bluuebunny/crossref_metadata_2025 huggingface dataset:
Aerobic Exercise Prevents Arterial Stiffness and Attenuates Hyperexcitation of Sympathetic Nerves in Perivascular Adipose Tissue of Mice after Transverse Aortic Constriction
Authors: Shi Niujin , Xia Jingbo , Wang Chaoge , Zhou Jie , Huang Junhao , Hu Min , Liao Jingwen
Published: September 2022

We aimed to investigate the efficacy of exercise on preventing arterial stiffness and the potential role of sympathetic nerves within perivascular adipose tissue (PVAT) in pressure-overload-induced heart failure (HF) mice. Eight-week-old male mice were subjected to sham operation (SHAM), transverse aortic constriction-sedentary (TAC-SE), and transverse aortic constriction-exercise (TAC-EX) groups. Six weeks of aerobic exercise training was performed using a treadmill. Arterial stiffness was determined by measuring the elastic modulus. The elastic and collagen fibers of the aorta and sympathetic nerve distribution in PVAT were observed. Circulating noradrenaline (NE), expressions of β3-adrenergic receptor (β3-AR), and adiponectin in PVAT were quantified. During the recovery of cardiac function by aerobic exercise, thoracic aortic collagen elastic modulus (CEM) and collagen fibers were significantly decreased (p < 0.05, TAC-SE vs. TAC-EX), and elastin elastic modulus (EEM) was significantly increased (p < 0.05, TAC-SE vs. TAC-EX). Circulating NE and sympathetic nerve distribution in PVAT were significantly decreased (p < 0.05, TAC-SE vs. TAC-EX). The expression of β3-AR was significantly reduced (p < 0.05, TAC-SE vs. TAC-EX), and adiponectin was significantly increased (p < 0.05, TAC-SE vs. TAC-EX) in PVAT. Regular aerobic exercise can effectively prevent arterial stiffness and extracellular matrix (ECM) remodeling in the developmental course of HF, during which sympathetic innervation and adiponectin within PVAT might be strongly implicated.
Integrating ATAC-seq and RNA-seq Reveals the Dynamics of Chromatin Accessibility and Gene Expression in Apple Response to Drought
Authors: Wang Shicong , He Jieqiang , Deng Mengting , Wang Caixia , Wang Ruifeng , Yan Jinjiao , Luo Minrong , Ma Fengwang , Guan Qingmei , Xu Jidi
Published: September 2022

Drought resistance in plants is influenced by multiple signaling pathways that involve various transcription factors, many target genes, and multiple types of epigenetic modifications. Studies on epigenetic modifications of drought focus on DNA methylation and histone modifications, with fewer on chromatin remodeling. Changes in chromatin accessibility can play an important role in abiotic stress in plants by affecting RNA polymerase binding and various regulatory factors. However, the changes in chromatin accessibility during drought in apples are not well understood. In this study, the landscape of chromatin accessibility associated with the gene expression of apple (GL3) under drought conditions was analyzed by Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) and RNA-seq. Differential analysis between drought treatment and control identified 23,466 peaks of upregulated chromatin accessibility and 2447 peaks of downregulated accessibility. The drought-induced chromatin accessibility changed genes were mainly enriched in metabolism, stimulus, and binding pathways. By combining results from differential analysis of RNA-seq and ATAC-seq, we identified 240 genes with higher chromatin accessibility and increased gene expression under drought conditions that may play important functions in the drought response process. Among them, a total of nine transcription factor genes were identified, including ATHB7, HAT5, and WRKY26. These transcription factor genes are differentially expressed with different chromatin accessibility motif binding loci that may participate in apple response to drought by regulating downstream genes. Our study provides a reference for chromatin accessibility under drought stress in apples and the results will facilitate subsequent studies on chromatin remodelers and transcription factors.
Changes in Proximal Tubular Reabsorption Modulate Microvascular Regulation via the TGF System
Authors: Poursharif Shayan , Hamza Shereen , Braam Branko
Published: September 2022

This review paper considers the consequences of modulating tubular reabsorption proximal to the macula densa by sodium–glucose co-transporter 2 (SGLT2) inhibitors, acetazolamide, and furosemide in states of glomerular hyperfiltration. SGLT2 inhibitors improve renal function in early and advanced diabetic nephropathy by decreasing the glomerular filtration rate (GFR), presumably by activating the tubuloglomerular feedback (TGF) mechanism. Central in this paper is that the renoprotective effects of SGLT2 inhibitors in diabetic nephropathy can only be partially explained by TGF activation, and there are alternative explanations. The sustained activation of TGF leans on two prerequisites: no or only partial adaptation should occur in reabsorption proximal to macula densa, and no or only partial adaptation should occur in the TGF response. The main proximal tubular and loop of Henle sodium transporters are sodium–hydrogen exchanger 3 (NHE3), SGLT2, and the Na-K-2Cl co-transporter (NKCC2). SGLT2 inhibitors, acetazolamide, and furosemide are the most important compounds; inhibiting these transporters would decrease sodium reabsorption upstream of the macula densa and increase TGF activity. This could directly or indirectly affect TGF responsiveness, which could oppose sustained TGF activation. Only SGLT2 inhibitors can sustainably activate the TGF as there is only partial compensation in tubular reabsorption and TGF response. SGLT2 inhibitors have been shown to preserve GFR in both early and advanced diabetic nephropathy. Other than for early diabetic nephropathy, a solid physiological basis for these effects in advanced nephropathy is lacking. In addition, TGF has hardly been studied in humans, and therefore this role of TGF remains elusive. This review also considers alternative explanations for the renoprotective effects of SGLT2 inhibitors in diabetic patients such as the enhancement of microvascular network function. Furthermore, combination use of SGLT2 inhibitors and angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs). in diabetes can decrease inflammatory pathways, improve renal oxygenation, and delay the progression of diabetic nephropathy.
The In Vitro Inhibitory Effect of Selected Asteraceae Plants on Pancreatic Lipase Followed by Phenolic Content Identification through Liquid Chromatography High Resolution Mass Spectrometry (LC-HRMS)
Authors: Tsagkaris Aristeidis S. , Louckova Anna , Jaegerova Tereza , Tokarova Viola , Hajslova Jana
Published: September 2022

Pancreatic lipase (PNLIP, EC 3.1.1.3) plays a pivotal role in the digestion of dietary lipids, a metabolic pathway directly related to obesity. One of the effective strategies in obesity treatment is the inhibition of PNLIP, which is possible to be achieved by specific phenolic compounds occurring in high abundance in some plants. In this study, a multidisciplinary approach is presented investigating the PNLIP inhibitory effect of 33 plants belonging in the Asteraceae botanical family. In the first stage of the study, a rapid and cost-efficient PNLIP assay in a 96-microwell plate format was developed and important parameters were optimized, e.g., the enzyme substrate. Upon PNLIP assay optimization, aqueous and dichloromethane Asteraceae plant extracts were tested and a cut-off inhibition level was set to further analyze only the samples with a significant inhibitory effect (inhibitory rate > 40%), using an ultra-high-performance liquid chromatography hybrid quadrupole time-of-flight mass spectrometry (UHPLC-q-TOF-MS) method. Specifically, a metabolomic suspect screening was performed and 69 phenolic compounds were tentatively identified, including phenolic acids, flavonoids, flavonoid-3-O-glycosides, and flavonoid-7-O-glycosides, amongst others. In the case of aqueous extracts, phytochemicals known for inducing PNLIP inhibitory effect, e.g., compounds containing galloyl molecules or caffeoylquinic acids, were monitored in Chrysanthemum morifolium, Grindella camporum and Hieracium pilosella extracts. All in all, the presented approach combines in vitro bioactivity measurements to high-end metabolomics to identify phenolic compounds with potential medicinal and/or dietary applications.
Roles of Regulatory T Cell-Derived Extracellular Vesicles in Human Diseases
Authors: Lin Can , Guo Jihua , Jia Rong
Published: September 2022

Regulatory T (Treg) cells play crucial roles in maintaining immune self-tolerance and immune homeostasis, and closely associated with many human diseases. Recently, Treg cells-derived extracellular vesicles (Treg-EVs) have been demonstrated as a novel cell-contact independent inhibitory mechanism of Treg cells. Treg-EVs contain many specific biological molecules, which are delivered to target cells and modulate immune responses by inhibiting T cell proliferation, inducing T cell apoptosis, and changing the cytokine expression profiles of target cells. The abnormal quantity or function of Treg-EVs is associated with several types of human diseases or conditions, such as transplant rejection, inflammatory diseases, autoimmune diseases, and cancers. Treg-EVs are promising novel potential targets for disease diagnosis, therapy, and drug transport. Moreover, Treg-EVs possess distinct advantages over Treg cell-based immunotherapies. However, the therapeutic potential of Treg-EVs is limited by some factors, such as the standardized protocol for isolation and purification, large scale production, and drug loading efficiency. In this review, we systematically describe the structure, components, functions, and basic mechanisms of action of Treg-EVs and discuss the emerging roles in pathogenesis and the potential application of Treg-EVs in human diseases.
A New Chemotactic Mechanism Governs Long-Range Angiogenesis Induced by Patching an Arterial Graft into a Vein
Authors: Minerva Dhisa , Othman Nuha Loling , Nakazawa Takashi , Ito Yukinobu , Yoshida Makoto , Goto Akiteru , Suzuki Takashi
Published: September 2022

Chemotaxis, the migration of cells in response to chemical stimulus, is an important concept in the angiogenesis model. In most angiogenesis models, chemotaxis is defined as the migration of a sprout tip in response to the upgradient of the VEGF (vascular endothelial growth factor). However, we found that angiogenesis induced by performing arterial patch grafting on rabbits occurred under the decreasing VEGFA gradient. Data show that the VEGFA concentration peaked at approximately 0.3 to 0.5 cm away from the arterial patch and decreased as the measurement approaches the patch. We also observed that the new blood vessels formed are twisted and congested in some areas, in a distinguishable manner from non-pathological blood vessels. To explain these observations, we developed a mathematical model and compared the results from numerical simulations with the experimental data. We introduced a new chemotactic velocity using the temporal change in the chemoattractant gradient to govern the sprout tip migration. We performed a hybrid simulation to illustrate the growth of new vessels. Results indicated the speed of growth of new vessels oscillated before reaching the periphery of the arterial patch. Crowded and congested blood vessel formation was observed during numerical simulations. Thus, our numerical simulation results agreed with the experimental data.
Role of Mesenchymal Stem Cells and Extracellular Vesicles in Idiopathic Pulmonary Fibrosis
Authors: Kletukhina Sevindzh , Mutallapova Guzel , Titova Angelina , Gomzikova Marina
Published: September 2022

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial fibrotic disease that leads to disability and death within 5 years of diagnosis. Pulmonary fibrosis is a disease with a multifactorial etiology. The concept of aberrant regeneration of the pulmonary epithelium reveals the pathogenesis of IPF, according to which repeated damage and death of alveolar epithelial cells is the main mechanism leading to the development of progressive IPF. Cell death provokes the migration, proliferation and activation of fibroblasts, which overproduce extracellular matrix, resulting in fibrotic deformity of the lung tissue. Mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) are promising therapies for pulmonary fibrosis. MSCs, and EVs derived from MSCs, modulate the activity of immune cells, inhibit the expression of profibrotic genes, reduce collagen deposition and promote the repair of damaged lung tissue. This review considers the molecular mechanisms of the development of IPF and the multifaceted role of MSCs in the therapy of IPF. Currently, EVs-MSCs are regarded as a promising cell-free therapy tool, so in this review we discuss the results available to date of the use of EVs-MSCs for lung tissue repair.
Genome-Wide Identification and Characterization of the NF-YA Gene Family and Its Expression in Response to Different Nitrogen Forms in Populus × canescens
Authors: Zhou Jing , Yang Lingyu , Chen Xin , Zhou Mengyan , Shi Wenguang , Deng Shurong , Luo Zhibin
Published: September 2022

The NF-YA gene family is a class of conserved transcription factors that play important roles in plant growth and development and the response to abiotic stress. Poplar is a model organism for studying the rapid growth of woody plants that need to consume many nutrients. However, studies on the response of the NF-YA gene family to nitrogen in woody plants are limited. In this study, we conducted a systematic and comprehensive bioinformatic analysis of the NF-YA gene family based on Populus × canescens genomic data. A total of 13 PcNF-YA genes were identified and mapped to 6 chromosomes. According to the amino acid sequence characteristics and genetic structure of the NF-YA domains, the PcNF-YAs were divided into five clades. Gene duplication analysis revealed five pairs of replicated fragments and one pair of tandem duplicates in 13 PcNF-YA genes. The PcNF-YA gene promoter region is rich in different cis-acting regulatory elements, among which MYB and MYC elements are the most abundant. Among the 13 PcNF-YA genes, 9 contained binding sites for P. × canescens miR169s. In addition, RT-qPCR data from the roots, wood, leaves and bark of P. × canescens showed different spatial expression profiles of PcNF-YA genes. Transcriptome data and RT-qPCR analysis showed that the expression of PcNF-YA genes was altered by treatment with different nitrogen forms. Furthermore, the functions of PcNF-YA genes in transgenic poplar were analyzed, and the potential roles of PcNF-YA genes in the response of poplar roots to different nitrogen forms were revealed, indicating that these genes regulate root growth and development.
Identification of the 14-3-3 Gene Family in Bamboo and Characterization of Pe14-3-3b Reveals Its Potential Role in Promoting Growth
Authors: Guo Dong , Zhu Chenglei , Yang Kebin , Liu Yan , Xiao Xiaoyan , Li Ziyang , Gao Zhimin
Published: September 2022

The 14-3-3 protein family plays an important role in regulating plant growth and development. The genes of the 14-3-3 family have been reported in multiple species. However, little is known about the 14-3-3 gene family in bamboo. In this study, a total of 58 genes belonging to the 14-3-3 family were identified in three representative bamboo species, i.e., Olyra latifolia, Phyllostachys edulis, and Bonia amplexicaulis, whose encoding proteins were grouped into ε and non-ε groups by phylogeny analysis with 14-3-3 proteins from Arabidopsis thaliana and Oryza sativa. The 14-3-3s had diverse gene structures and motif characteristics among the three bamboo species. Collinearity analysis suggested that the genes of the 14-3-3 family in bamboo had undergone a strong purification selection during evolution. Tissue-specific expression analysis showed the expression of Pe14-3-3s varied in different tissues of P. edulis, suggesting that they had functional diversity during growth and development. Co-expression analysis showed that four Pe14-3-3s co-expressed positively with eight ribosomal genes. Yeast two-hybrid (Y2H) assays showed that Pe14-3-3b/d could interact with Pe_ribosome-1/5/6, and qPCR results demonstrated that Pe14-3-3b/d and Pe_ribosome-1/5/6 had similar expression trends with the increase in shoot height, which further confirmed that they would work together to participate in the shoot growth and development of bamboo. Additionally, the transgenic Arabidopsis plants overexpressing Pe14-3-3b had longer roots, a larger stem diameter, an earlier bolting time and a faster growth rate than wild-type Arabidopsis, indicating that Pe14-3-3b acted as a growth promoter. Our results provide comprehensive information on 14-3-3 genes in bamboo and highlight Pe14-3-3b as a potential target for bamboo improvement.
Landscape of Cellular Bioeffects Triggered by Ultrasound-Induced Sonoporation
Authors: Przystupski Dawid , Ussowicz Marek
Published: September 2022

Sonoporation is the process of transient pore formation in the cell membrane triggered by ultrasound (US). Numerous studies have provided us with firm evidence that sonoporation may assist cancer treatment through effective drug and gene delivery. However, there is a massive gap in the body of literature on the issue of understanding the complexity of biophysical and biochemical sonoporation-induced cellular effects. This study provides a detailed explanation of the US-triggered bioeffects, in particular, cell compartments and the internal environment of the cell, as well as the further consequences on cell reproduction and growth. Moreover, a detailed biophysical insight into US-provoked pore formation is presented. This study is expected to review the knowledge of cellular effects initiated by US-induced sonoporation and summarize the attempts at clinical implementation.
Clinical Significance of Claudin Expression in Oral Squamous Cell Carcinoma
Authors: Zejc Tatjana , Piontek Jörg , Schulzke Jörg-Dieter , Fromm Michael , Ervens Jürgen , Rosenthal Rita
Published: September 2022

A change in claudin expression has been demonstrated in various tumors. The present study specifically compares claudin expression in oral squamous cell carcinoma (OSCC) with healthy oral epithelium from the same individual and analyzes the association between claudin expression and the clinically relevant course parameters. Our study includes tissue samples and clinically relevant follow-up data from 60 patients with primary and untreated OSCC. The oral mucosa was analyzed via Western blot for the expression of claudin-1, -2, -3, -4, -5, and -7. Importantly, the tumor and healthy tissues were obtained pairwise from patients, allowing for intraindividual comparisons. Both the healthy and tumor epithelium from the oral cavity did not express the claudin-3 protein. The intraindividual comparison revealed that, in OSCC, claudin-2 expression was higher, and the expression of claudin-4, -5, and -7 was lower than in healthy epithelium. An association was found between increased claudin-2 expression and shorter relapse-free survival. In addition, the reduced expression of claudin-4 had a negative impact on relapse-free survival. Furthermore, associations between the reduced expression of claudin-7 and the stage of a tumor, or the presence of lymph node metastases, were found. Thus, the expression level of claudin-2, -4, and -7 appears to be predictive of the diagnosis and prognosis of OSCC.
Increased NMUR1 Expression in Mast Cells in the Synovial Membrane of Obese Osteoarthritis Patients
Authors: Tsukada Ayumi , Takata Ken , Takano Shotaro , Ohashi Yoshihisa , Mukai Manabu , Aikawa Jun , Iwase Dai , Inoue Gen , Takaso Masashi , Uchida Kentaro
Published: September 2022

Obesity is a risk factor for knee osteoarthritis (KOA). Neuromedin U (NMU) and NMU receptors (NMUR1 and NMUR2) are associated with obesity-related disorders and found in mast cells (MCs), which are elevated in osteoarthritis. However, NMU/NMUR expression was not examined in the synovial membrane (SM) or synovial MCs of obese osteoarthritis patients. We compared expression of NMU, NMUR1, NMUR2, and the mast cell (MC) marker, CPA3, in the SM of KOA patients categorized as normal weight (NW; BMI < 25 kg/m2, n = 79), overweight (OW; BMI ≥ 25 and <30 kg/m2, n = 87), and obese (OB; ≥30 kg/m2, n = 40). To study NMU/NMUR expression in MCs, we compared the MC-rich fraction (MC-RF), CD88(+) MC-RF, and CD88(−) MC-RF, extracted using magnetic isolation, with the MC-poor fraction (MC-PF). While NMU and NMUR2 expression were comparable, NMUR1 was significantly elevated in OW and OB compared to NW. Moreover, CPA3 levels were significantly greater in OB than NW. NMUR1 and CPA3 expression were significantly higher in both the CD88(+) and CD88(−) MC-RF than MC-PF. Therefore, NMUR1 expression was elevated in the SM of OB KOA patients, and its expression was found in MCs. Further investigation to analyze the NMU/NMUR1 pathway in MC may provide a link between obesity and KOA pathology.
The Effects of Seven-Day Exposure to Silver Nanoparticles on Fertility and Homeostasis of Zebrafish (Danio rerio)
Authors: Szudrowicz Hubert , Kamaszewski Maciej , Adamski Antoni , Skrobisz Marek , Frankowska-Łukawska Justyna , Wójcik Maciej , Bochenek Joanna , Kawalski Kacper , Martynow Jakub , Bujarski Patryk , Pruchniak Pola , Latoszek Ewelina , Bury-Burzymski Paweł , Szczepański Adrian , Jaworski Sławomir , Matuszewski Arkadiusz , Herman Andrzej Przemysław
Published: September 2022

Silver nanoparticles (AgNPs) are found in open waters, but the effect of their low concentrations on an organism’s homeostasis is not fully understood. The aim of the study was to determine the short-term exposure effects of AgNPs coated by PvP (polyvinylpyrrolidone) on the homeostasis of livers and gonads in zebrafish. Sexually mature zebrafish were exposed for seven days to silver ions (0.01 mg/dm3) or AgNPs (0.01; 0.05; 0.1; 0.5; 1.0 mg/dm3). On the last day, the liver, testes, and ovaries were subjected to a histology analysis. In the liver, we analyzed the expression of the cat, gpx1a, gsr, sod1, and cyp1a genes. On the last day of the experiment, the lowest survival rate was found in the AgNPs 0.05 mg/dm3 group. The histological analysis showed that AgNPs and silver ions cause an increase in the area of hepatocytes. The highest proliferation index of hepatocytes was found in the AgNP 0.05 mg/dm3 group. Furthermore, AgNPs were found to interfere with spermatogenesis and oogonesis as well as reduce the expression levels of the cat, gpx1a, and sod1 genes in the liver compared with the control group. Based on the results, it can be concluded that exposure to AgNPs causes cytotoxic changes in zebrafish, activates the immune system, negatively affects the process of meiosis in the gonads, and generates oxidative stress.
Identification and Molecular Characterization of a Divergent Asian-like Canine Parvovirus Type 2b (CPV-2b) Strain in Southern Italy
Authors: Schirò Giorgia , Mira Francesco , Canuti Marta , Vullo Stefano , Purpari Giuseppa , Chiaramonte Gabriele , Di Bella Santina , Cannella Vincenza , Randazzo Vincenzo , Castronovo Calogero , Vicari Domenico , Guercio Annalisa
Published: September 2022

Canine parvovirus type 2 (CPV-2) is an infectious agent relevant to domestic and wild carnivorans. Recent studies documented the introduction and spread of CPV-2c strains of Asian origin in the Italian canine population. We investigated tissue samples from a puppy collected during necropsy for the presence of viral enteropathogens and all samples tested positive only for CPV-2. The full coding sequence of a CPV-2b (VP2 426Asp) strain was obtained. This virus was related to CPV-2c strains of Asian origin and unrelated to European CPV-2b strains. The sequence had genetic signatures typical of Asian strains (NS1: 60Val, 545Val, 630Pro; VP2: 5Gly, 267Tyr, 324Ile) and mutations rarely reported in Asian CPV-2b strains (NS1: 588N; VP2: 370Arg). Phylogenetic analyses placed this strain in well-supported clades, including Asian CPV-2c-like strains, but always as a basal, single-sequence long branch. No recombination was observed for this strain, and we speculate that it could have originated from an Asian CPV-2c-like strain that acquired the 426Asp mutation. This study reports the first evidence of an Asian-like CPV-2b strain in Italy, confirming the occurrence of continuous changes in the global CPV-2 spread. Since positive convergent mutations complicate data interpretation, a combination of phylogenetic and mutation pattern analyses is crucial in studying the origin and evolution of CPV-2 strains.
Effects of Drought and Host on the Growth of Santalum album Seedlings in Pot Culture
Authors: Zhang Qilei , Liu Xiaojin , Xu Daping , Hong Zhou , Zhang Ningnan , Cui Zhiyi
Published: September 2022

Santalum album is a semi parasitic plant and its growth is often restricted due to a lack of a host or water during plantation establishment. In this study, the effects of water and the host on the growth of S. album seedlings were studied in pot culture. The results showed that the net photosynthetic rate and height of S. album seedlings decreased significantly under drought stress. Compared with the seedlings of S. album grown without a host, the host could significantly increase the growth of S. album seedlings. The contents of soluble sugar and proline in S. album leaves increased significantly under drought stress. Drought stress resulted in a significant accumulation of malondialdehyde, increments of antioxidant enzymes activity, and non-enzymatic antioxidant substances. Antioxidant capacity was stronger and malondialdehyde content was lower in the seedling leaves of S. album with a host than in the seedlings without a host. RNA-seq was used to analyze the transcription expression profiles of S. album leaves and the results were consistent with the physiological data. These results indicate that the host can promote the seedling growth of S. album and it can increase the antioxidant capacity and osmotic adjustment substance content of the seedlings of S. album, alleviating the damage caused by drought.
Elevated and Sustained Intracellular Calcium Signalling Is Necessary for Efficacious Induction of the Human Sperm Acrosome Reaction
Authors: Prajapati Priyanka , Kane Shruti , McBrinn Rachel C. , Dean Morven S. , Martins da Silva Sarah J. , Brown Sean G.
Published: September 2022

Progesterone and prostaglandin E1 are postulated to trigger the human sperm acrosome reaction (AR). However, their reported efficacy is very variable which likely, in part, reflects the plethora of experimental conditions and methodologies used to detect this physiologically relevant event. The purpose of this study was to develop an assay for the robust induction and objective measurement of the complete AR. Sperm from healthy volunteers or patients undertaking IVF were treated with a variety of ligands (progesterone, prostaglandin E1 or NH4Cl, alone or in combinations). AR, motility and intracellular calcium measurements were measured using flow cytometry, computer-assisted sperm analysis (CASA) and fluorimetry, respectively. The AR was significantly increased by the simultaneous application of progesterone, prostaglandin E1 and NH4Cl, following an elevated and sustained intracellular calcium concentration. However, we observed notable inter- and intra-donor sample heterogeneity of the AR induction. When studying the patient samples, we found no relationship between the IVF fertilization rate and the AR. We conclude that progesterone and prostaglandin E1 alone do not significantly increase the percentage of live acrosome-reacted sperm. This assay has utility for drug discovery and sperm toxicology studies but is not predictive for IVF success.
Modulation of Aryl Hydrocarbon Receptor Expression Alleviated Neuropathic Pain in a Chronic Constriction Nerve Injury Animal Model
Authors: Sheu Meei-Ling , Pan Liang-Yi , Sheehan Jason , Yang Meng-Yin , Pan Hung-Chuan
Published: September 2022

Neuropathic pain is well known to occur after damage to the somatosensory system. Aryl hydrocarbon receptor (AhR) has neuroprotective effects when the central nervous system is subjected to internal and external stimulations. However, the exact mechanism by which AhR regulates neuropathic pain is poorly understood. Nerve explant culture and the chronic constrictive nerve injury (CCI) model in wild or AhR-knockout mice were used in this study. In the nerve explant culture, the ovoid number increased in the AhR−/− condition and was decreased by omeprazole (AhR agonist) in a dose-dependent manner. Increased nerve degeneration and the associated inflammation response appeared in the AhR−/− condition, and these changes were attenuated by omeprazole. High expression of AhR in the injured nerve was noted after CCI. Deletion of AhR aggravated nerve damages and this was restored by omeprazole. Deletion of AhR increased NGF expression and reduced axon number in the paw skin, but this was attenuated by omeprazole. A highly expressed inflammation reaction over the dorsal spinal cord, somatosensory cortex, and hippocampus was noted in the AhR-deleted animals. Administration of omeprazole attenuated not only the inflammatory response, but also the amplitude of somatosensory evoked potential. Deletion of AhR further aggravated the neurobehavior compared with the wild type, but such behavior was attenuated by omeprazole. Chronic constrictive nerve injury augmented AhR expression of the injured nerve, and AhR deletion worsened the damage, while AhR agonist omeprazole counteracted such changes. AhR agonists could be potential candidates for neuropathic pain treatment.
A Phosphorous-Based Bi-Functional Flame Retardant Based on Phosphaphenanthrene and Aluminum Hypophosphite for an Epoxy Thermoset
Authors: Xu Bo , Liu Yanting , Wei Simiao , Zhao Siheng , Qian Lijun , Chen Yajun , Shan Hao , Zhang Qinglei
Published: September 2022

A phosphorous-based bi-functional compound HPDAl was used as a reactive-type flame retardant (FR) in an epoxy thermoset (EP) aiming to improve the flame retardant efficiency of phosphorus-based compounds. HPDAl, consisting of two different P-groups of aluminum phosphinate (AHP) and phosphophenanthrene (DOPO) with different phosphorous chemical environments and thus exerting different FR actions, exhibited an intramolecular P-P groups synergy and possessed superior flame-retardant efficiency compared with DOPO or AHP alone or the physical combination of DOPO/AHP in EP. Adding 2 wt.% HPDAl made EP composites acquire a LOI value of 32.3%, pass a UL94 V-0 rating with a blowing-out effect, and exhibit a decrease in the heat/smoke release. The flame retardant modes of action of HPDAl were confirmed by the experiments of the scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), and thermogravimetry–Fourier transform infrared spectroscopy–gas chromatograph/mass spectrometer (TG-FTIR-GC/MS). The results indicate that the phosphorous-based FRs show different influences on the flame retardancy of composites, mainly depending on their chemical structures. HPDAl had a flame inhibition effect in the gas phase and a charring effect in the condensed phase, with a well-balanced distribution of P content in the gas/condensed phase. Furthermore, the addition of HPDAl hardly impaired the mechanical properties of the matrix due to the link by chemical bonds between them.
Polo-Like Kinase 2 Plays an Essential Role in Cytoprotection against MG132-Induced Proteasome Inhibition via Phosphorylation of Serine 19 in HSPB5
Authors: Ueda Shuji , Nishihara Moeka , Hioka Yuuki , Yoshino Ken-ichi , Yamada Soichiro , Yamanoue Minoru , Shirai Yasuhito
Published: September 2022

Protein homeostasis, including protein folding, refolding, and degradation, is thought to decline with aging. HSPB5 (also known as αB-crystallin) prevents target protein aggregation as a molecular chaperone and exhibits a cytoprotective function against various cell stresses. To elucidate the effect of HSPB5 on endoplasmic reticulum (ER) stress, we searched for novel binding proteins of HSPB5 using the proximity-dependent biotin labeling method. Proteins presumed to interact with HSPB5 in cells treated with the proteasome inhibitor MG132 were identified by a reversible biotin-binding capacity method combining tamavidin2-REV magnetic beads and mass spectrometry. We discovered a new binding protein for HSPB5, polo-like kinase 2 (PLK2), which is an apoptosis-related enzyme. The expression of PLK2 was upregulated by MG132 treatment, and it was co-localized with HSPB5 near the ER in L6 muscle cells. Inhibition of PLK2 decreased ER stress-induced phosphorylation of serine 19 in HSPB5 and increased apoptosis by activation of caspase 3 under ER stress. Overexpression of HSPB5 (WT) suppressed the ER stress-induced caspase 3 activity, but this was not observed with phospho-deficient HSPB5 (3A) mutants. These results clarify the role of HSPB5 phosphorylation during ER stress and suggest that the PLK2/HSPB5 pathway plays an essential role in cytoprotection against proteasome inhibition-induced ER stress.
Characterization of a Novel Myrosinase with High Activity from Marine Bacterium Shewanella baltica Myr-37
Authors: Ye Qinwen , Fang Yaowei , Li Mengjiao , Mi Haoyu , Liu Shu , Yang Guang , Lu Jing , Zhao Yaling , Liu Qitong , Zhang Wei , Hou Xiaoyue
Published: September 2022

Myrosinase can hydrolyze glucosinolates to generate isothiocyanates, which have cancer prevention and anti-cancer properties. The main sources of myrosinase are cruciferous plants. To further improve the efficiency of isothiocyanates preparation, it is necessary to explore novel sources of myrosinases. In this study, we described a bacterium, Shewanella baltica Myr-37, isolated from marine mud, capable of producing a novel myrosinase (Smyr37) with a molecular weight of 100 kDa. The crude enzyme of Smyr37 showed the highest activity at 50 °C and pH 8.0. The sinigrin- and glucoraphanin-hydrolyzing activities of Smyr37 were 6.95 and 5.87 U/mg, respectively. Moreover, when the reaction temperature was 40 °C and pH was 7.0, the crude enzyme of Smyr37 could efficiently degrade glucoraphanin into sulforaphane within 25 min with a yield of 0.57 mg/mL. The corresponding conversion efficiency of sulforaphane from glucoraphanin was 89%. In summary, S. baltica Myr-37 myrosinase Smyr37, a novel myrosinase, can be used in the preparation of isothiocyanates.
Discovery of the Cryptic Sites of SARS-CoV-2 Papain-like Protease and Analysis of Its Druggability
Authors: Qiu Yue , Liu Qing , Tu Gao , Yao Xiao-Jun
Published: September 2022

In late 2019, a new coronavirus (CoV) caused the outbreak of a deadly respiratory disease, resulting in the COVID-19 pandemic. In view of the ongoing pandemic, there is an immediate need to find drugs to treat patients. SARS-CoV-2 papain-like cysteine protease (PLpro) not only plays an important role in the pathogenesis of the virus but is also a target protein for the development of inhibitor drugs. Therefore, to develop targeted inhibitors, it is necessary to analyse and verify PLpro sites and explore whether there are other cryptic binding pockets with better activity. In this study, first, we detected the site of the whole PLpro protein by sitemap of Schrödinger (version 2018), the cavity of LigBuilder V3, and DeepSite, and roughly judged the possible activated binding site area. Then, we used the mixed solvent dynamics simulation (MixMD) of probe molecules to induce conformational changes in the protein to find the possible cryptic active sites. Finally, the TRAPP method was used to predict the druggability of cryptic pockets and analyse the changes in the physicochemical properties of residues around these sites. This work will help promote the research of SARS-CoV-2 PLpro inhibitors.
Efficacy and Safety of Ginger on the Side Effects of Chemotherapy in Breast Cancer Patients: Systematic Review and Meta-Analysis
Authors: Kim Soo-Dam , Kwag Eun-Bin , Yang Ming-Xiao , Yoo Hwa-Seung
Published: September 2022

Cancer is one of the leading causes of death in the world, with breast cancer being the most prevalent cancer. Chemotherapy-induced nausea and vomiting (CINV) is one of the most serious side effects of chemotherapy. Because the current CINV treatment option has several flaws, alternative treatment options are required. Ginger has traditionally been used to treat nausea and vomiting, and it also has anticancer properties in breast cancer cells. Based on these findings, researchers investigated whether using ginger to treat CINV in breast cancer patients is both effective and safe. We searched PubMed, Embase, Cochrane Library, CNKI, and Wanfang from inception to June 2022. Outcomes included Rhodes Index Scores of Nausea, Vomiting, and Retching, severity and frequency of CINV. Five RCTs were included. We pooled all included data and performed subgroup analysis by types of CINV. Overall, authors found that ginger was associated with a reduction in CINV. Subgroup and sensitivity analysis revealed that managing severity of acute CINV in breast cancer patients with ginger was efficient. In terms of managing delayed CINV in breast cancer patients, ginger was also statistically significant. The authors concluded that ginger may be helpful in lowering both acute and delayed CINV in breast cancer patients. Since there were no serious side effects, ginger is thought to be safe.
Resistance to Thyroid Hormones: A Case-Series Study
Authors: Cannarella Rossella , Musmeci Marco , Garofalo Vincenzo , Timpanaro Tiziana A. , Leone Guido , Caruso Manuela , Maltese Paolo E. , Condorelli Rosita A. , La Vignera Sandro , Calogero Aldo E.
Published: September 2022

The aim of the study is to describe the clinical features of two unrelated patients with resistance to thyroid hormones (RTH), the first, a total thyroidectomized patient, and the second, a pregnant woman. We report the features found in her newborn who also showed RTH. Patient 1 is a 38-year-old man with total thyroidectomy managed for excessive thyroid stimulating hormone (TSH) production, which poorly responded to the replacement therapy. He was found with a THRβ c.1378G>A p.(Glu460Lys) heterozygous mutation, which was also present in other members of his family (son, brother, and father). Interestingly, Patient 1 had hypertension, dyslipidemia, and hepatic steatosis, which have been recently suggested as RTH-related comorbidities. Patient 2 is a 32-year-old pregnant woman with multinodular goiter, and the THRβ heterozygous variant c.959G>C, that, to the best of our knowledge, has been reported in literature only once. Her newborn had tachycardia and increased thyroid hormone levels, and showed the same mutation. After delivery, high parathyroid hormone (PTH) and calcium serum levels were found in Patient 2 and the scintigraphy showed the presence of adenoma of a parathyroid gland. This case-series study provides a practical example of the management of RTH in a thyroidectomized patient, a pregnant woman, and a newborn. A novel RTH pathogenic mutation is described for the second time in literature. Furthermore, the importance of metabolic assessment in patients with RTHβ has been highlighted and the possible correlation between RTH and primary hyperparathyroidism is discussed.
Precision Medicine Approaches with Metabolomics and Artificial Intelligence
Authors: Barberis Elettra , Khoso Shahzaib , Sica Antonio , Falasca Marco , Gennari Alessandra , Dondero Francesco , Afantitis Antreas , Manfredi Marcello
Published: September 2022

Recent technological innovations in the field of mass spectrometry have supported the use of metabolomics analysis for precision medicine. This growth has been allowed also by the application of algorithms to data analysis, including multivariate and machine learning methods, which are fundamental to managing large number of variables and samples. In the present review, we reported and discussed the application of artificial intelligence (AI) strategies for metabolomics data analysis. Particularly, we focused on widely used non-linear machine learning classifiers, such as ANN, random forest, and support vector machine (SVM) algorithms. A discussion of recent studies and research focused on disease classification, biomarker identification and early diagnosis is presented. Challenges in the implementation of metabolomics–AI systems, limitations thereof and recent tools were also discussed.
QTL Mapping of Palmitic Acid Content Using Specific-Locus Amplified Fragment Sequencing (SLAF-Seq) Genotyping in Soybeans (Glycine max L.)
Authors: Xue Yongguo , Gao Huawei , Liu Xinlei , Tang Xiaofei , Cao Dan , Luan Xiaoyan , Zhao Lin , Qiu Lijuan
Published: September 2022

Soybeans are essential crops that supply protein and oil. The composition and contents of soybean fatty acids are relevant to human health and have a significant relationship with soybean oil processing and applications. Identifying quantitative trait locus (QTL) genes related to palmitic acid could facilitate the development of a range of nutritive soybean cultivars using molecular marker-assisted selection. In this study, we used a cultivar with higher palmitic acid content, ‘Dongnong42’, and a lower palmitic acid content cultivar, ‘Hobbit’, to establish F2:6 recombinant inbred lines. A high-density genetic map containing 9980 SLAF markers was constructed and distributed across 20 soybean chromosomes. The genetic map contained a total genetic distance of 2602.58 cM and an average genetic distance of 0.39 cM between adjacent markers. Two QTLs related to palmitic acid content were mapped using inclusive composite interval mapping, explaining 4.2–10.1% of the phenotypic variance in three different years and environments, including the QTL included in seed palmitic 7-3, which was validated by developing SSR markers. Based on the SNP/Indel and significant differential expression analyses of Dongnong42 and Hobbit, two genes, Glyma.15g119700 and Glyma.15g119800, were selected as candidate genes. The high-density genetic map, QTLs, and molecular markers will be helpful for the map-based cloning of palmitic acid content genes. These could be used to accelerate breeding for high nutritive value cultivars via molecular marker-assisted breeding.
Downregulation of miR-30b-5p Facilitates Chondrocyte Hypertrophy and Apoptosis via Targeting Runx2 in Steroid-Induced Osteonecrosis of the Femoral Head
Authors: Lin Lishan , Yu Yaling , Liu Kangping , Jiang Yixin , Zhou Zhenlei
Published: September 2022

As a widely used steroid hormone medicine, glucocorticoids have the potential to cause steroid-induced osteonecrosis of the femoral head (SONFH) due to mass or long-term use. The non-coding RNA hypothesis posits that they may contribute to the destruction and dysfunction of cartilages as a possible etiology of SONFH. MiR-30b-5p was identified as a regulatory factor in cartilage degeneration caused by methylprednisolone (MPS) exposure in our study through cell transfection. The luciferase reporter assay confirmed that miR-30b-5p was downregulated and runt-related transcription factor 2 (Runx2) was mediated by miR-30b-5p. The nobly increased expression of matrix metallopeptidase 13 (MMP13) and type X collagen (Col10a1) as Runx2 downstream genes contributed to the hypertrophic differentiation of chondrocytes, and the efficiently upregulated level of matrix metallopeptidase 9 (MMP9) may trigger chondrocyte apoptosis with MPS treatments. The cell transfection experiment revealed that miR-30b-5p inhibited chondrocyte hypertrophy and suppressed MPS-induced apoptosis. As a result, our findings showed that miR-30b-5p modulated Runx2, MMP9, MMP13, and Col10a1 expression, thereby mediating chondrocyte hypertrophic differentiation and apoptosis during the SONFH process. These findings revealed the mechanistic relationship between non-coding RNA and SONFH, providing a comprehensive understanding of SONFH and other bone diseases.
Microbiome in Hidradenitis Suppurativa—What We Know and Where We Are Heading
Authors: Świerczewska Zuzanna , Lewandowski Miłosz , Surowiecka Agnieszka , Barańska-Rybak Wioletta
Published: September 2022

Recently, interest in the microbiome of cutaneous diseases has increased tremendously. Of particular interest is the gut-brain-skin axis proposed by Stokes and Pillsbury in 1930. The microbiome has been suggested in the pathogenesis of hidradenitis suppurativa, however the link between the commensals and the host is yet to be established. Across all studies, the increased abundance of Porphyromonas, Peptoniphilus, and Prevotella spp., and a loss of skin commensal species, such as Cutibacterium in HS lesions, is a consistent finding. The role of gut and blood microbiome in hidradenitis suppurativa has not been fully elucidated. According to studies, the main link with the intestine is based on the increased risk of developing Crohn’s disease and ulcerative colitis, however, further research is highly needed in this area. Lifestyle, dietary approaches, and probiotics all seem to influence the microbiome, hence being a promising modality as adjuvant therapy. The aim of this review was to present the latest reports in the field of research on skin, blood, and gut microbiome in terms of hidradenitis suppurativa.
Carbon-Based Electrocatalyst Design with Phytic Acid—A Versatile Biomass-Derived Modifier of Functional Materials
Authors: Gwóźdź Magdalena , Brzęczek-Szafran Alina
Published: September 2022

Increasing energy demands exacerbated by energy shortages have highlighted the urgency of research on renewable energy technologies. Carbon materials that can be employed as advanced electrodes and catalysts can increase the accessibility of efficient and economical energy conversion and storage solutions based on electrocatalysis. In particular, carbon materials derived from biomass are promising candidates to replace precious-metal-based catalysts, owing to their low cost, anti-corrosion properties, electrochemical durability, and sustainability. For catalytic applications, the rational design and engineering of functional carbon materials in terms of their structure, morphology, and heteroatom doping are crucial. Phytic acid derived from natural, abundant, and renewable resources represents a versatile carbon precursor and modifier that can be introduced to tune the aforementioned properties. This review discusses synthetic strategies for preparing functional carbon materials using phytic acid and explores the influence of this precursor on the resulting materials’ physicochemical characteristics. We also summarize recent strategies that have been applied to improve the oxygen reduction performance of porous carbon materials using phytic acid, thereby offering guidance for the future design of functional, sustainable carbon materials with enhanced catalytic properties.
Proteomic Profiling Skin Mucus of European Eel Anguilla anguilla Infected with Anguillid Herpesvirus
Authors: Li Ying-Ying , Yang Jin-Xian , Chen Xi , Chen Qiang , Song Tie-Ying , Ge Jun-Qing
Published: September 2022

Anguillid herpesvirus 1 (AngHV) is an important viral pathogen affecting eel. This study was designed to investigate the potential molecular mechanisms and immune response elicited at the protein levels in the skin mucus of AngHV-infected Anguilla anguilla. Tandem mass tag (TMT)-labelling proteomics with the liquid chromatography tandem mass spectrometry (LC-MS/MS) was used for performing quantitative identification of the proteins. In addition, the quantitative protein amount was detected by parallel reaction monitoring (PRM) analysis. A total of 3486 proteins were identified, of which 2935 were quantified. When a protein fold change was greater than 1.3 or less than 0.76, it indicated a differentially expressed protein (DEP). Overall, 187 up-regulated proteins and 126 down-regulated proteins were detected, and most of the DEPs were enriched in the CAMs pathway, intestinal immune pathway, herpes simplex virus 1 infection pathway, phagosome pathway and p53 signaling pathway. The results of the DEPs detected by PRM were highly consistent with the results of the TMT-labelled quantitative proteomic analysis. The findings of this study provide an important research basis for further understanding the pathogenesis of AngHV.