bluuebunny/crossref_metadata_2025 huggingface dataset:
Cocaine-Induced Time-Dependent Alterations in Cytochrome P450 and Liver Function
Authors: Jastrzębska Joanna , Daniel Władysława Anna
Published: January 2023

Cytochrome P450 is responsible for the metabolism of endogenous substrates, drugs and substances of abuse. The brain and nervous system regulate liver cytochrome P450 via neuroendocrine mechanisms, as shown in rodents. Cocaine exerts its addictive effects through the dopaminergic system, the functioning of which undergoes changes during its continuous use. Therefore, it can be hypothesized that the regulation of cytochrome P450 by cocaine may also alter during the addiction process, cessation and relapse. We analyzed preclinical studies on the mechanisms of the pharmacological action of cocaine, the role of the brain’s dopaminergic system in the neuroendocrine regulation of cytochrome P450 and the in vitro and in vivo effects of cocaine on the cytochrome P450 expression/activity and hepatotoxicity. The results of passive cocaine administration indicate that cocaine affects liver cytochrome P450 enzymes (including those engaged in its own metabolism) via different mechanisms involving the expression of genes encoding cytochrome P450 enzymes and interaction with enzyme proteins. Thus, it may affect its own oxidative metabolism and the metabolism of endogenous substrates and other co-administered drugs and may lead to hepatotoxicity. Its effect depends on the specific cytochrome P450 enzyme affected, cocaine dosage, treatment duration and animal species. However, further complementary studies are needed to find out whether cocaine affects cytochrome P450 via the brain’s dopaminergic system. The knowledge of cocaine’s effect on cytochrome P450 function during the entire addiction process is still incomplete. There is a lack of information on the enzyme expression/activity in animals self-administering cocaine (addicted), in those withdrawn after cocaine self-administration, and during relapse in animals previously addicted; furthermore, there is no such information concerning humans. The subject of cytochrome P450 regulation by cocaine during the addiction process is an open issue, and addressing this topic may help in the treatment of drug abuse patients.
A Paternal Methylation Error in the Congenital Hydrocephalic Texas (H-Tx) Rat Is Partially Rescued with Natural Folate Supplements
Authors: Naz Naila , Moshkdanian Ghazaleh , Miyan Salma , Eljabri Sereen , James Charlotte , Miyan Jaleel
Published: January 2023

Folate deficiencies, folate imbalance and associated abnormal methylation are associated with birth defects, developmental delays, neurological conditions and diseases. In the hydrocephalic Texas (H-Tx) rat, 10-formyl tetrahydrofolate dehydrogenase (FDH) is reduced or absent from the CSF and the nuclei of cells in the brain and liver and this is correlated with decreased DNA methylation. In the present study, we tested whether impaired folate metabolism or methylation exists in sexually mature, unaffected H-Tx rats, which may explain the propagation of hydrocephalus in their offspring. We compared normal Sprague Dawley (SD, n = 6) rats with untreated H-Tx (uH-Tx, n = 6 and folate-treated H-Tx (TrH-Tx, n = 4). Structural abnormalities were observed in the testis of uH-Tx rats, with decreased methylation, increased demethylation, and cell death, particularly of sperm. FDH and FRα protein expression was increased in uH-Tx males but not in folate-treated males but tissue folate levels were unchanged. 5-Methylcytosine was significantly reduced in untreated and partially restored in treated individuals, while 5-hydroxymethylcytosine was not significantly changed. Similarly, a decrease in DNA-methyltransferase-1 expression in uH-Tx rats was partially reversed with treatment. The data expose a significant germline methylation error in unaffected adult male H-Tx rats from which hydrocephalic offspring are obtained. Reduced methylation in the testis and sperm was partially recovered by treatment with folate supplements leading us to conclude that this neurological disorder may not be completely eradicated by maternal supplementation alone.
ONC201 Suppresses Neuroblastoma Growth by Interrupting Mitochondrial Function and Reactivating Nuclear ATRX Expression While Decreasing MYCN
Authors: Wu Jian-Ching , Huang Chao-Cheng , Wang Pei-Wen , Chen Ting-Ya , Hsu Wen-Ming , Chuang Jiin-Haur , Chuang Hui-Ching
Published: January 2023

Neuroblastoma (NB) is characterized by several malignant phenotypes that are difficult to treat effectively without combination therapy. The therapeutic implication of mitochondrial ClpXP protease ClpP and ClpX has been verified in several malignancies, but is unknown in NB. Firstly, we observed a significant increase in ClpP and ClpX expression in immature and mature ganglion cells as compared to more malignant neuroblasts and less malignant Schwannian-stroma-dominant cell types in human neuroblastoma tissues. We used ONC201 targeting ClpXP to treat NB cells, and found a significant suppression of mitochondrial protease, i.e., ClpP and ClpX, expression and downregulation of mitochondrial respiratory chain subunits SDHB and NDUFS1. The latter was associated with a state of energy depletion, increased reactive oxygen species, and decreased mitochondrial membrane potential, consequently promoting apoptosis and suppressing cell growth of NB. Treatment of NB cells with ONC201 as well as the genetic attenuation of ClpP and ClpX through specific short interfering RNA (siRNA) resulted in the significant upregulation of the tumor suppressor alpha thalassemia/mental retardation X-linked (ATRX) and promotion of neurite outgrowth, implicating mitochondrial ClpXP proteases in MYCN-amplified NB cell differentiation. Furthermore, ONC201 treatment significantly decreased MYCN protein expression and suppressed tumor formation with the reactivation of ATRX expression in MYCN-amplified NB-cell-derived xenograft tumors. Taken together, ONC201 could be the potential agent to provide diversified therapeutic application in NB, particularly in NB with MYCN amplification.
Silver and Copper Nanoparticles as the New Biocidal Agents Used in Pre- and Post-Milking Disinfectants with the Addition of Cosmetic Substrates in Dairy Cows
Authors: Kalińska Aleksandra , Jaworski Sławomir , Wierzbicki Mateusz , Kot Magdalena , Radzikowski Daniel , Smulski Sebastian , Gołębiewski Marcin
Published: January 2023

Mastitis is one of the most common issues for milk producers around the world. Antibiotic therapy is often ineffective, and therefore, scientists must find a new solution. The aim of this paper is to estimate the influence of common and well-known cosmetic substrates and mixtures of nanoparticles (NPs) and cosmetic substrates on the viability of frequently occurring mastitis pathogens, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The obtained results suggest that only collagen + elastin and glycerine influenced and increased bacteria viability. In case of the rest of the cosmetic substrates, the viability of E. coli and S. aureus was decreased, and the results were statistically significant (p ≤ 0.01). Prepared pre-dipping and dipping mixtures decrease (p ≤ 0.01) the viability of the mentioned pathogens. The obtained results of the in vitro analysis are very promising. In the next step, prepared mixtures should be tested in different herd conditions if they can be used in mastitis prevention or decrease the number of subclinical mastitis cases. Furthermore, these mixtures could become an interesting alternative for organic milk production where conventional preparations and antibiotics are forbidden. However, further analysis, especially on the influence of prepared mixtures on other bacteria species and, algae, fungi, are necessary.
A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma
Authors: Lin Chih-Lang , Liang Kung-Hao , Hu Ching-Chih , Chien Cheng-Hung , Chen Li-Wei , Chien Rong-Nan , Lin Yang-Hsiang , Yeh Chau-Ting
Published: January 2023

Sorafenib is currently a targeted agent widely used in the treatment of advanced hepatocellular carcinoma (aHCC). However, to date there is still a lack of a reliable marker capable of predicting sorafenib therapeutic responses. Here, we conducted a genome-wide association study (GWAS) to identify candidate single-nucleotide polymorphism outcome predictors in aHCC patients. A total of 74 real-world sorafenib-treated aHCC patients were enrolled for GWAS and outcome analysis. GWAS showed that rs1010816 (p = 2.2 × 10−7) was associated with sorafenib therapeutic response in aHCC patients. Kaplan–Meier analysis indicated that the “TT” genotype was significantly associated with a favorable therapeutic response but not significantly associated with overall survival (OS). Univariate followed by multivariate Cox proportional hazard analysis showed that ascites, main portal vein thrombosis, lower platelet count, lower total sorafenib doses, higher PALBI score in model A and higher ALBI grade in model B were significantly associated with a shorter OS. Subgroup analysis showed that only in alcoholic aHCC patients treated by sorafenib, rs1010816 “TT” genotype was significantly associated with longer OS (p = 0.021). Sorafenib had a favorable therapeutic outcome in alcoholic aHCC patients carrying rs1010816 “TT” genotype.
Distribution of Cleaved SNAP-25 in the Rat Brain, following Unilateral Injection of Botulinum Neurotoxin-A into the Striatum
Authors: Schümann Friederike , Schmitt Oliver , Wree Andreas , Hawlitschka Alexander
Published: January 2023

In Parkinson’s disease, hypercholinism in the striatum occurs, with the consequence of disturbed motor functions. Direct application of Botulinum neurotoxin-A in the striatum of hemi-Parkinsonian rats might be a promising anticholinergic therapeutic option. Here, we aimed to determine the spread of intrastriatally injected BoNT-A in the brain as well as the duration of its action based on the distribution of cleaved SNAP-25. Rats were injected with 1 ng of BoNT-A into the right striatum and the brains were examined at different times up to one year after treatment. In brain sections immunohistochemically stained for BoNT-A, cleaved SNAP-25 area-specific densitometric analyses were performed. Increased immunoreactivity for cleaved SNAP-25 was found in brain regions other than the unilaterally injected striatum. Most cleaved SNAP-25-ir was found in widespread areas ipsilateral to the BoNT-A injection, in some regions, however, immunoreactivity was also measured in the contralateral hemisphere. There was a linear relationship between the distance of a special area from the injected striatum and the time until its maximum averaged immunoreactivity was reached. Moreover, we observed a positive relationship for the area-specific distance from the injected striatum and its maximum immunoreactivity as well as for the connection density with the striatum and its maximum immunoreactivity. The results speak for a bidirectional axonal transport of BoNT-A after its application into the striatum to its widespread connected parts of the brain. Even one year after BoNT-A injection, cleaved SNAP-25 could still be detected.
FM1-43 Dye Memorizes Piezo1 Activation in the Trigeminal Nociceptive System Implicated in Migraine Pain
Authors: Della Pietra Adriana , Mikhailov Nikita , Giniatullin Rashid
Published: January 2023

It has been proposed that mechanosensitive Piezo1 channels trigger migraine pain in trigeminal nociceptive neurons, but the mechanosensitivity of satellite glial cells (SGCs) supporting neuronal sensitization has not been tested before. Moreover, tools to monitor previous Piezo1 activation are not available. Therefore, by using live calcium imaging with Fluo-4 AM and labeling with FM1-43 dye, we explored a new strategy to identify Piezo channels’ activity in mouse trigeminal neurons, SGCs, and isolated meninges. The specific Piezo1 agonist Yoda1 induced calcium transients in both neurons and SGCs, suggesting the functional expression of Piezo1 channels in both types of cells. In Piezo1-transfected HEK cells, FM1-43 produced only a transient fluorescent response, whereas co-application with Yoda1 provided higher transient signals and a remarkable long-lasting FM1-43 ‘tail response’. A similar Piezo1-related FM1-43 trapping was observed in neurons and SGCs. The non-specific Piezo channel blocker, Gadolinium, inhibited the transient peak, confirming the involvement of Piezo1 receptors. Finally, FM1-43 labeling demonstrated previous activity in meningeal tissues 3.5 h after Yoda1 washout. Our data indicated that trigeminal neurons and SGCs express functional Piezo channels, and their activation provides sustained labeling with FM1-43. This long-lasting labelling can be used to monitor the ongoing and previous activation of Piezo1 channels in the trigeminal nociceptive system, which is implicated in migraine pain.
The Integrated mRNA and miRNA Approach Reveals Potential Regulators of Flowering Time in Arundina graminifolia
Authors: Ahmad Sagheer , Lu Chuqiao , Gao Jie , Wei Yonglu , Xie Qi , Jin Jianpeng , Zhu Genfa , Yang Fengxi
Published: January 2023

Orchids are among the most precious flowers in the world. Regulation of flowering time is one of the most important targets to enhance their ornamental value. The beauty of Arundina graminifolia is its year-round flowering, although the molecular mechanism of this flowering ability remains masked. Therefore, we performed a comprehensive assessment to integrate transcriptome and miRNA sequencing to disentangle the genetic regulation of flowering in this valuable species. Clustering analyses provided a set of molecular regulators of floral transition and floral morphogenesis. We mined candidate floral homeotic genes, including FCA, FPA, GI, FT, FLC, AP2, SOC1, SVP, GI, TCP, and CO, which were targeted by a variety of miRNAs. MiR11091 targeted the highest number of genes, including candidate regulators of phase transition and hormonal control. The conserved miR156-miR172 pathway of floral time regulation was evident in our data, and we found important targets of these miRNAs in the transcriptome. Moreover, endogenous hormone levels were determined to decipher the hormonal control of floral buds in A. graminifolia. The qRT-PCR analysis of floral and hormonal integrators validated the transcriptome expression. Therefore, miRNA-mediated mining of candidate genes with hormonal regulation forms the basis for comprehending the complex regulatory network of perpetual flowering in precious orchids. The findings of this study can do a great deal to broaden the breeding programs for flowering time manipulation of orchids.
Multi-Step Extracellular Matrix Remodelling and Stiffening in the Development of Idiopathic Pulmonary Fibrosis
Authors: Júnior Constança , Ulldemolins Anna , Narciso Maria , Almendros Isaac , Farré Ramon , Navajas Daniel , López Javier , Eroles Mar , Rico Felix , Gavara Núria
Published: January 2023

The extracellular matrix (ECM) of the lung is a filamentous network composed mainly of collagens, elastin, and proteoglycans that provides structural and physical support to its populating cells. Proliferation, migration and overall behaviour of those cells is greatly determined by micromechanical queues provided by the ECM. Lung fibrosis displays an aberrant increased deposition of ECM which likely changes filament organization and stiffens the ECM, thus upregulating the profibrotic profile of pulmonary cells. We have previously used AFM to assess changes in the Young’s Modulus (E) of the ECM in the lung. Here, we perform further ECM topographical, mechanical and viscoelastic analysis at the micro- and nano-scale throughout fibrosis development. Furthermore, we provide nanoscale correlations between topographical and elastic properties of the ECM fibres. Firstly, we identify a softening of the ECM after rats are instilled with media associated with recovery of mechanical homeostasis, which is hindered in bleomycin-instilled lungs. Moreover, we find opposite correlations between fibre stiffness and roughness in PBS- vs bleomycin-treated lung. Our findings suggest that changes in ECM nanoscale organization take place at different stages of fibrosis, with the potential to help identify pharmacological targets to hinder its progression.
Upregulation of Peridinin-Chlorophyll A-Binding Protein in a Toxic Strain of Prorocentrum hoffmannianum under Normal and Phosphate-Depleted Conditions
Authors: Lee Thomas Chun-Hung , Lai Kaze King-Yip , Xu Steven Jing-Liang , Lee Fred Wang-Fat
Published: January 2023

Some strains of the dinoflagellate species Prorocentrum hoffmannianum show contrasting ability to produce diarrhetic shellfish poisoning (DSP) toxins. We previously compared the okadaic acid (OA) production level between a highly toxic strain (CCMP2804) and a non-toxic strain (CCMP683) of P. hoffmannianum and revealed that the cellular concentration of OA in CCMP2804 would increase significantly under the depletion of phosphate. To understand the molecular mechanisms, here, we compared and analyzed the proteome changes of both strains growing under normal condition and at phosphate depletion using two-dimensional gel electrophoresis (2-DE). There were 41 and 33 differential protein spots observed under normal condition and phosphate depletion, respectively, of which most were upregulated in CCMP2804 and 22 were common to both conditions. Due to the lack of matched peptide mass fingerprints in the database, de novo peptide sequencing was applied to identify the differentially expressed proteins. Of those upregulated spots in CCMP2804, nearly 60% were identified as peridinin-chlorophyll a-binding protein (PCP), an important light-harvesting protein for photosynthesis in dinoflagellates. We postulated that the high expression of PCP encourages the production of DSP toxins by enhancing the yields of raw materials such as acetate, glycolate and glycine. Other possible mechanisms of toxicity related to PCP might be through triggering the transcription of non-ribosomal peptide synthetase/polyketide synthase genes and the transportation of dinophysistoxin-4 from chloroplast to vacuoles.
Scd1 Deficiency in Early Embryos Affects Blastocyst ICM Formation through RPs-Mdm2-p53 Pathway
Authors: Niu Huimin , Lei Anmin , Tian Huibin , Yao Weiwei , Liu Ying , Li Cong , An Xuetong , Chen Xiaoying , Zhang Zhifei , Wu Jiao , Yang Min , Huang Jiangtao , Cheng Fei , Zhao Jianqing , Hua Jinlian , Liu Shimin , Luo Jun
Published: January 2023

Embryos contain a large number of lipid droplets, and lipid metabolism is gradually activated during embryonic development to provide energy. However, the regulatory mechanisms remain to be investigated. Stearoyl-CoA desaturase 1 (Scd1) is a fatty acid desaturase gene that is mainly involved in intracellular monounsaturated fatty acid production, which takes part in many physiological processes. Analysis of transcripts at key stages of embryo development revealed that Scd1 was important and expressed at an increased level during the cleavage and blastocyst stages. Knockout Scd1 gene by CRISPR/Cas9 from zygotes revealed a decrease in lipid droplets (LDs) and damage in the inner cell mass (ICM) formation of blastocyst. Comparative analysis of normal and knockout embryo transcripts showed a suppression of ribosome protein (RPs) genes, leading to the arrest of ribosome biogenesis at the 2-cell stage. Notably, the P53-related pathway was further activated at the blastocyst stage, which eventually caused embryonic development arrest and apoptosis. In summary, Scd1 helps in providing energy for embryonic development by regulating intra-embryonic lipid droplet formation. Moreover, deficiency activates the RPs-Mdm2-P53 pathway due to ribosomal stress and ultimately leads to embryonic development arrest. The present results suggested that Scd1 gene is essential to maintain healthy development of embryos by regulating energy support.
Dose- and Segment-Dependent Disturbance of Rat Gut by Ionizing Radiation: Impact of Tight Junction Proteins
Authors: Livanova Alexandra A. , Fedorova Arina A. , Zavirsky Alexander V. , Krivoi Igor I. , Markov Alexander G.
Published: January 2023

The damaging effect of ionizing radiation (IR) exposure results in the disturbance of the gut natural barrier, followed by the development of severe gastrointestinal injury. However, the dose and application segment are known to determine the effects of IR. In this study, we demonstrated the dose- and segment-specificity of tight junction (TJ) alteration in IR-induced gastrointestinal injury in rats. Male Wistar rats were subjected to a total-body X-ray irradiation at doses of 2 or 10 Gy. Isolated jejunum and colon segments were tested in an Ussing chamber 72 h after exposure. In the jejunum, 10-Gy IR dramatically altered transepithelial resistance, short-circuit current and permeability for sodium fluorescein. These changes were accompanied by severe disturbance of histological structure and total rearrangement of TJ content (increased content of claudin-1, -2, -3 and -4; multidirectional changes in tricellulin and occludin). In the colon of 10-Gy irradiated rats, lesions of barrier and transport functions were less pronounced, with only claudin-2 and -4 altered among TJ proteins. The 2-Gy IR did not change electrophysiological characteristics or permeability in the colon or jejunum, although slight alterations in jejunum histology were noted, emphasized with claudin-3 increase. Considering that TJ proteins are critical for maintaining epithelial barrier integrity, these findings may have implications for countermeasures in gastrointestinal acute radiation injury.
Cajanus platycarpus Flavonoid 3′5′ Hydroxylase_2 (CpF3′5′H_2) Confers Resistance to Helicoverpa armigera by Modulating Total Polyphenols and Flavonoids in Transgenic Tobacco
Authors: Tyagi Shaily , Rathinam Maniraj , Dokka Narasimham , Chaudhary Nidhee , Satish Lakkakula , Dash Prasanta K. , Shasany Ajit Kumar , Sreevathsa Rohini
Published: January 2023

Pod borer Helicoverpa armigera, a polyphagus herbivorous pest, tremendously incurs crop damage in economically important crops. This necessitates the identification and utility of novel genes for the control of the herbivore. The present study deals with the characterization of a flavonoid 3′5′ hydroxylase_2 (F3′5′H_2) from a pigeonpea wild relative Cajanus platycarpus, possessing a robust chemical resistance response to H. armigera. Though F3′5′H_2 displayed a dynamic expression pattern in both C. platycarpus (Cp) and the cultivated pigeonpea, Cajanus cajan (Cc) during continued herbivory, CpF3′5′H_2 showed a 4.6-fold increase vis a vis 3-fold in CcF3′5′H_2. Despite similar gene copy numbers in the two Cajanus spp., interesting genic and promoter sequence changes highlighted the stress responsiveness of CpF3′5′H_2. The relevance of CpF3′5′H_2 in H. armigera resistance was further validated in CpF3′5′H_2-overexpressed transgenic tobacco based on reduced leaf damage and increased larval mortality through an in vitro bioassay. As exciting maiden clues, CpF3′5′H_2 deterred herbivory in transgenic tobacco by increasing total flavonoids, polyphenols and reactive oxygen species (ROS) scavenging capacity. To the best of our knowledge, this is a maiden attempt ascertaining the role of F3′5′H_2 gene in the management of H. armigera. These interesting leads suggest the potential of this pivotal branch-point gene in biotic stress management programs.
Seeing Neurodegeneration in a New Light Using Genetically Encoded Fluorescent Biosensors and iPSCs
Authors: Stellon David , Talbot Jana , Hewitt Alex W. , King Anna E. , Cook Anthony L.
Published: January 2023

Neurodegenerative diseases present a progressive loss of neuronal structure and function, leading to cell death and irrecoverable brain atrophy. Most have disease-modifying therapies, in part because the mechanisms of neurodegeneration are yet to be defined, preventing the development of targeted therapies. To overcome this, there is a need for tools that enable a quantitative assessment of how cellular mechanisms and diverse environmental conditions contribute to disease. One such tool is genetically encodable fluorescent biosensors (GEFBs), engineered constructs encoding proteins with novel functions capable of sensing spatiotemporal changes in specific pathways, enzyme functions, or metabolite levels. GEFB technology therefore presents a plethora of unique sensing capabilities that, when coupled with induced pluripotent stem cells (iPSCs), present a powerful tool for exploring disease mechanisms and identifying novel therapeutics. In this review, we discuss different GEFBs relevant to neurodegenerative disease and how they can be used with iPSCs to illuminate unresolved questions about causes and risks for neurodegenerative disease.
Drought-Stress Induced Physiological and Molecular Changes in Plants 2.0
Authors: Hura Tomasz , Hura Katarzyna , Ostrowska Agnieszka
Published: January 2023

Plant adaptation to soil drought is a topic that is currently under investigation [...]
Different Contacted Cell Types Contribute to Acquiring Different Properties in Brain Microglial Cells upon Intercellular Interaction
Authors: Nakano-Doi Akiko , Kubo Shuji , Sonoda Emiko , Taguchi Akihiko , Nakagomi Takayuki
Published: January 2023

Microglial cells (MGs), originally derived from progenitor cells in a yolk sac during early development, are glial cells located in a physiological and pathological brain. Since the brain contains various cell types, MGs could frequently interact with different cells, such as astrocytes (ACs), pericytes (PCs), and endothelial cells (ECs). However, how microglial traits are regulated via cell–cell interactions by ACs, PCs, or ECs and how they are different depending on the contacted cell types is unclear. This study aimed to clarify these questions by coculturing MGs with ACs, PCs, or ECs using mouse brain-derived cells, and microglial phenotypic changes were investigated under culture conditions that enabled direct cell–cell contact. Our results showed that ACs or PCs dose-dependently increased the number of MG, while ECs decreased it. Microarray and gene ontology analysis showed that cell fate-related genes (e.g., cell cycle, proliferation, growth, death, and apoptosis) of MGs were altered after a cell–cell contact with ACs, PCs, and ECs. Notably, microarray analysis showed that several genes, such as gap junction protein alpha 1 (Gja1), were prominently upregulated in MGs after coincubation with ACs, PCs, or ECs, regardless of cell types. Similarly, immunohistochemistry showed that an increased Gja1 expression was observed in MGs after coincubation with ACs, PCs, or ECs. Immunofluorescent and fluorescence-activated cell sorting analysis also showed that calcein-AM was transferred into MGs after coincubation with ACs, PCs, or ECs, confirming that intercellular interactions occurred between these cells. However, while Gja1 inhibition reduced the number of MGs after coincubation with ACs and PCs, this was increased after coincubation with ECs; this indicates that ACs and PCs positively regulate microglial numbers via Gja1, while ECs decrease it. Results show that ACs, PCs, or ECs exert both common and specific cell type-dependent effects on MGs through intercellular interactions. These findings also suggest that brain microglial phenotypes are different depending on their surrounding cell types, such as ACs, PCs, or ECs.
ATP13A2 Gene Silencing in Drosophila Affects Autophagic Degradation of A53T Mutant α-Synuclein
Authors: Dhanushkodi Nisha R. , Abul Khair Salema B. , Ardah Mustafa T. , Haque M. Emdadul
Published: January 2023

Mutations in ATP13A2 (PARK9), an autophagy-related protein, cause Kufor–Rakeb syndrome, an autosomal recessive, juvenile-onset form of parkinsonism. α-Synuclein (α-syn) is a presynaptic neuronal protein that forms toxic aggregates in Parkinson’s disease (PD). We studied α-syn aggregation and autophagic flux in ATP13A2-knockdown Drosophila expressing either wild-type (WT) or mutant α-syn. Dopaminergic (DA) neuron loss was studied by confocal microscopy. Sleep and circadian activity were evaluated in young and old flies using a Drosophila activity monitor. Thirty-day-old ATP13A2-RNAi A53T-α-syn flies had increased Triton-insoluble α-syn levels, compared to control A53T-α-syn flies without ATP13A2-RNAi. Whole-brain staining revealed significantly fewer dopaminergic (DA) neurons in the PPL2 cluster of 30-day-old ATP13A2-RNAi flies expressing WT-, A30P-, and A53T-α-syn than in that of controls. In ATP13A2-RNAi A53T-α-syn flies, autophagic flux was decreased, as indicated by increased accumulation of Ref(2)P, the Drosophila p62 homologue. ATP13A2 silencing decreased total locomotor activity in young, and enhanced sleep features, similar to PD (decreasing bout length), in old flies expressing A53T-α-syn. ATP13A2 silencing also altered the circadian locomotor activity of A30P- and A53T-α-syn flies. Thus, ATP13A2 may play a role in the autophagic degradation of A53T-α-syn.
Combined Omics Analysis Further Unveils the Specific Role of Butyrate in Promoting Growth in Early-Weaning Animals
Authors: Zhang Bin , Liu Mengqi , Yue Zhengkai , Chen Xiaoyang , Li Chenyang , Liu Lei , Li Fuchang
Published: January 2023

Abnormal mutations in the microbial structure of early-weaning mammals are an important cause of enteritis. Based on the multiple known beneficial functions of butyrate, we hypothesized that butyrate would alleviate the imbalance of intestinal homeostasis induced by early weaning in animals. However, the mechanisms of action between butyrate and intestinal microbes are still poorly explored. In this study, we aimed to investigate whether butyrate exerts beneficial effects on the structure of the intestinal flora of weanling rabbits and their intestinal homeostasis, growth and development, and we attempted to elucidate the potential mechanisms of action through a combined omics analysis. We found that dietary butyrate upregulated the transcription of tight junction-related proteins in the epithelial barrier and improved the intestinal microbial structure by suppressing harmful bacteria and promoting beneficial ones. Intestinal and plasma metabolomes were also altered. The bile acid secretion, α-linolenic acid, apoptotic, and prostate cancer pathways responded to the positive dietary butyrate-induced metabolic changes in the weanling rabbits, resulting in the inhibition of inflammation, improved antioxidant capacity, increased rates of cell proliferation and survival, and decreased levels of apoptosis. Additionally, dietary butyrate suppressed the release of pro-inflammatory factors and enhanced positive appetite regulation, which increased the average daily gain of the rabbits. These results demonstrated that dietary butyrate can help maintain the integrity of the intestinal epithelial barrier, improve the structural composition of the intestinal microflora, enhance organismal metabolism, inhibit inflammation, reduce post-weaning anorexia, and promote growth and development in early-weaning rabbits. These positive effects of dietary butyrate were exerted via the modulation of the microbe–gut–brain axis.
Ethnobotanical Diversity of Trees and Shrubs of Iran: A Comprehensive Review
Authors: Nadaf Mohabat , Amiri Mohammad Sadegh , Joharchi Mohammad Reza , Omidipour Reza , Moazezi Masomeh , Mohaddesi Behzad , Taghavizadeh Yazdi Mohammad Ehsan , Mottaghipisheh Javad
Published: January 2023

Iran, possessing unique topographic and diverse climatic conditions, is the home of 8167 vascular plant species. Iran has a historical tradition in using plants for medicinal purposes. Approximately 2075 species over the whole are popularly characterized as medicinal or aromatic. Medicinal trees and shrubs compose a significant percentage of Iranian medicinal flora. Nonetheless, there are no integrated databases on their applications and most of the publications and documents have been scattered to date. Therefore, the present investigation aims to integrate the published literature considering its ethnobotanical aspects that would serve as promising precursors for developing potent medicines of plant origin. In the study, we compile information about ethnobotany of trees and shrubs of Iran. Our survey found 174 taxa belonging to 109 genera and 56 families. The majority of species were classified in Rosaceae, Fabaceae, Rutaceae, Salicaceae, and Lamiaceae families. Rosaceae was the most dominant, representing 21.8% of the total plant species recorded, among them, the genus with the highest number of species was Prunus (16 species). Berberis vulgaris, Citrus limon, and Betula pendula have the highest number of medicinal uses (24 number of uses) in Iran. Leaves (22.7%) represented the most dominant usage of the plant parts, while the most commonly used preparation method was infusion (33.5%). Most of the plant species have been consumed for digestive system treatment (21%), followed by immune system treatment (20%). The present review highlights that different trees and shrubs taxa have great traditional applications in various healing throughout the Iranian territory. The represented data can potentially be a precious reference containing useful information for directing further phytochemical, biological, and pharmacological investigations. Several endemic species of trees and shrubs, particularly Ribes khorasanicum, are frequently used in Iranian traditional medicine. Because of overharvesting, these species are calling a wake-up alarm for conservation.
Electrochemical Activation and Its Prolonged Effect on the Durability of Bimetallic Pt-Based Electrocatalysts for PEMFCs
Authors: Pavlets Angelina , Pankov Ilya , Alekseenko Anastasia
Published: January 2023

The present study, concerned with high-performance ORR catalysts, may be a valuable resource for a wide range of researchers within the fields of nanomaterials, electrocatalysis, and hydrogen energy. The objects of the research are electrocatalysts based on platinum–copper nanoparticles with onion-like and solid-solution structures. To evaluate the functional characteristics of the catalysts, the XRD, XRF, TEM, HAADF-STEM, and EDX methods, as well as the voltammetry method on a rotating disk electrode have been used. This work draws the attention of researchers to the significance of applying a protocol of electrochemically activating bimetallic catalysts in terms of the study of their functional characteristics on the rotating disk electrode. The choice of the potential range during the pre-cycling stage has been shown to play a crucial role in maintaining the durability of the catalysts. The activation of the PtCu/C catalyst during cycling of up to 1.0 V allows for an increase in the durability of the catalysts with onion-like and solid-solution structures of nanoparticles by 28% and 23%, respectively, as compared with activation of up to 1.2 V.
Long-Term Results of Serial Exercise Testing and Echocardiography Examinations in Patients with Pulmonary Stenosis
Authors: Yang Chia-Hsin , Teng Li-Yun , Lai Ming-Wei , Weng Ken-Pen , Tsai Sen-Wei , Lin Ko-Long
Published: January 2023

Pulmonary stenosis (PS) affects cardiopulmonary function and exercise performance. Cardiopulmonary exercise testing (CPET) together with transthoracic echocardiography (TTE) can measure exercise performance, PS progression, and treatment effects. We assessed exercise capacity in PS patients using these methods. We enrolled 28 PS patients aged 6–35 years who received surgery, balloon pulmonary valvuloplasty, and follow-up care. The control population was selected by a 1:1 matching on age, sex, and body mass index. Baseline and follow-up peak pulmonary artery pulse wave velocity (PAV) were compared using TTE. Initial CPET revealed no significant differences in anaerobic metabolic equivalent (MET), peak oxygen consumption (VO2), and heart rate recovery between the two groups, nor were significant differences in pulmonary function identified. Within the PS group, there were no significant differences in MET, peak VO2, and heart rate recovery between the baseline and final CPET. Similarly, no significant differences were observed between the baseline and final PAV. The exercise capacity of patients with properly managed PS was comparable to that of healthy individuals. However, during the follow-up, declining trends in pulmonary function, aerobic metabolism, and peak exercise load capacity were observed among adolescents with PS. This study provides long-term data suggesting that PS patients should be encouraged to perform physical activity. Regular reevaluation should also be encouraged to limit performance deterioration.
Impact of Antifibrotic Treatment on Postoperative Complications in Patients with Interstitial Lung Diseases Undergoing Lung Transplantation: A Systematic Review and Meta-Analysis
Authors: Taweesedt Pahnwat , Lertjitbanjong Ploypin , Eksombatchai Dararat , Charoenpong Prangthip , Moua Teng , Thongprayoon Charat , Tangpanithandee Supawit , Petnak Tananchai
Published: January 2023

Antifibrotic treatment has been approved for reducing disease progression in fibrotic interstitial lung disease (ILD). As a result of increased bleeding risk, some experts suggest cessation of antifibrotics prior to lung transplantation (LT). However, extensive knowledge regarding the impact of antifibrotic treatment on postoperative complications remains unclear. We performed a comprehensive search of several databases from their inception through to 30 September 2021. Original studies were included in the final analysis if they compared postoperative complications, including surgical wound dehiscence, anastomosis complication, bleeding complications, and primary graft dysfunction, between those with and without antifibrotic treatment undergoing LT. Of 563 retrieved studies, 6 studies were included in the final analysis. A total of 543 ILD patients completing LT were included, with 161 patients continuing antifibrotic treatment up to the time of LT and 382 without prior treatment. Antifibrotic treatment was not significantly associated with surgical wound dehiscence (RR 1.05; 95% CI, 0.31–3.60; I2 = 0%), anastomotic complications (RR 0.88; 95% CI, 0.37–2.12; I2 = 31%), bleeding complications (RR 0.76; 95% CI, 0.33–1.76; I2 = 0%), or primary graft dysfunction (RR 0.87; 95% CI, 0.59–1.29; I2 = 0%). Finally, continuing antifibrotic treatment prior to LT was not significantly associated with decreased 1-year mortality (RR 0.80; 95% CI, 0.41–1.58; I2 = 0%). Our study suggests a similar risk of postoperative complications in ILD patients undergoing LT who received antifibrotic treatment compared to those not on antifibrotic therapy.
Depression, Anxiety, and Stress in Kazakhstani Women with Recurrent Pregnancy Loss: A Case–Control Study
Authors: Issakhanova Assylzhan , Issanov Alpamys , Ukybassova Talshyn , Kaldygulova Lyazzat , Marat Aizada , Imankulova Balkenzhe , Kamzayeva Nazira , Almawi Wassim Y. , Aimagambetova Gulzhanat
Published: January 2023

Background: Recurrent pregnancy loss (RPL) is associated with increased incidence and severity of depression, anxiety, and stress, and screening for these comorbidities following miscarriages is beneficial for women with RPL who are planning future pregnancies. This study aims to investigate depression, anxiety, and stress among Kazakhstani women with RPL. Methods: This was a case–control study involving 70 women with confirmed RPL and 78 ethnically matched control women. Depression, anxiety, and stress were evaluated using the Depression Anxiety Stress Scales (DASS)-21 instrument. Linear regression and correlation analysis were used in assessing the association of RPL with symptoms of depression, and/or anxiety, and/or stress, after adjusting for key covariates. Results: Women with RPL were found to have significantly higher mean scores for depression (p < 0.001), anxiety (p < 0.001), and stress (p < 0.001) symptoms. Mild–moderate stress and mild–moderate and severe–extreme depression and anxiety symptoms were more frequent in the RPL group than in the control group. Regression analysis demonstrated that RPL was the only significant variable associated with anxiety, depression, and stress symptoms. Conclusion: The results of this study suggest that women with RPL are more likely to experience heightened symptoms of depression, anxiety, and stress. Proper psychological counseling is recommended for women with RPL, as well as their spouses.
Quality of Life, Psychological Distress, and Nutritional Status of Polish Patients with Head and Neck Cancer Treated with Radiotherapy
Authors: Pytel Aleksandra , Zielińska Anna , Staś Jakub , Chabowski Mariusz
Published: January 2023

Introduction. Head and neck cancer (HNC) is a global epidemiological and clinical problem. In 2020, it was the seventh most common type of cancer worldwide. In 2019, HNC was the fourth most common cause of cancer death among men in Poland. Radiotherapy plays an important role in the treatment of patients with HNC at all clinical stages. However, it is associated with a significant rate of early and late adverse effects. As head and neck cancers are located close to vital anatomical structures, both the local progression of the disease and the treatments used can cause serious problems for patients with HNC, reducing their health-related quality of life (HRQoL) as well as increasing the risk of depressive disorders. Despite this, the current literature lacks research on these aspects of the therapeutic process in the Polish population. The aim of this study was to assess the early impact of radiotherapy on HRQoL outcomes, psychological distress, nutritional status, and overall performance of patients with HNC. Methods. The study was carried out among 85 patients with HNC treated in the Inpatient Radiotherapy Unit of the Radiotherapy Department of the Lower Silesian Oncology Center in Wrocław. The patients were asked to complete a set of questionnaires, including the EORTC QLQ-H&N35, the BDI, the NRS-2002, and the ECOG scale, at two time points: before the initiation of radiotherapy treatment and after a course of radiotherapy. The period between the assessments was 7 to 8 weeks. Results. Our findings demonstrated a negative impact of radiotherapy on scores in all the cancer-specific symptom and functioning scales used in the study. As regards functioning scales, the largest differences were observed for senses and swallowing, whereas with symptoms scales, the largest differences were noted for “sticky saliva” and “dry mouth”. Over half of the patients included in the study required nutritional support after radiotherapy treatment. We found statistically significant differences in the levels of depressive symptom severity before and after radiotherapy treatment. Conclusion. The present study showed significant changes in the physical and psychological functioning and nutritional status of the patients with HNC studied after radiotherapy treatment, which may have an impact on the effectiveness of cancer treatment.
Prevalence of and Risk Factors for Adhesive Capsulitis of the Shoulder in Older Adults from Germany
Authors: Jacob Louis , Gyasi Razak M. , Koyanagi Ai , Haro Josep Maria , Smith Lee , Kostev Karel
Published: January 2023

This study aimed to investigate the prevalence of and risk factors for adhesive capsulitis in older adults from Germany. The one-year and lifetime prevalence of adhesive capsulitis were assessed in adults aged ≥65 years with at least one visit to one of 1207 general practices in Germany in 2021. Associations between physical and psychiatric conditions and adhesive capsulitis were further assessed in older patients diagnosed for the first time with adhesive capsulitis in general practices in 2010–2021 (index date) and matched (1:5) to patients without adhesive capsulitis using a propensity score based on age, sex, and the index year. In adults without adhesive capsulitis, the index date was a randomly selected visit date in 2010–2021. The one-year and lifetime prevalence of adhesive capsulitis in older adults in 2021 were 0.4% and 2.4%, respectively. In 8439 patients with and 42,195 patients without adhesive capsulitis, 12 conditions were positively and significantly associated with adhesive capsulitis. Effect sizes were strongest for other and unspecified osteoarthritis (OR = 1.93), injury to the shoulder and upper arm (OR = 1.85), and injury to the thorax (OR = 1.47). Based on these findings, adhesive capsulitis can occur at older age, and osteoarthritis and injuries are major risk factors.
A Simplified Low-Dose 10-Day Quadruple Therapy with a Galenic Formulation of Bismuth Salicylate Is Highly Effective for Helicobacter pylori Eradication
Authors: Dore Maria Pina , Saba Francesco , Zanni Lucia , Rocca Anna , Piroddu Jessica , Gutierrez Giuseppe , Pes Giovanni Mario
Published: January 2023

Background: Earlier studies have shown that a modified low-dose bismuth quadruple therapy given for 10 to 14 days is highly effective for the treatment of Helicobacter pylori infection in Sardinia. However, bismuth is not universally available. Aim: We aimed to investigate the efficacy of a simplified low-dose 10-day quadruple therapy containing a galenic formulation of bismuth salicylate for H. pylori infection. Patients and Methods: Adult patients positive for H. pylori infection were assigned to a quadruple therapy containing a galenic formulation of bismuth salicylate (200 mg) plus tetracycline 500 mg, metronidazole 500 mg and rabeprazole 20 mg, given twice a day with the midday and evening meals for 10 days. A negative stool antigen test or 13C-Urea Breath Test defined successful eradication. Compliance and adverse events were recorded 30–40 days after the end of treatment. Results: In this open-label pilot study, 42 patients were enrolled (mean age 54.1 ± 12.0 years; 64% female). Among the study participants, 35 were naïve to H. pylori treatment. The treatment regimen was completed by 41 patients, with an overall success rate of 95.1%. More specifically, the eradication rate was 95.1% PP; 95% confidence interval (CI) = 86.6–100 and 92.9% by ITT; 95%CI = 85.1–100%, respectively. For naïve patients, the cure rate was 97.1%. Compliance was excellent. Side effects were absent or mild overall. Conclusions: The modified low-dose 10-day quadruple therapy provided high eradication rates of H. pylori infection, despite the replacement of colloidal bismuth subcitrate with bismuth salicylate. In regions where bismuth is unavailable in the market, the galenic formulation should be a valid option.
Personality Traits Predict 7-Year Risk of Diagnosis of Multiple Sclerosis: A Prospective Study
Authors: Kang Weixi
Published: January 2023

Objective: The objective of the current study is to investigate how Big Five personality traits could predict the risk of multiple sclerosis (MS) diagnosis in 7 years. Methods: A binary logistic regression was used to analyze data from 17,791 participants who responded to questions at Wave 3 (collected between 2011 to 2012) and Wave 10 (collected between 2018 to 2019) using a binary logistic regression from UKHLS with a mean age of 47.01 (S.D. = 16.31) years old with 42.62% males. Results: The current study found that Openness (OR = 0.68, p < 0.01, 95% C.I. (0.51, 0.89)) and Conscientiousness (OR = 0.70, p < 0.05, 95% C.I. (0.52, 0.93)) are positively associated with a reduced risk of MS diagnosis in 7 years. Conclusion: Health professionals can use findings from the current study as evidence for developing tools for assessing the risk of MS, and providing interventions for people who may be at high risk of MS based on their personality traits.