bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal Trends and Differences in Sexuality among Depressed and Non-Depressed Adults in the United States
Authors: Li Weiya , Wang Yu , Xu Mingyu , Liao Yingxue , Zhou Haofeng , Ma Huan , Geng Qingshan
Published: October 2022

This study aimed to examine temporal trends and differences in sexuality between depressed and non-depressed adults aged 18–59 in the United States from 2005 to 2016. A total of 21,437 people (5432 with depression) were enrolled in this cross-sectional study. From 2005–2008 to 2013–2016, the average age at first sexual intercourse decreased, while the proportion of normal frequency of sexual activity and heterosexual sexual orientation increased among all the participants. Some differences in sexuality were found between the depressed and non-depressed groups. The average age at first sexual intercourse (p < 0.001), the proportion of normal frequency of sexual activity (p < 0.001), and heterosexual sexual orientation (p < 0.001) were lower in depressed participants, and the differences did not change over time (pfor trend = 0.926 of average age at first sexual intercourse, pfor trend = 0.823 of normal frequency of sexual activity, pfor trend = 0.926 of heterosexual sexual orientation). Moreover, these differences were associated with marital status (pfor interaction < 0.001 by average age at first sexual intercourse), employment status (pfor interaction < 0.001 by average age at first sexual intercourse), education status (pfor interaction = 0.023 by heterosexual sexual orientation) and family income status (pfor interaction = 0.013 by average age at first sexual intercourse and pfor interaction = 0.017 by normal frequency of sexual activity). In conclusion, the study found that the age at first sexual intercourse decreased and the frequency of sexual intercourse increased in all the participants, and differences in sexuality between depressed and non-depressed participants were present; however, these differences had no further increase or decrease during the 12-year period. These differences were associated with marital status, employment status, education status, and family income status. These findings show differences in sexuality between depressed and non-depressed patients but are somewhat different from previous studies; the results may provide directions for future research and social work.
Reliability, Validity and Responsiveness of the Polish Version of the Western Ontario Shoulder Instability Index (WOSI-PL) in Patients after Arthroscopic Repair for Shoulder Instability
Authors: Bejer Agnieszka , Płocki Jędrzej , Kulczyk Marek , Griffin Sharon , Kotela Ireneusz , Kotela Andrzej
Published: October 2022

Apart from imaging and physical examination for shoulder instability (SI), medical history with patient feedback should be considered to assess the patient’s condition and recovery. The aim of this study was to evaluate psychometric properties of the Polish version of Western Ontario Shoulder Instability Index (WOSI)—one of the most frequently used patient-reported outcome measures for SI. During examination 1, 74 patients after arthroscopic repair for SI (age x¯ = 30.01 ± 8.98) were tested. Examinations 2 and 3 involved 71 and 51 patients, respectively. They completed the Polish version of the WOSI, the shortened version of the Disabilities of Arm, Shoulder and Hand Questionnaire (QuickDASH), the Short Form-36 version 2.0 (SF-36 v. 2.0) and 7-point Global Rating Change scale (GRC). The WOSI-PL demonstrated high internal consistency (Cronbach’s alpha for total = 0.94), and test–retest reliability (Total ICC2,1 = 0.99). High construct validity was found (89%) as the a priori hypotheses were confirmed. All domains and total scores of WOSI-PL showed a moderate to strong degree of responsiveness (ES = 0.37–0.44; SMR = 0.87–1.26). Minimal clinically important difference (MCID) for the Total WOSI-PL was 126.43 points/6% (95%CI 67.83–185.03) by the anchor-based method and 174.05 points/8% (95%CI 138.61–233.98) by the distribution-based method. The Polish version of the WOSI can be considered a reliable, valid and responsive PROM. It is recommended for assessing the quality of life in patients after arthroscopic repair for SI and can be applied in research and in the clinical setting for monitoring treatment and facilitating patient-centred therapeutic decisions.
Severe Air Pollution Exposure and Long-Term Health Outcomes
Authors: Kim Younoh , Radoias Vlad
Published: October 2022

Background: There is a large literature that documents the negative health implications of exposure to air pollution, particularly PM2.5. Much of this literature, however, relies on short-term cross-sectional data, which cannot establish a true causal link between pollution and health. There are also very few studies that document long- and very long-term effects. Purpose: This study intends to estimate a causal relationship between exposure to severe air pollution and negative health outcomes that persist over long periods of time. Methods: We use a large longitudinal dataset that spans almost 2 decades and that allows us to not only document the persistence of negative health effects, but also a pattern of recovery from a severe pollution episode. We use multivariate regression methods to estimate a causal link between air pollution and health over time. A large pollution shock that occurred in 1997 in Indonesia is used as a natural experiment to pinpoint the true causal effects of pollution exposure and not mere correlations. Results: Exposure to an additional unit of pollution in 1997 leads to a loss of roughly six units of lung capacity and to an increase of 4.3% in the probability of being in poor general health, as measured ten years after the pollution exposure. These effects somewhat diminish over time, to a loss of roughly three units of lung capacity and to an increase of only about 3% in the probability of being in poor general health, as measured 17 years after exposure. Conclusions: Our study finds significant health consequences of exposure to air pollution, which persist over long periods of time, with some patterns of recovery. Policymakers should pay special attention to such massive sources of pollution and try to mitigate these negative health consequences.
Somatostatin, Cortistatin and Their Receptors Exert Antitumor Actions in Androgen-Independent Prostate Cancer Cells: Critical Role of Endogenous Cortistatin
Authors: Sáez-Martínez Prudencio , Porcel-Pastrana Francisco , Pérez-Gómez Jesús M. , Pedraza-Arévalo Sergio , Gómez-Gómez Enrique , Jiménez-Vacas Juan M. , Gahete Manuel D. , Luque Raúl M.
Published: October 2022

Somatostatin (SST), cortistatin (CORT), and their receptors (SSTR1-5/sst5TMD4-TMD5) comprise a multifactorial hormonal system involved in the regulation of numerous pathophysiological processes. Certain components of this system are dysregulated and play critical roles in the development/progression of different endocrine-related cancers. However, the presence and therapeutic role of this regulatory system in prostate cancer (PCa) remain poorly explored. Accordingly, we performed functional (proliferation/migration/colonies-formation) and mechanistic (Western-blot/qPCR/microfluidic-based qPCR-array) assays in response to SST and CORT treatments and CORT-silencing (using specific siRNA) in different PCa cell models [androgen-dependent (AD): LNCaP; androgen-independent (AI)/castration-resistant PCa (CRPC): 22Rv1 and PC-3], and/or in the normal-like prostate cell-line RWPE-1. Moreover, the expression of SST/CORT system components was analyzed in PCa samples from two different patient cohorts [internal (n = 69); external (Grasso, n = 88)]. SST and CORT treatment inhibited key functional/aggressiveness parameters only in AI-PCa cells. Mechanistically, antitumor capacity of SST/CORT was associated with the modulation of oncogenic signaling pathways (AKT/JNK), and with the significant down-regulation of critical genes involved in proliferation/migration and PCa-aggressiveness (e.g., MKI67/MMP9/EGF). Interestingly, CORT was highly expressed, while SST was not detected, in all prostate cell-lines analyzed. Consistently, endogenous CORT was overexpressed in PCa samples (compared with benign-prostatic-hyperplasia) and correlated with key clinical (i.e., metastasis) and molecular (i.e., SSTR2/SSTR5 expression) parameters. Remarkably, CORT-silencing drastically enhanced proliferation rate and blunted the antitumor activity of SST-analogues (octreotide/pasireotide) in AI-PCa cells. Altogether, we provide evidence that SST/CORT system and SST-analogues could represent a potential therapeutic option for PCa, especially for CRPC, and that endogenous CORT could act as an autocrine/paracrine regulator of PCa progression.
The Potential Role of the Methionine Aminopeptidase Gene PxMetAP1 in a Cosmopolitan Pest for Bacillus thuringiensis Toxin Tolerance
Authors: Ye Min , Xiong Lei , Dong Yi , Xie Chao , Zhang Zhen , Shen Lingling , Li Zeyun , Yue Zhen , Jiang Puzi , Yuchi Zhiguang , You Minsheng , You Shijun
Published: October 2022

Methionine aminopeptidases (MetAPs) catalyze the cleavage of the N-terminal initiator methionine (iMet) in new peptide chains and arylamides, which is essential for protein and peptide synthesis. MetAP is differentially expressed in two diamondback moth (DBM; Plutella xylostella) strains: the G88 susceptible strain and the Cry1S1000 strain, which are resistant to the Bt toxin Cry1Ac, implicating that MetAP expression might be associated with Bt resistance. In this study, we identified and cloned a MetAP gene from DBMs, named PxMetAP1, which has a CDS of 1140 bp and encodes a 379 amino acid protein. The relative expression of PxMetAP1 was found to be ~2.2-fold lower in the Cry1S1000 strain compared to that in the G88 strain. PxMetAP1 presents a stage- and tissue-specific expression pattern, with higher levels in the eggs, adults, integument, and fatbody of DBMs. The linkage between PxMetAP1 and Cry1Ac resistance is verified by genetic linkage analysis. The knockout of PxMetAP1 in G88 by CRISPR/Cas9 leads to a ~5.6-fold decrease in sensitivity to the Cry1Ac toxin, further supporting the association between the PxMetAP1 gene and Bt tolerance. Our research sheds light on the role of MetAP genes in the development of Bt tolerance in P. xylostella and enriches the knowledge for the management of such a cosmopolitan pest.
Molecular Imaging in Nanomedical Research 2.0
Authors: Malatesta Manuela
Published: October 2022

Over the last two decades, imaging techniques have become irreplaceable tools in nanotechnology: electron microscopy techniques are routinely used to observe the structural features of newly manufactured nanoconstructs, while light and electron microscopy, magnetic resonance imaging, optical imaging, positron emission tomography, and ultrasound imaging allow dynamic monitoring of the biodistribution, targeting and clearance of nanoparticulates in living systems, either for the whole organism or at the level of single cells, tissues and organs [...]
Effect of Copper on the Function of Isolated Porcine Kidneys Stored Using Simple Hypothermia
Authors: Ostróżka-Cieślik Aneta , Dolińska Barbara , Ryszka Florian
Published: October 2022

Renal ischemia in the peri-transplant period causes a number of changes that adversely affect the initiation of normal vital functions in grafts after transplantation. To minimise the extent of ischemic damage, organs are stored in preservation fluid. The components of the fluid are supposed to ensure stabilisation of the cell cytoskeleton, protect against oxygen free radicals, reduce cell swelling, and ensure endothelial cell integrity. The aim of this study was to analyse the protective effect of Cu2+, as a component of Biolasol preservative fluid, in the prevention of nephron damage occurring during the graft storage period. Analyses of the effectiveness of copper in the presence of prolactin added to Biolasol fluid were also carried out. Forty isolated pig slaughter kidneys were used in the study, avoiding the use of laboratory animals. The kidneys were stored using simple hypothermia. After 2 h and 48 h of graft storage, selected biochemical indicators of renal function were determined in the collected perfusates. The addition of Cu2+ at a dose of 1 µg/L to the composition of Biolasol fluid was found to affect the generation of ischemic damage in the isolated pig kidney. The intensity of the occurrence of these processes is exacerbated by the presence of prolactin at a dose of 0.1 µg/L.
NLRP3-Mediated Piezo1 Upregulation in ACC Inhibitory Parvalbumin-Expressing Interneurons Is Involved in Pain Processing after Peripheral Nerve Injury
Authors: Li Qiao-Yun , Duan Yi-Wen , Zhou Yao-Hui , Chen Shao-Xia , Li Yong-Yong , Zang Ying
Published: October 2022

The anterior cingulate cortex (ACC) is particularly critical for pain information processing. Peripheral nerve injury triggers neuronal hyper-excitability in the ACC and mediates descending facilitation to the spinal dorsal horn. The mechanically gated ion channel Piezo1 is involved in the transmission of pain information in the peripheral nervous system. However, the pain-processing role of Piezo1 in the brain is unknown. In this work, we found that spared (sciatic) nerve injury (SNI) increased Piezo1 protein levels in inhibitory parvalbumin (PV)-expressing interneurons (PV-INs) but not in glutaminergic CaMKⅡ+ neurons, in the bilateral ACC. A reduction in the number of PV-INs but not in the number of CaMKⅡ+ neurons and a significant reduction in inhibitory synaptic terminals was observed in the SNI chronic pain model. Further, observation of morphological changes in the microglia in the ACC showed their activated amoeba-like transformation, with a reduction in process length and an increase in cell body area. Combined with the encapsulation of Piezo1-positive neurons by Iba1+ microglia, the loss of PV-INs after SNI might result from phagocytosis by the microglia. In cellular experiments, administration of recombinant rat TNF-α (rrTNF) to the BV2 cell culture or ACC neuron primary culture elevated the protein levels of Piezo1 and NOD-like receptor (NLR) family pyrin domain containing 3 (NLRP3). The administration of the NLRP3 inhibitor MCC950 in these cells blocked the rrTNF-induced expression of caspase-1 and interleukin-1β (key downstream factors of the activated NLRP3 inflammasome) in vitro and reversed the SNI-induced Piezo1 overexpression in the ACC and alleviated SNI-induced allodynia in vivo. These results suggest that NLRP3 may be the key factor in causing Piezo1 upregulation in SNI, promoting an imbalance between ACC excitation and inhibition by inducing the microglial phagocytosis of PV-INs and, thereby, facilitating spinal pain transmission.
Analysis of the Site-Specific Myoglobin Modifications in the Melibiose-Derived Novel Advanced Glycation End-Product
Authors: Gostomska-Pampuch Kinga , Wiśniewski Jacek R. , Sowiński Karol , Gruszecki Wieslaw I. , Gamian Andrzej , Staniszewska Magdalena
Published: October 2022

MAGE (melibiose-derived advanced glycation end-product) is the glycation product generated in the reaction of a model protein with melibiose. The in vivo analog accumulates in several tissues; however, its origin still needs explanation. In vitro MAGE is efficiently generated under dry conditions in contrast to the reaction carried in an aqueous solvent. Using liquid chromatography coupled with mass spectrometry, we analyzed the physicochemical properties and structures of myoglobin glycated with melibiose under different conditions. The targeted peptide analysis identified structurally different AGEs, including crosslinking and non-crosslinking modifications associated with lysine, arginine, and histidine residues. Glycation in a dry state was more efficient in the formation of structures containing an intact melibiose moiety (21.9%) compared to glycation under aqueous conditions (15.6%). The difference was reflected in characteristic fluorescence that results from protein structural changes and impact on a heme group of the model myoglobin protein. Finally, our results suggest that the formation of in vitro MAGE adduct is initiated by coupling melibiose to a model myoglobin protein. It is confirmed by the identification of intact melibiose moieties. The intermediate glycation product can further rearrange towards more advanced structures, including cross-links. This process can contribute to a pool of AGEs accumulating locally in vivo and affecting tissue biology.
Cathelicidin Treatment Silences Epithelial–Mesenchymal Transition Involved in Pulmonary Fibrosis in a Murine Model of Hypersensitivity Pneumonitis
Authors: Lemieszek Marta Kinga , Golec Marcin , Zwoliński Jacek , Dutkiewicz Jacek , Milanowski Janusz
Published: October 2022

Pulmonary fibrosis is becoming an increasingly common pathology worldwide. Unfortunately, this disorder is characterized by a bad prognosis: no treatment is known, and the survival rate is dramatically low. One of the most frequent reasons for pulmonary fibrosis is hypersensitivity pneumonitis (HP). As the main mechanism of pulmonary fibrosis is a pathology of the repair of wounded pulmonary epithelium with a pivotal role in epithelial–mesenchymal transition (EMT), we assumed that EMT silencing could prevent disease development. Because of several biological features including wound healing promotion, an ideal candidate for use in the treatment of pulmonary fibrosis seems to be cathelicidin. The aim of the studies was to understand the influence of cathelicidin on the EMT process occurring during lung fibrosis development in the course of HP. Cathelicidin’s impact on EMT was examined in a murine model of HP, wherein lung fibrosis was induced by chronic exposure to extract of Pantoea agglomerans (SE-PA) by real-time PCR and Western blotting. Studies revealed that mouse exposure to cathelicidin did not cause any side changes in the expression of investigated genes/proteins. Simultaneously, cathelicidin administered together or after SE-PA decreased the elevated level of myofibroblast markers (Acta2/α-smooth muscle actin, Cdh2/N-cadherin, Fn1/Fibronectin, Vim/vimentin) and increased the lowered level of epithelial markers (Cdh1/E-cadherin, Ocln/occludin). Cathelicidin provided with SE-PA or after cessation of SE-PA inhalations reduced the expression of EMT-associated factors (Ctnnd1/β-catenin, Nfkb1/NFκB, Snail1/Snail, Tgfb1/TGFβ1 Zeb1/ZEB1, Zeb2/ZEB2) elevated by P. agglomerans. Cathelicidin’s beneficial impact on the expression of genes/proteins involved in EMT was observed during and after the HP development; however, cathelicidin was not able to completely neutralize the negative changes. Nevertheless, significant EMT silencing in response to cathelicidin suggested the possibility of its use in the prevention/treatment of pulmonary fibrosis.
High Glycemia and Soluble Epoxide Hydrolase in Females: Differential Multiomics in Murine Brain Microvasculature
Authors: Nuthikattu Saivageethi , Milenkovic Dragan , Norman Jennifer E. , Rutledge John , Villablanca Amparo
Published: October 2022

The effect of a high glycemic diet (HGD) on brain microvasculature is a crucial, yet understudied research topic, especially in females. This study aimed to determine the transcriptomic changes in female brain hippocampal microvasculature induced by a HGD and characterize the response to a soluble epoxide hydrolase inhibitor (sEHI) as a mechanism for increased epoxyeicosatrienoic acids (EETs) levels shown to be protective in prior models of brain injury. We fed mice a HGD or a low glycemic diet (LGD), with/without the sEHI (t-AUCB), for 12 weeks. Using microarray, we assessed differentially expressed protein-coding and noncoding genes, functional pathways, and transcription factors from laser-captured hippocampal microvessels. We demonstrated for the first time in females that the HGD had an opposite gene expression profile compared to the LGD and differentially expressed 506 genes, primarily downregulated, with functions related to cell signaling, cell adhesion, cellular metabolism, and neurodegenerative diseases. The sEHI modified the transcriptome of female mice consuming the LGD more than the HGD by modulating genes involved in metabolic pathways that synthesize neuroprotective EETs and associated with a higher EETs/dihydroxyeicosatrienoic acids (DHETs) ratio. Our findings have implications for sEHIs as promising therapeutic targets for the microvascular dysfunction that accompanies vascular dementia.
Losartan Potassium and Verapamil Hydrochloride Compound Transdermal Drug Delivery System: Formulation and Characterization
Authors: Chen Yu-si , Sun Yi-yang , Qin Zi-chen , Zhang Sai-ya , Chen Wen-bo , Liu Yan-qiang
Published: October 2022

In this study, we developed a sustained-release transdermal delivery system containing losartan potassium (LP) and verapamil hydrochloride (VPH). LP and VPH have low bioavailability and long half-life. Therefore, the development of an optimum administration mode is necessary to overcome these drawbacks and enhance the antihypertensive effect. A transdermal diffusion meter was used to determine the optimal formulation of LP-VPH transdermal drug delivery systems (TDDS). Based on in vitro results, a sustained-release patch was prepared. Physical characteristics, including quality, stickiness, and appearance, were evaluated in vitro, while pharmacokinetics and skin irritation were evaluated in vivo. The results showed that 8.3% polyvinyl alcohol, 74.7% polyvinylpyrrolidone K30, 12% oleic acid-azone, and 5% polyacrylic acid resin II provided an optimized TDDS product for effective administration of LP and VPH. Furthermore, in vitro and in vivo release tests showed that the system continuously released LP and VPH for 24 h. The pharmacokinetic results indicated that although the maximum concentration was lower, both the area under the curve from 0–time and the mean residence time of the prepared patch were significantly higher than those of the oral preparations. Furthermore, the prepared LP-VPH transdermal patch showed good stability and no skin irritation. The developed LP-VPH TDDS showed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it is an ideal formulation.
Targeting Immune Senescence in Atherosclerosis
Authors: Vellasamy Danusha Michelle , Lee Sin-Jye , Goh Khang Wen , Goh Bey-Hing , Tang Yin-Quan , Ming Long Chiau , Yap Wei Hsum
Published: October 2022

Atherosclerosis is one of the main underlying causes of cardiovascular diseases (CVD). It is associated with chronic inflammation and intimal thickening as well as the involvement of multiple cell types including immune cells. The engagement of innate or adaptive immune response has either athero-protective or atherogenic properties in exacerbating or alleviating atherosclerosis. In atherosclerosis, the mechanism of action of immune cells, particularly monocytes, macrophages, dendritic cells, and B- and T-lymphocytes have been discussed. Immuno-senescence is associated with aging, viral infections, genetic predispositions, and hyperlipidemia, which contribute to atherosclerosis. Immune senescent cells secrete SASP that delays or accelerates atherosclerosis plaque growth and associated pathologies such as aneurysms and coronary artery disease. Senescent cells undergo cell cycle arrest, morphological changes, and phenotypic changes in terms of their abundances and secretome profile including cytokines, chemokines, matrix metalloproteases (MMPs) and Toll-like receptors (TLRs) expressions. The senescence markers are used in therapeutics and currently, senolytics represent one of the emerging treatments where specific targets and clearance of senescent cells are being considered as therapy targets for the prevention or treatment of atherosclerosis.
From Nature to Synthetic Compounds: Novel 1(N),2,3 Trisubstituted-5-oxopyrrolidines Targeting Multiple Myeloma Cells
Authors: Listro Roberta , Malacrida Alessio , Ambrosio Francesca Alessandra , Rossino Giacomo , Di Giacomo Marcello , Cavalloro Valeria , Garbagnoli Martina , Linciano Pasquale , Rossi Daniela , Cavaletti Guido , Costa Giosuè , Alcaro Stefano , Miloso Mariarosaria , Collina Simona
Published: October 2022

The insurgence of drug resistance in treating Multiple Myeloma (MM) still represents a major hamper in finding effective treatments, although over the past decades new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, have been discovered. Recently, our research team, within a Nature-Aided Drug Discovery project, isolated from Hibiscus Sabdariffa L. calyces the secondary metabolite called Hib-ester which possesses antiproliferative properties against human multiple myeloma RPMI 8226 cells, reduces migration and cell invasion and inhibits proteasome without neurotoxic effects. In the present study, we explored the chemical spaces of the hit compound Hib-ester. We explored the structure-activity relationships (SAR), and we optimized the scaffold through sequentially modifying Hib-ester subunits. Compound screening was performed based on cytotoxicity against the RPMI 8226 cells to assess the potential efficacy toward human MM. The ability of the most effective molecules to inhibit the proteasome was evaluated and the binding mode of the most promising compounds in the proteasome chymotrypsin binding pocket was deciphered through molecular modeling simulations. Compounds 13 and 14 are more potent than Hib-ester, demonstrating that our strategy was suitable for the identification of a novel chemotype for developing possible drug candidates and hopefully widening the drug armamentarium against MM.
The Cytogenetic Map of the Nile Crocodile (Crocodylus niloticus, Crocodylidae, Reptilia) with Fluorescence In Situ Localization of Major Repetitive DNAs
Authors: Romanenko Svetlana A. , Prokopov Dmitry Yu. , Proskuryakova Anastasia A. , Davletshina Guzel I. , Tupikin Alexey E. , Kasai Fumio , Ferguson-Smith Malcolm A. , Trifonov Vladimir A.
Published: October 2022

Tandemly arranged and dispersed repetitive DNA sequences are important structural and functional elements that make up a significant portion of vertebrate genomes. Using high throughput, low coverage whole genome sequencing followed by bioinformatics analysis, we have identified seven major tandem repetitive DNAs and two fragments of LTR retrotransposons in the genome of the Nile crocodile (Crocodylus niloticus, 2n = 32). The repeats showed great variability in structure, genomic organization, and chromosomal distribution as revealed by fluorescence in situ hybridization (FISH). We found that centromeric and pericentromeric heterochromatin of C. niloticus is composed of previously described in Crocodylus siamensis CSI-HindIII and CSI-DraI repetitive sequence families, a satellite revealed in Crocodylus porosus, and additionally contains at least three previously unannotated tandem repeats. Both LTR sequences identified here belong to the ERV1 family of endogenous retroviruses. Each pericentromeric region was characterized by a diverse set of repeats, with the exception of chromosome pair 4, in which we found only one type of satellite. Only a few repeats showed non-centromeric signals in addition to their centromeric localization. Mapping of 18S–28S ribosomal RNA genes and telomeric sequences (TTAGGG)n did not demonstrate any co-localization of these sequences with revealed centromeric and pericentromeric heterochromatic blocks.
SOX2 and SOX21 in Lung Epithelial Differentiation and Repair
Authors: Eenjes Evelien , Tibboel Dick , Wijnen Rene M. H. , Schnater Johannes Marco , Rottier Robbert J.
Published: October 2022

The lung originates from the ventral foregut and develops into an intricate branched structure of airways, alveoli, vessels and support tissue. As the lung develops, cells become specified and differentiate into the various cell lineages. This process is controlled by specific transcription factors, such as the SRY-related HMG-box genes SOX2 and SOX21, that are activated or repressed through intrinsic and extrinsic signals. Disturbances in any of these processes during the development of the lung may lead to various pediatric lung disorders, such as Congenital Diaphragmatic Hernia (CDH), Congenital Pulmonary Airway Malformation (CPAM) and Broncho-Pulmonary Dysplasia (BPD). Changes in the composition of the airways and the alveoli may result in reduced respiratory function and eventually lead to chronic lung disorders. In this concise review, we describe different intrinsic and extrinsic cellular processes required for proper differentiation of the epithelium during development and regeneration, and the influence of the microenvironment on this process with special focus on SOX2 and SOX21.
Electronic Structure, Optical and Magnetic Properties of Oxygen-Deficient Gray TiO2–δ(B)
Authors: Opra Denis P. , Sokolov Alexander A. , Sinebryukhov Sergey L. , Tkachenko Ivan A. , Ziatdinov Albert M. , Gnedenkov Sergey V.
Published: October 2022

The gray-colored oxygen-deficient TiO2–δ(B) nanobelts have been synthesized through a combination of the hydrothermal method followed by an ion exchange process and vacuum annealing. Electron paramagnetic resonance reveals an existence of F-centers in the form of electron-trapped oxygen vacancies within the anionic sublattice of the gray bronze TiO2 that induces its colouration. The diffuse reflectance spectroscopy showed that the formation of oxygen vacancies into TiO2(B) significantly increases its absorption intensity in both visible and near infrared ranges. The band gap of TiO2(B) with anionic defects is equal to 3.03 eV (against 3.24 eV for white TiO2(B) treated in air). Room temperature ferromagnetism associated with the defects was detected in gray TiO2–δ(B), thus indicating it belongs it to the class of dilute magnetic oxide semiconductors. It was found that in the low-temperature range (4 K), the magnetic properties of vacuum annealed TiO2(B) do not differ from those for TiO2(B) treated in air. We hope that the findings are defined here make a contribution to further progress in fabrication and manufacturing of defective TiO2-based nanomaterials for catalysis, magnetic applications, batteries, etc.
RNAi-Mediated Manipulation of Cuticle Coloration Genes in Lygus hesperus Knight (Hemiptera: Miridae)
Authors: Brent Colin S. , Heu Chan C. , Gross Roni J. , Fan Baochan , Langhorst Daniel , Hull J. Joe
Published: October 2022

Cuticle coloration in insects is a consequence of the accumulation of pigments in a species-specific pattern. Numerous genes are involved in regulating the underlying processes of melanization and sclerotization, and their manipulation can be used to create externally visible markers of successful gene editing. To clarify the roles for many of these genes and examine their suitability as phenotypic markers in Lygus hesperus Knight (western tarnished plant bug), transcriptomic data were screened for sequences exhibiting homology with the Drosophila melanogaster proteins. Complete open reading frames encoding putative homologs for six genes (aaNAT, black, ebony, pale, tan, and yellow) were identified, with two variants for black. Sequence and phylogenetic analyses supported preliminary annotations as cuticle pigmentation genes. In accord with observable difference in color patterning, expression varied for each gene by developmental stage, adult age, body part, and sex. Knockdown by injection of dsRNA for each gene produced varied effects in adults, ranging from the non-detectable (black 1, yellow), to moderate decreases (pale, tan) and increases (black 2, ebony) in darkness, to extreme melanization (aaNAT). Based solely on its expression profile and highly visible phenotype, aaNAT appears to be the best marker for tracking transgenic L. hesperus.
Chronic Cadmium Exposure Induces Impaired Olfactory Learning and Altered Brain Gene Expression in Honey Bees (Apis mellifera)
Authors: Li Zhiguo , Qiu Yuanmei , Li Jing , Wan Kunlin , Nie Hongyi , Su Songkun
Published: October 2022

The honey bee (Apis mellifera) plays vital ecological roles in the pollination of crops and the maintenance of ecological balance, and adult honey bees may be exposed to exogenous chemicals including heavy metals during their foraging activities. Cadmium (Cd) is regarded as a nonessential toxic metal and is readily accumulated in plants; honey bees can therefore acquire Cd through the collection of contaminated nectar. In the present study, honey bees were chronically exposed to Cd to investigate the effects of sublethal cadmium doses on the olfactory learning and brain gene expression profiles of honey bees. The results showed that Cd-treated bees exhibited significantly impaired olfactory learning performances in comparison with control bees. Moreover, the head weight was significantly lower in Cd-treated bees than in control bees after chronic exposure to Cd. Gene expression profiles between the Cd treatment and the control revealed that 79 genes were significantly differentially expressed. Genes encoding chemoreceptors and olfactory proteins were downregulated, whereas genes involved in response to oxidative stress were upregulated in Cd-treated bees. The results suggest that Cd exposure exerts oxidative stress in the brain of honey bees, and the dysregulated expression of genes encoding chemoreceptors, olfactory proteins, and cytochrome P450 enzymes is probably associated with impaired olfactory learning in honey bees.
National Trends in Prevalence of Depression in Men and Women with Chronic Obstructive Pulmonary Disease Hospitalized in Spain, 2016–2020
Authors: de Miguel-Díez Javier , Lopez-de-Andres Ana , Jimenez-Garcia Rodrigo , de Miguel-Yanes Jose M. , Hernández-Barrera Valentin , Carabantes-Alarcon David , Zamorano-Leon Jose J. , Noriega Concepcion
Published: October 2022

(1) Background: To describe trends in the prevalence of depression in men and women with COPD hospitalized in Spain (2016–2020). (2) Methods: We used a nationwide discharge database to select all patients ≥35 years with COPD. (3) Results: The prevalence of depression was 3.54-times higher in women with COPD than in men (OR 3.54; 95%CI 3.48–3.6). It decreased significantly between 2016 and 2020, although the reduction was only significant in women (12.27% in 2016 vs. 10.56% in 2020). Older age, comorbidity and the most recent years of hospital admission were associated with lower prevalence of depression in both men and women, while obesity, obstructive sleep apnea (OSA) and use of oxygen prior to admission were risk factors. In-hospital mortality (IHM) increased significantly over time. Older age, comorbidity, the use of oxygen prior to admission and having been hospitalized in 2020 increased the risk of IHM. Female sex was associated with a lower IHM in patients with depression and COPD. (4) Conclusions: The prevalence of depression has decreased over time in women with COPD while it has not changed significantly in men with this disease. IHM increased over time both in men and women with COPD and depression, with higher prevalence in the former.
Impact of Obstructive Sleep Apnea Syndrome on Ventricular Remodeling after Acute Myocardial Infarction: A Proof-of-Concept Study
Authors: Bughin François , Kovacsik Hélène , Jaussent Isabelle , Solecki Kamila , Aguilhon Sylvain , Vanoverschelde Juliette , Zarqane Hamid , Mercier Jacques , Gouzi Fares , Roubille François , Dauvilliers Yves
Published: October 2022

Background: Obstructive sleep apnea syndrome (OSA) is common in patients with acute myocardial infarction (AMI). Whether OSA impacts on the ventricular remodeling post-AMI remains unclear. We compared cardiac ventricular remodeling in patients assessed by cardiac magnetic resonance (CMR) imaging at baseline and six months after AMI based on the presence and severity of OSA. Methods: This prospective study included 47 patients with moderate to severe AMI. They all underwent CMR at inclusion and at six months after an AMI, and a polysomnography was performed three weeks after AMI. Left and right ventricular remodeling parameters were compared between patients based on the AHI, AHI in REM and NREM sleep, oxygen desaturation index, and daytime sleepiness. Results: Of the 47 patients, 49% had moderate or severe OSA with an AHI ≥ 15/h. No differences were observed between these patients and those with an AHI < 15/h for left ventricular end-diastolic and end-systolic volumes at six months. No association was found for left and right ventricular remodeling parameters at six months or for the difference between baseline and six months with polysomnographic parameters of OSA severity, nor with daytime sleepiness. Conclusions: Although with a limited sample size, our proof-of-concept study does not report an association between OSA and ventricular remodeling in patients with AMI. These results highlight the complexity of the relationships between OSA and post-AMI morbi-mortality.
Implant Site Changes in Three Different Clinical Approaches: Orthodontic Extrusion, Regenerative Surgery and Spontaneous Healing after Extraction: A Systematic Review
Authors: Isola Gaetano , Nucera Riccardo , Damonte Silvia , Ugolini Alessandro , De Mari Anna , Migliorati Marco
Published: October 2022

Both surgical and non-surgical techniques are employed for implant site development. However, the efficacy of these methods has not been thoroughly evaluated and compared. This systematic review aims to compare the biologic, functional and esthetic outcomes of three different approaches before implant placement in both the maxillary and mandibular arches: orthodontic extrusion, regenerative surgery and spontaneous healing after extraction. The systematic research of articles was conducted up to January 2020 in Medline, Scopus and the Cochrane Library databases. Studies were selected in a three-stage process according to the title, the abstract and the inclusion criteria. The methodological quality and the risk of bias of the included studies were evaluated using ROBINS-I tools for non-randomized studies, Rob 2.0 for RCT. Quality evaluation of case reports was performed using CARE guidelines. Through the digital search, 1607 articles were identified, and 25 of them were included in the systematic review. The qualitative evaluation showed a good methodological quality for RCT, sufficient for non-randomized studies and poor for case reports. Based on the available results, both orthodontic extrusion and regenerative surgery allowed the development of the implant site with satisfying esthetic and functional outcomes. Studies about the spontaneous healing of the extraction socket showed resorption of the edentulous ridge, which complicated the implant insertion. No study referred to failures or severe complications. Most of the studies reported only qualitative results. The present systematic review demonstrated that there is a substantial lack of data and evidence to determine which of the presented methods is better for developing a future implant site. Both surgical and non-surgical procedures appear effective in the regeneration of hard tissue, whereas not all the techniques can improve soft tissue volume, too. The orthodontic technique simultaneously enhances both hard and soft tissue.
Evaluation of IL-33R and Galectin-3 as New Biomarkers of Cardiac Damage after Polytrauma—Association with Cardiac Comorbidities and Risk Factors
Authors: Weber Birte , Voth Maika , Rottluff Katrin , Marzi Ingo , Henrich Dirk , Leppik Liudmila
Published: October 2022

Polytrauma is one of the disorders with the greatest economic impact on healthcare in society and one predictor for poor outcome is cardiac damage. Interleukin 33 receptors (IL-33R) and galectin-3 are two new potential cardiac trauma biomarkers that are the subjects of this investigation. Additionally, this study assesses pre-existing cardiac damage or risk factors as predictors of cardiac damage after polytrauma. This retrospective study includes 107 polytraumatized patients with an ISS ≥16 admitted in a Level 1 Trauma Centre. Plasma samples were taken at admission. IL-33R and galectin-3 concentrations were detected in plasma samples by ELISA. Both did not correlate with the cardiac damage measured by troponin. Next to troponin, IL-33R was increased in patients with pre-existing cardiac comorbidities. In the subgroup of patients with cardiac comorbidities, the BMI and the initial blood sugar level were significantly increased compared to patients without cardiac comorbidities. Galectin-3 and IL-33R were shown to not correlate with cardiac damage. However, our data suggests that IL-33R protein should be revised in future studies as a marker of cardiac comorbidities. Further, our data indicate that patients with cardiac comorbidities represent a separate group of polytrauma patients characterized by higher concentrations of troponin, IL-33R, BMI and initial sugar level.
The Relationship between the Frequency and Duration of Physical Activity and Depression in Older Adults with Multiple Chronic Diseases
Authors: Lee Jae-Moo , Ryan Edward J.
Published: October 2022

Research has demonstrated that older adults with multiple chronic diseases (CD) are particularly vulnerable to depression. Meeting current recommendations for physical activity (PA) may help ameliorate the impact of depression on this population. Nonetheless, the impact of frequency versus duration of PA on depression in older adults remains to be explored. Therefore, the purpose of the present study was to determine the combined effect of PA and multiple CD on depression and the combined effect of the frequency, duration, and multiple CD on depression in older adults. Methods: The present study utilized data from the 2017 and 2020 Living Profiles of Older People Surveys. Data from a total of 19,907 older adults (10,042 older adults from 2017 and 9865 older adults from 2020) were included in the present study. Depression was assessed using the Korean version of the Short Form of Geriatric Depression Scale (K-SGDS) and CD included cardiovascular disease, respiratory diseases, thyroid syndromes, orthopedic complications, and diabetes. Participants who participated in PA ≥ 150 min/week were categorized as the high PA group, and those who participated in PA < 150 min/week were categorized as the low PA group. Furthermore, the frequency of PA (FRE) was divided into high FRE (≥5 times/week) and low FRE (<5 times/week), and duration (DUR) was divided into DUR30 (≥30 min/bout) and DUR0 (<30 min/bout). Results: The high PA group exhibited a lower risk of depression relative to the low PA group (p < 0.001). Furthermore, the risk of depression was consistently lower at DUR30 than DUR0 regardless of FRE in all CD categories and this result was maintained after adjusting for age, gender, BMI, height, weight, income, education levels, smoking status, and cognitive function. Conclusion: These results interestingly demonstrated that it is important for older adults to participate in a longer duration of PA to impact and prevent depression symptoms regardless of FRE.
Assessing the Efficacy of Whole-Body Titanium Dental Implant Surface Modifications in Inducing Adhesion, Proliferation, and Osteogenesis in Human Adipose Tissue Stem Cells
Authors: Ferro Federico , Azzolin Federico , Spelat Renza , Bevilacqua Lorenzo , Maglione Michele
Published: October 2022

Background: Although the influence of titanium implants’ micro-surface properties on titanium discs has been extensively investigated, the research has not taken into consideration their whole-body effect, which may be considered possible using a combinatorial approach. Methods: Five titanium dental implants with a similar moderate roughness and different surface textures were thoroughly characterized. The cell adhesion and proliferation were assessed after adipose-tissue-derived stem cells (ADSCs) were seeded on whole-body implants. The implants’ inductive properties were assessed by evaluating the osteoblastic gene expression. Results: The surface micro-topography was analyzed, showing that hydroxyapatite (HA)-blasted and bland acid etching implants had the highest roughness and a lower number of surface particles. Cell adhesion was observed after 24 h on all the implants, with the highest score registered for the HA-blasted and bland acid etching implants. Cell proliferation was observed only on the laser-treated and double-acid-etched surfaces. The ADSCs expressed collagen type I, osteonectin, and alkaline phosphatase on all the implant surfaces, with high levels on the HA-treated surfaces, which also triggered osteocalcin expression on day seven. Conclusions: The findings of this study show that the morphology and treatment of whole titanium dental implants, primarily HA-treated and bland acid etching implants, impact the adherence and activity of ADSCs in osteogenic differentiation in the absence of specific osteo-inductive signals.
Photodynamic Inactivation Effectively Eradicates Candida auris Biofilm despite Its Interference with the Upregulation of CDR1 and MDR1 Efflux Genes
Authors: Štefánek Matúš , Černáková Lucia , Dekkerová Jaroslava , Bujdáková Helena
Published: October 2022

Candida auris, in recent years, has emerged as a dangerous nosocomial pathogen. It represents a challenge for effective treatment because of its multiresistance. Photodynamic inactivation (PDI) is a promising way to solve problems with a wide range of resistant microorganisms. This study aimed to use PDI for the eradication of C. auris biofilms. Moreover, the regulation of the CDR1, CDR2, and MDR1 resistance genes was studied. Experiments were performed on 24 h biofilms formed by three clinical isolates of C. auris in vitro. PDI was performed in the presence of the photosensitizer methylene blue (0.25 mM) and samples were irradiated with a red laser (λ = 660 nm, 190 mW/cm2) for 79, 120, and 300 s. To confirm the PDI effect, confocal laser scanning microscopy was performed after treatment. Effective PDI was achieved in all strains. The highest inhibition was observed after 300 s irradiation, with over 90% inhibition compared with the non-irradiated control sample. PDI was observed to upregulate the expression of the CDR1 gene, but mainly the MDR1 gene. Despite this observation, PDI significantly decreased the survival of C. auris biofilm cells and proved to have great potential for the eradication of problematic resistant yeasts.
Ilizarov Bone Transfer for Treatment of Large Tibial Bone Defects: Clinical Results and Management of Complications
Authors: Cao Zheming , Zhang Yiqian , Lipa Katelyn , Qing Liming , Wu Panfeng , Tang Juyu
Published: October 2022

Backgrounds: The purpose of this study is to present our clinical experience using the Ilizarov bone transfer technique and free-flap technique in the reconstruction of large tibial bone and soft tissue defects, including an evaluation of both the management of postoperative complications and long-term outcomes. Methods: From January 2010 to May 2020, 72 patients with tibia bone and soft tissue defects were retrospectively evaluated. Either an anterolateral thigh perforator flaps (ALTP) or latissimus dorsi musculocutaneous flaps (LD), solely or in combination, were used to cover soft tissue defects. Once the flap was stabilized, an Ilizarov external fixator was applied to the limb. Follow-up was postoperatively performed at 1, 3, 6, 9, and 12 months. Results: Postoperatively, there were two cases of total and five of partial flap necrosis, and two cases of subcutaneous ulcers, which were caused by vascular crisis, infection, and hematoma, respectively. All the patients underwent Ilizarov external fixator surgery after flap recovery. A total of 16 complications occurred, including 3 cases of simple needle tract infection (antibiotic treatment) and 13 cases of complications requiring reoperation. A correlation factor analysis revealed that the main factors affecting the healing time were the defect length and operative complications. All patients with complications treated with the vascularized iliac flap eventually healed completely. Conclusions: The Ilizarov method used together with an ALTP, LD, or a combination thereof yields good clinical results for repairing large bone and soft tissue defects of the tibia, thus reducing the incidence of amputations. However, longer treatment times may be involved, and postoperative complications can occur. The vascularized iliac flap may be a suitable choice for the treatment of postoperative complications of this type of Ilizarov bone transport.