bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Factors Affecting the Increased Percentage of CGA Recommendations among Patients on Geriatric Ward
Authors: Gołębiowska Justyna , Szymala-Pędzik Małgorzata , Żórawska Joanna , Sobieszczańska Małgorzata , Agrawal Siddarth
Published: January 2023

In Poland, the elderly population is noticeably increasing every year. Therefore, the current healthcare system has to rise to the challenge of treatment and prevention strategies targeting elderly persons. Based on the Vulnerable Elders Survey (VES-13 scale), consisting of international and validated scales, we put effort into identifying the factors affecting the increased percentage of CGA (Comprehensive Geriatric Assessment) recommendations by healthcare system physicians. The study group involved 78 patients from the Department of Geriatrics, Wroclaw Medical University, Poland, aged 60–91 (median Me = 81 years old). Of the studied patients, 51 were recommended for CGA (51/78; 64.6%). A statistically significant association was observed between CGA recommendation and age (p < 0.001); the likelihood of a CGA recommendation increased with age. Furthermore, the increased CGA recommendation was observed among geriatric patients with: (a) frailty syndrome (OR = 11.2, CI95% 2.88–43.5, p < 0.001), (b) high risk of malnutrition or malnutrition (OR = 3.87; CI95%, 1.00–14.9, p = 0.04), (c) low mental status (OR = 3.32, CI95% 1.22–9.09, p = 0.029), (d) low ability to perform basic daily duties (according to ADL scale—OR = 12.6, CI95% 1.57–101, p = 0.004 and IADL scale—OR = 4.71, CI95% 1.72–12.9, p = 0.003), and (e) fall risk (OR = 15.0, CI95% 4.67–48.3, p < 0.001). Moreover, homocysteine levels increased with age (p = 0.003) and decreased with sleep duration (p = 0.043). Taken together, all these factors seem to be important when implementing treatment programs adjusted to the individual geriatric patient.
Longitudinal Sleep Study in Pregnancy: Cohort Profile and Prevalence and Risk Factors for Sleep Symptoms in the First Trimester
Authors: Senaratna Chamara V. , Priyadarshanie Nirmala , Fernando Sharaine , Goonewardena Sampatha , Piyumanthi Pramodya , Perret Jennifer , Lodge Caroline , Hamilton Garun S. , Dharmage Shyamali C.
Published: January 2023

Sleep disorders could influence pregnancy outcomes but evidence for longitudinal associations is scarce. We established a prospective cohort of women to determine incident sleep issues and their adverse health outcomes during pregnancy and beyond, and present here the baseline cohort profile. Antenatal women in gestational weeks 8–12 were recruited (n = 535) and followed-up in each trimester and at 5–6 weeks postpartum (no attrition). Sleep symptoms and disorders were measured using STOP-Bang and Berlin questionnaires and Pittsburgh Sleep Quality Index. Incident health outcomes were extracted from clinical records. At the time of recruitment, habitual snoring was present in 13.8% of participants; “excessive sleepiness during the day” (EDS) in 42.8%; short (<7 h) sleep duration in 46.4%; “having trouble sleeping” in 15.3%; and “poor subjective sleep quality” in 8.6%. Habitual snoring was strongly associated with irregular menstrual periods for one year preceding pregnancy (p = 0.014) and higher BMI (p < 0.001). Higher age was associated with less “trouble sleeping” (OR 0.9, p = 0.033) and longer sleep duration was associated with better “subjective sleep quality” (OR 0.8, p = 0.005). Sleep issues were highly prevalent at baseline and associated with age, irregular menstruation, and obesity. This cohort will provide a robust platform to investigate incident sleep disorders during pregnancy and their effects on adverse pregnancy outcomes and long-term health of women and their offspring.
Usefulness of Plane-Based Augmented Geovisualization—Case of “The Crown of Polish Mountains 3D”
Authors: Halik Łukasz , Wielebski Łukasz
Published: January 2023

In this article, we suggest the introduction of a new method of generating AR content, which we propose to call plane-based augmented geovisualizations (PAGs). This method concerns cases in which AR geovisualizations are embedded directly on any plane detected by the AR device, as in the case of the investigated “Crown of Polish Mountains 3D” application. The study on the usefulness of the AR solution against a classic solution was conducted as part of an online survey of people from various age and social groups. The application in the monitor version showing 3D models of mountain peaks (without AR mode) was tested by the respondents themselves. The use of the application in the AR mode, which requires a smartphone with the appropriate module, was tested by the respondents based on a prepared video demonstrating its operation. The results of the research on three age groups show that the AR mode was preferred among users against all compared criteria, but some differences between age groups were clearly visible. In the case of the criterion of ease of use of the AR mode, the result was not so unambiguous, which is why further research is necessary. The research results show the potential of the AR mode in presenting 3D terrain models.
Proteins Found in the Triple-Negative Breast Cancer Secretome and Their Therapeutic Potential
Authors: McHenry Peter R. , Prosperi Jenifer R.
Published: January 2023

The cancer secretome comprises factors secreted by tumors, including cytokines, growth factors, proteins from the extracellular matrix (ECM), proteases and protease inhibitors, membrane and extracellular vesicle proteins, peptide hormones, and metabolic proteins. Secreted proteins provide an avenue for communication with other tumor cells and stromal cells, and these in turn promote tumor growth and progression. Breast cancer is the most commonly diagnosed cancer in women in the US and worldwide. Triple-negative breast cancer (TNBC) is characterized by its aggressiveness and its lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and HER2, making it unable to be treated with therapies targeting these protein markers, and leaving patients to rely on standard chemotherapy. In order to develop more effective therapies against TNBC, researchers are searching for targetable molecules specific to TNBC. Proteins in the TNBC secretome are involved in wide-ranging cancer-promoting processes, including tumor growth, angiogenesis, inflammation, the EMT, drug resistance, invasion, and development of the premetastatic niche. In this review, we catalog the currently known proteins in the secretome of TNBC tumors and correlate these secreted molecules with potential therapeutic opportunities to facilitate translational research.
Yet Another Similarity between Mitochondrial and Bacterial Ribosomal Small Subunit Biogenesis Obtained by Structural Characterization of RbfA from S. aureus
Authors: Bikmullin Aydar G. , Fatkhullin Bulat , Stetsenko Artem , Gabdulkhakov Azat , Garaeva Natalia , Nurullina Liliia , Klochkova Evelina , Golubev Alexander , Khusainov Iskander , Trachtmann Natalie , Blokhin Dmitriy , Guskov Albert , Validov Shamil , Usachev Konstantin , Yusupov Marat
Published: January 2023

Ribosome biogenesis is a complex and highly accurate conservative process of ribosomal subunit maturation followed by association. Subunit maturation comprises sequential stages of ribosomal RNA and proteins’ folding, modification and binding, with the involvement of numerous RNAses, helicases, GTPases, chaperones, RNA, protein-modifying enzymes, and assembly factors. One such assembly factor involved in bacterial 30S subunit maturation is ribosomal binding factor A (RbfA). In this study, we present the crystal (determined at 2.2 Å resolution) and NMR structures of RbfA as well as the 2.9 Å resolution cryo-EM reconstruction of the 30S–RbfA complex from Staphylococcus aureus (S. aureus). Additionally, we show that the manner of RbfA action on the small ribosomal subunit during its maturation is shared between bacteria and mitochondria. The obtained results clarify the function of RbfA in the 30S maturation process and its role in ribosome functioning in general. Furthermore, given that S. aureus is a serious human pathogen, this study provides an additional prospect to develop antimicrobials targeting bacterial pathogens.
Genome-Wide Identification and Functional Characterization of Stress Related Glyoxalase Genes in Brassica napus L.
Authors: Yan Guixin , Zhang Meili , Guan Wenjie , Zhang Fugui , Dai Wenjun , Yuan Lili , Gao Guizhen , Xu Kun , Chen Biyun , Li Lixia , Wu Xiaoming
Published: January 2023

Rapeseed (Brassica napus L.) is not only one of the most important oil crops in the world, but it is also an important vegetable crop with a high value nutrients and metabolites. However, rapeseed is often severely damaged by adverse stresses, such as low temperature, pathogen infection and so on. Glyoxalase I (GLYI) and glyoxalase II (GLYII) are two enzymes responsible for the detoxification of a cytotoxic metabolite methylglyoxal (MG) into the nontoxic S-D-lactoylglutathione, which plays crucial roles in stress tolerance in plants. Considering the important roles of glyoxalases, the GLY gene families have been analyzed in higher plans, such as rice, soybean and Chinese cabbage; however, little is known about the presence, distribution, localizations and expression of glyoxalase genes in rapeseed, a young allotetraploid. In this study, a total of 35 BnaGLYI and 30 BnaGLYII genes were identified in the B. napus genome and were clustered into six and eight subfamilies, respectively. The classification, chromosomal distribution, gene structure and conserved motif were identified or predicted. BnaGLYI and BnaGLYII proteins were mainly localized in chloroplast and cytoplasm. By using publicly available RNA-seq data and a quantitative real-time PCR analysis (qRT-PCR), the expression profiling of these genes of different tissues was demonstrated in different developmental stages as well as under stresses. The results indicated that their expression profiles varied among different tissues. Some members are highly expressed in specific tissues, BnaGLYI11 and BnaGLYI27 expressed in flowers and germinating seed. At the same time, the two genes were significantly up-regulated under heat, cold and freezing stresses. Notably, a number of BnaGLY genes showed responses to Plasmodiophora brassicae infection. Overexpression of BnGLYI11 gene in Arabidopsis thaliana seedlings confirmed that this gene conferred freezing tolerance. This study provides insight of the BnaGLYI and BnaGLYII gene families in allotetraploid B. napus and their roles in stress resistance, and important information and gene resources for developing stress resistant vegetable and rapeseed oil.
New Insights into Bitopic Orthosteric/Allosteric Ligands of Cannabinoid Receptor Type 2
Authors: Ferrisi Rebecca , Polini Beatrice , Ricardi Caterina , Gado Francesca , Mohamed Kawthar A. , Baron Giovanna , Faiella Salvatore , Poli Giulio , Rapposelli Simona , Saccomanni Giuseppe , Aldini Giancarlo , Chiellini Grazia , Laprairie Robert B. , Manera Clementina , Ortore Gabriella
Published: January 2023

Very recently, we have developed a new generation of ligands targeting the cannabinoid receptor type 2 (CB2R), namely JR compounds, which combine the pharmacophoric portion of the CB2R positive allosteric modulator (PAM), EC21a, with that of the CB2R selective orthosteric agonist LV62, both synthesized in our laboratories. The functional examination enabled us to identify JR14a, JR22a, and JR64a as the most promising compounds of the series. In the current study, we focused on the assessment of the bitopic (dualsteric) nature of these three compounds. Experiments in cAMP assays highlighted that only JR22a behaves as a CB2R bitopic (dualsteric) ligand. In parallel, computational studies helped us to clarify the binding mode of these three compounds at CB2R, confirming the bitopic (dualsteric) nature of JR22a. Finally, the potential of JR22a to prevent neuroinflammation was investigated on a human microglial cell inflammatory model.
Appressoria—Small but Incredibly Powerful Structures in Plant–Pathogen Interactions
Authors: Shi Ting-Ting , Li Guo-Hong , Zhao Pei-Ji
Published: January 2023

Plant-pathogenic fungi are responsible for many of the most severe crop diseases in the world and remain very challenging to control. Improving current protection strategies or designating new measures based on an overall understanding of molecular host–pathogen interaction mechanisms could be helpful for disease management. The attachment and penetration of the plant surface are the most important events among diverse plant–fungi interactions. Fungi evolved as small but incredibly powerful infection structure appressoria to facilitate attachment and penetration. Appressoria are indispensable for many diseases, such as rusts, powdery mildews, and blast diseases, as well as devastating oomycete diseases. Investigation into the formation of plant–pathogen appressoria contributes to improving the understanding of the molecular mechanisms of plant–pathogen interactions. Fungal host attachment is a vital step of fungal pathogenesis. Here, we review recent advances in the molecular mechanisms regulating the formation of appressoria. Additionally, some biocontrol agents were revealed to act on appressorium. The regulation of fungal adhesion during the infective process by acting on appressoria formation is expected to prevent the occurrence of crop disease caused by some pathogenic fungi.
Tailored Supramolecular Cage for Efficient Bio-Labeling
Authors: An Dongdong , Shi Linlin , Li Tianyu , Zhang Hong-Yu , Chen Yahong , Hao Xin-Qi , Song Mao-Ping
Published: January 2023

Fluorescent chemosensors are powerful imaging tools used in a broad range of biomedical fields. However, the application of fluorescent dyes in bioimaging still remains challenging, with small Stokes shifts, interfering signals, background noise, and self-quenching on current microscope configurations. In this work, we reported a supramolecular cage (CA) by coordination-driven self-assembly of benzothiadiazole derivatives and Eu(OTf)3. The CA exhibited high fluorescence with a quantum yield (QY) of 38.57%, good photoluminescence (PL) stability, and a large Stokes shift (153 nm). Furthermore, the CCK-8 assay against U87 glioblastoma cells verified the low cytotoxicity of CA. We revealed that the designed probes could be used as U87 cells targeting bioimaging.
Resveratrol Analogs and Prodrugs Differently Affect the Survival of Breast Cancer Cells Impairing Estrogen/Estrogen Receptor α/Neuroglobin Pathway
Authors: Montalesi Emiliano , Cracco Patrizio , Acconcia Filippo , Fiocchetti Marco , Iucci Giovanna , Battocchio Chiara , Orlandini Elisabetta , Ciccone Lidia , Nencetti Susanna , Muzzi Maurizio , Moreno Sandra , Venditti Iole , Marino Maria
Published: January 2023

Breast cancer is the first leading tumor in women in terms of incidence worldwide. Seventy percent of cases are estrogen receptor (ER) α-positive. In these malignancies, 17β-estradiol (E2) via ERα increases the levels of neuroglobin (NGB), a compensatory protein that protects cancer cells from stress-induced apoptosis, including chemotherapeutic drug treatment. Our previous data indicate that resveratrol (RSV), a plant-derived polyphenol, prevents E2/ERα-induced NGB accumulation in this cellular context, making E2-dependent breast cancer cells more prone to apoptosis. Unfortunately, RSV is readily metabolized, thus preventing its effectiveness. Here, four different RSV analogs have been developed, and their effect on the ERα/NGB pathway has been compared with RSV conjugated with highly hydrophilic gold nanoparticles as prodrug to evaluate if RSV derivatives maintain the breast cancer cells’ susceptibility to the chemotherapeutic drug paclitaxel as the original compound. Results demonstrate that RSV conjugation with gold nanoparticles increases RSV efficacy, with respect to RSV analogues, reducing NGB levels and enhancing the pro-apoptotic action of paclitaxel, even preventing the anti-apoptotic action exerted by E2 treatment on these cells. Overall, RSV conjugation with gold nanoparticles makes this complex a promising agent for medical application in breast cancer treatment.
Insulin Elevates ID2 Expression in Trophoblasts and Aggravates Preeclampsia in Obese ASB4-Null Mice
Authors: Kayashima Yukako , Townley-Tilson W. H. Davin , Vora Neeta L. , Boggess Kim , Homeister Jonathon W. , Maeda-Smithies Nobuyo , Li Feng
Published: January 2023

Obesity is a risk factor for preeclampsia. We investigated how obesity influences preeclampsia in mice lacking ankyrin-repeat-and-SOCS-box-containing-protein 4 (ASB4), which promotes trophoblast differentiation via degrading the inhibitor of DNA-binding protein 2 (ID2). Asb4−/− mice on normal chow (NC) develop mild preeclampsia-like phenotypes during pregnancy, including hypertension, proteinuria, and reduced litter size. Wild-type (WT) and Asb4−/− females were placed on a high-fat diet (HFD) starting at weaning. At the age of 8–9 weeks, they were mated with WT or Asb4−/− males, and preeclamptic phenotypes were assessed. HFD-WT dams had no obvious adverse outcomes of pregnancy. In contrast, HFD-Asb4−/− dams had significantly more severe preeclampsia-like phenotypes compared to NC-Asb4−/− dams. The HFD increased white fat weights and plasma leptin and insulin levels in Asb4−/− females. In the HFD-Asb4−/− placenta, ID2 amounts doubled without changing the transcript levels, indicating that insulin likely increases ID2 at a level of post-transcription. In human first-trimester trophoblast HTR8/SVneo cells, exposure to insulin, but not to leptin, led to a significant increase in ID2. HFD-induced obesity markedly worsens the preeclampsia-like phenotypes in the absence of ASB4. Our data indicate that hyperinsulinemia perturbs the timely removal of ID2 and interferes with proper trophoblast differentiation, contributing to enhanced preeclampsia.
Treatment Resulting Changes in Volumes of High-18F-FDG-Uptake Adipose Tissues over Orbit and Epicardium Correlate with Treatment Response for Non-Hodgkin’s Lymphoma
Authors: Huang Yu-Ming , Hsieh Chen-Hsi , Wang Shan-Ying , Tsao Chin-Ho , Lee Jehn-Chuan , Chen Yu-Jen
Published: January 2023

Background: A regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment for non-Hodgkin’s lymphoma. Brown adipose tissue possesses anti-cancer potential. This study aimed to explore practical biomarkers for non-Hodgkin’s lymphoma by analyzing the metabolic activity of adipose tissue. Methods: Twenty patients who received R-CHOP for non-Hodgkin’s lymphoma were reviewed. Positron emission tomography/computed tomography (PET/CT) images, lactate dehydrogenase (LDH) levels, and body mass index (BMI) before and after treatment were collected. Regions with a high standardized uptake value (SUV) in epicardial and orbital adipose tissue were selected and analyzed by a PET/CT viewer. The initial measurements and changes in the high SUV of epicardial and orbital adipose tissues, LDH levels, and BMI of treatment responders and non-responders, and complete and partial responders, were compared. Results: The volumes of high-SUV epicardial and orbital adipose tissues significantly increased in responders after R-CHOP (p = 0.03 and 0.002, respectively). There were significant differences between changes in the high-SUV volumes of epicardial and orbital adipose tissues (p = 0.03 and 0.001, respectively) and LDH levels (p = 0.03) between responders and non-responders. The changes in high-SUV epicardial adipose tissue volumes were greater among complete responders than partial responders (p = 0.04). Poorer treatment responses were observed in patients with lower high-SUV epicardial adipose tissue volumes and higher LDH levels after R-CHOP (p = 0.03 and 0.03, respectively). Conclusions: The preliminary results of greater changes in high-SUV epicardial and orbital adipose tissue volumes among responders indicate that brown adipose tissue could be considered a favorable prognostic biomarker.
Metabolic and Molecular Response to High-Fat Diet Differs between Rats with Constitutionally High and Low Serotonin Tone
Authors: Baković Petra , Kesić Maja , Kolarić Darko , Štefulj Jasminka , Čičin-Šain Lipa
Published: January 2023

Maintaining energy balance is a complex physiological function whose dysregulation can lead to obesity and associated metabolic disorders. The bioamine serotonin (5HT) is an important regulator of energy homeostasis, with its central and peripheral pools influencing energy status in opposing ways. Using sublines of rats with constitutionally increased (high-5HT) or decreased (low-5HT) whole-body 5HT tone, we have previously shown that under standard diet constitutionally higher 5HT activity is associated with increased body weight, adiposity, and impaired glucose homeostasis. Here, we investigated the response of 5HT sublines to an obesogenic diet. Consistent with previous findings, high-5HT animals fed a standard diet had poorer metabolic health. However, in response to a high-fat diet, only low-5HT animals increased body weight and insulin resistance. They also showed more pronounced changes in blood metabolic parameters and the expression of various metabolic genes in hypothalamus and adipose tissue. On the other hand, high-5HT animals appeared to be protected from major metabolic disturbances of the obesogenic diet. The results suggest that constitutionally low 5HT activity is associated with higher susceptibility to harmful effects of a high-energy diet. High-5HT subline, which developed less adverse metabolic outcomes on hypercaloric diets, may prove useful in understanding metabolically healthy obesity in humans.
Charge Transfer and Electron Production in Proton Collisions with Uracil: A Classical and Semiclassical Study
Authors: Illescas Clara , Méndez Luis , Bernedo Santiago , Rabadán Ismanuel
Published: January 2023

Cross sections for charge transfer and ionization in proton–uracil collisions are studied, for collision energies 0.05<E<2500 keV, using two computational models. At low energies, below 20 keV, the charge transfer total cross section is calculated employing a semiclassical close-coupling expansion in terms of the electronic functions of the supermolecule (H-uracil)+. At energies above 20 keV, a classical-trajectory Monte Carlo method is employed. The cross sections for charge transfer at low energies have not been previously reported and have high values of the order of 40 Å2, and, at the highest energies of the present calculation, they show good agreement with the previous results. The classical-trajectory Monte Carlo calculation provides a charge transfer and electron production cross section in reasonable agreement with the available experiments. The individual molecular orbital contributions to the total electron production and charge transfer cross sections are analyzed in terms of their energies; this permits the extension of the results to other molecular targets, provided the values of the corresponding orbital energies are known.
Dysregulated Cell Homeostasis and miRNAs in Human iPSC-Derived Cardiomyocytes from a Propionic Acidemia Patient with Cardiomyopathy
Authors: Álvarez Mar , Ruiz-Sala Pedro , Pérez Belén , Desviat Lourdes Ruiz , Richard Eva
Published: January 2023

Propionic acidemia (PA) disorder shows major involvement of the heart, among other alterations. A significant number of PA patients develop cardiac complications, and available evidence suggests that this cardiac dysfunction is driven mainly by the accumulation of toxic metabolites. To contribute to the elucidation of the mechanistic basis underlying this dysfunction, we have successfully generated cardiomyocytes through the differentiation of induced pluripotent stem cells (iPSCs) from a PCCB patient and its isogenic control. In this human cellular model, we aimed to examine microRNAs (miRNAs) profiles and analyze several cellular pathways to determine miRNAs activity patterns associated with PA cardiac phenotypes. We have identified a series of upregulated cardiac-enriched miRNAs and alterations in some of their regulated signaling pathways, including an increase in the expression of cardiac damage markers and cardiac channels, an increase in oxidative stress, a decrease in mitochondrial respiration and autophagy; and lipid accumulation. Our findings indicate that miRNA activity patterns from PA iPSC-derived cardiomyocytes are biologically informative and advance the understanding of the molecular mechanisms of this rare disease, providing a basis for identifying new therapeutic targets for intervention strategies.
Endometriosis of the Cervix: A Rare Clinical Case with the Possibility of Comparing the Eutopic and Ectopic Endometrium at the Cellular Level
Authors: Toniyan Konstantin A. , Gorbacheva Elena Yu. , Boyarintsev Valery V. , Ogneva Irina V.
Published: January 2023

Endometriosis of the cervix is a rare form of genital endometriosis, which is characterized by the appearance of tissue on the vaginal part of the cervix, similar to the tissue of the mucous membrane of the uterine cavity. We describe a clinical case in which we compared the content of cytoskeletal proteins, H3 histone modifications and DNA methylation (total and 5-hydroxymethylcytosine content) in the eutopic endometrium and in tissue from endometriosis foci on the cervix. The patient had elevated levels of estradiol, interleukin-1β and interleukin-8. At the cellular level, the content of tubulin and the marker of stable microtubules were reduced in the ectopic endometrium (by 45% and 37%, p < 0.05, respectively), but the alpha-actinin-1 content was increased (by 75%, p < 0.05) with an increase in the expression of its gene. At the same time, the total level of DNA methylation in the endometriotic focus was reduced by more than 2 times with the accumulation of the intermediate product 5-hydroxymethylcytosine (the content increased by more than 3 times), probably due to an increase in the content of tet methylcytosine dioxygenase 1 (more than 4 times).
Biomarkers of Aggressive Prostate Cancer at Diagnosis
Authors: Boehm Brock E. , York Monica E. , Petrovics Gyorgy , Kohaar Indu , Chesnut Gregory T.
Published: January 2023

In the United States, prostate cancer (CaP) remains the second leading cause of cancer deaths in men. CaP is predominantly indolent at diagnosis, with a small fraction (25–30%) representing an aggressive subtype (Gleason score 7–10) that is prone to metastatic progression. This fact, coupled with the criticism surrounding the role of prostate specific antigen in prostate cancer screening, demonstrates the current need for a biomarker(s) that can identify clinically significant CaP and avoid unnecessary biopsy procedures and psychological implications of being diagnosed with low-risk prostate cancer. Although several diagnostic biomarkers are available to clinicians, very few comparative trials have been performed to assess the clinical effectiveness of these biomarkers. It is of note, however, that a majority of these clinical trials have been over-represented by men of Caucasian origin, despite the fact that African American men have a 1.7 times higher incidence and 2.1 times higher rate of mortality from prostate cancer. Biomarkers for CaP diagnosis based on the tissue of origin include urine-based gene expression assays (PCA3, Select MDx, ExoDx Prostate IntelliScore, Mi-Prostate Score, PCA3-PCGEM1 gene panel), blood-based protein biomarkers (4K, PHI), and tissue-based DNA biomarker (Confirm MDx). Another potential direction that has emerged to aid in the CaP diagnosis include multi-parametric magnetic resonance imaging (mpMRI) and bi-parametric magnetic resonance imaging (bpMRI), which in conjunction with clinically validated biomarkers may provide a better approach to predict clinically significant CaP at diagnosis. In this review, we discuss some of the adjunctive biomarker tests along with newer imaging modalities that are currently available to help clinicians decide which patients are at risk of having high-grade CaP on prostate biopsy with the emphasis on clinical utility of the tests across African American (AA) and Caucasian (CA) men.
Enhanced Antitumor Efficacy of Radium-223 and Enzalutamide in the Intratibial LNCaP Prostate Cancer Model
Authors: Suominen Mari I. , Knuuttila Matias , Schatz Christoph A. , Schlicker Andreas , Vääräniemi Jukka , Sjöholm Birgitta , Alhoniemi Esa , Haendler Bernard , Mumberg Dominik , Käkönen Sanna-Maria , Scholz Arne
Published: January 2023

Radium-223 dichloride and enzalutamide are indicated for metastatic castration-resistant prostate cancer and their combination is currently being investigated in a large phase 3 clinical trial. Here, we evaluated the antitumor efficacy of radium-223, enzalutamide, and their combination in the intratibial LNCaP model mimicking prostate cancer metastasized to bone. In vitro experiments revealed that the combination of radium-223 and enzalutamide inhibited LNCaP cell proliferation and showed synergistic efficacy. The combination of radium-223 and enzalutamide also demonstrated enhanced in vivo antitumor efficacy, as determined by measuring serum PSA levels in the intratibial LNCaP model. A decreasing trend in the total area of tumor-induced abnormal bone was associated with the combination treatment. The serum levels of the bone formation marker PINP and the bone resorption marker CTX-I were lowest in the combination treatment group and markedly decreased compared with vehicle group. Concurrent administration of enzalutamide did not impair radium-223 uptake in tumor-bearing bone or the ability of radium-223 to inhibit tumor-induced abnormal bone formation. In conclusion, combination treatment with radium-223 and enzalutamide demonstrated enhanced antitumor efficacy without compromising the integrity of healthy bone. The results support the ongoing phase 3 trial of this combination.
Cap ‘n’ Collar C and Aryl Hydrocarbon Receptor Nuclear Translocator Facilitate the Expression of Glutathione S-Transferases Conferring Adaptation to Tannic Acid and Quercetin in Micromelalopha troglodyta (Graeser) (Lepidoptera: Notodontidae)
Authors: Wang Zhiqiang , Shi Xiaoling , Zhou Yujingyun , Tang Fang , Gao Xiwu , Liang Pei
Published: January 2023

Micromelalopha troglodyta (Graeser) (Lepidoptera: Notodontidae) is a notorious pest of poplar. Coevolution with poplars rich in plant secondary metabolites prompts M. troglodyta to expand effective detoxification mechanisms against toxic plant secondary metabolites. Although glutathione S-transferases (GSTs) play an important role in xenobiotic detoxification in M. troglodyta, it is unclear how GSTs act in response to toxic secondary metabolites in poplar. In this study, five GST gene core promoters were accurately identified by a 5’ loss luciferase reporter assay, and the core promoters were significantly induced by two plant secondary metabolites in vitro. Two transcription factors, cap ‘n’ collar C (CncC) and aryl hydrocarbon receptor nuclear translocator (ARNT), were cloned in M. troglodyta. MtCncC and MtARNT clustered well with other insect CncCs and ARNTs, respectively. In addition, MtCncC and MtARNT could bind the MtGSTt1 promoter and strongly improve transcriptional activity, respectively. However, MtCncC and MtARNT had no regulatory function on the MtGSTz1 promoter. Our findings revealed the molecular mechanisms of the transcription factors MtCncC and MtARNT in regulating the GST genes of M. troglodyta. These results provide useful information for the control of M. troglodyta.
Transglutaminase Activity Is Conserved in Stratified Epithelia and Skin Appendages of Mammals and Birds
Authors: Sachslehner Attila Placido , Surbek Marta , Golabi Bahar , Geiselhofer Miriam , Jäger Karin , Hess Claudia , Kuchler Ulrike , Gruber Reinhard , Eckhart Leopold
Published: January 2023

The cross-linking of structural proteins is critical for establishing the mechanical stability of the epithelial compartments of the skin and skin appendages. The introduction of isopeptide bonds between glutamine and lysine residues depends on catalysis by transglutaminases and represents the main protein cross-linking mechanism besides the formation of disulfide bonds. Here, we used a fluorescent labeling protocol to localize the activity of transglutaminases on thin sections of the integument and its appendages in mammals and birds. In human tissues, transglutaminase activity was detected in the granular layer of the epidermis, suprabasal layers of the gingival epithelium, the duct of sweat glands, hair follicles and the nail matrix. In the skin appendages of chickens, transglutaminase activity was present in the claw matrix, the feather follicle sheath, the feather sheath and in differentiating keratinocytes of feather barb ridges. During chicken embryogenesis, active transglutaminase was found in the cornifying epidermis, the periderm and the subperiderm. Transglutaminase activity was also detected in the filiform papillae on the tongue of mice and in conical papillae on the tongue of chickens. In summary, our study reveals that transglutaminase activities are widely distributed in integumentary structures and suggests that transglutamination contributes to the cornification of hard skin appendages such as nails and feathers.
Interactions between Bitter Taste Receptor Gene Variants and Dietary Intake Are Associated with the Incidence of Type 2 Diabetes Mellitus in Middle-Aged and Older Korean Adults
Authors: Lee Kyung Won , Shin Dayeon
Published: January 2023

The relationship between the variants of bitter taste receptor gene TAS2R4, dietary intake, and incidence of type 2 diabetes mellitus (T2DM) remains unclear. Hence, we aimed to examine the association of TAS2R4 rs2233998 variants with T2DM incidence in middle-aged and older Korean adults to understand if their association was modulated by dietary intake. Data of the Ansan-Ansung cohort from the Korean Genome and Epidemiology Study were used in this study. A total of 4552 Korean adults aged 40–69 years with no history of T2DM or cancer at baseline were followed-up for 16 years. Dietary intake was assessed using a 103-item food frequency questionnaire, and new T2DM cases were defined based on the World Health Organization and International Diabetes Federation criteria. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for T2DM incidence. During the mean follow-up period of 11.97 years, 1082 (23.77%) new T2DM cases were identified. Women carrying the TT genotype of TAS2R4 rs2233998 exhibited 1.48 times higher incidence of T2DM (HR: 1.48; 95 CI: 1.13–1.93) than those carrying the CC genotype. TAS2R4 rs2233998 variants were positively associated with the incidence of T2DM among Korean women with high intakes of carbohydrates or sugars and low intakes of fruits or vegetables. TT carrier women in the highest tertile of carbohydrate or sugar intake exhibited an increased incidence of T2DM (HR: 2.08, 95% CI: 1.33–3.27 for carbohydrates; HR: 2.31, 95% CI: 1.53–3.51 for sugars) than CC carrier women. Women carrying the TT genotype in the lowest tertile exhibited an increased incidence of T2DM (HR: 1.55, 95% CI: 1.02–2.37 for vegetables; HR: 1.62, 95% CI: 1.06–2.48 for fruits) than women carrying the CC genotype in the highest tertile of vegetable or fruit consumption. However, no association was observed between TAS2R4 rs2233998 variants and dietary intake with T2DM incidence in Korean men. Our findings suggest that variants of TAS2R4 rs2233998 are associated with T2DM incidence, and their associations are strengthened by excessive intake of carbohydrates or sugars and inadequate intake of fruits or vegetables. Diet encompassing optimal intake of carbohydrates or sugars and high intake of fruits or vegetables may minimize the risk of developing T2DM.
Comparison of Physicochemical Properties of Silver and Gold Nanocomposites Based on Potato Starch in Distilled and Cold Plasma-Treated Water
Authors: Janik Magdalena , Khachatryan Karen , Khachatryan Gohar , Krystyjan Magdalena , Oszczęda Zdzisław
Published: January 2023

Nanometal-containing biocomposites find wide use in many industries and fields of science. The physicochemical properties of these materials depend on the character of the polymer, the size and shape of the metallic nanoparticles, and the interactions between the biopolymer and the nanoparticles. The aim of the work was to synthesise and study the effect of plasma-treated water on the properties of the obtained metallic nanoparticles as well as the physicochemical and functional properties of nanocomposites based on potato starch. The metallic nanoparticles were synthesised within a starch paste made in distilled water and in distilled water exposed to low-temperature, low-pressure plasma. The materials produced were characterised in terms of their physicochemical properties. Studies have shown that gold and silver nanoparticles were successfully obtained in a matrix of potato starch in distilled water and plasma water. SEM (Scanning Electron Microscopy) images and UV-Vis spectra confirmed the presence of nanosilver and nanosilver in the obtained composites. On the basis of microscopic images, the size of nanoparticles was estimated in the range from 5 to 20 nm for nanoAg and from 15 to 40 nm for nanoAu. The analysis of FTIR-ATR spectra showed that the type of water used and the synthesis of gold and silver nanoparticles did not lead to changes in the chemical structure of potato starch. DLS analysis showed that the nanoAg obtained in the plasma water-based starch matrix were smaller than the Ag particles obtained using distilled water. Colour analysis showed that the nanocomposites without nanometals were colourless, while those containing nanoAg were yellow, while those with nanoAu were dark purple. This work shows the possibility of using plasma water in the synthesis of nanometals using potato starch, which is a very promising polysaccharide in terms of many potential applications.
Characterization and Safety Profile of a New Combined Advanced Therapeutic Medical Product Platelet Lysate-Based Fibrin Hydrogel for Mesenchymal Stromal Cell Local Delivery in Regenerative Medicine
Authors: Canceill Thibault , Jourdan Géraldine , Kémoun Philippe , Guissard Christophe , Monsef Yanad Abou , Bourdens Marion , Chaput Benoit , Cavalie Sandrine , Casteilla Louis , Planat-Bénard Valérie , Monsarrat Paul , Raymond-Letron Isabelle
Published: January 2023

Adipose-derived mesenchymal stromal cells (ASC) transplant to recover the optimal tissue structure/function relationship is a promising strategy to regenerate tissue lesions. Because filling local tissue defects by injection alone is often challenging, designing adequate cell carriers with suitable characteristics is critical for in situ ASC delivery. The aim of this study was to optimize the generation phase of a platelet–lysate-based fibrin hydrogel (PLFH) as a proper carrier for in situ ASC implantation and (1) to investigate in vitro PLFH biomechanical properties, cell viability, proliferation and migration sustainability, and (2) to comprehensively assess the local in vivo PLFH/ASC safety profile (local tolerance, ASC fate, biodistribution and toxicity). We first defined the experimental conditions to enhance physicochemical properties and microscopic features of PLFH as an adequate ASC vehicle. When ASC were mixed with PLFH, in vitro assays exhibited hydrogel supporting cell migration, viability and proliferation. In vivo local subcutaneous and subgingival PLFH/ASC administration in nude mice allowed us to generate biosafety data, including biodegradability, tolerance, ASC fate and engraftment, and the absence of biodistribution and toxicity to non-target tissues. Our data strongly suggest that this novel combined ATMP for in situ administration is safe with an efficient local ASC engraftment, supporting the further development for human clinical cell therapy.
Comparative Expression Profiling Reveals the Regulatory Effects of Dietary Mannan Oligosaccharides on the Intestinal Immune Response of Juvenile Megalobrama amblycephala against Aeromonas hydrophila Infection
Authors: Zhao Xiaoheng , Wang Xu , Li Hong , Liu Yunlong , Zheng Yancui , Li Hongping , Zhang Minying , Cheng Hanliang , Xu Jianhe , Chen Xiangning , Ding Zhujin
Published: January 2023

Mannan oligosaccharides (MOS) are functional oligosaccharides with beneficial effects on the non-specific immunity of Megalobrama amblycephala, but systematic studies on the immunomodulatory mechanisms of MOS are still lacking. To investigate the protective mechanisms of three different levels of dietary MOS supplementation on the intestinal immunity of juvenile M. amblycephala, comparative digital gene expression (DGE) profiling was performed. In this study, 622 differentially expressed genes (DEGs) were identified, while the similar expression tendency of 34 genes by qRT-PCR validated the accuracy of the DGE analyses. Gene Ontology (GO) enrichment revealed that the DEGs were mainly enriched in two functional categories of biological process and molecular function. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the DEGs were mainly related to complement and coagulation cascades, coagulation cascades, platelet activation, natural killer cell mediated cytotoxicity, Fc gamma R-mediated phagocytosis and antigen processing and presentation. In addition, the pro-inflammatory, apoptosis and tight junction-related genes were more significantly up-regulated upon infection in the dietary MOS groups to enhance host immune functions and maintain the stability of the intestinal barrier. These results will be helpful to clarify the regulatory mechanism of MOS on the intestinal immunity of M. amblycephala and lay the theoretical foundation for the prevention and protection of fish bacterial diseases.
Analysis of Genetic Relatedness between Gastric and Oral Helicobacter pylori in Patients with Early Gastric Cancer Using Multilocus Sequence Typing
Authors: Nagata Ryoko , Sato Hiroki , Takenaka Shoji , Yokoyama Junji , Terai Shuji , Mimuro Hitomi , Noiri Yuichiro
Published: January 2023

The oral cavity is the second most colonized site of Helicobacter pylori after the stomach. This study aimed to compare the genetic relatedness between gastric and oral H. pylori in Japanese patients with early gastric cancer through multilocus sequence typing (MLST) analysis using eight housekeeping genes. Gastric biopsy specimens and oral samples were collected from 21 patients with a fecal antigen test positive for H. pylori. The number of H. pylori allelic profiles ranged from zero to eight since the yield of DNA was small even when the nested PCR was performed. MLST analysis revealed that only one patient had a matching oral and gastric H. pylori genotype, suggesting that different genotypes of H. pylori inhabit the oral cavity and gastric mucosa. The phylogenetic analysis showed that oral H. pylori in six patients was similar to gastric H. pylori, implying that the two strains are related but not of the same origin, and those strains may be infected on separate occasions. It is necessary to establish a culture method for oral H. pylori to elucidate whether the oral cavity acts as the source of gastric infection, as our analysis was based on a limited number of allele sequences.
Deciphering the Immunomodulatory Role of Cyclin-Dependent Kinase 4/6 Inhibitors in the Tumor Microenvironment
Authors: Pandey Pratibha , Khan Fahad , Upadhyay Tarun Kumar , Sharangi Amit Baran
Published: January 2023

Cancer is characterized by persistent cell proliferation driven by aberrant cell cycle regulation and stimulation of cyclin-dependent kinases (CDKs). A very intriguing and potential approach for the development of antitumor medicines is the suppression of CDKs that lead to induction of apoptosis and cell cycle arrest. The shift of the cell cycle from the G0/G1 phase to the S phase, which is characterized by active transcription and synthesis, depends on the development of the cyclin D-CDK4/6 complex. A precise balance between anticancer activity and general toxicity is demonstrated by CDK inhibitors, which can specifically block CDK4/6 and control the cell cycle by reducing the G1 to S phase transition. CDK4/6 inhibitors have recently been reported to exhibit significant cell growth inhibition via modulating the tumour microenvironment in cancerous cells. One significant new understanding is that these inhibitors serve important functions in the interaction among tumour cells and the host immune system in addition to being cytostatic. Herein, we discuss the biological significance of CDK4/6 inhibitors in cancer therapeutics, as well as their biological impact on T cells and other important immune cells. Furthermore, we explore the integration of preclinical findings of these pharmaceuticals’ ability to enhance antitumor immunity.
Gestational Diabetes Mellitus and Small-for-Gestational-Age: An Insight into the Placental Molecular Biomarkers
Authors: Giommi Christian , Lombό Marta , Montik Nina , Paolucci Michela , Notarstefano Valentina , Delli Carpini Giovanni , Ciavattini Andrea , Ragusa Antonio , Maradonna Francesca , Giorgini Elisabetta , Carnevali Oliana
Published: January 2023

Gestational diabetes mellitus (GDM) and small-for-gestational-age (SGA) are two metabolic-related diseases that could affect women during pregnancy. Considering that the chorionic villi (CVs) are crucial structures for the feto-maternal exchange, the alterations in their conformation have been linked to an imbalanced metabolic environment of placenta. In this study, a multidisciplinary approach has been carried out to describe the changes occurring in the placental CVs of GDM and SGA patients. The results revealed higher levels of superoxide dismutase 1 (SOD-1) and catalase (CAT), especially in the GDM placentae, which could be correlated with the hyperglycemic environment characteristic of this pathology. Furthermore, spectroscopy and histologic analyses revealed that both pathologies modify the placental lipid composition altering its structure. However, SGA induces lipid peroxidation and reduces collagen deposition within the CVs. Since the endocannabinoid system (ECS) is involved in placentation and different metabolic activities, the cannabinoid receptor 1 (CB1) and transient receptor potential cation channel subfamily V member 1 (TRPV-1) were analyzed. No changes have been observed either at general or specific levels in the CVs comparing control and pathological samples, suggesting the non-involvement of the cannabinoid system in these two pathologies.
Creation of a Plant Metabolite Spectral Library for Untargeted and Targeted Metabolomics
Authors: Li Yangyang , Zhu Wei , Xiang Qingyuan , Kim Jeongim , Dufresne Craig , Liu Yufeng , Li Tianlai , Chen Sixue
Published: January 2023

Large-scale high throughput metabolomic technologies are indispensable components of systems biology in terms of discovering and defining the metabolite parts of the system. However, the lack of a plant metabolite spectral library limits the metabolite identification of plant metabolomic studies. Here, we have created a plant metabolite spectral library using 544 authentic standards, which increased the efficiency of identification for untargeted metabolomic studies. The process of creating the spectral library was described, and the mzVault library was deposited in the public repository for free download. Furthermore, based on the spectral library, we describe a process of creating a pseudo-targeted method, which was applied to a proof-of-concept study of Arabidopsis leaf extracts. As authentic standards become available, more metabolite spectra can be easily incorporated into the spectral library to improve the mzVault package.