bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of Brain-State Dynamics across Common Anesthetic Agents in Male Sprague-Dawley Rats
Authors: Ward-Flanagan Rachel , Lo Alto S. , Clement Elizabeth A. , Dickson Clayton T.
Published: March 2022

Anesthesia is a powerful tool in neuroscientific research, especially in sleep research where it has the experimental advantage of allowing surgical interventions that are ethically problematic in natural sleep. Yet, while it is well documented that different anesthetic agents produce a variety of brain states, and consequently have differential effects on a multitude of neurophysiological factors, these outcomes vary based on dosages, the animal species used, and the pharmacological mechanisms specific to each anesthetic agent. Thus, our aim was to conduct a controlled comparison of spontaneous electrophysiological dynamics at a surgical plane of anesthesia under six common research anesthetics using a ubiquitous animal model, the Sprague-Dawley rat. From this direct comparison, we also evaluated which anesthetic agents may serve as pharmacological proxies for the electrophysiological features and dynamics of unconscious states such as sleep and coma. We found that at a surgical plane, pentobarbital, isoflurane and propofol all produced a continuous pattern of burst-suppression activity, which is a neurophysiological state characteristically observed during coma. In contrast, ketamine-xylazine produced synchronized, slow-oscillatory activity, similar to that observed during slow-wave sleep. Notably, both urethane and chloral hydrate produced the spontaneous, cyclical alternations between forebrain activation (REM-like) and deactivation (non-REM-like) that are similar to those observed during natural sleep. Thus, choice of anesthesia, in conjunction with continuous brain state monitoring, are critical considerations in order to avoid brain-state confounds when conducting neurophysiological experiments.
Iron Metabolism in Aging and Age-Related Diseases
Authors: Tian Yao , Tian Yuanliangzi , Yuan Zhixiao , Zeng Yutian , Wang Shuai , Fan Xiaolan , Yang Deying , Yang Mingyao
Published: March 2022

Iron is a trace metal element necessary to maintain life and is also involved in a variety of biological processes. Aging refers to the natural life process in which the physiological functions of the various systems, organs, and tissues decline, affected by genetic and environmental factors. Therefore, it is imperative to investigate the relationship between iron metabolism and aging-related diseases, including neurodegenerative diseases. During aging, the accumulation of nonheme iron destroys the stability of the intracellular environment. The destruction of iron homeostasis can induce cell damage by producing hydroxyl free radicals, leading to mitochondrial dysfunction, brain aging, and even organismal aging. In this review, we have briefly summarized the role of the metabolic process of iron in the body, then discussed recent developments of iron metabolism in aging and age-related neurodegenerative diseases, and finally, explored some iron chelators as treatment strategies for those disorders. Understanding the roles of iron metabolism in aging and neurodegenerative diseases will fill the knowledge gap in the field. This review could provide new insights into the research on iron metabolism and age-related neurodegenerative diseases.
Effects Mediated by Dimethyl Fumarate on In Vitro Oligodendrocytes: Implications in Multiple Sclerosis
Authors: Guerriero Claudia , Puliatti Giulia , Di Marino Tamara , Tata Ada Maria
Published: March 2022

Background: Dimethyl fumarate (DMF) is a drug currently in use in oral therapy for the treatment of relapsing-remitting multiple sclerosis (RRMS) due to its immunomodulatory and neuroprotective effects. The mechanisms by which DMF exerts its therapeutic effects in MS and in particular its influence on the oligodendrocytes (OLs) survival or differentiation have not yet been fully understood. Methods: Characterization of Oli neu cells was performed by immunocytochemistry and RT-PCR. The effect of DMF on cell proliferation and morphology was assessed by MTT assay, trypan blue staining, RT-PCR and Western blot analysis. The antioxidant and anti-inflammatory properties of DMF were analysed by ROS detection through DCFDA staining and lipid content analysis by Oil Red O staining and TLC. Results: DMF has been observed to induce a slowdown of cell proliferation, favoring the oligodendrocyte lineage cells (OLCs) differentiation. DMF has an antioxidant effect and is able to modify the lipid content even after the LPS-mediated inflammatory stimulus in Oli neu cells. Conclusions: The results obtained confirm that DMF has anti-inflammatory and antioxidant effects also on Oli neu cells. Interestingly, it appears to promote the OLCs differentiation towards mature and potentially myelinating cells.
Differential Response of Wheat Rhizosphere Bacterial Community to Plant Variety and Fertilization
Authors: Cangioli Lisa , Mancini Marco , Napoli Marco , Fagorzi Camilla , Orlandini Simone , Vaccaro Francesca , Mengoni Alessio
Published: March 2022

The taxonomic assemblage and functions of the plant bacterial community are strongly influenced by soil and host plant genotype. Crop breeding, especially after the massive use of nitrogen fertilizers which led to varieties responding better to nitrogen fertilization, has implicitly modified the ability of the plant root to recruit an effective bacterial community. Among the priorities for harnessing the plant bacterial community, plant genotype-by-microbiome interactions are stirring attention. Here, we analyzed the effect of plant variety and fertilization on the rhizosphere bacterial community. In particular, we clarified the presence in the bacterial community of a varietal effect of N and P fertilization treatment. 16S rRNA gene amplicon sequence analysis of rhizospheric soil, collected from four wheat varieties grown under four N-P fertilization regimes, and quantification of functional bacterial genes involved in the nitrogen cycle (nifH; amoA; nirK and nosZ) were performed. Results showed that variety played the most important role and that treatments did not affect either bacterial community diversity or bacterial phyla abundance. Variety-specific response of rhizosphere bacterial community was detected, both in relation to taxa (Nitrospira) and metabolic functions. In particular, the changes related to amino acid and aerobic metabolism and abundance of genes involved in the nitrogen cycle (amoA and nosZ), suggested that plant variety may lead to functional changes in the cycling of the plant-assimilable nitrogen.
Control of Bacterial Diseases of Banana Using CRISPR/Cas-Based Gene Editing
Authors: Tripathi Leena , Ntui Valentine O. , Tripathi Jaindra N.
Published: March 2022

Banana is an important staple food crop and a source of income for smallholder farmers in about 150 tropical and sub-tropical countries. Several bacterial diseases, such as banana Xanthomonas wilt (BXW), blood, and moko disease, cause substantial impacts on banana production. There is a vast yield gap in the production of bananas in regions where bacterial pathogens and several other pathogens and pests are present together in the same field. BXW disease caused by Xanthomonas campestris pv. musacearum is reported to be the most destructive banana disease in East Africa. The disease affects all the banana varieties grown in the region. Only the wild-type diploid banana, Musa balbisiana, is resistant to BXW disease. Developing disease-resistant varieties of bananas is one of the most effective strategies to manage diseases. Recent advances in CRISPR/Cas-based gene editing techniques can accelerate banana improvement. Some progress has been made to create resistance against bacterial pathogens using CRISPR/Cas9-mediated gene editing by knocking out the disease-causing susceptibility (S) genes or activating the expression of the plant defense genes. A synopsis of recent advancements and perspectives on the application of gene editing for the control of bacterial wilt diseases are presented in this article.
Nutraceuticals as Modulators of Autophagy: Relevance in Parkinson’s Disease
Authors: Rakowski Michał , Porębski Szymon , Grzelak Agnieszka
Published: March 2022

Dietary supplements and nutraceuticals have entered the mainstream. Especially in the media, they are strongly advertised as safe and even recommended for certain diseases. Although they may support conventional therapy, sometimes these substances can have unexpected side effects. This review is particularly focused on the modulation of autophagy by selected vitamins and nutraceuticals, and their relevance in the treatment of neurodegenerative diseases, especially Parkinson’s disease (PD). Autophagy is crucial in PD; thus, the induction of autophagy may alleviate the course of the disease by reducing the so-called Lewy bodies. Hence, we believe that those substances could be used in prevention and support of conventional therapy of neurodegenerative diseases. This review will shed some light on their ability to modulate the autophagy.
Shhedding New Light on the Role of Hedgehog Signaling in Corneal Wound Healing
Authors: Zhang Xin , Mélik-Parsadaniantz Stéphane , Baudouin Christophe , Réaux-Le Goazigo Annabelle , Moreau Nathan
Published: March 2022

The cornea, an anterior ocular tissue that notably serves to protect the eye from external insults and refract light, requires constant epithelium renewal and efficient healing following injury to maintain ocular homeostasis. Although several key cell populations and molecular pathways implicated in corneal wound healing have already been thoroughly investigated, insufficient/impaired or excessive corneal wound healing remains a major clinical issue in ophthalmology, and new avenues of research are still needed to further improve corneal wound healing. Because of its implication in numerous cellular/tissular homeostatic processes and oxidative stress, there is growing evidence of the role of Hedgehog signaling pathway in physiological and pathological corneal wound healing. Reviewing current scientific evidence, Hedgehog signaling and its effectors participate in corneal wound healing mainly at the level of the corneal and limbal epithelium, where Sonic Hedgehog-mediated signaling promotes limbal stem cell proliferation and corneal epithelial cell proliferation and migration following corneal injury. Hedgehog signaling could also participate in corneal epithelial barrier homeostasis and in pathological corneal healing such as corneal injury-related neovascularization. By gaining a better understanding of the role of this double-edged sword in physiological and pathological corneal wound healing, fascinating new research avenues and therapeutic strategies will undoubtedly emerge.
Morphogen Signals Shaping the Gastric Glands in Health and Disease
Authors: Zagami Claudia , Papp Diana , Daddi Alice Anna , Boccellato Francesco
Published: March 2022

The adult gastric mucosa is characterised by deep invaginations of the epithelium called glands. These tissue architectural elements are maintained with the contribution of morphogen signals. Morphogens are expressed in specific areas of the tissue, and their diffusion generates gradients in the microenvironment. Cells at different positions in the gland sense a specific combination of signals that instruct them to differentiate, proliferate, regenerate, or migrate. Differentiated cells perform specific functions involved in digestion, such as the production of protective mucus and the secretion of digestive enzymes or gastric acid. Biopsies from gastric precancerous conditions usually display tissue aberrations and change the shape of the glands. Alteration of the morphogen signalling microenvironment is likely to underlie those conditions. Furthermore, genes involved in morphogen signalling pathways are found to be frequently mutated in gastric cancer. We summarise the most recent findings regarding alterations of morphogen signalling during gastric carcinogenesis, and we highlight the new stem cell technologies that are improving our understanding of the regulation of human tissue shape.
Anti-Inflammatory Effect of Beta-Caryophyllene Mediated by the Involvement of TRPV1, BDNF and trkB in the Rat Cerebral Cortex after Hypoperfusion/Reperfusion
Authors: Serra Maria Pina , Boi Marianna , Carta Antonella , Murru Elisabetta , Carta Gianfranca , Banni Sebastiano , Quartu Marina
Published: March 2022

We have previously shown that bilateral common carotid artery occlusion followed by reperfusion (BCCAO/R) is a model to study early hypoperfusion/reperfusion-induced changes in biomarkers of the tissue physiological response to oxidative stress and inflammation. Thus in this study, we investigate with immunochemical assays if a single dose of beta-caryophyllene (BCP), administered before the BCCAO/R, can modulate the TRPV1, BDNF, and trkB receptor in the brain cortex; the glial markers GFAP and Iba1 were also examined. Frontal and temporal-occipital cortical regions were analyzed in two groups of male rats, sham-operated and submitted to BCCAO/R. Six hours before surgery, one group was gavage fed a dose of BCP (40 mg/per rat in 300 μL of sunflower oil), the other was pre-treated with the vehicle alone. Western blot analysis showed that, in the frontal cortex of vehicle-treated rats, the BCCAO/R caused a TRPV1 decrease, an increment of trkB and GFAP, no change in BDNF and Iba1. The BCP treatment caused a decrease of BDNF and an increase of trkB levels in both sham and BCCAO/R conditions while inducing opposite changes in the case of TRPV1, whose levels became higher in BCCAO/R and lower in sham conditions. Present results highlight the role of BCP in modulating early events of the cerebral inflammation triggered by the BCCAO/R through the regulation of TRPV1 and the BDNF-trkB system.
Neutrophil to Lymphocyte Ratio: An Emerging Marker of the Relationships between the Immune System and Diseases
Authors: Buonacera Agata , Stancanelli Benedetta , Colaci Michele , Malatino Lorenzo
Published: March 2022

Over the last 10 years, the evaluation of the neutrophil-to-lymphocyte ratio (NLR) as an emerging marker of diseases has become a compelling field of bio-medical research. Although a precise and unique cut-off value has not been yet found, its role as a flag of immune system homeostasis is well established. NLR has a well-known prognostic value and independently correlates with mortality in the general population and in several specific subsets of disease (sepsis, pneumonia, COVID-19, cancer, etc.). Moreover, NLR was recently considered as part of the decision-making processes concerning the admission/recovery of patients with COVID-19 pneumonia. This review aims to provide an overview of the main use of this biomarker, focusing on the pathophysiology and the molecular basis underlying its central role as a reliable mirror of inflammatory status and adaptive immunity.
CRISPR/Cas9-Mediated Knockout of miR-130b Affects Mono- and Polyunsaturated Fatty Acid Content via PPARG-PGC1α Axis in Goat Mammary Epithelial Cells
Authors: Huang Lian , Luo Jun , Song Ning , Gao Wenchang , Zhu Lu , Yao Weiwei
Published: March 2022

MicroRNA (miRNA)-130b, as a regulator of lipid metabolism in adipose and mammary gland tissues, is actively involved in lipogenesis, but its endogenous role in fatty acid synthesis remains unclear. Here, we aimed to explore the function and underlying mechanism of miR-130b in fatty acid synthesis using the CRISPR/Cas9 system in primary goat mammary epithelial cells (GMEC). A single clone with deletion of 43 nucleotides showed a significant decrease in miR-130b-5p and miR-130b-3p abundances and an increase of target genes PGC1α and PPARG. In addition, knockout of miR-130b promoted triacylglycerol (TAG) and cholesterol accumulation, and decreased the proportion of monounsaturated fatty acids (MUFA) C16:1, C18:1 and polyunsaturated fatty acids (PUFA) C18:2, C20:3, C20:4, C20:5, C22:6. Similarly, the abundance of fatty acid synthesis genes ACACA and FASN and transcription regulators SREBP1c and SREBP2 was elevated. Subsequently, interference with PPARG instead of PGC1α in knockout cells restored the effect of miR-130b knockout, suggesting that PPARG is responsible for miR-130b regulating fatty acid synthesis. Moreover, disrupting PPARG inhibits PGC1α transcription and translation. These results reveal that miR-130b directly targets the PPARG–PGC1α axis, to inhibit fatty acid synthesis in GMEC. In conclusion, miR-130b could be a potential molecular regulator for improving the beneficial fatty acids content in goat milk.
Characteristics of Transfer RNA-Derived Fragments Expressed during Human Renal Cell Development: The Role of Dicer in tRF Biogenesis
Authors: Kazimierczyk Marek , Wojnicka Marta , Biała Ewa , Żydowicz-Machtel Paulina , Imiołczyk Barbara , Ostrowski Tomasz , Kurzyńska-Kokorniak Anna , Wrzesinski Jan
Published: March 2022

tRNA-derived fragments participate in the regulation of many processes, such as gene silencing, splicing and translation in many organisms, ranging from bacteria to humans. We were interested to know how tRF abundance changes during the different stages of renal cell development. The research model used here consisted of the following human renal cells: hESCs, HEK-293T, HK-2 and A-489 kidney tumor cells, which, together, mimic the different stages of kidney development. The characteristics of the most abundant tRFs, tRFGly(CCC), tRFVal(AAC) and tRFArg(CCU), were presented. It was found that these parental tRNAs present in cells are the source of many tRFs, thus increasing the pool of potential regulatory RNAs. Indeed, a bioinformatic analysis showed the possibility that tRFGly(CCC) and tRRFVal(AAC) could regulate the activity of a range of kidney proteins. Moreover, the distribution of tRFs and the efficiency of their expression is similar in adult and embryonic stem cells. During the formation of tRFs, HK-2 cells resemble A-498 cancer cells more than other cells. Additionally, we postulate the involvement of Dicer nuclease in the formation of tRF-5b in all the analyzed tRNAs. To confirm this, 293T NoDice cells, which in the absence of Dicer activity do not generate tRF-5b, were used.
Vascular Permeability in Diseases
Authors: Wautier Jean-Luc , Wautier Marie-Paule
Published: March 2022

Vascular permeability is a selective mechanism that maintains the exchange between vessels, tissues, and organs. The regulation was mostly studied during the nineteenth century by physiologists who defined physical laws and equations, taking blood, tissue interstitial, and oncotic pressure into account. During the last decades, a better knowledge of vascular cell functions and blood-vessel interactions opens a new area of vascular biology. Endothelial cell receptors vascular cell adhesion molecule (VCAM), intercellular cell adhesion molecule (ICAM), vascular endothelial growth factor receptor (VEGFR-2), receptor for advanced glycation end products (RAGE), and mediators were identified and their role in homeostasis and pathological situations was described. The molecular differences of endothelial cell junctions (tight, gap, and adherens junctions) and their role in vascular permeability were characterized in different organs. The main mediators of vasomotricity and permeability, such as prostaglandins, nitric oxide (NO), prostacyclin, vascular growth factor (VEGF), and cytokines, have been demonstrated to possess major functions in steady state and pathological situations. Leukocytes were shown to adhere to endothelium and migrate during inflammatory situations and infectious diseases. Increased vascular permeability is linked to endothelium integrity. Glycocalyx, when intact, may limit cancer cell metastasis. Biological modifications of blood and tissue constituents occurring in diabetes mellitus were responsible for increased permeability and, consequently, ocular and renal complications. Vascular pressure and fluidity are major determinants of pulmonary and cerebral edema. Beside the treatment of the infectious disease, of the blood circulation dysfunction and inflammatory condition, drugs (cyclooxygenase inhibitors) and specific antibodies anti-cytokine (anti-VEGF) have been demonstrated to reduce the severity and the mortality in diseases that exhibited enhanced vascular permeability.
An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors
Authors: Salvatore Teresa , Galiero Raffaele , Caturano Alfredo , Rinaldi Luca , Di Martino Anna , Albanese Gaetana , Di Salvo Jessica , Epifani Raffaella , Marfella Raffaele , Docimo Giovanni , Lettieri Miriam , Sardu Celestino , Sasso Ferdinando Carlo
Published: March 2022

Sodium-glucose co-transporter 2 (SGLT2) inhibitors block glucose reabsorption in the renal proximal tubule, an insulin-independent mechanism that plays a critical role in glycemic regulation in diabetes. In addition to their glucose-lowering effects, SGLT2 inhibitors prevent both renal damage and the onset of chronic kidney disease and cardiovascular events, in particular heart failure with both reduced and preserved ejection fraction. These unexpected benefits prompted changes in treatment guidelines and scientific interest in the underlying mechanisms. Aside from the target effects of SGLT2 inhibition, a wide spectrum of beneficial actions is described for the kidney and the heart, even though the cardiac tissue does not express SGLT2 channels. Correction of cardiorenal risk factors, metabolic adjustments ameliorating myocardial substrate utilization, and optimization of ventricular loading conditions through effects on diuresis, natriuresis, and vascular function appear to be the main underlying mechanisms for the observed cardiorenal protection. Additional clinical advantages associated with using SGLT2 inhibitors are antifibrotic effects due to correction of inflammation and oxidative stress, modulation of mitochondrial function, and autophagy. Much research is required to understand the numerous and complex pathways involved in SGLT2 inhibition. This review summarizes the current known mechanisms of SGLT2-mediated cardiorenal protection.
Involvement of E. coli 6S RNA in Oxidative Stress Response
Authors: Burenina Olga Y. , Elkina Daria A. , Ovcharenko Anna , Bannikova Valeria A. , Schlüter M. Amri C. , Oretskaya Tatiana S. , Hartmann Roland K. , Kubareva Elena A.
Published: March 2022

6S RNA, a small non-coding RNA present in almost all bacteria, inhibits transcription via direct binding to RNA polymerase holoenzymes. The mechanism of 6S RNA action was investigated to a large extent in E. coli, however, lack of 6S RNA (ΔssrS) was demonstrated to be unfavorable but not essential for cell survival under various growth conditions. In the present study, we revealed, for the first time, a lethal phenotype of the ΔssrS strain in the presence of high concentrations of H2O2. This phenotype was rescued by complementation of the ssrS gene on a plasmid. We performed comparative qRT-PCR analyses on an enlarged set of mRNAs of genes associated with the oxidative stress response, allowing us to identify four genes known to be involved in this pathway (soxS, ahpC, sodA and tpx) that had decreased mRNA levels in the ΔssrS strain. Finally, we performed comparative proteomic analyses of the wild-type and ΔssrS strains, confirming that ΔssrS bacteria have reduced levels of the proteins AhpC and Tpx involved in H2O2 reduction. Our findings substantiate the crucial role of the riboregulator 6S RNA for bacterial coping with extreme stresses.
Cross-Omics Analysis of Fenugreek Supplementation Reveals Beneficial Effects Are Caused by Gut Microbiome Changes Not Mammalian Host Physiology
Authors: Jones Katarina A. , Richard Allison J. , Salbaum J. Michael , Newman Susan , Carmouche Richard , Webb Sara , Bruce-Keller Annadora J. , Stephens Jacqueline M. , Campagna Shawn R.
Published: March 2022

Herbal remedies are increasing in popularity as treatments for metabolic conditions such as obesity and Type 2 Diabetes. One potential therapeutic option is fenugreek seeds (Trigonella foenum-graecum), which have been used for treating high cholesterol and Type 2 diabetes. A proposed mechanism for these benefits is through alterations in the microbiome, which impact mammalian host metabolic function. This study used untargeted metabolomics to investigate the fenugreek-induced alterations in the intestinal, liver, and serum profiles of mice fed either a 60% high-fat or low-fat control diet each with or without fenugreek supplementation (2% w/w) for 14 weeks. Metagenomic analyses of intestinal contents found significant alterations in the relative composition of the gut microbiome resulting from fenugreek supplementation. Specifically, Verrucomicrobia, a phylum containing beneficial bacteria which are correlated with health benefits, increased in relative abundance with fenugreek. Metabolomics partial least squares discriminant analysis revealed substantial fenugreek-induced changes in the large intestines. However, it was observed that while the magnitude of changes was less, significant modifications were present in the liver tissues resulting from fenugreek supplementation. Further analyses revealed metabolic processes affected by fenugreek and showed broad ranging impacts in multiple pathways, including carnitine biosynthesis, cholesterol and bile acid metabolism, and arginine biosynthesis. These pathways may play important roles in the beneficial effects of fenugreek.
Gliadin Peptide P31-43 Induces mTOR/NFkβ Activation and Reduces Autophagy: The Role of Lactobacillus paracasei CBA L74 Postbiotc
Authors: Conte Mariangela , Nigro Federica , Porpora Monia , Bellomo Claudia , Furone Francesca , Budelli Andrea Luigi , Nigro Roberto , Barone Maria Vittoria , Nanayakkara Merlin
Published: March 2022

Celiac disease (CD) is an autoimmune disease characterized by an altered immune response stimulated by gliadin peptides that are not digested and cause damage to the intestinal mucosa. The aim of this study was to investigate whether the postbiotic Lactobacillus paracasei (LP) could prevent the action of gliadin peptides on mTOR, autophagy, and the inflammatory response. Most of the experiments performed were conducted on intestinal epithelial cells Caco-2 treated with a peptic-tryptic digest of gliadin (PTG) and P31-43. Furthermore, we pretreated the Caco-2 with the postbiotic LP before treatment with the previously described stimuli. In both cases, we evaluated the levels of pmTOR, p70S6k, and p4EBP-1 for the mTOR pathway, pNFkβ, and pERK for inflammation and LC 3 and p62 for autophagy. For autophagy, we also used immunofluorescence analysis. Using intestinal organoids derivate from celiac (CD) patients, we analyzed the effect of gliadin after postbiotic pretreatment with LP on inflammation marker NFkβ. Through these experiments, we showed that gliadin peptides are able to induce the increase of the inflammatory response in a more complex model of intestinal epithelial cells. LP postbiotic was able to induce autophagy in Caco-2 cells and prevent gliadin effects. In conclusion, postbiotic pretreatment with LP could be considered for in vivo clinical trials.
Factors Affecting the Stability of Platinum(II) Complexes with 1,2,4-Triazolo[1,5-a]pyrimidine Derivatives and Tetrahydrothiophene-1-Oxide or Diphenyl Sulfoxide
Authors: Jakubowski Mateusz , Łakomska Iwona , Kaszuba Adriana , Wojtczak Andrzej , Sitkowski Jerzy , Jarzęcki Andrzej A.
Published: March 2022

The platinum(II) complexes of general formula [PtCl2(dstp)(S-donor)] were dstp 5,7-dimethyl-1,2,4-triazolo[1,5-a]-pyrimidine (dmtp), 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp), 5-methyl-7-isobutyl-1,2,4-triazolo[1,5-a]pyrimidine (ibmtp) or 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp), whereas S-tetrahydrothio-phene-1-oxide (TMSO) or diphenyl sulfoxide (DPSO) were synthesized in a one-pot reaction. Here, we present experimental data (1H, 13C, 15N, 195Pt NMR, IR, X-ray) combined with density functional theory (DFT) computations to support and characterize structure–spectra relationships and determine the geometry of dichloride platinum(II) complexes with selected triazolopyrimidines and sulfoxides. Based on the experimental and theoretical data, factors affecting the stability of platinum(II) complexes have been determined.
A Novel, Cell-Free Therapy to Enter Our Hearts: The Potential Role of Small EVs in Prevention and Treatment of CVD
Authors: Lazana Ioanna , Anagnostopoulos Constantinos
Published: March 2022

Heart disease constitutes one of the leading causes of morbidity and mortality worldwide. Current therapeutic techniques, such as interventional revascularization, although lifesaving, come along with myocardial injury related to the reperfusion itself, called ischemia-reperfusion injury, which is an added factor for increased morbidity. For that reason, there is an imperative need for novel therapies to be developed that would either prevent or treat myocardial injury. Extracellular vesicles (EVs), specifically small EVs (sEVs), have proven to be important mediators of intercellular communication. The fact that they carry information reflecting that of the parental cell makes them an ideal candidate for diagnostic purposes. sEVs derived from immunoregulatory cells, such as mesenchymal stem cells or cardiac progenitor cells, could also be used therapeutically to exert the primary immunomodulatory function but without carrying the side effects related to cell therapy. Furthermore, as a natural product, they have the added advantage of low immunogenicity, offering the potential for safe drug delivery. In the field of cardiology, there has been great interest in the therapeutic and diagnostic potential of sEVs with significant translational potential. Here, we review the potential use of sEVs in the context of myocardial ischemia and ischemia-reperfusion injury.
Protective Effects of Mitochondrial Uncoupling Protein 2 against Aristolochic Acid I-Induced Toxicity in HK-2 Cells
Authors: Feng Chen , Anger Etienne Empweb , Zhang Xiong , Su Shengdi , Su Chenlin , Zhao Shuxin , Yu Feng , Li Ji
Published: March 2022

Aristolochic acid I (AA I) is one of the most abundant and toxic aristolochic acids that is reported to cause Aristolochic acid nephropathy (AAN). This paper was designed to assess whether mitochondrial Uncoupling Protein 2 (UCP2), which plays an antioxidative and antiapoptotic role, could protect human renal proximal tubular epithelial (HK-2) cells from toxicity induced by AA I. In this study, HK-2 cells were treated with different concentrations of AA I with or without UCP2 inhibitor (genipin). To upregulate the expression of UCP2 in HK-2 cells, UCP2-DNA transfection was performed. The cell viability was evaluated by colorimetric method using MTT. A series of related biological events such as Reactive Oxygen Species (ROS), Glutathione peroxidase (GSH-Px), and Malondialdehyde (MDA) were evaluated. The results showed that the cytotoxicity of AA I with genipin group was much higher than that of AA I alone. Genipin dramatically boosted oxidative stress and exacerbated AA I-induced apoptosis. Furthermore, the increased expression of UCP2 can reduce the toxicity of AA I on HK-2 cells and upregulation of UCP2 expression can reduce AA I-induced oxidative stress and apoptosis. In conclusion, UCP2 might be a potential target for alleviating AA I-induced nephrotoxicity.
Apolipoprotein E, a Crucial Cellular Protein in the Lifecycle of Hepatitis Viruses
Authors: Tréguier Yannick , Bull-Maurer Anne , Roingeard Philippe
Published: March 2022

Apolipoprotein E (ApoE) is a multifunctional protein expressed in several tissues, including those of the liver. This lipoprotein component is responsible for maintaining lipid content homeostasis at the plasma and tissue levels by transporting lipids between the liver and peripheral tissues. The ability of ApoE to interact with host-cell surface receptors and its involvement in several cellular pathways raised questions about the hijacking of ApoE by hepatotropic viruses. Hepatitis C virus (HCV) was the first hepatitis virus reported to be dependent on ApoE for the completion of its lifecycle, with ApoE being part of the viral particle, mediating its entry into host cells and contributing to viral morphogenesis. Recent studies of the hepatitis B virus (HBV) lifecycle have revealed that this virus and its subviral envelope particles also incorporate ApoE. ApoE favors HBV entry and is crucial for the morphogenesis of infectious particles, through its interaction with HBV envelope glycoproteins. This review summarizes the data highlighting the crucial role of ApoE in the lifecycles of HBV and HCV and discusses its potential role in the lifecycle of other hepatotropic viruses.
Necroptosis in Solid Organ Transplantation: A Literature Overview
Authors: Lukenaite Beatrice , Griciune Erika , Leber Bettina , Strupas Kestutis , Stiegler Philipp , Schemmer Peter
Published: March 2022

Ischemia-reperfusion injury (IRI) is encountered in various stages during solid organ transplantation (SOT). IRI is known to be a multifactorial inflammatory condition involving hypoxia, metabolic stress, leukocyte extravasation, cellular death (including apoptosis, necrosis and necroptosis) and an activation of immune response. Although the cycle of sterile inflammation during IRI is consistent among different organs, the underlying mechanisms are poorly understood. Receptor-interacting protein kinase 3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL) are thought to be crucial in the implementation of necroptosis. Moreover, apart from “silent” apoptotic death, necrosis also causes sterile inflammation—necroinflammation, which is triggered by various damage-associated molecular patterns (DAMPs). Those DAMPs activate the innate immune system, causing local and systemic inflammatory responses, which can result in graft failure. In this overview we summarize knowledge on mechanisms of sterile inflammation processes during SOT with special focus on necroptosis and IRI and discuss protective strategies.
Environmental Phenol and Paraben Exposure Risks and Their Potential Influence on the Gene Expression Involved in the Prognosis of Prostate Cancer
Authors: Alwadi Diaaidden , Felty Quentin , Roy Deodutta , Yoo Changwon , Deoraj Alok
Published: March 2022

Prostate cancer (PCa) is one of the leading malignant tumors in US men. The lack of understanding of the molecular pathology on the risk of food supply chain exposures of environmental phenol (EP) and paraben (PB) chemicals limits the prevention, diagnosis, and treatment options. This research aims to utilize a risk assessment approach to demonstrate the association of EP and PB exposures detected in the urine samples along with PCa in US men (NHANES data 2005–2015). Further, we employ integrated bioinformatics to examine how EP and PB exposure influences the molecular pathways associated with the progression of PCa. The odds ratio, multiple regression model, and Pearson coefficients were used to evaluate goodness-of-fit analyses. The results demonstrated associations of EPs, PBs, and their metabolites, qualitative and quantitative variables, with PCa. The genes responsive to EP and PB exposures were identified using the Comparative Toxicogenomic Database (CTD). DAVID.6.8, GO, and KEGG enrichment analyses were used to delineate their roles in prostate carcinogenesis. The plug-in CytoHubba and MCODE completed identification of the hub genes in Cytoscape software for their roles in the PCa prognosis. It was then validated by using the UALCAN database by evaluating the expression levels and predictive values of the identified hub genes in prostate cancer prognosis using TCGA data. We demonstrate a significant association of higher levels of EPs and PBs in the urine samples, categorical and numerical confounders, with self-reported PCa cases. The higher expression levels of the hub genes (BUB1B, TOP2A, UBE2C, RRM2, and CENPF) in the aggressive stages (Gleason score > 8) of PCa tissues indicate their potential role(s) in the carcinogenic pathways. Our results present an innovative approach to extrapolate and validate hub genes responsive to the EPs and PBs, which may contribute to the severity of the disease prognosis, especially in the older population of US men.
Knockdown Resistance Mutations in the Voltage-Gated Sodium Channel of Aedes aegypti (Diptera: Culicidae) in Myanmar
Authors: Naw Haung , Võ Tuấn Cường , Lê Hương Giang , Kang Jung-Mi , Mya Yi Yi , Myint Moe Kyaw , Kim Tong-Soo , Shin Ho-Joon , Na Byoung-Kuk
Published: March 2022

Aedes aegypti is an important mosquito vector transmitting diverse arboviral diseases in Myanmar. Pyrethroid insecticides have been widely used in Myanmar as the key mosquito control measure, but the efforts are constrained by increasing resistance. Knockdown resistance (kdr) mutations in the voltage-gated sodium channel (VGSC) are related to pyrethroid resistance in Ae. aegypti. We analyzed the patterns and distributions of the kdr mutations in Ae. aegypti in the Mandalay area of Myanmar. The segment 6 regions of domains II and III of vgsc were separately amplified from individual Ae. aegypti genomic DNA via polymerase chain reaction. The amplified gene fragments were sequenced. High proportions of three major kdr mutations, including S989P (54.8%), V1016G (73.6%), and F1534C (69.5%), were detected in the vgsc of Ae. aegypti from all studied areas. Other kdr mutations, T1520I and F1534L, were also found. These kdr mutations represent 11 distinct haplotypes of the vgsc population. The S989P/V1016G/F1534C was the most prevalent, followed by S989P/V1016V and V1016G/F1534C. A quadruple mutation, S989P/V1016G/T1520I/F1534C, was also identified. High frequencies of concurrent kdr mutations were observed in vgsc of Myanmar Ae. aegypti, suggesting a high level of pyrethroid resistance in the population. These findings underscore the need for an effective vector control program in Myanmar.
Effects of Agro-Industrial Byproduct-Based Diets on the Growth Performance, Digestibility, Nutritional and Microbiota Composition of Mealworm (Tenebrio molitor L.)
Authors: Montalbán Ana , Sánchez Cristian , Hernández Fuensanta , Schiavone Achille , Madrid Josefa , Martínez-Miró Silvia
Published: March 2022

The aim of this study was to evaluate the effects of agro-industrial byproduct-based diets on the productive parameters, digestibility, insect composition, and gut microbiota of mealworm (Tenebrio molitor) larvae. Three formulations corresponding to three different levels of starch and protein were tested: one formulation based on bread remains and brewer’s yeast, representing a diet of high starch (61.1%) and low crude protein (18.5%) (HS-LP); and two formulations in which an additional four byproducts (courgette (Cucurbita pepo) remains, tigernut (Cyperus scelentus) pulp, brewer’s spent grains, and rice straw) were incorporated in different proportions, consistent with a diet of both moderate starch (29.8%) and crude protein (21.0%) (MS-MP); and another corresponding to a diet of low starch (20.0%) and high crude protein (26.3%) (LS-HP). A total of 1920 young larvae (average weight = 0.65 mg per larva) were used in this study. The larvae were randomly distributed into 16 replicates per treatment (boxes of 22.5 cm × 14.0 cm × 4.75 cm). Ten replicates for the growth performance–digestibility trial and six replicates for the complementary trial to determine uric acid levels in the frass were assigned per treatment. For growth performance, the diets were administered ad libitum during the experiment. The average number of days for the larvae to start pupating was lower in those reared on the HS-LP and LS-HP diets (88.90 and 91.00 days, respectively) than those on the MS-MP diet (120.09 days) (p < 0.001). The final individual weight was higher (p < 0.001) in larvae of the LS-HP group (168.69 mg) compared to those of the other groups (100.29 and 112.99 mg for HS-LP and MS-MP, respectively). However, the feed conversion ratio was better (p < 0.001) in the HS-LP group with the lowest value (1.39 g/g), with dry matter digestibility being the highest for the same diet (70.38%) (p < 0.001). Mealworms reared on LS-HP and MS-MP diets had a higher crude protein content than those reared on the HS-LP diet (p = 0.039). The most abundant phyla in the gut microbiota of larvae were Tenericutes, Proteobacteria, and Firmicutes, with their abundance depending on the rearing substrate. The representation of Tenericutes phylum was higher (p < 0.05) in the mealworms reared on MS-MP and HS-LP diets, whereas Proteobacteria and Cyanobacteria were higher in abundance (p < 0.001) in the insects reared on LS-HP. In conclusion, the larval growth, digestibility, insect composition, and gut microbiota of Tenebrio molitor were found to depend on the composition of the administered diet, and the results suggest great potential for the use of agro-industrial byproducts in their rearing and production.
CCHamide-2 Signaling Regulates Food Intake and Metabolism in Gryllus bimaculatus
Authors: Zhu Zhen , Tsuchimoto Maho , Nagata Shinji
Published: March 2022

Neuropeptides play vital roles in energy homeostasis in insects and other animals. Although the importance of the regulatory network of neuropeptides in feeding and metabolism has been illuminated, a complete understanding of the mechanisms has not been addressed as many factors are involved in the regulation. CCHamide-2 is a newly identified brain-gut neuropeptide that regulates feeding behavior in several insect species including Drosophila melanogaster. However, little is known about the mechanisms controlling the feeding-related behavior and metabolic functions modulated by CCHamide-2 in other insects. In this study, we addressed the functions of CCHamide-2 in the two-spotted cricket, Gryllus bimaculatus, which was used as the experimental material to research the mechanisms of feeding and metabolism in this omnivorous insect species. Knockdown crickets by RNA interference against GbCCHamide-2R increased the amount of food intake, while injection of chemically synthetic GbCCHamide-2 peptide reduced the amount of food intake. Further, knockdown and peptide injection experiments revealed that GbCCHamide-2 signaling increased the concentrations of circulating lipids and carbohydrates, and the carbohydrate-rich diet increased the transcript levels of GbCCHa-2R. Moreover, GbCCHa-2 injection decreased the transcript level of Gbilp. By contrast, GbCCHamide-2 signaling did not affect nymphal growth or the transcript level of GbAKH, as well as feeding preferences. Taken together, CCHamide-2 signaling in G. bimaculatus regulates food intake associated with alterations in lipid and carbohydrate levels in hemolymph.
Insecticidal Effect of Four Insecticides for the Control of Different Populations of Three Stored-Product Beetle Species
Authors: Baliota Georgia , Lampiri Evagelia , Batzogianni Evanthia , Athanassiou Christos
Published: March 2022

The protection of stored products from insect pests is mainly based on suppressive methods by using contact and gaseous insecticides, globally. Following their continuous and improper use, insecticide resistance has been observed in several major insect species and pose a continuous threat to the sustainability of a wide range of active ingredients that are currently in use in stored product protection. In the present work, on-site samplings of insect populations were carried out in local warehouses containing different types of cereals. The collected insects, Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae), Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae) and Cryptolestes ferrugineus (Stephens) (Coleoptera: Laemophloeidae), were reared under laboratory conditions to determine tolerance/resistance to widely used insecticides, using different diagnostic protocols. Laboratory populations of the same species were also examined for comparative purposes. Adult knock down and mortality of all populations indicated different patterns of tolerance to phosphine, deltamethrin, cypermethrin, and pirimiphos-methyl. In many cases, the recommended label doses were not able to completely control some of these populations, regardless of their origin, i.e., field-collected or laboratory. The results of the present work underline the importance of population on the efficacy of insecticides that are currently in use in stored product protection.
Population Genetic Structure of Chlorops oryzae (Diptera, Chloropidae) in China
Authors: Li Xianya , Wu Shunjiao , Xu Yonghong , Liu Yinghong , Wang Jia
Published: March 2022

Frequent outbreaks have made Chlorops oryzae one of the major pests of rice in some regions. In order to understand the ecological adaptation of C. oryzae at the molecular level, and provide a scientific basis for formulating management strategies, we used two molecular markers, COI and ITS1 sequences, to systematically analyze the genetic structure of 31 populations. The higher haplotype diversity and lower nucleotide diversity indicated that the C. oryzae populations experienced rapid expansion after a “Bottleneck effect”. The results of the mismatch distribution, neutrality test (Fu’s Fs < 0, p < 0.001), and haplotype network analysis suggested that the population has recently undergone an expansion. Although genetic differentiation among C. oryzae populations was found to have existed at low/medium levels (Fst: 0.183 for COI, 0.065 for ITS1), the frequent gene flow presented as well (Nm: 2.23 for COI, 3.60 for ITS1) was supposed to be responsible for frequent local outbreaks.
Vitrectomy Combined with Cataract Surgery for Retinal Detachment Using a Three-Dimensional Viewing System
Authors: Nowomiejska Katarzyna , Toro Mario Damiano , Bonfiglio Vincenza , Czarnek-Chudzik Aleksandra , Brzozowska Agnieszka , Torres Kamil , Rejdak Robert
Published: March 2022

Purpose: To evaluate the results of a pars plana vitrectomy (PPV) combined with cataract surgery for primary rhematogenous retinal detachment (RD) using a three-dimensional (3D) viewing system and a conventional microscope (CM). Methods: Medical reports of 82 patients were retrospectively reviewed: 26 patients were operated on with 3D and 56 patients were operated on with CM. The main outcome measures were visual acuity, duration of the surgery, and the rate of postoperative complications. Results: No statistically significant differences in pre- and postoperative visual acuity were found between both groups. There was significant improvement in the visual acuity in both groups. The best postoperative visual acuity was achieved with SF6 gas tamponade, followed by C3F8 gas and silicone oil in both groups. The duration of the surgery (60 min vs. 55 min) and the rate of postoperative complications (15% vs. 14%) were similar in both groups. Conclusions: The similar postoperative visual acuity and rate of complications detected using 3D and CM indicate that the 3D viewing system may be advantageous in the treatment of rhematogenous RD with PPV combined with cataract surgery, i.e., a complex procedure involving both anterior and posterior segment manipulations.