lipophilic fractions of these morphological parts of Z. lotus from Morocco were studied by gas chromatography–mass spectrometry (GC–MS), and their antiproliferative and antimicrobial activities were evaluated. GC–MS analysis allowed the identification and quantification of 99 lipophilic compounds, including fatty acids, long-chain aliphatic alcohols, pentacyclic triterpenic compounds, sterols, monoglycerides, aromatic compounds and other minor components. Lipophilic extracts of pulp, leaves and seeds were revealed to be mainly composed of fatty acids, representing 54.3–88.6% of the total compounds detected. The leaves and seeds were particularly rich in unsaturated fatty acids, namely, (9Z,12Z)-octadeca-9,12-dienoic acid (2431 mg kg−1 of dry weight) and (9Z)-octadec-9-enoic acid (6255 mg kg−1 of dry weight). In contrast, root bark contained a high content of pentacyclic triterpenic compounds, particularly betulinic acid, accounting for 9838 mg kg−1 of dry weight. Root bark extract showed promising antiproliferative activity against a triple-negative breast cancer cell line, MDA-MB-231, with a half-maximal inhibitory concentration (IC50) = 4.23 ± 0.18 µg mL−1 of extract. Leaf extract displayed interesting antimicrobial activity against Escherichia coli, methicillin-sensitive Staphylococcus aureus and Staphylococcus epidermis, presenting minimum inhibitory concentration (MIC) values from 1024 to 2048 µg mL−1 of extract. Our results demonstrate that Zizyphus lotus L. is a source of promising bioactive components, which can be exploited as natural ingredients in pharmaceutical formulations.
Astaxanthin as a Modulator of Nrf2, NF-κB, and Their Crosstalk: Molecular Mechanisms and Possible Clinical Applications
Authors: Davinelli Sergio , Saso Luciano , D’Angeli Floriana , Calabrese Vittorio , Intrieri Mariano , Scapagnini Giovanni
Published: January 2022

Astaxanthin (AST) is a dietary xanthophyll predominantly found in marine organisms and seafood. Due to its unique molecular features, AST has an excellent antioxidant activity with a wide range of applications in the nutraceutical and pharmaceutical industries. In the past decade, mounting evidence has suggested a protective role for AST against a wide range of diseases where oxidative stress and inflammation participate in a self-perpetuating cycle. Here, we review the underlying molecular mechanisms by which AST regulates two relevant redox-sensitive transcription factors, such as nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor κB (NF-κB). Nrf2 is a cellular sensor of electrophilic stress that coordinates the expression of a battery of defensive genes encoding antioxidant proteins and detoxifying enzymes. Likewise, NF-κB acts as a mediator of cellular stress and induces the expression of various pro-inflammatory genes, including those encoding cytokines, chemokines, and adhesion molecules. The effects of AST on the crosstalk between these transcription factors have also been discussed. Besides this, we summarize the current clinical studies elucidating how AST may alleviate the etiopathogenesis of oxidative stress and inflammation.
Measurement of Physical Fitness and 24/7 Physical Activity, Standing, Sedentary Behavior, and Time in Bed in Working-Age Finns: Study Protocol for FINFIT 2021
Authors: Husu Pauliina , Vähä-Ypyä Henri , Tokola Kari , Sievänen Harri , Mänttäri Ari , Kokko Sami , Kaikkonen Kaisu M. , Savonen Kai , Vasankari Tommi
Published: January 2022

Background: Population studies gathering measured data on fitness and physical behavior, covering physical activity, standing, sedentary behavior, and time in bed, are scarce. This article describes the protocol of the FINFIT 2021 study that measures fitness and physical behavior in a population-based sample of adults and analyzes their associations and dose–response relationships with several health indicators. Methods: The study comprises a stratified random sample of 20–69-year-old men and women (n = 16,500) from seven city-centered regions in Finland. Physical behavior is measured 24/7 by tri-axial accelerometry and analyzed with validated MAD-APE algorithms. Health and fitness examinations include fasting blood samples, measurements of blood pressure, anthropometry, and health-related fitness. Domains of health, functioning, well-being, and socio-demographics are assessed by a questionnaire. The data are being collected between September 2021 and February 2022. Discussion: The study provides population data on physical fitness and physical behavior 24/7. Physical behavior patterns by intensity and duration on an hour-by-hour basis will be provided. In the future, the baseline data will be assessed against prospective register-based data on incident diseases, healthcare utilization, sickness absence, premature retirement, and death. A similar study will be conducted every fourth year with a new random population sample.
Protocol of Co-Culture of Human Osteoblasts and Osteoclasts to Test Biomaterials for Bone Tissue Engineering
Authors: Borciani Giorgia , Montalbano Giorgia , Baldini Nicola , Vitale-Brovarone Chiara , Ciapetti Gabriela
Published: January 2022

New biomaterials and scaffolds for bone tissue engineering (BTE) applications require to be tested in a bone microenvironment reliable model. On this assumption, the in vitro laboratory protocols with bone cells represent worthy experimental systems improving our knowledge about bone homeostasis, reducing the costs of experimentation. To this day, several models of the bone microenvironment are reported in the literature, but few delineate a protocol for testing new biomaterials using bone cells. Herein we propose a clear protocol to set up an indirect co-culture system of human-derived osteoblasts and osteoclast precursors, providing well-defined criteria such as the cell seeding density, cell:cell ratio, the culture medium, and the proofs of differentiation. The material to be tested may be easily introduced in the system and the cell response analyzed. The physical separation of osteoblasts and osteoclasts allows distinguishing the effects of the material onto the two cell types and to evaluate the correlation between material and cell behavior, cell morphology, and adhesion. The whole protocol requires about 4 to 6 weeks with an intermediate level of expertise. The system is an in vitro model of the bone remodeling system useful in testing innovative materials for bone regeneration, and potentially exploitable in different application fields. The use of human primary cells represents a close replica of the bone cell cooperation in vivo and may be employed as a feasible system to test materials and scaffolds for bone substitution and regeneration.
Porous Polydimethylsiloxane Elastomer Hybrid with Zinc Oxide Nanowire for Wearable, Wide-Range, and Low Detection Limit Capacitive Pressure Sensor
Authors: Hsieh Gen-Wen , Shih Liang-Cheng , Chen Pei-Yuan
Published: January 2022

We propose a flexible capacitive pressure sensor that utilizes porous polydimethylsiloxane elastomer with zinc oxide nanowire as nanocomposite dielectric layer via a simple porogen-assisted process. With the incorporation of nanowires into the porous elastomer, our capacitive pressure sensor is not only highly responsive to subtle stimuli but vigorously so to gentle touch and verbal stimulation from 0 to 50 kPa. The fabricated zinc oxide nanowire–porous polydimethylsiloxane sensor exhibits superior sensitivity of 0.717 kPa−1, 0.360 kPa−1, and 0.200 kPa−1 at the pressure regimes of 0–50 Pa, 50–1000 Pa, and 1000–3000 Pa, respectively, presenting an approximate enhancement by 21−100 times when compared to that of a flat polydimethylsiloxane device. The nanocomposite dielectric layer also reveals an ultralow detection limit of 1.0 Pa, good stability, and durability after 4000 loading–unloading cycles, making it capable of perception of various human motions, such as finger bending, calligraphy writing, throat vibration, and airflow blowing. A proof-of-concept trial in hydrostatic water pressure sensing has been demonstrated with the proposed sensors, which can detect tiny changes in water pressure and may be helpful for underwater sensing research. This work brings out the efficacy of constructing wearable capacitive pressure sensors based on a porous dielectric hybrid with stress-sensitive nanostructures, providing wide prospective applications in wearable electronics, health monitoring, and smart artificial robotics/prosthetics.
Direct Comparison of Chol-siRNA Polyplexes and Chol-DsiRNA Polyplexes Targeting STAT3 in a Syngeneic Murine Model of TNBC
Authors: Ye Zhen , Abdelmoaty Mai Mohamed , Curran Stephen M. , Dyavar Shetty Ravi , Kumar Devendra , Alnouti Yazen , Coulter Don W. , Podany Anthony T. , Singh Rakesh K. , Vetro Joseph A.
Published: January 2022

RNA interference (RNAi) molecules have tremendous potential for cancer therapy but are limited by insufficient potency after intravenous (IV) administration. We previously found that polymer complexes (polyplexes) formed between 3′-cholesterol-modified siRNA (Chol-siRNA) or DsiRNA (Chol-DsiRNA) and the cationic diblock copolymer PLL[30]-PEG[5K] greatly increase RNAi potency against stably expressed LUC mRNA in primary syngeneic murine breast tumors after daily IV dosing. Chol-DsiRNA polyplexes, however, maintain LUC mRNA suppression for ~48 h longer after the final dose than Chol-siRNA polyplexes, which suggests that they are the better candidate formulation. Here, we directly compared the activities of Chol-siRNA polyplexes and Chol-DsiRNA polyplexes in primary murine 4T1 breast tumors against STAT3, a therapeutically relevant target gene that is overexpressed in many solid tumors, including breast cancer. We found that Chol-siSTAT3 polyplexes suppressed STAT3 mRNA in 4T1 tumors with similar potency (half-maximal ED50 0.3 mg/kg) and kinetics (over 96 h) as Chol-DsiSTAT3 polyplexes, but with slightly lower activity against total Stat3 protein (29% vs. 42% suppression) and tumor growth (11.5% vs. 8.6% rate-based T/C ratio) after repeated IV administration of equimolar, tumor-saturating doses every other day. Thus, both Chol-siRNA polyplexes and Chol-DsiRNA polyplexes may be suitable clinical candidates for the RNAi therapy of breast cancer and other solid tumors.
DANSR: A Tool for the Detection of Annotated and Novel Small RNAs
Authors: Zhang Jin , Eteleeb Abdallah M. , Rozycki Emily B. , Inkman Matthew J. , Ly Amy , Scharf Russell E. , Jayachandran Kay , Krasnick Bradley A. , Mazur Thomas , White Nicole M. , Fields Ryan C. , Maher Christopher A.
Published: January 2022

Existing small noncoding RNA analysis tools are optimized for processing short sequencing reads (17–35 nucleotides) to monitor microRNA expression. However, these strategies under-represent many biologically relevant classes of small noncoding RNAs in the 36–200 nucleotides length range (tRNAs, snoRNAs, etc.). To address this, we developed DANSR, a tool for the detection of annotated and novel small RNAs using sequencing reads with variable lengths (ranging from 17–200 nt). While DANSR is broadly applicable to any small RNA dataset, we applied it to a cohort of matched normal, primary, and distant metastatic colorectal cancer specimens to demonstrate its ability to quantify annotated small RNAs, discover novel genes, and calculate differential expression. DANSR is available as an open source tool.
BloodChain: A Blood Donation Network Managed by Blockchain Technologies
Authors: Le Hai Trieu , Nguyen Tran Thanh Lam , Nguyen Tuan Anh , Ha Xuan Son , Duong-Trung Nghia
Published: January 2022

Due to the rapid change of population structure, leading to lower birth rates and quick aging rates, the demand for blood supply is increasing significantly. In most countries, blood quality and origin are managed by blood management information systems, such as national authorities. Nevertheless, the traditional system has limitations in this field, such as a lack of detailed blood information, making it challenging to manage blood quality, supply, and demand. Hence, to solve these issues, this paper proposes a blockchain-based system called BloodChain, an improved system to support blood information management, providing more detailed information about blood, such as blood consumption and disposal. BloodChain exploits private blockchain techniques with a limited number of relatively fast and reliable participants, making them suitable for B2B (Business to Business) transactions. In this paper, we also develop a proposed system based on the architecture of Hyperledger Fabric. The evaluation of BloodChain is performed in several scenarios to prove our proposed model’s effectiveness.
Chronodisruption: Origin, Roots, and Developments of an 18-Year-Old Concept. Comment on Desmet et al. Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag. Nutrients 2021, 13, 3846
Authors: Erren Thomas C. , Piekarski Claus , Reiter Russel J.
Published: January 2022

We read with interest the article by Desmet and colleagues entitled “Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag” [...]
Vitamin D Status and SARS-CoV-2 Infection in a Cohort of Kidney Transplanted Patients
Authors: Regalia Anna , Benedetti Matteo , Malvica Silvia , Alfieri Carlo , Campise Mariarosaria , Cresseri Donata , Gandolfo Maria Teresa , Tripodi Federica , Castellano Giuseppe , Messa Piergiorgio
Published: January 2022

Background: Recently the protective role of 25-hydroxyvitamin D (25(OH)D) against viral infections has been hypothesized. We evaluated the association between vitamin D status and SARS-CoV-2 infection susceptibility and severity in a cohort of kidney transplanted patients (KTxp). Methods: A total of 61 KTxp with SARS-CoV-2 infection (COV+) were matched with 122 healthy KTxp controls (COV−). Main biochemical parameters at 1, 6, and 12 months before SARS-CoV-2 infection were recorded. Vitamin D status was considered as the mean of two 25(OH)D measures obtained 6 ± 2 months apart during the last year. The severity of SARS-CoV-2 infection was based on the need for hospitalization (HOSP+) and death (D+). Results: 25(OH)D levels were lower in COV+ than in controls [19(12–26) vs. 23(17–31) ng/mL, p = 0.01]. No differences among the other biochemical parameters were found. The SARS-CoV-2 infection discriminative power of 25(OH)D was evaluated by ROC-curve (AUC 0.61, 95% CI 0.5–0.7, p = 0.01). 25(OH)D was not significantly different between HOSP+ and HOSP− [17(8–25) vs. 20(15–26) ng/mL, p = 0.19] and between D+ and D− [14(6–23) vs. 20(14–26) ng/mL, p = 0.22] and had no significant correlation with disease length. Conclusions: During the year preceding the infection, 25(OH)D levels were lower in COV+ KTxp in comparison with controls matched for demographic features and comorbidities. No significant association between vitamin D status and SARS-CoV-2 infection related outcomes was found.
Does Oxidative Stress Management Help Alleviation of COVID-19 Symptoms in Patients Experiencing Diabetes?
Authors: Paul Alok K. , Hossain Md K. , Mahboob Tooba , Nissapatorn Veeranoot , Wilairatana Polrat , Jahan Rownak , Jannat Khoshnur , Bondhon Tohmina A. , Hasan Anamul , de Lourdes Pereira Maria , Rahmatullah Mohammed
Published: January 2022

Severe acute respiratory syndrome (SARS)-CoV-2 virus causes novel coronavirus disease 2019 (COVID-19) with other comorbidities such as diabetes. Diabetes is the most common cause of diabetic nephropathy, which is attributed to hyperglycemia. COVID-19 produces severe complications in people with diabetes mellitus. This article explains how SARS-CoV-2 causes more significant kidney damage in diabetic patients. Importantly, COVID-19 and diabetes share inflammatory pathways of disease progression. SARS-CoV-2 binding with ACE-2 causes depletion of ACE-2 (angiotensin-converting enzyme 2) from blood vessels, and subsequently, angiotensin-II interacts with angiotensin receptor-1 from vascular membranes that produce NADPH (nicotinamide adenine dinucleotide hydrogen phosphate) oxidase, oxidative stress, and constriction of blood vessels. Since diabetes and COVID-19 can create oxidative stress, we hypothesize that COVID-19 with comorbidities such as diabetes can synergistically increase oxidative stress leading to end-stage renal failure and death. Antioxidants may therefore prevent renal damage-induced death by inhibiting oxidative damage and thus can help protect people from COVID-19 related comorbidities. A few clinical trials indicated how effective the antioxidant therapy is against improving COVID-19 symptoms, based on a limited number of patients who experienced COVID-19. In this review, we tried to understand how effective antioxidants (such as vitamin D and flavonoids) can act as food supplements or therapeutics against COVID-19 with diabetes as comorbidity based on recently available clinical, preclinical, or in silico studies.
Bone Mineral Density Changes in Long-Term Kidney Transplant Recipients: A Real-Life Cohort Study of Native Vitamin D Supplementation
Authors: Battaglia Yuri , Bellasi Antonio , Bortoluzzi Alessandra , Tondolo Francesco , Esposito Pasquale , Provenzano Michele , Russo Domenico , Andreucci Michele , Cianciolo Giuseppe , Storari Alda
Published: January 2022

Vitamin D insufficiency has been associated with reduced bone mineral density (BMD) in kidney transplant patients (KTRs). However, the efficacy of vitamin D supplementation on BMD remains poorly defined, especially for long-term KTRs. We aimed to investigate the effect of native vitamin D supplementation on the BMD of KTRs during a 2-year follow-up. Demographic, clinical, and laboratory data were collected. BMD was evaluated with standard DEXA that was performed at baseline (before vitamin D supplementation) and at the end of study period. BMD was assessed at lumbar vertebral bodies (LV) and right femoral neck (FN) by a single operator. According to WHO criteria, results were expressed as the T-score (standard deviation (SD) relative to young healthy adults) and Z-score (SD relative to age-matched controls). Osteoporosis and osteopenia were defined as a T-score ≤ −2.5 SD and a T-score < −1 and a > −2.5 SD, respectively. Based on plasma levels, 25-OH-vitamin D (25-OH-D) was supplemented as recommended for the general population. Data from 100 KTRs were analyzed. The mean study period was 27.7 ± 3.4 months. At study inception, 25-OH-D insufficiency and deficiency were recorded in 65 and 35 patients. At the basal DEXA, the percentage of osteopenia and osteoporosis was 43.3% and 18.6% at LV and 54.1% and 12.2% at FN, respectively. At the end of the study, no differences in the Z-score and T-score gains were observed. During linear mixed model analysis, native vitamin D supplementation was found to have a negative nitration with Z-score changes at the right femoral neck in KTRs (p < 0.05). The mean dose of administered cholecalciferol was 13.396 ± 7.537 UI per week; increased 25-OH-D levels were found (p < 0.0001). Either low BMD or 25-OH-vitamin D concentration was observed in long-term KTRs. Prolonged supplementation with 25-OH-D did not modify BMD, Z-score, or T-score.
Physicochemical Properties of the Soluble Dietary Fiber from Laminaria japonica and Its Role in the Regulation of Type 2 Diabetes Mice
Authors: Wang Xixi , Zhang Liping , Qin Ling , Wang Yanfeng , Chen Fushan , Qu Changfeng , Miao Jinlai
Published: January 2022

Laminaria japonica is a large marine brown alga that is annually highly productive. However, due to its underutilization, its potential value is substantially wasted. For example, a lot of Laminaria japonica cellulose remains unused during production of algin. The soluble dietary fiber (SDF) was prepared from the byproducts of Laminaria japonica, and its physicochemical properties were explored. SDF exhibits good water-holding, oil-holding, water-absorbing swelling, glucose and cholesterol absorption capacity, and inhibitory activity of α-amylase and α-glucosidase. In addition, the beneficial effects of SDF in diabetic mice include reduced body weight, lower blood glucose, and relieved insulin resistance. Finally, the intestinal flora and metabolomic products were analyzed from feces using 16S amplicon and LC-MS/MS, respectively. SDF not only significantly changed the composition and structure of intestinal flora and intestinal metabolites, but also significantly increased the abundance of beneficial bacteria Akkermansia, Odoribacter and Bacteroides, decreased the abundance of harmful bacteria Staphylococcus, and increased the content of bioactive substances in intestinal tract, such as harmine, magnolol, arachidonic acid, prostaglandin E2, urimorelin and azelaic acid. Taken together, these findings suggest that dietary intake of SDF alleviates type 2 diabetes mellitus disease, and provides an important theoretical basis for SDF to be used as a functional food.
Dehydration Status Aggravates Early Renal Impairment in Children: A Longitudinal Study
Authors: Amaerjiang Nubiya , Li Menglong , Xiao Huidi , Zunong Jiawulan , Li Ziang , Huang Dayong , Vermund Sten H. , Pérez-Escamilla Rafael , Jiang Xiaofeng , Hu Yifei
Published: January 2022

Dehydration is common in children for physiological and behavioral reasons. The objective of this study was to assess changes in hydration status and renal impairment across school weekdays. We conducted a longitudinal study of three repeated measures of urinalysis within one week in November 2019 in a child cohort in Beijing, China. We measured urine specific gravity (USG) to determine the dehydration status, and the concentration of β2-microglobulin (β2-MG) and microalbumin (MA) to assess renal function impairment among 1885 children with a mean age of 7.7 years old. The prevalence of dehydration was 61.9%, which was significantly higher in boys (64.3%). Using chi-square tests and linear mixed-effects regression models, we documented the trends of the renal indicators’ change over time among different hydration statuses. Compared to Mondays, there were apparent increases of β2-MG concentrations on Wednesdays (β = 0.029, p < 0.001) and Fridays (β = 0.035, p < 0.001) in the dehydrated group, but not in the euhydrated group. As for the MA concentrations, only the decrease on Fridays (β = −1.822, p = 0.01) was significant in the euhydrated group. An increased trend of elevated β2-MG concentration was shown in both the euhydrated group (Z = −3.33, p < 0.001) and the dehydrated group (Z = −8.82, p < 0.001). By contrast, there was a decreased trend of elevated MA concentrations in the euhydrated group (Z = 3.59, p < 0.001) but not in the dehydrated group. A new indicator ratio, β2-MG/MA, validated the consistent trends of renal function impairment in children with dehydration. Renal impairment trends worsened as a function of school days during the week and the dehydration status aggravated renal impairment during childhood across school weekdays, especially tubular abnormalities in children.
Mobile Phone Radiation Deflects Brain Energy Homeostasis and Prompts Human Food Ingestion
Authors: Wardzinski Ewelina , Jauch-Chara Kamila , Haars Sarah , Melchert Uwe , Scholand-Engler Harald , Oltmanns Kerstin
Published: January 2022

Obesity and mobile phone usage have simultaneously spread worldwide. Radio frequency-modulated electromagnetic fields (RF-EMFs) emitted by mobile phones are largely absorbed by the head of the user, influence cerebral glucose metabolism, and modulate neuronal excitability. Body weight adjustment, in turn, is one of the main brain functions as food intake behavior and appetite perception underlie hypothalamic regulation. Against this background, we questioned if mobile phone radiation and food intake may be related. In a single-blind, sham-controlled, randomized crossover comparison, 15 normal-weight young men (23.47 ± 0.68 years) were exposed to 25 min of RF-EMFs emitted by two different mobile phone types vs. sham radiation under fasting conditions. Spontaneous food intake was assessed by an ad libitum standard buffet test and cerebral energy homeostasis was monitored by 31phosphorus-magnetic resonance spectroscopy measurements. Exposure to both mobile phones strikingly increased overall caloric intake by 22–27% compared with the sham condition. Differential analyses of macronutrient ingestion revealed that higher calorie consumption was mainly due to enhanced carbohydrate intake. Measurements of the cerebral energy content, i.e., adenosine triphosphate and phosphocreatine ratios to inorganic phosphate, displayed an increase upon mobile phone radiation. Our results identify RF-EMFs as a potential contributing factor to overeating, which underlies the obesity epidemic. Beyond that, the observed RF-EMFs-induced alterations of the brain energy homeostasis may put our data into a broader context because a balanced brain energy homeostasis is of fundamental importance for all brain functions. Potential disturbances by electromagnetic fields may therefore exert some generalized neurobiological effects, which are not yet foreseeable.
Targeting Abnormal Cell Cycle in Cancer: A Preface to the Special Issue
Authors: Takahashi Chiaki , Kato Jun-ya
Published: January 2022

The accelerated cell cycle progression is one of the hallmarks of human cancer [...]
Feeding-Induced Changes of Bacteriolytic Activity and the Pattern of Bacteriolytic Compounds in the Stomach and Small Intestine of the Haematophagous Bug Triatoma infestans (Klug, 1834) (Reduviidae, Triatominae)
Authors: Meiser Christian K. , Pausch Jennifer K. , Schaub Günter A.
Published: January 2022

Intestinal homeostasis mechanisms of the haematophagous triatomines regulate the development of mutualistic symbionts and other gut bacteria. Investigating antimicrobial compounds of these insects, we have determined spectrophotometrically that the bacteriolytic activity is between pH 3 and pH 9 using homogenates of fifth instar Triatoma infestans stomachs and small intestines from unfed bugs and up to 50 days after feeding. The activity against Gram-positive Micrococcus luteus was strongest at pH 4 and pH 7 and was higher in the stomach than in the small intestine. Symbiotic Rhodococcus triatomae were not lysed. Lysis of Gram-negative Escherichia coli showed a maximum at pH 7 in the stomach and at pH 5 in the small intestine. Bacteriolytic activity against both M. luteus and E. coli was reduced 24 h after feeding, then increased, and at 50 days after feeding was strongly reduced. In zymographs, the activity against M. luteus was mainly correlated to proteins of about 16 kDa. At different periods of time after feeding, seven bands of lysis appeared between 15 and 40 kDa and more bands using extracts of the small intestine than those of the stomach. This is the first proof for the synthesis of antibacterial proteins of 22–40 kDa in triatomines.
A Systematic Review of Zoonotic Enteric Parasites Carried by Flies, Cockroaches, and Dung Beetles
Authors: Patel Avi , Jenkins Meg , Rhoden Kelly , Barnes Amber N.
Published: January 2022

Filth flies, cockroaches, and dung beetles have been close neighbors with humans and animals throughout our joint histories. However, these insects can also serve as vectors for many zoonotic enteric parasites (ZEPs). Zoonoses by ZEPs remain a paramount public health threat due to our close contact with animals, combined with poor water, sanitation, and hygiene access, services, and behaviors in many global regions. Our objective in this systematic review was to determine which ZEPs have been documented in these vectors, to identify risk factors associated with their transmission, and to provide effectual One Health recommendations for curbing their spread. Using PRISMA guidelines, a total of 85 articles published from 1926 to 2021 were reviewed and included in this study. Qualitative analysis revealed that the most common parasites associated with these insects included, but were not limited to: Ascaris spp., Trichuris spp., Entamoeba spp., and Cryptosporidium spp. Additionally, prominent risk factors discovered in the review, such as poor household and community WASH services, unsafe food handling, and exposure to domestic animals and wildlife, significantly increase parasitic transmission and zoonoses. The risk of insect vector transmission in our shared environments makes it critically important to implement a One Health approach in reducing ZEP transmission.
Antimicrobial Susceptibility Profiles among Pseudomonas aeruginosa Isolated from Professional SCUBA Divers with Otitis Externa, Swimming Pools and the Ocean at a Diving Operation in South Africa
Authors: Maclean Kevin , Njamo Fernande Olpa J Pankendem , Serepa-Dlamini Mahloro Hope , Kondiah Kulsum , Green Ezekiel
Published: January 2022

SCUBA divers are predisposed to otitis externa caused by Pseudomonas aeruginosa, which is becoming increasingly multi-drug resistant (MDR). The present work assessed the antibiotic resistance profiles of P. aeruginosa obtained from SCUBA divers and their environment in Sodwana Bay, South Africa. Bacterial isolates from a total of 137 random water and ear swab samples were identified using biochemical and molecular methods. P. aeruginosa strains were further evaluated for antibiotic susceptibility using the Kirby–Bauer assay. Double disk synergy test (DDST) to confirm metallo-β-lactamase (MBL) production and PCR amplification of specific antibiotic resistance genes was performed. All (100%) 22 P. aeruginosa isolates recovered were resistant to 6 of the β-lactams tested including imipenem but exhibited susceptibility to trimethoprim–sulfamethoxazole. MBL production was observed in 77% of isolates while the most prevalent extended-spectrum β-lactamase (ESBL) genes present included blaAmpC (86.9%) followed by blaTEM (82.6%). Sulfonamide resistance was largely encoded by sul1 (63.6%) and sul2 (77.3%) genes with a high abundance of class 1 integrons (77.3%) of which 18.2% carried both Intl1 and Intl2. P. aeruginosa found in Sodwana Bay exhibits multi-drug resistance (MDRce) to several pharmaceutically important drugs with the potential to transfer antibiotic resistance to other bacteria if the judicious use of antibiotics for their treatment is not practiced.
Mirogabalin Decreases Pain-like Behaviours and Improves Opioid and Ketamine Antinociception in a Mouse Model of Neuropathic Pain
Authors: Zajączkowska Renata , Rojewska Ewelina , Ciechanowska Agata , Pawlik Katarzyna , Ciapała Katarzyna , Kocot-Kępska Magdalena , Makuch Wioletta , Wordliczek Jerzy , Mika Joanna
Published: January 2022

Neuropathic pain remains a difficult clinical challenge due to its diverse aetiology and complex pathomechanisms, which are yet to be fully understood. Despite the variety of available therapies, many patients suffer from ineffective pain relief; hence, the search for more efficacious treatments continues. The new gabapentinoid, mirogabalin has recently been approved for clinical use. Although its main mechanism of action occurs at the α2σ-1 and α2σ-2 subunits of calcium channels and is well documented, how the drug affects the disturbed neuropathic interactions at the spinal cord level has not been clarified, which is crucial information from a clinical perspective. The findings of our study suggest that several indirect mechanisms may be responsible for the beneficial analgesic effect of mirogabalin. This is the first study to report that mirogabalin enhances the mRNA expression of spinal antinociceptive factors, such as IL-10 and IL-18BP, and reduces the concentration of the pronociceptive substance P. Importantly, mirogabalin improves the morphine-, buprenorphine-, oxycodone-, and ketamine-induced antinociceptive effects in a neuropathic pain model. Our findings support the hypothesis that enhancing opioid and ketamine analgesia by combining these drugs with mirogabalin may represent a new strategy for the effective pharmacotherapy of neuropathic pain.
Bcl-XL but Not Bcl-2 Is a Potential Target in Medulloblastoma Therapy
Authors: Westhoff Mike-Andrew , Schuler-Ortoli Marie , Zerrinius Daniela , Hadzalic Amina , Schuster Andrea , Strobel Hannah , Scheuerle Angelika , Wong Tiana , Wirtz Christian Rainer , Debatin Klaus-Michael , Peraud Aurelia
Published: January 2022

Medulloblastoma (MB) is the most common solid tumour in children and, despite current treatment with a rather aggressive combination therapy, accounts for 10% of all deaths associated with paediatric cancer. Breaking the tumour cells’ intrinsic resistance to therapy-induced cell death should lead to less aggressive and more effective treatment options. In other tumour entities, this has been achieved by modulating the balance between the various pro- and anti-apoptotic members of the Bcl-2 family with small molecule inhibitors. To evaluate the therapeutic benefits of ABT-199 (Venetoclax), a Bcl-2 inhibitor, and ABT-263 (Navitoclax), a dual Bcl-XL/Bcl-2 inhibitor, increasingly more relevant model systems were investigated. Starting from established MB cell lines, progressing to primary patient-derived material and finally an experimental tumour system imbedded in an organic environment were chosen. Assessment of the metabolic activity (a surrogate readout for population viability), the induction of DNA fragmentation (apoptosis) and changes in cell number (the combined effect of alterations in proliferation and cell death induction) revealed that ABT-263, but not ABT-199, is a promising candidate for combination therapy, synergizing with cell death-inducing stimuli. Interestingly, in the experimental tumour setting, the sensitizing effect of ABT-263 seems to be predominantly mediated via an anti-proliferative and not a pro-apoptotic effect, opening a future line of investigation. Our data show that modulation of specific members of the Bcl-2 family might be a promising therapeutic addition for the treatment of MB.
Characterization of Drugs with Good Glass Formers in Loaded-Mesoporous Silica and Its Theoretical Value Relevance with Mesopores Surface and Pore-Filling Capacity
Authors: Budiman Arif , Aulifa Diah Lia
Published: January 2022

The incorporation of a drug into mesoporous silica (MPS) is a promising strategy to stabilize its amorphous form. However, the drug within MPS has shown incomplete release, despite a supersaturated solution being generated. This indicates the determination of maximum drug loading in MPS below what is experimentally necessary to maximize the drug doses in the system. Therefore, this study aimed to characterize the drugs with good glass former loaded-mesoporous silica, determine the maximum drug loading, and compare its theoretical value relevance to monolayer covering the mesoporous (MCM) surface, as well as pore-filling capacity (PFC). Solvent evaporation and melt methods were used to load each drug into MPS. In addition, the glass transition of ritonavir (RTV) and cyclosporine A (CYP), as well as the melting peak of indomethacin (IDM) and saccharin (SAC) in mesoporous silica, were not discovered in the modulated differential scanning calorimetry (MDSC) curve, demonstrating that each drug was successfully incorporated into the mesopores. The amorphization of RTV-loaded MPS (RTV/MPS), CYP-loaded MPS (CYP/MPS), and IDM-loaded MPS (IDM/MPS) were confirmed as a halo pattern in powder X-ray diffraction measurements and a single glass transition event in the MDSC curve. Additionally, the good glass formers, nanoconfinement effect of MPS and silica surface interaction contributed to the amorphization of RTV, CYP and IDM within MPS. Meanwhile, the crystallization of SAC was observed in SAC-loaded MPS (SAC/MPS) due to its weak silica surface interaction and high recrystallization tendency. The maximum loading amount of RTV/MPS was experimentally close to the theoretical amount of MCM, showing monomolecular adsorption of RTV on the silica surface. On the other hand, the maximum loading amount of CYP/MPS and IDM/MPS was experimentally lower than the theoretical amount of MCM due to the lack of surface interaction. However, neither CYP or IDM occupied the entire silica surface, even though some drugs were adsorbed on the MPS surface. Moreover, the maximum loading amount of SAC/MPS was experimentally close to the theoretical amount of PFC, suggesting the multilayers of SAC within the MPS. Therefore, this study demonstrates that the characterization of drugs within MPS, such as molecular size and interaction of drug-silica surface, affects the loading efficiency of drugs within MPS that influence its relevance with the theoretical value of drugs.
Receptor Specificity Engineering of TNF Superfamily Ligands
Authors: Suo Fengzhi , Zhou Xinyu , Setroikromo Rita , Quax Wim J.
Published: January 2022

The tumor necrosis factor (TNF) ligand family has nine ligands that show promiscuity in binding multiple receptors. As different receptors transduce into diverse pathways, the study on the functional role of natural ligands is very complex. In this review, we discuss the TNF ligands engineering for receptor specificity and summarize the performance of the ligand variants in vivo and in vitro. Those variants have an increased binding affinity to specific receptors to enhance the cell signal conduction and have reduced side effects due to a lowered binding to untargeted receptors. Refining receptor specificity is a promising research strategy for improving the application of multi-receptor ligands. Further, the settled variants also provide experimental guidance for engineering receptor specificity on other proteins with multiple receptors.
State-of-the-Art Review of Artificial Neural Networks to Predict, Characterize and Optimize Pharmaceutical Formulation
Authors: Wang Shan , Di Jinwei , Wang Dan , Dai Xudong , Hua Yabing , Gao Xiang , Zheng Aiping , Gao Jing
Published: January 2022

During the development of a pharmaceutical formulation, a powerful tool is needed to extract the key points from the complicated process parameters and material attributes. Artificial neural networks (ANNs), a promising and more flexible modeling technique, can address real intricate questions in a high parallelism and distributed pattern in the manner of biological neural networks. The data mined and analyzing based on ANNs have the ability to replace hundreds of trial and error experiments. ANNs have been used for data analysis by pharmaceutics researchers since the 1990s and it has now become a research method in pharmaceutical science. This review focuses on the latest application progress of ANNs in the prediction, characterization and optimization of pharmaceutical formulation to provide a reference for the further interdisciplinary study of pharmaceutics and ANNs.