bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammation Causes Exacerbation of COVID-19: How about Skin Inflammation?
Authors: Komine Mayumi , Ansary Tuba Mussarat , Hossain Md Razib , Kamiya Koji , Ohtsuki Mamitaro
Published: October 2022

COVID-19 is a recently emerged viral infection worldwide. SARS-CoV-2, the causative virus, is believed to have emerged from bat coronaviruses, probably through host conversion. The bat coronavirus which has the highest gene homology to SARS-CoV-2 specifically infects deep forest bats in China whose habitat extends through the Middle East to Southern Europe. Host conversion might have occurred due to the deforestation by humans exposing wild bats to the environment they had never encountered before. SARS-CoV-2 infects cells through two mechanisms: through its receptor ACE2 with the help of enzyme TMPRSS and through membrane fusion with the help of elastases in the inflammatory condition. Obesity, hypertension, diabetes mellitus, and pulmonary diseases cause poor prognosis of COVID-19. Aging is another factor promoting poor prognosis. These diseases and aging cause low-level and persistent inflammation in humans, which can promote poor prognosis of COVID-19. Psoriasis and atopic dermatitis are the major inflammatory skin diseases. These inflammatory skin conditions, however, do not seem to cause poor prognosis for COVID-19 based on the epidemiological data accumulated so far. These mechanisms need to be elucidated.
Radiovaccination Strategy for Cancer Treatment Integrating Photodynamic Therapy-Generated Vaccines with Radiotherapy
Authors: Korbelik Mladen
Published: October 2022

Therapeutic cancer vaccines have become firmly established as a reliable and proficient form of tumor immunotherapy. They represent a promising approach for substantial advancements in the successful treatment of malignant diseases. One attractive vaccine strategy is using, as the vaccine material, the whole tumor cells treated ex vivo by rapid tumor ablation therapies that instigate stress signaling responses culminating in immunogenic cell death (ICD). One such treatment is photodynamic therapy (PDT). The underlying mechanisms and critical elements responsible for the potency of these vaccines are discussed in this review. Radiotherapy has emerged as a suitable component for the combined therapy protocols with the vaccines. Arguments and prospects for optimizing tumor control using a radiovaccination strategy involving X-ray irradiation plus PDT vaccines are presented, together with the findings supporting its validity.
Chalcone-Acridine Hybrid Suppresses Melanoma Cell Progression via G2/M Cell Cycle Arrest, DNA Damage, Apoptosis, and Modulation of MAP Kinases Activity
Authors: Gazdova Maria , Michalkova Radka , Kello Martin , Vilkova Maria , Kudlickova Zuzana , Baloghova Janette , Mirossay Ladislav , Mojzis Jan
Published: October 2022

This study was focused on investigating the antiproliferative effects of chalcone hybrids in melanoma cancer cells. Among seven chalcone hybrids, the chalcone-acridine hybrid 1C was the most potent and was selected for further antiproliferative mechanism studies. This in vitro study revealed the potent antiproliferative effect of 1C via cell cycle arrest and apoptosis induction. Cell cycle arrest at the G2/M phase was associated with modulation of expression or phosphorylation of specific cell cycle-associated proteins (cyclin B1, p21, and ChK1), tubulins, as well as with the activation of the DNA damage response pathway. Chalcone 1C also induced apoptosis accompanied by mitochondrial dysfunction evidenced by a decrease in mitochondrial membrane potential, increase in Bax/Bcl-xL ratio and cytochrome c release followed by caspase 3/7 activation. In addition, increased phosphorylation of MAP kinases (Erk1/2, p38 and JNK) was observed in chalcone 1C-treated melanoma cells. The strong antiproliferative activities of this chalcone-acridine hybrid suggest that it may be useful as an antimelanoma agent in humans.
Chitosan versus Carboxymethyl Chitosan Cryogels: Bacterial Colonization, Human Embryonic Kidney 293T Cell Culturing and Co-Culturing
Authors: Boroda Andrey , Privar Yuliya , Maiorova Mariya , Beleneva Irina , Eliseikina Marina , Skatova Anna , Marinin Dmitry , Bratskaya Svetlana
Published: October 2022

The potential of chitosan and carboxymethyl chitosan (CMC) cryogels cross-linked with diglycidyl ether of 1,4-butandiol (BDDGE) and poly(ethylene glycol) (PEGDGE) have been compared in terms of 3D culturing HEK-293T cell line and preventing the bacterial colonization of the scaffolds. The first attempts to apply cryogels for the 3D co-culturing of bacteria and human cells have been undertaken toward the development of new models of host–pathogen interactions and bioimplant-associated infections. Using a combination of scanning electron microscopy, confocal laser scanning microscopy, and flow cytometry, we have demonstrated that CMC cryogels provided microenvironment stimulating cell–cell interactions and the growth of tightly packed multicellular spheroids, while cell–substrate interactions dominated in both chitosan cryogels, despite a significant difference in swelling capacities and Young’s modulus of BDDGE- and PEGDGE-cross-linked scaffolds. Chitosan cryogels demonstrated only mild antimicrobial properties against Pseudomonas fluorescence, and could not prevent the formation of Staphylococcus aureus biofilm in DMEM media. CMC cryogels were more efficient in preventing the adhesion and colonization of both P. fluorescence and S. aureus on the surface, demonstrating antifouling properties rather than the ability to kill bacteria. The application of CMC cryogels to 3D co-culture HEK-293T spheroids with P. fluorescence revealed a higher resistance of human cells to bacterial toxins than in the 2D co-culture.
Comprehensive In Silico Functional Prediction Analysis of CDKL5 by Single Amino Acid Substitution in the Catalytic Domain
Authors: Yoshimura Yuri , Morii Atsushi , Fujino Yuuki , Nagase Marina , Kitano Arisa , Ueno Shiho , Takeuchi Kyoka , Yamashita Riko , Inazu Tetsuya
Published: October 2022

Cyclin-dependent kinase-like 5 (CDKL5) is a serine/threonine protein kinase whose pathological mutations cause CDKL5 deficiency disorder. Most missense mutations are concentrated in the catalytic domain. Therefore, anticipating whether mutations in this region affect CDKL5 function is informative for clinical diagnosis. This study comprehensively predicted the pathogenicity of all 5700 missense substitutions in the catalytic domain of CDKL5 using in silico analysis and evaluating their accuracy. Each missense substitution was evaluated as “pathogenic” or “benign”. In silico tools PolyPhen-2 HumDiv mode/HumVar mode, PROVEAN, and SIFT were selected individually or in combination with one another to determine their performance using 36 previously reported mutations as a reference. Substitutions predicted as pathogenic were over 88.0% accurate using each of the three tools. The best performance score (accuracy, 97.2%; sensitivity, 100%; specificity, 66.7%; and Matthew’s correlation coefficient (MCC), 0.804) was achieved by combining PolyPhen-2 HumDiv, PolyPhen-2 HumVar, and PROVEAN. This provided comprehensive information that could accurately predict the pathogenicity of the disease, which might be used as an aid for clinical diagnosis.
Tolerability of Oral Supplementation with Microencapsulated Ferric Saccharate Compared to Ferrous Sulphate in Healthy Premenopausal Woman: A Crossover, Randomized, Double-Blind Clinical Trial
Authors: Friling Marina , García-Muñoz Ana María , Perrinjaquet-Moccetti Tania , Victoria-Montesinos Desirée , Pérez-Piñero Silvia , Abellán-Ruiz María Salud , Luque-Rubia Antonio J. , García-Guillén Ana Isabel , Cánovas Fernando , Ivanir Eran
Published: October 2022

A single-center, crossover, randomized, double-blind, and controlled clinical study was conducted to assess the tolerability profile, especially with regard to gastrointestinal complaints, of oral supplementation with AB-Fortis®, a microencapsulated ferric saccharate (MFS), as compared with conventional ferrous sulphate (FS) in healthy premenopausal women. A dose of 60 mg/day of elemental iron was used. The test products were administered for 14 consecutive days with a washout period of two menstrual episodes and a minimum of one month between the two intervention periods. The subjects completed simple-to-answer questionnaires daily for 14 days during both the intervention and the washout periods, capturing the symptoms associated with oral iron supplementation and overall health aspects. Following product consumption, the incidences of symptoms, numbers of complaints/symptoms, overall intensity, and total days with symptoms were found to be significantly higher for FS consumption as compared to MFS. The better tolerability profile of MFS over FS was further substantiated when both products were compared to a real-life setting (i.e., the washout period). Overall, the administration of both study products was safe with no serious or significant adverse events reported. In summary, the current study shows the better tolerability of the MFS preparation when compared to that of the FS, presenting MFS as a well-tolerated and safe option for improving iron nutrition.
Magneto-Fluorescent Mesoporous Nanocarriers for the Dual-Delivery of Ofloxacin and Doxorubicin to Tackle Opportunistic Bacterial Infections in Colorectal Cancer
Authors: Marcelo Gonçalo A. , Galhano Joana , Robalo Tiago T. , Cruz Maria Margarida , Marcos María D. , Martínez-Máñez Ramón , Duarte Maria Paula , Capelo-Martínez José Luis , Lodeiro Carlos , Oliveira Elisabete
Published: October 2022

Cancer-related opportunistic bacterial infections are one major barrier for successful clinical therapies, often correlated to the production of genotoxic factors and higher cancer incidence. Although dual anticancer and antimicrobial therapies are a growing therapeutic fashion, they still fall short when it comes to specific delivery and local action in in vivo systems. Nanoparticles are seen as potential therapeutic vectors, be it by means of their intrinsic antibacterial properties and effective delivery capacity, or by means of their repeatedly reported modulation and maneuverability. Herein we report on the production of a biocompatible, antimicrobial magneto-fluorescent nanosystem (NANO3) for the delivery of a dual doxorubicin–ofloxacin formulation against cancer-related bacterial infections. The drug delivery capacity, rendered by its mesoporous silica matrix, is confirmed by the high loading capacity and stimuli-driven release of both drugs, with preference for tumor-like acidic media. The pH-dependent emission of its surface fluorescent SiQDs, provides an insight into NANO3 surface behavior and pore availability, with the SiQDs working as pore gates. Hyperthermia induces heat generation to febrile temperatures, doubling drug release. NANO3-loaded systems demonstrate significant antimicrobial activity, specifically after the application of hyperthermia conditions. NANO3 structure and antimicrobial properties confirm their potential use in a future dual anticancer and antimicrobial therapeutical vector, due to their drug loading capacity and their surface availability for further modification with bioactive, targeting species.
The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment
Authors: Varesi Angelica , Campagnoli Lucrezia Irene Maria , Fahmideh Foroogh , Pierella Elisa , Romeo Marcello , Ricevuti Giovanni , Nicoletta Marchesi , Chirumbolo Salvatore , Pascale Alessia
Published: October 2022

The bidirectional interaction between the gut microbiota (GM) and the Central Nervous System, the so-called gut microbiota brain axis (GMBA), deeply affects brain function and has an important impact on the development of neurodegenerative diseases. In Parkinson’s disease (PD), gastrointestinal symptoms often precede the onset of motor and non-motor manifestations, and alterations in the GM composition accompany disease pathogenesis. Several studies have been conducted to unravel the role of dysbiosis and intestinal permeability in PD onset and progression, but the therapeutic and diagnostic applications of GM modifying approaches remain to be fully elucidated. After a brief introduction on the involvement of GMBA in the disease, we present evidence for GM alterations and leaky gut in PD patients. According to these data, we then review the potential of GM-based signatures to serve as disease biomarkers and we highlight the emerging role of probiotics, prebiotics, antibiotics, dietary interventions, and fecal microbiota transplantation as supportive therapeutic approaches in PD. Finally, we analyze the mutual influence between commonly prescribed PD medications and gut-microbiota, and we offer insights on the involvement also of nasal and oral microbiota in PD pathology, thus providing a comprehensive and up-to-date overview on the role of microbial features in disease diagnosis and treatment.
Flow-Seq Evaluation of Translation Driven by a Set of Natural Escherichia coli 5′-UTR of Variable Length
Authors: Komarova Ekaterina S. , Slesarchuk Anna N. , Rubtsova Maria P. , Osterman Ilya A. , Tupikin Alexey E. , Pyshnyi Dmitry V. , Dontsova Olga A. , Kabilov Marsel R. , Sergiev Petr V.
Published: October 2022

Flow-seq is a method that combines fluorescently activated cell sorting and next-generation sequencing to deduce a large amount of data about translation efficiency from a single experiment. Here, we constructed a library of fluorescent protein-based reporters preceded by a set of 648 natural 5′-untranslated regions (5′-UTRs) of Escherichia coli genes. Usually, Flow-seq libraries are constructed using uniform-length sequence elements, in contrast to natural situations, where functional elements are of heterogenous lengths. Here, we demonstrated that a 5′-UTR library of variable length could be created and analyzed with Flow-seq. In line with previous Flow-seq experiments with randomized 5′-UTRs, we observed the influence of an RNA secondary structure and Shine–Dalgarno sequences on translation efficiency; however, the variability of these parameters for natural 5′-UTRs in our library was smaller in comparison with randomized libraries. In line with this, we only observed a 30-fold difference in translation efficiency between the best and worst bins sorted with this factor. The results correlated with those obtained with ribosome profiling.
Rad17 Translocates to Nucleolus upon UV Irradiation through Nucleolar Localization Signal in the Central Basic Domain
Authors: Fukumoto Yasunori , Ikeuchi Masayoshi , Nakayama Yuji , Ogra Yasumitsu
Published: October 2022

The nucleolus is a non-membranous structure in the nucleus and forms around ribosomal DNA repeats. It plays a major role in ribosomal biogenesis through the transcription of ribosomal DNA and regulates mRNA translation in response to cellular stress including DNA damage. Rad17 is one of the proteins that initiate and maintain the activation of the ATR pathway, one of the major DNA damage checkpoints. We have recently reported that the central basic domain of Rad17 contains a nuclear localization signal and that the nuclear translocation of Rad17 promotes its proteasomal degradation. Here, we show that the central basic domain contains the nucleolar localization signal as well as the nuclear localization signal. The nucleolar localization signal overlaps with the nuclear localization signal and is capable of transporting an exogenous protein into the nucleolus. Phosphomimetic mutations of the central basic domain inhibit nucleolar accumulation, suggesting that the post-translational modification sites regulate the nucleolar localization. Nucleolar accumulation of Rad17 is promoted by proteasome inhibition and UV irradiation. Our data show the nucleolar localization of Rad17 and suggest a possible role of Rad17 in the nucleolus upon UV irradiation.
Hypertension Related to Obesity: Pathogenesis, Characteristics and Factors for Control
Authors: El Meouchy Paul , Wahoud Mohamad , Allam Sabine , Chedid Roy , Karam Wissam , Karam Sabine
Published: October 2022

The World Health Organization (WHO) refers to obesity as abnormal or excessive fat accumulation that presents a health risk. Obesity was first designated as a disease in 2012 and since then the cost and the burden of the disease have witnessed a worrisome increase. Obesity and hypertension are closely interrelated as abdominal obesity interferes with the endocrine and immune systems and carries a greater risk for insulin resistance, diabetes, hypertension, and cardiovascular disease. Many factors are at the interplay between obesity and hypertension. They include hemodynamic alterations, oxidative stress, renal injury, hyperinsulinemia, and insulin resistance, sleep apnea syndrome and the leptin-melanocortin pathway. Genetics, epigenetics, and mitochondrial factors also play a major role. The measurement of blood pressure in obese patients requires an adapted cuff and the search for other secondary causes is necessary at higher thresholds than the general population. Lifestyle modifications such as diet and exercise are often not enough to control obesity, and so far, bariatric surgery constitutes the most reliable method to achieve weight loss. Nonetheless, the emergence of new agents such as Semaglutide and Tirzepatide offers promising alternatives. Finally, several molecular pathways are actively being explored, and they should significantly extend the treatment options available.
Binding of Glycerol to Human Galectin-7 Expands Stability and Modulates Its Functions
Authors: Liang Yebing , Wang Yuxiang , Zhu Xingyu , Cai Jun , Shi Anqi , Huang Jing , Zhu Qiuju , Si Yunlong
Published: October 2022

Glycerol is seen in biological systems as an intermediate in lipid metabolism. In recent years, glycerol has been reported to act as a chemical chaperone to correct the conformation of proteins. Here, we investigate the role of glycerol in galectin-7 (Gal-7). The thermal shift and CD assays showed that the thermal stability of Gal-7 increased with glycerol concentration but with little secondary structure changes induced by glycerol. In addition, glycerol can inhibit Gal-7-mediated erythrocyte agglutination. We also solved the crystal structures of human Gal-7 in complex with glycerol in two different conditions. Glycerol binds at the carbohydrate-recognition binding sites of Gal-7, which indicates glycerol as a small ligand for Gal-7. Surprisingly, glycerol can bind a new pocket near the N-terminus of Gal-7, which can greatly reduce the flexibility and improve the stability of this region. Moreover, overexpression of Gal-7 decreased the intracellular triglyceride levels and increased mRNA expression of aquaporin-3 (AQP-3) when HeLa cells were incubated with glycerol. These findings indicate that Gal-7 might regulate glycerol metabolism. Overall, our results on human Gal-7 raise the perspective to systematically explore this so far unrecognized phenomenon for Gal-7 in glycerol metabolism.
Tissue Engineering in Gynecology
Authors: Brownell David , Chabaud Stéphane , Bolduc Stéphane
Published: October 2022

Female gynecological organ dysfunction can cause infertility and psychological distress, decreasing the quality of life of affected women. Incidence is constantly increasing due to growing rates of cancer and increase of childbearing age in the developed world. Current treatments are often unable to restore organ function, and occasionally are the cause of female infertility. Alternative treatment options are currently being developed in order to face the inadequacy of current practices. In this review, pathologies and current treatments of gynecological organs (ovaries, uterus, and vagina) are described. State-of-the-art of tissue engineering alternatives to common practices are evaluated with a focus on in vivo models. Tissue engineering is an ever-expanding field, integrating various domains of modern science to create sophisticated tissue substitutes in the hope of repairing or replacing dysfunctional organs using autologous cells. Its application to gynecology has the potential of restoring female fertility and sexual wellbeing.
PRMT7 Inhibitor SGC8158 Enhances Doxorubicin-Induced DNA Damage and Its Cytotoxicity
Authors: Jeong Ahyeon , Cho Yena , Cho Minkyeong , Bae Gyu-Un , Song Dae-Geun , Kim Su-Nam , Kim Yong Kee
Published: October 2022

Protein arginine methyltransferase 7 (PRMT7) regulates various cellular responses, including gene expression, cell migration, stress responses, and stemness. In this study, we investigated the biological role of PRMT7 in cell cycle progression and DNA damage response (DDR) by inhibiting PRMT7 activity with either SGC8158 treatment or its specific siRNA transfection. Suppression of PRMT7 caused cell cycle arrest at the G1 phase, resulting from the stabilization and subsequent accumulation of p21 protein. In addition, PRMT7 activity is closely associated with DNA repair pathways, including both homologous recombination and non-homologous end-joining. Interestingly, SGC8158, in combination with doxorubicin, led to a synergistic increase in both DNA damage and cytotoxicity in MCF7 cells. Taken together, our data demonstrate that PRMT7 is a critical modulator of cell growth and DDR, indicating that it is a promising target for cancer treatment.
Candesartan Does Not Activate PPARγ and Its Target Genes in Early Gestation Trophoblasts
Authors: Neuper Lena , Kummer Daniel , Forstner Désirée , Guettler Jacqueline , Ghaffari-Tabrizi-Wizsy Nassim , Fischer Cornelius , Juch Herbert , Nonn Olivia , Gauster Martin
Published: October 2022

Angiotensin II receptor 1 blockers are commonly used to treat hypertension in women of childbearing age. While the fetotoxic effects of these drugs in the second and third trimesters of pregnancy are well documented, their possible impacts on placenta development in early gestation are unknown. Candesartan, a member of this group, also acts as a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, a key regulator shown to be important for placental development. We have previously shown that trophoblasts do not express the candesartan target–receptor angiotensin II type 1 receptor AGTR1. This study investigated the possible role of candesartan on trophoblastic PPARγ and its hallmark target genes in early gestation. Candesartan did not affect the PPARγ protein expression or nuclear translocation of PPARγ. To mimic extravillous trophoblasts (EVTs) and cytotrophoblast/syncytiotrophoblast (CTB/SCT) responses to candesartan, we used trophoblast cell models BeWo (for CTB/SCT) and SGHPL-4 (EVT) cells as well as placental explants. In vitro, the RT-qPCR analysis showed no effect of candesartan treatment on PPARγ target genes in BeWo or SGHPL-4 cells. Treatment with positive control rosiglitazone, another PPARγ agonist, led to decreased expressions of LEP and PPARG1 in BeWo cells and an increased expression of PPARG1 in SGHPL-4 cells. Our previous data showed early gestation–placental AGTR1 expression in fetal myofibroblasts only. In a CAM assay, AGTR1 was stimulated with angiotensin II and showed increased on-plant vessel outgrowth. These results suggest candesartan does not negatively affect PPARγ or its target genes in human trophoblasts. More likely, candesartan from maternal serum may first act on fetal-placental AGTR1 and influence angiogenesis in the placenta, warranting further research.
Polytopal Rearrangement Governing Stereochemistry of Bicyclic Oxime Ether Synthesis
Authors: Spahić Zlatan , Hrenar Tomica , Primožič Ines
Published: October 2022

In the present study, four O-substituted oximes of quinuclidin-3-one were synthesized using appropriate O-substituted hydroxylamine hydrochlorides. In order to perform these reactions in a solvent, a mixture of (E) and (Z) products was yielded. Using mechanochemical and microwave synthesis, we then obtained pure (E) oximes. In almost all cases, the conversion to oxime ethers was completed. Reactions were monitored by ATR spectroscopy and the ratios of (E) and (Z) oxime ethers were deduced from 1H NMR data. Several reactions were very rapid (1 min) with 100% conversion and stereospecificity. To investigate the reaction mechanisms, full conformational analyses of the reaction intermediates were performed and the lowest energy conformers were determined. These conformers differed in spatial arrangement around the nitrogen atom of the amino group and were in the correct orientation for reactions to occur. Calculated standard Gibbs energies of the formation were in agreement with the experimentally obtained ratios of (E) and (Z) isomers. This work shows alternatives to the classical synthesis of O-substituted oxime ether precursors and highlights the fast reaction rate and stereoselectivity of microwave synthesis as well as the “green” aspects of mechanochemistry.
Anion-Exchange Chromatography at the Service of Gene Therapy: Baseline Separation of Full/Empty Adeno-Associated Virus Capsids by Screening of Conditions and Step Gradient Elution Mode
Authors: Aebischer Megane , Gizardin-Fredon Hugo , Lardeux Honorine , Kochardt Dominik , Elger Carsten , Haindl Markus , Ruppert Raphael , Guillarme Davy , D’Atri Valentina
Published: October 2022

Gene therapy is opening unprecedented opportunities for novel therapeutic approaches. Based on the concept of rescuing function mutations by co-expressing the correct gene to allow biological functions to be restored, it requires the use of viral vectors to ensure the proper delivery of therapeutic genes. In this context, recombinant adeno-associated viruses (rAAV) are the most widely used vectors. Their biomanufacturing process requires the insertion of the therapeutic gene into the rAAV (full capsids). However, a percentage of rAAV that do not contain the desired gene (empty capsids), as well as partly filled capsids, might also be produced, potentially impacting the efficiency of the therapy. Therefore, the determination of the rAAV capsids’ full/empty ratio needs to be monitored to ensure consistent product quality and efficacy. Anion-exchange chromatography (AEX) can serve this need. In this contribution, thorough AEX method development, including a mobile phase, a stationary phase and gradient conditions, has highlighted its potential in supporting gene therapy. Taking advantage of the fact that viral capsids follow an “on/off” retention behavior, the application of a step gradient approach to the rAAV serotype 8 (rAAV8) allowed the unprecedented separation of rAAV8 full/empty capsids, with a resolution gain of 3.7 as compared to the resolution obtained with a fully optimized linear gradient. Finally, the developed analytical approach allowed a precise and accurate baseline separation and quantification of full and empty rAAV8 capsids, with the potential to be applied as a high-throughput quality control (QC) method.
Role of Macrophages in Air Pollution Exposure Related Asthma
Authors: Li Chung-Hsiang , Tsai Mei-Lan , Chiou Hsin-Ying (Clair) , Lin Yi-Ching , Liao Wei-Ting , Hung Chih-Hsing
Published: October 2022

Asthma is a chronic inflammatory airway disease characterized by variable airflow obstruction, bronchial hyper-responsiveness, and airway inflammation. The chronic inflammation of the airway is mediated by many cell types, cytokines, chemokines, and inflammatory mediators. Research suggests that exposure to air pollution has a negative impact on asthma outcomes in adult and pediatric populations. Air pollution is one of the greatest environmental risks to health, and it impacts the lungs’ innate and adaptive defense systems. A major pollutant in the air is particulate matter (PM), a complex component composed of elemental carbon and heavy metals. According to the WHO, 99% of people live in air pollution where air quality levels are lower than the WHO air quality guidelines. This suggests that the effect of air pollution exposure on asthma is a crucial health issue worldwide. Macrophages are essential in recognizing and processing any inhaled foreign material, such as PM. Alveolar macrophages are one of the predominant cell types that process and remove inhaled PM by secreting proinflammatory mediators from the lung. This review focuses on macrophages and their role in orchestrating the inflammatory responses induced by exposure to air pollutants in asthma.
Drp1 Overexpression Decreases Insulin Content in Pancreatic MIN6 Cells
Authors: Kabra Uma D. , Moruzzi Noah , Berggren Per-Olof , Jastroch Martin
Published: October 2022

Mitochondrial dynamics and bioenergetics are central to glucose-stimulated insulin secretion by pancreatic beta cells. Previously, we demonstrated that a disturbance in glucose-invoked fission impairs insulin secretion by compromising glucose catabolism. Here, we investigated whether the overexpression of mitochondrial fission regulator Drp1 in MIN6 cells can improve or rescue insulin secretion. Although Drp1 overexpression slightly improves the triggering mechanism of insulin secretion of the Drp1-knockdown cells and has no adverse effects on mitochondrial metabolism in wildtype MIN6 cells, the constitutive presence of Drp1 unexpectedly impairs insulin content, which leads to a reduction in the absolute values of secreted insulin. Coherent with previous studies in Drp1-overexpressing muscle cells, we found that the upregulation of ER stress-related genes (BiP, Chop, and Hsp60) possibly impacts insulin production in MIN6 cells. Collectively, we confirm the important role of Drp1 for the energy-coupling of insulin secretion but unravel off-targets effects by Drp1 overexpression on insulin content that warrant caution when manipulating Drp1 in disease therapy.
Integrin Alpha v Beta 6 (αvβ6) and Its Implications in Cancer Treatment
Authors: Brzozowska Ewa , Deshmukh Sameer
Published: October 2022

Integrins are necessary for cell adhesion, migration, and positioning. Essential for inducing signalling events for cell survival, proliferation, and differentiation, they also trigger a variety of signal transduction pathways involved in mediating invasion, metastasis, and squamous-cell carcinoma. Several recent studies have demonstrated that the up- and down-regulation of the expression of αv and other integrins can be a potent marker of malignant diseases and patient prognosis. This review focuses on an arginine-glycine-aspartic acid (RGD)-dependent integrin αVβ6, its biology, and its role in healthy humans. We examine the implications of αVβ6 in cancer progression and the promotion of epithelial-mesenchymal transition (EMT) by contributing to the activation of transforming growth factor beta TGF-β. Although αvβ6 is crucial for proper function in healthy people, it has also been validated as a target for cancer treatment. This review briefly considers aspects of targeting αVβ6 in the clinic via different therapeutic modalities.
TiO2 Nanoparticles and Their Effects on Eukaryotic Cells: A Double-Edged Sword
Authors: Gojznikar Jan , Zdravković Bogdan , Vidak Marko , Leskošek Brane , Ferk Polonca
Published: October 2022

Nanoparticulate TiO2 (TiO2 NPs) is a widely used material, whose potential toxicity towards eukaryotic cells has been addressed by multiple studies. TiO2 NPs are considered toxic due to their production of reactive oxygen species (ROS), which can, among others, lead to cellular damage, inflammatory responses, and differences in gene expression. TiO2 NPs exhibited toxicity in multiple organs in animals, generating potential health risks also in humans, such as developing tumors or progress of preexisting cancer processes. On the other hand, the capability of TiO2 NPs to induce cell death has found application in photodynamic therapy of cancers. In aquatic environments, much has been done in understanding the impact of TiO2 on bivalves, in which an effect on hemocytes, among others, is reported. Adversities are also reported from other aquatic organisms, including primary producers. These are affected also on land and though some potential benefit might exist when it comes to agricultural plants, TiO2 can also lead to cellular damage and should be considered when it comes to transfer along the food chain towards human consumers. In general, much work still needs to be done to unravel the delicate balance between beneficial and detrimental effects of TiO2 NPs on eukaryotic cells.
Modulating p-AMPK/mTOR Pathway of Mitochondrial Dysfunction Caused by MTERF1 Abnormal Expression in Colorectal Cancer Cells
Authors: Liu Qianqian , Zhang Longlong , Zou Yayan , Tao Ying , Wang Bing , Li Bin , Liu Ruai , Wang Boyong , Ding Lei , Cui Qinghua , Lin Jie , Mao Bingyu , Xiong Wei , Yu Min
Published: October 2022

Human mitochondrial transcription termination factor 1 (MTERF1) has been demonstrated to play an important role in mitochondrial gene expression regulation. However, the molecular mechanism of MTERF1 in colorectal cancer (CRC) remains largely unknown. Here, we found that MTERF1 expression was significantly increased in colon cancer tissues compared with normal colorectal tissue by Western blotting, immunohistochemistry, and tissue microarrays (TMA). Overexpression of MTERF1 in the HT29 cell promoted cell proliferation, migration, invasion, and xenograft tumor formation, whereas knockdown of MTERF1 in HCT116 cells appeared to be the opposite phenotype to HT29 cells. Furthermore, MTERF1 can increase mitochondrial DNA (mtDNA) replication, transcription, and protein synthesis in colorectal cancer cells; increase ATP levels, the mitochondrial crista density, mitochondrial membrane potential, and oxygen consumption rate (OCR); and reduce the ROS production in colorectal cancer cells, thereby enhancing mitochondrial oxidative phosphorylation (OXPHOS) activity. Mechanistically, we revealed that MTERF1 regulates the AMPK/mTOR signaling pathway in cancerous cell lines, and we also confirmed the involvement of the AMPK/mTOR signaling pathway in both xenograft tumor tissues and colorectal cancer tissues. In summary, our data reveal an oncogenic role of MTERF1 in CRC progression, indicating that MTERF1 may represent a new therapeutic target in the future.
Phosphorylated Proteins from Serum: A Promising Potential Diagnostic Biomarker of Cancer
Authors: Ghosh Rishila , Ahmed Rakin , Ahmed Hafiz , Chatterjee Bishnu P.
Published: October 2022

Cancer is a fatal disease worldwide. Each year ten million people are diagnosed around the world, and more than half of patients eventually die from it in many countries. A majority of cancer remains asymptomatic in the earlier stages, with specific symptoms appearing in the advanced stages when the chances of adequate treatment are low. Cancer screening is generally executed by different imaging techniques like ultrasonography (USG), mammography, CT-scan, and magnetic resonance imaging (MRI). Imaging techniques, however, fail to distinguish between cancerous and non-cancerous cells for early diagnosis. To confirm the imaging result, solid and liquid biopsies are done which have certain limitations such as invasive (in case of solid biopsy) or missed early diagnosis due to extremely low concentrations of circulating tumor DNA (in case of liquid biopsy). Therefore, it is essential to detect certain biomarkers by a noninvasive approach. One approach is a proteomic or glycoproteomic study which mostly identifies proteins and glycoproteins present in tissues and serum. Some of these studies are approved by the Food and Drug Administration (FDA). Another non-expensive and comparatively easier method to detect glycoprotein biomarkers is by ELISA, which uses lectins of diverse specificities. Several of the FDA approved proteins used as cancer biomarkers do not show optimal sensitivities for precise diagnosis of the diseases. In this regard, expression of phosphoproteins is associated with a more specific stage of a particular disease with high sensitivity and specificity. In this review, we discuss the expression of different serum phosphoproteins in various cancers. These phosphoproteins are detected either by phosphoprotein enrichment by immunoprecipitation using phosphospecific antibody and metal oxide affinity chromatography followed by LC-MS/MS or by 2D gel electrophoresis followed by MALDI-ToF/MS analysis. The updated knowledge on phosphorylated proteins in clinical samples from various cancer patients would help to develop these serum phophoproteins as potential diagnostic/prognostic biomarkers of cancer.
Ella versus Simoa Serum Neurofilament Assessment to Monitor Treatment Response in Highly Active Multiple Sclerosis Patients
Authors: Nötzel Martin , Werder Luise Ina , Ziemssen Tjalf , Akgün Katja
Published: October 2022

The measurement of serum neurofilament light chain (sNfL) is of growing importance in the field of neurology. In the management of multiple sclerosis, it can serve as a useful marker to assess disease activity and treatment response. This paper compares two available methods, namely the Single Molecule Array (Simoa) and the Ella microfluid platform, to measure longitudinal sNfL levels of 42 highly active multiple sclerosis patients treated with alemtuzumab over a period of 36 months. In order to assess the methods agreement, Bland–Altman plots and Passing–Bablok regression were analyzed. Here, we show that despite the fact that Ella measures around 24% higher values than Simoa, both are equally suitable for longitudinal sNfL monitoring.
SARS-CoV-2 Spike Protein (RBD) Subunit Adsorption at Abiotic Surfaces and Corona Formation at Polymer Particles
Authors: Żeliszewska Paulina , Wasilewska Monika , Batys Piotr , Pogoda Katarzyna , Deptuła Piotr , Bucki Robert , Adamczyk Zbigniew
Published: October 2022

The adsorption kinetics of the SARS-CoV-2 spike protein subunit with the receptor binding domain at abiotic surfaces was investigated. A combination of sensitive methods was used such as atomic force microscopy yielding a molecular resolution, a quartz microbalance, and optical waveguide lightmode spectroscopy. The two latter methods yielded in situ information about the protein adsorption kinetics under flow conditions. It was established that at pH 3.5–4 the protein adsorbed on mica and silica surfaces in the form of compact quasi-spherical aggregates with an average size of 14 nm. The maximum coverage of the layers was equal to 3 and 1 mg m−2 at pH 4 and 7.4, respectively. The experimental data were successfully interpreted in terms of theoretical results derived from modeling. The experiments performed for flat substrates were complemented by investigations of the protein corona formation at polymer particles carried out using in situ laser Doppler velocimetry technique. In this way, the zeta potential of the protein layers was acquired as a function of the coverage. Applying the electrokinetic model, these primary data were converted to the dependence of the subunit zeta potential on pH. It was shown that a complete acid-base characteristic of the layer can be acquired only using nanomolar quantities of the protein.
Reciprocal Alterations in Osteoprogenitor and Immune Cell Populations in Rheumatoid Synovia
Authors: Barbarić Starčević Katarina , Lukač Nina , Jelić Mislav , Šućur Alan , Grčević Danka , Kovačić Nataša
Published: October 2022

Rheumatoid arthritis (RA) is chronic, autoimmune joint inflammation characterized by irreversible joint destruction. Besides increased resorption, destruction is a result of decreased bone formation, due to suppressed differentiation and function of the mesenchymal lineage-derived osteoblasts in inflammatory milieu. In this study, we analyzed the cellular composition of synovial tissue from 11 RA and 10 control patients harvested during planned surgeries in order to characterize resident synovial progenitor populations. Synovial cells were released by collagenase, and labeled for flow cytometry by two antibody panels: 1. CD3-FITC, CD14-PE, 7-AAD, CD11b-PECy7, CD235a-APC, CD19-APCeF780; and 2. 7-AAD, CD105-PECy7, CD45/CD31/CD235a-APC, and CD200-APCeF780. The proportions of lymphocytes (CD3+, CD19+) and myeloid (CD11b+, CD14+) cells were higher in synovial tissue from the patients with RA than in the controls. Among non-hematopoietic (CD45−CD31−CD235a−) cells, there was a decrease in the proportion of CD200+CD105− and increase in the proportion of CD200−CD105+ cells in synovial tissue from the patients with RA in comparison to the control patients. The proportions of both populations were associated with inflammatory activity and could discriminate between the RA and the controls.
Correlation between Sperm Micro Ribonucleic Acid-34b and -34c Levels and Clinical Outcomes of Intracytoplasmic Sperm Injection in Men with Male Factor Infertility
Authors: Yeh Ling-Yu , Lee Robert Kuo-Kuang , Lin Ming-Huei , Huang Chih-Hung , Li Sheng-Hsiang
Published: October 2022

Few studies have examined the correlation between sperm miRNA levels and clinical outcomes of intracytoplasmic sperm injection (ICSI). In this study, we aimed to assess the correlation of sperm miR-34b, miR-34c, miR-122, and miR-429 levels with ICSI outcomes in men with teratozoospermia and asthenozoospermia. TaqMan microRNA quantitative polymerase chain reaction was used to evaluate the relative expression of miRNAs in sperm. The relative miRNA levels quantified using a comparative method found that the four miRNAs were not associated with fertilization rate and early embryo development. However, revels of miR-34b and miR-34c in teratozoospermia sperm of the live birth group were significantly higher than those in the non-live birth group. Receiver operating characteristic curve analysis revealed that the optimal cut-off delta cycle threshold values of miR-34b and miR-34c were 8.630 and 7.883, respectively. Statistical analysis found that the levels of miR-34b and the miR-34c in teratozoospermic and asthenozoospermic sperm above the thresholds were not associated with the fertilization rate and the high-quality embryo rate above 50%; however, they were more likely to exhibit higher implantation, pregnancy, and live birth rates. miR-34b and miR-34c were significantly associated with ICSI clinical outcomes in male factor infertility, especially teratozoospermia. Further validation is required before it becomes a clinically valid reference indicator.
The Perspective of Arbuscular Mycorrhizal Symbiosis in Rice Domestication and Breeding
Authors: Huang Renliang , Li Zheng , Shen Xianhua , Choi Jeongmin , Cao Yangrong
Published: October 2022

In nature, symbiosis with arbuscular mycorrhizal (AM) fungi contributes to sustainable acquisition of phosphorus and other elements in over 80% of plant species; improving interactions with AM symbionts may mitigate some of the environmental problems associated with fertilizer application in grain crops such as rice. Recent developments of high-throughput genome sequencing projects of thousands of rice cultivars and the discovery of the molecular mechanisms underlying AM symbiosis suggest that interactions with AM fungi might have been an overlooked critical trait in rice domestication and breeding. In this review, we discuss genetic variation in the ability of rice to form AM symbioses and how this might have affected rice domestication. Finally, we discuss potential applications of AM symbiosis in rice breeding for more sustainable agriculture.
AMPK Amplifies IL2–STAT5 Signaling to Maintain Stability of Regulatory T Cells in Aged Mice
Authors: Pokhrel Ram Hari , Kang Ben , Timilshina Maheshwor , Chang Jae-Hoon
Published: October 2022

AMP-activated protein kinase (AMPK), an important regulator of the aging process, is expressed in various immune cells. However, its role in regulatory T cell (Treg) stability during aging is poorly understood. Here, we addressed the role of AMPK in Treg function and stability during aging by generating Treg-specific AMPKα1 knockout mice. In this study, we found that AMPKα1-deficient Tregs failed to control inflammation as effectively as normal Tregs did during aging. AMPK knockout from Tregs reduces STAT5 phosphorylation in response to interleukin (IL)-2 stimulation, thereby destabilizing Tregs by decreasing CD25 expression. Thus, our study addressed the role of AMPK in Tregs in sensing IL-2 signaling to amplify STAT5 phosphorylation, which, in turn, supports Treg stability by maintaining CD25 expression and controlling inflamm-aging.
Thermal Insulating Rigid Polyurethane Foams with Bio-Polyol from Rapeseed Oil Modified by Phosphorus Additive and Reactive Flame Retardants
Authors: Zemła Marcin , Prociak Aleksander , Michałowski Sławomir , Cabulis Ugis , Kirpluks Mikelis , Simakovs Kirils
Published: October 2022

In this article, rigid polyurethane foams obtained with the addition of a bio-polyol from rapeseed oil, were modified with the dimethyl propane phosphonate as additive flame retardant and two reactive flame retardants diethyl (hydroxymethyl)phosphonate and diethyl bis-(2-hydroxyethyl)-aminomethylphosphonate. The influence of used flame retardants on the foaming process and characteristic processing times of tested polyurethane systems were determined. The obtained foams were tested in terms of cell structure, physical and mechanical properties, as well as flammability. Modified foams had worse mechanical and thermal insulation properties, caused by lower cellular density and higher anisotropy coefficient in the cross-section parallel to the foam rise direction, compared to unmodified foam. However, the thermal conductivity of all tested foam materials was lower than 25.82 mW/m∙K. The applied modifiers effectively reduced the flammability of rigid polyurethane foams, among others, increasing the oxygen index above 21.4 vol.%, reducing the total heat released by about 41–51% and the rate of heat release by about 2–52%. A correlation between the limiting oxygen index values and both total heat released parameters from the pyrolysis combustion flow calorimetry and cone calorimetry was observed. The correlation was also visible between the value of the heat release capacity (HRC) parameter obtained from the pyrolysis combustion flow calorimetry and the maximum average rate of heat emission (MARHE) from the cone calorimeter test.
Editorial: Special Issue, “Molecular Advances in Skin Diseases”
Authors: Kanda Naoko
Published: October 2022

The pathomechanisms of various skin diseases have recently been elucidated progressively [...]
Thiosemicarbazones and Derived Antimony Complexes: Synthesis, Structural Analysis, and In Vitro Evaluation against Bacterial, Fungal, and Cancer Cells
Authors: Fathy Amany , Ibrahim Ahmed B. M. , Abd Elkhalik S. , Meurer Florian , Bodensteiner Michael , Abbas S. M.
Published: October 2022

Two antimony complexes {[Sb(L1)Cl2] C1 and [Sb(L2)Cl2] C2} with the thiosemicarbazone ligands {HL1 = 4-(2,4-dimethylphenyl)-1-((pyridin-2-yl)methylene)thiosemicarbazide and HL2 = 4-(2,5-dimethoxyphenyl)-1-((pyridin-2-yl)methylene)thiosemicarbazide} were introduced. The structures were elucidated on the basis of a CHNS analysis, spectroscopic techniques (UV-Vis and FT-IR), and DMF solution electrical conductivities. Single crystal X-ray diffraction analysis of complex C1 assigned the complex pseudo-octahedral geometry and triclinic P-1 space group. Only the ligand HL1 and its derived complex C1 displayed antifungal activities against Candida albicans and this activity was enhanced from 10 mm to 21 mm for the respective complex, which is the same activity given by the drug “Amphotericin B”. The ligands HL1 and HL2 gave inhibitions, respectively, of 14 and 10 mm against Staphylococcus aureus and 15 and 10 mm against Escherichia coli; however, complexes C1 and C2 increased these inhibitions to 36 and 32 mm against Staphylococcus aureus and 35 and 31 mm against Escherichia coli exceeding the activities given by the ampicillin standard (i.e., 21 mm against Staphylococcus aureus and 25 mm against Escherichia coli). Against MCF-7 human breast cancer cells, the IC50 values of HL1 (68.9 μM) and HL2 (145.4 μM) were notably enhanced to the values of 34.7 and 37.4 μM for both complexes, respectively. Further, the complexes induced less toxicity in normal BHK cells (HL1 (126.6 μM), HL2 (110.6 μM), C1 (>210.1 μM), and C2 (160.6 μM)). As a comparison, doxorubicin gave an IC50 value of 9.66 μM against MCF-7 cells and 36.42 μM against BHK cells.