bluuebunny/crossref_metadata_2025 huggingface dataset:
Near-Infrared Photobiomodulation of the Peripheral Nerve Inhibits the Neuronal Firing in a Rat Spinal Dorsal Horn Evoked by Mechanical Stimulation
Authors: Uta Daisuke , Ishibashi Naoya , Konno Takahiro , Okada Yuki , Kawase Yuki , Tao Shinichi , Kume Toshiaki
Published: January 2023

Photobiomodulation has analgesic effects via inhibition of nerve activity, but few reports have examined the effects on the spinal dorsal horn, the entry point for nociceptive information in the central nervous system. In this study, we evaluated the effects of laser irradiation of peripheral nerve axons, which are conduction pathways for nociceptive stimuli, on the neuronal firing in lamina II of the spinal dorsal horn of a rat evoked by mechanical stimulation with von Frey filaments (vFF). In order to record neuronal firing, electrodes were inserted into lamina II of the exposed rat spinal dorsal horn. The exposed sciatic nerve axons were irradiated with an 808 nm laser. The 26.0 g vFF-evoked firing frequency was inhibited from 5 min after laser irradiation and persisted for 3 h. Sham irradiation did not alter the firing frequency. Laser irradiation selectively inhibited 15.0 and 26.0 g vFF-evoked firing, which corresponded to nociceptive stimuli. Histopathological evaluation revealed no damage to the sciatic nerve due to laser irradiation. These results indicate that neuronal firing is inhibited in lamina II of the spinal dorsal horn, suggesting that laser irradiation inhibits Aδ and/or C fibers that conduct nociceptive stimuli.
Dendrobine Alleviates Cellular Senescence and Osteoarthritis via the ROS/NF-κB Axis
Authors: Chen Haitao , Tu Ming , Liu Siyi , Wen Yinxian , Chen Liaobin
Published: January 2023

Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and cartilage degradation. Dendrobine (DEN) is reported to inhibit inflammation and oxidative stress in some diseases, but its role in chondrocyte senescence and OA progress has not yet been elucidated. Our study aimed to explore the protective effects of DEN on OA both in vitro and in vivo. We found that DEN inhibited extracellular matrix (ECM) degradation and promoted ECM synthesis. Meanwhile, DEN inhibited senescence-associated secretory phenotype (SASP) factors expression and senescence phenotype in IL-1β-treated chondrocytes. Furthermore, DEN improved mitochondrial function and reduced the production of intracellular reactive oxygen species (ROS). Also, DEN suppressed IL-1β-induced activation of the NF-κB pathway. Further, using NAC (ROS inhibitor), we found that DEN might inhibit NF-κB cascades by reducing ROS. Additionally, X-ray, micro-CT, and histological analyses in vivo demonstrated that DEN significantly alleviated cartilage inflammation, ECM degradation, and subchondral alterations in OA progression. In conclusion, DEN inhibits SASP factors expression and senescence phenotype in chondrocytes and alleviated the progression of OA via the ROS/NF-κB axis, which provides innovative strategies for the treatment of OA.
Role of Melatonin in Daily Variations of Plasma Insulin Level and Pancreatic Clock Gene Expression in Chick Exposed to Monochromatic Light
Authors: Song Chao , Wang Zixu , Cao Jing , Dong Yulan , Chen Yaoxing
Published: January 2023

To clarify the effect of monochromatic light on circadian rhythms of plasma insulin level and pancreatic clock gene expression and its mechanism, 216 newly hatched chicks were divided into three groups (intact, sham operation and pinealectomy) and were raised under white (WL), red (RL), green (GL) or blue (BL) light for 21 days. Their plasma and pancreas were sampled at six four-hour intervals. For circadian rhythm analysis, measurements of plasma melatonin, insulin, and clock gene expression (cClock, cBmal1, cBmal2, cCry1, cCry2, cPer2, and cPer3) were made. Plasma melatonin, insulin, and the pancreatic clock gene all expressed rhythmically in the presence of monochromatic light. Red light reduced the mesor and amplitude of plasma melatonin in comparison to green light. The mesor and amplitude of the pancreatic clock gene in chickens exposed to red light were dramatically reduced, which is consistent with the drop in plasma melatonin levels. Red light, on the other hand, clearly raised the level of plasma insulin via raising the expression of cVamp2, but not cInsulin. After the pineal gland was removed, the circadian expressions of plasma melatonin and pancreatic clock gene were significantly reduced, but the plasma insulin level and the pancreatic cVamp2 expression were obviously increased, resulting in the disappearance of differences in insulin level and cVamp2 expression in the monochromatic light groups. Therefore, we hypothesize that melatonin may be crucial in the effect of monochromatic light on the circadian rhythm of plasma insulin level by influencing the expression of clock gene in chicken pancreas.
Comparative Analysis of Library Preparation Approaches for SARS-CoV-2 Genome Sequencing on the Illumina MiSeq Platform
Authors: Gladkikh Anna , Klyuchnikova Ekaterina , Pavlova Polina , Sbarzaglia Valeriya , Tsyganova Nadezhda , Popova Margarita , Arbuzova Tatiana , Sharova Alena , Ramsay Edward , Samoilov Andrei , Dedkov Vladimir , Totolian Areg
Published: January 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for over two years of the COVID-19 pandemic and a global health emergency. Genomic surveillance plays a key role in overcoming the ongoing COVID-19 pandemic despite its relative successive waves and the continuous emergence of new variants. Many technological approaches are currently applied for the whole genome sequencing (WGS) of SARS-CoV-2. They differ in key stages of the process, and they feature some differences in genomic coverage, sequencing depth, and in the accuracy of variant-calling options. In this study, three different protocols for SARS-CoV-2 WGS library construction are compared: an amplicon-based protocol with a commercial primer panel; an amplicon-based protocol with a custom panel; and a hybridization capture protocol. Specific differences in sequencing depth and genomic coverage as well as differences in SNP number were found. The custom panel showed suitable results and a predictable output applicable for the epidemiological surveillance of SARS-CoV-2 variants.
The Effects of Viruses on Insulin Sensitivity and Blood–Brain Barrier Function
Authors: Raber Jacob , Rhea Elizabeth M. , Banks William A.
Published: January 2023

In this review manuscript, we discuss the effects of select common viruses on insulin sensitivity and blood–brain barrier (BBB) function and the potential overlapping and distinct mechanisms involved in these effects. More specifically, we discuss the effects of human immunodeficiency virus (HIV), herpes, hepatitis, influenza, respiratory syncytial virus (RSV), and SARS-CoV-2 viruses on insulin sensitivity and BBB function and the proposed underlying mechanisms. These viruses differ in their ability to be transported across the BBB, disrupt the BBB, and/or alter the function of the BBB. For RSV and SARS-CoV-2, diabetes increases the risk of infection with the virus, in addition to viral infection increasing the risk for development of diabetes. For HIV and hepatitis C and E, enhanced TNF-a levels play a role in the detrimental effects. The winter of 2022–2023 has been labeled as a tridemic as influenza, RSV, and COVID-19 are all of concern during this flu season. There is an ongoing discussion about whether combined viral exposures of influenza, RSV, and COVID-19 have additive, synergistic, or interference effects. Therefore, increased efforts are warranted to determine how combined viral exposures affect insulin sensitivity and BBB function.
Appropriateness of Proton Pump Inhibitor Prescription Evaluated by Using Serological Markers
Authors: Russo Michele , Rodriguez-Castro Kryssia Isabel , Franceschi Marilisa , Ferronato Antonio , Panozzo Maria Piera , Brozzi Lorenzo , Di Mario Francesco , Crafa Pellegrino , Brandimarte Giovanni , Tursi Antonio
Published: January 2023

Inappropriate prescription of proton pump inhibitors (PPI) has been widely reported, often lacking initial exclusion of Helicobacter pylori (HP) infection and evaluation of gastric functional status. The aim of this study was to evaluate the utility of gastric functional tests to define the acid output, as well as HP status, in order to better direct PPI therapy prescription. Dyspeptic patients without alarm symptoms from a primary care population were evaluated. For each patient, serum Pepsinogen I (PGI) and II (PGII), gastrin 17 (G17) and anti-HP IgG antibodies (Biohit, Oyj, Finland) were determined. For each subject, data were collected regarding symptoms, past medical history of HP infection, and PPI use. Therapeutic response to PPIs was determined according to PGI and G17 values, where G17 > 7 in the presence of elevated PGI and absence of chronic atrophic gastritis (CAG) was considered an adequate response. Among 2583 dyspeptic patients, 1015/2583 (39.3%) were on PPI therapy for at least 3 months before serum sampling, and were therefore included in the study. Active HP infection and CAG were diagnosed in 206 (20.2%) and 37 (3.6%) patients, respectively. Overall, an adequate therapeutic response to PPIs was observed in 34.9%, reaching 66.7% at the highest dose. However, 41.1% and 20.4% of patients showed low (G17 1-7) or absent (G17 < 1) response to PPI, regardless of the dosage used. According to gastric functional response, most patients currently on PPI maintenance therapy lack a proper indication for continuing this medication, either because acid output is absent (as in CAG) or because gastrin levels fail to rise, indicating absence of gastric acid negative feedback. Lastly, HP eradication is warranted in all patients, and gastric function testing ensures this pathogen is sought for and adequately treated prior to initiating long-term PPI therapy.
Alterations in Circulating miRNA Levels after Infection with SARS-CoV-2 Could Contribute to the Development of Cardiovascular Diseases: What We Know So Far
Authors: Pieri Myrtani , Vayianos Panayiotis , Nicolaidou Vicky , Felekkis Kyriacos , Papaneophytou Christos
Published: January 2023

The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and poses significant complications for cardiovascular disease (CVD) patients. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and influence several physiological and pathological processes, including CVD. This critical review aims to expand upon the current literature concerning miRNA deregulation during the SARS-CoV-2 infection, focusing on cardio-specific miRNAs and their association with various CVDs, including cardiac remodeling, arrhythmias, and atherosclerosis after SARS-CoV-2 infection. Despite the scarcity of research in this area, our findings suggest that changes in the expression levels of particular COVID-19-related miRNAs, including miR-146a, miR-27/miR-27a-5p, miR-451, miR-486-5p, miR-21, miR-155, and miR-133a, may be linked to CVDs. While our analysis did not conclusively determine the impact of SARS-CoV-2 infection on the profile and/or expression levels of cardiac-specific miRNAs, we proposed a potential mechanism by which the miRNAs mentioned above may contribute to the development of these two pathologies. Further research on the relationship between SARS-CoV-2, CVDs, and microRNAs will significantly enhance our understanding of this connection and may lead to the use of these miRNAs as biomarkers or therapeutic targets for both pathologies.
Gut Microbiome Composition in Dystonia Patients
Authors: Timmers Elze R. , Swarte J. Casper , Gacesa Ranko , Björk Johannes R. , Weersma Rinse K. , Tijssen Marina A. J. , de Koning Tom J. , Harmsen Hermie J. M. , Niezen-Koning Klary E.
Published: January 2023

Dystonia is a movement disorder in which patients have involuntary abnormal movements or postures. Non-motor symptoms, such as psychiatric symptoms, sleep problems and fatigue, are common. We hypothesise that the gut microbiome might play a role in the pathophysiology of the (non-)motor symptoms in dystonia via the gut–brain axis. This exploratory study investigates the composition of the gut microbiome in dystonia patients compared to healthy controls. Furthermore, the abundance of neuro-active metabolic pathways, which might be implicated in the (non-)motor symptoms, was investigated. We performed both metagenomic and 16S rRNA sequencing on the stool samples of three subtypes of dystonia (27 cervical dystonia, 20 dopa-responsive dystonia and 24 myoclonus-dystonia patients) and 25 controls. While microbiome alpha and beta diversity was not different between dystonia patients and controls, dystonia patients had higher abundances of Ruminococcus torques and Dorea formicigenerans, and a lower abundance of Butyrivibrio crossotus compared to controls. For those with dystonia, non-motor symptoms and the levels of neurotransmitters in plasma explained the variance in the gut microbiome composition. Several neuro-active metabolic pathways, especially tryptophan degradation, were less abundant in the dystonia patients compared to controls. This suggest that the gut–brain axis might be involved in the pathophysiology of dystonia. Further studies are necessary to confirm our preliminary findings.
Salivary IgA and IgG Antibody Responses against Periodontitis-Associated Bacteria in Crohn’s Disease
Authors: Gürsoy Mervi , Rautava Jaana , Pussinen Pirkko , Kristoffersen Anna Karin , Enersen Morten , Loimaranta Vuokko , Gürsoy Ulvi Kahraman
Published: January 2023

Elevated serum immunoglobulin (Ig) antibody levels are observed in Crohn’s disease patients. The aim of this study was to evaluate the salivary IgA and IgG antibody levels against Porphyromonas gingivalis, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Prevotella intermedia in Crohn’s disease patients. Eighty-eight participants (47 Crohn’s disease patients and 41 systemically healthy age- and gender-matched controls) were included in the study. Oral and medical health statuses were recorded and salivary samples were collected. Salivary P. gingivalis, T. forsythia, A. actinomycetemcomitans, and P. intermedia carriage were analyzed with DNA sequencing technique, salivary levels of IgG1, IgG2, IgG3, IgG4, and IgM were measured with the Luminex® xMAP™ technique, and salivary IgA and IgG antibody levels against P. gingivalis, T. forsythia, A. actinomycetemcomitans, and P. intermedia were detected by ELISA. As result, higher salivary IgG2 (p = 0.011) and IgG3 (p = 0.006), P. gingivalis IgA (p < 0.001), A. actinomycetemcomitans IgG (p = 0.001), and P. intermedia IgG (p < 0.001) antibody levels were detected in the Crohn’s disease group compared to the controls. Salivary P. gingivalis carriage was lower in the Crohn’s disease group in comparison to the controls (p = 0.024). In conclusion, salivary IgA antibody responses against P. gingivalis and IgG antibody responses against P. intermedia have independent associations with Crohn’s disease.
Obtaining miRNA from Saliva—Comparison of Sampling and Purification Methods
Authors: Urbizu Aintzane , Arnaldo Laura , Beyer Katrin
Published: January 2023

The use of saliva as a biomarker source has advantages over other biofluids and imaging techniques, and miRNAs are ideal biomarker candidates. They are involved in numerous cellular processes, and their altered expression suggests that miRNAs play a crucial regulatory role in disease development. We wanted to find an easily reproducible and executable miRNA-obtaining methodology suitable for quantification. Three commercial miRNA extraction kits (mirVana, Nucleospin and miRNeasy) and three saliva collectors (50 mL tubes, Salimetrics and Oragene) were tested. Several features, including RNA quality and technical parameters, were evaluated. The expression of five synthetic spike-in controls and seven saliva-miRNAs was analyzed independently and grouped by the collectors and the extraction kits. The combination of Oragene and miRNeasy assured the most sensitive detection of all seven saliva miRNAs. Testing different combinations of saliva collectors and RNA purification kits permitted the establishment of combinations for different uses. The results of our study highlight that optimization of resources for biomarker studies is possible after careful planning of each study.
Construction of Biocatalysts Using the P450 Scaffold for the Synthesis of Indigo from Indole
Authors: Li Yanqing , Lin Yingwu , Wang Fang , Wang Jinghan , Shoji Osami , Xu Jiakun
Published: January 2023

With the increasing demand for blue dyes, it is of vital importance to develop a green and efficient biocatalyst to produce indigo. This study constructed a hydrogen peroxide-dependent catalytic system for the direct conversion of indole to indigo using P450BM3 with the assistance of dual-functional small molecules (DFSM). The arrangements of amino acids at 78, 87, and 268 positions influenced the catalytic activity. F87G/T268V mutant gave the highest catalytic activity with kcat of 1402 min−1 and with a yield of 73%. F87A/T268V mutant was found to produce the indigo product with chemoselectivity as high as 80%. Moreover, F87G/T268A mutant was found to efficiently catalyze indole oxidation with higher activity (kcat/Km = 1388 mM−1 min−1) than other enzymes, such as the NADPH-dependent P450BM3 (2.4-fold), the Ngb (32-fold) and the Mb (117-fold). Computer simulation results indicate that the arrangements of amino acid residues in the active site can significantly affect the catalytic activity of the protein. The DFSM-facilitated P450BM3 peroxygenase system provides an alternative, simple approach for a key step in the bioproduction of indigo.
Hair Follicles as a Critical Model for Monitoring the Circadian Clock
Authors: Liu Li-Ping , Li Meng-Huan , Zheng Yun-Wen
Published: January 2023

Clock (circadian) genes are heterogeneously expressed in hair follicles (HFs). The genes can be modulated by both the central circadian system and some extrinsic factors, such as light and thyroid hormones. These circadian genes participate in the regulation of several physiological processes of HFs, including hair growth and pigmentation. On the other hand, because peripheral circadian genes are synchronized with the central clock, HFs could provide a noninvasive and practical method for monitoring and evaluating multiple circadian-rhythm-related conditions and disorders among humans, including day and night shifts, sleep–wake disorders, physical activities, energy metabolism, and aging. However, due to the complexity of circadian biology, understanding how intrinsic oscillation operates using peripheral tissues only may be insufficient. Combining HF sampling with multidimensional assays such as detection of body temperature, blood samples, or certain validated questionnaires may be helpful in improving HF applications. Thus, HFs can serve as a critical model for monitoring the circadian clock and can help provide an understanding of the potential mechanisms of circadian-rhythm-related conditions; furthermore, chronotherapy could support personalized treatment scheduling based on the gene expression profile expressed in HFs.
Splicing Modulation Results in Aberrant Isoforms and Protein Products of p53 Pathway Genes and the Sensitization of B Cells to Non-Genotoxic MDM2 Inhibition
Authors: Aptullahoglu Erhan , Ciardullo Carmela , Wallis Jonathan P. , Marr Helen , Marshall Scott , Bown Nick , Willmore Elaine , Lunec John
Published: January 2023

Several molecular subtypes of cancer are highly dependent on splicing for cell survival. There is a general interest in the therapeutic targeting of splicing by small molecules. E7107, a first-in-class spliceosome inhibitor, showed strong growth inhibitory activities against a large variety of human cancer xenografts. Chronic lymphocytic leukaemia (CLL) is a clinically heterogeneous hematologic malignancy, with approximately 90% of cases being TP53 wild-type at diagnosis. An increasing number of studies are evaluating alternative targeted agents in CLL, including MDM2–p53 binding antagonists. In this study, we report the effect of splicing modulation on key proteins in the p53 signalling pathway, an important cell death pathway in B cells. Splicing modulation by E7107 treatment reduced full-length MDM2 production due to exon skipping, generating a consequent reciprocal p53 increase in TP53WT cells. It was especially noteworthy that a novel p21WAF1 isoform with compromised cyclin-dependent kinase inhibitory activity was produced due to intron retention. E7107 synergized with the MDM2 inhibitor RG7388, via dual MDM2 inhibition; by E7107 at the transcript level and by RG7388 at the protein level, producing greater p53 stabilisation and apoptosis. This study provides evidence for a synergistic MDM2 and spliceosome inhibitor combination as a novel approach to treat CLL and potentially other haematological malignancies.
Cytochrome P450 1B1 Expression Regulates Intracellular Iron Levels and Oxidative Stress in the Retinal Endothelium
Authors: Song Yong-Seok , Zaitoun Ismail S. , Wang Shoujian , Darjatmoko Soesiawati R. , Sorenson Christine M. , Sheibani Nader
Published: January 2023

Cytochrome P450 (CYP) 1B1 is a heme-containing monooxygenase found mainly in extrahepatic tissues, including the retina. CYP1B1 substrates include exogenous aromatic hydrocarbons, such as dioxins, and endogenous bioactive compounds, including 17β-estradiol (E2) and arachidonic acid. The endogenous compounds and their metabolites are mediators of various cellular and physiological processes, suggesting that CYP1B1 activity is likely important in maintaining proper cellular and tissue functions. We previously demonstrated that lack of CYP1B1 expression and activity are associated with increased levels of reactive oxygen species and oxidative stress in the retinal vasculature and vascular cells, including retinal endothelial cells (ECs). However, the detailed mechanism(s) of how CYP1B1 activity modulates redox homeostasis remained unknown. We hypothesized that CYP1B1 metabolism of E2 affects bone morphogenic protein 6 (BMP6)-hepcidin-mediated iron homeostasis and lipid peroxidation impacting cellular redox state. Here, we demonstrate retinal EC prepared from Cyp1b1-deficient (Cyp1b1−/−) mice exhibits increased estrogen receptor-α (ERα) activity and expresses higher levels of BMP6. BMP6 is an inducer of the iron-regulatory hormone hepcidin in the endothelium. Increased hepcidin expression in Cyp1b1−/− retinal EC resulted in decreased levels of the iron exporter protein ferroportin and, as a result, increased intracellular iron accumulation. Removal of excess iron or antagonism of ERα in Cyp1b1−/− retinal EC was sufficient to mitigate increased lipid peroxidation and reduce oxidative stress. Suppression of lipid peroxidation and antagonism of ERα also restored ischemia-mediated retinal neovascularization in Cyp1b1−/− mice. Thus, CYP1B1 expression in retinal EC is important in the regulation of intracellular iron levels, with a significant impact on ocular redox homeostasis and oxidative stress through modulation of the ERα/BMP6/hepcidin axis.
Pre-Molten, Wet, and Dry Molten Globules en Route to the Functional State of Proteins
Authors: Gupta Munishwar Nath , Uversky Vladimir N.
Published: January 2023

Transitions between the unfolded and native states of the ordered globular proteins are accompanied by the accumulation of several intermediates, such as pre-molten globules, wet molten globules, and dry molten globules. Structurally equivalent conformations can serve as native functional states of intrinsically disordered proteins. This overview captures the characteristics and importance of these molten globules in both structured and intrinsically disordered proteins. It also discusses examples of engineered molten globules. The formation of these intermediates under conditions of macromolecular crowding and their interactions with nanomaterials are also reviewed.
Overexpression of Insulin Receptor Substrate 1 (IRS1) Relates to Poor Prognosis and Promotes Proliferation, Stemness, Migration, and Oxidative Stress Resistance in Cholangiocarcinoma
Authors: Kaewlert Waleeporn , Sakonsinsiri Chadamas , Lert-itthiporn Worachart , Ungarreevittaya Piti , Pairojkul Chawalit , Pinlaor Somchai , Murata Mariko , Thanan Raynoo
Published: January 2023

Cholangiocarcinoma (CCA) is one of the oxidative stress-driven carcinogenesis through chronic inflammation. Insulin receptor substrate 1 (IRS1), an adaptor protein of insulin signaling pathways, is associated with the progression of many inflammation-related cancers. This study hypothesized that oxidative stress regulates IRS1 expression and that up-regulation of IRS1 induces CCA progression. The localizations of IRS1 and an oxidative stress marker (8-oxodG) were detected in CCA tissues using immunohistochemistry (IHC). The presence of IRS1 in CCA tissues was confirmed using immortal cholangiocyte cells (MMNK1), a long-term oxidative-stress-induced cell line (ox-MMNK1-L), and five CCA cell lines as cell culture models. IRS1 was overexpressed in tumor cells and this was associated with a shorter patient survival time and an increase in 8-oxodG. IRS1 expression was higher in ox-MMNK1-L cells than in MMNK1 cells. Knockdown of IRS1 by siRNA in two CCA cell lines led to inhibition of proliferation, cell cycle progression, migration, invasion, stemness, and oxidative stress resistance properties. Moreover, a transcriptomics study demonstrated that suppressing IRS1 in the KKU-213B CCA cell line reduced the expression levels of several genes and pathways involved in the cellular functions. The findings indicate that IRS1 is a key molecule in the connection between oxidative stress and CCA progression. Therefore, IRS1 and its related genes can be used as prognostic markers and therapeutic targets for CCA therapy.
A Dual-Crosslinked Hydrogel Based on Gelatin Methacryloyl and Sulfhydrylated Chitosan for Promoting Wound Healing
Authors: Ji Shunxian , Zhao Yushuang , Zhai Xinrang , Wang Lu , Luo Huali , Xu Zhiyong , Dong Wei , Wu Bingbing , Wei Wei
Published: January 2023

The skin is the largest organ of the human body. Skin injuries, especially full-thickness injuries, are a major treatment challenge in clinical practice. Therefore, wound dressing materials with therapeutic effects have great practical significance in healthcare. This study used photocrosslinkable gelatin methacryloyl (GelMA) and sulfhydrylated chitosan (CS-SH) to design a double-crosslinked hydrogel for wound dressing. When crosslinked together, the resulting hydrogels showed a highly porous inner structure, and enhanced mechanical properties and moisture retention capacity. The compression modulus of the GelMA/CS-SH hydrogel (GCH) reached up to about 40 kPa and was much higher than that of pure GelMA hydrogel, and the compression modulus was increased with the amount of CS-SH. In vitro study showed no cytotoxicity of obtained hydrogels. Interestingly, a higher concentration of CS-SH slightly promoted the proliferation of cells. Moreover, the double-crosslinked hydrogel exhibited antibacterial properties because of the presence of chitosan. In vivo study based on rats showed that full-thickness skin defects healed on the 15th day. Histological results indicate that the hydrogel accelerated the repair of hair follicles and encouraged the orderly growth of collagen fibers in the wound. Furthermore, better blood vessel formation and a higher expression of VEGFR were observed in the hydrogel group when compared with the untreated control group. Based on our findings, GCH could be a promising candidate for full-thickness wound dressing.
Severe Asthma Remissions Induced by Biologics Targeting IL5/IL5r: Results from a Multicenter Real-Life Study
Authors: Maglio Angelantonio , Vitale Carolina , Pelaia Corrado , D’Amato Maria , Ciampo Luigi , Sferra Eliana , Molino Antonio , Pelaia Giulia , Vatrella Alessandro
Published: January 2023

Add-on biological therapy has proven to be effective in many patients with severe eosinophilic asthma. In this observational multicenter retrospective study, we report the results obtained with mepolizumab and benralizumab in severe asthmatics treated for 12 months in a real-life setting. In these patients, peripheral eosinophil levels, pulmonary function trends, exacerbation rates, systemic corticosteroid use, and symptom control were evaluated during the observation period, to understand which patients met all the criteria in order to be considered in disease remission. The percentage of remittent patients was 30.12% in the mepolizumab-treated subgroup, while in the benralizumab-treated subgroup, patients in complete disease remission were 40%, after 12 months. The results of this study confirm the efficacy of anti-IL-5 biologic drugs in the treatment of severe eosinophilic asthma in a real-life setting.
A Comparative Study on the Effects of the Lysine Reagent Pyridoxal 5-Phosphate and Some Thiol Reagents in Opening the Tl+-Induced Mitochondrial Permeability Transition Pore
Authors: Korotkov Sergey M. , Novozhilov Artemy V.
Published: January 2023

Lysine residues are essential in regulating enzymatic activity and the spatial structure maintenance of mitochondrial proteins and functional complexes. The most important parts of the mitochondrial permeability transition pore are F1F0 ATPase, the adenine nucleotide translocase (ANT), and the inorganic phosphate cotransporter. The ANT conformation play a significant role in the Tl+-induced MPTP opening in the inner membrane of calcium-loaded rat liver mitochondria. The present study tests the effects of a lysine reagent, pyridoxal 5-phosphate (PLP), and thiol reagents (phenylarsine oxide, tert-butylhydroperoxide, eosin-5-maleimide, and mersalyl) to induce the MPTP opening that was accompanied by increased swelling, membrane potential decline, and decreased respiration in 3 and 3UDNP (2,4-dinitrophenol uncoupled) states. This pore opening was more noticeable in increasing the concentration of PLP and thiol reagents. However, more significant concentrations of PLP were required to induce the above effects comparable to those of these thiol reagents. This study suggests that the Tl+-induced MPTP opening can be associated not only with the state of functionally active cysteines of the pore parts, but may be due to a change in the state of the corresponding lysines forming the pore structure.
Microbiome Alterations in Alcohol Use Disorder and Alcoholic Liver Disease
Authors: Litwinowicz Kamil , Gamian Andrzej
Published: January 2023

Microbiome alterations are emerging as one of the most important factors that influence the course of alcohol use disorder (AUD). Recent advances in bioinformatics enable more robust and accurate characterization of changes in the composition of the microbiome. In this study, our objective was to provide the most comprehensive and up-to-date evaluation of microbiome alterations associated with AUD and alcoholic liver disease (ALD). To achieve it, we have applied consistent, state of art bioinformatic workflow to raw reads from multiple 16S rRNA sequencing datasets. The study population consisted of 122 patients with AUD, 75 with ALD, 54 with non-alcoholic liver diseases, and 260 healthy controls. We have found several microbiome alterations that were consistent across multiple datasets. The most consistent changes included a significantly lower abundance of multiple butyrate-producing families, including Ruminococcaceae, Lachnospiraceae, and Oscillospiraceae in AUD compared to HC and further reduction of these families in ALD compared with AUD. Other important results include an increase in endotoxin-producing Proteobacteria in AUD, with the ALD group having the largest increase. All of these alterations can potentially contribute to increased intestinal permeability and inflammation associated with AUD and ALD.
Combination of Enzymes with Materials to Give Them Antimicrobial Features: Modern Trends and Perspectives
Authors: Efremenko Elena , Stepanov Nikolay , Aslanli Aysel , Lyagin Ilya , Senko Olga , Maslova Olga
Published: January 2023

Multidrug-resistant bacteria form serious problems in many areas, including medicine and the food industry. At the same time, great interest is shown in the transfer or enhancement of antimicrobial properties to various materials by modifying them with enzymes. The use of enzymes in biomaterials with antimicrobial properties is important because enzymes can be used as the main active components providing antimicrobial properties of functionalized composite biomaterials, or can serve as enhancers of the antimicrobial action of certain substances (antibiotics, antimicrobial peptides, metal nanoparticles, etc.) against cells of various microorganisms. Enzymes can simultaneously widen the spectrum of antimicrobial activity of biomaterials. This review presents the most promising enzymes recently used for the production of antibacterial materials, namely hydrolases and oxidoreductases. Computer modeling plays an important role in finding the most effective combinations between enzymes and antimicrobial compounds, revealing their possible interactions. The range of materials that can be functionalized using enzymes looks diverse. The physicochemical characteristics and functionalization methods of the materials have a significant impact on the activity of enzymes. In this context, fibrous materials are of particular interest. The purpose of this review is to analyze the current state of the art in this area.
Particle Image Velocimetry of 3D-Printed Anatomical Blood Vascular Models Affected by Atherosclerosis
Authors: Antonowicz Arkadiusz , Wojtas Krzysztof , Makowski Łukasz , Orciuch Wojciech , Kozłowski Michał
Published: January 2023

Improvements in the diagnosis and treatment of cardiovascular diseases facilitate a better understanding of the ongoing process. The study of biomedical fluid dynamics using non-intrusive visualizing methods on a micro-scale has become possible using a proper 3D printing process. The computed tomography scan of a patient with atherosclerosis was processed, and a 3D-printed artery with an inlet diameter of 4.2 mm was developed and measured using three different constant flow rates. To mimic blood, a solution of glycerin and water was used. The procedure to obtain a proper 3D-printed model using low-force stereolithography technology with high-quality optical access usable for PIV was described and discussed. The paper presents the results of PIV as multi-stitched, color-coded vector maps from the axis cross section along the whole 3D-printed model. The obtained data allowed a resolution of 100 × 100 µm per single vector to be achieved. Furthermore, the results of the stitched 16 base images of the artery and the 3D-printed model prepared were included. The results of this study show that 3D prints allow for the creation of the desired geometry and can be used to investigate severe pathologies of the human circulatory system. The strengths and weaknesses of this methodology were discussed and compared to other techniques used to obtain transparent objects.
Express Synthesis of YAG:Ce Ceramics in the High-Energy Electrons Flow Field
Authors: Lisitsyn Victor , Tulegenova Aida , Kaneva Ekaterina , Mussakhanov Dossymkhan , Gritsenko Boris
Published: January 2023

YAG:Ce ceramics by the direct action of an electron beam with 1.4 MeV energy were synthesized on a mixture of a stoichiometric composition of Y, Al, and Ce oxides without adding any substances to facilitate the process. The synthesis is realized in a time less than 1 s. The main structural phase of the obtained ceramics is YAG and YAP can be additional. The luminescence characteristics of the synthesized samples, the excitation, luminescence, decay time, and pulsed cathodoluminescence spectra, are similar to those known for YAG:Ce phosphors. The conversion efficiency of the excitation energy into the luminescence of the samples reaches 60–70% of those used for the manufacture of LED phosphors. The set of processes that determine the rate and efficiency of radiation synthesis differs from those occurring during thermal methods by the existence of a high degree of the initial compositions’ ionization under the influence of a radiation flux and a high probability of the decay of electronic excitations into short-lived radiolysis products.
Metallographic Mechanism of Embrittlement of 15 μm Ultrafine Quaternary Silver Alloy Bonding Wire in Chloride Ions Environment
Authors: Zhao Jun-Ren , Hung Fei-Yi , Hsu Che-Wei
Published: January 2023

Chloride ions contained in the sealing compound currently used in the electronic packaging industry not only interact with intermetallic compounds but also have a serious impact on silver alloy wires. A 15 μm ultrafine quaternary silver-palladium-gold-platinum alloy wire was used in this study. The wire and its bonding were immersed in a 60 °C saturated sodium chloride solution (chlorination experiment), and the strength and elongation before and after chlorination were measured. Finally, the fracture surface and cross-section characteristics were observed using a scanning electron microscope and focused ion microscope. The results revealed that chloride ions invade the wire along the grain boundary, and chlorides have been generated inside the cracks to weaken the strength and elongation of the wire. In addition, chloride ions invade the interface of the wire bonding to erode the aluminum substrate after immersing it for enough long time, causing galvanic corrosion, which in turn causes the bonding joint to separate from the aluminum substrate.
Microwave-Assisted Extraction of Carrageenan from Sarcopeltis skottsbergii
Authors: Álvarez-Viñas Milena , Rivas Sandra , Torres María Dolores , Domínguez Herminia
Published: January 2023

The development of greener processes for the sustainable utilization of raw materials is increasingly demanded for environmental and economic reasons. A rapid and chemical-free technique was proposed for the extraction of hybrid kappa/iota (6/4) carrageenan from Sarcopeltis (ex Gigartina) skottsbergii. After separation, carrageenans were analyzed by Fourier transform infrared attenuated total reflectance, high-performance size-exclusion chromatography, and rheology. Maximum carrageenan extraction yields up to 63–64% were obtained operating at 110 or at 160 °C, for 5–7 min considering the sum of the heating and cooling periods, but the extraction of the phenolic fraction was favored at 220 °C. The recovered carrageenan showed apparent viscous values around 103 mPa at the lowest tested shear rates (0.1 1/s) and could be suitable to formulate films. Furthermore, those carrageenans obtained under 140 °C showed gel characteristics without previous separation from the liquid extract, avoiding ethanolic precipitation and energy consumption. The antiradical properties correlated with the phenolic content in the liquid phase, but no influence of temperature on the reducing properties was observed. The microwave-assisted hydrothermal treatment could be an efficient tool without needing chemicals for the extraction of carrageenans, which showed adequate rheological properties for commercial uses.
Interaction between γ-Hydroxybutyric Acid and Ethanol: A Review from Toxicokinetic and Toxicodynamic Perspectives
Authors: Jung Suryun , Kim Mingyu , Kim Suji , Lee Sooyeun
Published: January 2023

Gamma-hydroxybutyric acid (GHB) is a potent, short-acting central nervous system depressant as well as an inhibitory neurotransmitter or neuromodulator derived from gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter. The sodium salt of GHB, sodium oxybate, has been used for the treatment of narcolepsy and cataplexy, whereas GHB was termed as a date rape drug or a club drug in the 1990s. Ethanol is the most co-ingested drug in acute GHB intoxication. In this review, the latest findings on the combined effects of GHB and ethanol are summarized from toxicokinetic and toxicodynamic perspectives. For this purpose, we mainly discussed the pharmacology and toxicology of GHB, GHB intoxication under alcohol consumption, clinical cases of the combined intoxication of GHB and ethanol, and previous studies on the toxicokinetic and toxicodynamic interactions between GHB and ethanol in humans, animals, and an in vitro model. The combined administration of GHB and ethanol enhanced sedation and cardiovascular dysfunction, probably by the additive action of GABA receptors, while toxicokinetic changes of GHB were not significant. The findings of this review will contribute to clinical and forensic interpretation related to GHB intoxication. Furthermore, this review highlights the significance of studies aiming to further understand the enhanced inhibitory effects of GHB induced by the co-ingestion of ethanol.
Role of Metabolism and Metabolic Pathways in Prostate Cancer
Authors: Wanjari Uddesh Ramesh , Mukherjee Anirban Goutam , Gopalakrishnan Abilash Valsala , Murali Reshma , Dey Abhijit , Vellingiri Balachandar , Ganesan Raja
Published: January 2023

Prostate cancer (PCa) is the common cause of death in men. The pathophysiological factors contributing to PCa are not well known. PCa cells gain a protective mechanism via abnormal lipid signaling and metabolism. PCa cells modify their metabolism in response to an excessive intake of nutrients to facilitate advancement. Metabolic syndrome (MetS) is inextricably linked to the carcinogenic progression of PCa, which heightens the severity of the disease. It is hypothesized that changes in the metabolism of the mitochondria contribute to the onset of PCa. The studies of particular alterations in the progress of PCa are best accomplished by examining the metabolome of prostate tissue. Due to the inconsistent findings written initially, additional epidemiological research is required to identify whether or not MetS is an aspect of PCa. There is a correlation between several risk factors and the progression of PCa, one of which is MetS. The metabolic symbiosis between PCa cells and the tumor milieu and how this type of crosstalk may aid in the development of PCa is portrayed in this work. This review focuses on in-depth analysis and evaluation of the metabolic changes that occur within PCa, and also aims to assess the effect of metabolic abnormalities on the aggressiveness status and metabolism of PCa.
PMUTs Arrays for Structural Health Monitoring of Bolted-Joints
Authors: Abdalla Omer M. O. , Massimino Gianluca , Quaglia Fabio , Passoni Marco , Corigliano Alberto
Published: January 2023

Micro-electro-mechanical systems (MEMS) have enabled new techniques for the miniaturization of sensors suitable for Structural Health Monitoring (SHM) applications. In this study, MEMS-based sensors, specifically Piezoelectric Micromachined Ultrasonic Transducers (PMUT), are used to evaluate and monitor the pre-tensioning of a bolted joint structural system. For bolted joints to function properly, it is essential to maintain a suitable level of pre-tensioning. In this work, an array of PMUTs attached to the head and to the end of a bolt, serve as transmitter and receiver, respectively, in a pitch-catch Ultrasonic Testing (UT) scenario. The primary objective is to detect the Change in Time of Flight (CTOF) of the acoustic wave generated by the PMUT array and propagating along the bolt’s axis between a non-loaded bolt and a bolt in service. To model the pre-tensioning of bolted joints and the transmission of the acoustic wave to and from a group of PMUTs through the bolt, a set of numerical models is created. The CTOF is found to be linearly related to the amount of pre-tensioning. The numerical model is validated through comparisons with the results of a preliminary experimental campaign.
Comparing the Uptake of Arsenic by Barley and Oats Growing in a Semiarid Area Irrigated with Either Groundwater or Treated Wastewater
Authors: Ochoa-Rivero Jesus M. , Gutiérrez Mélida , Álvarez-Holguín Alan , Rubio-Arias Héctor O. , Rocha-Gutiérrez Beatriz A. , Ponce-García Omar C.
Published: January 2023

Groundwater and domestic wastewater are often used in conjunction with surface water to irrigate crops in semiarid areas. A concern associated with this practice is the potential accumulation of arsenic (As) and heavy metals in soil and plants, especially in places where irrigation water contains geogenic As. Studies on arsenic uptake in cereal crops growing under dry and oxidizing conditions are scarce. A one-year field experiment was conducted to evaluate the uptake and translocation of As in barley and oats irrigated with either groundwater (GW) or treated domestic wastewater (TWW) in northern Mexico. The content of As, as well as toxic metals Cd and Pb, were determined in soil and 24 sets each of barley and oat plants. Metal(loid)s accumulated more in the roots and leaves, and less in the stems and grains. Barley grains contained 0.2 mg/kg of As under GW or TWW, whereas oat grains contained twice this amount. Bioconcentration (BCF) and translocation (TF) factors were < 1 for As and Cd in plants irrigated with both GW and TWW indicating that neither barley nor oats are As-accumulators, and their grain and leaves can be safely used for fodder. However, oats irrigated with TWW bioaccumulated Pb in leaves. Conscientious monitoring of As and associated metals in soil and crops irrigated with TWW and GW is recommended.
Extraction Optimization, Antioxidant, Cosmeceutical and Wound Healing Potential of Echinacea purpurea Glycerolic Extracts
Authors: Ciganović Petar , Jakupović Lejsa , Momchev Plamen , Nižić Nodilo Laura , Hafner Anita , Zovko Končić Marijana
Published: January 2023

Echinacea purpurea is a plant with immunomodulating properties, often used in topical preparations for treatment of small superficial wounds. In the presented study, the best conditions for ultrasound-assisted extraction of caffeic acid derivatives (caftaric and cichoric acid) (TPA-opt extract), as well as the conditions best suited for preparation of the extract with high radical scavenging activity (RSA-opt extract), from E. purpurea aerial parts were determined. A Box–Behnken design based on glycerol content (%, w/w), temperature (°C), ultrasonication power (W) and time (min) as independent variables was performed. Antioxidant, antiaging and wound healing effects of the two prepared extracts were evaluated. The results demonstrate that glycerol extraction is a fast and efficient method for preparation of the extracts with excellent radical scavenging, Fe2+ chelating and antioxidant abilities. Furthermore, the extracts demonstrated notable collagenase, elastase and tyrosinase inhibitory activity, indicating their antiaging properties. Well-pronounced hyaluronidase-inhibitory activities, with IC50 values lower than 30 μL extract/mL, as well as the ability to promote scratch closure in HaCaT keratinocyte monolayers, even in concentrations as low as 2.5 μL extract/mL (for RSA-opt), demonstrate promising wound healing effects of E. purpurea. The fact that the investigated extracts were prepared using glycerol, a non-toxic and environmentally friendly solvent, widely used in cosmetics, makes them suitable for direct use in specialized cosmeceutical formulations.