bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucocorticoid-Responsive Tissue Plasminogen Activator (tPA) and Its Inhibitor Plasminogen Activator Inhibitor-1 (PAI-1): Relevance in Stress-Related Psychiatric Disorders
Authors: Mennesson Marie , Revest Jean-Michel
Published: February 2023

Stressful events trigger a set of complex biological responses which follow a bell-shaped pattern. Low-stress conditions have been shown to elicit beneficial effects, notably on synaptic plasticity together with an increase in cognitive processes. In contrast, overly intense stress can have deleterious behavioral effects leading to several stress-related pathologies such as anxiety, depression, substance use, obsessive-compulsive and stressor- and trauma-related disorders (e.g., post-traumatic stress disorder or PTSD in the case of traumatic events). Over a number of years, we have demonstrated that in response to stress, glucocorticoid hormones (GCs) in the hippocampus mediate a molecular shift in the balance between the expression of the tissue plasminogen activator (tPA) and its own inhibitor plasminogen activator inhibitor-1 (PAI-1) proteins. Interestingly, a shift in favor of PAI-1 was responsible for PTSD-like memory induction. In this review, after describing the biological system involving GCs, we highlight the key role of tPA/PAI-1 imbalance observed in preclinical and clinical studies associated with the emergence of stress-related pathological conditions. Thus, tPA/PAI-1 protein levels could be predictive biomarkers of the subsequent onset of stress-related disorders, and pharmacological modulation of their activity could be a potential new therapeutic approach for these debilitating conditions.
Functional Alteration and Differential Expression of the Bitter Taste Receptor T2R38 in Human Paranasal Sinus in Patients with Chronic Rhinosinusitis
Authors: Takemoto Kota , Lomude Luga Santo , Takeno Sachio , Kawasumi Tomohiro , Okamoto Yukako , Hamamoto Takao , Ishino Takashi , Ando Yuki , Ishikawa Chie , Ueda Tsutomu
Published: February 2023

The bitter taste receptors (T2Rs) expressed in human sinonasal mucosae are known to elicit innate immune responses involving the release of nitric oxide (NO). We investigated the expression and distribution of two T2Rs, T2R14 and T2R38, in patients with chronic rhinosinusitis (CRS) and correlated the results with fractional exhaled NO (FeNO) levels and genotype of the T2R38 gene (TAS2R38). Using the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) phenotypic criteria, we identified CRS patients as either eosinophilic (ECRS, n = 36) or non-eosinophilic (non-ECRS, n = 56) patients and compared these groups with 51 non-CRS subjects. Mucosal specimens from the ethmoid sinus, nasal polyps, and inferior turbinate were collected from all subjects, together with blood samples, for RT-PCR analysis, immunostaining, and single nucleotide polymorphism (SNP) typing. We observed significant downregulation of T2R38 mRNA levels in the ethmoid mucosa of non-ECRS patients and in the nasal polyps of ECRS patients. No significant differences in T2R14 or T2R38 mRNA levels were found among the inferior turbinate mucosae of the three groups. Positive T2R38 immunoreactivity was localized mainly in epithelial ciliated cells, whereas secretary goblet cells generally showed lack of staining. The patients in the non-ECRS group showed significantly lower oral and nasal FeNO levels compared with the control group. There was a trend towards higher CRS prevalence in the PAV/AVI and AVI/AVI genotype groups as compared to the PAV/PAV group. Our findings reveal complex but important roles of T2R38 function in ciliated cells associated with specific CRS phenotypes, suggesting the T2R38 pathway as a potential therapeutic target for promotion of endogenous defense mechanisms.
Polymer-Degrading Enzymes of Pseudomonas chloroaphis PA23 Display Broad Substrate Preferences
Authors: Mohanan Nisha , Wong Michael C.-H. , Budisa Nediljko , Levin David B.
Published: February 2023

Although many bacterial lipases and PHA depolymerases have been identified, cloned, and characterized, there is very little information on the potential application of lipases and PHA depolymerases, especially intracellular enzymes, for the degradation of polyester polymers/plastics. We identified genes encoding an intracellular lipase (LIP3), an extracellular lipase (LIP4), and an intracellular PHA depolymerase (PhaZ) in the genome of the bacterium Pseudomonas chlororaphis PA23. We cloned these genes into Escherichia coli and then expressed, purified, and characterized the biochemistry and substrate preferences of the enzymes they encode. Our data suggest that the LIP3, LIP4, and PhaZ enzymes differ significantly in their biochemical and biophysical properties, structural-folding characteristics, and the absence or presence of a lid domain. Despite their different properties, the enzymes exhibited broad substrate specificity and were able to hydrolyze both short- and medium-chain length polyhydroxyalkanoates (PHAs), para-nitrophenyl (pNP) alkanoates, and polylactic acid (PLA). Gel Permeation Chromatography (GPC) analyses of the polymers treated with LIP3, LIP4, and PhaZ revealed significant degradation of both the biodegradable as well as the synthetic polymers poly(ε-caprolactone) (PCL) and polyethylene succinate (PES).
Extraction, Structural, and Antioxidant Properties of Oligosaccharides Hydrolyzed from Panax notoginseng by Ultrasonic-Assisted Fenton Degradation
Authors: Xu Xiaoyan , Deng Guanfeng , Li Xiao , Li Pingjin , Chen Tao , Zhou Lijun , Huang Yan , Yuan Ming , Ding Chunbang , Feng Shiling
Published: February 2023

Plant polysaccharides exhibit many biological activities that are remarkably affected by molecular size and structures. This study aimed to investigate the degradation effect of ultrasonic-assisted Fenton reaction on the Panax notoginseng polysaccharide (PP). PP and its three degradation products (PP3, PP5, and PP7) were obtained from optimized hot water extraction and different Fenton reaction treatments, respectively. The results showed that the molecular weight (Mw) of the degraded fractions significantly decreased after treatment with the Fenton reaction. But the backbone characteristics and conformational structure were similar between PP and PP-degraded products, which was estimated by comparing monosaccharides composition, functional group signals in FT-IR spectra, X-ray differential patterns, and proton signals in 1H NMR. In addition, PP7, with an Mw of 5.89 kDa, exhibited stronger antioxidant activities in both the chemiluminescence-based and HHL5 cell-based methods. The results indicated that ultrasonic-assisted Fenton degradation might be used to improve the biological activities of natural polysaccharides by adjusting the molecular size.
A Semi-Automatic Method for the Quantification of Astrocyte Number and Branching in Bulk Immunohistochemistry Images
Authors: Marques Sandra I. , Carmo Helena , Carvalho Félix , Sá Susana I. , Silva João Pedro
Published: February 2023

Immunohistochemical staining of cell and molecular targets in brain samples is a powerful tool that can provide valuable information on neurological mechanisms. However, post-processing of photomicrographs acquired after 3,3′-Diaminobenzidine (DAB) staining is particularly challenging due to the complexity associated with the size, samples number, analyzed targets, image quality, and even the subjectivity inherent to the analysis by different users. Conventionally, this analysis relies on the manual quantification of distinct parameters (e.g., the number and size of cells and the number and length of cell branching) in a large set of images. These represent extremely time-consuming and complex tasks, defaulting the processing of high amounts of information. Here we describe an improved semi-automatic method to quantify glial fibrillary acidic protein (GFAP)-labelled astrocytes in immunohistochemistry images of rat brains, at magnifications as low as 20×. This method is a straightforward adaptation of the Young & Morrison method, using ImageJ’s plugin Skeletonize, coupled with intuitive data processing in datasheet-based software. It allows swifter and more efficient post-processing of brain tissue samples, regarding astrocyte size and number quantification, the total area occupied, as well as astrocyte branching and branch length (indicators of astrocyte activation), thus contributing to better understand the possible inflammatory response developed by astrocytes.
Multiphoton FLIM Analyses of Native and UVA-Modified Synthetic Melanins
Authors: Pena Ana-Maria , Ito Shosuke , Bornschlögl Thomas , Brizion Sébastien , Wakamatsu Kazumasa , Del Bino Sandra
Published: February 2023

To better understand the impact of solar light exposure on human skin, the chemical characterization of native melanins and their structural photo-modifications is of central interest. As the methods used today are invasive, we investigated the possibility of using multiphoton fluorescence lifetime (FLIM) imaging, along with phasor and bi-exponential fitting analyses, as a non-invasive alternative method for the chemical analysis of native and UVA-exposed melanins. We demonstrated that multiphoton FLIM allows the discrimination between native DHI, DHICA, Dopa eumelanins, pheomelanin, and mixed eu-/pheo-melanin polymers. We exposed melanin samples to high UVA doses to maximize their structural modifications. The UVA-induced oxidative, photo-degradation, and crosslinking changes were evidenced via an increase in fluorescence lifetimes along with a decrease in their relative contributions. Moreover, we introduced a new phasor parameter of a relative fraction of a UVA-modified species and provided evidence for its sensitivity in assessing the UVA effects. Globally, the fluorescence lifetime properties were modulated in a melanin-dependent and UVA dose-dependent manner, with the strongest modifications being observed for DHICA eumelanin and the weakest for pheomelanin. Multiphoton FLIM phasor and bi-exponential analyses hold promising perspectives for in vivo human skin mixed melanins characterization under UVA or other sunlight exposure conditions.
Overexpression of Potential Markers of Regulatory and Exhausted CD8+ T Cells in the Peripheral Blood Mononuclear Cells of Patients with B-Acute Lymphoblastic Leukemia
Authors: Naghavi Alhosseini Mahdieh , Palazzo Marianna , Cari Luigi , Ronchetti Simona , Migliorati Graziella , Nocentini Giuseppe
Published: February 2023

B-acute lymphoblastic leukemia (B-ALL) is one of the most common pediatric cancers, wherein regulatory T cells (Treg) and exhausted CD8+ T cells may be important in its development and maintenance. In this bioinformatics study, we evaluated the expression of 20 Treg/CD8 exhaustion markers and their possible roles in patients with B-ALL. The mRNA expression values of peripheral blood mononuclear cell samples from 25 patients with B-ALL and 93 healthy subjects (HSs) were downloaded from publicly available datasets. Treg/CD8 exhaustion marker expression was normalized with that of the T cell signature and correlated with the expression of Ki-67, regulatory transcription factors (FoxP3, Helios), cytokines (IL-10, TGF-β), CD8+ markers (CD8α chain, CD8β chain), and CD8+ activation markers (Granzyme B, Granulysin). The mean expression level of 19 Treg/CD8 exhaustion markers was higher in the patients than in the HSs. In patients, the expression of five markers (CD39, CTLA-4, TNFR2, TIGIT, and TIM-3) correlated positively with Ki-67, FoxP3, and IL-10 expression. Moreover, the expression of some of them correlated positively with Helios or TGF-β. Our results suggested that Treg/CD8+ T cells expressing CD39, CTLA-4, TNFR2, TIGIT, and TIM-3 favor B-ALL progression, and targeted immunotherapy against these markers could be a promising approach for treating B-ALL.
From Muscle to the Myofascial Unit: Current Evidence and Future Perspectives
Authors: Stecco Antonio , Giordani Federico , Fede Caterina , Pirri Carmelo , De Caro Raffaele , Stecco Carla
Published: February 2023

The “motor unit” or the “muscle” has long been considered the quantal element in the control of movement. However, in recent years new research has proved the strong interaction between muscle fibers and intramuscular connective tissue, and between muscles and fasciae, suggesting that the muscles can no longer be considered the only elements that organize movement. In addition, innervation and vascularization of muscle is strongly connected with intramuscular connective tissue. This awareness induced Luigi Stecco, in 2002, to create a new term, the “myofascial unit”, to describe the bilateral dependent relationship, both anatomical and functional, that occurs between fascia, muscle and accessory elements. The aim of this narrative review is to understand the scientific support for this new term, and whether it is actually correct to consider the myofascial unit the physiological basic element for peripheral motor control.
Bacillus subtilis RadA/Sms-Mediated Nascent Lagging-Strand Unwinding at Stalled or Reversed Forks Is a Two-Step Process: RadA/Sms Assists RecA Nucleation, and RecA Loads RadA/Sms
Authors: Torres Rubén , Carrasco Begoña , Alonso Juan C.
Published: February 2023

Replication fork rescue requires Bacillus subtilis RecA, its negative (SsbA) and positive (RecO) mediators, and fork-processing (RadA/Sms). To understand how they work to promote fork remodeling, reconstituted branched replication intermediates were used. We show that RadA/Sms (or its variant, RadA/Sms C13A) binds to the 5′-tail of a reversed fork with longer nascent lagging-strand and unwinds it in the 5′→3′ direction, but RecA and its mediators limit unwinding. RadA/Sms cannot unwind a reversed fork with a longer nascent leading-strand, or a gapped stalled fork, but RecA interacts with and activates unwinding. Here, the molecular mechanism by which RadA/Sms, in concert with RecA, in a two-step reaction, unwinds the nascent lagging-strand of reversed or stalled forks is unveiled. First, RadA/Sms, as a mediator, contributes to SsbA displacement from the forks and nucleates RecA onto single-stranded DNA. Then, RecA, as a loader, interacts with and recruits RadA/Sms onto the nascent lagging strand of these DNA substrates to unwind them. Within this process, RecA limits RadA/Sms self-assembly to control fork processing, and RadA/Sms prevents RecA from provoking unnecessary recombination.
Critical Overview on Endocrine Disruptors in Diabetes Mellitus
Authors: Hinault Charlotte , Caroli-Bosc Philippe , Bost Frédéric , Chevalier Nicolas
Published: February 2023

Diabetes mellitus is a major public health problem in all countries due to its high human and economic burden. Major metabolic alterations are associated with the chronic hyperglycemia that characterizes diabetes and causes devastating complications, including retinopathy, kidney failure, coronary disease and increased cardiovascular mortality. The most common form is type 2 diabetes (T2D) accounting for 90 to 95% of the cases. These chronic metabolic disorders are heterogeneous to which genetic factors contribute, but so do prenatal and postnatal life environmental factors including a sedentary lifestyle, overweight, and obesity. However, these classical risk factors alone cannot explain the rapid evolution of the prevalence of T2D and the high prevalence of type 1 diabetes in particular areas. Among environmental factors, we are in fact exposed to a growing amount of chemical molecules produced by our industries or by our way of life. In this narrative review, we aim to give a critical overview of the role of these pollutants that can interfere with our endocrine system, the so-called endocrine-disrupting chemicals (EDCs), in the pathophysiology of diabetes and metabolic disorders.
Altered Storage and Function of von Willebrand Factor in Human Cardiac Microvascular Endothelial Cells Isolated from Recipient Transplant Hearts
Authors: Meli Athinoula , McCormack Ann , Conte Ianina , Chen Qu , Streetley James , Rose Marlene L. , Bierings Ruben , Hannah Matthew J. , Molloy Justin E. , Rosenthal Peter B. , Carter Tom
Published: February 2023

The assembly of von Willebrand factor (VWF) into ordered helical tubules within endothelial Weibel–Palade bodies (WPBs) is required for the efficient deployment of the protein at sites of vascular injury. VWF trafficking and storage are sensitive to cellular and environmental stresses that are associated with heart disease and heart failure. Altered storage of VWF manifests as a change in WPB morphology from a rod shape to a rounded shape and is associated with impaired VWF deployment during secretion. In this study, we examined the morphology, ultrastructure, molecular composition and kinetics of exocytosis of WPBs in cardiac microvascular endothelial cells isolated from explanted hearts of patients with a common form of heart failure, dilated cardiomyopathy (DCM; HCMECD), or from nominally healthy donors (controls; HCMECC). Using fluorescence microscopy, WPBs in HCMECC (n = 3 donors) showed the typical rod-shaped morphology containing VWF, P-selectin and tPA. In contrast, WPBs in primary cultures of HCMECD (n = 6 donors) were predominantly rounded in shape and lacked tissue plasminogen activator (t-PA). Ultrastructural analysis of HCMECD revealed a disordered arrangement of VWF tubules in nascent WPBs emerging from the trans-Golgi network. HCMECD WPBs still recruited Rab27A, Rab3B, Myosin-Rab Interacting Protein (MyRIP) and Synaptotagmin-like protein 4a (Slp4-a) and underwent regulated exocytosis with kinetics similar to that seen in HCMECc. However, secreted extracellular VWF strings from HCMECD were significantly shorter than for endothelial cells with rod-shaped WPBs, although VWF platelet binding was similar. Our observations suggest that VWF trafficking, storage and haemostatic potential are perturbed in HCMEC from DCM hearts.
Assessment of Genetic Damage Induced via Glyphosate and Three Commercial Formulations with Adjuvants in Human Blood Cells
Authors: Alvarez-Moya Carlos , Reynoso-Silva Mónica
Published: February 2023

There is considerable controversy regarding the genotoxicity of glyphosate (N-(phosphonomethyl) glycine). It has been suggested that the genotoxicity of this herbicide is increased by the adjuvants added to commercial formulations based on glyphosate. The effect of various concentrations of glyphosate and three commercial glyphosate-based herbicides (GBH) on human lymphocytes was evaluated. Human blood cells were exposed to glyphosates of 0.1, 1, 10 and 50 mM as well as to equivalent concentrations of glyphosate on commercial formulations. Genetic damage (p < 0.05) was observed in all concentrations with glyphosate and with FAENA and TACKLE formulations. These two commercial formulations showed genotoxicity that was concentration-dependent but in a higher proportion compared to pure glyphosate only. Higher glyphosate concentrations increased the frequency and range of tail lengths of some migration groups, and the same was observed for FAENA and TACKLE, while in CENTELLA the migration range decreased but the frequency of migration groups increased. We show that pure glyphosate and commercial GBH (FAENA, TACKLE and CENTELLA) gave signals of genotoxicity in human blood samples in the comet assay. The genotoxicity increased in the formulations, indicating genotoxic activity also in the added adjuvants present in these products. The use of the MG parameter allowed us to detect a certain type of genetic damage associated with different formulations.
Skeletal Muscle-Derived Exosomal miR-146a-5p Inhibits Adipogenesis by Mediating Muscle-Fat Axis and Targeting GDF5-PPARγ Signaling
Authors: Qin Mengran , Xing Lipeng , Wu Jiahan , Wen Shulei , Luo Junyi , Chen Ting , Fan Yaotian , Zhu Jiahao , Yang Lekai , Liu Jie , Xiong Jiali , Chen Xingping , Zhu Canjun , Wang Songbo , Wang Lina , Shu Gang , Jiang Qingyan , Zhang Yongliang , Sun Jiajie , Xi Qianyun
Published: February 2023

Skeletal muscle-fat interaction is essential for maintaining organismal energy homeostasis and managing obesity by secreting cytokines and exosomes, but the role of the latter as a new mediator in inter-tissue communication remains unclear. Recently, we discovered that miR-146a-5p was mainly enriched in skeletal muscle-derived exosomes (SKM-Exos), 50-fold higher than in fat exosomes. Here, we investigated the role of skeletal muscle-derived exosomes regulating lipid metabolism in adipose tissue by delivering miR-146a-5p. The results showed that skeletal muscle cell-derived exosomes significantly inhibited the differentiation of preadipocytes and their adipogenesis. When the skeletal muscle-derived exosomes co-treated adipocytes with miR-146a-5p inhibitor, this inhibition was reversed. Additionally, skeletal muscle-specific knockout miR-146a-5p (mKO) mice significantly increased body weight gain and decreased oxidative metabolism. On the other hand, the internalization of this miRNA into the mKO mice by injecting skeletal muscle-derived exosomes from the Flox mice (Flox-Exos) resulted in significant phenotypic reversion, including down-regulation of genes and proteins involved in adipogenesis. Mechanistically, miR-146a-5p has also been demonstrated to function as a negative regulator of peroxisome proliferator-activated receptor γ (PPARγ) signaling by directly targeting growth and differentiation factor 5 (GDF5) gene to mediate adipogenesis and fatty acid absorption. Taken together, these data provide new insights into the role of miR-146a-5p as a novel myokine involved in the regulation of adipogenesis and obesity via mediating the skeletal muscle-fat signaling axis, which may serve as a target for the development of therapies against metabolic diseases, such as obesity.
Genetic Determinants of Leisure-Time Physical Activity in the Hungarian General and Roma Populations
Authors: Pikó Péter , Bácsné Bába Éva , Kósa Zsigmond , Sándor János , Kovács Nóra , Bács Zoltán , Ádány Róza
Published: February 2023

Leisure-time physical activity (LTPA) is one of the modifiable lifestyle factors that play an important role in the prevention of non-communicable (especially cardiovascular) diseases. Certain genetic factors predisposing to LTPA have been previously described, but their effects and applicability on different ethnicities are unknown. Our present study aims to investigate the genetic background of LTPA using seven single nucleotide polymorphisms (SNPs) in a sample of 330 individuals from the Hungarian general (HG) and 314 from the Roma population. The LTPA in general and three intensity categories of it (vigorous, moderate, and walking) were examined as binary outcome variables. Allele frequencies were determined, individual correlations of SNPs to LTPA, in general, were determined, and an optimized polygenetic score (oPGS) was created. Our results showed that the allele frequencies of four SNPs differed significantly between the two study groups. The C allele of rs10887741 showed a significant positive correlation with LTPA in general (OR = 1.48, 95% CI: 1.12–1.97; p = 0.006). Three SNPs (rs10887741, rs6022999, and rs7023003) were identified by the process of PGS optimization, whose cumulative effect shows a strong significant positive association with LTPA in general (OR = 1.40, 95% CI: 1.16–1.70; p < 0.001). The oPGS showed a significantly lower value in the Roma population compared with the HG population (oPGSRoma: 2.19 ± SD: 0.99 vs. oPGSHG: 2.70 ± SD: 1.06; p < 0.001). In conclusion, the coexistence of genetic factors that encourage leisure-time physical activity shows a more unfavorable picture among Roma, which may indirectly contribute to their poor health status.
Compositional Alteration of Gut Microbiota in Psoriasis Treated with IL-23 and IL-17 Inhibitors
Authors: Huang Yu-Huei , Chang Lun-Ching , Chang Ya-Ching , Chung Wen-Hung , Yang Shun-Fa , Su Shih-Chi
Published: February 2023

Alterations in the gut microbiota composition and their associated metabolic dysfunction exist in psoriasis. However, the impact of biologics on shaping gut microbiota is not well known. This study aimed to determine the association of gut microorganisms and microbiome-encoded metabolic pathways with the treatment in patients with psoriasis. A total of 48 patients with psoriasis, including 30 cases who received an IL-23 inhibitor (guselkumab) and 18 cases who received an IL-17 inhibitor (secukinumab or ixekizumab) were recruited. Longitudinal profiles of the gut microbiome were conducted by using 16S rRNA gene sequencing. The gut microbial compositions dynamically changed in psoriatic patients during a 24-week treatment. The relative abundance of individual taxa altered differently between patients receiving the IL-23 inhibitor and those receiving the IL-17 inhibitor. Functional prediction of the gut microbiome revealed microbial genes related to metabolism involving the biosynthesis of antibiotics and amino acids were differentially enriched between responders and non-responders receiving IL-17 inhibitors, as the abundance of the taurine and hypotaurine pathway was found to be augmented in responders treated with the IL-23 inhibitor. Our analyses showed a longitudinal shift in the gut microbiota in psoriatic patients after treatment. These taxonomic signatures and functional alterations of the gut microbiome could serve as potential biomarkers for the response to biologics treatment in psoriasis.
Polydeoxyribonucleotide in the Treatment of Tendon Disorders, from Basic Science to Clinical Practice: A Systematic Review
Authors: Bizzoca Davide , Brunetti Giovanni , Moretti Lorenzo , Piazzolla Andrea , Vicenti Giovanni , Moretti Francesco Luca , Solarino Giuseppe , Moretti Biagio
Published: February 2023

Polydeoxyribonucleotide (PDRN) is a proprietary and registered drug with several beneficial effects, including tissue repairing, anti-ischemic action, and anti-inflammatory properties. The present study aims to summarize the current evidence about PRDN’s clinical effectiveness in the management of tendon disorders. From January 2015 to November 2022, OVID-MEDLINE®, EMBASE, Cochrane Library, SCOPUS, Web of Science, Google Scholar and PubMed were searched to identify relevant studies. The methodological quality of the studies was evaluated, and relevant data were extracted. Nine studies (two in vivo studies and seven clinical studies) were finally included in this systematic review. Overall, 169 patients (male: 103) were included in the present study. The effectiveness and safeness of PDRN has been investigated in the management of the following diseases: plantar fasciitis; epicondylitis; Achilles tendinopathy; pes anserine bursitis; chronic rotator cuff disease. No adverse effects have been recorded in the included studies and all the patients showed an improvement in clinical symptoms during the follow-up. PDRN are a valid emerging therapeutic drug in the treatment of tendinopathies. Further multicentric randomized clinical studies are needed to better define the therapeutic role of PDRN, especially in combined clinical protocols.
Artificial Diets with Altered Levels of Sulfur Amino Acids Induce Anticancer Activity in Mice with Metastatic Colon Cancer, Ovarian Cancer and Renal Cell Carcinoma
Authors: Jiménez-Alonso Julio José , Guillén-Mancina Emilio , Calderón-Montaño José Manuel , Jiménez-González Víctor , Díaz-Ortega Patricia , Burgos-Morón Estefanía , López-Lázaro Miguel
Published: February 2023

Sulfur-containing amino acids methionine (Met), cysteine (Cys) and taurine (Tau) are common dietary constituents with important cellular roles. Met restriction is already known to exert in vivo anticancer activity. However, since Met is a precursor of Cys and Cys produces Tau, the role of Cys and Tau in the anticancer activity of Met-restricted diets is poorly understood. In this work, we screened the in vivo anticancer activity of several Met-deficient artificial diets supplemented with Cys, Tau or both. Diet B1 (6% casein, 2.5% leucine, 0.2% Cys and 1% lipids) and diet B2B (6% casein, 5% glutamine, 2.5% leucine, 0.2% Tau and 1% lipids) showed the highest activity and were selected for further studies. Both diets induced marked anticancer activity in two animal models of metastatic colon cancer, which were established by injecting CT26.WT murine colon cancer cells in the tail vein or peritoneum of immunocompetent BALB/cAnNRj mice. Diets B1 and B2B also increased survival of mice with disseminated ovarian cancer (intraperitoneal ID8 Tp53−/− cells in C57BL/6JRj mice) and renal cell carcinoma (intraperitoneal Renca cells in BALB/cAnNRj mice). The high activity of diet B1 in mice with metastatic colon cancer may be useful in colon cancer therapy.
A Novel Homodimer Peptide–Drug Conjugate Improves the Efficacy of HER2-Positive Breast Cancer Therapy
Authors: Liu Shurong , Tian Ye , Jiang Sujun , Wang Zihua
Published: February 2023

Tumor-targeting peptide–drug conjugates (PDCs) have become a focus of research in recent years. However, due to the instability of peptides and their short in vivo effective half-life, they have limited clinical application. Herein, we propose a new DOX PDC based on a homodimer HER-2-targeting peptide and acid-sensitive hydrazone bond, which could enhance the anti-tumor effect of DOX and reduce systemic toxicities. The PDC could accurately deliver DOX into HER2-positive SKBR-3 cells, with it showing 2.9 times higher cellular uptake than free DOX and enhanced cytotoxicity with respect to IC50 of 140 nM (vs. 410 nM for free DOX). In vitro assays showed that the PDC had high cellular internalization efficiency and cytotoxicity. In vivo anti-tumor experiments indicated that the PDC could significantly inhibit the growth of HER2-positive breast cancer xenografts in mice and reduce the side effects of DOX. In summary, we constructed a novel PDC molecule targeting HER2-positive tumors, which may overcome some deficiencies of DOX in breast cancer therapy.
Neurotensin and Its Involvement in Reproductive Functions: An Exhaustive Review of the Literature
Authors: Arbogast Pauline , Gauchotte Guillaume , Mougel Romane , Morel Olivier , Ziyyat Ahmed , Agopiantz Mikaël
Published: February 2023

Neurotensin (NTS) is a peptide discovered in 1973, which has been studied in many fields and mainly in oncology for its action in tumor growth and proliferation. In this review of the literature, we wanted to focus on its involvement in reproductive functions. NTS participates in an autocrine manner in the mechanisms of ovulation via NTS receptor 3 (NTSR3), present in granulosa cells. Spermatozoa express only its receptors, whereas in the female reproductive system (endometrial and tube epithelia and granulosa cells), we find both NTS secretion and the expression of its receptors. It consistently enhances the acrosome reaction of spermatozoa in mammals in a paracrine manner via its interaction with NTSR1 and NTSR2. Furthermore, previous results on embryonic quality and development are discordant. NTS appears to be involved in the key stages of fertilization and could improve the results of in vitro fertilization, especially through its effect on the acrosomal reaction.
Demyelinating Diseases: From Molecular Mechanisms to Therapeutic Strategies
Authors: Bernardo Antonietta , Visentin Sergio
Published: February 2023

Demyelinating diseases are a group of pathologies characterized by the alteration of myelin—that is, the coating that wraps around most of the nerve fibres of the central and peripheral nervous system, whose goal is the improvement of nerve conduction and the preservation of energy spent during action potential propagation [...]
Molecular Basis beyond Interrelated Bone Resorption/Regeneration in Periodontal Diseases: A Concise Review
Authors: Sadek Khadiga , El Moshy Sara , Radwan Israa , Rady Dina , Abbass Marwa , El-Rashidy Aiah , Dörfer Christof , Fawzy El-Sayed Karim
Published: February 2023

Periodontitis is the sixth most common chronic inflammatory disease, destroying the tissues supporting the teeth. There are three distinct stages in periodontitis: infection, inflammation, and tissue destruction, where each stage has its own characteristics and hence its line of treatment. Illuminating the underlying mechanisms of alveolar bone loss is vital in the treatment of periodontitis to allow for subsequent reconstruction of the periodontium. Bone cells, including osteoclasts, osteoblasts, and bone marrow stromal cells, classically were thought to control bone destruction in periodontitis. Lately, osteocytes were found to assist in inflammation-related bone remodeling besides being able to initiate physiological bone remodeling. Furthermore, mesenchymal stem cells (MSCs) either transplanted or homed exhibit highly immunosuppressive properties, such as preventing monocytes/hematopoietic precursor differentiation and downregulating excessive release of inflammatory cytokines. In the early stages of bone regeneration, an acute inflammatory response is critical for the recruitment of MSCs, controlling their migration, and their differentiation. Later during bone remodeling, the interaction and balance between proinflammatory and anti-inflammatory cytokines could regulate MSC properties, resulting in either bone formation or bone resorption. This narrative review elaborates on the important interactions between inflammatory stimuli during periodontal diseases, bone cells, MSCs, and subsequent bone regeneration or bone resorption. Understanding these concepts will open up new possibilities for promoting bone regeneration and hindering bone loss caused by periodontal diseases.
Emerging RNA-Based Therapeutic and Diagnostic Options: Recent Advances and Future Challenges in Genitourinary Cancers
Authors: Tortora Fabiana , La Civita Evelina , Trivedi Pankaj , Febbraio Ferdinando , Terracciano Daniela , Cimmino Amelia
Published: February 2023

Renal cell carcinoma, bladder cancer, and prostate cancer are the most widespread genitourinary tumors. Their treatment and diagnosis have significantly evolved over recent years, due to an increasing understanding of oncogenic factors and the molecular mechanisms involved. Using sophisticated genome sequencing technologies, the non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, have all been implicated in the occurrence and progression of genitourinary cancers. Interestingly, DNA, protein, and RNA interactions with lncRNAs and other biological macromolecules drive some of these cancer phenotypes. Studies on the molecular mechanisms of lncRNAs have identified new functional markers that could be potentially useful as biomarkers for effective diagnosis and/or as targets for therapeutic intervention. This review focuses on the mechanisms underlying abnormal lncRNA expression in genitourinary tumors and discusses their role in diagnostics, prognosis, and treatment.
Regulation of De Novo Lipid Synthesis by the Small GTPase Rac1 in the Adipogenic Differentiation of Progenitor Cells from Mouse White Adipose Tissue
Authors: Hasegawa Kiko , Takenaka Nobuyuki , Yamamoto Maaya , Sakoda Yoshiki , Aiba Atsu , Satoh Takaya
Published: February 2023

White adipocytes act as lipid storage, and play an important role in energy homeostasis. The small GTPase Rac1 has been implicated in the regulation of insulin-stimulated glucose uptake in white adipocytes. Adipocyte-specific rac1-knockout (adipo-rac1-KO) mice exhibit atrophy of subcutaneous and epididymal white adipose tissue (WAT); white adipocytes in these mice are significantly smaller than controls. Here, we aimed to investigate the mechanisms underlying the aberrations in the development of Rac1-deficient white adipocytes by employing in vitro differentiation systems. Cell fractions containing adipose progenitor cells were obtained from WAT and subjected to treatments that induced differentiation into adipocytes. In concordance with observations in vivo, the generation of lipid droplets was significantly attenuated in Rac1-deficient adipocytes. Notably, the induction of various enzymes responsible for de novo synthesis of fatty acids and triacylglycerol in the late stage of adipogenic differentiation was almost completely suppressed in Rac1-deficient adipocytes. Furthermore, the expression and activation of transcription factors, such as the CCAAT/enhancer-binding protein (C/EBP) β, which is required for the induction of lipogenic enzymes, were largely inhibited in Rac1-deficient cells in both early and late stages of differentiation. Altogether, Rac1 is responsible for adipogenic differentiation, including lipogenesis, through the regulation of differentiation-related transcription.
Block Image Encryption Algorithm Based on Novel Chaos and DNA Encoding
Authors: Zhao Jianfeng , Wang Shuying , Zhang Litao
Published: February 2023

To solve the problem of the low secret space and security of some image schemes, a novel 4D chaotic system is derived in this paper. Compared with other similar chaotic systems, the new system only has one equilibrium point and can exhibit hyperchaotic characteristics, under some parameter space. The system has better dynamic characters represented by calculation of the Lyapunov exponents, phase planes, and visual 0–1 test diagram. In this study, a novel image encryption algorithm is employed based on the new dynamic system, Zigzag transform, and DNA operation. Based on the improved Zigzag transformation, the plain image is block-scrambled, and DNA encoded with the treated chaotic sequences. The transformation efficiency is improved by combining multiple images at the same time. Numerical analysis has been carried out; the results show that our algorithm achieves much better performance in security, i.e., with enhanced pseudo-randomness, higher key sensitivity, weak correlation, fairly large key space, higher security, and a stronger ability to resist various attacks. Through visual analysis, the algorithm is deemed safe and effective for digital images.
Synthesis, In Silico, In Vivo, and Ex Vivo Evaluation of a Boron-Containing Quinolinate Derivative with Presumptive Action on mGluRs
Authors: Cuevas-Galindo Mario Emilio , Rubio-Velázquez Brenda Anaid , Jarillo-Luna Rosa Adriana , Padilla-Martínez Itzia I. , Soriano-Ursúa Marvin A. , Trujillo-Ferrara José G.
Published: February 2023

In the brain, canonical excitatory neurotransmission is mediated by L-glutamate and its ionotropic (iGluR) and metabotropic (mGluR) receptors. The wide diversity of these often limits the development of glutamatergic drugs. This is due to the arduousness of achieving selectivity with specific ligands. In the present article, encouraged by reports of bioactive organoboron compounds, a diphenylboroxazolidone derived from quinolinate (BZQuin) was evaluated. BZQuin was synthesized with a yield of 87%. Its LD50 was 174 mg/kg in male CD-1 mice, as estimated by a modified Lorke’s method. BZQuin exerted a reduced ability to cause seizures when compared against its precursor, quinolinate. The latter suggested that it does not directly stimulate the ionotropic NMDA receptors or other ionic channels. The observation that the antiglutamatergic drugs riluzole and memantine displaced the BZQuin effect left the mGluRs as their possible targets. This is in line with results from molecular-docking simulations. During these simulations, BZQuin bound only to orthosteric sites on mGluR1, mGluR2, and mGluR7, with higher affinity than quinolinate. The survival of the neurons of mice previously administered with BZQuin or quinolinate was quantified in four neuroanatomical structures of the brain. The BZQuin effect was more appreciable in brain regions with a high expression of the previously mentioned mGluRs, while both antiglutamatergic drugs exerted a neuroprotective effect against it. Together, these results suggest that BZQuin exerts a positive influence on glutamatergic neurotransmission while selectively interacting with certain mGluRs.
Host Plant Specificity in Web-Building Spiders
Authors: Hesselberg Thomas , Boyd Kieran M. , Styrsky John D. , Gálvez Dumas
Published: February 2023

Spiders are ubiquitous generalist predators playing an important role in regulating insect populations in many ecosystems. Traditionally they have not been thought to have strong influences on, or interactions with plants. However, this is slowly changing as several species of cursorial spiders have been reported engaging in either herbivory or inhabiting only one, or a handful of related plant species. In this review paper, we focus on web-building spiders on which very little information is available. We only find well-documented evidence from studies of host plant specificity in orb spiders in the genus Eustala, which are associated with specific species of swollen thorn acacias. We review what little is known of this group in the context of spider–plant interactions generally, and focus on how these interactions are established and maintained while providing suggestions on how spiders may locate and identify specific species of plants. Finally, we suggest ideas for future fruitful research aimed at understanding how web-building spiders find and utilise specific plant hosts.
Alpha-Cypermethrin Resistance in Musca domestica: Resistance Instability, Realized Heritability, Risk Assessment, and Insecticide Cross-Resistance
Authors: Abbas Naeem , Hafez Abdulwahab M.
Published: February 2023

Musca domestica L., the common house fly, is a cosmopolitan carrier of human and livestock disease pathogens. The species exhibits resistance to many insecticides; therefore, effective M. domestica insecticide resistance management programs are required worldwide. In the present study, the development of alpha-cypermethrin resistance, realized heritability (h2), instability of resistance trait (DR), and cross-resistance (CR) was investigated in an alpha-cypermethrin-selected M. domestica strain (Alpha-Sel) across 24 generations (Gs). Compared with an alpha-cypermethrin-unselected strain (Alpha-Unsel), resistance to alpha-cypermethrin increased from 46.4-fold (G5) to 474.2-fold (G24) in Alpha-Sel females and 41.0-fold (G5) to 253.2-fold (G24) in Alpha-Sel males. Alpha-cypermethrin resistance declined by between –0.10 (G5) and –0.05 (G24) in both M. domestica sexes without insecticide exposure for 24 generations. The h2 of alpha-cypermethrin resistance was 0.17 and 0.18 for males and females, respectively, in G1–G24. With selection intensities of 10–90%, the G values required for a tenfold increase in the LC50 of alpha-cypermethrin were 6.3–53.7, 4.1–33.8, and 3.0–24.7, given h2 values of 0.17, 0.27, and 0.37, respectively, and a constant slope of 2.1 for males and h2 values of 0.18, 0.28, and 0.38, respectively, and a constant slope of 2.0 for females. Compared with Alpha-Unsel, Alpha-Sel M. domestica exhibited moderate CR to bifenthrin (15.5-fold), deltamethrin (28.4-fold), and cyfluthrin (16.8-fold), low CR to two pyrethroids and five organophosphates, and no CR to insect growth regulators. The instability of resistance trait, low h2, and absent or low CR associated with alpha-cypermethrin resistance in M. domestica indicate resistance could be managed with rotational use of the insecticide.
Butterfly Wing Translucence Enables Enhanced Visual Signaling
Authors: Stavenga Doekele G. , Leertouwer Heinrich L. , Arikawa Kentaro
Published: February 2023

The light reflected by the dorsal side of butterfly wings often functions as a signal for, e.g., mate choice, thermoregulation, and/or predator deterrence, while the ventral wing reflections are generally used for crypsis and camouflage. Here, we propose that transmitted light can also have an important role in visual signaling because, in many butterfly species, the dorsal and ventral wing sides are similarly patterned and locally more or less translucent. Extreme examples are the Japanese yellow swallowtail (Papilio xuthus Linnaeus, 1758) and the Yellow glassy tiger (Parantica aspasia Fabricius, 1787). Their wings exhibit a similar color pattern in reflected and transmitted light, which allows enhanced visual signaling, especially in flight. Contrasting cases in which the coloration and patterning of dorsal and ventral wings strongly differ are the papilionid Papilio nireus Linnaeus, 1758, and the pierid Delias nigrina Fabricius, 1775. The wings observed in reflected or transmitted light then show very different color patterns. Wing translucence thus will strongly affect a butterfly’s visual signal.
Factors Affecting the Flight Capacity of Two Woodwasp Species, Sirex noctilio F. (Hymenoptera: Siricidae) and Sirex nitobei M. (Hymenoptera: Siricidae)
Authors: Liu Xiaobo , Shi Juan , Ren Lili , Luo Youqing
Published: February 2023

Sirex noctilio F. is an invasive woodwasp that causes pine mortality in plantations in China. Sirex nitobei M. is a native woodwasp in large areas of China. In this study, the flight capacity of the two woodwasps was studied and compared using a tethered-flight mill system to find individual factors affecting the flight capacity. After flight bioassays, woodwasps were dissected to determine nematode infestation. Post-eclosion-day (PED) age significantly influenced the flight capacity of S. noctilio females and males; as woodwasps become older, their flight capacity decreased. For S. nitobei, PED age did not significantly affect their flight capacity. In general, the flight capacity of S. noctilio was greater than that of S. nitobei. Females flew further and for longer than males for both Sirex species. The Deladenus spp. parasitism status of the two Sirex species did not significantly affect their flight performance parameters. PED age and body mass were key individual factors significantly affecting the flight capacity of the two Sirex species. In this study, detailed and accurate tethered-flight parameters of S. noctilio and S. nitobei were obtained. Although this is different from natural flight, it also provides us substantial laboratory data on their flight capacity, and facilitates risk analysis of the two woodwasp species.
An Efficient Ring-Shaped Electromagnetic Thruster
Authors: Funaro Daniele , Chiolerio Alessandro
Published: February 2023

An electromagnetic thruster is proposed and successfully tested. Its design is inspired by theoretical considerations whose qualitative predictions are well matched with the experimental results. The efficiency is higher than any other device so far reported in the literature, producing a directional thrust of approximately 2.7×10−6m, where m is the mass of the thruster itself, with a nominal power injected of approximately 10 Watts. The prototype has the shape of a ring and is powered by both radio frequency signals and a stationary high voltage. Improvements and generalizations can be easily devised by adjusting the geometry of the device.