bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut Microbiota Markers and Dietary Habits Associated with Extreme Longevity in Healthy Sardinian Centenarians
Authors: Palmas Vanessa , Pisanu Silvia , Madau Veronica , Casula Emanuela , Deledda Andrea , Cusano Roberto , Uva Paolo , Loviselli Andrea , Velluzzi Fernanda , Manzin Aldo
Published: June 2022

This study was aimed at characterizing the gut microbiota (GM) and its functional profile in two groups of Sardinian subjects with a long healthy life expectancy, overall named Long-Lived Subjects (LLS) [17 centenarians (CENT) and 29 nonagenarians (NON)] by comparing them to 46 healthy younger controls (CTLs). In addition, the contribution of genetics and environmental factors to the GM phenotype was assessed by comparing a subgroup of seven centenarian parents (CPAR) with a paired cohort of centenarians’ offspring (COFF). The analysis was performed through Next Generation Sequencing (NGS) of the V3 and V4 hypervariable region of the 16S rRNA gene on the MiSeq Illumina platform. The Verrucomicrobia phylum was identified as the main biomarker in CENT, together with its members Verrucomicrobiaceae, Akkermansia and Akkermansia muciniphila. In NON, the strongest associations concern Actinobacteria phylum, Bifidobacteriaceae and Bifidobacterium, while in CTLs were related to the Bacteroidetes phylum, Bacteroidaceae, Bacteroides and Bacteroides spp. Intestinal microbiota of CPAR and COFF did not differ significantly from each other. Significant correlations between bacterial taxa and clinical and lifestyle data, especially with Mediterranean diet adherence, were observed. We observed a harmonically balanced intestinal community structure in which the increase in taxa associated with intestinal health would limit and counteract the action of potentially pathogenic bacterial species in centenarians. The GM of long-lived individuals showed an intrinsic ability to adapt to changing environmental conditions, as confirmed by functional analysis. The GM analysis of centenarians’ offspring suggest that genetics and environmental factors act synergistically as a multifactorial cause in the modulation of GM towards a phenotype similar to that of centenarians, although these findings need to be confirmed by larger study cohorts and by prospective studies.
Usage of Mobile Applications or Mobile Health Technology to Improve Diet Quality in Adults
Authors: Scarry Alan , Rice Jennifer , O’Connor Eibhlís M. , Tierney Audrey C.
Published: June 2022

The use of mobile applications for dietary purposes has dramatically increased along with the consistent development of mobile technology. Assessing diet quality as a dietary pattern or an indicator across key food groups in comparison to those recommended by dietary guidelines is useful for identifying optimal nutrient intake. This systematic review aims to explore mobile applications and their impact on the diet quality of the user. The electronic databases of The Cumulative Index to Nursing and Allied Health Literature (Cinahl), The American Psychological Association’s (APA Psycinfo), and PubMed were systematically searched for randomised and non-randomised controlled trials to retrieve papers from inception to November 2021. Ten studies with 1638 participants were included. A total of 5342 studies were retrieved from the database searches, with 10 articles eligible for final inclusion in the review. The sample sizes ranged from 27 to 732 participants across the included studies, with 1638 total participants. The ratio of female to male participants in the studies was 4:1. The majority of the mobile applications or M-health interventions were used to highlight dietary health changes (six studies), with the remainder used to reduce weight or blood sugar levels (four studies). Each study used a different measure to quantify diet quality. Studies were either assessed by diet quality scoring or individual dietary assessment, of the ten studies, six studies reported an improvement in diet quality following diet-related mobile application use. Mobile applications may be an effective way to improve diet quality in adults; however, there is a need for more targeted and longer-term studies that are expressly designed to investigate the impact using mobile applications has on diet quality.
Comparison of Selected Immune Parameters in a Single Infection and Co-Infection with Infectious Pancreatic Necrosis Virus with Other Viruses in Rainbow Trout
Authors: Maj-Paluch Joanna , Wasiak Magdalena , Bocian Łukasz , Reichert Michał
Published: June 2022

Infectious pancreatic necrosis virus (IPNV) often occurs in an aquatic environment in co-infection with other viruses. In this study, we wanted to investigate the effect of this virus on the course of co-infection with other viruses in rainbow trout. For co-infection we used viral hemorrhagic septicemia virus (VHSV), infectious hematopoietic necrosis virus (IHNV) and salmonid alphavirus (SAV) field strains and infected rainbow trout divided into eight groups; I; IPNV, II; IHNV, III; VHSV, I; SAV, V; IPNV+IHNV, VI; IPNV+VHSV, VII; IPNV+SAV, and the control group. We assessed apoptosis in white blood cells and used a real time RT-PCR to analyze RNA obtained from the internal organs of the fish. During single infection and co-infection the level of expression of immune genes such as interferon and toll-like receptor 3 (TLR-3) was assessed. The highest mortality during the experiment was observed in group III infected by VHSV. The average percentage of apoptotic cells was higher in groups without co-infection, especially in groups II and III. Interferon expression was higher in singly infected groups, the highest being in the heart in group III, while expression of the TLR-3 gene was generally raised in all tested organs in all groups. We found that co-infection with IPNV had a positive impact on the course of infection with the viruses listed because it lowered mortality, reduced apoptosis in co-infected cells, and positively affected fish health.
Diagnostic Accuracy of LDBIO-Toxo II IgG and IgM Western Blot in Suspected Seroconversion in Pregnancy: A Multicentre Study
Authors: Meroni Valeria , Genco Francesca , Scudeller Luigia , Brenier-Pinchart Marie-Pierre , Fricker-Hidalgo Hélène , L’Ollivier Coralie , Paris Luc , Pelloux Hervé
Published: June 2022

The high sensitivity of the automated tests used for Toxoplasma gondii serology can yield false-positive IgM results due to aspecific reactions. On the other hand, specific therapy can delay IgG production and, therefore, the diagnosis of seroconversion. There is a need for confirmation tests to early detect seroconversions during pregnancy. We conducted a multicentre study to evaluate the diagnostic accuracy of the Toxo II IgG and a new, not yet commercialised Toxo II IgM western blot (WB) (LDBio diagnostics Lyon France) on 229 sera corresponding to 93 patients with seroconversions and 158 sera corresponding to 68 patients with nonspecific IgM. Sensitivity was 97.8% for IgM WB and 98.9% for IgG WB. Specificity was 89.7% and 100%, respectively. The concordance between IgM and IgG Toxo WB with the final diagnosis was very good, K = 0.89 and K = 0.99, respectively. In 5 cases (5.4%), the appearance of IgM, and in 55 cases (59.1%), the appearance of IgG was recorded by WB earlier than by traditional tests. In 10 cases (10.8%), IgM was detected after the traditional tests and in 2 cases (2.2%) for IgG. The association of IgG and IgM WB on the same sample not only detected all seroconversions but also correctly identified most of the false-positive results.
Frequency of Chlamydia trachomatis and Neisseria gonorrhoeae in Patients with Imminent Preterm Delivery on the Island of Curaçao
Authors: Hage Aglaia , Juliana Naomi C. A. , Steenhof Leonie , Voigt Ralph R. , Morré Servaas A. , Ambrosino Elena , Hammoud Nurah M.
Published: June 2022

Sexually transmitted infections are one of the important risk factors for preterm delivery, which is among the important contributors to perinatal morbidity and mortality. The aim of this study was to assess the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections in women with imminent preterm delivery in Curaçao, an island of the Dutch Caribbean. All women from Curaçao with either preterm premature rupture of the membranes or preterm labor, common indications of imminent preterm delivery, and presenting at the Curaçao Medical Center between 15 November 2019 and 31 December 2020, were included in this single cohort study. Data were retrospectively collected from medical records. The presence of Chlamydia trachomatis and Neisseria gonorrhoeae was assessed by Cepheid GeneXpert ® (Xpert) CT/NG assay (Sunnyvale, CA, USA). In the included cohort, the prevalence of Chlamydia trachomatis infection was 15.5% and of Neisseria gonorrhoeae infection was 2.1%. All patients infected with Neisseria gonorrhoeae were co-infected with Chlamydia trachomatis. The prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections in patients with imminent preterm delivery in Curaçao is high. It is recommended to test all patients with imminent preterm delivery for these sexually transmitted infections and possibly consider testing all women in early pregnancy on the island.
Cross-Sectional Study on the Prevalence of PCV Types 2 and 3 DNA in Suckling Piglets Compared to Grow–Finish Pigs in Downstream Production
Authors: Eddicks Matthias , Maurer Roland , Deffner Pauline , Eddicks Lina , Sipos Wolfgang , Reese Sven , Cvjetković Vojislav , Krejci Roman , Opriessnig Tanja , Ritzmann Mathias , Fux Robert
Published: June 2022

Vertical transmission is a consistently discussed pathway of porcine circovirus type 2 (PCV2) and porcine circovirus type 3 (PCV3) transmission in pigs. To evaluate the presence of PCV2 and PCV3 in piglets, we collected tissue samples from 185 piglets that were crushed within the first week of life from 16 farms located in Germany and Austria. Pooled samples consisting of thymus, inguinal lymph node, myocardium, lung and spleen were examined for PCV2 and PCV3 by qPCR. Furthermore, oral fluid samples (OFS) from grow–finish pigs were collected and examined the same way. In piglets, PCV2 was highly prevalent (litters: 69.4%; piglets: 61.6%), whereas PCV3 prevalence was low (litters: 13.4%; piglets: 13.0%). In total, 72.6% and 67.2% of all collected OFS were PCV2 or PCV3 positive, respectively. Sow vaccination against PCV2 was identified as a protective factor concerning PCV2 in piglets (OR: 0.279; CI: 0.134–0.578; p < 0.001), whereas the porcine reproductive and respiratory syndrome virus (PRRSV) vaccination of sows was identified as a protective factor concerning PCV3 in piglets (OR: 0.252 CI: 0.104–0.610; p = 0.002). Our results show that PCV2, but not PCV3, is ubiquitous in suckling piglets and that early PCV3 infections might be modulated by PRRSV–PCV3 interaction. However, the ubiquitous nature of both viruses in older pigs could be confirmed.
Utilization of Recombinant Baculovirus Expression System to Produce the RBD Domain of SARS-CoV-2 Spike Protein
Authors: Fan Youpeng , Wei Junhong , Wang Wei , Li Chunfeng , Pan Guoqing , Keiffer Timothy , Bao Jialing , Zhou Zeyang
Published: June 2022

Continuous outbreaks of viral diseases in humans facilitates a need for the rapid development of viral test kits and vaccines. These require expression systems to produce a pure and high yield of target viral proteins. We utilized a baculovirus–silkworm expression system to produce the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. First, we had to develop a strategy for constructing a recombinant baculovirus for RBD expression. For this, the coding region of the Bombyx mori cypovirus (BmCPV) polyhedron was assembled with the Bombyx mori nuclear polyhedrosis virus (BmNPV) promoter. We demonstrated that the recombinant baculovirus has the ability to form polyhedrons within host silkworm cells. In addition, the encapsulated BVs are able to infect silkworms by ingestion and induce foreign protein expression. In this way, we utilized this novel system to obtain a high yield of the target foreign protein, the RBD of the SARS-CoV-2 S protein. However, the viral infection rate of our recombinant BV needs to be improved. Our study shed light on developing a highly efficient expression system for the production of antigens and subsequent immunoassays and vaccines.
Genomic Analysis Reveals That Isolation Temperature on Selective Media Introduces Genetic Variation in Campylobacter jejuni from Bovine Feces
Authors: Fan Sicun , Foster Derek , Zhao Shaohua , Mukherjee Sampa , Shrestha Yesha , Parsons Cameron , Kathariou Sophia
Published: June 2022

Campylobacter jejuni is commonly isolated on selective media following incubation at 37 °C or 42 °C, but the impact of these temperatures on genome variation remains unclear. Previously, Campylobacter selective enrichments from the feces of steers before and after ceftiofur treatment were plated on selective agar media and incubated at either 37 °C or 42 °C. Here, we analyzed the whole genome sequence of C. jejuni strains of the same multilocus sequence typing (MLST)-based sequence type (ST) and isolated from the same sample upon incubation at both temperatures. Four such strain pairs (one ST8221 and three ST8567) were analyzed using core genome and whole genome MLST (cgMLST, wgMLST). Among the 1970 wgMLST loci, 7–25 varied within each pair. In all but one of the pairs more (1.7–8.5 fold) new alleles were found at 42 °C. Most frameshift, nonsense, or start-loss mutations were also found at 42 °C. Variable loci CAMP0575, CAMP0912, and CAMP0913 in both STs may regularly respond to different temperatures. Furthermore, frameshifts in four variable loci in ST8567 occurred at multiple time points, suggesting a persistent impact of temperature. These findings suggest that the temperature of isolation may impact the sequence of several loci in C. jejuni from cattle.
Copper-67-Labeled Bombesin Peptide for Targeted Radionuclide Therapy of Prostate Cancer
Authors: Huynh Truc T. , van Dam Ellen M. , Sreekumar Sreeja , Mpoy Cedric , Blyth Benjamin J. , Muntz Fenella , Harris Matthew J. , Rogers Buck E.
Published: June 2022

The gastrin-releasing peptide receptor (GRPR) is a promising molecular target for imaging and therapy of prostate cancer using bombesin peptides that bind to the receptor with high affinity. Targeted copper theranostics (TCTs) using copper radionuclides, 64Cu for imaging and 67Cu for therapy, offer significant advantages in the development of next-generation theranostics. [64Cu]Cu-SAR-BBN is in clinical development for PET imaging of GRPR-expressing cancers. This study explores the therapeutic efficacy of [67Cu]Cu-SAR-BBN in a pre-clinical mouse model. The peptide was radiolabeled with 67Cu, and specific binding of the radiolabeled peptide towards GRPR-positive PC-3 prostate cancer cells was confirmed with 52.2 ± 1.4% total bound compared to 5.8 ± 0.1% with blocking. A therapy study with [67Cu]Cu-SAR-BBN was conducted in mice bearing PC-3 tumors by injecting 24 MBq doses a total of six times. Tumor growth was inhibited by 93.3% compared to the control group on day 19, and median survival increased from 34.5 days for the control group to greater than 54 days for the treatment group. The ease and stability of the radiochemistry, favorable biodistribution, and the positive tumor inhibition demonstrate the suitability of this copper-based theranostic agent for clinical assessment in the treatment of cancers expressing GRPR.
Impact of the Gram-Negative-Selective Inhibitor MAC13243 on In Vitro Simulated Gut Microbiota
Authors: Svanberg Frisinger Frida , Pirolo Mattia , Ng Duncan Y. K. , Mao Xiaotian , Nielsen Dennis Sandris , Guardabassi Luca
Published: June 2022

New Gram-negative-selective antimicrobials are desirable to avoid perturbations in the gut microbiota leading to antibiotic-induced dysbiosis. We investigated the impact of a prototype drug (MAC13243) interfering with the Gram-negative outer membrane protein LolA on the faecal microbiota. Faecal suspensions from two healthy human donors were exposed to MAC13243 (16, 32, or 64 mg/L) using an in vitro gut model (CoMiniGut). Samples collected 0, 4, and 8 h after exposure were subjected to viable cell counts, 16S rRNA gene quantification and V3-V4 sequencing using the Illumina MiSeq platform. MAC13243 exhibited concentration-dependent killing of coliforms in both donors after 8 h. Concentrations of ≤32 mg/L reduced the growth of aerobic bacteria without influencing the microbiota composition and diversity. An expansion of Firmicutes at the expense of Bacteroidetes and Actinobacteria was observed in the faecal microbiota from one donor following exposure to 64 mg/L of MAC13242. At all concentrations tested, MAC13243 did not lead to the proliferation of Escherichia coli nor a reduced abundance of beneficial bacteria, which are typical changes observed in antibiotic-induced dysbiosis. These results support our hypothesis that a drug interfering with a specific target in Gram-negative bacteria has a low impact on the commensal gut microbiota and, therefore, a low risk of inducing dysbiosis.
HIF-PH Encoded by EGLN1 Is a Potential Therapeutic Target for Chronic Lymphocytic Leukemia
Authors: Guo Wancheng , Liang Daomiao , Wang Peilong , Yin Le , Zhang Huifang , Xing Cheng , Huang Zineng , Wu Yinghua , Li Heng , Cheng Zhao , Xiao Xiaojuan , Liu Jing , Wang Zhihua , Peng Hongling
Published: June 2022

Owing to the recent emergence of drug resistance to Bruton’s tyrosine kinase inhibitors (BTK) in chronic lymphocytic leukemia (CLL) treatment, it is crucial to identify alternative therapeutic targets. Therefore, we aimed to identify therapeutic options for CLL besides BTK. We identified that HIF1A expression was higher in CLL patients than in controls, which may suggest good prognosis. We used a lentiviral knockdown of EGLN1 (encoding hypoxia-inducible factor prolyl hydroxylase [HIF-PH]) and found that the growth of MEC-1 cells slowed in the knockdown group. Treatment of CLL cell lines MEC-1 and HG3 with the HIF-PH inhibitor molidustat showed that molidustat could induce apoptosis in a concentration-dependent manner in CLL cells and had low cytotoxicity at this concentration. CXCR4, HIF1A, SLC2AI, and VEGF, the downstream molecules of the HIF pathway, were upregulated after molidustat treatment. Western blotting results indicated that molidustat increased HIF1A expression in CLL cell lines and cells from CLL patients, and sequencing/quantitative PCR analysis demonstrated that the ribosome biogenesis pathway was inhibited in MEC-1 cells after molidustat treatment. We further identified synergistic cytotoxicity of molidustat in combination with ibrutinib on the MEC-1 and HG3 cell lines at certain concentrations. Therefore, molidustat is a potential therapeutic option for CLL.
Sirtuins and Hypoxia in EMT Control
Authors: Aventaggiato Michele , Barreca Federica , Sansone Luigi , Pellegrini Laura , Russo Matteo A. , Cordani Marco , Tafani Marco
Published: June 2022

Epithelial–mesenchymal transition (EMT), a physiological process during embryogenesis, can become pathological in the presence of different driving forces. Reduced oxygen tension or hypoxia is one of these forces, triggering a large number of molecular pathways with aberrant EMT induction, resulting in cancer and fibrosis onset. Both hypoxia-induced factors, HIF-1α and HIF-2α, act as master transcription factors implicated in EMT. On the other hand, hypoxia-dependent HIF-independent EMT has also been described. Recently, a new class of seven proteins with deacylase activity, called sirtuins, have been implicated in the control of both hypoxia responses, HIF-1α and HIF-2α activation, as well as EMT induction. Intriguingly, different sirtuins have different effects on hypoxia and EMT, acting as either activators or inhibitors, depending on the tissue and cell type. Interestingly, sirtuins and HIF can be activated or inhibited with natural or synthetic molecules. Moreover, recent studies have shown that these natural or synthetic molecules can be better conveyed using nanoparticles, representing a valid strategy for EMT modulation. The following review, by detailing the aspects listed above, summarizes the interplay between hypoxia, sirtuins, and EMT, as well as the possible strategies to modulate them by using a nanoparticle-based approach.
Structural and Functional Validation of a Full-Thickness Self-Assembled Skin Equivalent for Disease Modeling
Authors: Mok Bo Ram , Shon Su-Ji , Kim A Ram , Simard-Bisson Carolyne , Martel Israël , Germain Lucie , Kim Dong Hyun , Shin Jung U
Published: June 2022

Recently, various types of in vitro-reconstructed 3D skin models have been developed for drug testing and disease modeling. Herein, we structurally and functionally validated a self-assembled reconstructed skin equivalent (RSE) and developed an IL-17a-induced in vitro psoriasis-like model using a self-assembled RSE. The tissue engineering approach was used to construct the self-assembled RSE. The dermal layer was generated using fibroblasts secreting their own ECM, and the epidermal layer was reconstructed by seeding keratinocytes on the dermal layer. To generate the psoriatic model, IL-17A was added to the culture medium during the air–liquid interface culture period. Self-assembled RSE resulted in a fully differentiated epidermal layer, a well-established basement membrane, and dermal collagen deposition. In addition, self-assembled RSE was tested for 20 reference chemicals according to the Performance Standard of OECD TG439 and showed overall sensitivity, specificity, and accuracy of 100%, 90%, and 95%, respectively. The IL-17a-treated psoriatic RSE model exhibited psoriatic epidermal characteristics, such as epidermal hyperproliferation, parakeratosis, and increased expression of KRT6, KRT17, hBD2, and S100A9. Thus, our results suggest that a self-assembled RSE that structurally and functionally mimics the human skin has a great potential for testing various drugs or cosmetic ingredients and modeling inflammatory skin diseases.
Human Osteochondral Explants as an Ex Vivo Model of Osteoarthritis for the Assessment of a Novel Class of Orthobiologics
Authors: Giannasi Chiara , Mangiavini Laura , Niada Stefania , Colombo Andrea , Della Morte Elena , Vismara Valeria , Ambrosanio Andrea , Savadori Paolo , Casati Sara , Peretti Giuseppe M. , Brini Anna Teresa
Published: June 2022

Osteoarthritis (OA) is a highly prevalent joint disease still lacking effective treatments. Its multifactorial etiology hampers the development of relevant preclinical models to evaluate innovative therapeutic solutions. In the last decade, the potential of Mesenchymal Stem Cell (MSC) secretome, or conditioned medium (CM), has emerged as an alternative to cell therapy. Here, we investigated the effects of the CM from adipose MSCs (ASCs), accounting for both soluble factors and extracellular vesicles, on human osteochondral explants. Biopsies, isolated from total knee replacement surgery, were cultured without additional treatment or with the CM from 106 ASCs, both in the absence and in the presence of 10 ng/mL TNFα. Tissue viability and several OA-related hallmarks were monitored at 1, 3 and 6 days. Specimen viability was maintained over culture. After 3 days, TNFα induced the enhancement of matrix metalloproteinase activity and glycosaminoglycan release, both efficiently counteracted by CM. The screening of inflammatory lipids, proteases and cytokines outlined interesting modulations, driving the attention to new players in the OA process. Here, we confirmed the promising beneficial action of ASC secretome in the OA context and profiled several bioactive factors involved in its progression, in the perspective of accelerating an answer to its unmet clinical needs.
Peptides to Overcome the Limitations of Current Anticancer and Antimicrobial Nanotherapies
Authors: Del Genio Valentina , Bellavita Rosa , Falanga Annarita , Hervé-Aubert Katel , Chourpa Igor , Galdiero Stefania
Published: June 2022

Biomedical research devotes a huge effort to the development of efficient non-viral nanovectors (NV) to improve the effectiveness of standard therapies. NVs should be stable, sustainable and biocompatible and enable controlled and targeted delivery of drugs. With the aim to foster the advancements of such devices, this review reports some recent results applicable to treat two types of pathologies, cancer and microbial infections, aiming to provide guidance in the overall design of personalized nanomedicines and highlight the key role played by peptides in this field. Additionally, future challenges and potential perspectives are illustrated, in the hope of accelerating the translational advances of nanomedicine
Probability of Target Attainment of Tobramycin Treatment in Acute and Chronic Pseudomonas aeruginosa Lung Infection Based on Preclinical Population Pharmacokinetic Modeling
Authors: Dias Bruna Bernar , Carreño Fernando , Helfer Victória Etges , Garzella Priscila Martini Bernardi , de Lima Daiane Maria Fonseca , Barreto Fabiano , de Araújo Bibiana Verlindo , Dalla Costa Teresa
Published: June 2022

Biofilms and infectious process may alter free antimicrobial concentrations at the site of infection. Tobramycin (TOB), an aminoglycoside used to treat lung infections caused by Pseudomonas aeruginosa, binds to alginate present in biofilm extracellular matrix increasing its minimum inhibitory concentration (MIC). This work aimed to investigate the impact of biofilm-forming P. aeruginosa infection on TOB lung and epithelial lining fluid (ELF) penetration, using microdialysis, and to develop a population pharmacokinetic (popPK) model to evaluate the probability of therapeutic target attainment of current dosing regimens employed in fibrocystic and non-fibrocystic patients. The popPK model developed has three compartments including the lung. The ELF concentrations were described by a penetration factor derived from the lung compartment. Infection was a covariate in lung volume (V3) and only chronic infection was a covariate in central volume (V1) and total clearance (CL). Simulations of the recommended treatments for acute and chronic infection achieved >90% probability of target attainment (PTA) in the lung with 4.5 mg/kg q24h and 11 mg/kg q24h, respectively, for the most prevalent P. aeruginosa MIC (0.5 mg/mL). The popPK model was successfully applied to evaluate the PTA of current TOB dosing regimens used in the clinic, indicating the need to investigate alternative posology.
Individualized, Additively Manufactured Drug-Releasing External Ear Canal Implant for Prevention of Postoperative Restenosis: Development, In Vitro Testing, and Proof of Concept in an Individual Curative Trial
Authors: Matin-Mann Farnaz , Gao Ziwen , Schwieger Jana , Ulbricht Martin , Domsta Vanessa , Senekowitsch Stefan , Weitschies Werner , Seidlitz Anne , Doll Katharina , Stiesch Meike , Lenarz Thomas , Scheper Verena
Published: June 2022

Postoperative restenosis in patients with external ear canal (EEC) atresia or stenosis is a common complication following canaloplasty. Our aim in this study was to explore the feasibility of using a three dimensionally (3D)-printed, patient-individualized, drug ((dexamethasone (DEX)), and ciprofloxacin (cipro))-releasing external ear canal implant (EECI) as a postoperative stent after canaloplasty. We designed and pre-clinically tested this novel implant for drug release (by high-performance liquid chromatography), biocompatibility (by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay), bio-efficacy (by the TNF-α (tumor necrosis factor-alpha)-reduction test (DEX) and inhibition zone test (for cipro)), and microbial contamination (formation of turbidity or sediments in culture medium). The EECI was implanted for the first time to one patient with a history of congenital EEC atresia and state after three canaloplasties due to EEC restenosis. The preclinical tests revealed no cytotoxic effect of the used materials; an antibacterial effect was verified against the bacteria Staphylococcus aureus and Pseudomonas aeruginosa, and the tested UV-irradiated EECI showed no microbiological contamination. Based on the test results, the combination of silicone with 1% DEX and 0.3% cipro was chosen to treat the patient. The EECI was implantable into the EEC; the postoperative follow-up visits revealed no otogenic symptoms or infections and the EECI was explanted three months postoperatively. Even at 12 months postoperatively, the EEC showed good epithelialization and patency. Here, we report the first ever clinical application of an individualized, drug-releasing, mechanically flexible implant and suggest that our novel EECI represents a safe and effective method for postoperatively stenting the reconstructed EEC.
Integrating In Vitro and In Silico Analysis of a Cationic Antimicrobial Peptide Interaction with Model Membranes of Colistin-Resistant Pseudomonas aeruginosa Strains
Authors: Rivera-Sanchez Sandra Patricia , Ocampo-Ibáñez Iván Darío , Liscano Yamil , Martínez Natalia , Muñoz Isamar , Manrique-Moreno Marcela , Martinez-Martinez Luis , Oñate-Garzon José
Published: June 2022

Bacterial antibiotic resistance is a serious global public health concern. Infections caused by colistin-resistant Pseudomonas aeruginosa (CRPa) strains represent a serious threat due to their considerable morbidity and mortality rates, since most of the current empirical antibiotic therapies are ineffective against these strains. Accordingly, cationic antimicrobial peptides (CAMPs) have emerged as promising alternatives to control resistant bacteria. In this study, the interaction of a CAMP derived from cecropin D-like (∆M2) with model membranes mimicking bacterial biomembranes of wild-type (WTPa) strains of P. aeruginosa and CRPa was evaluated through in vitro and in silico approaches. In vitro interaction was determined by infrared spectroscopy, whereas in silico molecular dynamics was performed to predict specific interactions between amino acids of ∆M2 and lipids of model membrane systems. Experimental analysis showed this peptide interacted with the lipids of bacterial-like model membranes of WTPa and CRPa. In both cases, an increase in the concentration of peptides induced an increase in the phase transition temperature of the lipid systems. On the other hand, the peptides in solution underwent a transition from a random to a helical secondary structure after interacting with the membranes mostly favored in the CRPa system. The α-helix structure percentage for ΔM2 interacting with WTPa and CRPa lipid systems was 6.4 and 33.2%, respectively. Finally, molecular dynamics showed ∆M2 to have the most affinities toward the phospholipids palmitoyl-oleyl-phosphatidylglycerol (POPG) and palmitoyl-oleoyl-phosphatidylethanolamine (POPE) that mimic membranes of WTPa and CRPa, respectively. This work provides clues for elucidating the membrane-associated mechanism of action of ∆M2 against colistin-susceptible and -resistant strains of Pseudomonas aeruginosa.
Fruit Development in Sweet Cherry
Authors: Vignati Edoardo , Lipska Marzena , Dunwell Jim M. , Caccamo Mario , Simkin Andrew J.
Published: June 2022

Fruits are an important source of vitamins, minerals and nutrients in the human diet. They also contain several compounds of nutraceutical importance that have significant antioxidant and anti-inflammatory roles, which can protect the consumer from diseases, such as cancer, and cardiovascular disease as well as having roles in reducing the build-up of LDL-cholesterol in blood plasma and generally reduce the risks of disease and age-related decline in health. Cherries contain high concentrations of bioactive compounds and minerals, including calcium, phosphorous, potassium and magnesium, and it is, therefore, unsurprising that cherry consumption has a positive impact on health. This review highlights the development of sweet cherry fruit, the health benefits of cherry consumption, and the options for increasing consumer acceptance and consumption.
Response of the Phytoplankton Sinking Rate to Community Structure and Environmental Factors in the Eastern Indian Ocean
Authors: Wang Xingzhou , Sun Jun , Wei Yuqiu , Wu Xi
Published: June 2022

The phytoplankton sinking rate in the eastern Indian Ocean was measured during spring 2017 based on the SETCOL method. The range of phytoplankton sinking rates was −0.291 to 2.188 md−1, with an average of 0.420 ± 0.646 md−1. The phytoplankton sinking rate in the Equator (EQ) and the eastern boundary of the Indian Ocean near Sumatra (EB) was lower than that in the Bay of Bengal (BOB). The sinking rate above 100 m was low and increased rapidly below 100 m in all the three regions. The phytoplankton community composition had an important impact on the phytoplankton sinking rate in the east Indian Ocean. The strong stratification in BOB resulted in Trichodesmium spp. bloom and a lower phytoplankton diversity and evenness in BOB, while the phytoplankton in the deep layer are senescent cells that sink down from the upper layer and cannot actively regulate the state of the cells, resulting in a higher sinking rate. Depth and temperature have a great impact on the physiological state of phytoplankton. The sinking rate of phytoplankton depend on the dominant groups composing the phytoplankton community. For the eastern Indian Ocean, seawater stratification caused by temperature changes the distribution of nutrients in the upper layer, and phytoplankton are affected by temperature and nutrients, resulting in changes in community structure, and finally showing different subsidence characteristics.
Biogenic Volatile Organic Compounds and Protein Expressions of Chamaecyparis formosensis and Chamaecyparis obtusa var. formosana Leaves under Different Light Intensities and Temperatures
Authors: Chen Ying-Ju , Huang Ya-Lun , Chen Yu-Han , Chang Shang-Tzen , Yeh Ting-Feng
Published: June 2022

Both Chamaecyparis formosensis and C. obtusa var. formosana are representative cypresses of high economic value in Taiwan, the southernmost subtropical region where cypresses are found. Both species show differences of their habitats. To find out the effects of environmental factors on the CO2 assimilation rate and the biogenic volatile organic compound (BVOC) emission of both species, saplings from both species were grown under different light intensity and temperature regimes. The results indicated that the net CO2 assimilation rates and total BVOC emission rates of both species increased with increasing light intensity. C. formosensis showed a higher magnitude of change, but C. obtusa var. formosana had considerably increased sesquiterpenoid and diterpenoid emission in BVOC under high light intensity. Both species grown under higher temperatures had significantly lower BVOC emission rates. Proteomic analyses revealed that compared to C. formosensis saplings, C. obtusa var. formosana saplings had less differentially expressed proteins in terms of protein species and fold changes in response to the growth conditions. These proteins participated mainly in photosynthesis, carbon metabolism, amino acid and protein processing, signal transduction, and stress mechanisms. These proteins might be the major regulatory factors affecting BVOC emission of these two species under different environments.
Calcium and Potassium Accumulation during the Growing Season in Cabernet Sauvignon and Merlot Grape Varieties
Authors: Nistor Eleonora , Dobrei Alina Georgeta , Mattii Giovan Battista , Dobrei Alin
Published: June 2022

The evolution of calcium (Ca) and potassium (K) accumulation in grape berries during the growing season provided information on the productivity and quality of grape crops, considering that both elements have numerous physiological effects. The aim of the study was to determine and compare Ca and K accumulation in berries from ‘Cabernet Sauvignon’ and ‘Merlot’ grape varieties influenced by the number of days after flowering (DAF) over three consecutive growing seasons (2019–2021) in Recaş vineyards, from Banat Region in Western Romania. Results showed that Ca accumulation in the berries continued at slow rates after veraison when water was available for both varieties; accumulation was observed mainly in the skin, suggesting translocation from the flesh. Regression analysis showed a strong dependence on the interval of 65–75 DAF for Ca accumulation in the skin. K accumulation increased after the onset of veraison until 70 to 90 DAF in both varieties, with higher accumulation in the flesh than in the skin. No significant differences were found among varieties regarding the Ca and K content during the study period. In both varieties, the relationship between sugar accumulation and the Ca/K content was highly significant. Given the importance of both elements, new data may contribute to establishing the optimum grape ripeness in relation to the sugar concentration in the berries.
Improving Sesame (Sesamum indicum L.) Seed Yield through Selection under Infection of Fusarium oxysporum f. sp. sesami
Authors: Mahdy Rasha Ezzat , Gaber Dalia A. , Hashem Mohamed , Alamri Saad , Mahdy Ezzat E.
Published: June 2022

Sesame (Sesamum indicum L.), the Queen of oilseeds, is infected with different pathogens, restricting its yield. Fusarium oxysporum f. sp. sesami is the most destructive disease of sesame worldwide, causing economic losses. This work aimed to develop new high-yielding strains, resistant and/or tolerant to Fusarium. Two cycles of pedigree selection were achieved under infection of Fusarium oxysporum f. sp. sesami. Two populations in the F2 (600 plants each) were used. The selection criteria were five single traits and another three restricted by yield. The restricted selection was better in preserving variability than the single trait selection. The observed genetic gain in percentage from the mid-parent in the F4-generation was significant for the eight selection criteria. Single trait selection proved to be an effective method for improving the selection criterion, but it caused deleterious effects on the other correlated traits in most cases. The seed yield increased by 30.67% and 20.31% from the better parent in the first and second populations, respectively. The infection% was significantly reduced by 24.04% in the first, and 9.3% in the second, population. The selection index improved seed yield, and its attributes can be recommended.
Molecular Cloning and Analysis of an Acetyl-CoA C-acetyltransferase Gene (EkAACT) from Euphorbia kansui Liou
Authors: Wang Meng , Zheng Zhe , Tian Zheni , Zhang Hao , Zhu Chenyu , Yao Xiangyu , Yang Yixin , Cai Xia
Published: June 2022

Terpenoids are the largest class of natural products and are essential for cell functions in plants and their interactions with the environment. Acetyl-CoA acetyltransferase (AACT, EC2.3.1.9) can catalyze a key initiation step of the mevalonate pathway (MVA) for terpenoid biosynthesis and is modulated by many endogenous and external stimuli. Here, the function and expression regulation activities of AACT in Euphorbia kansui Liou (EkAACT) were reported. Compared with wild-type Arabidopsis, the root length, whole seedling fresh weight and growth morphology of EkAACT-overexpressing plants were slightly improved. The transcription levels of AtAACT, AtMDC, AtMK, AtHMGR, and AtHMGS in the MVA pathway and total triterpenoid accumulation increased significantly in transgenic Arabidopsis. Under NaCl and PEG treatment, EkAACT-overexpressing Arabidopsis showed a higher accumulation of total triterpenoids, higher enzyme activity of peroxidase (POD) and superoxide dismutase (SOD), increased root length and whole seedling fresh weight, and a decrease in the proline content, which indicated that plant tolerance to abiotic stress was enhanced. Thus, AACT, as the first crucial enzyme, plays a major role in the overall regulation of the MVA pathway.
The Promoter Analysis of VvPR1 Gene: A Candidate Gene Identified through Transcriptional Profiling of Methyl Jasmonate Treated Grapevine (Vitis vinifera L.)
Authors: Rahman Faiz Ur , Zhang Ying , Khan Irshad Ahmad , Liu Ruitao , Sun Lei , Wu Yandi , Jiang Jianfu , Fan Xiucai , Liu Chonghuai
Published: June 2022

Methyl jasmonate (MeJA) plays a vital role in plant disease resistance and also induces the expression of disease resistance genes in plants. In this study, a transcriptome analysis was performed on grapevine leaves after 12, 24 and 48 h of MeJA-100 μM treatment. A total of 1242 differentially expressed genes (DEGs) were identified from the transcriptome data, and the analysis of the DEGs showed that genes related to phytohormone signal transduction, jasmonic acid-mediated defense, Mitogen-activated protein kinase (MAPK), and flavonoid biosynthetic pathways were upregulated. As Pathogenesis-related gene 1 (PR1) is an important marker gene in plant defense also upregulated by MeJA treatment in RNA-seq data, the VvPR1 gene was selected for a promoter analysis with β-glucuronidase (GUS) through transient expression in tobacco leaves against abiotic stress. The results showed that the region from −1837 bp to −558 bp of the VvPR1 promoter is the key region in response to hormone and wound stress. In this study, we extended the available knowledge about induced defense by MeJA in a grapevine species that is susceptible to different diseases and identified the molecular mechanisms by which this defense might be mediated.
Natural Sources and Pharmacological Properties of Pinosylvin
Authors: Bakrim Saad , Machate Hamza , Benali Taoufiq , Sahib Nargis , Jaouadi Imane , Omari Nasreddine El , Aboulaghras Sara , Bangar Sneh Punia , Lorenzo José Manuel , Zengin Gokhan , Montesano Domenico , Gallo Monica , Bouyahya Abdelhakim
Published: June 2022

Pinosylvin (3,5-dihydroxy-trans-stilbene), a natural pre-infectious stilbenoid toxin, is a terpenoid polyphenol compound principally found in the Vitaceae family in the heartwood of Pinus spp. (e.g., Pinus sylvestris) and in pine leaf (Pinus densiflora). It provides defense mechanisms against pathogens and insects for many plants. Stilbenoids are mostly found in berries and fruits but can also be found in other types of plants, such as mosses and ferns. This review outlined prior research on pinosylvin, including its sources, the technologies used for its extraction, purification, identification, and characterization, its biological and pharmacological properties, and its toxicity. The collected data on pinosylvin was managed using different scientific research databases such as PubMed, SciFinder, SpringerLink, ScienceDirect, Wiley Online, Google Scholar, Web of Science, and Scopus. In this study, the findings focused on pinosylvin to understand its pharmacological and biological activities as well as its chemical characterization to explore its potential therapeutic approaches for the development of novel drugs. This analysis demonstrated that pinosylvin has beneficial effects for various therapeutic purposes such as antifungal, antibacterial, anticancer, anti-inflammatory, antioxidant, neuroprotective, anti-allergic, and other biological functions. It has shown numerous and diverse actions through its ability to block, interfere, and/or stimulate the major cellular targets responsible for several disorders.
Environmental Gradients Shaping the Freshwater Bryophyte Communities of Croatia (Western Balkans)
Authors: Rimac Anja , Alegro Antun , Šegota Vedran , Vuković Nina , Koletić Nikola
Published: June 2022

A comprehensive field survey of 527 sites on 293 watercourses across Croatia revealed 76 sites (14.42%) in which bryophytes were the dominant part of the macrophyte vegetation. Using classification and ordination analyses, we obtained five community types segregated across the gradients of several climatic, physiographic and water chemistry parameters. The Didymodon tophaceus–Apopellia endiviifolia and the Berula erecta-Cratoneuron filicinum communities were mostly confined to the clean and basic karstic rivers of the Dinaric Ecoregion under the influence of the Mediterranean climate, with the Didymodon tophaceus–Apopellia endiviifolia community being a tufa-forming community associated with the seasonally dry watercourses of small catchment areas and cascades along the larger karstic rivers, while the Berula erecta–Cratoneuton filicinum community was mostly associated with rivers with larger catchment areas and permanent flow. On the other hand, the Oxyrrhynchium hians–Chiloscyphus pallescens community and the Fissidens pusillus–Veronica beccabunga community were associated with eutrophic water restricted to small rivers of the Pannonian Ecoregion under the influence of the temperate climate and flowing over silicate bedrock. The most represented and widespread in Croatia was the Cinclidotus community, displaying the widest ecological range in the study. It was mostly associated with the relatively clean karstic rivers of large catchment areas belonging to the Dinaric Ecoregion, with the majority of the sites under the influence of a temperate climate with higher precipitation during the warm period of the year. The geographical patterns of the freshwater bryophyte communities showed that the relatively clean, fast and cold karstic rivers belonging to the Dinaric Ecoregion provide habitats that harbour a greater diversity of bryophyte communities than the watercourses of the Pannonian Ecoregion, where bryophyte-dominated communities are restricted to a small number of small lowland and semi-montane rivers and predominantly occupy periodically flooded microhabitats such as river margins.
QTL Mapping for Resistance to Bacterial Wilt Caused by Two Isolates of Ralstonia solanacearum in Chili Pepper (Capsicum annuum L.)
Authors: Lee Saeyoung , Chakma Nidhi , Joung Sunjeong , Lee Je Min , Lee Jundae
Published: June 2022

Bacterial wilt caused by the β-proteobacterium Ralstonia solanacearum is one of the most destructive soil-borne pathogens in peppers (Capsicum annuum L.) worldwide. Cultivated pepper fields in Korea face a continuous spread of this pathogen due to global warming. The most efficient and sustainable strategy for controlling bacterial wilt is to develop resistant pepper varieties. Resistance, which is quantitatively inherited, occurs differentially depending on R. solanacearum isolates. Therefore, in this study, we aimed to identify resistance quantitative trait loci (QTLs) in two F2 populations derived from self-pollination of a highly resistant pepper cultivar ‘Konesian hot’ using a moderately pathogenic ‘HS’ isolate and a highly pathogenic ‘HWA’ isolate of R. solanacearum for inoculation, via genotyping-by-sequencing analysis. QTL analysis revealed five QTLs, Bwr6w-7.2, Bwr6w-8.1, Bwr6w-9.1, Bwr6w-9.2, and Bwr6w-10.1, conferring resistance to the ‘HS’ isolate with R2 values of 13.05, 12.67, 15.07, 10.46, and 9.69%, respectively, and three QTLs, Bwr6w-5.1, Bwr6w-6.1, and Bwr6w-7.1, resistant to the ‘HWA’ isolate with phenotypic variances of 19.67, 16.50, and 12.56%, respectively. Additionally, six high-resolution melting (HRM) markers closely linked to the QTLs were developed. In all the markers, the mean disease index of the paternal genotype was significantly lower than that of the maternal genotype. The QTLs and HRM markers are expected to be useful for the development of pepper varieties with high resistance to bacterial wilt.