bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat-Killed Enterococcus faecalis Inhibit FL83B Hepatic Lipid Accumulation and High Fat Diet-Induced Fatty Liver Damage in Rats by Activating Lipolysis through the Regulation the AMPK Signaling Pathway
Authors: Lee Jin-Ho , Woo Keun-Jung , Hong Joonpyo , Han Kwon-Il , Kim Han Sung , Kim Tack-Joong
Published: February 2023

Continuous consumption of high-calorie meals causes lipid accumulation in the liver and liver damage, leading to non-alcoholic fatty liver disease (NAFLD). A case study of the hepatic lipid accumulation model is needed to identify the mechanisms underlying lipid metabolism in the liver. In this study, the prevention mechanism of lipid accumulation in the liver of Enterococcus faecalis 2001 (EF-2001) was extended using FL83B cells (FL83Bs) and high-fat diet (HFD)-induced hepatic steatosis. EF-2001 treatment inhibited the oleic acid (OA) lipid accumulation in FL83B liver cells. Furthermore, we performed lipid reduction analysis to confirm the underlying mechanism of lipolysis. The results showed that EF-2001 downregulated proteins and upregulated AMP-activated protein kinase (AMPK) phosphorylation in the sterol regulatory element-binding protein 1c (SREBP-1c) and AMPK signaling pathways, respectively. The effect of EF-2001 on OA-induced hepatic lipid accumulation in FL83Bs enhanced the phosphorylation of acetyl-CoA carboxylase and reduced the levels of lipid accumulation proteins SREBP-1c and fatty acid synthase. EF-2001 treatment increased the levels of adipose triglyceride lipase and monoacylglycerol during lipase enzyme activation, which, when increased, contributed to increased liver lipolysis. In conclusion, EF-2001 inhibits OA-induced FL83B hepatic lipid accumulation and HFD-induced hepatic steatosis in rats through the AMPK signaling pathway.
POSS and SSQ Materials in Dental Applications: Recent Advances and Future Outlooks
Authors: Ozimek Jan , Łukaszewska Izabela , Pielichowski Krzysztof
Published: February 2023

Recently, silsesquioxanes (SSQ) and polyhedral oligomeric silsesquioxanes (POSS) have gained much interest in the area of biomaterials, mainly due to their intrinsic properties such as biocompatibility, complete non-toxicity, the ability to self-assemble and to form a porous structure, facilitating cell proliferation, creating a superhydrophobic surface, osteoinductivity, and ability to bind hydroxyapatite. All the above has resulted in new developments in medicine. However, the application of POSS-containing materials in dentistry is still at initial stage and deserves a systematic description to ensure future development. Significant problems, such as reduction of polymerization shrinkage, water absorption, hydrolysis rate, poor adhesion and strength, unsatisfactory biocompatibility, and corrosion resistance of dental alloys, can be addressed by the design of multifunctional POSS-containing materials. Because of the presence of silsesquioxanes, it is possible to obtain smart materials that allow the stimulation of phosphates deposition and repairing of micro-cracks in dental fillings. Hybrid composites result in materials exhibiting shape memory, as well as antibacterial, self-cleaning, and self-healing properties. Moreover, introducing POSS into polymer matrix allows for materials for bone reconstruction, and wound healing. This review covers the recent developments in the field of POSS application in dental materials and gives the future perspectives within a promising field of biomedical material science and chemical engineering.
The Antigenic Membrane Protein (Amp) of Rice Orange Leaf Phytoplasma Suppresses Host Defenses and Is Involved in Pathogenicity
Authors: Wang Zhiyi , Yang Xiaorong , Zhou Siqi , Zhang Xishan , Zhu Yingzhi , Chen Biao , Huang Xiuqin , Yang Xin , Zhou Guohui , Zhang Tong
Published: February 2023

Phytoplasmas are uncultivable, phloem-limited, phytopathogenic bacteria that represent a major threat to agriculture worldwide. Phytoplasma membrane proteins are in direct contact with hosts and presumably play a crucial role in phytoplasma spread within the plant as well as by the insect vector. Three highly abundant types of immunodominant membrane proteins (IDP) have been identified within the phytoplasmas: immunodominant membrane protein (Imp), immunodominant membrane protein A (IdpA), and antigenic membrane protein (Amp). Although recent results indicate that Amp is involved in host specificity by interacting with host proteins such as actin, little is known about the pathogenicity of IDP in plants. In this study, we identified an antigenic membrane protein (Amp) of rice orange leaf phytoplasma (ROLP), which interacts with the actin of its vector. In addition, we generated Amp-transgenic lines of rice and expressed Amp in tobacco leaves by the potato virus X (PVX) expression system. Our results showed that the Amp of ROLP can induce the accumulation of ROLP and PVX in rice and tobacco plants, respectively. Although several studies have reported interactions between major phytoplasma antigenic membrane protein (Amp) and insect vector proteins, this example demonstrates that Amp protein can not only interact with the actin protein of its insect vector but can also directly inhibit host defense responses to promote the infection. The function of ROLP Amp provides new insights into the phytoplasma-host interaction.
Intracellular Nitric Oxide and cAMP Are Involved in Cellulolytic Enzyme Production in Neurospora crassa
Authors: Yu Nan-Nan , Ketya Wirinthip , Park Gyungsoon
Published: February 2023

Although molecular regulation of cellulolytic enzyme production in filamentous fungi has been actively explored, the underlying signaling processes in fungal cells are still not clearly understood. In this study, the molecular signaling mechanism regulating cellulase production in Neurospora crassa was investigated. We found that the transcription and extracellular cellulolytic activity of four cellulolytic enzymes (cbh1, gh6-2, gh5-1, and gh3-4) increased in Avicel (microcrystalline cellulose) medium. Intracellular nitric oxide (NO) and reactive oxygen species (ROS) detected by fluorescent dyes were observed in larger areas of fungal hyphae grown in Avicel medium compared to those grown in glucose medium. The transcription of the four cellulolytic enzyme genes in fungal hyphae grown in Avicel medium was significantly decreased and increased after NO was intracellularly removed and extracellularly added, respectively. Furthermore, we found that the cyclic AMP (cAMP) level in fungal cells was significantly decreased after intracellular NO removal, and the addition of cAMP could enhance cellulolytic enzyme activity. Taken together, our data suggest that the increase in intracellular NO in response to cellulose in media may have promoted the transcription of cellulolytic enzymes and participated in the elevation of intracellular cAMP, eventually leading to improved extracellular cellulolytic enzyme activity.
Pore-Forming Proteins: From Pore Assembly to Structure by Quantitative Single-Molecule Imaging
Authors: Margheritis Eleonora , Kappelhoff Shirin , Cosentino Katia
Published: February 2023

Pore-forming proteins (PFPs) play a central role in many biological processes related to infection, immunity, cancer, and neurodegeneration. A common feature of PFPs is their ability to form pores that disrupt the membrane permeability barrier and ion homeostasis and generally induce cell death. Some PFPs are part of the genetically encoded machinery of eukaryotic cells that are activated against infection by pathogens or in physiological programs to carry out regulated cell death. PFPs organize into supramolecular transmembrane complexes that perforate membranes through a multistep process involving membrane insertion, protein oligomerization, and finally pore formation. However, the exact mechanism of pore formation varies from PFP to PFP, resulting in different pore structures with different functionalities. Here, we review recent insights into the molecular mechanisms by which PFPs permeabilize membranes and recent methodological advances in their characterization in artificial and cellular membranes. In particular, we focus on single-molecule imaging techniques as powerful tools to unravel the molecular mechanistic details of pore assembly that are often obscured by ensemble measurements, and to determine pore structure and functionality. Uncovering the mechanistic elements of pore formation is critical for understanding the physiological role of PFPs and developing therapeutic approaches.
Evidence for Extensive Duplication and Subfunctionalization of FCRL6 in Armadillo (Dasypus novemcinctus)
Authors: Matos Maria Carolina , Pinheiro Ana , Davis Randall S. , Esteves Pedro J.
Published: February 2023

The control of infections by the vertebrate adaptive immune system requires careful modulation to optimize defense and minimize harm to the host. The Fc receptor-like (FCRL) genes encode immunoregulatory molecules homologous to the receptors for the Fc portion of immunoglobulin (FCR). To date, nine different genes (FCRL1–6, FCRLA, FCRLB and FCRLS) have been identified in mammalian organisms. FCRL6 is located at a separate chromosomal position from the FCRL1-5 locus, has conserved synteny in mammals and is situated between the SLAMF8 and DUSP23 genes. Here, we show that this three gene block underwent repeated duplication in Dasypus novemcinctus (nine-banded armadillo) resulting in six FCRL6 copies, of which five appear functional. Among 21 mammalian genomes analyzed, this expansion was unique to D. novemcinctus. Ig-like domains that derive from the five clustered FCRL6 functional gene copies show high structural conservation and sequence identity. However, the presence of multiple non-synonymous amino acid changes that would diversify individual receptor function has led to the hypothesis that FCRL6 endured subfunctionalization during evolution in D. novemcinctus. Interestingly, D. novemcinctus is noteworthy for its natural resistance to the Mycobacterium leprae pathogen that causes leprosy. Because FCRL6 is chiefly expressed by cytotoxic T and NK cells, which are important in cellular defense responses against M. leprae, we speculate that FCRL6 subfunctionalization could be relevant for the adaptation of D. novemcinctus to leprosy. These findings highlight the species-specific diversification of FCRL family members and the genetic complexity underlying evolving multigene families critical for modulating adaptive immune protection.
Targeted Delivery of Butyrate Improves Glucose Homeostasis, Reduces Hepatic Lipid Accumulation and Inflammation in db/db Mice
Authors: Pedersen Signe Schultz , Prause Michala , Sørensen Christina , Størling Joachim , Moritz Thomas , Mariño Eliana , Billestrup Nils
Published: February 2023

Butyrate produced by the gut microbiota has beneficial effects on metabolism and inflammation. Butyrate-producing bacteria are supported by diets with a high fiber content, such as high-amylose maize starch (HAMS). We investigated the effects of HAMS- and butyrylated HAMS (HAMSB)-supplemented diets on glucose metabolism and inflammation in diabetic db/db mice. Mice fed HAMSB had 8-fold higher fecal butyrate concentration compared to control diet-fed mice. Weekly analysis of fasting blood glucose showed a significant reduction in HAMSB-fed mice when the area under the curve for all five weeks was analyzed. Following treatment, fasting glucose and insulin analysis showed increased homeostatic model assessment (HOMA) insulin sensitivity in the HAMSB-fed mice. Glucose-stimulated insulin release from isolated islets did not differ between the groups, while insulin content was increased by 36% in islets of the HAMSB-fed mice. Expression of insulin 2 was also significantly increased in islets of the HAMSB-fed mice, while no difference in expression of insulin 1, pancreatic and duodenal homeobox 1, MAF bZIP transcription factor A and urocortin 3 between the groups was observed. Hepatic triglycerides in the livers of the HAMSB-fed mice were significantly reduced. Finally, mRNA markers of inflammation in liver and adipose tissue were reduced in mice fed HAMSB. These findings suggest that HAMSB-supplemented diet improves glucose metabolism in the db/db mice, and reduces inflammation in insulin-sensitive tissues.
Delayed TBI-Induced Neuronal Death in the Ipsilateral Hippocampus and Behavioral Deficits in Rats: Influence of Corticosterone-Dependent Survivorship Bias?
Authors: Komoltsev Ilia , Shalneva Daria , Kostyunina Olga , Volkova Aleksandra , Frankevich Stepan , Shirobokova Natalia , Belikova Anastasia , Balan Sofia , Chizhova Olesya , Salyp Olga , Bashkatova Daria , Kostrukov Pavel , Soloveva Aleksandra , Novikova Margarita , Gulyaeva Natalia
Published: February 2023

Acute and chronic corticosterone (CS) elevations after traumatic brain injury (TBI) may be involved in distant hippocampal damage and the development of late posttraumatic behavioral pathology. CS-dependent behavioral and morphological changes were studied 3 months after TBI induced by lateral fluid percussion in 51 male Sprague–Dawley rats. CS was measured in the background 3 and 7 days and 1, 2 and 3 months after TBI. Tests including open field, elevated plus maze, object location, new object recognition tests (NORT) and Barnes maze with reversal learning were used to assess behavioral changes in acute and late TBI periods. The elevation of CS on day 3 after TBI was accompanied by early CS-dependent objective memory impairments detected in NORT. Blood CS levels > 860 nmol/L predicted delayed mortality with an accuracy of 0.947. Ipsilateral neuronal loss in the hippocampal dentate gyrus, microgliosis in the contralateral dentate gyrus and bilateral thinning of hippocampal cell layers as well as delayed spatial memory deficits in the Barnes maze were revealed 3 months after TBI. Because only animals with moderate but not severe posttraumatic CS elevation survived, we suggest that moderate late posttraumatic morphological and behavioral deficits may be at least partially masked by CS-dependent survivorship bias.
Circular RNA- and microRNA-Mediated Post-Transcriptional Regulation of Preadipocyte Differentiation in Adipogenesis: From Expression Profiling to Signaling Pathway
Authors: Huang Chiu-Jung , Choo Kong Bung
Published: February 2023

Adipogenesis is an indispensable cellular process that involves preadipocyte differentiation into mature adipocyte. Dysregulated adipogenesis contributes to obesity, diabetes, vascular conditions and cancer-associated cachexia. This review aims to elucidate the mechanistic details on how circular RNA (circRNA) and microRNA (miRNA) modulate post-transcriptional expression of targeted mRNA and the impacted downstream signaling and biochemical pathways in adipogenesis. Twelve adipocyte circRNA profiling and comparative datasets from seven species are analyzed using bioinformatics tools and interrogations of public circRNA databases. Twenty-three circRNAs are identified in the literature that are common to two or more of the adipose tissue datasets in different species; these are novel circRNAs that have not been reported in the literature in relation to adipogenesis. Four complete circRNA–miRNA-mediated modulatory pathways are constructed via integration of experimentally validated circRNA–miRNA–mRNA interactions and the downstream signaling and biochemical pathways involved in preadipocyte differentiation via the PPARγ/C/EBPα gateway. Despite the diverse mode of modulation, bioinformatics analysis shows that the circRNA–miRNA–mRNA interacting seed sequences are conserved across species, supporting mandatory regulatory functions in adipogenesis. Understanding the diverse modes of post-transcriptional regulation of adipogenesis may contribute to the development of novel diagnostic and therapeutic strategies for adipogenesis-associated diseases and in improving meat quality in the livestock industries.
SARS-CoV-2 Transplacental Transmission: A Rare Occurrence? An Overview of the Protective Role of the Placenta
Authors: Wong Yin Ping , Tan Geok Chin , Khong T. Yee
Published: February 2023

The outbreak of the coronavirus disease 2019 (COVID-19) pandemic, caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global public health crisis, causing substantial concern especially to the pregnant population. Pregnant women infected with SARS-CoV-2 are at greater risk of devastating pregnancy complications such as premature delivery and stillbirth. Irrespective of the emerging reported cases of neonatal COVID-19, reassuringly, confirmatory evidence of vertical transmission is still lacking. The protective role of the placenta in limiting in utero spread of virus to the developing fetus is intriguing. The short- and long-term impact of maternal COVID-19 infection in the newborn remains an unresolved question. In this review, we explore the recent evidence of SARS-CoV-2 vertical transmission, cell-entry pathways, placental responses towards SARS-CoV-2 infection, and its potential effects on the offspring. We further discuss how the placenta serves as a defensive front against SARS-CoV-2 by exerting various cellular and molecular defense pathways. A better understanding of the placental barrier, immune defense, and modulation strategies involved in restricting transplacental transmission may provide valuable insights for future development of antiviral and immunomodulatory therapies to improve pregnancy outcomes.
Dietary Fatty Acids and Inflammation: Focus on the n-6 Series
Authors: Poli Andrea , Agostoni Carlo , Visioli Francesco
Published: February 2023

Among the polyunsaturated fatty acids (PUFAs), those belonging to the n-3 (or ω3) series, i.e., alpha-linolenic (ALA), eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids have been studied for decades from a pharma-nutritional viewpoint, namely in relation to cardiovascular health. More recent research is focusing on n-6 PUFAs, e.g., linoleic acid (LA), whose levels of consumption are much higher than those of n-3 and that cannot be used “pharmacologically”. Perhaps because of this, the biological actions of n-6 PUFAs have not been investigated in details as those of their n-3 counterparts. However, an increasing body of evidence underscores their healthful actions on the cardiovascular system. Among the critiques to n-6 PUFAs and, particularly, LA there is the fact that they are precursors of pro-inflammatory eicosanoids. Hence, the hypothesis posits that we should reduce their intakes precisely to avoid increasing systemic, low-grade inflammation, i.e., one of the major etiological agents in degenerative diseases. In this narrative review, we address the issue of whether n-6 PUFAs are indeed pro-inflammatory, we discuss the most recent evidence of their role(s) in human health and prognosis, and we conclude that adequate intakes of n-6 fatty acids are associated with better cardiovascular health and child development.
Simple In Vitro 18O Labeling for Improved Mass Spectrometry-Based Drug Metabolites Identification: Deep Drug Metabolism Study
Authors: Tupertsev Boris , Osipenko Sergey , Kireev Albert , Nikolaev Eugene , Kostyukevich Yury
Published: February 2023

The identification of drug metabolites formed with different in vitro systems by HPLC-MS is a standard step in preclinical research. In vitro systems allow modeling of real metabolic pathways of a drug candidate. Despite the emergence of various software and databases, identification of compounds is still a complex task. Measurement of the accurate mass, correlation of chromatographic retention times and fragmentation spectra are often insufficient for identification of compounds especially in the absence of reference materials. Metabolites can “slip under the nose”, since it is often not possible to reliably confirm that a signal belongs to a metabolite and not to other compounds in complex systems. Isotope labeling has proved to be a tool that aids in small molecule identification. The introduction of heavy isotopes is done with isotope exchange reactions or with complicated synthetic schemes. Here, we present an approach based on the biocatalytic insertion of oxygen-18 isotope under the action of liver microsomes enzymes in the presence of 18O2. Using the local anesthetic bupivacaine as an example, more than 20 previously unknown metabolites were reliably discovered and annotated in the absence of the reference materials. In combination with high-resolution mass spectrometry and modern methods of mass spectrometric metabolism data processing, we demonstrated the ability of the proposed approach to increase the degree of confidence in interpretating metabolism data.
The Landscape of Circular RNAs in Cardiovascular Diseases
Authors: Long Qi , Lv Bingjie , Jiang Shijiu , Lin Jibin
Published: February 2023

Cardiovascular disease (CVD) remains the leading cause of mortality globally. Circular RNAs (circRNAs) have attracted extensive attention for their roles in the physiological and pathological processes of various cardiovascular diseases (CVDs). In this review, we briefly describe the current understanding of circRNA biogenesis and functions and summarize recent significant findings regarding the roles of circRNAs in CVDs. These results provide a new theoretical basis for diagnosing and treating CVDs.
Multiparity and Aging Impact Chondrogenic and Osteogenic Potential at Symphyseal Enthesis: New Insights into Interpubic Joint Remodeling
Authors: de Sousa Lizandra Maia , Castelucci Bianca Gazieri , Suarez Paula Andrea Saenz , Damas Ingrid Iara , Mariano Fernanda Viviane , Joazeiro Paulo Pinto , Consonni Sílvio Roberto
Published: February 2023

Pregnancy and childbirth cause adaptations to the birth canal to allow for delivery and fast recovery. To accommodate delivery through the birth canal, the pubic symphysis undergoes changes that lead to the interpubic ligament (IpL) and enthesis formation in primiparous mice. However, successive deliveries influence joint recovery. We aimed to understand tissue morphology and chondrogenic and osteogenic potential at symphyseal enthesis during pregnancy and postpartum in primiparous and multiparous senescent female mice. Morphological and molecular differences were found at the symphyseal enthesis among the study groups. Despite the apparent incapacity to restore cartilage in multiparous senescent animals, the symphyseal enthesis cells are active. However, these cells have reduced expression of chondrogenic and osteogenic markers and are immersed in densely packed collagen fibers contiguous to the persistent IpL. These findings may indicate alterations of key molecules in the progenitor cell population maintenance of the chondrocytic and osteogenic lineages at the symphyseal enthesis in multiparous senescent animals, possibly compromising the mouse joint histoarchitecture recovery. This sheds light on the distention of the birth canal and the pelvic floor that may play a role in pubic symphysis diastasis (PSD) and pelvic organ prolapse (POP), both in orthopedic and urogynecological practice in women.
A Closer Look at Opioid-Induced Adrenal Insufficiency: A Narrative Review
Authors: Coluzzi Flaminia , LeQuang Jo Ann K. , Sciacchitano Salvatore , Scerpa Maria Sole , Rocco Monica , Pergolizzi Joseph
Published: February 2023

Among several opioid-associated endocrinopathies, opioid-associated adrenal insufficiency (OIAI) is both common and not well understood by most clinicians, particularly those outside of endocrine specialization. OIAI is secondary to long-term opioid use and differs from primary adrenal insufficiency. Beyond chronic opioid use, risk factors for OIAI are not well known. OIAI can be diagnosed by a variety of tests, such as the morning cortisol test, but cutoff values are not well established and it is estimated that only about 10% of patients with OIAI will ever be properly diagnosed. This may be dangerous, as OIAI can lead to a potentially life-threatening adrenal crisis. OIAI can be treated and for patients who must continue opioid therapy, it can be clinically managed. OIAI resolves with opioid cessation. Better guidance for diagnosis and treatment is urgently needed, particularly in light of the fact that 5% of the United States population has a prescription for chronic opioid therapy.
Organizational Principles of the Centrifugal Projections to the Olfactory Bulb
Authors: Wang Li , Li Xiangning , Chen Fengming , Liu Qing , Xu Fuqiang
Published: February 2023

Centrifugal projections in the olfactory system are critical to both olfactory processing and behavior. The olfactory bulb (OB), the first relay station in odor processing, receives a substantial number of centrifugal inputs from the central brain regions. However, the anatomical organization of these centrifugal connections has not been fully elucidated, especially for the excitatory projection neurons of the OB, the mitral/tufted cells (M/TCs). Using rabies virus-mediated retrograde monosynaptic tracing in Thy1-Cre mice, we identified that the three most prominent inputs of the M/TCs came from the anterior olfactory nucleus (AON), the piriform cortex (PC), and the basal forebrain (BF), similar to the granule cells (GCs), the most abundant population of inhibitory interneurons in the OB. However, M/TCs received proportionally less input from the primary olfactory cortical areas, including the AON and PC, but more input from the BF and contralateral brain regions than GCs. Unlike organizationally distinct inputs from the primary olfactory cortical areas to these two types of OB neurons, inputs from the BF were organized similarly. Furthermore, individual BF cholinergic neurons innervated multiple layers of the OB, forming synapses on both M/TCs and GCs. Taken together, our results indicate that the centrifugal projections to different types of OB neurons may provide complementary and coordinated strategies in olfactory processing and behavior.
Pyodermitis during Nivolumab Treatment for Non-Small Cell Lung Cancer: A Case Report and Review of the Literature
Authors: Cosio Terenzio , Coniglione Filadelfo , Flaminio Valeria , Gaziano Roberta , Coletta Deborah , Petruccelli Rosalba , Dika Emi , Bianchi Luca , Campione Elena
Published: February 2023

Immunotherapy in oncology is replacing traditional therapies due to it specific action and limited side effects. Despite the high efficacy of immunotherapy, side effects such as bacterial infection have been reported. Bacterial skin and soft tissue infections represent one of the most important differential diagnoses in patients presenting with reddened and swollen skin and soft tissue. Among these infections, cellulitis (phlegmon) and abscesses are the most frequent. In most cases, these infections occur locally with possible contiguous spread, or as a multifocal manifestation, especially in immunocompromised patients. Herein, we report a case of pyodermitis in an immunocompromised district in a patient treated with nivolumab for non-small cell lung cancer. A 64-year-old, smoker male patient showed cutaneous lesions at a different evolution level in the left arm, all in a tattooed area, with one phlegmon and two ulcerated lesions. Microbiological cultures and gram staining revealed an infection caused by a methicillin-susceptible but erythromycin-resistant (ER-R), clindamycin-resistant (CL-R), and gentamicin-resistant (GE-R) Staphylococcus aureus strain. Despite immunotherapy becoming a milestone in oncologic treatment, more than the spectrum of immune-mediated toxicities of these agents needs to be investigated. This report highlights the importance of considering lifestyle and cutaneous background before starting immunotherapy for cancer treatment, with an emphasis on pharmacogenomics and the possibility of modified skin microbiota predisposing to cutaneous infections in patients treated with PD-1 inhibitors.
Gamma-Aminobutyric Acid Signaling in Damage Response, Metabolism, and Disease
Authors: Kim Kimyeong , Yoon Haejin
Published: February 2023

Gamma-aminobutyric acid (GABA) plays a crucial role in signal transduction and can function as a neurotransmitter. Although many studies have been conducted on GABA in brain biology, the cellular function and physiological relevance of GABA in other metabolic organs remain unclear. Here, we will discuss recent advances in understanding GABA metabolism with a focus on its biosynthesis and cellular functions in other organs. The mechanisms of GABA in liver biology and disease have revealed new ways to link the biosynthesis of GABA to its cellular function. By reviewing what is known about the distinct effects of GABA and GABA-mediated metabolites in physiological pathways, we provide a framework for understanding newly identified targets regulating the damage response, with implications for ameliorating metabolic diseases. With this review, we suggest that further research is necessary to develop GABA’s beneficial and toxic effects on metabolic disease progression.
Hydrophobin Gene Cmhyd4 Negatively Regulates Fruiting Body Development in Edible Fungi Cordyceps militaris
Authors: Li Xiao , Liu Mengqian , Dong Caihong
Published: February 2023

A deep understanding of the mechanism of fruiting body development is important for mushroom breeding and cultivation. Hydrophobins, small proteins exclusively secreted by fungi, have been proven to regulate the fruiting body development in many macro fungi. In this study, the hydrophobin gene Cmhyd4 was revealed to negatively regulate the fruiting body development in Cordyceps militaris, a famous edible and medicinal mushroom. Neither the overexpression nor the deletion of Cmhyd4 affected the mycelial growth rate, the hydrophobicity of the mycelia and conidia, or the conidial virulence on silkworm pupae. There was also no difference between the micromorphology of the hyphae and conidia in WT and ΔCmhyd4 strains observed by SEM. However, the ΔCmhyd4 strain showed thicker aerial mycelia in darkness and quicker growth rates under abiotic stress than the WT strain. The deletion of Cmhyd4 could promote conidia production and increase the contents of carotenoid and adenosine. The biological efficiency of the fruiting body was remarkably increased in the ΔCmhyd4 strain compared with the WT strain by improving the fruiting body density, not the height. It was indicated that Cmhyd4 played a negative role in fruiting body development. These results revealed that the diverse negative roles and regulatory effects of Cmhyd4 were totally different from those of Cmhyd1 in C. militaris and provided insights into the developmental regulatory mechanism of C. militaris and candidate genes for C. militaris strain breeding.
Long-Term Results of Adjunct Autologous Platelet-Rich Plasma in Lamellar Macular Hole Surgery Showing Lasting Restoration of Foveal Anatomy
Authors: Hagenau Felix , Osterode Elisa V. , Klaas Julian E. , Vogt Denise , Keidel Leonie F. , Schworm Benedikt , Siedlecki Jakob , Mayer Wolfgang J. , Kreutzer Thomas C. , Priglinger Siegfried G.
Published: February 2023

The aim of this study was to evaluate the long-time results of highly concentrated autologous platelet-rich plasma (PRP) used as an adjunct in lamellar macular hole (LMH) surgery. Nineteen eyes of nineteen patients with progressive LMH were enrolled in this interventional case series, on which 23/25-gauge pars plana vitrectomy was performed and 0.1 mL of highly concentrated autologous platelet-rich plasma was applied under air tamponade. Posterior vitreous detachment was induced, and the peeling of tractive epiretinal membranes, whenever present, was performed. In cases of phakic lens status, combined surgery was carried out. Postoperatively, all patients were instructed to remain in a supine position for the first two postoperative hours. Best-corrected visual acuity (BCVA) testing, microperimetry, and spectral domain optical coherence tomography (SD-OCT) were carried out preoperatively and at minimum 6 months (in median 12 months) postoperatively. Foveal configuration was postoperatively restored in 19 of 19 patients. Two patients who had not undergone ILM peeling showed a recurring defect at 6-month follow-up. Best-corrected visual acuity improved significantly from 0.29 ± 0.08 to 0.14 ± 0.13 logMAR (p = 0.028, Wilcoxon signed-rank test). Microperimetry remained unchanged (23.38 ± 2.53 preoperatively; 23.0 ± 2.49 dB postoperatively; p = 0.67). No patients experienced vision loss after surgery, and no significant intra- or postoperative complications were observed. Using PRP as an adjunct in macular hole surgery significantly improves morphological and functional outcomes. Additionally, it might be an effective prophylaxis to further progression and also the formation of a secondary full-thickness macular hole. The results of this study might contribute to a paradigm shift in macular hole surgery towards early intervention.
dCas9-BE3 and dCas12a-BE3 Systems Mediated Base Editing in Kiwifruit Canker Causal Agent Pseudomonas syringae pv. actinidiae
Authors: Liu Bo , Song Wenpeng , Wang Linchao , Wu Yantao , Xu Xiaoting , Niu Xiangli , Huang Shengxiong , Liu Yongsheng , Tang Wei
Published: February 2023

Pseudomonas syringae pv. actinidiae (Psa) causes bacterial canker of kiwifruit with heavy economic losses. However, little is known about the pathogenic genes of Psa. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas-mediated genome editing technology has dramatically facilitated the characterization of gene function in various organisms. However, CRISPR genome editing could not be efficiently employed in Psa due to lacking homologous recombination repair. The base editor (BE) system, which depends on CRISPR/Cas, directly induces single nucleoside C to T without homology recombination repair. Here, we used dCas9-BE3 and dCas12a-BE3 systems to create substitutions of C to T and to convert CAG/CAA/CGA codons to stop codons (TAG/TAA/TGA) in Psa. The dCas9-BE3 system-induced single C-to-T conversion frequency of 3 to 10 base positions ranged from 0% to 100%, with a mean of 77%. The dCas12a-BE3 system-induced single C-to-T conversion frequency of 8 to 14 base positions in the spacer region ranged from 0% to 100%, with a mean of 76%. In addition, a relatively saturated Psa gene knockout system covering more than 95% of genes was developed based on dCas9-BE3 and dCas12a-BE3, which could knock out two or three genes at the same time in the Psa genome. We also found that hopF2 and hopAO2 were involved in the Psa virulence of kiwifruit. The HopF2 effector can potentially interact with proteins such as RIN, MKK5, and BAK1, while the HopAO2 effector can potentially interact with the EFR protein to reduce the host’s immune response. In conclusion, for the first time, we established a PSA.AH.01 gene knockout library that may promote research on elucidating the gene function and pathogenesis of Psa.
Plasma Apolipoprotein Concentrations Are Highly Altered in Severe Intensive Care Unit COVID-19 Patients: Preliminary Results from the LIPICOR Cohort Study
Authors: Begue Floran , Chemello Kévin , Veeren Bryan , Lortat-Jacob Brice , Tran-Dinh Alexy , Zappella Nathalie , Snauwaert Aurelie , Robert Tiphaine , Rondeau Philippe , Lagrange-Xelot Marie , Montravers Philippe , Couret David , Tanaka Sébastien , Meilhac Olivier
Published: February 2023

SARS-CoV-2 infection goes beyond acute pneumonia, as it also impacts lipid metabolism. Decreased HDL-C and LDL-C levels have been reported in patients with COVID-19. The lipid profile is a less robust biochemical marker than apolipoproteins, components of lipoproteins. However, the association of apolipoprotein levels during COVID-19 is not well described and understood. The objective of our study is to measure plasma levels of 14 apolipoproteins in patients with COVID-19 and to evaluate the relationships between apolipoprotein levels, severity factors and patient outcomes. From November to March 2021, 44 patients were recruited on admission to the intensive care unit because of COVID-19. Fourteen apolipoproteins and LCAT were measured by LC-MS/MS in plasma of 44 COVID-19 patients on admission to the ICU and 44 healthy control subjects. Absolute apolipoprotein concentrations were compared between COVID-19 patients and controls. Plasma apolipoproteins (Apo) A (I, II, IV), C(I, II), D, H, J and M and LCAT were lower in COVID-19 patients, whereas Apo E was higher. COVID-19 severity factors such as PaO2/FiO2 ratio, SO-FA score and CRP were correlated with certain apolipoproteins. Lower Apo B100 and LCAT levels were observed in non-survivors of COVID-19 versus survivors. To conclude, in this study, lipid and apolipoprotein profiles are altered in COVID-19 patients. Low Apo B100 and LCAT levels may be predictive of non-survival in COVID-19 patients.
MiR-146a in ALS: Contribution to Early Peripheral Nerve Degeneration and Relevance as Disease Biomarker
Authors: Giagnorio Eleonora , Malacarne Claudia , Cavalcante Paola , Scandiffio Letizia , Cattaneo Marco , Pensato Viviana , Gellera Cinzia , Riva Nilo , Quattrini Angelo , Dalla Bella Eleonora , Lauria Giuseppe , Mantegazza Renato , Bonanno Silvia , Marcuzzo Stefania
Published: February 2023

Amyotrophic lateral sclerosis (ALS) is characterized by the progressive, irreversible loss of upper and lower motor neurons (UMNs, LMNs). MN axonal dysfunctions are emerging as relevant pathogenic events since the early ALS stages. However, the exact molecular mechanisms leading to MN axon degeneration in ALS still need to be clarified. MicroRNA (miRNA) dysregulation plays a critical role in the pathogenesis of neuromuscular diseases. These molecules represent promising biomarkers for these conditions since their expression in body fluids consistently reflects distinct pathophysiological states. Mir-146a has been reported to modulate the expression of the NFL gene, encoding the light chain of the neurofilament (NFL) protein, a recognized biomarker for ALS. Here, we analyzed miR-146a and Nfl expression in the sciatic nerve of G93A-SOD1 ALS mice during disease progression. The miRNA was also analyzed in the serum of affected mice and human patients, the last stratified relying on the predominant UMN or LMN clinical signs. We revealed a significant miR-146a increase and Nfl expression decrease in G93A-SOD1 peripheral nerve. In the serum of both ALS mice and human patients, the miRNA levels were reduced, discriminating UMN-predominant patients from the LMN ones. Our findings suggest a miR-146a contribution to peripheral axon impairment and its potential role as a diagnostic and prognostic biomarker for ALS.
Paclitaxel—A Valuable Tool for Inducing Visceral Pain in Preclinical Testing?
Authors: Andrei Corina , Zanfirescu Anca , Mihai Dragoș Paul , Negreș Simona
Published: February 2023

Visceral pain is a unique clinical entity that lacks an effective and safe treatment. Proper preclinical models are essential for assessing new drugs developed for the treatment of this pathology. Few studies report that paclitaxel, an antineoplastic agent, can be used to induce visceral pain in laboratory animals. Our purpose was to investigate the reproducibility of these studies and to develop an animal method that would allow assessing consistent visceral pain. In this study, we used four doses of paclitaxel (3 mg × kg−1; 5 mg × kg−1; 10 mg × kg−1 and 15 mg × kg−1). Visceral pain was evaluated using a scale of abdominal pain immediately after the administration of a single dose of paclitaxel to rats. Tactile and thermal hypersensitivity were assessed using von Frey filaments and the tail flick test initially, at 24 h and 48 h after administration. Rats experienced visceral pain and mechanical and thermal hypersensitivity 24 h after the administration of paclitaxel. The intensity of the pain was increased in a dose-dependent manner with the highest intensity of effect being observed after the administration of a dose of 15 mg × kg−1. Paclitaxel induces visceral pain. The dosage varies depending on the employed strain of rat. This method allows for assessing the efficacy of analgesics to be useful against visceral pain if the paclitaxel dose is adjusted accordingly to the animal strain.
Modern Bronchoscopic Treatment Options for Patients with Chronic Bronchitis
Authors: Mayr Anna Katharina , Valipour Arschang
Published: February 2023

Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of death worldwide and has a large impact on a patient’s quality of life due to its wide range of symptoms and comorbidities. There are known to be different phenotypes in COPD with various extents on the burden of the disease and its prognosis. Chronic bronchitis with persistent cough and mucus production is regarded as one of the main symptoms of COPD with tremendous effects on subjectively reported symptom burden and frequency of exacerbations. Exacerbations in turn are known to have an impact on disease progression and increase health care costs. Modern bronchoscopic treatment options are currently under investigation targeting the problem of chronic bronchitis and frequent exacerbations. This review summarizes the existing literature about these modern interventional treatment options and provides perspectives on upcoming studies.
Is There Evidence for Intelligence-by-Conscientiousness Interaction in the Prediction of Change in School Grades from Age 11 to 15 Years?
Authors: Hufer-Thamm Anke , Starr Alexandra , Steinmayr Ricarda
Published: February 2023

Fluid intelligence and conscientiousness are the most important predictors of school grades. In addition to this main effect, researchers have suggested that the two traits might also interact with each other in the prediction of school success. A synergistic and a compensatory form of interaction have been suggested, but past evidence has been mixed so far. Most previous studies on this subject have been cross-sectional and many of them focused on older adolescents or adults in upper secondary school or university. We thus investigated the main and interaction effects of fluid intelligence and conscientiousness on school grades in math and German in a longitudinal sample of 1043 German students from age 11 to 15 years. Results from latent growth curve models with latent interaction terms showed a small compensatory interaction effect for baseline levels of math grades but not for their development. No interaction effect was found for German grades. These findings are discussed against the background that (synergistic) interaction effects between intelligence and conscientiousness might be more relevant in older students from higher secondary school or university context.
Natural Flora Is Indiscriminately Hosting High Loads of Generalist Fungal Pathogen Colletotrichum gloeosporioides Complex over Forest Niches, Vegetation Strata and Elevation Gradient
Authors: Dentika Pauline , Gumbau Margot , Ozier-Lafontaine Harry , Penet Laurent
Published: February 2023

Crop pathogenic fungi may originate from reservoir pools including wild vegetation surrounding fields, and it is thus important to characterize any potential source of pathogens. We therefore investigated natural vegetation’s potential for hosting a widespread pathogenic group, Colletotrichum gloeosporioides species complex. We stratified sampling in different forest environments and natural vegetation strata to determine whether the fungi were found preferentially in specific niches and areas. We found that the fungi complex was fairly broadly distributed in the wild flora, with high prevalence in every study environment and stratum. Some significant variation in prevalence nevertheless occurred and was possibly associated with fungal growth conditions (more humid areas had greater prevalence levels while drier places had slightly lower presence). Results also highlighted potential differences in disease effects of strains between strata components of study flora, suggesting that while natural vegetation is a highly probable source of inoculums for local crops nearby, differences in aggressiveness between vegetation strata might also lead to differential impact on cultivated crops.
Comparison of Multi-locus Genotypes Detected in Aspergillus fumigatus Isolated from COVID Associated Pulmonary Aspergillosis (CAPA) and from Other Clinical and Environmental Sources
Authors: Morais Susana , Toscano Cristina , Simões Helena , Carpinteiro Dina , Viegas Carla , Veríssimo Cristina , Sabino Raquel
Published: February 2023

Background: Aspergillus fumigatus is a saprophytic fungus, ubiquitous in the environment and responsible for causing infections, some of them severe invasive infections. The high morbidity and mortality, together with the increasing burden of triazole-resistant isolates and the emergence of new risk groups, namely COVID-19 patients, have raised a crescent awareness of the need to better comprehend the dynamics of this fungus. The understanding of the epidemiology of this fungus, especially of CAPA isolates, allows a better understanding of the interactions of the fungus in the environment and the human body. Methods: In the present study, the M3 markers of the STRAf assay were used as a robust typing technique to understand the connection between CAPA isolates and isolates from different sources (environmental and clinical-human and animal). Results: Of 100 viable isolates that were analyzed, 85 genotypes were found, 77 of which were unique. Some isolates from different sources presented the same genotype. Microsatellite genotypes obtained from A. fumigatus isolates from COVID+ patients were all unique, not being found in any other isolates of the present study or even in other isolates deposited in a worldwide database; these same isolates were heterogeneously distributed among the other isolates. Conclusions: Isolates from CAPA patients revealed high heterogeneity of multi-locus genotypes. A genotype more commonly associated with COVID-19 infections does not appear to exist.
Six Additions to the Genus Periconia (Dothideomycetes: Periconiaceae) from Graminaceous Plants in China
Authors: Su Pengwei , Lu Zhenghua , Tian Whenhui , Chen Yanpeng , Maharachchikumbura Sajeewa S. N.
Published: February 2023

Periconia is a polyphyletic and asexual morphic genus within the family Periconiaceae (Pleosporales). The genus is characterized by a pale to dark brown stipe with an apical conidial head and ellipsoidal to oblong conidia. Species of Periconia are widely distributed throughout the world in various hosts, while most species are isolated from graminaceous plants. During our investigations of microfungal in Sichuan Province, China, 26 Periconia isolates were collected from a wide variety of graminaceous plants. These isolates corresponded to 11 species based on the examination of morphology and multi-locus phylogenetic analysis (SSU, ITS, LSU, TEF1, RPB2). This includes six new species (P. chengduensis, P. cynodontis, P. festucae, P. imperatae, P. penniseti, and P. spodiopogonis) and five new records (P. byssoides, P. chimonanthi, P. cookie, P. pseudobyssoides, and P. verrucosa). A comprehensive description and illustrations of the new species are provided and discussed with comparable taxa. These discoveries expand our knowledge of the species diversity of Periconia taxa in graminaceous plants in China.