bluuebunny/crossref_metadata_2025 huggingface dataset:
Wellbeing in Addiction Recovery: Does It Differ across Addictions?
Authors: Corner Tessa , Arden-Close Emily , McAlaney John
Published: July 2023

Limited research has been conducted on the experiences of individuals in long-term recovery from addiction, and addictions are usually studied in isolation. However, no theories of addiction differentiate between addictions or assume that individuals will experience only one addiction. This study aimed to compare affect between individuals with addictions to drugs and alcohol and to explore how QoL changes in long-term recovery from addiction. Individuals in recovery from addiction (n = 115; 52.2% male) were recruited via snowball sampling on social media signposted by an addiction rehabilitation charity. Participants completed questionnaires about QoL (WHOQOL-Bref) and positive and negative affect (PANAS-X). The main primary addictions were drugs (76.5%) and alcohol (21.7%), with 69.7% reporting multiple addictions including food, sex, internet, and gambling. Affect and coping strategies did not differ by addiction. QoL appeared to improve with time in recovery. The high percentage of multiple addictions and greater similarities than differences between individuals with drug and alcohol addictions suggest that addictions should not be studied in isolation when studying psychological health during long-term recovery.
Strong Father–Child Relationships and Other Positive Childhood Experiences, Adverse Childhood Experiences, and Sexual Risk Factors for HIV among Young Adults Aged 19–24 Years, Namibia, 2019: A Cross-Sectional Study
Authors: Agathis Nickolas T. , Annor Francis B. , Xu Likang , Swedo Elizabeth , Chiang Laura , Coomer Rachel , Hegle Jennifer , Patel Pragna , Forster Norbert , O’Malley Gabrielle , Ensminger Alison L. , Kamuingona Rahimisa , Andjamba Helena , Nshimyimana Brigitte , Manyando Molisa , Massetti Greta M.
Published: July 2023

Using cross-sectional data from the 2019 Namibia Violence Against Children and Youth Survey and sex-stratified multivariable models, we assessed the associations between four different positive childhood experiences (PCEs) and having ≥3 adverse childhood experiences (ACEs), including ≥3 ACE–PCE interaction terms, and seven sexual risk factors for HIV acquisition among young adults aged 19–24 years. One PCE, having a strong father–child relationship, was inversely associated with two risk factors among women (lifetime transactional sex (OR, 0.4; 95% CI, 0.2–0.7) and recent age-disparate sexual relationships (OR, 0.3; 95% CI, 0.2–0.5)), and significantly interacted with having ≥3 ACEs for three risk factors among women (not knowing a partner’s HIV status, infrequently using condoms, and ever having an STI) and one among men (having multiple sexual partners in the past year). The other PCEs were significantly associated with ≤1 HIV risk factor and had no significant interaction terms. Strong father–child relationships may reduce HIV acquisition risk and mitigate the effect of childhood adversity on HIV risk among young adults in Namibia.
Rectal Cancer Tissue Lipidome Differs According to Response to Neoadjuvant Therapy
Authors: Sánchez-Vinces Salvador , Duarte Gustavo Henrique Bueno , Messias Marcia Cristina Fernandes , Gatinoni Caroline Fernanda Alves , Silva Alex Ap. Rosini , Sanches Pedro Henrique Godoy , Martinez Carlos Augusto Real , Porcari Andreia M. , Carvalho Patricia de Oliveira
Published: July 2023

Rectal cancer (RC) is a gastrointestinal cancer with a poor prognosis. While some studies have shown metabolic reprogramming to be linked to RC development, it is difficult to define biomolecules, like lipids, that help to understand cancer progression and response to therapy. The present study investigated the relative lipid abundance in tumoral tissue associated with neoadjuvant therapy response using untargeted liquid chromatography–mass spectrometry lipidomics. Locally advanced rectal cancer (LARC) patients (n = 13), clinically staged as T3–4 were biopsied before neoadjuvant chemoradiotherapy (nCRT). Tissue samples collected before nCRT (staging) and afterwards (restaging) were analyzed to discover lipidomic differences in RC cancerous tissue from Responders (n = 7) and Non-responders (n = 6) to nCRT. The limma method was used to test differences between groups and to select relevant feature lipids from tissue samples. Simple glycosphingolipids and differences in some residues of glycerophospholipids were more abundant in the Non-responder group before and after nCRT. Oxidized glycerophospholipids were more abundant in samples of Non-responders, especially those collected after nCRT. This work identified potential lipids in tissue samples that take part in, or may explain, nCRT failure. These results could potentially provide a lipid-based explanation for nCRT response and also help in understanding the molecular basis of RC and nCRT effects on the tissue matrix.
Catalytic Conversion of Carbohydrates into 5-Hydroxymethylfurfural by Phosphotungstic Acid Encapsulated in MIL-101 (Cr, Sn) Catalyst in Deep Eutectic Solvents
Authors: Mao Wei , Hao Jiawen , Zeng Lingyu , Wang Hao , Xu Hao , Zhou Jinghong
Published: July 2023

Herein, we report the synthesis of bimetal–organic frameworks (BMOFs) with both Brønsted and Lewis acidities, in which phosphotungstic acid (PTA) was encapsulated in BMOFs. It is efficient in converting starch to 5-hydroxymethyl-furfural (HMF) in deep eutectic solvents (DESs) such as choline chloride and formic acid. The highest yield of HMF (37.94%) was obtained using P0.5/BMOFs1.0 to catalyze starch in a mixed solvent system comprising DESs and ethyl acetate (EAC) (v/v; 2:3) at 180 °C and a reaction time of 10 min. Employing a DES as a cocatalyst and solvent reduced the use of organic solvents. The catalyst showed adequate reusability, and the HMF yield only decreased by 2.88% after six cycles of reuse compared with that of the initial catalyst. This study demonstrates the application potential of BMOFs in the conversion of biomass to useful molecules with commercial and/or research value.
Obacunone Photoprotective Effects against Solar-Simulated Radiation–Induced Molecular Modifications in Primary Keratinocytes and Full-Thickness Human Skin
Authors: Montero Paula , Villarroel Maria José , Roger Inés , Morell Anselm , Milara Javier , Cortijo Julio
Published: July 2023

Solar radiation can cause damage to the skin, leading to various adverse effects such as sunburn, reactive oxygen species production, inflammation, DNA damage, and photoaging. To study the potential of photoprotective agents, full-thickness skin models are increasingly being used as in vitro tools. One promising approach to photoprotection involves targeting the redox-sensitive transcription factor Nrf2, which is responsible for regulating various cellular defense mechanisms, including the antioxidant response, inflammatory signaling, and DNA repair. Obacunone, a natural triterpenoid, has been identified as a potent Nrf2 agonist. The present study aims to evaluate the relevance of full-thickness (FT) skin models in photoprotection studies and to explore the potential photoprotective effects of obacunone on those models and in human keratinocytes. Phenion® full-thickness skin models and keratinocytes were incubated with increasing concentrations of obacunone and irradiated with solar-simulated radiation (SSR). Various photodamage markers were evaluated, including histological integrity, oxidative stress, apoptosis, inflammation, photoaging-related dermal markers, and photocarcinogenesis markers. Increasing doses of SSR were found to modulate various biomarkers related to sun damage in the FT skin models. However, obacunone attenuated cytotoxicity, inflammation, oxidative stress, sunburn reaction, photoaging, and photocarcinogenesis in both keratinocytes and full thickness skin models exposed to SSR. These results suggest that obacunone may have potential as a photoprotective agent for preventing the harmful effects of solar radiation on the skin.
Fabrication, Structure, and Properties of Nonwoven Silk Fabrics Prepared with Different Cocoon Layers
Authors: Choi Yun Yeong , Jang Mi Jin , Park Byung-Dae , Um In Chul
Published: July 2023

In this study, five different nonwoven silk fabrics were fabricated with silk fibers from different cocoon layers, and the effect of the cocoon layer on the structural characteristics and properties of the nonwoven silk fabric was examined. The diameter of the silk fiber and thickness of the nonwoven silk fabric decreased from the outer to the inner cocoon layer. More amino acids with higher hydrophilicity (serine, aspartic acid, and glutamic acid) and lower hydrophilicity (glycine and alanine) were observed in the outer layers. From the outer to the inner layer, the overall crystallinity and contact angle of the nonwoven silk fabric increased, whereas its yellowness index, moisture retention, and mechanical properties decreased. Regardless of the cocoon layer at which the fiber was sourced, the thermal stability of fibroin and sericin and good cell viability remained unchanged. The results of this study indicate that the properties of nonwoven silk fabric can be controlled by choosing silk fibers from the appropriate cocoon layers. Moreover, the findings in this study will increase the applicability of nonwoven silk fabric in the biomedical and cosmetic fields, which require specific properties for industrialization.
6-Oxofurostane and (iso)Spirostane Types of Saponins in Smilax sieboldii: UHPLC-QToF-MS/MS and GNPS-Molecular Networking Approach for the Rapid Dereplication and Biodistribution of Specialized Metabolites
Authors: Avula Bharathi , Bae Ji-Yeong , Ahn Jongmin , Katragunta Kumar , Wang Yan-Hong , Wang Mei , Kwon Yongsoo , Khan Ikhlas A. , Chittiboyina Amar G.
Published: July 2023

Identifying novel phytochemical secondary metabolites following classical pharmacognostic investigations is tedious and often involves repetitive chromatographic efforts. During the past decade, Ultra-High Performance Liquid Chromatography-Quadrupole Time of Flight-Tandem Mass Spectrometry (UHPLC-QToF-MS/MS), in combination with molecular networking, has been successfully demonstrated for the rapid dereplication of novel natural products in complex mixtures. As a logical application of such innovative tools in botanical research, more than 40 unique 3-oxy-, 3, 6-dioxy-, and 3, 6, 27-trioxy-steroidal saponins were identified in aerial parts and rhizomes of botanically verified Smilax sieboldii. Tandem mass diagnostic fragmentation patterns of aglycones, diosgenin, sarsasapogenin/tigogenin, or laxogenin were critical to establishing the unique nodes belonging to six groups of nineteen unknown steroidal saponins identified in S. sieboldii. Mass fragmentation analysis resulted in the identification of 6-hydroxy sapogenins, believed to be key precursors in the biogenesis of characteristic smilaxins and sieboldins, along with other saponins identified within S. sieboldii. These analytes’ relative biodistribution and characteristic molecular networking profiles were established by analyzing the leaf, stem, and root/rhizome of S. sieboldii. Deducing such profiles is anticipated to aid the overall product integrity of botanical dietary supplements while avoiding tedious pharmacognostic investigations and helping identify exogenous components within the finished products.
Effect of Omega-3 Rich High-Fat Diet on Markers of Tissue Lipid Metabolism in Glucocorticoid-Treated Mice
Authors: Son Wangkuk , Brown Katie , Persinger Aaron , Pryke Ashley , Lin Jason , Powell Zereque , Wallace Noah , van der Merwe Marie , Puppa Melissa
Published: July 2023

Glucocorticoids (GCs) are some of the most widely prescribed therapies for treating numerous inflammatory diseases and multiple cancer types. With chronic use, GCs’ therapeutic benefits are concurrent with deleterious metabolic side effects, which worsen when combined with a high-fat diet (HFD). One characteristic of the common Western HFD is the presence of high omega-6 polyunsaturated fatty acids (PUFAs) and a deficiency in omega-3 PUFAs. The aim of this experiment was to determine whether fat composition resulting from HFD affects glucocorticoid-induced alterations in lipid-handling by the liver and skeletal muscle. Male wild-type C57BL/6 mice were randomized into two groups: n-6 (45% fat 177.5 g lard) and n-3 (45% fat 177.5 g Menhaden oil). After 4 weeks on their diets, groups were divided to receive either daily injections of dexamethasone (3 mg/kg/day) or sterile PBS for 1 week while continuing diets. The n-3 HFD diet attenuated adipose and hepatic fatty accumulation and prevented GC-induced increases in liver lipid metabolism markers Cd36 and Fabp. N-3 HFD had little effect on markers of lipid metabolism in oxidative and glycolytic skeletal muscle and was unable to attenuate GC-induced gene expression in the muscle. The present study’s result demonstrated that the change of fat composition in HFD could beneficially alter the fatty acid accumulation and associated lipid metabolism markers in mice treated with dexamethasone.
Plasma Exosomal microRNA Profile Reveals miRNA 148a-3p Downregulation in the Mucosal-Dominant Variant of Pemphigus Vulgaris
Authors: Valentino Anna , Leuci Stefania , Galderisi Umberto , Spagnuolo Gianrico , Mignogna Michele Davide , Peluso Gianfranco , Calarco Anna
Published: July 2023

The mucosal-dominant variant of pemphigus vulgaris (MPV) is an autoimmune disease characterized by oral mucosal blistering and circulating pathogenic IgG antibodies against desmoglein 3 (Dsg3), resulting in life-threatening bullae and erosion formation. Recently, microRNAs (miRNAs) have emerged as promising players in the diagnosis and prognosis of several pathological states. For the first time, we have identified a different expression profile of miRNAs isolated from plasma-derived exosomes (P-EVs) of MPV patients positive for antibodies against Dsg3 (Dsg3-positive) compared to healthy controls. Moreover, a dysregulated miRNA profile was confirmed in MPV tissue biopsies. In particular, a strong downregulation of the miR-148a-3p expression level in P-EVs of MPV patients compared to healthy controls was demonstrated. Bioinformatics prediction analysis identifies metalloproteinase-7 (MMP7) as a potential miR-148a-3p target. An in vitro acantholysis model revealed that the miR-148a-3p expression level was dramatically downregulated after treatment with Dsg3 autoantibodies, with a concomitant increase in MMP7 expression. The increased expression of MMP7 leads to the disruption of intercellular and/or extracellular matrix adhesion in an in vitro cellular model of MPV, with subsequent cell dissociation. Overexpression of miR-148a-3p prevented cell dissociation and regressed MMP7 upregulation. Our findings suggest a pivotal role of P-EV cargo in regulating molecular mechanisms involved in MPV pathogenesis and indicate them as potential MPV therapeutic targets.
Exploring the Antimicrobial Potential and Biofilm Inhibitory Properties of Hemocyanin from Hemifusus pugilinus (Born, 1778)
Authors: Jeyachandran Sivakamavalli , Chellapandian Hethesh , Park Kiyun , Kwak Ihn-Sil
Published: July 2023

The seafood industry plays a huge role in the blue economy, exploiting the advantage of the enriched protein content of marine organisms such as shrimps and molluscs, which are cultured in aquafarms. Diseases greatly affect these aquatic organisms in culture and, hence, there is need to study, in detail, their innate immune mechanisms. Hemocyanin is a non-specific innate defense molecule present in the blood cells of several invertebrates, especially molluscs, arthropods, and annelids. It is concerned with oxygen transport, blood clotting, and immune enhancement. In the present study, this macromolecular metalloprotein was isolated from the hemolymph of the marine snail Hemifusus pugilinus (Born, 1778) using Sephadex G-100 gel filtration column chromatography. It occurred as a single band (MW 80 kDa) on SDS-PAGE. High-performance liquid chromatography (HPLC) of the purified hemocyanin showed a single peak with a retention time of 4.3 min. The secondary structure and stability of the protein were detected using circular dichroism (CD), and the spectra demonstrated negative ellipticity bands close to 208 nm and 225 nm, indicating β-sheets. Further exploration of the purified hemocyanin revealed remarkable antimicrobial and antibiofilm activities against Gram-positive (Enterococcus faecalis and Staphylococcus aureus) and Gram-negative bacteria (Pseudomonas aeruginosa and Proteus vulgaris) at a concentration of 1–5 μg/mL. Spectrophotometric and in situ microscopic analyses (CLSM) unveiled the potential of the purified hemocyanin to inhibit biofilm formation in these bacteria with a minimal inhibitory concentration of 40 μg/mL. Furthermore, H. pugilinus hemocyanin (10 μg/mL concentration) displayed antifungal activity against Aspergillus niger. The purified hemocyanin was also assessed for cytotoxicity against human cancer cells using cell viability assays. Altogether, the present study shows that molluscan hemocyanin is a potential antimicrobial, antibiofilm, antifungal, anticancer, and immunomodulatory agent, with great scope for application in the enhancement of the immune system of molluscs, thereby facilitating their aquaculture.
Therapeutical Options in ROS1—Rearranged Advanced Non Small Cell Lung Cancer
Authors: Stanzione Brigida , Del Conte Alessandro , Bertoli Elisa , De Carlo Elisa , Revelant Alberto , Spina Michele , Bearz Alessandra
Published: July 2023

ROS proto-oncogene 1 (ROS1) rearrangements occur in 0.9–2.6% of patients with non small cell lung cancer (NSCLC), conferring sensitivity to treatment with specific tyrosine-kinase inhibitors (TKI). Crizotinib, a first-generation TKI, was the first target-therapy approved for the first-line treatment of ROS1-positive NSCLC. Recently, entrectinib, a multitarget inhibitor with an anti-ROS1 activity 40 times more potent than crizotinib and better activity on the central nervous system (CNS), received approval for treatment-naive patients. After a median time-to-progression of 5.5–20 months, resistance mechanisms can occur, leading to tumor progression. Therefore, newer generation TKI with greater potency and brain penetration have been developed and are currently under investigation. This review summarizes the current knowledge on clinicopathological characteristics of ROS1-positive NSCLC and its therapeutic options.
miRNAs as Modern Biomarkers in Asthma Therapy
Authors: Kierbiedź-Guzik Natalia , Sozańska Barbara
Published: July 2023

Asthma is a chronic inflammatory disease of the airways characterized by shortness of breath, chest tightness, coughing, and wheezing. For several decades (approximately 30 years), miRNAs and their role in asthma have been of constant interest among scientists. These small, non-coding RNA fragments, 18–25 nucleotides long, regulate gene expression at the post-transcriptional level by binding to the target mRNA. In this way, they affect several biological processes, e.g., shaping airway structures, producing cytokines and immune mediators, and controlling defense mechanisms. Publications confirm their potential role in the diagnosis and monitoring of the disease, but only some articles address the use of miRNAs in the treatment of asthma. The following paper reviews the latest available studies and presents miRNAs as a useful tool for predicting the effectiveness of the included treatment, early diagnosis of exacerbations, and in assessing patient compliance for different groups of drugs used in asthma. The latest known pathways underlying the pathogenesis of the disease, which are associated with a change in miRNA expression, may be precise targets of therapeutic activity in the future.
Crosstalk of Inflammation and Coagulation in Bothrops Snakebite Envenoming: Endogenous Signaling Pathways and Pathophysiology
Authors: Cavalcante Joeliton S. , de Almeida Denis Emanuel Garcia , Santos-Filho Norival A. , Sartim Marco Aurélio , de Almeida Baldo Amanda , Brasileiro Lisele , Albuquerque Polianna L. , Oliveira Sâmella S. , Sachett Jacqueline Almeida Gonçalves , Monteiro Wuelton Marcelo , Ferreira Rui Seabra
Published: July 2023

Snakebite envenoming represents a major health problem in tropical and subtropical countries. Considering the elevated number of accidents and high morbidity and mortality rates, the World Health Organization reclassified this disease to category A of neglected diseases. In Latin America, Bothrops genus snakes are mainly responsible for snakebites in humans, whose pathophysiology is characterized by local and systemic inflammatory and degradative processes, triggering prothrombotic and hemorrhagic events, which lead to various complications, organ damage, tissue loss, amputations, and death. The activation of the multicellular blood system, hemostatic alterations, and activation of the inflammatory response are all well-documented in Bothrops envenomings. However, the interface between inflammation and coagulation is still a neglected issue in the toxinology field. Thromboinflammatory pathways can play a significant role in some of the major complications of snakebite envenoming, such as stroke, venous thromboembolism, and acute kidney injury. In addition to exacerbating inflammation and cell interactions that trigger vaso-occlusion, ischemia–reperfusion processes, and, eventually, organic damage and necrosis. In this review, we discuss the role of inflammatory pathways in modulating coagulation and inducing platelet and leukocyte activation, as well as the inflammatory production mediators and induction of innate immune responses, among other mechanisms that are altered by Bothrops venoms.
The Modulation of Sucrose Nonfermenting 1-Related Protein Kinase 2.6 State by Persulfidation and Phosphorylation: Insights from Molecular Dynamics Simulations
Authors: Li Miaomiao , Wu Ting , Wang Shuhan , Duan Tianqi , Huang Siqi , Xie Yanjie
Published: July 2023

SnRK2.6 (SUCROSE NONFERMENTING 1-RELATED PROTEIN KINASE2.6) has been characterized as a molecular switch for the intracellular abscisic acid (ABA) signal-transduction pathway. Normally, SnRK2.6 is kept in an “off” state, forming a binary complex with protein phosphatase type 2Cs (PP2Cs). Upon stressful conditions, SnRK2.6 turns into an “on” state by its release from PP2Cs and then phosphorylation at Ser175. However, how the ”on” and “off” states for SnRK2.6 are fine-tuned, thereby controlling the initiation and braking processes of ABA signaling, is still largely unclear. SnRK2.6 activity was tightly regulated through protein post-translational modifications (PTM), such as persulfidation and phosphorylation. Taking advantage of molecular dynamics simulations, our results showed that Cys131/137 persulfidation on SnRK2.6 induces destabilized binding and weakened interactions between SnRK2.6 and HAB1 (HYPERSENSITIVE TO ABA1), an important PP2C family protein. This unfavorable effect on the association of the SnRK2.6–HAB1 complex suggests that persulfidation functions are a positive regulator of ABA signaling initiation. In addition, Ser267 phosphorylation in persulfidated SnRK2.6 renders a stable physical association between SnRK2.6 and HAB1, a key characterization for SnRK2.6 inhibition. Rather than Ser175, HAB1 cannot dephosphorylate Ser267 in SnRK2.6, which implies that the retained phosphorylation status of Ser267 could ensure that the activated SnRK2.6 reforms the binary complex to cease ABA signaling. Taken together, our findings expand current knowledge concerning the regulation of persulfidation and phosphorylation on the state transition of SnRK2.6 and provide insights into the fine-tuned mechanism of ABA signaling.
κO-SrVIA Conopeptide, a Novel Inhibitor Peptide for Two Members of the Human EAG Potassium Channel Family
Authors: Martínez-Hernández Luis , López-Vera Estuardo , Aguilar Manuel B. , Rodriguez-Ruiz Ximena C. , Ortíz-Arellano Mónica A.
Published: July 2023

The first conotoxin affecting the voltage-gated potassium channels of the EAG family was identified and characterized from the venom of the vermivorous species Conus spurius from the Gulf of Mexico. This conopeptide, initially named Cs68 and later designated κO-SrVIA, is extremely hydrophobic and comprises 31 amino acid residues, including six Cysteines in the framework VI/VII, and a free C-terminus. It inhibits the currents mediated by two human EAG subtypes, Kv10.1 (IC50 = 1.88 ± 1.08 µM) and Kv11.1 (IC50 = 2.44 ± 1.06 µM), and also the human subtype Kv1.6 (IC50 = 3.6 ± 1.04 µM). Despite its clear effects on potassium channels, it shares a high sequence identity with δ-like-AtVIA and δ-TsVIA. Also, κO-SrVIA is the third conopeptide from the venom of C. spurius with effects on potassium channels, and the seventh conotoxin that blocks Kv1.6 channels.
PDE4 Inhibitors: Profiling Hits through the Multitude of Structural Classes
Authors: Jin Jian , Mazzacuva Francesca , Crocetti Letizia , Giovannoni Maria Paola , Cilibrizzi Agostino
Published: July 2023

Cyclic nucleotide phosphodiesterases 4 (PDE4) are a family of enzymes which specifically promote the hydrolysis and degradation of cAMP. The inhibition of PDE4 enzymes has been widely investigated as a possible alternative strategy for the treatment of a variety of respiratory diseases, including chronic obstructive pulmonary disease and asthma, as well as psoriasis and other autoimmune disorders. In this context, the identification of new molecules as PDE4 inhibitors continues to be an active field of investigation within drug discovery. This review summarizes the medicinal chemistry journey in the design and development of effective PDE4 inhibitors, analyzed through chemical classes and taking into consideration structural aspects and binding properties, as well as inhibitory efficacy, PDE4 selectivity and the potential as therapeutic agents.
Acetyl-L-Carnitine and Liposomal Co-Enzyme Q10 Attenuate Hepatic Inflammation, Apoptosis, and Fibrosis Induced by Propionic Acid
Authors: Alhusaini Ahlam M. , Alsoghayer Rahaf , Alhushan Lina , Alanazi Abeer M. , Hasan Iman H.
Published: July 2023

Propionic acid (PRA) is a metabolic end-product of enteric bacteria in the gut, and it is commonly used as a food preservative. Despite the necessity of PRA for immunity in the body, excessive exposure to this product may result in disruptive effects. The purpose of this study is to examine the hepatoprotective effects of acetyl-L-carnitine (A-CAR) and liposomal-coenzyme Q10 (L-CoQ10) against PRA-induced injury. Liver injury in rats was induced by oral administration of PRA, and A-CAR and L-CoQ10 were administered concurrently with PRA for 5 days. Oxidative stress, inflammatory, apoptotic, and fibrotic biomarkers were analyzed; the histology of liver tissue was assessed as well to further explore any pathological alterations. PRA caused significant increases in the levels of serum liver enzymes and hepatic oxidative stress, inflammatory, and apoptotic biomarker levels, along with histopathological alterations. Concurrent treatment with A-CAR and/or L-CoQ10 with PRA prevented tissue injury and decreased the levels of oxidative stress, proinflammatory cytokines, and apoptotic markers. Additionally, A-CAR and/or L-CoQ10 modulated the expression of high-mobility group box-1, cytokeratin-18, transforming growth factor-beta1, and SMAD3 in liver tissue. In conclusion, A-CAR and/or L-CoQ10 showed hepatoprotective efficacy by reducing oxidative stress, the inflammatory response, apoptosis, and fibrosis in liver tissue.
In Silico Identification and Analysis of Proteins Containing the Phox Homology Phosphoinositide-Binding Domain in Kinetoplastea Protists: Evolutionary Conservation and Uniqueness of Phox-Homology-Domain-Containing Protein Architectures
Authors: Petsana Marina , Roumia Ahmed F. , Bagos Pantelis G. , Boleti Haralabia , Braliou Georgia G.
Published: July 2023

Kinetoplastea are free living and parasitic protists with unique features among Eukaryota. Pathogenic Kinetoplastea parasites (i.e., Trypanosoma and Leishmania spp.) undergo several developmental transitions essential for survival in their hosts. These transitions require membrane and cytoskeleton reorganizations that involve phosphoinositides (PIs). Phospholipids like PIs are key regulators of vital functions in all eukaryotes including signal transduction, protein transport and sorting, membrane trafficking, and cytoskeleton and membrane remodeling. A large repertoire of PI-metabolizing enzymes and PI-binding proteins/effectors carrying distinct PI-binding modules like the PX (phox homology) module could play significant roles in the life and virulence of pathogenic Kinetoplastea. The aim of this study was to retrieve the entire spectrum of Kinetoplastea protein sequences containing the PX module (PX-proteins), predict their structures, and identify in them evolutionary conserved and unique traits. Using a large array of bioinformatics tools, protein IDs from two searches (based on PFam’s pHMM for PX domain (PF00787)) were combined, aligned, and utilized for the construction of a new Kinetoplastea_PX pHMM. This three-step search retrieved 170 PX-protein sequences. Structural domain configuration analysis identified PX, Pkinase, Lipocalin_5, and Vps5/BAR3-WASP domains and clustered them into five distinct subfamilies. Phylogenetic tree and domain architecture analysis showed that some domain architectures exist in proteomes of all Kinetoplastea spp., while others are genus-specific. Finally, amino acid conservation logos of the Kinetoplastea spp. and Homo sapiens PX domains revealed high evolutionary conservation in residues forming the critical structural motifs for PtdIns3P recognition. This study highlights the PX-Pkinase domain architecture as unique within Trypanosoma spp. and forms the basis for a targeted functional analysis of Kinetoplastea PX-proteins as putative targets for a rational design of anti-parasitic drugs.
Transcriptomic Analysis of the Dehydration Rate of Mature Rice (Oryza sativa) Seeds
Authors: Liu Zhongqi , Gui Jinxin , Yan Yuntao , Zhang Haiqing , He Jiwai
Published: July 2023

In this study, a transcriptomic analysis of the dehydration rate of mature rice seeds was conducted to explore candidate genes related to the dehydration rate and provide a theoretical basis for breeding and utilization. We selected two rice cultivars for testing (Baghlani Nangarhar, an extremely rapid dehydration genotype, and Saturn, a slow dehydration genotype) based on the results determined by previous studies conducted on the screening of 165 germplasm materials for dehydration rate phenotypes. A rapid dehydration experiment performed on these two types of seeds was conducted. Four comparative groups were set up under control and dehydration conditions. The differentially expressed genes (DEGs) were quantified via transcriptome sequencing and real-time quantitative PCR (RT-qPCR). GO (Gene ontology) and KEGG(Kyoto Encyclopedia of Genes and Genomes) analyses were also conducted. In Baghlani Nangarhar, 53 DEGs were screened, of which 33 were up-regulated and 20 were down-regulated. In Saturn, 25 DEGs were screened, of which 19 were up-regulated and 6 were down-regulated. The results of the GO analysis show that the sites of action of the differentially expressed genes enriched in the rapid dehydration modes are concentrated in the cytoplasm, internal components of the membrane, and nucleosomes. They play regulatory roles in the processes of catalysis, binding, translocation, transcription, protein folding, degradation, and replication. They are also involved in adaptive responses to adverse external environments, such as reactive oxygen species and high temperature. The KEGG analysis showed that protein processing in the endoplasmic reticulum, amino acid biosynthesis, and oxidative phosphorylation were the main metabolic pathways that were enriched. The key differentially expressed genes and the most important metabolic pathways identified in the rapidly and slowly dehydrated genotypes were protein processing in the endoplasmic reticulum and oxidative phosphorylation metabolism. They were presumed to have important regulatory roles in the mechanisms of stress/defense, energy metabolism, protein synthesis/folding, and signal transduction during the dehydration and drying of mature seeds. The results of this study can potentially provide valuable information for further research on the genes and metabolic pathways related to the dehydration rate of mature rice seeds, and provide theoretical guidance for the selection and breeding of new rice germplasm that can be rapidly dehydrated at the mature stage.
Increase in TPSB2 and TPSD1 Expression in Synovium of Hip Osteoarthritis Patients Who Are Overweight
Authors: Tsuchiya Maho , Fukushima Kensuke , Takata Ken , Ohashi Yoshihisa , Uchiyama Katsufumi , Takahira Naonobu , Saito Hiroki , Tsukada Ayumi , Inoue Gen , Takaso Masashi , Uchida Kentaro
Published: July 2023

While research suggests that increasing body mass index (BMI) is a risk factor for hip osteoarthritis (HOA), the mechanisms of this effect are not fully understood. Tryptases are among the main proteases found in mast cells (MCs) and contribute to OA pathology. TPSB2, which encodes β-tryptase, is increased in the synovium of overweight and obese knee OA patients. However, it remains unclear whether tryptase in the synovium of HOA is increased with increasing BMI. Here, we investigated tryptase genes (TPSB2 and TPSD1) in the synovium of overweight HOA patients. Forty-six patients radiographically diagnosed with HOA were allocated to two groups based on BMI, namely normal (<25 kg/m2) and overweight (25–29.99 kg/m2). TPSB2 and TPSD1 expression in the synovium of the two groups was compared using real-time polymerase chain reaction. To compare TPSB2 and TPSD1 expression in MCs between the groups, we isolated the MC-rich fraction (MC-RF) and MC-poor fraction (MC-PF), extracted using magnetic isolation. TPSB2 and TPSD1 expression was increased in the overweight group compared with the normal group. Expression of both genes in the MC-RF was significantly higher than that in MC-PF in both groups. However, TPSB2 and TPSD1 expression levels in the MC-RF did not differ between the groups. Tryptase genes were highly expressed in the synovium of overweight HOA patients. Further investigation to reveal the role of tryptase in the relationship between increasing BMI and HOA pathology is required.
Use of Chitosan-Based Polyelectrolyte Complexes for Its Potential Application in Active Food Packaging: A Review of Recent Literature
Authors: Alvarado Nancy , Abarca Romina L. , Linares-Flores Cristian
Published: July 2023

The current challenges in the food packaging field are, on one side, replacing plastic from non-renewable sources with biopolymers and, on the other hand, generating a packaging material with attractive properties for the consumer. Currently, the consumer is ecologically concerned; the food packaging industry must think ahead to satisfy their needs. In this context, the utilization of polyelectrolyte complexes (PECs) in this industry presents itself as an excellent candidate for fulfilling these requirements. PECs possess enticing characteristics such as encapsulation, protection, and transportation, among others. On the other hand, diverse types of biopolymers have been used in the formation of PECs, such as alginate, cellulose, gelatin, collagen, and so on. Hence, this paper reviews the use of PECs in food packaging where chitosan forms polyelectrolyte complexes.
Investigating the Prevalence of RNA-Binding Metabolic Enzymes in E. coli
Authors: Klein Thomas , Funke Franziska , Rossbach Oliver , Lehmann Gerhard , Vockenhuber Michael , Medenbach Jan , Suess Beatrix , Meister Gunter , Babinger Patrick
Published: July 2023

An open research field in cellular regulation is the assumed crosstalk between RNAs, metabolic enzymes, and metabolites, also known as the REM hypothesis. High-throughput assays have produced extensive interactome data with metabolic enzymes frequently found as hits, but only a few examples have been biochemically validated, with deficits especially in prokaryotes. Therefore, we rationally selected nineteen Escherichia coli enzymes from such datasets and examined their ability to bind RNAs using two complementary methods, iCLIP and SELEX. Found interactions were validated by EMSA and other methods. For most of the candidates, we observed no RNA binding (12/19) or a rather unspecific binding (5/19). Two of the candidates, namely glutamate-5-kinase (ProB) and quinone oxidoreductase (QorA), displayed specific and previously unknown binding to distinct RNAs. We concentrated on the interaction of QorA to the mRNA of yffO, a grounded prophage gene, which could be validated by EMSA and MST. Because the physiological function of both partners is not known, the biological relevance of this interaction remains elusive. Furthermore, we found novel RNA targets for the MS2 phage coat protein that served us as control. Our results indicate that RNA binding of metabolic enzymes in procaryotes is less frequent than suggested by the results of high-throughput studies, but does occur.
Morphological Observation and Transcriptome Analysis of Ciliogenesis in Urechis unicinctus (Annelida, Echiura)
Authors: Kong Dexu , Wei Maokai , Liu Danwen , Zhang Zhengrui , Ma Yubin , Zhang Zhifeng
Published: July 2023

During the early development of marine invertebrates, planktic larvae usually occur, and their body surfaces often form specific types of cilia that are involved in locomotion and feeding. The echiuran worm Urechis unicinctus sequentially undergoes the formation and disappearance of different types of body surface cilia during embryonic and larval development. The morphological characteristics and molecular mechanisms involved in the process remain unclear. In this study, we found that body surface cilia in U. unicinctus embryos and larvae can be distinguished into four types: body surface short cilia, apical tufts, circumoral cilia and telotrochs. Further, distribution and genesis of the body surface cilia were characterized using light microscope and electron microscope. To better understand the molecular mechanism during ciliogenesis, we revealed the embryonic and larval transcriptome profile of the key stages of ciliogenesis in U. unicinctus using RNA-Seq technology. A total of 29,158 differentially expressed genes (DEGs) were obtained from 24 cDNA libraries by RNA-Seq. KEGG pathway enrichment results showed that Notch, Wnt and Ca2+ signaling pathways were significantly enriched during the occurrence of apical tufts and circumoral cilia. Furthermore, all DEGs were classified according to their expression pattern, and DEGs with similar expression pattern were grouped into a module. All DEG co-expression modules were correlated with traits (body surface short cilia, apical tufts, circumoral cilia and telotrochs) by WGCNA, the results showed DEGs were divided into 13 modules by gene expression patterns and that the genes in No. 7, No. 8 and No. 10 modules were to be highly correlated with the occurrence of apical tufts, circumoral cilia and telotrochs. The top 10 hub genes in the above three modules were identified to be highly correlated with ciliogenesis, including the reported cilium-related gene Cnbd2 and unreported cilium-related candidate genes FAM181B, Capsl, Chst3, TMIE and Innexin. Notably, Innexin was included in the top10 hub genes of the two modules (No. 7 and No. 8), suggesting that Innexin may play an important role in U. unicinctus apical tufts, circumoral cilia and telotrochs genesis. This study revealed the characteristics of ciliogenesis on the body surface of U. unicinctus embryos and larvae, providing basic data for exploring the molecular mechanism of ciliogenesis on the body surface.
Unravelling the Therapeutic Potential of Antibiotics in Hypoxia in a Breast Cancer MCF-7 Cell Line Model
Authors: Akhunzianov Almaz A. , Nesterova Alfiya I. , Wanrooij Sjoerd , Filina Yulia V. , Rizvanov Albert A. , Miftakhova Regina R.
Published: July 2023

Antibiotics inhibit breast cancer stem cells (CSCs) by suppressing mitochondrial biogenesis. However, the effectiveness of antibiotics in clinical settings is inconsistent. This inconsistency raises the question of whether the tumor microenvironment, particularly hypoxia, plays a role in the response to antibiotics. Therefore, the goal of this study was to evaluate the effectiveness of five commonly used antibiotics for inhibiting CSCs under hypoxia using an MCF-7 cell line model. We assessed the number of CSCs through the mammosphere formation assay and aldehyde dehydrogenase (ALDH)-bright cell count. Additionally, we examined the impact of antibiotics on the mitochondrial stress response and membrane potential. Furthermore, we analyzed the levels of proteins associated with therapeutic resistance. There was no significant difference in the number of CSCs between cells cultured under normoxic and hypoxic conditions. However, hypoxia did affect the rate of CSC inhibition by antibiotics. Specifically, azithromycin was unable to inhibit sphere formation in hypoxia. Erythromycin and doxycycline did not reduce the ratio of ALDH-bright cells, despite decreasing the number of mammospheres. Furthermore, treatment with chloramphenicol, doxycycline, and tetracycline led to the overexpression of the breast cancer resistance protein. Our findings suggest that hypoxia may weaken the inhibitory effects of antibiotics on the breast cancer model.
Embryonic Development of Parthenogenetic and Sexual Eggs in Lower Termites
Authors: Peng Xin , Khan Zahid , Liu Xiao-Min , Deng Shi-Lin , Fang Yong-Gang , Zhang Min , Su Xiao-Hong , Xing Lian-Xi , Yan Xing-Rong
Published: July 2023

Worldwide, termites are one of few social insects. In this research, the stages of embryonic development in the parthenogenetic and sexual eggs of Reticulitermes aculabialis and R. flaviceps were observed and described. In R. flaviceps, the egg development of the FF and FM groups happened during the early phases of development, whereas in R. aculabialis, this appeared mainly during the late phase of development. The variance in the number of micropyles between the R. flaviceps FF colony type and the R. aculabialis FF colony type was statistically significant. Five stages of egg development were found in both types of R. aculabialis but only the sexual eggs of R. flaviceps. In R. flaviceps, 86% of the parthenogenetic eggs stopped growing during the blastoderm development, with the yolk cell assembling frequently in the center of the egg. According to the results of the single-cell transcriptome sequencing, we investigated the egg-to-larval expression level of genes (pka, map2k1, mapk1/3, hgk, mkp, and pax6) and indicated that the levels of essential gene expression in RaFF were considerably higher than in RfFF (p < 0.05). We also discovered that the oocyte cleavage rate in the FF colony type was considerably lower in R. flaviceps compared to R. aculabialis, which gave rise to a smaller number of mature oocytes in R. flaviceps. During ovulation in both species, oocytes underwent activation and one or two cleavage events, but the development of unfertilized eggs ceased in R. flaviceps. It was shown that termite oocyte and embryonic development were heavily influenced by genes with significant expressions. Results from the databases KEGG, COG, and GO unigenes revealed the control of numerous biological processes. This study is the first to complete a database of parthenogenetic and sexual eggs of R. flaviceps and R. aculabialis.
The Impact of Blood Transfusion in Developing Postoperative Delirium in Patients with Hip Fracture Surgery
Authors: Lee Sang-Soo , Kim Jong-Ho , Lee Jae-Jun , Kwon Young-Suk , Seo Eun-Min
Published: July 2023

Background: Many studies have been conducted to explore the risk factors associated with postoperative delirium (POD) in order to understand its underlying causes and develop prevention strategies, especially for hip fracture surgery. However, the relationship between blood transfusion and POD has been heatedly debated. The purpose of this study was to evaluate the risk factors of POD and the relationship between blood transfusions and the occurrence of POD in hip fracture surgery through big data analysis. Methods: Medical data (including medication history, clinical and laboratory findings, and perioperative variables) were acquired from the clinical data warehouse (CDW) of the five hospitals of Hallym University Medical Center and were compared between patients without POD and with POD. Results: The occurrence of POD was 18.7% (228 of 2398 patients). The risk factors of POD included old age (OR 4.38, 95% CI 2.77–6.91; p < 0.001), American Society of Anesthesiology physical status > 2 (OR 1.84 95% CI 1.4–2.42; p < 0.001), dementia (OR 1.99, 95% CI 1.53–2.6; p < 0.001), steroid (OR 0.53 95% CI 0.34–0.82; p < 0.001), Antihistamine (OR 1.53 95% CI 1.19–1.96; p < 0.001), and postoperative erythrocyte sedimentation rate (mm/h) (OR 0.97 95% CI 0.97–0.98; p < 0.001) in multivariate logistic regression analysis. The postoperative transfusion (OR 2.53, 95% CI 1.88–3.41; p < 0.001) had a significant effect on the incidence of POD. Conclusions: big data analytics using a CDW was a good option to identify the risk factors of POD and to prevent POD in hip fracture surgery.
Patterns of Dickkopf-3 Serum and Urine Levels at Different Stages of Chronic Kidney Disease
Authors: Dziamałek-Macioszczyk Paulina , Winiarska Agata , Pawłowska Anna , Wojtacha Paweł , Stompór Tomasz
Published: July 2023

Dickkopf 3 (Dkk3) is a WNT/β-catenin signaling pathway regulator secreted by tubular epithelial cells upon the influence of different stressors. Recently Dkk3 was described as a biomarker of tubular cell injury and a tool that may estimate the risk of chronic kidney disease (CKD) progression. The data about Dkk3 concentrations at particular stages of CKD are lacking. The aim of this study was to measure serum and urine Dkk3 levels in patients with different ‘renal status’ and evaluate its role as a biomarker of renal damage. One hundred individuals, aged between 24 and 85 years (mean 53.1 ± 17.1), were enrolled in the study. Five groups of 20 subjects each were recruited based on their kidney function. Serum and urine Dkk3 levels were measured by ELISA. The highest median urinary Dkk3 normalized to urinary creatinine was found in patients with established CKD (7051 pg/mg). It was two times higher in renal transplant patients (5705 pg/mg) than in healthy individuals (2654 pg/mg) and the glomerulonephritis group (2470 pg/mg). Urinary Dkk3 was associated with serum creatinine in participants with established CKD and following transplantation. Our results confirm the potential role of Dkk3 as a biomarker of an ongoing renal injury.
Peripapillary Intrachoroidal Cavitation
Authors: Ehongo Adèle , Bacq Noélie
Published: July 2023

Peripapillary intrachoroidal cavitation (PICC) is a yellow-orange lesion, located at the outer border of the myopic conus. First described as a localized detachment of the retinal pigment epithelium, its intrachoroidal location was later revealed, justifying its current name. PICC is related to other myopic complications such as posterior staphyloma, but its pathogenesis is not clear to date. Although it has been considered a benign condition, most eyes with PICC show visual field defects, which leads to diagnostic uncertainty as these deficits resemble those seen in glaucoma. Furthermore, eyes with PICC may develop macular detachment with retinoschisis. Finally, misdiagnosis of PICC as a metastatic choroidal tumor may lead to unnecessary and anxiety-inducing investigations. Advances in optical coherence tomography (OCT) imaging have improved the visualization of ocular structures, contributing to the understanding of PICC. Recently, high optic nerve sheath traction forces during eye movements in highly myopic eyes have been suggested as promoters of PICC, renewing interest around this condition. However, a review of PICC is still lacking. Therefore, we aimed to provide a concise yet comprehensive overview of the current state of the art, focusing on OCT illustrations, pathophysiology and potential future perspectives based on the biomechanics of the optic nerve.